Deep Phenotyping the Anterior Urethral Stricture: Characterizing the Relationship Between Inflammation, Fibrosis, Patient History, and Disease Pathophysiology.

PURPOSE: Anterior urethral stricture disease (aUSD) is a complex, heterogeneous condition that is idiopathic in origin for most men. This gap in knowledge rarely affects the current management strategy for aUSD, as urethroplasty does not generally consider etiology. However, as we transition towards personalized, minimally invasive treatments for aUSD and begin to consider aUSD prevention strategies, disease pathophysiology will become increasingly important. The purpose of this study was to perform a deep phenotype of men undergoing anterior urethroplasty for aUSD. We hypothesized that unique biologic signatures and potential targets for intervention would emerge based on stricture presence/absence, stricture etiology, and the presence/absence of stricture inflammation. MATERIALS AND METHODS: Men with aUSD undergoing urethroplasty were recruited from one of 5 participating centers. Enrollees provided urethral stricture tissue and blood/serum on the day of surgery and completed patient-reported outcome measure questionnaires both pre- and postoperatively. The initial study had 3 aims: (1) to determine pediatric and adult subacute and repeated perineal trauma (SRPT) exposures using a study-specific SRPT questionnaire, (2) to determine the degree of inflammation and fibrosis in aUSD and peri-aUSD (normal urethra) tissue, and (3) to determine levels of systemic inflammatory and fibrotic cytokines. Two controls groups provided serum (normal vasectomy patients) and urethral tissue (autopsy patients). Cohorts were based on the presence/absence of stricture, by presumed stricture etiology (idiopathic, traumatic/iatrogenic, lichen sclerosus [LS]), and by the presence/absence of stricture inflammation. RESULTS: Of 138 enrolled men (120 tissue/serum; 18 stricture tissue only), 78 had idiopathic strictures, 33 had trauma-related strictures, and 27 had LS-related strictures. BMI, stricture length, and stricture location significantly differed between cohorts (P < .001 for each). The highest BMIs and the longest strictures were observed in the LS cohort. SRPT exposures did not significantly differ between etiology cohorts, with > 60% of each reporting low/mild risk. Stricture inflammation significantly differed between cohorts, with mild to severe inflammation present in 27% of trauma-related strictures, 54% of idiopathic strictures, and 48% of LS strictures (P = .036). Stricture fibrosis did not significantly differ between cohorts (P = .7). Three serum cytokines were significantly higher in patients with strictures compared to stricture-free controls: interleukin-9 (IL-9; P = .001), platelet-derived growth factor-BB (P = .004), and CCL5 (P = .01). No differences were observed in the levels of these cytokines based on stricture etiology. However, IL-9 levels were significantly higher in patients with inflamed strictures than in patients with strictures lacking inflammation (P = .019). Degree of stricture inflammation positively correlated with serum levels of IL-9 (Spearman's rho 0.224, P = .014). CONCLUSIONS: The most common aUSD etiology is idiopathic. Though convention has implicated SRPT as causative for idiopathic strictures, here we found that patients with idiopathic strictures had low SRPT rates that were similar to rates in patients with a known stricture etiology. Stricture and stricture-adjacent inflammation in idiopathic stricture were similar to LS strictures, suggesting shared pathophysiologic mechanisms. IL-9, platelet-derived growth factor-BB, and CCL5, which were elevated in patients with strictures, have been implicated in fibrotic conditions elsewhere in the body. Further work will be required to determine if this shared biologic signature represents a potential mechanism for an aUSD predisposition.

Peripheral Neural Synchrony in Postlingually Deafened Adult Cochlear Implant Users.

OBJECTIVES: This paper reports a noninvasive method for quantifying neural synchrony in the cochlear nerve (i.e., peripheral neural synchrony) in cochlear implant (CI) users, which allows for evaluating this physiological phenomenon in human CI users for the first time in the literature. In addition, this study assessed how peripheral neural synchrony was correlated with temporal resolution acuity and speech perception outcomes measured in quiet and in noise in postlingually deafened adult CI users. It tested the hypothesis that peripheral neural synchrony was an important factor for temporal resolution acuity and speech perception outcomes in noise in postlingually deafened adult CI users. DESIGN: Study participants included 24 postlingually deafened adult CI users with a Cochlear™ Nucleus® device. Three study participants were implanted bilaterally, and each ear was tested separately. For each of the 27 implanted ears tested in this study, 400 sweeps of the electrically evoked compound action potential (eCAP) were measured at four electrode locations across the electrode array. Peripheral neural synchrony was quantified at each electrode location using the phase-locking value (PLV), which is a measure of trial-by-trial phase coherence among eCAP sweeps/trials. Temporal resolution acuity was evaluated by measuring the within-channel gap detection threshold (GDT) using a three-alternative, forced-choice procedure in a subgroup of 20 participants (23 implanted ears). For each ear tested in these participants, GDTs were measured at two electrode locations with a large difference in PLVs. For 26 implanted ears tested in 23 participants, speech perception performance was evaluated using consonant-nucleus-consonant (CNC) word lists presented in quiet and in noise at signal to noise ratios (SNRs) of +10 and +5 dB. Linear Mixed effect Models were used to evaluate the effect of electrode location on the PLV and the effect of the PLV on GDT after controlling for the stimulation level effects. Pearson product-moment correlation tests were used to assess the correlations between PLVs, CNC word scores measured in different conditions, and the degree of noise effect on CNC word scores. RESULTS: There was a significant effect of electrode location on the PLV after controlling for the effect of stimulation level. There was a significant effect of the PLV on GDT after controlling for the effects of stimulation level, where higher PLVs (greater synchrony) led to lower GDTs (better temporal resolution acuity). PLVs were not significantly correlated with CNC word scores measured in any listening condition or the effect of competing background noise presented at an SNR of +10 dB on CNC word scores. In contrast, there was a significant negative correlation between the PLV and the degree of noise effect on CNC word scores for a competing background noise presented at an SNR of +5 dB, where higher PLVs (greater synchrony) correlated with smaller noise effects on CNC word scores. CONCLUSIONS: This newly developed method can be used to assess peripheral neural synchrony in CI users, a physiological phenomenon that has not been systematically evaluated in electrical hearing. Poorer peripheral neural synchrony leads to lower temporal resolution acuity and is correlated with a larger detrimental effect of competing background noise presented at an SNR of 5 dB on speech perception performance in postlingually deafened adult CI users.

Development of the Children's English and Spanish Speech Recognition Test: Psychometric Properties, Feasibility, Reliability, and Normative Data.

OBJECTIVES: The Children's English and Spanish Speech Recognition (ChEgSS) test is a computer-based tool for assessing closed-set word recognition in English and in Spanish, with a masker that is either speech-shaped noise or competing speech. The present study was conducted to (1) characterize the psychometric properties of the ChEgSS test, (2) evaluate feasibility and reliability for a large cohort of Spanish/English bilingual children with normal hearing, and (3) establish normative data. DESIGN: Three experiments were conducted to evaluate speech perception in children (4-17 years) and adults (19-40 years) with normal hearing using the ChEgSS test. In Experiment 1, data were collected from Spanish/English bilingual and English monolingual adults at multiple, fixed signal-to-noise ratios. Psychometric functions were fitted to the word-level data to characterize variability across target words in each language and in each masker condition. In Experiment 2, Spanish/English bilingual adults were tested using an adaptive tracking procedure to evaluate the influence of different target-word normalization approaches on the reliability of estimates of masked-speech recognition thresholds corresponding to 70.7% correct word recognition and to determine the optimal number of reversals needed to obtain reliable estimates. In Experiment 3, Spanish/English bilingual and English monolingual children completed speech perception testing using the ChEgSS test to (1) characterize feasibility across age and language group, (2) evaluate test-retest reliability, and (3) establish normative data. RESULTS: Experiments 1 and 2 yielded data that are essential for stimulus normalization, optimizing threshold estimation procedures, and interpreting threshold data across test language and masker type. Findings obtained from Spanish/English bilingual and English monolingual children with normal hearing in Experiment 3 support feasibility and demonstrate reliability for use with children as young as 4 years of age. Equivalent results for testing in English and Spanish were observed for Spanish/English bilingual children, contingent on adequate proficiency in the target language. Regression-based threshold norms were established for Spanish/English bilingual and English monolingual children between 4 and 17 years of age. CONCLUSIONS: The present findings indicate the ChEgSS test is appropriate for testing a wide age range of children with normal hearing in either Spanish, English, or both languages. The ChEgSS test is currently being evaluated in a large cohort of patients with hearing loss at pediatric audiology clinics across the United States. Results will be compared with normative data established in the present study and with established clinical measures used to evaluate English- and Spanish-speaking children. Questionnaire data from parents and clinician feedback will be used to further improve test procedures.

Introduction to Bayesian Analyses for Clinical Research.

Bayesian analyses are becoming more popular as a means of analyzing data, yet the Bayesian approach is novel to many members of the broad clinical audience. While Bayesian analyses are foundational to anesthesia pharmacokinetic/pharmacodynamic modeling, they also can be used for analyzing data from clinical trials or observational studies. The traditional null hypothesis significance testing (frequentist) approach uses only the data collected from the current study to make inferences. On the other hand, the Bayesian approach quantifies the external information or expert knowledge and combines the external information with the study data, then makes inference from this combined information. We introduce to the clinical and translational science researcher what it means to do Bayesian statistics, why a researcher would choose to perform their analyses using the Bayesian approach, when it would be advantageous to use a Bayesian instead of a frequentist approach, and how Bayesian analyses and interpretations differ from the more traditional frequentist methods. Throughout this paper, we use various pain- and anesthesia-related examples to highlight the ideas and statistical concepts that should be relatable to other areas of research as well.

Contribution of macrophages to neural survival and intracochlear tissue remodeling responses following cochlear implantation.

BACKGROUND: Cochlear implants (CIs) restore hearing to deafened patients. The foreign body response (FBR) following cochlear implantation (post-CI) comprises an infiltration of macrophages, other immune and non-immune cells, and fibrosis into the scala tympani, a space that is normally devoid of cells. This FBR is associated with negative effects on CI outcomes including increased electrode impedances and loss of residual acoustic hearing. This study investigates the extent to which macrophage depletion by an orally administered CSF-1R specific kinase (c-FMS) inhibitor, PLX-5622, modulates the tissue response to CI and neural health. MAIN TEXT: 10- to 12-week-old CX3CR1 + /GFP Thy1 + /YFP mice on C57BL/6J/B6 background was fed chow containing 1200 mg/kg PLX5622 or control chow for the duration of the study. 7 days after starting the diet, 3-channel cochlear implants were implanted in the ear via the round window. Serial impedance and neural response telemetry (NRT) measurements were acquired throughout the study. Electric stimulation began 7 days post-CI until 28 days post-CI for 5 h/day, 5 days/week, with programming guided by NRT and behavioral responses. Cochleae harvested at 10, 28 or 56 days post-CI were cryosectioned and labeled with an antibody against α-smooth muscle actin (α-SMA) to identify myofibroblasts and quantify the fibrotic response. Using IMARIS image analysis software, the outlines of scala tympani, Rosenthal canal, modiolus, and lateral wall for each turn were traced manually to measure region volume. The density of nuclei, CX3CR1 + macrophages, Thy1 + spiral ganglion neuron (SGN) numbers, and the ratio of the α-SMA + volume/scala tympani volume were calculated. Cochlear implantation in control diet subjects caused infiltration of cells, including macrophages, into the cochlea. Fibrosis was evident in the scala tympani adjacent to the electrode array. Mice fed PLX5622 chow showed reduced macrophage infiltration throughout the implanted cochleae across all time points. However, scala tympani fibrosis was not reduced relative to control diet subjects. Further, mice treated with PLX5622 showed increased electrode impedances compared to controls. Finally, treatment with PLX5622 decreased SGN survival in implanted and contralateral cochleae. CONCLUSION: The data suggest that macrophages play an important role in modulating the intracochlear tissue response following CI and neural survival.

An individual level infectious disease model in the presence of uncertainty from multiple, imperfect diagnostic tests.

Bayesian compartmental infectious disease models yield important inference on disease transmission by appropriately accounting for the dynamics and uncertainty of infection processes. In addition to estimating transition probabilities and reproductive numbers, these statistical models allow researchers to assess the probability of disease risk and quantify the effectiveness of interventions. These infectious disease models rely on data collected from all individuals classified as positive based on various diagnostic tests. In infectious disease testing, however, such procedures produce both false-positives and false-negatives at varying rates depending on the sensitivity and specificity of the diagnostic tests being used. We propose a novel Bayesian spatio-temporal infectious disease modeling framework that accounts for the additional uncertainty in the diagnostic testing and classification process that provides estimates of the important transmission dynamics of interest to researchers. The method is applied to data on the 2006 mumps epidemic in Iowa, in which over 6,000 suspected mumps cases were tested using a buccal or oral swab specimen, a urine specimen, and/or a blood specimen. Although all procedures are believed to have high specificities, the sensitivities can be low and vary depending on the timing of the test as well as the vaccination status of the individual being tested.

Changes of creative ability and underlying brain network connectivity throughout the lifespan.

Creativity, or divergent thinking, is essential to and supported by cognitive functions necessary for everyday tasks. The current study investigates divergent thinking and its neural mechanisms from adolescence to late adulthood. To do this, 180 healthy participants completed a creativity task called the egg task including 86 adolescents (mean age (SD) = 13.62 (1.98)), 52 young adults (24.92 (3.60), and 42 older adults (62.84 (7.02)). Additionally, a subsample of 111 participants completed a resting-state fMRI scan. After investigating the impact of age on different divergent thinking metrics, we investigated the impact of age on the association between divergent thinking and resting-state functional connectivity within and between major resting-state brain networks associated with creative thinking: the DMN, ECN, and SN. Adolescents tended to be less creative than both young and older adults in divergent thinking scores related to expansion creativity, and not in persistent creativity, while young and older adults performed relatively similar. We found that adolescents' functional integrity of the executive control network (ECN) was positively associated with expansion creativity, which was significantly different from the negative association in both the young and older adults. These results suggest that creative performance and supporting brain networks change throughout the lifespan.

Entropy as a Measure of Auditory Environment Diversity: An Ecological Momentary Assessment (EMA) Approach.

OBJECTIVES: To determine the validity and usefulness of entropy computed using ecological momentary assessment (EMA) data as a measure of auditory environment diversity. DESIGN: We conducted two secondary analyses on existing EMA datasets. The first determined the construct validity of auditory environment entropy by examining the effect of COVID-19 on entropy. To demonstrate entropy's usefulness, the second examined if entropy could predict the benefit of hearing aid (HA) noise reduction features. RESULTS: Consistent with the known effect of COVID-19 on social lifestyle, COVID-19 significantly reduced auditory environment diversity, supporting entropy's construct validity. HA users with higher entropy reported poorer outcomes and perceived more benefit from HA features, supporting the feasibility of using entropy to predict communication performance and feature benefit. CONCLUSIONS: Entropy derived from EMA data is a valid and useful auditory environment diversity measure. This measure could allow researchers to better understand the communication needs of people with hearing loss.

Auditory Environments and Hearing Aid Feature Activation Among Younger and Older Listeners in an Urban and Rural Area.

OBJECTIVES: The purpose of this study was to investigate differences in auditory environments and hearing aid feature activation between younger listeners with normal hearing and older listeners with hearing loss in an urban and rural location. We hypothesized that (1) urban dwellers and younger listeners would encounter more diverse and demanding auditory environments than rural dwellers and older listeners, respectively; (2) the advanced hearing aid features (noise reduction and directional microphone) of urban dwellers and younger listeners would be activated more frequently than rural dwellers and older listeners, respectively. DESIGN: The design of this study was cross-sectional with repeated measures. A total of 12 older adults with hearing loss (OHL-U) and 11 younger adults with normal hearing (YNH-U) were recruited from an urban area (Berkeley, California) and 13 older adults with hearing loss (OHL-R) and 10 YNH-U were recruited from a rural area (Iowa City, Iowa). Participants wore hearing aids that recorded data about their listening environments and completed ecological momentary assessments for 1 week. RESULTS: The YNH-U group experienced higher sound pressure levels and hearing aid features were activated more frequently than in the OHL groups. The OHL-R group experienced significantly less diverse sound pressure levels than the YNH-U group. The YNH-R group had sound levels between the YNH-U group and the OHL groups but without significant differences from any other group. The YNH groups showed a greater likelihood of hearing aid feature activation than the OHL-R group. CONCLUSIONS: Demographics affect auditory environments and the activation of hearing aid features. Younger urban dwellers have the most diverse or demanding auditory environments and hearing aid feature activation, and older, rural dwellers with hearing loss have the least diverse or demanding auditory environments and hearing aid feature activation. Future studies of real-world auditory environments and audiology intervention effectiveness should consider location in recruitment and interpretation of results.

Descriptions of Hearing Loss Severity Differentially Influence Parental Concern about the Impact of Childhood Hearing Loss.

PURPOSE: The purpose of this study was to measure how parent concern about childhood hearing loss varies under different description conditions: classification-based, audibility-based, and simulation-based descriptions. METHOD: We randomly allocated study participants (n = 143) to complete an online survey about expected child difficulties with listening situations with hearing loss. Our participants were parents of children with typical hearing in the 0- to 12-month age range. Participants were exposed to one type of description (classification-based, audibility-based, or simulation-based) and one level of hearing loss (slight, mild, and moderate or their audibility and simulation equivalents), producing nine total groups. Participants rated the level of expected difficulty their child would experience performing age-appropriate listening tasks with the given hearing loss. They also selected what they perceived as the most appropriate intervention from a list of increasingly intense options. RESULTS: Our findings revealed that audibility-based descriptions elicited significantly higher levels of parent concerns about hearing loss than classification-based strategies, but that simulation-based descriptions elicited the highest levels of concern. Those assigned to simulation-based and audibility-based groups also judged relatively more intense intervention options as appropriate compared to those assigned to classification-based groups. CONCLUSIONS: This study expands our knowledge base about descriptive factors that impact levels of parent concern about hearing loss after diagnosis. This has potentially cascading effects on later intervention actions such as fitting hearing technology. It also provides a foundation for developing and testing clinical applications of audibility-based counseling strategies.

The Relationship Between Cochlear Implant Speech Perception Outcomes and Electrophysiological Measures of the Electrically Evoked Compound Action Potential.

OBJECTIVE: This study assessed the relationship between electrophysiological measures of the electrically evoked compound action potential (eCAP) and speech perception scores measured in quiet and in noise in postlingually deafened adult cochlear implant (CI) users. It tested the hypothesis that how well the auditory nerve (AN) responds to electrical stimulation is important for speech perception with a CI in challenging listening conditions. DESIGN: Study participants included 24 postlingually deafened adult CI users. All participants used Cochlear Nucleus CIs in their test ears. In each participant, eCAPs were measured at multiple electrode locations in response to single-pulse, paired-pulse, and pulse-train stimuli. Independent variables included six metrics calculated from the eCAP recordings: the electrode-neuron interface (ENI) index, the neural adaptation (NA) ratio, NA speed, the adaptation recovery (AR) ratio, AR speed, and the amplitude modulation (AM) ratio. The ENI index quantified the effectiveness of the CI electrodes in stimulating the targeted AN fibers. The NA ratio indicated the amount of NA at the AN caused by a train of constant-amplitude pulses. NA speed was defined as the speed/rate of NA. The AR ratio estimated the amount of recovery from NA at a fixed time point after the cessation of pulse-train stimulation. AR speed referred to the speed of recovery from NA caused by previous pulse-train stimulation. The AM ratio provided a measure of AN sensitivity to AM cues. Participants' speech perception scores were measured using Consonant-Nucleus-Consonant (CNC) word lists and AzBio sentences presented in quiet, as well as in noise at signal-to-noise ratios (SNRs) of +10 and +5 dB. Predictive models were created for each speech measure to identify eCAP metrics with meaningful predictive power. RESULTS: The ENI index and AR speed individually explained at least 10% of the variance in most of the speech perception scores measured in this study, while the NA ratio, NA speed, the AR ratio, and the AM ratio did not. The ENI index was identified as the only eCAP metric that had unique predictive power for each of the speech test results. The amount of variance in speech perception scores (both CNC words and AzBio sentences) explained by the eCAP metrics increased with increased difficulty under the listening condition. Over half of the variance in speech perception scores measured in +5 dB SNR noise (both CNC words and AzBio sentences) was explained by a model with only three eCAP metrics: the ENI index, NA speed, and AR speed. CONCLUSIONS: Of the six electrophysiological measures assessed in this study, the ENI index is the most informative predictor for speech perception performance in CI users. In agreement with the tested hypothesis, the response characteristics of the AN to electrical stimulation are more important for speech perception with a CI in noise than they are in quiet.

Predicting speech-in-speech recognition: Short-term audibility and spatial separation.

Quantifying the factors that predict variability in speech-in-speech recognition represents a fundamental challenge in auditory science. Stimulus factors associated with energetic and informational masking (IM) modulate variability in speech-in-speech recognition, but energetic effects can be difficult to estimate in spectro-temporally dynamic speech maskers. The current experiment characterized the effects of short-term audibility and differences in target and masker location (or perceived location) on the horizontal plane for sentence recognition in two-talker speech. Thirty young adults with normal hearing (NH) participated. Speech reception thresholds and keyword recognition at a fixed signal-to-noise ratio (SNR) were measured in each spatial condition. Short-term audibility for each keyword was quantified using a glimpsing model. Results revealed that speech-in-speech recognition depended on the proportion of audible glimpses available in the target + masker keyword stimulus in each spatial condition, even across stimuli presented at a fixed global SNR. Short-term audibility requirements were greater for colocated than spatially separated speech-in-speech recognition, and keyword recognition improved more rapidly as a function of increases in target audibility with spatial separation. Results indicate that spatial cues enhance glimpsing efficiency in competing speech for young adults with NH and provide a quantitative framework for estimating IM for speech-in-speech recognition in different spatial configurations.

Incorporating infectious duration-dependent transmission into Bayesian epidemic models.

Compartmental models are commonly used to describe the spread of infectious diseases by estimating the probabilities of transitions between important disease states. A significant challenge in fitting Bayesian compartmental models lies in the need to estimate the duration of the infectious period, based on limited data providing only symptom onset date or another proxy for the start of infectiousness. Commonly, the exponential distribution is used to describe the infectious duration, an overly simplistic approach, which is not biologically plausible. More flexible distributions can be used, but parameter identifiability and computational cost can worsen for moderately sized or large epidemics. In this article, we present a novel approach, which considers a curve of transmissibility over a fixed infectious duration. The incorporation of infectious duration-dependent (IDD) transmissibility, which decays to zero during the infectious period, is biologically reasonable for many viral infections and fixing the length of the infectious period eases computational complexity in model fitting. Through simulation, we evaluate different functional forms of IDD transmissibility curves and show that the proposed approach offers improved estimation of the time-varying reproductive number. We illustrate the benefit of our approach through a new analysis of the 1995 outbreak of Ebola Virus Disease in the Democratic Republic of the Congo.

Causal decomposition maps: An exploratory tool for designing area-level interventions aimed at reducing health disparities.

Methods for decomposition analyses have been developed to partition between-group differences into explained and unexplained portions. In this paper, we introduce the concept of causal decomposition maps, which allow researchers to test the effect of area-level interventions on disease maps before implementation. These maps quantify the impact of interventions that aim to reduce differences in health outcomes between groups and illustrate how the disease map might change under different interventions. We adapt a new causal decomposition analysis method for the disease mapping context. Through the specification of a Bayesian hierarchical outcome model, we obtain counterfactual small area estimates of age-adjusted rates and reliable estimates of decomposition quantities. We present two formulations of the outcome model, with the second allowing for spatial interference of the intervention. Our method is utilized to determine whether the addition of gyms in different sets of rural ZIP codes could reduce any of the rural-urban difference in age-adjusted colorectal cancer incidence rates in Iowa ZIP codes.

Gynecologic oncologist impact on adjuvant chemotherapy care for stage II-IV ovarian cancer patients.

OBJECTIVE: We aim to evaluate the impact gynecologic oncologists have on ovarian cancer adjuvant chemotherapy care from their role as surgeons recommending adjuvant chemotherapy care and their role as adjuvant chemotherapy providers while considering rural-urban differences. METHODS: Multivariable adjusted logistic regressions and Cox proportional hazards models were developed using a population-based, retrospective cohort of stage II-IV and unknown stage ovarian cancer patients diagnosed in Iowa, Kansas, and Missouri in 2010-2012 whose medical records were abstracted in 2017-2018. RESULTS: Gynecologic oncologist surgeons (versus other type of surgeon) were associated with increased odds of adjuvant chemotherapy initiation (adjusted odds ratio (OR) 2.18; 95% confidence interval (CI) 1.10-4.33) and having a gynecologic oncologist adjuvant chemotherapy provider (OR 10.0; 95% CI 4.58-21.8). Independent of type of surgeon, rural patients were less likely to have a gynecologic oncologist chemotherapy provider (OR 0.52; 95% CI 0.30-0.91). Gynecologic oncologist adjuvant chemotherapy providers (versus other providers) were associated with decreased surgery-to-chemotherapy time (rural: 6 days; urban: 8 days) and increased distance to chemotherapy (rural: 22 miles; urban: 11 miles). Rural women (versus urban) traveled 38 miles farther when their chemotherapy provider was a gynecologic oncologist and 27 miles farther when it was not. CONCLUSION: Gynecologic oncologist surgeons may impact adjuvant chemotherapy initiation. Gynecologic oncologists serving as adjuvant chemotherapy providers were associated with some care benefits, such as reduced time from surgery-to-chemotherapy, and some care barriers, such as travel distance. The barriers and benefits of having a gynecologic oncologist involved in adjuvant chemotherapy care, including rural-urban differences, warrant further research in other populations.

Studying children's growth in self-regulation using changing measures to account for heterotypic continuity: A Bayesian approach to developmental scaling.

Self-regulation is thought to show heterotypic continuity-its individual differences endure but its behavioral manifestations change across development. Thus, different measures across time may be necessary to account for heterotypic continuity of self-regulation. This longitudinal study examined children's (N = 108) self-regulation development using 17 measures, including 15 performance-based measures, two questionnaires, and three raters across seven time points. It is the first to use different measures of self-regulation over time to account for heterotypic continuity while using developmental scaling to link the measures onto the same scale for more accurate growth estimates. Assessed facets included inhibitory control, delayed gratification, sustained attention, and executive functions. Some measures differed across ages to retain construct validity and account for heterotypic continuity. A Bayesian longitudinal mixed model for developmental scaling was developed to link the differing measures onto the same scale. This allowed charting children's self-regulation growth across ages 3-7 years and relating it to both predictors and outcomes. Rapid growth occurred from ages 3-6. As a validation of the developmental scaling approach, greater self-regulation was associated with better school readiness (math and reading skills) and fewer externalizing problems. Our multi-wave, multi-facet, multi-method, multi-measure, multi-rater, developmental scaling approach is the most comprehensive to date for assessing the development of self-regulation. This approach demonstrates that developmental scaling may enable studying development of self-regulation across the lifespan.

Pre-pregnancy exposure to arsenic in diet and non-cardiac birth defects.

OBJECTIVES: To explore associations between maternal pre-pregnancy exposure to arsenic in diet and non-cardiac birth defects. DESIGN: This is a population-based, case-control study using maternal responses to a dietary assessment and published arsenic concentration estimates in food items to calculate average daily total and inorganic arsenic exposure during the year before pregnancy. Assigning tertiles of total and inorganic arsenic exposure, logistic regression analysis was used to estimate OR for middle and high tertiles, compared to the low tertile. SETTING: US National Birth Defects Prevention Study, 1997-2011. PARTICIPANTS: Mothers of 10 446 children without birth defects and 14 408 children diagnosed with a non-cardiac birth defect. RESULTS: Maternal exposure to total dietary arsenic in the middle and high tertiles was associated with a threefold increase in cloacal exstrophy, with weak positive associations (1·2-1·5) observed either in both tertiles (intercalary limb deficiency) or the high tertile only (encephalocele, glaucoma/anterior chamber defects and bladder exstrophy). Maternal exposure to inorganic arsenic showed mostly weak, positive associations in both tertiles (colonic atresia/stenosis, oesophageal atresia, bilateral renal agenesis/hypoplasia, hypospadias, cloacal exstrophy and gastroschisis), or the high (glaucoma/anterior chamber defects, choanal atresia and intestinal atresia stenosis) or middle (encephalocele, intercalary limb deficiency and transverse limb deficiency) tertiles only. The remaining associations estimated were near the null or inverse. CONCLUSIONS: This exploration of arsenic in diet and non-cardiac birth defects produced several positive, but mostly weak associations. Limitations in exposure assessment may have resulted in exposure misclassification. Continued research with improved exposure assessment is recommended to identify if these associations are true signals or chance findings.

Predicting speech-in-speech recognition: Short-term audibility, talker sex, and listener factors.

Speech-in-speech recognition can be challenging, and listeners vary considerably in their ability to accomplish this complex auditory-cognitive task. Variability in performance can be related to intrinsic listener factors as well as stimulus factors associated with energetic and informational masking. The current experiments characterized the effects of short-term audibility of the target, differences in target and masker talker sex, and intrinsic listener variables on sentence recognition in two-talker speech and speech-shaped noise. Participants were young adults with normal hearing. Each condition included the adaptive measurement of speech reception thresholds, followed by testing at a fixed signal-to-noise ratio (SNR). Short-term audibility for each keyword was quantified using a computational glimpsing model for target+masker mixtures. Scores on a psychophysical task of auditory stream segregation predicted speech recognition, with stronger effects for speech-in-speech than speech-in-noise. Both speech-in-speech and speech-in-noise recognition depended on the proportion of audible glimpses available in the target+masker mixture, even across stimuli presented at the same global SNR. Short-term audibility requirements varied systematically across stimuli, providing an estimate of the greater informational masking for speech-in-speech than speech-in-noise recognition and quantifying informational masking for matched and mismatched talker sex.

Rural disparities in surgical care from gynecologic oncologists among Midwestern ovarian cancer patients.

OBJECTIVE: Up to one-third of women with ovarian cancer in the United States do not receive surgical care from a gynecologic oncologist specialist despite guideline recommendations. We aim to investigate the impact of rurality on receiving surgical care from a specialist, referral to a specialist, and specialist surgery after referral, and the consequences of specialist care. METHODS: We utilized a retrospective cohort created through an extension of standard cancer surveillance in three Midwestern states. Multivariable adjusted logistic regression was utilized to assess gynecologic oncologist treatment of women 18-89 years old, who were diagnosed with primary, histologically confirmed, malignant ovarian cancer in 2010-2012 in Kansas, Missouri and Iowa by rurality. RESULTS: Rural women were significantly less likely to receive surgical care from a gynecologic oncologist specialist (adjusted odds ratio (OR) 0.37, 95% confidence interval (CI) 0.24-0.58) and referral to a specialist (OR 0.37, 95% CI 0.23-0.59) compared to urban women. There was no significant difference in specialist surgery after a referral (OR 0.56, 95% CI 0.26-1.20). Rural women treated surgically by a gynecologic oncologist versus non-specialist were more likely to receive cytoreduction and more complete tumor removal to ≤1 cm. CONCLUSION: There is a large rural-urban difference in receipt of ovarian cancer surgery from a gynecologic oncologist specialist (versus a non-specialist). Disparities in referral rates contribute to the rural-urban difference. Further research will help define the causes of referral disparities, as well as promising strategies to address them.

A Bayesian approach for estimating age-adjusted rates for low-prevalence diseases over space and time.

Age-adjusted rates are frequently used by epidemiologists to compare disease incidence and mortality across populations. In small geographic regions, age-adjusted rates computed directly from the data are subject to considerable variability and are generally unreliable. Therefore, we desire an approach that accounts for the excessive number of zero counts in disease mapping datasets, which are naturally present for low-prevalence diseases and are further innated when stratifying by age group. Bayesian modeling approaches are naturally suited to employ spatial and temporal smoothing to produce more stable estimates of age-adjusted rates for small areas. We propose a Bayesian hierarchical spatio-temporal hurdle model for counts and demonstrate how age-adjusted rates can be estimated from the hurdle model. We perform a simulation study to evaluate the performance of the proposed model vs a traditional Poisson model on datasets with varying characteristics. The approach is illustrated using two applications to cancer mortality at the county level.