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

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.

Genomic Research with Organs and Tissues Originating from Transplant Donors: Ethical Considerations for the GTEx Project.

The Genotype-Tissue Expression (GTEx) project aims to study human gene expression and regulation in multiple tissues from individual post-mortem biospecimen donors. This case report involves GTEx donors who were discovered after biospecimen collection to have been the recipients of solid organ or tissue transplants for therapeutic purposes. This scenario prompted us to consider whether authorization from the GTEx research donor’s next of kin was legally and ethically acceptable to allow genomic research on tissue originally derived from a therapeutic organ donor.

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

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.

Meeting research needs with postmortem biospecimen donation: summary of recommendations for postmortem recovery of normal human biospecimens for research.

Normal human tissues, bodily fluids, and other biospecimens of known quality are essential for research to understand the development of cancer and other diseases and to develop new diagnostics and therapies. However, obtaining normal biospecimens appropriate for contemporary large-scale molecular and genomic research is one of the most challenging biospecimen acquisition problems for scientists and biospecimen resources that support research. Recognizing this challenge, the U.

The Ethical, Legal, and Social Implications Program of the National Human Genome Research Institute: reflections on an ongoing experiment.

For more than 20 years, the Ethical, Legal, and Social Implications (ELSI) Program of the National Human Genome Research Institute has supported empirical and conceptual research to anticipate and address the ethical, legal, and social implications of genomics. As a component of the agency that funds much of the underlying science, the program has always been an experiment. The ever-expanding number of issues the program addresses and the relatively low level of commitment on the part of other funding agencies to support such research make setting priorities especially challenging.

NCI think tank concerning the identifiability of biospecimens and "omic" data.

Purpose: On 11 and 12 June 2012, the National Cancer Institute hosted a think tank concerning the identifiability of biospecimens and "omic" data in order to explore challenges surrounding this complex and multifaceted topic.

Methods: The think tank brought together 46 leaders from several fields, including cancer genomics, bioinformatics, human subject protection, patient advocacy, and commercial genetics.

Results: The first day involved presentations regarding the state of the science of reidentification; current and proposed regulatory frameworks for assessing identifiability; developments in law, industry, and biotechnology; and the expectations of patients and research participants.

The evolution of biobanking best practices.

Biobanks and biospecimens are critical components for many areas of clinical and basic research. The quality of biospecimens and associated data must be consistent and collected according to standardized methods in order to prevent spurious analytical results that can lead to artifacts being interpreted as valid findings. A number of international institutions have taken the initiative to develop and publish best practices, which include technical recommendations for handling biospecimens as well as recommendations for ethical and regulatory practices in biobanking.

Intersection of biobanking and clinical care: should discrepant diagnoses and pathological findings be returned to research participants?

Diagnostic discrepancies occur when the diagnosis made on a biospecimen during the course of review at a biobank differs from the original clinical diagnosis. These diagnostic discrepancies detected during biobanking present unique challenges that are distinct from other types of research results or incidental findings. The proposed process for reporting diagnostic discrepancies or pathological incidental findings identified through a quality assurance evaluation at the biobank includes verification of the biospecimen identity, verification of the diagnosis within the biobank, and re-review of the case by the pathologist at the biospecimen collection site.

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

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.

Neutrophil accumulation following passive stretches contributes to adaptations that reduce contraction-induced skeletal muscle injury in mice.

Skeletal muscles can be injured by their own contractions, especially when the muscle is stretched during a lengthening contraction. Exposing a muscle to a conditioning protocol of stretches without activation (passive stretches) before lengthening contractions reduces contraction-induced injury. Although passive stretching does not damage muscle fibers, neutrophils are elevated in the muscle after passive stretches.

Protection from contraction-induced injury provided to skeletal muscles of young and old mice by passive stretch is not due to a decrease in initial mechanical damage.

Contraction-induced injury occurs when muscles are stretched while activated (lengthening contractions). The injury is initiated by mechanical damage followed by an inflammatory response. Old animals are particularly susceptible to contraction-induced injury, yet exposure to stretches without activation (passive stretches) before lengthening contractions lessens the injury.

Activation of Akt as a potential mediator of adaptations that reduce muscle injury.

Unlabelled: Contraction-induced injury occurs when a muscle is stretched while activated (lengthening contraction). Exposure to a bout of lengthening contractions results in protection from subsequent lengthening contraction-induced injury as well as an elevation in phosphorylated Akt and p70S6K. Whether Akt or p70S6K is involved in the protection from contraction-induced injury is unclear.