Direct neurotization of free nipple grafts with cadaveric nerve grafts following mastectomy for gender affirming surgery.

BACKGROUND: Free nipple grafting makes sensory recovery challenging. Permanent decreased sensation to touch and temperature in skin-grafted skin is common. Direct neurotization of the nipple-areolar complex (NAC) graft has been described. However, quantitative data regarding degree of nipple reinnervation possible is unknown. This study aims to quantify and qualify sensation recovery following nerve coaptation to reinnervate the NAC. METHODS: Patients undergoing mastectomy for gender dysphoria from 2020 to 2022 were offered nerve allograft to restore nipple sensation. A lateral intercostal nerve was selected and coapted to allograft which was embedded beneath the nipple graft. Semmes Weinstein testing was used to assess nipple sensation. Assessments were made at visits <1 year and >1 year from surgery. Filaments used represented normal sensation, minor diminished sensation, diminished sensation, loss of protective sensation, and deep pressure sensation only. RESULTS: A total of 115 patients elected for direct neurotization. Semmes Weinstein testing was limited to 46 patients representing 46 encounters and 92 nipples in the <1 year group and 24 encounters and 48 nipples in the >1 year group. Of the 92 nipples in the <1 year group, 17 (18.5%) noted return of normal sensation and 37 (40.2%) noted minor diminished or diminished sensation, indicating nerve reinnervation. There were 38 (41%) nipples with loss of protective sensation or deep sensation only. There were 48 nipples included in the >1 year group. Of the 48 nipples, 4 (8.3%) noted normal sensation and 30 (62.5%) noted minor diminished or diminished sensation, indicating nerve reinnervation. For the remaining 14 nipples, 14 (29%) noted loss of protective sensation or deep sensation only. CONCLUSION: Sensory outcomes in NAC grafts used for reconstruction in patients undergoing double incision mastectomy remain poor. Sensation restoration beyond that expected from full thickness skin grafts can be achieved in the majority of patients with nerve allograft via direct neurotization.

Detection and identification of cis-regulatory elements using change-point and classification algorithms.

BACKGROUND: Transcriptional regulation is primarily mediated by the binding of factors to non-coding regions in DNA. Identification of these binding regions enhances understanding of tissue formation and potentially facilitates the development of gene therapies. However, successful identification of binding regions is made difficult by the lack of a universal biological code for their characterisation. RESULTS: We extend an alignment-based method, changept, and identify clusters of biological significance, through ontology and de novo motif analysis. Further, we apply a Bayesian method to estimate and combine binary classifiers on the clusters we identify to produce a better performing composite. CONCLUSIONS: The analysis we describe provides a computational method for identification of conserved binding sites in the human genome and facilitates an alternative interrogation of combinations of existing data sets with alignment data.

Identification of community structure-based brain states and transitions using functional MRI.

Brain function relies on a precisely coordinated and dynamic balance between the functional integration and segregation of distinct networks. Characterizing the way in which brain regions reconfigure their interactions to give rise to distinct but hidden brain states remains an open challenge. In this paper, we propose a Bayesian method for characterizing community structure-based latent brain states and showcase a novel strategy based on posterior predictive discrepancy using the latent block model to detect transitions between community structures in blood oxygen level-dependent (BOLD) time series. The set of estimated parameters in the model includes a latent label vector that assigns network nodes to communities, and also block model parameters that reflect the weighted connectivity within and between communities. Besides extensive in-silico model evaluation, we also provide empirical validation (and replication) using the Human Connectome Project (HCP) dataset of 100 healthy adults. Our results obtained through an analysis of task-fMRI data during working memory performance show appropriate lags between external task demands and change-points between brain states, with distinctive community patterns distinguishing fixation, low-demand and high-demand task conditions.

Chest Masculinization Technique and Outcomes in 72 Double-incision Chest-contouring Procedures with Free Nipple Grafting.

Chest masculinization for gender affirmation is the removal of breast tissue and excess skin, often with repositioning of the nipple areola complexes to achieve a male-appearing chest. A double-incision technique with free nipple grafting (FNG) is the preferred method for trans men with large, ptotic breasts. The authors present the outcomes of 72 consecutive chest masculinization cases using this technique. METHODS: A retrospective chart review was performed between 2015 and 2020 on all patients who underwent chest masculinization surgery for gender dysphoria by the senior author (JDK). Patients who underwent masculinization by concentric circle or liposuction-only techniques were excluded. Potential risk factors for complications were analyzed with Chi-square and logistic regression techniques. P < 0.05 was considered significant. RESULTS: Seventy-two patients underwent bilateral mastectomy with free nipple grafting. There were 6 major complications resulting in return to operating room, re-admission, or need for interventional procedure. These included 4 hematomas, 1 infection, and 1 hospital admission for shortness of breath and pain.Minor complications treated conservatively included 3 seromas, 1 instance of delayed wound healing, 1 case of superficial thrombophlebitis, and 4 hypertrophic scars. Eleven patients experienced nipple areolar complex complications. Four patients underwent revision surgery. Nicotine use was associated with a higher rate of hematoma (χ2: 9.95, P = 0.007). Later operative date, a surrogate for experience, was associated with decreased return to the operating room (Odds ratio: 0.99, P = 0.025). CONCLUSION: Double-incision chest contouring with free nipple grafting provides good chest contour for transgender men,with low complication rates.

Recent advances and future perspectives for automated parameterisation, Bayesian inference and machine learning in voltammetry.

Advanced data analysis tools such as mathematical optimisation, Bayesian inference and machine learning have the capability to revolutionise the field of quantitative voltammetry. Nowadays such approaches can be implemented routinely with widely available, user-friendly modern computing languages, algorithms and high speed computing to provide accurate and robust methods for quantitative comparison of experimental data with extensive simulated data sets derived from models proposed to describe complex electrochemical reactions. While the methodology is generic to all forms of dynamic electrochemistry, including the widely used direct current cyclic voltammetry, this review highlights advances achievable in the parameterisation of large amplitude alternating current voltammetry. One significant advantage this technique offers in terms of data analysis is that Fourier transformation provides access to the higher order harmonics that are almost devoid of background current. Perspectives on the technical advances needed to develop intelligent data analysis strategies and make them generally available to users of voltammetry are provided.

Pathological Evaluation of Breast Specimens in Transgender Chest Masculinization: Incidental Findings and Effect of Prior Chest Binding and Androgen Therapy in 74 Consecutive Patients.

Background: The rate of masculinizing chest surgery for gender affirmation continues to increase. With a paucity of literature on pathological evaluation of breast specimens in this patient population, there is a need for these data and for protocols on the handling of these specimens. Methods: A retrospective chart review was performed between 2015 and 2020 on all patients who underwent chest masculinization surgery for gender dysphoria by the senior author (J.D.K.). Inclusion criteria were any patient with sex assigned female at birth who underwent removal of breast and/or nipple areolar complex tissue for gender affirmation. Patient demographics were recorded. Bilateral breast tissue was sent for routine pathology in all cases and findings were recorded. A p-value of <0.05 was considered significant. Results: Seventy-four consecutive patients and 148 breast specimen reports were identified from a database and included in the study. The mean age was 26 years (15-49). Thirty-nine patients had a known history of chest wall binding and 60 patients had undergone preoperative androgen therapy. There was no invasive or in situ carcinoma found in any breast tissue specimens. Thirty-four patients had a benign lesion in one or both breast specimens. Atypical lobular hyperplasia was found in one patient's specimen. A history of chest wall binding was not correlated with any benign lesions (p=0.79) or stromal fibrosis (p=0.94). A history of testosterone use was not correlated with any benign lesions (p=0.35) or stromal fibrosis (p=0.20). Conclusions: The prevalence (1.4%) of significant breast pathology and of benign findings (46%) in our study closely correlates with the rates in the literature. We found no correlation between significant breast pathology or benign lesions and a history of chest wall binding or preoperative androgen therapy. We recommend all breast specimens removed during chest masculinization surgery be sent for pathological evaluation.

Superficial temporal artery perforator flaps for reconstruction of intraoral defects.

BACKGROUND: Intraoral defects after tumor resection are often reconstructed with free tissue transfer. However, in patients who are not good candidates for free tissue transfer, regional flaps based on the superficial temporal artery can be utilized. The authors present our technique to reconstruct intraoral defects with the superficial temporal artery perforator (STAP) flap and early outcomes. METHODS: Five patients underwent STAP flaps for defects including the hard palate, buccal sulcus, floor of mouth, and retromolar trigone between 2017 and 2019. The mean defect size was 5.6 × 3.4 cm2 (3 × 3 cm2 - 7 × 4 cm2 ). The mean age was 74 (57-88) and all patients had recurrent cancer. External Doppler, indocyanine green laser angiography, and FLIR thermal imaging were used intra-operatively to identify the best perforators and plan for flap design. RESULTS: The mean flap size was 7.6 × 3.5 cm2 (6 × 3 cm2 - 10 × 5 cm2 ). Four flaps were based off of the posterior branch of the STA, while the fifth was based off of the anterior branch. Two donor sites were closed primarily, and three required skin grafts. One patient experienced partial flap necrosis. There were no complete flap losses and no donor site complications. Average follow up was 14.6 months (9-20 months). All patients maintained preoperative level of speech, mastication, and oral continence. CONCLUSIONS: The STAP flap can be based on the anterior or posterior branch of the superficial temporal artery and is a useful regional flap for intraoral defects after tumor resection.

Crowdsourcing the Ideal Nipple-Areolar Complex Position for Chest Masculinization Surgery.

Chest masculinization surgery is increasing in prevalence. However, the ideal location of the nipple-areolar complex (NAC) is unknown. Our purpose was to determine the most aesthetically favorable male NAC position for use in chest masculinization through crowdsourcing. METHODS: Using Adobe Photoshop CC 2017, 8 locations for the NAC were created based on previous literature descriptions. Amazon Mechanical Turk was utilized as a crowdsourcing interface-respondents were asked to rank the top 3 most favorable and least favorable images. Analysis of variance with subsequent Tukey HSD was used for a statistical comparison of favorability scores for different NAC localizations. Values were considered significant with P < 0.05. RESULTS: Eight hundred nineteen respondents participated in the survey. NAC positions of Images C (mean score = 1.9222) and A (mean score = 1.7365) received higher favorability scores than those of Images D, E, F, G, and H (all P < 0.05). There were no significant differences between Images C and A (C versus A: P = 0.6412). NAC localizations from Images G (mean score = -2.0353) and H (mean score = -1.6908) received lower favorability scores than Images A, B, C, D, E, and F (all P < 0.05). There were no significant differences between Images G and H (P = 0.2279). CONCLUSIONS: Most respondents preferred Images C and A, and few favored Images G and H, suggesting that lateral NAC placement is favored over more medial localizations. Additionally, both Images C and A utilize relatively inferior NAC placements. Therefore, we recommend a location inferior and lateral to the NAC. Ultimately, NAC localization during chest masculinization will be the result of shared decision-making between the patient and the surgeon to fulfill each patient's aesthetic goals.

Barriers To Finding A Gender Affirming Surgeon.

BACKGROUND: Gender affirmation surgery is increasingly prevalent; however, finding a surgeon continues to be difficult. Additionally, the majority of transgender patients utilize the internet for information before elective surgery. Therefore, it is imperative to explore potential online barriers in finding a gender affirming surgeon. AIMS: The authors sought to use the Internet to search for gender affirming surgeons practicing in the USA, and therefore, reflect the process that patients potentially undergo. We highlight the barriers to information and care that we encountered. METHODS: We conducted a comprehensive review of public online transgender surgery directories for currently practicing surgeons that provide facial feminization, facial masculinization, breast augmentation, chest masculinization, vaginoplasty, metoidioplasty, and/or phalloplasty in the USA. Each surgeon's name, surgical specialty, the current practice's name, state, and zip code, and procedures provided were recorded. Chi-square analysis was used for comparisons of categorical variables. RESULTS: There are currently 660 gender affirmation surgeons in the USA, with most specializing in plastic surgery, followed by otolaryngology and urology. In total, 30.5% of surgeons practice in the West, 25.6% in the Northeast, 25.3% in the South, and 18.6% in the Midwest. The most common surgery provided was chest masculinization (70.2%), followed by facial feminization (42.7%) and chest feminization (42.6%). CONCLUSION: Plastic surgeons are most likely to perform gender affirmation surgery compared to other specialties. Geographic distribution of surgeons, does not, however, match the distribution of patients. Additionally, we encountered significant hardship in confirming that a surgeon performs the procedure listed in their profile on popular online gender affirmation surgeon directories. LEVEL OF EVIDENCE: V.

Influencing public health policy with data-informed mathematical models of infectious diseases: Recent developments and new challenges.

Modern data and computational resources, coupled with algorithmic and theoretical advances to exploit these, allow disease dynamic models to be parameterised with increasing detail and accuracy. While this enhances models' usefulness in prediction and policy, major challenges remain. In particular, lack of identifiability of a model's parameters may limit the usefulness of the model. While lack of parameter identifiability may be resolved through incorporation into an inference procedure of prior knowledge, formulating such knowledge is often difficult. Furthermore, there are practical challenges associated with acquiring data of sufficient quantity and quality. Here, we discuss recent progress on these issues.

A Three-Step Technique for Optimal Nipple Position in Transgender Chest Masculinization.

BACKGROUND: The ideal position of the nipple-areola complex (NAC) in the transgender population can be a challenge to determine. OBJECTIVES: The authors sought to determine the best location and aesthetics of the female to male NAC. METHODS: Patients who underwent female to male mastectomy with free nipple grafting were included. NAC position is confirmed utilizing a vertical coordinate at the level of the 4th rib near the border of the pectoralis muscle and a horizontal coordinate determined by dividing each unilateral chest into vertical thirds from midline to anterior axillary line laterally. The NAC position is confirmed at the junction of the middle and lateral third. Symmetry is ensured bilaterally by creating a triangle and transposing it side to side; the base lies from sternal notch to inframammary fold in the midline and the apex is adjusted to the NAC. A 24-question survey utilizing a 5-point Likert scale was distributed postoperatively to assess the patient's thoughts about their chest, nipples, scar, and overall experience with the gender affirmation process. RESULTS: Thirty-one patients were included in this study. Eighteen patients responded to the postmastectomy survey, all of whom were highly satisfied with the aesthetic result postoperatively. All patients felt comfortable with their exposed chest. Nipple location was particularly highly received with 100% satisfaction rate (mean Likert score, 4.72). Nipple size and shape received a mean Likert score of 4.17 and 3.89, respectively. CONCLUSIONS: The triple confirmation technique is an easy, reproducible method to guide the surgeon in relocation of the NAC.

A comparison of approximate versus exact techniques for Bayesian parameter inference in nonlinear ordinary differential equation models.

The behaviour of many processes in science and engineering can be accurately described by dynamical system models consisting of a set of ordinary differential equations (ODEs). Often these models have several unknown parameters that are difficult to estimate from experimental data, in which case Bayesian inference can be a useful tool. In principle, exact Bayesian inference using Markov chain Monte Carlo (MCMC) techniques is possible; however, in practice, such methods may suffer from slow convergence and poor mixing. To address this problem, several approaches based on approximate Bayesian computation (ABC) have been introduced, including Markov chain Monte Carlo ABC (MCMC ABC) and sequential Monte Carlo ABC (SMC ABC). While the system of ODEs describes the underlying process that generates the data, the observed measurements invariably include errors. In this paper, we argue that several popular ABC approaches fail to adequately model these errors because the acceptance probability depends on the choice of the discrepancy function and the tolerance without any consideration of the error term. We observe that the so-called posterior distributions derived from such methods do not accurately reflect the epistemic uncertainties in parameter values. Moreover, we demonstrate that these methods provide minimal computational advantages over exact Bayesian methods when applied to two ODE epidemiological models with simulated data and one with real data concerning malaria transmission in Afghanistan.

The forearm fillet flap: 'spare parts' reconstruction for forequarter amputations.

Radical forequarter amputation is often performed for recurrent proximal extremity tumors. A free forearm fillet flap is used to provide excellent coverage of the resultant defect without donor site morbidity. Use of a free flap from the distal portion of the extremity with proximal tumor burden is safe and effective.

Delimiting a species' geographic range using posterior sampling and computational geometry.

Accurate delimitation of the geographic range of a species is important for control of biological invasions, conservation of threatened species, and understanding species range dynamics under environmental change. However, estimating range boundaries is challenging because monitoring methods are imperfect, the area that might contain individuals is often incompletely surveyed, and species may have patchy distributions. In these circumstances, large areas can be surveyed without finding individuals despite occupancy extending beyond surveyed areas, resulting in underestimation of range limits. We developed a delimitation method that can be applied with imperfect survey data and patchy distributions. The approach is to construct polygons indicative of the geographic range of a species. Each polygon is associated with a specific probability such that each interior point of the polygon has at least that posterior probability of being interior to the true boundary according to a Bayesian model. The method uses the posterior distribution of latent quantities derived from an agent-based Bayesian model and calculates the posterior distribution of the range as a derived quantity from Markov chain Monte Carlo samples. An application of this method described here informed the Australian campaign to eradicate red imported fire ants (Solenopsis invicta).

Female-to-Male Transgender Chest Contouring: A Systematic Review of Outcomes and Knowledge Gaps.

PURPOSE: The number of gender affirmation surgeries performed in the United States is increasing. Frequently, chest contouring is the first surgery for female-to-male transgender patients; it fosters assimilation into the new gender role with a desired sense of masculinity. Creating an aesthetic male chest requires adjustment of breast tissue volume, proper nipple-areolar complex placement, and abolishment of the inframammary fold. Although much has been published on various techniques and outcomes, there is no consensus on how to approach transmale top surgery. We have reviewed the most up-to-date literature and in so doing have uncovered significant knowledge gaps. METHODS: An electronic literature review was performed. PubMed search keywords included combinations of "female-to-male," "transgender surgery," "chest contour," and "nipple-areolar complex." Articles were included if the patients were transgender female to male. RESULTS: Our literature search yielded 67 unique articles, 22 of which met our inclusion criteria. A total of 2447 unique patients were analyzed. The articles discussed aspects of chest surgery in female-to-male transsexuals including mastectomy and nipple aesthetics. Relevant data trends were extracted and subsequently investigated. DISCUSSION: Female-to-male transgender patients often undergo chest contouring as their initial gender affirmation surgery. As the surgical treatment of gender dysphoria continues to grow, it is imperative for plastic surgeons to understand the surgical options and associated outcomes for transmasculine top surgery. Future research is needed to improve patient selection, surgical decision making, and patient-reported outcomes for different chest contouring techniques. In addition, there is a significant knowledge gap for the ideal nipple-areolar complex shape, size, and location.

Outcomes in Chest Wall Reconstruction Using Methyl Methacrylate Prostheses: A Review of the Literature and Case Series Utilizing a Novel Approach with Biologic Mesh.

BACKGROUND: Composite defects after chest wall resection may leave patients at risk with lack of protection of vital structures and potentially respiratory compromise secondary to flail segments. Reconstruction of the chest wall with various alloplastic materials is possible and well described. Here, the authors present a novel technique in chest wall reconstruction utilizing a methyl methacrylate (MMA) "sandwich" with biologic mesh. The authors also sought to determine outcomes in chest wall reconstruction with MMA to optimize surgical decision making and minimize patient morbidity. METHODS: A literature review was conducted using MEDLINE and the Cochrane Collaboration Library for primary research articles on chest wall reconstruction using MMA. Data related to surgical techniques and patient outcomes were extracted and analyzed. The authors also present their case series and outcomes utilizing a novel technique with biologic mesh. RESULTS: Seventy-four articles met inclusion criteria, which included a total of 562 patients. Reconstruction methods included three main variations of the MMA prosthesis and six institution-specific variations. Complications were reported in 13.7% of patients; the most common complications included infection (5.6%), respiratory failure (3.3%), and atelectasis (1.7%). Less commonly reported complications included prosthesis dislocation (1.2%), pneumonia (1.0%), and lung collapse (0.4%). Overall mortality due to respiratory causes was observed in nine patients (1.6%). In our case series, complications included respiratory failure and seroma was reported in one patient, with no complications at long-term follow-up. CONCLUSION: There are a variety of options available for rigid and nonrigid prosthetic repair of the chest wall. We present the first successful reported case series of reconstruction using biologic mesh as a component of the MMA sandwich prosthesis. MMA appears to be a safe and effective choice for rigid reconstruction when used alone or in conjunction with synthetic or biologic mesh.