Norm conflicts and epistemic modals.

Statements containing epistemic modals (e.g., "by spring 2023 most European countries may have the Covid-19 pandemic under control") are common expressions of epistemic uncertainty. In this paper, previous published findings (Knobe & Yalcin, 2014; Khoo & Phillips, 2018) on the opposition between Contextualism and Relativism for epistemic modals are re-examined. It is found that these findings contain a substantial degree of individual variation. To investigate whether participants differ in their interpretations of epistemic modals, an experiment with multiple phases and sessions is conducted to classify participants according to the three semantic theories of Relativism, Contextualism, and Objectivism. Through this study, some of the first empirical evidence for the kind of truth-value shifts postulated by semantic Relativism is presented. It is furthermore found that participants' disagreement judgments match their truth evaluations and that participants are capable of distinguishing between truth and justification. In a second experimental session, it is investigated whether participants thus classified follow the norm of retraction which Relativism uses to account for argumentation with epistemic modals. Here the results are less favorable for Relativism. In a second experiment, these results are replicated and the normative beliefs of participants concerning the norm of retraction are investigated following work on measuring norms by Bicchieri (2017). Again, it is found that on average participants show no strong preferences concerning the norm of retraction for epistemic modals. Yet, it was found that participants who had committed to Objectivism and had training in logic applied the norm of retraction to might-statements. These results present a substantial challenge to the account of argumentation with epistemic modals presented in MacFarlane (2014), as discussed.

Navigating a medical mystery in an elite athlete-severe dystonia induced by swimming.

Dystonia is a state of involuntary muscle contractions that cause repetitive or twisting movements. It may affect one or more parts of the body and sometimes the entire body. The condition can be mild or severe. In this unusual case, high-intensity swimming triggered the episodes of atypical functional movement disorder.

Neurosurgical Causes of Pulsatile Tinnitus: Contemporary Update.

Traditionally in the domain of the otolaryngologist, pulsatile tinnitus (PT) has become increasingly relevant to neurosurgeons. PT may prove to be a harbinger of life-threatening pathology; however, often, it is a marker of a more benign process. Irrespectively, the neurosurgeon should be familiar with the many potential etiologies of this unique and challenging patient population. In this review, we discuss the myriad causes of PT, categorized by pulse-phase rhythmicity.

Pivotal trial of the Neuroform Atlas stent for treatment of posterior circulation aneurysms: one-year outcomes.

BACKGROUND: Stent-assisted coiling of wide-necked intracranial aneurysms (IAs) using the Neuroform Atlas Stent System (Atlas) has shown promising results. OBJECTIVE: To present the primary efficacy and safety results of the ATLAS Investigational Device Exemption (IDE) trial in a cohort of patients with posterior circulation IAs. METHODS: The ATLAS trial is a prospective, multicenter, single-arm, open-label study of unruptured, wide-necked, IAs treated with the Atlas stent and adjunctive coiling. This study reports the results of patients with posterior circulation IAs. The primary efficacy endpoint was complete aneurysm occlusion (Raymond-Roy (RR) class I) on 12-month angiography, in the absence of re-treatment or parent artery stenosis >50%. The primary safety endpoint was any major ipsilateral stroke or neurological death within 12 months. Adjudication of the primary endpoints was performed by an imaging core laboratory and a Clinical Events Committee. RESULTS: The ATLAS trial enrolled and treated 116 patients at 25 medical centers with unruptured, wide-necked, posterior circulation IAs (mean age 60.2±10.5 years, 81.0% (94/116) female). Stents were placed in all patients with 100% technical success rate. A total of 95/116 (81.9%) patients had complete angiographic follow-up at 12 months, of whom 81 (85.3%) had complete aneurysm occlusion (RR class I). The primary effectiveness outcome was achieved in 76.7% (95% CI 67.0% to 86.5%) of patients. Overall, major ipsilateral stroke and secondary persistent neurological deficit occurred in 4.3% (5/116) and 1.7% (2/116) of patients, respectively. CONCLUSIONS: In the ATLAS IDE posterior circulation cohort, the Neuroform Atlas Stent System with adjunctive coiling demonstrated high rates of technical and safety performance. Trial registration number https://clinicaltrials.gov/ct2/show/NCT02340585.

First-Line Stent Retriever versus Direct Aspiration for Acute Basilar Artery Occlusions: A Systematic Review and Meta-analysis.

BACKGROUND: Mechanical thrombectomy (MT) for anterior circulation stroke has been proven to be highly effective. In comparison, MT for basilar artery occlusion (BAO) continues to lack definitive evidence of efficacy. The main MT modalities are stent retriever (SR) and direct aspiration (DA). Several studies have been published comparing the 2 approaches. OBJECTIVE: We sought to directly compare and synthesize safety and efficacy outcomes with SR versus DA for acute BAO. METHODS: A systematic review and meta-analysis was conducted according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. RESULTS: Overall, 8 studies comprising 693 patients with BAO were included (SR: 457; DA: 236). The SR group was associated with statistically significant lower odds of modified Thrombolysis in Cerebral Infarction (mTICI) 2b/3 (odds ratio [OR]: 0.54; 95% confidence interval [CI]: 0.31-0.94) and mTICI3 (OR: 0.47; 95% CI: 0.23-0.95) compared with DA. Favorable outcome rates were similar between the 2 groups (OR: 0.83; 95% CI: 0.60-1.16). The rates of symptomatic intracerebral hemorrhage (OR: 3.57; 95% CI: 0.75-16.95), subarachnoid hemorrhage (SAH) (OR: 4.71; 95% CI: 0.82-26.90), and vessel perforation (OR: 2.64; 95% CI: 0.43-16.33) were higher in the SR group, but statistical significance was not reached. The rates of 90-day mortality were similar between the 2 groups (OR: 1.07; 95% CI: 0.67-1.70). Procedure duration was significantly shorter when DA was used compared with SR (weighted mean difference: 26.10 minutes; 95% CI: 13.28-38.92). CONCLUSIONS: SR is associated with statistically significant lower odds of mTICI 2b/3 and mTICI 3 recanalization rates compared with DA. SR appears to be associated with a higher complication rate, but significance was not reached.

A Consensus Study: Generational Differences in Neurosurgeons' Perception of Retirement and Practice Limits.

BACKGROUND: Concerns about the changing demographics in the United States and the aging of the neurosurgical workforce exist. Both the importance and inherent risk of surgical responsibilities suggest that thought be given to whether workloads should change later in surgeons' careers. We sought to assess current neurosurgeons' expectations concerning their late-stage careers. METHODS: A survey was sent to 3317 U.S. board-certified neurosurgeons. It was designed to assess surgeons' perceptions of call and operative responsibilities in the later stages of their careers. Statistical analyses were completed in R version 3.6.1, with an alpha set to 0.05. RESULTS: Six-hundred and fifty-nine neurosurgeons completed the questionnaire. Seventy-seven percent believed that the call burden should decrease later in practice, and 66% planned to decrease their own call burden later in their career. The most common age range for planned retirement was 65 to 69 years (36%), followed by 70+ years (33%). Most (67%) believed that there should not be a mandatory age to stop operating. More recent year of residency completion was negatively associated with the belief that call burden should decrease at older age groups and positively associated with support for a mandatory age to stop operating as well as an earlier retirement age. CONCLUSIONS: This study suggests that neurosurgeons have differing views on how workloads should change later in their careers. Younger neurosurgeons support an earlier decrease in workload or even a policy-mandated stop to operating after a certain age. These results may give insight into future trends and turnover in neurosurgery and provide a valuable tool to help practices anticipate workforce changes.

Neuroform Atlas Stent for Treatment of Middle Cerebral Artery Aneurysms: 1-Year Outcomes From Neuroform Atlas Stent Pivotal Trial.

BACKGROUND: Heterogeneous effect of endovascular aneurysm therapy has been observed across different anatomic locations. There is a paucity of data for stent-assisted coiling of middle cerebral artery (MCA) aneurysms. OBJECTIVE: To present the results of the MCA aneurysm group from the Neuroform Atlas (Stryker Neurovascular) investigational device exemption (IDE) trial. METHODS: The Atlas IDE trial is a prospective, multicenter, single-arm, open-label study of wide-neck aneurysms (neck ≥ 4 mm or dome-to-neck ratio < 2) in the anterior circulation treated with the Neuroform Atlas Stent and approved coils. Follow-up was obtained immediately postprocedure and 2, 6, and 12 mo postoperatively. We herein describe safety and efficacy outcomes, and functional independence of the subjects with aneurysms from all segments of MCA. RESULTS: A total of 35 patients were included (27 MCA bifurcation, 5 M1, 3 M2). The mean aneurysm size was 6.0 ± 1.8 mm, and the mean neck was 4.4 ± 1.2 mm. Technical procedural success was achieved in all patients. A total of 26 patients had follow-up digital subtraction angiography available at 12 mo, with 80.8% (21/26) having complete aneurysm occlusion. Twelve-month safety data were collected for 91.4% (32/35), 8.5% (3/35) had primary safety endpoint, all 3 major ischemic strokes. Mortality occurred in 2 patients beyond 30 d unrelated to procedure (1 gallbladder cancer and 1 fentanyl intoxication). At 1 yr, modified Rankin Score was 0 to 2 in 84.4% (27/32), 3 in 9.4%, and 3 patients were missing. Approximately 5.7% (2/35) of patients were retreated at 12 mo. CONCLUSION: Stent-assisted coiling with the Neuroform Atlas Stent is a viable alternative to clipping for selected MCA aneurysms. Complete aneurysm occlusion rates have improved compared to historical data. Proper case selection can lead to acceptable endovascular results.

Carotid cavernous fistula (CCF) treatment approaches: A systematic literature review and meta-analysis of transarterial and transvenous embolization for direct and indirect CCFs.

BACKGROUND: Carotid Cavernous Fistulas (CCFs) are the result of an abnormal communication between the carotid artery and its branches and the venous system of the cavernous sinus. The mainstay of therapy for CCFs consists of transarterial or transvenous embolization, while other treatment options such as open surgery or radiosurgery are still utilized as second-line or adjuvant therapeutic options. OBJECTIVE: Our aim was to systematically review and summarize available data regarding short- and long-term outcomes of all available treatment modalities for CCFs. METHODS: This systematic review was conducted according to the PRISMA guidelines. A random effects model meta-analysis was conducted. RESULTS: Fifty-seven studies comprising 1575 patients were included in this systematic review. Transarterial embolization for direct and indirect CCFs offered a complete obliteration rate of 93.93% (N = 589/627) and 81.51% (N = 119/146), respectively. Transvenous embolization for direct and indirect lesions achieved obliteration in 91.67% (N = 33/36) and 86.03% (N = 425/494) of patients, respectively. Comparison between transarterial and transvenous embolization did not reveal statistically significant differences in terms of fistula obliteration for direct (OR: 1.42; 95% CI: 0.23-8.90; I2 0.0%) and indirect CCFs (OR: 0.62; 95% CI: 0.31-1.23; I2 0.0%). CONCLUSIONS: Endovascular embolization techniques are the preferred treatment modality for the management of CCFs. No differences were identified between transarterial and transvenous embolization by synthesizing studies with available data. Future prospective cohorts are warranted to compare the different materials and techniques implemented especially within the rapidly expanding realm of endovascular approaches.

The local co-evolution of firms and governments in the Information Age.

The governance structures of the value-creating activities of MNEs have evolved towards more networked forms that are geographically highly concentrated and involve partnering with diverse actors. The experimentation that takes place within these corporate networks has a parallel on the government side, where subnational governments, and particularly cities as hubs of economic activity, have increased their profile and level of cooperative activity. We argue that engagement in these partnerships is an essential way in which firms and governments co-evolve and create the basis for sustainable economic growth in the Information Age. While the origins of this collaborative form of governance reside in the increasing knowledge intensity of value creation, its implications go far beyond MNE value creation and capture, extending to issues of global governance such as climate change and sustainable development goals. We examine the implications of this process of co-evolution both in terms of the costs of developing the requisite corporate capabilities as well as the legitimacy of these efforts as part of a deliberative democracy.

Les structures de gouvernance des activités de création de valeur des EMN ont évolué vers des formes plus réticulaires qui sont géographiquement très concentrées et qui impliquent des partenariats avec divers acteurs. L'expérimentation qui a lieu au sein de ces réseaux d'entreprises a un parallèle du côté gouvernemental, où les gouvernements infranationaux, et en particulier les villes en tant que centres d'activité économique, ont accru leur profil et leur niveau d'activité coopérative. Nous soutenons que l'engagement dans ces partenariats est un moyen essentiel pour les entreprises et les gouvernements de co-évoluer et de créer les bases d'une croissance économique durable à l'ère de l'information. Bien que les origines de cette forme de gouvernance collaborative résident dans l'intensité croissante des connaissances en matière de création de valeur, ses implications vont bien au-delà de la création et de la récupération de valeur par les EMN, s'étendant aux questions de gouvernance mondiale telles que le changement climatique et les objectifs de développement durable. Nous examinons les implications de ce processus de co-évolution à la fois en termes de coûts de développement des capacités d'entreprise requises, ainsi que de légitimité de ces efforts dans le cadre d'une démocratie délibérative.

Las estructuras de gobernanza en las actividades de creación de valor de las empresas multinacionales han evolucionado hacia formas más interconectadas que están altamente concentradas geográficamente y que implican asociarse con diversos actores. La experimentación que se lleva a cabo dentro de estas redes corporativas tiene un paralelo con el lado gubernamental en donde los gobiernos sub-nacionales, y en particular las ciudades como centros de actividad económica, han aumentado su perfil y nivel de actividad cooperativa. Argumentamos que la participación en estas asociaciones es una manera esencial en que las empresas y los gobiernos co-evolucionan y crean las bases para el crecimiento económico sostenible en la Era de la Información. Mientras que los orígenes de esta forma colaborativa de gobernanza residen en la creciente intensidad de conocimiento de la creación de valor, sus implicaciones van más allá de la creación y captura de valor de las empresas multinacionales, extendiéndose a los asuntos de gobernanza global como son el cambio climático y los objetivos de desarrollo sostenible. Examinamos las implicaciones de este proceso de co-evolución tanto en términos de los costos de desarrollar las capacidades corporativas necesarias, como de la legitimidad de estos esfuerzos como parte de una democracia deliberativa.

As estruturas de governança das atividades de criação de valor de MNEs evoluíram para formas mais interligadas que são geograficamente altamente concentradas e que envolvem parcerias com diversos atores. A experimentação que ocorre dentro dessas redes empresariais tem um paralelo no lado governamental, onde governos subnacionais, e particularmente cidades como pólos de atividade econômica, têm aumentado seu perfil e nível de atividade cooperativa. Argumentamos que o envolvimento nessas parcerias é uma forma essencial pela qual empresas e governos coevoluem e criam a base para crescimento econômico sustentável na Era da Informação. Embora as origens dessa forma colaborativa de governança residam na crescente intensidade de conhecimento da criação de valor, suas implicações vão muito além da criação e captura de valor da MNE, estendendo-se a questões de governança global, como mudanças climáticas e metas de desenvolvimento sustentável. Examinamos as implicações desse processo de coevolução, tanto em termos dos custos de desenvolvimento das capacidades corporativas necessárias, como da legitimidade desses esforços como parte de uma democracia deliberativa.

Biochemical Characterization of Respiratory Syncytial Virus RNA-Dependent RNA Polymerase Complex.

RNA-dependent RNA polymerases (RdRPs) from nonsegmented negative strand (NNS) RNA viruses perform both mRNA transcription and genome replication, and these activities are regulated by their interactions with RNA and other accessory proteins within the ribonucleoprotein (RNP) complex. Detailed biochemical characterization of these enzymatic activities and their regulation is essential for understanding the life cycles of many pathogenic RNA viruses and for antiviral drug discovery. We developed biochemical and biophysical kinetic methods to study the RNA synthesis and RNA binding activities of respiratory syncytial virus (RSV) L/P RdRP. We determined that the intact L protein is essential for RdRP activity, and in truncated L protein constructs, RdRP activity is abrogated due to their deficiency in RNA template binding. These results are in agreement with the observation of an RNA template-binding tunnel at the interface of RdRP and capping domains in RSV and vesicular stomatitis virus (VSV) L protein cryo-EM structures. We also describe nonradiometric assays for measuring RNA binding and RNA polymerization activity of RSV RdRP, which are amenable to compound screening and profiling.