Characterizing Gender Eligibility Descriptions for Clinical Trials Registered on ClinicalTrials.gov.

This cross-sectional, exploratory study uses ClinicalTrials.gov data from trials initiated on or after January 18, 2017, to characterize the use of a new free-text "gender eligibility description" data field; reports the frequency of gender identity terms used; and assesses the correct or incorrect use of the field.

Reproducibility and Rigor in Animal-Based Research.

Increasing focus on issues of research reproducibility affords us the opportunity to review some of the key issues related in vivo research. First, we set out some key definitions, to guide the reader through the rest of the paper. Next we consider issues of epistemology, of how animal experiments lead to changes in our understanding of biomedicine and, potentially, to the development of new therapeutics. Here we consider the meaning of statistical significance; the importance of understanding whether findings have general truth; and the advances in knowledge which can result from 'failed' replication. Then, we consider weaknesses in the design, conduct and reporting of experiments, and review evidence for this from systematic reviews and from experimental studies addressing these issues. We consider the impact that these weaknesses have on the development of new treatments for human disease, and reflect on the response to these issues from the biomedical research community. Finally, we consider strategies for improvement including increased use of brief, pre-registered study protocols; pre-registration, open publication and open data; and the central importance of education in improving research performance.

Everything You Need to Know About Satisfying IACUC Protocol Requirements.

There have been recent efforts to reduce the administrative burden imposed on investigators. Although a complete and thorough review of proposed animal studies is an essential function of the Institutional Animal Care and Use Committee (IACUC), efforts to streamline and clarify this process may help investigators spend less time writing animal use protocols and responding to committee comments. The IACUC relies on well-written protocols for an efficient review process. A well-designed protocol form is also critical in guiding investigators through the process. However, it is ultimately the investigators' responsibility to ensure that the information they provide answers all the IACUC's questions with enough detail and quality for a fast and effective review. This article, aimed primarily for researchers but also IACUC administrators, provides an overview of the IACUC protocol review and approval process, the criteria that the IACUC uses for evaluations, and the type of information that should be included in the various sections of the protocol form. Some specific examples are also provided.

Contribution of the Breadth and Depth of IACUC Membership to Experimental Design as a Factor in Research Reproducibility.

The IACUC comprises the key component of animal research oversight at any institution or facility and thus has the responsibility to review and approve proposed animal activities. As the primary oversight unit that ensures the quality of animal welfare and therefore contributes to overall research quality, the IACUC can support reproducibility in research by ensuring rigorous experimental design, standardization of care and management, and assessment of the validity of research. An IACUC that is constituted as required by the Animal Welfare Act and the PHS Policy incorporates a wide range of expertise. Here we explore the contributions of the various IACUC members and discuss how each can help to enhance rigor and mitigate issues regarding irreproducibility in biomedical research involving animals.

Mammalian BTBD12 (SLX4) protects against genomic instability during mammalian spermatogenesis.

The mammalian ortholog of yeast Slx4, BTBD12, is an ATM substrate that functions as a scaffold for various DNA repair activities. Mutations of human BTBD12 have been reported in a new sub-type of Fanconi anemia patients. Recent studies have implicated the fly and worm orthologs, MUS312 and HIM-18, in the regulation of meiotic crossovers arising from double-strand break (DSB) initiating events and also in genome stability prior to meiosis. Using a Btbd12 mutant mouse, we analyzed the role of BTBD12 in mammalian gametogenesis. BTBD12 localizes to pre-meiotic spermatogonia and to meiotic spermatocytes in wildtype males. Btbd12 mutant mice have less than 15% normal spermatozoa and are subfertile. Loss of BTBD12 during embryogenesis results in impaired primordial germ cell proliferation and increased apoptosis, which reduces the spermatogonial pool in the early postnatal testis. During prophase I, DSBs initiate normally in Btbd12 mutant animals. However, DSB repair is delayed or impeded, resulting in persistent γH2AX and RAD51, and the choice of repair pathway may be altered, resulting in elevated MLH1/MLH3 focus numbers at pachynema. The result is an increase in apoptosis through prophase I and beyond. Unlike yeast Slx4, therefore, BTBD12 appears to function in meiotic prophase I, possibly during the recombination events that lead to the production of crossovers. In line with its expected regulation by ATM kinase, BTBD12 protein is reduced in the testis of Atm(-/-) males, and Btbd12 mutant mice exhibit increased genomic instability in the form of elevated blood cell micronucleus formation similar to that seen in Atm(-/-) males. Taken together, these data indicate that BTBD12 functions throughout gametogenesis to maintain genome stability, possibly by co-ordinating repair processes and/or by linking DNA repair events to the cell cycle via ATM.