BACKGROUND: Despite similar numbers of women and men in internal medicine (IM) residency, women face unique challenges. Stereotype threat is hypothesized to contribute to underrepresentation of women in academic leadership, and exploring how it manifests in residency may provide insight into forces that perpetuate gender disparities. OBJECTIVE: To quantify the prevalence of stereotype threat in IM residency and explore experiences contributing to that stereotype threat. DESIGN: We used a mixed methods study design. First, we surveyed IM residents using the Stereotype Vulnerability Scale (SVS) to screen for stereotype threat. Second, we conducted focus groups with women who scored high on the SVS to understand experiences that led to stereotype threat. PARTICIPANTS: The survey was sent to all IM residents at University of California, San Francisco (UCSF), in September-November 2019. Focus groups were conducted at UCSF in Spring 2020. APPROACH: The survey included an adapted version of the SVS. For focus groups, we developed a focus group guide informed by literature on stereotype threat. We used a thematic approach to data analysis. The mixed methods design enabled us to draw metainferences by integrating the two data sources. KEY RESULTS: Survey response rate was 61% (110/181). Women were significantly more likely than men to have a score indicating stereotype threat vulnerability (77% vs 0%, p < 0.001). Four themes from focus groups characterized womens experiences of gender bias and stereotype threat: gender norm tension, microaggressions and sexual harassment, authority questioned, and support and allyship. CONCLUSIONS: Gender-based stereotype threat is highly prevalent among women IM residents. This phenomenon poses a threat to confidence and ability to execute patient care responsibilities, detracting from well-being and professional development. These findings indicate that, despite robust representation of women in IM training, further attention is needed to address gendered experiences and contributors to womens vulnerability to stereotype threat.

Congenital hypogonadotropic hypogonadism (CHH) and its anosmia-associated form (Kallmann syndrome [KS]) are genetically heterogeneous. Among the >15 genes implicated in these conditions, mutations in FGF8 and FGFR1 account for ~12% of cases; notably, KAL1 and HS6ST1 are also involved in FGFR1 signaling and can be mutated in CHH. We therefore hypothesized that mutations in genes encoding a broader range of modulators of the FGFR1 pathway might contribute to the genetics of CHH as causal or modifier mutations. Thus, we aimed to (1) investigate whether CHH individuals harbor mutations in members of the so-called "FGF8 synexpression" group and (2) validate the ability of a bioinformatics algorithm on the basis of protein-protein interactome data (interactome-based affiliation scoring [IBAS]) to identify high-quality candidate genes. On the basis of sequence homology, expression, and structural and functional data, seven genes were selected and sequenced in 386 unrelated CHH individuals and 155 controls. Except for FGF18 and SPRY2, all other genes were found to be mutated in CHH individuals: FGF17 (n = 3 individuals), IL17RD (n = 8), DUSP6 (n = 5), SPRY4 (n = 14), and FLRT3 (n = 3). Independently, IBAS predicted FGF17 and IL17RD as the two top candidates in the entire proteome on the basis of a statistical test of their protein-protein interaction patterns to proteins known to be altered in CHH. Most of the FGF17 and IL17RD mutations altered protein function in vitro. IL17RD mutations were found only in KS individuals and were strongly linked to hearing loss (6/8 individuals). Mutations in genes encoding components of the FGF pathway are associated with complex modes of CHH inheritance and act primarily as contributors to an oligogenic genetic architecture underlying CHH.