Faculty Bibliography

Flow diverters (FDs) have changed the management of brain aneurysms; not only for complex aneurysms (giant, fusiform and blister) refractory to conventional therapies, but also for unruptured lesions previously managed by traditional surgical or coil-based endovascular methods. Since 2011 when the PipelineTM Embolization Device (Medtronic) was cleared by the Food and Drug Administration for adults with large or giant wide-neck intracranial aneurysms of the internal carotid artery proximal to the posterior communicating segment, the role of flow diversion for aneurysm treatment has expanded-supported by favorably low complication and high cure rates compared with alternative treatments. Here we review the key clinical trials and the long term outcomes that have demonstrated safety and efficacy of minimized porosity endoluminal devices in the treatment of cerebral aneurysms.

This paper is a contribution to a theory of duration and subjective time in dream and waking consciousness. According to microgenetic theory, an act of thought begins, Wittgenstein wrote, and psychoanalysts would agree, as would I, with instinct as the animal inheritance traverses the evolutionary core of the brain, the drives arousing acquired experience and knowledge. These strands of the inherited and acquired constitute the core self, the "me," which is bound up with bodily function, immediacy and the largely innate determinants of behavior. This construct passes a liminal threshold leading to a conscious self in relation to desire for objects or conditions in the future. Thus, the self appears early in the mental state prior to thought and the endpoint of object-perception. A mental state enfolds a transition from instinct to thought to perception in a fraction of a second. The partial overlap of early segments in a series of mental states arouses preliminary phases out of which thoughts and perceptions actualize. Long-term or experiential memories, revised but not erased by the oncoming state, serve as a foundation for thought and perception, while segments at the surface or endpoint of the state that transition to an object, which are not enfolded in the overlap, are receptive to new perceptions. In dreaming, the specious or illusory present arises in the overlap of mental states and the incomplete revival of their predecessors. Incompleteness of revival is the key to recall as fading states lapse to successive planes of iconic, short- and long-term memory. The present arises in the forgetting of perceptions, or the passage of perceptual to memorial content, as the disparity between the floor of the mental state"“the endpoint of withdrawal beneath recall"“and conscious revival"“the ceiling of the mental state"“in the final actuality. This disparity is converted to a longitudinal epoch of duration. The degree to which each state is revived"“the forgetting of each state, in dream and waking"“accounts for the rapid decay in dream recall on waking, as well as the predominance of imagery.

Evidence suggests exposure to particulate matter with aerodynamic diameter <2.5 μm (PM2.5) may increase the risk for Alzheimer's disease and related dementias. Whether PM2.5 alters brain structure and accelerates the preclinical neuropsychological processes remains unknown. Early decline of episodic memory is detectable in preclinical Alzheimer's disease. Therefore, we conducted a longitudinal study to examine whether PM2.5 affects the episodic memory decline, and also explored the potential mediating role of increased neuroanatomic risk of Alzheimer's disease associated with exposure. Participants included older females (n = 998; aged 73-87) enrolled in both the Women's Health Initiative Study of Cognitive Aging and the Women's Health Initiative Memory Study of Magnetic Resonance Imaging, with annual (1999-2010) episodic memory assessment by the California Verbal Learning Test, including measures of immediate free recall/new learning (List A Trials 1-3; List B) and delayed free recall (short- and long-delay), and up to two brain scans (MRI-1: 2005-06; MRI-2: 2009-10). Subjects were assigned Alzheimer's disease pattern similarity scores (a brain-MRI measured neuroanatomical risk for Alzheimer's disease), developed by supervised machine learning and validated with data from the Alzheimer's Disease Neuroimaging Initiative. Based on residential histories and environmental data on air monitoring and simulated atmospheric chemistry, we used a spatiotemporal model to estimate 3-year average PM2.5 exposure preceding MRI-1. In multilevel structural equation models, PM2.5 was associated with greater declines in immediate recall and new learning, but no association was found with decline in delayed-recall or composite scores. For each interquartile increment (2.81 μg/m3) of PM2.5, the annual decline rate was significantly accelerated by 19.3% [95% confidence interval (CI) = 1.9% to 36.2%] for Trials 1-3 and 14.8% (4.4% to 24.9%) for List B performance, adjusting for multiple potential confounders. Long-term PM2.5 exposure was associated with increased Alzheimer's disease pattern similarity scores, which accounted for 22.6% (95% CI: 1% to 68.9%) and 10.7% (95% CI: 1.0% to 30.3%) of the total adverse PM2.5 effects on Trials 1-3 and List B, respectively. The observed associations remained after excluding incident cases of dementia and stroke during the follow-up, or further adjusting for small-vessel ischaemic disease volumes. Our findings illustrate the continuum of PM2.5 neurotoxicity that contributes to early decline of immediate free recall/new learning at the preclinical stage, which is mediated by progressive atrophy of grey matter indicative of increased Alzheimer's disease risk, independent of cerebrovascular damage.

Unprecedented media coverage of concussion in sport has led to increased fears regarding the potential negative effects of participation in contact sports including North American football and ice hockey. Initial responses of professional sports leagues to implementation of acute concussion management practices and reports of a neurodegenerative condition known as chronic traumatic encephalopathy (CTE) developing in retired players caused an atmosphere of distrust whereby the leagues were accused of maintaining cover-ups analogous to what had been seen in association with studies of tobacco and smoking. This article reviews the important role that psychology has played in the study of sports concussion and in the establishment of methods currently used to diagnose and track concussion symptoms. Results of existing studies have shown that the neurobiological effects of concussion are rather short-lived with development of persisting symptoms in some individuals associated more with psychosocial factors than underlying physiological effects. With regard to CTE, the status of the science remains preliminary with little definitive information known about its epidemiology or cause. In the midst of the ongoing controversy, a polarized climate has developed in association with concussion and CTE, divided by believers in the dangers of long-term consequences and deniers who question the status of the existing science. The conclusion is that it is important for psychology to extend its scope of study to provide increased understanding of the social factors underlying the current polarized climate while continuing to provide the public with an accurate and reliable account of the existing science. (PsycInfo Database Record (c) 2020 APA, all rights reserved)Public Significance Statement"”Continued media reporting of the sports concussion and its potential long-term effects has been accompanied by public concerns about the safety of contact sports and potential development of chronic traumatic encephalopathy (CTE). Controversies have emerged about the status of the science, creating polarization on the topic. Psychology has provided significant contributions to our scientific knowledge on sports concussion and has the potential to provide a key to understanding the factors underlying division on these topics. (PsycInfo Database Record (c) 2020 APA, all rights reserved)Une couverture médiatique sans précédent des commotions cérébrales dans le sport a entraîné une augmentation des craintes quant aux effets négatifs potentiels de la participation aux sports de contact, notamment au football et au hockey sur glace en Amérique du Nord. Les premières réponses des ligues sportives professionnelles à la mise en Å“uvre de pratiques de gestion des commotions aiguës et les déclarations de maladie neurodégénérative connue sous le nom d"™encéphalopathie traumatique chronique (CTE) en développement chez les joueurs retraités ont provoqué une atmosphère de méfiance où les ligues ont été accusées de dissimulations de manière similaire à ce qui avait été observé avec les études sur le tabac et le tabagisme. Le présent article examine le rôle important que la psychologie a joué dans l"™Ã©tude des commotions liées au sport et dans l"™Ã©tablissement de méthodes actuellement utilisées pour diagnostiquer et surveiller les symptômes de commotion cérébrale. Les résultats des études existantes ont montré que les effets neurobiologiques de commotion cérébrale sont plutôt de courte durée avec l"™apparition de symptômes persistants, chez certaines personnes, plutôt associés à des facteurs psychosociaux qu"™aux effets physiologiques sous-jacents. En ce qui concerne la CTE, le statut de la science reste préliminaire, avec peu de renseignements définitifs connus sur son épidémiologie ou sa cause. Au cÅ“ur de la controverse actuelle, un climat polarisé s"™est développé en lien avec la commotion cérébrale et la CTE, divisé par les croyants aux dangers des conséquences à long terme et les négateurs qui remettent en question le statut de la science existante. En conclusion, il est important pour la psychologie d"™Ã©tendre sa portée d"™Ã©tude afin de mieux comprendre les facteurs sociaux sous-jacents au climat polarisé actuel tout en continuant à fournir au public un compte rendu exact et fiable de la science existante. (PsycInfo Database Record (c) 2020 APA, all rights reserved)

OBJECTIVE:To determine the influence of self-reported Black African and Latin American identity on peripheral blood antibody-secreting cell (ASC) frequency in the context of relapsing-remitting MS. METHODS:In this cross-sectional study, we recruited 74 subjects with relapsing-remitting MS and 24 age-, and self-reported ethno-ancestral identity-matched healthy donors (HDs) to provide peripheral blood study samples. Subjects with MS were either off therapy at the time of study draw or on monthly natalizumab therapy infusions. Using flow cytometry, we assessed peripheral blood mononuclear cells for antibody-secreting B-cell subsets. RESULTS:subsets, were among those significantly increased. CONCLUSION:The enhanced peripheral blood plasmablast signature revealed among Black African or Latin American subjects with MS points to distinct underlying mechanisms associated with MS immunopathogenesis. This dysregulation may contribute to the disease disparity experienced by patient populations of Black African or Latin American ethno-ancestry.

Objective/UNASSIGNED:To determine the safety and efficacy of flow reversal following proximal flow arrest as an embolic protection strategy for carotid angioplasty and stenting (CAS) with short-term follow-up. Method/UNASSIGNED:We performed a retrospective review of our CAS database for patients who underwent stent-supported carotid revascularization in the setting of acute/subacute stroke or TIA. We reviewed clinical and radiographic data during a 36-month period. Primary outcome was clinical evidence of ipsilateral stroke in the first 30 days. Secondary outcomes include clinical outcomes and sonographic and/or angiographic follow-up over 6 months, 6-month functional scale, and all-cause mortality. Results/UNASSIGNED:Fifty-five patients underwent CAS using flow reversal: 26 females and 29 males with a mean age of 69.7 years. Median time to treatment from index event was 3 days. 11% underwent stenting as part of hyperacute stroke therapy. Average luminal stenosis was 86%. The 9-Fr Mo.Ma device was used in combination with Penumbra aspiration in all cases. There were no ipsilateral strokes. Incidence of any ischemic event was 3.64%, but only 1 (1.82%) patient had a postoperative stroke. Clinical follow-up was available for 94.5%, while lesion follow-up was available for 73% of patients. Three patients had evidence of restenosis, but none were symptomatic. Luminal restenosis was ≤30% in all three. Median pre- and post-NIHSS were 1 and 1, respectively. Conclusion/UNASSIGNED:Flow reversal using the Mo.Ma device is a safe and effective strategy in preventing distal embolization during carotid artery revascularization.

OBJECTIVES/OBJECTIVE:This study aims to investigate the role and mechanism of FGFR3 in macrophages and their biological effects on the pathology of arthritis. METHODS:Mice with conditional knockout of FGFR3 in myeloid cells (R3cKO) were generated. Gait behaviours of the mice were monitored at different ages. Spontaneous synovial joint destruction was evaluated by digital radiographic imaging and μCT analysis; changes of articular cartilage and synovitis were determined by histological analysis. The recruitment of macrophages in the synovium was examined by immunostaining and monocyte trafficking assay. RNA-seq analysis, Western blotting and chemotaxis experiment were performed on control and FGFR3-deficient macrophages. The peripheral blood from non-osteoarthritis (OA) donors and patients with OA were analysed. Mice were treated with neutralising antibody against CXCR7 to investigate the role of CXCR7 in arthritis. RESULTS:R3cKO mice but not control mice developed spontaneous cartilage destruction in multiple synovial joints at the age of 13 months. Moreover, the synovitis and macrophage accumulation were observed in the joints of 9-month-old R3cKO mice when the articular cartilage was not grossly destructed. FGFR3 deficiency in myeloid cells also aggravated joint destruction in DMM mouse model. Mechanically, FGFR3 deficiency promoted macrophage chemotaxis partly through activation of NF-κB/CXCR7 pathway. Inhibition of CXCR7 could significantly reverse FGFR3-deficiency-enhanced macrophage chemotaxis and the arthritic phenotype in R3cKO mice. CONCLUSIONS:Our study identifies the role of FGFR3 in synovial macrophage recruitment and synovitis, which provides a new insight into the pathological mechanisms of inflammation-related arthritis.

INTRODUCTION:There is little data on the cost of treating brain arteriovenous malformations (AVMs). The goal of this study then is to identify cost determinants in multimodal management of brain AVMs. METHODS:One hundred forty patients with brain AVMs prospectively enrolled in the UCSF brain AVM registry and treated between 2012 and 2015 were included in the study. Patient and AVM characteristics, treatment type, and length of stay and radiographic evidence of obliteration were collected from the registry. We then calculated the cost of all inpatient and outpatient encounters, interventions, and imaging attributable to the AVM. We used generalized linear models to test whether there was an association between patient and AVM characteristics, treatment type, and cost and length of stay. We tested whether the proportion of patients with radiographic evidence of obliteration differed between treatment modalities using Fisher's exact test. RESULTS:The overall median cost of treatment and interquartile range was $77,865 (49,566-107,448). Surgery with preoperative embolization was the costliest treatment at $91,948 (79,914-140,600), while radiosurgery was the least at $20,917 (13,915-35,583). In multi-predictor analyses, hemorrhage, Spetzler-Martin grade, and treatment type were significant predictors of cost. Patients who had surgery had significantly higher rates of obliteration compared with radiosurgery patients. CONCLUSIONS:Hemorrhage, AVM grade, and treatment modality are significant cost determinants in AVM management. Surgery with preoperative embolization was the costliest treatment and radiosurgery the least; however, surgical cases had significantly higher rates of obliteration.