NIH funding longevity by gender.

Women have achieved parity with men among biomedical science degree holders but remain underrepresented in academic positions. The National Institutes of Health (NIH)-the world's largest public funder of biomedical research-receives less than one-third of its new grant applications from women. Correspondingly, women compose less than one-third of NIH research grantees, even though they are as successful as men in obtaining first-time grants. Our study examined women's and men's NIH funding trajectories over time (n = 34,770), exploring whether women remain funded at the same rate as men after receiving their first major research grants. A survival analysis demonstrated a slightly lower funding longevity for women. We next examined gender differences in application, review, and funding outcomes. Women individually held fewer grants, submitted fewer applications, and were less successful in renewing grants-factors that could lead to gender differences in funding longevity. Finally, two adjusted survival models that account for initial investigator characteristics or subsequent application behavior showed no gender differences, suggesting that the small observed longevity differences are affected by both sets of factors. Overall, given men's and women's generally comparable funding longevities, the data contradict the common assumption that women experience accelerated attrition compared with men across all career stages. Women's likelihood of sustaining NIH funding may be better than commonly perceived. This suggests a need to explore women's underrepresentation among initial NIH grantees, as well as their lower rates of new and renewal application submissions.

An Analysis of Recent FDA Oncology Scientific Publications.

In addition to its primary regulatory role, the Office of Hematology and Oncology Products at the U.S. Food and Drug Administration (FDA) is engaged in many forms of scientific authorship. During the period of 2010 to 2018, FDA oncology staff contributed to 356 publications in the scientific literature. Here, we collaborated with analysts in the Office of Program Planning, Analysis, and Evaluation at the National Institute of General Medical Sciences, National Institutes of Health (NIH), to present a series of analyses aimed at quantifying the characteristics and potential impact of these contributions, as well as characterizing the areas of work addressed. We found that FDA oncology papers are enriched for high-impact publications and have about two times the number of citations as an average NIH-funded paper. Further impact of the publications was measured based on the presence of 65 publications that were cited by guidelines and 12 publications cited by publicly listed clinical trials. The results seen here are promising in determining the impact of FDA oncology publication work but prompt further investigation into longer-term impacts, such as the influence of this work on other regulatory activities at FDA. IMPLICATIONS FOR PRACTICE: This article describes the first comprehensive study of scientific publications produced by U.S. Food and Drug Administration (FDA) oncology staff. The analysis illustrates that staff are highly engaged in publishing in the scientific literature in addition to completing regulatory review work. Publications are generally in clinical medicine, consistent with the large number of medical oncologists working at the Office of Hematology and Oncology Products (OHOP). OHOP publications generally focus either on communicating important regulatory work (approval summaries) or highlighting regulatory science issues to encourage dialogue with the scientific community (commentaries, reviews, and expert working papers). The analysis also suggests that several FDA oncology publications may influence clinical guidelines, but further work is needed to evaluate impact.

Tracing Long-Term Outcomes of Basic Research Using Citation Networks.

In recent years, the science of science policy has been facilitated by the greater availability of and access to digital data associated with the science, technology, and innovation enterprise. Historically, most of the studies from which such data are derived have been econometric or "scientometric" in nature, focusing on the development of quantitative data, models, and metrics of the scientific process as well as outputs and outcomes. Broader definitions of research impact, however, necessitate the use of qualitative case-study methods. For many years, U.S. federal science agencies such as the National Institutes of Health have demonstrated the impact of the research they support through tracing studies that document critical events in the development of successful technologies. A significant disadvantage and barrier of such studies is the labor-intensive nature of a case study approach. Currently, however, the same data infrastructures that have been developed to support scientometrics may also facilitate historical tracing studies. In this paper, we describe one approach we used to discover long-term, downstream outcomes of research supported in the late 1970's and early 1980's by the National Institute of General Medical Sciences, a component of the National Institutes of Health.

Geographically-related outcomes of U.S. funding for small business research and development: Results of the research grant programs of a component of the National Institutes of Health.

This article examines the geographic distribution of funding for the U.S. Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) programs sponsored by the National Institute of General Medical Sciences (NIGMS). Despite a significant investment in SBIR/STTR and an interest in increasing geographic diversity in the institute's research portfolio, there has not been an assessment of the distribution of NIGMS's SBIR/STTR funding, outcomes associated with that investment, and relationships between the two. The geographic distribution of NIGMS' SBIR/STTR funding was highly concentrated in a small number of states, with a high correlation between each state's funding and its number of small scientific research and development businesses. Affiliation with a major research university was correlated with several measures of innovation and firm success. Our findings are consistent with earlier research showing that economic activity in research and development and research output tend to cluster in geographic regions where knowledge can be generated and shared more efficiently. These findings lend support to an investment strategy for small business research and development that creates networks between major research universities and small businesses.

Using database linkages to measure innovation, commercialization, and survival of small businesses.

Here, we report the results of an outcomes evaluation of the Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) Programs at the National Institute of General Medical Sciences (NIGMS). Since the programs' inception, assessments of the SBIR/STTR programs at several federal agencies have utilized surveys of former grantees as the primary source of data. Response rates have typically been low, making non-response bias a potential threat to the validity of some of these studies' results. Meanwhile, the availability of large publicly-available datasets continues to grow and methods of text mining and linking databases continue to improve. By linking NIGMS grant funding records, U.S. Patent and Trademark Office data, and business intelligence databases, we explored innovation, commercialization and survival for recipients of NIGMS SBIR/STTR funding. In doing so, we were able to more completely assess several key outcomes of the NIGMS SBIR/STTR program. Our evaluation demonstrated that the NIGMS program performed above baseline expectations along all dimensions, and comparably to other federal agency SBIR/STTR grant programs. In addition, we show that the use of extant data increasingly is a viable, less expensive, and more reliable approach to gathering data for evaluation studies.

Haplotype-based localization of an alcohol dependence gene to the 5q34 {gamma}-aminobutyric acid type A gene cluster.

CONTEXT: Pharmacobehavioral and pharmacogenetic evidence links gamma-aminobutyric acid type A (GABA(A)) receptors and chromosomal regions containing GABA(A) receptor genes to ethanol-related responses. The GABA(A) gene cluster on chromosome 5q34 is of particular interest in the genetics of alcohol dependence because of the gamma2 subunit requirement for ethanol's modulatory action on GABA(A) receptors, previous linkage findings in mice and humans implicating both GABRA6 and GABRG2, and reported associations of GABRA6, GABRB2, and GABRG2 alleles with alcohol dependence. OBJECTIVE: To determine whether variation at the 5q34 GABA(A) gene cluster is implicated in differential susceptibility to alcohol dependence. METHODS: Two large psychiatrically interviewed samples, a Southwestern Native American population sample (N = 433) and a Finnish sample (N = 511) with alcohol-dependent subjects and unaffected individuals, were genotyped for 6 single nucleotide polymorphisms at the 5q34 GABA(A) gene cluster. In addition to sib-pair linkage and case-control association analyses, linkage disequilibrium mapping with haplotypes was used. RESULTS: Sib-pair linkage of GABRG2 to alcohol dependence was observed in Finns (P = .008). Association of the GABRB2 1412T allele with alcohol dependence was detected in both populations (Finns, P = .01; Southwestern Native Americans, P = .008), and the GABRA6 1519T allele was associated in both Finns (P = .01) and Southwestern Native Americans (P = .03). Linkage disequilibrium mapping with 3-locus haplotypes yielded evidence for an alcohol-dependence locus at the GABA(A) gene cluster region in both populations. The most highly significant signals were at 3-locus haplotypes that included 1 or more GABRA6 polymorphisms, with the peak signal at a GABRA6 3-locus haplotype (Finns, empirical P = .004; Southwestern Native Americans, empirical P = .02). CONCLUSIONS: We detected sib-pair linkage of 5q34 GABA(A) receptor genes to alcohol dependence in Finns and found association both in Finns and in Southwestern Native Americans. In both populations, the haplotype localization implicates the region containing the Pro385Ser GABRA6 polymorphism and 2 other polymorphisms at GABRA6.

Thinking outside the box: fostering innovation and non-hypothesis-driven research at NIH.

The National Institutes of Health (NIH) has long been known as an institution that supports biomedical advances through hypothesis-driven research. Another aspect of NIH, however, has received comparatively little attention and may be critical to advancing translational science beyond its current limitations. Specifically, this aspect of NIH focuses on supporting innovation through the development of high-risk technologies that have the potential to empower research.

Increased oxidation and degradation of cytosolic proteins in alcohol-exposed mouse liver and hepatoma cells.

We recently developed a sensitive method using biotin-N-maleimide (biotin-NM) as a probe to positively identify oxidized mitochondrial proteins. In this study, biotin-NM was used to identify oxidized cytosolic proteins in alcohol-fed mouse livers. Alcohol treatment for 6 wk elevated the levels of CYP2E1 and nitrotyrosine, a marker of oxidative stress. Markedly increased levels of oxidized proteins were detected in alcohol-fed mouse livers compared to pair-fed controls. The biotin-NM-labeled oxidized proteins from alcohol-exposed mouse livers were subsequently purified with streptavidin-agarose and resolved on 2-DE. More than 90 silver-stained protein spots that displayed differential intensities on 2-D gels were identified by MS. Peptide sequence analysis revealed that many enzymes or proteins involved in stress response, chaperone activity, intermediary metabolism, and antioxidant defense systems such as peroxiredoxin were oxidized after alcohol treatment. Smaller fragments of many proteins were repeatedly detected only in alcohol-fed mice, indicating that many oxidized proteins after alcohol exposure were degraded. Immunoblot results showed that the level of oxidized peroxiredoxin (inactivated) was markedly increased in the alcohol-exposed mouse livers and ethanol-sensitive hepatoma cells compared to the corresponding controls. Our results may explain the underlying mechanism for cellular dysfunction and increased susceptibility to other toxic agents following alcohol-mediated oxidative stress.