Dyani Gaudilliere

Gender disparities in scholarly productivity of US academic surgeons

BACKGROUND Female surgeons have faced significant challenges to promotion over the past decades, with attrition rates supporting a lack of improvement in womens position in academia. We examine gender disparities in research productivity, as measured by the number of citations, publications, and h-indices, across six decades. MATERIALS AND METHODS The online profiles of full-time faculty members of surgery departments of three academic centers were reviewed. Faculty members were grouped into six cohorts by decade, based on year of graduation from medical school. Differences between men and women across cohorts as well as by academic rank were examined. RESULTS The profiles of 978 surgeons (234 women and 744 men) were reviewed. The number of female faculty members in the institutions increased significantly over time, reaching the current percentage of 35.3%. Significant differences in number of articles published were noted at the assistant and full but not at the associate, professor level. Women at these ranks had fewer publications than men. Gender differences were also found in all age cohorts except among the most recent who graduated in the 2000s. The impact of publications, as measured by h-index and number of citations, was not consistently significantly different between the genders at any age or rank. CONCLUSIONS We identified a consistent gender disparity in the number of publications for female faculty members across a 60-year span. Although the youngest cohort, those who graduated in the 2000s, appeared to avoid the gender divide, our data indicate that overall women still struggle with productivity in the academic arena.

An immune clock of human pregnancy

High-dimensional analysis reveals the chronology of immunological adaptations during the course of human pregnancies. Following the hand of the immunological clock Immune function is altered during pregnancy to protect the fetus from an immunological attack without disrupting protection against infection. Now, Aghaeepour et al. use mass cytometry to examine the precise timing of these pregnancy-induced changes in immune function and regulation. They developed an algorithm that captures the immunological timeline during pregnancy that both validates previous findings and sheds new light on immune cell interaction during gestation. By defining this immunological chronology during normal term pregnancy, they can now begin to determine which alterations associate with pregnancy-related pathologies. The maintenance of pregnancy relies on finely tuned immune adaptations. We demonstrate that these adaptations are precisely timed, reflecting an immune clock of pregnancy in women delivering at term. Using mass cytometry, the abundance and functional responses of all major immune cell subsets were quantified in serial blood samples collected throughout pregnancy. Cell signaling–based Elastic Net, a regularized regression method adapted from the elastic net algorithm, was developed to infer and prospectively validate a predictive model of interrelated immune events that accurately captures the chronology of pregnancy. Model components highlighted existing knowledge and revealed previously unreported biology, including a critical role for the interleukin-2–dependent STAT5ab signaling pathway in modulating T cell function during pregnancy. These findings unravel the precise timing of immunological events occurring during a term pregnancy and provide the analytical framework to identify immunological deviations implicated in pregnancy-related pathologies.

Mapping the Fetomaternal Peripheral Immune System at Term Pregnancy.

Preterm labor and infections are the leading causes of neonatal deaths worldwide. During pregnancy, immunological cross talk between the mother and her fetus is critical for the maintenance of pregnancy and the delivery of an immunocompetent neonate. A precise understanding of healthy fetomaternal immunity is the important first step to identifying dysregulated immune mechanisms driving adverse maternal or neonatal outcomes. This study combined single-cell mass cytometry of paired peripheral and umbilical cord blood samples from mothers and their neonates with a graphical approach developed for the visualization of high-dimensional data to provide a high-resolution reference map of the cellular composition and functional organization of the healthy fetal and maternal immune systems at birth. The approach enabled mapping of known phenotypical and functional characteristics of fetal immunity (including the functional hyperresponsiveness of CD4+ and CD8+ T cells and the global blunting of innate immune responses). It also allowed discovery of new properties that distinguish the fetal and maternal immune systems. For example, examination of paired samples revealed differences in endogenous signaling tone that are unique to a mother and her offspring, including increased ERK1/2, MAPK-activated protein kinase 2, rpS6, and CREB phosphorylation in fetal Tbet+CD4+ T cells, CD8+ T cells, B cells, and CD56loCD16+ NK cells and decreased ERK1/2, MAPK-activated protein kinase 2, and STAT1 phosphorylation in fetal intermediate and nonclassical monocytes. This highly interactive functional map of healthy fetomaternal immunity builds the core reference for a growing data repository that will allow inferring deviations from normal associated with adverse maternal and neonatal outcomes.

Computer-aided trauma simulation system with haptic feedback is easy and fast for oral-maxillofacial surgeons to learn and use.

PURPOSE Computer-assisted surgical (CAS) planning tools have become widely available in craniomaxillofacial surgery, but are time consuming and often require professional technical assistance to simulate a case. An initial oral and maxillofacial (OM) surgical user experience was evaluated with a newly developed CAS system featuring a bimanual sense of touch (haptic). MATERIALS AND METHODS Three volunteer OM surgeons received a 5-minute verbal introduction to the use of a newly developed haptic-enabled planning system. The surgeons were instructed to simulate mandibular fracture reductions of 3 clinical cases, within a 15-minute time limit and without a time limit, and complete a questionnaire to assess their subjective experience with the system. Standard landmarks and linear and angular measurements between the simulated results and the actual surgical outcome were compared. RESULTS After the 5-minute instruction, all 3 surgeons were able to use the system independently. The analysis of standardized anatomic measurements showed that the simulation results within a 15-minute time limit were not significantly different from those without a time limit. Mean differences between measurements of surgical and simulated fracture reductions were within current resolution limitations in collision detection, segmentation of computed tomographic scans, and haptic devices. All 3 surgeons reported that the system was easy to learn and use and that they would be comfortable integrating it into their daily clinical practice for trauma cases. CONCLUSION A CAS system with a haptic interface that capitalizes on touch and force feedback experience similar to operative procedures is fast and easy for OM surgeons to learn and use.

Body Dysmorphic Disorder and Psychological Distress in Orthognathic Surgery Patients

PURPOSE Body dysmorphic disorder (BDD) is a distressing condition involving preoccupation with an imagined or exaggerated deformity. The purpose of our study was to investigate the presence of BDD and its comorbidity with anxiety, depression, and obsessive-compulsive disorder (OCD) in patients undergoing orthognathic surgery (OS). MATERIALS AND METHODS The present prospective study included 99 patients from the outpatient oral and maxillofacial surgery clinic at Stanford University who requested OS. The incidence of BDD, depression, anxiety, and OCD was assessed preoperatively using validated self-report measures. To determine the prevalence of Axis I psychological symptoms among patients, the descriptive and bivariate statistics were computed. P < .05 was considered significant. RESULTS In our sample, 13 patients (13%) screened positive for BDD. We did not find any significant correlations between the presence of BDD and gender, race, age, or marital status. Depressive symptoms were reported by 42% of the patients, OCD symptoms by 29%, and mild, moderate, and severe anxiety by 14%, 5%, and 4%, respectively. Using Spearman correlations, we found significant correlations between BDD and anxiety, depression, and OCD (P < .01). CONCLUSIONS The results of the present study suggest that the rates of BDD, depression, anxiety, and OCD are high in patients undergoing OS. Furthermore, we found a strong correlation between BDD and anxiety, OCD, and depression in these patients. Future studies are necessary to determine the postoperative changes in these psychological disorders and whether these changes are affected by having positive BDD screening results at baseline.

A Comparative Assessment of Implant Site Viability in Humans and Rats

Our long-term objective is to devise methods to improve osteotomy site preparation and, in doing so, facilitate implant osseointegration. As a first step in this process, we developed a standardized oral osteotomy model in ovariectomized rats. There were 2 unique features to this model: first, the rats exhibited an osteopenic phenotype, reminiscent of the bone health that has been reported for the average dental implant patient population. Second, osteotomies were produced in healed tooth extraction sites and therefore represented the placement of most implants in patients. Commercially available drills were then used to produce osteotomies in a patient cohort and in the rat model. Molecular, cellular, and histologic analyses demonstrated a close alignment between the responses of human and rodent alveolar bone to osteotomy site preparation. Most notably in both patients and rats, all drilling tools created a zone of dead and dying osteocytes around the osteotomy. In rat tissues, which could be collected at multiple time points after osteotomy, the fate of the dead alveolar bone was followed. Over the course of a week, osteoclast activity was responsible for resorbing the necrotic bone, which in turn stimulated the deposition of a new bone matrix by osteoblasts. Collectively, these analyses support the use of an ovariectomy surgery rat model to gain insights into the response of human bone to osteotomy site preparation. The data also suggest that reducing the zone of osteocyte death will improve osteotomy site viability, leading to faster new bone formation around implants.

Haptic feedback improves surgeons' user experience and fracture reduction in facial trauma simulation.

Computer-assisted surgical (CAS) planning tools are available for craniofacial surgery, but are usually based on computer-aided design (CAD) tools that lack the ability to detect the collision of virtual objects (i.e., fractured bone segments). We developed a CAS system featuring a sense of touch (haptic) that enables surgeons to physically interact with individual, patient-specific anatomy and immerse in a three-dimensional virtual environment. In this study, we evaluated initial user experience with our novel system compared to an existing CAD system. Ten surgery resident trainees received a brief verbal introduction to both the haptic and CAD systems. Users simulated mandibular fracture reduction in three clinical cases within a 15 min time limit for each system and completed a questionnaire to assess their subjective experience. We compared standard landmarks and linear and angular measurements between the simulated results and the actual surgical outcome and found that haptic simulation results were not significantly different from actual postoperative outcomes. In contrast, CAD results significantly differed from both the haptic simulation and actual postoperative results. In addition to enabling a more accurate fracture repair, the haptic system provided a better user experience than the CAD system in terms of intuitiveness and self-reported quality of repair.

Caries management by risk assessment in a cleft and craniofacial center.

Abstract Patients with craniofacial anomalies have an increased incidence of dental caries. The prevention program “Caries Management By Risk Assessment” (CAMBRA) has been previously validated but has not yet been introduced at a widespread level in a medical setting, particularly for this high-risk population. In this cross-sectional study, we aimed to evaluate the feasibility of implementing CAMBRA during the medical visit at an institutional tertiary care center, which treats children with craniofacial anomalies. The study included 161 participants aged 1 to 18 years. Patients and parents received a personalized educational session, toothbrushing tutorial, and fluoride varnish application. We assessed the prevalence of dental caries, caries risk factors, and knowledge of oral hygiene in this patient population. The overall caries prevalence in this group was higher than average (57% compared with 42%, according to the Centers for Disease Control and Prevention1). The most prevalent risk factors were developmental delay, deep pits/fissures, low socioeconomic status, orthodontic appliances, and carbohydrate snacks. The greatest predictors of dental caries were having 1 or more risk factors and having low socioeconomic status. In summary, children with craniofacial anomalies were at high risk for dental caries, with high rates of risk factors and low rates of preventive factors. Our findings revealed that basic oral hygiene standards are not being met in this high-risk population, highlighting the need for implementation of protocols such as CAMBRA. The results of this study can aid healthcare workers in craniofacial centers and children’s hospitals to improve the understanding of oral hygiene and dental care of their patients.

Multiomics modeling of the immunome, transcriptome, microbiome, proteome and metabolome adaptations during human pregnancy

Motivation: Multiple biological clocks govern a healthy pregnancy. These biological mechanisms produce immunologic, metabolomic, proteomic, genomic and microbiomic adaptations during the course of pregnancy. Modeling the chronology of these adaptations during full‐term pregnancy provides the frameworks for future studies examining deviations implicated in pregnancy‐related pathologies including preterm birth and preeclampsia. Results: We performed a multiomics analysis of 51 samples from 17 pregnant women, delivering at term. The datasets included measurements from the immunome, transcriptome, microbiome, proteome and metabolome of samples obtained simultaneously from the same patients. Multivariate predictive modeling using the Elastic Net (EN) algorithm was used to measure the ability of each dataset to predict gestational age. Using stacked generalization, these datasets were combined into a single model. This model not only significantly increased predictive power by combining all datasets, but also revealed novel interactions between different biological modalities. Future work includes expansion of the cohort to preterm‐enriched populations and in vivo analysis of immune‐modulating interventions based on the mechanisms identified. Availability and implementation: Datasets and scripts for reproduction of results are available through: https://nalab.stanford.edu/multiomics‐pregnancy/. Supplementary information: Supplementary data are available at Bioinformatics online.

Deep Immune Profiling of an Arginine-Enriched Nutritional Intervention in Patients Undergoing Surgery

Application of high-content immune profiling technologies has enormous potential to advance medicine. Whether these technologies reveal pertinent biology when implemented in interventional clinical trials is an important question. The beneficial effects of preoperative arginine-enriched dietary supplements (AES) are highly context specific, as they reduce infection rates in elective surgery, but possibly increase morbidity in critically ill patients. This study combined single-cell mass cytometry with the multiplex analysis of relevant plasma cytokines to comprehensively profile the immune-modifying effects of this much-debated intervention in patients undergoing surgery. An elastic net algorithm applied to the high-dimensional mass cytometry dataset identified a cross-validated model consisting of 20 interrelated immune features that separated patients assigned to AES from controls. The model revealed wide-ranging effects of AES on innate and adaptive immune compartments. Notably, AES increased STAT1 and STAT3 signaling responses in lymphoid cell subsets after surgery, consistent with enhanced adaptive mechanisms that may protect against postsurgical infection. Unexpectedly, AES also increased ERK and P38 MAPK signaling responses in monocytic myeloid-derived suppressor cells, which was paired with their pronounced expansion. These results provide novel mechanistic arguments as to why AES may exert context-specific beneficial or adverse effects in patients with critical illness. This study lays out an analytical framework to distill high-dimensional datasets gathered in an interventional clinical trial into a fairly simple model that converges with known biology and provides insight into novel and clinically relevant cellular mechanisms.