Heteronormative biases and distinctive experiences with prostate cancer among men who have sex with men: a qualitative focus group study.

BACKGROUND: Men who have sex with men (MSM) face many challenges and biases in healthcare. Within urology there is a need to better understand how prostate cancer impacts MSM given the unique ways in which side effects that accompany treatment may affect this population. The goal of this study is to explore the experience of MSM with prostate cancer to advance the existing literature in this area and inform implementation and delivery of clinical practice and policy guidelines. METHODS: Four focus groups were conducted with a semi-structured interview guide. Using a phenomenological qualitative approach consistent with grounded theory [1] and naturalistic inquiry principles we sought to better understand the direct experiences of MSM with prostate cancer. Audio transcriptions were thematically analyzed to identify themes that impact MSM throughout their prostate cancer journey. An iterative, team-wide classification process was used to identify, organize, and group common codes into higher-order categories and themes. RESULTS: Patient's choice of provider and their interactions with the healthcare system were strongly impacted by their sexual identities. Participants commented on navigating the heteronormative healthcare environment and the impact of assumptions they encountered. MSM experienced the sexual side effects of prostate cancer treatment in unique ways. Issues with erectile dysfunction and ejaculatory dysfunction had significant impacts on patient's sexual experience, with some describing being forced to explore new modes of sexual expression. Anejaculation was a theme that was distressing for many participants. The emotional impact of a prostate cancer diagnosis was significant in the men interviewed. Common themes included loss of identity and fear for future relationships. CONCLUSIONS: MSM have unique concerns after prostate cancer treatment that differ from men who don't identify as MSM. It is critical that providers familiarize themselves with the concerns of this patient population regarding prostate cancer treatment. An important step toward reducing heteronormative bias in prostate cancer care is to better understand the goals, identity, and sexual practices of MSM and to provide informed anticipatory guidance.

Urologists and Lesbian, Gay, Bisexual, Transgender, or Queer Patients: A Survey-based Study of the Practice Patterns, Attitudes, and Knowledge Base of Urologists Toward Their Lesbian, Gay, Bisexual, Transgender, or Queer Patients.

OBJECTIVE: To assess urologists' attitudes toward treating lesbian, gay, bisexual, transgender, or queer (LGBT) patients and counseling practices during diagnosis and treatment of prostate cancer. METHODS: A 35-question survey was sent to program directors of U.S. urology residency programs. RESULTS: 154 responses met the inclusion criteria. Respondents were primarily male, heterosexual, in academia, representing a range of ages and geography. 54.2% of respondents don't assume patients are heterosexual. While 88% of providers feel comfortable discussing sexual health with LGBTQ patients, 42.9% disagree that knowing sexual orientation is necessary to providing optimal care. 57.8% of respondents don't provide intake forms to indicate sexual orientation and 60.4% don't inquire about sexual orientation during history-taking. A majority (32.7%) reported 1-5 hours of LGBTQ health training. 74.3% believe more training is needed. 74.5% agreed to being listed as an LGBTQ-Friendly Provider currently, 65.8% felt they needed additional training. 63.6% agreed the prostate is a source of sexual pleasure. 55.9% believed it important to assess sexual satisfaction in patients who engage in receptive anal intercourse after prostate cancer treatment. Responses were mixed regarding the timing of resuming receptive anal intercourse after treatment and whether patients are counseled to refrain from anal stimulation before PSA testing. Answers to knowledge questions regarding anal cancer and communication were primarily correct; answers to questions regarding anejaculation and differences in health concerns were mixed. CONCLUSION: Ongoing education is necessary on specific differences between heterosexual and lesbian, gay, bisexual, transgender, or queer (LGBTQ) patient concerns and how to apply this knowledge in order to address the needs of a rapidly aging LGBTQ population.

Baseline Comparisons of Complementary Sampling Methods for Assembly Driven by Short-Ranged Pair Potentials toward Fast and Flexible Hybridization.

This work measures baseline sampling characteristics that highlight fundamental differences between sampling methods for assembly driven by short-ranged pair potentials. Such granular comparison is essential for fast, flexible, and accurate hybridization of complementary methods. Besides sampling speed, efficiency, and accuracy of uniform grid coverage, other sampling characteristics measured are (i) accuracy of covering narrow low energy regions that have low effective dimension (ii) ability to localize sampling to specific basins, and (iii) flexibility in sampling distributions. As a proof of concept, we compare a recently developed geometric methodology EASAL (Efficient Atlasing and Search of Assembly Landscapes) and the traditional Monte Carlo (MC) method for sampling the energy landscape of two assembling trans-membrane helices, driven by short-range pair potentials. By measuring the above-mentioned sampling characteristics, we demonstrate that EASAL provides localized and accurate coverage of crucial regions of the energy landscape of low effective dimension, under flexible sampling distributions, with much fewer samples and computational resources than MC sampling. EASAL's empirically validated theoretical guarantees permit credible extrapolation of these measurements and comparisons to arbitrary number and size of assembling units. Promising avenues for hybridizing the complementary advantages of the two methods are discussed.

Rapid prediction of crucial hotspot interactions for icosahedral viral capsid self-assembly by energy landscape atlasing validated by mutagenesis.

Icosahedral viruses are under a micrometer in diameter, their infectious genome encapsulated by a shell assembled by a multiscale process, starting from an integer multiple of 60 viral capsid or coat protein (VP) monomers. We predict and validate inter-atomic hotspot interactions between VP monomers that are important for the assembly of 3 types of icosahedral viral capsids: Adeno Associated Virus serotype 2 (AAV2) and Minute Virus of Mice (MVM), both T = 1 single stranded DNA viruses, and Bromo Mosaic Virus (BMV), a T = 3 single stranded RNA virus. Experimental validation is by in-vitro, site-directed mutagenesis data found in literature. We combine ab-initio predictions at two scales: at the interface-scale, we predict the importance (cruciality) of an interaction for successful subassembly across each interface between symmetry-related VP monomers; and at the capsid-scale, we predict the cruciality of an interface for successful capsid assembly. At the interface-scale, we measure cruciality by changes in the capsid free-energy landscape partition function when an interaction is removed. The partition function computation uses atlases of interface subassembly landscapes, rapidly generated by a novel geometric method and curated opensource software EASAL (efficient atlasing and search of assembly landscapes). At the capsid-scale, cruciality of an interface for successful assembly of the capsid is based on combinatorial entropy. Our study goes all the way from resource-light, multiscale computational predictions of crucial hotspot inter-atomic interactions to validation using data on site-directed mutagenesis' effect on capsid assembly. By reliably and rapidly narrowing down target interactions, (no more than 1.5 hours per interface on a laptop with Intel Core i5-2500K @ 3.2 Ghz CPU and 8GB of RAM) our predictions can inform and reduce time-consuming in-vitro and in-vivo experiments, or more computationally intensive in-silico analyses.

Atlasing of Assembly Landscapes using Distance Geometry and Graph Rigidity.

This Article describes a novel geometric methodology for analyzing free energy and kinetics of assembly driven by short-range pair-potentials in an implicit solvent and provides a proof-of-concept illustration of its unique capabilities. An atlas is a labeled partition of the assembly landscape into a roadmap of maximal, contiguous, nearly-equipotential-energy conformational regions or macrostates, together with their neighborhood relationships. The new methodology decouples the roadmap generation from sampling and produces: (1) a queryable atlas of local potential energy minima, their basin structure, energy barriers, and neighboring basins; (2) paths between a specified pair of basins, each path being a sequence of conformational regions or macrostates below a desired energy threshold; and (3) approximations of relative path lengths, basin volumes (configurational entropy), and path probabilities. Results demonstrating the core algorithm's capabilities and high computational efficiency have been generated by a resource-light, curated open source software implementation EASAL (Efficient Atlasing and Search of Assembly Landscapes, ACM Trans. Math. Softw. 2018 44, 1-48. 10.1145/3204472; see software, Efficient Atlasing and Search of Assembly Landscapes, 2016. https://bitbucket.org/geoplexity/easal; video, Video Illustrating the opensource software EASAL, 2016. https://cise.ufl.edu/~sitharam/EASALvideo.mpeg; and user guide, EASAL software user guide, 2016. https://bitbucket.org/geoplexity/easal/src/master/CompleteUserGuide.pdf). Running on a laptop with Intel(R) Core(TM) i7-7700@3.60 GHz CPU with 16GB of RAM, EASAL atlases several hundred thousand conformational regions or macrostates in minutes using a single compute core. Subsequent path and basin computations each take seconds. A parallelized EASAL version running on the same laptop with 4 cores gives a 3× speedup for atlas generation. The core algorithm's correctness, time complexity, and efficiency-accuracy trade-offs are formally guaranteed using modern distance geometry, geometric constraint systems and combinatorial rigidity. The methodology further links the shape of the input assembling units to a type of intuitive and queryable bar-code of the output atlas, which in turn determine stable assembled structures and kinetics. This succinct input-output relationship facilitates reverse analysis and control toward design. A novel feature that is crucial to both the high sampling efficiency and decoupling of roadmap generation from sampling is a recently developed theory of convex Cayley (distance-based) custom parametrizations specific to assembly, as opposed to folding. Representing microstates with macrostate-specific Cayley parameters, to generate microstate samples, avoids gradient-descent search used by all prevailing methods. Further, these parametrizations convexify conformational regions or macrostates. This ratchets up sampling efficiency, significantly reducing number of repeated and discarded samples. These features of the new stand-alone methodology can also be used to complement the strengths of prevailing methodologies including Molecular Dynamics, Monte Carlo, and Fast Fourier Transform based methods.