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Background and Purpose: Hemispatial neglect is characterized by a reduced awareness to stimuli on the contralateral side. Current literature suggesting that damage to the right parietal lobe and attention networks may cause hemispatial neglect is conflicting and can be improved by investigating a connectomic model of the "neglect system" and the anatomical specificity of regions involved in it., Methods: A meta-analysis of voxel-based morphometry magnetic resonance imaging (MRI) studies of hemispatial neglect was used to identify regions associated with neglect. We applied parcellation schemes to these regions and performed diffusion spectrum imaging (DSI) tractography to determine their connectivity. By overlaying neglect areas and maps of the attention networks, we studied the relationship between them., Results: The meta-analysis generated a list of 13 right hemisphere parcellations. These 13 neglect-related parcellations were predominantly linked by the superior longitudinal fasciculus (SLF) throughout a fronto-parietal-temporal network. We found that the dorsal and ventral attention networks showed partial overlap with the neglect system and included various other higher-order networks., Conclusions: We provide an anatomically specific connectomic model of the neurobehavioral substrates underlying hemispatial neglect. Our model suggests a fronto-parietal-temporal network linked via the SLF supports the functions impaired in neglect and implicates various higher-order networks which are not limited to the attention networks., (© 2023 American Society of Neuroimaging.)

Objective: We sought to assess the practice patterns of ventriculoperitoneal shunt (VPS) placement by neurosurgeons at academic, community, and government-based institutions., Methods: Using the American Association of Neurological Surgeons directory, a total of 3673 practicing neurosurgeons were contacted. The survey received 495 responses (57% academic, 41% community, 3% other/government based). The survey consisted of 9 questions to assess the frequency of general surgery assistance for distal VPS placement and the use of cranial neuronavigation for proximal placement and to assess subjective beliefs of personal practice pattern and the influence on shunt failure rates., Results: Almost half of the respondents reported using general surgery less than half of the time for distal VPS placement. Regardless of personal practice patterns, roughly one third of respondents reported that general surgery assistance is a common or somewhat common practice at their institution. The most common reasons for recruiting general surgery assistance were cases of higher complexity. Although commonly used, almost 40% of respondents believe that general surgery assistance does not decrease shunt failure rates. Cranial neuronavigation is used less than half of the time, and the most common reason was for improved accuracy. Almost half of the respondents believe navigation does decrease shunt failure rates., Conclusions: General surgery assistance for distal placement and neuronavigation for the proximal placement of VPS catheters are both commonly used by neurosurgeons in academic, community, and other practice locations. This survey provides the first assessment of practice patterns nationally. The results demonstrate that roughly half of the practicing neurosurgeons use general surgery assistance and neuronavigation, particularly for complex or high-risk cases., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Nontraumatic subarachnoid hemorrhage (SAH) refers to high pressure extravasation of blood into the subarachnoid space that typically occurs spontaneously from rupture of cerebral aneurysm. The purpose of this study was to identify postoperative complications requiring increased surveillance in obese, diabetic, and hypertensive patients., Methods: Patients who underwent surgical treatment for nontraumatic SAH were queried in the American College of Surgeons National Surgical Quality Improvement Program database from the years 2012-2018. Cases were identified using International Classification of Diseases codes and then classified independently by 3 dichotomous diagnoses: obesity, diabetes, and hypertension., Results: Among 1002 patients meeting inclusion criteria, 311 (31%) were obese (body mass index >30), 86 (9%) had diabetes treated with insulin or noninsulin agents, and 409 (41%) required medication for hypertension. There was a statistically significant association between diabetes and postoperative pneumonia (odds ratio [OR] = 1.694; 95% confidence interval [CI] = 0.995-2.883; P = 0.050), prolonged ventilator dependence (OR = 1.700; 95% CI = 1.087-2.661; P = 0.019), and death (OR = 1.846; 95% CI = 1.071-3.179; P = 0.025). Medication-dependent hypertension was statistically associated with incidence of stroke/cerebrovascular accident (OR = 1.763; 95% CI = 1.056-2.943; P = 0.023). Obesity was not associated with adverse outcomes in this population., Conclusions: In patients undergoing surgical management of SAH, hypertensive and diabetic patients had poorer outcomes, including prolonged ventilator dependence, pneumonia, stroke/cerebrovascular accident, and death. Surprisingly, preexisting obesity was not associated with poor outcomes. In fact, overweight body mass index, class I obesity, and class II obesity had decreased need for transfusion in the 30-day postoperative period., (Published by Elsevier Inc.)

Background: How long do nonoperative cervical fractures have to be followed and with how many imaging studies?, Methods: We reviewed 69 adult patients with 122 (31 occiptocervical and 91 sub-axial) cervical fractures; at least one of the cervical fractures was managed nonoperatively. Outcomes were assessed along with the optimal follow-up duration and frequency of various diagnostic studies., Results: An average of four follow-up visits occurred on average 28-, 66-, 94-, and 158-day post hospital discharge. The average time between discharge and orthotic clearance was 70 days (±32.4 days). Radiographic studies were obtained at follow-up visits, respectively, in, 82.6%, 83.6%, 94.7%, and 100% of patients., Conclusion: The trend for managing nonoperative cervical fractures was an unduly prolonged follow-up duration that included obtaining too many imaging studies., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Surgical Neurology International.)

Machine learning is a rapidly evolving field that offers physicians an innovative and comprehensive mechanism to examine various aspects of patient data. Cervical and lumbar degenerative spine disorders are commonly age-related disease processes that can utilize machine learning to improve patient outcomes with careful patient selection and intervention. The aim of this study is to examine the current applications of machine learning in cervical and lumbar degenerative spine disease. A systematic review was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A search of PubMed, Embase, Medline, and Cochrane was conducted through May 31st, 2020, using the following terms: "artificial intelligence" OR "machine learning" AND "neurosurgery" AND "spine." Studies were included if original research on machine learning was utilized in patient care for degenerative spine disease, including radiographic machine learning applications. Studies focusing on robotic applications in neurosurgery, navigation, or stereotactic radiosurgery were excluded. The literature search identified 296 papers, with 35 articles meeting inclusion criteria. There were nine studies involving cervical degenerative spine disease and 26 studies on lumbar degenerative spine disease. The majority of studies for both cervical and lumbar spines utilized machine learning for the prediction of postoperative outcomes, with 5 (55.6%) and 15 (61.5%) studies, respectively. Machine learning applications focusing on degenerative lumbar spine greatly outnumber the current volume of cervical spine studies. The current research in lumbar spine also demonstrates more advanced clinical applications of radiographic, diagnostic, and predictive machine learning models., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The response assessment in neuro-oncology (RANO) criteria have been the gold standard for monitoring treatment response in glioblastoma (GBM) and differentiating tumor progression from pseudoprogression. While the RANO criteria have played a key role in detecting early tumor progression, their ability to identify pseudoprogression is limited by post-treatment damage to the blood-brain barrier (BBB), which often leads to contrast enhancement on MRI and correlates poorly to tumor status. Amino acid positron emission tomography (AA PET) is a rapidly growing imaging modality in neuro-oncology. While contrast-enhanced MRI relies on leaky vascularity or a compromised BBB for delivery of contrast agents, amino acid tracers can cross the BBB, making AA PET particularly well-suited for monitoring treatment response and diagnosing pseudoprogression. The authors performed a systematic review of PubMed, MEDLINE, and Embase through December 2021 with the search terms "temozolomide" OR "Temodar," "glioma" OR "glioblastoma," "PET," and "amino acid." There were 19 studies meeting inclusion criteria. Thirteen studies utilized [ 18 F]FET, five utilized [ 11 C]MET, and one utilized both. All studies used static AA PET parameters to evaluate TMZ treatment in glioma patients, with nine using dynamic tracer parameters in addition. Throughout these studies, AA PET demonstrated utility in TMZ treatment monitoring and predicting patient survival., (© The Author(s) 2022. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)

Background: Lateralized alterations in hippocampal function in the resting-state have been demonstrated for patients with temporal lobe epilepsy (TLE). However, resting-state fMRI of the hippocampus has yet to be substantiated as an adjunct to standard pre-operative assessments of the seizure focus., Objective: Here we report the results of a systematic review of resting-state fMRI studies investigating laterality of hippocampal network connectivity in TLE patients., Methods: A search of the PubMed, SCOPUS, Web of Science, and Embase databases for full-length articles written in English was conducted through June 2020 using the following terms: 'resting state fMRI,' 'hippocampus,' 'epilepsy,' and 'laterality.', Results: Our literature search yielded a total of 42 papers. After excluding studies that did not include patients with epilepsy, utilize resting-state fMRI, or explore the relationship between functional connectivity and disease lateralization, 20 publications were selected for inclusion. From these studies, a total of 528 patients, 258 with left TLE and 270 with right TLE, and 447 healthy controls were included. Of the 20 studies included, 18 found that patients with TLE demonstrated decreased hippocampal functional connectivity ipsilateral to the epileptogenic focus and 10 additionally reported increased hippocampal functional connectivity contralateral to the epileptogenic focus. Several studies demonstrated that the duration of disease was correlated with these changes in functional connectivity. This implies that a compensatory mechanism may be present in patients with treatment-refractory TLE., Conclusion: The consistency of this hippocampal connectivity pattern across multiple studies suggests resting-state fMRI may be useful as a non-invasive diagnostic tool for preoperative evaluation of TLE patients., (© 2021. Springer-Verlag GmbH, DE part of Springer Nature.)

Background: Women have been a minority in neurosurgery since the foundation of the specialty. Women who choose to pursue neurosurgery or advance in their career must overcome various obstacles. In this article, we discuss the proportion of women in neurosurgery globally and the obstacles they face, as well as the solutions being implemented., Methods: A systematic review of studies concerning international women in neurosurgery was conducted. Article inclusion was assessed based on relevance to women of neurosurgery, geographic region, date, and classification (rates/data, barriers, or solutions)., Results: From the specified search, 127 articles were retrieved, and 27 met the inclusion criteria. Of the total, 25 countries were represented and discussed in the articles. Primary classification of articles resulted in 50 for data/rates, 22 for barriers, and 17 for possible solutions., Discussion: Despite cultural differences among unique regions of the globe, women face similar challenges when pursuing neurosurgery, such as difficulty advancing their careers, balancing duties at work and at home, meeting social and cultural expectations, and finding support and mentorship. Encouragingly, measures are already being implemented worldwide to allow women to fulfill their multiple other roles through maternity leave policies, increasing their access to mentors, and enabling promotions throughout their careers., Conclusions: With the shortage of neurosurgeons in many regions of the world, the recruitment of female neurosurgeons plays a vital role in meeting those demands. Our cultures and professional societies should celebrate their inclusion and promotion and accommodate the complex role of women as neurosurgeons, mothers, partners, scientists, and leaders., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Transcranial magnetic stimulation is a noninvasive treatment used to modulate cortical excitability. Its use over the last two decades has expanded, ranging from psychiatric disorders to traumatic brain injury and poststroke rehabilitation., Objectives: We present the case of a 59-year-old male patient who presented in a decreased state of consciousness due to a right frontal glioblastoma, wherein his state was not improved by a successful surgery and could not be explained by any other condition. Due to his poor prognosis, we examine the benefits of receiving transcranial magnetic stimulation treatment to improve his akinetic mutism., Methods: We utilized independent component analysis with resting-state functional magnetic resonance imaging (rsfMRI) to better understand his cortical functionality. The imaging suggested absence of the default mode network (DMN). The patient underwent five sessions of navigated intermittent theta burst stimulation to the ipsilesional inferior parietal lobule and inferior frontal gyrus, with the aim of improving his default mode network functionality., Results: No other treatments resulted in an improvement of this patient's condition; however, 3 weeks following transcranial magnetic stimulation treatment, the patient was more alert and interactive, and his follow-up rsfMRI scan demonstrated a partially intact default mode network., Conclusion: This case raises important questions regarding the clinical utility of transcranial magnetic stimulation to improve the connectivity of important cerebral networks and subsequent related functional recovery., (© 2021 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Giant intracranial aneurysms represent a complex pathology that pose challenges for management, especially in the pediatric population. With emerging endovascular techniques, combined endovascular and open surgical approaches may be a favorable alternative for complex cases. In this systematic review, we characterize the treatment modalities of giant aneurysms in the pediatric population and provide an update on the number of giant aneurysms reported in the literature by anatomic location. We conducted a literature search of PubMed, Embase, and Medline databases with the following terms: 'pediatric' AND 'giant' AND 'intracranial aneurysm.' Studies were included if data on treatment modality and aneurysm location were available for pediatric patients with giant intracranial aneurysms. The literature search yielded a total of 188 papers, with 82 pediatric patients from 33 articles ultimately meeting inclusion criteria. There were significantly more male than female patients (p = 0.011), with 52 and 29 respectively. Patients presenting with a ruptured aneurysm were significantly younger than patients presenting without rupture (p = 0.018), with a median age of 8.0 and 12.0 years, respectively. There were 45 giant aneurysms reported in the anterior circulation and 37 in the posterior circulation. Anterior aneurysms were most often treated with surgical approaches, while posterior aneurysms were typically treated with endovascular interventions (p = 0.002). Although combined surgical and endovascular approaches were the least frequently utilized, we suggest a combined approach may be particularly useful for patients with complex cases that require a management plan tailored to their needs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021. Published by Elsevier Ltd.)

Background: Patients with ideomotor apraxia (IMA) present with selective impairments in higher-order motor cognition and execution without damage to any motor or sensory pathways. Although extensive research has been conducted to determine the regions of interest (ROIs) underlying these unique impairments, previous models are heterogeneous and may be further clarified based on their structural connectivity, which has been far less described., Objective: The goal of this research is to propose an anatomically concise network model for the neurophysiologic basis of IMA, specific to the voluntary pantomime, imitation and tool execution, based on intrinsic white matter connectivity., Methods: We utilized meta-analytic software to identify relevant ROIs in ideomotor apraxia as reported in the literature based on functional neuroimaging data with healthy participants. After generating an activation likelihood estimation (ALE) of relevant ROIs, cortical parcellations overlapping the ALE were used to construct an anatomically precise model of anatomic substrates using the parcellation scheme outlined by the Human Connectome Project (HCP). Deterministic tractography was then performed on 25 randomly selected, healthy HCP subjects to determine the structural connectivity underlying the identified ROIs., Results: 10 task-based fMRI studies met our inclusion criteria and the ALE analysis demonstrated 6 ROIs to constitute the IMA network: SCEF, FOP4, MIP, AIP, 7AL, and 7PC. These parcellations represent a fronto-parietal network consisting mainly of intra-parietal, U-shaped association fibers (40%) and long-range inferior fronto-occipital fascicle (IFOF) fibers (50%). These findings support previous functional models based on dual-stream motor processing., Conclusion: We constructed a preliminary model demonstrating the underlying structural interconnectedness of anatomic substrates involved in higher-order motor functioning which is seen impaired in IMA. Our model provides support for previous dual-stream processing frameworks discussed in the literature, but further clarification is necessary with voxel-based lesion studies of IMA to further refine these findings., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Robotic systems to assist with pedicle screw placement have recently emerged in the field of spine surgery. Here, the authors systematically reviewed the literature for evidence of these robotic systems and their utility. Thirty-four studies that reported the use of spinal instrumentation with robotic assistance and met inclusion criteria were identified. The outcome measures gathered included: pedicle screw accuracy, indications for surgery, rates of conversion to an alternative surgical method, radiation exposure, and learning curve. In our search there were five different robotic systems identified. All studies reported accuracy and the most commonly used accuracy grading scale was the Gertzbein Robbins scale (GRS). Accuracy of clinically acceptable pedicle screws, defined as < 2 mm cortical breech, ranged from 80% to 100%. Many studies categorized indications for robotic surgery with the most common being degenerative entities. Some studies reported rates of conversion from robotic assistance to manual instrumentation due to many reasons, with robotic failure as the most common. Radiation exposure data revealed a majority of studies reported less radiation using robotic systems. Studies looking at a learning curve effect with surgeon use of robotic assistance were not consistent across the literature. Robotic systems for assistance in spine surgery have continued to improve and the accuracy of pedicle screw placement remains superior when compared to free-hand technique, however rates of manual conversion are significant. Currently, these systems are successfully employed in various pathological entities where trained spine surgeons can be safe and accurate regardless of robotic training., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Currently, bevacizumab (BEV), an antiangiogenic agent, is used as an adjunctive therapy to re-irradiation and surgery in patients with recurrent high-grade gliomas (rHGG). BEV has shown to decrease enhancement on MRI, but it is often unclear if these changes are due to tumor response to BEV or treatment-induced changes in the blood brain barrier. Preliminary studies show that amino acid PET can aid in distinguishing these changes on MRI., Methods: The authors performed a systematic review of PubMed and Embase through July 2020 with the search terms 'bevacizumab' or 'Avastin' and 'recurrent glioma' and 'PET,' yielding 38 papers, with 14 meeting inclusion criteria., Results: Thirteen out of fourteen studies included in this review used static PET and three studies used dynamic PET to evaluate the use of BEV in rHGG. Six studies used the amino acid tracer [18F]FET, four studies used [11C]MET, and four studies used [18F]FDOPA., Conclusion: [18F]FET, [11C]MET, and [18F]FDOPA PET in combination with MRI have shown promising results for improving accuracy in diagnosing tumor recurrence, detecting early treatment failure, and distinguishing between tumor progression and treatment-induced changes in patients with rHGG treated with BEV., (© The Author(s) 2021. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)

Introduction: The supplementary motor area (SMA) plays an important role in the initiation and coordination of internally and externally cued movements. Such movements include reaching, grasping, speaking, and bilateral hand coordination. While many studies discuss the SMA and its relationship to other parts of the motor network, there is minimal literature examining the connectivity of the SMA outside of the motor network. Using region-based fMRI studies, we built a neuroanatomical model to account for these extra-motor connections., Methods: Thirty region-based fMRI studies were used to generate an activation likelihood estimation (ALE) using BrainMap software. Cortical parcellations overlapping the ALE were used to construct a preliminary model of the SMA connections outside the motor network. DSI-based fiber tractography was performed to determine the connectivity between cortical parcellations. The resulting connections were described using the cortical parcellation scheme developed by the Human Connectome Project (HCP)., Results: Four left hemisphere regions were found to comprise the SMA. These included areas SFL, SCEF, 6ma, and 6mp. Across mapped brains, these areas showed consistent interconnections between each other. Additionally, ipsilateral connections to the primary motor cortex, left inferior and middle frontal gyri, the anterior cingulate gyrus, and insula were demonstrated. Connections to the contralateral SMA, anterior cingulate, lateral premotor, and inferior frontal cortices were also identified., Conclusions: We describe a preliminary cortical model for the underlying structural connectivity of the supplementary motor area outside the motor network. Future studies should further characterize the neuroanatomic underpinnings of this network for the purposes of medical application., (Copyright © 2021. Published by Elsevier B.V.)

Introduction: The auditory network plays an important role in interaction with the environment. Multiple cortical areas, such as the inferior frontal gyrus, superior temporal gyrus and adjacent insula have been implicated in this processing. However, understanding of this network's connectivity has been devoid of tractography specificity., Methods: Using attention task-based functional magnetic resonance imaging (MRI) studies, an activation likelihood estimation (ALE) of the auditory network was generated. Regions of interest corresponding to the cortical parcellation scheme previously published under the Human Connectome Project were co-registered onto the ALE in the Montreal Neurological Institute coordinate space, and visually assessed for inclusion in the network. Diffusion spectrum MRI-based fiber tractography was performed to determine the structural connections between cortical parcellations comprising the network., Results: Fifteen cortical regions were found to be part of the auditory network: areas 44 and 8C, auditory area 1, 4, and 5, frontal operculum area 4, the lateral belt, medial belt and parabelt, parietal area F centromedian, perisylvian language area, retroinsular cortex, supplementary and cingulate eye field and the temporoparietal junction area 1. These regions showed consistent interconnections between adjacent parcellations. The frontal aslant tract was found to connect areas within the frontal lobe, while the arcuate fasciculus was found to connect the frontal and temporal lobe, and subcortical U-fibers were found to connect parcellations within the temporal area. Further studies may refine this model with the ultimate goal of clinical application., Competing Interests: Declaration of Competing Interest Dr Sughrue is the Chief Medical Officer of Omniscient Neurotechnology, however this does not pose a conflict of interest in this study. The other authors have no conflicts of interest., (Copyright © 2020. Published by Elsevier B.V.)

Objective: One of the greatest challenges of achieving successful surgical outcomes in patients with epilepsy is the ability to properly localize the seizure onset zone (SOZ). Many techniques exist for localizing the SOZ, including intracranial electroencephalography, magnetoencephalography, and stereoelectroencephalography. Recently, resting-state functional magnetic resonance imaging (rs-fMRI) in conjunction with independent component analysis (ICA) has been utilized for presurgical planning of SOZ resection, with varying results. In this meta-analysis, we analyze the current role of rs-fMRI in identifying the SOZ for presurgical planning for patients with drug-resistant epilepsy. Specifically, we seek to demonstrate its current effectiveness compared to other methods of SOZ localization., Methods: A literature review was conducted using the PubMed, MEDLINE, and Embase databases up to May of 2020. A total of 253 articles were screened, and seven studies were chosen for analysis. Each study was analyzed for SOZ localization by ground truth, SOZ localization by rs-fMRI with ICA, principal component analysis, or intrinsic connectivity contrast, and outcomes of surgery. A meta-analysis was performed to analyze how ground truth compares to rs-fMRI in SOZ localization., Results: The odds ratio comparing ground truth to rs-fMRI was 2.63 (95% confidence interval = 0.66-10.56). Average concordance of rs-fMRI SOZ localization compared with ground truth localization across studies was 71.3%., Significance: In the hunt for less invasive presurgical planning for epilepsy surgery, rs-fMRI with ICA provides a promising avenue for future standard practice. Our preliminary results show no significant difference in surgical outcomes between traditional standards of SOZ localization and rs-fMRI with ICA. We believe that rs-fMRI could be a step forward in this search. Further investigation comparing rs-fMRI to traditional methods of SOZ localization should be conducted, with the hope of moving toward relying solely on noninvasive screening methods., (© 2020 International League Against Epilepsy.)

Introduction: The ventral attention network (VAN) is an important mediator of stimulus-driven attention. Multiple cortical areas, such as the middle and inferior frontal gyri, anterior insula, inferior parietal lobule, and temporo-parietal junction have been linked in this processing. However, knowledge of network connectivity has been devoid of structural specificity., Methods: Using relevant task-based fMRI studies, an activation likelihood estimation (ALE) of the VAN was generated Regions of interest corresponding to the HCP cortical parcellation scheme were co-registered onto this ALE in MNI coordinate space and visually assessed for inclusion in the network. DSI-based fiber tractography was performed to determine the structural connections between cortical areas comprising the VAN., Results: Fourteen regions within the right cerebral hemisphere were found to overlap the ALE of the VAN: 6a, 6r, 7AM, 7PM, 8C, AVI, FOP4, MIP, p9-46v, PCV, PFm, PGi, TPOJ1, and TPOJ2. Regions demonstrated consistent U-shaped interconnections between adjacent parcellations, and the SLF was found to connect frontal and parietal areas of the network., Conclusions: We present a tractographic model of the VAN. This model comprises parcellations within the frontal and parietal cortices that are linked via the SLF. Future studies may refine this model with the ultimate goal of clinical application., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Introduction: The dorsal attention network (DAN) is an important mediator of goal-directed attentional processing. Multiple cortical areas, such as the frontal eye fields, intraparietal sulcus, superior parietal lobule, and visual cortex, have been linked in this processing. However, knowledge of network connectivity has been devoid of structural specificity., Methods: Using attention-related task-based fMRI studies, an anatomic likelihood estimation (ALE) of the DAN was generated. Regions of interest corresponding to the cortical parcellation scheme previously published under the Human Connectome Project were co-registered onto the ALE in MNI coordinate space and visually assessed for inclusion in the network. DSI-based fiber tractography was performed to determine the structural connections between relevant cortical areas comprising the network., Results: Twelve cortical regions were found to be part of the DAN: 6a, 7AM, 7PC, AIP, FEF, LIPd, LIPv, MST, MT, PH, V4t, VIP. All regions demonstrated consistent u-shaped interconnections between adjacent parcellations. The superior longitudinal fasciculus connects the frontal, parietal, and occipital areas of the network., Conclusions: We present a tractographic model of the DAN. This model comprises parcellations within the frontal, parietal, and occipital cortices principally linked through the superior longitudinal fasciculus. Future studies may refine this model with the ultimate goal of clinical application., (© 2019 The Authors. Brain and Behavior published by Wiley Periodicals, Inc.)

The history of psychosurgery is filled with tales of researchers pushing the boundaries of science and ethics. These stories often create a dark historical framework for some of the most important medical and surgical advancements. Dr. Robert G. Heath, a board-certified neurologist, psychiatrist, and psychoanalyst, holds a debated position within this framework and is most notably remembered for his research on schizophrenia. Dr. Heath was one of the first physicians to implant electrodes in deep cortical structures as a psychosurgical intervention. He used electrical stimulation in an attempt to cure patients with schizophrenia and as a method of conversion therapy in a homosexual man. This research was highly controversial, even prior to the implementation of current ethics standards for clinical research and often goes unmentioned within the historical narrative of deep brain stimulation (DBS). While distinction between the modern practice of DBS and its controversial origins is necessary, it is important to examine Dr. Heath's work as it allows for reflection on current neurosurgical practices and questioning the ethical implication of these advancements.

Purpose: With the implementation of strict 80-hour work week in general surgery training, serious questions have been raised concerning the quality of surgical education and the ability of newly trained general surgeons to independently operate. Programs that were randomized to the interventional arm of the Flexibility In duty-hour Requirements for Surgical Trainees (FIRST) Trial were able to decrease transitions and allow for better continuity by virtue of less constraints on duty-hour rules. Using National Surgical Quality Improvement Program Quality In-Training Initiative data along with duty-hour violations compared with old rules, it was hypothesized that quality of care would be improved and outcomes would be equivalent or better than the traditional duty-hour rules. It was also hypothesized that resident perception of compliance with duty hour would not change with implementation of new regulations based on FIRST trial., Methods: Flexible work hours were implemented on July 1, 2014. National Surgical Quality Improvement Program Quality In-Training Initiative information was reviewed from July 2014 to January 2015. Patient risk factors and outcomes were compared between institutional resident cases and the national cohort for comparison. Residents' duty-hour logs and violations during this period were compared to the 6-month period before the implementation of the FIRST trial. The annual Accreditation Council for Graduate Medical Education resident survey was used to assess the residents' perception of compliance with duty hours., Results: With respect to the postoperative complications, the only statistically significant measures were higher prevalence of pneumonia (3.4% vs. 1.5%, p < 0.05) and lower prevalence of sepsis (0% vs. 1.5%, p < 0.05) among cases covered by residents with flexible duty hours. All other measures of postoperative surgical complications showed no difference. The total number of duty-hour violations decreased from 54 to 16. Had the institution not been part of the interventional arm of the FIRST trial, this number would have increased to 238. The residents' perception of compliance with 80-hour work week from the Accreditation Council for Graduate Medical Education survey improved from 68% to 91%., Conclusions: Residents with flexible work hours on the interventional arm of the FIRST trial at our institution took care of a significantly sicker cohort of patients as compared with the national dataset with equivalent outcomes. Flexible duty-hour policy under the FIRST trial has enabled the residents to have fewer work-hour violations while improving continuity of care to the patients. Additionally, the overall perception of resident compliance with the duty-hour requirements was improved., (Copyright © 2016 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Venous thromboembolisms (VTEs) occur more frequently in patients with traumatic brain injuries (TBIs) and spinal cord injuries, yet the use of chemoprophylaxis is controversial. The purpose of this study was to investigate the relationship between the timing of chemical VTE prophylaxis initiation and the development of VTE events in these patients., Methods: Prospective data were collected and retrospectively reviewed on 1425 patients sustaining TBIs or spinal injuries from 2010 to 2014. Patients were reviewed with respect to age, gender, injury severity score, Glasgow coma score, and mechanism of injury as well as timing of initiation of chemical VTE prophylaxis and presence or absence of VTE., Results: Patients who developed a VTE had a significantly longer time to initiation of chemical VTE prophylaxis (6.7 ± 4.9 d versus 4.7 ± 4.9 d, P < 0.001) compared with those that did not develop a VTE. Also, for each 1 d increase in time to prophylaxis initiation, the odds of developing a VTE increased significantly (odds ratio = 1.055, P < 0.001). The combination subarachnoid hemorrhage/subdural hemorrhage group was started on VTE prophylaxis significantly later (8.3 ± 6.1 d versus 6.7 ± 3.9 d, P < 0.01) than the overall TBI group and had a higher incidence of VTE (14.4 versus 10.4%, P = NS). In contrast, patients sustaining isolated spinal injuries received chemical VTE prophylaxis significantly earlier (3.4 ± 4.2 d versus 6.7 ± 3.9 d, P < 0.001) and had a significant decrease in their VTE rate (4.4 versus 10.4%, P < 0.0001) compared with the overall TBI group., Conclusions: Patients with VTEs had a significant delay in time to initiation of chemoprophylaxis compared with patients without VTEs. Patients sustaining a TBI had a 2-fold delay in initiation of chemoprophylaxis and an associated 2-fold increase in VTE events compared with patients who sustained spinal injuries. Of those patients who developed a TBI, patients who sustained a combination subarachnoid hemorrhage and/or subdural hemorrhage had a significant delay in initiation of chemoprophylaxis with a higher rate of VTE events., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: To quantify the effects of race, measures of socioeconomic status and geographic residency status on pancreatic cancer survival time., Design: Retrospective review., Setting: A southeastern safety-net academic medical centre in the United States., Participants: The study population consisted of all patients who were diagnosed, referred to or treated at the medical centre between 2009 and 2012 (n = 245). To ensure completeness and accuracy of the data, follow-up treatment and survival information about the cases were collected from the Georgia Comprehensive Cancer Registry in 2013., Main Outcome Measures: The odds of receiving first-course treatment (surgery, radiation or chemotherapy) and overall survival following a pancreatic cancer diagnosis., Results: There were no observed differences in receipt of initial treatment; however, patients from low socioeconomic and rural areas had significant increase in risk of death compared to patients from affluent and urban areas., Conclusions: Results from this single site study suggests the significance of factors other than treatment differences that contribute to geographic disparities in mortality., (© 2015 National Rural Health Alliance Inc.)

Background: The development of critical consciousness, anchored in principles of social justice, is an essential component of medical education., Aim: In order to assist faculty instructors in facilitating small-group discussions on potentially contentious issues involving race, gender, sexual orientation, and socioeconomic class, a faculty development workshop was created., Methods: The workshop used 'Forum Theater' techniques in which the audience was directly involved in determining the course of a simulated classroom discussion and conflict. We assessed the workshop's impact on the instructors' attitudes regarding facilitation of small-group discussions through two surveys: one to gauge immediate impressions, and another, 9-15 months later, to assess impact over time., Results: Immediately after the workshop, participants reported that the topics covered in the sketch and in the discussion were highly relevant. In the follow-up survey, the instructors agreed that the workshop had raised their awareness of the classroom experiences of minorities and women and had offered strategies for addressing destructive classroom dynamics. 72% reported that the workshop led to changes in their behavior as facilitators. Differences in responses according to gender were observed., Conclusions: A workshop using interactive theater was effective in training faculty to facilitate small-group discussions about multicultural issues. This approach emphasizes and models the need to foster critical consciousness in medical education.

Critical factors that are important in protection from rotavirus infection have remained elusive. We demonstrate here that inbred mice (C57BL/6 and BALB/c) exhibit differences in: (1) susceptibility to and (2) VLP-induced protection from rotavirus infection. Comparing protection induced by 2/4/6/7-VLPs with inactivated and live rotavirus, intranasally induced protection was dependent on dsRNA or minor structural proteins and correlated with intestinal antibody, while orally induced protection required immunization with replicating virus. Combination oral/intranasal vaccination did not improve VLP protective efficacy. These studies indicate that host, viral, and vaccine factors determine the level of protective efficacy induced by VLPs.

Immunoglobulin A (IgA) is the primary immune response induced in the intestine by rotavirus infection, but vaccination with virus-like particles induces predominantly IgG, not IgA. To definitively assess the role of IgA in protection from rotavirus infection, IgA knockout mice, which are devoid of serum and secretory IgA, were infected and then rechallenged with murine rotavirus at either 6 weeks or 10 months. Following primary rotavirus infection, IgA knockout mice cleared virus as effectively as IgA normal control mice. Rotavirus-infected IgA knockout mice produced no serum or fecal IgA but did have high levels of antirotavirus serum IgG and IgM and fecal IgG, whereas IgA normal control mice made both serum IgA and IgG and fecal IgA. Both IgA normal and IgA knockout mice were totally protected from rotavirus challenge at 42 days. Ten months following a primary infection, both IgA normal and knockout mice still had high levels of serum and fecal antirotavirus antibody and were totally protected from rotavirus challenge. To determine if compensatory mechanisms other than IgG were responsible for protection from rotavirus infection in IgA knockout mice, mice were depleted of CD4(+) T cells or CD8(+) T cells. No changes in the level of protection were seen in depleted mice. These data show that fecal or systemic IgA is not essential for protection from rotavirus infection and suggest that in the absence of IgA, IgG may play a significant role in protection from mucosal pathogens.

The recognition that rotaviruses are the major cause of life-threatening diarrheal disease and significant morbidity in young children has focused efforts on disease prevention and control of these viruses. Although the correlates of protection in children remain unclear, some studies indicate that serotype-specific antibody is important. Based on this premise, current live attenuated reassortant rotavirus vaccines include the four predominant serotypes of virus. We are evaluating subunit rotavirus vaccines, 2/6/7-VLPs and 2/4/6/7-VLPs, that contain only a single VP7 of serotype G1 or G3. In mice immunized parenterally twice, G3 virus-like particles (VLPs) induced a homotypic, whereas G1 VLPs induced a homotypic and heterotypic (G3) serum neutralizing immune response. Administration of three doses of G1 or G3 VLPs induced serum antibodies that neutralized five of seven different serotype test viruses. The inclusion of VP4 in the VLPs was not essential for the induction of heterotypic neutralizing antibody in mice. To confirm these results in another species, rabbits were immunized parenterally with two doses of 2/4/6/7-VLPs containing a G3 or G1 VP7, sequentially with G3 VLPs followed by G1 (G3/G1) VLPs, or with live or psoralen-inactivated SA11. High-titer homotypic serum neutralizing antibody was induced in all rabbits, and low-level heterotypic neutralizing antibody was induced in a subset of rabbits. The rabbits immunized with the G1 or G3/G1 VLPs in QS-21 were challenged orally with live G3 ALA rotavirus. Protection levels were similar in rabbits immunized with homotypic G3 2/4/6/7-VLPs, heterotypic G1 2/4/6/7-VLPs, or G3/G1 2/4/6/7-VLPs. Therefore, G1 2/4/6/7-VLPs can induce protective immunity against a live heterotypic rotavirus challenge in an adjuvant with potential use in humans. Following challenge, broad serum heterotypic neutralizing antibody responses were detected in rabbits parenterally immunized with G1, G3/G1, or G3 VLPs but not with SA11. Immunization with VLPs may provide sufficient priming of the immune system to induce protective anamnestic heterotypic neutralizing antibody responses upon subsequent rotavirus infection. Therefore, a limited number of serotypes of VLPs may be sufficient to provide a broadly protective subunit vaccine.

Virus-like particles (VLPs) composed of rotavirus VP2, VP6, and VP7 of G1 or G3 serotype specificity were produced in insect cells coinfected with recombinant baculoviruses expressing single rotavirus genes. The VLPs were purified and subsequently evaluated for immunogenicity and protection in the adult mouse model of rotavirus infection. Mice were vaccinated twice intramuscularly with G1 VLPs formulated with Quillaja saponaria (QS-21) or adsorbed to aluminium hydroxide (AlOH), or with G1 VLPs alone. G3 VLPs, G1 plus G3 VLPs, inactivated SA11 virions formulated with QS-21, or adjuvants were similarly inoculated as controls. Mice were examined for serum and fecal antibody responses by ELISA or microneutralization assays. Protective efficacy of the VLP vaccine formulations against oral challenge with the G3 murine ECwt rotavirus was assessed by comparing the antigen shed in stool of the VLP-vaccinated mice to that of the adjuvant-immunized mice. G1 VLPs in QS-21 induced significantly higher serum and intestinal antibody titers than G1 VLPs in AlOH or G1 VLPs alone. QS-21 also heightened serum and fecal antibody responses to G3 VLPs. These QS-21-augmented antibody responses were further characterized by equivalent IgG1 and IgG2a titers in sera, suggesting that G1 or G3 VLPs in QS-21 induced a balanced Th1/Th2 response. G1 VLPs in QS-21 induced partial protection (88%) against oral challenge with the heterotypic ECwt virus, whereas G3 VLPs in QS-21 induced complete protection (100%). In contrast, G1 VLPs when formulated with AlOH induced a predominant Th2 response and did not protect (1%) mice from virus challenge. Our results indicate that the type of adjuvant used clearly influences both antibody responses to rotavirus VLPs and the protective efficacy against rotavirus infections. These data have important implications for the development of parenteral vaccines to ameliorate rotavirus disease.

We have shown that rotavirus 2/6 viruslike particles composed of proteins VP2 and VP6 (2/6-VLPs) administered to mice intranasally with cholera toxin (CT) induced protection from rotavirus challenge, as measured by virus shedding. Since it is unclear if CT will be approved for human use, we evaluated the adjuvanticity of Escherichia coli heat-labile toxin (LT) and LT-R192G. Mice were inoculated intranasally with 10 microg of 2/6-VLPs combined with CT, LT, or LT-R192G. All three adjuvants induced equivalent geometric mean titers of rotavirus-specific serum antibody and intestinal immunoglobulin G (IgG). Mice inoculated with 2/6-VLPs with LT produced significantly higher titers of intestinal IgA than mice given CT as the adjuvant. All mice inoculated with 2/6-VLPs mixed with LT and LT-R192G were totally protected (100%) from rotavirus challenge, while mice inoculated with 2/6-VLPs mixed with CT showed a mean 91% protection from challenge. The availability of a safe, effective mucosal adjuvant such as LT-R192G will increase the practicality of administering recombinant vaccines mucosally.

We have evaluated the immunogenicity and protective efficacy of rotavirus subunit vaccines administered by mucosal routes. Virus-like particles (VLPs) produced by self-assembly of individual rotavirus structural proteins coexpressed by baculovirus recombinants in insect cells were the subunit vaccine tested. We first compared the immunogenicities and protective efficacies of VLPs containing VP2 and VP6 (2/6-VLPs) and G3 2/6/7-VLPs mixed with cholera toxin and administered by oral and intranasal routes in the adult mouse model of rotavirus infection. VLPs administered orally induced serum antibody and intestinal immunoglobulin A (IgA) and IgG. The highest oral dose (100 microg) of VLPs induced protection from rotavirus challenge (> or = 50% reduction in virus shedding) in 50% of the mice. VLPs administered intranasally induced higher serum and intestinal antibody responses than VLPs administered orally. All mice receiving VLPs intranasally were protected from challenge; no virus was shed after challenge. Since there was no difference in immunogenicity or protective efficacy between 2/6- and 2/6/7-VLPs, protection was achieved without inclusion of the neutralization antigens VP7 and VP4. We also tested the immunogenicities and protective efficacies of 2/6-VLPs administered intranasally without the addition of cholera toxin. 2/6-VLPs administered intranasally without cholera toxin induced lower serum and intestinal antibody titers than 2/6-VLPs administered with cholera toxin. The highest dose (100 microg) of 2/6-VLPs administered intranasally without cholera toxin resulted in a mean reduction in shedding of 38%. When cholera toxin was added, higher levels of protection were achieved with 10-fold less immunogen. VLPs administered mucosally offer a promising, safe, nonreplicating vaccine for rotavirus.