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Background: Eosinophilic esophagitis (EoE) is an increasingly common inflammatory condition of the esophagus; however, the underlying immunologic mechanisms remain poorly understood. The epithelium-derived cytokine IL-33 is associated with type 2 immune responses and elevated in esophageal biopsy specimens from patients with EoE., Objective: We hypothesized that overexpression of IL-33 by the esophageal epithelium would promote the immunopathology of EoE., Methods: We evaluated the functional consequences of esophageal epithelial overexpression of a secreted and active form of IL-33 in a novel transgenic mouse, EoE33. EoE33 mice were analyzed for clinical and immunologic phenotypes. Esophageal contractility was assessed. Epithelial cytokine responses were analyzed in three-dimensional organoids. EoE33 phenotypes were further characterized in ST2 -/- , eosinophil-deficient, and IL-13 -/- mice. Finally, EoE33 mice were treated with dexamethasone., Results: EoE33 mice displayed ST2-dependent, EoE-like pathology and failed to thrive. Esophageal tissue remodeling and inflammation included basal zone hyperplasia, eosinophilia, mast cells, and T H 2 cells. Marked increases in levels of type 2 cytokines, including IL-13, and molecules associated with immune responses and tissue remodeling were observed. Esophageal organoids suggested reactive epithelial changes. Genetic deletion of IL-13 in EoE33 mice abrogated pathologic changes in vivo. EoE33 mice were responsive to steroids., Conclusions: IL-33 overexpression by the esophageal epithelium generated immunopathology and clinical phenotypes resembling human EoE. IL-33 may play a pivotal role in the etiology of EoE by activating the IL-13 pathway. EoE33 mice are a robust experimental platform for mechanistic investigation and translational discovery., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Atopic dermatitis (AD) is an inflammatory skin condition with multiple systemic treatments and uncertainty regarding their comparative impact on AD outcomes., Objective: We sought to systematically synthesize the benefits and harms of AD systemic treatments., Methods: For the 2023 American Academy of Allergy, Asthma & Immunology and American College of Allergy, Asthma, and Immunology Joint Task Force on Practice Parameters AD guidelines, we searched MEDLINE, EMBASE, CENTRAL, Web of Science, and GREAT databases from inception to November 29, 2022, for randomized trials addressing systemic treatments and phototherapy for AD. Paired reviewers independently screened records, extracted data, and assessed risk of bias. Random-effects network meta-analyses addressed AD severity, itch, sleep, AD-related quality of life, flares, and harms. The Grading of Recommendations Assessment, Development and Evaluation approach informed certainty of evidence ratings. This review is registered in the Open Science Framework (https://osf.io/e5sna)., Results: The 149 included trials (28,686 patients with moderate-to-severe AD) evaluated 75 interventions. With high-certainty evidence, high-dose upadacitinib was among the most effective for 5 of 6 patient-important outcomes; high-dose abrocitinib and low-dose upadacitinib were among the most effective for 2 outcomes. These Janus kinase inhibitors were among the most harmful in increasing adverse events. With high-certainty evidence, dupilumab, lebrikizumab, and tralokinumab were of intermediate effectiveness and among the safest, modestly increasing conjunctivitis. Low-dose baricitinib was among the least effective. Efficacy and safety of azathioprine, oral corticosteroids, cyclosporine, methotrexate, mycophenolate, phototherapy, and many novel agents are less certain., Conclusions: Among individuals with moderate-to-severe AD, high-certainty evidence demonstrates that high-dose upadacitinib is among the most effective in addressing multiple patient-important outcomes, but also is among the most harmful. High-dose abrocitinib and low-dose upadacitinib are effective, but also among the most harmful. Dupilumab, lebrikizumab, and tralokinumab are of intermediate effectiveness and have favorable safety., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Secondary Furlow (Furlow) and buccal myomucosal flaps (BMMF) treat velopharyngeal insufficiency by lengthening the palate and retropositioning the levator veli palatini muscles. The criteria for choosing one operation over the other remain unclear., Methods: A single-center retrospective cohort study was conducted. Thirty-two patients with nonsyndromic, repaired cleft palate were included. All patients underwent a Furlow or BMMF. Outcome measures included (1) resolution of hypernasality 12 months postoperatively, (2) degree of improvement of hypernasality severity; and (3) change in velar length, as measured on magnetic resonance imaging scans obtained preoperatively and 12 months postoperatively. All measures were performed by raters blinded to participants' medical and surgical history., Results: Hypernasality was corrected to normal in 80% of the Furlow group and in 56% of the BMMF group. Patients receiving BMMF had more severe hypernasality during preoperative speech evaluation. Both groups had a median decrease of two scalar rating points for severity of hypernasality ( P = 0.58). On postoperative magnetic resonance imaging, patients who underwent Furlow had a median increased velar length of 6.9 mm. Patients who received BMMF had a median increased velar length of 7.5 mm. There was no statistically significant difference between groups regarding increase in velar length ( P = 0.95)., Conclusions: Furlow and BMMF procedures increase velar length with favorable speech outcomes. The same degree of improvement for hypernasality was observed across groups, likely explained by the similar increase in velar length achieved. Anatomic changes in palate length and levator veli palatini retropositioning persist 1 year after surgery., Competing Interests: The authors have no financial interest to declare in relation to the content of this article. This study was supported by the National Institute of Dental & Craniofacial Research of the National Institutes of Health under award numbers K23DE025023 and U01DE029750., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

Background: The gut-lung axis is generally recognized, but there are few large studies of the gut microbiome and incident respiratory disease in adults., Objective: We sought to investigate the association and predictive capacity of the gut microbiome for incident asthma and chronic obstructive pulmonary disease (COPD)., Methods: Shallow metagenomic sequencing was performed for stool samples from a prospective, population-based cohort (FINRISK02; N = 7115 adults) with linked national administrative health register-derived classifications for incident asthma and COPD up to 15 years after baseline. Generalized linear models and Cox regressions were used to assess associations of microbial taxa and diversity with disease occurrence. Predictive models were constructed using machine learning with extreme gradient boosting. Models considered taxa abundances individually and in combination with other risk factors, including sex, age, body mass index, and smoking status., Results: A total of 695 and 392 statistically significant associations were found between baseline taxonomic groups and incident asthma and COPD, respectively. Gradient boosting decision trees of baseline gut microbiome abundance predicted incident asthma and COPD in the validation data sets with mean area under the curves of 0.608 and 0.780, respectively. Cox analysis showed that the baseline gut microbiome achieved higher predictive performance than individual conventional risk factors, with C-indices of 0.623 for asthma and 0.817 for COPD. The integration of the gut microbiome and conventional risk factors further improved prediction capacities., Conclusions: The gut microbiome is a significant risk factor for incident asthma and incident COPD and is largely independent of conventional risk factors., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Abstract: The topic of vaping is becoming increasingly prevalent in healthcare, especially regarding adolescents as their use of electronic cigarette products continues to increase. The many factors to consider include the safety of these products, human health and behavior, and social effects. Healthcare providers need to be aware of these issues to provide appropriate education and care to adolescent patients., (Copyright © 2022 American Academy of Physician Associates.)

Background: Targeted muscle reinnervation (TMR) has shown promise in reducing postsurgical limb pain in amputees. However, there has been little evidence on the increased risk of complications and cost as compared with traditional amputations. This study was designed to assess the rate of complications and healthcare costs between those treated with TMR and traditional amputations., Methods: Patients undergoing amputation were selected from the PearlDiver Mariner dataset and categorized into one of two treatment groups depending on the use of TMR versus traditional amputation. Rates of postsurgical complications and overall healthcare costs were compared between the two groups, while controlling for differences in patient demographics and comorbidities., Results: One hundred sixteen TMR procedures and 76,412 traditional amputations were included in the study. The rate of complications did not differ between groups, with a complication rate of 77% in the TMR and 87% in the traditional amputation groups. Overall healthcare costs also did not differ 1 year after surgery, with an average cost of $32,632 in the TMR group and $36,219 in the traditional amputation group., Conclusions: Amputees experience high rates of postsurgical complications, morbidity, and mortality. However, there is no increased risk of complications or cost with the use of TMR. TMR has the potential benefits of reducing overall postsurgical pain and reestablishing activities of daily living. Although TMR is more expensive up front, it may reduce the overall healthcare costs by reducing the need for subsequent care. Further work is needed in large, randomized trials to examine these findings., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

Background Improving diagnosis of ductal carcinoma in situ (DCIS) before surgery is important in choosing optimal patient management strategies. However, patients may harbor occult invasive disease not detected until definitive surgery. Purpose To assess the performance and clinical utility of mammographic radiomic features in the prediction of occult invasive cancer among women diagnosed with DCIS on the basis of core biopsy findings. Materials and Methods In this Health Insurance Portability and Accountability Act-compliant retrospective study, digital magnification mammographic images were collected from women who underwent breast core-needle biopsy for calcifications that was performed at a single institution between September 2008 and April 2017 and yielded a diagnosis of DCIS. The database query was directed at asymptomatic women with calcifications without a mass, architectural distortion, asymmetric density, or palpable disease. Logistic regression with regularization was used. Differences across training and internal test set by upstaging rate, age, lesion size, and estrogen and progesterone receptor status were assessed by using the Kruskal-Wallis or χ 2 test. Results The study consisted of 700 women with DCIS (age range, 40-89 years; mean age, 59 years ± 10 [standard deviation]), including 114 with lesions (16.3%) upstaged to invasive cancer at subsequent surgery. The sample was split randomly into 400 women for the training set and 300 for the testing set (mean ages: training set, 59 years ± 10; test set, 59 years ± 10; P = .85). A total of 109 radiomic and four clinical features were extracted. The best model on the test set by using all radiomic and clinical features helped predict upstaging with an area under the receiver operating characteristic curve of 0.71 (95% CI: 0.62, 0.79). For a fixed high sensitivity (90%), the model yielded a specificity of 22%, a negative predictive value of 92%, and an odds ratio of 2.4 (95% CI: 1.8, 3.2). High specificity (90%) corresponded to a sensitivity of 37%, positive predictive value of 41%, and odds ratio of 5.0 (95% CI: 2.8, 9.0). Conclusion Machine learning models that use radiomic features applied to mammographic calcifications may help predict upstaging of ductal carcinoma in situ, which can refine clinical decision making and treatment planning. © RSNA, 2022.

Background: The Superficial Femoral Artery-Popliteal EvidencE Development Study Group developed contemporary objective performance goals (OPGs) for peripheral vascular interventions (PVI) for superficial femoral artery (SFA)-popliteal artery disease using the Registry Assessment of Peripheral Interventional Devices., Methods: The Society for Vascular Surgery Vascular Quality Initiative PVI registry from January 2010 to October 2016 was used to develop OPGs based on SFA-popliteal procedures (n = 21,377) for intermittent claudication and critical limb ischemia (CLI). OPGs included 1-year rates for target lesion revascularization (TLR), major amputation, and 1 and 4-year survival rates. OPGs were calculated for the SFA and popliteal arteries and stratified by four treatments: angioplasty alone (percutaneous transluminal angioplasty [PTA]), self-expanding stenting, atherectomy, and any treatment type. Outcomes were illustrated by unadjusted Kaplan-Meier analyses., Results: Cohorts included PTA (n = 7505), stenting (n = 9217), atherectomy (n = 2510) and any treatment (n = 21,377). The mean age was 69 years, 58% were male, 79% were White, and 52% had CLI. The freedom from TLR OPGs at 1 year in the SFA were 80.3% (PTA), 83.2% (stenting), 83.9% (atherectomy), and 81.9% (any treatments). The freedom from TLR OPGs at 1 year in the popliteal were 81.3% (PTA), 81.3% (stenting), 80.2% (atherectomy), and 81.1% (any treatments). The freedom from major amputation OPGs at 1 year after SFA PVI were 93.4% (PTA), 95.7% (stenting), 95.1% (atherectomy), and 94.8% (any treatments). The freedom from major amputation OPG at 1 year after popliteal PVI were 90.5% (PTA), 93.7% (stenting), 91.8% (atherectomy), and 91.8%, (any treatments). The 4-year survival OPGs after SFA PVI were 76% (PTA), 80% (stenting), 82% (atherectomy), and 79% (any treatments), and for the popliteal artery were 72% (PTA), 77% (stenting), 82% (atherectomy), and 75% (any treatment). On a multivariable analysis, which included patient-level, leg-level, and lesion-level covariates, CLI was the single independent factor associated with increased TLR, amputation, and mortality., Conclusions: The Superficial Femoral Artery-Popliteal EvidencE Development OPGs define a new, contemporary benchmark for SFA-popliteal interventions using a large subset of real-world evidence to inform more efficient peripheral device clinical trial designs to support regulatory and clinical decision-making. It is appropriate to discuss proposals intended for regulatory approval with the US Food and Drug Administration to refine the OPG to match the specific trial population. The OPGs may be updated using coordinated registry networks to assess long-term real-world device performance., (Copyright © 2020 Society for Vascular Surgery. All rights reserved.)

Morbihan's disease is classically defined as primarily a Caucasian disease of chronic, recurrent erythema and nonpitting edema of the middle and upper thirds of the face. The disease is often difficult to diagnose and challenging to treat. Medical management is the primary treatment modality; however, if there is progression of the disease that causes visual impairment, surgical debulking is often required. We present the first reported case of Morbihan's disease in a Navajo patient in conjunction with a review of the literature on surgical management of this challenging disease., Competing Interests: Disclosure: The authors have no financial interest to declare in relation to the content of this article., (Copyright © 2020 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

Leiomyosarcoma is an aggressive soft-tissue malignancy derived from smooth muscle cells that rarely affects the oral cavity. We discuss the case of an 11-year-old boy with leiomyosarcoma that presented initially as a gingival swelling over his unerupted mandibular right permanent second molar. We highlight how appropriate imaging, prompt follow-up, and biopsy led to early diagnosis and ultimately a favorable clinical outcome.

A membrane potential change in cells is accompanied with mechanical deformation. This electromechanical response can play a significant role in regulating action potential in neurons and in controlling voltage-gated ion channels. However, measuring this subtle deformation in mammalian cells has been a difficult task. We show a plasmonic imaging method to image mechanical deformation in single cells upon a change in the membrane potential. Using this method, we have studied the electromechanical response in mammalian cells and have observed the local deformation within the cells that are associated with cell-substrate interactions. By analyzing frequency dependence of the response, we have further examined the electromechanical deformation in terms of mechanical properties of cytoplasm and cytoskeleton. We demonstrate a plasmonic imaging approach to quantify the electromechanical responses of single mammalian cells and determine local variability related to cell-substrate interactions.

Background: Clinical, pathological, and molecular information combined with cancer stage in prognostication algorithms can offer more personalized estimates of survival, which might guide treatment choices. Our aim was to evaluate the quality of prognostication tools in esophageal cancer., Methods: We systematically searched MedLine and Embase from 2005 to 2017 for studies reporting development or validation of models predicting long-term survival in esophageal cancer. We evaluated tools using the Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies guidelines and the American Joint Committee on Cancer acceptance criteria for risk models., Results: We identified 16 prognostication tools for patients treated with curative intent and 1 for patients with metastatic disease. These tools frequently excluded adenocarcinoma, contained outdated data, and were developed with a limited sample size. Nine tools were developed in China for squamous cell cancer, and 11 used data on patients diagnosed before 2010. Most tools excluded key prognostic factors such as age and sex. Tumor stage and grade were the most commonly, but not universally, included factors. Twelve tools were designed to predict overall survival; 5 predicted cancer-specific survival. Bootstrap internal validation was performed for most tools; c-statistics ranged from 0.63 to 0.77 and graphically evaluated calibration was "good." Five tools were externally validated; c-statistics ranged from 0.70 to 0.77., Conclusions: Existing tools cannot be confidently used for esophageal cancer prognostication in current clinical practice. Better-quality tools might help to more individually and accurately estimate disease course, select further treatments, and risk-stratify for future clinical trials., (Copyright © 2018. Published by Elsevier Inc.)

De facto reuse is the percentage of drinking water treatment plant (DWTP) intake potentially composed of effluent discharged from upstream wastewater treatment plants (WWTPs). Results from grab samples and a De Facto Reuse in our Nation's Consumable Supply (DRINCS) geospatial watershed model were used to quantify contaminants of emerging concern (CECs) concentrations at DWTP intakes to qualitatively compare exposure risks obtained by the two approaches. Between nine and 71 CECs were detected in grab samples. The number of upstream WWTP discharges ranged from 0 to >1,000; comparative de facto reuse results from DRINCS ranged from <0.1 to 13% during average flow and >80% during lower streamflows. Correlation between chemicals detected and DRINCS modeling results were observed, particularly DWTPs withdrawing from midsize water bodies. This comparison advances the utility of DRINCS to identify locations of DWTPs for future CEC sampling and treatment technology testing.

Objective: The current state of evaluating patients with peripheral artery disease and more specifically of evaluating medical devices used for peripheral vascular intervention (PVI) remains challenging because of the heterogeneity of the disease process, the multiple physician specialties that perform PVI, the multitude of devices available to treat peripheral artery disease, and the lack of consensus about the best treatment approaches. Because PVI core data elements are not standardized across clinical care, clinical trials, and registries, aggregation of data across different data sources and physician specialties is currently not feasible., Methods: Under the auspices of the U.S. Food and Drug Administration's Medical Device Epidemiology Network initiative-and its PASSION (Predictable and Sustainable Implementation of the National Registries) program, in conjunction with other efforts to align clinical data standards-the Registry Assessment of Peripheral Interventional Devices (RAPID) workgroup was convened. RAPID is a collaborative, multidisciplinary effort to develop a consensus lexicon and to promote interoperability across clinical care, clinical trials, and national and international registries of PVI., Results: The current manuscript presents the initial work from RAPID to standardize clinical data elements and definitions, to establish a framework within electronic health records and health information technology procedural reporting systems, and to implement an informatics-based approach to promote the conduct of pragmatic clinical trials and registry efforts in PVI., Conclusions: Ultimately, we hope this work will facilitate and improve device evaluation and surveillance for patients, clinicians, health outcomes researchers, industry, policymakers, and regulators., (Copyright © 2017 Society for Vascular Surgery. All rights reserved.)

The first and second articles in this three-part series on mindfulness described the production of the video "In the Moment: Stories of Mindfulness in Nursing" as part of the authors' Robert Wood Johnson Foundation Executive Nurse Fellowship program. In this final installment, we discuss our leadership approaches and lessons learned, both as a team and individuals.

In this second installment of a three-part series on mindfulness, we describe the process of producing video vignettes to illustrate how clinical nurses draw on the power of mindfulness to build their own resiliency while delivering compassionate care.

In this first installment of a three-part series on mindfulness, we describe a dynamic project aimed at elevating the importance of mindfulness, compassion, and presence as key competencies for professional nurses across the career span in all healthcare settings.

Objective: The purpose of this study was to explore graduates' perceptions of the efficacy and perceived utility of postgraduate physician assistant (PA) programs., Methods: Using an online tool, a survey was sent to postgraduate PA program graduates that contained demographic questions and descriptive questions examining the perceived utility of completing a postgraduate PA program., Results: Surveys were e-mailed to 149 graduates of postgraduate PA programs; 113 responded (75% response rate). After completing postgraduate training, 97% of graduates felt their training made them more competitive in the job market; 74% believed time from orientation to full productivity was reduced; and 95% would recommend completion of a postgraduate training program., Conclusions: Completion of a postgraduate PA program is an alternative to on-the-job training. Graduates perceived that the benefits from these programs include increased competitiveness in the job market, decreased onboarding time, and overall enhancement of their professional careers.

Objective: Our primary aim was to determine whether listeners in the following patient groups achieve localization accuracy within the 95th percentile of accuracy shown by younger or older normal-hearing (NH) listeners: (1) hearing impaired with bilateral hearing aids, (2) bimodal cochlear implant (CI), (3) bilateral CI, (4) hearing preservation CI, (5) single-sided deaf CI and (6) combined bilateral CI and bilateral hearing preservation., Design: The listeners included 57 young NH listeners, 12 older NH listeners, 17 listeners fit with hearing aids, 8 bimodal CI listeners, 32 bilateral CI listeners, 8 hearing preservation CI listeners, 13 single-sided deaf CI listeners and 3 listeners with bilateral CIs and bilateral hearing preservation. Sound source localization was assessed in a sound-deadened room with 13 loudspeakers arrayed in a 180-degree arc., Results: The root mean square (rms) error for the NH listeners was 6 degrees. The 95th percentile was 11 degrees. Nine of 16 listeners with bilateral hearing aids achieved scores within the 95th percentile of normal. Only 1 of 64 CI patients achieved a score within that range. Bimodal CI listeners scored at a level near chance, as did the listeners with a single CI or a single NH ear. Listeners with (1) bilateral CIs, (2) hearing preservation CIs, (3) single-sided deaf CIs and (4) both bilateral CIs and bilateral hearing preservation, all showed rms error scores within a similar range (mean scores between 20 and 30 degrees of error)., Conclusion: Modern CIs do not restore a normal level of sound source localization for CI listeners with access to sound information from two ears., (© 2016 S. Karger AG, Basel.)

Background: Although the use of a physician and nurse team at triage has been shown to improve emergency department (ED) throughput, the mechanism(s) by which these improvements occur is less clear., Objectives: 1) To describe the effect of a Rapid Medical Assessment (RMA) team on ED length of stay (LOS) and rate of left without being seen (LWBS); 2) To estimate the effect of RMA on different groups of patients., Methods: For Objective 1, we compared LOS and LWBS on dates when we utilized RMA to comparable dates when we did not. For Objective 2, we utilized patient logs to divide patients into groups and estimated the effects of the RMA on each., Results: Objective 1. LOS fell from 297.8 min pre-RMA to 261.7 min during RMA, an improvement of 36.1 (95% confidence interval 21.8-50.4) min; LWBS did not change significantly. Objective 2. Patients seen and dispositioned by the RMA had an estimated decrease in LOS of 117.8 min (estimated decrease in LOS of 45%), but patients seen by the RMA whose care was transitioned to the main ED had an estimated increase in LOS of 25.0 min (estimated increase in LOS of 8%)., Conclusions: On a system level, the addition of an RMA shift at a single facility was associated with an improvement in LOS, but not LWBS. On a mechanistic level, it seems that improvements occurred as a result of the rapid disposition component of the RMA rather than placing advanced orders at triage., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The aim of this article was to study sound source localization by cochlear implant (CI) listeners with low-frequency (LF) acoustic hearing in both the operated ear and in the contralateral ear. Eight CI listeners had symmetrical LF acoustic hearing and 4 had asymmetrical LF acoustic hearing. The effects of two variables were assessed: (i) the symmetry of the LF thresholds in the two ears and (ii) the presence/absence of bilateral acoustic amplification. Stimuli consisted of low-pass, high-pass, and wideband noise bursts presented in the frontal horizontal plane. Localization accuracy was 23° of error for the symmetrical listeners and 76° of error for the asymmetrical listeners. The presence of a unilateral CI used in conjunction with bilateral LF acoustic hearing does not impair sound source localization accuracy, but amplification for acoustic hearing can be detrimental to sound source localization accuracy.

In this report, we used filtered noise bands to constrain listeners' access to interaural level differences (ILDs) and interaural time differences (ITDs) in a sound source localization task. The samples of interest were listeners with single-sided deafness (SSD) who had been fit with a cochlear implant in the deafened ear (SSD-CI). The comparison samples included listeners with normal hearing and bimodal hearing, i.e., with a cochlear implant in 1 ear and low-frequency acoustic hearing in the other ear. The results indicated that (i) sound source localization was better in the SSD-CI condition than in the SSD condition, (ii) SSD-CI patients rely on ILD cues for sound source localization, (iii) SSD-CI patients show functional localization abilities within 1-3 months after device activation and (iv) SSD-CI patients show better sound source localization than bimodal CI patients but, on average, poorer localization than normal-hearing listeners. One SSD-CI patient showed a level of localization within normal limits. We provide an account for the relative localization abilities of the groups by reference to the differences in access to ILD cues.

The aim of this project was to determine for bimodal cochlear implant (CI) patients, i.e. patients with low-frequency hearing in the ear contralateral to the implant, how speech understanding varies as a function of the difference in level between the CI signal and the acoustic signal. The data suggest that (1) acoustic signals perceived as significantly softer than a CI signal can contribute to speech understanding in the bimodal condition, (2) acoustic signals that are slightly softer than, or balanced with, a CI signal provide the largest benefit to speech understanding, and (3) acoustic signals presented at maximum comfortable loudness levels provide nearly as much benefit as signals that have been balanced with a CI signal.

Background/aims: The purpose of this article is to outline multilevel structural equation modeling (MSEM) for mediation analysis of longitudinal data. The introduction of mediating variables can improve experimental and nonexperimental studies of child growth in several ways as discussed throughout this article. Single-mediator individual-level and multilevel mediation models illustrate several current issues in the estimation of mediation with longitudinal data. The strengths of incorporating structural equation modeling (SEM) with multilevel mediation modeling are described. SUMMARY AND KEY MESSAGES: Longitudinal mediation models are pervasive in many areas of research including child growth. Longitudinal mediation models are ideally modeled as repeated measurements clustered within individuals. Further, the combination of MSEM and SEM provides an ideal approach for several reasons, including the ability to assess effects at different levels of analysis, incorporation of measurement error and possible random effects that vary across individuals., (© 2014 S. Karger AG, Basel.)

Background/aims: The increased occurrence of type 2 diabetes and its clinical correlates is a global public health issue, and there are continued efforts to find its genetic determinant across ethnically diverse populations. The aims of this study were to determine the heritability of diabetes and metabolic syndrome phenotypes in the Arizona Insulin Resistance (AIR) registry and to perform an association analysis of common single nucleotide polymorphisms (SNPs) identified by GWAS with these traits. All study participants were Mexican Americans from the AIR registry., Methods: Metabolic, anthropometric, demographic and medical history information was obtained on the 667 individuals enrolled in the registry., Results: The heritability estimates were moderate to high in magnitude and significant, indicating that the AIR registry is well suited for the identification of genetic factors contributing to diabetes and the metabolic syndrome. From the 30 GWAS genes selected (some genes were represented by multiple SNPs), 20 SNPs exhibited associations with one or more of the diabetes related traits with nominal significance (p ≤ 0.05). In addition, 25 SNPs were nominally significantly associated with one or more of the metabolic phenotypes tested (p ≤ 0.05). Most notably, 5 SNPs from 5 genes [body mass index (BMI), hip circumference: rs3751812/FTO; fasting plasma glucose, hemoglobin A1c: rs4607517/GCK; very-low-density lipoprotein: rs10830963/MTNR1B; BMI: rs13266634/SLC30A8, and total cholesterol, low-density lipoprotein: rs7578597/THADA] were significantly associated with obesity, glycemic, and lipid phenotypes when using the multiple testing significance threshold of 0.0015., Conclusion: These findings extend previous work on Mexican Americans to suggest that metabolic disease is strongly influenced by genetic background in this high-risk population., (© 2014 S. Karger AG, Basel.)

Background: Applications in clinical medicine can benefit from fusion of spectroscopy data with anatomical imagery. For example, new 3-dimensional (3D) spectroscopy techniques allow for improved correlation of metabolite profiles with specific regions of interest in anatomical tumor images, which can be useful in characterizing and treating heterogeneous tumors that appear structurally homogeneous., Objectives: We sought to develop a clinical workflow and uniquely capable custom software tool to integrate advanced 3-tesla 3D proton magnetic resonance spectroscopic imaging ((1)H-MRSI) into industry standard image-guided neuronavigation systems, especially for use in brain tumor surgery., Methods: (1)H-MRSI spectra from preoperative scanning on 15 patients with recurrent or newly diagnosed meningiomas were processed and analyzed, and specific voxels were selected based on their chemical contents. 3D neuronavigation overlays were then generated and applied to anatomical image data in the operating room. The proposed 3D methods fully account for scanner calibration and comprise tools that we have now made publicly available., Results: The new methods were quantitatively validated through a phantom study and applied successfully to mitigate biopsy uncertainty in a clinical study of meningiomas., Conclusions: The proposed methods improve upon the current state of the art in neuronavigation through the use of detailed 3D (1)H-MRSI data. Specifically, 3D MRSI-based overlays provide comprehensive, quantitative visual cues and location information during neurosurgery, enabling a progressive new form of online spectroscopy-guided neuronavigation., (© 2014 S. Karger AG, Basel.)

The purpose of this study was to examine the availability of binaural cues for adult, bilateral cochlear implant (CI) patients, bimodal patients and hearing preservation patients using a multiple-baseline, observational study design. Speech recognition was assessed using the Bamford-Kowal-Bench Speech-in-Noise (BKB-SIN) test as well as the AzBio sentences [Spahr AJ, et al: Ear Hear 2012;33:112-117] presented in a multi-talker babble at a +5 dB signal-to-noise ratio (SNR). Test conditions included speech at 0° with noise presented at 0° (S0N0), 90° (S0N90) and 270° (S0N270). Estimates of summation, head shadow (HS), squelch and spatial release from masking (SRM) were calculated. Though nonwwe of the subject groups consistently showed access to binaural cues, the hearing preservation patients exhibited a significant correlation between summation and squelch whereas the bilateral and bimodal participants did not. That is to say, the two effects associated with binaural hearing - summation and squelch - were positively correlated only for the listeners with bilateral acoustic hearing. This finding provides evidence for the supposition that implant recipients with bilateral acoustic hearing have access to binaural cues, which should, in theory, provide greater benefit in noisy listening environments. It is likely, however, that the chosen test environment negatively affected the outcomes. Specifically, the spatially separated noise conditions directed noise toward the microphone (mic) port of the behind-the-ear (BTE) hearing aid and implant processor. Thus, it is possible that in more realistic listening environments for which the diffuse noise is not directed toward the processor/hearing aid mic, hearing preservation patients have binaural cues for improved speech understanding.

Background: Rhythmic disturbances are a hallmark of motor speech disorders, in which the motor control deficits interfere with the outward flow of speech and by extension speech understanding. As the functions of rhythm are language-specific, breakdowns in rhythm should have language-specific consequences for communication., Objective: The goals of this paper are to (i) provide a review of the cognitive-linguistic role of rhythm in speech perception in a general sense and crosslinguistically; (ii) present new results of lexical segmentation challenges posed by different types of dysarthria in American English, and (iii) offer a framework for crosslinguistic considerations for speech rhythm disturbances in the diagnosis and treatment of communication disorders associated with motor speech disorders., Summary: This review presents theoretical and empirical reasons for considering speech rhythm as a critical component of communication deficits in motor speech disorders, and addresses the need for crosslinguistic research to explore language-universal versus language-specific aspects of motor speech disorders., (Copyright © 2013 S. Karger AG, Basel.)

This manuscript presents the usefulness of various experimental models in research with the purpose to elucidate mechanisms of disease and help create treatment modalities. The emphasis is on the use of models primarily for the study and treatment of amyloidosis. This is a rare condition that has attracted much attention recently. Amyloidosis is a disease in which the information obtained in the research laboratory has played a key role in advancing our understanding of the mechanisms associated with this group of disorders and in the development of new avenues for therapeutic intervention. Both in-vivo and in-vitro models are addressed. The early animal models and the more recent transgenic models are presented along with their usefulness to study the pathogenesis and dissect gene expression profiles where appropriate. Their pros and cons of the various experimental settings are highlighted. In-vitro models are presented with examples from the literature as to how they have or are being used to study a variety of conditions, renal as well as others. They also serve the purpose of resolving questions primarily relating to patho-genesis and to test the value of novel interventions prior to using in vivo models that are generally more expensive and difficult to work with. Since all models have their limitations, perhaps the best way is to utilize both in-vitro and in-vivo platforms, selecting them depending upon the questions to be answered. Employing a large variety of experimental techniques can serve to obtain and validate the data. The advantages of this approach will become obvious in the book chapters that follow., (Copyright © 2011 S. Karger AG, Basel.)

We investigated the regulation of luteinizing hormone (LH) in the male Rufous-winged Sparrow,Aimophila carpalis, a resident of the Sonoran desert that breeds after irregular summer rains. Although the testes develop in March due to increasing photoperiod and regress in September due to decreasing photoperiod, LH does not consistently increase in the spring as in other photoperiodic birds. However, throughout the year increased plasma LH is correlated with rainfall. To investigate this rainfall-associated regulation of LH secretion, we quantified immunocytochemical labeling for gonadotropin-releasing hormone I (GnRH-I), proGnRH (the GnRH precursor), and gonadotropin-inhibitory hormone (GnIH) in the hypothalamus of free-living adult males caught before (low LH), and during (high LH) the monsoon rainy season. Compared to pre-monsoon birds, birds caught during the monsoon season had larger immunoreactive GnRH-I (GnRH-I-ir) and proGnRH-ir cell bodies, as well as fewer, less densely labeled proGnRH-ir cell bodies. Birds caught during the monsoon had fewer, less densely labeled GnIH-ir cell bodies than birds caught before the monsoon. Further, there was no GnIH-ir labeling in the median eminence on either capture dates, suggesting that GnIH is not released to the pituitary gland via the portal vein at this time of year, but there were fewer GnIH-ir fibers in the preoptic area of birds caught during the monsoon season. Our data support the hypothesis that environmental factors associated with increased rainfall during the monsoon season stimulate GnRH synthesis and release to increase LH secretion. These data also suggest that GnIH could inhibit GnRH neuronal activity prior to the monsoon season., (Copyright 2007 S. Karger AG, Basel.)

Introduction: A tripling in the number of overweight adolescents has occurred during the past two decades, with type 2 diabetes reaching epidemic proportions. Although obesity has been identified as a correlate of depression and low self-esteem in adolescents, the relationships among key cognitive/mental health variables and healthy attitudes, beliefs, choices, and behaviors in overweight teens have yet to be explored. Therefore, the aim of this study was to describe these relationships so that an effective intervention program to promote and sustain healthy lifestyle behaviors could be implemented., Methods: A descriptive correlational study was conducted with 23 overweight teens. Key variables measured included depressive symptoms, state and trait anxiety, self-esteem, beliefs/confidence about engaging in a healthy lifestyle, perceived difficulty in leading a healthy lifestyle, and healthy attitudes, choices, and behaviors., Findings: Teens with higher state and trait anxiety as well as depressive symptoms had less healthy lifestyle beliefs, and teens with higher self-esteem had stronger beliefs about their ability to engage in a healthy lifestyle. Stronger beliefs about the ability to engage in healthy lifestyles were related to healthier living attitudes and healthier lifestyle choices. Teens who perceived healthy lifestyles as more difficult had less healthy attitudes and reported less healthier choices and behaviors., Discussion: Including a strong cognitive behavioral skills building component into clinical interventions with overweight teens may be key in boosting their beliefs/confidence about being able to engage in healthy behaviors and lessening their perceived difficulty in performing them, which should result in healthier choices and lifestyle behaviors.