Safety and Utility of Hybrid Depth Electrodes for Seizure Localization and Single-Unit Neuronal Recording

Background: Invasive electrode monitoring provides more precise localization of epileptogenic foci in patients with medically refractory epilepsy. The use of hybrid depth electrodes that include microwires for simultaneous single-neuron monitoring is becoming more widespread. Objective: To determine the safety and utility of hybrid depth electrodes for intracranial monitoring of medically refractory epilepsy. Methods: We reviewed the medical charts of 53 cases of medically refractory epilepsy operated on from 2006 to 2017, where both non-hybrid and hybrid microwire depth electrodes were used for intracranial monitoring. We assessed the localization accuracy and complications that arose to assess the relative safety and utility of hybrid depth electrodes compared with standard electrodes. Results: A total of 555 electrodes were implanted in 52 patients. The overall per-electrode complication rate was 2.3%, with a per-case complication rate of 20.8%. There were no infections or deaths. Serious or hemorrhagic complications occurred in 2 patients (0.4% per-electrode risk). Complications did not correlate with the use of any particular electrode type, and hybrids were equally as reliable as standard electrodes in localizing seizure onset zones. Conclusions: Hybrid depth electrodes appear to be as safe and effective as standard depth electrodes for intracranial monitoring and provide unique opportunities to study the human brain at single-neuron resolution

High-throughput functional analysis of autism genes in zebrafish identifies convergence in dopaminergic and neuroimmune pathways

Advancing from gene discovery in autism spectrum disorders (ASDs) to the identification of biologically relevant mechanisms remains a central challenge. Here, we perform parallel in vivo functional analysis of 10 ASD genes at the behavioral, structural, and circuit levels in zebrafish mutants, revealing both unique and overlapping effects of gene loss of function. Whole-brain mapping identifies the forebrain and cerebellum as the most significant contributors to brain size differences, while regions involved in sensory-motor control, particularly dopaminergic regions, are associated with altered baseline brain activity. Finally, we show a global increase in microglia resulting from ASD gene loss of function in select mutants, implicating neuroimmune dysfunction as a key pathway relevant to ASD biology

Topoisomerase II alpha gene copy loss has adverse prognostic significance in ERBB2-amplified breast cancer: a retrospective study of paraffin-embedded tumor specimens and medical charts

<p>Abstract</p> <p>Background</p> <p>Amplification of the <it>ERBB2 </it>(<it>Her-2/neu</it>) oncogene, which occurs in approximately 25% of breast carcinomas, is a known negative prognostic factor. Available data indicate that a variable number of nearby genes on chromosome 17q may be co-amplified or deleted, forming a continuous amplicon of variable size. In approximately 25% of these patients, the amplicon extends to the gene for <it>topoisomerase II alpha </it>(<it>TOP2A</it>), a target for anthracyclines. We sought to understand the significance of these associated genomic changes for breast cancer prognosis and predicting response to therapy.</p> <p>Methods and patients</p> <p>Archival tissue samples from 63 breast cancer patients with <it>ERBB2 </it>amplification, stages 0–IV, were previously analyzed with FISH probes for genes located near <it>ERBB2</it>. In the present study, the clinical outcome data were determined for all patients presenting at stages I–III for whom adequate clinical follow up was available.</p> <p>Results</p> <p>Four amplicon patterns (Classes) were identified. These were significantly associated with the clinical outcome, specifically, recurrence of breast cancer. The Amplicon class IV with deleted <it>TOP2A </it>had 67% (6/9) cases with recurrence, whereas the other three classes combined had only 12% (3/25) cases (p-value = 0.004) at the time of last follow-up. <it>TOP2A </it>deletion was also significantly associated with time to recurrence (p-value = 0.0002). After adjusting for age in Cox regression analysis, the association between <it>TOP2A </it>deletion and time to recurrence remains strongly significant (p-value = 0.002) whereas the association with survival is marginally significant (p-value = 0.06).</p> <p>Conclusion</p> <p><it>TOP2A </it>deletion is associated with poor prognosis in <it>ERBB2</it>-amplified breast carcinomas. Clarification of the mechanism of this association will require additional study.</p

Risk of peri-intubation adverse events during emergency department intubation of overdose patients: a national emergency airway registry (near) analysis

More than 20,000 emergency department (ED) patients undergo intubation for overdose each year. While the characteristics of patients intubated for overdose and poisoning are well described, little is known about the intubation outcomes of overdose patients in the ED. We quantify the frequency of peri-intubation adverse events for patients intubated in the ED for overdose, and determine whether first attempt success without adverse events differs between patients intubated for overdose and patients intubated for other reasons. We analyzed data from the National Emergency Airway Registry (NEAR), a prospective multicenter registry of ED intubations collected from an international network of 22 academic and community hospitals. We included patients 14 years and older whose first attempt was oral intubation, with data entered into NEAR between 1 January 2016 and 31 December 2018. The primary outcome was successful intubation on the first attempt. We used multivariable logistic regression to determine whether indication was independently associated with successful intubation on the first attempt after adjusting for age, gender, obesity, initial impression of difficult airway, presence of difficult airway characteristics, and use of video laryngoscopy. Secondary outcomes included successful intubation on the first attempt without adverse events, the occurrence of rescue surgical airways, and the occurrence of adverse events. Adverse events included hypoxemia, hypotension, peri-intubation cardiac arrest, bradycardia, mechanical injury to oral or airway structures, vomiting, tachydysrhythmia, esophageal intubation, laryngospasm, and pneumothorax. We analyzed 17,984 patients, including 1,983 (11%) intubated for overdose, and 16,001 (89%) intubated for other indications. Patients intubated for overdose were younger (median age 38 vs 55 years), were less frequently obese (26% vs 34%), and fewer had difficult airway characteristics (38% vs 53%). Overdose patients were more likely to have preoxygenation performed (45% vs 35%), more likely to have apenic oxygenation (39% vs 31%), and more likely to have bougie used (33% vs 17%). First attempt success was 90.5% in patients intubated for overdose and 87.5% in patients intubated for other reasons (absolute difference 3.0%; 95% CI: −1.3 to 7.3). First attempt success without adverse events was higher in overdose patients (85.0%) compared to other patients (78.7%) (absolute difference, 6.3%; 95% CI 1.0 to 11.7%). Overdose patients experienced significantly less hypotension (1.5% vs 4.1%), and tended to have fewer adverse events overall. Multivariable model results were consistent with the unadjusted results including no difference in first pass success (adjusted odd ratio 1.02 [95% CI 0.86–1.23]). There was a higher first pass success without complication in patients intubated for overdose (adjusted odds ratio 1.23; 95% CI 1.07 to1.43). For patients in whom the primary indication for intubation is overdose there is an increased chance of first attempt success without adverse event.</p

Data from: Dataset of human medial temporal lobe single neuron activity during declarative memory encoding and recognition

We present a dataset of 1,576 single neurons recorded from the human amygdala and hippocampus in 65 sessions from 42 patients undergoing intracranial monitoring for localization of epileptic seizures. Subjects performed a recognition memory task with pictures as stimuli. Subjects were asked to identify whether they had seen a particular image the first time (‘new’) or second time (‘old’) on a 1–6 confidence scale. This comprehensive dataset includes the spike times of all neurons and their extracellular waveforms, behavior, electrode locations determined from post-operative MRI scans, demographics, and the stimuli shown. As technical validation, we provide spike sorting quality metrics and assessment of tuning of cells to verify the presence of visually-and memory selective cells. We also provide analysis code that reproduces key scientific findings published previously on a smaller version of this dataset. Together, this large dataset will facilitate the investigation of the neural mechanism of declarative memory by providing a substantial number of hard to obtain human single-neuron recordings during a well characterized behavioral task

Data from: Dataset of human medial temporal lobe single neuron activity during declarative memory encoding and recognition

We present a dataset of 1,576 single neurons recorded from the human amygdala and hippocampus in 65 sessions from 42 patients undergoing intracranial monitoring for localization of epileptic seizures. Subjects performed a recognition memory task with pictures as stimuli. Subjects were asked to identify whether they had seen a particular image the first time (‘new’) or second time (‘old’) on a 1–6 confidence scale. This comprehensive dataset includes the spike times of all neurons and their extracellular waveforms, behavior, electrode locations determined from post-operative MRI scans, demographics, and the stimuli shown. As technical validation, we provide spike sorting quality metrics and assessment of tuning of cells to verify the presence of visually-and memory selective cells. We also provide analysis code that reproduces key scientific findings published previously on a smaller version of this dataset. Together, this large dataset will facilitate the investigation of the neural mechanism of declarative memory by providing a substantial number of hard to obtain human single-neuron recordings during a well characterized behavioral task

Teacher pedagogical content knowledge, practice, and student achievement^†

<p>In this exploratory study, we attempted to measure potential changes in teacher knowledge and practice as a result of an intervention, as well as trace such changes through a theoretical path of influence that could inform a model of teacher professional knowledge. We created an instrument to measure pedagogical content knowledge (PCK), studied the impact of a two-year professional development intervention, explored the relationships among teacher variables to attempt to validate a model of teacher professional knowledge, and examined the relationship of teacher professional knowledge and classroom practice on student achievement. Teacher professional knowledge and skill was measured in terms of academic content knowledge (ACK), general pedagogical knowledge (GenPK), PCK and teacher practice. Our PCK instrument identified two factors within PCK: PCK-content knowledge and PCK-pedagogical knowledge. Teacher gains existed for all variables. Only GenPK had a significant relationship to teacher practice. ACK was the only variable that explained a substantial portion of student achievement. Our findings provide empirical evidence that we interpret through the lens of the model of teacher professional knowledge and skill, including PCK [Gess-Newsome, J. (2015). A model of teacher professional knowledge and skill including PCK: Results of the thinking from the PCK summit. In A. Berry, P. Friedrichsen, & J. Loughran (Eds.), <i>Re-examining pedagogical content knowledge in science education</i> (pp. 28–42). London: Routledge Press], highlighting the complexity of measuring teacher professional knowledge and skill.</p

Data, Code, Stimuli

This file contains a set of 1576 single neurons recorded from the human MTL during a recognition memory "new/old" task with confidence ratings. This data was acquired using hybrid depth electrodes from human epilepsy patients undergoing invasive monitoring for localizing seizures. All data is provided in *.mat files (Matlab format). Also part of this file is code that reproduces the plots of the data descriptor and the stimuli (images) shown to patients. Please refer to the accompanying data descriptor paper for details on how to use this data