Comparison of recovery of sheep, goats, and calves from reversible electrical head-only and head-to-body stunning for halal meat production.

AIMS: To compare the recovery of lambs, goats, and calves from head-only (HO) or high-frequency head-to-body stunning and evaluate the complementary use of behaviour and electroencephalography (EEG) to assess return to consciousness after electrical stunning in these species. METHODS: Six-month-old lambs, adult goats and calves (< 7 days old) were subjected to reversible head-only stunning (50 Hz, 1 A, 2 seconds) or reversible high-frequency head-to-body stunning (RHTB: HO followed by 2,000 Hz, 2 A, 4-second stun to body). Following stunning, behavioural recovery was assessed in 21 lambs, 22 goats, and 20 calves. Latencies to first perform behaviours (end of convulsions, head lift, attempt to right, successful righting, attempt to stand, successful standing) after stunning were scored from video recordings. Recovery of electrical brain activity indicative of consciousness was assessed using EEG in a separate cohort of minimally-anaesthetised lambs, goats and calves (n = 20 per species). EEG traces collected before and after stunning were classified as normal, epileptiform, isoelectric, or transitional activity. Following stunning, the duration of epileptiform and isoelectric activity combined (states of brain activity incompatible with conscious awareness) was calculated, as was latency to return of normal (pre-stun) EEG. RESULTS: The RHTB stun was reversible in all three species, although one sheep failed to recover and was euthanised. Both methods caused tonic and clonic convulsions in all species. Behavioural recovery of sheep and calves was similar for both methods while goats took longer to recover from RHTB than HO stunning. There was no evidence of differences between methods in the duration of EEG incompatible with consciousness or the latency to recovery of normal EEG. CONCLUSIONS: Head-to-body stunning as applied here produced a reversible electrical stun in lambs, adult goats and young calves, although the benefits in terms of meat quality and operator safety are uncertain. Goats took longer to recover behaviourally from head-to-body stunning, possibly due to disrupted motor function, but there was no indication that post-stun unconsciousness lasted longer than following head-only stunning in any species. The normal behaviour for the animals' developmental age should be considered when deciding on behavioural indicators of recovery. The minimal anaesthesia model provided excellent quality EEG data that was valuable for interpretation of the behavioural responses. CLINICAL RELEVANCE: For the purposes of pre-slaughter stunning of sheep, goats and young calves, recovery appears comparable between the two methods, with all but 1/63 animals in the behaviour study recovering normal function.

Eye care following pre-school vision screening: Data from the Growing Up in New Zealand study.

AIM: This study aimed to determine adherence with follow-up from the New Zealand pre-school vision screening programme. The study also examined associations between pre-school vision screening outcomes and cognitive measures assessed at the 54-month follow-up in the Growing Up in New Zealand study cohort. METHODS: A cross-sectional retrospective record review of pre-school vision screening outcomes and hospital ophthalmology records with linkage to Growing Up in New Zealand cohort study data. RESULTS: Of 176 children referred from vision screening, 21.6% did not attend a referral appointment. Of 138 children who attended a referral appointment, 21.0% did not attend one or more follow-up appointments. Ethnic differences were observed in attendance at referral appointments (attended Maori 13%, Pacific 22.5%, European/Other 64.5%; not attended Maori 26.3%, Pacific 28.9%, European/Other 44.7%; P = 0.04) and follow-up appointments (attended Maori 11.9%, Pacific 15.6%, European/Other 72.5%; not attended Maori 17.2%, Pacific 48.3%, European/Other 34.5%; P = 0.001). Vision screening outcome was significantly associated with letter naming fluency scores (P = 0.01) but not name and numbers scores (P = 0.05). CONCLUSIONS: Non-attendance at referral and follow-up appointments limits the efficacy of vision screening, particularly for children of Maori and Pacific ethnicity. Children referred from vision screening achieve lower scores on letter naming fluency, a key predictor of reading ability in later childhood. Equity-based improvements are required to ensure that all children referred from vision screening receive appropriate follow-up eye care.

Comparison of Patterns and Demographics of Isolated Traumatic Mandibular Fracture Between Incarcerated and General Populations.

Introduction The management of maxillofacial trauma can be challenging in different unique clinical presentations. While maxillofacial fractures vary in location based on the mechanism of injury, the mandibular fracture is noted to be one of the most common facial fractures. The objective of this study was to explore the differences in injury patterns, outcomes, and demographics of isolated traumatic mandibular fractures between incarcerated and general populations. Methods This retrospective study analyzed consecutive patients presenting for trauma care from January 1, 2010, to December 31, 2020, at the Arrowhead Regional Medical Center (ARMC). Patients 18 years and older were included in this study. Patients diagnosed with mandibular fracture as the primary diagnosis at admission and discharge were identified using the International Classification of Disease, Ninth and Tenth Revision (ICD-9, ICD-10) Code. Patient demographics were extracted from their electronic medical records and included race, marital status, and insurance status. Results A total of 1080 patients with confirmed mandibular fractures were included in the final analysis. Among these patients, 87.5% (n=945) were males, 40% (n=432) of the patients were Hispanic, and the average age was 31.55 years old. The most common mechanism of injury was blunt trauma secondary to assault. Compared to the general population with mandibular fracture, the incarcerated patients with mandibular fracture were more likely to be males (96.1% vs 86.1% for incarcerated population vs. general population respectively, p=0.0005). No other variables were statistically different between these two groups. Conclusion The evidence from this study suggests that the patterns, outcomes, and demographics of mandibular fracture in both incarcerated and general populations are similar.

Characterization of the zebrafish gabra1sa43718/sa43718 germline loss of function allele confirms a function for Gabra1 in motility and nervous system development.

Mutation of the GABRA1 gene is associated with neurodevelopmental defects and epilepsy. GABRA1 encodes for the α1 subunit of the γ-aminobutyric acid type A receptor (GABAAR), which regulates the fast inhibitory impulses of the nervous system. Multiple model systems have been developed to understand the function of GABRA1, but these models have produced complex and, at times, incongruent data. Thus, additional model systems are required to validate and substantiate previous results. We sought to provide initial phenotypic analysis of a novel germline mutant allele. Our analysis provides a solid foundation for the future use of this allele to characterize gabra1 functionally and pharmacologically using zebrafish. We investigated the behavioral swim patterns associated with a nonsense mutation of the zebrafish gabra1 (sa43718 allele) gene. The sa43718 allele causes a decrease in gabra1 mRNA expression, which is associated with light induced hypermotility, one phenotype previously associated with seizure like behavior in zebrafish. Mutation of gabra1 was accompanied by decreased mRNA expression of gabra2, gabra3, and gabra5, indicating a reduction in the expression of additional α sub-units of the GABAAR. Although multiple sub-units were decreased, larvae continued to respond to pentylenetetrazole (PTZ), indicating that a residual GABAAR exists in the sa43718 allele. Proteomics analysis demonstrated that mutation of gabra1 is associated with abnormal expression of proteins that regulate synaptic vesicle fusion, vesicle transport, synapse development, and mitochondrial protein complexes. These data support previous studies performed in a zebrafish nonsense allele created by CRISPR/Cas9 and validate that loss of function mutations in the gabra1 gene result in seizure-like phenotypes with abnormal development of the GABA synapse. Our results add to the existing body of knowledge as to the function of GABRA1 during development and validate that zebrafish can be used to provide complete functional characterization of the gene.

Optimization of an anatomically and electrically detailed rodent subthalamic nucleus neuron model.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for Parkinson's disease, but its mechanisms of action remain unclear. Detailed multicompartment computational models of STN neurons are often used to study how DBS electric fields modulate the neurons. However, currently available STN neuron models have some limitations in their biophysical realism. In turn, the goal of this study was to update a detailed rodent STN neuron model originally developed by Gillies and Willshaw in 2006. Our design requirements consisted of explicitly representing an axon connected to the neuron and updating the ion channel distributions based on the experimental literature to match established electrophysiological features of rodent STN neurons. We found that adding an axon to the STN neuron model substantially altered its firing characteristics. We then used a genetic algorithm to optimize biophysical parameters of the model. The updated model exhibited spontaneous firing, action potential shape, hyperpolarization response, and frequency-current curve that aligned well with experimental recordings from STN neurons. Subsequently, we evaluated the general compatibility of the updated biophysics by applying them to 26 different STN neuron morphologies derived from three-dimensional anatomical reconstructions. The different morphologies affected the firing behavior of the model, but the updated biophysics were robustly capable of maintaining the desired electrophysiological features. The new STN neuron model developed in this work offers a valuable tool for studying STN neuron firing properties and may find application in simulating STN local field potentials and analyzing the effects of STN DBS.NEW & NOTEWORTHY This study presents an anatomically and biophysically realistic rodent STN neuron model. The work showcases the use of a genetic algorithm to optimize the model parameters. We noted a substantial influence of the axon on the electrophysiological characteristics of STN neurons. The updated model offers a valuable tool to investigate the firing of STN neurons and their modulation by intrinsic and/or extrinsic factors.

Neural pathway activation in the subthalamic region depends on stimulation polarity.

Deep brain stimulation (DBS) is an effective treatment for Parkinson's disease (PD); however, there is limited understanding of which subthalamic pathways are recruited in response to stimulation. Here, by focusing on the polarity of the stimulus waveform (cathodic vs. anodic), our goal was to elucidate biophysical mechanisms that underlie electrical stimulation in the human brain. In clinical studies, cathodic stimulation more easily triggers behavioral responses, but anodic DBS broadens the therapeutic window. This suggests that neural pathways involved respond preferentially depending on stimulus polarity. To experimentally compare the activation of therapeutically relevant pathways during cathodic and anodic subthalamic nucleus (STN) DBS, pathway activation was quantified by measuring evoked potentials resulting from antidromic or orthodromic activation in 15 PD patients undergoing DBS implantation. Cortical evoked potentials (cEP) were recorded using subdural electrocorticography, DBS local evoked potentials (DLEP) were recorded from non-stimulating contacts and EMG activity was recorded from arm and face muscles. We measured: 1) the amplitude of short-latency cEP, previously demonstrated to reflect activation of the cortico-STN hyperdirect pathway, 2) DLEP amplitude thought to reflect activation of STN-globus pallidus (GP) pathway, and 3) amplitudes of very short-latency cEP and motor evoked potentials (mEP) for activation of cortico-spinal/bulbar tract (CSBT). We constructed recruitment and strength-duration curves for each EP/pathway to compare the excitability for different stimulation polarities. We compared experimental data with the most advanced DBS computational models. Our results provide experimental evidence that subcortical cathodic and anodic stimulation activate the same pathways in the STN region and that cathodic stimulation is in general more efficient. However, relative efficiency varies for different pathways so that anodic stimulation is the least efficient in activating CSBT, more efficient in activating the HDP and as efficient as cathodic in activating STN-GP pathway. Our experiments confirm biophysical model predictions regarding neural activations in the central nervous system and provide evidence that stimulus polarity has differential effects on passing axons, terminal synapses, and local neurons. Comparison of experimental results with clinical DBS studies provides further evidence that the hyperdirect pathway may be involved in the therapeutic mechanisms of DBS.

Circulating Blood Prognostic Biomarker Signatures for Hemorrhagic Cerebral Cavernous Malformations (CCMs).

Cerebral cavernous malformations (CCMs) are a neurological disorder characterized by enlarged intracranial capillaries in the brain, increasing the susceptibility to hemorrhagic strokes, a major cause of death and disability worldwide. The limited treatment options for CCMs underscore the importance of prognostic biomarkers to predict the likelihood of hemorrhagic events, aiding in treatment decisions and identifying potential pharmacological targets. This study aimed to identify blood biomarkers capable of diagnosing and predicting the risk of hemorrhage in CCM1 patients, establishing an initial set of circulating biomarker signatures. By analyzing proteomic profiles from both human and mouse CCM models and conducting pathway enrichment analyses, we compared groups to identify potential blood biomarkers with statistical significance. Specific candidate biomarkers primarily associated with metabolism and blood clotting pathways were identified. These biomarkers show promise as prognostic indicators for CCM1 deficiency and the risk of hemorrhagic stroke, strongly correlating with the likelihood of hemorrhagic cerebral cavernous malformations (CCMs). This lays the groundwork for further investigation into blood biomarkers to assess the risk of hemorrhagic CCMs.

Developing culturally relevant leadership educators.

This article demonstrates how educators can create opportunities for students to learn about leadership in a variety of circumstances. Through the integrated model for contextualizing leadership learning, educators can center culturally relevant leadership while considering the environment where leadership learning is provided as well as the context in which the identity, capacity, and effectiveness of leadership educators are developed. The implications of this integrated approach emerged from 26 narratives and are explored through three themes centered on co-curricular program development and implementation, as well as personal and professional development. These themes include examining organizations' histories and structures, the developmental readiness of educators and students, and the significance of context.

Unicorn paradox: Understanding undergraduate Black men's leader identity, capacity, and efficacy.

This study highlights opportunities for developing programs and initiatives to assist Black men in understanding leadership and seeing themselves as leaders, and for decreasing low college retention and persistence rates. The themes from this qualitative narrative inquiry highlight leader identity, capacity, and efficacy for undergraduate Black men. Narrative inquiry was appropriate for this study because the researchers sought to better understand how Black undergraduate male student leaders make meaning of their experience in higher education related to their comprehension of leadership and identity as leaders.

Ixekizumab Demonstrates Rapid and Consistent Efficacy for Patients with Psoriatic Arthritis, Regardless of Psoriasis Severity.

INTRODUCTION: Skin involvement in patients with psoriatic arthritis (PsA) worsens the severity and burden of disease. Ixekizumab (IXE), a selective interleukin (IL)-17A antagonist, was compared to placebo (PBO) in the SPIRIT-P1 (NCT01695239) and SPIRIT-P2 (NCT02349295) studies in patients with PsA and evidence of plaque psoriasis. This post hoc analysis reports musculoskeletal, skin, and nail outcomes through week 24 in patients from SPIRIT-P1 and SPIRIT-P2, stratified by mild, moderate, or psoriasis at baseline. METHODS: This post hoc analysis pooled patients from SPIRIT-P1 and SPIRIT-P2 who were randomly assigned to PBO or IXE 80 mg every 4 weeks (Q4W) or every 2 weeks (Q2W). Efficacy outcomes were analyzed through week 24 by baseline psoriasis severity, defined by percent body surface area (BSA) affected; mild = BSA < 3%, moderate = 3% ≤ BSA ≤ 10%, severe = BSA > 10%. The primary outcomes assessed were the proportion of patients achieving American College of Rheumatology (ACR)20, ACR50, and ACR70 responses. Secondary outcomes included musculoskeletal, disease activity, skin and nail, and health-related quality-of-life measures. RESULTS: Similar proportions of patients achieved ACR20/ACR50/ACR70 over time across all severity subgroups and treatment arms. More than one-third of IXE-treated patients achieved ACR20 at week 4, or ACR50 at week 24, with no significant differences according to psoriasis severity at baseline. Disease activity outcomes were similar through week 24 with both IXEQ4W and IXEQ2W, regardless of psoriasis severity at baseline. There were no significant differences over 24 weeks in the proportions of IXE-treated patients with mild, moderate, or severe baseline psoriasis who achieved Minimal Disease Activity (MDA). Across all severity subgroups, IXE demonstrated Psoriasis Area Severity Index 100 response as early as week 4, and approximately one-third of IXE-treated patients achieved total skin clearance at week 24. CONCLUSION: IXE demonstrated rapid and consistent efficacy in joint, skin, and nail for patients with PsA, regardless of baseline psoriasis severity. TRIAL REGISTRATION: SPIRIT-P1 (NCT01695239), SPIRIT-P2 (NCT02349295).

Associations Between Neighborhood Resources and Youths' Response to Reward Omission in a Task Modeling Negatively Biased Environments.

OBJECTIVE: Neighborhoods provide essential resources (eg, education, safe housing, green space) that influence neurodevelopment and mental health. However, we need a clearer understanding of the mechanisms mediating these relationships. Limited access to neighborhood resources may hinder youths from achieving their goals and, over time, shape their behavioral and neurobiological response to negatively biased environments blocking goals and rewards. METHOD: To test this hypothesis, 211 youths (aged ∼13.0 years, 48% boys, 62% identifying as White, 75% with a psychiatric disorder diagnosis) performed a task during functional magnetic resonance imaging. Initially, rewards depended on performance (unbiased condition); but later, rewards were randomly withheld under the pretense that youths did not perform adequately (negatively biased condition), a manipulation that elicits frustration, sadness, and a broad response in neural networks. We investigated associations between the Childhood Opportunity Index (COI), which quantifies access to youth-relevant neighborhood features in 1 metric, and the multimodal response to the negatively biased condition, controlling for age, sex, medication, and psychopathology. RESULTS: Youths from less-resourced neighborhoods responded with less anger (p < .001, marginal R2 = 0.42) and more sadness (p < .001, marginal R2 = 0.46) to the negatively biased condition than youths from well-resourced neighborhoods. On the neurobiological level, lower COI scores were associated with a more localized processing mode (p = .039, marginal R2 = 0.076), reduced connectivity between the somatic-motor-salience and the control network (p = .041, marginal R2 = 0.040), and fewer provincial hubs in the somatic-motor-salience, control, and default mode networks (all pFWE < .05). CONCLUSION: The present study adds to a growing literature documenting how inequity may affect the brain and emotions in youths. Future work should test whether findings generalize to more diverse samples and should explore effects on neurodevelopmental trajectories and emerging mood disorders during adolescence. DIVERSITY & INCLUSION STATEMENT: One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented sexual and/or gender groups in science. One or more of the authors of this paper received support from a program designed to increase minority representation in science. We actively worked to promote sex and gender balance in our author group. We actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our author group.

Development and validation of a reliable DNA copy-number-based machine learning algorithm (CopyClust) for breast cancer integrative cluster classification.

The Integrative Cluster subtypes (IntClusts) provide a framework for the classification of breast cancer tumors into 10 distinct groups based on copy number and gene expression, each with unique biological drivers of disease and clinical prognoses. Gene expression data is often lacking, and accurate classification of samples into IntClusts with copy number data alone is essential. Current classification methods achieve low accuracy when gene expression data are absent, warranting the development of new approaches to IntClust classification. Copy number data from 1980 breast cancer samples from METABRIC was used to train multiclass XGBoost machine learning algorithms (CopyClust). A piecewise constant fit was applied to the average copy number profile of each IntClust and unique breakpoints across the 10 profiles were identified and converted into ~ 500 genomic regions used as features for CopyClust. These models consisted of two approaches: a 10-class model with the final IntClust label predicted by a single multiclass model and a 6-class model with binary reclassification in which four pairs of IntClusts were combined for initial multiclass classification. Performance was validated on the TCGA dataset, with copy number data generated from both SNP arrays and WES platforms. CopyClust achieved 81% and 79% overall accuracy with the TCGA SNP and WES datasets, respectively, a nine-percentage point or greater improvement in overall IntClust subtype classification accuracy. CopyClust achieves a significant improvement over current methods in classification accuracy of IntClust subtypes for samples without available gene expression data and is an easily implementable algorithm for IntClust classification of breast cancer samples with copy number data.

Neurodevelopmental Outcomes Following Childhood Viral Meningitis in Canterbury New Zealand.

BACKGROUND: Most childhood meningitis is viral in countries with widespread conjugate vaccine use. This study assessed clinical features and neurodevelopmental outcomes in preschool children following enteroviral and parechoviral meningitis. METHODS: Children 18-42 months of age in Canterbury, New Zealand were included, who had enterovirus (EV) or parechovirus (HPEV) meningitis from 2015 to 2021. Comprehensive neurodevelopmental assessments were completed by a psychologist using the Bayley Scale for Infant Development-3 (BSID-3). Mean composite and scaled scores and proportion below the cutoff were assessed in each domain. Clinical data was analyzed. RESULTS: There were 79 children 18-42 months old with previous EV or HPEV meningitis. BSID assessments were completed for 33 children (55% male), median age 32 months, from 2019 to 2022 including 23 with EV and 10 HPEV meningitis. At diagnosis, 32 (97%) received intravenous/intramuscular antibiotics, and 6 received a fluid bolus. Parents reported developmental speech concerns in 6 children, and delayed motor milestones in 1 child. There was no reported sensorineural hearing loss. BSID mean composite scores were in the expected range for cognition 102 (confidence interval: 98-106), language 96 (93-100) and motor 102 (98-106) domains. Overall, 12/33 (36%) children had below expected scores in 1 developmental domain, including scores 1-2 SD below the normative mean for cognition (2/33; 6%), receptive language (6/33; 18%), expressive language (5/33; 15%) and gross motor (6/33; 18%). There were no differences between scores in EV and HPEV meningitis. CONCLUSION: Following viral meningitis, more than a third of preschool children had a mild developmental delay with comprehensive neurodevelopmental assessment, suggesting targeted follow-up should be considered.

Small-Angle X-ray Scattering Study of the Amphiphilic Bulk Nanostructure of Tetraalkylammonium Deep Eutectic Solvents.

Deep eutectic solvents (DESs) are low-melting mixtures, often prepared from a salt and a molecular hydrogen bond donor. Like ionic liquids, DESs that contain at least one sufficiently amphiphilic component can form bicontinuous nanostructures consisting of polar and nonpolar domains, although this has not been widely explored for many DES combinations. Here, the bulk nanostructures of DESs comprising tetraalkylammonium bromide salts (tetrabutylammonium bromide, tetraoctylammonium bromide, and methyltrioctylammonium bromide) with alkanols and alkanoic acids of systematically varied chain lengths (C2, C6, C8, and C10) as hydrogen bond donors have been studied. Small-angle X-ray scattering techniques were used to identify the relationship between the alkyl chain length and functionality of the hydrogen bond donor on the nature of the amphiphilic nanostructures formed. These findings demonstrated that the amphiphilic nanostructures of the DESs were not affected by the functional group on the hydrogen bond donor, with these nanostructures influenced primarily by both the absolute and relative alkyl chain lengths of the salt and hydrogen bond donor.

Dissecting deep brain stimulation evoked neural activity in the basal ganglia.

Deep brain stimulation (DBS) is an established therapeutic tool for the treatment of Parkinson's disease (PD). The mechanisms of DBS for PD are likely rooted in modulation of the subthalamo-pallidal network. However, it can be difficult to electrophysiologically interrogate that network in human patients. The recent identification of large amplitude evoked potential (EP) oscillations from DBS in the subthalamic nucleus (STN) or globus pallidus internus (GPi) are providing new scientific opportunities to expand understanding of human basal ganglia network activity. In turn, the goal of this review is to provide a summary of DBS-induced EPs in the basal ganglia and attempt to explain various components of the EP waveforms from their likely network origins. Our analyses suggest that DBS-induced antidromic activation of globus pallidus externus (GPe) is a key driver of these oscillatory EPs, independent of stimulation location (i.e. STN or GPi). This suggests a potentially more important role for GPe in the mechanisms of DBS for PD than typically assumed. And from a practical perspective, DBS EPs are poised to become clinically useful electrophysiological biomarker signals for verification of DBS target engagement.

Trends in ototoxicity monitoring among cisplatin-treated patients with cancer.

PURPOSE: This study aims to characterize patterns in ototoxicity monitoring and identify potential barriers to audiologic follow-up. METHODS: We performed a single-institution retrospective cohort study on adult (≥ 18 years old) cancer patients treated with cisplatin from January 2014 to September 2021. Our primary outcomes were rates of baseline and post-treatment audiograms at the following time points: 3, 6, 12, and greater than 12 months. Time-to-event analyses were performed to describe additional insights to ototoxicity monitoring patterns. RESULTS: Nine hundred fifty-five patients with cancer were included for analysis. The most common primary cancer sites were head and neck (64%), followed by cervical (24%). Three hundred seventy-three patients (39%) underwent baseline audiometric assessment, 38 patients (4%) received audiologic evaluation during chemotherapy, and 346 patients (36%) obtained at least one post-treatment audiogram. Audiologic follow-up was greatest within 3 months of completing chemotherapy (26%), but this tapered dramatically to less than 10% at every other post-treatment time point. Patients with head and neck cancer achieved higher rates of audiologic follow-up at every time point than patients with non-head and neck cancer except for during treatment. CONCLUSIONS: Ototoxicity monitoring is an inconsistent practice, particularly during chemotherapy and for long-term surveillance of hearing loss. Patients with non-head and neck cancer may be at increased risk for loss of audiologic follow-up. IMPLICATIONS FOR CANCER SURVIVORS: Cisplatin ototoxicity is a common occurrence that can be effectively managed with auditory rehabilitation. Therefore, referrals to audiology and counseling on treatment-related ototoxicity are recommended throughout chemotherapy and cancer survivorship.

Modeling Shared and Specific Variances of Irritability, Inattention, and Hyperactivity Yields Novel Insights Into White Matter Perturbations.

OBJECTIVE: Irritability, inattention, and hyperactivity, which are common presentations of childhood psychopathology, have been associated with perturbed white matter microstructure. However, similar tracts have been implicated across these phenotypes; such non-specificity could be rooted in their high co-occurrence. To address this problem, we use a bifactor approach parsing unique and shared components of irritability, inattention, and hyperactivity, which we then relate to white matter microstructure. METHOD: We developed a bifactor model based on the Conners Comprehensive Behavioral Rating Scale in a sample of youth with no psychiatric diagnosis or a primary diagnosis of attention-deficit/hyperactivity disorder or disruptive mood dysregulation disorder (n = 521). We applied the model to an independent yet sociodemographically and clinically comparable sample (n = 152), in which we tested associations between latent variables and fractional anisotropy (FA). RESULTS: The bifactor model fit well (comparative fit index = 0.99; root mean square error of approximation = 0.07). The shared factor was positively associated with an independent measure of impulsivity (ρS = 0.88, pFDR < .001) and negatively related to whole-brain FA (r = -0.20), as well as FA of the corticospinal tract (all pFWE < .05). FA increased with age and deviation from this curve, indicating that altered white matter maturation was associated with the hyperactivity-specific factor (r = -0.16, pFWE < .05). Inattention-specific and irritability-specific factors were not linked to FA. CONCLUSION: Perturbed white matter microstructure may represent a shared neurobiological mechanism of irritability, inattention, and hyperactivity related to heightened impulsivity. Furthermore, hyperactivity might be uniquely associated with a delay in white matter maturation.

Individual Patient Comorbidities and Effect on Cochlear Implant Performance.

OBJECTIVE: To examine the association between preoperative comorbidities and cochlear implant speech outcomes. STUDY DESIGN: Retrospective cohort. SETTING: Tertiary referral center. PATIENTS: A total of 976 patients who underwent cochlear implantation (CI) between January 2015 and May 2022. Adult patients with follow-up, preoperative audiologic data, and a standardized anesthesia preoperative note were included. EXPOSURE: Adult Comorbidity Evaluation 27 (ACE-27) based on standardized anesthesia preoperative notes. MAIN OUTCOME MEASURES: Postoperative change in consonant-nucleus-consonant (CNC) score, AzBio Sentence score in quiet, and AzBio + 10 dB signal-to-noise ratio (SNR). Sentence score of the implanted ear at 3, 6, and 12 months. RESULTS: A total of 560 patients met inclusion criteria; 112 patients (20%) had no comorbidity, 204 patients (36.4%) had mild comorbidities, 161 patients (28.8%) had moderate comorbidities, and 83 patients (14.8%) had severe comorbidities. Mixed model analysis revealed all comorbidity groups achieved a clinically meaningful improvement in all speech outcome measures over time. This improvement was significantly different between comorbidity groups over time for AzBio Quiet ( p = 0.045) and AzBio + 10 dB SNR ( p = 0.0096). Patients with severe comorbidities had worse outcomes. From preop to 12 months, the estimated marginal mean difference values (95% confidence interval) between the no comorbidity group and the severe comorbidity group were 52.3 (45.7-58.9) and 32.5 (24.6-40.5), respectively, for AzBio Quiet; 39.5 (33.8-45.2) and 21.2 (13.6-28.7), respectively, for AzBio + 10 dB SNR; and 43.9 (38.7-49.0) and 31.1 (24.8-37.4), respectively, for CNC. CONCLUSIONS: Comorbidities as assessed by ACE-27 are associated with CI performance. Patients with more severe comorbidities have clinically meaningful improvement but have worse outcome compared to patients with no comorbidities.