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With climate change causing rising sea-levels around the globe, multiple recent efforts in the United States have focused on the prediction of various meteorological factors that can lead to periods of anomalously high-tides despite seemingly benign atmospheric conditions. As part of these efforts, this research explores monthly-scale relationships between sea-level variability and atmospheric circulation patterns, and demonstrates two options for sub-seasonal to seasonal (S2S) predictions of anomalous sea-levels using these patterns as inputs to artificial neural network (ANN) models. Results on the monthly scale are similar to previous research on the daily scale, with above-average sea-levels and an increased risk of high-water events on days with anomalously low atmospheric pressure patterns and wind patterns leading to on-shore or downwelling-producing wind stress. Some wind patterns show risks of high-water events to be over 6-times higher than baseline risk, and exhibit an average water level anomaly of +94mm above normal. In terms of forecasting, nonlinear autoregressive ANN models with exogenous input (NARX models) and pattern-based lagged ANN (PLANN) models show skill over post-processed numerical forecast model output, and simple climatology. Damped-persistence forecasts and PLANN models show nearly the same skill in terms of predicting anomalous sea-levels out to 9 months of lead time, with a slight edge to PLANN models, especially with regard to error statistics. This perspective on forecasting – using predefined circulation patterns along with ANN models – should aid in the real-time prediction of coastal flooding events, among other applications.

This project will examine the cross-sectional and longitudinal relations among parent-reported irritability, parent-reported ADHD symptoms, and a behavioral measure of inhibitory control in adolescents enrolled in The Adolescent Brain Cognitive Development℠ Study (ABCD Study®).

Deep brain stimulation (DBS) devices capable of measuring differential local field potentials (∂LFP) enable neural recordings alongside clinical therapy. Efforts to identify oscillatory correlates of various brain disorders, or disease readouts, are growing but must proceed carefully to ensure readouts are not distorted by brain environment. In this report we identified, characterized, and mitigated a major source of distortion in ∂LFP that we introduce as mismatch compression (MC). Using in vivo, in silico, and in vitro models of MC, we showed that impedance mismatches in the two recording electrodes can yield incomplete rejection of stimulation artifact and subsequent gain compression that distorts oscillatory power. We then developed and validated an opensource mitigation pipeline that mitigates the distortions arising from MC. This work enables more reliable oscillatory readouts for adaptive DBS applications.

Perfluorosulfonic acids (PFSAs) are a recalcitrant subclass of per- and polyfluoroalkyl substances (PFASs) linked to numerous negative health effects in humans. Scalable technologies that effectively destroy PFSAs will greatly reduce the future health and ecological impact of these "forever chemicals". Herein, we show that several PFSAs undergo facile mechanochemical destruction (MCD) in the presence of quartz sand (SiO

1) To determine the relationship of electrocochleography (ECochG) responses measured on the promontory with responses measured at the round window (RW) and various intracochlear sites. 2) To evaluate if promontory ECochG responses correlate with postoperative speech-perception performance using the cochlear implant (CI).Prospective cohort study.Tertiary referral center.Ninety-six adult CI recipients with no cochlear malformations or previous otologic surgery.Acoustically evoked ECochG responses were measured intraoperatively at both extracochlear and intracochlear locations. ECochG total response (ECochG-TR), a measure of residual cochlear function, was calculated by summing the fast Fourier transformation amplitudes in response to 250-Hz to 2-kHz acoustic stimuli. Speech-perception performance was measured at 3 months.There were strong linear correlations for promontory ECochG-TR with the ECochG-TRs measured at the RW ( r = 0.95), just inside scala tympani ( r = 0.91), and after full insertion ( r = 0.83). For an individual subject, the morphology of the ECochG response was similar in character across all positions; however, the response amplitude increased from promontory to RW (~1.6-fold) to just inside scala tympani (~2.6-fold), with the largest response at full insertion (~13.1-fold). Promontory ECochG-TR independently explained 51.8% of the variability ( r2 ) in consonant-nucleus-consonant at 3 months.Promontory ECochG recordings are strongly correlated with responses previously recorded at extracochlear and intracochlear sites and explain a substantial portion of the variability in CI performance. These findings are a critical step in supporting translation of transtympanic ECochG into the clinic preoperatively to help predict postoperative CI performance.

To characterize the catchment area and patient profile of large cochlear implant (CI) centers in the United States.Multi-institutional retrospective case series.Tertiary referral CI centers.Patients who underwent CI surgery at 7 participating CI centers between 2015 and 2020 were identified. Patients' residential zip codes were used to approximate travel distances and urban vs rural residential areas.Over the 6-year study period (2015-2020), 6313 unique CI surgical procedures occurred (4529 adult, 1784 pediatric). Between 2015 and 2019, CI procedures increased by 43%. Patients traveled a median 52 miles (interquartile range, 21-110) each way; patients treated at rural CI centers traveled greater distances vs those treated at urban centers (72 vs 46 miles,While large CI centers serve geographically dispersed populations, most patients reside within a 200-mile radius. Strategies to expand CI utilization may leverage remote programming, telemedicine, and strategic placement of new centers and satellite clinics to ameliorate travel burden.

OBJECTIVE The clinical response of patients with bipolar disorder to medical treatment is variable. A better understanding of the underlying neural circuitry involved in bipolar treatment responsivity subtypes may provide insight into treatment resistance and aid in identifying an effective surgical target for deep brain stimulation (DBS) specific to the disorder. Despite considerable imaging research related to the disease, a paucity of comparative imaging analyses of treatment responsiveness exists. There are also no DBS targets designed expressly for patients with bipolar disorder. Therefore, the authors analyzed cingulum bundle axonal connectivity in relation to cortico-striatal-thalamo-cortical (CSTC) loops implicated in bipolar disorder across subjects who are responsive to treatment (RSP) and those who are refractory to therapy (REF), compared to healthy controls (HCs). METHODS Twenty-five subjects with bipolar disorder (13 RSP and 12 REF), diagnosed using the Mini International Neuropsychiatric Interview and classified with standardized rating scales, and 14 HCs underwent MRI with diffusion sequences for probabilistic diffusion-weighted tractography analysis. Image processing and tractography were performed using MRTrix. Region of interest (ROI) masks were created manually for 10 anterior cingulum bundle subregions, including surgical targets previously evaluated for the treatment of bipolar disorder (cingulotomy and subgenual cingulate DBS targets). Cortical and subcortical ROIs of brain areas thought to be associated with bipolar disorder and described in animal tract-tracing models were created via FreeSurfer. The number of axonal projections from the cingulum bundle subregion ROIs to cortical/subcortical ROIs for each group was compared. RESULTS Significant differences were found across groups involving cingulum bundle and CSTC loops. Subjects in the RSP group had increased connections from rostral cingulum bundle to medial orbitofrontal cortex, which is part of the limbic CSTC loop, whereas subjects in the REF group had increased connectivity from rostral cingulum bundle to thalamus. Additionally, compared to HCs, both RSP and REF subjects had decreased cingulum bundle dorsal connectivity (dorsal anterior/posterior cingulate, dorsomedial/lateral frontal cortex) and increased cingulum bundle ventral connectivity (subgenual cingulate, frontal pole, lateral orbitofrontal cortex) involving limbic and associative CSTC loops. CONCLUSIONS Findings demonstrate that bipolar treatment responsivity may be associated with significant differences in cingulum bundle connectivity in relation to CSTC loops, which may help identify a surgical target for bipolar disorder treatment via DBS in the future.

To assess the clinical application of five recently published cochlear implant (CI) candidacy evaluation (CICE) referral screening tools through external validation.Retrospective cohort study.Tertiary otology/neurotology practice.Adults who underwent CICE between December 2020 and September 2021.CICE referral screening tools versus CI candidacy criteria.CICE screening tool performance, based on the ability to identify patients who met the CI candidacy criteria, was evaluated. CI candidacy criteria were defined as best-aided AzBio sentences at +10 signal-to-noise ratio and either 60% or less accuracy to reflect traditional criteria used in clinical settings or 40% or less accuracy (only patients 65 years or older) to reflect Medicare-eligible criteria.Screening criteria of proposed CICE referral tools vary widely across pure-tone average and word recognition scores. When screened by traditional criteria, the sensitivities and specificities of these referral tools varied from 40 to 77% and from 22 to 86%, respectively. When screened by Medicare-eligible criteria, sensitivities and specificities varied from 41 to 81% and from 24 to 91%, respectively. The screening tool proposed by Zwolan et al. ( Otol Neurotol 2020;41(7):895-900) demonstrated the best overall performance for traditional (Youden's J , 0.37; sensitivity, 62%; specificity, 75%) and Medicare-eligible patients (Youden's J , 0.44; sensitivity, 66%; specificity, 78%). All screening tools performed worse on the validation cohort compared with their respective development cohorts.Current tools for determining CICE referral have diverse screening criteria. These combinations of pure-tone average and word recognition score are modestly successful at identifying CI candidates.

Perception of our linear motion – heading – is critical for postural control, gait, and locomotion, and it is impaired in Parkinson’s Disease (PD). Deep brain stimulation (DBS) has variable effects on vestibular heading perception, depending on the location of the electrodes within the subthalamic nucleus (STN). Here, we aimed to find the anatomical correlates of heading perception in PD. Fourteen PD participants with bilateral STN DBS performed a two-alternative forced-choice discrimination task where a motion platform delivered translational forward movements with a heading angle varying between 0 and 30 degrees to the left or to the right with respect to the straight-ahead direction. Using psychometric curves, we derived the heading discrimination threshold angle of each patient from the response data. We created patient-specific DBS models and calculated the percentages of stimulated axonal pathways that are anatomically adjacent to the STN and known to play a major role in vestibular information processing. We performed correlation analyses to investigate the extent of these white matter tracts’ involvement in heading perception. Significant positive correlations were identified between improved heading discrimination for rightward heading and the percentage of activated streamlines of the contralateral hyperdirect, pallido-subthalamic, and subthalamo-pallidal pathways. The hyperdirect pathways are thought to provide top-down control over STN connections to the cerebellum. In addition, STN may also antidromically activate collaterals of hyperdirect pathway that projects to the precerebellar pontine nuclei. In select cases there was strong activation of the cerebello-thalamic projections, but it was not consistently present in all participants. Large volumetric overlap between the volume of tissue activation and the STN in the left hemisphere positively impacted rightward heading perception. Altogether, the results suggest heavy involvement of basal ganglia cerebellar network in STN-induced modulation of vestibular heading perception in PD.

Introduction: Models of structural connectivity in the human brain are typically simulated using tractographic approaches. However, the nonlinear fitting of anatomical pathway atlases to de novo subject brains represents a simpler alternative that is hypothesized to provide more anatomically realistic results. Therefore, the goal of this study was to perform a side-by-side comparison of the streamline estimates generated by either pathway atlas fits or tractographic reconstructions in the same subjects. Methods: Our analyses focused on reconstruction of the corticospinal tract (CST), cerebellothalamic (CBT), and pallidothalamic (PT) pathways using example datasets from the Human Connectome Project (HCP). We used MRtrix3 to explore whole brain, as well as manual seed-to-target, tractography approaches. In parallel, we performed nonlinear fits of an axonal pathway atlas to each HCP dataset using Advanced Normalization Tools (ANTs). Results: The different methods produced notably different estimates for each pathway in each subject. The fitted atlas pathways were highly stereotyped and exhibited low variability in their streamline trajectories. Manual tractography resulted in pathway estimates that generally corresponded with the fitted atlas pathways, but with a higher degree of variability in the individual streamlines. Pathway reconstructions derived from whole-brain tractography exhibited the highest degree of variability and struggled to create anatomically realistic representations for either the CBT or PT pathways. Conclusion: The speed, simplicity, reproducibility, and realism of anatomical pathway model fits makes them an appealing option for some forms of structural connectivity modeling in the human brain. Impact statement Axonal pathway modeling is an important component of deep brain stimulation (DBS) research studies that seek to identify the brain connections that are directly activated by stimulation. The corticospinal tract, cerebellothalamic (CBT), and pallidothalamic (PT) pathways are specifically relevant to the study of subthalamic DBS for the treatment of Parkinson's disease. Our results suggest that anatomical pathway model fits of the CBT and PT pathways to de novo subject brains represent a more anatomically realistic option than tractographic approaches when studying subthalamic DBS.

Aseptic meningitis, including culture negative and viral meningitis, contributes a significant health-care burden, including unnecessary antibiotic use and hospitalisation to treat possible bacterial meningitis. This study analysed aseptic meningitis hospitalisations in New Zealand (NZ) children over 29 years.In this population-based study, aseptic meningitis hospitalisations in NZ children15 years old were analysed from 1991 to 2020. Incident rate ratios were calculated using Poisson regression models. Variations in hospitalisations by age, year, sex, ethnicity, geographical region and socio-economic deprivation were analysed.There were 5142 paediatric aseptic meningitis hospitalisations from 1991 to 2020. Most were unspecified viral meningitis (64%), followed by enterovirus (29%). Hospitalisation rates varied annually with a median of 18.4/100 000 children including a peak in 2001 of 56.4/100 000 (51.7-61.6). From 2002 to 2019, rates increased by 8.4%/year (7.2-9.5%) in infants90 days old but decreased in all other age groups. In 2020, a reduction in hospitalisations to 9.6/100 000 (7.9-11.8) occurred, and in infants90 days old were 0.37 times expected. Hospitalisations were 1.50 times (1.49-1.68) higher in males than females; higher in children of Māori (P 0.001) and Pacific (P 0.001) versus European ethnicity; and higher for children living in the most (2.44 times, (2.16-2.75)) versus least deprived households; and in northern versus southern NZ.Aseptic meningitis hospitalisations increased in young infants during 29 years of surveillance, apart from 2020 when admissions reduced during the COVID-19 pandemic. In contrast, hospitalisations decreased in children aged1 year. Further investigation into reasons for higher admissions by ethnic group, geographical location and increased deprivation are required.

The incidence of older patients undergoing orthognathic surgery is increasing. The purpose of this study is to evaluate the association between age and perioperative adverse outcomes in patients undergoing orthognathic surgery.This is a retrospective cohort study of patients undergoing orthognathic surgery in the 2011 to 2019 American College of Surgeons National Surgical Quality Improvement Program databases. The primary predictor variable was age group (≥40 or40 years). The primary outcome variable was adverse outcomes occurring within 30 days of the index operation. Descriptive, bivariate, and Firth logistic regression statistics were utilized to evaluate association between age and adverse outcomes.During the study period, 1,226 patients underwent an orthognathic procedure and 835 subjects were included. Of these subjects, 145 were 40 years or older (17.4%) and 690 were less than 40 years (82.6%). Subjects 40 years or older were more likely to be American Society of Anesthesiologists (ASA) classification II (P ≤ .001), ASA III (P ≤ .001), or diagnosed with obstructive sleep apnea (P ≤ .001). A total of 34 subjects experienced an adverse outcome (4.07%), though there was no significant difference in the incidence of adverse outcomes between age groups (P = .152). In bivariate analysis, hypertension on medication (P = .037), procedure type (P = .001), and segmented Le Fort I osteotomies (P = .039) were associated with adverse outcomes. After controlling for age, hypertension on medication, segmented Le Fort I osteotomies, and diagnosis of obstructive sleep apnea, isolated mandibular osteotomies were the only independent predictors of adverse outcomes (odds ratio 2.64; 95% confidence interval, 1.06 to 7.24; P = .038). Length of stay was 1.38 ± 1.43 days for the 40 years or older group compared to 1.06 ± 1.18 in the40 group (P = .012).Despite higher ASA classifications, older patients did not have a significantly greater incidence of perioperative adverse outcomes including airway complications, nor was increased age associated with adverse outcomes in bivariate or multivariate analysis.

Rainfall components likely differ in the magnitude and direction of their long-term changes for any given location, and some rainfall components may carry a greater regional signal of change than rainfall totals. This study evaluates the magnitude of change of multiple rainfall components relative to other components, and the greatest regions of change across all rainfall components in West Africa. Hourly rainfall data from the ERA5 reanalysis dataset was used to derive twelve rainfall components, which were evaluated for long-term means, interannual variability, and long-term changes. For rainfall totals and rainfall intensity, the central Sahel is witnessing increasing trends while the western Sahel is experiencing significant decreasing trends. In general, decreasing trends predominate in the study domain, especially in the northwestern Congo Basin, where annual rainfall is decreasing by 120mm per decade. Importantly, rainfall frequency accounts for 49% of all significant grid-point trends for the whole domain. In contrast, rainfall totals account for 26% of all combined significant trends across the domain, while rainfall intensity (12.6%), rainy season length (9.5%), and seasonality (3.3%) account for the remaining signals of change. Most of the changes among the rainfall components are in the Tropical Wet and Dry regions (59% of all significant trends); the Saharan and Equatorial regions account for the least changes. This study finds evidence that rainfall frequency is changing more across the regions compared to rainfall totals and should be explored as rainfall inputs in climate models to potentially improve regional predictions of future rainfall.

A nationally generalisable cohort (n 5770) was used to determine the prevalence of non-timely (early/late) introduction of complementary food and core food groups and associations with maternal sociodemographic and health behaviours in New Zealand (NZ). Variables describing maternal characteristics and infant food introduction were sourced, respectively, from interviews completed antenatally and during late infancy. The NZ Infant Feeding Guidelines were used to define early (≤ 4 months) and late (≥ 7 months) introduction. Associations were examined using multivariable multinomial regression, presented as adjusted relative risk ratios and 95 % confidence intervals (RRR; 95% CI). Complementary food introduction was early for 40·2 % and late for 3·2 %. The prevalence of early food group introduction were fruit/vegetables (23·8 %), breads/cereals (36·3 %), iron-rich foods (34·1 %) and of late were meat/meat alternatives (45·9 %), dairy products (46·2 %) and fruits/vegetables (9·9 %). Compared with infants with timely food introduction, risk of early food introduction was increased for infants: breastfed < 6months (2·52; 2·19–2·90), whose mothers were < 30 years old (1·69; 1·46–1·94), had a diploma/trade certificate v. tertiary education (1·39; 1·1–1·70), of Māori v. European ethnicity (1·40; 1·12–1·75) or smoked during pregnancy (1·88; 1·44–2·46). Risk of late food introduction decreased for infants breastfed < 6 months (0·47; 0.27–0·80) and increased for infants whose mothers had secondary v. tertiary education (2·04; 1·16–3·60) were of Asian v. European ethnicity (2·22; 1·35, 3·63) or did not attend childbirth preparation classes (2·23; 1·24–4·01). Non-timely food introduction, specifically early food introduction, is prevalent in NZ. Interventions to improve food introduction timeliness should be ethnic-specific and support longer breast-feeding.

Purpose This study compared opioid prescription patterns among oral and maxillofacial surgeons (OMSs) treating Medicare beneficiaries in urban and rural settings, in an effort to identify avenues to further promote responsible opioid prescribing in a patient demographic vulnerable to opioid diversion. Methods This study used Medicare Provider Utilization and Payment Data from 2014 to 2018, focusing on providers labeled as an OMS. Rural-Urban Commuting Area Codes were used to categorize each OMS as urban or rural. Demographic variables included total number of OMSs, provider gender, beneficiaries per provider, beneficiaries age, and beneficiary hierarchal condition category (proxy for clinical complexity). Outcome variables included opioid prescribing rate, opioid claims per provider, opioid claims per beneficiary, and number of days’ supply of opioids per claim. Descriptive statistics, chi-squared tests, 2-tailed t-tests, and Wilcoxon rank-sum tests were used as appropriate. Results Across all years, the data consisted of mostly urban and male OMSs. The mean number of Medicare beneficiaries prescribed opioids per OMS varied widely, and the mean age of beneficiaries was 70.4 ± 4.4 and 69.9 ± 4.1 years for urban and rural OMSs, respectively. Mean opioid claims per provider were higher among rural OMSs, with large standard deviations among both rural and urban OMSs. However, there were no significant differences in the opioid prescribing rate or in the mean opioid claims per beneficiary in all 5 years included in the study. There were also no clinically significant differences between urban and rural OMSs in the number of days’ supply per claim (between 3 to 4 days in all periods). However, in each year, there was a significantly higher proportion of urban OMSs who prescribed more than 7 days’ supply per claim. Conclusions Opioid prescription practices were generally similar between rural and urban OMSs treating Medicare beneficiaires. The small subset of longer-term opioid prescribers, which were more prevalent in urban areas, warrants further investigation.

Treating chronic migraine (CM) effectively is one of the greatest challenges a primary care provider (PCP) may encounter. Many patients with CM report dissatisfaction and minimal gains from treatment, despite using the best medical interventions available. For this study, patients with CM and their partners provided insight into how PCPs could improve CM treatment.Using the immersion/crystallization phenomenological method, we collected data from 11 patients with CM and 8 of their partners (N = 19). We analyzed open-ended survey responses about migraine treatment from patients with CM, as well as transcripts from interviews with patients with CM and their partners (14 interviews total) about their medical experiences.Participants used a variety of pharmacological and alternative treatments in search of a cure; wanted to be treated more collaboratively; and repeatedly gave up on medical care, but then sought treatment again.PCPs could be trained to encourage patients with CM to shift toward accepting and managing migraines rather than endlessly hoping for a cure. Patients could be taught to manage CM using a holistic, biopsychosocial approach.

While deaths from pneumonia during childhood in New Zealand (NZ) are now infrequent, childhood pneumonia remains a significant cause of morbidity. In this viewpoint, we describe pneumonia epidemiology in NZ and identify modifiable risk factors. During recent decades, pneumonia hospitalisation rates decreased, attributable in part to inclusion of pneumococcal conjugate vaccine in NZ's immunisation schedule. Irrespective of these decreases, pneumonia hospitalisation rates are four times higher for Pacific and 60% higher for Māori compared with children of other ethnic groups. Consistent with other developed countries, hospitalisation rates for pneumonia with pleural empyema increased in NZ during the 2000s. Numerous factors contribute to childhood pneumonia acquisition, hospitalisation and morbidity in NZ include poor quality living environments, malnutrition during pregnancy and early childhood, incomplete and delayed vaccination during pregnancy and childhood and variable primary and secondary care management. To reduce childhood pneumonia disease burden, interventions should focus on addressing modifiable risk factors for pneumonia. These include using non-polluting forms of household heating; decreasing cigarette smoke exposure; reducing household acute respiratory infection transmission; improving dietary nutritional content and nutrition during pregnancy and early childhood; breastfeeding promotion; vaccination during pregnancy and childhood and improving the quality of and decreasing the variance in primary and secondary care management of pneumonia.

Anomalous sea levels along the mid-Atlantic and South Atlantic coasts of the United States are often linked to atmosphere–ocean dynamics, remote- and local-scale forcing, and other factors linked to cyclone passage, winds, waves, and storm surge. Herein, we examine sea level variability along the U.S. Atlantic coast through satellite altimeter and coastal tide gauge data within the context of synoptic-scale weather pattern forcing. Altimetry data, derived from sea level anomaly (SLA) data between 1993 and 2019, were compared with self-organizing map (SOM)-based atmospheric circulation and surface wind field categorizations to reveal spatiotemporal patterns and their interrelationships with high-water-level conditions at tide gauges. Regional elevated sea level patterns and variability were strongly associated with synergistic patterns of atmospheric circulation and wind. Recurring atmospheric patterns associated with high-tide flooding events and flood risk were identified, as were specific regional oceanographic variability patterns of SLA response. The incorporation of combined metrics of wind and circulation patterns further isolate atmospheric drivers of high-tide flood events and may have particular significance for predicting future flood events over multiple spatial and temporal scales. Significance Statement Mean sea level and minor to moderate coastal flood events, also called blue-sky or high-tide floods, are increasing along many U.S. coastlines. While the drivers of such events are numerous, here we identified key contributing weather patterns and environmental factors linked to increased risk of regional and local high-water conditions along the Atlantic coast. Our results indicate that the predictability of elevated sea levels and high-tide floods is highly dependent upon atmospheric drivers including wind and circulation patterns and, if applied in a tested modeling framework, may prove useful for predicting future floods at various time scales.

Context The significance of thyroid peroxidase (TPOAb) and thyroglobulin antibody (TgAb) in the pathogenesis of thyroid immune-related adverse events (irAEs) is unknown. Objective To characterize the association of anti-thyroid antibodies with the development of thyroid immune related adverse events. Methods A retrospective cohort study was conducted of patients with melanoma receiving immune checkpoint inhibitor (ICI) treatment. TPOAb, TgAb, and interleukin-6 (IL-6) were measured retrospectively using tumor-banked samples at baseline and at time of diagnosis of a thyroid irAE. In euthyroid patients (without thyroid irAEs) measures were repeated 30 to 60 days after ICI commencement, which was similar to the median time to onset of thyroid irAEs in other patients. Results A total of 122 patients were included—31 remained euthyroid, 47 developed subclinical thyrotoxicosis, 37 developed overt thyrotoxicosis, and 7 developed overt hypothyroidism without preceding thyrotoxicosis. Baseline elevation of TPOAb or TgAb was present in 19 (16%) and 28 (23%) patients, respectively. Positive TPOAb or TgAb at baseline was 97% and 100% specific for eventual development of a thyroid irAE, respectively. During ICI treatment, overt thyrotoxicosis, but not other subtypes of thyroid irAE, was associated with statistically significant increases in the titer of TgAb and TPOAb. Baseline IL-6 levels were not associated with thyroid irAE onset but statistically significantly increased during treatment in patients who developed overt hypothyroidism. Conclusions TPOAb and TgAb positivity at baseline was more prevalent in patients who developed thyroid irAEs. Statistically significant increases or new antibody positivity was observed in association with overt thyrotoxicosis. TPOAb and TgAb positivity or increases during ICI treatment may be a useful biomarker to identify patients at increased risk of thyroid irAEs, particularly overt thyrotoxicosis.

Purpose Perioperative outcomes following cleft orthognathic surgery are not well established. The purpose of this study was to compare the incidence of orthognathic specific complications (OSCs) in patients with and without cleft lip and/or palate. Methods The American College of Surgeons National Surgical Quality Improvement Program adult and pediatric databases were used to enroll patients undergoing orthognathic surgery. The primary predictor variable was a prior diagnosis of cleft lip and/or palate: cleft versus noncleft. The primary outcome variable was OSCs (yes/no) within 30 days of the index operation. Descriptive, bivariate, and multiple logistic regression statistics were computed to measure the association between cleft status and OSCs. Results The study sample was composed of 1,149 subjects: 98 in the cleft group and 1,051 in the noncleft group. The incidence of OSCs was 6.1 and 4.7% for the cleft and noncleft groups, respectively (P = .461). After adjusting for age, cleft status, bone grafting, segmentation of the maxilla, and history of bleeding disorder, classification as American Society of Anesthesiologists (ASA) III (P = .002, odds ratio [OR] = 3.92, 95% confidence interval [CI] 1.63-9.40), ASA IV (P = .039, OR = 9.47, 95% CI 1.12-80.4), and isolated mandibular osteotomies (P = .006, OR = 3.23, 95% CI 1.40-7.48) were independent predictors of OSCs. Length of stay was 1.66 ± 1.14 days compared to 1.37 ± 3.74 days for the cleft and noncleft groups, respectively (P = .443). Conclusions There was no significant difference in the incidence of perioperative OSCs and length of hospital stay between cleft and noncleft patients. Cleft status was not an independent predictor of OSCs; instead, greater ASA classification and isolated mandibular osteotomies were the only predisposing factors. Patients with clefts undergoing orthognathic surgery do not have an increased risk of short term OSCs within the limitations of this study.

OBJECTIVE: Describe early hearing preservation (HP) cochlear implantation (CI) outcomes using a new slim lateral wall electrode (SLWE). STUDY DESIGN: Prospective cohort study. SETTING: Tertiary referral center. PATIENTS: Adult CI candidates with preoperative low-frequency pure tone average (LFPTA; 125, 250, 500Hz) ≤60 dB HL INTERVENTION(S): CI with and without intracochlear real-time electrocochleography (RT-ECochG) MAIN OUTCOME MEASURE(S): HP (LFPTA ≤80dB HL), LFPTA shift, speech-perception performance measures, postoperative CT reconstruction RESULTS: Forty-two subjects were implanted with the SLWE. Thirty patients underwent full insertion without RT-ECochG feedback, and HP was maintained at 3-months postactivation for 7 (23.3%) patients with mean LFPTA shift of 57.5 ± 25.6 dB HL. RT-ECochG feedback was utilized on 12 patients, of which 6 patients had full insertions and 6 patients had anywhere from 1–3 electrodes left outside of the cochlea based on RT-ECochG feedback. At 3-months postoperatively, HP was achieved on 10 (83.3%) patients and mean LFPTA shift was 18.9 c 11.7 dB HL. Mean difference between LFPTA threshold shift at 3-months postactivation with and without RT-ECochG was 38.6 dB HL (95% CI, 25.6 – 51.67). There was an improvement in delta CNC from preoperative to 3-months postactivation when using RT-ECochG, with mean difference 20.7% (95% CI, 3.3 to 38.1). CONCLUSIONS: Use of RT-ECochG monitoring during SLWE placement results in fewer full electrode insertions and significantly better HP rates and speech-perception outcomes when compared to unmonitored insertions. Further investigation is needed to evaluate long-term audiologic outcomes to better understand the relationships among ECochG, cochlear trauma, functional outcomes, and HP.

Shows the biodistribution data for [18F]αvβ6-BP in mice bearing paired αvβ6-expressing DX3puroβ6 and non-αvβ6-expressing DX3puro xenograft tumors at 1, 2 and 4 h p.i. and at 1 h p.i. after pre-administration of blocking peptide. Tissue uptake is expressed as decay-corrected percent injected dose per gram of tissue (dc % ID/g)

Purpose:The study was undertaken to develop and evaluate the potential of an integrin αvβ6-binding peptide (αvβ6-BP) for noninvasive imaging of a diverse range of malignancies with PET.Experimental Design:The peptide αvβ6-BP was prepared on solid phase and radiolabeled with 4-[18F]fluorobenzoic acid. In vitro testing included ELISA, serum stability, and cell binding studies using paired αvβ6-expressing and αvβ6-null cell lines. In vivo evaluation (PET/CT, biodistribution, and autoradiography) was performed in a mouse model bearing the same paired αvβ6-expressing and αvβ6-null cell xenografts. A first-in-human PET/CT imaging study was performed in patients with metastatic lung, colon, breast, or pancreatic cancer.Results:[18F]αvβ6-BP displayed excellent affinity and selectivity for the integrin αvβ6 in vitro [IC50(αvβ6) = 1.2 nmol/L vs IC50(αvβ3) >10 μmol/L] in addition to rapid target-specific cell binding and internalization (72.5% ± 0.9% binding and 52.5% ± 1.8%, respectively). Favorable tumor affinity and selectivity were retained in the mouse model and excretion of unbound [18F]αvβ6-BP was rapid, primarily via the kidneys. In patients, [18F]αvβ6-BP was well tolerated without noticeable adverse side effects. PET images showed significant uptake of [18F]αvβ6-BP in both the primary lesion and metastases, including metastasis to brain, bone, liver, and lung.Conclusions:The clinical impact of [18F]αvβ6-BP PET imaging demonstrated in this first-in-human study is immediate for a broad spectrum of malignancies.

Shows the maximum standard uptake values (SUVmax) for primary and metastatic lesions observed in the three subjects, decay corrected to the time of injection.

Shows the in vivo stability of [18F]αvβ6-BP in human blood. Representative radio-HPLC of blood sample taken 30 min post injection. Top: Sample only; bottom: sample spiked with [18F]αvβ6-BP. X-axis: retention time [min]; Y-axis: detector response [volts].

Describes additional methods

Shows the quality assurance release criteria for [18F]αvβ6-BP

Shows the maximum standard uptake values (SUVmax) at the 1 and 3 hour time points for the five subjects, decay corrected to the time of injection.

Shows a representative time-activity curves of [18F]αvβ6-BP for whole blood and plasma. Data are expressed as decay-corrected percent of injected dose per gram of sample [dc %ID/g].