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.

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.

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.

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.

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.

AAAPT: Assessment of the Acute Pain Trajectory.

OBJECTIVE: Define and contrast acute pain trajectories vs. the aggregate pain measurements, summarize appropriate linear and nonlinear statistical analyses for pain trajectories at the patient level, and present methods to classify individual pain trajectories. Clinical applications of acute pain trajectories are also discussed. SETTING: In 2016, an expert panel involving the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION), American Pain Society (APS), and American Academy of Pain Medicine (AAPM) established an initiative to create a pain taxonomy, named the ACTTION-APS-AAPM Pain Taxonomy (AAAPT), for the multidimensional classification of acute pain. The AAAPT panel commissioned the present report to provide further details on analysis of the individual acute pain trajectory as an important component of comprehensive pain assessment. METHODS: Linear mixed models and nonlinear models (e.g., regression splines and polynomial models) can be applied to analyze the acute pain trajectory. Alternatively, methods for classifying individual pain trajectories (e.g., using the 50% confidence interval of the random slope approach or using latent class analyses) can be applied in the clinical context to identify different trajectories of resolving pain (e.g., rapid reduction or slow reduction) or persisting pain. Each approach has advantages and disadvantages that may guide selection. Assessment of the acute pain trajectory may guide treatment and tailoring to anticipated symptom recovery. The acute pain trajectory can also serve as a treatment outcome measure, informing further management. CONCLUSIONS: Application of trajectory approaches to acute pain assessments enables more comprehensive measurement of acute pain, which forms the cornerstone of accurate classification and treatment of pain.

Bayesian compartmental models and associated reproductive numbers for an infection with multiple transmission modes.

Zoonotic visceral leishmaniasis (ZVL) is a serious neglected tropical disease that is endemic in 98 countries. ZVL is primarily transmitted via a sand fly vector. In the United States, it is enzootic in some canine populations; it is transmitted from infectious mother to pup transplacentally, and vector-borne transmission is absent. This absence affords a unique opportunity to study (1) vertical transmission dynamics in dogs and (2) the importance of vertical transmission in maintaining an infectious reservoir in the presence of a vector. In this paper, we present Bayesian compartmental models and reproductive number formulations to examine (1) and (2), providing a mechanism to plan and evaluate interventions in regions where both transmission modes are present. First, we propose an individual-level susceptible, infectious, removed (SIR) model to study the effect of maternal infection status during pregnancy on pup infection progression. We provide evidence that pups born to diagnostically positive mothers during pregnancy are more likely to become diagnostically positive both earlier in life, and at some point during their lifetime, than those born to diagnostically negative mothers. Second, we propose a population-level SIR model to study the impact of a vertically maintained reservoir on propagating infection in a naive canine population through emergent vector transmission using simulation studies. We also present reproductive numbers to quantify contributions of vertically infected and vector-infected dogs to maintaining infection in the population. We show that a vertically maintained canine reservoir can propagate infection in a theoretical naive population in the presence of a vector.

Comparison of T1Rho MRI, Glucose Metabolism, and Amyloid Burden Across the Cognitive Spectrum: A Pilot Study.

OBJECTIVE: The pathological cascades associated with the development of Alzheimer's disease (AD) have a common element: acidosis. T1rho MRI is a pH-sensitive measure, with higher values associated with greater neuropathological burden. The authors investigated the relationship between T1rho imaging and AD-associated pathologies as determined by available diagnostic imaging techniques. METHODS: Twenty-seven participants (men, N=13, women, N=14; ages 55-90) across the cognitive spectrum (healthy control subjects [HCs] with normal cognition, N=17; participants with mild cognitive impairment [MCI], N=7; participants with mild AD, N=3) underwent neuropsychological testing, MRI (T1-weighted and T1rho [spin-lattice relaxation time in the rotating frame]), and positron emission tomography imaging ([11C]Pittsburg compound B for amyloid burden [N=26] and [18F]fluorodeoxyglucose for cerebral glucose metabolism [N=12]). The relationships between global T1rho values and neuropsychological, demographic, and imaging measures were explored. RESULTS: Global mean and median T1rho were positively associated with age. After controlling for age, higher global T1rho was associated with poorer cognitive function, poorer memory function (immediate and delayed memory scores), higher amyloid burden, and more abnormal cerebral glucose metabolism. Regional T1rho values, when controlling for age, significantly differed between HCs and participants with MCI or AD in select frontal, cingulate, and parietal regions. CONCLUSIONS: Higher T1rho values were associated with greater cognitive impairment and pathological burden. T1rho, a biomarker that varies according to a feature common to each cascade rather than one that is unique to a particular pathology, has the potential to serve as a metric of neuropathology, theoretically providing a measure for assessing pathological status and for monitoring the neurodegeneration trajectory.

An empirically adjusted approach to reproductive number estimation for stochastic compartmental models: A case study of two Ebola outbreaks.

The various thresholding quantities grouped under the "Basic Reproductive Number" umbrella are often confused, but represent distinct approaches to estimating epidemic spread potential, and address different modeling needs. Here, we contrast several common reproduction measures applied to stochastic compartmental models, and introduce a new quantity dubbed the "empirically adjusted reproductive number" with several advantages. These include: more complete use of the underlying compartmental dynamics than common alternatives, use as a potential diagnostic tool to detect the presence and causes of intensity process underfitting, and the ability to provide timely feedback on disease spread. Conceptual connections between traditional reproduction measures and our approach are explored, and the behavior of our method is examined under simulation. Two illustrative examples are developed: First, the single location applications of our method are established using data from the 1995 Ebola outbreak in the Democratic Republic of the Congo and a traditional stochastic SEIR model. Second, a spatial formulation of this technique is explored in the context of the ongoing Ebola outbreak in West Africa with particular emphasis on potential use in model selection, diagnosis, and the resulting applications to estimation and prediction. Both analyses are placed in the context of a newly developed spatial analogue of the traditional SEIR modeling approach.

A spatial epidemic model for disease spread over a heterogeneous spatial support.

Data from the Iowa mumps epidemic of 2006 were collected on a spatial lattice over a regular temporal interval. Without access to a person-to-person contact graph, it is sensible to analyze these data as homogenous within each areal unit and to use the spatial graph to derive a contact structure. The spatio-temporal partition is fine, and the counts of new infections at each location at each time are sparse. Therefore, we propose a spatial compartmental epidemic model with general latent time distributions (spatial PS SEIR) that is capable of smoothing the contact structure, while accounting for spatial heterogeneity in the mixing process between locations. Because the model is an extension of the PS SEIR model, it simultaneously handles non-exponentially distributed latent and infectious time distributions. The analysis within focuses on the progression of the disease over both space and time while assessing the impact of a large proportion of the infected people dispersing at the same time because of spring break and the impact of public awareness on the spread of the mumps epidemic. We found that the effect of spring break increased the mixing rate in the population and that the spatial transmission of the disease spreads across multiple conduits.

Integrating independent spatio-temporal replications to assess population trends in disease spread.

Glaucoma is the second leading cause of blindness in the USA. A visual field test (perimetry) is used to sample and quantitate visual field function in preselected regions in the eye. These regions can be considered a spatial field with replications across independently measured individuals. At return visits, a new set of visual field measurements is obtained producing a subject specific spatio-temporal dataset. We develop a Bayesian hierarchical modeling framework to analyze these spatio-temporal datasets both for individual level spread and as aggregate population level trends. Our model extends previous research utilizing a dimension reduction matrix and individual specific latent variables. Human characteristics are incorporated into the model to help explain glaucoma progression. One beneficial product of our model is smoothed estimates for individuals. We also specify how progression rates are computed for monitoring purposes so that clinicians can track changes and predict forward in time. Copyright © 2016 John Wiley & Sons, Ltd.

Cognitive changes associated with switching to frequent nocturnal hemodialysis or renal transplantation.

BACKGROUND: It is uncertain whether switching to frequent nocturnal hemodialysis improves cognitive function in well-dialyzed patients and how this compares to patients who receive a kidney transplant. METHODS: We conducted a multicenter observational study with longitudinal follow-up of the effect on cognitive performance of switching dialysis treatment modality from conventional thrice-weekly hemodialysis to frequent nocturnal hemodialysis, a functioning renal transplant or remaining on thrice-weekly conventional hemodialysis. Neuropsychological tests of memory, attention, psychomotor processing speed, executive function and fluency as well as measures of solute clearance were performed at baseline and again after switching modality. The change in cognitive performance measured by neuropsychological tests assessing multiple cognitive domains at baseline, 4 and 12 months after switching dialysis modality were analyzed using a linear mixed model. RESULTS: Seventy-seven patients were enrolled; 21 of these 77 patients were recruited from the randomized Frequent Hemodialysis Network (FHN) Nocturnal Trial. Of these, 18 patients started frequent nocturnal hemodialysis, 28 patients received a kidney transplant and 31 patients remained on conventional thrice-weekly hemodialysis. Forty-eight patients (62 %) returned for the 12-month follow-up. Despite a significant improvement in solute clearance, 12 months treatment with frequent nocturnal hemodialysis was not associated with substantial improvement in cognitive performance. By contrast, renal transplantation, which led to near normalization of solute clearance was associated with clinically relevant and significant improvements in verbal learning and memory with a trend towards improvements in psychomotor processing speed. Cognitive performance in patients on conventional hemodialysis remained stable with the exception of an improvement in psychomotor processing speed and a decline in verbal fluency. CONCLUSIONS: In patients on conventional thrice-weekly hemodialysis, receiving a functioning renal transplant was associated with improvement in auditory-verbal memory and psychomotor processing speed, which was not observed after 12 months of frequent nocturnal hemodialysis.

Lower urinary tract pain and anterior urethral stricture disease: prevalence and effects of urethral reconstruction.

PURPOSE: Anterior urethral stricture disease most commonly presents as urinary obstruction. Lower urinary tract pain is not commonly reported as a presenting symptom. We prospectively characterized lower urinary tract pain in association with urethral stricture disease and assessed the effects of urethroplasty on this pain. MATERIALS AND METHODS: Men (18 years old or older) with anterior urethral stricture disease were prospectively enrolled in a longitudinal, multi-institutional, urethral reconstruction outcomes study from June 2010 to January 2013 as part of TURNS (Trauma and Urologic Reconstruction Network of Surgeons). Preoperative and postoperative lower urinary tract pain was assessed by the validated CLSS. Voiding and sexual function was assessed using validated patient-reported measures, including I-PSS. RESULTS: Preoperatively 118 of 167 men (71%) reported urethral pain and 68 (41%) reported bladder pain. Age was the only predictor of urethral pain with men 40 years or younger reporting more pain than those 60 years old or older (81% vs 58%, p = 0.0104). Lower urinary tract pain was associated with worse quality of life and overall voiding symptoms on CLSS and I-PSS (each p <0.01). Postoperatively lower urinary tract pain completely resolved in 64% of men with urethral pain and in 73.5% with bladder pain. There were no predictive factors for changes in lower urinary tract pain after urethral reconstruction. CONCLUSIONS: Lower urinary tract pain is common in urethral stricture disease, especially in younger men. It is associated with worse quality of life and voiding function. In most men lower urinary tract pain resolves after urethral reconstruction.