Recurrent respiratory papillomatosis disease course in immunosuppressed populations.

OBJECTIVE: Recurrent respiratory papillomatosis is a benign manifestation of human papillomavirus types 6 and 11 in the respiratory tract. Disease is recurrent, and factors predicting these recurrences and severity of disease are incompletely characterised. This retrospective cohort study examined the relationship of immunosuppression with recurrent respiratory papillomatosis morbidity. METHODS: A retrospective cohort of 97 adult patients with recurrent respiratory papillomatosis treated at a tertiary referral centre from 2005 to 2020 was conducted. Measures assessed included inter-surgical interval, Voice Handicap Index ('VHI-10') and anatomical Derkay scores. RESULTS: Bivariate analyses comparing average inter-surgical interval, Voice Handicap Index and Derkay scores in immunosuppressed and healthy patients were insignificant. When controlling for diabetes mellitus and comparing immunosuppressed to healthy patients, inter-surgical interval and Voice Handicap Index change were insignificant (p = 0.458 and p = 0.465, respectively). CONCLUSION: Recurrent respiratory papillomatosis morbidity for immunosuppressed patients did not significantly differ from that of immunocompetent patients.

Endoscopic endonasal marsupialization of rathke cleft cysts: clinical outcomes and risk factors analysis of visual impairment, pituitary dysfunction, and CSF leak.

OBJECTIVE: This paper assesses the clinical and imaging characteristics, histopathological findings, and treatment outcomes of patients with Rathke's cleft cyst (RCC), as well as identifies potential risk factors for preoperative visual and pituitary dysfunction, intraoperative cerebrospinal fluid (CSF) leak, and recurrence. Through analyzing these factors, the study aims to contribute to the current understanding of the management of RCCs and identify opportunities for improving patient outcomes. METHODS: We performed a retrospective analysis of 45 RCC patients between ages 18-80 treated by Endoscopic Endonasal Approach (EEA) and cyst marsupialization between 2010 and 2022 at a single institution. RESULTS: The median patient age was 34, and 73% were female. The mean follow-up was 70 ± 43 months. Preoperative visual impairment correlated with cyst diameter (OR = 1.41, 95% CI = 1.07 to 1.85, p-value = 0.01) and older age (OR = 1.06, 95% CI = 1.01 to 1.11, p-value = 0.02). Intraoperative CSF leaks were 11 times more likely for cysts ≥ 2 cm (OR = 11.3, 95% CI = 1.25 to 97.37, p-value = 0.03), with the odds of leakage doubling for every 0.1 cm increase in cyst size (OR = 1.41, 95% CI = 1.08 to 1.84, p-value = 0.01). Preoperative RCC appearing hypointense on T1 images demonstrated significantly higher CSF leak rates than hyperintense lesions (OR = 122.88, 95% CI = 1.5 to 10077.54, p-value = 0.03). Preoperative pituitary hypofunction was significantly more likely in patients with the presence of inflammation on histopathology (OR = 20.53, 95% CI = 2.20 to 191.45, p-value = 0.008 ) and T2 hyperintensity on magnetic resonance imaging (MRI) sequences (OR = 23.2, 95% CI = 2.56 to 211.02, p-value = 0.005). Notably, except for the hyperprolactinemia, no postoperative improvement was observed in pituitary function. CONCLUSION: Carefully considering risk factors, surgeons can appropriately counsel patients and deliver expectations for complications and long-term results. In contrast to preoperative visual impairment, preoperative pituitary dysfunction was found to have the least improvement post-surgery. It was the most significant permanent complication, with our data indicating the link to the cyst signal intensity on T2 MR and inflammation on histopathology. Earlier surgical intervention might improve the preservation of pituitary function.

Biomarkers of Tumor Heterogeneity in Glioblastoma Multiforme Cohort of TCGA.

Tumor Whole Slide Images (WSI) are often heterogeneous, which hinders the discovery of biomarkers in the presence of confounding clinical factors. In this study, we present a pipeline for identifying biomarkers from the Glioblastoma Multiforme (GBM) cohort of WSIs from TCGA archive. The GBM cohort endures many technical artifacts while the discovery of GBM biomarkers is challenged because "age" is the single most confounding factor for predicting outcomes. The proposed approach relies on interpretable features (e.g., nuclear morphometric indices), effective similarity metrics for heterogeneity analysis, and robust statistics for identifying biomarkers. The pipeline first removes artifacts (e.g., pen marks) and partitions each WSI into patches for nuclear segmentation via an extended U-Net for subsequent quantitative representation. Given the variations in fixation and staining that can artificially modulate hematoxylin optical density (HOD), we extended Navab's Lab method to normalize images and reduce the impact of batch effects. The heterogeneity of each WSI is then represented either as probability density functions (PDF) per patient or as the composition of a dictionary predicted from the entire cohort of WSIs. For PDF- or dictionary-based methods, morphometric subtypes are constructed based on distances computed from optimal transport and linkage analysis or consensus clustering with Euclidean distances, respectively. For each inferred subtype, Kaplan-Meier and/or the Cox regression model are used to regress the survival time. Since age is the single most important confounder for predicting survival in GBM and there is an observed violation of the proportionality assumption in the Cox model, we use both age and age-squared coupled with the Likelihood ratio test and forest plots for evaluating competing statistics. Next, the PDF- and dictionary-based methods are combined to identify biomarkers that are predictive of survival. The combined model has the advantage of integrating global (e.g., cohort scale) and local (e.g., patient scale) attributes of morphometric heterogeneity, coupled with robust statistics, to reveal stable biomarkers. The results indicate that, after normalization of the GBM cohort, mean HOD, eccentricity, and cellularity are predictive of survival. Finally, we also stratified the GBM cohort as a function of EGFR expression and published genomic subtypes to reveal genomic-dependent morphometric biomarkers.

Smoking and Carcinoma Trends in Recurrent Respiratory Papillomatosis Patients.

INTRODUCTION: Recurrent respiratory papillomatosis (RRP) is a chronic disease of the upper respiratory tract caused by human papillomavirus types 6 and 11. The disease course is characteristically unpredictable, ranging from spontaneous remission to aggressive, recurrent disease. Thus, management is often challenging and requires unique approaches tailored to each individual patient. While recent literature has described risk factors for more aggressive disease, few sources have investigated the impact of smoking on RRP disease course and risk for malignant transformation. METHODS: A retrospective chart review was conducted for adult RRP patients evaluated at an academic tertiary care center between 2005 and 2020. A total of 188 patients were identified. Demographic and clinical data were collected, including smoking and alcohol history, HPV subtype, history of dysplasia and/or carcinoma, voice handicap index scores, Derkay scores, debulkings (in office and operating room), and days to papilloma recurrence. RESULTS: Malignant degeneration in RRP occurred in 16.3% of smokers and 3.6% of nonsmokers. Smokers who developed carcinoma had less debulkings per years of evaluation than those not developing carcinoma (0.21 vs 0.92, P = .004). Additionally, patients that either presented with or developed carcinoma during their course had a higher pack-year smoking history (18.0 vs 12.21, P = .0002). No difference in days to recurrence or inter-surgical interval was demonstrated between smokers and nonsmokers. CONCLUSIONS: The report demonstrates that smoking can increase the risk of malignant transformation in RRP patients.

Response to induction chemotherapy in sinonasal malignancies: A single-institutional experience.

BACKGROUND: Sinonasal malignancy (SNM) is a heterogeneous group of diseases for which induction chemotherapy (IC) may reduce tumor burden. The purpose of this study was to characterize the response to IC in SNM as a prognostic factor through its effect on survival. METHODS: Retrospective cohort of patients undergoing IC for SNM between 2010 and 2019 at our quaternary referral center. RESULTS: Forty-two patients with advanced SNM were included in the analysis. Patients with a favorable response to IC had higher survival rates than those who had an unfavorable response (5-year OS: 66.8% vs. 9.7%; p < 0.001; PFS: 56.8% vs. 0%; p < 0.001). CONCLUSIONS: Response to IC in our patient cohort was a prognostic indicator of overall response to treatment. Further elucidation of predictors of response is needed for appropriate patient selection.

Relationships Between the Auditory Nerve Sensitivity to Amplitude Modulation, Perceptual Amplitude Modulation Rate Discrimination Sensitivity, and Speech Perception Performance in Postlingually Deafened Adult Cochlear Implant Users.

OBJECTIVE: This study assessed the relationships between the salience of amplitude modulation (AM) cues encoded at the auditory nerve (AN), perceptual sensitivity to changes in AM rate (i.e., AM rate discrimination threshold, AMRDT), and speech perception scores in postlingually deafened adult cochlear implant (CI) users. DESIGN: Study participants were 18 postlingually deafened adults with Cochlear Nucleus devices, including five bilaterally implanted patients. For each of 23 implanted ears, neural encoding of AM cues at 20 Hz at the AN was evaluated at seven electrode locations across the electrode array using electrophysiological measures of the electrically evoked compound action potential (eCAP). The salience of AM neural encoding was quantified by the Modulated Response Amplitude Ratio (MRAR). Psychophysical measures of AMRDT for 20 Hz modulation were evaluated in 16 ears using a three-alternative, forced-choice procedure, targeting 79.4% correct on the psychometric function. AMRDT was measured at up to five electrode locations for each test ear, including the electrode pair that showed the largest difference in the MRAR. Consonant-Nucleus-Consonant (CNC) word scores presented in quiet and in speech-shaped noise at a signal to noise ratio (SNR) of +10 dB were measured in all 23 implanted ears. Simulation tests were used to assess the variations in correlation results when using the MRAR and AMRDT measured at only one electrode location in each participant to correlate with CNC word scores. Linear Mixed Models (LMMs) were used to evaluate the relationship between MRARs/AMRDTs measured at individual electrode locations and CNC word scores. Spearman Rank correlation tests were used to evaluate the strength of association between CNC word scores measured in quiet and in noise with (1) the variances in MRARs and AMRDTs, and (2) the averaged MRAR or AMRDT across multiple electrodes tested for each participant. RESULTS: There was no association between the MRAR and AMRDT. Using the MRAR and AMRDT measured at only one, randomly selected electrode location to assess their associations with CNC word scores could lead to opposite conclusions. Both the results of LMMs and Spearman Rank correlation tests showed that CNC word scores measured in quiet or at 10 dB SNR were not significantly correlated with the MRAR or AMRDT. In addition, the results of Spearman Rank correlation tests showed that the variances in MRARs and AMRDTs were not significantly correlated with CNC word scores measured in quiet or in noise. CONCLUSIONS: The difference in AN sensitivity to AM cues is not the primary factor accounting for the variation in AMRDTs measured at different stimulation sites within individual CI users. The AN sensitivity to AM per se may not be a crucial factor for CNC word perception in quiet or at 10 dB SNR in postlingually deafened adult CI users. Using electrophysiological or psychophysical results measured at only one electrode location to correlate with speech perception scores in CI users can lead to inaccurate, if not wrong, conclusions.

Reliability of Multifrequency Bioelectrical Impedance Analysis to Quantify Body Composition in Patients After Musculoskeletal Trauma.

Background: Changes in body composition, especially loss of lean mass, commonly occur in the orthopedic trauma population due to physical inactivity and inadequate nutrition. The purpose of this study was to assess inter-rater and intra-rater reliability of a portable bioelectrical impedance analysis (BIA) device to measure body composition in an orthopedic trauma population after operative fracture fixation. BIA uses a weak electric current to measure impedance (resistance) in the body and uses this to calculate the components of body composition using extensively studied formulas. Methods: Twenty subjects were enrolled, up to 72 hours after operative fixation of musculoskeletal injuries and underwent body composition measurements by two independent raters. One measurement was obtained by each rater at the time of enrollment and again between 1-4 hours after the initial measurement. Reliability was assessed using intraclass correlation coefficients (ICC) and minimum detectable change (MDC) values were calculated from these results. Results: Inter-rater reliability was excellent with ICC values for body fat mass (BFM), lean body mass (LBM), skeletal muscle mass (SMM), dry lean mass (DLM), and percent body fat (PBF) of 0.993, 0.984, 0.984, 0.979, and 0.986 respectively. Intra-rater reliability was also high for BFM, LBM, SMM, DLM, and PBF, at 0.994, 0.989, 0.990, 0.983, 0.987 (rater 1) and 0.994, 0.988, 0.989, 0.985, 0.989 (rater 2). MDC values were calculated to be 4.05 kg for BFM, 4.10 kg for LBM, 2.45 kg for SMM, 1.21 kg for DLM, and 4.83% for PBF. Conclusion: Portable BIA devices are a versatile and attractive option that can reliably be used to assess body composition and changes in lean body mass in the orthopedic trauma population for both research and clinical endeavors. Level of Evidence: III.

Identification of Non-Fatal Opioid Overdose Cases Using 9-1-1 Computer Assisted Dispatch and Prehospital Patient Clinical Record Variables.

Background: The current epidemic of opioid overdoses in the United States necessitates a robust public health and clinical response. We described patterns of non-fatal opioid overdoses (NFOODs) in a small western region using data from the 9-1-1 Computer Assisted Dispatch (CAD) record and electronic Patient Clinical Records (ePCR) completed by EMS responders. We determined whether CAD and ePCR variables could identify NFOOD cases in 9-1-1 data for intervention and surveillance efforts. Methods: We conducted a retrospective analysis of 1 year of 9-1-1 emergency medical CAD and ePCR (including naloxone administration) data from the sole EMS provider in the response area. Cases were identified based on clinician review of the ePCR, and categorized as definitive NFOOD, probable NFOOD, or non-OOD. Sensitivity, specificity, positive and negative predictive values (PPV and NPV) of the most prevalent CAD and ePCR variables were calculated. We used a machine learning technique-Random-Forests (RF) modeling-to optimize our ability to accurately predict NFOOD cases within census blocks. Results: Of 37,960 9-1-1 calls, clinical review identified 158 NFOOD cases (0.4%), of which 123 (77.8%) were definitive and 35 (22.2%) were probable cases. Overall, 106 (67.1%) received naloxone from the EMS responder at the scene. As a predictor of NFOOD, naloxone administration by paramedics had 67.1% sensitivity, 99.6% specificity, 44% PPV, and 99.9% NPV. Using CAD variables alone achieved a sensitivity of 36.7% and specificity of 99.7%. Combining ePCR variables with CAD variables increased the diagnostic accuracy with the best RF model yielding 75.9% sensitivity, 99.9% specificity, 71.4% PPV, and 99.9% NPV. Conclusion: CAD problem type variables and naloxone administration, used alone or in combination, had sub-optimal predictive accuracy. However, a Random Forests modeling approach improved accuracy of identification, which could foster improved surveillance and intervention efforts. We identified the set of NFOODs that EMS encountered in a year and may be useful for future surveillance efforts.

Assessing effect heterogeneity of a randomized treatment using conditional inference trees.

Treatment effect heterogeneity occurs when individual characteristics influence the effect of a treatment. We propose a novel approach that combines prognostic score matching and conditional inference trees to characterize effect heterogeneity of a randomized binary treatment. One key feature that distinguishes our method from alternative approaches is that it controls the Type I error rate, that is, the probability of identifying effect heterogeneity if none exists and retains the underlying subgroups. This feature makes our technique particularly appealing in the context of clinical trials, where there may be significant costs associated with erroneously declaring that effects differ across population subgroups. Treatment effect heterogeneity trees are able to identify heterogeneous subgroups, characterize the relevant subgroups and estimate the associated treatment effects. We demonstrate the efficacy of the proposed method using a comprehensive simulation study and illustrate our method using a nutrition trial dataset to evaluate effect heterogeneity within a patient population.

Factors Associated With Calling 911 for an Overdose: An Ethnographic Decision Tree Modeling Approach.

Objectives. To identify factors that influence when people who use drugs (PWUDs) call 911 for an overdose. Methods. We conducted 45 qualitative interviews and 180 surveys with PWUDs who had recently witnessed overdoses in Southern California from 2017 to 2019. We used conditional inference tree and random forest models to generate and validate a model to predict whether 911 would be called. Results. Our model had good in- (83%) and out-of-sample (84%) predictive accuracy. Three aspects of the social and policy environment influenced calling 911 for an overdose: the effectiveness of response strategies employed, the behavior of other bystanders, and whether the responder believes it is their responsibility to call. Conclusions. Even in the presence of policies that provide some protections, PWUDs are faced with difficult decisions about calling 911 and must weigh their own safety against that of an overdose victim. Potential interventions include strengthening training and safety planning for PWUDs, bolstering protections for PWUDs when they call 911, and separating law enforcement response from emergency medical response to overdoses.

Correlates of Medical Mistrust Among Minority Women at Risk for HIV and Their Networks.

BACKGROUND: Medical mistrust is a barrier to engaging in HIV prevention and treatment, including testing and adherence to antiretroviral therapy. Research often focuses on how race and experiences of discrimination relate to medical mistrust, overlooking the role that other characteristics may play (e.g., history of physical abuse, diagnosis of mental illness). Furthermore, studies are often restricted to samples of men who have sex with men and findings may not generalize to other at-risk groups. AIMS: The current study explores a range of demographic, cognitive, behavioral, and social network correlates of medical mistrust. METHOD: This study employed an egocentric network design among a racially diverse sample of at-risk women and women in their social networks (n = 165). RESULTS: Results from multivariable linear regressions stratified by race (Black vs. others) indicate that medical mistrust is associated with both individual-level and network-level characteristics. Across both groups, age and experiences of racial discrimination were associated with higher medical mistrust. Having a regular sex partner and having a higher proportion of network members who are family was significantly associated with medical mistrust among non-Black women. DISCUSSION: Individual-level and network-level variables were significantly associated with medical mistrust. Therefore, interventions that attempt to mitigate medical mistrust as a barrier to HIV prevention and treatment should consider how mistrust may be related to characteristics of individuals and broader contexts. CONCLUSION: Health interventions may benefit from conceiving of medical mistrust as a complex, rational response to cumulative discriminatory life experiences and a reflection of the networks within which individuals are embedded.

Intensive Longitudinal Study of the Relationship Between Cigalike E-cigarette Use and Cigarette Smoking Among Adult Cigarette Smokers Without Immediate Plans to Quit Smoking.

INTRODUCTION: This study examined the association between the introduction of an e-cigarette and subsequent change in cigarette smoking among smokers who were not immediately interested in quitting. AIMS AND METHODS: The Moment Study was a 21-day intensive longitudinal study with an online follow-up survey at 30 days. After observing baseline cigarette smoking for 1 week, participants received 10 cigalike e-cigarettes on study days 6 and 13. Participants reported cigarettes per day, e-cigarette puffs per day, and e-cigarette satisfaction using text-message-based surveys. RESULTS: The sample of 96 daily smokers was majority female (53.1%), African American (67.7%), and non-Hispanic (95.8%). When e-cigarettes were provided (day 6), average cigarettes per day dropped by 1.82 cigarettes (p < .0001). The within-person e-cigarette puff effect on daily cigarette smoking was significantly negative (ß = -0.023; p = .005); a participant who consumed 100 more e-cigarette puffs in a day than usual for that person was expected to smoke 2.3 fewer cigarettes that day, but this was only true for non-menthol smokers (p = .006). Smokers older than 45 and those who started smoking at a younger age rated e-cigarettes as less satisfying (ps < .05). Participants with greater than the median reported satisfaction were 6.5 times more likely to use an e-cigarette at follow-up. CONCLUSIONS: Giving e-cigarettes to smokers who did not intend to quit reduced their cigarette smoking on days when they used e-cigarette more frequently, but this relationship did not hold for menthol smokers. Satisfaction with e-cigarette use was predictive of continued use 30 days later. IMPLICATIONS: A greater amount of cigalike e-cigarette use resulted in less smoking among adult daily smokers without immediate plans to quit, but a lack of nicotine delivery and satisfaction for these devices may have limited their utility as a replacement for cigarette smoking, especially among menthol smokers. The global concept of "satisfaction" may be an important driver of e-cigarette use among adult smokers.

Role of Social Networks and Social Norms in Future PrEP Use in a Racially Diverse Sample of At-Risk Women and Members of Their Social Networks.

OBJECTIVE: Despite the efficacy of pre-exposure prophylaxis (PrEP) in reducing the risk of HIV infection, uptake remains low among many who are most vulnerable to HIV, such as Black and Latinx women. Interventions that target social networks to encourage at-risk women to initiate PrEP are underused. DESIGN: This study used an egocentric network design and sampled Black/African American and Latinx women at risk of HIV as well as people from their social networks (N = 211) in a small, western city. METHODS: Multivariable generalized linear mixed effects regression models investigated individual-level and network-level characteristics associated with likely future PrEP use. RESULTS: PrEP awareness was low, but once informed, 36% considered themselves likely to take it in the future. Perceived risk of HIV, perceived barriers to HIV testing, and participation in a 12-step program increased odds of anticipated PrEP use. A higher proportion of friends in one's network decreased odds of future PrEP use, whereas a higher proportion of network members who tested regularly for HIV increased odds of future PrEP use. A marginally significant interaction was detected between proportion of friends in one's network and proportion of the network perceived to test for HIV regularly (ie, testing norms). When HIV testing norms were low, a higher proportion of friends in the network decreased odds of likely PrEP use. However, this effect was reversed in contexts with strong testing norms. CONCLUSION: Women who are interested in PrEP may be embedded within social and normative contexts that can foster or inhibit PrEP uptake.

Mental Health Risk Among Members of the Millennial Population Cohort: A Concern for Public Health.

PURPOSE: Within the millennial population cohort, identify groups reporting increased risk of nonspecific psychological distress. As the largest living population cohort, taking stock of health and well-being early is necessary as substantial national resources may be needed as this cohort ages. DESIGN: The 2017 National Health Interview Survey data, an annual multipurpose survey of the US population, was used. SAMPLE: A sample of 7303 respondents were created by limiting data set to birth years 1980 to 1998. MEASURES: Outcomes were feeling like everything is an effort, worthlessness, hopelessness, restlessness, nervousness, and sadness. Combined these statements of feeling make up a measure of nonspecific psychological distress, past 30 days. ANALYSIS: A logistic regression was performed on each outcome. All models controlled for demographic variables known to be associated with psychological distress. RESULTS: Females are 1.4 times more likely than males to report nonspecific psychological distress (P < .001), whereas Hispanics and Blacks are less likely to report nonspecific psychological distress (odds ratio [OR] = 0.49, OR = 0.57, P < .001). American Indians were less likely to report worthlessness (OR = 0.30, P < .05). However, multiple race individuals increasingly reported hopelessness (OR = 1.55, P < .05). Young adults are less likely than emerging adults to report sadness (OR = 0.85, P < .05). CONCLUSION: In this sample, racial/ethnic groups fared better than referent groups. Health programs need to integrate intersectional identities into promotion of mental health.

Does education about local vaccination rates and the importance of herd immunity change US parents' concern about measles?

It is unclear how broadly aware parents are of the concept of herd immunity and whether parents consider community benefits of vaccination when making decisions about their child's vaccinations. We aimed to determine whether educating parents about community-level benefits of measles, mumps, and rubella (MMR) vaccination and local vaccination rates would impact concern about their child's risk of measles and risk of a measles outbreak. We conducted an electronic survey among Minnesota parents of children aged 6-18 years in August 2016. We assessed baseline knowledge of herd immunity, asked participants to estimate MMR vaccination coverage in their county, and asked participants to estimate the minimum coverage needed to prevent measles outbreaks. We then delivered a short, educational intervention via the survey to inform participants about the benefits of herd immunity, the actual MMR vaccination coverage in their county, and that at least 95% MMR vaccination coverage is needed to prevent measles outbreaks. Pre- and post-intervention, participants were asked to report how concerned they were that their child might get measles. We used logistic regression models to assess factors associated with awareness of herd immunity, change in concern about one's child's measles risk, and overall concern for a measles outbreak. Among 493 participants, 67.8% were aware of herd immunity at baseline. Post-intervention, 40.2% (n = 198) of parents learned that MMR vaccination rates in their county were higher than they expected. All participants found out that their county MMR rates were lower than the measles herd immunity threshold of 95%. Overall, 27.0% (n = 133) of participants reported an increase in concern that their child might get measles after learning about local vaccination coverage and the coverage needed to achieve herd immunity. We found that our short, educational intervention aimed to increase awareness about herd immunity and local vaccination led to an increase in concern about disease risk among less than a third of parents.

Decreasing the prospect of upper extremity neuropraxia during robotic assisted laparoscopic prostatectomy: a novel technique.

Risk of intraoperative neuropathic injury in minimally invasive surgery has been established as a leading complication. Continuous intraoperative neuromonitoring (IONM), such as upper extremity somatosensory evoked potentials (ueSSEPs), to decrease peripheral nerve injury due to positional stress has been described. Robotic-assisted laparoscopic prostatectomy (RALP) requires steep Trendelenberg, which may predispose patients to upper extremity neuropraxia. Subdermal stimulating electrodes were placed on the patients' bilateral wrists over the ulnar nerve and the nerve was stimulated. Realtime waveforms were compared to baseline data to prevent and detect injury to the ulnar nerve. Established intervention criteria, indicating risk for neuropathic damage necessitating intraoperative patient repositioning, was a 50% loss in amplitude or a 10% increase in latency. One hundred and forty three patients received RALP with IONM. 17 of 143 patients (11.8%) met ueSSEP intervention criteria. Only weight was significantly different between the two groups (p = 0.04). Mean reduction in amplitude was 79.9% (SE 4.1). Average amplitude loss duration was 22 min (SE 4.0). Weight and BMI were correlated to the degree of amplitude reduction (p = 0.03 and < 0.01), while operative time and DM approached significance (p = 0.09 and p = 0.14). This is the first study to use IONM to reduce the risk of nerve injury during genitourinary surgery. Realtime nerve monitoring using ueSSEP allowed for upper extremity intraoperative monitoring and repositioning. This may decrease the risk of upper extremity neuropraxia due to malpositioning during RALP. Weight and BMI were identified as risk factors for possible nerve injury. Further data collection and analysis to preoperatively stratify patients for application of IONM during RALP is currently ongoing.

Variable selection and estimation in causal inference using Bayesian spike and slab priors.

Unbiased estimation of causal effects with observational data requires adjustment for confounding variables that are related to both the outcome and treatment assignment. Standard variable selection techniques aim to maximize predictive ability of the outcome model, but they ignore covariate associations with treatment and may not adjust for important confounders weakly associated to outcome. We propose a novel method for estimating causal effects that simultaneously considers models for both outcome and treatment, which we call the bilevel spike and slab causal estimator (BSSCE). By using a Bayesian formulation, BSSCE estimates the posterior distribution of all model parameters and provides straightforward and reliable inference. Spike and slab priors are used on each covariate coefficient which aim to minimize the mean squared error of the treatment effect estimator. Theoretical properties of the treatment effect estimator are derived justifying the prior used in BSSCE. Simulations show that BSSCE can substantially reduce mean squared error over numerous methods and performs especially well with large numbers of covariates, including situations where the number of covariates is greater than the sample size. We illustrate BSSCE by estimating the causal effect of vasoactive therapy vs. fluid resuscitation on hypotensive episode length for patients in the Multiparameter Intelligent Monitoring in Intensive Care III critical care database.

DSS1 interacts with and stimulates RAD52 to promote the repair of DSBs.

The proper repair of deleterious DNA lesions such as double strand breaks prevents genomic instability and carcinogenesis. In yeast, the Rad52 protein mediates DSB repair via homologous recombination. In mammalian cells, despite the presence of the RAD52 protein, the tumour suppressor protein BRCA2 acts as the predominant mediator during homologous recombination. For decades, it has been believed that the RAD52 protein played only a back-up role in the repair of DSBs performing an error-prone single strand annealing (SSA). Recent studies have identified several new functions of the RAD52 protein and have drawn attention to its important role in genome maintenance. Here, we show that RAD52 activities are enhanced by interacting with a small and highly acidic protein called DSS1. Binding of DSS1 to RAD52 changes the RAD52 oligomeric conformation, modulates its DNA binding properties, stimulates SSA activity and promotes strand invasion. Our work introduces for the first time RAD52 as another interacting partner of DSS1 and shows that both proteins are important players in the SSA and BIR pathways of DSB repair.

Ergot alkaloid exposure during gestation alters. I. Maternal characteristics and placental development of pregnant ewes1.

Tall fescue [Lolium arundinaceum (Scheyreb.) Darbysh] is the primary cool season forage grass in the Southeastern United States. Most tall fescue contains an endophytic fungus (Epichloë coenophiala) that produces ergot alkaloids and upon ingestion induces fescue toxicosis. The objective of this study was to assess how exposure to endophyte-infected (E+; 1.77 mg hd-1 d-1 ergovaline and ergovalinine) or endophyte-free (E-; 0 mg hd-1 d-1 ergovaline and ergovalinine) tall fescue seed fed during 2 stages of gestation (MID, days 35-85/LATE, days 86-133) alters placental development. Thirty-six, fescue naïve Suffolk ewes were randomly assigned to 1 of 4 fescue treatments: E-/E-, E-/E+, E+/E-, or E+/E+. Ewes were individually fed the same amount of E+ or E- seed mixed into total mixed ration during MID and LATE gestation. Terminal surgeries were conducted on day 133 of gestation. Ewes fed E+ fescue seed had elevated (P < 0.001) ergot alkaloid excretion and reduced (P < 0.001) prolactin levels during the periods when fed E+ seed. Ewes switched on day 86 from E- to E+ seed had a 4% reduction (P = 0.005) in DMI during LATE gestation, which translated to a 2% reduction (P = 0.07) in DMI overall. Average daily gain was also reduced (P = 0.049) by 64% for E-/E+ ewes during LATE gestation and tended to be reduced (P = 0.06) by 33% overall. Ewes fed E+ seed during LATE gestation exhibited a 14% and 23% reduction in uterine (P = 0.03) and placentome (P = 0.004) weights, respectively. Caruncle weights were also reduced by 28% (P = 0.003) for E-/E+ ewes compared with E-/E- and E+/E-. Ewes fed E+ seed during both MID and LATE gestation exhibited a 32% reduction in cotyledon (P = 0.01) weights, whereas ewes fed E+ seed only during MID gestation (E+/E-) had improved (P = 0.01) cotyledon weights. The percentage of type A placentomes tended to be greater (P = 0.08) for E+/E+ ewes compared with other treatments. Other placentome types (B, C, or D) did not differ (P > 0.05). Total fetal weight per ewe was reduced (P = 0.01) for ewes fed E+ seed during LATE gestation compared with E-; however, feeding E+ seed during MID gestation did not alter (P = 0.70) total fetal weight per ewe. These results suggest that exposure to ergot alkaloids during LATE (days 86-133) gestation has the greatest impact on placental development by reducing uterine and placentome weights. This, in turn, reduced total fetal weight per ewe by 15% in ewes fed E+ seed during LATE gestation (E-/E+ and E+/E+).

'What have you HEARD about the HERD?' Does education about local influenza vaccination coverage and herd immunity affect willingness to vaccinate?

BACKGROUND: Vaccination protects individuals directly and communities indirectly by reducing transmission. We aimed to determine whether information about herd immunity and local vaccination coverage could change an individual's vaccination plans and concern about influenza. METHODS: We surveyed Minnesota residents ≥18 years during the 2016 Minnesota State Fair. Participants were asked to identify the definition of herd immunity, to report their history of and plans to receive influenza vaccine, to report their concern about influenza, and to estimate the reported influenza vaccination coverage in their county. After providing educational information about herd immunity and local vaccination rates, we reassessed vaccination plans and concerns. We used logistic regression to estimate predicted percentages for those willing to be vaccinated, for concern about influenza, and for changes in these outcomes after the intervention. We then compared those individuals with and without prior knowledge of herd immunity, accounting for other characteristics. RESULTS: Among 554 participants, the median age was 57 years; most were female (65.9%), white (91.0%), and non-Hispanic/Latino (93.9%). Overall, 37.2% of participants did not know about herd immunity and 75.6% thought that the influenza vaccination coverage in their county was higher than it was reported. Those not knowledgeable about herd immunity were significantly less likely than those knowledgeable about the concept to report plans to be vaccinated at baseline (67.8% versus 78.9%; p = 0.004). After learning about herd immunity and influenza vaccination coverage, the proportion of those not knowledgeable about herd immunity who were willing to be vaccinated increased significantly by 7.3 percentage points (p = 0.001). Educating participants eliminated the significant difference in the proportion planning to be vaccinated between these two groups (80.1% of those knowledgeable and 75.1% of those who were not initially knowledgeable became willing; p = 0.148). CONCLUSIONS: Education about herd immunity and local vaccination coverage could be a useful tool for increasing willingness to vaccinate, generating benefits both to individuals and communities.