An experimentally informed computational model of neurovestibular adaptation to altered gravity.

Transitions to altered gravity environments result in acute sensorimotor impairment for astronauts, leading to serious mission and safety risks in the crucial first moments in a new setting. Our understanding of the time course and severity of impairment in the early stages of adaptation remains limited and confounded by unmonitored head movements, which are likely to impact the rate of adaptation. Here, we aimed to address this gap by using a human centrifuge to simulate the first hour of hypergravity (1.5g) exposure and the subsequent 1g readaptation period, with precisely controlled head tilt activity. We quantified head tilt overestimation via subjective visual vertical and found ∼30% tilt overestimation that did not decrease over the course of 1 h of exposure to the simulated gravity environment. These findings extended the floor of the vestibular adaptation window (with controlled vestibular cueing) to 1 h of exposure to altered gravity. We then used the empirical data to inform a computational model of neurovestibular adaptation to changes in the magnitude of gravity, which can offer insight into the adaptation process and, with further tuning, can be used to predict the temporal dynamics of vestibular-mediated misperceptions in altered gravity.

Modeling orientation perception adaptation to altered gravity environments with memory of past sensorimotor states.

Transitioning between gravitational environments results in a central reinterpretation of sensory information, producing an adapted sensorimotor state suitable for motor actions and perceptions in the new environment. Critically, this central adaptation is not instantaneous, and complete adaptation may require weeks of prolonged exposure to novel environments. To mitigate risks associated with the lagging time course of adaptation (e.g., spatial orientation misperceptions, alterations in locomotor and postural control, and motion sickness), it is critical that we better understand sensorimotor states during adaptation. Recently, efforts have emerged to model human perception of orientation and self-motion during sensorimotor adaptation to new gravity stimuli. While these nascent computational frameworks are well suited for modeling exposure to novel gravitational stimuli, they have yet to distinguish how the central nervous system (CNS) reinterprets sensory information from familiar environmental stimuli (i.e., readaptation). Here, we present a theoretical framework and resulting computational model of vestibular adaptation to gravity transitions which captures the role of implicit memory. This advancement enables faster readaptation to familiar gravitational stimuli, which has been observed in repeat flyers, by considering vestibular signals dependent on the new gravity environment, through Bayesian inference. The evolution and weighting of hypotheses considered by the CNS is modeled via a Rao-Blackwellized particle filter algorithm. Sensorimotor adaptation learning is facilitated by retaining a memory of past harmonious states, represented by a conditional state transition probability density function, which allows the model to consider previously experienced gravity levels (while also dynamically learning new states) when formulating new alternative hypotheses of gravity. In order to demonstrate our theoretical framework and motivate future experiments, we perform a variety of simulations. These simulations demonstrate the effectiveness of this model and its potential to advance our understanding of transitory states during which central reinterpretation occurs, ultimately mitigating the risks associated with the lagging time course of adaptation to gravitational environments.

Early Identification of Post-Traumatic Stress Disorder in Trauma Patients: Development of a Multivariable Risk Prediction Model.

BACKGROUND: The purpose of this study was to build a risk prediction model to identify trauma patients at the time of injury who are at high risk for post-traumatic stress disorder (PTSD) 1 year later. METHODS: Patients 18+ with operative orthopedic trauma injuries were enrolled in prospective social determinants of health cohort. Data were collected through initial surveys, medical records at time of injury, and 1-year follow-up phone screenings. Univariate analysis examined associations between factors and PTSD at 1 year. The best fit multivariable logistic regression model led to a novel PTSD risk prediction tool based on weights assigned similar to the Charlson index methods. RESULTS: Of 329 enrolled patients, 87 (26%) completed follow-up surveys; 58% screened positive for chronic PTSD. The best fit model predicting PTSD included age, insurance, violent mechanism, and 2 acute stress screening questions (AUC .89). Using these parameters, the maximum possible TIPPS index was 19. Those with PTSD at 1 year had a mean TIPPS index of 12.9 ± 4.0, compared to 5.9 ± 4.2 for those who did not (P < .001). DISCUSSION: Traumatic injury often leads to PTSD, which can be predicted by a novel risk score incorporating age, insurance status, violent injury mechanism, and acute stress reaction symptoms. Stability in life and relationships with primary care physicians may be protective of PTSD. LEVEL OF EVIDENCE: Diagnostic level II.

Humans gradually integrate sudden gain or loss of visual information into spatial orientation perception.

Introduction: Vestibular and visual information is used in determining spatial orientation. Existing computational models of orientation perception focus on the integration of visual and vestibular orientation information when both are available. It is well-known, and computational models capture, differences in spatial orientation perception with visual information or without (i.e., in the dark). For example, during earth vertical yaw rotation at constant angular velocity without visual information, humans perceive their rate of rotation to decay. However, during the same sustained rotation with visual information, humans can continue to more accurately perceive self-rotation. Prior to this study, there was no existing literature on human motion perception where visual information suddenly become available or unavailable during self-motion. Methods: Via a well verified psychophysical task, we obtained perceptual reports of self-rotation during various profiles of Earth-vertical yaw rotation. The task involved transitions in the availability of visual information (and control conditions with visual information available throughout the motion or unavailable throughout). Results: We found that when visual orientation information suddenly became available, subjects gradually integrated the new visual information over ~10 seconds. In the opposite scenario (visual information suddenly removed), past visual information continued to impact subject perception of self-rotation for ~30 seconds. We present a novel computational model of orientation perception that is consistent with the experimental results presented in this study. Discussion: The gradual integration of sudden loss or gain of visual information is achieved via low pass filtering in the visual angular velocity sensory conflict pathway. In conclusion, humans gradually integrate sudden gain or loss of visual information into their existing perception of self-motion.

From Self-efficacy to Imposter Syndrome: The Intrapersonal Traits of Surgeons.

BACKGROUND: Demographic differences among surgical trainees regarding intrapersonal traits, such as imposter syndrome and assertiveness, have become widely acknowledged. However, many of these characteristics have not been examined in tandem, nor among both trainees and surgeons in practice. This study aimed to address these knowledge gaps. METHODS: This was an anonymous, voluntary survey study comprised of validated measures of (1) self-efficacy, (2) imposter syndrome, (3) assertiveness, (4) perfectionism, and (5) self-rated likeability. A multimodal recruitment strategy was used and surgeons across all subspecialties were eligible for inclusion. RESULTS: A total of 296 participants were included, with 54% identifying as female (n = 161) and 72% between the ages of 25 and 40 years of age (n = 212). Imposter syndrome, assertiveness, and perfectionism scales were normally distributed; self-efficacy and self-rated likeability scales demonstrated slight negative skew. Self-identified male sex was associated with less imposter syndrome (P < 0.001) and perfectionism (P = 0.035) and higher assertiveness (P < 0.001). Imposter syndrome was less common among older age groups (P = 0.001). CONCLUSIONS: Surgeons are a self-efficacious group of perfectionists with widespread variability in imposter syndrome and assertiveness. Female sex and younger age were associated with more imposter syndrome and less assertiveness, highlighting an opportunity for early career coaching.

The Metabolic Syndrome Paradox: Increased Morbidity and Decreased Mortality in Operative Orthopedic Trauma.

We examined the impact of metabolic syndrome (MetS) on operative outcomes with orthopedic trauma, particularly among patients with pelvic, acetabular, and lower extremity fractures. This retrospective cohort study used the American College of Surgeons National Surgical Quality Improvement Program database to identify patients who had operative pelvic, acetabular, and lower extremity trauma from 2006 through 2014. We defined MetS as type 2 diabetes, a history of hypertension requiring medication, and body mass index of 30 kg/m2 or greater. Patients with MetS were compared with unaffected patients and assessed for association with in-hospital complications and mortality. The study population included 37,495 patients; 5.7% (n=2154) had MetS. On multivariable logistic regression, MetS was associated with increased odds of any hospital complication (odds ratio [OR], 1.30; 95% CI, 1.13-1.51; P<.001), Clavien-Dindo grade IV complications (OR, 1.51; 95% CI, 1.23-1.87; P<.001), readmission (OR, 1.39; 95% CI, 1.18-1.63; P<.001), and reoperation (OR, 1.40; 95% CI, 1.11-1.76; P=.004). Conversely, MetS significantly decreased the odds of mortality (OR, 0.67; 95% CI, 0.49-0.92; P=.01). Although MetS is a risk factor for postoperative complications, longer length of stay, and increased readmission after surgical intervention for orthopedic lower extremity trauma, MetS appears to decrease the odds of mortality in this specific patient population, which merits further investigation. [Orthopedics. 2022;45(2):103-108.].

COMPASS: Computations for Orientation and Motion Perception in Altered Sensorimotor States.

Reliable perception of self-motion and orientation requires the central nervous system (CNS) to adapt to changing environments, stimuli, and sensory organ function. The proposed computations required of neural systems for this adaptation process remain conceptual, limiting our understanding and ability to quantitatively predict adaptation and mitigate any resulting impairment prior to completing adaptation. Here, we have implemented a computational model of the internal calculations involved in the orientation perception system's adaptation to changes in the magnitude of gravity. In summary, we propose that the CNS considers parallel, alternative hypotheses of the parameter of interest (in this case, the CNS's internal estimate of the magnitude of gravity) and uses the associated sensory conflict signals (i.e., difference between sensory measurements and the expectation of them) to sequentially update the posterior probability of each hypothesis using Bayes rule. Over time, an updated central estimate of the internal magnitude of gravity emerges from the posterior probability distribution, which is then used to process sensory information and produce perceptions of self-motion and orientation. We have implemented these hypotheses in a computational model and performed various simulations to demonstrate quantitative model predictions of adaptation of the orientation perception system to changes in the magnitude of gravity, similar to those experienced by astronauts during space exploration missions. These model predictions serve as quantitative hypotheses to inspire future experimental assessments.

Emotional intelligence, burnout, and professional fulfillment in clinical year medical students.

BACKGROUND: Emotional intelligence (EI) has been associated with decreased burnout in surgical residents but has not been extensively studied in medical students. We hypothesized that higher EI would lead to decreased levels of burnout among medical students at a US medical school. METHODS: The authors administered three separate EI measures and compiled an EI score by adding the normalized score on each test. These measures were the DRS-15, the Grit Scale, and the Reading the Mind Between the Eyes Quiz. The Professional Fulfillment Index (PFI) was used to determine levels of burnout experienced two weeks before survey completion. RESULTS: The population included 68 medical students. PFI and EI scores were positively correlated (R = 0.55, p < .001). The separate EI measures indicated that both Grit (R = 0.43, p < .001) and DRS-15 (R = 0.56, p < .001) were correlated with PFI. The Eyes Quiz did not show a significant correlation with PFI (p = .2). CONCLUSIONS: The results confirmed our hypothesis that EI would be correlated with decreased levels of burnout among this group of students. Some areas of potential future study include whether these same results hold true at other medical schools and if improving EI has a benefit of decreasing burnout.

Impact of Frailty and Malnutrition on Outcomes After Surgical Fixation of Lower Extremity Fractures in Young Patients.

OBJECTIVES: Evaluate the relationship of nutrition parameters and the modified frailty index (mFI) on postsurgical complications within a young patient population sustaining lower extremity orthopaedic trauma. DESIGN: Retrospective observational cohort study. SETTING: Urban, American College of Surgeons-Verified, Level-1, Trauma Center. PATIENTS/PARTICIPANTS: Seventeen-thousand one hundred nine adult patients under the age of 65 sustaining lower extremity fractures undergoing operative intervention from 2006 to 2018. MAIN OUTCOME MEASURES: On admission, mFI and albumin levels were obtained, as well as complication data. Statistical analysis was used to analyze the association between frailty, malnutrition, and postoperative complications. Patients were stratified, healthy (mFI ≤1, albumin ≥3.5 g/dL), malnourished (mFI ≤1, albumin <3.5 g/dL), frail (mFI ≥2, albumin ≥3.5 g/dL), and frail and malnourished (mFI ≥2, albumin <3.5 g/dL). RESULTS: 60.4% of patients were healthy, 18.8% were malnourished, 11.7% were frail, and 9.0% were frail and malnourished. Frailty and/or malnourishment on admission predicted significantly higher odds of postoperative complications and mortality when compared with healthy patients. Frailty and malnourishment in conjunction predicted a significantly higher odds ratio of 1.46 (1.22-1.75) for developing postoperative complications when compared with the only malnourished. This was also observed when compared with the only frail (odd ratio: 1.61, P < 0.001); however, there was also a 2.72 (P < 0.001) increased odds of mortality. CONCLUSIONS: Frailty and malnutrition in conjunction predicts a subset of patients with a higher risk of postoperative complications beyond that of frailty or malnutrition in isolation. Identification of these physiological states on admission allows for interventional opportunities during hospitalization. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Chimeric-Antigen-Receptor (CAR) T Cells and the Factors Influencing their Therapeutic Efficacy.

Immunotherapeutic treatments for malignant cancers have revolutionized the medical and scientific fields. Lymphocytes engineered to display chimeric antigen receptor (CAR) molecules contribute to the exciting advancements that have stemmed from a greater understanding of cell structure and function, biological interactions, and the unique tumor microenvironment. CAR T cells circumvent the unique immune evasion capability of tumors by acting in a major histocompatibility complex (MHC) independent manner. Various factors contribute to the efficacy of CAR therapy, including CAR structure, gene transfer strategies, in vitro culture system, target selection, and preconditioning regimens. While recent clinical trials have shown promising success, cytotoxicity and other various challenges need to be addressed before CAR therapy can reach its full clinical potency. This review will discuss factors associated with CAR therapeutic success and the difficulties that continue to be a focus of research around the world.