The Establishment of an ISO Compliant Cancer Biobank for Jordan and its Neighboring Countries Through Knowledge Transfer and Training

PubMed Central

Barr, Martin; Souan, Lina; MacGabhann, Peadar; Müller, Jeanette; Al Ashhab, Maxim; Jasser, Mohammed; Hamza, Khetam; Al Hassoon, Sallam; Kuhn, Uwe; Infante, Daniela; Lawlor, Denise; Gately, Kathy; Amireh, Eyad; O'Byrne, Kenneth

2014-01-01

Research studies aimed at advancing cancer prevention, diagnosis, and treatment depend on a number of key resources, including a ready supply of high-quality annotated biospecimens from diverse ethnic populations that can be used to test new drugs, assess the validity of prognostic biomarkers, and develop tailor-made therapies. In November 2011, KHCCBIO was established at the King Hussein Cancer Center (KHCC) with the support of Seventh Framework Programme (FP7) funding from the European Union (khccbio.khcc.jo). KHCCBIO was developed for the purpose of achieving an ISO accredited cancer biobank through the collection, processing, and preservation of high-quality, clinically annotated biospecimens from consenting cancer patients, making it the first cancer biobank of its kind in Jordan. The establishment of a state-of-the-art, standardized biospecimen repository of matched normal and lung tumor tissue, in addition to blood components such as serum, plasma, and white blood cells, was achieved through the support and experience of its European partners, Trinity College Dublin, Biostór Ireland, and accelopment AG. To date, KHCCBIO along with its partners, have worked closely in establishing an ISO Quality Management System (QMS) under which the biobank will operate. A Quality Policy Manual, Validation, and Training plan have been developed in addition to the development of standard operating procedures (SOPs) for consenting policies on ethical issues, data privacy, confidentiality, and biobanking bylaws. SOPs have also been drafted according to best international practices and implemented for the donation, procurement, processing, testing, preservation, storage, and distribution of tissues and blood samples from lung cancer patients, which will form the basis for the procurement of other cancer types. KHCCBIO will be the first ISO accredited cancer biobank from a diverse ethnic Middle Eastern and North African population. It will provide a unique and valuable resource of high-quality human biospecimens and anonymized clinicopathological data to the cancer research communities world-wide. PMID:24620764

A Federated Network for Translational Cancer Research Using Clinical Data and Biospecimens

PubMed Central

Becich, Michael J.; Bollag, Roni J.; Chavan, Girish; Corrigan, Julia; Dhir, Rajiv; Feldman, Michael D.; Gaudioso, Carmelo; Legowski, Elizabeth; Maihle, Nita J.; Mitchell, Kevin; Murphy, Monica; Sakthivel, Mayur; Tseytlin, Eugene; Weaver, JoEllen

2015-01-01

Advances in cancer research and personalized medicine will require significant new bridging infrastructures, including more robust biorepositories that link human tissue to clinical phenotypes and outcomes. In order to meet that challenge, four cancer centers formed the TIES Cancer Research Network, a federated network that facilitates data and biospecimen sharing among member institutions. Member sites can access pathology data that is de-identified and processed with the TIES natural language processing system, which creates a repository of rich phenotype data linked to clinical biospecimens. TIES incorporates multiple security and privacy best practices that, combined with legal agreements, network policies and procedures, enable regulatory compliance. The TIES Cancer Research Network now provides integrated access to investigators at all member institutions, where multiple investigator-driven pilot projects are underway. Examples of federated search across the network illustrate the potential impact on translational research, particularly for studies involving rare cancers, rare phenotypes, and specific biologic behaviors. The network satisfies several key desiderata including local control of data and credentialing, inclusion of rich phenotype information, and applicability to diverse research objectives. The TIES Cancer Research Network presents a model for a national data and biospecimen network. PMID:26670560

SEER Cancer Registry Biospecimen Research: Yesterday and Tomorrow

PubMed Central

Altekruse, Sean F.; Rosenfeld, Gabriel E.; Carrick, Danielle M.; Pressman, Emilee J.; Schully, Sheri D.; Mechanic, Leah E.; Cronin, Kathleen A.; Hernandez, Brenda Y.; Lynch, Charles F.; Cozen, Wendy; Khoury, Muin J.; Penberthy, Lynne T.

2014-01-01

The National Cancer Institute's (NCI) Surveillance, Epidemiology, and End Results (SEER) registries have been a source of biospecimens for cancer research for decades. Recently, registry-based biospecimen studies have become more practical, with the expansion of electronic networks for pathology and medical record reporting. Formalin-fixed paraffin-embedded specimens are now used for next-generation sequencing and other molecular techniques. These developments create new opportunities for SEER biospecimen research. We evaluated 31 research articles published during 2005–2013 based on author confirmation that these studies involved linkage of SEER data to biospecimens. Rather than providing an exhaustive review of all possible articles, our intent was to indicate the breadth of research made possible by such a resource. We also summarize responses to a 2012 questionnaire that was broadly distributed to the NCI intra- and extramural biospecimen research community. This included responses from 30 investigators who had used SEER biospecimens in their research. The survey was not intended to be a systematic sample, but instead to provide anecdotal insight on strengths, limitations, and the future of SEER biospecimen research. Identified strengths of this research resource include biospecimen availability, cost, and annotation of data, including demographic information, stage, and survival. Shortcomings include limited annotation of clinical attributes such as detailed chemotherapy history and recurrence, and timeliness of turnaround following biospecimen requests. A review of selected SEER biospecimen articles, investigator feedback, and technological advances reinforced our view that SEER biospecimen resources should be developed. This would advance cancer biology, etiology, and personalized therapy research. PMID:25472677

Planned Variation in Preanalytical Conditions to Evaluate Biospecimen Stability in the National Children’s Study (NCS)

PubMed Central

Mechanic, Leah; Mendez, Armando; Merrill, Lori; Rogers, John; Layton, Marnie; Todd, Deborah; Varanasi, Arti; O’Brien, Barbara; Meyer, William A.; Zhang, Ming; Schleicher, Rosemary L.; Moye, Jack

2014-01-01

BACKGROUND Preanalytical conditions encountered during collection, processing, and storage of biospecimens may influence laboratory results. The National Children’s Study (NCS) is a planned prospective cohort study of 100,000 families to examine the influence of a wide variety of exposures on child health. In developing biospecimen collection, processing, and storage procedures for the NCS, we identified several analytes of different biochemical categories for which it was unclear to what extent deviations from NCS procedures could influence measurement results. METHODS A pilot study was performed to examine effects of preanalytic sample handling conditions (delays in centrifugation, freezing delays, delays in separation from cells, additive delay, and tube type) on concentrations of eight different analytes. 2,825 measurements were made to assess 15 unique combinations of analyte and handling conditions in blood collected from 151 women of childbearing age (≥20 individuals per handling condition). RESULTS The majority of analytes were stable under the conditions evaluated. However, levels of plasma interleukin-6 and serum insulin were decreased in response to sample centrifugation delays of up to 5.5 hours post collection (P<0.0001). In addition, delays in freezing centrifuged plasma samples (comparing 24, 48 and 72 hours to immediate freezing) resulted in increased levels of adrenocorticotropic hormone (P=0.0014). CONCLUSIONS Determining stability of proposed analytes in response to preanalytical conditions and handling helps to ensure high-quality specimens for study now and in the future. The results inform development of procedures, plans for measurement of analytes, and interpretation of laboratory results. PMID:23924524

Factors associated with willingness to participate in biospecimen research among Chinese Americans.

PubMed

Gao, Wanzhen; Ma, Grace X; Tan, Yin; Fang, Carolyn; Weaver, JoEllen; Jin, Ming; Lai, Philip

2014-04-01

A paucity of information exists on the recruitment of Asian Americans for biospecimen research. Although studies show that Chinese Americans are at high risk for hepatitis B virus (HBV) infection, little is known about their willingness to participate in HBV-related biospecimen research and how knowledge, attitudes, and cultural factors impact their willingness to participate. The study was guided by Community-Based Participatory Research principles. Data were derived from an assessment study on HBV-related biospecimen research participation among Chinese Americans in the Philadelphia region. The assessment was conducted with 415 Chinese Americans recruited from eight Chinese community-based organizations. Cultural beliefs, knowledge, and attitudes toward biospecimen research were examined for associations with their willingness to participate in biospecimen banking research. Overall, 192 (46.3%) of 415 participants who completed the assessment indicated they were willing to participate if they were invited to donate blood to be frozen and stored for future HBV biospecimen studies. Cultural variables significant in bivariate analysis included collectivism, knowledge about biospecimen research, and Yin-Yang beliefs. Fatalism and individualism were not associated with participation willingness. In multivariate analysis, age, health care attitudes, and trust were significantly associated with willingness to participate in biospecimen banking research. Asian American communities have little knowledge of biospecimen banking and will benefit from educational campaigns that emphasize collective benefits and attitudes towards and trust in the health care system. Understanding cultural factors is important for improving Chinese Americans' knowledge, awareness, and intentions of participation in biospecimen research. Similar efforts need to be undertaken to develop culturally appropriate educational intervention programs to increase participation in biospecimen research among other Asian American groups.

Factors Associated with Willingness to Participate in Biospecimen Research Among Chinese Americans

PubMed Central

Gao, Wanzhen; Tan, Yin; Fang, Carolyn; Weaver, JoEllen; Jin, Ming; Lai, Philip

2014-01-01

A paucity of information exists on the recruitment of Asian Americans for biospecimen research. Although studies show that Chinese Americans are at high risk for hepatitis B virus (HBV) infection, little is known about their willingness to participate in HBV-related biospecimen research and how knowledge, attitudes, and cultural factors impact their willingness to participate. The study was guided by Community-Based Participatory Research principles. Data were derived from an assessment study on HBV-related biospecimen research participation among Chinese Americans in the Philadelphia region. The assessment was conducted with 415 Chinese Americans recruited from eight Chinese community-based organizations. Cultural beliefs, knowledge, and attitudes toward biospecimen research were examined for associations with their willingness to participate in biospecimen banking research. Overall, 192 (46.3%) of 415 participants who completed the assessment indicated they were willing to participate if they were invited to donate blood to be frozen and stored for future HBV biospecimen studies. Cultural variables significant in bivariate analysis included collectivism, knowledge about biospecimen research, and Yin-Yang beliefs. Fatalism and individualism were not associated with participation willingness. In multivariate analysis, age, health care attitudes, and trust were significantly associated with willingness to participate in biospecimen banking research. Asian American communities have little knowledge of biospecimen banking and will benefit from educational campaigns that emphasize collective benefits and attitudes towards and trust in the health care system. Understanding cultural factors is important for improving Chinese Americans' knowledge, awareness, and intentions of participation in biospecimen research. Similar efforts need to be undertaken to develop culturally appropriate educational intervention programs to increase participation in biospecimen research among other Asian American groups. PMID:24749880

[Research and development of medical case database: a novel medical case information system integrating with biospecimen management].

PubMed

Pan, Shiyang; Mu, Yuan; Wang, Hong; Wang, Tong; Huang, Peijun; Ma, Jianfeng; Jiang, Li; Zhang, Jie; Gu, Bing; Yi, Lujiang

2010-04-01

To meet the needs of management of medical case information and biospecimen simultaneously, we developed a novel medical case information system integrating with biospecimen management. The database established by MS SQL Server 2000 covered, basic information, clinical diagnosis, imaging diagnosis, pathological diagnosis and clinical treatment of patient; physicochemical property, inventory management and laboratory analysis of biospecimen; users log and data maintenance. The client application developed by Visual C++ 6.0 was used to implement medical case and biospecimen management, which was based on Client/Server model. This system can perform input, browse, inquest, summary of case and related biospecimen information, and can automatically synthesize case-records based on the database. Management of not only a long-term follow-up on individual, but also of grouped cases organized according to the aim of research can be achieved by the system. This system can improve the efficiency and quality of clinical researches while biospecimens are used coordinately. It realizes synthesized and dynamic management of medical case and biospecimen, which may be considered as a new management platform.

Ethics of clear health communication: applying the CLEAN Look approach to communicate biobanking information for cancer research.

PubMed

Koskan, Alexis; Arevalo, Mariana; Gwede, Clement K; Quinn, Gwendolyn P; Noel-Thomas, Shalewa A; Luque, John S; Wells, Kristen J; Meade, Cathy D

2012-11-01

Cancer innovations, such as biobanking technologies, are continuously evolving to improve our understanding and knowledge about cancer prevention and treatment modalities. However, the public receives little communication about biobanking and is often unaware about this innovation until asked to donate biospecimens. It is the researchers' ethical duty to provide clear communications about biobanking and biospecimen research. Such information allows the public to understand biobanking processes and facilitates informed decision making about biospecimen donation. The aims of this paper are 1) to examine the importance of clear communication as an ethical imperative when conveying information about cancer innovations and 2) to illustrate the use of an organizing framework, the CLEAN ( C ulture, L iteracy, E ducation, A ssessment, and N etworking) Look approach for creating educational priming materials about the topic of biobanking.

A Community-Driven Intervention for Improving Biospecimen Donation in African American Communities.

PubMed

Patel, Kushal; Inman, Wendelyn; Gishe, Jemal; Johnson, Owen; Brown, Elizabeth; Kanu, Mohamed; Theriot, Rosemary; Sanderson, Maureen; Hull, Pamela; Hargreaves, Margaret

2018-02-01

Human biospecimens are an invaluable resource for addressing cancers and other chronic diseases. The purpose of this study was to assess the impact of an educational intervention on biospecimen knowledge and attitudes. The participants consisted of 112 African Americans, 18 years and older, and who had not provided biospecimens for any health-related research in the past. A total of 55 participants received the educational brochure, and 57 received the educational video. The main outcomes of the study were knowledge and attitudes for biospecimen donation. This information was collected pre- and post-intervention. The average knowledge scores increased (p < 0.0001) and the average attitude scores for biospecimen donation improved (p < 0.0001) post-intervention for both the video and brochure conditions. There was an interaction between the intervention condition and knowledge where the participants who received the educational video showed a greater increase in knowledge pre-to-post compared to those who received the educational brochure (p = 0.0061). There were no significant interactions between the two intervention conditions for attitudes toward biospecimen donation. The results of this study demonstrated the feasibility and efficacy of an academic institution collaborating with the African American community in developing educational tools for biospecimen donation.

Impact of a biospecimen collection seminar on willingness to donate biospecimens among Chinese Americans: results from a randomized, controlled community-based trial.

PubMed

Tong, Elisa K; Fung, Lei-Chun; Stewart, Susan L; Paterniti, Debora A; Dang, Julie H T; Chen, Moon S

2014-03-01

Biospecimen collection from diverse populations can advance cancer disparities research, but is currently underrepresented. We partnered with a community-based clinic serving Cantonese-speaking Chinese Americans to develop and revise an educational seminar on biospecimen collection. Through a randomized controlled trial (n = 395), the intervention seminar was compared with a control seminar (cancer prevention) on change in willingness to donate biospecimens. At baseline, many were willing to donate a biospecimen (saliva, urine, hair, toenails, blood, unused cancerous tissue) whether healthy or hypothetically had cancer. Also, many would donate because future generations would benefit, and few had concerns about donation. In logistic regression analyses, there was an intervention effect for willingness to donate: urine if had cancer [OR, 2.2; 95% confidence interval (CI), 1.3-3.7], toenails if healthy (OR, 2.1; 95% CI, 1.4-3.2) or had cancer (OR, 2.3; 95% CI, 2.0-2.7), hair if healthy (OR, 1.8; 95% CI, 1.3-2.5) or had cancer (OR, 2.8; 95% CI, 1.9-4.0), and unused cancerous tissue (OR, 1.8; 95% CI, 1.2-2.9). There was also an intervention effect for donating because future generations would benefit (OR, 2.0; 95% CI, 1.4-3.0), and this attitude was a strong independent predictor for willingness to donate all biospecimens, whether healthy or had cancer (OR, 2.9-4.2). Cantonese-speaking Chinese American participants of an educational seminar on biospecimen collection showed greater increases in willingness to donate biospecimens and donating for the benefit of future generations, than participants who attended a control seminar. Donating for the benefit of future generations is a theme that should be incorporated in messages that encourage biospecimen donation for Chinese Americans. ©2014 AACR.

Impact of a Biospecimen Collection Seminar on Willingness to Donate Biospecimens among Chinese Americans: Results from a Randomized, Controlled Community-Based Trial

PubMed Central

Tong, Elisa K.; Fung, Lei-Chun; Stewart, Susan L.; Paterniti, Debora A.; Dang, Julie H.T.; Chen, Moon S.

2014-01-01

Background Biospecimen collection from diverse populations can advance cancer disparities research, but is currently underrepresented. Methods We partnered with a community-based clinic serving Cantonese-speaking Chinese Americans to develop and revise an educational seminar on biospecimen collection. Through a randomized controlled trial (n = 395), the intervention seminar was compared with a control seminar (cancer prevention) on change in willingness to donate biospecimens. Results At baseline, many were willing to donate a biospecimen (saliva, urine, hair, toenails, blood, unused cancerous tissue) whether healthy or hypothetically had cancer. Also, many would donate because future generations would benefit, and few had concerns about donation. In logistic regression analyses, there was an intervention effect for willingness to donate: urine if had cancer [OR, 2.2; 95% confidence interval (CI), 1.3–3.7], toenails if healthy (OR, 2.1; 95% CI, 1.4–3.2) or had cancer (OR, 2.3; 95% CI, 2.0–2.7), hair if healthy (OR, 1.8; 95% CI, 1.3–2.5) or had cancer (OR, 2.8; 95% CI, 1.9–4.0), and unused cancerous tissue (OR, 1.8; 95% CI, 1.2–2.9). There was also an intervention effect for donating because future generations would benefit (OR, 2.0; 95% CI, 1.4–3.0), and this attitude was a strong independent predictor for willingness to donate all biospecimens, whether healthy or had cancer (OR, 2.9–4.2). Conclusion Cantonese-speaking Chinese American participants of an educational seminar on biospecimen collection showed greater increases in willingness to donate biospecimens and donating for the benefit of future generations, than participants who attended a control seminar. Impact Donating for the benefit of future generations is a theme that should be incorporated in messages that encourage biospecimen donation for Chinese Americans. PMID:24609848

Application Period Open for NCI Biospecimen Use | Division of Cancer Prevention

Cancer.gov

The application period for investigators interested in obtaining biospecimens and data from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial re-opened June 1. A separate application for obtaining biospecimens and data with research funding is also open. |

Assays for Qualification and Quality Stratification of Clinical Biospecimens Used in Research: A Technical Report from the ISBER Biospecimen Science Working Group.

PubMed

Betsou, Fay; Bulla, Alexandre; Cho, Sang Yun; Clements, Judith; Chuaqui, Rodrigo; Coppola, Domenico; De Souza, Yvonne; De Wilde, Annemieke; Grizzle, William; Guadagni, Fiorella; Gunter, Elaine; Heil, Stacey; Hodgkinson, Verity; Kessler, Joseph; Kiehntopf, Michael; Kim, Hee Sung; Koppandi, Iren; Shea, Katheryn; Singh, Rajeev; Sobel, Marc; Somiari, Stella; Spyropoulos, Demetri; Stone, Mars; Tybring, Gunnel; Valyi-Nagy, Klara; Van den Eynden, Gert; Wadhwa, Lalita

2016-10-01

This technical report presents quality control (QC) assays that can be performed in order to qualify clinical biospecimens that have been biobanked for use in research. Some QC assays are specific to a disease area. Some QC assays are specific to a particular downstream analytical platform. When such a qualification is not possible, QC assays are presented that can be performed to stratify clinical biospecimens according to their biomolecular quality.

Assays for Qualification and Quality Stratification of Clinical Biospecimens Used in Research: A Technical Report from the ISBER Biospecimen Science Working Group

PubMed Central

Bulla, Alexandre; Cho, Sang Yun; Clements, Judith; Chuaqui, Rodrigo; Coppola, Domenico; De Souza, Yvonne; De Wilde, Annemieke; Grizzle, William; Guadagni, Fiorella; Gunter, Elaine; Heil, Stacey; Hodgkinson, Verity; Kessler, Joseph; Kiehntopf, Michael; Kim, Hee Sung; Koppandi, Iren; Shea, Katheryn; Singh, Rajeev; Sobel, Marc; Somiari, Stella; Spyropoulos, Demetri; Stone, Mars; Tybring, Gunnel; Valyi-Nagy, Klara; Van den Eynden, Gert; Wadhwa, Lalita

2016-01-01

This technical report presents quality control (QC) assays that can be performed in order to qualify clinical biospecimens that have been biobanked for use in research. Some QC assays are specific to a disease area. Some QC assays are specific to a particular downstream analytical platform. When such a qualification is not possible, QC assays are presented that can be performed to stratify clinical biospecimens according to their biomolecular quality. PMID:27046294

A survey of patient perspectives on the research use of health information and biospecimens.

PubMed

Page, Stacey A; Manhas, Kiran Pohar; Muruve, Daniel A

2016-08-15

Personal health information and biospecimens are valuable research resources essential for the advancement of medicine and protected by national standards and provincial statutes. Research ethics and privacy standards attempt to balance individual interests with societal interests. However these standards may not reflect public opinion or preferences. The purpose of this study was to assess the opinions and preferences of patients with kidney disease about the use of their health information and biospecimens for medical research. A 45-item survey was distributed to a convenience sample of patients at an outpatient clinic in a large urban centre. The survey briefly addressed sociodemographic and illness characteristics. Opinions were sought on the research use of health information and biospecimens including consent preferences. Two hundred eleven of 400 distributed surveys were completed (response rate 52.8 %). Respondents were generally supportive of medical research and trusting of researchers. Many respondents supported the use of their information and biospecimens for health research and also preferred consent be sought for use of health information and biospecimens. Some supported the use of their information and biospecimens for research without consent. There were significant differences in the opinions people offered regarding the research use of biospecimens compared to health information. Some respondent perspectives about consent were at odds with current regulatory and legal standards. Clinical health data and biospecimens are valuable research resources, critical to the advancement of medicine. Use of these data for research requires balancing respect for individual autonomy, privacy and the societal interest in the greater good. Incongruence between some respondent perspectives and the regulatory standards suggest both a need for public education and review of legislation to increase understanding and ensure the public's trust is maintained.

Generation and validation of a universal perinatal database and biospecimen repository: PeriBank.

PubMed

Antony, K M; Hemarajata, P; Chen, J; Morris, J; Cook, C; Masalas, D; Gedminas, M; Brown, A; Versalovic, J; Aagaard, K

2016-11-01

There is a dearth of biospecimen repositories available to perinatal researchers. In order to address this need, here we describe the methodology used to establish such a resource. With the collaboration of MedSci.net, we generated an online perinatal database with 847 fields of clinical information. Simultaneously, we established a biospecimen repository of the same clinical participants. The demographic and clinical outcomes data are described for the first 10 000 participants enrolled. The demographic characteristics are consistent with the demographics of the delivery hospitals. Quality analysis of the biospecimens reveals variation in very few analytes. Furthermore, since the creation of PeriBank, we have demonstrated validity of the database and tissue integrity of the biospecimen repository. Here we establish that the creation of a universal perinatal database and biospecimen collection is not only possible, but allows for the performance of state-of-the-science translational perinatal research and is a potentially valuable resource to academic perinatal researchers.

Tissue Banking, Bioinformatics, and Electronic Medical Records: The Front-End Requirements for Personalized Medicine

PubMed Central

Suh, K. Stephen; Sarojini, Sreeja; Youssif, Maher; Nalley, Kip; Milinovikj, Natasha; Elloumi, Fathi; Russell, Steven; Pecora, Andrew; Schecter, Elyssa; Goy, Andre

2013-01-01

Personalized medicine promises patient-tailored treatments that enhance patient care and decrease overall treatment costs by focusing on genetics and “-omics” data obtained from patient biospecimens and records to guide therapy choices that generate good clinical outcomes. The approach relies on diagnostic and prognostic use of novel biomarkers discovered through combinations of tissue banking, bioinformatics, and electronic medical records (EMRs). The analytical power of bioinformatic platforms combined with patient clinical data from EMRs can reveal potential biomarkers and clinical phenotypes that allow researchers to develop experimental strategies using selected patient biospecimens stored in tissue banks. For cancer, high-quality biospecimens collected at diagnosis, first relapse, and various treatment stages provide crucial resources for study designs. To enlarge biospecimen collections, patient education regarding the value of specimen donation is vital. One approach for increasing consent is to offer publically available illustrations and game-like engagements demonstrating how wider sample availability facilitates development of novel therapies. The critical value of tissue bank samples, bioinformatics, and EMR in the early stages of the biomarker discovery process for personalized medicine is often overlooked. The data obtained also require cross-disciplinary collaborations to translate experimental results into clinical practice and diagnostic and prognostic use in personalized medicine. PMID:23818899

A tissue retrieval and postharvest processing regimen for rodent reproductive tissues compatible with long-term storage on the international space station and postflight biospecimen sharing program.

PubMed

Gupta, Vijayalaxmi; Holets-Bondar, Lesya; Roby, Katherine F; Enders, George; Tash, Joseph S

2015-01-01

Collection and processing of tissues to preserve space flight effects from animals after return to Earth is challenging. Specimens must be harvested with minimal time after landing to minimize postflight readaptation alterations in protein expression/translation, posttranslational modifications, and expression, as well as changes in gene expression and tissue histological degradation after euthanasia. We report the development of a widely applicable strategy for determining the window of optimal species-specific and tissue-specific posteuthanasia harvest that can be utilized to integrate into multi-investigator Biospecimen Sharing Programs. We also determined methods for ISS-compatible long-term tissue storage (10 months at -80°C) that yield recovery of high quality mRNA and protein for western analysis after sample return. Our focus was reproductive tissues. The time following euthanasia where tissues could be collected and histological integrity was maintained varied with tissue and species ranging between 1 and 3 hours. RNA quality was preserved in key reproductive tissues fixed in RNAlater up to 40 min after euthanasia. Postfixation processing was also standardized for safe shipment back to our laboratory. Our strategy can be adapted for other tissues under NASA's Biospecimen Sharing Program or similar multi-investigator tissue sharing opportunities.

Extracting DNA from FFPE Tissue Biospecimens Using User-Friendly Automated Technology: Is There an Impact on Yield or Quality?

PubMed

Mathieson, William; Guljar, Nafia; Sanchez, Ignacio; Sroya, Manveer; Thomas, Gerry A

2018-05-03

DNA extracted from formalin-fixed, paraffin-embedded (FFPE) tissue blocks is amenable to analytical techniques, including sequencing. DNA extraction protocols are typically long and complex, often involving an overnight proteinase K digest. Automated platforms that shorten and simplify the process are therefore an attractive proposition for users wanting a faster turn-around or to process large numbers of biospecimens. It is, however, unclear whether automated extraction systems return poorer DNA yields or quality than manual extractions performed by experienced technicians. We extracted DNA from 42 FFPE clinical tissue biospecimens using the QiaCube (Qiagen) and ExScale (ExScale Biospecimen Solutions) automated platforms, comparing DNA yields and integrities with those from manual extractions. The QIAamp DNA FFPE Spin Column Kit was used for manual and QiaCube DNA extractions and the ExScale extractions were performed using two of the manufacturer's magnetic bead kits: one extracting DNA only and the other simultaneously extracting DNA and RNA. In all automated extraction methods, DNA yields and integrities (assayed using DNA Integrity Numbers from a 4200 TapeStation and the qPCR-based Illumina FFPE QC Assay) were poorer than in the manual method, with the QiaCube system performing better than the ExScale system. However, ExScale was fastest, offered the highest reproducibility when extracting DNA only, and required the least intervention or technician experience. Thus, the extraction methods have different strengths and weaknesses, would appeal to different users with different requirements, and therefore, we cannot recommend one method over another.

National Mesothelioma Virtual Bank: a standard based biospecimen and clinical data resource to enhance translational research.

PubMed

Amin, Waqas; Parwani, Anil V; Schmandt, Linda; Mohanty, Sambit K; Farhat, Ghada; Pople, Andrew K; Winters, Sharon B; Whelan, Nancy B; Schneider, Althea M; Milnes, John T; Valdivieso, Federico A; Feldman, Michael; Pass, Harvey I; Dhir, Rajiv; Melamed, Jonathan; Becich, Michael J

2008-08-13

Advances in translational research have led to the need for well characterized biospecimens for research. The National Mesothelioma Virtual Bank is an initiative which collects annotated datasets relevant to human mesothelioma to develop an enterprising biospecimen resource to fulfill researchers' need. The National Mesothelioma Virtual Bank architecture is based on three major components: (a) common data elements (based on College of American Pathologists protocol and National North American Association of Central Cancer Registries standards), (b) clinical and epidemiologic data annotation, and (c) data query tools. These tools work interoperably to standardize the entire process of annotation. The National Mesothelioma Virtual Bank tool is based upon the caTISSUE Clinical Annotation Engine, developed by the University of Pittsburgh in cooperation with the Cancer Biomedical Informatics Grid (caBIG, see http://cabig.nci.nih.gov). This application provides a web-based system for annotating, importing and searching mesothelioma cases. The underlying information model is constructed utilizing Unified Modeling Language class diagrams, hierarchical relationships and Enterprise Architect software. The database provides researchers real-time access to richly annotated specimens and integral information related to mesothelioma. The data disclosed is tightly regulated depending upon users' authorization and depending on the participating institute that is amenable to the local Institutional Review Board and regulation committee reviews. The National Mesothelioma Virtual Bank currently has over 600 annotated cases available for researchers that include paraffin embedded tissues, tissue microarrays, serum and genomic DNA. The National Mesothelioma Virtual Bank is a virtual biospecimen registry with robust translational biomedical informatics support to facilitate basic science, clinical, and translational research. Furthermore, it protects patient privacy by disclosing only de-identified datasets to assure that biospecimens can be made accessible to researchers.

The State of Cloud-Based Biospecimen and Biobank Data Management Tools.

PubMed

Paul, Shonali; Gade, Aditi; Mallipeddi, Sumani

2017-04-01

Biobanks are critical for collecting and managing high-quality biospecimens from donors with appropriate clinical annotation. The high-quality human biospecimens and associated data are required to better understand disease processes. Therefore, biobanks have become an important and essential resource for healthcare research and drug discovery. However, collecting and managing huge volumes of data (biospecimens and associated clinical data) necessitate that biobanks use appropriate data management solutions that can keep pace with the ever-changing requirements of research. To automate biobank data management, biobanks have been investing in traditional Laboratory Information Management Systems (LIMS). However, there are a myriad of challenges faced by biobanks in acquiring traditional LIMS. Traditional LIMS are cost-intensive and often lack the flexibility to accommodate changes in data sources and workflows. Cloud technology is emerging as an alternative that provides the opportunity to small and medium-sized biobanks to automate their operations in a cost-effective manner, even without IT personnel. Cloud-based solutions offer the advantage of heightened security, rapid scalability, dynamic allocation of services, and can facilitate collaboration between different research groups by using a shared environment on a "pay-as-you-go" basis. The benefits offered by cloud technology have resulted in the development of cloud-based data management solutions as an alternative to traditional on-premise software. After evaluating the advantages offered by cloud technology, several biobanks have started adopting cloud-based tools. Cloud-based tools provide biobanks with easy access to biospecimen data for real-time sharing with clinicians. Another major benefit realized by biobanks by implementing cloud-based applications is unlimited data storage on the cloud and automatic backups for protecting any data loss in the face of natural calamities.

A Novel Approach to High-Quality Postmortem Tissue Procurement: The GTEx Project.

PubMed

Carithers, Latarsha J; Ardlie, Kristin; Barcus, Mary; Branton, Philip A; Britton, Angela; Buia, Stephen A; Compton, Carolyn C; DeLuca, David S; Peter-Demchok, Joanne; Gelfand, Ellen T; Guan, Ping; Korzeniewski, Greg E; Lockhart, Nicole C; Rabiner, Chana A; Rao, Abhi K; Robinson, Karna L; Roche, Nancy V; Sawyer, Sherilyn J; Segrè, Ayellet V; Shive, Charles E; Smith, Anna M; Sobin, Leslie H; Undale, Anita H; Valentino, Kimberly M; Vaught, Jim; Young, Taylor R; Moore, Helen M

2015-10-01

The Genotype-Tissue Expression (GTEx) project, sponsored by the NIH Common Fund, was established to study the correlation between human genetic variation and tissue-specific gene expression in non-diseased individuals. A significant challenge was the collection of high-quality biospecimens for extensive genomic analyses. Here we describe how a successful infrastructure for biospecimen procurement was developed and implemented by multiple research partners to support the prospective collection, annotation, and distribution of blood, tissues, and cell lines for the GTEx project. Other research projects can follow this model and form beneficial partnerships with rapid autopsy and organ procurement organizations to collect high quality biospecimens and associated clinical data for genomic studies. Biospecimens, clinical and genomic data, and Standard Operating Procedures guiding biospecimen collection for the GTEx project are available to the research community.

The Gulf Long-Term Follow-Up Study (GuLF STUDY): Biospecimen collection at enrollment.

PubMed

Engel, Lawrence S; Kwok, Richard K; Miller, Aubrey K; Blair, Aaron; Curry, Matthew D; McGrath, John A; Sandler, Dale P

2017-01-01

The 2010 Deepwater Horizon (DWH) explosion in the Gulf of Mexico led to the largest ever marine oil spill by volume. The GuLF STUDY is investigating possible adverse human health effects associated with oil spill activities. One objective of the study was to utilize biological specimens from study participants to examine spill-related adverse health effects. This study describes the methods for collecting, processing, shipping, and storing specimens during the enrollment phase of the study. GuLF STUDY participants living in Gulf States (Alabama, Florida, Louisiana, Mississippi, and eastern Texas) were eligible to complete a home visit at enrollment, one to three years after the DWH explosion. During this visit, blood, urine, toenail and hair clippings, and house dust samples were collected. Specimens were shipped overnight to a central processing laboratory in containers with cold and ambient temperature compartments. Most blood and urine specimens were then aliquoted and stored in liquid nitrogen vapor or at -80°C, with some samples stored at -20°C. A total of 11,193 participants completed a home visit, and over 99% provided at least one biospecimen. Most participants provided blood (93%), urine (99%), and toenail clippings (89%), and 40% provided hair. Nearly all participants (95%) provided house-dust samples. Most samples were received by the laboratory one (58%) or two (25%) days after collection. These biospecimens enable investigation of a range of biomarkers of spill-related adverse health effects, and possibly some biomarkers of spill-related exposures. The biospecimen collection, handling, and storage protocols were designed to maximize current and future scientific value within logistical and budgetary constraints and might serve as a template for future studies conducted in similar time-critical and geographically dispersed settings.

Development of a consensus approach for return of pathology incidental findings in the Genotype-Tissue Expression (GTEx) project.

PubMed

Lockhart, Nicole C; Weil, Carol J; Carithers, Latarsha J; Koester, Susan E; Little, A Roger; Volpi, Simona; Moore, Helen M; Berkman, Benjamin E

2018-06-14

The active debate about the return of incidental or secondary findings in research has primarily focused on return to research participants, or in some cases, family members. Particular attention has been paid to return of genomic findings. Yet, research may generate other types of findings that warrant consideration for return, including findings related to the pathology of donated biospecimens. In the case of deceased biospecimen donors who are also organ and/or tissue transplant donors, pathology incidental findings may be relevant not to family members, but to potential organ or tissue transplant recipients. This paper will describe the ethical implications of pathology incidental findings in the Genotype-Tissue Expression (GTEx) project, the process for developing a consensus approach as to if/when such findings should be returned, possible implications for other research projects collecting postmortem tissues and how the scenario encountered in GTEx fits into the larger return of results/incidental findings debate. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

To Share or Not to Share? A Survey of Biomedical Researchers in the U.S. Southwest, an Ethnically Diverse Region.

PubMed

Oushy, Mai H; Palacios, Rebecca; Holden, Alan E C; Ramirez, Amelie G; Gallion, Kipling J; O'Connell, Mary A

2015-01-01

Cancer health disparities research depends on access to biospecimens from diverse racial/ethnic populations. This multimethodological study, using mixed methods for quantitative and qualitative analysis of survey results, assessed barriers, concerns, and practices for sharing biospecimens/data among researchers working with biospecimens from minority populations in a 5 state region of the United States (Arizona, Colorado, New Mexico, Oklahoma, and Texas). The ultimate goals of this research were to understand data sharing barriers among biomedical researchers; guide strategies to increase participation in biospecimen research; and strengthen collaborative opportunities among researchers. Email invitations to anonymous participants (n = 605 individuals identified by the NIH RePORT database), resulted in 112 responses. The survey assessed demographics, specimen collection data, and attitudes about virtual biorepositories. Respondents were primarily principal investigators at PhD granting institutions (91.1%) conducting basic (62.3%) research; most were non-Hispanic White (63.4%) and men (60.6%). The low response rate limited the statistical power of the analyses, further the number of respondents for each survey question was variable. Findings from this study identified barriers to biospecimen research, including lack of access to sufficient biospecimens, and limited availability of diverse tissue samples. Many of these barriers can be attributed to poor annotation of biospecimens, and researchers' unwillingness to share existing collections. Addressing these barriers to accessing biospecimens is essential to combating cancer in general and cancer health disparities in particular. This study confirmed researchers' willingness to participate in a virtual biorepository (n = 50 respondents agreed). However, researchers in this region listed clear specifications for establishing and using such a biorepository: specifications related to standardized procedures, funding, and protections of human subjects and intellectual property. The results help guide strategies to increase data sharing behaviors and to increase participation of researchers with multiethnic biospecimen collections in collaborative research endeavors. Data sharing by researchers is essential to leveraging knowledge and resources needed for the advancement of research on cancer health disparities. Although U.S. funding entities have guidelines for data and resource sharing, future efforts should address researcher preferences in order to promote collaboration to address cancer health disparities.

Knowledge and Beliefs About Biospecimen Research Among Chinese Older Women in Chicago's Chinatown.

PubMed

Simon, Melissa A; Tom, Laura S; Dong, XinQi

2017-07-01

Enhancing the participation of Chinese older women in biobanking efforts is important for precision medicine efforts, as underrepresented groups risk benefiting less than others from medical advancements in individualized therapies. Focusing on a sample of Chinese older women in Chicago's Chinatown, this qualitative study seeks to describe attitudes toward, and barriers and facilitators of, participation in biospecimen research. We conducted six focus groups among Chinese-speaking adult women age 45 and above. Focus groups were transcribed, coded, and analyzed for emergent themes. Forty-seven women participated in focus groups, the majority (66.0%) were age 66 and over and half (50.1%) had less than a high school education. Participants expressed predominantly positive attitudes toward biospecimen research, but also identified multifaceted barriers to participation that included cultural beliefs of the body, perceived physical and privacy risks, as well as perceptions related to aging. Use of minimally invasive biospecimen collection and education to promote awareness of biospecimen research were suggested facilitators to increasing biospecimen research participation. Culturally and linguistically isolated populations like Chinese older women are at risk of exclusion from advancements in precision medicine. Our findings provide cultural insights for tailoring interventions for Chinese older women to increase knowledge, change attitudes, and increase intention and participation in biospecimen research. We also highlight the need for individual, family, and community level interventions to promote healthy aging among Chinese older women. © The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Culturally appropriate education intervention on biospecimen research participation among Chinese Americans.

PubMed

Gao, Wanzhen; Ma, Grace X; Tan, Yin; Fang, Carolyn; Weaver, Joellen; Jin, Ming; Lai, Philip; Godwin, Andrew K

2014-03-01

Chinese Americans are at increased risk for hepatitis B virus (HBV) infection. To reduce or eliminate disparities in HBV-related infection rates, participation in scientific investigations of HBV risk and treatment, including biospecimen sampling, is important. However, Asian Americans have low rates of participation in biospecimen research, and little is known about how educational interventions affect knowledge and participation in HBV-related biospecimen research. Eight Chinese community-based organizations participated in a quasi-experimental, two-group design with education assessments at pre- and postworkshop and a 3-month follow-up. Four sites were randomly assigned to receive the intervention (n = 175) and four sites to receive general health education (control; n = 240). Participant knowledge about biospecimen research increased from pre- to posteducation in the intervention but not in the control condition. Of intervention participants, 83.4% (146/175) donated one tube of blood for future HBV biospecimen research, and 50.9% (89/175) donated another tube of blood for HBV testing. In contrast, only 1.1% of participants in the control condition reported donating a blood sample at follow-up assessment. The intervention program significantly increased knowledge of and participation in HBV biospecimen research among Chinese Americans. Community-based participatory research (CBPR) methods featured active support by community leaders, a culturally specific curriculum, and convenient, immediate access to blood sampling, which resulted in high donation rates. HBV-related morbidity and mortality is an urgent problem faced by Chinese Americans. CBPR provides a model for engaging communities in early detection, vaccination, and treatment that can reduce this health threat. ©2014 AACR.

Biobanking of blood and bone marrow: emerging challenges for custodians of public resources.

PubMed

Aparicio, Lorena; Lipworth, Wendy; Then, Shih-Ning; Stewart, Cameron; Coghlan, Patrick; Kerridge, Ian; Fleming, Jennifer

2013-12-01

The Australian Bone Marrow Donor Registry (ABMDR) is a publicly funded company that is part of an international network that facilitates unrelated bone marrow transplantation. This role means that the ABMDR has access to a large biospecimen repository therefore making it a highly valuable research resource. Recognising the potential value of these biospecimens for research purposes, the ABMDR is in the process of determining whether, and how, to share its biospecimens with other biobanks. While this would undoubtedly be of value to the scientific community, and ultimately to the wider community, it would also inevitably transform the role of an institution whose primary role is therapeutic, and would compromise the degree of control that a custodian has over donated material. This article describe the challenges confronting the ABMDR, and organisations like it, in balancing their duties to donors, patients, researchers and the general public. These problems have led inevitably to the use of "property" rights language in the discussion of these issues but notions of gift, ownership, trusteeship and transfer might also be considered.

To Share or Not to Share? A Survey of Biomedical Researchers in the U.S. Southwest, an Ethnically Diverse Region

PubMed Central

Oushy, Mai H.; Palacios, Rebecca; Holden, Alan E. C.; Ramirez, Amelie G.; Gallion, Kipling J.; O’Connell, Mary A.

2015-01-01

Background Cancer health disparities research depends on access to biospecimens from diverse racial/ethnic populations. This multimethodological study, using mixed methods for quantitative and qualitative analysis of survey results, assessed barriers, concerns, and practices for sharing biospecimens/data among researchers working with biospecimens from minority populations in a 5 state region of the United States (Arizona, Colorado, New Mexico, Oklahoma, and Texas). The ultimate goals of this research were to understand data sharing barriers among biomedical researchers; guide strategies to increase participation in biospecimen research; and strengthen collaborative opportunities among researchers. Methods and Population Email invitations to anonymous participants (n = 605 individuals identified by the NIH RePORT database), resulted in 112 responses. The survey assessed demographics, specimen collection data, and attitudes about virtual biorepositories. Respondents were primarily principal investigators at PhD granting institutions (91.1%) conducting basic (62.3%) research; most were non-Hispanic White (63.4%) and men (60.6%). The low response rate limited the statistical power of the analyses, further the number of respondents for each survey question was variable. Results Findings from this study identified barriers to biospecimen research, including lack of access to sufficient biospecimens, and limited availability of diverse tissue samples. Many of these barriers can be attributed to poor annotation of biospecimens, and researchers’ unwillingness to share existing collections. Addressing these barriers to accessing biospecimens is essential to combating cancer in general and cancer health disparities in particular. This study confirmed researchers’ willingness to participate in a virtual biorepository (n = 50 respondents agreed). However, researchers in this region listed clear specifications for establishing and using such a biorepository: specifications related to standardized procedures, funding, and protections of human subjects and intellectual property. The results help guide strategies to increase data sharing behaviors and to increase participation of researchers with multiethnic biospecimen collections in collaborative research endeavors Conclusions Data sharing by researchers is essential to leveraging knowledge and resources needed for the advancement of research on cancer health disparities. Although U.S. funding entities have guidelines for data and resource sharing, future efforts should address researcher preferences in order to promote collaboration to address cancer health disparities. PMID:26378445

From in vivo to in vitro: How the Guatemala STD Experiments Transformed Bodies Into Biospecimens.

PubMed

Spector-Bagdady, Kayte; Lombardo, Paul A

2018-06-01

Policy Points: While most scholarship regarding the US Public Health Service's STD experiments in Guatemala during the 1940s has focused on the intentional exposure experiments, secondary research was also conducted on biospecimens collected from these subjects. These biospecimen experiments continued after the Guatemala grant ended, and the specimens were used in conjunction with those from the Tuskegee syphilis experiments for ongoing research. We argue there should be a public accounting of whether there are still biospecimens from the Guatemala and Tuskegee experiments held in US government biorepositories today. If such specimens exist, they should be retired from US government research archives because they were collected unethically as understood at the time. The US Public Health Service's Guatemala STD experiments (1946-1948) included intentional exposure to pathogens and testing of postexposure prophylaxis methods for syphilis, gonorrhea, and chancroid in over 1,300 soldiers, commercial sex workers, prison inmates, and psychiatric patients. Though the experiments had officially ended, the biospecimens collected from these subjects continued to be used for research at least into the 1950s. We analyzed historical documents-including clinical and laboratory records, correspondence, final reports, and medical records-for information relevant to these biospecimen experiments from the US National Archives. In addition, we researched material from past governmental investigations into the Guatemala STD experiments, including those of the US Presidential Commission for the Study of Bioethical Issues and the Guatemalan Comisión Presidencial para el Esclarecimiento de los Experimentos Practicados con Humanos en Guatemala. Identified spinal fluid, blood specimens, and tissue collected during the Guatemala diagnostic methodology and intentional exposure experiments were subsequently distributed to laboratories throughout the United States for use in ongoing research until at least 1957. Five psychiatric patient subjects involved in these biospecimen experiments died soon after experimental exposure to STDs. The same US government researchers working with the Guatemala biospecimens after the exposure experiments ended were also working with specimens taken from the Tuskegee syphilis study. There should be a complete public accounting of whether biospecimens from the Guatemala and Tuskegee experiments are held in US government biorepositories today. If they still exist, these specimens should be retired from such biorepositories and their future disposition determined by stakeholders, including representatives from the communities from which they were derived. © 2018 Milbank Memorial Fund.

Attitudes and Perceptions of Cancer Patients Toward Biospecimen Donation for Cancer Research: A Cross-Sectional Survey Among Chinese Cancer Patients.

PubMed

He, Na; Guo, Yan; He, Min; Qiang, Wanmin; Li, Haixin

2017-08-01

High-quality biospecimen collection from consented patients is crucial for cancer research activities. Patients' attitudes and willingness toward specimen donation influence high-quality biospecimen collection for cancer research activities. We carried out a cross-sectional study among randomly selected patients from 11 cancer departments of Tianjin Medical University Cancer Institute and Hospital between August 2014 and August 2015. A total of 784 patients were included to complete a 30-item self-administered survey. We evaluated the patients' willingness to consider providing leftover samples and additional samples for cancer research purposes. Among 784 patients, 683 (87.1%) and 653 (83.3%) were willing to donate leftover tissue and surplus blood after diagnosis, respectively. Six hundred thirty-one (80.5%) were favorably disposed to consider donating both tissue and blood samples for future cancer research. Female patients showed less willingness to donate biospecimens or related clinical data for research. First-hospitalized or older patients were less willing to provide leftover biospecimens or additional blood samples or even clinical data for research. By contrast, patients with a higher education level were more likely to donate leftover tissues after biopsy or surgery for research activities. Most Chinese cancer patients were willing to consider donating blood and tissue samples for cancer research. Several factors, including age, gender, first hospitalization, and education level, can influence their willingness to donate biospecimens. We need to provide proper education to increase understanding of patients in biobanking activities. This study provides novel empirical data on the likelihood of donating surplus and additional biospecimens and clinical health information among Chinese cancer patients.

75 FR 51830 - National Cancer Institute's Best Practices for Biospecimen Resources

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-23

... current federal guidance documents and recommendations from international biospecimen organizations. DATES... be directed to senior staff of the relevant NCI Extramural and Intramural Program offices...

Advancing Translational Space Research Through Biospecimen Sharing: Amplified Impact of Studies Utilizing Analogue Space Platforms

NASA Technical Reports Server (NTRS)

Staten, B.; Moyer, E.; Vizir, V.; Gompf, H.; Hoban-Higgins, T.; Lewis, L.; Ronca, A.; Fuller, C. A.

2016-01-01

Biospecimen Sharing Programs (BSPs) have been organized by NASA Ames Research Center since the 1960s with the goal of maximizing utilization and scientific return from rare, complex and costly spaceflight experiments. BSPs involve acquiring otherwise unused biological specimens from primary space research experiments for distribution to secondary experiments. Here we describe a collaboration leveraging Ames expertise in biospecimen sharing to magnify the scientific impact of research informing astronaut health funded by the NASA Human Research Program (HRP) Human Health Countermeasures (HHC) Element. The concept expands biospecimen sharing to one-off ground-based studies utilizing analogue space platforms (e.g., Hindlimb Unloading (HLU), Artificial Gravity) for rodent experiments, thereby significantly broadening the range of research opportunities with translational relevance for protecting human health in space and on Earth.

Broad Consent for Research on Biospecimens: The Views of Actual Donors at Four U.S. Medical Centers.

PubMed

Warner, Teddy D; Weil, Carol J; Andry, Christopher; Degenholtz, Howard B; Parker, Lisa; Carithers, Latarsha J; Feige, Michelle; Wendler, David; Pentz, Rebecca D

2018-04-01

Commentators are concerned that broad consent may not provide biospecimen donors with sufficient information regarding possible future research uses of their tissue. We surveyed with interviews 302 cancer patients who had recently provided broad consent at four diverse academic medical centers. The majority of donors believed that the consent form provided them with sufficient information regarding future possible uses of their biospecimens. Donors expressed very positive views regarding tissue donation in general and endorsed the use of their biospecimens in future research across a wide range of contexts. Concerns regarding future uses were limited to for-profit research and research by investigators in other countries. These results support the use of broad consent to store and use biological samples in future research.

Regulating Research with Biospecimens under the Revised Common Rule.

PubMed

Lynch, Holly Fernandez; Meyer, Michelle N

2017-05-01

Since 2011, the research community had waited with bated breath as regulators contemplated for the first time bringing secondary research with nonidentifiable biospecimens under the Common Rule and dramatically tightening the criteria for waiving consent to biospecimen research. After considerable pushback from both researchers and patients and amid rumors of intractable disagreement among Common Rule agencies, the Final Rule published on the last day of President Obama's administration left out these troubling changes, and there was a collective sigh of relief. Relief is appropriate, but celebration premature: researchers have little reason to avail themselves of the new broad consent option offered in the Final Rule, and the question of whether biospecimens ought to be treated as inherently identifiable has merely been postponed. © 2017 The Hastings Center.

Negotiating Commercial Interests in Biospecimens.

PubMed

Roberts, Jessica L

2017-03-01

Proposed changes to the Common Rule would require publicly funded researchers to disclose whether a subject's biospecimens could be used for commercial profit and whether the subject will share in those proceeds. Disclosing commercial interests will inform research participants that their tissue may have commercial value, a possibility that those individuals might not have previously considered. The proposed changes may then provide people with an opportunity to negotiate commercial rights in their biospecimens despite the well-accepted legal precedent that individuals maintain no interests in their excised tissue.

Intratumoral Agreement of High-Resolution Magic Angle Spinning Magnetic Resonance Spectroscopic Profiles in the Metabolic Characterization of Breast Cancer

PubMed Central

Park, Vivian Youngjean; Yoon, Dahye; Koo, Ja Seung; Kim, Eun-Kyung; Kim, Seung Il; Choi, Ji Soo; Park, Seho; Park, Hyung Seok; Kim, Suhkmann; Kim, Min Jung

2016-01-01

Abstract High-resolution magic angle spinning (HR-MAS) magnetic resonance (MR) spectroscopy data may serve as a biomarker for breast cancer, with only a small volume of tissue sample required for assessment. However, previous studies utilized only a single tissue sample from each patient. The aim of this study was to investigate whether intratumoral location and biospecimen type affected the metabolic characterization of breast cancer assessed by HR-MAS MR spectroscopy This prospective study was approved by the institutional review board and informed consent was obtained. Preoperative core-needle biopsies (CNBs), central, and peripheral surgical tumor specimens were prospectively collected under ultrasound (US) guidance in 31 patients with invasive breast cancer. Specimens were assessed with HR-MAS MR spectroscopy. The reliability of metabolite concentrations was evaluated and multivariate analysis was performed according to intratumoral location and biospecimen type. There was a moderate or higher agreement between the relative concentrations of 94.3% (33 of 35) of metabolites in the center and periphery, 80.0% (28 of 35) of metabolites in the CNB and central surgical specimens, and 82.9% (29 of 35) of metabolites between all 3 specimen types. However, there was no significant agreement between the concentrations of phosphocholine (PC) and phosphoethanolamine (PE) in the center and periphery. The concentrations of several metabolites (adipate, arginine, fumarate, glutamate, PC, and PE) had no significant agreement between the CNB and central surgical specimens. In conclusion, most HR-MAS MR spectroscopic data do not differ based on intratumoral location or biospecimen type. However, some metabolites may be affected by specimen-related variables, and caution is recommended in decision-making based solely on metabolite concentrations, particularly PC and PE. Further validation through future studies is needed for the clinical implementation of these biomarkers based on data from a single tissue sample. PMID:27082613

Assessment of knowledge about biobanking among healthcare students and their willingness to donate biospecimens.

PubMed

Merdad, Leena; Aldakhil, Lama; Gadi, Rawan; Assidi, Mourad; Saddick, Salina Y; Abuzenadah, Adel; Vaught, Jim; Buhmeida, Abdelbaset; Al-Qahtani, Mohammed H

2017-05-02

Biobanks and biospecimen collections are becoming a primary means of delivering personalized diagnostics and tailoring individualized therapeutics. This shift towards precision medicine (PM) requires interactions among a variety of stakeholders, including the public, patients, healthcare providers, government, and donors. Very few studies have investigated the role of healthcare students in biobanking and biospecimen donations. The main aims of this study were (1) to evaluate the knowledge of senior healthcare students about biobanks and (2) to assess the students' willingness to donate biospecimens and the factors influencing their attitudes. A cross-sectional study was conducted among senior healthcare students at King Abdulaziz University (KAU), Saudi Arabia. The data were obtained using a self-administered questionnaire in English. In addition to the respondents' biographical data section, the questionnaire assessed the respondents' general knowledge about biobanking, the factors influencing their willingness to donate biospecimens to biobanks and their general attitudes towards biomedical research. A total of 597 senior healthcare students were included in the study. The general knowledge score was 3.2 (±1.6) out of 7. Only approximately 44% and 27% of students were aware of the terms "Human Genome Project" (HGP) and "biobank," respectively. The majority of the students (89%) were willing to donate biospecimens to biobanks. Multiple factors were significantly associated with their willingness to donate, including their perceived general health (p < 0.001), past experience with both tissue testing (p < 0.04) and tissue donation (p < 0.001), biobanking knowledge score (p < 0.001) and biomedical research attitude score (p < 0.001). The main reasons for students' willingness to donate were advancement of medical research and societal benefits, whereas misuse of biospecimens and confidentiality breaches were the main reasons for a reluctance to donate. Despite their strong willingness to donate biospecimens, students exhibited a notable lack of knowledge about biobanking and the HGP. To expedite the transition towards PM, it is highly recommended to enhance healthcare curricula by including more educational and awareness programmes to familiarize students with OMICs technologies in addition to the scope of research and clinical applications.

NCI’s Cooperative Human Tissue Network

Cancer.gov

Quality biospecimens are a foundational resource for cancer research. One of NCI’s longest running biospecimen programs is the Cooperative Human Tissue Network, a resource mainly for basic discovery and early translational research.

Osteosarcoma enters a post genomic era with in silico opportunities: Generation of the High Dimensional Database for facilitating sarcoma biology research: A report from the Children's Oncology Group and the QuadW Foundation.

PubMed

Glover, Jason; Man, Tsz-Kwong; Barkauskas, Donald A; Hall, David; Tello, Tanya; Sullivan, Mary Beth; Gorlick, Richard; Janeway, Katherine; Grier, Holcombe; Lau, Ching; Toretsky, Jeffrey A; Borinstein, Scott C; Khanna, Chand; Fan, Timothy M

2017-01-01

The prospective banking of osteosarcoma tissue samples to promote research endeavors has been realized through the establishment of a nationally centralized biospecimen repository, the Children's Oncology Group (COG) biospecimen bank located at the Biopathology Center (BPC)/Nationwide Children's Hospital in Columbus, Ohio. Although the physical inventory of osteosarcoma biospecimens is substantive (>15,000 sample specimens), the nature of these resources remains exhaustible. Despite judicious allocation of these high-value biospecimens for conducting sarcoma-related research, a deeper understanding of osteosarcoma biology, in particular metastases, remains unrealized. In addition the identification and development of novel diagnostics and effective therapeutics remain elusive. The QuadW-COG Childhood Sarcoma Biostatistics and Annotation Office (CSBAO) has developed the High Dimensional Data (HDD) platform to complement the existing physical inventory and to promote in silico hypothesis testing in sarcoma biology. The HDD is a relational biologic database derived from matched osteosarcoma biospecimens in which diverse experimental readouts have been generated and digitally deposited. As proof-of-concept, we demonstrate that the HDD platform can be utilized to address previously unrealized biologic questions though the systematic juxtaposition of diverse datasets derived from shared biospecimens. The continued population of the HDD platform with high-value, high-throughput and mineable datasets allows a shared and reusable resource for researchers, both experimentalists and bioinformatics investigators, to propose and answer questions in silico that advance our understanding of osteosarcoma biology.

Adsorbing/dissolving Lyoprotectant Matrix Technology for Non-cryogenic Storage of Archival Human Sera

NASA Astrophysics Data System (ADS)

Solivio, Morwena J.; Less, Rebekah; Rynes, Mathew L.; Kramer, Marcus; Aksan, Alptekin

2016-04-01

Despite abundant research conducted on cancer biomarker discovery and validation, to date, less than two-dozen biomarkers have been approved by the FDA for clinical use. One main reason is attributed to inadvertent use of low quality biospecimens in biomarker research. Most proteinaceous biomarkers are extremely susceptible to pre-analytical factors such as collection, processing, and storage. For example, cryogenic storage imposes very harsh chemical, physical, and mechanical stresses on biospecimens, significantly compromising sample quality. In this communication, we report the development of an electrospun lyoprotectant matrix and isothermal vitrification methodology for non-cryogenic stabilization and storage of liquid biospecimens. The lyoprotectant matrix was mainly composed of trehalose and dextran (and various low concentration excipients targeting different mechanisms of damage), and it was engineered to minimize heterogeneity during vitrification. The technology was validated using five biomarkers; LDH, CRP, PSA, MMP-7, and C3a. Complete recovery of LDH, CRP, and PSA levels was achieved post-rehydration while more than 90% recovery was accomplished for MMP-7 and C3a, showing promise for isothermal vitrification as a safe, efficient, and low-cost alternative to cryogenic storage.

Proposed regulations for research with biospecimens: responses from stakeholders at CTSA consortium institutions.

PubMed

Botkin, Jeffrey R; Anderson, Rebecca; Murray, Tom; Beskow, Laura M; Maschke, Karen; Cuttler, Leona

2014-04-01

Secondary research with biospecimens acquired through clinical care and through research is often conducted without the informed consent of individuals from whom the specimens were acquired. While such uses are consistent with the current federal regulations, surveys of the general public suggest that many individuals would prefer more information and choice regarding research use of biospecimens. The federal government issued an Advance Notice of Proposed Rulemaking (ANPRM) in 2011 that proposed a number of potential changes in the regulations governing human subjects. These proposed regulations are particularly pertinent to institutions committed to research involving human subjects-including institutions in the NIH-funded Clinical and Translational Science Awards (CTSA) consortium. In this study, we reviewed public responses by CTSA-funded institutions and CTSA-affiliated organizations and groups regarding the proposed changes in the ANPRM with respect to research with biospecimens. Our results indicate that the majority of responses to the ANPRM from CTSA institutions were not supportive of the proposed changes. While many responses acknowledge a need to change current research practices regarding biospecimens, the proposed changes in the ANPRM received only limited support from this subgroup of academic research institutions. © 2014 Wiley Periodicals, Inc.

Proposed Regulations for Research with Biospecimens: Responses from Stakeholders at CTSA Consortium Institutions

PubMed Central

Botkin, Jeffrey R; Anderson, Rebecca; Murray, Tom; Beskow, Laura M.; Maschke, Karen; Cuttler, Leona

2014-01-01

Secondary research with biospecimens acquired through clinical care and through research is often conducted without the informed consent of individuals from whom the specimens were acquired. While such uses are consistent with the current federal regulations, surveys of the general public suggest that many individuals would prefer more information and choice regarding research use of biospecimens. The federal government issued an Advance Notice of Proposed Rulemaking (ANPRM) in 2011 that proposed a number of potential changes in the regulations governing human subjects. These proposed regulations are particularly pertinent to institutions committed to research involving human subjects – including institutions in the NIH-funded Clinical and Translational Science Awards (CTSA) consortium. In this study, we reviewed public responses by CTSA-funded institutions and CTS-affiliated organizations and groups regarding the proposed changes in the ANPRM with respect to research with biospecimens. Our results indicate that the majority of responses to the ANPRM from CTSA institutions were not supportive of the proposed changes. While many responses acknowledge a need to change current research practices regarding biospecimens, the proposed changes in the ANPRM received only limited support from this subgroup of academic research institutions. PMID:24459038

Utilizing Existing Clinical and Population Biospecimen Resources for Discovery or Validation of Markers for Early Cancer Detection

Cancer.gov

Utilizing Existing Clinical and Population Biospecimen Resources for Discovery or Validation of Markers for Early Cancer Detection, a 2013 workshop sponsored by the Epidemiology and Genomics Research Program.

Lessons from HeLa Cells: The Ethics and Policy of Biospecimens.

PubMed

Beskow, Laura M

2016-08-31

Human biospecimens have played a crucial role in scientific and medical advances. Although the ethical and policy issues associated with biospecimen research have long been the subject of scholarly debate, the story of Henrietta Lacks, her family, and the creation of HeLa cells captured the attention of a much broader audience. The story has been a catalyst for policy change, including major regulatory changes proposed in the United States surrounding informed consent. These proposals are premised in part on public opinion data, necessitating a closer look at what such data tell us. The development of biospecimen policy should be informed by many considerations-one of which is public input, robustly gathered, on acceptable approaches that optimize shared interests, including access for all to the benefits of research. There is a need for consent approaches that are guided by realistic aspirations and a balanced view of autonomy within an expanded ethical framework.

Lessons from HeLa Cells: The Ethics and Policy of Biospecimens

PubMed Central

Beskow, Laura M.

2016-01-01

Human biospecimens have played a crucial role in scientific and medical advances. Although the ethical and policy issues associated with biospecimen research have long been the subject of scholarly debate, the story of attention of a much broader audience. The story has been a catalyst for policy change, including major regulatory changes proposed in the United States surrounding informed consent. These proposals are premised in part on public opinion data, necessitating a closer look at what such data tell us. The development of biospecimen policy should be informed by many considerations—one of which is public input, robustly gathered, on acceptable approaches that optimize shared interests, including access for all to the benefits of research. There is a need for consent approaches that are guided by realistic aspirations and a balanced view of autonomy within an expanded ethical framework. PMID:26979405

The NASA Ames Life Sciences Data Archive: Biobanking for the Final Frontier

NASA Technical Reports Server (NTRS)

Rask, Jon; Chakravarty, Kaushik; French, Alison J.; Choi, Sungshin; Stewart, Helen J.

2017-01-01

The NASA Ames Institutional Scientific Collection involves the Ames Life Sciences Data Archive (ALSDA) and a biospecimen repository, which are responsible for archiving information and non-human biospecimens collected from spaceflight and matching ground control experiments. The ALSDA also manages a biospecimen sharing program, performs curation and long-term storage operations, and facilitates distribution of biospecimens for research purposes via a public website (https:lsda.jsc.nasa.gov). As part of our best practices, a tissue viability testing plan has been developed for the repository, which will assess the quality of samples subjected to long-term storage. We expect that the test results will confirm usability of the samples, enable broader science community interest, and verify operational efficiency of the archives. This work will also support NASA open science initiatives and guides development of NASA directives and policy for curation of biological collections.

Unexpected findings in the exploration of African American underrepresentation in biospecimen collection and biobanks

PubMed Central

Hagiwara, Nao; Berry-Bobovski, Lisa; Francis, Carie; Ramsey, Lauren; Chapman, Robert A.; Albrecht, Terrance L.

2014-01-01

Racial/ethnic minorities are underrepresented in current biobanking programs. The current study utilized community-based participatory research to identify motivating factors and barriers that affect older African Americans’ willingness to donate biospecimens. The standardized phone survey was administered to 78 African Americans who are 55 years old or older and live in the metropolitan Detroit area to assess their overall willingness to donate biospecimens and what factors were associated with it. The majority of the participants were willing to donate biospecimens, along with their personal information, for medical research and indicated that they did donate biospecimens when they were asked. However, African Americans were rarely asked to participate in biobanking programs. Furthermore, African Americans were not as concerned with research exploitation or as mistrusting of medical researchers as previously thought by the medical researchers. Even if African Americans were concerned over potential research exploitation or mistrust of medical researchers, these concerns or mistrust did not translate into an actual unwillingness to participate in biobanking programs. Rather, transparency in medical research and biobanking programs was more important when predicting African Americans’ willingness to donate biospecimens for medical research. The findings suggest that underrepresentation of African Americans in current biobanking programs may not be due to their willingness/unwillingness to participate in such programs, but rather due to a failure of medical researchers to approach them. Additionally, researchers and clinicians should focus on increasing the transparency of medical research and biobanking programs rather than changing African Americans’ potential negative attitudes toward them. PMID:24243440

Osteosarcoma enters a post genomic era with in silico opportunities: Generation of the High Dimensional Database for facilitating sarcoma biology research: A report from the Children's Oncology Group and the QuadW Foundation

PubMed Central

Glover, Jason; Man, Tsz-Kwong; Barkauskas, Donald A.; Hall, David; Tello, Tanya; Sullivan, Mary Beth; Gorlick, Richard; Janeway, Katherine; Grier, Holcombe; Lau, Ching; Toretsky, Jeffrey A.; Borinstein, Scott C.; Khanna, Chand

2017-01-01

The prospective banking of osteosarcoma tissue samples to promote research endeavors has been realized through the establishment of a nationally centralized biospecimen repository, the Children’s Oncology Group (COG) biospecimen bank located at the Biopathology Center (BPC)/Nationwide Children’s Hospital in Columbus, Ohio. Although the physical inventory of osteosarcoma biospecimens is substantive (>15,000 sample specimens), the nature of these resources remains exhaustible. Despite judicious allocation of these high-value biospecimens for conducting sarcoma-related research, a deeper understanding of osteosarcoma biology, in particular metastases, remains unrealized. In addition the identification and development of novel diagnostics and effective therapeutics remain elusive. The QuadW-COG Childhood Sarcoma Biostatistics and Annotation Office (CSBAO) has developed the High Dimensional Data (HDD) platform to complement the existing physical inventory and to promote in silico hypothesis testing in sarcoma biology. The HDD is a relational biologic database derived from matched osteosarcoma biospecimens in which diverse experimental readouts have been generated and digitally deposited. As proof-of-concept, we demonstrate that the HDD platform can be utilized to address previously unrealized biologic questions though the systematic juxtaposition of diverse datasets derived from shared biospecimens. The continued population of the HDD platform with high-value, high-throughput and mineable datasets allows a shared and reusable resource for researchers, both experimentalists and bioinformatics investigators, to propose and answer questions in silico that advance our understanding of osteosarcoma biology. PMID:28732082

Health professionals' opinions on supporting a cancer biobank: identification of barriers to combat biobanking pitfalls.

PubMed

Caixeiro, Nicole J; Byun, Hei Lan; Descallar, Joseph; Levesque, Janelle V; de Souza, Paul; Soon Lee, Cheok

2016-05-01

Although rarely acknowledged, a successful biobank is highly dependent on the support of the health professionals who assist the biobank in all aspects of its activities. In many cases, the lack of health professional support can be a limiting factor in the biobanking process of collecting and processing high-quality biospecimens. The aim of this study was to determine the attitudes of health professionals towards cancer biobanking. Using a 5-point Likert scale questionnaire, important aspects of biobanking, including accrual, quality, knowledge, responsiveness, impact, access, trust, governance and accreditation, were investigated. In total, 95 of 124 health and medical practitioners who were approached participated in this study (77% response rate). Health professionals in general supported the aims of biobanking with 56% of participants showing willingness to create a biobank and recruit donors (accrual), 85% understanding the importance in the storage and distribution of biospecimens (quality), 88% having an appreciation for the role of a biobank in furthering cancer research (knowledge), 70% showing awareness of the use of biospecimens in future research initiatives (responsiveness) and 73% demonstrating support for a biobank with proper control, authority and credibility measures in place (governance and accreditation). Overall, provided that proper information about the activities of the biobank and researcher access was transparent, health professionals were very willing to support cancer biobanking. These findings may assist in developing strategies for the establishment and maintenance of biobanks and aid the implementation of more effective policies and procedures to embed biobanking into routine hospital practices.

A role for research ethics committees in exchanges of human biospecimens through material transfer agreements.

PubMed

Chalmers, Donald; Nicol, Dianne; Nicolás, Pilar; Zeps, Nikolajs

2014-09-01

International transfers of human biological material (biospecimens) and data are increasing, and commentators are starting to raise concerns about how donor wishes are protected in such circumstances. These exchanges are generally made under contractual material transfer agreements (MTAs). This paper asks what role, if any, should research ethics committees (RECs) play in ensuring legal and ethical conduct in such exchanges. It is recommended that RECs should play a more active role in the future development of best practice MTAs involving exchange of biospecimens and data and in monitoring compliance.

Broad Consent For Research With Biological Samples: Workshop Conclusions

PubMed Central

Grady, Christine; Eckstein, Lisa; Berkman, Ben; Brock, Dan; Cook-Deegan, Robert; Fullerton, Stephanie M.; Greely, Hank; Hansson, Mats G.; Hull, Sara; Kim, Scott; Lo, Bernie; Pentz, Rebecca; Rodriguez, Laura; Weil, Carol; Wilfond, Benjamin S.; Wendler, David

2016-01-01

Different types of consent are used to obtain human biospecimens for future research. This variation has resulted in confusion regarding what research is permitted, inadvertent constraints on future research, and research proceeding without consent. The NIH Clinical Center’s Department of Bioethics held a workshop to consider the ethical acceptability of addressing these concerns by using broad consent for future research on stored biospecimens. Multiple bioethics scholars, who have written on these issues, discussed the reasons for consent, the range of consent strategies, gaps in our understanding, and concluded with a proposal for broad initial consent coupled with oversight and, when feasible, ongoing provision of information to donors. The manuscript describes areas of agreement as well as areas that need more research and dialogue. Given recent proposed changes to the Common Rule, and new guidance regarding storing and sharing data and samples, this is an important and timely topic. PMID:26305750

[Current modalities and concepts on access and use of biospecimen samples and associated data for research from human biobanks].

PubMed

Siddiqui, Roman; Semler, Sebastian Claudius

2016-03-01

It is accepted worldwide that biospecimen and data sharing (BDS) play an essential role for the future of medical research to improve diagnostics and prognostics, e.g. by validated biomarkers. BDS is also pivotal to the development of new therapeutic treatments and for the improvement of population health. Human biobanks can generate an added value to this need by providing biospecimens and/or associated data to researchers. An inspection of several examples of epidemiological as well as clinical/disease-oriented biobanks in Germany shows that best practice procedures (BPP) that are internationally agreed on are being installed for biospecimen and/or data access. In general, fair access is aimed at requiring a written application by the requesting scientist, which is then peer-reviewed for scientific and ethical validity by the Biobank. Applied BPP take into account (i) patient education/agreement according to the informed consent model, (ii) privacy protection, (iii) intellectual property rights, the (iv) notification obligation of health-related findings (including incidental findings), the (v) use of material (MTA) and data transfer agreements (DTA) for mutual legal security, the avoidance of conflicts of interests, as well as for cost recovery/fee for service as a basis for sustainability of the biobank. BPP are rooted in the self-regulation efforts of life sciences and are supported by parent ethics committees in Germany. Central biobank registries displaying aggregated information on biospecimens stored and the research foci constitute an important tool to make biobanks that are scattered across the country visible to each other, and, can thus promote access to hitherto unknown biospecimen and data resources.

Contrasting the ethical perspectives of biospecimen research among individuals with familial risk for hereditary cancer and biomedical researchers: implications for researcher training.

PubMed

Quinn, Gwendolyn P; Koskan, Alexis; Sehovic, Ivana; Pal, Tuya; Meade, Cathy; Gwede, Clement K

2014-07-01

While ethical concerns about participating in biospecimen research have been previously identified, few studies have reported the concerns among individuals with familial risk for hereditary cancer (IFRs). At the same time, biomedical researchers often lack training in discussing such concerns to potential donors. This study explores IFRs' and biomedical researchers' perceptions of ethical concerns about participating in biobanking research. In separate focus groups, IFRs and biomedical researchers participated in 90-min telephone focus groups. Focus group questions centered on knowledge about laws that protect the confidentiality of biospecimen donors, understanding of informed consent and study procedures, and preferences for being recontacted about potential incidental discovery and also study results. A total of 40 IFRs and 32 biomedical researchers participated in the focus groups. Results demonstrated discrepancies between the perceptions of IFRs and researchers. IFRs' concerns centered on health information protection; potential discrimination by insurers and employers; and preferences for being recontacted upon discovery of gene mutations or to communicate study results. Researchers perceived that participants understood laws protecting donors' privacy and (detailed study information outlined in the informed consent process), study outcomes were used to create a training tool kit to increase researchers' understanding of IFRs' concerns about biobanking.

Contrasting the Ethical Perspectives of Biospecimen Research Among Individuals with Familial Risk for Hereditary Cancer and Biomedical Researchers: Implications for Researcher Training

PubMed Central

Koskan, Alexis; Sehovic, Ivana; Pal, Tuya; Meade, Cathy; Gwede, Clement K.

2014-01-01

While ethical concerns about participating in biospecimen research have been previously identified, few studies have reported the concerns among individuals with familial risk for hereditary cancer (IFRs). At the same time, biomedical researchers often lack training in discussing such concerns to potential donors. This study explores IFRs' and biomedical researchers' perceptions of ethical concerns about participating in biobanking research. In separate focus groups, IFRs and biomedical researchers participated in 90-min telephone focus groups. Focus group questions centered on knowledge about laws that protect the confidentiality of biospecimen donors, understanding of informed consent and study procedures, and preferences for being recontacted about potential incidental discovery and also study results. A total of 40 IFRs and 32 biomedical researchers participated in the focus groups. Results demonstrated discrepancies between the perceptions of IFRs and researchers. IFRs' concerns centered on health information protection; potential discrimination by insurers and employers; and preferences for being recontacted upon discovery of gene mutations or to communicate study results. Researchers perceived that participants understood laws protecting donors' privacy and (detailed study information outlined in the informed consent process), study outcomes were used to create a training tool kit to increase researchers' understanding of IFRs' concerns about biobanking. PMID:24786355

Community-Based Participatory Research Integrates Behavioral and Biological Research to Achieve Health Equity for Native Hawaiians.

PubMed

Townsend, Claire K M; Dillard, Adrienne; Hosoda, Kelsea K; Maskarinec, Gregory G; Maunakea, Alika K; Yoshimura, Sheryl R; Hughes, Claire; Palakiko, Donna-Marie; Kehauoha, Bridget Puni; Kaholokula, Joseph Keawe'aimoku

2015-12-22

Native Hawaiians bear a disproportionate burden of type-2 diabetes and related complications compared to all other groups in Hawai'i (e.g., Whites, Japanese, Korean). Distrust in these communities is a significant barrier to participation in epigenetic research studies seeking to better understand disease processes. The purpose of this paper is to describe the community-based participatory research (CBPR) approach and research process we employed to integrate behavior and biological sciences with community health priorities. A CBPR approach was used to test a 3-month evidence-based, diabetes self-management intervention (N = 65). To investigate the molecular mechanisms linking inflammation with glucose homeostasis, a subset of participants (n = 16) provided peripheral blood mononuclear cells. Community and academic researchers collaborated on research design, assessment protocols, and participant recruitment, prioritizing participants' convenience and education and strictly limiting the use of the data collected. Preliminary results indicate significant changes in DNA methylation at gene regions associated with inflammation and diabetes signaling pathways and significant improvements in hemoglobin A1c, self-care activities, and diabetes distress and understanding. This study integrates community, behavioral, and epigenomic expertise to better understand the outcomes of a diabetes self-management intervention. Key lessons learned suggest the studies requiring biospecimen collection in indigenous populations require community trust of the researchers, mutual benefits for the community and researchers, and for the researchers to prioritize the community's needs. CBPR may be an important tool in providing communities the voice and protections to participate in studies requiring biospecimens.

THE VALUE OF HOME-BASED COLLECTION OF BIOSPECIMENS IN REPRODUCTIVE EPIDEMIOLOGY

EPA Science Inventory

The Value of Home-Based Collection of Biospecimens in Reproductive Epidemiology
John C. Rockett1, Germaine M. Buck2, Courtney D. Johnson2 and Sally D. Perreault1
1Reproductive Toxicology Division, National Health and Environmental Effects Research Laboratory, Office of Rese...

Factors that affect willingness to donate blood for the purpose of biospecimen research in the Korean American community.

PubMed

Yen, Glorian P; Davey, Adam; Ma, Grace X

2015-04-01

Biorepositories have been key resources in examining genetically-linked diseases, particularly cancer. Asian Americans contribute to biorepositories at lower rates than other racial groups, but the reasons for this are unclear. We hypothesized that attitudes toward biospecimen research mediate the relationship between demographic and healthcare access factors, and willingness to donate blood for research purposes among individuals of Korean heritage. Descriptive statistics and bivariate analyses were utilized to characterize the sample with respect to demographic, psychosocial, and behavioral variables. Structural equation modeling with 5000 re-sample bootstrapping was used to assess each component of the proposed simple mediation models. Attitudes towards biospecimen research fully mediate associations between age, income, number of years lived in the United States, and having a regular physician and willingness to donate blood for the purpose of research. Participants were willing to donate blood for the purpose of research despite having neutral feelings towards biospecimen research as a whole. Participants reported higher willingness to donate blood for research purposes when they were older, had lived in the United States longer, had higher income, and had a regular doctor that they visited. Many of the significant relationships between demographic and health care access factors, attitudes towards biospecimen research, and willingness to donate blood for the purpose of research may be explained by the extent of acculturation of the participants in the United States.

Biospecimen User Fees: Global Feedback on a Calculator Tool.

PubMed

Matzke, Lise A M; Babinszky, Sindy; Slotty, Alex; Meredith, Anna; Castillo-Pelayo, Tania; Henderson, Marianne K; Simeon-Dubach, Daniel; Schacter, Brent; Watson, Peter H

2017-02-01

The notion of attributing user fees to researchers for biospecimens provided by biobanks has been discussed frequently in the literature. However, the considerations around how to attribute the cost for these biospecimens and data have, until recently, not been well described. Common across most biobank disciplines are similar factors that influence user fees such as capital and operating costs, internal and external demand, and market competition. A biospecimen user fee calculator tool developed by CTRNet, a tumor biobank network, was published in 2014 and is accessible online at www.biobanking.org . The next year a survey was launched that tested the applicability of this user fee tool among a global health research biobank user base, including both cancer and noncancer biobanking. Participants were first asked to estimate user fee pricing for three hypothetical user scenarios based on their biobanking experience (estimated pricing) and then to calculate fees for the same scenarios using the calculator tool (calculated pricing). Results demonstrated variation in estimated pricing that was reduced by calculated pricing. These results are similar to those found in a similar previous study restricted to a group of Canadian tumor biobanks. We conclude that the use of a biospecimen user fee calculator contributes to reduced variation of user fees and for biobank groups (e.g., biobank networks), could become an important part of a harmonization strategy.

Biospecimen User Fees: Global Feedback on a Calculator Tool

PubMed Central

Babinszky, Sindy; Slotty, Alex; Meredith, Anna; Castillo-Pelayo, Tania; Henderson, Marianne K.; Simeon-Dubach, Daniel; Schacter, Brent; Watson, Peter H.

2017-01-01

The notion of attributing user fees to researchers for biospecimens provided by biobanks has been discussed frequently in the literature. However, the considerations around how to attribute the cost for these biospecimens and data have, until recently, not been well described. Common across most biobank disciplines are similar factors that influence user fees such as capital and operating costs, internal and external demand, and market competition. A biospecimen user fee calculator tool developed by CTRNet, a tumor biobank network, was published in 2014 and is accessible online at www.biobanking.org. The next year a survey was launched that tested the applicability of this user fee tool among a global health research biobank user base, including both cancer and noncancer biobanking. Participants were first asked to estimate user fee pricing for three hypothetical user scenarios based on their biobanking experience (estimated pricing) and then to calculate fees for the same scenarios using the calculator tool (calculated pricing). Results demonstrated variation in estimated pricing that was reduced by calculated pricing. These results are similar to those found in a similar previous study restricted to a group of Canadian tumor biobanks. We conclude that the use of a biospecimen user fee calculator contributes to reduced variation of user fees and for biobank groups (e.g., biobank networks), could become an important part of a harmonization strategy. PMID:27576065

Establishment of a cervical cancer bio-bank for the Chinese population: from project-based sample collection to routine management.

PubMed

Yang, Ru; Li, Xiong; Zhou, Hang; Jia, Yao; Zhou, Jin; Huang, Kecheng; Tang, Fangxu; Hu, Ting; Shen, Jian; Chen, Zhilan; Wang, Shaoshuai; Sun, Haiying; Guo, Lili; Wang, Lin; Wang, Hui; Ma, Ding; Li, Shuang

2015-08-01

There is an increasing need for the establishment of a cervical cancer bio-bank that will facilitate both clinical and basic research. The cervical cancer bio-bank was first established in January 1999 and included two stages. First, a GWAS-based sample collection was conducted with special emphasis on the diagnosis and the retrieval of the corresponding bio-specimens, especially blood samples. Second, clinical data and their corresponding bio-specimens were routinely collected and handled. Notably, these bio-specimens also included samples from Wufeng Tujia Autonomous County, which has the highest incidence of cervical cancer in China. The specimens were collected from patients with cervical cancer and those with cervical intraepithelial neoplasia, while the control samples were collected from normal individuals. With special emphasis on clinical data and blood samples for the GWAS analysis, the collection of other bio-specimens was slow, and the pairing of specimens and clinical data was poor during the first stage. However, in the second stage, the pairing of the clinical data and its corresponding bio-specimens improved. At present, the samples procured and preserved in the bio-bank cover most regions of China and different ethnic groups for both the normal controls and cervical cancer patients of different pathological categories. This bio-bank of cervical cancer specimens from the Chinese population will greatly promote the studies of cervical cancer in China.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gregory Reaman

The initiative will enable the COG Biopathology Center (Biospecimen Repository), the Molecular Genetics Laboratory and other participating reference laboratories to upload large data sets to the eRDES. The capability streamlines data currency and accuracy allowing the centers to export data from local systems and import the defined data to the eRDES. The process will aid in the best practices which have been defined by the Office of Biorepository and Biospecimen Research (OBBR) and the Group Banking Committee (GBC). The initiative allows for batch import and export, a data validation process and reporting mechanism, and a model for other labs tomore » incorporate. All objectives are complete. The solutions provided and the defined process eliminates dual data entry resulting in data consistency. The audit trail capabilities allow for complete tracking of the data exchange between laboratories and the Statistical Data Center (SDC). The impact is directly on time and efforts. In return, the process will save money and improve the data utilized by the COG. Ongoing efforts include implementing new technologies to further enhance the current solutions and process currently in place. Web Services and Reporting Services are technologies that have become industry standards and will allow for further harmonization with caBIG (cancer Biolnforrnatics Grid). Additional testing and implementation of the model for other laboratories is in process.« less

Public biobanks: calculation and recovery of costs.

PubMed

Clément, Bruno; Yuille, Martin; Zaltoukal, Kurt; Wichmann, Heinz-Erich; Anton, Gabriele; Parodi, Barbara; Kozera, Lukasz; Bréchot, Christian; Hofman, Paul; Dagher, Georges

2014-11-05

A calculation grid developed by an international expert group was tested across biobanks in six countries to evaluate costs for collections of various types of biospecimens. The assessment yielded a tool for setting specimen-access prices that were transparently related to biobank costs, and the tool was applied across three models of collaborative partnership. Copyright © 2014, American Association for the Advancement of Science.

75 FR 66110 - Guidelines for Use of Stored Specimens and Access to Ancillary Data and Proposed Cost Schedule...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-27

... repository of datasets from completed studies, biospecimens, and ancillary data. The Division intends to make... Sharing Policy. The Division has established an internal committee, the Biospecimen Repository Access and Data Sharing Committee (BRADSC), to oversee the repository access and data sharing program. The purpose...

Factors that Affect Willingness to Donate Blood for the Purpose of Biospecimen Research in the Korean American Community

PubMed Central

Yen, Glorian P.; Davey, Adam

2015-01-01

Objective: Biorepositories have been key resources in examining genetically-linked diseases, particularly cancer. Asian Americans contribute to biorepositories at lower rates than other racial groups, but the reasons for this are unclear. We hypothesized that attitudes toward biospecimen research mediate the relationship between demographic and healthcare access factors, and willingness to donate blood for research purposes among individuals of Korean heritage. Methods: Descriptive statistics and bivariate analyses were utilized to characterize the sample with respect to demographic, psychosocial, and behavioral variables. Structural equation modeling with 5000 re-sample bootstrapping was used to assess each component of the proposed simple mediation models. Results: Attitudes towards biospecimen research fully mediate associations between age, income, number of years lived in the United States, and having a regular physician and willingness to donate blood for the purpose of research. Conclusion: Participants were willing to donate blood for the purpose of research despite having neutral feelings towards biospecimen research as a whole. Participants reported higher willingness to donate blood for research purposes when they were older, had lived in the United States longer, had higher income, and had a regular doctor that they visited. Many of the significant relationships between demographic and health care access factors, attitudes towards biospecimen research, and willingness to donate blood for the purpose of research may be explained by the extent of acculturation of the participants in the United States. PMID:25853387

Challenges and Driving Forces for Business Plans in Biobanking.

PubMed

Macheiner, Tanja; Huppertz, Berthold; Bayer, Michaela; Sargsyan, Karine

2017-04-01

Due to increased utilization of biospecimens for research and emergence of new technologies, the availability and quality of biospecimens and their collection are coming more and more into focus. However, the long-term economic situation of biobanks is still mostly unclear. Also, the common sustainable utilization of various international biobanks is challenging due to local differences in sample processing, law and ethics. This article discusses possible strategies to achieve a sustainable utilization of biospecimens as part of the business plan of biobanks. The following questions were addressed as part of a business plan: (1) How can a biobank build up and maintain an up-to-date infrastructure? (2) What kind of funding can support the sustainability of a biobank? (3) Is there an international solution for informed consents to enable sample and data sharing? (4) How can a biobank react during economically unstable periods? (5) Which kind of biobanking research is innovative? (6) What kind of education could be most needful for knowledge transfer in biobanking? (7) Does an expiration date for a biobank make sense according to the period of funding? A strategy for optimal utilization begins with sharing of resources, infrastructure, and investments at the planning stage of a biobank, and continues to the transfer of knowledge and know-how by education. For clinical biobanks in particular, a long-term funding and cost recovery strategy is necessary for sustainable utilization.

The NASA Ames Research Center Institutional Scientific Collection: History, Best Practices and Scientific Opportunities

NASA Technical Reports Server (NTRS)

Rask, Jon C.; Chakravarty, Kaushik; French, Alison; Choi, Sungshin; Stewart, Helen

2017-01-01

The NASA Ames Life Sciences Institutional Scientific Collection (ISC), which is composed of the Ames Life Sciences Data Archive (ALSDA) and the Biospecimen Storage Facility (BSF), is managed by the Space Biosciences Division and has been operational since 1993. The ALSDA is responsible for archiving information and animal biospecimens collected from life science spaceflight experiments and matching ground control experiments. Both fixed and frozen spaceflight and ground tissues are stored in the BSF within the ISC. The ALSDA also manages a Biospecimen Sharing Program, performs curation and long-term storage operations, and makes biospecimens available to the scientific community for research purposes via the Life Science Data Archive public website (https:lsda.jsc.nasa.gov). As part of our best practices, a viability testing plan has been developed for the ISC, which will assess the quality of archived samples. We expect that results from the viability testing will catalyze sample use, enable broader science community interest, and improve operational efficiency of the ISC. The current viability test plan focuses on generating disposition recommendations and is based on using ribonucleic acid (RNA) integrity number (RIN) scores as a criteria for measurement of biospecimen viablity for downstream functional analysis. The plan includes (1) sorting and identification of candidate samples, (2) conducting a statiscally-based power analysis to generate representaive cohorts from the population of stored biospecimens, (3) completion of RIN analysis on select samples, and (4) development of disposition recommendations based on the RIN scores. Results of this work will also support NASA open science initiatives and guides development of the NASA Scientific Collections Directive (a policy on best practices for curation of biological collections). Our RIN-based methodology for characterizing the quality of tissues stored in the ISC since the 1980s also creates unique scientific opportunities for temporal assessment across historical missions. Support from the NASA Space Biology Program and the NASA Human Research Program is gratefully acknowledged.

Biospecimen repositories and cytopathology.

PubMed

Krishnamurthy, Savitri

2015-03-01

Biospecimen repositories are important for the advancement of biomedical research. Literature on the potential for biobanking of fine-needle aspiration, gynecologic, and nongynecologic cytology specimens is very limited. The potential for biobanking of these specimens as valuable additional resources to surgically excised tissues appears to be excellent. The cervicovaginal specimens that can be used for biobanking include Papanicolaou-stained monolayer preparations and residual material from liquid-based cytology preparations. Different types of specimen preparations of fine-needle aspiration and nongynecologic specimens, including Papanicolaou-stained and Diff-Quik-stained smears, cell blocks. and dedicated passes/residual material from fine-needle aspiration stored frozen in a variety of solutions, can be used for biobanking. Because of several gaps in knowledge regarding the standard of operative procedures for the procurement, storage, and quality assessment of cytology specimens, further studies as well as national conferences and workshops are needed not only to create awareness but also to facilitate the use of cytopathology specimens for biobanking. © 2014 American Cancer Society.

Wetlab-2 - Quantitative PCR Tools for Spaceflight Studies of Gene Expression Aboard the International Space Station

NASA Technical Reports Server (NTRS)

Schonfeld, Julie E.

2015-01-01

Wetlab-2 is a research platform for conducting real-time quantitative gene expression analysis aboard the International Space Station. The system enables spaceflight genomic studies involving a wide variety of biospecimen types in the unique microgravity environment of space. Currently, gene expression analyses of space flown biospecimens must be conducted post flight after living cultures or frozen or chemically fixed samples are returned to Earth from the space station. Post-flight analysis is limited for several reasons. First, changes in gene expression can be transient, changing over a timescale of minutes. The delay between sampling on Earth can range from days to months, and RNA may degrade during this period of time, even in fixed or frozen samples. Second, living organisms that return to Earth may quickly re-adapt to terrestrial conditions. Third, forces exerted on samples during reentry and return to Earth may affect results. Lastly, follow up experiments designed in response to post-flight results must wait for a new flight opportunity to be tested.

Cryopreservation of Viable Human Lung Tissue for Versatile Post-thaw Analyses and Culture

PubMed Central

Baatz, John E.; Newton, Danforth A.; Riemer, Ellen C.; Denlinger, Chadrick E.; Jones, E. Ellen; Drake, Richard R.; Spyropoulos, Demetri D.

2018-01-01

Clinical trials are currently used to test therapeutic efficacies for lung cancer, infections and diseases. Animal models are also used as surrogates for human disease. Both approaches are expensive and time-consuming. The utility of human biospecimens as models is limited by specialized tissue processing methods that preserve subclasses of analytes (e.g. RNA, protein, morphology) at the expense of others. We present a rapid and reproducible method for the cryopreservation of viable lung tissue from patients undergoing lobectomy or transplant. This method involves the pseudo-diaphragmatic expansion of pieces of fresh lung tissue with cryoprotectant formulation (pseudo-diaphragmatic expansion-cryoprotectant perfusion or PDX-CP) followed by controlled-rate freezing in cryovials. Expansion-perfusion rates, volumes and cryoprotectant formulation were optimized to maintain tissue architecture, decrease crystal formation and increase long-term cell viability. Rates of expansion of 4 cc/min or less and volumes ranging from 0.8–1.2 × tissue volume were well-tolerated by lung tissue obtained from patients with chronic obstructive pulmonary disease or idiopathic pulmonary fibrosis, showing minimal differences compared to standard histopathology. Morphology was greatly improved by the PDX-CP procedure compared to simple fixation. Fresh versus post-thawed lung tissue showed minimal differences in histology, RNA integrity numbers and post-translational modified protein integrity (2-dimensional differential gel electrophoresis). It was possible to derive numerous cell types, including alveolar epithelial cells, fibroblasts and stem cells, from the tissue for at least three months after cryopreservation. This new method should provide a uniform, cost-effective approach to the banking of biospecimens, with versatility to be amenable to any post-acquisition process applicable to fresh tissue samples. PMID:24982205

iss047e066248

NASA Image and Video Library

2016-04-19

ISS047e066248 (04/19/2016) --- NASA astronaut and Expedition 47 Flight Engineer Jeff Williams works with the Wet Lab RNA SmartCycler on-board the International Space Station. Wetlab RNA SmartCycler is a research platform for conducting real-time quantitative gene expression analysis aboard the ISS. The system enables spaceflight genomic studies involving a wide variety of biospecimen types in the unique microgravity environment of space.

Feasibility of Linking Population-Based Cancer Registries and Cancer Center Biorepositories

PubMed Central

McCusker, Margaret E.; Allen, Mark; Fernandez-Ami, Allyn; Gandour-Edwards, Regina

2012-01-01

Purpose: Biospecimen-based research offers tremendous promise as a way to increase understanding of the molecular epidemiology of cancers. Population-based cancer registries can augment this research by providing more clinical detail and long-term follow-up information than is typically available from biospecimen annotations. In order to demonstrate the feasibility of this concept, we performed a pilot linkage between the California Cancer Registry (CCR) and the University of California, Davis Cancer Center Biorepository (UCD CCB) databases to determine if we could identify patients with records in both databases. Methods: We performed a probabilistic data linkage between 2180 UCD CCB biospecimen records collected during the years 2005–2009 and all CCR records for cancers diagnosed from 1988–2009 based on standard data linkage procedures. Results: The 1040 UCD records with a unique medical record number, tissue site, and pathology date were linked to 3.3 million CCR records. Of these, 844 (81.2%) were identified in both databases. Overall, record matches were highest (100%) for cancers of the cervix and testis/other male genital system organs. For the most common cancers, matches were highest for cancers of the lung and respiratory system (93%), breast (91.7%), and colon and rectum (89.5%), and lower for prostate (72.9%). Conclusions: This pilot linkage demonstrated that information on existing biospecimens from a cancer center biorepository can be linked successfully to cancer registry data. Linkages between existing biorepositories and cancer registries can foster productive collaborations and provide a foundation for virtual biorepository networks to support population-based biospecimen research. PMID:24845042

Development and Validation of the Biobanking Attitudes and Knowledge Survey (BANKS)

PubMed Central

Wells, Kristen J.; Arevalo, Mariana; Meade, Cathy D.; Gwede, Clement K.; Quinn, Gwendolyn P.; Luque, John S.; Miguel, Gloria San; Watson, Dale; Phillips, Rebecca; Reyes, Carmen; Romo, Margarita; West, Jim; Jacobsen, Paul B.

2014-01-01

Background No validated multi-scale instruments exist that measure community members’ views on biobanking and biospecimen donation. This study describes the development and psychometric properties of the English-language BANKS (Biobanking Attitudes aNd Knowledge Survey). Methods The BANKS was created by item generation through review of scientific literature, focus groups with community members, and input from a community advisory board. Items were refined through cognitive interviews. Content validity was assessed through an expert panel review. Psychometric properties of the BANKS were assessed in a sample of 85 community members. Results The final BANKS includes 3 scales: Attitudes, Knowledge, and Self-Efficacy; as well as 3 single items, which evaluated receptivity and intention to donate a biospecimen for research. Cronbach's alpha coefficients for two scales that use Likert response format indicated high internal consistency (Attitudes: α=.88; Self-Efficacy: α=.95). Content validity indices were moderate, ranging from 0.69 to 0.89. Intention to donate blood and intention to donate urine were positively correlated with attitudes, knowledge, self-efficacy, and receptivity to learning more about biobanking (p's range from .029 to <.001). Conclusions The final BANKS shows evidence of satisfactory reliability and validity, is easy to administer, and is a promising tool to inform biospecimen research. Additional studies should be conducted with larger samples considering biospecimen donation to further assess the instrument's reliability and validity. Impact A valid and reliable instrument measuring community members’ views about biobanking may help researchers evaluate relevant communication interventions to enhance understanding, intention, and actual biospecimen donation. A Spanish-language BANKS is under development. PMID:24609846

Prostate Cancer Biorepository Network

DTIC Science & Technology

2016-10-01

Cancer Biorepository Network (PCBN). The aim of the PCBN is to provide prostate researchers with high- quality , well-annotated biospecimens obtained...patients and stores them to maintain high quality biospecimens. Additionally, clinical data including pathology and outcome data are annotated with the...that can provide to the wider research community. The major goal of the PCBN is to develop a biorepository with high- quality , well-annotated

A review of room temperature storage of biospecimen tissue and nucleic acids for anatomic pathology laboratories and biorepositories

PubMed Central

Lou, Jerry J; Mirsadraei, Leili; Sanchez, Desiree E; Wilson, Ryan W; Shabihkhani, Maryam; Lucey, Gregory M; Wei, Bowen; Singer, Elyse J; Mareninov, Sergey; Yong, William H

2014-01-01

Frozen biospecimens are crucial for translational research and contain well preserved nucleic acids and protein. However, the risk for catastrophic freezer failure as well as space, cost, and environmental concerns argue for evaluating long-term room temperature storage alternatives. Formalin-fixed paraffin embedded (FFPE) tissues have great value but their use is limited by cross-linking and fragmentation of nucleic acids, as well as loss of enzymatic activity. Stabilization solutions can now robustly preserve fresh tissue for up to 7 days at room temperature. For longer term storage, commercial vendors of chemical matrices claim real time stability of nucleic acids of over 2 years and their accelerated aging studies to date suggest stability for 12 years for RNA and 60 years for DNA. However, anatomic pathology biorepositories store mostly frozen tissue rather than nucleic acids. Small quantities of tissue can be directly placed on some chemical matrices to stabilize DNA, however RNA and proteins are not preserved. Current lyophilization approaches can preserve histomorphology, DNA, RNA, and proteins though RNA shows moderate degradation after 1–2 years. Formalin free fixatives show improved but varying abilities to preserve nucleic acids and face validation as well as cost barriers in replacing FFPE specimens. The paraffin embedding process can degrade RNA. Development of robust long-term room temperature biospecimen tissue storage technology can potentially reduce costs for the biomedical community in the face of growing targeted therapy needs and decreasing budgets. PMID:24362270

Prostate Cancer Pathology Resource Network

DTIC Science & Technology

2013-07-01

The PCBN is organized with a Coordinating Center (JHU – led by Bruce Trock, Ph.D.), and Network Sites at NYU (led by Jonathan Melamed, M.D. and Peng...Resource Network Site must contribute biospecimens from a minimum of 50 patients per year, with the expectation that biospecimen contribution will...available to the Pathology Resource Network Site . o Each year both sites have contributed over 500 newly accrued specimens, with specimens obtained as

Transmissive liquid-crystal device for correcting primary coma aberration and astigmatism in biospecimen in two-photon excitation laser scanning microscopy

NASA Astrophysics Data System (ADS)

Tanabe, Ayano; Hibi, Terumasa; Ipponjima, Sari; Matsumoto, Kenji; Yokoyama, Masafumi; Kurihara, Makoto; Hashimoto, Nobuyuki; Nemoto, Tomomi

2016-12-01

All aberrations produced inside a biospecimen can degrade the quality of a three-dimensional image in two-photon excitation laser scanning microscopy. Previously, we developed a transmissive liquid-crystal device to correct spherical aberrations that improved the image quality of a fixed-mouse-brain slice treated with an optical clearing reagent. In this study, we developed a transmissive device that corrects primary coma aberration and astigmatism. The motivation for this study is that asymmetric aberration can be induced by the shape of a biospecimen and/or by a complicated refractive-index distribution in a sample; this can considerably degrade optical performance even near the sample surface. The device's performance was evaluated by observing fluorescence beads. The device was inserted between the objective lens and microscope revolver and succeeded in improving the spatial resolution and fluorescence signal of a bead image that was originally degraded by asymmetric aberration. Finally, we implemented the device for observing a fixed whole mouse brain with a sloping surface shape and complicated internal refractive-index distribution. The correction with the device improved the spatial resolution and increased the fluorescence signal by ˜2.4×. The device can provide a simple approach to acquiring higher-quality images of biospecimens.

Accelerating the Development and Validation of New Value-Based Diagnostics by Leveraging Biobanks.

PubMed

Schneider, Daniel; Riegman, Peter H J; Cronin, Maureen; Negrouk, Anastassia; Moch, Holger; Balling, Rudi; Penault-Llorca, Frederiques; Zatloukal, Kurt; Horgan, Denis

The challenges faced in developing value-based diagnostics has resulted in few of these tests reaching the clinic, leaving many treatment modalities without matching diagnostics to select patients for particular therapies. Many patients receive therapies from which they are unlikely to benefit, resulting in worse outcomes and wasted health care resources. The paucity of value-based diagnostics is a result of the scientific challenges in developing predictive markers, specifically: (1) complex biology, (2) a limited research infrastructure supporting diagnostic development, and (3) the lack of incentives for diagnostic developers to invest the necessary resources. Better access to biospecimens can address some of these challenges. Methodologies developed to evaluate biomarkers from biospecimens archived from patients enrolled in randomized clinical trials offer the greatest opportunity to develop and validate high-value molecular diagnostics. An alternative opportunity is to access high-quality biospecimens collected from large public and private longitudinal observational cohorts such as the UK Biobank, the US Million Veteran Program, the UK 100,000 Genomes Project, or the French E3N cohort. Value-based diagnostics can be developed to work in a range of samples including blood, serum, plasma, urine, and tumour tissue, and better access to these high-quality biospecimens with clinical data can facilitate biomarker research. © 2016 S. Karger AG, Basel.

Public perspectives on biospecimen procurement: what biorepositories should consider.

PubMed

L'Heureux, Jamie; Murray, Jeffrey C; Newbury, Elizabeth; Shinkunas, Laura; Simon, Christian M

2013-06-01

Human biospecimens are central to biobanking efforts, yet how members of the public think about biobank procurement strategies is not well understood. This study aimed to explore public perspectives toward the procurement of residual clinical material versus "direct" procurement strategies such as the drawing of blood. Members of the public residing in and beyond the biobank catchment area of the University of Iowa Hospitals and Clinics were randomly selected to participate in focus groups and a telephone survey. The majority of survey participants (75%, n=559) found both residual and direct procurement strategies equally workable. Small proportions preferred either residual (15%; n=117) or direct (5%; n=40) procurement. Focus group participants (n=48) could identify benefits to both procurement strategies, but raised concerns about possible donor inconvenience/discomfort and reduced biospecimen accrual in the case of direct procurement. Residual procurement raised concerns about lower-quality samples being procured without full donor awareness. Biobanks should consider that members of the public in their research programs may be willing to make specimen donations regardless of whether a residual or direct procurement strategy is employed. Limiting patient discomfort and inconvenience may make direct procurement strategies more acceptable to some members of the public. Ensuring donor awareness through effective informed consent may allay public concerns about the indirectness of donating clinical biospecimens.

Translating Metabolomics to Cardiovascular Biomarkers

PubMed Central

Senn, Todd; Hazen, Stanley L.; Tang, W. H. Wilson

2012-01-01

Metabolomics is the systematic study of the unique chemical fingerprints of small-molecules, or metabolite profiles, that are related to a variety of cellular metabolic processes in a cell, organ, or organism. While mRNA gene expression data and proteomic analyses do not tell the whole story of what might be happening in a cell, metabolic profiling provides direct and indirect physiologic insights that can potentially be detectable in a wide range of biospecimens. Although not specific to cardiac conditions, translating metabolomics to cardiovascular biomarkers has followed the traditional path of biomarker discovery from identification and confirmation to clinical validation and bedside testing. With technological advances in metabolomic tools (such as nuclear magnetic resonance spectroscopy and mass spectrometry) and more sophisticated bioinformatics and analytical techniques, the ability to measure low-molecular-weight metabolites in biospecimens provides a unique insight into established and novel metabolic pathways. Systemic metabolomics may provide physiologic understanding of cardiovascular disease states beyond traditional profiling, and may involve descriptions of metabolic responses of an individual or population to therapeutic interventions or environmental exposures. PMID:22824112

Prostate Cancer Biorepository Network

DTIC Science & Technology

2017-10-01

Department of the Army position, policy or decision unless so designated by other documentation. REPORT DOCUMENTATION PAGE Form Approved OMB No. 0704...clinical data including pathology and outcome data are annotated with the biospecimens. Specialized processing consists of tissue microarray design ...Months 1- 6): Completed in 1st quarter Task 5. Report on performance metrics: Ongoing (accrual reports are provided on quarterly basis) Task 6

Participation in Pediatric Oncology Research Protocols: Racial/ethnic, Language and Age-based Disparities

PubMed Central

Aristizabal, Paula; Singer, Jenelle; Cooper, Renee; Wells, Kristen J.; Nodora, Jesse; Milburn, Mehrzad; Gahagan, Sheila; Schiff, Deborah E.; Martinez, Maria Elena

2015-01-01

Background Survival rates in pediatric oncology have improved dramatically, in part due to high patient participation in clinical trials. Although racial/ethnic inequalities in clinical trial participation have been reported in adults, pediatric data and studies comparing participation rates by socio-demographic characteristics are scarce. The goal of this study was to assess differences in research protocol participation for childhood cancer by age, sex, race/ethnicity, parental language, cancer type and insurance status. Procedure Data on enrollment in any protocol, biospecimen, or therapeutic protocols were collected and analyzed for newly diagnosed pediatric patients with cancer from 2008–2012 at Rady Children’s Hospital. Results Among the 353 patients included in the analysis, 304 (86.1%) were enrolled in any protocol. Enrollment in biospecimen and therapeutic protocols was 84.2% (261/310) and 81.1% (206/254), respectively. Logistic regression analyses revealed significant enrollment underrepresentation in any protocol for Hispanics compared to Non-Hispanic whites (81% vs. 91%; Odds Ratio [OR], 0.43; 95% Confidence Interval [CI], 0.21–0.90; p=0.021) and among children of Spanish-speaking vs. English-speaking parents (78% vs. 89%; OR, 0.45; 95%CI, 0.23–0.87; p=0.016). Compared to patients aged 0–4 years, significant underrepresentation was also found among patients 15–21 years old (92% vs.72%; OR, 0.21; 95% CI, 0.09–0.48; p<0.001). Similar trends were observed when analyzing enrollment in biospecimen and therapeutic protocols separately. Conclusions There was significant underrepresentation in protocol participation for Hispanics, children of Spanish-speaking parents, and patients ages 15–21. Research is urgently needed to understand barriers to research participation among these groups underrepresented in pediatric oncology clinical trials. PMID:25755225

Assessment of Salivary Adipokines Resistin, Visfatin, and Ghrelin as Type 2 Diabetes Mellitus Biomarkers

PubMed Central

Meadows, Melinda L.; Maxwell, Lisa

2018-01-01

Type 2 diabetes mellitus (T2DM) is emerging as a metabolic epidemic worldwide. Pathologically, dysregulation of many biological pathways precedes hyperglycemia and the clinical diagnosis of T2DM. Changing trajectories along the process of T2DM development necessitates frequent measurement of biomarkers for early identification of at-risk individuals and successful prevention. Increase in circulating inflammatory adipokines has been suggested as predictive of T2DM. Human saliva is an easily accessible biospecimen amenable for painless frequent collection and possesses nearly 50% of serum proteome. In this study, we measured the adipokines resistin, visfatin, TNF-α, and ghrelin as markers for T2DM in unstimulated whole saliva (UWS) using specific assay kits. Resistin and visfatin concentrations were significantly higher in T2DM saliva. Although the concentration of acylated or unacylated ghrelin was lower in diabetic saliva, the decrease was not significant. Since resistin and visfatin are biomarkers integral to T2DM pathology, their salivary assessments may receive clinical acceptance. PMID:29487749

Safeguarding donors' personal rights and biobank autonomy in biobank networks: the CRIP privacy regime.

PubMed

Schröder, Christina; Heidtke, Karsten R; Zacherl, Nikolaus; Zatloukal, Kurt; Taupitz, Jochen

2011-08-01

Governance, underlying general ICT (Information and Communication Technology) architecture, and workflow of the Central Research Infrastructure for molecular Pathology (CRIP) are discussed as a model enabling biobank networks to form operational "meta biobanks" whilst respecting the donors' privacy, biobank autonomy and confidentiality, and the researchers' needs for appropriate biospecimens and information, as well as confidentiality. Tailored to these needs, CRIP efficiently accelerates and facilitates research with human biospecimens and data.

Population Based Analysis of Hematologic Malignancy Referrals to a Comprehensive Cancer Center, Referrals for Blood and Marrow Transplantation, and Participation in Clinical Trials, Survey and Biospecimen Research by Race

PubMed Central

Clay, Alyssa; Peoples, Brittany; Zhang, Yali; Moysich, Kirsten; Ross, Levi; McCarthy, Philip; Hahn, Theresa

2017-01-01

Racial and ethnic disparities have been reported in clinical trial/research participation, utilization of autologous and allogeneic BMT and availability of allogeneic donors. We performed a population-based cohort study to investigate adult hematologic malignancy referrals to a U.S tertiary cancer center, utilization of BMT and participation in clinical trials, survey and biospecimen research, by race. U.S. Census Data and the New York State Public Access Cancer Epidemiology Database identified the racial distribution of the general population and new hematologic malignancy cases in the primary catchment area. From 2005–2011, 1,106 patients aged 18–75 years were referred for BMT consultation; while the rate of BMT among hematologic malignancy referrals did not differ by race, the reasons for not receiving a BMT did. Participation in biospecimen research did not vary by race, however African-Americans and other minorities were significantly less likely to participate in survey research than European-Americans. While rates of hematologic malignancy referrals and use of BMT for minorities appear low (<10%), they closely reflect the race distribution of all hematologic malignancy cases and the Western New York population. African-Americans are equally likely as other races to participate in biospecimen banking, but further study is needed to understand reasons for lower participation in survey research. PMID:25899454

Public Perspectives on Biospecimen Procurement: What Biorepositories Should Consider

PubMed Central

L'Heureux, Jamie; Murray, Jeffrey C.; Newbury, Elizabeth; Shinkunas, Laura

2013-01-01

Purpose Human biospecimens are central to biobanking efforts, yet how members of the public think about biobank procurement strategies is not well understood. This study aimed to explore public perspectives toward the procurement of residual clinical material versus “direct” procurement strategies such as the drawing of blood. Methods Members of the public residing in and beyond the biobank catchment area of the University of Iowa Hospitals and Clinics were randomly selected to participate in focus groups and a telephone survey. Results The majority of survey participants (75%, n=559) found both residual and direct procurement strategies equally workable. Small proportions preferred either residual (15%; n=117) or direct (5%; n=40) procurement. Focus group participants (n=48) could identify benefits to both procurement strategies, but raised concerns about possible donor inconvenience/discomfort and reduced biospecimen accrual in the case of direct procurement. Residual procurement raised concerns about lower-quality samples being procured without full donor awareness. Conclusion Biobanks should consider that members of the public in their research programs may be willing to make specimen donations regardless of whether a residual or direct procurement strategy is employed. Limiting patient discomfort and inconvenience may make direct procurement strategies more acceptable to some members of the public. Ensuring donor awareness through effective informed consent may allay public concerns about the indirectness of donating clinical biospecimens. PMID:24850089

Microfluidics enables multiplex evaluation of the same cells for further studies.

PubMed

Mojica, W D; Oh, K W; Lee, H; Furlani, E P; Sykes, D; Sands, A M

2016-08-01

The continuous discovery of biomarkers and their evolving use for the diagnosis and guidance of therapy for patients with cancer has increased awareness of the need to triage biospecimens properly. On occasion, cytology samples are the only type of biospecimen available for analysis. Often, the current approach for these latter specimens is cytopathology-centric, with cells limited to examination by bright field microscopy. When specimens are paucicellular, there is often insufficient material for ancillary testing. Therefore, a need exists to develop an alternative approach that allows for the multiplexed analysis of cells when they are limited in number. In recent previous publications, we demonstrated that clinically derived cells from tissue are suitable for evaluation in a microfluidic device. In our current endeavour, we seek to expand upon those findings and determine if those same cells can be recovered for further analysis. A microfluidic channel was designed, fabricated and tested using cytology specimens generated from tissue specimens. The cytological features of the cells tested were examined prior to entering the channel; they were then compared to similar cells while in the channel, and upon recovery from the channel. Recovery of DNA and proteins were also tested. The morphology of the tested cells was not compromised in either the channel or upon recovery. More importantly, the integrity of the cells remained intact, with the recovery of proteins and high molecular weight DNA possible. We developed and tested an alternative approach to the processing of cytopathology specimens that enables multiplexed evaluation. Using microfluidics, cytological examination of biopecimens can be performed, but in contrast to existing approaches, the same cells examined can be recovered for downstream analysis. © 2015 John Wiley & Sons Ltd.

Biobankonomics: developing a sustainable business model approach for the formation of a human tissue biobank.

PubMed

Vaught, Jimmie; Rogers, Joyce; Carolin, Todd; Compton, Carolyn

2011-01-01

The preservation of high-quality biospecimens and associated data for research purposes is being performed in variety of academic, government, and industrial settings. Often these are multimillion dollar operations, yet despite these sizable investments, the economics of biobanking initiatives is not well understood. Fundamental business principles must be applied to the development and operation of such resources to ensure their long-term sustainability and maximize their impact. The true costs of developing and maintaining operations, which may have a variety of funding sources, must be better understood. Among the issues that must be considered when building a biobank economic model are: understanding the market need for the particular type of biobank under consideration and understanding and efficiently managing the biobank's "value chain," which includes costs for case collection, tissue processing, storage management, sample distribution, and infrastructure and administration. By using these value chain factors, a Total Life Cycle Cost of Ownership (TLCO) model may be developed to estimate all costs arising from owning, operating, and maintaining a large centralized biobank. The TLCO approach allows for a better delineation of a biobank's variable and fixed costs, data that will be needed to implement any cost recovery program. This article represents an overview of the efforts made recently by the National Cancer Institute's Office of Biorepositories and Biospecimen Research as part of its effort to develop an appropriate cost model and cost recovery program for the cancer HUman Biobank (caHUB) initiative. All of these economic factors are discussed in terms of maximizing caHUB's potential for long-term sustainability but have broad applicability to the wide range of biobanking initiatives that currently exist.

International Charter of principles for sharing bio-specimens and data.

PubMed

Mascalzoni, Deborah; Dove, Edward S; Rubinstein, Yaffa; Dawkins, Hugh J S; Kole, Anna; McCormack, Pauline; Woods, Simon; Riess, Olaf; Schaefer, Franz; Lochmüller, Hanns; Knoppers, Bartha M; Hansson, Mats

2015-06-01

There is a growing international agreement on the need to provide greater access to research data and bio-specimen collections to optimize their long-term value and exploit their potential for health discovery and validation. This is especially evident for rare disease research. Currently, the rising value of data and bio-specimen collections does not correspond with an equal increase in data/sample-sharing and data/sample access. Contradictory legal and ethical frameworks across national borders are obstacles to effective sharing: more specifically, the absence of an integrated model proves to be a major logistical obstruction. The Charter intends to amend the obstacle by providing both the ethical foundations on which data sharing should be based, as well as a general Material and Data Transfer Agreement (MTA/DTA). This Charter is the result of a careful negotiation of different stakeholders' interest and is built on earlier consensus documents and position statements, which provided the general international legal framework. Further to this, the Charter provides tools that may help accelerate sharing. The Charter has been formulated to serve as an enabling tool for effective and transparent data and bio-specimen sharing and the general MTA/DTA constitutes a mechanism to ensure uniformity of access across projects and countries, and may be regarded as a consistent basic agreement for addressing data and material sharing globally. The Charter is forward looking in terms of emerging issues from the perspective of a multi-stakeholder group, and where possible, provides strategies that may address these issues.

Population-Based Analysis of Hematologic Malignancy Referrals to a Comprehensive Cancer Center, Referrals for Blood and Marrow Transplantation, and Participation in Clinical Trial, Survey, and Biospecimen Research by Race.

PubMed

Clay, Alyssa; Peoples, Brittany; Zhang, Yali; Moysich, Kirsten; Ross, Levi; McCarthy, Philip; Hahn, Theresa

2015-08-01

Racial and ethnic disparities have been reported in clinical trial/research participation, utilization of autologous and allogeneic blood and marrow transplantation (BMT), and availability of allogeneic donors. We performed a population-based cohort study to investigate adult hematologic malignancy referrals to a US tertiary cancer center, utilization of BMT, and participation in clinical trial, survey, and biospecimen research by race. US Census Data and the New York State Public Access Cancer Epidemiology Database identified the racial distribution of the general population and new hematologic malignancy cases in the primary catchment area. From 2005 to 2011, 1106 patients aged 18 to 75 years were referred for BMT consultation; although the rate of BMT among hematologic malignancy referrals did not differ by race, the reasons for not receiving a BMT did. Participation in biospecimen research did not vary by race; however, African Americans and other minorities were significantly less likely to participate in survey research than European Americans. Although rates of hematologic malignancy referrals and use of BMT for minorities appear to be low (<10%), they closely reflect the race distribution of all hematologic malignancy cases and the western New York population. African Americans are equally likely as other races to participate in biospecimen banking, but further study is needed to understand reasons for lower participation in survey research. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Biobanking for Personalized Medicine.

PubMed

Liu, Angen; Pollard, Kai

2015-01-01

A biobank is an entity that collects, processes, stores, and distributes biospecimens and relevant data for use in basic, translational, and clinical research. Biobanking of high-quality human biospecimens such as tissue, blood and other bodily fluids along with associated patient clinical information provides a fundamental scientific infrastructure for personalized medicine. Identification of biomarkers that are specifically associated with particular medical conditions such as cancer, cardiovascular disease and neurological disorders are useful for early detection, prevention, and treatment of the diseases. The ability to determine individual tumor biomarkers and to use those biomarkers for disease diagnosis, prognosis and prediction of response to therapy is having a very significant impact on personalized medicine and is rapidly changing the way clinical care is conducted. As a critical requirement for personalized medicine is the availability of a large collection of patient samples with well annotated patient clinical and pathological data, biobanks thus play an important role in personalized medicine advancement. The goal of this chapter is to explore the role of biobanks in personalized medicine and discuss specific needs regarding biobank development for translational and clinical research, especially for personalized medicine advancement.

Background | Office of Cancer Clinical Proteomics Research

Cancer.gov

The term "proteomics" refers to a large-scale comprehensive study of a specific proteome resulting from its genome, including abundances of proteins, their variations and modifications, and interacting partners and networks in order to understand cellular processes involved.  Similarly, “Cancer proteomics” refers to comprehensive analyses of proteins and their derivatives translated from a specific cancer genome using a human biospecimen or a preclinical model (e.g., cultured cell or animal model).

Barriers and strategies to participation in tissue research among African-American men

PubMed Central

Boyd, Danielle; Carter, Kimberly; Gehlert, Sarah; Thompson, Vetta Sanders

2015-01-01

Before the burgeoning field of biospecimen collection can advance prevention and treatment methods, researchers must access diverse molecular data samples. However minorities, especially African American men, remain reticent to join these studies. This study, using theory based approaches, investigated African American men’s barriers to participating in biorepository research. Fourteen focus groups were conducted among 70 African American men (ages 40 to 80). The groups were stratified by prostate cancer history and educational attainment background. Participants identified perceived factors that promoted or hindered study participation when questioned about their knowledge and attitudes about biospecimen research. Ninety-four percent of participants indicated never participating in a study that collected biological samples. Barriers to their participation included lack of knowledge and understanding regarding biospecimen research practices and uses. In addition they extensively cited a prevalent mistrust of the medical community and discomfort with study recruitment practices. African American males were more willing to participate in biorepository studies with physician endorsement or if they understood that participation could benefit future generations. Men also wanted more recruitment and advertising done in familiar places. PMID:26341221

Mechanistic and Technical Challenges in Studying the Human Microbiome and Cancer Epidemiology.

PubMed

Verma, Mukesh

2017-04-01

This article reviews the significance of the microbiome in cancer epidemiology, mechanistic and technical challenges in the field, and characterization of the microbiome in different tumor types to identify biomarkers of risk, progression, and prognosis. Publications on the microbiome and cancer epidemiology were reviewed to analyze sample collection and processing, microbiome taxa characterization by 16S ribosomal RNA sequencing, and microbiome metabolite characterization (metabotyping) by nuclear magnetic resonance and mass spectrometry. The analysis identified methodology types, research design, sample types, and issues in integrating data from different platforms. Aerodigestive cancer epidemiology studies conducted by different groups demonstrated the significance of microbiome information in developing approaches to improve health. Challenges exist in sample preparation and processing (eg, standardization of methods for collection and analysis). These challenges relate to technology, data integration from "omics" studies, inherent bias in primer selection during 16S ribosomal RNA sequencing, the need for large consortia with well-characterized biospecimens, cause and effect issues, resilience of microbiota to exposure events (requires longitudinal studies), and expanding studies for fungal and viral diversity (most studies used bacterial 16S ribosomal RNA sequencing for microbiota characterization). Despite these challenges, microbiome and cancer epidemiology studies are significant and may facilitate cancer risk assessment, diagnosis, and prognosis. In the future, clinical trials likely will use microbiota modifications to improve the efficacy of existing treatments.

Mechanistic and Technical Challenges in Studying the Human Microbiome and Cancer Epidemiology

PubMed Central

2016-01-01

This article reviews the significance of the microbiome in cancer epidemiology, mechanistic and technical challenges in the field, and characterization of the microbiome in different tumor types to identify biomarkers of risk, progression, and prognosis. Publications on the microbiome and cancer epidemiology were reviewed to analyze sample collection and processing, microbiome taxa characterization by 16S ribosomal RNA sequencing, and microbiome metabolite characterization (metabotyping) by nuclear magnetic resonance and mass spectrometry. The analysis identified methodology types, research design, sample types, and issues in integrating data from different platforms. Aerodigestive cancer epidemiology studies conducted by different groups demonstrated the significance of microbiome information in developing approaches to improve health. Challenges exist in sample preparation and processing (eg, standardization of methods for collection and analysis). These challenges relate to technology, data integration from “omics” studies, inherent bias in primer selection during 16S ribosomal RNA sequencing, the need for large consortia with well-characterized biospecimens, cause and effect issues, resilience of microbiota to exposure events (requires longitudinal studies), and expanding studies for fungal and viral diversity (most studies used bacterial 16S ribosomal RNA sequencing for microbiota characterization). Despite these challenges, microbiome and cancer epidemiology studies are significant and may facilitate cancer risk assessment, diagnosis, and prognosis. In the future, clinical trials likely will use microbiota modifications to improve the efficacy of existing treatments. PMID:27121074

Is Your Biobank Up to Standards? A Review of the National Canadian Tissue Repository Network Required Operational Practice Standards and the Controlled Documents of a Certified Biobank.

PubMed

Hartman, Victoria; Castillo-Pelayo, Tania; Babinszky, Sindy; Dee, Simon; Leblanc, Jodi; Matzke, Lise; O'Donoghue, Sheila; Carpenter, Jane; Carter, Candace; Rush, Amanda; Byrne, Jennifer; Barnes, Rebecca; Mes-Messons, Anne-Marie; Watson, Peter

2018-02-01

Ongoing quality management is an essential part of biobank operations and the creation of high quality biospecimen resources. Adhering to the standards of a national biobanking network is a way to reduce variability between individual biobank processes, resulting in cross biobank compatibility and more consistent support for health researchers. The Canadian Tissue Repository Network (CTRNet) implemented a set of required operational practices (ROPs) in 2011 and these serve as the standards and basis for the CTRNet biobank certification program. A review of these 13 ROPs covering 314 directives was conducted after 5 years to identify areas for revision and update, leading to changes to 7/314 directives (2.3%). A review of all internal controlled documents (including policies, standard operating procedures and guides, and forms for actions and processes) used by the BC Cancer Agency's Tumor Tissue Repository (BCCA-TTR) to conform to these ROPs was then conducted. Changes were made to 20/106 (19%) of BCCA-TTR documents. We conclude that a substantial fraction of internal controlled documents require updates at regular intervals to accommodate changes in best practices. Reviewing documentation is an essential aspect of keeping up to date with best practices and ensuring the quality of biospecimens and data managed by biobanks.

A practical tool for modeling biospecimen user fees.

PubMed

Matzke, Lise; Dee, Simon; Bartlett, John; Damaraju, Sambasivarao; Graham, Kathryn; Johnston, Randal; Mes-Masson, Anne-Marie; Murphy, Leigh; Shepherd, Lois; Schacter, Brent; Watson, Peter H

2014-08-01

The question of how best to attribute the unit costs of the annotated biospecimen product that is provided to a research user is a common issue for many biobanks. Some of the factors influencing user fees are capital and operating costs, internal and external demand and market competition, and moral standards that dictate that fees must have an ethical basis. It is therefore important to establish a transparent and accurate costing tool that can be utilized by biobanks and aid them in establishing biospecimen user fees. To address this issue, we built a biospecimen user fee calculator tool, accessible online at www.biobanking.org . The tool was built to allow input of: i) annual operating and capital costs; ii) costs categorized by the major core biobanking operations; iii) specimen products requested by a biobank user; and iv) services provided by the biobank beyond core operations (e.g., histology, tissue micro-array); as well as v) several user defined variables to allow the calculator to be adapted to different biobank operational designs. To establish default values for variables within the calculator, we first surveyed the members of the Canadian Tumour Repository Network (CTRNet) management committee. We then enrolled four different participants from CTRNet biobanks to test the hypothesis that the calculator tool could change approaches to user fees. Participants were first asked to estimate user fee pricing for three hypothetical user scenarios based on their biobanking experience (estimated pricing) and then to calculate fees for the same scenarios using the calculator tool (calculated pricing). Results demonstrated significant variation in estimated pricing that was reduced by calculated pricing, and that higher user fees are consistently derived when using the calculator. We conclude that adoption of this online calculator for user fee determination is an important first step towards harmonization and realistic user fees.

Creating a global rare disease patient registry linked to a rare diseases biorepository database: Rare Disease-HUB (RD-HUB).

PubMed

Rubinstein, Yaffa R; Groft, Stephen C; Bartek, Ronald; Brown, Kyle; Christensen, Ronald A; Collier, Elaine; Farber, Amy; Farmer, Jennifer; Ferguson, John H; Forrest, Christopher B; Lockhart, Nicole C; McCurdy, Kate R; Moore, Helen; Pollen, Geraldine B; Richesson, Rachel; Miller, Vanessa Rangel; Hull, Sara; Vaught, Jim

2010-09-01

A movement to create a global patient registry for as many as 7,000 rare diseases was launched at a workshop, "Advancing Rare Disease Research: The Intersection of Patient Registries, Biospecimen Repositories, and Clinical Data." http://rarediseases.info.nih.gov/PATIENT_REGISTRIES_WORKSHOP/. The workshop was sponsored by the Office of Rare Diseases Research (ORDR). The focus was the building of an infrastructure for an internet-based global registry linking to biorepositories. Such a registry would serve the patients, investigators, and drug companies. To aid researchers the participants suggested the creation of a centralized database of biorepositories for rare biospecimens (RD-HUB)http://biospecimens.ordr.info.nih.gov/ that could be linked to the registry. Over two days of presentations and breakout sessions, several hundred attendees discussed government rules and regulations concerning privacy and patients' rights and the nature and scope of data to be entered into a central registry as well as concerns about how to validate patient and clinician-entered data to ensure data accuracy. Mechanisms for aggregating data from existing registries were also discussed. The attendees identified registry best practices, model coding systems, international systems for recruiting patients into clinical trials and novel ways of using the internet directly to invite participation in research. They also speculated about who would bear ultimate responsibility for the informatics in the registry and who would have access to the information. Hurdles associated with biospecimen collection and how to overcome them were detailed. The development of the recommendations was, in itself, an indication of the commitment of the rare disease community as never before. Published by Elsevier Inc.

The BioFIND study: Characteristics of a clinically typical Parkinson's disease biomarker cohort

PubMed Central

Goldman, Jennifer G.; Alcalay, Roy N.; Xie, Tao; Tuite, Paul; Henchcliffe, Claire; Hogarth, Penelope; Amara, Amy W.; Frank, Samuel; Rudolph, Alice; Casaceli, Cynthia; Andrews, Howard; Gwinn, Katrina; Sutherland, Margaret; Kopil, Catherine; Vincent, Lona; Frasier, Mark

2016-01-01

ABSTRACT Background Identifying PD‐specific biomarkers in biofluids will greatly aid in diagnosis, monitoring progression, and therapeutic interventions. PD biomarkers have been limited by poor discriminatory power, partly driven by heterogeneity of the disease, variability of collection protocols, and focus on de novo, unmedicated patients. Thus, a platform for biomarker discovery and validation in well‐characterized, clinically typical, moderate to advanced PD cohorts is critically needed. Methods BioFIND (Fox Investigation for New Discovery of Biomarkers in Parkinson's Disease) is a cross‐sectional, multicenter biomarker study that established a repository of clinical data, blood, DNA, RNA, CSF, saliva, and urine samples from 118 moderate to advanced PD and 88 healthy control subjects. Inclusion criteria were designed to maximize diagnostic specificity by selecting participants with clinically typical PD symptoms, and clinical data and biospecimen collection utilized standardized procedures to minimize variability across sites. Results We present the study methodology and data on the cohort's clinical characteristics. Motor scores and biospecimen samples including plasma are available for practically defined off and on states and thus enable testing the effects of PD medications on biomarkers. Other biospecimens are available from off state PD assessments and from controls. Conclusion Our cohort provides a valuable resource for biomarker discovery and validation in PD. Clinical data and biospecimens, available through The Michael J. Fox Foundation for Parkinson's Research and the National Institute of Neurological Disorders and Stroke, can serve as a platform for discovering biomarkers in clinically typical PD and comparisons across PD's broad and heterogeneous spectrum. © 2016 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society PMID:27113479

Advancing Translational Space Research Through Biospecimen Sharing: Amplifying the Impact of Ground-Based Studies

NASA Technical Reports Server (NTRS)

Ronca, A.; Lewis, L.; Staten, B.; Moyer, E.; Vizir, V.; Gompf, H.; Hoban-Higgins, T.; Fuller, C. A.

2017-01-01

Biospecimen Sharing Programs (BSPs) have been organized by NASA Ames Research Center since the 1960s with the goal of maximizing utilization and scientific return from rare, complex and costly spaceflight experiments. BSPs involve acquiring otherwise unused biological specimens from primary space research experiments for distribution to secondary experiments. Here we describe a collaboration leveraging Ames expertise in biospecimen sharing to magnify the scientific impact of research informing astronaut health funded by the NASA Human Research Program (HRP) Human Health Countermeasures (HHC) Element. The concept expands biospecimen sharing to one-off ground-based studies utilizing analogue space platforms (e.g., Hind limb Unloading (HLU), Artificial Gravity) for rodent experiments, thereby significantly broadening the range of research opportunities with translational relevance for protecting human health in space and on Earth. In this presentation, we will report on biospecimens currently being acquired from HHC Award Head-Down Tilt as a Model for Intracranial and Intraocular Pressures, and Retinal Changes during Spaceflight, and their availability. The BSP add-on to the project described herein has already yielded for HHC-funded investigators more than 4,700 additional tissues that would otherwise have been discarded as waste, with additional tissues available for analysis. Young (3-mo old) male and female rats and Older (9-mo old) male rats are being exposed to HLU for either 7, 14, 28, or 90 days. Additional groups are exposed to 90 days of unloading followed by either 7, 14, 28 days or 90 days of recovery (normal loading). Comparisons are made with non-suspended controls. Unused tissues are: Skin, Lungs, Thymus, Adrenals, Kidneys, Spleen, Hindlimb Muscles (Soleus, Extensor Digitorum Longus, Tibialis Anterior, Plantaris Gastrocnemius), Fat Pads, Reproductive Organs, and Intestines. Tissues are harvested, weighed, preserved then archived (with metadata) using a sample tracking system (CryoTrack). Preservation techniques include snap-freezing and RNALatersnap-freezing. Specimens were weighed at the time of dissection, and organ mass: body mass ratios analyzed to determine unloading effects across conditions and durations. The results corroborate previously reported effects of short-term exposure to microgravity or unloading exposure on various organs, and provide new insights into adaptation to long-duration unloading relevant to sustained spaceflight exposures on ISS. Supported by the Human Research Program (HRP) Human Health Countermeasures (HHC) Element and NASA Grant NNX13AD94G (CAF).

Evaluation of a novel material, Diomics X-Swab™, for collection of DNA.

PubMed

Marshall, Pamela L; Stoljarova, Monika; Larue, Bobby L; King, Jonathan L; Budowle, Bruce

2014-09-01

Success of DNA typing is related to the amount of target material recovered from an evidentiary item. Generally, the more DNA that is recovered, the better the chance is of obtaining a typing result that will be robust and reliable. One method of collecting stain materials is by swabbing. Recovery of DNA from a number of commercially available swabs is not an efficient process. The X-Swab™ (Diomics Corporation, La Jolla, CA) is a unique bio-specimen collection material with highly absorptive properties and can be dissolved during certain extraction conditions. Therefore, more DNA may be collected from a substrate and be released from the swab matrix than other swabs. The ability to recover DNA from X-Swab material and success in STR typing were compared with the Copan 4N6FLOQSwab™ (Brescia, Italy), a device which utilizes a proprietary flocked-swab technology to maximize DNA collection and elution efficiency. Both types of swabs were impregnated with known amounts of DNA and body fluids and allowed to air dry. In addition, blood was placed onto glass slides, allowed to dry and collected using both types of swabs. DNA recovery was assessed by DNA quantitation and by STR typing. Results suggested that X-Swab material yielded greater DNA recovery, particularly of low quantity samples (defined as diluted neat samples), compared with the 4N6FLOQSwab. Results also indicated that X-Swab material itself enhances yield of PCR products. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

A decade of experience in the development and implementation of tissue banking informatics tools for intra and inter-institutional translational research

PubMed Central

Amin, Waqas; Singh, Harpreet; Pople, Andre K.; Winters, Sharon; Dhir, Rajiv; Parwani, Anil V.; Becich, Michael J.

2010-01-01

Context: Tissue banking informatics deals with standardized annotation, collection and storage of biospecimens that can further be shared by researchers. Over the last decade, the Department of Biomedical Informatics (DBMI) at the University of Pittsburgh has developed various tissue banking informatics tools to expedite translational medicine research. In this review, we describe the technical approach and capabilities of these models. Design: Clinical annotation of biospecimens requires data retrieval from various clinical information systems and the de-identification of the data by an honest broker. Based upon these requirements, DBMI, with its collaborators, has developed both Oracle-based organ-specific data marts and a more generic, model-driven architecture for biorepositories. The organ-specific models are developed utilizing Oracle 9.2.0.1 server tools and software applications and the model-driven architecture is implemented in a J2EE framework. Result: The organ-specific biorepositories implemented by DBMI include the Cooperative Prostate Cancer Tissue Resource (http://www.cpctr.info/), Pennsylvania Cancer Alliance Bioinformatics Consortium (http://pcabc.upmc.edu/main.cfm), EDRN Colorectal and Pancreatic Neoplasm Database (http://edrn.nci.nih.gov/) and Specialized Programs of Research Excellence (SPORE) Head and Neck Neoplasm Database (http://spores.nci.nih.gov/current/hn/index.htm). The model-based architecture is represented by the National Mesothelioma Virtual Bank (http://mesotissue.org/). These biorepositories provide thousands of well annotated biospecimens for the researchers that are searchable through query interfaces available via the Internet. Conclusion: These systems, developed and supported by our institute, serve to form a common platform for cancer research to accelerate progress in clinical and translational research. In addition, they provide a tangible infrastructure and resource for exposing research resources and biospecimen services in collaboration with the clinical anatomic pathology laboratory information system (APLIS) and the cancer registry information systems. PMID:20922029

A decade of experience in the development and implementation of tissue banking informatics tools for intra and inter-institutional translational research.

PubMed

Amin, Waqas; Singh, Harpreet; Pople, Andre K; Winters, Sharon; Dhir, Rajiv; Parwani, Anil V; Becich, Michael J

2010-08-10

Tissue banking informatics deals with standardized annotation, collection and storage of biospecimens that can further be shared by researchers. Over the last decade, the Department of Biomedical Informatics (DBMI) at the University of Pittsburgh has developed various tissue banking informatics tools to expedite translational medicine research. In this review, we describe the technical approach and capabilities of these models. Clinical annotation of biospecimens requires data retrieval from various clinical information systems and the de-identification of the data by an honest broker. Based upon these requirements, DBMI, with its collaborators, has developed both Oracle-based organ-specific data marts and a more generic, model-driven architecture for biorepositories. The organ-specific models are developed utilizing Oracle 9.2.0.1 server tools and software applications and the model-driven architecture is implemented in a J2EE framework. The organ-specific biorepositories implemented by DBMI include the Cooperative Prostate Cancer Tissue Resource (http://www.cpctr.info/), Pennsylvania Cancer Alliance Bioinformatics Consortium (http://pcabc.upmc.edu/main.cfm), EDRN Colorectal and Pancreatic Neoplasm Database (http://edrn.nci.nih.gov/) and Specialized Programs of Research Excellence (SPORE) Head and Neck Neoplasm Database (http://spores.nci.nih.gov/current/hn/index.htm). The model-based architecture is represented by the National Mesothelioma Virtual Bank (http://mesotissue.org/). These biorepositories provide thousands of well annotated biospecimens for the researchers that are searchable through query interfaces available via the Internet. These systems, developed and supported by our institute, serve to form a common platform for cancer research to accelerate progress in clinical and translational research. In addition, they provide a tangible infrastructure and resource for exposing research resources and biospecimen services in collaboration with the clinical anatomic pathology laboratory information system (APLIS) and the cancer registry information systems.

Inhibition in a microgravity environment of the recovery of Escherichia coli cells damaged by heavy ion beams during the NASDA ISS phase I program of NASA Shuttle/Mir mission no. 6.

PubMed

Harada, K; Sugahara, T; Ohnishi, T; Ozaki, Y; Obiya, Y; Miki, S; Miki, T; Imamura, M; Kobayashi, Y; Watanabe, H; Akashi, M; Furusawa, Y; Mizuma, N; Yamanaka, H; Ohashi, E; Yamaoka, C; Yajima, M; Fukui, M; Nakano, T; Takahashi, S; Amano, T; Sekikawa, K; Yanagawa, K; Nagaoka, S

1998-05-01

We participated in a space experiment, part of the National Space Development Agency of Japan (NASDA) Phase I Space Radiation Environment Measurement Program, conducted during the National Aeronautics and Space Administration (NASA) Shuttle/Mir Mission No. 6 (S/MM-6) project. The aim of our study was to investigate the effects of microgravity on the DNA repair processes of living organisms in the in orbit. Heavy ion beam radiation- or ç-irradiation-damaged biological samples of Escherichia coli and the radioresistant bacterium Deinococcus radiodurans were prepared and placed in a biospecimen box, which was loaded into the RRMD III sensor unit of the Space Shuttle. Two identical sets of samples were left in the Spacehab's Payload Processing Facility (SPPF) in Florida, USA, as a control. (flight No. STS-84) was launched from NASA John F. Kennedy Space Center (KSC) in Florida, USA, on May 15, 1997. The mission duration was 9.22 days. An astronaut activated the biological samples in the biospecimen box in the Spacehab during orbit in order to start repair of the DNA damaged by heavy ion beams or ç-irradiation and the samples were incubated for 19 h 35 min at about 22ûC, the cabin temperature. The control specimens in the SPPF were subjected to the same treatment under terrestrial gravity. After returned to earth, we investigated cell recovery by comparing the repair of the radiation-damaged DNA of E. coli and D. radiodurans in the microgravity environment in space with that on Earth. The results indicated that the DNA repair process of E. coli, but not of D. radiodurans, cells was inhibited in a microgravity environment.

An optimized library for reference-based deconvolution of whole-blood biospecimens assayed using the Illumina HumanMethylationEPIC BeadArray.

PubMed

Salas, Lucas A; Koestler, Devin C; Butler, Rondi A; Hansen, Helen M; Wiencke, John K; Kelsey, Karl T; Christensen, Brock C

2018-05-29

Genome-wide methylation arrays are powerful tools for assessing cell composition of complex mixtures. We compare three approaches to select reference libraries for deconvoluting neutrophil, monocyte, B-lymphocyte, natural killer, and CD4+ and CD8+ T-cell fractions based on blood-derived DNA methylation signatures assayed using the Illumina HumanMethylationEPIC array. The IDOL algorithm identifies a library of 450 CpGs, resulting in an average R 2  = 99.2 across cell types when applied to EPIC methylation data collected on artificial mixtures constructed from the above cell types. Of the 450 CpGs, 69% are unique to EPIC. This library has the potential to reduce unintended technical differences across array platforms.

Statistical Design for Biospecimen Cohort Size in Proteomics-based Biomarker Discovery and Verification Studies

PubMed Central

Skates, Steven J.; Gillette, Michael A.; LaBaer, Joshua; Carr, Steven A.; Anderson, N. Leigh; Liebler, Daniel C.; Ransohoff, David; Rifai, Nader; Kondratovich, Marina; Težak, Živana; Mansfield, Elizabeth; Oberg, Ann L.; Wright, Ian; Barnes, Grady; Gail, Mitchell; Mesri, Mehdi; Kinsinger, Christopher R.; Rodriguez, Henry; Boja, Emily S.

2014-01-01

Protein biomarkers are needed to deepen our understanding of cancer biology and to improve our ability to diagnose, monitor and treat cancers. Important analytical and clinical hurdles must be overcome to allow the most promising protein biomarker candidates to advance into clinical validation studies. Although contemporary proteomics technologies support the measurement of large numbers of proteins in individual clinical specimens, sample throughput remains comparatively low. This problem is amplified in typical clinical proteomics research studies, which routinely suffer from a lack of proper experimental design, resulting in analysis of too few biospecimens to achieve adequate statistical power at each stage of a biomarker pipeline. To address this critical shortcoming, a joint workshop was held by the National Cancer Institute (NCI), National Heart, Lung and Blood Institute (NHLBI), and American Association for Clinical Chemistry (AACC), with participation from the U.S. Food and Drug Administration (FDA). An important output from the workshop was a statistical framework for the design of biomarker discovery and verification studies. Herein, we describe the use of quantitative clinical judgments to set statistical criteria for clinical relevance, and the development of an approach to calculate biospecimen sample size for proteomic studies in discovery and verification stages prior to clinical validation stage. This represents a first step towards building a consensus on quantitative criteria for statistical design of proteomics biomarker discovery and verification research. PMID:24063748

Statistical design for biospecimen cohort size in proteomics-based biomarker discovery and verification studies.

PubMed

Skates, Steven J; Gillette, Michael A; LaBaer, Joshua; Carr, Steven A; Anderson, Leigh; Liebler, Daniel C; Ransohoff, David; Rifai, Nader; Kondratovich, Marina; Težak, Živana; Mansfield, Elizabeth; Oberg, Ann L; Wright, Ian; Barnes, Grady; Gail, Mitchell; Mesri, Mehdi; Kinsinger, Christopher R; Rodriguez, Henry; Boja, Emily S

2013-12-06

Protein biomarkers are needed to deepen our understanding of cancer biology and to improve our ability to diagnose, monitor, and treat cancers. Important analytical and clinical hurdles must be overcome to allow the most promising protein biomarker candidates to advance into clinical validation studies. Although contemporary proteomics technologies support the measurement of large numbers of proteins in individual clinical specimens, sample throughput remains comparatively low. This problem is amplified in typical clinical proteomics research studies, which routinely suffer from a lack of proper experimental design, resulting in analysis of too few biospecimens to achieve adequate statistical power at each stage of a biomarker pipeline. To address this critical shortcoming, a joint workshop was held by the National Cancer Institute (NCI), National Heart, Lung, and Blood Institute (NHLBI), and American Association for Clinical Chemistry (AACC) with participation from the U.S. Food and Drug Administration (FDA). An important output from the workshop was a statistical framework for the design of biomarker discovery and verification studies. Herein, we describe the use of quantitative clinical judgments to set statistical criteria for clinical relevance and the development of an approach to calculate biospecimen sample size for proteomic studies in discovery and verification stages prior to clinical validation stage. This represents a first step toward building a consensus on quantitative criteria for statistical design of proteomics biomarker discovery and verification research.

Biospecimens | Division of Cancer Prevention

Cancer.gov

The PLCO Biorepository stores approximately 2.9 million biologic specimens collected from PLCO participants. Some of characteristics that make PLCO samples particularly valuable for etiologic and early marker research are: |

International Childhood Cancer Cohort Consortium

Cancer.gov

An alliance of several large-scale prospective cohort studies of children to pool data and biospecimens from individual cohorts to study various modifiable and genetic factors in relation to cancer risk

Views on clinical trial recruitment, biospecimen collection, and cancer research: population science from landscapes of the Haudenosaunee (People of the Longhouse).

PubMed

Haring, Rodney C; Henry, Whitney Ann; Hudson, Maui; Rodriguez, Elisa M; Taualii, Maile

2018-02-01

Biomedical research in culturally distinct communities is often a challenge. Potential barriers to participation occur because science is presented in a format that lacks cultural acknowledgement. Investigations may also fail to showcase beneficial relevance to the communities or include them in true partnership. The history of biomedical research within Native American societies has been complicated by these issues. Historical trauma among many Native groups sometimes transcends into contemporary challenges in both recruitment to and participation particularly in biobanking research. The participants for this study included members of the Haudenosaunee, the People of the Longhouse. Native Americans, including the Haudenosaunee, endure some of the worst health disparities in the country. These include high rates of cancer, obesity, and diabetes which may be linked at least partially to genetic predisposition. Results from a Haudenosaunee urban population shared response on ways to improve recruitment strategies for biospecimen, cancer, and other health-related clinical trials. Mixed methods approaches were used, and community responses indicated the importance of creating trust through respectful partnership; promoting culturally appropriate recruitment materials; the need for a greater understanding of consenting and signature processes; the necessity for concise summary sheets; and a desire to have information that community member understand. Discussion items also include international Indigenous perspectives to biobanking and genetic-related health disparity research.

A National Virtual Specimen Database for Early Cancer Detection

NASA Technical Reports Server (NTRS)

Crichton, Daniel; Kincaid, Heather; Kelly, Sean; Thornquist, Mark; Johnsey, Donald; Winget, Marcy

2003-01-01

Access to biospecimens is essential for enabling cancer biomarker discovery. The National Cancer Institute's (NCI) Early Detection Research Network (EDRN) comprises and integrates a large number of laboratories into a network in order to establish a collaborative scientific environment to discover and validate disease markers. The diversity of both the institutions and the collaborative focus has created the need for establishing cross-disciplinary teams focused on integrating expertise in biomedical research, computational and biostatistics, and computer science. Given the collaborative design of the network, the EDRN needed an informatics infrastructure. The Fred Hutchinson Cancer Research Center, the National Cancer Institute,and NASA's Jet Propulsion Laboratory (JPL) teamed up to build an informatics infrastructure creating a collaborative, science-driven research environment despite the geographic and morphology differences of the information systems that existed within the diverse network. EDRN investigators identified the need to share biospecimen data captured across the country managed in disparate databases. As a result, the informatics team initiated an effort to create a virtual tissue database whereby scientists could search and locate details about specimens located at collaborating laboratories. Each database, however, was locally implemented and integrated into collection processes and methods unique to each institution. This meant that efforts to integrate databases needed to be done in a manner that did not require redesign or re-implementation of existing system

Spanning the genomics era: the vital role of a single institution biorepository for childhood cancer research over a decade

PubMed Central

Zhou, Li

2015-01-01

The ‘genomics era’ is considered to have begun with the commencement of the Human Genome Project. As translational genomic studies can only be established when human tissue samples are available for analysis, biospecimens are now proven to be an essential element for their success. During the genomics era the necessity for more extensive biobanking infrastructure has been highlighted. With the increased number of genomic studies into cancer, it is considered that the availability of biospecimens will become the rate limiting step. Despite the efforts in international biobanking, translational genomics is hampered when there low numbers of biospecimens for a particular rare diseases and is most apparent for paediatric cancer. As there is a call for biobanking practice to be responsive to the current experimental needs of the time and for more expansive systems of tissue procurement to be established we have asked the question what role does a single institution biorepository play in the current highly networked world of translational genomics. Here we describe such a case. The Tumour Bank at The Children’s Hospital at Westmead (TB-CHW) in the western suburbs of Sydney was formally established in 1998 as a key resource for translational paediatric cancer research. During the genomics era, we show that the TB-CHW has developed into a key biospecimen repository for the cancer research community, during which time it has increasingly found itself having a vital role in the establishment of translational genomics for paediatric cancer. Here we detail metrics that demonstrate how as a single institution biorepository, the TB-CHW has been a strong participant in the advancement of translational genomics throughout the genomics era. This paper describes the significant contribution of a single institutional hospital embedded tumour biobank to the genomic research community. Despite the increased stringencies placed on biobanking practice, the TB-CHW has shown that a single institution biorespository can have a consistent and effective contribution to translational research into rare paediatric malignancy demonstrating its long term benefit throughout the genomics era. PMID:26835365

CPTAC Prospective Biospecimen Collection Solicitation | Office of Cancer Clinical Proteomics Research

Cancer.gov

A new funding opportunity in support of the National Cancer Institute’s Clinical Proteomic Tumor Analysis Consortium (CPTAC) seeks to prospectively procure tumor samples, collected for proteomics investigation.

Grantee Spotlight: Elisa Rodriguez, Ph.D., M.S.

Cancer.gov

Dr. Elisa M. Rodriguez tests the feasibility of community-based participatory research approaches to engaging Hispanics, African Americans, and the medically underserved in the Buffalo, NY area in biospecimen donation for cancer research.

Utility of inverse probability weighting in molecular pathological epidemiology.

PubMed

Liu, Li; Nevo, Daniel; Nishihara, Reiko; Cao, Yin; Song, Mingyang; Twombly, Tyler S; Chan, Andrew T; Giovannucci, Edward L; VanderWeele, Tyler J; Wang, Molin; Ogino, Shuji

2018-04-01

As one of causal inference methodologies, the inverse probability weighting (IPW) method has been utilized to address confounding and account for missing data when subjects with missing data cannot be included in a primary analysis. The transdisciplinary field of molecular pathological epidemiology (MPE) integrates molecular pathological and epidemiological methods, and takes advantages of improved understanding of pathogenesis to generate stronger biological evidence of causality and optimize strategies for precision medicine and prevention. Disease subtyping based on biomarker analysis of biospecimens is essential in MPE research. However, there are nearly always cases that lack subtype information due to the unavailability or insufficiency of biospecimens. To address this missing subtype data issue, we incorporated inverse probability weights into Cox proportional cause-specific hazards regression. The weight was inverse of the probability of biomarker data availability estimated based on a model for biomarker data availability status. The strategy was illustrated in two example studies; each assessed alcohol intake or family history of colorectal cancer in relation to the risk of developing colorectal carcinoma subtypes classified by tumor microsatellite instability (MSI) status, using a prospective cohort study, the Nurses' Health Study. Logistic regression was used to estimate the probability of MSI data availability for each cancer case with covariates of clinical features and family history of colorectal cancer. This application of IPW can reduce selection bias caused by nonrandom variation in biospecimen data availability. The integration of causal inference methods into the MPE approach will likely have substantial potentials to advance the field of epidemiology.

Distributed Cognition and Process Management Enabling Individualized Translational Research: The NIH Undiagnosed Diseases Program Experience

PubMed Central

Links, Amanda E.; Draper, David; Lee, Elizabeth; Guzman, Jessica; Valivullah, Zaheer; Maduro, Valerie; Lebedev, Vlad; Didenko, Maxim; Tomlin, Garrick; Brudno, Michael; Girdea, Marta; Dumitriu, Sergiu; Haendel, Melissa A.; Mungall, Christopher J.; Smedley, Damian; Hochheiser, Harry; Arnold, Andrew M.; Coessens, Bert; Verhoeven, Steven; Bone, William; Adams, David; Boerkoel, Cornelius F.; Gahl, William A.; Sincan, Murat

2016-01-01

The National Institutes of Health Undiagnosed Diseases Program (NIH UDP) applies translational research systematically to diagnose patients with undiagnosed diseases. The challenge is to implement an information system enabling scalable translational research. The authors hypothesized that similar complex problems are resolvable through process management and the distributed cognition of communities. The team, therefore, built the NIH UDP integrated collaboration system (UDPICS) to form virtual collaborative multidisciplinary research networks or communities. UDPICS supports these communities through integrated process management, ontology-based phenotyping, biospecimen management, cloud-based genomic analysis, and an electronic laboratory notebook. UDPICS provided a mechanism for efficient, transparent, and scalable translational research and thereby addressed many of the complex and diverse research and logistical problems of the NIH UDP. Full definition of the strengths and deficiencies of UDPICS will require formal qualitative and quantitative usability and process improvement measurement. PMID:27785453

Intact stable isotope labeled plasma proteins from the SILAC-labeled HepG2 secretome.

PubMed

Mangrum, John B; Martin, Erika J; Brophy, Donald F; Hawkridge, Adam M

2015-09-01

The plasma proteome remains an attractive biospecimen for MS-based biomarker discovery studies. The success of these efforts relies on the continued development of quantitative MS-based proteomics approaches. Herein we report the use of the SILAC-labeled HepG2 secretome as a source for stable isotope labeled plasma proteins for quantitative LC-MS/MS measurements. The HepG2 liver cancer cell line secretes the major plasma proteins including serum albumin, apolipoproteins, protease inhibitors, coagulation factors, and transporters that represent some of the most abundant proteins in plasma. The SILAC-labeled HepG2 secretome was collected, spiked into human plasma (1:1 total protein), and then processed for LC-MS/MS analysis. A total of 62 and 56 plasma proteins were quantified (heavy:light (H/L) peptide pairs) from undepleted and depleted (serum albumin and IgG), respectively, with log2 H/L = ± 6. Major plasma proteins quantified included albumin, apolipoproteins (e.g., APOA1, APOA2, APOA4, APOB, APOC3, APOE, APOH, and APOM), protease inhibitors (e.g., A2M and SERPINs), coagulation factors (e.g., Factor V, Factor X, fibrinogen), and transport proteins (e.g., TTR). The average log2 H/L values for shared plasma proteins in both undepleted and depleted plasma samples were 0.43 and 0.44, respectively. This work further expands the SILAC strategy into MS-based biomarker discovery of clinical biospecimens. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

NCI Cohort Consortium

Cancer.gov

The NCI Cohort Consortium is an extramural-intramural partnership formed by the National Cancer Institute to address the need for large-scale collaborations to pool the large quantity of data and biospecimens necessary to conduct a wide range of cancer studies.

Measuring molecular biomarkers in epidemiologic studies: laboratory techniques and biospecimen considerations.

PubMed

Erickson, Heidi S

2012-09-28

The future of personalized medicine depends on the ability to efficiently and rapidly elucidate a reliable set of disease-specific molecular biomarkers. High-throughput molecular biomarker analysis methods have been developed to identify disease risk, diagnostic, prognostic, and therapeutic targets in human clinical samples. Currently, high throughput screening allows us to analyze thousands of markers from one sample or one marker from thousands of samples and will eventually allow us to analyze thousands of markers from thousands of samples. Unfortunately, the inherent nature of current high throughput methodologies, clinical specimens, and cost of analysis is often prohibitive for extensive high throughput biomarker analysis. This review summarizes the current state of high throughput biomarker screening of clinical specimens applicable to genetic epidemiology and longitudinal population-based studies with a focus on considerations related to biospecimens, laboratory techniques, and sample pooling. Copyright © 2012 John Wiley & Sons, Ltd.

A New Paradigm for Biospecimen Banking in the Personalized Medicine Era

PubMed Central

McDonald, Sandra A.; Watson, Mark A.; Rossi, Joan; Becker, Colleen M.; Jaques, David P.; Pfeifer, John D.

2012-01-01

Banking of high-quality, appropriately consented human tissue is crucial for the understanding of disease pathogenesis and translation of such knowledge into improvements in patient care. Traditionally, tissue banking has been thought of as primarily an academic research activity, but tissue and biospecimen banking is increasingly assuming clinical importance, especially with the advent of genetic and proteomic testing approaches that rely on fresh or fresh frozen tissue. These approaches are part of the revolution in personalized medicine. This revolution’s impact on biorepositories—their mission and day-to-day function—will be profound. Direct patient care will require structuring tissue procurement to become a routine part of patient care. Accordingly tissue banking will expand from its traditional research role in large academic medical centers into the everyday practice of surgical pathology. Successful implementation of this model will require consideration of several financial, medicolegal, and administrative issues. PMID:22031304

Selecting a Laboratory Information Management System for Biorepositories in Low- and Middle-Income Countries: The H3Africa Experience and Lessons Learned

PubMed Central

Musinguzi, Henry; Lwanga, Newton; Kezimbira, Dafala; Kigozi, Edgar; Katabazi, Fred Ashaba; Wayengera, Misaki; Joloba, Moses Lutaakome; Abayomi, Emmanuel Akin; Swanepoel, Carmen; Croxton, Talishiea; Ozumba, Petronilla; Thankgod, Anazodo; van Zyl, Lizelle; Mayne, Elizabeth Sarah; Kader, Mukthar; Swartz, Garth

2017-01-01

Biorepositories in Africa need significant infrastructural support to meet International Society for Biological and Environmental Repositories (ISBER) Best Practices to support population-based genomics research. ISBER recommends a biorepository information management system which can manage workflows from biospecimen receipt to distribution. The H3Africa Initiative set out to develop regional African biorepositories where Uganda, Nigeria, and South Africa were successfully awarded grants to develop the state-of-the-art biorepositories. The biorepositories carried out an elaborate process to evaluate and choose a laboratory information management system (LIMS) with the aim of integrating the three geographically distinct sites. In this article, we review the processes, African experience, lessons learned, and make recommendations for choosing a biorepository LIMS in the African context.

Biobanking 3.0: evidence based and customer focused biobanking.

PubMed

Simeon-Dubach, Daniel; Watson, Peter

2014-03-01

Biobanking is a new and very dynamic field. To achieve long term financial sustainability of biobank infrastructures we propose that a new focus is needed on activities, products and services provided by the biobank that relate to the external stakeholder: biobanking 3.0. Earlier stages of biobanking are biobanking 1.0 (primary focus on the number of biospecimens and data) and biobanking 2.0 (primary focus on the quality of biospecimens and data). Both stages 1.0 and 2.0 are predominantly product oriented areas and have required a mostly internal focus on operational development within the biobank itself. In this paper we will introduce our concept of biobanking 3.0 which capitalizes on the earlier stages but dictates a shift in focus to enhancing the value and impact for the three major sets of external stakeholders (people/patients, funders, and research customers) and creating a path to balanced and planned investment in biobank infrastructure and the sustainability of biobanking. Biobanking 3.0 will improve real understanding as well as perceptions of value across different stakeholders. Patients and donors will appreciate seeing how their biospecimens and data are effectively used for research. Funders will value the ability to plan efficient targeting of funding and to monitor the impact of their support. Researchers will capitalize on the ability to translate their ideas into effective knowledge. Ultimately adoption of biobanking 3.0 will impact on the sustainability in the three main dimensions relevant to biobanking: social sustainability (acceptability), operational sustainability (efficiency), and financial sustainability (accomplishment). Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.

The Greater Cincinnati Pediatric Clinic Repository: A Novel Framework for Childhood Asthma and Allergy Research

PubMed Central

Butsch Kovacic, Melinda; Biagini Myers, Jocelyn M.; Lindsey, Mark; Patterson, Tia; Sauter, Sharon; Ericksen, Mark B.; Ryan, Patrick; Assa'ad, Amal; Lierl, Michelle; Fischer, Thomas; Kercsmar, Carolyn; McDowell, Karen; Lucky, Anne W.; Sheth, Anita P.; Hershey, Andrew D.; Ruddy, Richard M.; Rothenberg, Marc E.

2012-01-01

Background Allergic disorders, including asthma, allergic rhinitis, atopic dermatitis, eosinophilic esophagitis, and food allergy, are a major global health burden. The study and management of allergic disorders is complicated by the considerable heterogeneity in both the presentation and natural history of these disorders. Biorepositories serve as an excellent source of data and biospecimens for delineating subphenotypes of allergic disorders, but such resources are lacking. Methods In order to define subphenotypes of allergic disease accurately, we established an infrastructure to link and efficiently utilize clinical and epidemiologic data with biospecimens into a single biorepository called the Greater Cincinnati Pediatric Clinic Repository (GCPCR). Children with allergic disorders as well as healthy controls are followed longitudinally at hospital clinic, emergency department, and inpatient visits. Subjects' asthma, allergy, and skin symptoms; past medical, family, social, diet, and environmental histories; physical activity; medication adherence; perceived quality of life; and demographics are ascertained. DNA is collected from all participants, and other biospecimens such as blood, hair, and nasal epithelial cells are collected on a subset. Results To date, the GCPCR has 6,317 predominantly Caucasian and African American participants, and 93% have banked DNA. This large sample size supports adequately powered genetic, epidemiologic, environmental, and health disparities studies of childhood allergic diseases. Conclusions The GCPCR is a unique biorepository that is continuously evaluated and refined to achieve and maintain rigorous clinical phenotype and biological data. Development of similar disease-specific repositories using common data elements is necessary to enable studies across multiple populations of comprehensively phenotyped patients. PMID:22768387

A Rapid Filter Insert-based 3D Culture System for Primary Prostate Cell Differentiation

PubMed Central

Tricoli, Lucas; Berry, Deborah L.; Albanese, Chris

2018-01-01

Conditionally reprogrammed cells (CRCs) provide a sustainable method for primary cell culture and the ability to develop extensive “living biobanks” of patient derived cell lines. For many types of epithelial cells, various three dimensional (3D) culture approaches have been described that support an improved differentiated state. While CRCs retain their lineage commitment to the tissue from which they are isolated, they fail to express many of the differentiation markers associated with the tissue of origin when grown under normal two dimensional (2D) culture conditions. To enhance the application of patient-derived CRCs for prostate cancer research, a 3D culture format has been defined that enables a rapid (2 weeks total) luminal cell differentiation in both normal and tumor-derived prostate epithelial cells. Herein, a filter insert-based format is described for the culturing and differentiation of both normal and malignant prostate CRCs. A detailed description of the procedures required for cell collection and processing for immunohistochemical and immunofluorescent staining are provided. Collectively the 3D culture format described, combined with the primary CRC lines, provides an important medium- to high- throughput model system for biospecimen-based prostate research. PMID:28287583

Steps Towards Precision Medicine: Utilizing FFPE Specimens - TCGA

Cancer.gov

Roy W. Tarnuzzer, Ph.D., the Biospecimen Core Resource Program Manager at the TCGA Program Office, provides an overview of the Formalin-fixed Paraffin Pilot Project, an initiative to investigate best practices for use of FFPE specimens in genomic studies.

Business Process Flow Diagrams in Tissue Bank Informatics System Design, and Identification and Communication of Best Practices: The Pharmaceutical Industry Experience.

PubMed

McDonald, Sandra A; Velasco, Elizabeth; Ilasi, Nicholas T

2010-12-01

Pfizer, Inc.'s Tissue Bank, in conjunction with Pfizer's BioBank (biofluid repository), endeavored to create an overarching internal software package to cover all general functions of both research facilities, including sample receipt, reconciliation, processing, storage, and ordering. Business process flow diagrams were developed by the Tissue Bank and Informatics teams as a way of characterizing best practices both within the Bank and in its interactions with key internal and external stakeholders. Besides serving as a first step for the software development, such formalized process maps greatly assisted the identification and communication of best practices and the optimization of current procedures. The diagrams shared here could assist other biospecimen research repositories (both pharmaceutical and other settings) for comparative purposes or as a guide to successful informatics design. Therefore, it is recommended that biorepositories consider establishing formalized business process flow diagrams for their laboratories, to address these objectives of communication and strategy.

75 FR 34146 - Proposed Collection; Comment Request Resource for the Collection and Evaluation of Human Tissues...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-16

... summaries of proposed projects to be submitted to the Office of Management and Budget (OMB) for review and... obtain the personal histories to compare to the life styles and exposures and the biospecimens will serve...

[Tissue repositories for research at Sheba Medical Center(SMC].

PubMed

Cohen, Yehudit; Barshack, Iris; Onn, Amir

2013-06-01

Cancer is the number one cause of death in both genders. Breakthroughs in the understanding of cancer biology, the identification of prognostic factors, and the development of new treatments are increasingly dependent on access to human cancer tissues with linked clinicopathological data. Access to human tumor samples and a large investment in translational research are needed to advance this research. The SMC tissue repositories provide researchers with biological materials, which are essential tools for cancer research. SMC tissue repositories for research aim to collect, document and preserve human biospecimens from patients with cancerous diseases. This is in order to provide the highest quality and well annotated biological biospecimens, used as essential tools to achieve the growing demands of scientific research needs. Such repositories are partners in acceLerating biomedical research and medical product development through clinical resources, in order to apply best options to the patients. Following Institutional Review Board approval and signing an Informed Consent Form, the tumor and tumor-free specimens are coLLected by a designated pathologist at the operating room only when there is a sufficient amount of the tumor, in excess of the routine needs. Blood samples are collected prior to the procedure. Other types of specimens collected include ascites fluid, pleural effusion, tissues for Optimal Cutting Temperature [OCT] and primary culture etc. Demographic, clinical, pathologicaL, and follow-up data are collected in a designated database. SMC has already established several organ or disease-specific tissue repositories within different departments. The foundation of tissue repositories requires the concentrated effort of a multidisciplinary team composed of paramedical, medical and scientific professionals. Research projects using these specimens facilitate the development of 'targeted therapy', accelerate basic research aimed at clarifying molecular mechanisms involved in cancer, and support the development of novel diagnostic tools.

An empirical assessment of the short-term impacts of a reading of Deborah Zoe Laufer's drama Informed Consent on attitudes and intentions to participate in genetic research.

PubMed

Rothwell, Erin; Botkin, Jeffrey R; Cheek-O'Donnell, Sydney; Wong, Bob; Case, Gretchen A; Johnson, Erin; Matheson, Trent; Wilson, Alena; Robinson, Nicole R; Rawlings, Jared; Horejsi, Brooke; Lopez, Ana Maria; Byington, Carrie L

2018-01-01

This study assessed the short-term impact of the play "Informed Consent" by Deborah Zoe Laufer (a fictionalized look at the controversy over specimens collected from the Havasupai Tribe for diabetes research in 1989) on perceptions of trust, willingness to donate biospecimens, and attitudes toward harm and privacy among the medical and undergraduate students, faculty, and the public in the Intermountain West. Surveys were administered before and after a staged reading of the play by professional actors. Survey items included the short form Trust in Medical Researchers, and single-item questions about group identity, ethics of genetic testing in children, and willingness to donate biospecimens. In addition, respondents were given the option to answer open-ended questions through e-mail. Out of the 481 who attended the play, 421 completed both the pre and post surveys, and 166 participants completed open-ended questions online approximately 1 week after the play. Across all participants, there were significant declines for trust in medical researchers and for the survey item "is it ethical for investigators to test children for adult onset diseases" (p < .001 for both) following the play. There was a significant increase in agreement to improve group identity protections (p < .001) and there were no differences on willingness to donate biospecimens to research (p = .777). Qualitative data provided extensive contextual data supporting these perspectives. This is one of the first studies to document short-term impacts of a theatrical performance on both attitudes and behavioral intentions toward research ethics and clinical research participation. Future research should continue to explore the impact of theatrical performances among public and investigators on the ethical issues and complexities in clinical research.

The Breast Cancer Family Registry: an infrastructure for cooperative multinational, interdisciplinary and translational studies of the genetic epidemiology of breast cancer

PubMed Central

John, Esther M; Hopper, John L; Beck, Jeanne C; Knight, Julia A; Neuhausen, Susan L; Senie, Ruby T; Ziogas, Argyrios; Andrulis, Irene L; Anton-Culver, Hoda; Boyd, Norman; Buys, Saundra S; Daly, Mary B; O'Malley, Frances P; Santella, Regina M; Southey, Melissa C; Venne, Vickie L; Venter, Deon J; West, Dee W; Whittemore, Alice S; Seminara, Daniela

2004-01-01

Introduction The etiology of familial breast cancer is complex and involves genetic and environmental factors such as hormonal and lifestyle factors. Understanding familial aggregation is a key to understanding the causes of breast cancer and to facilitating the development of effective prevention and therapy. To address urgent research questions and to expedite the translation of research results to the clinical setting, the National Cancer Institute (USA) supported in 1995 the establishment of a novel research infrastructure, the Breast Cancer Family Registry, a collaboration of six academic and research institutions and their medical affiliates in the USA, Canada, and Australia. Methods The sites have developed core family history and epidemiology questionnaires, data dictionaries, and common protocols for biospecimen collection and processing and pathology review. An Informatics Center has been established to collate, manage, and distribute core data. Results As of September 2003, 9116 population-based and 2834 clinic-based families have been enrolled, including 2346 families from minority populations. Epidemiology questionnaire data are available for 6779 affected probands (with a personal history of breast cancer), 4116 unaffected probands, and 16,526 relatives with or without a personal history of breast or ovarian cancer. The biospecimen repository contains blood or mouthwash samples for 6316 affected probands, 2966 unaffected probands, and 10,763 relatives, and tumor tissue samples for 4293 individuals. Conclusion This resource is available to internal and external researchers for collaborative, interdisciplinary, and translational studies of the genetic epidemiology of breast cancer. Detailed information can be found at the URL . PMID:15217505

The Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial and Its Associated Research Resource

PubMed Central

2013-01-01

The Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial is a large-scale research effort conducted by the National Cancer Institute. PLCO offers an example of coordinated research by both the extramural and intramural communities of the National Institutes of Health. The purpose of this article is to describe the PLCO research resource and how it is managed and to assess the productivity and the costs associated with this resource. Such an in-depth analysis of a single large-scale project can shed light on questions such as how large-scale projects should be managed, what metrics should be used to assess productivity, and how costs can be compared with productivity metrics. A comprehensive publication analysis identified 335 primary research publications resulting from research using PLCO data and biospecimens from 2000 to 2012. By the end of 2012, a total of 9679 citations (excluding self-citations) have resulted from this body of research publications, with an average of 29.7 citations per article, and an h index of 45, which is comparable with other large-scale studies, such as the Nurses’ Health Study. In terms of impact on public health, PLCO trial results have been used by the US Preventive Services Task Force in making recommendations concerning prostate and ovarian cancer screening. The overall cost of PLCO was $454 million over 20 years, adjusted to 2011 dollars, with approximately $37 million for the collection, processing, and storage of biospecimens, including blood samples, buccal cells, and pathology tissues. PMID:24115361

President Signs STAR Act for Kids' Cancers.

PubMed

2018-06-07

On June 5, President Donald Trump signed the Childhood Cancer Survivorship, Treatment, Access and Research Act, which aims to support pediatric cancer research by expanding the collection of patient biospecimens and records, improving surveillance, and investigating pediatric survivorship. ©2018 American Association for Cancer Research.

A review of radio frequency identification technology for the anatomic pathology or biorepository laboratory: Much promise, some progress, and more work needed.

PubMed

Lou, Jerry J; Andrechak, Gary; Riben, Michael; Yong, William H

2011-01-01

Patient safety initiatives throughout the anatomic laboratory and in biorepository laboratories have mandated increasing emphasis on the need for accurately identifying and tracking biospecimen assets throughout their production lifecycle and for archiving/retrieval purposes. However, increasing production volume along with complex workflow characteristics, reliance on manual production processes, and required asset movement to disparate destinations throughout asset lifecycles continue to challenge laboratory efforts. Radio Frequency Identification (RFID) technology, use of radio waves to communicate data between electronic tags attached to objects and a reader, shows significant potential to facilitate and overcome these hurdles. Advantages over traditional barcode labeling include readability without direct line-of-sight alignment to the reader, ability to read multiple tags simultaneously, higher data storage capacity, faster data transmission rate, and capacity to perform multiple read-writes of data to the tag. Most importantly, use of radio waves decreases the need to manually scan each asset, and at each step, identification or tracking event is needed. Temperature monitoring by on-board sensors and three-dimensional position tracking are additional potential benefits of using RFID technology. To date, barriers to implementation of RFID systems in the anatomic laboratory include increased associated costs of tags and readers, system software, data security concerns, lack of specific data standards for stored information, and potential for technological obsolescence during decades of specimen storage. Novel RFID production techniques and increased production capacity are projected to lower costs of some tags to a few cents each. Potentially, information security concerns can be addressed by techniques such as shielding, data encryption, and tag pseudonyms. Commitment by stakeholder groups to develop RFID tag data standards for anatomic pathology and biorepository laboratories could avoid or mitigate the "islands of data" dilemma presented by barcode usage where there are innumerable standards and a consequent paucity of hardware or software "plug and play" interoperability. Work remains to be done to establish the durability and appropriate shielding of individual tag types for use in harsh laboratory environmental conditions, and for long-term archival storage. Finally, given the requirements for long-term storage of biospecimen assets, consideration should be given to ways of mitigating data isolation due to eventual technological obsolescence of a particular RFID technology or software.

A review of radio frequency identification technology for the anatomic pathology or biorepository laboratory: Much promise, some progress, and more work needed

PubMed Central

Lou, Jerry J.; Andrechak, Gary; Riben, Michael; Yong, William H.

2011-01-01

Patient safety initiatives throughout the anatomic laboratory and in biorepository laboratories have mandated increasing emphasis on the need for accurately identifying and tracking biospecimen assets throughout their production lifecycle and for archiving/retrieval purposes. However, increasing production volume along with complex workflow characteristics, reliance on manual production processes, and required asset movement to disparate destinations throughout asset lifecycles continue to challenge laboratory efforts. Radio Frequency Identification (RFID) technology, use of radio waves to communicate data between electronic tags attached to objects and a reader, shows significant potential to facilitate and overcome these hurdles. Advantages over traditional barcode labeling include readability without direct line-of-sight alignment to the reader, ability to read multiple tags simultaneously, higher data storage capacity, faster data transmission rate, and capacity to perform multiple read-writes of data to the tag. Most importantly, use of radio waves decreases the need to manually scan each asset, and at each step, identification or tracking event is needed. Temperature monitoring by on-board sensors and three-dimensional position tracking are additional potential benefits of using RFID technology. To date, barriers to implementation of RFID systems in the anatomic laboratory include increased associated costs of tags and readers, system software, data security concerns, lack of specific data standards for stored information, and potential for technological obsolescence during decades of specimen storage. Novel RFID production techniques and increased production capacity are projected to lower costs of some tags to a few cents each. Potentially, information security concerns can be addressed by techniques such as shielding, data encryption, and tag pseudonyms. Commitment by stakeholder groups to develop RFID tag data standards for anatomic pathology and biorepository laboratories could avoid or mitigate the “islands of data” dilemma presented by barcode usage where there are innumerable standards and a consequent paucity of hardware or software “plug and play” interoperability. Work remains to be done to establish the durability and appropriate shielding of individual tag types for use in harsh laboratory environmental conditions, and for long-term archival storage. Finally, given the requirements for long-term storage of biospecimen assets, consideration should be given to ways of mitigating data isolation due to eventual technological obsolescence of a particular RFID technology or software. PMID:21886890

Biospecimen Retrieval from NASA's Rodent Research-1: Maximizing Science Return from Flight Missions

NASA Technical Reports Server (NTRS)

Choi, S. Y.; Chen, Y.- C.; Reyes, A.; Verma, V.; Dinh, M.; Globus, R. K.

2016-01-01

Rodent Research (RR)-1 was conducted to validate flight hardware, operations, and science capabilities that were developed to support long duration missions on the International Space Station. After 37 days in microgravity twenty mice were euthanized and frozen on orbit. Upon return to Earth the carcasses were dissected and yielded 32 different types of tissues from each mouse and over 3200 tissue aliquots. Many tissues were distributed to the Space Life and Physical Sciences (SLPS) Biospecimen Sharing Program (BSP) Principal Investigators (PIs) through the Ames Life Science Data Archive (ALSDA). A second round of dissections was performed to collect additional tissues from the remaining carcasses thawed for a second time for additional BSP PIs. Tissues retrieved included vaginal walls, aorta, pelvis, brown adipose tissue, tail, spine and forearms. Although the analyses are still in progress, some of the PIs have reported that the quality of the tissues was acceptable for their study. In a separate experiment we tested the RNA quality of the tissues that were dissected from frozen carcasses that were subjected to euthanasia, freezing, first and second thaw dissections. Timelines simulated the on-orbit RR-1 procedures to assess the quality of the tissues retrieved from the second thaw dissections. We analyzed the RIN values of select tissues including kidney, brain, white adipose tissue (WAT) and brown adipose tissue (BAT). Overall the RIN values from the second thaw were lower compared to those from the first by about a half unit; however, the tissues yielded RNA that are acceptable quality for some quantitative gene expression assays. Interestingly, RIN values of brain tissues were 8.4+/-0.6 and 7.9+/-0.7 from first and second round dissections, respectively (n=5). Kidney and WAT yielded RIN values less than 8 but they can still be used for qPCR. BAT yielded higher quality RNA (8.2+/-0.5) than WAT (5.22+/-0.9), possibly due to the high fat content. Together, these data show that select tissues can be utilized for gene expression studies even if they are retrieved from carcasses that were subjected to at least two freezing and thawing processes; this further expands science return from valuable and infrequent rodent experiments in space.

Biospecimen Retrieval from NASA's Rodent Research-1: Maximizing Science Return from Flight Missions

NASA Technical Reports Server (NTRS)

Choi, Sungshin Y.; Chen, Yi-Chun; Reyes, America; Verma, Vandana; Dinh, Marie; Globus, Ruth K.

2016-01-01

Rodent Research (RR)-1 was conducted to validate flight hardware, operations, and science capabilities that were developed to support long duration missions on the International Space Station. After 37 days in microgravity twenty mice were euthanized and frozen on orbit. Upon return to Earth the carcasses were dissected and yielded 32 different types of tissues from each mouse and over 3200 tissue aliquots. Many tissues were distributed to the Space Life and Physical Sciences (SLPS) Biospecimen Sharing Program (BSP) Principal Investigators (PIs) through the Ames Life Science Data Archive (ALSDA). A second round of dissections was performed to collect additional tissues from the remaining carcasses thawed for a second time for additional BSP PIs. Tissues retrieved included vaginal walls, aorta, pelvis, brown adipose tissue, tail, spine and forearms. Although the analyses are still in progress, some of the PIs have reported that the quality of the tissues was acceptable for their study. In a separate experiment we tested the RNA quality of the tissues that were dissected from frozen carcasses that were subjected to euthanasia, freezing, first and second thaw dissections. Timelines simulated the on-orbit RR-1 procedures to assess the quality of the tissues retrieved from the second thaw dissections. We analyzed the RIN values of select tissues including kidney, brain, white adipose tissue (WAT) and brown adipose tissue (BAT). Overall the RIN values from the second thaw were lower compared to those from the first by about a half unit; however, the tissues yielded RNA that are acceptable quality for some quantitative gene expression assays. Interestingly, RIN values of brain tissues were 8.4+/-0.6 and 7.9+/-0.7 from first and second round dissections, respectively (n5). Kidney and WAT yielded RIN values less than 8 but they can still be used for qPCR. BAT yielded higher quality RNA (8.2+/-0.5) than WAT (5.2+/-20.9), possibly due to the high fat content. Together, these data show that select tissues can be utilized for gene expression studies even if they are retrieved from carcasses that were subjected to at least two freezing and thawing processes; this further expands science return from valuable and infrequent rodent experiments in space.

The Establishment of an Inflammatory Breast Cancer Registry and Biospecimen Repository

DTIC Science & Technology

2005-08-01

8217Tamoxifen and Exemestane Triar) study, women will receive an LHRH agonist ( Triptorelin ) immediately after surgery. They will be randomised to...combine Triptorelin with Tamoxifen versus Exemestane. In both the SOFT and the TEXT studies, the new combination of ovarian ablation plus an aromatase

Biorepositories | Division of Cancer Prevention

Cancer.gov

Carefully collected and controlled high-quality human biospecimens, annotated with clinical data and properly consented for investigational use, are available through the Division of Cancer Prevention Biorepositories listed in the charts below. Biorepositories Managed by the Division of Cancer Prevention Biorepositories Supported by the Division of Cancer Prevention Related

76 FR 38191 - New Proposed Collection; Comment Request; Biospecimen and Physical Measures Formative Research...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-29

... Institute of Child Health and Human Development (NICHD), the National Institutes of Health (NIH) will..., chemical, biological, and psychosocial) on children's health and development. (b) In General.--The Director of the National Institute of Child Health and Human Development* shall establish a consortium of...

NCI International EBV-Gastric Cancer Consortium

Cancer.gov

A collaboration among NCI and extramural investigators, established by DCEG in 2006, that utilizes data and biospecimens from completed and ongoing case series and observational studies of gastric cancer to replicate and extend findings from previous studies hindered by small numbers of EBV-positive cases, and to stimulate multidisciplinary research in this area.

Smartphone-based colorimetric ELISA implementation for determination of women's reproductive steroid hormone profiles.

PubMed

Ogirala, Tejaswi; Eapen, Ashley; Salvante, Katrina G; Rapaport, Tomas; Nepomnaschy, Pablo A; Parameswaran, Ash M

2017-10-01

Biologists frequently collect and analyze biospecimens in naturalistic (i.e., field) conditions to ascertain information regarding the physiological status of their study participants. Generally, field-collected biospecimens need to be stored frozen in the field and then transported frozen to laboratory facilities where traditional biomarker assays, such as enzyme-linked immunosorbent assays (ELISAs), are conducted. As proper storage and transport of frozen specimens is often logistically difficult and expensive, particularly in nonurban field settings, methods that reduce the need for specimen storage and transport would benefit field-research dependent disciplines such as biology, ecology and epidemiology. One limiting factor to running assays in the field is the use of large and expensive equipment to visualize and quantify the assays, such as microplate readers. Here, we describe an implementation of colorimetric ELISA visualization and quantification using two novel and portable imaging instrumentation systems and data processing techniques for the determination of women's reproductive steroid hormone profiles. Using the light absorbance and transmittance properties of the chemical compounds that make up the hormone assay, we were able to estimate unknown hormone concentrations using a smartphone system and a webcam system. These estimates were comparable to those from a standard laboratory multiple reader (smartphone: accuracy = 82.20%, R 2  > 0.910; webcam: accuracy = 87.59%, R 2  > 0.942). This line of applied research, in the long run, is expected to provide necessary information for examining the extent to which reproductive function varies within and between populations and how it is influenced by psychosocial, energetic and environmental challenges. Our validation of these novel, portable visualization and quantification systems allows for the eventual development of a compact and economical closed system which can be used to quantify biomarker concentrations in remote areas.

The "North German Tumor Bank of Colorectal Cancer": status report after the first 2 years of support by the German Cancer Aid Foundation.

PubMed

Oberländer, Martina; Linnebacher, Michael; König, Alexandra; Bogoevska, Valentina; Brodersen, Christiane; Kaatz, Regina; Krohn, Mathias; Hackmann, Michael; Ingenerf, Josef; Christoph, Jan; Mate, Sebastian; Prokosch, Hans-Ulrich; Yekebas, Emre F; Thorns, Christoph; Büning, Jürgen; Prall, Friedrich; Uhlig, Ria; Roblick, Uwe J; Izbicki, Jakob R; Klar, Ernst; Bruch, Hans-Peter; Vollmar, Brigitte; Habermann, Jens K

2013-02-01

Research projects and clinical trials strongly rely on high-quality biospecimens which are provided by biobanks. Since differences in sample processing and storage can strongly affect the outcome of such studies, standardization between biobanks is necessary to guarantee reliable results of large, multicenter studies. The German Cancer Aid Foundation (Deutsche Krebshilfe e.V.) has therefore initiated the priority program "tumor tissue banks" in 2010 by funding four biobank networks focusing on central nervous system tumors, melanomas, breast carcinomas, and colorectal carcinomas. The latter one, the North German Tumor Bank of Colorectal Cancer (ColoNet) is managed by surgeons, pathologists, gastroenterologists, oncologists, scientists, and medical computer scientists. The ColoNet consortium has developed and harmonized standard operating procedures concerning all biobanking aspects. Crucial steps for quality assurance have been implemented and resulted in certification according to DIN EN ISO 9001. A further achievement is the construction of a web-based database for exploring available samples. In addition, common scientific projects have been initiated. Thus, ColoNet's repository will be used for research projects in order to improve early diagnosis, therapy, follow-up, and prognosis of colorectal cancer patients. Apart from the routine sample storage at -170 °C, the tumor banks' unique characteristic is the participation of outpatient clinics and private practices to further expand the sample and clinical data collection. The first 2 years of funding by the German Cancer Aid Foundation have already led to a closer scientific connection between the participating institutions and to a substantial collection of biospecimens obtained under highly standardized conditions.

76 FR 23609 - New Proposed Collection; Comment Request; Biospecimen and Physical Measures Formative Research...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-27

... has obtained an OMB generic clearance to conduct survey and instrument design and administration... conduct the detailed preparation needed for a study of this size and complexity, the NCS was designed to... methodological studies conducted during the Vanguard phase will inform the implementation and analysis plan for...

76 FR 54474 - Submission for OMB Review; Comment Request New proposed collection, Biospecimen and Physical...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-01

... authorize the National Institute of Child Health and Human Development* to conduct a national longitudinal... children's health and development. (b) IN GENERAL.--The Director of the National Institute of Child Health... effects of both chronic and intermittent exposures on child health and human development; and (2...

Small non-coding RNA profiling in human biofluids and surrogate tissues from healthy individuals: description of the diverse and most represented species.

PubMed

Ferrero, Giulio; Cordero, Francesca; Tarallo, Sonia; Arigoni, Maddalena; Riccardo, Federica; Gallo, Gaetano; Ronco, Guglielmo; Allasia, Marco; Kulkarni, Neha; Matullo, Giuseppe; Vineis, Paolo; Calogero, Raffaele A; Pardini, Barbara; Naccarati, Alessio

2018-01-09

The role of non-coding RNAs in different biological processes and diseases is continuously expanding. Next-generation sequencing together with the parallel improvement of bioinformatics analyses allows the accurate detection and quantification of an increasing number of RNA species. With the aim of exploring new potential biomarkers for disease classification, a clear overview of the expression levels of common/unique small RNA species among different biospecimens is necessary. However, except for miRNAs in plasma, there are no substantial indications about the pattern of expression of various small RNAs in multiple specimens among healthy humans. By analysing small RNA-sequencing data from 243 samples, we have identified and compared the most abundantly and uniformly expressed miRNAs and non-miRNA species of comparable size with the library preparation in four different specimens (plasma exosomes, stool, urine, and cervical scrapes). Eleven miRNAs were commonly detected among all different specimens while 231 miRNAs were globally unique across them. Classification analysis using these miRNAs provided an accuracy of 99.6% to recognize the sample types. piRNAs and tRNAs were the most represented non-miRNA small RNAs detected in all specimen types that were analysed, particularly in urine samples. With the present data, the most uniformly expressed small RNAs in each sample type were also identified. A signature of small RNAs for each specimen could represent a reference gene set in validation studies by RT-qPCR. Overall, the data reported hereby provide an insight of the constitution of the human miRNome and of other small non-coding RNAs in various specimens of healthy individuals.

About the Early Detection Research Group | Division of Cancer Prevention

Cancer.gov

The Early Detection Research Group supports research that seeks to determine the effectiveness, operating characteristics and clinical impact (harms as well as benefits) of cancer early detection technologies and practices, such as imaging and molecular biomarker approaches.   The group ran two large-scale early detection trials for which data and biospecimens are available

New Funding Opportunity: Tissue Purchase Order Acquisitions | Office of Cancer Clinical Proteomics Research

Cancer.gov

The National Cancer Institute (NCI) is expanding its basic and translational research programs that rely heavily on sufficient availability of high quality, well annotated biospecimens suitable for use in genomic and proteomic studies.  The NCI’s overarching goal with such programs is to improve the ability to diagnose, treat, and prevent cancer.

Mining the Human Phenome using Semantic Web Technologies: A Case Study for Type 2 Diabetes

PubMed Central

Pathak, Jyotishman; Kiefer, Richard C.; Bielinski, Suzette J.; Chute, Christopher G.

2012-01-01

The ability to conduct genome-wide association studies (GWAS) has enabled new exploration of how genetic variations contribute to health and disease etiology. However, historically GWAS have been limited by inadequate sample size due to associated costs for genotyping and phenotyping of study subjects. This has prompted several academic medical centers to form “biobanks” where biospecimens linked to personal health information, typically in electronic health records (EHRs), are collected and stored on large number of subjects. This provides tremendous opportunities to discover novel genotype-phenotype associations and foster hypothesis generation. In this work, we study how emerging Semantic Web technologies can be applied in conjunction with clinical and genotype data stored at the Mayo Clinic Biobank to mine the phenotype data for genetic associations. In particular, we demonstrate the role of using Resource Description Framework (RDF) for representing EHR diagnoses and procedure data, and enable federated querying via standardized Web protocols to identify subjects genotyped with Type 2 Diabetes for discovering gene-disease associations. Our study highlights the potential of Web-scale data federation techniques to execute complex queries. PMID:23304343

Mining the human phenome using semantic web technologies: a case study for Type 2 Diabetes.

PubMed

Pathak, Jyotishman; Kiefer, Richard C; Bielinski, Suzette J; Chute, Christopher G

2012-01-01

The ability to conduct genome-wide association studies (GWAS) has enabled new exploration of how genetic variations contribute to health and disease etiology. However, historically GWAS have been limited by inadequate sample size due to associated costs for genotyping and phenotyping of study subjects. This has prompted several academic medical centers to form "biobanks" where biospecimens linked to personal health information, typically in electronic health records (EHRs), are collected and stored on large number of subjects. This provides tremendous opportunities to discover novel genotype-phenotype associations and foster hypothesis generation. In this work, we study how emerging Semantic Web technologies can be applied in conjunction with clinical and genotype data stored at the Mayo Clinic Biobank to mine the phenotype data for genetic associations. In particular, we demonstrate the role of using Resource Description Framework (RDF) for representing EHR diagnoses and procedure data, and enable federated querying via standardized Web protocols to identify subjects genotyped with Type 2 Diabetes for discovering gene-disease associations. Our study highlights the potential of Web-scale data federation techniques to execute complex queries.

Moving-Boundary Problems Associated with Lyopreservation

NASA Astrophysics Data System (ADS)

Gruber, Christopher Andrew

The work presented in this Dissertation is motivated by research into the preservation of biological specimens by way of vitrification, a technique known as lyopreservation. The operative principle behind lyopreservation is that a glassy material forms as a solution of sugar and water is desiccated. The microstructure of this glass impedes transport within the material, thereby slowing metabolism and effectively halting the aging processes in a biospecimen. This Dissertation is divided into two segments. The first concerns the nature of diffusive transport within a glassy state. Experimental studies suggest that diffusion within a glass is anomalously slow. Scaled Brownian motion (SBM) is proposed as a mathematical model which captures the qualitative features of anomalously slow diffusion while minimizing computational expense. This model is applied to several moving-boundary problems and the results are compared to a more well-established model, fractional anomalous diffusion (FAD). The virtues of SBM are based on the model's relative mathematical simplicity: the governing equation under FAD dynamics involves a fractional derivative operator, which precludes the use of analytical methods in almost all circumstances and also entails great computational expense. In some geometries, SBM allows similarity solutions, though computational methods are generally required. The use of SBM as an approximation to FAD when a system is "nearly classical'' is also explored. The second portion of this Dissertation concerns spin-drying, which is an experimental approach to biopreservation in a laboratory setting. A biospecimen is adhered to a glass wafer and this substrate is covered with sugar solution and rapidly spun on a turntable while water is evaporated from the film surface. The mathematical model for the spin-drying process includes diffusion, viscous fluid flow, and evaporation, among other contributions to the dynamics. Lubrication theory is applied to the model and an expansion in orthogonal polynomials is applied. The resulting system of equations is solved computationally. The influence of various experimental parameters upon the system dynamics is investigated, particularly the role of the spin rate. A convergence study of the solution verifies that the polynomial expansion method yields accurate results.

75 FR 52351 - Submission for OMB Review; Comment Request; Resource for the Collection and Evaluation of Human...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-25

... submitted to the Office of Management and Budget (OMB) a request to review and approve the information... the life styles and exposures and the biospecimens will serve as controls for the assay results... of Management and Budget, at [email protected] or by fax to 202-395-6974. To request more...

Funding sources for Canadian biorepositories: the role of user fees and strategies to help fill the gap.

PubMed

Barnes, Rebecca O; Schacter, Brent; Kodeeswaran, Sugy; Watson, Peter H

2014-10-01

Biorepositories, the coordinating hubs for the collection and annotation of biospecimens, are under increasing financial pressure and are challenged to remain sustainable. To gain a better understanding of the current funding situation for Canadian biorepositories and the relative contributions they receive from different funding sources, the Canadian Tumour Repository Network (CTRNet) conducted two surveys. The first survey targeted CTRNet's six main nodes to ascertain the relative funding sources and levels of user fees. The second survey was targeted to a broader range of biorepositories (n=45) to ascertain business practices in application of user fees. The results show that >70% of Canadian biorepositories apply user fees and that the majority apply differential fees to different user groups (academic vs. industry, local vs. international). However, user fees typically comprise only 6% of overall operational budgets. We conclude that while strategies to drive up user fee levels need to be implemented, it is essential for the many stakeholders in the biomedical health research sector to consider this issue in order to ensure the ongoing availability of research biospecimens and data that are standardized, high-quality, and that are therefore capable of meeting research needs.

NCI Think Tank Concerning the Identifiability of Biospecimens and “-Omic” Data

PubMed Central

Weil, Carol J.; Mechanic, Leah E.; Green, Tiffany; Kinsinger, Christopher; Lockhart, Nicole C.; Nelson, Stefanie A.; Rodriguez, Laura L.; Buccini, Laura D.

2014-01-01

On June 11 and 12, 2012, the National Cancer Institute (NCI) hosted a think tank concerning the identifiability of biospecimens and “omic” Data in order to explore challenges surrounding this complex and multifaceted topic. The think tank brought together forty-six leaders from several fields, including cancer genomics, bioinformatics, human subject protection, patient advocacy, and commercial genetics. The first day involved presentations regarding the state of the science of re-identification; current and proposed regulatory frameworks for assessing identifiability; developments in law, industry and biotechnology; and the expectations of patients and research participants. The second day was spent by think tank participants in small break-out groups designed to address specific sub-topics under the umbrella issue of identifiability, including considerations for the development of best practices for data sharing and consent, and targeted opportunities for further empirical research. We describe the outcomes of this two day meeting, including two complimentary themes that emerged from moderated discussions following the presentations on Day 1, and ideas presented for further empirical research to discern the preferences and concerns of research participants about data sharing and individual identifiability. PMID:23579437

Silk-based blood stabilization for diagnostics.

PubMed

Kluge, Jonathan A; Li, Adrian B; Kahn, Brooke T; Michaud, Dominique S; Omenetto, Fiorenzo G; Kaplan, David L

2016-05-24

Advanced personalized medical diagnostics depend on the availability of high-quality biological samples. These are typically biofluids, such as blood, saliva, or urine; and their collection and storage is critical to obtain reliable results. Without proper temperature regulation, protein biomarkers in particular can degrade rapidly in blood samples, an effect that ultimately compromises the quality and reliability of laboratory tests. Here, we present the use of silk fibroin as a solid matrix to encapsulate blood analytes, protecting them from thermally induced damage that could be encountered during nonrefrigerated transportation or freeze-thaw cycles. Blood samples are recovered by simple dissolution of the silk matrix in water. This process is demonstrated to be compatible with a number of immunoassays and provides enhanced sample preservation in comparison with traditional air-drying paper approaches. Additional processing can remediate interactions with conformational structures of the silk protein to further enhance blood stabilization and recovery. This approach can provide expanded utility for remote collection of blood and other biospecimens empowering new modalities of temperature-independent remote diagnostics.

Molecular Diagnostics in Pathology: Time for a Next-Generation Pathologist?

PubMed

Fassan, Matteo

2018-03-01

- Comprehensive molecular investigations of mainstream carcinogenic processes have led to the use of effective molecular targeted agents in most cases of solid tumors in clinical settings. - To update readers regarding the evolving role of the pathologist in the therapeutic decision-making process and the introduction of next-generation technologies into pathology practice. - Current literature on the topic, primarily sourced from the PubMed (National Center for Biotechnology Information, Bethesda, Maryland) database, were reviewed. - Adequate evaluation of cytologic-based and tissue-based predictive diagnostic biomarkers largely depends on both proper pathologic characterization and customized processing of biospecimens. Moreover, increased requests for molecular testing have paralleled the recent, sharp decrease in tumor material to be analyzed-material that currently comprises cytology specimens or, at minimum, small biopsies in most cases of metastatic/advanced disease. Traditional diagnostic pathology has been completely revolutionized by the introduction of next-generation technologies, which provide multigene, targeted mutational profiling, even in the most complex of clinical cases. Combining traditional and molecular knowledge, pathologists integrate the morphological, clinical, and molecular dimensions of a disease, leading to a proper diagnosis and, therefore, the most-appropriate tailored therapy.

Representing life as opposed to being: the bio-objectification process of the HeLa cells and its relation to personalized medicine

PubMed Central

Svalastog, Anna Lydia; Martinelli, Lucia

2013-01-01

The immortal HeLa cells case is an intriguing example of bio-objectification processes with great scientific, social, and symbolic impacts. These cells generate questions about representation, significance, and value of the exceptional, variety, individuality, and property. Of frightening (a lethal cancer) and emarginated (a black, poor woman) origins, with their ability to “contaminate” cultures and to “spread” into spaces for becoming of extraordinary value for human knowledge, well-being, and economy advancements, HeLa cells have represented humanity, and emphasized the importance of individual as a core concept of the personalized medicine. Starting from the process leading from HeLa “cells” to HeLa “bio-objects,” we focus on their importance as high quality bio-specimen. We discuss the tension between phenomenological characteristic of fundamental biological research and the variety of material and methodologies in epidemiology and personalized medicine. The emerging methodologies and societal changes reflect present EU policies and lead toward a new paradigm of science. PMID:23986283

Sustainability in Biobanking: Model of Biobank Graz.

PubMed

Sargsyan, Karine; Macheiner, Tanja; Story, Petra; Strahlhofer-Augsten, Manuela; Plattner, Katharina; Riegler, Skaiste; Granitz, Gabriele; Bayer, Michaela; Huppertz, Berthold

2015-12-01

Research infrastructures remain the key for state-of-the-art and successful research. In the last few decades, biobanks have become increasingly important in this field through standardization of biospecimen processing, sample storage, and standardized data management. Research infrastructure in cohort studies and other sample collection activities are currently experiencing a lack of long-term funding. In this article, the Biobank Graz discusses these aspects of sustainability including the definition of sustainability and necessity of a business plan, as well as cost calculation model in the field of biobanking. The economic state, critical success factors, and important operational issues are reviewed and described by the authors, using the example of the Biobank Graz. Sustainability in the field of biobanking is a globally important matter of necessity, starting from policy making and ending with security and documentation on each operational level.

Patient-derived Models of Human Breast Cancer: Protocols for In vitro and In vivo Applications in Tumor Biology and Translational Medicine

PubMed Central

DeRose, Yoko S.; Gligorich, Keith M.; Wang, Guoying; Georgelas, Ann; Bowman, Paulette; Courdy, Samir J.; Welm, Alana L.; Welm, Bryan E.

2013-01-01

Research models that replicate the diverse genetic and molecular landscape of breast cancer are critical for developing the next generation therapeutic entities that can target specific cancer subtypes. Patient-derived tumorgrafts, generated by transplanting primary human tumor samples into immune-compromised mice, are a valuable method to model the clinical diversity of breast cancer in mice, and are a potential resource in personalized medicine. Primary tumorgrafts also enable in vivo testing of therapeutics and make possible the use of patient cancer tissue for in vitro screens. Described in this unit are a variety of protocols including tissue collection, biospecimen tracking, tissue processing, transplantation, and 3-dimensional culturing of xenografted tissue, that enable use of bona fide uncultured human tissue in designing and validating cancer therapies. PMID:23456611

Prostate Cancer Biospecimen Cohort Study

DTIC Science & Technology

2017-10-01

opinions and/or findings contained in this report are those of the author(s) and should not be construed as an official Department of the Army...SPONSOR/MONITOR’S REPORT NUMBER(S) 12. DISTRIBUTION / AVAILABILITY STATEMENT Approved for Public Release; Distribution Unlimited 13. SUPPLEMENTARY NOTES...14. ABSTRACT The goal of the study is development of a Prostate Cancer Biorepository Network (PCBN) resource site with high quality and well

Prostate Cancer Biospecimen Cohort Study

DTIC Science & Technology

2016-10-01

goal of the study is development of a Prostate Cancer Biorepository Network (PCBN) resource site with high quality and well-annotated urine , blood...with no coordinating center and each site will be responsible for maintaining/storing their own data/ samples . 15. SUBJECT TERMS Prostate cancer...Biorepository Network (PCBN) resource site with high quality and well-annotated urine , blood, and tissue specimens as part of a multi-institutional Department of

Security controls in an integrated Biobank to protect privacy in data sharing: rationale and study design.

PubMed

Takai-Igarashi, Takako; Kinoshita, Kengo; Nagasaki, Masao; Ogishima, Soichi; Nakamura, Naoki; Nagase, Sachiko; Nagaie, Satoshi; Saito, Tomo; Nagami, Fuji; Minegishi, Naoko; Suzuki, Yoichi; Suzuki, Kichiya; Hashizume, Hiroaki; Kuriyama, Shinichi; Hozawa, Atsushi; Yaegashi, Nobuo; Kure, Shigeo; Tamiya, Gen; Kawaguchi, Yoshio; Tanaka, Hiroshi; Yamamoto, Masayuki

2017-07-06

With the goal of realizing genome-based personalized healthcare, we have developed a biobank that integrates personal health, genome, and omics data along with biospecimens donated by volunteers of 150,000. Such a large-scale of data integration involves obvious risks of privacy violation. The research use of personal genome and health information is a topic of global discussion with regard to the protection of privacy while promoting scientific advancement. The present paper reports on our plans, current attempts, and accomplishments in addressing security problems involved in data sharing to ensure donor privacy while promoting scientific advancement. Biospecimens and data have been collected in prospective cohort studies with the comprehensive agreement. The sample size of 150,000 participants was required for multiple researches including genome-wide screening of gene by environment interactions, haplotype phasing, and parametric linkage analysis. We established the T ohoku M edical M egabank (TMM) data sharing policy: a privacy protection rule that requires physical, personnel, and technological safeguards against privacy violation regarding the use and sharing of data. The proposed policy refers to that of NCBI and that of the Sanger Institute. The proposed policy classifies shared data according to the strength of re-identification risks. Local committees organized by TMM evaluate re-identification risk and assign a security category to a dataset. Every dataset is stored in an assigned segment of a supercomputer in accordance with its security category. A security manager should be designated to handle all security problems at individual data use locations. The proposed policy requires closed networks and IP-VPN remote connections. The mission of the biobank is to distribute biological resources most productively. This mission motivated us to collect biospecimens and health data and simultaneously analyze genome/omics data in-house. The biobank also has the mission of improving the quality and quantity of the contents of the biobank. This motivated us to request users to share the results of their research as feedback to the biobank. The TMM data sharing policy has tackled every security problem originating with the missions. We believe our current implementation to be the best way to protect privacy in data sharing.

Urinary concentrations of environmental phenols in pregnant women in a pilot study of the National Children's Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mortensen, Mary E., E-mail: MMortensen@cdc.gov; Calafat, Antonia M.; Ye, Xiaoyun

Environmental phenols are a group of chemicals with widespread uses in consumer and personal care products, food and beverage processing, and in pesticides. We assessed exposure to benzophenone-3, bisphenol A (BPA), triclosan, methyl- and propyl parabens, and 2,4- and 2,5-dichlorophenol or their precursors in 506 pregnant women enrolled in the National Children's Study (NCS) Vanguard Study. We measured the urinary concentrations of the target phenols by using online solid-phase extraction–isotope dilution high performance liquid chromatography–tandem mass spectrometry. NCS women results were compared to those of 524 similar-aged women in the National Health and Nutrition Examination Survey (NHANES) 2009–2010, and tomore » 174 pregnant women in NHANES 2005–2010. In the NCS women, we found significant racial/ethnic differences (p<0.05) in regression adjusted mean concentrations of benzophenone-3, triclosan, 2,4- and 2,5-dichlorophenol, but not of BPA. Urinary 2,4- and 2,5-dichlorophenol concentrations were highly correlated (r=0.66, p<0.0001). Except for BPA and triclosan, adjusted mean concentrations were significantly different across the 7 study sites. Education was marginally significant for benzophenone-3, triclosan, propyl paraben, and 2,5-dichlorophenol. Urinary concentrations of target phenols in NCS pregnant women and U.S. women and pregnant women were similar. In NCS pregnant women, race/ethnicity and geographic location determined urinary concentrations of most phenols (except BPA), suggesting differential exposures. NCS Main Study protocols should collect urine biospecimens and information about exposures to environmental phenols. - Highlights: • Limited biomonitoring data are available in pregnant women. • Seven urinary phenols were measured in 506 third trimester women enrolled in the NCS. • Urine benzophenone-3, triclosan, 2,4- and 2,5-dichlorophenol differed by race/ethnicity. • Urinary concentrations of 2,4- and 2,5-dichlorophenol were highly correlated. • Exposure information can expand the utility of biospecimens in the NCS Main Study.« less

Molecular Profiles for Lung Cancer Pathogenesis and Detection in U.S. Veterans

DTIC Science & Technology

2014-12-01

airway epithelium [1, 6, 7], and 2) these changes can be detected and serve as biomarker for early detection of lung cancer [8, 9], in the current...biospecimens from seven locations: nasal epithelium , proximal and distal bronchial airway epithelium obtained at bronchoscopy (ipsilateral and...contralateral to the tumor) as well as the tumor/benign lesion, adjacent normal parenchyma, and sub- segmental bronchial epithelium at time of lobectomy

CPTAC Biospecimen Collection Solicitation | Office of Cancer Clinical Proteomics Research

Cancer.gov

A funding opportunity in support of the National Cancer Institute’s Clinical Proteomic Tumor Analysis Consortium (CPTAC) seeks to prospectively procure tumor samples, collected for proteomics investigation. The scope of work under this Statement of Work encompasses the activities needed to prospectively procure high quality, clinically annotated human tumor samples, blood and plasma, and when feasible, normal tissue from volunteer patients suffering from colon, ovarian, and breast cancer.

The Establishment of an Inflammatory Breast Cancer Registry and Biospecimen Repository

DTIC Science & Technology

2004-08-01

will be presented at the San Antonio Breast Cancer Conference in December, 2004. The clinical data include the observation that approximately one third...of IBC patients are initially diagnosed as having mastitis and are treated with up to five months of antibiotics before the diagnosis of cancer is...developed a national registry of patients with IBC which contains standardized clinical , epidemiological and pathological information. Our registry includes

Fee-for-service as a business model of growing importance: the academic biobank experience.

PubMed

McDonald, Sandra A; Sommerkamp, Kara; Egan-Palmer, Maureen; Kharasch, Karen; Holtschlag, Victoria

2012-10-01

Biorepositories offer tremendous scientific value to a wide variety of customer groups (academic, commercial, industrial) in their ability to deliver a centralized, standardized service model, encompassing both biospecimen storage and related laboratory services. Generally, the scientific expertise and economies of scale that are offered in centralized, properly resourced research biobanks has yielded value that has been well-recognized by universities, pharmaceutical companies, and other sponsoring institutions. However, like many facets of the economy, biobanks have been under increasing cost pressure in recent years. This has been a particular problem in the academic arena, where direct support from grant sources (both governmental and philanthropic) typically now is more difficult to secure, or provides reduced financial support, relative to previous years. One way to address this challenge is to establish or enhance a well-defined fee-for-service model which is properly calibrated to cover operational costs while still offering competitive value to users. In this model, customers are never charged for the biospecimens themselves, but rather for the laboratory services associated with them. Good communication practices, proper assessment of value, implementation of best practices, and a sound business plan are all needed for this initiative to succeed. Here we summarize our experiences at Washington University School of Medicine in the expectation they will be useful to others.

Willingness to Participate in a National Precision Medicine Cohort: Attitudes of Chronic Kidney Disease Patients at a Cleveland Public Hospital.

PubMed

Cooke Bailey, Jessica N; Crawford, Dana C; Goldenberg, Aaron; Slaven, Anne; Pencak, Julie; Schachere, Marleen; Bush, William S; Sedor, John R; O'Toole, John F

2018-06-26

Multiple ongoing, government-funded national efforts longitudinally collect health data and biospecimens for precision medicine research with ascertainment strategies increasingly emphasizing underrepresented groups in biomedical research. We surveyed chronic kidney disease patients from an academic, public integrated tertiary care system in Cleveland, Ohio, to examine local attitudes toward participation in large-scale government-funded studies. Responses ( n = 103) indicate the majority (71%) would participate in a hypothetical national precision medicine cohort and were willing to send biospecimens to a national repository and share de-identified data, but <50% of respondents were willing to install a phone app to track personal data. The majority of participants (62%) indicated that return of research results was very important, and the majority (54%) also wanted all of their research-collected health and genetic data returned. Response patterns did not differ by race/ethnicity. Overall, we found high willingness to participate among this Cleveland patient population already participating in a local genetic study. These data suggest that despite common perceptions, subjects from communities traditionally underrepresented in genetic research will participate and agree to store samples and health data in repositories. Furthermore, most participants want return of research results, which will require a plan to provide these data in a secure, accessible, and understandable manner.

Baobab Laboratory Information Management System: Development of an Open-Source Laboratory Information Management System for Biobanking

PubMed Central

Bendou, Hocine; Sizani, Lunga; Reid, Tim; Swanepoel, Carmen; Ademuyiwa, Toluwaleke; Merino-Martinez, Roxana; Meuller, Heimo; Abayomi, Akin

2017-01-01

A laboratory information management system (LIMS) is central to the informatics infrastructure that underlies biobanking activities. To date, a wide range of commercial and open-source LIMSs are available and the decision to opt for one LIMS over another is often influenced by the needs of the biobank clients and researchers, as well as available financial resources. The Baobab LIMS was developed by customizing the Bika LIMS software (www.bikalims.org) to meet the requirements of biobanking best practices. The need to implement biobank standard operation procedures as well as stimulate the use of standards for biobank data representation motivated the implementation of Baobab LIMS, an open-source LIMS for Biobanking. Baobab LIMS comprises modules for biospecimen kit assembly, shipping of biospecimen kits, storage management, analysis requests, reporting, and invoicing. The Baobab LIMS is based on the Plone web-content management framework. All the system requirements for Plone are applicable to Baobab LIMS, including the need for a server with at least 8 GB RAM and 120 GB hard disk space. Baobab LIMS is a server–client-based system, whereby the end user is able to access the system securely through the internet on a standard web browser, thereby eliminating the need for standalone installations on all machines. PMID:28375759

Baobab Laboratory Information Management System: Development of an Open-Source Laboratory Information Management System for Biobanking.

PubMed

Bendou, Hocine; Sizani, Lunga; Reid, Tim; Swanepoel, Carmen; Ademuyiwa, Toluwaleke; Merino-Martinez, Roxana; Meuller, Heimo; Abayomi, Akin; Christoffels, Alan

2017-04-01

A laboratory information management system (LIMS) is central to the informatics infrastructure that underlies biobanking activities. To date, a wide range of commercial and open-source LIMSs are available and the decision to opt for one LIMS over another is often influenced by the needs of the biobank clients and researchers, as well as available financial resources. The Baobab LIMS was developed by customizing the Bika LIMS software ( www.bikalims.org ) to meet the requirements of biobanking best practices. The need to implement biobank standard operation procedures as well as stimulate the use of standards for biobank data representation motivated the implementation of Baobab LIMS, an open-source LIMS for Biobanking. Baobab LIMS comprises modules for biospecimen kit assembly, shipping of biospecimen kits, storage management, analysis requests, reporting, and invoicing. The Baobab LIMS is based on the Plone web-content management framework. All the system requirements for Plone are applicable to Baobab LIMS, including the need for a server with at least 8 GB RAM and 120 GB hard disk space. Baobab LIMS is a server-client-based system, whereby the end user is able to access the system securely through the internet on a standard web browser, thereby eliminating the need for standalone installations on all machines.

Thyroid Cancer and Tumor Collaborative Registry (TCCR).

PubMed

Shats, Oleg; Goldner, Whitney; Feng, Jianmin; Sherman, Alexander; Smith, Russell B; Sherman, Simon

2016-01-01

A multicenter, web-based Thyroid Cancer and Tumor Collaborative Registry (TCCR, http://tccr.unmc.edu) allows for the collection and management of various data on thyroid cancer (TC) and thyroid nodule (TN) patients. The TCCR is coupled with OpenSpecimen, an open-source biobank management system, to annotate biospecimens obtained from the TCCR subjects. The demographic, lifestyle, physical activity, dietary habits, family history, medical history, and quality of life data are provided and may be entered into the registry by subjects. Information on diagnosis, treatment, and outcome is entered by the clinical personnel. The TCCR uses advanced technical and organizational practices, such as (i) metadata-driven software architecture (design); (ii) modern standards and best practices for data sharing and interoperability (standardization); (iii) Agile methodology (project management); (iv) Software as a Service (SaaS) as a software distribution model (operation); and (v) the confederation principle as a business model (governance). This allowed us to create a secure, reliable, user-friendly, and self-sustainable system for TC and TN data collection and management that is compatible with various end-user devices and easily adaptable to a rapidly changing environment. Currently, the TCCR contains data on 2,261 subjects and data on more than 28,000 biospecimens. Data and biological samples collected by the TCCR are used in developing diagnostic, prevention, treatment, and survivorship strategies against TC.

Community Perceptions of Biobanking Participation: A Qualitative Study among Mexican-Americans in Three Texas Cities.

PubMed

Heredia, Natalia I; Krasny, Sarah; Strong, Larkin L; Von Hatten, Laura; Nguyen, Lynne; Reininger, Belinda M; McNeill, Lorna H; Fernández, María E

2017-01-01

Most biospecimens in the US are collected from non-Hispanic Whites, limiting the generalizability of findings. There is a need to increase participation in biobanking among ethnic and racial minorities. The purpose of this study was to use qualitative methods to identify factors that may influence Mexican-American individuals' willingness to participate in biobanking. We conducted 15 focus groups in three Texas cities with Mexican-American individuals, in both Spanish and English. Lack of knowledge about medical research and biobanks, lack of information about the specifics of biobanking participation, lack of communication of the results, fear of pain or harm, and distrust of the healthcare system or health research were identified as barriers to biobanking participation. Facilitators to participation were altruism, safety, understanding biobanking procedures and purposes, perceived benefits to participation, and culturally appropriate recruitment strategies. Although Mexican-Americans living in Texas are willing to donate biospecimens for altruistic reasons, such as helping society or advancing science, they want more information about what biobanking entails. They want to be assured that participation will not cause them harm and that the research is conducted with good intentions. Results from this study can inform educational materials or interventions to increase Hispanic participation in biobanking. © 2016 S. Karger AG, Basel.

Community perceptions of biobanking participation: A qualitative study among Mexican-Americans in three Texas cities

PubMed Central

Heredia, Natalia I.; Krasny, Sarah; Strong, Larkin L.; Von Hatten, Laura; Nguyen, Lynne; Reininger, Belinda M.; McNeill, Lorna H.; Fernández, María E.

2016-01-01

Background Most biospecimens in the U.S. are collected from Non-Hispanic Whites, limiting the generalizability of findings. There is a need to increase participation in biobanking among ethnic and racial minorities. The purpose of this study was to use qualitative methods to identify factors that may influence Mexican-American individuals’ willingness to participate in biobanking. Methods We conducted 15 focus groups in three Texas cities with Mexican-American individuals, in both Spanish and English. Results Lack of knowledge about medical research and biobanks, lack of information about the specifics of biobanking participation, lack of communication of the results, fear of pain or harm, and distrust of the healthcare system or health research were identified as barriers to biobanking participation. Facilitators to participation were altruism, safety, understanding biobanking procedures and purposes, perceived benefits to participation, and culturally-appropriate recruitment strategies. Although Mexican-Americans living in Texas are willing to donate biospecimens for altruistic reasons, such as helping society or advancing science, they want more information about what biobanking entails. They want to be assured that participation will not cause them harm, and that the research is conducted with good intentions. Conclusion Results from this study can inform educational materials or interventions to increase Hispanic participation in biobanking. PMID:27926908

Current state of the art for enhancing urine biomarker discovery

PubMed Central

Harpole, Michael; Davis, Justin; Espina, Virginia

2016-01-01

Urine is a highly desirable biospecimen for biomarker analysis because it can be collected recurrently by non-invasive techniques, in relatively large volumes. Urine contains cellular elements, biochemicals, and proteins derived from glomerular filtration of plasma, renal tubule excretion, and urogenital tract secretions that reflect, at a given time point, an individual's metabolic and pathophysiologic state. High-resolution mass spectrometry, coupled with state of the art fractionation systems are revealing the plethora of diagnostic/prognostic proteomic information existing within urinary exosomes, glycoproteins, and proteins. Affinity capture pre-processing techniques such as combinatorial peptide ligand libraries and biomarker harvesting hydrogel nanoparticles are enabling measurement/identification of previously undetectable urinary proteins. Future challenges in the urinary proteomics field include a) defining either single or multiple, universally applicable data normalization methods for comparing results within and between individual patients/data sets, and b) defining expected urinary protein levels in healthy individuals. PMID:27232439

The Biomarker Knowledge System Informatics Pilot Project Supplement To The Biomarker Development Laboratory at Moffitt (Bedlam) — EDRN Public Portal

Cancer.gov

The Biomarker Knowledge System Informatics Pilot Project goal will develop network interfaces among databases that contain information about existing clinical populations and biospecimens and data relating to those specimens that are important in biomarker assay validation. This protocol comprises one of two that will comprise the Moffitt participation in the Biomarker Knowledge System Informatics Pilot Project. THIS PROTOCOL (58) is the Sput-Epi Database.

Infrastructure resources for clinical research in amyotrophic lateral sclerosis.

PubMed

Sherman, Alexander V; Gubitz, Amelie K; Al-Chalabi, Ammar; Bedlack, Richard; Berry, James; Conwit, Robin; Harris, Brent T; Horton, D Kevin; Kaufmann, Petra; Leitner, Melanie L; Miller, Robert; Shefner, Jeremy; Vonsattel, Jean Paul; Mitsumoto, Hiroshi

2013-05-01

Clinical trial networks, shared clinical databases, and human biospecimen repositories are examples of infrastructure resources aimed at enhancing and expediting clinical and/or patient oriented research to uncover the etiology and pathogenesis of amyotrophic lateral sclerosis (ALS), a rapidly progressive neurodegenerative disease that leads to the paralysis of voluntary muscles. The current status of such infrastructure resources, as well as opportunities and impediments, were discussed at the second Tarrytown ALS meeting held in September 2011. The discussion focused on resources developed and maintained by ALS clinics and centers in North America and Europe, various clinical trial networks, U.S. government federal agencies including the National Institutes of Health (NIH), the Agency for Toxic Substances and Disease Registry (ATSDR) and the Centers for Disease Control and Prevention (CDC), and several voluntary disease organizations that support ALS research activities. Key recommendations included 1) the establishment of shared databases among individual ALS clinics to enhance the coordination of resources and data analyses; 2) the expansion of quality-controlled human biospecimen banks; and 3) the adoption of uniform data standards, such as the recently developed Common Data Elements (CDEs) for ALS clinical research. The value of clinical trial networks such as the Northeast ALS (NEALS) Consortium and the Western ALS (WALS) Consortium was recognized, and strategies to further enhance and complement these networks and their research resources were discussed.

Fundamental Considerations for Biobank Legacy Planning

PubMed Central

Fombonne, Benjamin; Watson, Peter Hamilton; Moore, Helen Marie

2016-01-01

Biobanking in its various forms is an activity involving the collection of biospecimens and associated data and their storage for differing lengths of time before use. In some cases, biospecimens are immediately used, but in others, they are stored typically for the term of a specified project or in perpetuity until the materials are used up or declared to be of little scientific value. Legacy planning involves preparing for the phase that follows either biobank closure or a significant change at an operational level. In the case of a classical finite collection, this may be brought about by the completion of the initial scientific goals of a project, a loss of funding, or loss of or change in leadership. Ultimately, this may require making a decision about when and where to transfer materials or whether to destroy them. Because biobanking in its entirety is a complex endeavour, legacy planning touches on biobank operations as well as ethical, legal, financial, and governance parameters. Given the expense and time that goes into setting up and maintaining biobanks, coupled with the ethical imperative to appropriately utilize precious resources donated to research, legacy planning is an activity that every biobanking entity should think about. This article describes some of the fundamental considerations for preparing and executing a legacy plan, and we envisage that this article will facilitate dialogue to help inform best practices and policy development in the future. PMID:26890981

Cancer pharmacogenomics and pharmacoepidemiology: setting a research agenda to accelerate translation.

PubMed

Freedman, Andrew N; Sansbury, Leah B; Figg, William D; Potosky, Arnold L; Weiss Smith, Sheila R; Khoury, Muin J; Nelson, Stefanie A; Weinshilboum, Richard M; Ratain, Mark J; McLeod, Howard L; Epstein, Robert S; Ginsburg, Geoffrey S; Schilsky, Richard L; Liu, Geoffrey; Flockhart, David A; Ulrich, Cornelia M; Davis, Robert L; Lesko, Lawrence J; Zineh, Issam; Randhawa, Gurvaneet; Ambrosone, Christine B; Relling, Mary V; Rothman, Nat; Xie, Heng; Spitz, Margaret R; Ballard-Barbash, Rachel; Doroshow, James H; Minasian, Lori M

2010-11-17

Recent advances in genomic research have demonstrated a substantial role for genomic factors in predicting response to cancer therapies. Researchers in the fields of cancer pharmacogenomics and pharmacoepidemiology seek to understand why individuals respond differently to drug therapy, in terms of both adverse effects and treatment efficacy. To identify research priorities as well as the resources and infrastructure needed to advance these fields, the National Cancer Institute (NCI) sponsored a workshop titled "Cancer Pharmacogenomics: Setting a Research Agenda to Accelerate Translation" on July 21, 2009, in Bethesda, MD. In this commentary, we summarize and discuss five science-based recommendations and four infrastructure-based recommendations that were identified as a result of discussions held during this workshop. Key recommendations include 1) supporting the routine collection of germline and tumor biospecimens in NCI-sponsored clinical trials and in some observational and population-based studies; 2) incorporating pharmacogenomic markers into clinical trials; 3) addressing the ethical, legal, social, and biospecimen- and data-sharing implications of pharmacogenomic and pharmacoepidemiologic research; and 4) establishing partnerships across NCI, with other federal agencies, and with industry. Together, these recommendations will facilitate the discovery and validation of clinical, sociodemographic, lifestyle, and genomic markers related to cancer treatment response and adverse events, and they will improve both the speed and efficiency by which new pharmacogenomic and pharmacoepidemiologic information is translated into clinical practice.

Thyroid Cancer and Tumor Collaborative Registry (TCCR)

PubMed Central

Shats, Oleg; Goldner, Whitney; Feng, Jianmin; Sherman, Alexander; Smith, Russell B.; Sherman, Simon

2016-01-01

A multicenter, web-based Thyroid Cancer and Tumor Collaborative Registry (TCCR, http://tccr.unmc.edu) allows for the collection and management of various data on thyroid cancer (TC) and thyroid nodule (TN) patients. The TCCR is coupled with OpenSpecimen, an open-source biobank management system, to annotate biospecimens obtained from the TCCR subjects. The demographic, lifestyle, physical activity, dietary habits, family history, medical history, and quality of life data are provided and may be entered into the registry by subjects. Information on diagnosis, treatment, and outcome is entered by the clinical personnel. The TCCR uses advanced technical and organizational practices, such as (i) metadata-driven software architecture (design); (ii) modern standards and best practices for data sharing and interoperability (standardization); (iii) Agile methodology (project management); (iv) Software as a Service (SaaS) as a software distribution model (operation); and (v) the confederation principle as a business model (governance). This allowed us to create a secure, reliable, user-friendly, and self-sustainable system for TC and TN data collection and management that is compatible with various end-user devices and easily adaptable to a rapidly changing environment. Currently, the TCCR contains data on 2,261 subjects and data on more than 28,000 biospecimens. Data and biological samples collected by the TCCR are used in developing diagnostic, prevention, treatment, and survivorship strategies against TC. PMID:27168721

An Efficient Design Strategy for Logistic Regression Using Outcome- and Covariate-Dependent Pooling of Biospecimens Prior to Assay

PubMed Central

Lyles, Robert H.; Mitchell, Emily M.; Weinberg, Clarice R.; Umbach, David M.; Schisterman, Enrique F.

2016-01-01

Summary Potential reductions in laboratory assay costs afforded by pooling equal aliquots of biospecimens have long been recognized in disease surveillance and epidemiological research and, more recently, have motivated design and analytic developments in regression settings. For example, Weinberg and Umbach (1999, Biometrics 55, 718–726) provided methods for fitting set-based logistic regression models to case-control data when a continuous exposure variable (e.g., a biomarker) is assayed on pooled specimens. We focus on improving estimation efficiency by utilizing available subject-specific information at the pool allocation stage. We find that a strategy that we call “(y,c)-pooling,” which forms pooling sets of individuals within strata defined jointly by the outcome and other covariates, provides more precise estimation of the risk parameters associated with those covariates than does pooling within strata defined only by the outcome. We review the approach to set-based analysis through offsets developed by Weinberg and Umbach in a recent correction to their original paper. We propose a method for variance estimation under this design and use simulations and a real-data example to illustrate the precision benefits of (y,c)-pooling relative to y-pooling. We also note and illustrate that set-based models permit estimation of covariate interactions with exposure. PMID:26964741

Genetic Testing and Tissue Banking for Personalized Oncology: Analytical and Institutional Factors

PubMed Central

Miles, George; Rae, James; Ramalingam, Suresh S.; Pfeifer, John

2016-01-01

Personalized oncology, or more aptly precision oncogenomics, refers to the identification and implementation of clinically actionable targets tailored to an individual patient’s cancer genomic information. Banking of human tissue and other biospecimens establishes a framework to extract and collect the data essential to our understanding of disease pathogenesis and treatment. Cancer cooperative groups in the United States have led the way in establishing robust biospecimen collection mechanisms to facilitate translational research, and combined with technological advances in molecular testing, tissue banking has expanded from its traditional base in academic research and is assuming an increasingly pivotal role in directing the clinical care of cancer patients. Comprehensive screening of tumors by DNA sequencing and the ability to mine and interpret these large data sets from well-organized tissue banks have defined molecular subtypes of cancer. Such stratification by genomic criteria has revolutionized our perspectives on cancer diagnosis and treatment, offering insight into prognosis, progression, and susceptibility or resistance to known therapeutic agents. In turn, this has enabled clinicians to offer treatments tailored to patients that can greatly improve their chances of survival. Unique challenges and opportunities accompany the rapidly evolving interplay between tissue banking and genomic sequencing, and are the driving forces underlying the revolution in precision medicine. Molecular testing and precision medicine clinical trials are now becoming the major thrust behind the cooperative groups’ clinical research efforts. PMID:26433552

Clinical genomics, big data, and electronic medical records: reconciling patient rights with research when privacy and science collide.

PubMed

Kulynych, Jennifer; Greely, Henry T

2017-04-01

Widespread use of medical records for research, without consent, attracts little scrutiny compared to biospecimen research, where concerns about genomic privacy prompted recent federal proposals to mandate consent. This paper explores an important consequence of the proliferation of electronic health records (EHRs) in this permissive atmosphere: with the advent of clinical gene sequencing, EHR-based secondary research poses genetic privacy risks akin to those of biospecimen research, yet regulators still permit researchers to call gene sequence data 'de-identified', removing such data from the protection of the federal Privacy Rule and federal human subjects regulations. Medical centers and other providers seeking to offer genomic 'personalized medicine' now confront the problem of governing the secondary use of clinical genomic data as privacy risks escalate. We argue that regulators should no longer permit HIPAA-covered entities to treat dense genomic data as de-identified health information. Even with this step, the Privacy Rule would still permit disclosure of clinical genomic data for research, without consent, under a data use agreement, so we also urge that providers give patients specific notice before disclosing clinical genomic data for research, permitting (where possible) some degree of choice and control. To aid providers who offer clinical gene sequencing, we suggest both general approaches and specific actions to reconcile patients' rights and interests with genomic research.

Fee-For-Service as a Business Model of Growing Importance: The Academic Biobank Experience

PubMed Central

Sommerkamp, Kara; Egan-Palmer, Maureen; Kharasch, Karen; Holtschlag, Victoria

2012-01-01

Biorepositories offer tremendous scientific value to a wide variety of customer groups (academic, commercial, industrial) in their ability to deliver a centralized, standardized service model, encompassing both biospecimen storage and related laboratory services. Generally, the scientific expertise and economies of scale that are offered in centralized, properly resourced research biobanks has yielded value that has been well-recognized by universities, pharmaceutical companies, and other sponsoring institutions. However, like many facets of the economy, biobanks have been under increasing cost pressure in recent years. This has been a particular problem in the academic arena, where direct support from grant sources (both governmental and philanthropic) typically now is more difficult to secure, or provides reduced financial support, relative to previous years. One way to address this challenge is to establish or enhance a well-defined fee-for-service model which is properly calibrated to cover operational costs while still offering competitive value to users. In this model, customers are never charged for the biospecimens themselves, but rather for the laboratory services associated with them. Good communication practices, proper assessment of value, implementation of best practices, and a sound business plan are all needed for this initiative to succeed. Here we summarize our experiences at Washington University School of Medicine in the expectation they will be useful to others. PMID:23386922

Clinical genomics, big data, and electronic medical records: reconciling patient rights with research when privacy and science collide

PubMed Central

Greely, Henry T.

2017-01-01

Abstract Widespread use of medical records for research, without consent, attracts little scrutiny compared to biospecimen research, where concerns about genomic privacy prompted recent federal proposals to mandate consent. This paper explores an important consequence of the proliferation of electronic health records (EHRs) in this permissive atmosphere: with the advent of clinical gene sequencing, EHR-based secondary research poses genetic privacy risks akin to those of biospecimen research, yet regulators still permit researchers to call gene sequence data ‘de-identified’, removing such data from the protection of the federal Privacy Rule and federal human subjects regulations. Medical centers and other providers seeking to offer genomic ‘personalized medicine’ now confront the problem of governing the secondary use of clinical genomic data as privacy risks escalate. We argue that regulators should no longer permit HIPAA-covered entities to treat dense genomic data as de-identified health information. Even with this step, the Privacy Rule would still permit disclosure of clinical genomic data for research, without consent, under a data use agreement, so we also urge that providers give patients specific notice before disclosing clinical genomic data for research, permitting (where possible) some degree of choice and control. To aid providers who offer clinical gene sequencing, we suggest both general approaches and specific actions to reconcile patients’ rights and interests with genomic research. PMID:28852559

DRAQ5 and Eosin (‘D&E’) as an Analog to Hematoxylin and Eosin for Rapid Fluorescence Histology of Fresh Tissues

PubMed Central

Elfer, Katherine N.; Sholl, Andrew B.; Wang, Mei; Tulman, David B.; Mandava, Sree H.; Lee, Benjamin R.; Brown, J. Quincy

2016-01-01

Real-time on-site histopathology review of biopsy tissues at the point-of-procedure has great potential for significant clinical value and improved patient care. For instance, on-site review can aid in rapid screening of diagnostic biopsies to reduce false-negative results, or in quantitative assessment of biospecimen quality to increase the efficacy of downstream laboratory and histopathology analysis. However, the only currently available rapid pathology method, frozen section analysis (FSA), is too time- and labor-intensive for use in screening large quantities of biopsy tissues and is too destructive for maximum tissue conservation in multiple small needle core biopsies. In this work we demonstrate the spectrally-compatible combination of the nuclear stain DRAQ5 and the anionic counterstain eosin as a dual-component fluorescent staining analog to hematoxylin and eosin intended for use on fresh, unsectioned tissues. Combined with optical sectioning fluorescence microscopy and pseudo-coloring algorithms, DRAQ5 and eosin (“D&E”) enables very fast, non-destructive psuedohistological imaging of tissues at the point-of-acquisition with minimal tissue handling and processing. D&E was validated against H&E on a one-to-one basis on formalin-fixed paraffin-embedded and frozen section tissues of various human organs using standard epi-fluorescence microscopy, demonstrating high fidelity of the staining mechanism as an H&E analog. The method was then applied to fresh, whole 18G renal needle core biopsies and large needle core prostate biospecimen biopsies using fluorescence structured illumination optical sectioning microscopy. We demonstrate the ability to obtain high-resolution histology-like images of unsectioned, fresh tissues similar to subsequent H&E staining of the tissue. The application of D&E does not interfere with subsequent standard-of-care H&E staining and imaging, preserving the integrity of the tissue for thorough downstream analysis. These results indicate that this dual-stain pseudocoloring method could provide a real-time histology-like image at the time of acquisition and valuable objective tissue analysis for the clinician at the time of service. PMID:27788264

Telethon Network of Genetic Biobanks: a key service for diagnosis and research on rare diseases.

PubMed

Filocamo, Mirella; Baldo, Chiara; Goldwurm, Stefano; Renieri, Alessandra; Angelini, Corrado; Moggio, Maurizio; Mora, Marina; Merla, Giuseppe; Politano, Luisa; Garavaglia, Barbara; Casareto, Lorena; Bricarelli, Francesca Dagna

2013-08-30

Several examples have always illustrated how access to large numbers of biospecimens and associated data plays a pivotal role in the identification of disease genes and the development of pharmaceuticals. Hence, allowing researchers to access to significant numbers of quality samples and data, genetic biobanks are a powerful tool in basic, translational and clinical research into rare diseases. Recently demand for well-annotated and properly-preserved specimens is growing at a high rate, and is expected to grow for years to come. The best effective solution to this issue is to enhance the potentialities of well-managed biobanks by building a network.Here we report a 5-year experience of the Telethon Network of Genetic Biobanks (TNGB), a non-profit association of Italian repositories created in 2008 to form a virtually unique catalogue of biospecimens and associated data, which presently lists more than 750 rare genetic defects. The process of TNGB harmonisation has been mainly achieved through the adoption of a unique, centrally coordinated, IT infrastructure, which has enabled (i) standardisation of all the TNGB procedures and activities; (ii) creation of an updated TNGB online catalogue, based on minimal data set and controlled terminologies; (iii) sample access policy managed via a shared request control panel at web portal. TNGB has been engaged in disseminating information on its services into both scientific/biomedical - national and international - contexts, as well as associations of patients and families. Indeed, during the last 5-years national and international scientists extensively used the TNGB with different purposes resulting in more than 250 scientific publications. In addition, since its inception the TNGB is an associated member of the Biobanking and Biomolecular Resources Research Infrastructure and recently joined the EuroBioBank network. Moreover, the involvement of patients and families, leading to the formalization of various agreements between TNGB and Patients' Associations, has demonstrated how promoting Biobank services can be instrumental in gaining a critical mass of samples essential for research, as well as, raising awareness, trust and interest of the general public in Biobanks. This article focuses on some fundamental aspects of networking and demonstrates how the translational research benefits from a sustained infrastructure.

Preservation of Biospecimens at Ambient Temperature: Special Focus on Nucleic Acids and Opportunities for the Biobanking Community.

PubMed

Muller, Rolf; Betsou, Fay; Barnes, Michael G; Harding, Keith; Bonnet, Jacques; Kofanova, Olga; Crowe, John H

2016-04-01

Several approaches to the preservation of biological materials at ambient temperature and the relative impact on sample stability and degradation are reviewed, with a focus on nucleic acids. This appraisal is undertaken within the framework of biobank risk, quality management systems, and accreditation, with a view to assessing how best to apply ambient temperature sample storage to ensure stability, reduce costs, improve handling logistics, and increase the efficiency of biobank procedures.

A Medical Center Network for Optimized Lung Cancer Biospecimen Banking

DTIC Science & Technology

2013-10-01

Carcinoma Stage IIB N N .149 1 8 .132 1 8 .092 1 No - Quit Smoking 50 AR Agent Orange , Nuclear weapons, Second-hand smoke Agent Orange , Nuclear weapons...Smoking 30 None Agent Orange , Asbestos, Second-hand smoke Agent Orange , Asbestos, Second-hand smoke S0159 Squamous Cell Carcinoma Stage IIB Y N...2.560 100 80 25 6 7 0.670 4 4 0.370 1 No - Quit Smoking 30 NV Agent Orange , Asbestos, Nuclear weapons, Second- hand smoke Agent Orange , Asbestos

Comprehensive Reproductive System Care Program - Clinical Breast Care Project (CRSCP-CBCP)

DTIC Science & Technology

2013-04-01

tumor heterogeneity. The tumor microenvironment and stromal interactions, metastasis and recurrence, as well as the role of cancer stem cells and tumor...biospecimens (Figure BB-1) donated by 5,977 fully consented subjects to our IRB approved tissue and blood protocols. (Figure BB-2) 10 1/1 c Cll ...E ’(3 Cll c. 1/1 c;; 0 1- CBCP Total Biological Specimens, Cumulative Annual Total thru 3/31/13 60000 50000 40000 30000 20000 10000 0

The Image and Data Archive at the Laboratory of Neuro Imaging.

PubMed

Crawford, Karen L; Neu, Scott C; Toga, Arthur W

2016-01-01

The LONI Image and Data Archive (IDA)(1) is a repository for sharing and long-term preservation of neuroimaging and biomedical research data. Originally designed to archive strictly medical image files, the IDA has evolved over the last ten years and now encompasses the storage and dissemination of neuroimaging, clinical, biospecimen, and genetic data. In this article, we report upon the genesis of the IDA and how it currently securely manages data and protects data ownership. Copyright © 2015 Elsevier Inc. All rights reserved.

Tissue Preservation Assessment Preliminary Results

NASA Technical Reports Server (NTRS)

Globus, Ruth; Costes, Sylvain

2017-01-01

Pre-flight groundbased testing done to prepare for the first Rodent Research mission validation flight, RR1 (Choi et al, 2016 PlosOne). We purified RNA and measured RIN values to assess quality of the samples. For protein, we measured liver enzyme activities. We tested protocol and methods of preservation to date. Here we present an overview of results related to tissue preservation from the RR1 validation mission and a summary of findings to date from investigators who received RR1 teissues various Biospecimen Sharing Program.

Current projects in Pre-analytics: where to go?

PubMed

Sapino, Anna; Annaratone, Laura; Marchiò, Caterina

2015-01-01

The current clinical practice of tissue handling and sample preparation is multifaceted and lacks strict standardisation: this scenario leads to significant variability in the quality of clinical samples. Poor tissue preservation has a detrimental effect thus leading to morphological artefacts, hampering the reproducibility of immunocytochemical and molecular diagnostic results (protein expression, DNA gene mutations, RNA gene expression) and affecting the research outcomes with irreproducible gene expression and post-transcriptional data. Altogether, this limits the opportunity to share and pool national databases into European common databases. At the European level, standardization of pre-analytical steps is just at the beginning and issues regarding bio-specimen collection and management are still debated. A joint (public-private) project entitled on standardization of tissue handling in pre-analytical procedures has been recently funded in Italy with the aim of proposing novel approaches to the neglected issue of pre-analytical procedures. In this chapter, we will show how investing in pre-analytics may impact both public health problems and practical innovation in solid tumour processing.

Establishing an academic biobank in a resource-challenged environment.

PubMed

Soo, Cassandra Claire; Mukomana, Freedom; Hazelhurst, Scott; Ramsay, Michele

2017-05-24

Past practices of informal sample collections and spreadsheets for data and sample management fall short of best-practice models for biobanking, and are neither cost effective nor efficient to adequately serve the needs of large research studies. The biobank of the Sydney Brenner Institute for Molecular Bioscience serves as a bioresource for institutional, national and international research collaborations. It provides high-quality human biospecimens from African populations, secure data and sample curation and storage, as well as monitored sample handling and management processes, to promote both non-communicable and infectious-disease research. Best-practice guidelines have been adapted to align with a low-resource setting and have been instrumental in the development of a quality-management system, including standard operating procedures and a quality-control regimen. Here, we provide a summary of 10 important considerations for initiating and establishing an academic research biobank in a low-resource setting. These include addressing ethical, legal, technical, accreditation and/or certification concerns and financial sustainability.

A Plan for Academic Biobank Solvency-Leveraging Resources and Applying Business Processes to Improve Sustainability.

PubMed

Uzarski, Diane; Burke, James; Turner, Barbara; Vroom, James; Short, Nancy

2015-10-01

Researcher-initiated biobanks based at academic institutions contribute valuable biomarker and translational research advances to medicine. With many legacy banks once supported by federal funding, reductions in fiscal support threaten the future of existing and new biobanks. When the Brain Bank at Duke University's Bryan Alzheimer's Disease Center (ADRC) faced a funding crisis, a collaborative, multidisciplinary team embarked on a 2-year biobank sustainability project utilizing a comprehensive business strategy, dedicated project management, and a systems approach involving many Duke University entities. By synthesizing and applying existing knowledge, Duke Translational Medicine Institute created and launched a business model that can be adjusted and applied to legacy and start-up academic biobanks. This model provides a path to identify new funding mechanisms, while also emphasizing improved communication, business development, and a focus on collaborating with industry to improve access to biospecimens. Benchmarks for short-term Brain Bank stabilization have been successfully attained, and the evaluation of long-term sustainability metrics is ongoing. © 2015 Wiley Periodicals, Inc.

Establishing an academic biobank in a resource-challenged environment

PubMed Central

Soo, C C; Mukomana, F; Hazelhurst, S; Ramsay, M

2018-01-01

Past practices of informal sample collections and spreadsheets for data and sample management fall short of best-practice models for biobanking, and are neither cost effective nor efficient to adequately serve the needs of large research studies. The biobank of the Sydney Brenner Institute for Molecular Bioscience serves as a bioresource for institutional, national and international research collaborations. It provides high-quality human biospecimens from African populations, secure data and sample curation and storage, as well as monitored sample handling and management processes, to promote both non-communicable and infectious-disease research. Best-practice guidelines have been adapted to align with a low-resource setting and have been instrumental in the development of a quality-management system, including standard operating procedures and a quality-control regimen. Here, we provide a summary of 10 important considerations for initiating and establishing an academic research biobank in a low-resource setting. These include addressing ethical, legal, technical, accreditation and/or certification concerns and financial sustainability. PMID:28604319

A Plan for Academic Biobank Solvency—Leveraging Resources and Applying Business Processes to Improve Sustainability

PubMed Central

Burke, James; Turner, Barbara; Vroom, James; Short, Nancy

2015-01-01

Abstract Researcher‐initiated biobanks based at academic institutions contribute valuable biomarker and translational research advances to medicine. With many legacy banks once supported by federal funding, reductions in fiscal support threaten the future of existing and new biobanks. When the Brain Bank at Duke University's Bryan Alzheimer's Disease Center (ADRC) faced a funding crisis, a collaborative, multidisciplinary team embarked on a 2‐year biobank sustainability project utilizing a comprehensive business strategy, dedicated project management, and a systems approach involving many Duke University entities. By synthesizing and applying existing knowledge, Duke Translational Medicine Institute created and launched a business model that can be adjusted and applied to legacy and start‐up academic biobanks. This model provides a path to identify new funding mechanisms, while also emphasizing improved communication, business development, and a focus on collaborating with industry to improve access to biospecimens. Benchmarks for short‐term Brain Bank stabilization have been successfully attained, and the evaluation of long‐term sustainability metrics is ongoing. PMID:25996355

Consensus-Driven Development of a Terminology for Biobanking, the Duke Experience.

PubMed

Ellis, Helena; Joshi, Mary-Beth; Lynn, Aenoch J; Walden, Anita

2017-04-01

Biobanking at Duke University has existed for decades and has grown over time in silos and based on specialized needs, as is true with most biomedical research centers. These silos developed informatics systems to support their own individual requirements, with no regard for semantic or syntactic interoperability. Duke undertook an initiative to implement an enterprise-wide biobanking information system to serve its many diverse biobanking entities. A significant part of this initiative was the development of a common terminology for use in the commercial software platform. Common terminology provides the foundation for interoperability across biobanks for data and information sharing. We engaged experts in research, informatics, and biobanking through a consensus-driven process to agree on 361 terms and their definitions that encompass the lifecycle of a biospecimen. Existing standards, common terms, and data elements from published articles provided a foundation on which to build the biobanking terminology; a broader set of stakeholders then provided additional input and feedback in a secondary vetting process. The resulting standardized biobanking terminology is now available for sharing with the biobanking community to serve as a foundation for other institutions who are considering a similar initiative.

Consensus-Driven Development of a Terminology for Biobanking, the Duke Experience

PubMed Central

Joshi, Mary-Beth; Lynn, Aenoch J.; Walden, Anita

2017-01-01

Biobanking at Duke University has existed for decades and has grown over time in silos and based on specialized needs, as is true with most biomedical research centers. These silos developed informatics systems to support their own individual requirements, with no regard for semantic or syntactic interoperability. Duke undertook an initiative to implement an enterprise-wide biobanking information system to serve its many diverse biobanking entities. A significant part of this initiative was the development of a common terminology for use in the commercial software platform. Common terminology provides the foundation for interoperability across biobanks for data and information sharing. We engaged experts in research, informatics, and biobanking through a consensus-driven process to agree on 361 terms and their definitions that encompass the lifecycle of a biospecimen. Existing standards, common terms, and data elements from published articles provided a foundation on which to build the biobanking terminology; a broader set of stakeholders then provided additional input and feedback in a secondary vetting process. The resulting standardized biobanking terminology is now available for sharing with the biobanking community to serve as a foundation for other institutions who are considering a similar initiative. PMID:28338350

Quantification of Inflammasome Adaptor Protein ASC in Biological Samples by Multiple-Reaction Monitoring Mass Spectrometry.

PubMed

Ulke-Lemée, Annegret; Lau, Arthur; Nelson, Michelle C; James, Matthew T; Muruve, Daniel A; MacDonald, Justin A

2018-06-09

Inflammation is an integral component of many diseases, including chronic kidney disease (CKD). ASC (apoptosis-associated speck-like protein containing CARD, also PYCARD) is the key inflammasome adaptor protein in the innate immune response. Since ASC specks, a macromolecular condensate of ASC protein, can be released by inflammasome-activated cells into the extracellular space to amplify inflammatory responses, the ASC protein could be an important biomarker in diagnostic applications. Herein, we describe the development and validation of a multiple reaction monitoring mass spectrometry (MRM-MS) assay for the accurate quantification of ASC in human biospecimens. Limits of detection and quantification for the signature DLLLQALR peptide (used as surrogate for the target ASC protein) were determined by the method of standard addition using synthetic isotope-labeled internal standard (SIS) peptide and urine matrix from a healthy donor (LOQ was 8.25 pM, with a ~ 1000-fold linear range). We further quantified ASC in the urine of CKD patients (8.4 ± 1.3 ng ASC/ml urine, n = 13). ASC was positively correlated with proteinuria and urinary IL-18 in CKD samples but not with urinary creatinine. Unfortunately, the ASC protein is susceptible to degradation, and patient urine that was thawed and refrozen lost 85% of the ASC signal. In summary, the MRM-MS assay provides a robust means to quantify ASC in biological samples, including clinical biospecimens; however, sample collection and storage conditions will have a critical impact on assay reliability.

Survey Field Methods for Expanded Biospecimen and Biomeasure Collection in NSHAP Wave 2

PubMed Central

Jaszczak, Angela; Hoffmann, Joscelyn N.; You, Hannah M.; Kern, David W.; Pagel, Kristina; McPhillips, Jane; Schumm, L. Philip; Dale, William; Huang, Elbert S.; McClintock, Martha K.

2014-01-01

Objectives. The National Social Life, Health, and Aging Project is a nationally representative, longitudinal survey of older adults. A main component is the collection of biomeasures to objectively assess physiological status relevant to psychosocial variables, aging conditions, and disease. Wave 2 added novel biomeasures, refined those collected in Wave 1, and provides a reference for the collection protocols and strategy common to the biomeasures. The effects of aging, gender, and their interaction are presented in the specific biomeasure papers included in this Special Issue. Method. A transdisciplinary working group expanded the biomeasures collected to include physiological, genetic, anthropometric, functional, neuropsychological, and sensory measures, yielding 37 more than in Wave 1. All were designed for collection in respondents’ homes by nonmedically trained field interviewers. Results. Both repeated and novel biomeasures were successful. Those in Wave 1 were refined to improve quality, and ensure consistency for longitudinal analysis. Four new biospecimens yielded 27 novel measures. During the interview, 19 biomeasures were recorded covering anthropometric, functional, neuropsychological, and sensory measures and actigraphy provided data on activity and sleep. Discussion. Improved field methods included in-home collection, temperature control, establishment of a central survey biomeasure laboratory, and shipping, all of which were crucial for successful collection by the field interviewers and accurate laboratory assay of the biomeasures (92.1% average co-operation rate and 97.3% average assay success rate). Developed for home interviews, these biomeasures are readily applicable to other surveys. PMID:25360025

A Medical Center Network for Optimized Lung Cancer Biospecimen Banking

DTIC Science & Technology

2014-10-01

Y N 0.519 60 70 5 2 2 1.620 2 0.250 2 Yes - Current Smoker AF Jet fuel , Second-hand smoke Jet fuel , Second-hand smoke S0018 Squamous Cell...Second-hand smoke Second-hand smoke S0028 Squamous Cell Carcinoma Stage IIIB N N No - Quit Smoking 150 AF Jet fuel , Nuclear weapons, Second-hand... Jet fuel , Nuclear weapons, Second-hand S0029 Squamous Cell Carcinoma Stage IIA Y N 0.06 100 40 0 1 3 .571 1 8 .043 1 No - Quit Smoking AR Second

Resources available for autism research in the big data era: a systematic review

PubMed Central

Milne, Elizabeth

2017-01-01

Recently, there has been a move encouraged by many stakeholders towards generating big, open data in many areas of research. One area where big, open data is particularly valuable is in research relating to complex heterogeneous disorders such as Autism Spectrum Disorder (ASD). The inconsistencies of findings and the great heterogeneity of ASD necessitate the use of big and open data to tackle important challenges such as understanding and defining the heterogeneity and potential subtypes of ASD. To this end, a number of initiatives have been established that aim to develop big and/or open data resources for autism research. In order to provide a useful data reference for autism researchers, a systematic search for ASD data resources was conducted using the Scopus database, the Google search engine, and the pages on ‘recommended repositories’ by key journals, and the findings were translated into a comprehensive list focused on ASD data. The aim of this review is to systematically search for all available ASD data resources providing the following data types: phenotypic, neuroimaging, human brain connectivity matrices, human brain statistical maps, biospecimens, and ASD participant recruitment. A total of 33 resources were found containing different types of data from varying numbers of participants. Description of the data available from each data resource, and links to each resource is provided. Moreover, key implications are addressed and underrepresented areas of data are identified. PMID:28097074

The AIDS and Cancer Specimen Resource: Role in HIV/AIDS scientific discovery

PubMed Central

Ayers, Leona W; Silver, Sylvia; McGrath, Michael S; Orenstein, Jan M

2007-01-01

The AIDS Cancer and Specimen Resource (ACSR) supports scientific discovery in the area of HIV/AIDS-associated malignancies. The ACSR was established as a cooperative agreement between the NCI (Office of the Director, Division of Cancer Treatment and Diagnosis) and regional consortia, University of California, San Francisco (West Coast), George Washington University (East Coast) and Ohio State University (Mid-Region) to collect, preserve and disperse HIV-related tissues and biologic fluids and controls along with clinical data to qualified investigators. The available biological samples with clinical data and the application process are described on the ACSR web site. The ACSR tissue bank has more than 100,000 human HIV positive specimens that represent different processing (43), specimen (15), and anatomical site (50) types. The ACSR provides special biospecimen collections and prepares speciality items, e.g., tissue microarrays (TMA), DNA libraries. Requests have been greatest for Kaposi's sarcoma (32%) and non-Hodgkin's lymphoma (26%). Dispersed requests include 83% tissue (frozen and paraffin embedded), 18% plasma/serum and 9% other. ACSR also provides tissue microarrays of, e.g., Kaposi's sarcoma and non-Hodgkin's lymphoma, for biomarker assays and has developed collaborations with other groups that provide access to additional AIDS-related malignancy specimens. ACSR members and associates have completed 63 podium and poster presentations. Investigators have submitted 125 letters of intent requests. Discoveries using ACSR have been reported in 61 scientific publications in notable journals with an average impact factor of 7. The ACSR promotes the scientific exploration of the relationship between HIV/AIDS and malignancy by participation at national and international scientific meetings, contact with investigators who have productive research in this area and identifying, collecting, preserving, enhancing, and dispersing HIV/AIDS-related malignancy specimens to funded, approved researchers at no fee. Scientific discovery has been advanced by this unique biorepository. Investigators are encouraged to browse the ACSR Internet site for materials to enhance their own scientific initiatives. PMID:17335575

US experiments flown on the Soviet biosatellite Cosmos 2044. Volume 1: Mission description, experiments K-7-01 - K-7-15

NASA Technical Reports Server (NTRS)

Connolly, James P. (Editor); Grindeland, Richard E. (Editor); Ballard, Rodney W. (Editor)

1994-01-01

Cosmos 2044 was launched on September 15, 1989, containing radiation dosimetry experiments and a biological payload including two young male rhesus monkeys, ten adult male Wistar rats, insects, amphibians, protozoa, cell cultures, worms, plants and fish. The biosatellite was launched from the Plesetsk Cosmodrome in the Soviet Union for a mission duration of 14 days, as planned. The major research objectives were: (1) Study adaptive response mechanisms of mammals during flight; (2) Study physiological mechanisms underlying vestibular, motor system and brain function in primates during early and later adaptation phases; (3) Study the tissue regeneration processes of mammals; (4) Study the development of single-celled organisms, cell cultures and embryos in microgravity; (5) Study radiation characteristics during the mission and investigate doses, fluxes and spectra of cosmic radiation for various types of shielding. American and Soviet specialists jointly conducted 29 experiments on this mission including extensive preflight and post flight studies with rhesus monkeys, and tissue processing and cell culturing post flight. Biosamples and data were subsequently transferred to the United States. The U.S. responsibilities for this flight included development of flight and ground-based hardware, the preparation of rat tissue sample procedures, the verification testing of hardware and experiment procedures, and the post flight analysis of biospecimens and data for the joint experiments. The U.S. investigations included four primate experiments, 24 rat experiments, and one radiation dosimetry experiment. Three scientists investigated tissue repair during flight for a subgroup of rats injured preflight by surgical intervention. A description of the Cosmos 2044 mission is presented in this report including preflight, on-orbit and post flight activities. The flight and ground-based bioinstrumentation which was developed by the U.S. and U.S.S.R. is also described, along with the associated preflight testing of the U.S. hardware.

Transmissive liquid-crystal device correcting primary coma aberration and astigmatism in laser scanning microscopy

NASA Astrophysics Data System (ADS)

Tanabe, Ayano; Hibi, Terumasa; Ipponjima, Sari; Matsumoto, Kenji; Yokoyama, Masafumi; Kurihara, Makoto; Hashimoto, Nobuyuki; Nemoto, Tomomi

2016-03-01

Laser scanning microscopy allows 3D cross-sectional imaging inside biospecimens. However, certain aberrations produced can degrade the quality of the resulting images. We previously reported a transmissive liquid-crystal device that could compensate for the predominant spherical aberrations during the observations, particularly in deep regions of the samples. The device, inserted between the objective lens and the microscope revolver, improved the image quality of fixed-mouse-brain slices that were observed using two-photon excitation laser scanning microscopy, which was originally degraded by spherical aberration. In this study, we developed a transmissive device that corrects primary coma aberration and astigmatism, motivated by the fact that these asymmetric aberrations can also often considerably deteriorate image quality, even near the sample surface. The device's performance was evaluated by observing fluorescent beads using single-photon excitation laser scanning microscopy. The fluorescence intensity in the image of the bead under a cover slip tilted in the y-direction was increased by 1.5 times after correction by the device. Furthermore, the y- and z-widths of the imaged bead were reduced to 66% and 65%, respectively. On the other hand, for the imaged bead sucked into a glass capillary in the longitudinal x-direction, correction with the device increased the fluorescence intensity by 2.2 times compared to that of the aberrated image. In addition, the x-, y-, and z-widths of the bead image were reduced to 75%, 53%, and 40%, respectively. Our device successfully corrected several asymmetric aberrations to improve the fluorescent signal and spatial resolution, and might be useful for observing various biospecimens.

Lung Cancer and Chronic Obstructive Pulmonary Disease: Needs and Opportunities for Integrated Research

PubMed Central

Szabo, Eva; Croxton, Thomas L.; Shapiro, Steven D.; Dubinett, Steven M.

2009-01-01

Lung cancer and chronic obstructive pulmonary disease (COPD) are leading causes of morbidity and mortality in the United States and worldwide. They share a common environmental risk factor in cigarette smoke exposure and a genetic predisposition represented by the incidence of these diseases in only a fraction of smokers. The presence of COPD increases the risk of lung cancer up to 4.5-fold. To investigate commonalities in disease mechanisms and perspectives for disease chemoprevention, the National Heart, Lung, and Blood Institute (NHLBI) and the National Cancer Institute (NCI) held a workshop. The participants identified four research objectives: 1) clarify common epidemiological characteristics of lung cancer and COPD; 2) identify shared genetic and epigenetic risk factors; 3) identify and validate biomarkers, molecular signatures, and imaging-derived measurements of each disease; and 4) determine common and disparate pathogenetic mechanisms. These objectives should be reached via four research approaches: 1) identify, publicize, and enable the evaluation and analysis of existing datasets and repositories of biospecimens; 2) obtain phenotypic and outcome data and biospecimens from large studies of subjects with and/or at risk for COPD and lung cancer; 3) develop and use animal and other preclinical models to investigate pathogenetic links between the diseases; and 4) conduct early-phase clinical trials of potential chemopreventive agents. To foster much needed research interactions, two final recommendations were made by the participants: 1) incorporate baseline phenotyping and outcome measures for both diseases in future longitudinal studies of each disease and 2) expand collaborative efforts between the NCI and NHLBI. PMID:19351920

Hepatocellular carcinoma Early Detection Strategy study — EDRN Public Portal

Cancer.gov

Part 1: The first part of this study is to conduct follow-up for patients that were enrolled in the EDRN Phase 2 Validation Study called DCP (13). For this part of the study, four groups are defined as follows: a) Vanguard Controls are cirrhotic controls, from the Phase 2 trial that have not developed HCC and sign a new consent form for HEDS participation. These patients will be followed for a minimum of an additional 24 months and have biospecimens collected every 6 months. b) Vanguard Interval Controls are cirrhotic controls, from the Phase 2 trial that have not developed HCC and do not sign a new consent form for HEDS participation. This group will have outcome data abstracted from their medical records. c) Vanguard Interval Cases are cirrhotic controls from the Phase 2 trial that developed HCC after completion of the Phase 2 trial but prior to the current study. This group will have outcome data abstracted from their medical records. d) Vanguard Cases are HCC cases from the Phase 2 trial. This group will have outcome data abstracted from their medical records. Part 2: New Controls - The second part of this study is the new accrual of cirrhotic controls at the seven participating sites. These patients will be followed for a minimum of 24 months and have biospecimens collected every 6 months. Data will be collected every 6 months: ultrasound, AFP, liver function tests, complete blood counts, MELD scores and any changes in medical history, personal cancer history and family cancer history.

Biomarker of Long-Chain n-3 Fatty Acid Intake and Breast Cancer: Accumulative Evidence from an Updated Meta-Analysis of Epidemiological Studies.

PubMed

Yang, Bo; Ren, Xiao L; Wang, Zhi Y; Wang, Liang; Zhao, Feng; Guo, Xiao J; Li, Duo

2018-06-14

We aimed to summarize the up-to-date epidemiology evidence on biomarkers of long-chain (LC) n-3 fatty acid (FA) intake in relation to breast cancer (BC). Epidemiology studies determining FA levels in biospecimen (circulating blood or adipose tissue (AT)) were identified from PubMed, EMBASE, and Cochrane Library databases until March 2018. Multivariate-adjusted risk ratios (RRs) with 95% confidence intervals (CIs) were pooled using a random-effect model. Difference in biospecimen proportions of LC n-3 FA between BC cases and non-cases were analyzed as a standardized mean difference (SMD). Thirteen cohort and eleven case-control studies were eligible for the present meta-analysis. The estimated SMD was -0.14 (95% CI: -0.27, -0.11) for LC n-3 FA and -0.27 (95% CI: -0.42, -0.11) for LC n-3/n-6 FA ratio. When comparing the top tertiles with the bottom baseline levels, circulating LC n-3 FA was significantly associated with a lower risk of BC (RR: 0.84, 95% CI: 0.74, 0.96), but not AT (RR: 1.02, 95% CI: 0.70, 1.48). Significant inverse dose-response associations were observed for each 1% increment of circulating 20:5n-3 and 22:6n-3. This meta-analysis highlights that circulating LC n-3 FA as a biomarker of intake may be an independent predictive factor for BC, especially 20:5n-3 and 22:6n-3.

The NINDS Parkinson's disease biomarkers program: The Ninds Parkinson's Disease Biomarkers Program

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rosenthal, Liana S.; Drake, Daniel; Alcalay, Roy N.

Background: Neuroprotection for Parkinson Disease (PD) remains elusive. Biomarkers hold the promise of removing roadblocks to therapy development. The National Institute of Neurological Disorders and Stroke (NINDS) has therefore established the Parkinson’s Disease Biomarkers Program (PDBP) to promote discovery of biomarkers for use in phase II-III clinical trials in PD. Methods: The PDBP facilitates biomarker development to improve neuroprotective clinical trial design, essential for advancing therapeutics for PD. To date, eleven consortium projects in the PDBP are focused on the development of clinical and laboratory-based PD biomarkers for diagnosis, progression tracking, and/or the prediction of prognosis. Seven of these projectsmore » also provide detailed longitudinal data and biospecimens from PD patients and controls, as a resource for all PD researchers. Standardized operating procedures and pooled reference samples have been created in order to allow cross-project comparisons and assessment of batch effects. A web-based Data Management Resource facilitates rapid sharing of data and biosamples across the entire PD research community for additional biomarker projects. Results: Here we describe the PDBP, highlight standard operating procedures for the collection of biospecimens and data, and provide an interim report with quality control analysis on the first 1082 participants and 1033 samples with quality control analysis collected as of October 2014. Conclusions: By making samples and data available to academics and industry, encouraging the adoption of existing standards, and providing a resource which complements existing programs, the PDBP will accelerate the pace of PD biomarker research, with the goal of improving diagnostic methods and treatment.« less

The LEGACY Girls Study: Growth and Development in the Context of Breast Cancer Family History.

PubMed

John, Esther M; Terry, Mary Beth; Keegan, Theresa H M; Bradbury, Angela R; Knight, Julia A; Chung, Wendy K; Frost, Caren J; Lilge, Lothar; Patrick-Miller, Linda; Schwartz, Lisa A; Whittemore, Alice S; Buys, Saundra S; Daly, Mary B; Andrulis, Irene L

2016-05-01

Although the timing of pubertal milestones has been associated with breast cancer risk, few studies of girls' development include girls at increased breast cancer risk due to their family history. The Lessons in Epidemiology and Genetics of Adult Cancer from Youth (LEGACY) Girls Study was initiated in 2011 in the USA and Canada to assess the relation between early life exposures and intermediate markers of breast cancer risk (e.g., pubertal development, breast tissue characteristics) and to investigate psychosocial well being and health behaviors in the context of family history. We describe the methods used to establish and follow a cohort of 1,040 girls ages 6-13 years at baseline, half with a breast cancer family history, and the collection of questionnaire data (family history, early life exposures, growth and development, psychosocial and behavioral), anthropometry, biospecimens, and breast tissue characteristics using optical spectroscopy. During this initial 5-year phase of the study, follow-up visits are conducted every 6 months for repeated data and biospecimen collection. Participation in baseline components was high (98% for urine, 97.5% for blood or saliva, and 98% for anthropometry). At enrollment, 77% of girls were premenarcheal and 49% were at breast Tanner stage T1. This study design allows thorough examination of events affecting girls' growth and development and how they differ across the spectrum of breast cancer risk. A better understanding of early life breast cancer risk factors will be essential to enhance prevention across the lifespan for those with and without a family history of the disease.

The Ontario Birth Study: A prospective pregnancy cohort study integrating perinatal research into clinical care.

PubMed

Anderson, Laura N; Knight, Julia A; Hung, Rayjean J; Hewko, Sheryl L; Seeto, Ryan A; Martin, Mary-Jean; Fleming, Alison; Maguire, Jonathon L; Matthews, Stephen G; Murphy, Kellie E; Okun, Nan; Jenkins, Jennifer M; Lye, Stephen J; Bocking, Alan

2018-05-01

Pregnancy and early childhood represent critical periods that impact health throughout the life-course. The Ontario Birth Study (OBS) is a pregnancy cohort study designed as a platform for research on pregnancy complications, maternal and infant health, and the developmental origins of health and disease. Pregnant women <17 weeks gestational age were recruited between 2013 and 2015 from antenatal clinics at Mount Sinai Hospital, Toronto, Canada. Life style and diet questionnaires, biospecimens, and clinical data were collected throughout the pregnancy and postpartum period at the time of clinical care. The OBS was integrated into clinical care to reduce participant burden, improve efficiency, and increase research potential. There were 3181 eligible women approached for recruitment and 1374 (43%) participated in the study. Among the 1374 participants, 1272 (93%) delivered a liveborn infant and were followed to 6-10 weeks postpartum. Of the 1272 women who completed the study, 98% had at least one pregnancy blood sample collected, 97% had vaginal swabs collected, 90% completed the prenatal life style questionnaires, and 78% completed the Diet History Questionnaire. Most women (88%) were ≥30 years of age, 55% had no previous children, 24% were overweight or obese pre-pregnancy and 78% of parents had postsecondary education. Most pregnancies were singleton (3% twins), 34% delivered by caesarean section, and 6% preterm (<37 weeks gestation). The OBS is a contemporary cohort with detailed data including banked biospecimens for studies of pregnancy health and the gene-environment interactions that establish developmental trajectories to health, learning, and social functioning. © 2018 John Wiley & Sons Ltd.

Religiousness, Spirituality, and Salivary Cortisol in Breast Cancer Survivorship: A Pilot Study.

PubMed

Hulett, Jennifer M; Armer, Jane M; Leary, Emily; Stewart, Bob R; McDaniel, Roxanne; Smith, Kandis; Millspaugh, Rami; Millspaugh, Joshua

Psychoneuroimmunological theory suggests a physiological relationship exists between stress, psychosocial-behavioral factors, and neuroendocrine-immune outcomes; however, evidence has been limited. The primary aim of this pilot study was to determine feasibility and acceptability of a salivary cortisol self-collection protocol with a mail-back option for breast cancer survivors. A secondary aim was to examine relationships between religiousness/spirituality (R/S), perceptions of health, and diurnal salivary cortisol (DSC) as a proxy measure for neuroendocrine activity. This was an observational, cross-sectional study. Participants completed measures of R/S, perceptions of health, demographics, and DSC. The sample was composed of female breast cancer survivors (n = 41). Self-collection of DSC using a mail-back option was feasible; validity of mailed salivary cortisol biospecimens was established. Positive spiritual beliefs were the only R/S variable associated with the peak cortisol awakening response (rs = 0.34, P = .03). Poorer physical health was inversely associated with positive spiritual experiences and private religious practices. Poorer mental health was inversely associated with spiritual coping and negative spiritual experiences. Feasibility, validity, and acceptability of self-collected SDC biospecimens with an optional mail-back protocol (at moderate temperatures) were demonstrated. Positive spiritual beliefs were associated with neuroendocrine-mediated peak cortisol awakening response activity; however, additional research is recommended. Objective measures of DSC sampling that include enough collection time points to assess DSC parameters would increase the rigor of future DSC measurement. Breast cancer survivors may benefit from nursing care that includes spiritual assessment and therapeutic conversations that support positive spiritual beliefs.

The LEGACY Girls Study: Growth and development in the context of breast cancer family history

PubMed Central

John, Esther M.; Terry, Mary Beth; Keegan, Theresa H.M.; Bradbury, Angela R.; Knight, Julia A.; Chung, Wendy K.; Frost, Caren J.; Lilge, Lothar; Patrick-Miller, Linda; Schwartz, Lisa A.; Whittemore, Alice S.; Buys, Saundra S.; Daly, Mary B.; Andrulis, Irene L.

2017-01-01

Background Although the timing of pubertal milestones has been associated with breast cancer risk, few studies of girls’ development include girls at increased breast cancer risk due to their family history. Methods The LEGACY (Lessons in Epidemiology and Genetics of Adult Cancer from Youth) Girls Study was initiated in 2011 in the USA and Canada to assess the relation between early-life exposures and intermediate markers of breast cancer risk (e.g., pubertal development, breast tissue characteristics) and to investigate psychosocial well-being and health behaviors in the context of family history. We describe the methods used to establish and follow a cohort of 1,040 girls ages 6–13 years at baseline, half with a breast cancer family history, and the collection of questionnaire data (family history, early-life exposures, growth and development, psychosocial and behavioral), anthropometry, biospecimens, and breast tissue characteristics using optical spectroscopy. Results During this initial 5-year phase of the study, follow-up visits are conducted every six months for repeated data and biospecimen collection. Participation in baseline components was high (98% for urine, 97.5% for blood or saliva, and 98% for anthropometry). At enrollment, 77% of girls were pre-menarcheal and 49% were at breast Tanner stage T1. Conclusions This study design allows thorough examination of events affecting girls’ growth and development and how they differ across the spectrum of breast cancer risk. A better understanding of early-life breast cancer risk factors will be essential to enhance prevention across the lifespan for those with and without a family history of the disease. PMID:26829160

Qualitative study of knowledge and attitudes to biobanking among lay persons in Nigeria.

PubMed

Igbe, Michael A; Adebamowo, Clement A

2012-10-16

Interest in biobanking for collection of specimens for non-communicable diseases research has grown in recent times. This paper explores the perspectives of Nigerians on donation of specimen for the biobanking research. We conducted 16 Focus Group Discussions (FGD) with individuals from different ethnic, age and socio-economic groups in Kano (North), Enugu (Southeast), Oyo States (Southwest) and Abuja, the Federal Capital Territory (Central) of Nigeria. We used topic guides and prompt statements to explore the knowledge and understanding of interviewees to general issues about biobanking of biospecimens, their use and specifically about role of biobanking in non-communicable diseases research. A total of 123 individuals participated in 16 focus group discussions in 2011. Our participants had limited knowledge of the concept of biobanking but accepted it once they were educated about it and saw it as a worthwhile venture. Half of our study participants supported use of broad consent, a quarter supported restricted consent while the remaining quarter were in favour of tiered consent. Most discussants support shipment of their samples to other countries for further research, but they prefer those collaborations to be done only with competent, ethical researchers and they would like to receive feedback about such projects. The majority preferred health care as a benefit from participation, particularly for any unexpected condition that may be discovered during the course of the research instead of financial compensation. Participants emphasized the need to ensure that donated samples were not used for research that contradicts their religious beliefs. Our study demonstrates that our participants accepted biobanking once they understand it but there were different attitudes to elements of biobanking such as type of consent. Our study highlights the need to carefully document population attitudes to elements of modern scientific research and the consenting process.

The Cryoprotectant Effect of Polysaccharides from Plants and Microalgae on Human White Blood Cells.

PubMed

Khudyakov, Andrey Nikolayevich; Polezhaeva, Tatyana Vitalyevna; Zaitseva, Oksana Olegovna; Gűnter, Elena Aleksandrovna; Solomina, Olga Nurzadinovna; Popeyko, Oksana Viktorovna; Shubakov, Anatolyi Aleksandrovich; Vetoshkin, Konstantin Aleksandrovich

2015-08-01

The use of carbohydrates as cryoprotectants is increasing. In this study the effects of incorporating polysaccharides extracted from plants and microalgae originating in northern Russia, into cryoprotectant solutions used to preserve human white blood cells were investigated. Cells in the presence of the polysaccharides were cooled to either -40°C or -80°C, using a two-step cooling process. The morphological and functional indicators of the cryopreserved leukocytes were assessed by light microscopy. When combined with glycerol, the pectin-polysaccharides Lemnan from common duckweed (Lemna minor L.) and Comaruman from marsh cinquefoil (Comarum palustre L), were capable of lowering the freezing point of the cryoprotectant solution and helped to preserve the integrity of the human white blood cell membranes at temperatures below zero. In addition, the increase in phagocytic activity of neutrophils was confirmed. In the context of the contemporary search for effective cell cryoprotectants, the results of this research demonstrate that the cryopreservation of biospecimens in a polysaccharide environment is a promising trend in applied medicine, which can be considered an alternative to traditional cryogenic nitrogen techniques.

A Medical Center Network for Optimized Lung Cancer Biospecimen Banking

DTIC Science & Technology

2017-10-01

10 7 4.903 10 8 0.300 3 No - Quit Smoking 75 AR Asbestos, Coal mining, Second-hand smoke Asbestos, Coal mining, Second- hand smoke S0004 Squamous...Cell Carcinoma Stage IIB Y N 1.942 100 75 5 10 7 4.903 10 8 0.300 3 No - Quit Smoking 75 AR Asbestos, Coal mining, Second-hand smoke Asbestos... Coal mining, Second- hand smoke S0006 Adenocarcinoma Stage IB Y N 0.38 80 40 0 2 3 0.310 2 4 No - Quit Smoking 37 None None S0007 Squamous Cell

A Medical Center Network for Optimized Lung Cancer Biospecimen Banking

DTIC Science & Technology

2015-10-01

Y N 1.942 20 80 5 10 7 4.903 10 8 0.300 3 No - Quit Smoking 75 AR Asbestos , Coal mining, Second- hand smoke Asbestos , Coal mining, Second...hand smoke S0004 Squamous Cell Carcinoma Stage IIB Y N 1.942 100 75 5 10 7 4.903 10 8 0.300 3 No - Quit Smoking 75 AR Asbestos , Coal mining, Second...hand smoke Asbestos , Coal mining, Second- hand smoke S0006 Adenocarcinoma Stage IB Y N 0.38 80 40 0 2 3 0.310 2 4 No - Quit Smoking 37 None None

TCGA2BED: extracting, extending, integrating, and querying The Cancer Genome Atlas.

PubMed

Cumbo, Fabio; Fiscon, Giulia; Ceri, Stefano; Masseroli, Marco; Weitschek, Emanuel

2017-01-03

Data extraction and integration methods are becoming essential to effectively access and take advantage of the huge amounts of heterogeneous genomics and clinical data increasingly available. In this work, we focus on The Cancer Genome Atlas, a comprehensive archive of tumoral data containing the results of high-throughout experiments, mainly Next Generation Sequencing, for more than 30 cancer types. We propose TCGA2BED a software tool to search and retrieve TCGA data, and convert them in the structured BED format for their seamless use and integration. Additionally, it supports the conversion in CSV, GTF, JSON, and XML standard formats. Furthermore, TCGA2BED extends TCGA data with information extracted from other genomic databases (i.e., NCBI Entrez Gene, HGNC, UCSC, and miRBase). We also provide and maintain an automatically updated data repository with publicly available Copy Number Variation, DNA-methylation, DNA-seq, miRNA-seq, and RNA-seq (V1,V2) experimental data of TCGA converted into the BED format, and their associated clinical and biospecimen meta data in attribute-value text format. The availability of the valuable TCGA data in BED format reduces the time spent in taking advantage of them: it is possible to efficiently and effectively deal with huge amounts of cancer genomic data integratively, and to search, retrieve and extend them with additional information. The BED format facilitates the investigators allowing several knowledge discovery analyses on all tumor types in TCGA with the final aim of understanding pathological mechanisms and aiding cancer treatments.

A widefield fluorescence microscope with a linear image sensor for image cytometry of biospecimens: Considerations for image quality optimization

NASA Astrophysics Data System (ADS)

Hutcheson, Joshua A.; Majid, Aneeka A.; Powless, Amy J.; Muldoon, Timothy J.

2015-09-01

Linear image sensors have been widely used in numerous research and industry applications to provide continuous imaging of moving objects. Here, we present a widefield fluorescence microscope with a linear image sensor used to image translating objects for image cytometry. First, a calibration curve was characterized for a custom microfluidic chamber over a span of volumetric pump rates. Image data were also acquired using 15 μm fluorescent polystyrene spheres on a slide with a motorized translation stage in order to match linear translation speed with line exposure periods to preserve the image aspect ratio. Aspect ratios were then calculated after imaging to ensure quality control of image data. Fluorescent beads were imaged in suspension flowing through the microfluidics chamber being pumped by a mechanical syringe pump at 16 μl min-1 with a line exposure period of 150 μs. The line period was selected to acquire images of fluorescent beads with a 40 dB signal-to-background ratio. A motorized translation stage was then used to transport conventional glass slides of stained cellular biospecimens. Whole blood collected from healthy volunteers was stained with 0.02% (w/v) proflavine hemisulfate was imaged to highlight leukocyte morphology with a 1.56 mm × 1.28 mm field of view (1540 ms total acquisition time). Oral squamous cells were also collected from healthy volunteers and stained with 0.01% (w/v) proflavine hemisulfate to demonstrate quantifiable subcellular features and an average nuclear to cytoplasmic ratio of 0.03 (n = 75), with a resolution of 0.31 μm pixels-1.

The Childhood Leukemia International Consortium

PubMed Central

Metayer, Catherine; Milne, Elizabeth; Clavel, Jacqueline; Infante-Rivard, Claire; Petridou, Eleni; Taylor, Malcolm; Schüz, Joachim; Spector, Logan G.; Dockerty, John D.; Magnani, Corrado; Pombo-de-Oliveira, Maria S.; Sinnett, Daniel; Murphy, Michael; Roman, Eve; Monge, Patricia; Ezzat, Sameera; Mueller, Beth A.; Scheurer, Michael E.; Armstrong, Bruce K.; Birch, Jill; Kaatsch, Peter; Koifman, Sergio; Lightfoot, Tracy; Bhatti, Parveen; Bondy, Melissa L.; Rudant, Jérémie; O’Neill, Kate; Miligi, Lucia; Dessypris, Nick; Kang, Alice Y.; Buffler, Patricia A.

2013-01-01

Background Acute leukemia is the most common cancer in children under 15 years of age; 80% are acute lymphoblastic leukemia (ALL) and 17% are acute myeloid leukemia (AML). Childhood leukemia shows further diversity based on cytogenetic and molecular characteristics, which may relate to distinct etiologies. Case–control studies conducted worldwide, particularly of ALL, have collected a wealth of data on potential risk factors and in some studies, biospecimens. There is growing evidence for the role of infectious/immunologic factors, fetal growth, and several environmental factors in the etiology of childhood ALL. The risk of childhood leukemia, like other complex diseases, is likely to be influenced both by independent and interactive effects of genes and environmental exposures. While some studies have analyzed the role of genetic variants, few have been sufficiently powered to investigate gene–environment interactions. Objectives The Childhood Leukemia International Consortium (CLIC) was established in 2007 to promote investigations of rarer exposures, gene–environment interactions and subtype-specific associations through the pooling of data from independent studies. Methods By September 2012, CLIC included 22 studies (recruitment period: 1962–present) from 12 countries, totaling approximately 31 000 cases and 50 000 controls. Of these, 19 case–control studies have collected detailed epidemiologic data, and DNA samples have been collected from children and child–parent trios in 15 and 13 of these studies, respectively. Two registry-based studies and one study comprising hospital records routinely obtained at birth and/or diagnosis have limited interview data or biospecimens. Conclusions CLIC provides a unique opportunity to fill gaps in knowledge about the role of environmental and genetic risk factors, critical windows of exposure, the effects of gene–environment interactions and associations among specific leukemia subtypes in different ethnic groups. PMID:23403126

The biobank for the molecular classification of kidney disease: research translation and precision medicine in nephrology.

PubMed

Muruve, Daniel A; Mann, Michelle C; Chapman, Kevin; Wong, Josee F; Ravani, Pietro; Page, Stacey A; Benediktsson, Hallgrimur

2017-07-26

Advances in technology and the ability to interrogate disease pathogenesis using systems biology approaches are exploding. As exemplified by the substantial progress in the personalized diagnosis and treatment of cancer, the application of systems biology to enable precision medicine in other disciplines such as Nephrology is well underway. Infrastructure that permits the integration of clinical data, patient biospecimens and advanced technologies is required for institutions to contribute to, and benefit from research in molecular disease classification and to devise specific and patient-oriented treatments. We describe the establishment of the Biobank for the Molecular Classification of Kidney Disease (BMCKD) at the University of Calgary, Alberta, Canada. The BMCKD consists of a fully equipped wet laboratory, an information technology infrastructure, and a formal operational, ethical and legal framework for banking human biospecimens and storing clinical data. The BMCKD first consolidated a large retrospective cohort of kidney biopsy specimens to create a population-based renal pathology database and tissue inventory of glomerular and other kidney diseases. The BMCKD will continue to prospectively bank all kidney biopsies performed in Southern Alberta. The BMCKD is equipped to perform molecular, clinical and epidemiologic studies in renal pathology. The BMCKD also developed formal biobanking procedures for human specimens such as blood, urine and nucleic acids collected for basic and clinical research studies or for advanced diagnostic technologies in clinical care. The BMCKD is guided by standard operating procedures, an ethics framework and legal agreements with stakeholders that include researchers, data custodians and patients. The design and structure of the BMCKD permits its inclusion in a wide variety of research and clinical activities. The BMCKD is a core multidisciplinary facility that will bridge basic and clinical research and integrate precision medicine into renal pathology and nephrology.

Effect of multiple cycles of freeze-thawing on the RNA quality of lung cancer tissues.

PubMed

Yu, Keke; Xing, Jie; Zhang, Jie; Zhao, Ruiying; Zhang, Ye; Zhao, Lanxiang

2017-09-01

RNA degradation is a major problem in tissue banking. We explored the effect of thawing flash-frozen biospecimens on the quality and integrity of RNA for genetic testing as well as for other cancer research studies. The histological quality of the frozen tumor sections was evaluated by using hematoxylin and eosin staining. RNA extraction from 60 lung cancer tissue samples subjected to various freeze/thaw cycles was performed using the RNeasy Plus isolation kit. RNA integrity was assessed by using an Agilent bioanalyzer to obtain RNA integrity numbers (RIN). Furthermore, RNA from different groups was used for fluorescence Reverse transcription-polymerase chain reaction (RT-PCR) analysis of the echinoderm microtubule-associated protein-like 4 and anaplastic lymphoma kinase (EML4-ALK) fusion gene mutation to verify whether it can be used for research or clinical testing. Highly variable RIN values were observed among the samples, which showed no correlation with the number of freeze/thaw cycles conducted. However, after 3 freeze/thaw cycles (each thaw event lasted for 10 min), an increasing number of changes in peak intensity in RINs were observed. After 5 freeze/thaw cycles, RNA integrity decreased to approximately 35%. After 3 freeze/thaw cycles, the RNA could still be used for RT-PCR analysis of EML4-ALK fusion gene mutations; whereas those subjected to 5 freeze/thaw cycles could not. Limited (<3) freeze/thaw cycles did not adversely affect the quality of RNA extracted from tumor tissues and subsequent RT-PCR analysis. Our data could be utilized in the establishment of a standardized procedure for tissue biospecimen collection and storage.

A widefield fluorescence microscope with a linear image sensor for image cytometry of biospecimens: Considerations for image quality optimization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hutcheson, Joshua A.; Majid, Aneeka A.; Powless, Amy J.

Linear image sensors have been widely used in numerous research and industry applications to provide continuous imaging of moving objects. Here, we present a widefield fluorescence microscope with a linear image sensor used to image translating objects for image cytometry. First, a calibration curve was characterized for a custom microfluidic chamber over a span of volumetric pump rates. Image data were also acquired using 15 μm fluorescent polystyrene spheres on a slide with a motorized translation stage in order to match linear translation speed with line exposure periods to preserve the image aspect ratio. Aspect ratios were then calculated aftermore » imaging to ensure quality control of image data. Fluorescent beads were imaged in suspension flowing through the microfluidics chamber being pumped by a mechanical syringe pump at 16 μl min{sup −1} with a line exposure period of 150 μs. The line period was selected to acquire images of fluorescent beads with a 40 dB signal-to-background ratio. A motorized translation stage was then used to transport conventional glass slides of stained cellular biospecimens. Whole blood collected from healthy volunteers was stained with 0.02% (w/v) proflavine hemisulfate was imaged to highlight leukocyte morphology with a 1.56 mm × 1.28 mm field of view (1540 ms total acquisition time). Oral squamous cells were also collected from healthy volunteers and stained with 0.01% (w/v) proflavine hemisulfate to demonstrate quantifiable subcellular features and an average nuclear to cytoplasmic ratio of 0.03 (n = 75), with a resolution of 0.31 μm pixels{sup −1}.« less

Comparative biomarker expression and RNA integrity in biospecimens derived from radical retropubic and robot-assisted laparoscopic prostatectomies.

PubMed

Ricciardelli, Carmela; Bianco-Miotto, Tina; Jindal, Shalini; Dodd, Thomas J; Cohen, Penelope A; Marshall, Villis R; Sutherland, Peter D; Samaratunga, Hemamali; Kench, James G; Dong, Ying; Wang, Hong; Clements, Judith A; Risbridger, Gail P; Sutherland, Robert L; Tilley, Wayne D; Horsfall, David J

2010-07-01

Knowledge of preanalytic conditions that biospecimens are subjected to is critically important because novel surgical procedures, tissue sampling, handling, and storage might affect biomarker expression or invalidate tissue samples as analytes for some technologies. We investigated differences in RNA quality, gene expression by quantitative real-time PCR, and immunoreactive protein expression of selected prostate cancer biomarkers between tissues from retropubic radical prostatectomy (RRP) and robot-assisted laparoscopic prostatectomy (RALP). Sections of tissue microarray of 23 RALP and 22 RRP samples were stained with antibodies to androgen receptor (AR) and prostate-specific antigen (PSA) as intersite controls, and 14 other candidate biomarkers of research interest to three laboratories within the Australian Prostate Cancer BioResource tissue banking network. Quantitative real-time PCR was done for AR, PSA (KLK3), KLK2, KLK4, and HIF1A on RNA extracted from five RALP and five RRP frozen tissue cores. No histologic differences were observed between RALP and RRP tissue. Biomarker staining grouped these samples into those with increased (PSA, CK8/18, CKHMW, KLK4), decreased (KLK2, KLK14), or no change in expression (AR, ghrelin, Ki67, PCNA, VEGF-C, PAR2, YB1, p63, versican, and chondroitin 0-sulfate) in RALP compared with RRP tissue. No difference in RNA quality or gene expression was detected between RALP and RRP tissue. Changes in biomarker expression between RALP and RRP tissue exist at the immunoreactive protein level, but the etiology is unclear. Future studies should account for changes in biomarker expression when using RALP tissues, and mixed cohorts of RALP and RRP tissue should be avoided.

Genetic Basis of Autoantibody Positive and Negative Rheumatoid Arthritis Risk in a Multi-ethnic Cohort Derived from Electronic Health Records

PubMed Central

Kurreeman, Fina; Liao, Katherine; Chibnik, Lori; Hickey, Brendan; Stahl, Eli; Gainer, Vivian; Li, Gang; Bry, Lynn; Mahan, Scott; Ardlie, Kristin; Thomson, Brian; Szolovits, Peter; Churchill, Susanne; Murphy, Shawn N.; Cai, Tianxi; Raychaudhuri, Soumya; Kohane, Isaac; Karlson, Elizabeth; Plenge, Robert M.

2011-01-01

Discovering and following up on genetic associations with complex phenotypes require large patient cohorts. This is particularly true for patient cohorts of diverse ancestry and clinically relevant subsets of disease. The ability to mine the electronic health records (EHRs) of patients followed as part of routine clinical care provides a potential opportunity to efficiently identify affected cases and unaffected controls for appropriate-sized genetic studies. Here, we demonstrate proof-of-concept that it is possible to use EHR data linked with biospecimens to establish a multi-ethnic case-control cohort for genetic research of a complex disease, rheumatoid arthritis (RA). In 1,515 EHR-derived RA cases and 1,480 controls matched for both genetic ancestry and disease-specific autoantibodies (anti-citrullinated protein antibodies [ACPA]), we demonstrate that the odds ratios and aggregate genetic risk score (GRS) of known RA risk alleles measured in individuals of European ancestry within our EHR cohort are nearly identical to those derived from a genome-wide association study (GWAS) of 5,539 autoantibody-positive RA cases and 20,169 controls. We extend this approach to other ethnic groups and identify a large overlap in the GRS among individuals of European, African, East Asian, and Hispanic ancestry. We also demonstrate that the distribution of a GRS based on 28 non-HLA risk alleles in ACPA+ cases partially overlaps with ACPA- subgroup of RA cases. Our study demonstrates that the genetic basis of rheumatoid arthritis risk is similar among cases of diverse ancestry divided into subsets based on ACPA status and emphasizes the utility of linking EHR clinical data with biospecimens for genetic studies. PMID:21211616

Nursing and genetic biobanks.

PubMed

Sanner, Jennifer E; Yu, Erica; Udtha, Malini; Williams, Pamela Holtzclaw

2013-12-01

Biobanks function as vital components in genetic research, which often requires large disease-based or population-based biospecimens and clinical data to study complex or rare diseases. Genetic biobanks aim to provide resources for translational research focusing on rapidly moving scientific findings from the laboratory into health care practice. The nursing profession must evolve as genetic biobanking practices advance. Nursing involvement in genetic biobanking practices comes with a distinct set of educational, ethical, and practice competencies. In response to these growing competency standards, nursing science developed a conceptual framework and continues to study ethical considerations to guide genetic biobanking initiatives. Copyright © 2013 Elsevier Inc. All rights reserved.

Collaboration to Accelerate Proteogenomics Cancer Care: The Department of Veterans Affairs, Department of Defense, and the National Cancer Institute's Applied Proteogenomics OrganizationaL Learning and Outcomes (APOLLO) Network.

PubMed

Fiore, L D; Rodriguez, H; Shriver, C D

2017-05-01

A tri-federal initiative arising out of the Cancer Moonshot has resulted in the formation of a program to utilize advanced genomic and proteomic expression platforms on high-quality human biospecimens in near-real-time in order to identify potentially actionable therapeutic molecular targets, study the relationship of molecular findings to cancer treatment outcomes, and accelerate novel clinical trials with biomarkers of prognostic and predictive value. © 2017 Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

Biobanking human endometrial tissue and blood specimens: standard operating procedure and importance to reproductive biology research and diagnostic development.

PubMed

Sheldon, Elizabeth; Vo, Kim Chi; McIntire, Ramsey A; Aghajanova, Lusine; Zelenko, Zara; Irwin, Juan C; Giudice, Linda C

2011-05-01

To develop a standard operating procedure (SOP) for collection, transport, storage of human endometrial tissue and blood samples, subject and specimen annotation, and establishing sample priorities. The SOP synthesizes sound scientific procedures, the literature on ischemia research, sample collection and gene expression profiling, good laboratory practices, and the authors' experience of workflow and sample quality. The National Institutes of Health, University of California, San Francisco, Human Endometrial Tissue and DNA Bank. Women undergoing endometrial biopsy or hysterectomy for nonmalignant indications. Collecting, processing, storing, distributing endometrial tissue and blood samples under approved institutional review board protocols and written informed consent from participating subjects. Standard operating procedure. The SOP addresses rigorous and consistent subject annotation, specimen processing and characterization, strict regulatory compliance, and a reference for researchers to track collection and storage times that may influence their research. The comprehensive and systematic approach to the procurement of human blood and endometrial tissue in this SOP ensures the high quality, reliability, and scientific usefulness of biospecimens made available to investigators by the National Institutes of Health, University of California, San Francisco, Human Endometrial Tissue and DNA Bank. The detail and perspective in this SOP also provides a blueprint for implementation of similar collection programs at other institutions. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

World Endometriosis Research Foundation Endometriosis Phenome and Biobanking Harmonisation Project: IV. Tissue collection, processing, and storage in endometriosis research

PubMed Central

Fassbender, Amelie; Rahmioglu, Nilufer; Vitonis, Allison F.; Viganò, Paola; Giudice, Linda C.; D’Hooghe, Thomas M.; Hummelshoj, Lone; Adamson, G. David; Becker, Christian M.; Missmer, Stacey A.; Zondervan, Krina T.; Adamson, G.D.; Allaire, C.; Anchan, R.; Becker, C.M.; Bedaiwy, M.A.; Buck Louis, G.M.; Calhaz-Jorge, C.; Chwalisz, K.; D'Hooghe, T.M.; Fassbender, A.; Faustmann, T.; Fazleabas, A.T.; Flores, I.; Forman, A.; Fraser, I.; Giudice, L.C.; Gotte, M.; Gregersen, P.; Guo, S.-W.; Harada, T.; Hartwell, D.; Horne, A.W.; Hull, M.L.; Hummelshoj, L.; Ibrahim, M.G.; Kiesel, L.; Laufer, M.R.; Machens, K.; Mechsner, S.; Missmer, S.A.; Montgomery, G.W.; Nap, A.; Nyegaard, M.; Osteen, K.G.; Petta, C.A.; Rahmioglu, N.; Renner, S.P.; Riedlinger, J.; Roehrich, S.; Rogers, P.A.; Rombauts, L.; Salumets, A.; Saridogan, E.; Seckin, T.; Stratton, P.; Sharpe-Timms, K.L.; Tworoger, S.; Vigano, P.; Vincent, K.; Vitonis, A.F.; Wienhues-Thelen, U.-H.; Yeung, P.P.; Yong, P.; Zondervan, K.T.

2014-01-01

Objective To harmonize standard operating procedures (SOPs) and standardize the recording of associated data for collection, processing, and storage of human tissues relevant to endometriosis. Design An international collaboration involving 34 clinical/academic centers and three industry collaborators from 16 countries on five continents. Setting In 2013, two workshops were conducted followed by global consultation, bringing together 54 leaders in endometriosis research and sample processing from around the world. Patient(s) None. Intervention(s) Consensus SOPs were based on: 1) systematic comparison of SOPs from 24 global centers collecting tissue samples from women with and without endometriosis on a medium or large scale (publication on >100 cases); 2) literature evidence where available, or consultation with laboratory experts otherwise; and 3) several global consultation rounds. Main Outcome Measure(s) Standard recommended and minimum required SOPs for tissue collection, processing, and storage in endometriosis research. Result(s) We developed “recommended standard” and “minimum required” SOPs for the collection, processing, and storage of ectopic and eutopic endometrium, peritoneum, and myometrium, and a biospecimen data collection form necessary for interpretation of sample-derived results. Conclusion(s) The EPHect SOPs allow endometriosis research centers to decrease variability in tissue-based results, facilitating between-center comparisons and collaborations. The procedures are also relevant to research into other gynecologic conditions involving endometrium, myometrium, and peritoneum. The consensus SOPs are based on the best available evidence; areas with limited evidence are identified as requiring further pilot studies. The SOPs will be reviewed based on investigator feedback and through systematic triannual follow-up. Updated versions will be made available at: http://endometriosisfoundation.org/ephect. PMID:25256928

The Biobanking Analysis Resource Catalogue (BARCdb): a new research tool for the analysis of biobank samples

PubMed Central

Galli, Joakim; Oelrich, Johan; Taussig, Michael J.; Andreasson, Ulrika; Ortega-Paino, Eva; Landegren, Ulf

2015-01-01

We report the development of a new database of technology services and products for analysis of biobank samples in biomedical research. BARCdb, the Biobanking Analysis Resource Catalogue (http://www.barcdb.org), is a freely available web resource, listing expertise and molecular resource capabilities of research centres and biotechnology companies. The database is designed for researchers who require information on how to make best use of valuable biospecimens from biobanks and other sample collections, focusing on the choice of analytical techniques and the demands they make on the type of samples, pre-analytical sample preparation and amounts needed. BARCdb has been developed as part of the Swedish biobanking infrastructure (BBMRI.se), but now welcomes submissions from service providers throughout Europe. BARCdb can help match resource providers with potential users, stimulating transnational collaborations and ensuring compatibility of results from different labs. It can promote a more optimal use of European resources in general, both with respect to standard and more experimental technologies, as well as for valuable biobank samples. This article describes how information on service and reagent providers of relevant technologies is made available on BARCdb, and how this resource may contribute to strengthening biomedical research in academia and in the biotechnology and pharmaceutical industries. PMID:25336620

Implementation of Electronic Consent at a Biobank: An Opportunity for Precision Medicine Research

PubMed Central

Boutin, Natalie T.; Mathieu, Kathleen; Hoffnagle, Alison G.; Allen, Nicole L.; Castro, Victor M.; Morash, Megan; O’Rourke, P. Pearl; Hohmann, Elizabeth L.; Herring, Neil; Bry, Lynn; Slaugenhaupt, Susan A.; Karlson, Elizabeth W.; Weiss, Scott T.; Smoller, Jordan W.

2016-01-01

The purpose of this study is to characterize the potential benefits and challenges of electronic informed consent (eIC) as a strategy for rapidly expanding the reach of large biobanks while reducing costs and potentially enhancing participant engagement. The Partners HealthCare Biobank (Partners Biobank) implemented eIC tools and processes to complement traditional recruitment strategies in June 2014. Since then, the Partners Biobank has rigorously collected and tracked a variety of metrics relating to this novel recruitment method. From June 2014 through January 2016, the Partners Biobank sent email invitations to 184,387 patients at Massachusetts General Hospital and Brigham and Women’s Hospital. During the same time period, 7078 patients provided their consent via eIC. The rate of consent of emailed patients was 3.5%, and the rate of consent of patients who log into the eIC website at Partners Biobank was 30%. Banking of biospecimens linked to electronic health records has become a critical element of genomic research and a foundation for the NIH’s Precision Medicine Initiative (PMI). eIC is a feasible and potentially game-changing strategy for these large research studies that depend on patient recruitment. PMID:27294961

Involving citizens in the ethics of biobank research: informing institutional policy through structured public deliberation.

PubMed

O'Doherty, Kieran C; Hawkins, Alice K; Burgess, Michael M

2012-11-01

This paper reports on the design, implementation, and results of a structured public deliberation on human tissue biobanking conducted in Vancouver, Canada, in 2009. This study builds on previous work on the use of deliberative democratic principles and methods to engage publics on the social and ethical implications of human tissue biobanking. In a significant refinement of methods, we focus on providing public input to institutional practice and governance of biobanks using a tailored workbook structure to guide participants' discussion. Our focus is on the local context and practices of a particular institution, the BC BioLibrary. However, elements of both the methodological innovations and the ethical guidance implied by our findings are generalisable for biobanking internationally. Recommendations from the deliberative forum include issues of informed consent, privacy protections, collection of biospecimens, governance of biobanks, and how to manage the process of introduction between biobanks and potential donors. Notable findings include public support for research use of anonymised un-consented tissue samples when these come from archived collections, but lack of support when they are collected prospectively. Copyright © 2012 Elsevier Ltd. All rights reserved.

Precision Medicine for Advanced Pancreas Cancer: The Individualized Molecular Pancreatic Cancer Therapy (IMPaCT) Trial.

PubMed

Chantrill, Lorraine A; Nagrial, Adnan M; Watson, Clare; Johns, Amber L; Martyn-Smith, Mona; Simpson, Skye; Mead, Scott; Jones, Marc D; Samra, Jaswinder S; Gill, Anthony J; Watson, Nicole; Chin, Venessa T; Humphris, Jeremy L; Chou, Angela; Brown, Belinda; Morey, Adrienne; Pajic, Marina; Grimmond, Sean M; Chang, David K; Thomas, David; Sebastian, Lucille; Sjoquist, Katrin; Yip, Sonia; Pavlakis, Nick; Asghari, Ray; Harvey, Sandra; Grimison, Peter; Simes, John; Biankin, Andrew V

2015-05-01

Personalized medicine strategies using genomic profiling are particularly pertinent for pancreas cancer. The Individualized Molecular Pancreatic Cancer Therapy (IMPaCT) trial was initially designed to exploit results from genome sequencing of pancreatic cancer under the auspices of the International Cancer Genome Consortium (ICGC) in Australia. Sequencing revealed small subsets of patients with aberrations in their tumor genome that could be targeted with currently available therapies. The pilot stage of the IMPaCT trial assessed the feasibility of acquiring suitable tumor specimens for molecular analysis and returning high-quality actionable genomic data within a clinically acceptable timeframe. We screened for three molecular targets: HER2 amplification; KRAS wild-type; and mutations in DNA damage repair pathways (BRCA1, BRCA2, PALB2, ATM). Tumor biopsy and archived tumor samples were collected from 93 patients and 76 were screened. To date 22 candidate cases have been identified: 14 KRAS wild-type, 5 cases of HER2 amplification, 2 mutations in BRCA2, and 1 ATM mutation. Median time from consent to the return of validated results was 21.5 days. An inability to obtain a biopsy or insufficient tumor content in the available specimen were common reasons for patient exclusion from molecular analysis while deteriorating performance status prohibited a number of patients from proceeding in the study. Documenting the feasibility of acquiring and screening biospecimens for actionable molecular targets in real time will aid other groups embarking on similar trials. Key elements include the need to better prescreen patients, screen more patients, and offer more attractive clinical trial options. ©2015 American Association for Cancer Research.

Health behavior change: can genomics improve behavioral adherence?

PubMed

McBride, Colleen M; Bryan, Angela D; Bray, Molly S; Swan, Gary E; Green, Eric D

2012-03-01

The National Human Genome Research Institute recommends pursuing "genomic information to improve behavior change interventions" as part of its strategic vision for genomics. The limited effectiveness of current behavior change strategies may be explained, in part, by their insensitivity to individual variation in adherence responses. The first step in evaluating whether genomics can inform customization of behavioral recommendations is evidence reviews to identify adherence macrophenotypes common across behaviors and individuals that have genetic underpinnings. Conceptual models of how biological, psychological, and environmental factors influence adherence also are needed. Researchers could routinely collect biospecimens and standardized adherence measurements of intervention participants to enable understanding of genetic and environmental influences on adherence, to guide intervention customization and prospective comparative effectiveness studies.

Approaches in methodology for population-based longitudinal study on neuroprotective model for healthy longevity (TUA) among Malaysian Older Adults.

PubMed

Shahar, Suzana; Omar, Azahadi; Vanoh, Divya; Hamid, Tengku Aizan; Mukari, Siti Zamratol Mai-Sarah; Din, Normah Che; Rajab, Nor Fadilah; Mohammed, Zainora; Ibrahim, Rahimah; Loo, Won Hui; Meramat, Asheila; Kamaruddin, Mohd Zul Amin; Bagat, Mohamad Fazdillah; Razali, Rosdinom

2016-12-01

A number of longitudinal studies on aging have been designed to determine the predictors of healthy longevity, including the neuroprotective factors, however, relatively few studies included a wide range of factors and highlighted the challenges faced during data collection. Thus, the longitudinal study on neuroprotective model for healthy longevity (LRGS TUA) has been designed to prospectively investigate the magnitude of cognitive decline and its risk factors through a comprehensive multidimensional assessment comprising of biophysical health, auditory and visual function, nutrition and dietary pattern and psychosocial aspects. At baseline, subjects were interviewed for their status on sociodemographic, health, neuropsychological test, psychosocial and dietary intake. Subjects were also measured for anthropometric and physical function and fitness. Biospecimens including blood, buccal swap, hair and toenail were collected, processed and stored. A subsample was assessed for sensory function, i.e., vision and auditory. During follow-up, at 18 and 36 months, most of the measurements, along with morbidity and mortality outcomes will be collected. The description of mild cognitive impairment, successful aging and usual aging process is presented here. A total 2322 respondents were recruited in the data analysis at baseline. Most of the respondents were categorized as experiencing usual aging (73 %), followed by successful aging (11 %) and mild cognitive impairment (16 %). The LRGS TUA study is the most comprehensive longitudinal study on aging in Malaysia, and will contribute to the understanding of the aging process and factors associated with healthy aging and mental well-being of a multiethnic population in Malaysia.

Generating a comprehensive set of standard operating procedures for a biorepository network-The CTRNet experience.

PubMed

Barnes, Rebecca; Albert, Monique; Damaraju, Sambasivarao; de Sousa-Hitzler, Jean; Kodeeswaran, Sugy; Mes-Masson, Anne-Marie; Watson, Peter; Schacter, Brent

2013-12-01

Despite the integral role of biorepositories in fueling translational research and the advancement of medicine, there are significant gaps in harmonization of biobanking practices, resulting in variable biospecimen collection, storage, and processing. This significantly impacts accurate downstream analysis and, in particular, creates a problem for biorepository networks or consortia. The Canadian Tumour Repository Network (CTRNet; www.ctrnet.ca ) is a consortium of Canadian tumor biorepositories that aims to enhance biobanking capacity and quality through standardization. To minimize the issue of variable biobanking practices throughout its network, CTRNet has developed and maintained a comprehensive set of 45 standard operating procedures (SOPs). There were four key elements to the CTRNet SOP development process: 1) an SOP development team was formed from members across CTRNet to co-produce each SOP; 2) a principal author was appointed with responsibility for overall coordination of the SOP development process; 3) the CTRNet Management Committee (composed of principal investigators for each member biorepository) reviewed/revised each SOP completed by the development team; and 4) external expert reviewers provided feedback and recommendations on each SOP. Once final Management Committee approval was obtained, the ratified SOP was published on the CTRNet website for public access. Since the SOPs were first published on the CTRNet website (June 2008), there have been approximately 15,000 downloads of one or more CTRNet SOPs/Policies by users from over 60 countries. In accordance with biobanking best practices, CTRNet performs an exhaustive review of its SOPs at set intervals, to coincide with each granting cycle. The last revision was completed in May 2012.

Designing prospective cohort studies for assessing reproductive and developmental toxicity during sensitive windows of human reproduction and development--the LIFE Study.

PubMed

Buck Louis, Germaine M; Schisterman, Enrique F; Sweeney, Anne M; Wilcosky, Timothy C; Gore-Langton, Robert E; Lynch, Courtney D; Boyd Barr, Dana; Schrader, Steven M; Kim, Sungduk; Chen, Zhen; Sundaram, Rajeshwari

2011-09-01

The relationship between the environment and human fecundity and fertility remains virtually unstudied from a couple-based perspective in which longitudinal exposure data and biospecimens are captured across sensitive windows. In response, we completed the LIFE Study with methodology that intended to empirically evaluate a priori purported methodological challenges: implementation of population-based sampling frameworks suitable for recruiting couples planning pregnancy; obtaining environmental data across sensitive windows of reproduction and development; home-based biospecimen collection; and development of a data management system for hierarchical exposome data. We used two sampling frameworks (i.e., fish/wildlife licence registry and a direct marketing database) for 16 targeted counties with presumed environmental exposures to persistent organochlorine chemicals to recruit 501 couples planning pregnancies for prospective longitudinal follow-up while trying to conceive and throughout pregnancy. Enrolment rates varied from <1% of the targeted population (n = 424,423) to 42% of eligible couples who were successfully screened; 84% of the targeted population could not be reached, while 36% refused screening. Among enrolled couples, ∼ 85% completed daily journals while trying; 82% of pregnant women completed daily early pregnancy journals, and 80% completed monthly pregnancy journals. All couples provided baseline blood/urine samples; 94% of men provided one or more semen samples and 98% of women provided one or more saliva samples. Women successfully used urinary fertility monitors for identifying ovulation and home pregnancy test kits. Couples can be recruited for preconception cohorts and will comply with intensive data collection across sensitive windows. However, appropriately sized sampling frameworks are critical, given the small percentage of couples contacted found eligible and reportedly planning pregnancy at any point in time. © Published 2011. This article is a US Government work and is in the public domain in the USA.

A Multidisciplinary Biospecimen Bank of Renal Cell Carcinomas Compatible with Discovery Platforms at Mayo Clinic, Scottsdale, Arizona

PubMed Central

Ho, Thai H.; Nateras, Rafael Nunez; Yan, Huihuang; Park, Jin G.; Jensen, Sally; Borges, Chad; Lee, Jeong Heon; Champion, Mia D.; Tibes, Raoul; Bryce, Alan H.; Carballido, Estrella M.; Todd, Mark A.; Joseph, Richard W.; Wong, William W.; Parker, Alexander S.; Stanton, Melissa L.; Castle, Erik P.

2015-01-01

To address the need to study frozen clinical specimens using next-generation RNA, DNA, chromatin immunoprecipitation (ChIP) sequencing and protein analyses, we developed a biobank work flow to prospectively collect biospecimens from patients with renal cell carcinoma (RCC). We describe our standard operating procedures and work flow to annotate pathologic results and clinical outcomes. We report quality control outcomes and nucleic acid yields of our RCC submissions (N=16) to The Cancer Genome Atlas (TCGA) project, as well as newer discovery platforms, by describing mass spectrometry analysis of albumin oxidation in plasma and 6 ChIP sequencing libraries generated from nephrectomy specimens after histone H3 lysine 36 trimethylation (H3K36me3) immunoprecipitation. From June 1, 2010, through January 1, 2013, we enrolled 328 patients with RCC. Our mean (SD) TCGA RNA integrity numbers (RINs) were 8.1 (0.8) for papillary RCC, with a 12.5% overall rate of sample disqualification for RIN <7. Banked plasma had significantly less albumin oxidation (by mass spectrometry analysis) than plasma kept at 25°C (P<.001). For ChIP sequencing, the FastQC score for average read quality was at least 30 for 91% to 95% of paired-end reads. In parallel, we analyzed frozen tissue by RNA sequencing; after genome alignment, only 0.2% to 0.4% of total reads failed the default quality check steps of Bowtie2, which was comparable to the disqualification ratio (0.1%) of the 786-O RCC cell line that was prepared under optimal RNA isolation conditions. The overall correlation coefficients for gene expression between Mayo Clinic vs TCGA tissues ranged from 0.75 to 0.82. These data support the generation of high-quality nucleic acids for genomic analyses from banked RCC. Importantly, the protocol does not interfere with routine clinical care. Collections over defined time points during disease treatment further enhance collaborative efforts to integrate genomic information with outcomes. PMID:26181416

Overcoming challenges in designing and implementing a phase II randomized controlled trial using a presurgical model to test a dietary intervention in prostate cancer

PubMed Central

George, Stephen L; Switzer, Boyd R; Snyder, Denise C; Madden, John F; Polascik, Thomas J; Ruffin, Mack T; Vollmer, Robin T

2008-01-01

Background The time between the diagnosis of cancer and a planned definitive surgical procedure offers a strong and direct approach for assessing the impact of interventions (including lifestyle interventions) on the biology of the target tissue and the tumor. Despite the many strengths of presurgical models, there are practical issues and challenges that arise when using this approach. Purpose/Methods We recently completed an NIH-funded phase II trial that utilized a presurgical model in testing the comparative effects of flaxseed supplementation and/or dietary fat restriction on the biology and biomarkers associated with prostatic carcinoma. Herein, we report the rationale for our original design, discuss modifications in strategy, and relay experiences in implementing this trial related to the following topics: (1) subject accrual; (2) subject retention; (3) intervention delivery; and (4) retrieval and completion rates regarding the collection of paraffin-embedded and fresh frozen prostate tissue, blood, urine, ejaculate, anthropometric measures and survey data. Results This trial achieved its accrual target, i.e., a racially-representative (70% white, 30% minority) sample of 161 participants, low rates of attrition (7%); and collection rates that exceeded 90% for almost all biospecimens and survey data. While the experience gained from pilot studies was invaluable in designing this trial, the complexity introduced by the collection of several biospecimens, inclusion of a team of pathologists (to provide validated readings), and shifts in practice patterns related to prostatectomy, made it necessary to revise our protocol; lessons from our experiences are offered within this article. Conclusions While our experience specifically relates to the implementation of a presurgical model-based trial in prostate cancer aimed at testing flaxseed-supplemented and fat-restricted diets, many of the lessons learned have broad application to trials that utilize a presurgical model or dietary modification within various cancer populations. PMID:18559416

Benefits and Risks in Secondary Use of Digitized Clinical Data: Views of Community Members Living in a Predominantly Ethnic Minority Urban Neighborhood

PubMed Central

Lucero, Robert J.; Kearney, Joan; Cortes, Yamnia; Arcia, Adriana; Appelbaum, Paul; Fernández, Roberto Lewis; Luchsinger, Jose

2015-01-01

Background There is potential to increase the speed of scientific discovery and implement personalized health care by using digitized clinical data collected on the patient care experience. The use of these data in research raises concerns about the privacy and confidentiality of personal health information. This study explored community members’ views on the secondary use of digitized clinical data to (1) recruit participants for clinical studies; (2) recruit family members of persons with an index condition for primary studies; and (3) conduct studies of information related to stored biospecimens. Methods A qualitative descriptive design was used to examine the bioethical issues outlined from the perspective of urban-dwelling community members. Focus groups were used for data collection, and emergent content analysis was employed to organize and interpret the data. Results Thirty community members attended one of four focus groups ranging in size from 4 to 11 participants. Five critical themes emerged from the focus-group material: (1) perceived motivators for research participation; (2) objective or “real-life” barriers to research participation; (3) a psychological component of uncertainty and mistrust; (4) preferred mechanisms for recruitment and participation; and (5) cultural characteristics that can impact understanding and willingness to engage in research. Conclusions The overriding concern of community members regarding research participation and/or secondary clinical and nonclinical use of digitized information was that their involvement would be safe and the outcome would be meaningful to them and to others. According to participants, biospecimens acquired during routine clinical visits or for research are no longer possessions of the participant. Although the loss of privacy was a concern for participants, they preferred that researchers access their personal health information using a digitized clinical file rather than through a paper-based medical record. PMID:26101782

National ethics guidance in Sub-Saharan Africa on the collection and use of human biological specimens: a systematic review.

PubMed

Barchi, Francis; Little, Madison T

2016-10-22

Ethical and regulatory guidance on the collection and use of human biospecimens (HBS) for research forms an essential component of national health systems in Sub-Saharan Africa (SSA), where rapid advances in genetic- and genomic-based technologies are fueling clinical trials involving HBS and the establishment of large-scale biobanks. An extensive multi-level search for publicly available ethics regulatory guidance was conducted for each SSA country. A second review documented active trials listed in the WHO International Clinical Trials Registry Platform as of January 2015 in which HBS collection was specified in the protocol. Findings were combined to determine the extent to which countries that are study sites for HBS-related research are supported by regulatory guidance language on the collection, use, ownership and storage of biospecimens. Of the 49 SSA countries, 29 had some form of national ethics guidance, yet only 17 provided language relating to HBS-related research, with specific guidance on consent (14), ownership (6), reuse (10), storage (9), and export/import/transfer (13). Ten countries accounted for 84 % of the active clinical trials involving the collection of HBS in SSA. All except one of these countries were found to have some national guidance in the form of regulations, codes of ethics, and/or standard operating procedures; however, only seven of the ten offered any language specific to HBS. Despite the fact that the bulk of registered clinical trials in SSA involving HBS, as well as existing and proposed sites for biorepositories under the H3Africa Initiative, are currently situated in countries with the most complete ethics and regulatory guidance, variability in the regulations themselves may create challenges for planned and future pan-African collaborations and may require legislative action at the national level to revise. Countries in SSA that still lack regulatory guidance on HBS will require extensive health system strengthening in ethics governance before they can be full participants in the modern research enterprise.

Forging stronger partnerships between academic health centers and patient-driven organizations.

PubMed

Gallin, Elaine K; Bond, Enriqueta; Califf, Robert M; Crowley, William F; Davis, Pamela; Galbraith, Richard; Reece, E Albert

2013-09-01

In this article, the authors review the unique role that patient-driven organizations, such as patient advocacy groups and voluntary health organizations (PAG/VHOs), play in translational and clinical research. The importance of fostering collaborations between these organizations and U.S. academic health centers (AHCs) is also discussed. Although both the PAG/VHO community and AHCs are heterogeneous, and although not all organizations are well governed or provide independent, well-researched views, there are many outstanding, well-managed, independent PAG/VHOs in the United States whose missions overlap with those of AHCs. The characteristics of effective PAG/VHOs that would serve as excellent partners for AHCs are discussed, and examples are provided regarding their many contributions, which have included advancing research on rare diseases, recruiting patients for clinical trials, and establishing patient registries and biospecimen banks. The authors present feedback obtained from informal discussions with PAG/VHO staff, as well as a survey of a small sample of organizations, that has identified bureaucratic processes, negotiating intellectual property rights, and institutional review board (IRB) delays as the most problematic areas of interactions with AHCs. Actions are suggested for building effective partnerships between the two sectors and the activities that AHCs should undertake to facilitate their interactions with PAG/VHOs including streamlining contract review and IRB processes and finding ways to better align the incentives motivating academic clinical and translational investigators with the goals of PAG/VHOs. This article is one product of the Clinical Research Forum's Partnering with Patient Advocacy Groups Initiative.

In Vivo Assessment of Protease Dynamics in Cutaneous Wound Healing by Degradomics Analysis of Porcine Wound Exudates*

PubMed Central

Sabino, Fabio; Hermes, Olivia; Egli, Fabian E.; Kockmann, Tobias; Schlage, Pascal; Croizat, Pierre; Kizhakkedathu, Jayachandran N.; Smola, Hans; auf dem Keller, Ulrich

2015-01-01

Proteases control complex tissue responses by modulating inflammation, cell proliferation and migration, and matrix remodeling. All these processes are orchestrated in cutaneous wound healing to restore the skin's barrier function upon injury. Altered protease activity has been implicated in the pathogenesis of healing impairments, and proteases are important targets in diagnosis and therapy of this pathology. Global assessment of proteolysis at critical turning points after injury will define crucial events in acute healing that might be disturbed in healing disorders. As optimal biospecimens, wound exudates contain an ideal proteome to detect extracellular proteolytic events, are noninvasively accessible, and can be collected at multiple time points along the healing process from the same wound in the clinics. In this study, we applied multiplexed Terminal Amine Isotopic Labeling of Substrates (TAILS) to globally assess proteolysis in early phases of cutaneous wound healing. By quantitative analysis of proteins and protein N termini in wound fluids from a clinically relevant pig wound model, we identified more than 650 proteins and discerned major healing phases through distinctive abundance clustering of markers of inflammation, granulation tissue formation, and re-epithelialization. TAILS revealed a high degree of proteolysis at all time points after injury by detecting almost 1300 N-terminal peptides in ∼450 proteins. Quantitative positional proteomics mapped pivotal interdependent processing events in the blood coagulation and complement cascades, temporally discerned clotting and fibrinolysis during the healing process, and detected processing of complement C3 at distinct time points after wounding and by different proteases. Exploiting data on primary cleavage specificities, we related candidate proteases to cleavage events and revealed processing of the integrin adapter protein kindlin-3 by caspase-3, generating new hypotheses for protease-substrate relations in the healing skin wound in vivo. The data have been deposited to the ProteomeXchange Consortium with identifier PXD001198. PMID:25516628

Health Behavior Change: Can Genomics Improve Behavioral Adherence?

PubMed Central

Bryan, Angela D.; Bray, Molly S.; Swan, Gary E.; Green, Eric D.

2012-01-01

The National Human Genome Research Institute recommends pursuing “genomic information to improve behavior change interventions” as part of its strategic vision for genomics. The limited effectiveness of current behavior change strategies may be explained, in part, by their insensitivity to individual variation in adherence responses. The first step in evaluating whether genomics can inform customization of behavioral recommendations is evidence reviews to identify adherence macrophenotypes common across behaviors and individuals that have genetic underpinnings. Conceptual models of how biological, psychological, and environmental factors influence adherence also are needed. Researchers could routinely collect biospecimens and standardized adherence measurements of intervention participants to enable understanding of genetic and environmental influences on adherence, to guide intervention customization and prospective comparative effectiveness studies. PMID:22390502

A Survey of the Current Situation of Clinical Biobanks in China.

PubMed

Li, Haiyan; Ni, Mingyu; Wang, Peng; Wang, Xiaomin

2017-06-01

The development of biomedical research urgently needs the support of a large number of high-quality clinical biospecimens. Therefore, human biobanks at different levels have been established successively in China and other countries at a significantly increasing pace in recent years. To better understand the general current state of clinical biobanks in China, we surveyed 42 clinical biobanks based in hospitals and collected information involving their management systems, sharing mechanisms, quality control systems, and informational management systems using closed questionnaire methods. Based on our current information, there has not been such a large-scale survey in China. An understanding of the status and challenges current clinical biobanks face will provide valuable insights for the construction and sustainable development of higher quality clinical biobanks.

Applying semantic web technologies for phenome-wide scan using an electronic health record linked Biobank

PubMed Central

2012-01-01

Background The ability to conduct genome-wide association studies (GWAS) has enabled new exploration of how genetic variations contribute to health and disease etiology. However, historically GWAS have been limited by inadequate sample size due to associated costs for genotyping and phenotyping of study subjects. This has prompted several academic medical centers to form “biobanks” where biospecimens linked to personal health information, typically in electronic health records (EHRs), are collected and stored on a large number of subjects. This provides tremendous opportunities to discover novel genotype-phenotype associations and foster hypotheses generation. Results In this work, we study how emerging Semantic Web technologies can be applied in conjunction with clinical and genotype data stored at the Mayo Clinic Biobank to mine the phenotype data for genetic associations. In particular, we demonstrate the role of using Resource Description Framework (RDF) for representing EHR diagnoses and procedure data, and enable federated querying via standardized Web protocols to identify subjects genotyped for Type 2 Diabetes and Hypothyroidism to discover gene-disease associations. Our study highlights the potential of Web-scale data federation techniques to execute complex queries. Conclusions This study demonstrates how Semantic Web technologies can be applied in conjunction with clinical data stored in EHRs to accurately identify subjects with specific diseases and phenotypes, and identify genotype-phenotype associations. PMID:23244446

Postpartum Remodeling, Lactation, and Breast Cancer Risk: Summary of a National Cancer Institute–Sponsored Workshop

PubMed Central

2013-01-01

The pregnancy–lactation cycle (PLC) is a period in which the breast is transformed from a less-developed, nonfunctional organ into a mature, milk-producing gland that has evolved to meet the nutritional, developmental, and immune protection needs of the newborn. Cessation of lactation initiates a process whereby the breast reverts to a resting state until the next pregnancy. Changes during this period permanently alter the morphology and molecular characteristics of the breast (molecular histology) and produce important, yet poorly understood, effects on breast cancer risk. To provide a state-of-the-science summary of this topic, the National Cancer Institute invited a multidisciplinary group of experts to participate in a workshop in Rockville, Maryland, on March 2, 2012. Topics discussed included: 1) the epidemiology of the PLC in relation to breast cancer risk, 2) breast milk as a biospecimen for molecular epidemiological and translational research, and 3) use of animal models to gain mechanistic insights into the effects of the PLC on breast carcinogenesis. This report summarizes conclusions of the workshop, proposes avenues for future research on the PLC and its relationship with breast cancer risk, and identifies opportunities to translate this knowledge to improve breast cancer outcomes. PMID:23264680

Assessing needs and assets for building a regional network infrastructure to reduce cancer related health disparities.

PubMed

Wells, Kristen J; Lima, Diana S; Meade, Cathy D; Muñoz-Antonia, Teresita; Scarinci, Isabel; McGuire, Allison; Gwede, Clement K; Pledger, W Jack; Partridge, Edward; Lipscomb, Joseph; Matthews, Roland; Matta, Jaime; Flores, Idhaliz; Weiner, Roy; Turner, Timothy; Miele, Lucio; Wiese, Thomas E; Fouad, Mona; Moreno, Carlos S; Lacey, Michelle; Christie, Debra W; Price-Haywood, Eboni G; Quinn, Gwendolyn P; Coppola, Domenico; Sodeke, Stephen O; Green, B Lee; Lichtveld, Maureen Y

2014-06-01

Significant cancer health disparities exist in the United States and Puerto Rico. While numerous initiatives have been implemented to reduce cancer disparities, regional coordination of these efforts between institutions is often limited. To address cancer health disparities nation-wide, a series of regional transdisciplinary networks through the Geographic Management Program (GMaP) and the Minority Biospecimen/Biobanking Geographic Management Program (BMaP) were established in six regions across the country. This paper describes the development of the Region 3 GMaP/BMaP network composed of over 100 investigators from nine institutions in five Southeastern states and Puerto Rico to develop a state-of-the-art network for cancer health disparities research and training. We describe a series of partnership activities that led to the formation of the infrastructure for this network, recount the participatory processes utilized to develop and implement a needs and assets assessment and implementation plan, and describe our approach to data collection. Completion, by all nine institutions, of the needs and assets assessment resulted in several beneficial outcomes for Region 3 GMaP/BMaP. This network entails ongoing commitment from the institutions and institutional leaders, continuous participatory and engagement activities, and effective coordination and communication centered on team science goals. Copyright © 2014 Elsevier Ltd. All rights reserved.

Assessing Needs and Assets for Building a Regional Network Infrastructure to Reduce Cancer Related Health Disparities

PubMed Central

Wells, Kristen J.; Lima, Diana S.; Meade, Cathy D.; Muñoz-Antonia, Teresita; Scarinci, Isabel; McGuire, Allison; Gwede, Clement K.; Pledger, W. Jack; Partridge, Edward; Lipscomb, Joseph; Matthews, Roland; Matta, Jaime; Flores, Idhaliz; Weiner, Roy; Turner, Timothy; Miele, Lucio; Wiese, Thomas E.; Fouad, Mona; Moreno, Carlos S.; Lacey, Michelle; Christie, Debra W.; Price-Haywood, Eboni G.; Quinn, Gwendolyn P.; Coppola, Domenico; Sodeke, Stephen O.; Green, B. Lee; Lichtveld, Maureen Y.

2015-01-01

Significant cancer health disparities exist in the United States and Puerto Rico. While numerous initiatives have been implemented to reduce cancer disparities, regional coordination of these efforts between institutions is often limited. To address cancer health disparities nationwide, a series of regional transdisciplinary networks through the Geographic Management Program (GMaP) and the Minority Biospecimen/Biobanking Geographic Management Program (BMaP) were established in six regions across the country. This paper describes the development of the Region 3 GMaP/BMaP network composed of over 100 investigators from nine institutions in five Southeastern states and Puerto Rico to develop a state-of-the-art network for cancer health disparities research and training. We describe a series of partnership activities that led to the formation of the infrastructure for this network, recount the participatory processes utilized to develop and implement a needs and assets assessment and implementation plan, and describe our approach to data collection. Completion, by all nine institutions, of the needs and assets assessment resulted in several beneficial outcomes for Region 3 GMaP/BMaP. This network entails ongoing commitment from the institutions and institutional leaders, continuous participatory and engagement activities, and effective coordination and communication centered on team science goals. PMID:24486917

Dietary Fiber Intake Is Associated with HbA1c Level among Prevalent Patients with Type 2 Diabetes in Pudong New Area of Shanghai, China

PubMed Central

Jiang, Junyi; Qiu, Hua; Zhao, Genming; Zhou, Yi; Zhang, Zhijie; Zhang, Hong; Jiang, Qingwu; Sun, Qiao; Wu, Hongyan; Yang, Liming; Ruan, Xiaonan; Xu, Wang-Hong

2012-01-01

Background Dietary factors play an important role in glycemic control in diabetic patients. However, little is known about their effects among Chinese diabetic patients, whose diets are typically abundant in fiber and high in glycemic index (GI) values. Methodology/Principal Findings 934 patients with type 2 diabetes and 918 healthy volunteers from Pudong New Area, Shanghai, China, were interviewed during the period of Oct-Dec, 2006 to elicit demographic characteristics and lifestyle factors. Dietary habits were assessed using a validated food frequency questionnaire. Anthropometric measurements, bio-specimen collection and biochemical assays were conducted at the interview according to a standard protocol. In this population, diabetic patients consumed lower levels of energy and macronutrients but had higher levels of fasting plasma glucose (FPG), glycolated hemoglobin A1c (HbA1c), triglyceride and body mass index than healthy adults. While the average consumption levels of the nutrients among diabetic patients did not vary along duration of the disease, the average levels of FPG and HbA1c increased with increasing duration. Regardless of diabetes duration, HbA1c level was observed lower in patients having a higher fiber or lower GI intake. Compared with those with the lowest tertile intake of fiber, the adjusted odds ratios (ORs) for poor glycemic control reduced from 0.75 (95%CI: 0.54–1.06) to 0.51 (95%CI: 0.34–0.75) with increasing tertile intake (P for trend <0.001). Conclusions Dietary fiber may play an important role in reducing HbA1c level. Increasing fiber intake may be an effective approach to improve glycemic control among Chinese diabetic patients. PMID:23077514

The TCAR Report: Translational Cell and Animal Research Space (1965-2011) Sponsored by NASA Ames Research Center

NASA Technical Reports Server (NTRS)

Ronca, A. E.; Mains, Richard; Alwood, J. S.; French, A. J.; Smith, J. D.; Miller, Virginia; Tash, Joseph; Jenkins, Marjorie

2015-01-01

Five decades ago, NASA Ames Research Center (ARC) began a vigorous program of space biology research utilizing animal cells, tissues and whole organisms. Since its inception, this program has yielded exciting new insights into how spaceflight influences fundamental processes of living systems. These are findings with important translational implications for human health in space and on Earth. The TCAR Report is a compilation of 394 flight experiments conducted across the period spanning 1965 - 2011 with individual chapters devoted to: (1) Bone Physiology, (2) Cardiovascular/Cardiopulmonary Physiology, (3) Developmental Biology, (4) Immunology, (5) Microbial Growth and Virulence, (6) Muscle Physiology, (7) Neurophysiology and (8) Regulatory Physiology. Specialists in those disciplines reviewed the research and each prepared an overview including the translational relevance of the findings for human health in space and on Earth. The Report will be made available in early 2015 through standard NASA publication resources and on the NASA Life Sciences Data Archive (http://lsda.jsc.nasa.gov/lsda_home1.aspx). The LSDA can be mined for detailed information, including Experiment, Mission, Available Biospecimens, Document, Hardware, Dataset, Personnel, and includes a searchable Photo Gallery. Space biology translational topic highlights include: Inflight centrifugation protection of bone strength losses; Assessment of evidence related to visual impairment in astronauts; Mammalian development including vestibular system plasticity and vestibular-visual integration; Verification of limb unloading ground-based studies as a model for spaceflight unloading; Immune system impairment and increased microbiological virulence aligned with immune dysfunction; and Rapid bone and muscle tissue and functional losses associated with unloading. In addition to astronauts, these results may help humans on Earth, by providing insight into the definition of fundamental mechanisms and potential treatments for debilitating changes that result from human aging and disease. The TCAR effort has resulted in significant new insights. Modern tools now widely available for "Omics" research with model organisms and humans provide new opportunities for translational research. Omics research at various levels is greatly complemented by studies at the tissue and organismal levels. Key discoveries can occur at either the basic research or the health surveillance level such as vision problems observed in astronauts stimulating studies of eye tissues in rodents that identified relevant changes. The Ames Biospecimen Sharing Program (BSP), serving the NASA Space Biology and HRP programs, was created to maximize utilization and scientific return from unique animal specimens derived from rare, complex and costly NASA spaceflight and ground-based analog experiments. The BSP is a valuable tool for advancing translational science at NASA. Dynamic methods for tracking translational linkages across NASA space life sciences and medicine are strongly encouraged for translational science.

Standardizing in vitro diagnostics tasks in clinical trials: a call for action.

PubMed

Lippi, Giuseppe; Simundic, Ana-Maria; Rodriguez-Manas, Leocadio; Bossuyt, Patrick; Banfi, Giuseppe

2016-05-01

Translational research is defined as the process of applying ideas, insights and discoveries generated through basic scientific inquiry to treatment or prevention of human diseases. Although precise information is lacking, several lines of evidence attest that up to 95% early-phase studies may not translate into tangible outcomes for improving clinical management. Major theoretical hurdles exist in the translational process, but is it also undeniable that many studies may have failed for practical reasons, such as the use of inappropriate diagnostic testing for evaluating efficacy, effectiveness or safety of a given medical intervention, or poor quality in laboratory testing. This can generate biased test results and result in misconceptions during data interpretation, eventually leading to no clinical benefit, possible harm, and a waste of valuable resources. From a genuine economic perspective, it can be estimated that over 10 million euros of funding may be lost each year in clinical trials in the European Union due to preanalytical and analytical problems. These are mostly attributions to the heterogeneity of current guidelines and recommendations for the testing process, to the poor evidence base for basic pre-analytical, analytical and post-analytical requirements in clinical trials, and to the failure to thoughtfully integrate the perspectives of clinicians, patients, nurses and diagnostic companies in laboratory best practices. The most rational means for filling the gap between what we know and what we practice in clinical trials cannot discount the development of multidisciplinary teams including research scientists, clinicians, nurses, patients associations and representative of in vitro diagnostic (IVD) companies, who should actively interplay and collaborate with laboratory professionals to adapt and disseminate evidence-based recommendations about biospecimen collection and management into the research settings, from preclinical to phase III studies.

Establishment of reference intervals for osteoarthritis-related soluble biomarkers: the FNIH/OARSI OA Biomarkers Consortium.

PubMed

Kraus, Virginia B; Hargrove, David E; Hunter, David J; Renner, Jordan B; Jordan, Joanne M

2017-01-01

To establish reference intervals for osteoarthritis (OA)-related biomarkers used in the Foundation for the National Institutes of Health (FNIH) OA Biomarkers Consortium Project. A total of 129 'multijoint controls' were selected from 2722 African-American and Caucasian men and women in the Johnston County Osteoarthritis Project. The majority (79%) of those eligible (with biospecimens and baseline data) also had one or more follow-up evaluations 5-15 years later. Multijoint controls were selected to be free of radiographic hand, hip, knee and lumbar spine osteoarthritis (OA), to have no knee or hip symptoms, and minimal hand and spine symptoms at all available time points. Eighteen biomarkers were evaluated in serum (s) and/or urine (u) by ELISA. Reference intervals and partitioning by gender and race were performed with EP Evaluator software. Controls were 64% women, 33% African-Americans, mean age 59 years and mean body mass index 29 kg/m 2 . Three biomarkers were associated with age: sHyaluronan (positively), sN-terminal propeptide of collagen IIA (positively) and sCol2-3/4 C-terminal cleavage product of types I and II collagen (negatively). Exploratory analyses suggested that separate reference intervals may be warranted on the basis of gender for uC-terminal cross-linked telopeptide of type II collagen (uCTXII), sMatrix metalloproteinase-3, uNitrated type II collagen degradation fragment (uCol2-1 NO2) and sHyaluronan, and on the basis of race for uCTXII, sCartilage oligomeric matrix protein, sC-terminal cross-linked telopeptide of type I collagen and uCol2-1 NO2. To our knowledge, this represents the best and most stringent control group ever assayed for OA-related biomarkers. These well-phenotyped controls, representing a similar age demographic to that of the OA Initiative-FNIH main study sample, provide a context for interpretation of OA subject biomarker data. The freely available data set also provides a reference for future human studies. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

A strategic plan for the second phase (2013-2015) of the Korea biobank project.

PubMed

Park, Ok; Cho, Sang Yun; Shin, So Youn; Park, Jae-Sun; Kim, Jun Woo; Han, Bok-Ghee

2013-04-01

The Korea Biobank Project (KBP) was led by the Ministry of Health and Welfare to establish a network between the National Biobank of Korea and biobanks run by university-affiliated general hospitals (regional biobanks). The Ministry of Health and Welfare started the project to enhance medical and health technology by collecting, managing, and providing researchers with high-quality human bioresources. The National Biobank of Korea, under the leadership of the Ministry of Health and Welfare, collects specimens through various cohorts and regional biobanks within university hospitals gather specimens from patients. The project began in 2008, and the first phase ended in 2012, which meant that there needed to be a plan for the second phase that begins in 2013. Consequently, professionals from within and outside the project were gathered to develop a plan for the second phase. Under the leadership of the planning committee, six working groups were formed to formulate a practical plan. By conducting two workshops with experts in the six working groups and the planning committee and three forums in 2011 and 2012, they have developed a strategic plan for the second phase of the KBP. This document presents a brief report of the second phase of the project based on a discussion with them. During the first phase of the project (2008-2012), a network was set up between the National Biobank of Korea and 17 biobanks at university-affiliated hospitals in an effort to unify informatics and governance among the participating biobanks. The biobanks within the network manage data on their biospecimens with a unified Biobank Information Management System. Continuous efforts are being made to develop a common standard operating procedure for resource collection, management, distribution, and personal information security, and currently, management of these data is carried out in a somewhat unified manner. In addition, the KBP has trained and educated professionals to work within the biobanks, and has also carried out various publicity promotions to the public and researchers. During the first phase, biospecimens from more than 300,000 participants through various cohorts and biospecimens from more than 200,000 patients from hospitals were collected, which were distributed to approximately 600 research projects. The planning committee for the second phase evaluated that the first phase of the KBP was successful. However, the first phase of the project was meant to allow autonomy to the individual biobanks. The biobanks were able to choose the kind of specimens they were going to collect and the amount of specimen they would set as a goal, as well as being allowed to choose their own methods to manage their biobanks (autonomy). Therefore, some biobanks collected resources that were easy to collect and the resources needed by researchers were not strategically collected. In addition, there was also a low distribution rate to researchers outside of hospitals, who do not have as much access to specimens and cases as those in hospitals. There were also many cases in which researchers were not aware of the KBP, and the distribution processes were not set up to be convenient to the demands of researchers. Accordingly, the second phase of the KBP will be focused on increasing the integration and cooperation between the biobanks within the network. The KBP plans to set goals for the strategic collection of the needed human bioresources. Although the main principle of the first phase was to establish infrastructure and resource collection, the key objective of the second phase is the efficient utilization of gathered resources. In order to fully utilize the gathered resources in an efficient way, distribution systems and policies must be improved. Vitalization of distribution, securing of high-value resource and related clinical and laboratory information, international standardization of resource management systems, and establishment of a virtuous cycle between research and development (R&D) and biobanks are the four main strategies. Based on these strategies, 12 related objectives have been set and are planned to be executed.

Incorporating Salivary Biomarkers into Nursing Research: An Overview and Review of Best Practices

PubMed Central

Granger, Douglas A.; Johnson, Sara B.; Szanton, Sarah L.; Out, Dorothée; Schumann, Lynette Lau

2014-01-01

Analytes and biomarkers present in saliva may provide insight into individual differences in environmental chemical exposures, variation in reproductive hormones, therapeutic and illegal substance use, changes in stress-related physiology, and the immunologic footprints of infectious disease. The wealth of information provided by salivary analytes has the potential to enrich biobehavioral nursing research by enabling researchers to measure these individual differences in the clinic as well as in patients' and participants' everyday social worlds. In this paper we provide a roadmap for researchers new to this area who would like to learn more about integrating salivary biospecimens into the next generation of health research. In addition, we highlight best practices and strategies to avoid common pitfalls for researchers already engaged in this field. PMID:22593229

Ongoing Use of Data and Specimens from NCI Sponsored Cancer Prevention Clinical Trials in the Community Clinical Oncology Program

PubMed Central

Minasian, Lori; Tangen, Catherine M.; Wickerham, D. Lawrence

2015-01-01

Large cancer prevention trials provide opportunities to collect a wide array of data and biospecimens at study entry and longitudinally, for a healthy, aging population without cancer. This provides an opportunity to use pre-diagnostic data and specimens to evaluate hypotheses about the initial development of cancer. This paper reports on strides made by, and future possibilities for, the use of accessible biorepositories developed from precisely annotated samples obtained through large-scale National Cancer Institute (NCI)-sponsored cancer prevention clinical trials conducted by the NCI Cooperative Groups. These large cancer prevention studies, which have enrolled over 80,000 volunteers, continue to contribute to our understanding of cancer development more than 10 years after they were closed. PMID:26433556

Nanoplatforms for highly sensitive fluorescence detection of cancer-related proteases.

PubMed

Wang, Hongwang; Udukala, Dinusha N; Samarakoon, Thilani N; Basel, Matthew T; Kalita, Mausam; Abayaweera, Gayani; Manawadu, Harshi; Malalasekera, Aruni; Robinson, Colette; Villanueva, David; Maynez, Pamela; Bossmann, Leonie; Riedy, Elizabeth; Barriga, Jenny; Wang, Ni; Li, Ping; Higgins, Daniel A; Zhu, Gaohong; Troyer, Deryl L; Bossmann, Stefan H

2014-02-01

Numerous proteases are known to be necessary for cancer development and progression including matrix metalloproteinases (MMPs), tissue serine proteases, and cathepsins. The goal of this research is to develop an Fe/Fe3O4 nanoparticle-based system for clinical diagnostics, which has the potential to measure the activity of cancer-associated proteases in biospecimens. Nanoparticle-based "light switches" for measuring protease activity consist of fluorescent cyanine dyes and porphyrins that are attached to Fe/Fe3O4 nanoparticles via consensus sequences. These consensus sequences can be cleaved in the presence of the correct protease, thus releasing a fluorescent dye from the Fe/Fe3O4 nanoparticle, resulting in highly sensitive (down to 1 × 10(-16) mol l(-1) for 12 proteases), selective, and fast nanoplatforms (required time: 60 min).

Pooling biomarker data from different studies of disease risk, with a focus on endogenous hormones

PubMed Central

Key, Timothy J; Appleby, Paul N; Allen, Naomi E; Reeves, Gillian K

2010-01-01

Large numbers of observations are needed to provide adequate power in epidemiological studies of biomarkers and cancer risk. However, there are currently few large mature studies with adequate numbers of cases with biospecimens available. Therefore pooling biomarker measures from different studies is a valuable approach, enabling investigators to make robust estimates of risk and to examine associations in subgroups of the population. The ideal situation is to have standardized methods in all studies so that the biomarker data can be pooled in their original units. However, even when the studies do not have standardized methods, as with existing studies on hormones and cancer, a simple approach using study-specific quantiles or percentage increases can provide substantial information on the relationship of the biomarker with cancer risk. PMID:20233851

Topic model-based mass spectrometric data analysis in cancer biomarker discovery studies.

PubMed

Wang, Minkun; Tsai, Tsung-Heng; Di Poto, Cristina; Ferrarini, Alessia; Yu, Guoqiang; Ressom, Habtom W

2016-08-18

A fundamental challenge in quantitation of biomolecules for cancer biomarker discovery is owing to the heterogeneous nature of human biospecimens. Although this issue has been a subject of discussion in cancer genomic studies, it has not yet been rigorously investigated in mass spectrometry based proteomic and metabolomic studies. Purification of mass spectometric data is highly desired prior to subsequent analysis, e.g., quantitative comparison of the abundance of biomolecules in biological samples. We investigated topic models to computationally analyze mass spectrometric data considering both integrated peak intensities and scan-level features, i.e., extracted ion chromatograms (EICs). Probabilistic generative models enable flexible representation in data structure and infer sample-specific pure resources. Scan-level modeling helps alleviate information loss during data preprocessing. We evaluated the capability of the proposed models in capturing mixture proportions of contaminants and cancer profiles on LC-MS based serum proteomic and GC-MS based tissue metabolomic datasets acquired from patients with hepatocellular carcinoma (HCC) and liver cirrhosis as well as synthetic data we generated based on the serum proteomic data. The results we obtained by analysis of the synthetic data demonstrated that both intensity-level and scan-level purification models can accurately infer the mixture proportions and the underlying true cancerous sources with small average error ratios (<7 %) between estimation and ground truth. By applying the topic model-based purification to mass spectrometric data, we found more proteins and metabolites with significant changes between HCC cases and cirrhotic controls. Candidate biomarkers selected after purification yielded biologically meaningful pathway analysis results and improved disease discrimination power in terms of the area under ROC curve compared to the results found prior to purification. We investigated topic model-based inference methods to computationally address the heterogeneity issue in samples analyzed by LC/GC-MS. We observed that incorporation of scan-level features have the potential to lead to more accurate purification results by alleviating the loss in information as a result of integrating peaks. We believe cancer biomarker discovery studies that use mass spectrometric analysis of human biospecimens can greatly benefit from topic model-based purification of the data prior to statistical and pathway analyses.

Progressive Consent and Specimen Accrual Models to Address Sustainability: A Decade's Experience at an Oregon Biorepository.

PubMed

Ost, John A; Newton, Paul W; Neilson, Duncan R; Cioffi, Joseph A; Wackym, P Ashley; Perkins, R Serene

2017-02-01

The Legacy Biorepository is a College of American Pathologists-accredited biorepository operating within a seven-hospital healthcare system, with a decade's experience in specimen accrual, storage, and distribution. While standardization of our practices through accreditation remains a priority, we along with others face challenges with regard to sustainability. Purposeful changes in our consent process, which we term "progressive consent," are expected to improve sustainability and operational flexibility while increasing our scientific impact. Until 2015, informed consent was performed primarily by biorepository staff at an estimated time of 1 hour per case. After a process improvement exercise, we successfully changed our informed consent process to a modified front-door model, with use of material and data for research as an opt-in or opt-out selection on the institutional patient informed consent form provided to surgery patients in the healthcare system. Successful implementation of this change required the engagement and participation of multiple stakeholders in healthcare system leadership, hospital administration, research, legal, regulatory, and patient care levels. A modified front-door consent enabled us to collect an additional 38 specimens in the first two quarters of 2016, with a time commitment of 15.75 hours, a time savings per specimen increasing in Q2 over Q1. We estimate a potential savings of 43 hours in 2016. This progressive model allowed us to maintain our frozen sample collection while increasing the availability of paraffin-embedded tissue and bodily fluids. Augmenting our tissue collection added little expense per case (approximately half that of each frozen tissue aliquot) and increased the range of biospecimens collected. Biorepository financial sustainability is a critical issue. Thorough evaluation and modification of existing procedures and collection models, as well as cost recovery initiatives, can translate into savings. Sustainability, process improvement, and scientific impact broadly overlap and continue to require operational critique and implementation of strategic changes.

Cohort Profile: The Malaysian Cohort (TMC) project: a prospective study of non-communicable diseases in a multi-ethnic population

PubMed Central

Jamal, Rahman; Syed Zakaria, Syed Zulkifli; Kamaruddin, Mohd Arman; Abd Jalal, Nazihah; Ismail, Norliza; Mohd Kamil, Norkhamiwati; Abdullah, Noraidatulakma; Baharudin, Norhafizah; Hussin, Noor Hamidah; Othman, Hanita; Mahadi, Nor Muhammad

2015-01-01

The Malaysian Cohort study was initiated in 2005 by the Malaysian government. The top-down approach to this population-based cohort study ensured the allocation of sufficient funding for the project which aimed to recruit 100 000 individuals aged 35–70 years. Participants were recruited from rural and urban areas as well as from various socioeconomic groups. The main objectives of the study were to identify risk factors, to study gene-environment interaction and to discover biomarkers for the early detection of cancers and other diseases. At recruitment, a questionnaire-based interview was conducted, biophysical measurements were performed and biospecimens were collected, processed and stored. Baseline investigations included fasting blood sugar, fasting lipid profile, renal profile and full blood count. From April 2006 to the end of September 2012 we recruited a total of 106 527participants. The baseline prevalence data showed 16.6% participants with diabetes, 46.5% with hypertension, 44.9% with hypercholesterolaemia and 17.7% with obesity. The follow-up phase commenced in June 2013. This is the most comprehensive and biggest cohort study in Malaysia, and has become a valuable resource for epidemiological and biological research. For information on collaboration and also data access, investigators can contact the project leader at (rahmanj@ppukm.ukm.edu.my). PMID:24729425

A general framework for the regression analysis of pooled biomarker assessments.

PubMed

Liu, Yan; McMahan, Christopher; Gallagher, Colin

2017-07-10

As a cost-efficient data collection mechanism, the process of assaying pooled biospecimens is becoming increasingly common in epidemiological research; for example, pooling has been proposed for the purpose of evaluating the diagnostic efficacy of biological markers (biomarkers). To this end, several authors have proposed techniques that allow for the analysis of continuous pooled biomarker assessments. Regretfully, most of these techniques proceed under restrictive assumptions, are unable to account for the effects of measurement error, and fail to control for confounding variables. These limitations are understandably attributable to the complex structure that is inherent to measurements taken on pooled specimens. Consequently, in order to provide practitioners with the tools necessary to accurately and efficiently analyze pooled biomarker assessments, herein, a general Monte Carlo maximum likelihood-based procedure is presented. The proposed approach allows for the regression analysis of pooled data under practically all parametric models and can be used to directly account for the effects of measurement error. Through simulation, it is shown that the proposed approach can accurately and efficiently estimate all unknown parameters and is more computational efficient than existing techniques. This new methodology is further illustrated using monocyte chemotactic protein-1 data collected by the Collaborative Perinatal Project in an effort to assess the relationship between this chemokine and the risk of miscarriage. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Cohort Profile: The Malaysian Cohort (TMC) project: a prospective study of non-communicable diseases in a multi-ethnic population.

PubMed

Jamal, Rahman; Syed Zakaria, Syed Zulkifli; Kamaruddin, Mohd Arman; Abd Jalal, Nazihah; Ismail, Norliza; Mohd Kamil, Norkhamiwati; Abdullah, Noraidatulakma; Baharudin, Norhafizah; Hussin, Noor Hamidah; Othman, Hanita; Mahadi, Nor Muhammad

2015-04-01

The Malaysian Cohort study was initiated in 2005 by the Malaysian government. The top-down approach to this population-based cohort study ensured the allocation of sufficient funding for the project which aimed to recruit 100,000 individuals aged 35-70 years. Participants were recruited from rural and urban areas as well as from various socioeconomic groups. The main objectives of the study were to identify risk factors, to study gene-environment interaction and to discover biomarkers for the early detection of cancers and other diseases. At recruitment, a questionnaire-based interview was conducted, biophysical measurements were performed and biospecimens were collected, processed and stored. Baseline investigations included fasting blood sugar, fasting lipid profile, renal profile and full blood count. From April 2006 to the end of September 2012 we recruited a total of 106,527 participants. The baseline prevalence data showed 16.6% participants with diabetes, 46.5% with hypertension, 44.9% with hypercholesterolaemia and 17.7% with obesity. The follow-up phase commenced in June 2013. This is the most comprehensive and biggest cohort study in Malaysia, and has become a valuable resource for epidemiological and biological research. For information on collaboration and also data access, investigators can contact the project leader at (rahmanj@ppukm.ukm.edu.my). © The Author 2014. Published by Oxford University Press on behalf of the International Epidemiological Association.

21st century paradigm of tissue banking: the Clinical Breast Care Project.

PubMed

Shriver, Craig D

2010-07-01

The Clinical Breast Care Project (CBCP) is a congressionally mandated program that began in the year 2000. The military-civilian collaboration was founded on five pillars: (1) center of excellence in clinical care, (2) risk reduction for women at risk for developing breast cancer, (3) tissue banking to develop and maintain the world's finest repository of human biospecimens of breast diseases, (4) targeted research into the molecular signatures of breast diseases and cancer, and (5) biomedical informatics core to support the data warehouse needs of the project. Now in its eighth year of operation, these efforts have resulted in more than 300 peer-reviewed scientific publications and dozens of collaborations with world leaders in cancer research. In this short time, CBCP has created what is believed to be the world's largest breast tissue biorepository.

The risk of re-identification versus the need to identify individuals in rare disease research

PubMed Central

Hansson, Mats G; Lochmüller, Hanns; Riess, Olaf; Schaefer, Franz; Orth, Michael; Rubinstein, Yaffa; Molster, Caron; Dawkins, Hugh; Taruscio, Domenica; Posada, Manuel; Woods, Simon

2016-01-01

There is a growing concern in the ethics literature and among policy makers that de-identification or coding of personal data and biospecimens is not sufficient for protecting research subjects from privacy invasions and possible breaches of confidentiality due to the possibility of unauthorized re-identification. At the same time, there is a need in medical science to be able to identify individual patients. In particular for rare disease research there is a special and well-documented need for research collaboration so that data and biosamples from multiple independent studies can be shared across borders. In this article, we identify the needs and arguments related to de-identification and re-identification of patients and research subjects and suggest how the different needs may be balanced within a framework of using unique encrypted identifiers. PMID:27222291

The risk of re-identification versus the need to identify individuals in rare disease research.

PubMed

Hansson, Mats G; Lochmüller, Hanns; Riess, Olaf; Schaefer, Franz; Orth, Michael; Rubinstein, Yaffa; Molster, Caron; Dawkins, Hugh; Taruscio, Domenica; Posada, Manuel; Woods, Simon

2016-11-01

There is a growing concern in the ethics literature and among policy makers that de-identification or coding of personal data and biospecimens is not sufficient for protecting research subjects from privacy invasions and possible breaches of confidentiality due to the possibility of unauthorized re-identification. At the same time, there is a need in medical science to be able to identify individual patients. In particular for rare disease research there is a special and well-documented need for research collaboration so that data and biosamples from multiple independent studies can be shared across borders. In this article, we identify the needs and arguments related to de-identification and re-identification of patients and research subjects and suggest how the different needs may be balanced within a framework of using unique encrypted identifiers.

Beyond isolated cells: microfluidic transport of large tissue for pancreatic cancer diagnosis

NASA Astrophysics Data System (ADS)

Das, Ronnie; Murphy, Rachel G.; Seibel, Eric J.

2015-03-01

For cancer diagnoses, core biopsies (CBs) obtained from patients using coring needles (CNs) are traditionally visualized and assessed on microscope slides by pathologists after samples are processed and sectioned. A fundamental gain in optical information (i.e., diagnosis/staging) may be achieved when whole, unsectioned CBs (L = 5-20, D = 0.5-2.0 mm) are analyzed in 3D. This approach preserves CBs for traditional pathology and maximizes the diagnostic potential of patient samples. To bridge CNs/CBs with imaging, our group developed a microfluidic device that performs biospecimen preparation on unsectioned CBs for pathology. The ultimate goal is an automated and rapid point-of-care system that aids pathologists by processing tissue for advanced 3D imaging platforms. An inherent, but essential device feature is the microfluidic transport of CBs, which has not been previously investigated. Early experiments demonstrated proof-of-concept: pancreas CBs (D = 0.3-2.0 mm) of set lengths were transported in straight/curved microchannels, but dimensional tolerance and flow rates were variable, and preservation of CB integrity was uncontrolled. A second study used metal cylinder substitutes (L = 10, D = 1 mm) in microchannels to understand the transport mechanism. However, CBs are imperfectly shaped, rough, porous and viscoelastic. In this study, fresh/formalin-fixed porcine and human pancreas CBs were deposited into our device through a custom interface using clinical CNs. CB integrity (i.e., sample viability) may be assessed at every stage using an optomechanical metric: physical breaks were determined when specimen intensity profile data deviated beyond xavg + 2σ. Flow rates for human CBs were determined for several CNs, and microfluidic transport of fresh and formalin-fixed CBs was analyzed.

The Establishment of the First Cancer Tissue Biobank at a Hispanic-Serving Institution: A National Cancer Institute–Funded Initiative between Moffitt Cancer Center in Florida and the Ponce School of Medicine and Health Sciences in Puerto Rico

PubMed Central

Flores, Idhaliz; Muñoz-Antonia, Teresita; Matta, Jaime; García, Miosotis; Fenstermacher, David; Gutierrez, Sylvia; Seijo, Edward; Torres-Ruiz, Jose’; Pledger, W. Jack

2011-01-01

Population-based studies are important to address emerging issues in health disparities among populations. The Partnership between the Moffitt Cancer Center (MCC) in Florida and the Ponce School of Medicine and Health Sciences (PSMHS) in Puerto Rico (the PSMHS-MCC Partnership) was developed to facilitate high-quality research, training, and community outreach focusing on the Puerto Rican population in the island and in the mainland, with funding from the National Cancer Institute. We report here the establishment of a Tissue Biobank at PSMHS, modeled after the MCC tissue biorepository, to support translational research projects on this minority population. This facility, the Puerto Rico Tissue Biobank, was jointly developed by a team of basic and clinical scientists from both institutions in close collaboration with the administrators and clinical faculty of the tissue accrual sites. The efforts required and challenges that needed to be overcome to establish the first functional, centralized cancer-related biobank in Puerto Rico, and to ensure that it continuously evolves to address new needs of this underserved Hispanic population, are described. As a result of the collaborative efforts between PSMHS and MCC, a tissue procurement algorithm was successfully established to acquire, process, store, and conduct pathological analyses of cancer-related biospecimens and their associated clinical-pathological data from Puerto Rican patients with cancer recruited at a tertiary hospital setting. All protocols in place are in accordance with standard operational procedures that ensure high quality of biological materials and patient confidentiality. The processes described here provide a model that can be applied to achieve the establishment of a functional biobank in similar settings. PMID:24836632

Femtosecond X-ray Fourier holography imaging of free-flying nanoparticles

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gorkhover, Tais; Ulmer, Anatoli; Ferguson, Ken

Ultrafast X-ray imaging on individual fragile specimens such as aerosols, metastable particles, superfluid quantum systems and live biospecimens provides high-resolution information that is inaccessible with conventional imaging techniques. Coherent X-ray diffractive imaging, however, suffers from intrinsic loss of phase, and therefore structure recovery is often complicated and not always uniquely defined. Here in this paper, we introduce the method of in-flight holography, where we use nanoclusters as reference X-ray scatterers to encode relative phase information into diffraction patterns of a virus. The resulting hologram contains an unambiguous three-dimensional map of a virus and two nanoclusters with the highest lateral resolutionmore » so far achieved via single shot X-ray holography. Our approach unlocks the benefits of holography for ultrafast X-ray imaging of nanoscale, non-periodic systems and paves the way to direct observation of complex electron dynamics down to the attosecond timescale.« less

Femtosecond X-ray Fourier holography imaging of free-flying nanoparticles

NASA Astrophysics Data System (ADS)

Gorkhover, Tais; Ulmer, Anatoli; Ferguson, Ken; Bucher, Max; Maia, Filipe R. N. C.; Bielecki, Johan; Ekeberg, Tomas; Hantke, Max F.; Daurer, Benedikt J.; Nettelblad, Carl; Andreasson, Jakob; Barty, Anton; Bruza, Petr; Carron, Sebastian; Hasse, Dirk; Krzywinski, Jacek; Larsson, Daniel S. D.; Morgan, Andrew; Mühlig, Kerstin; Müller, Maria; Okamoto, Kenta; Pietrini, Alberto; Rupp, Daniela; Sauppe, Mario; van der Schot, Gijs; Seibert, Marvin; Sellberg, Jonas A.; Svenda, Martin; Swiggers, Michelle; Timneanu, Nicusor; Westphal, Daniel; Williams, Garth; Zani, Alessandro; Chapman, Henry N.; Faigel, Gyula; Möller, Thomas; Hajdu, Janos; Bostedt, Christoph

2018-03-01

Ultrafast X-ray imaging on individual fragile specimens such as aerosols1, metastable particles2, superfluid quantum systems3 and live biospecimens4 provides high-resolution information that is inaccessible with conventional imaging techniques. Coherent X-ray diffractive imaging, however, suffers from intrinsic loss of phase, and therefore structure recovery is often complicated and not always uniquely defined4,5. Here, we introduce the method of in-flight holography, where we use nanoclusters as reference X-ray scatterers to encode relative phase information into diffraction patterns of a virus. The resulting hologram contains an unambiguous three-dimensional map of a virus and two nanoclusters with the highest lateral resolution so far achieved via single shot X-ray holography. Our approach unlocks the benefits of holography for ultrafast X-ray imaging of nanoscale, non-periodic systems and paves the way to direct observation of complex electron dynamics down to the attosecond timescale.

A basis for translational cancer research on aetiology, pathogenesis and prognosis: Guideline for standardised and population-based linkages of biobanks to cancer registries.

PubMed

Dillner, Joakim

2015-06-01

Population-based cancer research is paramount for controlling cancer. Cancer research is increasingly dependent on access to biospecimens from subjects that have been followed-up for future health outcomes. This is achieved using longitudinal follow-up of cohorts and biobanks using cancer registry linkages. All over the world, more and more large population-based cohorts and advanced biobanking facilities are established. International standardisation and networking in the linkage of cohorts and biobanks to cancer registries is required in order to enable international cancer research and comparability of research results. An international operating procedure and standard minimum dataset for linkages of biobanks, cohorts and cancer registries is proposed. An internationally comparable provision of well characterised study bases for molecular cancer research will be an essential prerequisite for the success of translational medicine. Copyright © 2013 Elsevier Ltd. All rights reserved.

Femtosecond X-ray Fourier holography imaging of free-flying nanoparticles

DOE PAGES

Gorkhover, Tais; Ulmer, Anatoli; Ferguson, Ken; ...

2018-02-26

Ultrafast X-ray imaging on individual fragile specimens such as aerosols, metastable particles, superfluid quantum systems and live biospecimens provides high-resolution information that is inaccessible with conventional imaging techniques. Coherent X-ray diffractive imaging, however, suffers from intrinsic loss of phase, and therefore structure recovery is often complicated and not always uniquely defined. Here in this paper, we introduce the method of in-flight holography, where we use nanoclusters as reference X-ray scatterers to encode relative phase information into diffraction patterns of a virus. The resulting hologram contains an unambiguous three-dimensional map of a virus and two nanoclusters with the highest lateral resolutionmore » so far achieved via single shot X-ray holography. Our approach unlocks the benefits of holography for ultrafast X-ray imaging of nanoscale, non-periodic systems and paves the way to direct observation of complex electron dynamics down to the attosecond timescale.« less

The Study to Explore Early Development (SEED): A Multisite Epidemiologic Study of Autism by the Centers for Autism and Developmental Disabilities Research and Epidemiology (CADDRE) Network

PubMed Central

Schendel, Diana; DiGuiseppi, Carolyn; Croen, Lisa; Fallin, M Danielle; Reed, Philip L.; Schieve, Laura; Wiggins, Lisa; Daniels, Julie; Grether, Judith; Levy, Susan; Miller, Lisa; Newschaffer, Craig; Pinto-Martin, Jennifer; Robinson, Cordelia; Windham, Gayle; Alexander, Aimee; Aylsworth, Arthur; Bernal, Pilar; Bonner, Joseph D.; Blaskey, Lisa; Bradley, Chyrise; Collins, Jack; Ferretti, Casara; Farzadegan, Homayoon; Giarelli, Ellen; Harvey, Marques; Hepburn, Susan; Herr, Matthew; Kaparich, Kristina; Landa, Rebecca; Lee, Li-Ching; Levenseller, Brooke; Meyerer, Stacey; Rahbar, Mohammad H.; Ratchford, Andria; Reynolds, Ann; Rosenberg, Steve; Rusyniak, Julie; Shapira, Stuart K.; Smith, Karen; Souders, Margaret; AaronThompson, Patrick; Young, Lisa; Yeargin-Allsopp, Marshalyn

2015-01-01

The Study to Explore Early Development (SEED), a multisite investigation addressing knowledge gaps in autism phenotype and etiology, aims to: (1) characterize the autism behavioral phenotype and associated developmental, medical, and behavioral conditions and (2) investigate genetic and environmental risks with emphasis on immunologic, hormonal, gastrointestinal, and sociodemographic characteristics. SEED uses a case–control design with population-based ascertainment of children aged 2–5 years with an autism spectrum disorder (ASD) and children in two control groups—one from the general population and one with non-ASD developmental problems. Data from parent-completed questionnaires, interviews, clinical evaluations, biospecimen sampling, and medical record abstraction focus on the prenatal and early postnatal periods. SEED is a valuable resource for testing hypotheses regarding ASD characteristics and causes. PMID:22350336

Disruptive Influences on Research in Academic Pathology Departments: Proposed Changes to the Common Rule Governing Informed Consent for Research Use of Biospecimens and to Rules Governing Return of Research Results.

PubMed

Sobel, Mark E; Dreyfus, Jennifer C

2017-01-01

Academic pathology departments will be dramatically affected by proposed United States federal government regulatory initiatives. Pathology research will be substantially altered if proposed changes to the Common Rule (Code of Federal Regulations: Protection of Human Subjects title 45 CFR 46) and regulations governing the return of individual research results are approved and finalized, even more so now that the Precision Medicine initiative has been launched. Together, these changes are disruptive influences on academic pathology research as we know it, straining limited resources and compromising advances in diagnostic and academic pathology. Academic research pathologists will be challenged over the coming years and must demonstrate leadership to ensure the continued availability of and the ethical use of research pathology specimens. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

National Institutes of Health Hematopoietic Cell Transplantation Late Effects Initiative: The Research Methodology and Study Design Working Group Report.

PubMed

Shaw, Bronwen E; Hahn, Theresa; Martin, Paul J; Mitchell, Sandra A; Petersdorf, Effie W; Armstrong, Gregory T; Shelburne, Nonniekaye; Storer, Barry E; Bhatia, Smita

2017-01-01

The increasing numbers of hematopoietic cell transplantations (HCTs) performed each year, the changing demographics of HCT recipients, the introduction of new transplantation strategies, incremental improvement in survival, and the growing population of HCT survivors demand a comprehensive approach to examining the health and well-being of patients throughout life after HCT. This report summarizes strategies for the conduct of research on late effects after transplantation, including consideration of the study design and analytic approaches; methodologic challenges in handling complex phenotype data; an appreciation of the changing trends in the practice of transplantation; and the availability of biospecimens to support laboratory-based research. It is hoped that these concepts will promote continued research and facilitate the development of new approaches to address fundamental questions in transplantation outcomes. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Patient Electronic Health Records as a Means to Approach Genetic Research in Gastroenterology

PubMed Central

Ananthakrishnan, Ashwin N; Lieberman, David

2015-01-01

Electronic health records (EHR) are being increasingly utilized and form a unique source of extensive data gathered during routine clinical care. Through use of codified and free text concepts identified using clinical informatics tools, disease labels can be assigned with a high degree of accuracy. Analysis linking such EHR-assigned disease labels to a biospecimen repository has demonstrated that genetic associations identified in prospective cohorts can be replicated with adequate statistical power, and novel phenotypic associations identified. In addition, genetic discovery research can be performed utilizing clinical, laboratory, and procedure data obtained during care. Challenges with such research include the need to tackle variability in quality and quantity of EHR data and importance of maintaining patient privacy and data security. With appropriate safeguards, this novel and emerging field of research offers considerable promise and potential to further scientific research in gastroenterology efficiently, cost-effectively, and with engagement of patients and communities. PMID:26073373

STANDARDIZING THE STRUCTURE OF STROKE CLINICAL AND EPIDEMIOLOGIC RESEARCH DATA: THE NINDS STROKE COMMON DATA ELEMENT (CDE) PROJECT

PubMed Central

Saver, Jeffrey L.; Warach, Steven; Janis, Scott; Odenkirchen, Joanne; Becker, Kyra; Benavente, Oscar; Broderick, Joseph; Dromerick, Alexander W.; Duncan, Pamela; Elkind, Mitchell S. V.; Johnston, Karen; Kidwell, Chelsea S.; Meschia, James F.; Schwamm, Lee

2012-01-01

Background and Purpose The National Institute of Neurological Disorders and Stroke initiated development of stroke-specific Common Data Elements (CDEs) as part of a project to develop data standards for funded clinical research in all fields of neuroscience. Standardizing data elements in translational, clinical and population research in cerebrovascular disease could decrease study start-up time, facilitate data sharing, and promote well-informed clinical practice guidelines. Methods A Working Group of diverse experts in cerebrovascular clinical trials, epidemiology, and biostatistics met regularly to develop a set of Stroke CDEs, selecting among, refining, and adding to existing, field-tested data elements from national registries and funded trials and studies. Candidate elements were revised based on comments from leading national and international neurovascular research organizations and the public. Results The first iteration of the NINDS stroke-specific CDEs comprises 980 data elements spanning nine content areas: 1) Biospecimens and Biomarkers; 2) Hospital Course and Acute Therapies; 3) Imaging; 4) Laboratory Tests and Vital Signs; 5) Long Term Therapies; 6) Medical History and Prior Health Status; 7) Outcomes and Endpoints; 8) Stroke Presentation; 9) Stroke Types and Subtypes. A CDE website provides uniform names and structures for each element, a data dictionary, and template case report forms (CRFs) using the CDEs. Conclusion Stroke-specific CDEs are now available as standardized, scientifically-vetted variable structures to facilitate data collection and data sharing in cerebrovascular patient-oriented research. The CDEs are an evolving resource that will be iteratively improved based on investigator use, new technologies, and emerging concepts and research findings. PMID:22308239

Plasma glutamine and glutamic acid are potential biomarkers for predicting diabetic retinopathy.

PubMed

Rhee, Sang Youl; Jung, Eun Sung; Park, Hye Min; Jeong, Su Jin; Kim, Kiyoung; Chon, Suk; Yu, Seung-Young; Woo, Jeong-Taek; Lee, Choong Hwan

2018-01-01

Diabetic patients with a long disease duration usually accompanied complication such as diabetic retinopathy, but in some patients had no complication. We analyzed differences in plasma metabolites according to the presence or absence of diabetic retinopathy (DR) in type 2 diabetic (T2D) patients with disease duration ≥ 15 years. A cohort of 183 T2D patients was established. Their biospecimens and clinical information were collected in accordance with the guidelines of the National Biobank of Korea, and the Korean Diabetes Association. DR phenotypes of the subjects were verified by ophthalmologic specialists. Plasma metabolites were analyzed using gas chromatography time-of-flight mass spectrometry and ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. And these results were analyzed using multivariate statistics. For metabolomic study, propensity score matched case and control subjects were chosen. Mean age of the subjects was 66.4 years and mean T2D duration was 22.2 years. Metabolomic identification revealed various carbohydrates, amino acids, and organic compounds that distinguished between age- and sex-matched non-diabetic controls and T2D subjects. Among these, glutamine and glutamic acid were suggested as the most distinctive metabolites for the presence of DR. Receiver operating characteristics curves showed an excellent diagnostic value of combined (AUC = 0.739) and the ratio (AUC = 0.742) of glutamine and glutamic acid for DR. And these results were consistent in validation analyses. Our results imply that plasma glutamine, glutamic acid, and their ratio may be valuable as novel biomarkers for anticipating DR in T2D subjects.

Somatic Mutations and Ancestry Markers in Hispanic Lung Cancer Patients.

PubMed

Gimbrone, Nicholas T; Sarcar, Bhaswati; Gordian, Edna R; Rivera, Jason I; Lopez, Christian; Yoder, Sean J; Teer, Jamie K; Welsh, Eric A; Chiappori, Alberto A; Schabath, Matthew B; Reuther, Gary W; Dutil, Julie; Garcia, Miosotis; Ventosilla-Villanueva, Ronald; Vera-Valdivia, Luis; Yabar-Berrocal, Alejandro; Motta-Guerrero, Rodrigo; Santiago-Cardona, Pedro G; Muñoz-Antonia, Teresita; Cress, W Douglas

2017-12-01

To address the lack of genomic data from Hispanic/Latino (H/L) patients with lung cancer, the Latino Lung Cancer Registry was established to collect patient data and biospecimens from H/L patients. This retrospective observational study examined lung cancer tumor samples from 163 H/L patients, and tumor-derived DNA was subjected to targeted-exome sequencing (>1000 genes, including EGFR, KRAS, serine/threonine kinase 11 gene [STK11], and tumor protein p53 gene [TP53]) and ancestry analysis. Mutation frequencies in this H/L cohort were compared with those in a similar cohort of non-Hispanic white (NHW) patients and correlated with ancestry, sex, smoking status, and tumor histologic type. Of the adenocarcinomas in the H/L cohort (n = 120), 31% had EGFR mutations, versus 17% in the NHW control group (p < 0.001). KRAS (20% versus 38% [p = 0.002]) and STK11 (8% versus 16% [p = 0.065]) mutations occurred at lower frequency, and mutations in TP53 occurred at similar frequency (46% versus 40% [p = 0.355]) in H/L and NHW patients, respectively. Within the Hispanic cohort, ancestry influenced the rate of TP53 mutations (p = 0.009) and may have influenced the rate of EGFR, KRAS, and STK11 mutations. Driver mutations in H/L patients with lung adenocarcinoma differ in frequency from those in NHW patients associated with their indigenous American ancestry. The spectrum of driver mutations needs to be further assessed in the H/L population. Copyright © 2017 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Establishment and maintenance of a standardized glioma tissue bank: Huashan experience.

PubMed

Aibaidula, Abudumijiti; Lu, Jun-feng; Wu, Jin-song; Zou, He-jian; Chen, Hong; Wang, Yu-qian; Qin, Zhi-yong; Yao, Yu; Gong, Ye; Che, Xiao-ming; Zhong, Ping; Li, Shi-qi; Bao, Wei-min; Mao, Ying; Zhou, Liang-fu

2015-06-01

Cerebral glioma is the most common brain tumor as well as one of the top ten malignant tumors in human beings. In spite of the great progress on chemotherapy and radiotherapy as well as the surgery strategies during the past decades, the mortality and morbidity are still high. One of the major challenges is to explore the pathogenesis and invasion of glioma at various "omics" levels (such as proteomics or genomics) and the clinical implications of biomarkers for diagnosis, prognosis or treatment of glioma patients. Establishment of a standardized tissue bank with high quality biospecimens annotated with clinical information is pivotal to the solution of these questions as well as the drug development process and translational research on glioma. Therefore, based on previous experience of tissue banks, standardized protocols for sample collection and storage were developed. We also developed two systems for glioma patient and sample management, a local database for medical records and a local image database for medical images. For future set-up of a regional biobank network in Shanghai, we also founded a centralized database for medical records. Hence we established a standardized glioma tissue bank with sufficient clinical data and medical images in Huashan Hospital. By September, 2013, tissues samples from 1,326 cases were collected. Histological diagnosis revealed that 73 % were astrocytic tumors, 17 % were oligodendroglial tumors, 2 % were oligoastrocytic tumors, 4 % were ependymal tumors and 4 % were other central nervous system neoplasms.

Establishing an Iso-Compliant Modern Cancer-Biobank in a Developing Country: A Model for International Cooperation.

PubMed

Sughayer, Maher A; Souan, Lina

2015-01-01

King Hussein Cancer (KHCC) is a specialized cancer center that treats both adult and pediatric cancer patients from Jordan and the neighboring countries. KHCC is acknowledged as a leader in cancer treatment in the Middle East and its vision is to maintain its leading position in cancer therapy and research. Hence, KHCC embarked on establishing the first ISO compliant cancer biobank (KHCCBIO) in Jordan.Currently, there are very few biobanks in the Middle East, hence, KHCC wanted to change this situation by establishing an ISO-compliant cancer biobank which would incorporate all current international guidelines and best-in class practices under an approved quality management system for the benefit of researchers in Jordan, its neighboring countries, and throughout the world. The established biobank would follow the highest ethical standards in collecting, processing, storing and distributing high-quality, clinically annotated biospecimens.The strategy used in establishing KHCCBIO was based on taking advantage of international networking and collaboration. This in essence led to knowledge transfer between well established organizations, institutions and individuals from Europe and Jordan, in existing technological innovation and internationally recognized quality standards. KHCC efforts were facilitated by a grant from the European Union under the seventh frame work program.Future aims of KHCCBIO are to develop KHCC's research infrastructure, increase its scope and visibility and improve its competitiveness throughout the biomedical science arena. Moreover, KHCCBIO is aiming to establish a platform for future knowledge transfer and collaborative research; develop partnerships between European and Middle Eastern organizations.

Biomarkers for Uranium Risk Assessment for the Development of the CURE (Concerted Uranium Research in Europe) Molecular Epidemiological Protocol.

PubMed

Guéguen, Yann; Roy, Laurence; Hornhardt, Sabine; Badie, Christophe; Hall, Janet; Baatout, Sarah; Pernot, Eileen; Tomasek, Ladislav; Laurent, Olivier; Ebrahimian, Teni; Ibanez, Chrystelle; Grison, Stephane; Kabacik, Sylwia; Laurier, Dominique; Gomolka, Maria

2017-01-01

Despite substantial experimental and epidemiological research, there is limited knowledge of the uranium-induce health effects after chronic low-dose exposures in humans. Biological markers can objectively characterize pathological processes or environmental responses to uranium and confounding agents. The integration of such biological markers into a molecular epidemiological study would be a useful approach to improve and refine estimations of uranium-induced health risks. To initiate such a study, Concerted Uranium Research in Europe (CURE) was established, and involves biologists, epidemiologists and dosimetrists. The aims of the biological work package of CURE were: 1. To identify biomarkers and biological specimens relevant to uranium exposure; 2. To define standard operating procedures (SOPs); and 3. To set up a common protocol (logistic, questionnaire, ethical aspects) to perform a large-scale molecular epidemiologic study in uranium-exposed cohorts. An intensive literature review was performed and led to the identification of biomarkers related to: 1. retention organs (lungs, kidneys and bone); 2. other systems/organs with suspected effects (cardiovascular system, central nervous system and lympho-hematopoietic system); 3. target molecules (DNA damage, genomic instability); and 4. high-throughput methods for the identification of new biomarkers. To obtain high-quality biological materials, SOPs were established for the sampling and storage of different biospecimens. A questionnaire was developed to assess potential confounding factors. The proposed strategy can be adapted to other internal exposures and should improve the characterization of the biological and health effects that are relevant for risk assessment.

Clinical relevance of molecular diagnostics in gastrointestinal (GI) cancer: European Society of Digestive Oncology (ESDO) expert discussion and recommendations from the 17th European Society for Medical Oncology (ESMO)/World Congress on Gastrointestinal Cancer, Barcelona.

PubMed

Baraniskin, Alexander; Van Laethem, Jean-Luc; Wyrwicz, Lucjan; Guller, Ulrich; Wasan, Harpreet S; Matysiak-Budnik, Tamara; Gruenberger, Thomas; Ducreux, Michel; Carneiro, Fatima; Van Cutsem, Eric; Seufferlein, Thomas; Schmiegel, Wolff

2017-11-01

In the epoch of precision medicine and personalised oncology, which aims to deliver the right treatment to the right patient, molecular genetic biomarkers are a topic of growing interest. The aim of this expert discussion and position paper is to review the current status of various molecular tests for gastrointestinal (GI) cancers and especially considering their significance for the clinical routine use. Opinion leaders and experts from diverse nationalities selected on scientific merit were asked to answer to a prepared set of questions about the current status of molecular diagnostics in different GI cancers. All answers were then discussed during a plenary session and reported here in providing a well-balanced reflection of both clinical expertise and updated evidence-based medicine. Preselected molecular genetic biomarkers that are described and disputed in the current medical literature in different GI cancers were debated, and recommendations for clinical routine practice were made whenever possible. Furthermore, the preanalytical variations were commented and proposals for quality controls of biospecimens were made. The current article summarises the recommendations of the expert committee regarding prognostic and predictive molecular genetic biomarkers in different entities of GI cancers. The briefly and comprehensively formulated guidelines should assist clinicians in the process of decision making in daily clinical practice. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Tohoku Medical Megabank Project: Design and Mission.

PubMed

Kuriyama, Shinichi; Yaegashi, Nobuo; Nagami, Fuji; Arai, Tomohiko; Kawaguchi, Yoshio; Osumi, Noriko; Sakaida, Masaki; Suzuki, Yoichi; Nakayama, Keiko; Hashizume, Hiroaki; Tamiya, Gen; Kawame, Hiroshi; Suzuki, Kichiya; Hozawa, Atsushi; Nakaya, Naoki; Kikuya, Masahiro; Metoki, Hirohito; Tsuji, Ichiro; Fuse, Nobuo; Kiyomoto, Hideyasu; Sugawara, Junichi; Tsuboi, Akito; Egawa, Shinichi; Ito, Kiyoshi; Chida, Koichi; Ishii, Tadashi; Tomita, Hiroaki; Taki, Yasuyuki; Minegishi, Naoko; Ishii, Naoto; Yasuda, Jun; Igarashi, Kazuhiko; Shimizu, Ritsuko; Nagasaki, Masao; Koshiba, Seizo; Kinoshita, Kengo; Ogishima, Soichi; Takai-Igarashi, Takako; Tominaga, Teiji; Tanabe, Osamu; Ohuchi, Noriaki; Shimosegawa, Toru; Kure, Shigeo; Tanaka, Hiroshi; Ito, Sadayoshi; Hitomi, Jiro; Tanno, Kozo; Nakamura, Motoyuki; Ogasawara, Kuniaki; Kobayashi, Seiichiro; Sakata, Kiyomi; Satoh, Mamoru; Shimizu, Atsushi; Sasaki, Makoto; Endo, Ryujin; Sobue, Kenji; Tohoku Medical Megabank Project Study Group, The; Yamamoto, Masayuki

2016-09-05

The Great East Japan Earthquake (GEJE) and resulting tsunami of March 11, 2011 gave rise to devastating damage on the Pacific coast of the Tohoku region. The Tohoku Medical Megabank Project (TMM), which is being conducted by Tohoku University Tohoku Medical Megabank Organization (ToMMo) and Iwate Medical University Iwate Tohoku Medical Megabank Organization (IMM), has been launched to realize creative reconstruction and to solve medical problems in the aftermath of this disaster. We started two prospective cohort studies in Miyagi and Iwate Prefectures: a population-based adult cohort study, the TMM Community-Based Cohort Study (TMM CommCohort Study), which will recruit 80 000 participants, and a birth and three-generation cohort study, the TMM Birth and Three-Generation Cohort Study (TMM BirThree Cohort Study), which will recruit 70 000 participants, including fetuses and their parents, siblings, grandparents, and extended family members. The TMM CommCohort Study will recruit participants from 2013 to 2016 and follow them for at least 5 years. The TMM BirThree Cohort Study will recruit participants from 2013 to 2017 and follow them for at least 4 years. For children, the ToMMo Child Health Study, which adopted a cross-sectional design, was also started in November 2012 in Miyagi Prefecture. An integrated biobank will be constructed based on the two prospective cohort studies, and ToMMo and IMM will investigate the chronic medical impacts of the GEJE. The integrated biobank of TMM consists of health and clinical information, biospecimens, and genome and omics data. The biobank aims to establish a firm basis for personalized healthcare and medicine, mainly for diseases aggravated by the GEJE in the two prefectures. Biospecimens and related information in the biobank will be distributed to the research community. TMM itself will also undertake genomic and omics research. The aims of the genomic studies are: 1) to construct an integrated biobank; 2) to return genomic research results to the participants of the cohort studies, which will lead to the implementation of personalized healthcare and medicine in the affected areas in the near future; and 3) to contribute the development of personalized healthcare and medicine worldwide. Through the activities of TMM, we will clarify how to approach prolonged healthcare problems in areas damaged by large-scale disasters and how useful genomic information is for disease prevention.

Functional signaling pathway analysis of lung adenocarcinomas identifies novel therapeutic targets for KRAS mutant tumors

PubMed Central

Baldelli, Elisa; Bellezza, Guido; Haura, Eric B.; Crinó, Lucio; Cress, W. Douglas; Deng, Jianghong; Ludovini, Vienna; Sidoni, Angelo; Schabath, Matthew B.; Puma, Francesco; Vannucci, Jacopo; Siggillino, Annamaria; Liotta, Lance A.; Petricoin, Emanuel F.; Pierobon, Mariaelena

2015-01-01

Little is known about the complex signaling architecture of KRAS and the interconnected RAS-driven protein-protein interactions, especially as it occurs in human clinical specimens. This study explored the activated and interconnected signaling network of KRAS mutant lung adenocarcinomas (AD) to identify novel therapeutic targets. Thirty-four KRAS mutant (MT) and twenty-four KRAS wild-type (WT) frozen biospecimens were obtained from surgically treated lung ADs. Samples were subjected to laser capture microdissection and reverse phase protein microarray analysis to explore the expression/activation levels of 150 signaling proteins along with co-activation concordance mapping. An independent set of 90 non-small cell lung cancers (NSCLC) was used to validate selected findings by immunohistochemistry (IHC). Compared to KRAS WT tumors, the signaling architecture of KRAS MT ADs revealed significant interactions between KRAS downstream substrates, the AKT/mTOR pathway, and a number of Receptor Tyrosine Kinases (RTK). Approximately one-third of the KRAS MT tumors had ERK activation greater than the WT counterpart (p<0.01). Notably 18% of the KRAS MT tumors had elevated activation of the Estrogen Receptor alpha (ER-α) (p=0.02). This finding was verified in an independent population by IHC (p=0.03). KRAS MT lung ADs appear to have a more intricate RAS linked signaling network than WT tumors with linkage to many RTKs and to the AKT-mTOR pathway. Combination therapy targeting different nodes of this network may be necessary to treat this group of patients. In addition, for patients with KRAS MT tumors and activation of the ER-α, anti-estrogen therapy may have important clinical implications. PMID:26468985

Surrogate Receptivity to Participation in Critical Illness Genetic Research

PubMed Central

Butler, Kevin; Bolcic-Jankovic, Dragana; Clarridge, Brian R.; Kennedy, Carie R.; LeBlanc, Jessica; Chandros Hull, Sara

2015-01-01

BACKGROUND: Collection of genetic biospecimens as part of critical illness investigations is increasingly commonplace. Oversight bodies vary in restrictions imposed on genetic research, introducing inconsistencies in study design, potential for sampling bias, and the possibility of being overly prohibitive of this type of research altogether. We undertook this study to better understand whether restrictions on genetic data collection beyond those governing research on cognitively intact subjects reflect the concerns of surrogates for critically ill patients. METHODS: We analyzed survey data collected from 1,176 patients in nonurgent settings and 437 surrogates representing critically ill adults. Attitudes pertaining to genetic data (familiarity, perceptions, interest in participation, concerns) and demographic information were examined using univariate and multivariate techniques. RESULTS: We explored differences among respondents who were receptive (1,333) and nonreceptive (280) to genetic sample collection. Whereas factors positively associated with receptivity to research participation were “complete trust” in health-care providers (OR, 2.091; 95% CI, 1.544-2.833), upper income strata (OR, 2.319; 95% CI, 1.308-4.114), viewing genetic research “very positively” (OR, 3.524; 95% CI, 2.122-5.852), and expressing “no worry at all” regarding disclosure of results (OR, 2.505; 95% CI, 1.436-4.369), black race was negatively associated with research participation (OR, 0.410; 95% CI, 0.288-0.585). We could detect no difference in receptivity to genetic sample collection comparing ambulatory patients and surrogates (OR, 0.738; 95% CI, 0.511-1.066). CONCLUSIONS: Expressing trust in health-care providers and viewing genetic research favorably were associated with increased willingness for study enrollment, while concern regarding breach of confidentiality and black race had the opposite effect. Study setting had no bearing on willingness to participate. PMID:25340645

Surrogate receptivity to participation in critical illness genetic research: aligning research oversight and stakeholder concerns.

PubMed

Freeman, Bradley D; Butler, Kevin; Bolcic-Jankovic, Dragana; Clarridge, Brian R; Kennedy, Carie R; LeBlanc, Jessica; Chandros Hull, Sara

2015-04-01

Collection of genetic biospecimens as part of critical illness investigations is increasingly commonplace. Oversight bodies vary in restrictions imposed on genetic research, introducing inconsistencies in study design, potential for sampling bias, and the possibility of being overly prohibitive of this type of research altogether. We undertook this study to better understand whether restrictions on genetic data collection beyond those governing research on cognitively intact subjects reflect the concerns of surrogates for critically ill patients. We analyzed survey data collected from 1,176 patients in nonurgent settings and 437 surrogates representing critically ill adults. Attitudes pertaining to genetic data (familiarity, perceptions, interest in participation, concerns) and demographic information were examined using univariate and multivariate techniques. We explored differences among respondents who were receptive (1,333) and nonreceptive (280) to genetic sample collection. Whereas factors positively associated with receptivity to research participation were "complete trust" in health-care providers (OR, 2.091; 95% CI, 1.544-2.833), upper income strata (OR, 2.319; 95% CI, 1.308-4.114), viewing genetic research "very positively" (OR, 3.524; 95% CI, 2.122-5.852), and expressing "no worry at all" regarding disclosure of results (OR, 2.505; 95% CI, 1.436-4.369), black race was negatively associated with research participation (OR, 0.410; 95% CI, 0.288-0.585). We could detect no difference in receptivity to genetic sample collection comparing ambulatory patients and surrogates (OR, 0.738; 95% CI, 0.511-1.066). Expressing trust in health-care providers and viewing genetic research favorably were associated with increased willingness for study enrollment, while concern regarding breach of confidentiality and black race had the opposite effect. Study setting had no bearing on willingness to participate.

Standardizing the structure of stroke clinical and epidemiologic research data: the National Institute of Neurological Disorders and Stroke (NINDS) Stroke Common Data Element (CDE) project.

PubMed

Saver, Jeffrey L; Warach, Steven; Janis, Scott; Odenkirchen, Joanne; Becker, Kyra; Benavente, Oscar; Broderick, Joseph; Dromerick, Alexander W; Duncan, Pamela; Elkind, Mitchell S V; Johnston, Karen; Kidwell, Chelsea S; Meschia, James F; Schwamm, Lee

2012-04-01

The National Institute of Neurological Disorders and Stroke initiated development of stroke-specific Common Data Elements (CDEs) as part of a project to develop data standards for funded clinical research in all fields of neuroscience. Standardizing data elements in translational, clinical, and population research in cerebrovascular disease could decrease study start-up time, facilitate data sharing, and promote well-informed clinical practice guidelines. A working group of diverse experts in cerebrovascular clinical trials, epidemiology, and biostatistics met regularly to develop a set of stroke CDEs, selecting among, refining, and adding to existing, field-tested data elements from national registries and funded trials and studies. Candidate elements were revised on the basis of comments from leading national and international neurovascular research organizations and the public. The first iteration of the National Institute of Neurological Disorders and Stroke (NINDS) stroke-specific CDEs comprises 980 data elements spanning 9 content areas: (1) biospecimens and biomarkers; (2) hospital course and acute therapies; (3) imaging; (4) laboratory tests and vital signs; (5) long-term therapies; (6) medical history and prior health status; (7) outcomes and end points; (8) stroke presentation; and (9) stroke types and subtypes. A CDE website provides uniform names and structures for each element, a data dictionary, and template case report forms, using the CDEs. Stroke-specific CDEs are now available as standardized, scientifically vetted, variable structures to facilitate data collection and data sharing in cerebrovascular patient-oriented research. The CDEs are an evolving resource that will be iteratively improved based on investigator use, new technologies, and emerging concepts and research findings.

Neutrophil-Related Gene Expression And Low-Density Granulocytes Associated with Disease Activity and Response to Treatment in ANCA-Associated Vasculitis

PubMed Central

Grayson, Peter C.; Carmona-Rivera, Carmelo; Xu, Lijing; Lim, Noha; Gao, Zhong; Asare, Adam L.; Specks, Ulrich; Stone, John H.; Seo, Philip; Spiera, Robert F.; Langford, Carol A.; Hoffman, Gary S.; Kallenberg, Cees G.M.; St Clair, E. William; Tchao, Nadia K.; Ytterberg, Steven R.; Phippard, Deborah J.; Merkel, Peter A.; Kaplan, Mariana J.; Monach, Paul A.

2015-01-01

Objectives To discover biomarkers involved in the pathophysiology of ANCA-associated vasculitis (AAV) and determine if low-density granulocytes (LDGs) contribute to gene expression signatures in AAV. Methods The source of clinical data and linked biospecimens was a randomized controlled treatment trial in AAV. RNA-sequencing of whole blood from patients with AAV was performed during active disease at the baseline visit (BL) and during remission 6 months later (6M). Gene expression was compared between patients who met versus did not meet the primary trial outcome of clinical remission at 6M (responders vs. nonresponders). Measurement of neutrophil-related gene expression was confirmed in PBMCs to validate findings in whole blood. A negative selection strategy isolated LDGs from PBMC fractions. Results Differential expression between responders (n=77) and nonresponders (n=35) was detected in 2,346 transcripts at BL visit (p<0.05). Unsupervised hierarchical clustering demonstrated a cluster of granulocyte-related genes, including myeloperoxidase (MPO) and proteinase 3 (PR3). A granulocyte multi-gene composite score was significantly higher in nonresponders than responders (p<0.01) and during active disease compared to remission (p<0.01). This signature strongly overlapped an LDG signature identified previously in lupus (FDRGSEA<0.01). Transcription of PR3 measured in PBMCs was associated with active disease and treatment response (p<0.01). LDGs isolated from patients with AAV spontaneously formed neutrophil extracellular traps containing PR3 and MPO. Conclusions In AAV an increased expression of a granulocyte gene signature is associated with disease activity and decreased response to treatment. The source of this signature is likely LDGs, a potentially pathogenic cell type in AAV. PMID:25891759

Object-oriented regression for building predictive models with high dimensional omics data from translational studies.

PubMed

Zhao, Lue Ping; Bolouri, Hamid

2016-04-01

Maturing omics technologies enable researchers to generate high dimension omics data (HDOD) routinely in translational clinical studies. In the field of oncology, The Cancer Genome Atlas (TCGA) provided funding support to researchers to generate different types of omics data on a common set of biospecimens with accompanying clinical data and has made the data available for the research community to mine. One important application, and the focus of this manuscript, is to build predictive models for prognostic outcomes based on HDOD. To complement prevailing regression-based approaches, we propose to use an object-oriented regression (OOR) methodology to identify exemplars specified by HDOD patterns and to assess their associations with prognostic outcome. Through computing patient's similarities to these exemplars, the OOR-based predictive model produces a risk estimate using a patient's HDOD. The primary advantages of OOR are twofold: reducing the penalty of high dimensionality and retaining the interpretability to clinical practitioners. To illustrate its utility, we apply OOR to gene expression data from non-small cell lung cancer patients in TCGA and build a predictive model for prognostic survivorship among stage I patients, i.e., we stratify these patients by their prognostic survival risks beyond histological classifications. Identification of these high-risk patients helps oncologists to develop effective treatment protocols and post-treatment disease management plans. Using the TCGA data, the total sample is divided into training and validation data sets. After building up a predictive model in the training set, we compute risk scores from the predictive model, and validate associations of risk scores with prognostic outcome in the validation data (P-value=0.015). Copyright © 2016 Elsevier Inc. All rights reserved.

Object-Oriented Regression for Building Predictive Models with High Dimensional Omics Data from Translational Studies

PubMed Central

Zhao, Lue Ping; Bolouri, Hamid

2016-01-01

Maturing omics technologies enable researchers to generate high dimension omics data (HDOD) routinely in translational clinical studies. In the field of oncology, The Cancer Genome Atlas (TCGA) provided funding support to researchers to generate different types of omics data on a common set of biospecimens with accompanying clinical data and to make the data available for the research community to mine. One important application, and the focus of this manuscript, is to build predictive models for prognostic outcomes based on HDOD. To complement prevailing regression-based approaches, we propose to use an object-oriented regression (OOR) methodology to identify exemplars specified by HDOD patterns and to assess their associations with prognostic outcome. Through computing patient’s similarities to these exemplars, the OOR-based predictive model produces a risk estimate using a patient’s HDOD. The primary advantages of OOR are twofold: reducing the penalty of high dimensionality and retaining the interpretability to clinical practitioners. To illustrate its utility, we apply OOR to gene expression data from non-small cell lung cancer patients in TCGA and build a predictive model for prognostic survivorship among stage I patients, i.e., we stratify these patients by their prognostic survival risks beyond histological classifications. Identification of these high-risk patients helps oncologists to develop effective treatment protocols and post-treatment disease management plans. Using the TCGA data, the total sample is divided into training and validation data sets. After building up a predictive model in the training set, we compute risk scores from the predictive model, and validate associations of risk scores with prognostic outcome in the validation data (p=0.015). PMID:26972839

GeneLab: Multi-Omics Investigation of Rodent Research-1 Bio-Banked Tissues

NASA Technical Reports Server (NTRS)

Lai, San-Huei; Boyko, Valery; Chakravarty, Kaushik; Chen, Rick; Dueck, Sandra; Berrios, Daniel C.; Fogle, Homer; Marcu, Oana; Timucin, Linda; Reinsch, Sigrid;

All in the Blood: A Review of Aboriginal Australians' Cultural Beliefs About Blood and Implications for Biospecimen Research.

PubMed

Kowal, Emma; Greenwood, Ashley; McWhirter, Rebekah E

2015-10-01

Public participation in medical research and biobanking is considered key to advances in scientific discovery and translation to improved health care. Cultural concerns relating to blood have been found to affect the participation of indigenous peoples and minorities in research, but such concerns are rarely specified in the literature. This article presents a review of the role of blood in Australian Aboriginal cultures. We discuss the range of meanings and uses of blood in traditional culture, including their use in ceremonies, healing, and sorcery. We draw on more recent literature on Aboriginal Australians and biomedicine to consider how traditional beliefs may be changing over time. These findings provide an empirical basis for researchers and bioethicists to develop culturally grounded strategies to boost the participation of Aboriginal Australians in biomedical research. They also serve as a model for integrating anthropological literature with bioethical concerns that could be applied to other indigenous and minority groups. © The Author(s) 2015.

A concept of a MIABIS based register of biosample collections at the Medical University of Innsbruck.

PubMed

Hofer, Philipp; Fiegl, Heidi; Angerer, Justina; Mueller-Holzner, Elisabeth; Chamson, Martina; Klocker, Helmut; Steiner, Eberhardt; Hauffe, Helga; Zschocke, Johannes; Goebel, Georg

2014-01-01

The knowledge about the quality of samples and associated clinical data in biospecimen collections is a premise of clinical research. An electronic biosample register aims to facilitate the discovery of information about biosample collections in a hospital. Moreover, it might improve scientific collaboration and research quality through a shared access to harmonized sample collection description data. The aim of this paper is to present a concept of a web-based biosample register of the existing biosample collections at the Medical University of Innsbruck. A uniform description model is built based on an analysis of the sample collection data of independent sample management systems from two departments within the hospital. An extended set of attributes of the minimum dataset used by the Swedish sample collection register (MIABIS) has been applied to all biosample collections as a common description model. The results of the analysis and the data model are presented together with a first concept of a sample collection search register.

Efficiently Maintaining a National Resource of Historical and Contemporary Biological Collections: The NHLBI Biorepository Model.

PubMed

Shea, Katheryn E; Wagner, Elizabeth L; Marchesani, Leah; Meagher, Kevin; Giffen, Carol

2017-02-01

Reducing costs by improving storage efficiency has been a focus of the National Heart, Lung, and Blood Institute (NHLBI) Biologic Specimen Repository (Biorepository) and Biologic Specimen and Data Repositories Information Coordinating Center (BioLINCC) programs for several years. Study specimen profiles were compiled using the BioLINCC collection catalog. Cost assessments and calculations on the return on investments to consolidate or reduce a collection, were developed and implemented. Over the course of 8 months, the NHLBI Biorepository evaluated 35 collections that consisted of 1.8 million biospecimens. A total of 23 collections were selected for consolidation, with a total of 1.2 million specimens located in 21,355 storage boxes. The consolidation resulted in a savings of 4055 boxes of various sizes and 10.2 mechanical freezers (∼275 cubic feet) worth of space. As storage costs in a biorepository increase over time, the development and use of information technology tools to assess the potential advantage and feasiblity of vial consolidation can reduce maintenance expenses.

Summary of the ISEV workshop on extracellular vesicles as disease biomarkers, held in Birmingham, UK, during December 2017

PubMed Central

Carter, David R. F.; Cheng, Lesley; Compton, Carolyn; Daaboul, George; Devitt, Andrew; Falcon-Perez, Juan Manuel; Gardiner, Chris; Helmbrecht, Clemens; Hendrix, An; Hoffman, Andrew; Kalluri, Raghu; Kang, Ji Yoon; Lässer, Cecilia; Lawson, Charlotte; Lenassi, Metka; Levin, Carina; Llorente, Alicia; Martens-Uzunova, Elena S.; Möller, Andreas; Ochiya, Takahiro; Pink, Ryan C; Tahara, Hidetoshi; Wauben, Marca H. M.; Webber, Jason P.; Yin, Hang; Nieuwland, Rienk

2018-01-01

ABSTRACT This report summarises the presentations and activities of the ISEV Workshop on extracellular vesicle biomarkers held in Birmingham, UK during December 2017. Among the key messages was broad agreement about the importance of biospecimen science. Much greater attention needs to be paid towards the provenance of collected samples. The workshop also highlighted clear gaps in our knowledge about pre-analytical factors that alter extracellular vesicles (EVs). The future utility of certified standards for credentialing of instruments and software, to analyse EV and for tracking the influence of isolation steps on the structure and content of EVs were also discussed. Several example studies were presented, demonstrating the potential utility for EVs in disease diagnosis, prognosis, longitudinal serial testing and stratification of patients. The conclusion of the workshop was that more effort focused on pre-analytical issues and benchmarking of isolation methods is needed to strengthen collaborations and advance more effective biomarkers.

16S rRNA Gene Sequencing for Deciphering the Colorectal Cancer Gut Microbiome: Current Protocols and Workflows.

PubMed

Osman, Muhammad-Afiq; Neoh, Hui-Min; Ab Mutalib, Nurul-Syakima; Chin, Siok-Fong; Jamal, Rahman

2018-01-01

The human gut holds the densest microbiome ecosystem essential in maintaining a healthy host physiology, whereby disruption of this ecosystem has been linked to the development of colorectal cancer (CRC). The advent of next-generation sequencing technologies such as the 16S rRNA gene sequencing has enabled characterization of the CRC gut microbiome architecture in an affordable and culture-free approach. Nevertheless, the lack of standardization in handling and storage of biospecimens, nucleic acid extraction, 16S rRNA gene primer selection, length, and depth of sequencing and bioinformatics analyses have contributed to discrepancies found in various published studies of this field. Accurate characterization of the CRC microbiome found in different stages of CRC has the potential to be developed into a screening tool in the clinical setting. This mini review aims to concisely compile all available CRC microbiome studies performed till end of 2016 and to suggest standardized protocols that are crucial in developing a gut microbiome screening panel for CRC.

The Alaska Area Specimen Bank: a tribal-federal partnership to maintain and manage a resource for health research.

PubMed

Parkinson, Alan J; Hennessy, Thomas; Bulkow, Lisa; Smith, H Sally

2013-01-01

Banked biospecimens from a defined population are a valuable resource that can be used to assess early markers for illness or to determine the prevalence of a disease to aid the development of intervention strategies to reduce morbidity and mortality. The Alaska Area Specimen Bank (AASB) currently contains 266,353 residual biologic specimens (serum, plasma, whole blood, tissue, bacterial cultures) from 83,841 persons who participated in research studies, public health investigations and clinical testing conducted by the U.S. Public Health Service and Alaska Native tribal health organisations dating back to 1961. The majority (95.7%) are serum specimens, 77% were collected between 1981 and 1994 and 85% were collected from Alaska Native people. Oversight of the specimen bank is provided by a working group with representation from tribal, state and federal health organisations, the Alaska Area IRB and a specimen bank committee which ensures the specimens are used in accordance with policies and procedures developed by the working group.

Effect of spaceflight on oxidative and antioxidant enzyme activity in rat diaphragm and intercostal muscles

NASA Technical Reports Server (NTRS)

Lee, Mona D.; Tuttle, Ronald; Girten, Beverly

1995-01-01

There are limited data regarding changes in oxidative and antioxidant enzymes induced by simulated or actual weightlessness, and any additional information would provide insight into potential mechanisms involving other changes observed in muscles from animals previously flown in space. Thus, the NASA Biospecimen Sharing Program was an opportunity to collect valuable information. Oxidative and antioxidant enzyme levels, as well as lipid peroxidation, were measured in respiratory muscles from rates flown on board Space Shuttle mission STS-54. The results indicated that there was an increasing trend in citrate synthase activity in the flight diaphragm when compared to ground based controls, and there were no significant changes observed in the intercostal muscles for any of the parameters. However, the lipid peroxidation was significantly (p less than 0.05) decreased in the flight diaphragm. These results indicate that 6 day exposure to microgravity may have a different effect on oxidative and antioxidant activity in rat respiratory muscles when compared to data from previous 14 day hindlimb suspension studies.

Femtosecond X-ray Fourier holography imaging of freeflying nanoparticles

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gorkhover, Tais; Ulmer, Anatoli; Ferguson, Ken R.

Ultrafast X-ray imaging on individual fragile specimens such as aerosols1, metastable particles2, superfluid quantum systems3 and live biospecimen4 provides high resolution information, which is inaccessible with conventional imaging techniques. Coherent X-ray diffractive imag- 2 ing, however, suffers from intrinsic loss of phase, and therefore structure recovery is often complicated and not always uniquely-defined4, 5. Here, we introduce the method of in-flight holography, where we use nanoclusters as reference X-ray scatterers in order to encode relative phase information into diffraction patterns of a virus. The resulting hologram contains an unambiguous three-dimensional map of a virus and two nanoclusters with the highestmore » lateral resolution so far achieved via single shot X-ray holography. Our approach unlocks the benefits of holography for ultrafast X-ray imaging of nanoscale, non-periodic systems and paves the way to direct observation of complex electron dynamics down to the attosecond time scale.« less

JAX Colony Management System (JCMS): an extensible colony and phenotype data management system.

PubMed

Donnelly, Chuck J; McFarland, Mike; Ames, Abigail; Sundberg, Beth; Springer, Dave; Blauth, Peter; Bult, Carol J

2010-04-01

The Jackson Laboratory Colony Management System (JCMS) is a software application for managing data and information related to research mouse colonies, associated biospecimens, and experimental protocols. JCMS runs directly on computers that run one of the PC Windows operating systems, but can be accessed via web browser interfaces from any computer running a Windows, Macintosh, or Linux operating system. JCMS can be configured for a single user or multiple users in small- to medium-size work groups. The target audience for JCMS includes laboratory technicians, animal colony managers, and principal investigators. The application provides operational support for colony management and experimental workflows, sample and data tracking through transaction-based data entry forms, and date-driven work reports. Flexible query forms allow researchers to retrieve database records based on user-defined criteria. Recent advances in handheld computers with integrated barcode readers, middleware technologies, web browsers, and wireless networks add to the utility of JCMS by allowing real-time access to the database from any networked computer.

Patient Electronic Health Records as a Means to Approach Genetic Research in Gastroenterology.

PubMed

Ananthakrishnan, Ashwin N; Lieberman, David

2015-10-01

Electronic health records (EHRs) are being increasingly utilized and form a unique source of extensive data gathered during routine clinical care. Through use of codified and free text concepts identified using clinical informatics tools, disease labels can be assigned with a high degree of accuracy. Analysis linking such EHR-assigned disease labels to a biospecimen repository has demonstrated that genetic associations identified in prospective cohorts can be replicated with adequate statistical power and novel phenotypic associations identified. In addition, genetic discovery research can be performed utilizing clinical, laboratory, and procedure data obtained during care. Challenges with such research include the need to tackle variability in quality and quantity of EHR data and importance of maintaining patient privacy and data security. With appropriate safeguards, this novel and emerging field of research offers considerable promise and potential to further scientific research in gastroenterology efficiently, cost-effectively, and with engagement of patients and communities. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

Roadmap to a Comprehensive Clinical Data Warehouse for Precision Medicine Applications in Oncology

PubMed Central

Foran, David J; Chen, Wenjin; Chu, Huiqi; Sadimin, Evita; Loh, Doreen; Riedlinger, Gregory; Goodell, Lauri A; Ganesan, Shridar; Hirshfield, Kim; Rodriguez, Lorna; DiPaola, Robert S

2017-01-01

Leading institutions throughout the country have established Precision Medicine programs to support personalized treatment of patients. A cornerstone for these programs is the establishment of enterprise-wide Clinical Data Warehouses. Working shoulder-to-shoulder, a team of physicians, systems biologists, engineers, and scientists at Rutgers Cancer Institute of New Jersey have designed, developed, and implemented the Warehouse with information originating from data sources, including Electronic Medical Records, Clinical Trial Management Systems, Tumor Registries, Biospecimen Repositories, Radiology and Pathology archives, and Next Generation Sequencing services. Innovative solutions were implemented to detect and extract unstructured clinical information that was embedded in paper/text documents, including synoptic pathology reports. Supporting important precision medicine use cases, the growing Warehouse enables physicians to systematically mine and review the molecular, genomic, image-based, and correlated clinical information of patient tumors individually or as part of large cohorts to identify changes and patterns that may influence treatment decisions and potential outcomes. PMID:28469389

The California HIV/AIDS Research Program: History, Impact, and HIV Cure Initiative.

PubMed

Stanga, Lisa Loeb; Mujeeb, Anwer; Packel, Laura; Martz, Tyler; Lemp, George

2017-11-01

This Special Issue of AIDS Research and Human Retroviruses features results from the HIV Cure Initiative, funded by the California HIV/AIDS Research Program (CHRP). As a publicly funded grant maker, CHRP has served for more than three decades as a unique resource for innovative researchers in California, whose work seeks to address all aspects of the HIV epidemic and the communities affected by it. Early initiatives at CHRP pioneered what would become enduring cornerstones of HIV science: isolation of the virus; efficacy and toxicities of the first HIV treatments; the emergence of drug resistance; the first biospecimen banks for HIV-related research; the first community-based laboratory service for HIV diagnostic serology; and the first longitudinal case-control study of progression from HIV to AIDS-The San Francisco General Hospital Cohort. More recently, CHRP-funded conceptual studies of zinc-finger nuclease-mediated disruption of CCR5 genomic sequences and the safety of solid organ transplantation for HIV-positive patients have progressed from brilliant ideas to clinical realities, and CHRP is currently funding the first multisite trial of HIV preexposure prophylaxis for transgender persons in the United States. The present article outlines the founding of CHRP, our current grantmaking process, and our impact on HIV research over time. In 2013, CHRP launched a new initiative aimed at moving the then nascent frontier of HIV cure science forward: the CHRP HIV Cure Initiative provided over $1.4 million to multiple basic biomedical research projects, and selected results are presented in this Special Issue.

Building a pipeline to discover and validate novel therapeutic targets and lead compounds for Alzheimer's disease

PubMed Central

Bennett, David A.; Yu, Lei; De Jager, Philip L.

2014-01-01

Cognitive decline, Alzheimer's disease (AD) and other causes are major public health problems worldwide. With changing demographics, the number of persons with dementia will increase rapidly. The treatment and prevention of AD and other dementias, therefore, is an urgent unmet need. There have been considerable advances in understanding the biology of many age-related disorders that cause dementia. Gains in understanding AD have led to the development of ante-mortem biomarkers of traditional neuropathology and the conduct of several phase III interventions in the amyloid-β cascade early in the disease process. Many other intervention strategies are in various stages of development. However, efforts to date have met with limited success. A recent National Institute on Aging Research Summit led to a number of requests for applications. One was to establish multi-disciplinary teams of investigators who use systems biology approaches and stem cell technology to identify a new generation of AD targets. We were recently awarded one of three such grants to build a pipeline that integrates epidemiology, systems biology, and stem cell technology to discover and validate novel therapeutic targets and lead compounds for AD treatment and prevention. Here we describe the two cohorts that provide the data and biospecimens being exploited for our pipeline and describe the available unique datasets. Second, we present evidence in support of a chronic disease model of AD that informs our choice of phenotypes as the target outcome. Third, we provide an overview of our approach. Finally, we present the details of our planned drug discovery pipeline. PMID:24508835

A review of international biobanks and networks: success factors and key benchmarks.

PubMed

Vaught, Jim; Kelly, Andrea; Hewitt, Robert

2009-09-01

Biobanks and biobanking networks are involved in varying degrees in the collection, processing, storage, and dissemination of biological specimens. This review outlines the approaches that 16 of the largest biobanks and biobanking networks in Europe, North America, Australia, and Asia have taken to collecting and distributing human research specimens and managing scientific initiatives while covering operating costs. Many are small operations that exist as either a single or a few freezers in a research laboratory, hospital clinical laboratory, or pathology suite. Larger academic and commercial biobanks operate to support large clinical and epidemiological studies. Operational and business models depend on the medical and research missions of their institutions and home countries. Some national biobanks operate with a centralized physical biobank that accepts samples from multiple locations. Others operate under a "federated" model where each institution maintains its own collections but agrees to list them on a central shared database. Some collections are "project-driven" meaning that specimens are collected and distributed to answer specific research questions. "General" collections are those that exist to establish a reference collection, that is, not to meet particular research goals but to be available to respond to multiple requests for an assortment of research uses. These individual and networked biobanking systems operate under a variety of business models, usually incorporating some form of partial cost recovery, while requiring at least partial public or government funding. Each has a well-defined biospecimen-access policy in place that specifies requirements that must be met-such as ethical clearance and the expertise to perform the proposed experiments-to obtain samples for research. The success of all of these biobanking models depends on a variety of factors including well-defined goals, a solid business plan, and specimen collections that are developed according to strict quality and operational controls.

A UHPLC-MS/MS method for profiling multifunctional steroids in human hair.

PubMed

Dong, Zhen; Wang, Caihong; Zhang, Jinlan; Wang, Zhe

2017-08-01

It is important to profile steroids in many physiological and pathological processes. Recently, hair has been used for the long-term measurement of endogenous steroid hormones. Analyzing hair has advantages of being noninvasive and time sequential compared with other bio-specimens. Liquid chromatography-mass spectrometry (LC-MS) techniques have been widely used over the past decades; however, it is challenging to profile estrogens in hair by LC-MS, and more comprehensive steroid profiling is required. In this paper, an ultra high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed to simultaneously profile 28 multifunctional steroids, including corticosteroids (n = 6), estrogens (n = 13), androgens (n = 5) and progestogens (n = 4), in human scalp hair in a single run. To optimize the sample preparation procedure, we evaluated extraction time, post-incubation purification and hair fragment length; 30 mg hair samples were washed with hexane, cut into 5 mm pieces and incubated in methanol for 18 h at 25 °C. Methanol extraction derivatized using Girard P and dansyl chloride reagent was analyzed within 25 min using an automated injection program combined with a diverter valve switch and step analysis (AIDSA). The method was well validated in terms of linearity, limit of detection (LOD), limit of quantification (LOQ), precision, accuracy, matrix effect and recovery, and was successfully applied to a steroid profile from male and female hairs. Significant differences were observed between genders. In addition, steroids showed a declining trend from the proximal to more distal hair segments; thus, care should be taken when obtaining hair samples for analysis to account for this difference in steroid levels along the length of hair. Graphical Abstract The workflow of the estabished UHPLC-MS/MS method.

Genomics, Telomere Length, Epigenetics, and Metabolomics in the Nurses’ Health Studies

PubMed Central

Aschard, Hugues; De Vivo, Immaculata; Michels, Karin B.; Kraft, Peter

2016-01-01

Objectives. To review the contribution of the Nurses’ Health Study (NHS) and NHS II to genomics, epigenetics, and metabolomics research. Methods. We performed a narrative review of the publications of the NHS and NHS II between 1990 and 2016 based on biospecimens, including blood and tumor tissue, collected from participants. Results. The NHS has contributed to the discovery of genetic loci influencing more than 45 complex human phenotypes, including cancers, diabetes, cardiovascular disease, reproductive characteristics, and anthropometric traits. The combination of genomewide genotype data with extensive exposure and lifestyle data has enabled the evaluation of gene–environment interactions. Furthermore, data suggest that longer telomere length increases risk of cancers not related to smoking, and that modifiable factors (e.g., diet) may have an impact on telomere length. “Omics” research in the NHS continues to expand, with epigenetics and metabolomics becoming greater areas of focus. Conclusions. The combination of prospective biomarker data and broad exposure information has enabled the NHS to participate in a variety of “omics” research, contributing to understanding of the epidemiology and biology of multiple complex diseases. PMID:27459442

Genomics, Telomere Length, Epigenetics, and Metabolomics in the Nurses' Health Studies.

PubMed

Townsend, Mary K; Aschard, Hugues; De Vivo, Immaculata; Michels, Karin B; Kraft, Peter

2016-09-01

To review the contribution of the Nurses' Health Study (NHS) and NHS II to genomics, epigenetics, and metabolomics research. We performed a narrative review of the publications of the NHS and NHS II between 1990 and 2016 based on biospecimens, including blood and tumor tissue, collected from participants. The NHS has contributed to the discovery of genetic loci influencing more than 45 complex human phenotypes, including cancers, diabetes, cardiovascular disease, reproductive characteristics, and anthropometric traits. The combination of genomewide genotype data with extensive exposure and lifestyle data has enabled the evaluation of gene-environment interactions. Furthermore, data suggest that longer telomere length increases risk of cancers not related to smoking, and that modifiable factors (e.g., diet) may have an impact on telomere length. "Omics" research in the NHS continues to expand, with epigenetics and metabolomics becoming greater areas of focus. The combination of prospective biomarker data and broad exposure information has enabled the NHS to participate in a variety of "omics" research, contributing to understanding of the epidemiology and biology of multiple complex diseases.

Translating cryobiology principles into trans-disciplinary storage guidelines for biorepositories and biobanks: a concept paper.

PubMed

Benson, E; Betson, F; Fuller, B J; Harding, K; Kofanova, O

2013-01-01

Low temperatures are used routinely to preserve diverse biospecimens, genetic resources and non-viable or viable biosamples for medical and clinical research in hospital-based biobanks and non-medical biorepositories, such as genebanks and culture, scientific, museum, and environmental collections. However, the basic knowledge underpinning preservation can sometimes be overlooked by practitioners who are unfamiliar with fundamental cryobiological principles which are more usually described in research literature rather than in quality and risk management documents. Whilst procedures vary, low temperature storage is a common requirement and reaching consensus as to how best it is applied could facilitate the entire biopreservation sector. This may be achieved by encouraging an understanding of cryoprotection theory and emphasizing the criticality of thermal events (glass transitions, ice nucleation, thawing) for sample integrity, functionality and stability. The objective of this paper is to inspire diverse biopreservation sectors to communicate more clearly about low temperature storage and, raise awareness of the importance of cryobiology principles to field newcomers and biopreservation practitioners, by considering how the principles may be translated into evidence-based guidelines for biobank and biorepository operations.

Recommendations for Soluble Biomarker Assessments in Osteoarthritis Clinical Trials

PubMed Central

Kraus, Virginia Byers; Blanco, Francisco J; Englund, Martin; Henrotin, Yves; Lohmander, L Stefan; Losina, Elena; Önnerfjord, Patrik; Persiani, Stefano

2015-01-01

Objective To describe requirements for inclusion of soluble biomarkers in osteoarthritis (OA) clinical trials and progress toward OA-related biomarker qualification. Methods The Guidelines for Biomarkers Working Group, representing experts in the field of OA biomarker research from both academia and industry, convened to discuss issues related to soluble biomarkers and to make recommendations for their use in OA clinical trials based on current knowledge and anticipated benefits. Results This document summarizes current guidance on use of biomarkers in OA clinical trials and their utility at 5 stages, including preclinical development and phase I to phase IV trials. Conclusions Biomarkers can provide value at all stages of therapeutics development. When resources permit, we recommend collection of biospecimens in all OA clinical trials for a wide variety of reasons but in particular, to determine whether biomarkers are useful in identifying those individuals most likely to receive clinically important benefits from an intervention; and to determine whether biomarkers are useful for identifying individuals at earlier stages of OA in order to institute treatment at a time more amenable to disease modification. PMID:25952342

Experimental and Study Design Considerations for Uncovering Oncometabolites.

PubMed

Haznadar, Majda; Mathé, Ewy A

2017-01-01

Metabolomics as a field has gained attention due to its potential for biomarker discovery, namely because it directly reflects disease phenotype and is the downstream effect of posttranslational modifications. The field provides a "top-down," integrated view of biochemistry in complex organisms, as opposed to the traditional "bottom-up" approach that aims to analyze networks of interactions between genes, proteins and metabolites. It also allows for the detection of thousands of endogenous metabolites in various clinical biospecimens in a high-throughput manner, including tissue and biofluids such as blood and urine. Of note, because biological fluid samples can be collected relatively easily, the time-dependent fluctuations of metabolites can be readily studied in detail.In this chapter, we aim to provide an overview of (1) analytical methods that are currently employed in the field, and (2) study design concepts that should be considered prior to conducting high-throughput metabolomics studies. While widely applicable, the concepts presented here are namely applicable to high-throughput untargeted studies that aim to search for metabolite biomarkers that are associated with a particular human disease.

Qualification of imaging biomarkers for oncology drug development.

PubMed

Waterton, John C; Pylkkanen, Liisa

2012-03-01

Although many imaging biomarkers have been described for cancer research, few are sufficiently robust, reliable and well-characterised to be used as routine tools in clinical cancer research. In particular, biomarkers which show that investigational therapies have reduced tumour cell proliferation, or induced necrotic or apoptotic cell death are not commonly used to support decision-making in drug development, even though such pharmacodynamic effects are common goals of many classes of investigational drugs. Moreover we lack well-qualified biomarkers of propensity to metastasise. The qualification and technical validation of imaging biomarkers poses unique challenges not always encountered when validating biospecimen biomarkers. These include standardisation of acquisition and analysis, imaging-pathology correlation, cross-sectional clinical-biomarker correlations and correlation with outcome. Such work is ideally suited to precompetitive research and public-private partnerships, and this has been recognised within the Innovative Medicines Initiative (IMI), a Joint Undertaking between the European Union and the European Federation of Pharmaceutical Industries and Associations, which has initiated projects in the areas of drug safety, drug efficacy, knowledge management and training. Copyright © 2011 Elsevier Ltd. All rights reserved.

Filipino women's diet and health study (FiLWHEL): design and methods.

PubMed

Abris, Grace P; Hong, Sangmo; Provido, Sherlyn Mae P; Lee, Jung Eun; Lee, Chang Beom

2017-02-01

Immigration to South Korea from neighboring Asian countries has risen dramatically, primarily due to marriage between Korean men and foreign women. Although Filipino women rank fourth among married immigrant women, little is known about the health condition of this population. This manuscript focuses on the design and methods of Filipino women's diet and health study (FiLWHEL). FiLWHEL is a cohort of Filipino women married to Korean men, aged 19 years old or over. The data collection comprised three parts: questionnaire, physical examination, and biospecimen collection. Questionnaires focused on demographic factors, diet, other health-related behaviors, acculturation and immigration-related factors, medical history, quality of life, and children's health information. Participants visited the recruitment site and answered the structured questionnaires through a face-to-face interview. We also measured their anthropometric features and collected fasting blood samples, toenails, and DNA samples. Recruitment started in 2014. Collection of data is ongoing, and we plan to prospectively follow our cohort participants. We expect that our study, which is focused on married Filipino women immigrants, can elucidate nutritional/health status and the effects of transitional experiences from several lifestyle factors.

Gender-based screening for chlamydial infection and divergent infection trends in men and women.

PubMed

Rogers, Susan M; Turner, Charles F; Miller, William C; Erbelding, Emily; Eggleston, Elizabeth; Tan, Sylvia; Roman, Anthony; Hobbs, Marcia; Chromy, James; Muvva, Ravikiran; Ganapathi, Laxminarayana

2014-01-01

To assess the potential impact of chlamydial screening policy that recommends routine screening of women but not men. Population surveys of probability samples of Baltimore adults aged 18 to 35 years in 1997-1998 and 2006-2009 collected biospecimens to estimate trends in undiagnosed chlamydial infection. Survey estimates are compared to surveillance data on diagnosed chlamydial infections reported to the Health Department. Prevalence of undiagnosed chlamydial infection among men increased from 1.6% to 4.0%, but it declined from 4.3% to 3.1% among women (p = 0.028 for test of interaction). The annual (average) number of diagnosed infections was substantially higher among women than men in both time periods and increased among both men and women. Undiagnosed infection prevalence was substantially higher among black than non-black adults (4.0% vs 1.2%, p = 0.042 in 1997-98 and 5.5% vs 0.7%, p<0.001 in 2006-09). Divergent trends in undiagnosed chlamydial infection by gender parallel divergent screening recommendations that encourage chlamydial testing for women but not for men.

Life Sciences Data Archives (LSDA) in the Post-Shuttle Era

NASA Technical Reports Server (NTRS)

Fitts, Mary A.; Johnson-Throop, Kathy; Havelka, Jacque; Thomas, Diedre

2010-01-01

Now, more than ever before, NASA is realizing the value and importance of their intellectual assets. Principles of knowledge management-the systematic use and reuse of information, experience, and expertise to achieve a specific goal-are being applied throughout the agency. LSDA is also applying these solutions, which rely on a combination of content and collaboration technologies, to enable research teams to create, capture, share, and harness knowledge to do the things they do well, even better. In the early days of spaceflight, space life sciences data were collected and stored in numerous databases, formats, media-types and geographical locations. These data were largely unknown/unavailable to the research community. The Biomedical Informatics and Health Care Systems Branch of the Space Life Sciences Directorate at JSC and the Data Archive Project at ARC, with funding from the Human Research Program through the Exploration Medical Capability Element, are fulfilling these requirements through the systematic population of the Life Sciences Data Archive. This project constitutes a formal system for the acquisition, archival and distribution of data for HRP-related experiments and investigations. The general goal of the archive is to acquire, preserve, and distribute these data and be responsive to inquiries for the science communities. Information about experiments and data, as well as non-attributable human data and data from other species' are available on our public Web site http://lsda.jsc.nasa.gov. The Web site also includes a repository for biospecimens, and a utilization process. NASA has undertaken an initiative to develop a Shuttle Data Archive repository. The Shuttle program is nearing its end in 2010 and it is critical that the medical and research data related to the Shuttle program be captured, retained, and usable for research, lessons learned, and future mission planning. Communities of practice are groups of people who share a concern or a passion for something they do, and learn how to do it better as they interact regularly. LSDA works with the HRP community of practice to ensure that we are preserving the relevant research and data they need in the LSDA repository. An evidence-based approach to risk management is required in space life sciences. Evidence changes over time. LSDA has a pilot project with Collexis, a new type of Web-based search engine. Collexis differentiates itself from full-text search engines by making use of thesauri for information retrieval. The high-quality search is based on semantics that have been defined in a life sciences ontology. Additionally, Collexis' matching technology is unique, allowing discovery of partially matching dicuments. Users do not have to construct a complicated (Boolean) search query, but can simply enter a free text search without the risk of getting "no results". Collexis may address these issues by virtue of its retrieval and discovery capabilities across multiple repositories.

Understanding the Public's Reservations about Broad Consent and Study-By-Study Consent for Donations to a Biobank: Results of a National Survey.

PubMed

De Vries, Raymond Gene; Tomlinson, Tom; Kim, Hyungjin Myra; Krenz, Chris; Haggerty, Diana; Ryan, Kerry A; Kim, Scott Y H

2016-01-01

Researchers and policymakers do not agree about the most appropriate way to get consent for the use of donations to a biobank. The most commonly used method is blanket-or broad-consent where donors allow their donation to be used for any future research approved by the biobank. This approach does not account for the fact that some donors may have moral concerns about the uses of their biospecimens. This problem can be avoided using "real-time"-or study-by-study-consent, but this policy places a significant burden on biobanks. In order to better understand the public's preferences regarding biobank consent policy, we surveyed a sample that was representative of the population of the United States. Respondents were presented with 5 biobank consent policies and were asked to indicate which policies were acceptable/unacceptable and to identify the best/worst policies. They were also given 7 research scenarios that could create moral concern (e.g. research intending to make abortions safer and more effective) and asked how likely they would be to provide broad consent knowing that their donation might be used in that research. Substantial minorities found both broad and study-by-study consent to be unacceptable and identified those two options as the worst policies. Furthermore, while the type of moral concern (e.g., regarding abortion, the commercial use of donations, or stem cell research) had no effect on policy preferences, an increase in the number of research scenarios generating moral concerns was related to an increased likelihood of finding broad consent to be the worst policy. The rejection of these ethically problematic and costly extremes is good news for biobanks. The challenge now is to design a policy that combines consent with access to information in a way that assures potential donors that their interests and moral concerns are being respected.

Phenome-Wide Association Studies as a Tool to Advance Precision Medicine

PubMed Central

Denny, Joshua C.; Bastarache, Lisa; Roden, Dan M.

2017-01-01

Beginning in the early 2000s, the accumulation of biospecimens linked to electronic health records (EHRs) made possible genome-phenome studies (i.e., comparative analyses of genetic variants and phenotypes) using only data collected as a by-product of typical health care. In addition to disease and trait genetics, EHRs proved a valuable resource for analyzing pharmacogenetic traits and developing reverse genetics approaches such as phenome-wide association studies (PheWASs). PheWASs are designed to survey which of many phenotypes may be associated with a given genetic variant. PheWAS methods have been validated through replication of hundreds of known genotype-phenotype associations, and their use has differentiated between true pleiotropy and clinical comorbidity, added context to genetic discoveries, and helped define disease subtypes, and may also help repurpose medications. PheWAS methods have also proven to be useful with research-collected data. Future efforts that integrate broad, robust collection of phenotype data (e.g., EHR data) with purpose-collected research data in combination with a greater understanding of EHR data will create a rich resource for increasingly more efficient and detailed genome-phenome analysis to usher in new discoveries in precision medicine. PMID:27147087

Implementation of proteomics for cancer research: past, present, and future.

PubMed

Karimi, Parisa; Shahrokni, Armin; Ranjbar, Mohammad R Nezami

2014-01-01

Cancer is the leading cause of the death, accounts for about 13% of all annual deaths worldwide. Many different fields of science are collaborating together studying cancer to improve our knowledge of this lethal disease, and find better solutions for diagnosis and treatment. Proteomics is one of the most recent and rapidly growing areas in molecular biology that helps understanding cancer from an omics data analysis point of view. The human proteome project was officially initiated in 2008. Proteomics enables the scientists to interrogate a variety of biospecimens for their protein contents and measure the concentrations of these proteins. Current necessary equipment and technologies for cancer proteomics are mass spectrometry, protein microarrays, nanotechnology and bioinformatics. In this paper, we provide a brief review on proteomics and its application in cancer research. After a brief introduction including its definition, we summarize the history of major previous work conducted by researchers, followed by an overview on the role of proteomics in cancer studies. We also provide a list of different utilities in cancer proteomics and investigate their advantages and shortcomings from theoretical and practical angles. Finally, we explore some of the main challenges and conclude the paper with future directions in this field.

Current status and recommendations for biomarkers and biobanking in neurofibromatosis.

PubMed

Hanemann, C Oliver; Blakeley, Jaishri O; Nunes, Fabio P; Robertson, Kent; Stemmer-Rachamimov, Anat; Mautner, Victor; Kurtz, Andreas; Ferguson, Michael; Widemann, Brigitte C; Evans, D Gareth; Ferner, Rosalie; Carroll, Steven L; Korf, Bruce; Wolkenstein, Pierre; Knight, Pamela; Plotkin, Scott R

2016-08-16

Clinically validated biomarkers for neurofibromatosis 1 (NF1), neurofibromatosis 2 (NF2), and schwannomatosis (SWN) have not been identified to date. The biomarker working group's goals are to (1) define biomarker needs in NF1, NF2, and SWN; (2) summarize existing data on biomarkers in NF1, NF2, and SWN; (3) outline recommendations for sample collection and biomarker development; and (4) standardize sample collection and methodology protocols where possible to promote comparison between studies by publishing standard operating procedures (SOPs). The biomarker group reviewed published data on biomarkers in NF1, NF2, and SWN and on biobanking efforts outside these diseases via literature search, defined the need for biomarkers in NF, and developed recommendations in a series of consensus meetings. We describe existing biomarkers in NF and report consensus recommendations for SOP and a minimal clinical dataset to accompany samples derived from patients with NF1, NF2, and SWN in decentralized biobanks. These recommendations are intended to provide clinicians and researchers with a common set of guidelines to collect and store biospecimens and for establishment of biobanks for NF1, NF2, and SWN. © 2016 American Academy of Neurology.

Current status and recommendations for biomarkers and biobanking in neurofibromatosis

PubMed Central

Blakeley, Jaishri O.; Nunes, Fabio P.; Robertson, Kent; Stemmer-Rachamimov, Anat; Mautner, Victor; Kurtz, Andreas; Ferguson, Michael; Widemann, Brigitte C.; Evans, D. Gareth; Ferner, Rosalie; Carroll, Steven L.; Korf, Bruce; Wolkenstein, Pierre; Knight, Pamela; Plotkin, Scott R.

2016-01-01

Objective: Clinically validated biomarkers for neurofibromatosis 1 (NF1), neurofibromatosis 2 (NF2), and schwannomatosis (SWN) have not been identified to date. The biomarker working group's goals are to (1) define biomarker needs in NF1, NF2, and SWN; (2) summarize existing data on biomarkers in NF1, NF2, and SWN; (3) outline recommendations for sample collection and biomarker development; and (4) standardize sample collection and methodology protocols where possible to promote comparison between studies by publishing standard operating procedures (SOPs). Methods: The biomarker group reviewed published data on biomarkers in NF1, NF2, and SWN and on biobanking efforts outside these diseases via literature search, defined the need for biomarkers in NF, and developed recommendations in a series of consensus meetings. Results: We describe existing biomarkers in NF and report consensus recommendations for SOP and a minimal clinical dataset to accompany samples derived from patients with NF1, NF2, and SWN in decentralized biobanks. Conclusions: These recommendations are intended to provide clinicians and researchers with a common set of guidelines to collect and store biospecimens and for establishment of biobanks for NF1, NF2, and SWN. PMID:27527649

Biobank classification in an Australian setting.

PubMed

Rush, Amanda; Christiansen, Jeffrey H; Farrell, Jake P; Goode, Susan M; Scott, Rodney J; Spring, Kevin J; Byrne, Jennifer A

2015-06-01

In 2011, Watson and Barnes proposed a schema for classifying biobanks into 3 groups (mono-, oligo-, and poly-user), primarily based upon biospecimen access policies. We used results from a recent comprehensive survey of cancer biobanks in New South Wales, Australia to assess the applicability of this biobank classification schema in an Australian setting. Cancer biobanks were identified using publically available data, and by consulting with research managers. A comprehensive survey was developed and administered through a face-to-face setting. Data were analyzed using Microsoft Excel™ 2010 and IBM SPSS Statistics™ version 21.0. The cancer biobank cohort (n=23) represented 5 mono-user biobanks, 7 oligo-user biobanks, and 11 poly-user biobanks, and was analyzed as two groups (mono-/oligo- versus poly-user biobanks). Poly-user biobanks employed significantly more full-time equivalent staff, and were significantly more likely to have a website, share staff between biobanks, access governance support, utilize quality control measures, be aware of biobanking best practice documents, and offer staff training. Mono-/oligo-user biobanks were significantly more likely to seek advice from other biobanks. Our results further delineate a biobank classification system that is primarily based on access policy, and demonstrate its relevance in an Australian setting.

Tenure Track Investigator | Center for Cancer Research

Cancer.gov

The Neuro-Oncology Branch (NOB), Center for Cancer Research (CCR) of the National Cancer Institute (NCI), National Institutes of Health (NIH), Department of Health and Human Services (HHS), Bethesda, MD, is actively recruiting for a tenure-track principal investigator to work in the area of immunology and/or immunotherapy.  The NOB Immunology/Immunotherapy Investigator will be tasked with forming and leading an independent research program.  This position will build the basic immunology program in the NOB and complement ongoing and planned translational research and clinical trials evaluating the effects of immunotherapy in patients with primary brain tumors.  This program will be able to access biospecimens generated from ongoing and planned immunotherapy protocols within the NOB, thus creating an opportunity to perform correlative studies to interrogate the complex biology of immunologic response, toxicity, and treatment resistance.  Demonstrated expertise in scientific inquiries in immunotherapy and/or immunology are essential, but prior work in brain tumors is not required.  This is an exciting opportunity to join a growing trans-institutional research team that promotes and supports collaborations across the basic, translational, and clinical research spectrum to develop novel therapeutics for individuals with primary central nervous system malignancies that will globally influence the field.

Validation of Early Detection Ovarian Cancer Biomarkers (Team Project) — EDRN Public Portal

Cancer.gov

Early detection of Ovarian Cancer (OC) is one of the key clinical problems in this disease. We propose a team EDRN project to address the issue of early detection of OC by performing a validation study on candidate protein markers already identified in previous EDRN research or in the literature (e.g. protein products of TCGA identified mutations specific to ovarian cancer). (See appendix for full listing) Biospecimen sources have been identified which include samples obtained at diagnosis and matched controls (Urban, Godwin, Marks, Skates), and longitudinal samples obtained prior to diagnosis (Urban, Skates, Godwin). Bioinformatic filters will be applied to rank the candidates (Diamandis). In order of ranking, candidate proteins for which high quality antibodies are available will be measured by development of ELISAs at JHU (Chan/Zhang) or through NAPPA at DFCI (Anderson/LaBaer), while for other candidates mass spectrometry based selective reaction monitoring (SRM) assays will be developed at PNNL (Rodland). Three milestones are defined. The first two milestones are to assemble the necessary specimens and to develop the qualifying assay(s). The final milestone is to estimate the markers’ sensitivity one year prior to diagnosis at a given high specificity.

Metabolomic profiling in perinatal asphyxia: a promising new field.

PubMed

Denihan, Niamh M; Boylan, Geraldine B; Murray, Deirdre M

2015-01-01

Metabolomics, the latest "omic" technology, is defined as the comprehensive study of all low molecular weight biochemicals, "metabolites" present in an organism. As a systems biology approach, metabolomics has huge potential to progress our understanding of perinatal asphyxia and neonatal hypoxic-ischaemic encephalopathy, by uniquely detecting rapid biochemical pathway alterations in response to the hypoxic environment. The study of metabolomic biomarkers in the immediate neonatal period is not a trivial task and requires a number of specific considerations, unique to this disease and population. Recruiting a clearly defined cohort requires standardised multicentre recruitment with broad inclusion criteria and the participation of a range of multidisciplinary staff. Minimally invasive biospecimen collection is a priority for biomarker discovery. Umbilical cord blood presents an ideal medium as large volumes can be easily extracted and stored and the sample is not confounded by postnatal disease progression. Pristine biobanking and phenotyping are essential to ensure the validity of metabolomic findings. This paper provides an overview of the current state of the art in the field of metabolomics in perinatal asphyxia and neonatal hypoxic-ischaemic encephalopathy. We detail the considerations required to ensure high quality sampling and analysis, to support scientific progression in this important field.

Metabolomic Profiling in Perinatal Asphyxia: A Promising New Field

PubMed Central

Denihan, Niamh M.; Boylan, Geraldine B.; Murray, Deirdre M.

2015-01-01

Metabolomics, the latest “omic” technology, is defined as the comprehensive study of all low molecular weight biochemicals, “metabolites” present in an organism. As a systems biology approach, metabolomics has huge potential to progress our understanding of perinatal asphyxia and neonatal hypoxic-ischaemic encephalopathy, by uniquely detecting rapid biochemical pathway alterations in response to the hypoxic environment. The study of metabolomic biomarkers in the immediate neonatal period is not a trivial task and requires a number of specific considerations, unique to this disease and population. Recruiting a clearly defined cohort requires standardised multicentre recruitment with broad inclusion criteria and the participation of a range of multidisciplinary staff. Minimally invasive biospecimen collection is a priority for biomarker discovery. Umbilical cord blood presents an ideal medium as large volumes can be easily extracted and stored and the sample is not confounded by postnatal disease progression. Pristine biobanking and phenotyping are essential to ensure the validity of metabolomic findings. This paper provides an overview of the current state of the art in the field of metabolomics in perinatal asphyxia and neonatal hypoxic-ischaemic encephalopathy. We detail the considerations required to ensure high quality sampling and analysis, to support scientific progression in this important field. PMID:25802843

Public-private relationships in biobanking: a still underestimated key component of open innovation.

PubMed

Hofman, Paul; Bréchot, Christian; Zatloukal, Kurt; Dagher, Georges; Clément, Bruno

2014-01-01

Access to human bioresources is essential to the understanding of human diseases and to the discovery of new biomarkers aimed at improving the diagnosis, prognosis, and the predictive response of patients to treatments. The use of biospecimens is strictly controlled by ethical assessment, which complies with the laws of the country. These laws regulate the partnerships between the biobanks and industrial actors. However, private-public partnerships (PPP) can be limiting for several reasons, which can hamper the discovery of new biological tests and new active molecules targeted to human diseases. The bottlenecks and roadblocks in establishing these partnerships include: poor organization of the biobank in setting up PPP, evaluation of the cost of human samples, the absence of experience on the public side in setting up contracts with industry, and the fact that public and private partners may not share the same objectives. However, it is critical, in particular for academic biobanks, to establish strong PPP to accelerate translational research for the benefits of patients, and to allow the sustainability of the biobank. The purpose of this review is to discuss the main bottlenecks and roadblocks that can hamper the establishment of PPP based on solid and trusting relationships.

A lateral electrophoretic flow diagnostic assay

PubMed Central

Lin, Robert; Skandarajah, Arunan; Gerver, Rachel E.; Neira, Hector D.; Fletcher, Daniel A.

2015-01-01

Immunochromatographic assays are a cornerstone tool in disease screening. To complement existing lateral flow assays (based on wicking flow) we introduce a lateral flow format that employs directed electrophoretic transport. The format is termed a “lateral e-flow assay” and is designed to support multiplexed detection using immobilized reaction volumes of capture antigen. To fabricate the lateral e-flow device, we employ mask-based UV photopatterning to selectively immobilize unmodified capture antigen along the microchannel in a barcode-like pattern. The channel-filling polyacrylamide hydrogel incorporates a photoactive moiety (benzophenone) to immobilize capture antigen to the hydrogel without a priori antigen modification. We report a heterogeneous sandwich assay using low-power electrophoresis to drive biospecimen through the capture antigen barcode. Fluorescence barcode readout is collected via a low-resource appropriate imaging system (CellScope). We characterize lateral e-flow assay performance and demonstrate a serum assay for antibodies to the hepatitis C virus (HCV). In a pilot study, the lateral e-flow assay positively identifies HCV+ human sera in 60 min. The lateral e-flow assay provides a flexible format for conducting multiplexed immunoassays relevant to confirmatory diagnosis in near-patient settings. PMID:25608872

OARSI Clinical Trials Recommendations: Soluble biomarker assessments in clinical trials in osteoarthritis.

PubMed

Kraus, V B; Blanco, F J; Englund, M; Henrotin, Y; Lohmander, L S; Losina, E; Önnerfjord, P; Persiani, S

2015-05-01

The objective of this work was to describe requirements for inclusion of soluble biomarkers in osteoarthritis (OA) clinical trials and progress toward OA-related biomarker qualification. The Guidelines for Biomarkers Working Group, representing experts in the field of OA biomarker research from both academia and industry, convened to discuss issues related to soluble biomarkers and to make recommendations for their use in OA clinical trials based on current knowledge and anticipated benefits. This document summarizes current guidance on use of biomarkers in OA clinical trials and their utility at five stages, including preclinical development and phase I to phase IV trials. As demonstrated by this summary, biomarkers can provide value at all stages of therapeutics development. When resources permit, we recommend collection of biospecimens in all OA clinical trials for a wide variety of reasons but in particular, to determine whether biomarkers are useful in identifying those individuals most likely to receive clinically important benefits from an intervention; and to determine whether biomarkers are useful for identifying individuals at earlier stages of OA in order to institute treatment at a time more amenable to disease modification. Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Filipino women's diet and health study (FiLWHEL): design and methods

PubMed Central

Abris, Grace P.; Hong, Sangmo; Provido, Sherlyn Mae P.

2017-01-01

BACKGROUND Immigration to South Korea from neighboring Asian countries has risen dramatically, primarily due to marriage between Korean men and foreign women. Although Filipino women rank fourth among married immigrant women, little is known about the health condition of this population. This manuscript focuses on the design and methods of Filipino women's diet and health study (FiLWHEL). SUBJECTS/METHODS FiLWHEL is a cohort of Filipino women married to Korean men, aged 19 years old or over. The data collection comprised three parts: questionnaire, physical examination, and biospecimen collection. Questionnaires focused on demographic factors, diet, other health-related behaviors, acculturation and immigration-related factors, medical history, quality of life, and children's health information. Participants visited the recruitment site and answered the structured questionnaires through a face-to-face interview. We also measured their anthropometric features and collected fasting blood samples, toenails, and DNA samples. Recruitment started in 2014. RESULTS/CONCLUSIONS Collection of data is ongoing, and we plan to prospectively follow our cohort participants. We expect that our study, which is focused on married Filipino women immigrants, can elucidate nutritional/health status and the effects of transitional experiences from several lifestyle factors. PMID:28194268

Gender-Based Screening for Chlamydial Infection and Divergent Infection Trends in Men and Women

PubMed Central

Rogers, Susan M.; Turner, Charles F.; Miller, William C.; Erbelding, Emily; Eggleston, Elizabeth; Tan, Sylvia; Roman, Anthony; Hobbs, Marcia; Chromy, James; Muvva, Ravikiran; Ganapathi, Laxminarayana

2014-01-01

Objectives To assess the potential impact of chlamydial screening policy that recommends routine screening of women but not men. Methods Population surveys of probability samples of Baltimore adults aged 18 to 35 years in 1997–1998 and 2006–2009 collected biospecimens to estimate trends in undiagnosed chlamydial infection. Survey estimates are compared to surveillance data on diagnosed chlamydial infections reported to the Health Department. Results Prevalence of undiagnosed chlamydial infection among men increased from 1.6% to 4.0%, but it declined from 4.3% to 3.1% among women (p = 0.028 for test of interaction). The annual (average) number of diagnosed infections was substantially higher among women than men in both time periods and increased among both men and women. Undiagnosed infection prevalence was substantially higher among black than non-black adults (4.0% vs 1.2%, p = 0.042 in 1997–98 and 5.5% vs 0.7%, p<0.001 in 2006–09). Conclusion Divergent trends in undiagnosed chlamydial infection by gender parallel divergent screening recommendations that encourage chlamydial testing for women but not for men. PMID:24586491

Epigenetic Research in Cancer Epidemiology: Trends, Opportunities, and Challenges

PubMed Central

Verma, Mukesh; Rogers, Scott; Divi, Rao L.; Schully, Sheri D.; Nelson, Stefanie; Su, L. Joseph; Ross, Sharon; Pilch, Susan; Winn, Deborah M.; Khoury, Muin J.

2014-01-01

Epigenetics is emerging as an important field in cancer epidemiology that promises to provide insights into gene regulation and facilitate cancer control throughout the cancer care continuum. Increasingly, investigators are incorporating epigenetic analysis into the studies of etiology and outcomes. To understand current progress and trends in the inclusion of epigenetics in cancer epidemiology, we evaluated the published literature and the National Cancer Institute (NCI) supported research grant awards in this field to identify trends in epigenetics research. We present a summary of the epidemiological studies in NCI’s grant portfolio (from January 2005 through December 2012) and in the scientific literature published during the same period, irrespective of support from NCI. Blood cells and tumor tissue were the most commonly used biospecimens in these studies, although buccal cells, cervical cells, sputum, and stool samples also were used. DNA methylation profiling was the focus of the majority of studies, but several studies also measured microRNA profiles. We illustrate here the current status of epidemiologic studies that are evaluating epigenetic changes in large populations. The incorporation of epigenomic assessments in cancer epidemiology studies has and is likely to continue to provide important insights into the field of cancer research. PMID:24326628

Challenges of Biobanking in South Africa to Facilitate Indigenous Research in an Environment Burdened with Human Immunodeficiency Virus, Tuberculosis, and Emerging Noncommunicable Diseases

PubMed Central

Christoffels, Alan; Grewal, Ravnit; Karam, Locunda A.; Rossouw, Catherine; Staunton, Ciara; Swanepoel, Carmen; van Rooyen, Beverley

2013-01-01

The high burden of infectious diseases and the growing problem of noncommunicable and metabolic disease syndromes in South Africa (SA) forces a more focused research approach to facilitate cutting-edge scientific growth and public health development. Increased SA research on these diseases and syndromes and the collection of associated biospecimens has ensured a plethora of biobanks created by individuals, albeit without the foresight of prospective and collective use by other local and international researchers. As the need for access to high-quality specimens in statistically relevant numbers has increased, so has the necessity for the development of national human biobanks in SA and across the Continent. The prospects of achieving sustainable centralized biobanks are still an emerging and evolving concept, primarily and recently driven by the launch of the H3Africa consortium, which includes the development of harmonized and standardized biobanking operating procedures. This process is hindered by a myriad of complex societal considerations and ethico-legal challenges. Efforts to consolidate and standardize biological sample collections are further compromised by the lack of full appreciation by national stakeholders of the biological value inherent in these collections, and the availability of high quality human samples with well-annotated data for future scientific research and development. Inadequate or nonexistent legislative structures that specifically regulate the storage, use, dispersal, and disposal of human biological samples are common phenomena and pose further challenges. Furthermore, concerns relating to consent for unspecified future uses, as well as access to information and data protection, are all new paradigms that require further consideration and public engagement. This article reviews important fundamental issues such as governance, ethics, infrastructure, and bioinformatics that are important foundational prerequisites for the establishment and evolution of successful human biobanking in South Africa. PMID:24835364

Soy Food Intake and Circulating Levels of Inflammatory Markers in Chinese Women

PubMed Central

Wu, Sheng Hui; Shu, Xiao Ou; Chow, Wong-Ho; Xiang, Yong-Bing; Zhang, Xianglan; Li, Hong-Lan; Cai, Qiuyin; Ji, Bu-Tian; Cai, Hui; Rothman, Nathaniel; Gao, Yu-Tang; Zheng, Wei; Yang, Gong

2013-01-01

Background Soy and some of its constituents, such as isoflavones, have been shown to affect the inflammatory process in animal studies. The association between soy food intake and inflammatory markers has not been evaluated adequately in humans. Objective Our aim was to evaluate whether higher intake of soy foods was inversely associated with inflammatory markers in 1,005 middle-aged Chinese women. Design In this cross-sectional study, dietary intake of soy foods was assessed by a validated food frequency questionnaire and by a 24-hour recall when biospecimens were procured. A general linear model was used to estimate the geometric means of selected inflammatory markers, including interleukin-6 (IL-6), IL-1β, tumor necrosis factor-α (TNFα), soluble IL-6 receptor, soluble GP130, soluble TNF receptors 1 and 2, and C-reactive protein, across categories of soy food intake after adjusting for age, lifestyle and dietary factors, and history of infectious or inflammation-related diseases. Results We found that multivariable-adjusted geometric mean concentrations of IL-6 and TNFα were inversely associated with quintiles of soy food intake, with a difference between the highest and lowest quintiles of 25.5% for IL-6 (P for trend = 0.008) and 14% for TNFα (P for trend = 0.04). Similar inverse associations were found for TNFα (P for trend = 0.003), soluble TNF receptor 1 (P for trend=0.01), soluble TNF receptor 2 (P for trend=0.02), IL-1β (P for trend=0.05), and IL-6 (P for trend=0.04) when soy food consumption was assessed by the frequency of consumption in the preceding 24 hours. No significant associations were found for other markers studied. Conclusions This study suggests that soy food consumption is related to lower circulating levels of IL-6, TNFα, and soluble TNF receptors 1 and 2 in Chinese women. PMID:22889631

Method to Biomonitor the Cooked Meat Carcinogen 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine in Dyed Hair by Ultra-Performance Liquid Chromatography-Orbitrap High Resolution Multistage Mass Spectrometry.

PubMed

Guo, Jingshu; Yonemori, Kim; Le Marchand, Loïc; Turesky, Robert J

2015-06-16

2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a carcinogenic heterocyclic aromatic amine formed in cooked meat. The use of naturally colored hair containing PhIP can serve as a long-term biomarker of exposure to this carcinogen. However, the measurement of PhIP in dyed hair, a cosmetic treatment commonly used by the adult population, is challenging because the dye process introduces into the hair matrix a complex mixture of chemicals that interferes with the measurement of PhIP. The high-resolution scanning features of the Orbitrap Fusion mass spectrometer were employed to biomonitor PhIP in dyed hair. Because of the complexity of chemicals in the hair dye, the consecutive reaction monitoring of PhIP at the MS(3) scan stage was employed to selectively remove the isobaric interferences. The limit of quantification (LOQ) of PhIP was 84 parts-per-trillion (ppt) employing 50 mg of hair. Calibration curves were generated in dyed hair matrixes and showed good linearity (40-1000 pg PhIP/g hair) with a goodness-of-fit regression value of r(2) > 0.9978. The within-day (between-day) coefficients of variation were 7.7% (17%) and 5.4% (6.1%), respectively, with dyed hair samples spiked with PhIP at 200 and 600 ppt. The levels of PhIP accrued in dyed hair from volunteers on a semicontrolled feeding study who ingested known levels of PhIP were comparable to the levels of PhIP accrued in hair of subjects with natural hair color. The method was successfully employed to measure PhIP in nondyed and dyed hair biospecimens of participants in a case-control study of colorectal adenoma on their regular diet.

A Method to Biomonitor the Cooked Meat Carcinogen 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in Dyed Hair by Ultra Performance Liquid Chromatography-Orbitrap High Resolution Multistage Mass Spectrometry

PubMed Central

Guo, Jingshu; Yonemori, Kim; Le Marchand, Loïc; Turesky, Robert J.

2015-01-01

2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a carcinogenic heterocyclic aromatic amine formed in cooked meat. The use of naturally colored hair containing PhIP can serve as a long-term biomarker of exposure to this carcinogen. However, the measurement of PhIP in dyed hair, a cosmetic treatment commonly used by the adult population, is challenging because the dye process introduces a complex mixture of chemicals into the hair matrix, which interfere with the measurement of PhIP. The high-resolution scanning features of the Orbitrap Fusion™ mass spectrometer were employed to biomonitor PhIP in dyed hair. Because of the complexity of chemicals in the hair dye, the consecutive reaction monitoring of PhIP at the MS3 scan stage was employed to selectively remove the isobaric interferences. The limit of quantification (LOQ) of PhIP was 84 parts-per-trillion (ppt) employing 50 mg hair. Calibration curves were generated in dyed hair matrices and showed good linearity (40 to 1000 pg PhIP/g hair) with a goodness-of-fit regression value r2 > 0.9978. The within-day (between-day) coefficients of variation were 7.7% (17%) and 5.4% (6.1%), respectively, with dyed hair samples spiked with PhIP at 200 and 600 ppt. The levels of PhIP accrued in dyed hair from volunteers on a semi-controlled feeding study who ingested known levels of PhIP were comparable to the levels of PhIP accrued in hair of subjects with natural hair color. The method was successfully employed to measure PhIP in non-dyed and dyed hair biospecimens of participants in a case-control study of colorectal adenoma on their regular diet. PMID:25969997

Imaging biomarker roadmap for cancer studies

PubMed Central

O’Connor, James P. B.; Aboagye, Eric O.; Adams, Judith E.; Aerts, Hugo J. W. L.; Barrington, Sally F.; Beer, Ambros J.; Boellaard, Ronald; Bohndiek, Sarah E.; Brady, Michael; Brown, Gina; Buckley, David L.; Chenevert, Thomas L.; Clarke, Laurence P.; Collette, Sandra; Cook, Gary J.; deSouza, Nandita M.; Dickson, John C.; Dive, Caroline; Evelhoch, Jeffrey L.; Faivre-Finn, Corinne; Gallagher, Ferdia A.; Gilbert, Fiona J.; Gillies, Robert J.; Goh, Vicky; Griffiths, John R.; Groves, Ashley M.; Halligan, Steve; Harris, Adrian L.; Hawkes, David J.; Hoekstra, Otto S.; Huang, Erich P.; Hutton, Brian F.; Jackson, Edward F.; Jayson, Gordon C.; Jones, Andrew; Koh, Dow-Mu; Lacombe, Denis; Lambin, Philippe; Lassau, Nathalie; Leach, Martin O.; Lee, Ting-Yim; Leen, Edward L.; Lewis, Jason S.; Liu, Yan; Lythgoe, Mark F.; Manoharan, Prakash; Maxwell, Ross J.; Miles, Kenneth A.; Morgan, Bruno; Morris, Steve; Ng, Tony; Padhani, Anwar R.; Parker, Geoff J. M.; Partridge, Mike; Pathak, Arvind P.; Peet, Andrew C.; Punwani, Shonit; Reynolds, Andrew R.; Robinson, Simon P.; Shankar, Lalitha K.; Sharma, Ricky A.; Soloviev, Dmitry; Stroobants, Sigrid; Sullivan, Daniel C.; Taylor, Stuart A.; Tofts, Paul S.; Tozer, Gillian M.; van Herk, Marcel; Walker-Samuel, Simon; Wason, James; Williams, Kaye J.; Workman, Paul; Yankeelov, Thomas E.; Brindle, Kevin M.; McShane, Lisa M.; Jackson, Alan; Waterton, John C.

2017-01-01

Imaging biomarkers (IBs) are integral to the routine management of patients with cancer. IBs used daily in oncology include clinical TNM stage, objective response and left ventricular ejection fraction. Other CT, MRI, PET and ultrasonography biomarkers are used extensively in cancer research and drug development. New IBs need to be established either as useful tools for testing research hypotheses in clinical trials and research studies, or as clinical decision-making tools for use in healthcare, by crossing ‘translational gaps’ through validation and qualification. Important differences exist between IBs and biospecimen-derived biomarkers and, therefore, the development of IBs requires a tailored ‘roadmap’. Recognizing this need, Cancer Research UK (CRUK) and the European Organisation for Research and Treatment of Cancer (EORTC) assembled experts to review, debate and summarize the challenges of IB validation and qualification. This consensus group has produced 14 key recommendations for accelerating the clinical translation of IBs, which highlight the role of parallel (rather than sequential) tracks of technical (assay) validation, biological/clinical validation and assessment of cost-effectiveness; the need for IB standardization and accreditation systems; the need to continually revisit IB precision; an alternative framework for biological/clinical validation of IBs; and the essential requirements for multicentre studies to qualify IBs for clinical use. PMID:27725679

Rare Disease Biospecimens and Patient Registries: Interoperability for Research Promotion, a European Example: EuroBioBank and SpainRDR-BioNER.

PubMed

Rubinstein, Yaffa R; Posada de la Paz, Manuel; Mora, Marina

2017-01-01

Well-annotated and properly preserved specimens are crucial both for diagnostic purposes and for use in basic and pre-clinical research, and are especially important for rare disease (RD) studies. Several consortia have been established in the recent years in order to facilitate research and to maximise access to rare biological samples and data stored in rare disease biobanks and registries, among them the EuroBioBank network and the Spain National Rare Disease Registry (RDR) and Biobank (BioNER).EuroBioBank, established in 2001, was the first network of RD biobanks to operate in Europe as a service distributing human DNA, cells, and tissue to the scientific community conducting research on rare diseases.The Spanish RDR and BioNER were created for facilitating rare disease research and health-related matters. The coordination of these two bodies represents an example of great scientific value as biological samples donated by patients at BioNER are linked to clinical information collected in the RDR.Rare disease biobanks and registries will need for the future to increase their effort to improve interconnection so to enable investigators to better locate samples and associated data, while protecting security of the data and privacy of the participants and adhering to international ethical and legal requirements.

Improving the quality of biomarker discovery research: the right samples and enough of them.

PubMed

Pepe, Margaret S; Li, Christopher I; Feng, Ziding

2015-06-01

Biomarker discovery research has yielded few biomarkers that validate for clinical use. A contributing factor may be poor study designs. The goal in discovery research is to identify a subset of potentially useful markers from a large set of candidates assayed on case and control samples. We recommend the PRoBE design for selecting samples. We propose sample size calculations that require specifying: (i) a definition for biomarker performance; (ii) the proportion of useful markers the study should identify (Discovery Power); and (iii) the tolerable number of useless markers amongst those identified (False Leads Expected, FLE). We apply the methodology to a study of 9,000 candidate biomarkers for risk of colon cancer recurrence where a useful biomarker has positive predictive value ≥ 30%. We find that 40 patients with recurrence and 160 without recurrence suffice to filter out 98% of useless markers (2% FLE) while identifying 95% of useful biomarkers (95% Discovery Power). Alternative methods for sample size calculation required more assumptions. Biomarker discovery research should utilize quality biospecimen repositories and include sample sizes that enable markers meeting prespecified performance characteristics for well-defined clinical applications to be identified. The scientific rigor of discovery research should be improved. ©2015 American Association for Cancer Research.

Final Science Reports of the US Experiments Flown on the Russian Biosatellite Cosmos 2229

NASA Technical Reports Server (NTRS)

Connolly, James P. (Editor); Skidmore, Michael G. (Editor); Helwig, Denice A. (Editor)

1997-01-01

Cosmos 2229 was launched on December 29, 1992, containing a biological payload including two young male rhesus monkeys, insects, amphibians, and cell cultures. The biosatellite was launched from the Plesetsk Cosmodrome in Russia for a mission duration of 11.5 days. The major research objectives were: (1) Study of adaptive response mechanisms of mammals during flight; and (2) Study of physiological mechanisms underlying vestibular, motor system and brain function in primates during early and later adaptation phases. American scientists and their Russian collaborators conducted 11 experiments on this mission which included extensive preflight and postflight studies with rhesus monkeys. Biosamples and data were subsequently transferred to the United States. The U.S. responsibilities for this flight included the development of experiment protocols, the fabrication of some flight instrumentation and experiment-specific ground-based hardware, the conducting of preflight and postflight testing and the analysis of biospecimens and data for the U.S. experiments. A description of the Cosmos 2229 mission is presented in this report including preflight, on-orbit and postflight activities. The flight and ground-based bioinstrumentation which was developed by the U.S. and Russia is also described, along with the associated preflight testing ot the U.S. hardware. Final Science Reports for the experiments are also included.

CREST biorepository for translational studies on malignant mesothelioma, lung cancer and other respiratory tract diseases: Informatics infrastructure and standardized annotation.

PubMed

Ugolini, Donatella; Neri, Monica; Bennati, Luca; Canessa, Pier Aldo; Casanova, Georgia; Lando, Cecilia; Leoncini, Giacomo; Marroni, Paola; Parodi, Barbara; Simonassi, Claudio; Bonassi, Stefano

2012-03-01

Advances in molecular epidemiology and translational research have led to the need for biospecimen collection. The Cancer of the Respiratory Tract (CREST) biorepository is concerned with pleural malignant mesothelioma (MM) and lung cancer (LC). The biorepository staff has collected demographic and epidemiological data directly from consenting subjects using a structured questionnaire, in agreement with The Public Population Project in Genomics (P(3)G). Clinical and follow-up data were collected. Sample data were also recorded. The architecture is based on a database designed with Microsoft Access. Data standardization was carried out to conform with established conventions or procedures. As from January 31, 2011, the overall number of recruited subjects was 1,857 (454 LC, 245 MM, 130 other cancers and 1,028 controls). Due to its infrastructure, CREST was able to join international projects, sharing samples and/or data with other research groups in the field. The data management system allows CREST to be involved, through a minimum data set, in the national project for the construction of the Italian network of Oncologic BioBanks (RIBBO), and in the infrastructure of a pan-European biobank network (BBMRI). The CREST biorepository is a valuable tool for translational studies on respiratory tract diseases, because of its simple and efficient infrastructure.

Optimization of Inflammatory Bowel Disease Cohort Studies in Asia.

PubMed

Leung, Wai K

2015-07-01

With the incidence of inflammatory bowel disease (IBD) increasing rapidly in many Asian countries, including Hong Kong, it is important that patient characteristics are better understood. For example, are the phenotypes, behaviors, complications, and even treatment responses found in Asian patients similar to those of their Western counterparts? To formally address these questions, a properly designed local cohort study is needed. Whilst IBD is still relatively uncommon in Asia, the establishment of a local IBD registry will significantly contribute to the answering of these questions. The Hong Kong IBD registry was established to fill the gap in the understanding of IBD patients, and to foster research into IBD in Hong Kong. The Hong Kong IBD registry is a territory-wide registry that includes all public hospitals in Hong Kong. We included all IBD patients who were currently receiving medical care at these hospitals. With the help of the central computer medical record system of the Hospital Authority of Hong Kong, all clinical events, medications usage, endoscopy records, and laboratory results of patients in the registry were captured. Apart from data collection, the registry is also establishing a bio-specimen bank of blood and stool samples of IBD patients for future research. The IBD registry is a very useful platform for population-based studies on IBD in Asia.

Legal & ethical compliance when sharing biospecimen.

PubMed

Klingstrom, Tomas; Bongcam-Rudloff, Erik; Reichel, Jane

2018-01-01

When obtaining samples from biobanks, resolving ethical and legal concerns is a time-consuming task where researchers need to balance the needs of privacy, trust and scientific progress. The Biobanking and Biomolecular Resources Research Infrastructure-Large Prospective Cohorts project has resolved numerous such issues through intense communication between involved researchers and experts in its mission to unite large prospective study sets in Europe. To facilitate efficient communication, it is useful for nonexperts to have an at least basic understanding of the regulatory system for managing biological samples.Laws regulating research oversight are based on national law and normally share core principles founded on international charters. In interview studies among donors, chief concerns are privacy, efficient sample utilization and access to information generated from their samples. Despite a lack of clear evidence regarding which concern takes precedence, scientific as well as public discourse has largely focused on privacy concerns and the right of donors to control the usage of their samples.It is therefore important to proactively deal with ethical and legal issues to avoid complications that delay or prevent samples from being accessed. To help biobank professionals avoid making unnecessary mistakes, we have developed this basic primer covering the relationship between ethics and law, the concept of informed consent and considerations for returning findings to donors. © The Author 2017. Published by Oxford University Press.

Plasma carotenoids, retinol, and tocopherols and postmenopausal breast cancer risk in the Multiethnic Cohort Study: a nested case-control study

PubMed Central

Epplein, Meira; Shvetsov, Yurii B; Wilkens, Lynne R; Franke, Adrian A; Cooney, Robert V; Le Marchand, Loïc; Henderson, Brian E; Kolonel, Laurence N; Goodman, Marc T

2009-01-01

Introduction Assessments by the handful of prospective studies of the association of serum antioxidants and breast cancer risk have yielded inconsistent results. This multiethnic nested case-control study sought to examine the association of plasma carotenoids, retinol, and tocopherols with postmenopausal breast cancer risk. Methods From the biospecimen subcohort of the Multiethnic Cohort Study, 286 incident postmenopausal breast cancer cases were matched to 535 controls on age, sex, ethnicity, study location (Hawaii or California), smoking status, date/time of collection and hours of fasting. We measured prediagnostic circulating levels of individual carotenoids, retinol, and tocopherols. Conditional logistic regression was used to compute odds ratios and 95% confidence intervals. Results Women with breast cancer tended to have lower levels of plasma carotenoids and tocopherols than matched controls, but the differences were not large or statistically significant and the trends were not monotonic. No association was seen with retinol. A sensitivity analysis excluding cases diagnosed within 1 year after blood draw did not alter the findings. Conclusions The lack of significant associations in this multiethnic population is consistent with previously observed results from less racially-diverse cohorts and serves as further evidence against a causal link between plasma micronutrient concentrations and postmenopausal breast cancer risk. PMID:19619335

Legal & ethical compliance when sharing biospecimen

PubMed Central

Klingstrom, Tomas; Bongcam-Rudloff, Erik; Reichel, Jane

2018-01-01

Abstract When obtaining samples from biobanks, resolving ethical and legal concerns is a time-consuming task where researchers need to balance the needs of privacy, trust and scientific progress. The Biobanking and Biomolecular Resources Research Infrastructure-Large Prospective Cohorts project has resolved numerous such issues through intense communication between involved researchers and experts in its mission to unite large prospective study sets in Europe. To facilitate efficient communication, it is useful for nonexperts to have an at least basic understanding of the regulatory system for managing biological samples. Laws regulating research oversight are based on national law and normally share core principles founded on international charters. In interview studies among donors, chief concerns are privacy, efficient sample utilization and access to information generated from their samples. Despite a lack of clear evidence regarding which concern takes precedence, scientific as well as public discourse has largely focused on privacy concerns and the right of donors to control the usage of their samples. It is therefore important to proactively deal with ethical and legal issues to avoid complications that delay or prevent samples from being accessed. To help biobank professionals avoid making unnecessary mistakes, we have developed this basic primer covering the relationship between ethics and law, the concept of informed consent and considerations for returning findings to donors. PMID:28460118

The EuroBioBank Network: 10 years of hands-on experience of collaborative, transnational biobanking for rare diseases

PubMed Central

Mora, Marina; Angelini, Corrado; Bignami, Fabrizia; Bodin, Anne-Mary; Crimi, Marco; Di Donato, Jeanne- Hélène; Felice, Alex; Jaeger, Cécile; Karcagi, Veronika; LeCam, Yann; Lynn, Stephen; Meznaric, Marija; Moggio, Maurizio; Monaco, Lucia; Politano, Luisa; de la Paz, Manuel Posada; Saker, Safaa; Schneiderat, Peter; Ensini, Monica; Garavaglia, Barbara; Gurwitz, David; Johnson, Diana; Muntoni, Francesco; Puymirat, Jack; Reza, Mojgan; Voit, Thomas; Baldo, Chiara; Bricarelli, Franca Dagna; Goldwurm, Stefano; Merla, Giuseppe; Pegoraro, Elena; Renieri, Alessandra; Zatloukal, Kurt; Filocamo, Mirella; Lochmüller, Hanns

2015-01-01

The EuroBioBank (EBB) network (www.eurobiobank.org) is the first operating network of biobanks in Europe to provide human DNA, cell and tissue samples as a service to the scientific community conducting research on rare diseases (RDs). The EBB was established in 2001 to facilitate access to RD biospecimens and associated data; it obtained funding from the European Commission in 2002 (5th framework programme) and started operation in 2003. The set-up phase, during the EC funding period 2003–2006, established the basis for running the network; the following consolidation phase has seen the growth of the network through the joining of new partners, better network cohesion, improved coordination of activities, and the development of a quality-control system. During this phase the network participated in the EC-funded TREAT-NMD programme and was involved in planning of the European Biobanking and Biomolecular Resources Research Infrastructure. Recently, EBB became a partner of RD-Connect, an FP7 EU programme aimed at linking RD biobanks, registries, and bioinformatics data. Within RD-Connect, EBB contributes expertise, promotes high professional standards, and best practices in RD biobanking, is implementing integration with RD patient registries and ‘omics' data, thus challenging the fragmentation of international cooperation on the field. PMID:25537360

Chlamydia trachomatis infection among 15- to 35-year-olds in Baltimore, MD.

PubMed

Eggleston, Elizabeth; Rogers, Susan M; Turner, Charles F; Miller, William C; Roman, Anthony M; Hobbs, Marcia M; Erbelding, Emily; Tan, Sylvia; Villarroel, Maria A; Ganapathi, Laxminarayana

2011-08-01

Chlamydia trachomatis (Ct) is the most frequently reported infectious disease in the United States. This article reports population and subpopulation prevalence estimates of Ct and correlates of infection among 15- to 35-year-olds in Baltimore, MD. The Monitoring STIs Survey Program (MSSP) monitored sexually transmitted infection (STI) prevalence among probability samples of residents of Baltimore, a city with high STI rates. MSSP respondents completed telephone audio computer-assisted self-interviews and provided biospecimens for STI testing. Among 2120 Baltimore residents aged 15 to 35 years, the estimated prevalence of chlamydia was 3.9% (95% confidence interval [CI]: 2.8, 5.0). Prevalence was 5.8% (95% CI: 4.1, 7.6) among black MSSP respondents versus 0.7% (95% CI: 0.0, 1.4) among nonblack respondents; all but 4 infections detected were among black respondents. Sexual behaviors and other factors associated with infection were far more prevalent among black than nonblack Baltimore residents. Racial disparities persisted after adjustment for sociodemographic, behavioral, and health factors. The MSSP highlights a higher Ct prevalence among young people in Baltimore than in the United States overall, with notable racial disparities in infection and associated risk behaviors. Public health efforts are needed to improve the diagnosis and treatment of asymptomatic infections in this population.

Chlamydia trachomatis infection among 15-35 year-olds in Baltimore, MD, USA

PubMed Central

Eggleston, Elizabeth; Rogers, Susan M; Turner, Charles F; Miller, William C.; Roman, Anthony M; Hobbs, Marcia M.; Erbelding, Emily; Tan, Sylvia; Villarroel, Maria A.; Ganapathi, Laxminarayana

2011-01-01

Background Chlamydia trachomatis (Ct) is the most frequently reported infectious disease in the U.S. This article reports population and subpopulation prevalence estimates of Ct and correlates of infection among 15-35 year-olds in Baltimore, MD, USA. Methods The Monitoring STIs Survey Program (MSSP) monitored STI prevalence among probability samples of residents of Baltimore, a city with high STI rates. MSSP respondents completed telephone audio computer-assisted self-interviews and provided biospecimens for STI testing. Results Among 2120 Baltimore residents aged 15 to 35 years, the estimated prevalence of chlamydia was 3.9% (95% Cl: 2.8, 5.0). Prevalence was 5.8% (95% Cl: 4.1, 7.6) among black MSSP respondents versus 0.7% (95% Cl: 0.0, 1.4) among nonblack respondents; all but four infections detected were among black respondents. Sexual behaviors and other factors associated with infection were far more prevalent among black than nonblack Baltimore residents. Racial disparities persisted after adjustment for sociodemographic, behavioral and health factors. Conclusion The MSSP highlights a higher Ct prevalence among young people in Baltimore than in the U.S. overall, with notable racial disparities in infection and associated risk behaviors. Public health efforts are needed to improve the diagnosis and treatment of asymptomatic infections in this population. PMID:21844726

Email-Based Informed Consent: Innovative Method for Reaching Large Numbers of Subjects for Data Mining Research

NASA Technical Reports Server (NTRS)

Lee, Lesley R.; Mason, Sara S.; Babiak-Vazquez, Adriana; Ray, Stacie L.; Van Baalen, Mary

2015-01-01

Since the 2010 NASA authorization to make the Life Sciences Data Archive (LSDA) and Lifetime Surveillance of Astronaut Health (LSAH) data archives more accessible by the research and operational communities, demand for data has greatly increased. Correspondingly, both the number and scope of requests have increased, from 142 requests fulfilled in 2011 to 224 in 2014, and with some datasets comprising up to 1 million data points. To meet the demand, the LSAH and LSDA Repositories project was launched, which allows active and retired astronauts to authorize full, partial, or no access to their data for research without individual, study-specific informed consent. A one-on-one personal informed consent briefing is required to fully communicate the implications of the several tiers of consent. Due to the need for personal contact to conduct Repositories consent meetings, the rate of consenting has not kept up with demand for individualized, possibly attributable data. As a result, other methods had to be implemented to allow the release of large datasets, such as release of only de-identified data. However the compilation of large, de-identified data sets places a significant resource burden on LSAH and LSDA and may result in diminished scientific usefulness of the dataset. As a result, LSAH and LSDA worked with the JSC Institutional Review Board Chair, Astronaut Office physicians, and NASA Office of General Counsel personnel to develop a "Remote Consenting" process for retrospective data mining studies. This is particularly useful since the majority of the astronaut cohort is retired from the agency and living outside the Houston area. Originally planned as a method to send informed consent briefing slides and consent forms only by mail, Remote Consenting has evolved into a means to accept crewmember decisions on individual studies via their method of choice: email or paper copy by mail. To date, 100 emails have been sent to request participation in eight HRP-funded studies. The development of the Remote Consent process, the laws allowing transmission of consent via electronic means, total metrics to date, and remaining challenges (e.g., response issues, use of International Partner data, biospecimens/genetic data) for the research use of LSAH/LSDA data will be described.

Exposure to microgravity for 30 days onboard Bion M1 caused muscle atrophy and impaired regeneration in murine femoral Quadriceps

NASA Astrophysics Data System (ADS)

Radugina, E. A.; Almeida, E. A. C.; Blaber, E.; Poplinskaya, V. A.; Markitantova, Y. V.; Grigoryan, E. N.

2018-02-01

Mechanical unloading in microgravity during spaceflight is known to cause muscular atrophy, changes in muscle fiber composition, gene expression, and reduction in regenerative muscle growth. Although some limited data exists for long-term effects of microgravity in human muscle, these processes have mostly been studied in rodents for short periods of time. Here we report on how long-term (30-day long) mechanical unloading in microgravity affects murine muscles of the femoral Quadriceps group. To conduct these studies we used muscle tissue from 6 microgravity mice, in comparison to habitat (7), and vivarium (14) ground control mice from the NASA Biospecimen Sharing Program conducted in collaboration with the Institute for Biomedical Problems of the Russian Academy of Sciences, during the Russian Bion M1 biosatellite mission in 2013. Muscle histomorphology from microgravity specimens showed signs of extensive atrophy and regenerative hypoplasia relative to ground controls. Specifically, we observed a two-fold decrease in the number of myonuclei, compared to vivarium and ground controls, and central location of myonuclei, low density of myofibers in the tissue, and of myofibrils within a fiber, as well as fragmentation and swelling of myofibers. Despite obvious atrophy, muscle regeneration nevertheless appeared to have continued after 30 days in microgravity as evidenced by thin and short newly formed myofibers. Many of them, however, showed evidence of apoptotic cells and myofibril degradation, suggesting that long-term unloading in microgravity may affect late stages of myofiber differentiation. Ground asynchronous and vivarium control animals demonstrated normal, well-developed tissue structure with sufficient blood and nerve supply and evidence of regenerative formation of new myofibers free of apoptotic nuclei. Regenerative activity of satellite cells in muscles was observed both in microgravity and ground control groups, using Pax7 and Myogenin immunolocalization, as well as Myogenin expression analysis. In addition, we have detected positive nuclear immunolocalization of c-Jun and c-Myc proteins indicating their sensitivity to changes in gravitational loading in a given model. In summary, long-term spaceflight in microgravity caused significant atrophy and degeneration of the femoral Quadriceps muscle group, and it may interfere with muscle regenerative processes by inducing apoptosis in newly-formed myofibrils during their differentiation phase.

Association of Distinct Mutational Signatures With Correlates of Increased Immune Activity in Pancreatic Ductal Adenocarcinoma.

PubMed

Connor, Ashton A; Denroche, Robert E; Jang, Gun Ho; Timms, Lee; Kalimuthu, Sangeetha N; Selander, Iris; McPherson, Treasa; Wilson, Gavin W; Chan-Seng-Yue, Michelle A; Borozan, Ivan; Ferretti, Vincent; Grant, Robert C; Lungu, Ilinca M; Costello, Eithne; Greenhalf, William; Palmer, Daniel; Ghaneh, Paula; Neoptolemos, John P; Buchler, Markus; Petersen, Gloria; Thayer, Sarah; Hollingsworth, Michael A; Sherker, Alana; Durocher, Daniel; Dhani, Neesha; Hedley, David; Serra, Stefano; Pollett, Aaron; Roehrl, Michael H A; Bavi, Prashant; Bartlett, John M S; Cleary, Sean; Wilson, Julie M; Alexandrov, Ludmil B; Moore, Malcolm; Wouters, Bradly G; McPherson, John D; Notta, Faiyaz; Stein, Lincoln D; Gallinger, Steven

2017-06-01

Outcomes for patients with pancreatic ductal adenocarcinoma (PDAC) remain poor. Advances in next-generation sequencing provide a route to therapeutic approaches, and integrating DNA and RNA analysis with clinicopathologic data may be a crucial step toward personalized treatment strategies for this disease. To classify PDAC according to distinct mutational processes, and explore their clinical significance. We performed a retrospective cohort study of resected PDAC, using cases collected between 2008 and 2015 as part of the International Cancer Genome Consortium. The discovery cohort comprised 160 PDAC cases from 154 patients (148 primary; 12 metastases) that underwent tumor enrichment prior to whole-genome and RNA sequencing. The replication cohort comprised 95 primary PDAC cases that underwent whole-genome sequencing and expression microarray on bulk biospecimens. Somatic mutations accumulate from sequence-specific processes creating signatures detectable by DNA sequencing. Using nonnegative matrix factorization, we measured the contribution of each signature to carcinogenesis, and used hierarchical clustering to subtype each cohort. We examined expression of antitumor immunity genes across subtypes to uncover biomarkers predictive of response to systemic therapies. The discovery cohort was 53% male (n = 79) and had a median age of 67 (interquartile range, 58-74) years. The replication cohort was 50% male (n = 48) and had a median age of 68 (interquartile range, 60-75) years. Five predominant mutational subtypes were identified that clustered PDAC into 4 major subtypes: age related, double-strand break repair, mismatch repair, and 1 with unknown etiology (signature 8). These were replicated and validated. Signatures were faithfully propagated from primaries to matched metastases, implying their stability during carcinogenesis. Twelve of 27 (45%) double-strand break repair cases lacked germline or somatic events in canonical homologous recombination genes-BRCA1, BRCA2, or PALB2. Double-strand break repair and mismatch repair subtypes were associated with increased expression of antitumor immunity, including activation of CD8-positive T lymphocytes (GZMA and PRF1) and overexpression of regulatory molecules (cytotoxic T-lymphocyte antigen 4, programmed cell death 1, and indolamine 2,3-dioxygenase 1), corresponding to higher frequency of somatic mutations and tumor-specific neoantigens. Signature-based subtyping may guide personalized therapy of PDAC in the context of biomarker-driven prospective trials.

An ICT infrastructure to integrate clinical and molecular data in oncology research

PubMed Central

2012-01-01

Background The ONCO-i2b2 platform is a bioinformatics tool designed to integrate clinical and research data and support translational research in oncology. It is implemented by the University of Pavia and the IRCCS Fondazione Maugeri hospital (FSM), and grounded on the software developed by the Informatics for Integrating Biology and the Bedside (i2b2) research center. I2b2 has delivered an open source suite based on a data warehouse, which is efficiently interrogated to find sets of interesting patients through a query tool interface. Methods Onco-i2b2 integrates data coming from multiple sources and allows the users to jointly query them. I2b2 data are then stored in a data warehouse, where facts are hierarchically structured as ontologies. Onco-i2b2 gathers data from the FSM pathology unit (PU) database and from the hospital biobank and merges them with the clinical information from the hospital information system. Our main effort was to provide a robust integrated research environment, giving a particular emphasis to the integration process and facing different challenges, consecutively listed: biospecimen samples privacy and anonymization; synchronization of the biobank database with the i2b2 data warehouse through a series of Extract, Transform, Load (ETL) operations; development and integration of a Natural Language Processing (NLP) module, to retrieve coded information, such as SNOMED terms and malignant tumors (TNM) classifications, and clinical tests results from unstructured medical records. Furthermore, we have developed an internal SNOMED ontology rested on the NCBO BioPortal web services. Results Onco-i2b2 manages data of more than 6,500 patients with breast cancer diagnosis collected between 2001 and 2011 (over 390 of them have at least one biological sample in the cancer biobank), more than 47,000 visits and 96,000 observations over 960 medical concepts. Conclusions Onco-i2b2 is a concrete example of how integrated Information and Communication Technology architecture can be implemented to support translational research. The next steps of our project will involve the extension of its capabilities by implementing new plug-in devoted to bioinformatics data analysis as well as a temporal query module. PMID:22536972

NASA's Rodent Research Project: Validation of Flight Hardware, Operations and Science Capabilities for Conducting Long Duration Experiments in Space

NASA Technical Reports Server (NTRS)

Choi, S. Y.; Beegle, J. E.; Wigley, C. L.; Pletcher, D.; Globus, R. K.

2015-01-01

Research using rodents is an essential tool for advancing biomedical research on Earth and in space. Rodent Research (RR)-1 was conducted to validate flight hardware, operations, and science capabilities that were developed at the NASA Ames Research Center. Twenty C57BL/6J adult female mice were launched on Sept 21, 2014 in a Dragon Capsule (SpaceX-4), then transferred to the ISS for a total time of 21-22 days (10 commercial mice) or 37 (10 validation mice). Tissues collected on-orbit were either rapidly frozen or preserved in RNA later at less than or equal to -80 C (n=2/group) until their return to Earth. Remaining carcasses were rapidly frozen for dissection post-flight. The three controls groups at Kennedy Space Center consisted of: Basal mice euthanized at the time of launch, Vivarium controls, housed in standard cages, and Ground Controls (GC), housed in flight hardware within an environmental chamber. FLT mice appeared more physically active on-orbit than GC, and behavior analysis are in progress. Upon return to Earth, there were no differences in body weights between FLT and GC at the end of the 37 days in space. RNA was of high quality (RIN greater than 8.5). Liver enzyme activity levels of FLT mice and all control mice were similar in magnitude to those of the samples that were optimally processed in the laboratory. Liver samples collected from the intact frozen FLT carcasses had RNA RIN of 7.27 +/- 0.52, which was lower than that of the samples processed on-orbit, but similar to those obtained from the control group intact carcasses. Nonetheless, the RNA samples from the intact carcasses were acceptable for the most demanding transcriptomic analyses. Adrenal glands, thymus and spleen (organs associated with stress response) showed no significant difference in weights between FLT and GC. Enzymatic activity was also not significantly different. Over 3,000 tissues collected from the four groups of mice have become available for the Biospecimen Sharing Program. Together, these validation flight findings demonstrate the capability to support long-duration RR on the ISS to achieve both basic science and biomedical objectives.

An informatics model for tissue banks--lessons learned from the Cooperative Prostate Cancer Tissue Resource.

PubMed

Patel, Ashokkumar A; Gilbertson, John R; Parwani, Anil V; Dhir, Rajiv; Datta, Milton W; Gupta, Rajnish; Berman, Jules J; Melamed, Jonathan; Kajdacsy-Balla, Andre; Orenstein, Jan; Becich, Michael J

2006-05-05

Advances in molecular biology and growing requirements from biomarker validation studies have generated a need for tissue banks to provide quality-controlled tissue samples with standardized clinical annotation. The NCI Cooperative Prostate Cancer Tissue Resource (CPCTR) is a distributed tissue bank that comprises four academic centers and provides thousands of clinically annotated prostate cancer specimens to researchers. Here we describe the CPCTR information management system architecture, common data element (CDE) development, query interfaces, data curation, and quality control. Data managers review the medical records to collect and continuously update information for the 145 clinical, pathological and inventorial CDEs that the Resource maintains for each case. An Access-based data entry tool provides de-identification and a standard communication mechanism between each group and a central CPCTR database. Standardized automated quality control audits have been implemented. Centrally, an Oracle database has web interfaces allowing multiple user-types, including the general public, to mine de-identified information from all of the sites with three levels of specificity and granularity as well as to request tissues through a formal letter of intent. Since July 2003, CPCTR has offered over 6,000 cases (38,000 blocks) of highly characterized prostate cancer biospecimens, including several tissue microarrays (TMA). The Resource developed a website with interfaces for the general public as well as researchers and internal members. These user groups have utilized the web-tools for public query of summary data on the cases that were available, to prepare requests, and to receive tissues. As of December 2005, the Resource received over 130 tissue requests, of which 45 have been reviewed, approved and filled. Additionally, the Resource implemented the TMA Data Exchange Specification in its TMA program and created a computer program for calculating PSA recurrence. Building a biorepository infrastructure that meets today's research needs involves time and input of many individuals from diverse disciplines. The CPCTR can provide large volumes of carefully annotated prostate tissue for research initiatives such as Specialized Programs of Research Excellence (SPOREs) and for biomarker validation studies and its experience can help development of collaborative, large scale, virtual tissue banks in other organ systems.

Ex Vivo Maintenance of Primary Human Multiple Myeloma Cells through the Optimization of the Osteoblastic Niche.

PubMed

Zhang, Wenting; Gu, Yexin; Sun, Qiaoling; Siegel, David S; Tolias, Peter; Yang, Zheng; Lee, Woo Y; Zilberberg, Jenny

2015-01-01

We previously reported a new approach for culturing difficult-to-preserve primary patient-derived multiple myeloma cells (MMC) using an osteoblast (OSB)-derived 3D tissue scaffold constructed in a perfused microfluidic environment and a culture medium supplemented with patient plasma. In the current study, we used this biomimetic model to show, for the first time, that the long-term survival of OSB is the most critical factor in maintaining the ex vivo viability and proliferative capacity of MMC. We found that the adhesion and retention of MMC to the tissue scaffold was meditated by osteoblastic N-cadherin, as one of potential mechanisms that regulate MMC-OSB interactions. However, in the presence of MMC and patient plasma, the viability and osteogenic activity of OSB became gradually compromised, and consequently MMC could not remain viable over 3 weeks. We demonstrated that the long-term survival of both OSB and MMC could be enhanced by: (1) optimizing perfusion flow rate and patient-derived plasma composition in the culture medium and (2) replenishing OSB during culture as a practical means of prolonging MMC's viability beyond several weeks. These findings were obtained using a high-throughput well plate-based perfusion device from the perspective of optimizing the ex vivo preservation of patient-derived MM biospecimens for downstream use in biological studies and chemosensitivity analyses.

Ex Vivo Maintenance of Primary Human Multiple Myeloma Cells through the Optimization of the Osteoblastic Niche

PubMed Central

Zhang, Wenting; Gu, Yexin; Sun, Qiaoling; Siegel, David S.; Tolias, Peter; Yang, Zheng

2015-01-01

We previously reported a new approach for culturing difficult-to-preserve primary patient-derived multiple myeloma cells (MMC) using an osteoblast (OSB)-derived 3D tissue scaffold constructed in a perfused microfluidic environment and a culture medium supplemented with patient plasma. In the current study, we used this biomimetic model to show, for the first time, that the long-term survival of OSB is the most critical factor in maintaining the ex vivo viability and proliferative capacity of MMC. We found that the adhesion and retention of MMC to the tissue scaffold was meditated by osteoblastic N-cadherin, as one of potential mechanisms that regulate MMC-OSB interactions. However, in the presence of MMC and patient plasma, the viability and osteogenic activity of OSB became gradually compromised, and consequently MMC could not remain viable over 3 weeks. We demonstrated that the long-term survival of both OSB and MMC could be enhanced by: (1) optimizing perfusion flow rate and patient-derived plasma composition in the culture medium and (2) replenishing OSB during culture as a practical means of prolonging MMC’s viability beyond several weeks. These findings were obtained using a high-throughput well plate-based perfusion device from the perspective of optimizing the ex vivo preservation of patient-derived MM biospecimens for downstream use in biological studies and chemosensitivity analyses. PMID:25973790

Genetic variations in GPSM3 associated with protection from rheumatoid arthritis affect its transcript abundance

PubMed Central

Gall, BJ; Wilson, A; Schroer, AB; Gross, JD; Stoilov, P; Setola, V; Watkins, CM; Siderovski, DP

2015-01-01

G protein signaling modulator 3 (GPSM3) is a regulator of G protein-coupled receptor signaling, with expression restricted to leukocytes and lymphoid organs. Previous genome-wide association studies have highlighted single-nucleotide polymorphisms (SNPs rs204989, rs204991) in a region upstream of the GPSM3 transcription start site as being inversely correlated to the prevalence of rheumatoid arthritis (RA) -- this association is supported by the protection afforded to Gpsm3-deficient mice in models of inflammatory arthritis. Here, we assessed the functional consequences of these polymorphisms. We collected biospecimens from 50 volunteers with RA diagnoses, 50 RA-free volunteers matched to the aforementioned group, and 100 unmatched healthy young volunteers. We genotyped these individuals for GPSM3 (rs204989, rs204991), CCL21 (rs2812378), and HLA gene region (rs6457620) polymorphisms, and found no significant differences in minor allele frequencies between the RA and disease-free cohorts. However, we identified that individuals homozygous for SNPs rs204989 and rs204991 had decreased GPSM3 transcript abundance relative to individuals homozygous for the major allele. In vitro promoter activity studies suggest that SNP rs204989 is the primary cause of this decrease in transcript levels. Knockdown of GPSM3 in THP-1 cells, a human monocytic cell line, was found to disrupt ex vivo migration to the chemokine MCP-1. PMID:26821282

Dual-view inverted selective plane illumination microscopy (diSPIM) with improved background rejection for accurate 3D digital pathology

NASA Astrophysics Data System (ADS)

Hu, Bihe; Bolus, Daniel; Brown, J. Quincy

2018-02-01

Current gold-standard histopathology for cancerous biopsies is destructive, time consuming, and limited to 2D slices, which do not faithfully represent true 3D tumor micro-morphology. Light sheet microscopy has emerged as a powerful tool for 3D imaging of cancer biospecimens. Here, we utilize the versatile dual-view inverted selective plane illumination microscopy (diSPIM) to render digital histological images of cancer biopsies. Dual-view architecture enabled more isotropic resolution in X, Y, and Z; and different imaging modes, such as adding electronic confocal slit detection (eCSD) or structured illumination (SI), can be used to improve degraded image quality caused by background signal of large, scattering samples. To obtain traditional H&E-like images, we used DRAQ5 and eosin (D&E) staining, with 488nm and 647nm laser illumination, and multi-band filter sets. Here, phantom beads and a D&E stained buccal cell sample have been used to verify our dual-view method. We also show that via dual view imaging and deconvolution, more isotropic resolution has been achieved for optical cleared human prostate sample, providing more accurate quantitation of 3D tumor architecture than was possible with single-view SPIM methods. We demonstrate that the optimized diSPIM delivers more precise analysis of 3D cancer microarchitecture in human prostate biopsy than simpler light sheet microscopy arrangements.

Genetic variations in GPSM3 associated with protection from rheumatoid arthritis affect its transcript abundance.

PubMed

Gall, B J; Wilson, A; Schroer, A B; Gross, J D; Stoilov, P; Setola, V; Watkins, C M; Siderovski, D P

2016-03-01

G protein signaling modulator 3 (GPSM3) is a regulator of G protein-coupled receptor signaling, with expression restricted to leukocytes and lymphoid organs. Previous genome-wide association studies have highlighted single-nucleotide polymorphisms (SNPs; rs204989 and rs204991) in a region upstream of the GPSM3 transcription start site as being inversely correlated to the prevalence of rheumatoid arthritis (RA)-this association is supported by the protection afforded to Gpsm3-deficient mice in models of inflammatory arthritis. Here, we assessed the functional consequences of these polymorphisms. We collected biospecimens from 50 volunteers with RA diagnoses, 50 RA-free volunteers matched to the aforementioned group and 100 unmatched healthy young volunteers. We genotyped these individuals for GPSM3 (rs204989, rs204991), CCL21 (rs2812378) and HLA gene region (rs6457620) polymorphisms, and found no significant differences in minor allele frequencies between the RA and disease-free cohorts. However, we identified that individuals homozygous for SNPs rs204989 and rs204991 had decreased GPSM3 transcript abundance relative to individuals homozygous for the major allele. In vitro promoter activity studies suggest that SNP rs204989 is the primary cause of this decrease in transcript levels. Knockdown of GPSM3 in THP-1 cells, a human monocytic cell line, was found to disrupt ex vivo migration to the chemokine MCP-1.

Exposure Measurements in Japan Environment and Children's Study.

PubMed

Nakayama, Shoji

2016-01-01

The Japan Ministry of the Environment is conducting a large-scale birth cohort study called the Japan Environment and Children's Study (JECS), which involves 100000 mother-child pairs. Mothers are enrolled during pregnancy, and their children are followed up and studied until they reach the age of 13 years. The JECS started recruiting mothers in January 2011 and completed the registration of more than 103000 mothers in March 2014. The National Institute for Environmental Studies takes the lead in the study programming and implementation in cooperation with the National Centre for Child Health and Development and 15 Regional Centres that reach out to the study participants. In the study, the effects of environmental factors on children's health and development are investigated. The environment in this study is defined not only as air, soil, water, and indoor environments but also as various chemical substances, physical conditions, socioeconomic factors, psychological conditions, lifestyles and community situations. Mothers' and children's exposures to these environmental factors are measured through chemical analyses of biospecimens collected during pregnancy and after birth, questionnaires and computer modelling. The homes of the randomly selected participants (5000) are visited to measure the concentrations of volatile organic compounds, nitrogen and sulphuric oxides and particulate matter. Vacuum dust samples are also collected for chemical analysis. All these data will be combined with the information collected by the dwelling unit observation to assess the exposure of children aged 1.5 and 3 years.

Cohort Profile: the Avon Longitudinal Study of Parents and Children: ALSPAC mothers cohort.

PubMed

Fraser, Abigail; Macdonald-Wallis, Corrie; Tilling, Kate; Boyd, Andy; Golding, Jean; Davey Smith, George; Henderson, John; Macleod, John; Molloy, Lynn; Ness, Andy; Ring, Susan; Nelson, Scott M; Lawlor, Debbie A

2013-02-01

Summary The Avon Longitudinal Study of Children and Parents (ALSPAC) was established to understand how genetic and environmental characteristics influence health and development in parents and children. All pregnant women resident in a defined area in the South West of England, with an expected date of delivery between 1st April 1991 and 31st December 1992, were eligible and 13761 women (contributing 13867 pregnancies) were recruited. These women have been followed over the last 19-22 years and have completed up to 20 questionnaires, have had detailed data abstracted from their medical records and have information on any cancer diagnoses and deaths through record linkage. A follow-up assessment was completed 17-18 years postnatal at which anthropometry, blood pressure, fat, lean and bone mass and carotid intima media thickness were assessed, and a fasting blood sample taken. The second follow-up clinic, which additionally measures cognitive function, physical capability, physical activity (with accelerometer) and wrist bone architecture, is underway and two further assessments with similar measurements will take place over the next 5 years. There is a detailed biobank that includes DNA, with genome-wide data available on >10000, stored serum and plasma taken repeatedly since pregnancy and other samples; a wide range of data on completed biospecimen assays are available. Details of how to access these data are provided in this cohort profile.

Experiences with premorbid SUDEP discussion among participants in the North American SUDEP Registry (NASR).

PubMed

Louik, Jay; Doumlele, Kyra; Hussain, Fizza; Crandall, Laura; Buchhalter, Jeffrey; Hesdorffer, Dale; Donner, Elizabeth; Devinsky, Orrin; Friedman, Daniel

2017-05-01

The North American SUDEP Registry (NASR) is a repository of clinical data and biospecimens in cases of sudden unexpected death in epilepsy (SUDEP), a leading cause of epilepsy-related deaths. We assessed whether bereaved families were aware of SUDEP before their family member's death and their preferences for SUDEP disclosure. At enrollment, next-of-kin of SUDEP cases completed an intake interview, including questions assessing premorbid SUDEP discussions. Only 18.1% of the 138 next-of-kin recalled a previous discussion of SUDEP with a healthcare provider or support resource. Of the 112 who did not recall such a discussion, 72.3% wished it was discussed, 10.7% were satisfied it was not discussed, and 17% were unsure. A history of status epilepticus predicted SUDEP discussion. Rates of SUDEP discussion were not significantly higher among SUDEPs after 2013 (the approximate study midpoint) compared with those before then. Our study suggests that SUDEP remains infrequently discussed with family members of persons with epilepsy. Nearly three-quarters of family members wished they had known of SUDEP before the death. However, some were indifferent or were satisfied that this discussion had not occurred. We must balance more systematic education of patients and families about SUDEP while respecting individual preferences about having this discussion. Copyright © 2017 Elsevier Inc. All rights reserved.

Rationale and study design of the Japan environment and children's study (JECS).

PubMed

Kawamoto, Toshihiro; Nitta, Hiroshi; Murata, Katsuyuki; Toda, Eisaku; Tsukamoto, Naoya; Hasegawa, Manabu; Yamagata, Zentaro; Kayama, Fujio; Kishi, Reiko; Ohya, Yukihiro; Saito, Hirohisa; Sago, Haruhiko; Okuyama, Makiko; Ogata, Tsutomu; Yokoya, Susumu; Koresawa, Yuji; Shibata, Yasuyuki; Nakayama, Shoji; Michikawa, Takehiro; Takeuchi, Ayano; Satoh, Hiroshi

2014-01-10

There is global concern over significant threats from a wide variety of environmental hazards to which children face. Large-scale and long-term birth cohort studies are needed for better environmental management based on sound science. The primary objective of the Japan Environment and Children's Study (JECS), a nation-wide birth cohort study that started its recruitment in January 2011, is to elucidate environmental factors that affect children's health and development. Approximately 100,000 expecting mothers who live in designated study areas will be recruited over a 3-year period from January 2011. Participating children will be followed until they reach 13 years of age. Exposure to environmental factors will be assessed by chemical analyses of bio-specimens (blood, cord blood, urine, breast milk, and hair), household environment measurements, and computational simulations using monitoring data (e.g. ambient air quality monitoring) as well as questionnaires. JECS' priority outcomes include reproduction/pregnancy complications, congenital anomalies, neuropsychiatric disorders, immune system disorders, and metabolic/endocrine system disorders. Genetic factors, socioeconomic status, and lifestyle factors will also be examined as covariates and potential confounders. To maximize representativeness, we adopted provider-mediated community-based recruitment. Through JECS, chemical substances to which children are exposed during the fetal stage or early childhood will be identified. The JECS results will be translated to better risk assessment and management to provide healthy environment for next generations.

Public Preferences Regarding Informed Consent Models for Participation in Population-based Genomic Research

PubMed Central

Platt, Jodyn; Bollinger, Juli; Dvoskin, Rachel; Kardia, Sharon LR; Kaufman, David

2013-01-01

Purpose Some large population biobanks that house biospecimens and health information for research seek broad consent from participants, while others re-consent for specific new studies. Understanding research participants’ attitudes and preferences about broad and narrow consent may improve recruitment, retention, and public support. Methods An online survey was conducted among a representative sample of 4,659 US adults to examine relationships between consent preferences and demographic factors, beliefs about privacy, the value of research, and the perceived trustworthiness of researchers. Results Participants preferred broad consent (52%) over study-by-study consent models (48%). Higher preferences for study-by-study consent observed among Black non-Hispanic respondents, and respondents with lower income and education were explained by differences in the prevalence of one or more beliefs about the study. Respondents with fears about research and those that would feel respected if asked for permission for each research use preferred study-by-study consent. Preference for broad consent was related to the desire not to be bothered with multiple requests and the belief that the study could lead to improved treatments, cures, and lives saved. Conclusion These data suggest that support for broad consent is contingent on sufficient information about data use. Work with research participants and community leaders to understand, respond to, and influence opinions about a given, ongoing study may improve uptake of broad consent. PMID:23660530

SUMMIT (Serially Unified Multicenter Multiple Sclerosis Investigation): creating a repository of deeply phenotyped contemporary multiple sclerosis cohorts.

PubMed

Bove, Riley; Chitnis, Tanuja; Cree, Bruce Ac; Tintoré, Mar; Naegelin, Yvonne; Uitdehaag, Bernard Mj; Kappos, Ludwig; Khoury, Samia J; Montalban, Xavier; Hauser, Stephen L; Weiner, Howard L

2017-08-01

There is a pressing need for robust longitudinal cohort studies in the modern treatment era of multiple sclerosis. Build a multiple sclerosis (MS) cohort repository to capture the variability of disability accumulation, as well as provide the depth of characterization (clinical, radiologic, genetic, biospecimens) required to adequately model and ultimately predict a patient's course. Serially Unified Multicenter Multiple Sclerosis Investigation (SUMMIT) is an international multi-center, prospectively enrolled cohort with over a decade of comprehensive follow-up on more than 1000 patients from two large North American academic MS Centers (Brigham and Women's Hospital (Comprehensive Longitudinal Investigation of Multiple Sclerosis at the Brigham and Women's Hospital (CLIMB; BWH)) and University of California, San Francisco (Expression/genomics, Proteomics, Imaging, and Clinical (EPIC))). It is bringing online more than 2500 patients from additional international MS Centers (Basel (Universitätsspital Basel (UHB)), VU University Medical Center MS Center Amsterdam (MSCA), Multiple Sclerosis Center of Catalonia-Vall d'Hebron Hospital (Barcelona clinically isolated syndrome (CIS) cohort), and American University of Beirut Medical Center (AUBMC-Multiple Sclerosis Interdisciplinary Research (AMIR)). We provide evidence for harmonization of two of the initial cohorts in terms of the characterization of demographics, disease, and treatment-related variables; demonstrate several proof-of-principle analyses examining genetic and radiologic predictors of disease progression; and discuss the steps involved in expanding SUMMIT into a repository accessible to the broader scientific community.

Pancreatic cancer ascites xenograft–an expeditious model mirroring advanced therapeutic resistant disease

PubMed Central

Schvimer, Michael; Atias, Dikla; Halperin, Sharon; Buzhor, Ella; Raitses-Gurevich, Maria; Cohen, Keren; Pri-Chen, Sara; Wilson, Julie; Denroche, Robert E.; Lungu, Ilinca; Bartlett, John M.S.; Mbabaali, Faridah; Yarden, Yosef; Nataraj, Nishanth Belugali; Gallinger, Steven; Berger, Raanan

2017-01-01

Pancreatic ductal adenocarcinoma has limited treatment options. There is an urgent need for developing appropriate pre-clinical models recapitulating metastatic disease, the most common clinical scenario at presentation. Ascites accumulation occurs in up to 20–30% of patients with pancreatic cancer; this milieu represents a highly cellular research resource of metastatic peritoneal spread. In this study, we utilized pancreatic ascites/pleural effusion cancer cells to establish patient derived xenografts. Ascites/pleural effusion-patient derived xenografts were established from twelve independent cases. Xenografts were serially passed in nude mice and tissue bio-specimen banking has been established. Histopathology of emergent tumors demonstrates poorly to moderately differentiated, glandular and mucin producing tumors, mirroring morphology of primary pancreatic cancer tumors. Whole genome sequencing of six patient derived xenografts samples demonstrates common mutations and structural variations similar to those reported in primary pancreatic cancer. Xenograft tumors were dissociated to single-cells and in-vitro drug sensitivity screen assays demonstrated chemo-resistance, correlating with patient clinical scenarios, thus serving as a platform for clinically relevant translational research. Therefore, establishment of this novel ascites/pleural effusion patient derived xenograft model, with extensive histopathology and genomic characterization, opens an opportunity for the study of advanced aggressive pancreatic cancer. Characterization of metastatic disease and mechanisms of resistance to therapeutics may lead to the development of novel drug combinations. PMID:28489577

Frequent alteration of the protein synthesis of enzymes for glucose metabolism in hepatocellular carcinomas.

PubMed

Shimizu, Takayuki; Inoue, Ken-ichi; Hachiya, Hiroyuki; Shibuya, Norisuke; Shimoda, Mitsugi; Kubota, Keiichi

2014-09-01

Cancer cells show enhanced glycolysis and inhibition of oxidative phosphorylation, even in the presence of sufficient oxygen (aerobic glycolysis). Glycolysis is much less efficient for energy production than oxidative phosphorylation, and the reason why cancer cells selectively use glycolysis remains unclear. Biospecimens were collected from 45 hepatocellular carcinoma patients. Protein samples were prepared through subcellular localization or whole-cell lysis. Protein synthesis was measured by SDS-PAGE and immunoblotting. mRNA transcription was measured using quantitative RT-PCR. Statistical correlation among immunoblotting data and clinicolaboratory factors were analyzed using SPSS. Enzymes for oxidative phosphorylation (SDHA and SDHB) were frequently decreased (56 and 48 % of patients, respectively) in hepatocellular carcinomas. The lowered amount of the SDH protein complex was rarely accompanied by stabilization of HIF1α and subsequent activation of the hypoxia response. On the other hand, protein synthesis of G6PD and TKT, enzymes critical for pentose phosphate pathway (PPP), was increased (in 45 and 55 % of patients, respectively), while that of ALDOA, an enzyme for mainstream glycolysis, was eliminated (in 55 % of patients). Alteration of protein synthesis was correlated with gene expression for G6PD and TKT, but not for TKTL1, ALDOA, SDHA or SDHB. Augmented transcription and synthesis of PPP enzymes were accompanied by nuclear accumulation of NRF2. Hepatocellular carcinomas divert glucose metabolism to the anabolic shunt by activating transcription factor NRF2.

Behavioral Genetics in Criminal and Civil Courts.

PubMed

Sabatello, Maya; Appelbaum, Paul S

Although emerging findings in psychiatric and behavioral genetics create hope for improved prevention, diagnosis, and treatment of disorders, the introduction of such data as evidence in criminal and civil proceedings raises a host of ethical, legal, and social issues. Should behavioral and psychiatric genetic data be admissible in judicial proceedings? If so, what are the various means for obtaining such evidence, and for what purposes should its admission be sought and permitted? How could-and should-such evidence affect judicial outcomes in criminal and civil proceedings? And what are the potential implications of using behavioral and psychiatric genetic evidence for individuals and communities, and for societal values of equality and justice? This article provides an overview of the historical and current developments in behavioral genetics. We then explore the extent to which behavioral genetic evidence has-and should-affect determinations of criminal responsibility and sentencing, as well as the possible ramifications of introducing such evidence in civil courts, with a focus on tort litigation and child custody disputes. We also consider two ways in which behavioral genetic evidence may come to court in the future-through genetic theft or the subpoena of a litigant's biospecimen data that was previously obtained for clinical or research purposes-and the concerns that these possibilities raise. Finally, we highlight the need for caution and for approaches to prevent the misuse of behavioral genetic evidence in courts.

NASA's Rodent Research Project: Validation of Capabilities for Conducting Long Duration Experiments in Space

NASA Technical Reports Server (NTRS)

Choi, Sungshin Y.; Cole, Nicolas; Reyes, America; Lai, San-Huei; Klotz, Rebecca; Beegle, Janet E.; Wigley, Cecilia L.; Pletcher, David; Globus, Ruth K.

2015-01-01

Research using rodents is an essential tool for advancing biomedical research on Earth and in space. Prior rodent experiments on the Shuttle were limited by the short flight duration. The International Space Station (ISS) provides a new platform for conducting rodent experiments under long duration conditions. Rodent Research (RR)-1 was conducted to validate flight hardware, operations, and science capabilities that were developed at the NASA Ames Research Center. Twenty C57BL6J adult female mice were launched on Sept 21, 2014 in a Dragon Capsule (SpaceX-4), then transferred to the ISS for a total time of 21-22 days (10 commercial mice) or 37 days (10 validation mice). Tissues collected on-orbit were either rapidly frozen or preserved in RNAlater at -80C (n2group) until their return to Earth. Remaining carcasses on-orbit were rapidly frozen for dissection post-flight. The three controls groups at Kennedy Space Center consisted of: Basal mice euthanized at the time of launch, Vivarium controls housed in standard cages, and Ground Controls (GC) housed in flight hardware within an environmental chamber. Upon return to Earth, there were no differences in body weights between Flight (FLT) and GC at the end of the 37 days in space. Liver enzyme activity levels of FLT mice and all control mice were similar in magnitude to those of the samples that were processed under optimal conditions in the laboratory. Liver samples dissected on-orbit yielded high quality RNA (RIN8.99+-0.59, n7). Liver samples dissected post-flight from the intact, frozen FLT carcasses yielded RIN of 7.27 +- 0.52 (n6). Additionally, wet weights of various tissues were measured. Adrenal glands and spleen showed no significant differences in FLT compared to GC although thymus and livers weights were significantly greater in FLT compared to GC. Over 3,000 tissue aliquots collected post-flight from the four groups of mice were deposited into the Ames Life Science Data Archives for future Biospecimen Sharing Program. Together, the RR validation flight successfully demonstrates the capability to support long-duration experimentation on the ISS to achieve both basic science and biomedical objectives.

Environment And Genetics in Lung cancer Etiology (EAGLE) study: an integrative population-based case-control study of lung cancer.

PubMed

Landi, Maria Teresa; Consonni, Dario; Rotunno, Melissa; Bergen, Andrew W; Goldstein, Alisa M; Lubin, Jay H; Goldin, Lynn; Alavanja, Michael; Morgan, Glen; Subar, Amy F; Linnoila, Ilona; Previdi, Fabrizio; Corno, Massimo; Rubagotti, Maurizia; Marinelli, Barbara; Albetti, Benedetta; Colombi, Antonio; Tucker, Margaret; Wacholder, Sholom; Pesatori, Angela C; Caporaso, Neil E; Bertazzi, Pier Alberto

2008-06-06

Lung cancer is the leading cause of cancer mortality worldwide. Tobacco smoking is its primary cause, and yet the precise molecular alterations induced by smoking in lung tissue that lead to lung cancer and impact survival have remained obscure. A new framework of research is needed to address the challenges offered by this complex disease. We designed a large population-based case-control study that combines a traditional molecular epidemiology design with a more integrative approach to investigate the dynamic process that begins with smoking initiation, proceeds through dependency/smoking persistence, continues with lung cancer development and ends with progression to disseminated disease or response to therapy and survival. The study allows the integration of data from multiple sources in the same subjects (risk factors, germline variation, genomic alterations in tumors, and clinical endpoints) to tackle the disease etiology from different angles. Before beginning the study, we conducted a phone survey and pilot investigations to identify the best approach to ensure an acceptable participation in the study from cases and controls. Between 2002 and 2005, we enrolled 2101 incident primary lung cancer cases and 2120 population controls, with 86.6% and 72.4% participation rate, respectively, from a catchment area including 216 municipalities in the Lombardy region of Italy. Lung cancer cases were enrolled in 13 hospitals and population controls were randomly sampled from the area to match the cases by age, gender and residence. Detailed epidemiological information and biospecimens were collected from each participant, and clinical data and tissue specimens from the cases. Collection of follow-up data on treatment and survival is ongoing. EAGLE is a new population-based case-control study that explores the full spectrum of lung cancer etiology, from smoking addiction to lung cancer outcome, through examination of epidemiological, molecular, and clinical data. We have provided a detailed description of the study design, field activities, management, and opportunities for research following this integrative approach, which allows a sharper and more comprehensive vision of the complex nature of this disease. The study is poised to accelerate the emergence of new preventive and therapeutic strategies with potentially enormous impact on public health.

Toward an integrative account of social cognition: marrying theory of mind and interactionism to study the interplay of Type 1 and Type 2 processes

PubMed Central

Bohl, Vivian; van den Bos, Wouter

2012-01-01

Traditional theory of mind (ToM) accounts for social cognition have been at the basis of most studies in the social cognitive neurosciences. However, in recent years, the need to go beyond traditional ToM accounts for understanding real life social interactions has become all the more pressing. At the same time it remains unclear whether alternative accounts, such as interactionism, can yield a sufficient description and explanation of social interactions. We argue that instead of considering ToM and interactionism as mutually exclusive opponents, they should be integrated into a more comprehensive account of social cognition. We draw on dual process models of social cognition that contrast two different types of social cognitive processing. The first type (labeled Type 1) refers to processes that are fast, efficient, stimulus-driven, and relatively inflexible. The second type (labeled Type 2) refers to processes that are relatively slow, cognitively laborious, flexible, and may involve conscious control. We argue that while interactionism captures aspects of social cognition mostly related to Type 1 processes, ToM is more focused on those based on Type 2 processes. We suggest that real life social interactions are rarely based on either Type 1 or Type 2 processes alone. On the contrary, we propose that in most cases both types of processes are simultaneously involved and that social behavior may be sustained by the interplay between these two types of processes. Finally, we discuss how the new integrative framework can guide experimental research on social interaction. PMID:23087631

Toward an integrative account of social cognition: marrying theory of mind and interactionism to study the interplay of Type 1 and Type 2 processes.

PubMed

Bohl, Vivian; van den Bos, Wouter

2012-01-01

Traditional theory of mind (ToM) accounts for social cognition have been at the basis of most studies in the social cognitive neurosciences. However, in recent years, the need to go beyond traditional ToM accounts for understanding real life social interactions has become all the more pressing. At the same time it remains unclear whether alternative accounts, such as interactionism, can yield a sufficient description and explanation of social interactions. We argue that instead of considering ToM and interactionism as mutually exclusive opponents, they should be integrated into a more comprehensive account of social cognition. We draw on dual process models of social cognition that contrast two different types of social cognitive processing. The first type (labeled Type 1) refers to processes that are fast, efficient, stimulus-driven, and relatively inflexible. The second type (labeled Type 2) refers to processes that are relatively slow, cognitively laborious, flexible, and may involve conscious control. We argue that while interactionism captures aspects of social cognition mostly related to Type 1 processes, ToM is more focused on those based on Type 2 processes. We suggest that real life social interactions are rarely based on either Type 1 or Type 2 processes alone. On the contrary, we propose that in most cases both types of processes are simultaneously involved and that social behavior may be sustained by the interplay between these two types of processes. Finally, we discuss how the new integrative framework can guide experimental research on social interaction.

40 CFR 98.98 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-07-01

... this definition. (1) In situ plasma process sub-type consists of the cleaning of thin-film production... within a broad process type. For example, the chamber cleaning process type includes in-situ plasma chamber cleaning, remote plasma chamber cleaning, and in-situ thermal chamber cleaning sub-types. Process...

40 CFR 98.98 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-07-01

... this definition. (1) In situ plasma process sub-type consists of the cleaning of thin-film production... within a broad process type. For example, the chamber cleaning process type includes in-situ plasma chamber cleaning, remote plasma chamber cleaning, and in-situ thermal chamber cleaning sub-types. Process...

40 CFR 98.98 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-07-01

... definition. (1) In situ plasma process sub-type consists of the cleaning of thin-film production chambers... within a broad process type. For example, the chamber cleaning process type includes in-situ plasma chamber cleaning, remote plasma chamber cleaning, and in-situ thermal chamber cleaning sub-types. Process...

Organic electronic devices with multiple solution-processed layers

DOEpatents

Forrest, Stephen R.; Lassiter, Brian E.; Zimmerman, Jeramy D.

2015-08-04

A method of fabricating a tandem organic photosensitive device involves depositing a first layer of an organic electron donor type material film by solution-processing of the organic electron donor type material dissolved in a first solvent; depositing a first layer of an organic electron acceptor type material over the first layer of the organic electron donor type material film by a dry deposition process; depositing a conductive layer over the interim stack by a dry deposition process; depositing a second layer of the organic electron donor type material over the conductive layer by solution-processing of the organic electron donor type material dissolved in a second solvent, wherein the organic electron acceptor type material and the conductive layer are insoluble in the second solvent; depositing a second layer of an organic electron acceptor type material over the second layer of the organic electron donor type material film by a dry deposition process, resulting in a stack.

Dependent Neyman type A processes based on common shock Poisson approach

NASA Astrophysics Data System (ADS)

Kadilar, Gamze Özel; Kadilar, Cem

2016-04-01

The Neyman type A process is used for describing clustered data since the Poisson process is insufficient for clustering of events. In a multivariate setting, there may be dependencies between multivarite Neyman type A processes. In this study, dependent form of the Neyman type A process is considered under common shock approach. Then, the joint probability function are derived for the dependent Neyman type A Poisson processes. Then, an application based on forest fires in Turkey are given. The results show that the joint probability function of the dependent Neyman type A processes, which is obtained in this study, can be a good tool for the probabilistic fitness for the total number of burned trees in Turkey.

Large basolateral processes on type II hair cells comprise a novel processing unit in mammalian vestibular organs

PubMed Central

Pujol, Rémy; Pickett, Sarah B.; Nguyen, Tot Bui; Stone, Jennifer S.

2014-01-01

Sensory receptors in the vestibular system (hair cells) encode head movements and drive central motor reflexes that control gaze, body movements, and body orientation. In mammals, type I and II vestibular hair cells are defined by their shape, contacts with vestibular afferent nerves, and membrane conductance. Here, we describe unique morphological features of type II vestibular hair cells in mature rodents (mice and gerbils) and bats. These features are cytoplasmic processes that extend laterally from the hair cell’s base and project under type I hair cells. Closer analysis of adult mouse utricles demonstrated that the basolateral processes of type II hair cells range in shape, size, and branching, with the longest processes extending 3–4 hair cell widths. The hair cell basolateral processes synapse upon vestibular afferent nerves and receive inputs from vestibular efferent nerves. Further, some basolateral processes make physical contacts with the processes of other type II hair cells, forming some sort of network amongst type II hair cells. Basolateral processes are rare in perinatal mice and do not attain their mature form until 3–6 weeks of age. These observations demonstrate that basolateral processes are significant signaling regions of type II vestibular hair cells, and they suggest type II hair cells may directly communicate with each other, which has not been described in vertebrates. PMID:24825750

Large basolateral processes on type II hair cells are novel processing units in mammalian vestibular organs.

PubMed

Pujol, Rémy; Pickett, Sarah B; Nguyen, Tot Bui; Stone, Jennifer S

2014-10-01

Sensory receptors in the vestibular system (hair cells) encode head movements and drive central motor reflexes that control gaze, body movements, and body orientation. In mammals, type I and II vestibular hair cells are defined by their shape, contacts with vestibular afferent nerves, and membrane conductance. Here we describe unique morphological features of type II vestibular hair cells in mature rodents (mice and gerbils) and bats. These features are cytoplasmic processes that extend laterally from the hair cell base and project under type I hair cells. Closer analysis of adult mouse utricles demonstrated that the basolateral processes of type II hair cells vary in shape, size, and branching, with the longest processes extending three to four hair cell widths. The hair cell basolateral processes synapse upon vestibular afferent nerves and receive inputs from vestibular efferent nerves. Furthermore, some basolateral processes make physical contacts with the processes of other type II hair cells, forming some sort of network among type II hair cells. Basolateral processes are rare in perinatal mice and do not attain their mature form until 3-6 weeks of age. These observations demonstrate that basolateral processes are significant signaling regions of type II vestibular hair cells and suggest that type II hair cells may directly communicate with each other, which has not been described in vertebrates. © 2014 Wiley Periodicals, Inc.

Can NMR solve some significant challenges in metabolomics?

PubMed Central

Gowda, G.A. Nagana; Raftery, Daniel

2015-01-01

The field of metabolomics continues to witness rapid growth driven by fundamental studies, methods development, and applications in a number of disciplines that include biomedical science, plant and nutrition sciences, drug development, energy and environmental sciences, toxicology, etc. NMR spectroscopy is one of the two most widely used analytical platforms in the metabolomics field, along with mass spectrometry (MS). NMR's excellent reproducibility and quantitative accuracy, its ability to identify structures of unknown metabolites, its capacity to generate metabolite profiles using intact biospecimens with no need for separation, and its capabilities for tracing metabolic pathways using isotope labeled substrates offer unique strengths for metabolomics applications. However, NMR's limited sensitivity and resolution continue to pose a major challenge and have restricted both the number and the quantitative accuracy of metabolites analyzed by NMR. Further, the analysis of highly complex biological samples has increased the demand for new methods with improved detection, better unknown identification, and more accurate quantitation of larger numbers of metabolites. Recent efforts have contributed significant improvements in these areas, and have thereby enhanced the pool of routinely quantifiable metabolites. Additionally, efforts focused on combining NMR and MS promise opportunities to exploit the combined strength of the two analytical platforms for direct comparison of the metabolite data, unknown identification and reliable biomarker discovery that continue to challenge the metabolomics field. This article presents our perspectives on the emerging trends in NMR-based metabolomics and NMR's continuing role in the field with an emphasis on recent and ongoing research from our laboratory. PMID:26476597

Multi-Site Clinical Assessment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (MCAM): Design and Implementation of a Prospective/Retrospective Rolling Cohort Study

PubMed Central

Unger, Elizabeth R.; Lin, Jin-Mann S.; Tian, Hao; Natelson, Benjamin H.; Lange, Gudrun; Vu, Diana; Blate, Michelle; Klimas, Nancy G.; Balbin, Elizabeth G.; Bateman, Lucinda; Allen, Ali; Lapp, Charles W.; Springs, Wendy; Kogelnik, Andreas M.; Phan, Catrina C.; Danver, Joan; Podell, Richard N.; Fitzpatrick, Trisha; Peterson, Daniel L.; Gottschalk, C. Gunnar; Rajeevan, Mangalathu S.

2017-01-01

In the Multi-Site Clinical Assessment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (MCAM), we relied on expert clinician diagnoses to enroll patients from 7 specialty clinics in the United States in order to perform a systematic collection of data on measures of myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS). Healthy persons and those with other illnesses that share some features with ME/CFS were enrolled in comparison groups. The major objectives were to: 1) use standardized questionnaires to measure illness domains of ME/CFS and to evaluate patient heterogeneity overall and between clinics; 2) describe the course of illness, identify the measures that best correlate with meaningful clinical differences, and assess the performances of questionnaires as patient/person-reported outcome measures; 3) describe prescribed medications, orders for laboratory and other tests, and management tools used by expert clinicians to care for persons with ME/CFS; 4) collect biospecimens for future hypothesis testing and for evaluation of morning cortisol profiles; and 5) identify measures that best distinguish persons with ME/CFS from those in the comparison groups and detect subgroups of persons with ME/CFS who may have different underlying causes. Enrollment began in 2012 and is planned to continue in multiple stages through 2017. We present the MCAM methods in detail, along with an initial description of the 471 patients with ME/CFS who were enrolled in stage 1. PMID:28338983

Is spaceflight-induced immune dysfunction linked to systemic changes in metabolism?

PubMed Central

Mao, Xiao Wen; Bellinger, Denise L.; Jonscher, Karen R.; Stodieck, Louis S.; Ferguson, Virginia L.; Bateman, Ted A.; Mohney, Robert P.; Gridley, Daila S.

2017-01-01

The Space Shuttle Atlantis launched on its final mission (STS-135) on July 8, 2011. After just under 13 days, the shuttle landed safely at Kennedy Space Center (KSC) for the last time. Female C57BL/6J mice flew as part of the Commercial Biomedical Testing Module-3 (CBTM-3) payload. Ground controls were maintained at the KSC facility. Subsets of these mice were made available to investigators as part of NASA’s Bio-specimen Sharing Program (BSP). Our group characterized cell phenotype distributions and phagocytic function in the spleen, catecholamine and corticosterone levels in the adrenal glands, and transcriptomics/metabolomics in the liver. Despite decreases in most splenic leukocyte subsets, there were increases in reactive oxygen species (ROS)-related activity. Although there were increases noted in corticosterone levels in both the adrenals and liver, there were no significant changes in catecholamine levels. Furthermore, functional analysis of gene expression and metabolomic profiles suggest that the functional changes are not due to oxidative or psychological stress. Despite changes in gene expression patterns indicative of increases in phagocytic activity (e.g. endocytosis and formation of peroxisomes), there was no corresponding increase in genes related to ROS metabolism. In contrast, there were increases in expression profiles related to fatty acid oxidation with decreases in glycolysis-related profiles. Given the clear link between immune function and metabolism in many ground-based diseases, we propose a similar link may be involved in spaceflight-induced decrements in immune and metabolic function. PMID:28542224

The Congenital Heart Disease Genetic Network Study: rationale, design, and early results.

PubMed

Gelb, Bruce; Brueckner, Martina; Chung, Wendy; Goldmuntz, Elizabeth; Kaltman, Jonathan; Kaski, Juan Pablo; Kim, Richard; Kline, Jennie; Mercer-Rosa, Laura; Porter, George; Roberts, Amy; Rosenberg, Ellen; Seiden, Howard; Seidman, Christine; Sleeper, Lynn; Tennstedt, Sharon; Kaltman, Jonathan; Schramm, Charlene; Burns, Kristin; Pearson, Gail; Rosenberg, Ellen

2013-02-15

Congenital heart defects (CHD) are the leading cause of infant mortality among birth defects, and later morbidities and premature mortality remain problematic. Although genetic factors contribute significantly to cause CHD, specific genetic lesions are unknown for most patients. The National Heart, Lung, and Blood Institute-funded Pediatric Cardiac Genomics Consortium established the Congenital Heart Disease Genetic Network Study to investigate relationships between genetic factors, clinical features, and outcomes in CHD. The Pediatric Cardiac Genomics Consortium comprises 6 main and 4 satellite sites at which subjects are recruited, and medical data and biospecimens (blood, saliva, cardiovascular tissue) are collected. Core infrastructure includes an administrative/data-coordinating center, biorepository, data hub, and core laboratories (genotyping, whole-exome sequencing, candidate gene evaluation, and variant confirmation). Eligibility includes all forms of CHD. Annual follow-up is obtained for probands <1-year-old. Parents are enrolled whenever available. Enrollment from December 2010 to June 2012 comprised 3772 probands. One or both parents were enrolled for 72% of probands. Proband median age is 5.5 years. The one third enrolled at age <1 year are contacted annually for follow-up information. The distribution of CHD favors more complex lesions. Approximately, 11% of probands have a genetic diagnosis. Adequate DNA is available from 97% and 91% of blood and saliva samples, respectively. Genomic analyses of probands with heterotaxy, atrial septal defects, conotruncal, and left ventricular outflow tract obstructive lesions are underway. The scientific community's use of Pediatric Cardiac Genomics Consortium resources is welcome.

Dopamine receptor gene d4 polymorphisms and early sexual onset: gender and environmental moderation in a sample of african-american youth.

PubMed

Kogan, Steven M; Lei, Man-Kit; Beach, Steven R H; Brody, Gene H; Windle, Michael; Lee, Sunbok; MacKillop, James; Chen, Yi-Fu

2014-08-01

Early sexual onset and its consequences disproportionately affect African-American youth, particularly male youth. The dopamine receptor D4 gene (DRD4) has been linked to sexual activity and other forms of appetitive behavior, particularly for male youth and in combination with environmental factors (gene × environment [G × E] effects). The differential susceptibility perspective suggests that DRD4 may exert this effect by amplifying the effects of both positive and negative environments. We hypothesized that DRD4 status would amplify the influence of both positive and negative neighborhood environments on early sexual onset among male, but not female, African-Americans. Hypotheses were tested with self-report, biospecimen, and census data from five prospective studies of male and female African-American youth in rural Georgia communities, N = 1,677. Early sexual onset was defined as intercourse before age 14. No significant G × E findings emerged for female youth. Male youth with a DRD4 long allele were more likely than those with two DRD4 short alleles to report early sexual onset in negative community environments and not to report early onset in positive community environments. Dopaminergic regulation of adolescent sexual behaviors may operate differently by gender. DRD4 operated as an environmental amplification rather than a vulnerability factor. Copyright © 2014 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

High DNA stability in white blood cells and buffy coat lysates stored at ambient temperature under anoxic and anhydrous atmosphere

PubMed Central

Luis, Aurélie; Colotte, Marthe; Tuffet, Sophie; Bonnet, Jacques

2017-01-01

Conventional storage of blood-derived fractions relies on cold. However, lately, ambient temperature preservation has been evaluated by several independent institutions that see economic and logistic advantages in getting rid of the cold chain. Here we validated a novel procedure for ambient temperature preservation of DNA in white blood cell and buffy coat lysates based on the confinement of the desiccated biospecimens under anoxic and anhydrous atmosphere in original hermetic minicapsules. For this validation we stored encapsulated samples either at ambient temperature or at several elevated temperatures to accelerate aging. We found that DNA extracted from stored samples was of good quality with a yield of extraction as expected. Degradation rates were estimated from the average fragment size of denatured DNA run on agarose gels and from qPCR reactions. At ambient temperature, these rates were too low to be measured but the degradation rate dependence on temperature followed Arrhenius’ law, making it possible to extrapolate degradation rates at 25°C. According to these values, the DNA stored in the encapsulated blood products would remain larger than 20 kb after one century at ambient temperature. At last, qPCR experiments demonstrated the compatibility of extracted DNA with routine DNA downstream analyses. Altogether, these results showed that this novel storage method provides an adequate environment for ambient temperature long term storage of high molecular weight DNA in dehydrated lysates of white blood cells and buffy coats. PMID:29190767

High DNA stability in white blood cells and buffy coat lysates stored at ambient temperature under anoxic and anhydrous atmosphere.

PubMed

Fabre, Anne-Lise; Luis, Aurélie; Colotte, Marthe; Tuffet, Sophie; Bonnet, Jacques

2017-01-01

Conventional storage of blood-derived fractions relies on cold. However, lately, ambient temperature preservation has been evaluated by several independent institutions that see economic and logistic advantages in getting rid of the cold chain. Here we validated a novel procedure for ambient temperature preservation of DNA in white blood cell and buffy coat lysates based on the confinement of the desiccated biospecimens under anoxic and anhydrous atmosphere in original hermetic minicapsules. For this validation we stored encapsulated samples either at ambient temperature or at several elevated temperatures to accelerate aging. We found that DNA extracted from stored samples was of good quality with a yield of extraction as expected. Degradation rates were estimated from the average fragment size of denatured DNA run on agarose gels and from qPCR reactions. At ambient temperature, these rates were too low to be measured but the degradation rate dependence on temperature followed Arrhenius' law, making it possible to extrapolate degradation rates at 25°C. According to these values, the DNA stored in the encapsulated blood products would remain larger than 20 kb after one century at ambient temperature. At last, qPCR experiments demonstrated the compatibility of extracted DNA with routine DNA downstream analyses. Altogether, these results showed that this novel storage method provides an adequate environment for ambient temperature long term storage of high molecular weight DNA in dehydrated lysates of white blood cells and buffy coats.

Liposomal membrane disruption by means of miniaturized dielectric-barrier discharge in air: liposome characterization

NASA Astrophysics Data System (ADS)

Svarnas, P.; Asimakoulas, L.; Katsafadou, M.; Pachis, K.; Kostazos, N.; Antimisiaris, S. G.

2017-08-01

The increasing interest of the plasma community in the application of atmospheric-pressure cold plasmas to bio-specimen treatment has led to the creation of the emerging field of plasma biomedicine. Accordingly, plasma setups based on dielectric-barrier discharges have already been widely tested for the inactivation of various cells. Most of these systems refer to the plasma jet concept where noble gases penetrate atmospheric air and are subjected to the influence of high electric fields, thus forming guided streamers. Following the original works of our group where liposomal membranes were proposed as models for studying the interaction between plasma jets and cells, we present herein a study on liposomal membrane disruption by means of miniaturized dielectric-barrier discharge running in atmospheric air. Liposomal membranes of various lipid compositions, lamellarities, and sizes are treated at different times. It is shown that the dielectric-barrier discharge of low mean power leads to efficient liposomal membrane disruption. The latter is achieved in a controllable manner and depends on liposome properties. Additionally, it is clearly demonstrated that liposomal membrane disruption takes place even after plasma extinction, i.e. during post-treatment, resembling thus an ‘apoptosis’ effect, which is well known today mainly for cell membranes. Thus, the adoption of the present concept would be beneficial for tailoring studies on plasma-treated cell-mimics. Finally, the liposome treatment is discussed with respect to possible physicochemical mechanisms and potential discharge modification due to the various compositions of the liquid electrode.

Cys34 Adductomes Differ between Patients with Chronic Lung or Heart Disease and Healthy Controls in Central London.

PubMed

Liu, Sa; Grigoryan, Hasmik; Edmands, William M B; Dagnino, Sonia; Sinharay, Rudy; Cullinan, Paul; Collins, Peter; Chung, Kian Fan; Barratt, Benjamin; Kelly, Frank J; Vineis, Paolo; Rappaport, Stephen M

2018-02-20

Oxidative stress generates reactive species that modify proteins, deplete antioxidant defenses, and contribute to chronic obstructive pulmonary disease (COPD) and ischemic heart disease (IHD). To determine whether protein modifications differ between COPD or IHD patients and healthy subjects, we performed untargeted analysis of adducts at the Cys34 locus of human serum albumin (HSA). Biospecimens were obtained from nonsmoking participants from London, U.K., including healthy subjects (n = 20) and patients with COPD (n = 20) or IHD (n = 10). Serum samples were digested with trypsin and analyzed by liquid chromatography-high resolution mass spectrometry. Effects of air pollution on adduct levels were also investigated based on estimated residential exposures to PM 2.5 , O 3 and NO 2 . For the 39 adducts with sufficient data, levels were essentially identical in blood samples collected from the same subjects on two consecutive days, consistent with the 28 day residence time of HSA. Multivariate linear regression revealed 21 significant associations, mainly with the underlying diseases but also with air-pollution exposures (p-value < 0.05). Interestingly, most of the associations indicated that adduct levels decreased with the presence of disease or increased pollutant concentrations. Negative associations of COPD and IHD with the Cys34 disulfide of glutathione and two Cys34 sulfoxidations, were consistent with previous results from smoking and nonsmoking volunteers and nonsmoking women exposed to indoor combustion of coal and wood.

Cross-Disciplinary Biomarkers Research: Lessons Learned by the CKD Biomarkers Consortium.

PubMed

Hsu, Chi-Yuan; Ballard, Shawn; Batlle, Daniel; Bonventre, Joseph V; Böttinger, Erwin P; Feldman, Harold I; Klein, Jon B; Coresh, Josef; Eckfeldt, John H; Inker, Lesley A; Kimmel, Paul L; Kusek, John W; Liu, Kathleen D; Mauer, Michael; Mifflin, Theodore E; Molitch, Mark E; Nelsestuen, Gary L; Rebholz, Casey M; Rovin, Brad H; Sabbisetti, Venkata S; Van Eyk, Jennifer E; Vasan, Ramachandran S; Waikar, Sushrut S; Whitehead, Krista M; Nelson, Robert G

2015-05-07

Significant advances are needed to improve the diagnosis, prognosis, and management of persons with CKD. Discovery of new biomarkers and improvements in currently available biomarkers for CKD hold great promise to achieve these necessary advances. Interest in identification and evaluation of biomarkers for CKD has increased substantially over the past decade. In 2009, the National Institute of Diabetes and Digestive and Kidney Diseases established the CKD Biomarkers Consortium (http://www.ckdbiomarkersconsortium.org/), a multidisciplinary, collaborative study group located at over a dozen academic medical centers. The main objective of the consortium was to evaluate new biomarkers for purposes related to CKD in established prospective cohorts, including those enriched for CKD. During the first 5 years of the consortium, many insights into collaborative biomarker research were gained that may be useful to other investigators involved in biomarkers research. These lessons learned are outlined in this Special Feature and include a wide range of issues related to biospecimen collection, storage, and retrieval, and the internal and external quality assessment of laboratories that performed the assays. The authors propose that investigations involving biomarker discovery and validation are greatly enhanced by establishing and following explicit quality control metrics, including the use of blind replicate and proficiency samples, by carefully considering the conditions under which specimens are collected, handled, and stored, and by conducting pilot and feasibility studies when there are concerns about the condition of the specimens or the accuracy or reproducibility of the assays. Copyright © 2015 by the American Society of Nephrology.

p-BioSPRE—an information and communication technology framework for transnational biomaterial sharing and access

PubMed Central

Weiler, Gabriele; Schröder, Christina; Schera, Fatima; Dobkowicz, Matthias; Kiefer, Stephan; Heidtke, Karsten R; Hänold, Stefanie; Nwankwo, Iheanyi; Forgó, Nikolaus; Stanulla, Martin; Eckert, Cornelia; Graf, Norbert

2014-01-01

Biobanks represent key resources for clinico-genomic research and are needed to pave the way to personalised medicine. To achieve this goal, it is crucial that scientists can securely access and share high-quality biomaterial and related data. Therefore, there is a growing interest in integrating biobanks into larger biomedical information and communication technology (ICT) infrastructures. The European project p-medicine is currently building an innovative ICT infrastructure to meet this need. This platform provides tools and services for conducting research and clinical trials in personalised medicine. In this paper, we describe one of its main components, the biobank access framework p-BioSPRE (p-medicine Biospecimen Search and Project Request Engine). This generic framework enables and simplifies access to existing biobanks, but also to offer own biomaterial collections to research communities, and to manage biobank specimens and related clinical data over the ObTiMA Trial Biomaterial Manager. p-BioSPRE takes into consideration all relevant ethical and legal standards, e.g., safeguarding donors’ personal rights and enabling biobanks to keep control over the donated material and related data. The framework thus enables secure sharing of biomaterial within open and closed research communities, while flexibly integrating related clinical and omics data. Although the development of the framework is mainly driven by user scenarios from the cancer domain, in this case, acute lymphoblastic leukaemia and Wilms tumour, it can be extended to further disease entities. PMID:24567758

Chronic psychosocial stressors and salivary biomarkers in emerging adults.

PubMed

Bergen, Andrew W; Mallick, Aditi; Nishita, Denise; Wei, Xin; Michel, Martha; Wacholder, Aaron; David, Sean P; Swan, Gary E; Reid, Mark W; Simons, Anne; Andrews, Judy A

2012-08-01

We investigated whole saliva as a source of biomarkers to distinguish individuals who have, and who have not, been chronically exposed to severe and threatening life difficulties. We evaluated RNA and DNA metrics, expression of 37 candidate genes, and cortisol release in response to the Trier Social Stress Test, as well as clinical characteristics, from 48 individuals stratified on chronic exposure to psychosocial stressors within the last year as measured by the Life Events and Difficulties Schedule. Candidate genes were selected based on their differential gene expression ratio in circulating monocytes from a published genome-wide analysis of adults experiencing different levels of exposure to a chronic stressor. In univariate analyses, we observed significantly decreased RNA integrity (RIN) score (P = 0.04), and reduced expression of glucocorticoid receptor-regulated genes (Ps < 0.05) in whole saliva RNA from individuals exposed to chronic stressors, as compared to those with no exposure. In those exposed, we observed significantly decreased BMI (P < 0.001), increased ever-smoking and increased lifetime alcohol abuse or dependence (P ≤ 0.03), and a reduction of cortisol release. In post hoc multivariate analyses including clinical and biospecimen-derived variables, we consistently observed significantly decreased expression of IL8 (Ps<0.05) in individuals exposed, with no significant association to RIN score. Alcohol use disorders, tobacco use, a reduced acute stress response and decreased salivary IL8 gene expression characterize emerging adults chronically exposed to severe and threatening psychosocial stressors. Copyright © 2011 Elsevier Ltd. All rights reserved.

A Highly Efficient Design Strategy for Regression with Outcome Pooling

PubMed Central

Mitchell, Emily M.; Lyles, Robert H.; Manatunga, Amita K.; Perkins, Neil J.; Schisterman, Enrique F.

2014-01-01

The potential for research involving biospecimens can be hindered by the prohibitive cost of performing laboratory assays on individual samples. To mitigate this cost, strategies such as randomly selecting a portion of specimens for analysis or randomly pooling specimens prior to performing laboratory assays may be employed. These techniques, while effective in reducing cost, are often accompanied by a considerable loss of statistical efficiency. We propose a novel pooling strategy based on the k-means clustering algorithm to reduce laboratory costs while maintaining a high level of statistical efficiency when predictor variables are measured on all subjects, but the outcome of interest is assessed in pools. We perform simulations motivated by the BioCycle study to compare this k-means pooling strategy with current pooling and selection techniques under simple and multiple linear regression models. While all of the methods considered produce unbiased estimates and confidence intervals with appropriate coverage, pooling under k-means clustering provides the most precise estimates, closely approximating results from the full data and losing minimal precision as the total number of pools decreases. The benefits of k-means clustering evident in the simulation study are then applied to an analysis of the BioCycle dataset. In conclusion, when the number of lab tests is limited by budget, pooling specimens based on k-means clustering prior to performing lab assays can be an effective way to save money with minimal information loss in a regression setting. PMID:25220822

The Congenital Heart Disease Genetic Network Study

PubMed Central

2013-01-01

Congenital heart defects (CHD) are the leading cause of infant mortality among birth defects, and later morbidities and premature mortality remain problematic. Although genetic factors contribute significantly to cause CHD, specific genetic lesions are unknown for most patients. The National Heart, Lung, and Blood Institute-funded Pediatric Cardiac Genomics Consortium established the Congenital Heart Disease Genetic Network Study to investigate relationships between genetic factors, clinical features, and outcomes in CHD. The Pediatric Cardiac Genomics Consortium comprises 6 main and 4 satellite sites at which subjects are recruited, and medical data and biospecimens (blood, saliva, cardiovascular tissue) are collected. Core infrastructure includes an administrative/data-coordinating center, biorepository, data hub, and core laboratories (genotyping, whole-exome sequencing, candidate gene evaluation, and variant confirmation). Eligibility includes all forms of CHD. Annual follow-up is obtained for probands <1-year-old. Parents are enrolled whenever available. Enrollment from December 2010 to June 2012 comprised 3772 probands. One or both parents were enrolled for 72% of probands. Proband median age is 5.5 years. The one third enrolled at age <1 year are contacted annually for follow-up information. The distribution of CHD favors more complex lesions. Approximately, 11% of probands have a genetic diagnosis. Adequate DNA is available from 97% and 91% of blood and saliva samples, respectively. Genomic analyses of probands with heterotaxy, atrial septal defects, conotruncal, and left ventricular outflow tract obstructive lesions are underway. The scientific community’s use of Pediatric Cardiac Genomics Consortium resources is welcome. PMID:23410879

Metabolomic applications in radiation biodosimetry: exploring radiation effects through small molecules.

PubMed

Pannkuk, Evan L; Fornace, Albert J; Laiakis, Evagelia C

2017-10-01

Exposure of the general population to ionizing radiation has increased in the past decades, primarily due to long distance travel and medical procedures. On the other hand, accidental exposures, nuclear accidents, and elevated threats of terrorism with the potential detonation of a radiological dispersal device or improvised nuclear device in a major city, all have led to increased needs for rapid biodosimetry and assessment of exposure to different radiation qualities and scenarios. Metabolomics, the qualitative and quantitative assessment of small molecules in a given biological specimen, has emerged as a promising technology to allow for rapid determination of an individual's exposure level and metabolic phenotype. Advancements in mass spectrometry techniques have led to untargeted (discovery phase, global assessment) and targeted (quantitative phase) methods not only to identify biomarkers of radiation exposure, but also to assess general perturbations of metabolism with potential long-term consequences, such as cancer, cardiovascular, and pulmonary disease. Metabolomics of radiation exposure has provided a highly informative snapshot of metabolic dysregulation. Biomarkers in easily accessible biofluids and biospecimens (urine, blood, saliva, sebum, fecal material) from mouse, rat, and minipig models, to non-human primates and humans have provided the basis for determination of a radiation signature to assess the need for medical intervention. Here we provide a comprehensive description of the current status of radiation metabolomic studies for the purpose of rapid high-throughput radiation biodosimetry in easily accessible biofluids and discuss future directions of radiation metabolomics research.

Cohort Profile: The Avon Longitudinal Study of Parents and Children: ALSPAC mothers cohort

PubMed Central

Fraser, Abigail; Macdonald-Wallis, Corrie; Tilling, Kate; Boyd, Andy; Golding, Jean; Davey Smith, George; Henderson, John; Macleod, John; Molloy, Lynn; Ness, Andy; Ring, Susan; Nelson, Scott M; Lawlor, Debbie A

2013-01-01

Summary The Avon Longitudinal Study of Children and Parents (ALSPAC) was established to understand how genetic and environmental characteristics influence health and development in parents and children. All pregnant women resident in a defined area in the South West of England, with an expected date of delivery between 1st April 1991 and 31st December 1992, were eligible and 13 761 women (contributing 13 867 pregnancies) were recruited. These women have been followed over the last 19–22 years and have completed up to 20 questionnaires, have had detailed data abstracted from their medical records and have information on any cancer diagnoses and deaths through record linkage. A follow-up assessment was completed 17–18 years postnatal at which anthropometry, blood pressure, fat, lean and bone mass and carotid intima media thickness were assessed, and a fasting blood sample taken. The second follow-up clinic, which additionally measures cognitive function, physical capability, physical activity (with accelerometer) and wrist bone architecture, is underway and two further assessments with similar measurements will take place over the next 5 years. There is a detailed biobank that includes DNA, with genome-wide data available on >10 000, stored serum and plasma taken repeatedly since pregnancy and other samples; a wide range of data on completed biospecimen assays are available. Details of how to access these data are provided in this cohort profile. PMID:22507742

Rationale and study design of the Japan environment and children’s study (JECS)

PubMed Central

2014-01-01

Background There is global concern over significant threats from a wide variety of environmental hazards to which children face. Large-scale and long-term birth cohort studies are needed for better environmental management based on sound science. The primary objective of the Japan Environment and Children’s Study (JECS), a nation-wide birth cohort study that started its recruitment in January 2011, is to elucidate environmental factors that affect children’s health and development. Methods/Design Approximately 100,000 expecting mothers who live in designated study areas will be recruited over a 3-year period from January 2011. Participating children will be followed until they reach 13 years of age. Exposure to environmental factors will be assessed by chemical analyses of bio-specimens (blood, cord blood, urine, breast milk, and hair), household environment measurements, and computational simulations using monitoring data (e.g. ambient air quality monitoring) as well as questionnaires. JECS’ priority outcomes include reproduction/pregnancy complications, congenital anomalies, neuropsychiatric disorders, immune system disorders, and metabolic/endocrine system disorders. Genetic factors, socioeconomic status, and lifestyle factors will also be examined as covariates and potential confounders. To maximize representativeness, we adopted provider-mediated community-based recruitment. Discussion Through JECS, chemical substances to which children are exposed during the fetal stage or early childhood will be identified. The JECS results will be translated to better risk assessment and management to provide healthy environment for next generations. PMID:24410977

A highly efficient design strategy for regression with outcome pooling.

PubMed

Mitchell, Emily M; Lyles, Robert H; Manatunga, Amita K; Perkins, Neil J; Schisterman, Enrique F

2014-12-10

The potential for research involving biospecimens can be hindered by the prohibitive cost of performing laboratory assays on individual samples. To mitigate this cost, strategies such as randomly selecting a portion of specimens for analysis or randomly pooling specimens prior to performing laboratory assays may be employed. These techniques, while effective in reducing cost, are often accompanied by a considerable loss of statistical efficiency. We propose a novel pooling strategy based on the k-means clustering algorithm to reduce laboratory costs while maintaining a high level of statistical efficiency when predictor variables are measured on all subjects, but the outcome of interest is assessed in pools. We perform simulations motivated by the BioCycle study to compare this k-means pooling strategy with current pooling and selection techniques under simple and multiple linear regression models. While all of the methods considered produce unbiased estimates and confidence intervals with appropriate coverage, pooling under k-means clustering provides the most precise estimates, closely approximating results from the full data and losing minimal precision as the total number of pools decreases. The benefits of k-means clustering evident in the simulation study are then applied to an analysis of the BioCycle dataset. In conclusion, when the number of lab tests is limited by budget, pooling specimens based on k-means clustering prior to performing lab assays can be an effective way to save money with minimal information loss in a regression setting. Copyright © 2014 John Wiley & Sons, Ltd.

ABO blood group phenotype frequency estimation using molecular phenotyping in rhesus and cynomolgus macaques.

PubMed

Kanthaswamy, S; Ng, J; Oldt, R F; Valdivia, L; Houghton, P; Smith, D G

2017-11-01

A much larger sample (N = 2369) was used to evaluate a previously reported distribution of the A, AB and B blood group phenotypes in rhesus and cynomolgus macaques from six different regional populations. These samples, acquired from 15 different breeding and research facilities in the United States, were analyzed using a real-time quantitative polymerase chain reaction (qPCR) assay that targets single nucleotide polymorphisms (SNPs) responsible for the macaque A, B and AB phenotypes. The frequency distributions of blood group phenotypes of the two species differ significantly from each other and significant regional differentiation within the geographic ranges of each species was also observed. The B blood group phenotype was prevalent in rhesus macaques, especially those from India, while the frequencies of the A, B and AB phenotypes varied significantly among cynomolgus macaques from different geographic regions. The Mauritian cynomolgus macaques, despite having originated in Indonesia, showed significant (P ≪ .01) divergence from the Indonesian animals at the ABO blood group locus. Most Mauritian animals belonged to the B blood group while the Indonesian animals were mostly A. The close similarity in blood group frequency distributions between the Chinese rhesus and Indochinese cynomolgus macaques demonstrates that the introgression between these two species extends beyond the zone of intergradation in Indochina. This study underscores the importance of ABO blood group phenotyping of the domestic supply of macaques and their biospecimens. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The impact of the privacy rule on cancer research: variations in attitudes and application of regulatory standards.

PubMed

Goss, Elizabeth; Link, Michael P; Bruinooge, Suanna S; Lawrence, Theodore S; Tepper, Joel E; Runowicz, Carolyn D; Schilsky, Richard L

2009-08-20

The American Society of Clinical Oncology (ASCO) Cancer Research Committee designed a qualitative research project to assess the attitudes of cancer researchers and compliance officials regarding compliance with the US Privacy Rule and to identify potential strategies for eliminating perceived or real barriers to achieving compliance. A team of three interviewers asked 27 individuals (13 investigators and 14 compliance officials) from 13 institutions to describe the anticipated approach of their institutions to Privacy Rule compliance in three hypothetical research studies. The interviews revealed that although researchers and compliance officials share the view that patients' cancer diagnoses should enjoy a high level of privacy protection, there are significant tensions between the two groups related to the proper standards for compliance necessary to protect patients. The disagreements are seen most clearly with regard to the appropriate definition of a "future research use" of protected health information in biospecimen and data repositories and the standards for a waiver of authorization for disclosure and use of such data. ASCO believes that disagreements related to compliance and the resulting delays in certain projects and abandonment of others might be eased by additional institutional training programs and consultation on Privacy Rule issues during study design. ASCO also proposes the development of best practices documents to guide 1) creation of data repositories, 2) disclosure and use of data from such repositories, and 3) the design of survivorship and genetics studies.

Aflatoxin exposure during the first 36 months of life was not associated with impaired growth in Nepalese children: An extension of the MAL-ED study

PubMed Central

Hsu, Hui-Husan; Chandyo, Ram Krishna; Shrestha, Binob; Bodhidatta, Ladaporn; Tu, Yu-Kang; Gong, Yun-Yun; Egner, Patricia A.; Ulak, Manjeswori; Groopman, John D.; Wu, Felicia

2017-01-01

Exposure to aflatoxin, a mycotoxin common in many foods, has been associated with child growth impairment in sub-Saharan Africa. To improve our understanding of growth impairment in relation to aflatoxin and other risk factors, we assessed biospecimens collected in Nepalese children at 15, 24, and 36 months of age for aflatoxin exposure. Children (N = 85) enrolled in the Bhaktapur, Nepal MAL-ED study encompassed the cohort analysed in this study. Exposure was assessed through a plasma biomarker of aflatoxin exposure: the AFB1-lysine adduct. The aflatoxin exposures in the study participants were compared to anthropometrics at each time period (length-for-age [LAZ], weight-for-age [WAZ], and weight-for-length [WLZ] z-scores), growth trajectories over time, age, and breastfeeding status. Results demonstrated chronic aflatoxin exposure in this cohort of children, with a geometric mean of 3.62 pg AFB1-lysine/mg albumin. However, the chronic aflatoxin exposure in this cohort was not significantly associated with anthropometric z-scores, growth trajectories, age, or feeding status, based on the available time points to assess aflatoxin exposure. Low mean levels of aflatoxin exposure and infrequent occurrence of stunting, wasting, or underweight z-score values in this cohort are possible contributing factors to a lack of evidence for an association. Further research is needed to examine whether a threshold dose of aflatoxin exists that could induce child growth impairment. PMID:28212415

DogMATIC--A Remote Biospecimen Collection Kit for Biobanking.

PubMed

Milley, Kristi M; Nimmo, Judith S; Bacci, Barbara; Ryan, Stewart D; Richardson, Samantha J; Danks, Janine A

2015-08-01

Canine tumors are valuable comparative oncology models. This research was designed to create a sustainable biobank of canine mammary tumors for breast cancer research. The aim was to provide a well-characterized sample cohort for specimen sharing, data mining, and long-term research aims. Canine mammary tumors are most frequently managed at a local veterinary clinic or hospital. We adopted a biobank framework based on a large number of participating veterinary hospitals and clinics acting as collection centers that were serviced by a centralized storage facility. Recruitment was targeted at rural veterinary clinics. A tailored, stable collection kit (DogMATIC) was designed that was used by veterinarians in remote or rural locations to collect both fresh and fixed tissue for submission to the biobank. To validate this methodology the kit design, collection rate, and sample quality were analyzed. The Australian Veterinary Cancer Biobank was established as a network of 47 veterinary clinics and three veterinary pathology laboratories spanning over 200,000 km(2). In the first 12 months, 30 canine mammary tumor cases were submitted via the DogMATIC kit. Pure intact RNA was isolated in over 80% of samples with an average yield of 14.49 μg. A large network biobank, utilizing off-site collection with the DogMATIC kit, was successfully coordinated. The creation of the Australian Veterinary Cancer Biobank has established a long-term, sustainable, comparative oncology research resource in Australia. There are broader implications for biobanking with this very different form of collection and banking.

The Surveillance, Epidemiology and End Results (SEER) Program and Pathology: Towards Strengthening the Critical Relationship

PubMed Central

Duggan, Máire A.; Anderson, William F.; Altekruse, Sean; Penberthy, Lynne; Sherman, Mark E.

2016-01-01

The Surveillance, Epidemiology and End Results (SEER) program of the National Cancer Institute collects data on cancer diagnoses, treatment and survival for approximately 30% of the United States (U.S.) population. To reflect advances in research and oncology practice, approaches to cancer control are evolving from simply enumerating the development of cancers by organ sites in populations to include monitoring of cancer occurrence by histopathologic and molecular subtype, as defined by driver mutations and other alterations. SEER is an important population-based resource for understanding the implications of pathology diagnoses across demographic groups, geographic regions, and time, and provides unique insights into the practice of oncology in the U.S that are not attainable from other sources. It provides incidence, survival and mortality data for histopathologic cancer subtypes, and data by molecular subtyping is expanding. The program is developing systems to capture additional biomarker data, results from special populations, and expand bio-specimen banking to enable cutting edge cancer research that can improve oncology practice. Pathology has always been central and critical to the effectiveness of SEER, and strengthening this relationship in this modern era of cancer diagnosis could be mutually beneficial. Achieving this goal requires close interactions between pathologists and the SEER program. This review provides a brief overview of SEER, focuses on facets relevant to pathology practice and research, and highlights the opportunities and challenges for pathologists to benefit from and enhance the value of SEER data. PMID:27740970

Can NMR solve some significant challenges in metabolomics?

NASA Astrophysics Data System (ADS)

Nagana Gowda, G. A.; Raftery, Daniel

2015-11-01

The field of metabolomics continues to witness rapid growth driven by fundamental studies, methods development, and applications in a number of disciplines that include biomedical science, plant and nutrition sciences, drug development, energy and environmental sciences, toxicology, etc. NMR spectroscopy is one of the two most widely used analytical platforms in the metabolomics field, along with mass spectrometry (MS). NMR's excellent reproducibility and quantitative accuracy, its ability to identify structures of unknown metabolites, its capacity to generate metabolite profiles using intact bio-specimens with no need for separation, and its capabilities for tracing metabolic pathways using isotope labeled substrates offer unique strengths for metabolomics applications. However, NMR's limited sensitivity and resolution continue to pose a major challenge and have restricted both the number and the quantitative accuracy of metabolites analyzed by NMR. Further, the analysis of highly complex biological samples has increased the demand for new methods with improved detection, better unknown identification, and more accurate quantitation of larger numbers of metabolites. Recent efforts have contributed significant improvements in these areas, and have thereby enhanced the pool of routinely quantifiable metabolites. Additionally, efforts focused on combining NMR and MS promise opportunities to exploit the combined strength of the two analytical platforms for direct comparison of the metabolite data, unknown identification and reliable biomarker discovery that continue to challenge the metabolomics field. This article presents our perspectives on the emerging trends in NMR-based metabolomics and NMR's continuing role in the field with an emphasis on recent and ongoing research from our laboratory.

Is spaceflight-induced immune dysfunction linked to systemic changes in metabolism?

PubMed

Pecaut, Michael J; Mao, Xiao Wen; Bellinger, Denise L; Jonscher, Karen R; Stodieck, Louis S; Ferguson, Virginia L; Bateman, Ted A; Mohney, Robert P; Gridley, Daila S

2017-01-01

The Space Shuttle Atlantis launched on its final mission (STS-135) on July 8, 2011. After just under 13 days, the shuttle landed safely at Kennedy Space Center (KSC) for the last time. Female C57BL/6J mice flew as part of the Commercial Biomedical Testing Module-3 (CBTM-3) payload. Ground controls were maintained at the KSC facility. Subsets of these mice were made available to investigators as part of NASA's Bio-specimen Sharing Program (BSP). Our group characterized cell phenotype distributions and phagocytic function in the spleen, catecholamine and corticosterone levels in the adrenal glands, and transcriptomics/metabolomics in the liver. Despite decreases in most splenic leukocyte subsets, there were increases in reactive oxygen species (ROS)-related activity. Although there were increases noted in corticosterone levels in both the adrenals and liver, there were no significant changes in catecholamine levels. Furthermore, functional analysis of gene expression and metabolomic profiles suggest that the functional changes are not due to oxidative or psychological stress. Despite changes in gene expression patterns indicative of increases in phagocytic activity (e.g. endocytosis and formation of peroxisomes), there was no corresponding increase in genes related to ROS metabolism. In contrast, there were increases in expression profiles related to fatty acid oxidation with decreases in glycolysis-related profiles. Given the clear link between immune function and metabolism in many ground-based diseases, we propose a similar link may be involved in spaceflight-induced decrements in immune and metabolic function.

Increasing Cognitive Inhibition with a Difficult Prior Task: Implications for Mathematical Thinking

ERIC Educational Resources Information Center

Attridge, Nina; Inglis, Matthew

2015-01-01

Dual-process theories posit two distinct types of cognitive processing: Type 1, which does not use working memory making it fast and automatic, and Type 2, which does use working memory making it slow and effortful. Mathematics often relies on the inhibition of pervasive Type 1 processing to apply new skills or knowledge that require Type 2…

Study of residue type defect formation mechanism and the effect of advanced defect reduction (ADR) rinse process

NASA Astrophysics Data System (ADS)

Arima, Hiroshi; Yoshida, Yuichi; Yoshihara, Kosuke; Shibata, Tsuyoshi; Kushida, Yuki; Nakagawa, Hiroki; Nishimura, Yukio; Yamaguchi, Yoshikazu

2009-03-01

Residue type defect is one of yield detractors in lithography process. It is known that occurrence of the residue type defect is dependent on resist development process and the defect is reduced by optimized rinsing condition. However, the defect formation is affected by resist materials and substrate conditions. Therefore, it is necessary to optimize the development process condition by each mask level. Those optimization steps require a large amount of time and effort. The formation mechanism is investigated from viewpoint of both material and process. The defect formation is affected by resist material types, substrate condition and development process condition (D.I.W. rinse step). Optimized resist formulation and new rinse technology significantly reduce the residue type defect.

7 CFR 52.3182 - Varietal types of dried prunes.

Code of Federal Regulations, 2013 CFR

2013-01-01

... MARKETING ACT OF 1946 AND THE EGG PRODUCTS INSPECTION ACT PROCESSED FRUITS AND VEGETABLES, PROCESSED PRODUCTS THEREOF, AND CERTAIN OTHER PROCESSED FOOD PRODUCTS 1 United States Standards for Grades of Dried...; or Sugar; or a mixture of Imperial and Sugar. (d) Type IV. Any other types; or mixtures of any types...

7 CFR 52.3182 - Varietal types of dried prunes.

Code of Federal Regulations, 2014 CFR

2014-01-01

... MARKETING ACT OF 1946 AND THE EGG PRODUCTS INSPECTION ACT PROCESSED FRUITS AND VEGETABLES, PROCESSED PRODUCTS THEREOF, AND CERTAIN OTHER PROCESSED FOOD PRODUCTS 1 United States Standards for Grades of Dried...; or Sugar; or a mixture of Imperial and Sugar. (d) Type IV. Any other types; or mixtures of any types...

The Processing on Different Types of English Formulaic Sequences

ERIC Educational Resources Information Center

Qian, Li

2015-01-01

Formulaic sequences are found to be processed faster than their matched novel phrases in previous studies. Given the variety of formulaic types, few studies have compared processing on different types of formulaic sequences. The present study explored the processing among idioms, speech formulae and written formulae. It has been found that in…

Dual-Process Theories of Reasoning: Contemporary Issues and Developmental Applications

ERIC Educational Resources Information Center

Evans, Jonathan St. B. T.

2011-01-01

In this paper, I discuss the current state of theorising about dual processes in adult performance on reasoning and decision making tasks, in which Type 1 intuitive processing is distinguished from Type 2 reflective thinking. I show that there are many types of theory some of which distinguish modes rather than types of thinking and that…

What makes us think? A three-stage dual-process model of analytic engagement.

PubMed

Pennycook, Gordon; Fugelsang, Jonathan A; Koehler, Derek J

2015-08-01

The distinction between intuitive and analytic thinking is common in psychology. However, while often being quite clear on the characteristics of the two processes ('Type 1' processes are fast, autonomous, intuitive, etc. and 'Type 2' processes are slow, deliberative, analytic, etc.), dual-process theorists have been heavily criticized for being unclear on the factors that determine when an individual will think analytically or rely on their intuition. We address this issue by introducing a three-stage model that elucidates the bottom-up factors that cause individuals to engage Type 2 processing. According to the model, multiple Type 1 processes may be cued by a stimulus (Stage 1), leading to the potential for conflict detection (Stage 2). If successful, conflict detection leads to Type 2 processing (Stage 3), which may take the form of rationalization (i.e., the Type 1 output is verified post hoc) or decoupling (i.e., the Type 1 output is falsified). We tested key aspects of the model using a novel base-rate task where stereotypes and base-rate probabilities cued the same (non-conflict problems) or different (conflict problems) responses about group membership. Our results support two key predictions derived from the model: (1) conflict detection and decoupling are dissociable sources of Type 2 processing and (2) conflict detection sometimes fails. We argue that considering the potential stages of reasoning allows us to distinguish early (conflict detection) and late (decoupling) sources of analytic thought. Errors may occur at both stages and, as a consequence, bias arises from both conflict monitoring and decoupling failures. Copyright © 2015 Elsevier Inc. All rights reserved.

The Causes of Errors in Clinical Reasoning: Cognitive Biases, Knowledge Deficits, and Dual Process Thinking.

PubMed

Norman, Geoffrey R; Monteiro, Sandra D; Sherbino, Jonathan; Ilgen, Jonathan S; Schmidt, Henk G; Mamede, Silvia

2017-01-01

Contemporary theories of clinical reasoning espouse a dual processing model, which consists of a rapid, intuitive component (Type 1) and a slower, logical and analytical component (Type 2). Although the general consensus is that this dual processing model is a valid representation of clinical reasoning, the causes of diagnostic errors remain unclear. Cognitive theories about human memory propose that such errors may arise from both Type 1 and Type 2 reasoning. Errors in Type 1 reasoning may be a consequence of the associative nature of memory, which can lead to cognitive biases. However, the literature indicates that, with increasing expertise (and knowledge), the likelihood of errors decreases. Errors in Type 2 reasoning may result from the limited capacity of working memory, which constrains computational processes. In this article, the authors review the medical literature to answer two substantial questions that arise from this work: (1) To what extent do diagnostic errors originate in Type 1 (intuitive) processes versus in Type 2 (analytical) processes? (2) To what extent are errors a consequence of cognitive biases versus a consequence of knowledge deficits?The literature suggests that both Type 1 and Type 2 processes contribute to errors. Although it is possible to experimentally induce cognitive biases, particularly availability bias, the extent to which these biases actually contribute to diagnostic errors is not well established. Educational strategies directed at the recognition of biases are ineffective in reducing errors; conversely, strategies focused on the reorganization of knowledge to reduce errors have small but consistent benefits.

7 CFR 52.3182 - Varietal types of dried prunes.

Code of Federal Regulations, 2011 CFR

2011-01-01

... MARKETING ACT OF 1946 PROCESSED FRUITS AND VEGETABLES, PROCESSED PRODUCTS THEREOF, AND CERTAIN OTHER PROCESSED FOOD PRODUCTS 1 United States Standards for Grades of Dried Prunes Product Description, Varietal... of French and Robe. (b) Type II. Italian. (c) Type III. Imperial; or Sugar; or a mixture of Imperial...

7 CFR 52.3182 - Varietal types of dried prunes.

Code of Federal Regulations, 2012 CFR

2012-01-01

... MARKETING ACT OF 1946 PROCESSED FRUITS AND VEGETABLES, PROCESSED PRODUCTS THEREOF, AND CERTAIN OTHER PROCESSED FOOD PRODUCTS 1 United States Standards for Grades of Dried Prunes Product Description, Varietal... of French and Robe. (b) Type II. Italian. (c) Type III. Imperial; or Sugar; or a mixture of Imperial...

Direct social perception and dual process theories of mindreading.

PubMed

Herschbach, Mitchell

2015-11-01

The direct social perception (DSP) thesis claims that we can directly perceive some mental states of other people. The direct perception of mental states has been formulated phenomenologically and psychologically, and typically restricted to the mental state types of intentions and emotions. I will compare DSP to another account of mindreading: dual process accounts that posit a fast, automatic "Type 1" form of mindreading and a slow, effortful "Type 2" form. I will here analyze whether dual process accounts' Type 1 mindreading serves as a rival to DSP or whether some Type 1 mindreading can be perceptual. I will focus on Apperly and Butterfill's dual process account of mindreading epistemic states such as perception, knowledge, and belief. This account posits a minimal form of Type 1 mindreading of belief-like states called registrations. I will argue that general dual process theories fit well with a modular view of perception that is considered a kind of Type 1 process. I will show that this modular view of perception challenges and has significant advantages over DSP's phenomenological and psychological theses. Finally, I will argue that if such a modular view of perception is accepted, there is significant reason for thinking Type 1 mindreading of belief-like states is perceptual in nature. This would mean extending the scope of DSP to at least one type of epistemic state. Copyright © 2015 Elsevier Inc. All rights reserved.

Process for forming pure silver ohmic contacts to N- and P-type gallium arsenide materials

DOEpatents

Hogan, S.J.

1983-03-13

Disclosed is an improved process for manufacturing gallium arsenide semiconductor devices having as its components a n-type gallium arsenide substrate layer and a p-type gallium arsenide diffused layer. The improved process comprises forming a pure silver ohmic contact to both the diffuse layer and the substrate layer wherein the n-type layer comprises a substantially low doping carrier concentration.

Arguments for fundamental emission by the parametric process L yields T + S in interplanetary type III bursts. [langmuir, electromagnetic, ion acoustic waves (L, T, S)

NASA Technical Reports Server (NTRS)

Cairns, I. H.

1984-01-01

Observations of low frequency ion acoustic-like waves associated with Langmuir waves present during interplanetary Type 3 bursts are used to study plasma emission mechanisms and wave processes involving ion acoustic waves. It is shown that the observed wave frequency characteristics are consistent with the processes L yields T + S (where L = Langmuir waves, T = electromagnetic waves, S = ion acoustic waves) and L yields L' + S proceeding. The usual incoherent (random phase) version of the process L yields T + S cannot explain the observed wave production time scale. The clumpy nature of the observed Langmuir waves is vital to the theory of IP Type 3 bursts. The incoherent process L yields T + S may encounter difficulties explaining the observed Type 3 brightness temperatures when Langmuir wave clumps are incorporated into the theory. The parametric process L yields T + S may be the important emission process for the fundamental radiation of interplanetary Type 3 bursts.

Collecting conditions usage metadata to optimize current and future ATLAS software and processing

NASA Astrophysics Data System (ADS)

Rinaldi, L.; Barberis, D.; Formica, A.; Gallas, E. J.; Oda, S.; Rybkin, G.; Verducci, M.; ATLAS Collaboration

2017-10-01

Conditions data (for example: alignment, calibration, data quality) are used extensively in the processing of real and simulated data in ATLAS. The volume and variety of the conditions data needed by different types of processing are quite diverse, so optimizing its access requires a careful understanding of conditions usage patterns. These patterns can be quantified by mining representative log files from each type of processing and gathering detailed information about conditions usage for that type of processing into a central repository.

The Precision Medicine Initiative's All of Us Research Program: an agenda for research on its ethical, legal, and social issues.

PubMed

Sankar, Pamela L; Parker, Lisa S

2017-07-01

The Precision Medicine Initiative (PMI) is an innovative approach to developing a new model of health care that takes into account individual differences in people's genes, environments, and lifestyles. A cornerstone of the initiative is the PMI All of Us Research Program (formerly known as PMI-Cohort Program) which will create a cohort of 1 million volunteers who will contribute their health data and biospecimens to a centralized national database to support precision medicine research. The PMI All of US Research Program is the largest longitudinal study in the history of the United States. The designers of the Program anticipated and addressed some of the ethical, legal, and social issues (ELSI) associated with the initiative. To date, however, there is no plan to call for research regarding ELSI associated with the Program-PMI All of Us program. Based on analysis of National Institutes of Health (NIH) funding announcements for the PMI All of Us program, we have identified three ELSI themes: cohort diversity and health disparities, participant engagement, and privacy and security. We review All of Us Research Program plans to address these issues and then identify additional ELSI within each domain that warrant ongoing investigation as the All of Us Research Program develops. We conclude that PMI's All of Us Research Program represents a significant opportunity and obligation to identify, analyze, and respond to ELSI, and we call on the PMI to initiate a research program capable of taking on these challenges.Genet Med advance online publication 01 December 2016.

Can NMR solve some significant challenges in metabolomics?

PubMed

Nagana Gowda, G A; Raftery, Daniel

2015-11-01

The field of metabolomics continues to witness rapid growth driven by fundamental studies, methods development, and applications in a number of disciplines that include biomedical science, plant and nutrition sciences, drug development, energy and environmental sciences, toxicology, etc. NMR spectroscopy is one of the two most widely used analytical platforms in the metabolomics field, along with mass spectrometry (MS). NMR's excellent reproducibility and quantitative accuracy, its ability to identify structures of unknown metabolites, its capacity to generate metabolite profiles using intact bio-specimens with no need for separation, and its capabilities for tracing metabolic pathways using isotope labeled substrates offer unique strengths for metabolomics applications. However, NMR's limited sensitivity and resolution continue to pose a major challenge and have restricted both the number and the quantitative accuracy of metabolites analyzed by NMR. Further, the analysis of highly complex biological samples has increased the demand for new methods with improved detection, better unknown identification, and more accurate quantitation of larger numbers of metabolites. Recent efforts have contributed significant improvements in these areas, and have thereby enhanced the pool of routinely quantifiable metabolites. Additionally, efforts focused on combining NMR and MS promise opportunities to exploit the combined strength of the two analytical platforms for direct comparison of the metabolite data, unknown identification and reliable biomarker discovery that continue to challenge the metabolomics field. This article presents our perspectives on the emerging trends in NMR-based metabolomics and NMR's continuing role in the field with an emphasis on recent and ongoing research from our laboratory. Copyright © 2015 Elsevier Inc. All rights reserved.

Genetic and clinical determinants of constitutional mismatch repair deficiency syndrome: report from the constitutional mismatch repair deficiency consortium.

PubMed

Bakry, Doua; Aronson, Melyssa; Durno, Carol; Rimawi, Hala; Farah, Roula; Alharbi, Qasim Kholaif; Alharbi, Musa; Shamvil, Ashraf; Ben-Shachar, Shay; Mistry, Matthew; Constantini, Shlomi; Dvir, Rina; Qaddoumi, Ibrahim; Gallinger, Steven; Lerner-Ellis, Jordan; Pollett, Aaron; Stephens, Derek; Kelies, Steve; Chao, Elizabeth; Malkin, David; Bouffet, Eric; Hawkins, Cynthia; Tabori, Uri

2014-03-01

Constitutional mismatch repair deficiency (CMMRD) is a devastating cancer predisposition syndrome for which data regarding clinical manifestations, molecular screening tools and management are limited. We established an international CMMRD consortium and collected comprehensive clinical and genetic data. Molecular diagnosis of tumour and germline biospecimens was performed. A surveillance protocol was developed and implemented. Overall, 22/23 (96%) of children with CMMRD developed 40 different tumours. While childhood CMMRD related tumours were observed in all families, Lynch related tumours in adults were observed in only 2/14 families (p=0.0007). All children with CMMRD had café-au-lait spots and 11/14 came from consanguineous families. Brain tumours were the most common cancers reported (48%) followed by gastrointestinal (32%) and haematological malignancies (15%). Importantly, 12 (30%) of these were low grade and resectable cancers. Tumour immunohistochemistry was 100% sensitive and specific in diagnosing mismatch repair (MMR) deficiency of the corresponding gene while microsatellite instability was neither sensitive nor specific as a diagnostic tool (p<0.0001). Furthermore, screening of normal tissue by immunohistochemistry correlated with genetic confirmation of CMMRD. The surveillance protocol detected 39 lesions which included asymptomatic malignant gliomas and gastrointestinal carcinomas. All tumours were amenable to complete resection and all patients undergoing surveillance are alive. CMMRD is a highly penetrant syndrome where family history of cancer may not be contributory. Screening tumours and normal tissues using immunohistochemistry for abnormal expression of MMR gene products may help in diagnosis and early implementation of surveillance for these children. Copyright © 2013 Elsevier Ltd. All rights reserved.

BRIDG: a domain information model for translational and clinical protocol-driven research.

PubMed

Becnel, Lauren B; Hastak, Smita; Ver Hoef, Wendy; Milius, Robert P; Slack, MaryAnn; Wold, Diane; Glickman, Michael L; Brodsky, Boris; Jaffe, Charles; Kush, Rebecca; Helton, Edward

2017-09-01

It is critical to integrate and analyze data from biological, translational, and clinical studies with data from health systems; however, electronic artifacts are stored in thousands of disparate systems that are often unable to readily exchange data. To facilitate meaningful data exchange, a model that presents a common understanding of biomedical research concepts and their relationships with health care semantics is required. The Biomedical Research Integrated Domain Group (BRIDG) domain information model fulfills this need. Software systems created from BRIDG have shared meaning "baked in," enabling interoperability among disparate systems. For nearly 10 years, the Clinical Data Standards Interchange Consortium, the National Cancer Institute, the US Food and Drug Administration, and Health Level 7 International have been key stakeholders in developing BRIDG. BRIDG is an open-source Unified Modeling Language-class model developed through use cases and harmonization with other models. With its 4+ releases, BRIDG includes clinical and now translational research concepts in its Common, Protocol Representation, Study Conduct, Adverse Events, Regulatory, Statistical Analysis, Experiment, Biospecimen, and Molecular Biology subdomains. The model is a Clinical Data Standards Interchange Consortium, Health Level 7 International, and International Standards Organization standard that has been utilized in national and international standards-based software development projects. It will continue to mature and evolve in the areas of clinical imaging, pathology, ontology, and vocabulary support. BRIDG 4.1.1 and prior releases are freely available at https://bridgmodel.nci.nih.gov . © The Author 2017. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Doxycycline improves clinical outcomes during cystic fibrosis exacerbations.

PubMed

Xu, Xin; Abdalla, Tarek; Bratcher, Preston E; Jackson, Patricia L; Sabbatini, Gina; Wells, J Michael; Lou, Xiang-Yang; Quinn, Rebecca; Blalock, J Edwin; Clancy, J P; Gaggar, Amit

2017-04-01

Matrix metalloprotease-9 (MMP-9) plays a role in progression of cystic fibrosis, and doxycycline can reduce MMP-9 in vitro Here, we explore the effect of doxycycline during cystic fibrosis exacerbation treatment on MMP-9 related readouts and clinical end-points.This randomised, double-blind, placebo-controlled study enrolled hospitalised patients with cystic fibrosis undergoing exacerbation. In total, 20 participants were given doxycycline and 19 participants were given placebo over an 8-day period during hospitalisation. Biospecimens were collected at the beginning and the end of the study period. Primary end-points were total MMP-9 levels in the sputum and safety/tolerability. Secondary end-points included change in lung function, time to next exacerbation, and markers of MMP-9-related protease activity (active MMP-9 and TIMP-1). Nonparametric testing was used for within-group and between-group analyses.Doxycycline was well tolerated, with no treatment discontinuations or serious adverse events. Doxycycline reduced total sputum MMP-9 levels by 63.2% (p<0.05), and was also associated with a 56.5% reduction in active MMP-9 levels (p<0.05), a 1.6-fold increase in sputum TIMP-1 (p<0.05), improvement in forced expiratory volume in 1 s (p<0.05), and an increase in time to next exacerbation (p<0.01).Adjunctive use of doxycycline improved dysregulated MMP-9 levels in sputum, along with biomarkers consistent with a reduced proteolytic pulmonary environment. Improvement in clinical outcome measures suggests an important therapeutic benefit of doxycycline for individuals with cystic fibrosis. Copyright ©ERS 2017.

Harmonising and linking biomedical and clinical data across disparate data archives to enable integrative cross-biobank research

PubMed Central

Spjuth, Ola; Krestyaninova, Maria; Hastings, Janna; Shen, Huei-Yi; Heikkinen, Jani; Waldenberger, Melanie; Langhammer, Arnulf; Ladenvall, Claes; Esko, Tõnu; Persson, Mats-Åke; Heggland, Jon; Dietrich, Joern; Ose, Sandra; Gieger, Christian; Ried, Janina S; Peters, Annette; Fortier, Isabel; de Geus, Eco JC; Klovins, Janis; Zaharenko, Linda; Willemsen, Gonneke; Hottenga, Jouke-Jan; Litton, Jan-Eric; Karvanen, Juha; Boomsma, Dorret I; Groop, Leif; Rung, Johan; Palmgren, Juni; Pedersen, Nancy L; McCarthy, Mark I; van Duijn, Cornelia M; Hveem, Kristian; Metspalu, Andres; Ripatti, Samuli; Prokopenko, Inga; Harris, Jennifer R

2016-01-01

A wealth of biospecimen samples are stored in modern globally distributed biobanks. Biomedical researchers worldwide need to be able to combine the available resources to improve the power of large-scale studies. A prerequisite for this effort is to be able to search and access phenotypic, clinical and other information about samples that are currently stored at biobanks in an integrated manner. However, privacy issues together with heterogeneous information systems and the lack of agreed-upon vocabularies have made specimen searching across multiple biobanks extremely challenging. We describe three case studies where we have linked samples and sample descriptions in order to facilitate global searching of available samples for research. The use cases include the ENGAGE (European Network for Genetic and Genomic Epidemiology) consortium comprising at least 39 cohorts, the SUMMIT (surrogate markers for micro- and macro-vascular hard endpoints for innovative diabetes tools) consortium and a pilot for data integration between a Swedish clinical health registry and a biobank. We used the Sample avAILability (SAIL) method for data linking: first, created harmonised variables and then annotated and made searchable information on the number of specimens available in individual biobanks for various phenotypic categories. By operating on this categorised availability data we sidestep many obstacles related to privacy that arise when handling real values and show that harmonised and annotated records about data availability across disparate biomedical archives provide a key methodological advance in pre-analysis exchange of information between biobanks, that is, during the project planning phase. PMID:26306643

Conducting Precision Medicine Research with African Americans.

PubMed

Halbert, Chanita Hughes; McDonald, Jasmine; Vadaparampil, Susan; Rice, LaShanta; Jefferson, Melanie

2016-01-01

Precision medicine is an approach to detecting, treating, and managing disease that is based on individual variation in genetic, environmental, and lifestyle factors. Precision medicine is expected to reduce health disparities, but this will be possible only if studies have adequate representation of racial minorities. It is critical to anticipate the rates at which individuals from diverse populations are likely to participate in precision medicine studies as research initiatives are being developed. We evaluated the likelihood of participating in a clinical study for precision medicine. Observational study conducted between October 2010 and February 2011 in a national sample of African Americans. Intentions to participate in a government sponsored study that involves providing a biospecimen and generates data that could be shared with other researchers to conduct future studies. One third of respondents would participate in a clinical study for precision medicine. Only gender had a significant independent association with participation intentions. Men had a 1.86 (95% CI = 1.11, 3.12, p = 0.02) increased likelihood of participating in a precision medicine study compared to women in the model that included overall barriers and facilitators. In the model with specific participation barriers, distrust was associated with a reduced likelihood of participating in the research described in the vignette (OR = 0.57, 95% CI = 0.34, 0.96, p = 0.04). African Americans may have low enrollment in PMI research. As PMI research is implemented, extensive efforts will be needed to ensure adequate representation. Additional research is needed to identify optimal ways of ethically describing precision medicine studies to ensure sufficient recruitment of racial minorities.

The Cancer Epidemiology Descriptive Cohort Database: A Tool to Support Population-Based Interdisciplinary Research

PubMed Central

Kennedy, Amy E.; Khoury, Muin J.; Ioannidis, John P.A.; Brotzman, Michelle; Miller, Amy; Lane, Crystal; Lai, Gabriel Y.; Rogers, Scott D.; Harvey, Chinonye; Elena, Joanne W.; Seminara, Daniela

2017-01-01

Background We report on the establishment of a web-based Cancer Epidemiology Descriptive Cohort Database (CEDCD). The CEDCD’s goals are to enhance awareness of resources, facilitate interdisciplinary research collaborations, and support existing cohorts for the study of cancer-related outcomes. Methods Comprehensive descriptive data were collected from large cohorts established to study cancer as primary outcome using a newly developed questionnaire. These included an inventory of baseline and follow-up data, biospecimens, genomics, policies, and protocols. Additional descriptive data extracted from publicly available sources were also collected. This information was entered in a searchable and publicly accessible database. We summarized the descriptive data across cohorts and reported the characteristics of this resource. Results As of December 2015, the CEDCD includes data from 46 cohorts representing more than 6.5 million individuals (29% ethnic/racial minorities). Overall, 78% of the cohorts have collected blood at least once, 57% at multiple time points, and 46% collected tissue samples. Genotyping has been performed by 67% of the cohorts, while 46% have performed whole-genome or exome sequencing in subsets of enrolled individuals. Information on medical conditions other than cancer has been collected in more than 50% of the cohorts. More than 600,000 incident cancer cases and more than 40,000 prevalent cases are reported, with 24 cancer sites represented. Conclusions The CEDCD assembles detailed descriptive information on a large number of cancer cohorts in a searchable database. Impact Information from the CEDCD may assist the interdisciplinary research community by facilitating identification of well-established population resources and large-scale collaborative and integrative research. PMID:27439404

Review Article: The Role of Molecular Pathological Epidemiology in the Study of Neoplastic and Non-neoplastic Diseases in the Era of Precision Medicine.

PubMed

Ogino, Shuji; Nishihara, Reiko; VanderWeele, Tyler J; Wang, Molin; Nishi, Akihiro; Lochhead, Paul; Qian, Zhi Rong; Zhang, Xuehong; Wu, Kana; Nan, Hongmei; Yoshida, Kazuki; Milner, Danny A; Chan, Andrew T; Field, Alison E; Camargo, Carlos A; Williams, Michelle A; Giovannucci, Edward L

2016-07-01

Molecular pathology diagnostics to subclassify diseases based on pathogenesis are increasingly common in clinical translational medicine. Molecular pathological epidemiology (MPE) is an integrative transdisciplinary science based on the unique disease principle and the disease continuum theory. While it has been most commonly applied to research on breast, lung, and colorectal cancers, MPE can investigate etiologic heterogeneity in non-neoplastic diseases, such as cardiovascular diseases, obesity, diabetes mellitus, drug toxicity, and immunity-related and infectious diseases. This science can enhance causal inference by linking putative etiologic factors to specific molecular biomarkers as outcomes. Technological advances increasingly enable analyses of various -omics, including genomics, epigenomics, transcriptomics, proteomics, metabolomics, metagenomics, microbiome, immunomics, interactomics, etc. Challenges in MPE include sample size limitations (depending on availability of biospecimens or biomedical/radiological imaging), need for rigorous validation of molecular assays and study findings, and paucities of interdisciplinary experts, education programs, international forums, and standardized guidelines. To address these challenges, there are ongoing efforts such as multidisciplinary consortium pooling projects, the International Molecular Pathological Epidemiology Meeting Series, and the Strengthening the Reporting of Observational Studies in Epidemiology-MPE guideline project. Efforts should be made to build biorepository and biobank networks, and worldwide population-based MPE databases. These activities match with the purposes of the Big Data to Knowledge (BD2K), Genetic Associations and Mechanisms in Oncology (GAME-ON), and Precision Medicine Initiatives of the United States National Institute of Health. Given advances in biotechnology, bioinformatics, and computational/systems biology, there are wide open opportunities in MPE to contribute to public health.

Comparison of initial stream urine samples and cervical samples for detection of human papillomavirus.

PubMed

Hagihara, Mao; Yamagishi, Yuka; Izumi, Koji; Miyazaki, Narimi; Suzuki, Takayoshi; Kato, Hideo; Nishiyama, Naoya; Koizumi, Yusuke; Suematsu, Hiroyuki; Mikamo, Hiroshige

2016-08-01

Uterine cervical cancer is a treatable and preventable cancer. Medical efforts to reduce rates of cervical cancer focus on the promotion of human papillomavirus (HPV) vaccination and the promotion of routine cervical cancer screening done by cervical cytology and cervical HPV testing. Urine-based HPV testing would be simple and noninvasive approach to screen for cervical cancer. Two biospecimens (clinician-taken sample from cervix and initial stream urine sample) were provided from a total of 240 healthy women attending for cancer screening provided for HPV testing. We have assessed the HPV detection rates among cervical samples and pellet fraction of urine samples using HPV test (Anyplex™ II HPV28 Detection kit, Seegene, Korea). Among 240 samples screened, HPV prevalence was 42.9% in pellet fractions of urine samples. The agreement between the two kinds of samples was 98.4%, k = 0.792. Discordant results were observed in 27 cases; 5 were positive only by urine samples and 22 were positive only by smear samples. Sensitivity and specificity for all HPV DNA in pellet fractions of urine using cervical samples as reference was 68.4% and 99.9%. Comparing methodologies of collection of samples for HPV detection, they showed the higher agreements for almost genotypes between cervical samples and pellet fractions of urine samples. These results suggest that urine could be a good noninvasive tool to monitor HPV infection in women. Additional research in a larger and general screening population would be needed. Copyright © 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Leveraging biospecimen resources for discovery or validation of markers for early cancer detection.

PubMed

Schully, Sheri D; Carrick, Danielle M; Mechanic, Leah E; Srivastava, Sudhir; Anderson, Garnet L; Baron, John A; Berg, Christine D; Cullen, Jennifer; Diamandis, Eleftherios P; Doria-Rose, V Paul; Goddard, Katrina A B; Hankinson, Susan E; Kushi, Lawrence H; Larson, Eric B; McShane, Lisa M; Schilsky, Richard L; Shak, Steven; Skates, Steven J; Urban, Nicole; Kramer, Barnett S; Khoury, Muin J; Ransohoff, David F

2015-04-01

Validation of early detection cancer biomarkers has proven to be disappointing when initial promising claims have often not been reproducible in diagnostic samples or did not extend to prediagnostic samples. The previously reported lack of rigorous internal validity (systematic differences between compared groups) and external validity (lack of generalizability beyond compared groups) may be effectively addressed by utilizing blood specimens and data collected within well-conducted cohort studies. Cohort studies with prediagnostic specimens (eg, blood specimens collected prior to development of clinical symptoms) and clinical data have recently been used to assess the validity of some early detection biomarkers. With this background, the Division of Cancer Control and Population Sciences (DCCPS) and the Division of Cancer Prevention (DCP) of the National Cancer Institute (NCI) held a joint workshop in August 2013. The goal was to advance early detection cancer research by considering how the infrastructure of cohort studies that already exist or are being developed might be leveraged to include appropriate blood specimens, including prediagnostic specimens, ideally collected at periodic intervals, along with clinical data about symptom status and cancer diagnosis. Three overarching recommendations emerged from the discussions: 1) facilitate sharing of existing specimens and data, 2) encourage collaboration among scientists developing biomarkers and those conducting observational cohort studies or managing healthcare systems with cohorts followed over time, and 3) conduct pilot projects that identify and address key logistic and feasibility issues regarding how appropriate specimens and clinical data might be collected at reasonable effort and cost within existing or future cohorts. © Published by Oxford University Press 2015.

Leveraging Biospecimen Resources for Discovery or Validation of Markers for Early Cancer Detection

PubMed Central

Carrick, Danielle M.; Mechanic, Leah E.; Srivastava, Sudhir; Anderson, Garnet L.; Baron, John A.; Berg, Christine D.; Cullen, Jennifer; Diamandis, Eleftherios P.; Doria-Rose, V. Paul; Goddard, Katrina A. B.; Hankinson, Susan E.; Kushi, Lawrence H.; Larson, Eric B.; McShane, Lisa M.; Schilsky, Richard L.; Shak, Steven; Skates, Steven J.; Urban, Nicole; Kramer, Barnett S.; Khoury, Muin J.; Ransohoff, David F.

2015-01-01

Validation of early detection cancer biomarkers has proven to be disappointing when initial promising claims have often not been reproducible in diagnostic samples or did not extend to prediagnostic samples. The previously reported lack of rigorous internal validity (systematic differences between compared groups) and external validity (lack of generalizability beyond compared groups) may be effectively addressed by utilizing blood specimens and data collected within well-conducted cohort studies. Cohort studies with prediagnostic specimens (eg, blood specimens collected prior to development of clinical symptoms) and clinical data have recently been used to assess the validity of some early detection biomarkers. With this background, the Division of Cancer Control and Population Sciences (DCCPS) and the Division of Cancer Prevention (DCP) of the National Cancer Institute (NCI) held a joint workshop in August 2013. The goal was to advance early detection cancer research by considering how the infrastructure of cohort studies that already exist or are being developed might be leveraged to include appropriate blood specimens, including prediagnostic specimens, ideally collected at periodic intervals, along with clinical data about symptom status and cancer diagnosis. Three overarching recommendations emerged from the discussions: 1) facilitate sharing of existing specimens and data, 2) encourage collaboration among scientists developing biomarkers and those conducting observational cohort studies or managing healthcare systems with cohorts followed over time, and 3) conduct pilot projects that identify and address key logistic and feasibility issues regarding how appropriate specimens and clinical data might be collected at reasonable effort and cost within existing or future cohorts. PMID:25688116

Baseline Profile of Participants in the Japan Environment and Children's Study (JECS).

PubMed

Michikawa, Takehiro; Nitta, Hiroshi; Nakayama, Shoji F; Yamazaki, Shin; Isobe, Tomohiko; Tamura, Kenji; Suda, Eiko; Ono, Masaji; Yonemoto, Junzo; Iwai-Shimada, Miyuki; Kobayashi, Yayoi; Suzuki, Go; Kawamoto, Toshihiro

2018-02-05

The Japan Environment and Children's Study (JECS), known as Ecochil-Chosa in Japan, is a nationwide birth cohort study investigating the environmental factors that might affect children's health and development. We report the baseline profiles of the participating mothers, fathers, and their children. Fifteen Regional Centres located throughout Japan were responsible for recruiting women in early pregnancy living in their respective recruitment areas. Self-administered questionnaires and medical records were used to obtain such information as demographic factors, lifestyle, socioeconomic status, environmental exposure, medical history, and delivery information. In the period up to delivery, we collected bio-specimens, including blood, urine, hair, and umbilical cord blood. Fathers were also recruited, when accessible, and asked to fill in a questionnaire and to provide blood samples. The total number of pregnancies resulting in delivery was 100,778, of which 51,402 (51.0%) involved program participation by male partners. Discounting pregnancies by the same woman, the study included 95,248 unique mothers and 49,189 unique fathers. The 100,778 pregnancies involved a total of 101,779 fetuses and resulted in 100,148 live births. The coverage of children in 2013 (the number of live births registered in JECS divided by the number of all live births within the study areas) was approximately 45%. Nevertheless, the data on the characteristics of the mothers and children we studied showed marked similarity to those obtained from Japan's 2013 Vital Statistics Survey. Between 2011 and 2014, we established one of the largest birth cohorts in the world.

Baseline Profile of Participants in the Japan Environment and Children’s Study (JECS)

PubMed Central

Nitta, Hiroshi; Nakayama, Shoji F.; Yamazaki, Shin; Isobe, Tomohiko; Tamura, Kenji; Suda, Eiko; Ono, Masaji; Yonemoto, Junzo; Iwai-Shimada, Miyuki; Kobayashi, Yayoi; Suzuki, Go; Kawamoto, Toshihiro

2018-01-01

Background The Japan Environment and Children’s Study (JECS), known as Ecochil-Chosa in Japan, is a nationwide birth cohort study investigating the environmental factors that might affect children’s health and development. We report the baseline profiles of the participating mothers, fathers, and their children. Methods Fifteen Regional Centres located throughout Japan were responsible for recruiting women in early pregnancy living in their respective recruitment areas. Self-administered questionnaires and medical records were used to obtain such information as demographic factors, lifestyle, socioeconomic status, environmental exposure, medical history, and delivery information. In the period up to delivery, we collected bio-specimens, including blood, urine, hair, and umbilical cord blood. Fathers were also recruited, when accessible, and asked to fill in a questionnaire and to provide blood samples. Results The total number of pregnancies resulting in delivery was 100,778, of which 51,402 (51.0%) involved program participation by male partners. Discounting pregnancies by the same woman, the study included 95,248 unique mothers and 49,189 unique fathers. The 100,778 pregnancies involved a total of 101,779 fetuses and resulted in 100,148 live births. The coverage of children in 2013 (the number of live births registered in JECS divided by the number of all live births within the study areas) was approximately 45%. Nevertheless, the data on the characteristics of the mothers and children we studied showed marked similarity to those obtained from Japan’s 2013 Vital Statistics Survey. Conclusions Between 2011 and 2014, we established one of the largest birth cohorts in the world. PMID:29093304

The LIFE-Adult-Study: objectives and design of a population-based cohort study with 10,000 deeply phenotyped adults in Germany.

PubMed

Loeffler, Markus; Engel, Christoph; Ahnert, Peter; Alfermann, Dorothee; Arelin, Katrin; Baber, Ronny; Beutner, Frank; Binder, Hans; Brähler, Elmar; Burkhardt, Ralph; Ceglarek, Uta; Enzenbach, Cornelia; Fuchs, Michael; Glaesmer, Heide; Girlich, Friederike; Hagendorff, Andreas; Häntzsch, Madlen; Hegerl, Ulrich; Henger, Sylvia; Hensch, Tilman; Hinz, Andreas; Holzendorf, Volker; Husser, Daniela; Kersting, Anette; Kiel, Alexander; Kirsten, Toralf; Kratzsch, Jürgen; Krohn, Knut; Luck, Tobias; Melzer, Susanne; Netto, Jeffrey; Nüchter, Matthias; Raschpichler, Matthias; Rauscher, Franziska G; Riedel-Heller, Steffi G; Sander, Christian; Scholz, Markus; Schönknecht, Peter; Schroeter, Matthias L; Simon, Jan-Christoph; Speer, Ronald; Stäker, Julia; Stein, Robert; Stöbel-Richter, Yve; Stumvoll, Michael; Tarnok, Attila; Teren, Andrej; Teupser, Daniel; Then, Francisca S; Tönjes, Anke; Treudler, Regina; Villringer, Arno; Weissgerber, Alexander; Wiedemann, Peter; Zachariae, Silke; Wirkner, Kerstin; Thiery, Joachim

2015-07-22

The LIFE-Adult-Study is a population-based cohort study, which has recently completed the baseline examination of 10,000 randomly selected participants from Leipzig, a major city with 550,000 inhabitants in the east of Germany. It is the first study of this kind and size in an urban population in the eastern part of Germany. The study is conducted by the Leipzig Research Centre for Civilization Diseases (LIFE). Our objective is to investigate prevalences, early onset markers, genetic predispositions, and the role of lifestyle factors of major civilization diseases, with primary focus on metabolic and vascular diseases, heart function, cognitive impairment, brain function, depression, sleep disorders and vigilance dysregulation, retinal and optic nerve degeneration, and allergies. The study covers a main age range from 40-79 years with particular deep phenotyping in elderly participants above the age of 60. The baseline examination was conducted from August 2011 to November 2014. All participants underwent an extensive core assessment programme (5-6 h) including structured interviews, questionnaires, physical examinations, and biospecimen collection. Participants over 60 underwent two additional assessment programmes (3-4 h each) on two separate visits including deeper cognitive testing, brain magnetic resonance imaging, diagnostic interviews for depression, and electroencephalography. The participation rate was 33 %. The assessment programme was accepted well and completely passed by almost all participants. Biomarker analyses have already been performed in all participants. Genotype, transcriptome and metabolome analyses have been conducted in subgroups. The first follow-up examination will commence in 2016.

The assessment, serial evaluation, and subsequent sequelae of acute kidney injury (ASSESS-AKI) study: design and methods.

PubMed

Go, Alan S; Parikh, Chirag R; Ikizler, T Alp; Coca, Steven; Siew, Edward D; Chinchilli, Vernon M; Hsu, Chi-Yuan; Garg, Amit X; Zappitelli, Michael; Liu, Kathleen D; Reeves, W Brian; Ghahramani, Nasrollah; Devarajan, Prasad; Faulkner, Georgia Brown; Tan, Thida C; Kimmel, Paul L; Eggers, Paul; Stokes, John B

2010-08-27

The incidence of acute kidney injury (AKI) has been increasing over time and is associated with a high risk of short-term death. Previous studies on hospital-acquired AKI have important methodological limitations, especially their retrospective study designs and limited ability to control for potential confounding factors. The Assessment, Serial Evaluation, and Subsequent Sequelae of Acute Kidney Injury (ASSESS-AKI) Study was established to examine how a hospitalized episode of AKI independently affects the risk of chronic kidney disease development and progression, cardiovascular events, death, and other important patient-centered outcomes. This prospective study will enroll a cohort of 1100 adult participants with a broad range of AKI and matched hospitalized participants without AKI at three Clinical Research Centers, as well as 100 children undergoing cardiac surgery at three Clinical Research Centers. Participants will be followed for up to four years, and will undergo serial evaluation during the index hospitalization, at three months post-hospitalization, and at annual clinic visits, with telephone interviews occurring during the intervening six-month intervals. Biospecimens will be collected at each visit, along with information on lifestyle behaviors, quality of life and functional status, cognitive function, receipt of therapies, interim renal and cardiovascular events, electrocardiography and urinalysis. ASSESS-AKI will characterize the short-term and long-term natural history of AKI, evaluate the incremental utility of novel blood and urine biomarkers to refine the diagnosis and prognosis of AKI, and identify a subset of high-risk patients who could be targeted for future clinical trials to improve outcomes after AKI.

The MURDOCK Study: a long-term initiative for disease reclassification through advanced biomarker discovery and integration with electronic health records

PubMed Central

Tenenbaum, Jessica D; Christian, Victoria; Cornish, Melissa A; Dolor, Rowena J; Dunham, Ashley A; Ginsburg, Geoffrey S; Kraus, Virginia B; McHutchison, John G; Nahm, Meredith L; Newby, L Kristin; Svetkey, Laura P; Udayakumar, Krishna; Califf, Robert M

2012-01-01

Background Facing critically low return per dollar invested on clinical research and clinical care, the American biomedical enterprise is in need of a significant transformation. A confluence of high-throughput “omic” technologies and increasing adoption of the electronic health record has fueled excitement for a new paradigm for biomedical research and practice. The ability to simultaneously measure thousands of molecular variables and assess their relationships with clinical data collected during the course of care could enable reclassification of disease not only by gross phenotypic observation but according to underlying molecular mechanism and influence of social determinants.In turn, this reclassification could enable development of targeted therapeutic interventions as well as disease prevention strategies at the individual and population levels. Methods/Design The MURDOCK Study consists of distinct project “horizons” or stages. Horizon 1 entailed the generation and analysis of molecular data for existing large,clinically well-annotated cohorts in four disease areas. Horizon 1.5 involves creating and maintaining a 50,000-person,community volunteer registry for biomarker signature validation and prospective studies, including integration of environmental and social data. Horizon 2 leverages and prospectively recruits Horizon 1.5 volunteers, and extends the study to additional disease areas of interest. Horizon 3 will expand the study through regional, national,and international partnerships. Discussion The MURDOCK Study embodies a new model of team science investigation and represents a significant resource for translational research. The study team invites inquiries to form new collaborations to exploit the rich resources provided by these biospecimens and associated study data. PMID:22937207

7 CFR 52.3752 - Types of canned ripe olives.

Code of Federal Regulations, 2010 CFR

2010-01-01

... MARKETING ACT OF 1946 PROCESSED FRUITS AND VEGETABLES, PROCESSED PRODUCTS THEREOF, AND CERTAIN OTHER PROCESSED FOOD PRODUCTS 1 United States Standards for Grades of Canned Ripe Olives 1 Product Description... either “ripe-type” or “green-ripe type.” (a) Ripe type. “Ripe type” olives are those which have been...

CRT image recording evaluation

NASA Technical Reports Server (NTRS)

1971-01-01

Performance capabilities and limitations of a fiber optic coupled line scan CRT image recording system were investigated. The test program evaluated the following components: (1). P31 phosphor CRT with EMA faceplate; (2). P31 phosphor CRT with clear clad faceplate; (3). Type 7743 semi-gloss dry process positive print paper; (4). Type 777 flat finish dry process positive print paper; (5). Type 7842 dry process positive film; and (6). Type 1971 semi-gloss wet process positive print paper. Detailed test procedures used in each test are provided along with a description of each test, the test data, and an analysis of the results.

Manufacture and quality control of interconnecting wire hardnesses, Volume 1

NASA Technical Reports Server (NTRS)

1972-01-01

A standard is presented for manufacture, installation, and quality control of eight types of interconnecting wire harnesses. The processes, process controls, and inspection and test requirements reflected are based on acknowledgment of harness design requirements, acknowledgment of harness installation requirements, identification of the various parts, materials, etc., utilized in harness manufacture, and formulation of a typical manufacturing flow diagram for identification of each manufacturing and quality control process, operation, inspection, and test. The document covers interconnecting wire harnesses defined in the design standard, including type 1, enclosed in fluorocarbon elastomer convolute, tubing; type 2, enclosed in TFE convolute tubing lines with fiberglass braid; type 3, enclosed in TFE convolute tubing; and type 5, combination of types 3 and 4. Knowledge gained through experience on the Saturn 5 program coupled with recent advances in techniques, materials, and processes was incorporated.

The Relationship between Sensory Processing Difficulties and Leisure Activity Preference of Children with Different Types of ADHD

ERIC Educational Resources Information Center

Engel-Yeger, Batya; Ziv-On, Daniella

2011-01-01

Sensory processing difficulties (SPD) are prevalent among children with ADHD. Yet, the question whether different SPD characterize children with different types of ADHD has not received enough attention in the literature. The current study characterized sensory processing difficulties (SPD) of children with different types of ADHD and explored the…

Examining the Affordances of Dual Cognitive Processing to Explain the Development of High School Students' Nature of Science Views

NASA Astrophysics Data System (ADS)

Jackson, Luke M.

This mixed method study was aimed at examining the influence of dual processing (Type 1 and Type 2 thinking) on the development of high school students' nature of science (NOS) views. Type 1 thinking is intuitive, experiential, and heuristic. Type 2 thinking is rational, analytical, and explicit. Three research questions were asked: (1) Do the experiential process (Type 1) and the logical process (Type 2) influence the development of students' NOS views? (2) If there is an influence on students' NOS views, then what is the nature of relationship between the experiential process (Type 1) and the development of NOS views? (3) What is the nature of relationship between the logical process (Type 2) and the development of NOS views? The Views of Nature of Science Questionnaire C (VNOS-C; Lederman, Abd-El-Khalick, Bell, & Schwartz, 2002) was administered to 29 high school students at the beginning and at the end of an explicit-reflective NOS intervention offered in an Advanced Placement environmental science course. Changes in students' NOS views were calculated through a chi-square test and examining the percentage of students holding NOS views at various levels of sophistication. With the chi-square goodness of fit test performed, the relationship between pre and post NOS scores was not significant, X2(3, 29) = 4.78, p <.05. The informed and preinformed NOS views increased (14%, 17%) in frequency while the mixed and uninformed NOS views decreased (i.e. improved 26%, 24%) in frequency from pre to posttest. The reading discussions were coded based on the EBR framework (Furtak et al., 2010) to analyze the use of dual processing. Type1 and Type 2 thinking were both used during the intervention and reading reflections. Type 2 thinking was more prominent when analyzing a problem, formulating a hypothesis, or stating logical claims. The association of NOS education and Type 1 and Type 2 thinking in scientific literacy was examined, and implications and future research are discussed.

Execution and pauses in writing narratives: processing time, cognitive effort and typing skill.

PubMed

Alves, Rui Alexandre; Castro, São Luís; Olive, Thierry

2008-12-01

At the behavioural level, the activity of a writer can be described as periods of typing separated by pauses. Although some studies have been concerned with the functions of pauses, few have investigated motor execution periods. Precise estimates of the distribution of writing processes, and their cognitive demands, across periods of typing and pauses are lacking. Furthermore, it is uncertain how typing skill affects these aspects of writing. We addressed these issues, selecting writers of low and high typing skill who performed dictation and composition tasks. The occurrences of writing processes were assessed through directed verbalization, and their cognitive demands were measured through interference in reaction times (IRT). Before writing a narrative, 34 undergraduates learned to categorize examples of introspective thoughts as different types of activities related to writing (planning, translating, or revising). Then, while writing, they responded to random auditory probes, and reported their ongoing activity according to the learned categories. Convergent with previous findings, translating was most often reported, and revising and planning had fewer occurrences. Translating was mostly activated during motor execution, whereas revising and planning were mainly activated during pauses. However, none of the writing processes can be characterized as being typical of pauses, since translating was activated to a similar extent as the other two processes. Regarding cognitive demands, revising is likely to be the most demanding process in narrative writing. Typing skill had an impact on IRTs of motor execution. The demands of execution were greater in the low than in the high typing skill group, but these greater demands did not affect the strategy of writing processes activation. Nevertheless, low typing skill had a detrimental impact on text quality.

The development and deployment of Common Data Elements for tissue banks for translational research in cancer - an emerging standard based approach for the Mesothelioma Virtual Tissue Bank.

PubMed

Mohanty, Sambit K; Mistry, Amita T; Amin, Waqas; Parwani, Anil V; Pople, Andrew K; Schmandt, Linda; Winters, Sharon B; Milliken, Erin; Kim, Paula; Whelan, Nancy B; Farhat, Ghada; Melamed, Jonathan; Taioli, Emanuela; Dhir, Rajiv; Pass, Harvey I; Becich, Michael J

2008-04-08

Recent advances in genomics, proteomics, and the increasing demands for biomarker validation studies have catalyzed changes in the landscape of cancer research, fueling the development of tissue banks for translational research. A result of this transformation is the need for sufficient quantities of clinically annotated and well-characterized biospecimens to support the growing needs of the cancer research community. Clinical annotation allows samples to be better matched to the research question at hand and ensures that experimental results are better understood and can be verified. To facilitate and standardize such annotation in bio-repositories, we have combined three accepted and complementary sets of data standards: the College of American Pathologists (CAP) Cancer Checklists, the protocols recommended by the Association of Directors of Anatomic and Surgical Pathology (ADASP) for pathology data, and the North American Association of Central Cancer Registry (NAACCR) elements for epidemiology, therapy and follow-up data. Combining these approaches creates a set of International Standards Organization (ISO) - compliant Common Data Elements (CDEs) for the mesothelioma tissue banking initiative supported by the National Institute for Occupational Safety and Health (NIOSH) of the Center for Disease Control and Prevention (CDC). The purpose of the project is to develop a core set of data elements for annotating mesothelioma specimens, following standards established by the CAP checklist, ADASP cancer protocols, and the NAACCR elements. We have associated these elements with modeling architecture to enhance both syntactic and semantic interoperability. The system has a Java-based multi-tiered architecture based on Unified Modeling Language (UML). Common Data Elements were developed using controlled vocabulary, ontology and semantic modeling methodology. The CDEs for each case are of different types: demographic, epidemiologic data, clinical history, pathology data including block level annotation, and follow-up data including treatment, recurrence and vital status. The end result of such an effort would eventually provide an increased sample set to the researchers, and makes the system interoperable between institutions. The CAP, ADASP and the NAACCR elements represent widely established data elements that are utilized in many cancer centers. Herein, we have shown these representations can be combined and formalized to create a core set of annotations for banked mesothelioma specimens. Because these data elements are collected as part of the normal workflow of a medical center, data sets developed on the basis of these elements can be easily implemented and maintained.

Development of Bioinformatics Infrastructure for Genomics Research.

PubMed

Mulder, Nicola J; Adebiyi, Ezekiel; Adebiyi, Marion; Adeyemi, Seun; Ahmed, Azza; Ahmed, Rehab; Akanle, Bola; Alibi, Mohamed; Armstrong, Don L; Aron, Shaun; Ashano, Efejiro; Baichoo, Shakuntala; Benkahla, Alia; Brown, David K; Chimusa, Emile R; Fadlelmola, Faisal M; Falola, Dare; Fatumo, Segun; Ghedira, Kais; Ghouila, Amel; Hazelhurst, Scott; Isewon, Itunuoluwa; Jung, Segun; Kassim, Samar Kamal; Kayondo, Jonathan K; Mbiyavanga, Mamana; Meintjes, Ayton; Mohammed, Somia; Mosaku, Abayomi; Moussa, Ahmed; Muhammd, Mustafa; Mungloo-Dilmohamud, Zahra; Nashiru, Oyekanmi; Odia, Trust; Okafor, Adaobi; Oladipo, Olaleye; Osamor, Victor; Oyelade, Jellili; Sadki, Khalid; Salifu, Samson Pandam; Soyemi, Jumoke; Panji, Sumir; Radouani, Fouzia; Souiai, Oussama; Tastan Bishop, Özlem

2017-06-01

Although pockets of bioinformatics excellence have developed in Africa, generally, large-scale genomic data analysis has been limited by the availability of expertise and infrastructure. H3ABioNet, a pan-African bioinformatics network, was established to build capacity specifically to enable H3Africa (Human Heredity and Health in Africa) researchers to analyze their data in Africa. Since the inception of the H3Africa initiative, H3ABioNet's role has evolved in response to changing needs from the consortium and the African bioinformatics community. H3ABioNet set out to develop core bioinformatics infrastructure and capacity for genomics research in various aspects of data collection, transfer, storage, and analysis. Various resources have been developed to address genomic data management and analysis needs of H3Africa researchers and other scientific communities on the continent. NetMap was developed and used to build an accurate picture of network performance within Africa and between Africa and the rest of the world, and Globus Online has been rolled out to facilitate data transfer. A participant recruitment database was developed to monitor participant enrollment, and data is being harmonized through the use of ontologies and controlled vocabularies. The standardized metadata will be integrated to provide a search facility for H3Africa data and biospecimens. Because H3Africa projects are generating large-scale genomic data, facilities for analysis and interpretation are critical. H3ABioNet is implementing several data analysis platforms that provide a large range of bioinformatics tools or workflows, such as Galaxy, the Job Management System, and eBiokits. A set of reproducible, portable, and cloud-scalable pipelines to support the multiple H3Africa data types are also being developed and dockerized to enable execution on multiple computing infrastructures. In addition, new tools have been developed for analysis of the uniquely divergent African data and for downstream interpretation of prioritized variants. To provide support for these and other bioinformatics queries, an online bioinformatics helpdesk backed by broad consortium expertise has been established. Further support is provided by means of various modes of bioinformatics training. For the past 4 years, the development of infrastructure support and human capacity through H3ABioNet, have significantly contributed to the establishment of African scientific networks, data analysis facilities, and training programs. Here, we describe the infrastructure and how it has affected genomics and bioinformatics research in Africa. Copyright © 2017 World Heart Federation (Geneva). Published by Elsevier B.V. All rights reserved.

The development and deployment of Common Data Elements for tissue banks for translational research in cancer – An emerging standard based approach for the Mesothelioma Virtual Tissue Bank

PubMed Central

Mohanty, Sambit K; Mistry, Amita T; Amin, Waqas; Parwani, Anil V; Pople, Andrew K; Schmandt, Linda; Winters, Sharon B; Milliken, Erin; Kim, Paula; Whelan, Nancy B; Farhat, Ghada; Melamed, Jonathan; Taioli, Emanuela; Dhir, Rajiv; Pass, Harvey I; Becich, Michael J

2008-01-01

Background Recent advances in genomics, proteomics, and the increasing demands for biomarker validation studies have catalyzed changes in the landscape of cancer research, fueling the development of tissue banks for translational research. A result of this transformation is the need for sufficient quantities of clinically annotated and well-characterized biospecimens to support the growing needs of the cancer research community. Clinical annotation allows samples to be better matched to the research question at hand and ensures that experimental results are better understood and can be verified. To facilitate and standardize such annotation in bio-repositories, we have combined three accepted and complementary sets of data standards: the College of American Pathologists (CAP) Cancer Checklists, the protocols recommended by the Association of Directors of Anatomic and Surgical Pathology (ADASP) for pathology data, and the North American Association of Central Cancer Registry (NAACCR) elements for epidemiology, therapy and follow-up data. Combining these approaches creates a set of International Standards Organization (ISO) – compliant Common Data Elements (CDEs) for the mesothelioma tissue banking initiative supported by the National Institute for Occupational Safety and Health (NIOSH) of the Center for Disease Control and Prevention (CDC). Methods The purpose of the project is to develop a core set of data elements for annotating mesothelioma specimens, following standards established by the CAP checklist, ADASP cancer protocols, and the NAACCR elements. We have associated these elements with modeling architecture to enhance both syntactic and semantic interoperability. The system has a Java-based multi-tiered architecture based on Unified Modeling Language (UML). Results Common Data Elements were developed using controlled vocabulary, ontology and semantic modeling methodology. The CDEs for each case are of different types: demographic, epidemiologic data, clinical history, pathology data including block level annotation, and follow-up data including treatment, recurrence and vital status. The end result of such an effort would eventually provide an increased sample set to the researchers, and makes the system interoperable between institutions. Conclusion The CAP, ADASP and the NAACCR elements represent widely established data elements that are utilized in many cancer centers. Herein, we have shown these representations can be combined and formalized to create a core set of annotations for banked mesothelioma specimens. Because these data elements are collected as part of the normal workflow of a medical center, data sets developed on the basis of these elements can be easily implemented and maintained. PMID:18397527

Hospital strategic planning diversity integration based organizational type and CEO tenure.

PubMed

Newhouse, John J

2007-01-01

The author investigated the strategic planning processes used by five different hospital types to integrate diversity practices into their operations. Chief executive officers from Delaware, New Jersey, New York, and Pennsylvania were surveyed to examine how their hospitals used strategic planning in this process. The central research question was: Does this process vary on the basis of hospital type? The findings indicated that some differences do exist by hospital type, as well as the length of tenure for CEOs in their positions.

41 CFR 102-193.25 - What type of records management business process improvements should my agency strive to achieve?

Code of Federal Regulations, 2013 CFR

2013-07-01

... 41 Public Contracts and Property Management 3 2013-07-01 2013-07-01 false What type of records management business process improvements should my agency strive to achieve? 102-193.25 Section 102-193.25...-193.25 What type of records management business process improvements should my agency strive to...

41 CFR 102-193.25 - What type of records management business process improvements should my agency strive to achieve?

Code of Federal Regulations, 2011 CFR

2011-01-01

... 41 Public Contracts and Property Management 3 2011-01-01 2011-01-01 false What type of records management business process improvements should my agency strive to achieve? 102-193.25 Section 102-193.25...-193.25 What type of records management business process improvements should my agency strive to...

41 CFR 102-193.25 - What type of records management business process improvements should my agency strive to achieve?

Code of Federal Regulations, 2014 CFR

2014-01-01

... 41 Public Contracts and Property Management 3 2014-01-01 2014-01-01 false What type of records management business process improvements should my agency strive to achieve? 102-193.25 Section 102-193.25...-193.25 What type of records management business process improvements should my agency strive to...

41 CFR 102-193.25 - What type of records management business process improvements should my agency strive to achieve?

Code of Federal Regulations, 2012 CFR

2012-01-01

... 41 Public Contracts and Property Management 3 2012-01-01 2012-01-01 false What type of records management business process improvements should my agency strive to achieve? 102-193.25 Section 102-193.25...-193.25 What type of records management business process improvements should my agency strive to...

Estimating the Propagation of Interdependent Cascading Outages with Multi-Type Branching Processes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Qi, Junjian; Ju, Wenyun; Sun, Kai

In this paper, the multi-type branching process is applied to describe the statistics and interdependencies of line outages, the load shed, and isolated buses. The offspring mean matrix of the multi-type branching process is estimated by the Expectation Maximization (EM) algorithm and can quantify the extent of outage propagation. The joint distribution of two types of outages is estimated by the multi-type branching process via the Lagrange-Good inversion. The proposed model is tested with data generated by the AC OPA cascading simulations on the IEEE 118-bus system. The largest eigenvalues of the offspring mean matrix indicate that the system ismore » closer to criticality when considering the interdependence of different types of outages. Compared with empirically estimating the joint distribution of the total outages, good estimate is obtained by using the multitype branching process with a much smaller number of cascades, thus greatly improving the efficiency. It is shown that the multitype branching process can effectively predict the distribution of the load shed and isolated buses and their conditional largest possible total outages even when there are no data of them.« less

Synergistic responses of superficial chemistry and micro topography of titanium created by wire-type electric discharge machining.

PubMed

Kataoka, Yu; Tamaki, Yukimichi; Miyazaki, Takashi

2011-01-01

Wire-type electric discharge machining has been applied to the manufacture of endosseous titanium implants as this computer associated technique allows extremely accurate complex sample shaping with an optimal micro textured surface during the processing. Since the titanium oxide layer is sensitively altered by each processing, the authors hypothesized that this technique also up-regulates biological responses through the synergistic effects of the superficial chemistry and micro topography. To evaluate the respective in vitro cellular responses on the superficial chemistry and micro topography of titanium surface processed by wire-type electric discharge, we used titanium-coated epoxy resin replica of the surface. An oxide layer on the titanium surface processed by wire-type electric discharge activated the initial responses of osteoblastic cells through an integrin-mediated mechanism. Since the mRNA expression of ALP on those replicas was up-regulated compared to smooth titanium samples, the micro topography of a titanium surface processed by wire-type electric discharge promotes the osteogenic potential of cells. The synergistic response of the superficial chemistry and micro topography of titanium processed by wire-type electric discharge was demonstrated in this study.

Monolithic high voltage nonlinear transmission line fabrication process

DOEpatents

Cooper, Gregory A.

1994-01-01

A process for fabricating sequential inductors and varactor diodes of a monolithic, high voltage, nonlinear, transmission line in GaAs is disclosed. An epitaxially grown laminate is produced by applying a low doped active n-type GaAs layer to an n-plus type GaAs substrate. A heavily doped p-type GaAs layer is applied to the active n-type layer and a heavily doped n-type GaAs layer is applied to the p-type layer. Ohmic contacts are applied to the heavily doped n-type layer where diodes are desired. Multiple layers are then either etched away or Oxygen ion implanted to isolate individual varactor diodes. An insulator is applied between the diodes and a conductive/inductive layer is thereafter applied on top of the insulator layer to complete the process.

Turbine blade processing

NASA Technical Reports Server (NTRS)

1975-01-01

Space processing of directionally solidified eutectic-alloy type turbine blades is envisioned as a simple remelt operations in which precast blades are remelted in a preformed mold. Process systems based on induction melting, continuous resistance furnaces, and batch resistance furnaces were evaluated. The batch resistance furnace type process using a multiblade mold is considered to offer the best possibility for turbine blade processing.

Polymer dispensing and embossing technology for the lens type LED packaging

NASA Astrophysics Data System (ADS)

Chien, Chien-Lin Chang; Huang, Yu-Che; Hu, Syue-Fong; Chang, Chung-Min; Yip, Ming-Chuen; Fang, Weileun

2013-06-01

This study presents a ring-type micro-structure design on the substrate and its corresponding micro fabrication processes for a lens-type light-emitting diode (LED) package. The dome-type or crater-type silicone lenses are achieved by a dispensing and embossing process rather than a molding process. Silicone with a high viscosity and thixotropy index is used as the encapsulant material. The ring-type micro structure is adopted to confine the dispensed silicone encapsulant so as to form the packaged lens. With the architecture and process described, this LED package technology herein has three merits: (1) the flexibility of lens-type LED package designs is enhanced; (2) a dome-type package design is used to enhance the intensity; (3) a crater-type package design is used to enhance the view angle. Measurement results show the ratio between the lens height and lens radius can vary from 0.4 to 1 by changing the volume of dispensed silicone. The view angles of dome-type and crater-type packages can reach 155° ± 5° and 175° ± 5°, respectively. As compared with the commercial plastic leaded chip carrier-type package, the luminous flux of a monochromatic blue light LED is improved by 15% by the dome-type package (improved by 7% by the crater-type package) and the luminous flux of a white light LED is improved by 25% by the dome-type package (improved by 13% by the crater-type package). The luminous flux of monochromatic blue light LED and white light LED are respectively improved by 8% and 12% by the dome-type package as compare with the crater-type package.

Health-Related Intensity Profiles of Physical Education Classes at Different Phases of the Teaching/Learning Process

ERIC Educational Resources Information Center

Bronikowski, Michal; Bronikowska, Malgorzata; Kantanista, Adam; Ciekot, Monika; Laudanska-Krzeminska, Ida; Szwed, Szymon

2009-01-01

Study aim: To assess the intensities of three types of physical education (PE) classes corresponding to the phases of the teaching/learning process: Type 1--acquiring and developing skills, Type 2--selecting and applying skills, tactics and compositional principles and Type 3--evaluating and improving performance skills. Material and methods: A…

Urban land use monitoring from computer-implemented processing of airborne multispectral data

NASA Technical Reports Server (NTRS)

Todd, W. J.; Mausel, P. W.; Baumgardner, M. F.

1976-01-01

Machine processing techniques were applied to multispectral data obtained from airborne scanners at an elevation of 600 meters over central Indianapolis in August, 1972. Computer analysis of these spectral data indicate that roads (two types), roof tops (three types), dense grass (two types), sparse grass (two types), trees, bare soil, and water (two types) can be accurately identified. Using computers, it is possible to determine land uses from analysis of type, size, shape, and spatial associations of earth surface images identified from multispectral data. Land use data developed through machine processing techniques can be programmed to monitor land use changes, simulate land use conditions, and provide impact statistics that are required to analyze stresses placed on spatial systems.

Visualizing tissue molecular structure of a black type of canola (Brassica) seed with a thick seed coat after heat-related processing in a chemical way.

PubMed

Yu, Peiqiang

2013-02-20

Heat-related processing of cereal grains, legume seeds, and oil seeds could be used to improve nutrient availability in ruminants. However, different types of processing may have a different impact on intrinsic structure of tissues. To date, there is little research on structure changes after processing within intact tissues. The synchrotron-based molecular imaging technique enables us to detect inherent structure change on a molecular level. The objective of this study was to visualize tissue of black-type canola (Brassica) seed with a thick seed coat after heat-related processing in a chemical way using the synchrotron imaging technique. The results showed that the chemical images of protein amides were obtained through the imaging technique for the raw, wet, and dry heated black type of canola seed tissues. It seems that different types of processing have a different impact on the protein spectral profile in the black type of canola tissues. Wet heating had a greater impact on the protein α-helix to β-sheet ratio than dry heating. Both dry and wet heating resulted in different patterns in amide I, the second derivative, and FSD spectra. However, the exact differences in the tissue images are relatively difficult to be obtained through visual comparison. Future studies should focus on (1) comparing the response and sensitivity of canola seeds to various processing methods between the yellow-type and black-type of canola seeds; (2) developing a sensitive method to compare the image difference between tissues and between treatments; (3) developing a method to link images to nutrient digestion, and (4) revealing how structure changes affect nutrient absorption in humans and animals.

Processable high temperature resistant addition type polyimide laminating resins

NASA Technical Reports Server (NTRS)

Serafini, T. T.; Delvigs, P.

1973-01-01

Basic studies that were performed using model compounds to elucidate the polymerization mechanism of the so-called addition-type (A-type) polyimides are reviewed. The fabrication and properties of polyimide/graphite fiber composites using A-type polyimide prepolymers as the matrix are also reviewed. An alternate method for preparing processable A-type polyimides by means of in situ polymerization of monomer reactants (PMR) on the fiber reinforcement is described. The elevated temperature properties of A-type PMR/graphite fiber composites are also presented.

Incidence and properties of Staphylococcus aureus associated with turkeys during processing and further-processing operations.

PubMed

Adams, B W; Mead, G C

1983-12-01

The incidence of Staphylococcus aureus on turkeys sampled at various stages of processing and further-processing was determined on four occasions at each of three different processing plants. For freshly-slaughtered birds, counts from neck skin varied from plant to plant over the range less than 10(2) to greater than 10(5)/g but in all cases the corresponding counts obtained from carcasses sampled after chilling rarely exceeded 10(3)/g and the same was true for samples of mechanically recovered meat (MRM), the final raw product examined. Despite the limited susceptibility of isolates from the different factories to typing by means of either standard human or poultry bacteriophages (55-94% untypable), evidence was obtained with the aid of biotyping for the presence of both human and animal-derived strains. However, some biotypes isolated from MRM were not detected at earlier stages of processing. At one processing plant, an "indigenous' type of S. aureus was clearly demonstrated. It occurred in high numbers in the defeathering machines (up to 10(5)/swab), was found on carcasses at all subsequent stages of processing over the survey period and was shown to survive routine cleaning and disinfection procedures. Isolates of this type produced unusually large amounts of extracellular "slime' in artificial culture. Two of the three processing plants yielded isolates which were enterotoxigenic. Of 55 strains from Plant 1, 60% produced enterotoxin C and all were of the "indigenous' type. In the case of Plant 2, only two type D- and one type F-producing strain were found.

Incidence and properties of Staphylococcus aureus associated with turkeys during processing and further-processing operations.

PubMed Central

Adams, B. W.; Mead, G. C.

1983-01-01

The incidence of Staphylococcus aureus on turkeys sampled at various stages of processing and further-processing was determined on four occasions at each of three different processing plants. For freshly-slaughtered birds, counts from neck skin varied from plant to plant over the range less than 10(2) to greater than 10(5)/g but in all cases the corresponding counts obtained from carcasses sampled after chilling rarely exceeded 10(3)/g and the same was true for samples of mechanically recovered meat (MRM), the final raw product examined. Despite the limited susceptibility of isolates from the different factories to typing by means of either standard human or poultry bacteriophages (55-94% untypable), evidence was obtained with the aid of biotyping for the presence of both human and animal-derived strains. However, some biotypes isolated from MRM were not detected at earlier stages of processing. At one processing plant, an "indigenous' type of S. aureus was clearly demonstrated. It occurred in high numbers in the defeathering machines (up to 10(5)/swab), was found on carcasses at all subsequent stages of processing over the survey period and was shown to survive routine cleaning and disinfection procedures. Isolates of this type produced unusually large amounts of extracellular "slime' in artificial culture. Two of the three processing plants yielded isolates which were enterotoxigenic. Of 55 strains from Plant 1, 60% produced enterotoxin C and all were of the "indigenous' type. In the case of Plant 2, only two type D- and one type F-producing strain were found. PMID:6663063

Monolithic high voltage nonlinear transmission line fabrication process

DOEpatents

Cooper, G.A.

1994-10-04

A process for fabricating sequential inductors and varistor diodes of a monolithic, high voltage, nonlinear, transmission line in GaAs is disclosed. An epitaxially grown laminate is produced by applying a low doped active n-type GaAs layer to an n-plus type GaAs substrate. A heavily doped p-type GaAs layer is applied to the active n-type layer and a heavily doped n-type GaAs layer is applied to the p-type layer. Ohmic contacts are applied to the heavily doped n-type layer where diodes are desired. Multiple layers are then either etched away or Oxygen ion implanted to isolate individual varistor diodes. An insulator is applied between the diodes and a conductive/inductive layer is thereafter applied on top of the insulator layer to complete the process. 6 figs.

Morphological evidence for local microcircuits in rat vestibular maculae

NASA Technical Reports Server (NTRS)

Ross, M. D.

1997-01-01

Previous studies suggested that intramacular, unmyelinated segments of vestibular afferent nerve fibers and their large afferent endings (calyces) on type I hair cells branch. Many of the branches (processes) contain vesicles and are presynaptic to type II hair cells, other processes, intramacular nerve fibers, and calyces. This study used serial section transmission electron microscopy and three-dimensional reconstruction methods to document the origins and distributions of presynaptic processes of afferents in the medial part of the adult rat utricular macula. The ultrastructural research focused on presynaptic processes whose origin and termination could be observed in a single micrograph. Results showed that calyces had 1) vesiculated, spine-like processes that invaginated type I cells and 2) other, elongate processes that ended on type II cells pre- as well as postsynaptically. Intramacular, unmyelinated segments of afferent nerve fibers gave origin to branches that were presynaptic to type II cells, calyces, calyceal processes, and other nerve fibers in the macula. Synapses with type II cells occurred opposite subsynaptic cisternae (C synapses); all other synapses were asymmetric. Vesicles were pleomorphic but were differentially distributed according to process origin. Small, clear-centered vesicles, approximately 40-60 nm in diameter, predominated in processes originating from afferent nerve fibers and basal parts of calyces. Larger vesicles approximately 70-120 nm in diameter having approximately 40-80 nm electron-opaque cores were dominant in processes originating from the necks of calyces. Results are interpreted to indicate the existence of a complex system of intrinsic feedforward (postsynaptic)-feedback (presynaptic) connections in a network of direct and local microcircuits. The morphological findings support the concept that maculae dynamically preprocess linear acceleratory information before its transmission to the central nervous system.

[Advance in interferogram data processing technique].

PubMed

Jing, Juan-Juan; Xiangli, Bin; Lü, Qun-Bo; Huang, Min; Zhou, Jin-Song

2011-04-01

Fourier transform spectrometry is a type of novel information obtaining technology, which integrated the functions of imaging and spectra, but the data that the instrument acquired is the interference data of the target, which is an intermediate data and couldn't be used directly, so data processing must be adopted for the successful application of the interferometric data In the present paper, data processing techniques are divided into two classes: general-purpose and special-type. First, the advance in universal interferometric data processing technique is introduced, then the special-type interferometric data extracting method and data processing technique is illustrated according to the classification of Fourier transform spectroscopy. Finally, the trends of interferogram data processing technique are discussed.

Exploring the Image Types of Secondary School Students' Perception about the Talented Person in Convergence

NASA Astrophysics Data System (ADS)

Lee, Jun-Ki; Chung, Duk Ho

2014-05-01

This study aims to identify the image types of secondary school students' perception about the talented person in convergence and to find the differences in drawing images of the talented person in convergence among the students who have taken STEAM class and the ones who haven't. One hundred and eighty seven students in middle and high schools located in the southern part of South Korea participated in this study and they were asked to draw a picture of the talented person in convergence with a brief explanation. Based on students' pictures, researchers categorized their perception about convergence and talented person in convergence by using an inductive method. The result indicated that secondary school students' perceptions were categorized into convergence as individual cognitive processing and collective cognitive processing and convergence as outcomes. The image of the convergence in a talented person leaning toward individual cognitive processing was divided into the following seven types: idea banker type, various talented celebrity type, multi-tasking master type, multi-talented career type, active problem-solver type, creative developer type, and unrealistic ideal man type. Another image of collective cognitive processing was split into expert group type and interactive-mates group type. The other image was transformer type which is the subcategory of convergence as outcomes. From this study, it can be suggested that secondary school students express the various images of the talented person in convergence depending on experiencing STEAM or not. Keywords: talented person in convergence, secondary school students, STEAM, image types

Hermite-Hadamard type inequality for φ{sub h}-convex stochastic processes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sarıkaya, Mehmet Zeki, E-mail: sarikayamz@gmail.com; Kiriş, Mehmet Eyüp, E-mail: kiris@aku.edu.tr; Çelik, Nuri, E-mail: ncelik@bartin.edu.tr

2016-04-18

The main aim of the present paper is to introduce φ{sub h}-convex stochastic processes and we investigate main properties of these mappings. Moreover, we prove the Hadamard-type inequalities for φ{sub h}-convex stochastic processes. We also give some new general inequalities for φ{sub h}-convex stochastic processes.

Development of iFab (Instant Foundry Adaptive Through Bits) Manufacturing Process and Machine Library

DTIC Science & Technology

2012-08-01

loaded joints including bearing -type shear loaded joints and friction type shear loaded joints . Appendix Figure 2f.A-3 shows an illustration of each... Loaded Joint Bearing Type Shear Loaded Joint Friction Type Shear Loaded Joint Tension Loaded Joint 62 Approved for public release...Joining of materials and structures: from pragmatic process to enabling technology.

PIDs, Types and the Semantic Web

NASA Astrophysics Data System (ADS)

Schwardmann, Ulrich

2017-04-01

PID Information Types are becoming a crucial role in scientific data management because they can provide state (what) and binding (where) information about digital objects as attributes of the PID. This is a similar but much more flexible approach than the well known mime type characterization, because both of these types concepts allow to decide about preconditions for processes in advance and before touching the data. One aspect of this is the need for standards and correctness of the used types to ensure reliability for the processes operating on the digital objects. This requires registries and schemas for PID InfoTypes and suggests an automated schema generation process. Such a process in combination with data type registries will be described in more detail in the intended talk. Another aspect of PID InfoTypes is its intrinsic grammar as subject-predicate-object triple, with the PID as subject, the type as predicate and its value (often again a PID) as object in this relation. Given the registration of types and the proposed syntactical rigidness of the value, guaranteed by the schema, together with the use of PIDs in subject and predicate, the type concept has the ability to overcome the fuzziness and lack of reliability of semantic web categories with its URL references and possibly changing locations and content. The intended talk will also describe this approach in more detail, discusses the differences to linked data and describes some necessary technological developments for the type concept to keep up with the possibilities currently provided by the semantic web.

A Computer-Aided Type-II Fuzzy Image Processing for Diagnosis of Meniscus Tear.

PubMed

Zarandi, M H Fazel; Khadangi, A; Karimi, F; Turksen, I B

2016-12-01

Meniscal tear is one of the prevalent knee disorders among young athletes and the aging population, and requires correct diagnosis and surgical intervention, if necessary. Not only the errors followed by human intervention but also the obstacles of manual meniscal tear detection highlight the need for automatic detection techniques. This paper presents a type-2 fuzzy expert system for meniscal tear diagnosis using PD magnetic resonance images (MRI). The scheme of the proposed type-2 fuzzy image processing model is composed of three distinct modules: Pre-processing, Segmentation, and Classification. λ-nhancement algorithm is used to perform the pre-processing step. For the segmentation step, first, Interval Type-2 Fuzzy C-Means (IT2FCM) is applied to the images, outputs of which are then employed by Interval Type-2 Possibilistic C-Means (IT2PCM) to perform post-processes. Second stage concludes with re-estimation of "η" value to enhance IT2PCM. Finally, a Perceptron neural network with two hidden layers is used for Classification stage. The results of the proposed type-2 expert system have been compared with a well-known segmentation algorithm, approving the superiority of the proposed system in meniscal tear recognition.

There is more than one way to turn a spherical cellular monolayer inside out: type B embryo inversion in Volvox globator

PubMed Central

2011-01-01

Background Epithelial folding is a common morphogenetic process during the development of multicellular organisms. In metazoans, the biological and biomechanical processes that underlie such three-dimensional (3D) developmental events are usually complex and difficult to investigate. Spheroidal green algae of the genus Volvox are uniquely suited as model systems for studying the basic principles of epithelial folding. Volvox embryos begin life inside out and then must turn their spherical cell monolayer outside in to achieve their adult configuration; this process is called 'inversion.' There are two fundamentally different sequences of inversion processes in Volvocaceae: type A and type B. Type A inversion is well studied, but not much is known about type B inversion. How does the embryo of a typical type B inverter, V. globator, turn itself inside out? Results In this study, we investigated the type B inversion of V. globator embryos and focused on the major movement patterns of the cellular monolayer, cell shape changes and changes in the localization of cytoplasmic bridges (CBs) connecting the cells. Isolated intact, sectioned and fragmented embryos were analyzed throughout the inversion process using light microscopy, confocal laser scanning microscopy, scanning electron microscopy and transmission electron microscopy techniques. We generated 3D models of the identified cell shapes, including the localizations of CBs. We show how concerted cell-shape changes and concerted changes in the position of cells relative to the CB system cause cell layer movements and turn the spherical cell monolayer inside out. The type B inversion of V. globator is compared to the type A inversion in V. carteri. Conclusions Concerted, spatially and temporally coordinated changes in cellular shapes in conjunction with concerted migration of cells relative to the CB system are the causes of type B inversion in V. globator. Despite significant similarities between type A and type B inverters, differences exist in almost all details of the inversion process, suggesting analogous inversion processes that arose through parallel evolution. Based on our results and due to the cellular biomechanical implications of the involved tensile and compressive forces, we developed a global mechanistic scenario that predicts epithelial folding during embryonic inversion in V. globator. PMID:22206406

Controlling the type and the form of chip when machining steel

NASA Astrophysics Data System (ADS)

Gruby, S. V.; Lasukov, A. A.; Nekrasov, R. Yu; Politsinsky, E. V.; Arkhipova, D. A.

2016-08-01

The type of the chip produced in the process of machining influences many factors of production process. Controlling the type of chip when cutting metals is important for producing swarf chips and for easing its utilization as well as for protecting the machined surface, cutting tool and the worker. In the given work we provide the experimental data on machining structural steel with implanted tool. The authors show that it is possible to control the chip formation process to produce the required type of chip by selecting the material for machining the tool surface.

Convergence to Diagonal Form of Block Jacobi-type Processes

NASA Astrophysics Data System (ADS)

Hari, Vjeran

2008-09-01

The main result of recent research on convergence to diagonal form of block Jacobi-type processes is presented. For this purpose, all notions needed to describe the result are introduced. In particular, elementary block transformation matrices, simple and non-simple algorithms, block pivot strategies together with the appropriate equivalence relations are defined. The general block Jacobi-type process considered here can be specialized to take the form of almost any known Jacobi-type method for solving the ordinary or the generalized matrix eigenvalue and singular value problems. The assumptions used in the result are satisfied by many concrete methods.

Information Use Differences in Hot and Cold Risk Processing: When Does Information About Probability Count in the Columbia Card Task?

PubMed

Markiewicz, Łukasz; Kubińska, Elżbieta

2015-01-01

This paper aims to provide insight into information processing differences between hot and cold risk taking decision tasks within a single domain. Decision theory defines risky situations using at least three parameters: outcome one (often a gain) with its probability and outcome two (often a loss) with a complementary probability. Although a rational agent should consider all of the parameters, s/he could potentially narrow their focus to only some of them, particularly when explicit Type 2 processes do not have the resources to override implicit Type 1 processes. Here we investigate differences in risky situation parameters' influence on hot and cold decisions. Although previous studies show lower information use in hot than in cold processes, they do not provide decision weight changes and therefore do not explain whether this difference results from worse concentration on each parameter of a risky situation (probability, gain amount, and loss amount) or from ignoring some parameters. Two studies were conducted, with participants performing the Columbia Card Task (CCT) in either its Cold or Hot version. In the first study, participants also performed the Cognitive Reflection Test (CRT) to monitor their ability to override Type 1 processing cues (implicit processes) with Type 2 explicit processes. Because hypothesis testing required comparison of the relative importance of risky situation decision weights (gain, loss, probability), we developed a novel way of measuring information use in the CCT by employing a conjoint analysis methodology. Across the two studies, results indicated that in the CCT Cold condition decision makers concentrate on each information type (gain, loss, probability), but in the CCT Hot condition they concentrate mostly on a single parameter: probability of gain/loss. We also show that an individual's CRT score correlates with information use propensity in cold but not hot tasks. Thus, the affective dimension of hot tasks inhibits correct information processing, probably because it is difficult to engage Type 2 processes in such circumstances. Individuals' Type 2 processing abilities (measured by the CRT) assist greater use of information in cold tasks but do not help in hot tasks.

Information Use Differences in Hot and Cold Risk Processing: When Does Information About Probability Count in the Columbia Card Task?

PubMed Central

Markiewicz, Łukasz; Kubińska, Elżbieta

2015-01-01

Objective: This paper aims to provide insight into information processing differences between hot and cold risk taking decision tasks within a single domain. Decision theory defines risky situations using at least three parameters: outcome one (often a gain) with its probability and outcome two (often a loss) with a complementary probability. Although a rational agent should consider all of the parameters, s/he could potentially narrow their focus to only some of them, particularly when explicit Type 2 processes do not have the resources to override implicit Type 1 processes. Here we investigate differences in risky situation parameters' influence on hot and cold decisions. Although previous studies show lower information use in hot than in cold processes, they do not provide decision weight changes and therefore do not explain whether this difference results from worse concentration on each parameter of a risky situation (probability, gain amount, and loss amount) or from ignoring some parameters. Methods: Two studies were conducted, with participants performing the Columbia Card Task (CCT) in either its Cold or Hot version. In the first study, participants also performed the Cognitive Reflection Test (CRT) to monitor their ability to override Type 1 processing cues (implicit processes) with Type 2 explicit processes. Because hypothesis testing required comparison of the relative importance of risky situation decision weights (gain, loss, probability), we developed a novel way of measuring information use in the CCT by employing a conjoint analysis methodology. Results: Across the two studies, results indicated that in the CCT Cold condition decision makers concentrate on each information type (gain, loss, probability), but in the CCT Hot condition they concentrate mostly on a single parameter: probability of gain/loss. We also show that an individual's CRT score correlates with information use propensity in cold but not hot tasks. Thus, the affective dimension of hot tasks inhibits correct information processing, probably because it is difficult to engage Type 2 processes in such circumstances. Individuals' Type 2 processing abilities (measured by the CRT) assist greater use of information in cold tasks but do not help in hot tasks. PMID:26635652

How to select combination operators for fuzzy expert systems using CRI

NASA Technical Reports Server (NTRS)

Turksen, I. B.; Tian, Y.

1992-01-01

A method to select combination operators for fuzzy expert systems using the Compositional Rule of Inference (CRI) is proposed. First, fuzzy inference processes based on CRI are classified into three categories in terms of their inference results: the Expansion Type Inference, the Reduction Type Inference, and Other Type Inferences. Further, implication operators under Sup-T composition are classified as the Expansion Type Operator, the Reduction Type Operator, and the Other Type Operators. Finally, the combination of rules or their consequences is investigated for inference processes based on CRI.

Examining the Affordances of Dual Cognitive Processing to Explain the Development of High School Students' Nature of Science Views

ERIC Educational Resources Information Center

Jackson, Luke M.

2017-01-01

This mixed method study was aimed at examining the influence of dual processing (Type 1 and Type 2 thinking) on the development of high school students' nature of science (NOS) views. Type 1 thinking is intuitive, experiential, and heuristic. Type 2 thinking is rational, analytical, and explicit. Three research questions were asked: (1) Do the…

Pure silver ohmic contacts to N- and P- type gallium arsenide materials

DOEpatents

Hogan, Stephen J.

1986-01-01

Disclosed is an improved process for manufacturing gallium arsenide semiconductor devices having as its components an n-type gallium arsenide substrate layer and a p-type gallium arsenide diffused layer. The improved process comprises forming a pure silver ohmic contact to both the diffused layer and the substrate layer, wherein the n-type layer comprises a substantially low doping carrier concentration.

48 CFR 1513.507 - Clauses.

Code of Federal Regulations, 2013 CFR

2013-10-01

... automatic data processing equipment, word processing, and similar types of commercially available equipment... CONTRACT TYPES SIMPLIFIED ACQUISITION PROCEDURES Purchase Orders 1513.507 Clauses. (a) It is the general...

Fast logic?: Examining the time course assumption of dual process theory.

PubMed

Bago, Bence; De Neys, Wim

2017-01-01

Influential dual process models of human thinking posit that reasoners typically produce a fast, intuitive heuristic (i.e., Type-1) response which might subsequently be overridden and corrected by slower, deliberative processing (i.e., Type-2). In this study we directly tested this time course assumption. We used a two response paradigm in which participants have to give an immediate answer and afterwards are allowed extra time before giving a final response. In four experiments we used a range of procedures (e.g., challenging response deadline, concurrent load) to knock out Type 2 processing and make sure that the initial response was intuitive in nature. Our key finding is that we frequently observe correct, logical responses as the first, immediate response. Response confidence and latency analyses indicate that these initial correct responses are given fast, with high confidence, and in the face of conflicting heuristic responses. Findings suggest that fast and automatic Type 1 processing also cues a correct logical response from the start. We sketch a revised dual process model in which the relative strength of different types of intuitions determines reasoning performance. Copyright © 2016 Elsevier B.V. All rights reserved.

The effects of intermittent calorie restriction on metabolic health: Rationale and study design of the HELENA Trial.

PubMed

Schübel, Ruth; Graf, Mirja E; Nattenmüller, Johanna; Nabers, Diana; Sookthai, Disorn; Gruner, Laura F; Johnson, Theron; Schlett, Christopher L; von Stackelberg, Oyunbileg; Kirsten, Romy; Habermann, Nina; Kratz, Mario; Kauczor, Hans-Ulrich; Ulrich, Cornelia M; Kaaks, Rudolf; Kühn, Tilman

2016-11-01

Mechanistic studies suggest benefits of intermittent calorie restriction (ICR) in chronic disease prevention that may exceed those of continuous calorie restriction (CCR), even at equal net calorie intake. Despite promising results from first trials, it remains largely unknown whether ICR-induced metabolic alterations reported from experimental studies can also be observed in humans, and whether ICR diets are practicable and effective in real life situations. Thus, we initiated the HELENA Trial to test the effects of ICR (eu-caloric diet on five days and very low energy intake on two days per week) on metabolic parameters and body composition over one year. We will assess the effectiveness of ICR compared to CCR and a control diet over a 12-week intervention, 12-week maintenance phase and 24-week follow-up in 150 overweight or obese non-smoking adults (50 per group, 50% women). Our primary endpoint is the difference between ICR and CCR with respect to fold-changes in expression levels of 82 candidate genes in abdominal subcutaneous adipose tissue biopsies (SATb) during the intervention phase. The candidate genes represent pathways, which may link obesity-related metabolic alterations with the risk for major chronic diseases. In secondary and exploratory analyses, changes in metabolic, hormonal, inflammatory and metagenomic parameters measured in different biospecimens (SATb, blood, urine, stool) are investigated and effects of ICR/CCR/control on imaging-based measures of subcutaneous, visceral and hepatic fat are evaluated. Our study is the first randomized trial over one year testing the effects of ICR on metabolism, body composition and psychosocial factors in humans. Copyright © 2016 Elsevier Inc. All rights reserved.

Can we unlock the potential of IGF-1R inhibition in cancer therapy?

PubMed Central

King, Helen; Aleksic, Tamara; Haluska, Paul; Macaulay, Valentine M.

2014-01-01

IGF-1R inhibitors arrived in the clinic accompanied by optimism based on preclinical activity of IGF-1R targeting, and recognition that low IGF bioactivity protects from cancer. This was tempered by concerns about toxicity to normal tissue IGF-1R and cross-reactivity with insulin receptor (InsR). In fact, toxicity is not a show-stopper; the key issue is efficacy. While IGF-1R inhibition induces responses as monotherapy in sarcomas and with chemotherapy or targeted agents in common cancers, negative Phase 2/3 trials in unselected patients prompted the cessation of several Pharma programs. Here, we review completed and on-going trials of IGF-1R antibodies, kinase inhibitors and ligand antibodies. We assess candidate bio-markers for patient selection, highlighting the potential predictive value of circulating IGFs/IGFBPs, the need for standardized assays for IGF-1R, and preclinical evidence that variant InsRs mediate resistance to IGF-1R antibodies. We review hypothesis-led and unbiased approaches to evaluate IGF-1R inhibitors with other agents, and stress the need to consider sequencing with chemotherapy. The last few years were a tough time for IGF-1R therapeutics, but also brought progress in understanding IGF biology. Even failed studies include patients who derived benefit; they should be investigated to identify features distinguishing the tumors and host environment of responders from non-responders. We emphasize the importance of incorporating biospecimen collection into trial design, and wording patient consents to allow post hoc analysis of trial material as new data become available. Such information represents the key to unlocking the potential of this approach, to inform the next generation of trials of IGF signalling inhibitors. PMID:25123819

Longitudinal Change in Telomere Length and the Chronic Stress Response in a Randomized Pilot Biobehavioral Clinical Study: Implications for Cancer Prevention

PubMed Central

Biegler, Kelly A.; Anderson, Amanda K. L.; Wenzel, Lari B.; Osann, Kathryn; Nelson, Edward L.

2015-01-01

Shortened telomere length is associated with increased cancer incidence and mortality. Populations experiencing chronic stress have accelerated telomere shortening. In this exploratory study, we examined associations between longitudinal changes in patient reported outcomes (PRO) of psychologic distress and peripheral blood mononuclear cell (PBMC) telomere length to test the hypothesis that modulation of the chronic stress response would also modulate telomere dynamics. Archived PBMC specimens (N = 22) were analyzed from a completed and reported randomized, longitudinal trial that showed a psychosocial telephone counseling intervention improved quality of life (QOL) and modulated stress-associated biomarkers in cervical cancer survivors. PROs and biospecimens were collected at baseline and 4 months postenrollment. Telomere length of archived PBMCs was evaluated using the flow-FISH assay. Longitudinal changes in psychologic distress, measured by the Brief Symptom Inventory-18, were significantly associated with increased telomere length within the CD14+ (monocyte) population (r = 0.46, P = 0.043); a similar trend was observed for the CD14− population. Longitudinal changes in telomere length of the CD14− subset, primarily T lymphocytes, were associated with longitudinal increases in the naive T-cell population (r = 0.49, P = 0.052). Alterations in the chronic stress response were associated with modulation of telomere length in PBMCs, with evidence for mobilization of “younger” cells from progenitor populations. These data provide preliminary support for the (i) capacity to modulate the chronic stress response and the associated accelerated telomere shortening, (ii) inclusion of telomere length in the biobehavioral paradigm, and (iii) potential link between the chronic stress response and biologic mechanisms responsible for genomic integrity and carcinogenesis. PMID:22827974