Faculty Bibliography

Despite increased awareness of the lack of gender equity in academia and a growing number of initiatives to address issues of diversity, change is slow, and inequalities remain. A major source of inequity is gender bias, which has a substantial negative impact on the careers, work-life balance, and mental health of underrepresented groups in science. Here, we argue that gender bias is not a single problem but manifests as a collection of distinct issues that impact researchers' lives. We disentangle these facets and propose concrete solutions that can be adopted by individuals, academic institutions, and society.

Despite ongoing advances in our understanding of local single-cellular and network-level activity of neuronal populations in the human brain, extraordinarily little is known about their "intermediate" microscale local circuit dynamics. Here, we utilized ultra-high-density microelectrode arrays and a rare opportunity to perform intracranial recordings across multiple cortical areas in human participants to discover three distinct classes of cortical activity that are not locked to ongoing natural brain rhythmic activity. The first included fast waveforms similar to extracellular single-unit activity. The other two types were discrete events with slower waveform dynamics and were found preferentially in upper cortical layers. These second and third types were also observed in rodents, nonhuman primates, and semi-chronic recordings from humans via laminar and Utah array microelectrodes. The rates of all three events were selectively modulated by auditory and electrical stimuli, pharmacological manipulation, and cold saline application and had small causal co-occurrences. These results suggest that the proper combination of high-resolution microelectrodes and analytic techniques can capture neuronal dynamics that lay between somatic action potentials and aggregate population activity. Understanding intermediate microscale dynamics in relation to single-cell and network dynamics may reveal important details about activity in the full cortical circuit.

OBJECTIVE:Sporadic brain arteriovenous malformation (BAVM) is a tangled vascular lesion characterized by direct artery-to-vein connections that can cause life-threatening intracerebral hemorrhage (ICH). Recently, somatic mutations in KRAS have been reported in sporadic BAVM, and mutations in other mitogen-activated protein kinase (MAPK) signaling pathway genes have been identified in other vascular malformations. The objectives of this study were to systematically evaluate somatic mutations in MAPK pathway genes in patients with sporadic BAVM lesions and to evaluate the association of somatic mutations with phenotypes of sporadic BAVM severity. METHODS:The authors performed whole-exome sequencing on paired lesion and blood DNA samples from 14 patients with sporadic BAVM, and 295 genes in the MAPK signaling pathway were evaluated to identify genes with somatic mutations in multiple patients with BAVM. Digital droplet polymerase chain reaction was used to validate KRAS G12V and G12D mutations and to assay an additional 56 BAVM samples. RESULTS:The authors identified a total of 24 candidate BAVM-associated somatic variants in 11 MAPK pathway genes. The previously identified KRAS G12V and G12D mutations were the only recurrent mutations. Overall, somatic KRAS G12V was present in 14.5% of BAVM lesions and G12D was present in 31.9%. The authors did not detect a significant association between the presence or allelic burden of KRAS mutation and three BAVM phenotypes: lesion size (maximum diameter), age at diagnosis, and age at ICH. CONCLUSIONS:The authors confirmed the high prevalence of somatic KRAS mutations in sporadic BAVM lesions and identified several candidate somatic variants in other MAPK pathway genes. These somatic variants may contribute to understanding of the etiology of sporadic BAVM and the clinical characteristics of patients with this condition.

OBJECTIVE:To identify priorities for administrative, epidemiologic and diagnostic research in sepsis. DESIGN/METHODS:As a follow-up to a previous consensus statement about sepsis research, members of the Surviving Sepsis Campaign Research Committee, representing the European Society of Intensive Care Medicine and the Society of Critical Care Medicine addressed six questions regarding care delivery, epidemiology, organ dysfunction, screening, identification of septic shock, and information that can predict outcomes in sepsis. METHODS:Six questions from the Scoring/Identification and Administration sections of the original Research Priorities publication were explored in greater detail to better examine the knowledge gaps and rationales for questions that were previously identified through a consensus process. RESULTS:The document provides a framework for priorities in research to address the following questions: (1) What is the optimal model of delivering sepsis care?; (2) What is the epidemiology of sepsis susceptibility and response to treatment?; (3) What information identifies organ dysfunction?; (4) How can we screen for sepsis in various settings?; (5) How do we identify septic shock?; and (6) What in-hospital clinical information is associated with important outcomes in patients with sepsis? CONCLUSIONS:There is substantial knowledge of sepsis epidemiology and ways to identify and treat sepsis patients, but many gaps remain. Areas of uncertainty identified in this manuscript can help prioritize initiatives to improve an understanding of individual patient and demographic heterogeneity with sepsis and septic shock, biomarkers and accurate patient identification, organ dysfunction, and ways to improve sepsis care.

PURPOSE/OBJECTIVE:The purpose of this study is to evaluate the effectiveness of Extracellular Matrix Cartilage Allograft (EMCA) as an adjuvant to bone marrow stimulation (BMS) compared to BMS alone in the treatment of osteochondral lesions of the talus (OLT). METHODS:or Fisher exact test for categorical variables. RESULTS:Twenty-four patients underwent BMS with EMCA (BMS-EMCA group) and 24 patients underwent BMS alone (BMS group). The mean age was 40.8 years (range, 19 to 60 years) in BMS-EMCA group and 47.8 years (range, 24 to 60 years) in BMS group (p=0.060). The mean follow-up time was 20.0 months (range, 12-36 months) in BMS-EMCA group and 26.9 months (range, 12 to 55 months) in BMS group (p=0.031). Both groups showed significant improvements in all FAOS subscales. No significant differences between groups were found in all postoperative FAOS. The mean MOCART score in BMS-EMCA group was higher (76.3 vs 66.3), but not statistically significant (p=0.176). The MRI analysis showed that 87.5% of BMS-EMCA group had complete infill of the defect with repair tissue, however less than half (46.5%) of BMS group had complete infill (p=0.015). CONCLUSION/CONCLUSIONS:BMS with EMCA is an effective treatment strategy for the treatment of OLT and provides better cartilage infill in the defect on MRI. However, this did not translate to improved functional outcomes compared with BMS alone in the short-term. Additionally, according to the minimal clinically important difference (MCID) analysis, there was no significant difference in clinical function scoring between either group postoperatively. LEVEL OF EVIDENCE/METHODS:Level III retrospective comparative study.

BACKGROUND AND PURPOSE/OBJECTIVE:In symptomatic intracranial atherosclerotic stenosis (ICAS), borderzone infarct pattern and perfusion mismatch are associated with increased risk of recurrent strokes, which may reflect the shared underlying mechanism of hypoperfusion distal to the intracranial atherosclerosis. Accordingly, we hypothesized a correlation between hypoperfusion volumes and ICAS infarct patterns based on the respective underlying mechanistic subtypes. METHODS:We conducted a retrospective analysis of consecutive symptomatic ICAS cases, acute strokes due to subocclusive (50%-99%) intracranial stenosis. The following mechanistic subtypes were assigned based on the infarct pattern on the diffusion-weighted imaging: Branch occlusive disease (BOD), internal borderzone (IBZ), and thromboembolic (TE). Perfusion parameters, obtained concurrently with the MRI, were studied in each group. RESULTS: > 6 s) was substantially greater. CONCLUSION/CONCLUSIONS:ICAS infarct patterns, in keeping with their respective underlying mechanisms, may correlate with distinct perfusion profiles.

BACKGROUND: The treatment of spinal intramedullary arteriovenous malformations (AVMs) presents the risk of spinal cord ischemia because of the vascular nidus and their feeding arteries involving and supplying the spinal cord parenchyma. The multimodal approach includes endovascular embolization and microsurgical excision, both benefiting from intraoperative neurophysiologic monitoring. We present a case study of a patient who underwent several staged embolizations and open surgery for microsurgical excision. PATIENT/METHODS: A 32-year-old man who presented with a recurrent glomus-type intramedullary AVM in the cervical spinal cord, located at the C5-C6 segment, with progressive neurologic deterioration. METHODS: Somatosensory evoked potentials (SEPs) and transcranial motor evoked potentials (MEPs) were performed during three embolizations, a provocative test, and surgery, in addition to D-wave during microsurgical excision. RESULTS: Abolished hand MEP and drop in SEP during a provocative test guided the surgeon to embolize from a safer vessel with no acute neurologic deficit after three embolizations. Before surgery, an angiography showed the left posterior spinal artery supplying the AVM. After resecting the vascular nidus from the spinal parenchyma, left-hand MEP decreased in amplitude and later abolished, and SEP decreased. Interestingly, no D-wave or distal MEPs were affected. Weakness in the left hand immediately and 2 weeks postoperatively advocates for metameric spinal cord ischemia with preservation of long spinal cord pathways. CONCLUSIONS: Intraoperative neurophysiologic monitoring correlates with neurologic outcome after endovascular and surgical treatment of a cervical AVM. Intraoperative monitoring provides continuous functional information of long and metameric spinal cord pathways, which is critical when deciding on the vessel to be embolized and during microsurgical excision where the surgeon is in less control of the AVM hemodynamic flow.