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Metaphysics asks questions about existence: for example, do numbers really exist? Metametaphysics asks questions about metaphysics: for example, do its questions have determinate answers? If so, are these answers deep and important, or are they merely a matter of how we use words? What is the proper methodology for their resolution? These questions have received a heightened degree of attention lately with new varieties of ontological deflationism and pluralism challenging the kind of realism that has become orthodoxy in contemporary analytic metaphysics. This volume concerns the status and ambitions of metaphysics as a discipline. It brings together many of the central figures in the debate with their most recent work on the semantics, epistemology, and methodology of metaphysics.

Background Management algorithms for adult severe traumatic brain injury (sTBI) were omitted in later editions of the Brain Trauma Foundation’s sTBI Management Guidelines, as they were not evidence-based. Methods We used a Delphi-method-based consensus approach to address management of sTBI patients undergoing intracranial pressure (ICP) monitoring. Forty-two experienced, clinically active sTBI specialists from six continents comprised the panel. Eight surveys iterated queries and comments. An in-person meeting included whole- and small-group discussions and blinded voting. Consensus required 80% agreement. We developed heatmaps based on a traffic-light model where panelists’ decision tendencies were the focus of recommendations. Results We provide comprehensive algorithms for ICP-monitor-based adult sTBI management. Consensus established 18 interventions as fundamental and ten treatments not to be used. We provide a three-tier algorithm for treating elevated ICP. Treatments within a tier are considered empirically equivalent. Higher tiers involve higher risk therapies. Tiers 1, 2, and 3 include 10, 4, and 3 interventions, respectively. We include inter-tier considerations, and recommendations for critical neuroworsening to assist the recognition and treatment of declining patients. Novel elements include guidance for autoregulation-based ICP treatment based on MAP Challenge results, and two heatmaps to guide (1) ICP-monitor removal and (2) consideration of sedation holidays for neurological examination. Conclusions Our modern and comprehensive sTBI-management protocol is designed to assist clinicians managing sTBI patients monitored with ICP-monitors alone. Consensus-based (class III evidence), it provides management recommendations based on combined expert opinion. It reflects neither a standard-of-care nor a substitute for thoughtful individualized management.

In this phase 3 trial, progesterone had no benefit as a neuroprotective agent in patients with blunt traumatic brain injury. Together with a second negative clinical trial of progesterone for acute TBI (SYNAPSE), the findings provide no support for this therapeutic approach. More than 2.4 million emergency department visits, hospitalizations, or deaths are related to traumatic brain injury (TBI) annually, and approximately 5.3 million Americans are living with disability from TBI. The aggregate annual cost of TBI in the United States now approaches $76.5 billion. 1 Survivors of severe TBI typically require 5 to 10 years of intensive therapy and are often left with substantial disability. 2 Despite decades of research, no pharmacologic agent has been shown to improve outcomes after TBI. Progesterone is a potent neurosteroid synthesized in the central nervous system. Preclinical studies in laboratory animals indicated that the early administration of . . .

Correspondence to Dr Paul McCrory, The Florey Institute of Neuroscience and Mental Health, Heidelberg 3084, Victoria, Australia; paulmccrory@icloud.com Preamble The 2017 Concussion in Sport Group (CISG) consensus statement is designed to build on the principles outlined in the previous statements1–4 and to develop further conceptual understanding of sport-related concussion (SRC) using an expert consensus-based approach. First and foremost, this document is intended to guide clinical practice; however, the authors feel that it can also help form the agenda for future research relevant to SRC by identifying knowledge gaps. At present, there is no perfect diagnostic test or marker that clinicians can rely on for an immediate diagnosis of SRC in the sporting environment. Because of this evolving process, it is not possible to rule out SRC when an injury event occurs associated with a transient neurological symptom. [...]tests include the SCAT5, which incorporates the Maddocks' questions6 7 and the Standardised Assessment of Concussion (SAC).8–10 It is worth noting that standard orientation questions (eg, time, place, person) are unreliable in the sporting situation when compared with memory assessment.7 11 It is recognised, however, that abbreviated testing paradigms are designed for rapid SRC screening on the sidelines and are not meant to replace a comprehensive neurological evaluation; nor should they be used as a standalone tool for the ongoing management of SRC.

BackgroundCurrent guidelines for the treatment of adult severe traumatic brain injury (sTBI) consist of high-quality evidence reports, but they are no longer accompanied by management protocols, as these require expert opinion to bridge the gap between published evidence and patient care. We aimed to establish a modern sTBI protocol for adult patients with both intracranial pressure (ICP) and brain oxygen monitors in place.MethodsOur consensus working group consisted of 42 experienced and actively practicing sTBI opinion leaders from six continents. Having previously established a protocol for the treatment of patients with ICP monitoring alone, we addressed patients who have a brain oxygen monitor in addition to an ICP monitor. The management protocols were developed through a Delphi-method-based consensus approach and were finalized at an in-person meeting.ResultsWe established three distinct treatment protocols, each with three tiers whereby higher tiers involve therapies with higher risk. One protocol addresses the management of ICP elevation when brain oxygenation is normal. A second addresses management of brain hypoxia with normal ICP. The third protocol addresses the situation when both intracranial hypertension and brain hypoxia are present. The panel considered issues pertaining to blood transfusion and ventilator management when designing the different algorithms.ConclusionsThese protocols are intended to assist clinicians in the management of patients with both ICP and brain oxygen monitors but they do not reflect either a standard-of-care or a substitute for thoughtful individualized management. These protocols should be used in conjunction with recommendations for basic care, management of critical neuroworsening and weaning treatment recently published in conjunction with the Seattle International Brain Injury Consensus Conference.

What ties these three essays of together is not that they support a single idea, but that they all grew out of reflections on a single idea, and they all involve applications of it. The guiding principle is that there are knowledge-undermining dangers for a belief that p beyond the threat of false belief that p, such as the danger of having a similar and false belief with a different content, and the danger of failing to believe anything at all. Each of the essays involves applications of this theme. Essay 1 begins by motivating a revision to the standard account of safety, and then applies the result to problems about a priori knowledge, including privileged access and KK principles. A picture of a priority emerges that allows us to treat 'McKinsey's puzzle' as a standard closure puzzle. Essay 2 explores applications to the issues of analyticity and concept-possession conditions, arguing that a recent approach to analytic knowledge is flawed. Essay 3 uses the new safety condition to examine the threat of contingent a priori knowledge that can arise if we allow the introduction of names by description. I conclude that this threat provides no reason to adopt an acquaintance constraint on singular thought.

BACKGROUND:Conventional management for concussion involves prescribed rest and progressive return to activity. Recent evidence challenges this notion and suggests that active approaches may be effective for some patients. Previous concussion consensus statements provide limited guidance regarding active treatment. OBJECTIVE:To describe the current landscape of treatment for concussion and to provide summary agreements related to treatment to assist clinicians in the treatment of concussion. METHODS:On October 14 to 16, 2015, the Targeted Evaluation and Active Management (TEAM) Approaches to Treating Concussion meeting was convened in Pittsburgh, Pennsylvania. Thirty-seven concussion experts from neuropsychology, neurology, neurosurgery, sports medicine, physical medicine and rehabilitation, physical therapy, athletic training, and research and 12 individuals representing sport, military, and public health organizations attended the meeting. The 37 experts indicated their agreement on a series of statements using an audience response system clicker device. RESULTS:A total of 16 statements of agreement were supported covering (1) Summary of the Current Approach to Treating Concussion, (2) Heterogeneity and Evolving Clinical Profiles of Concussion, (3) TEAM Approach to Concussion TreatmentSpecific Strategies, and (4) Future DirectionsA Call to Research. Support (ie, response of agree or somewhat agree) for the statements ranged from to 97% to 100%. CONCLUSION:Concussions are characterized by diverse symptoms and impairments and evolving clinical profiles; recovery varies on the basis of modifying factors, injury severity, and treatments. Active and targeted treatments may enhance recovery after concussion. Research is needed on concussion clinical profiles, biomarkers, and the effectiveness and timing of treatments. ABBREVIATIONS:ARS, audience response systemCDC, Centers for Disease Control and PreventionDoD, Department of DefensemTBI, mild traumatic brain injuryNCAA, National Collegiate Athletic AssociationNFL, National Football LeagueNIH, National Institutes of HealthRCT, randomized controlled trialRTP, return to playSRC, sport- and recreation-related concussionTBI, traumatic brain injuryTEAM, Targeted Evaluation and Active Management

Knowledge of differences in mild traumatic brain injury (mTBI) recovery by sex and age may inform individualized treatment of these patients. To identify sex-related differences in symptom recovery from mTBI; secondarily, to explore age differences within women, who demonstrate poorer outcomes after TBI. The prospective cohort study Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) recruited 2000 patients with mTBI from February 26, 2014, to July 3, 2018, and 299 patients with orthopedic trauma (who served as controls) from January 26, 2016, to July 27, 2018. Patients were recruited from 18 level I trauma centers and followed up for 12 months. Data were analyzed from August 19, 2020, to March 3, 2021. Patients with mTBI (defined by a Glasgow Coma Scale score of 13-15) triaged to head computed tomography in 24 hours or less; patients with orthopedic trauma served as controls. Measured outcomes included (1) the Rivermead Post Concussion Symptoms Questionnaire (RPQ), a 16-item self-report scale that assesses postconcussion symptom severity over the past 7 days relative to preinjury; (2) the Posttraumatic Stress Disorder Checklist for the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) (PCL-5), a 20-item test that measures the severity of posttraumatic stress disorder symptoms; (3) the Patient Health Questionnaire-9 (PHQ-9), a 9-item scale that measures depression based on symptom frequency over the past 2 weeks; and (4) the Brief Symptom Inventory-18 (BSI-18), an 18-item scale of psychological distress (split into Depression and Anxiety subscales). A total of 2000 patients with mTBI (1331 men [67%; mean (SD) age, 41.0 (17.3) years; 1026 White (78%)] and 669 women [33%; mean (SD) age, 43.0 (18.5) years; 505 (76%) White]). After adjustment of multiple comparisons, significant TBI × sex interactions were observed for cognitive symptoms (B = 0.76; 5% false discovery rate-corrected P = .02) and somatic RPQ symptoms (B = 0.80; 5% false discovery rate-corrected P = .02), with worse symptoms in women with mTBI than men, but no sex difference in symptoms in control patients with orthopedic trauma. Within the female patients evaluated, there was a significant TBI × age interaction for somatic RPQ symptoms, which were worse in female patients with mTBI aged 35 to 49 years compared with those aged 17 to 34 years (B = 1.65; P = .02) or older than 50 years (B = 1.66; P = .02). This study found that women were more vulnerable than men to persistent mTBI-related cognitive and somatic symptoms, whereas no sex difference in symptom burden was seen after orthopedic injury. Postconcussion symptoms were also worse in women aged 35 to 49 years than in younger and older women, but further investigation is needed to corroborate these findings and to identify the mechanisms involved. Results suggest that individualized clinical management of mTBI should consider sex and age, as some women are especially predisposed to chronic postconcussion symptoms even 12 months after injury.

BackgroundTwo randomised trials assessing the effectiveness of decompressive craniectomy (DC) following traumatic brain injury (TBI) were published in recent years: DECRA in 2011 and RESCUEicp in 2016. As the results have generated debate amongst clinicians and researchers working in the field of TBI worldwide, it was felt necessary to provide general guidance on the use of DC following TBI and identify areas of ongoing uncertainty via a consensus-based approach.MethodsThe International Consensus Meeting on the Role of Decompressive Craniectomy in the Management of Traumatic Brain Injury took place in Cambridge, UK, on the 28th and 29th September 2017. The meeting was jointly organised by the World Federation of Neurosurgical Societies (WFNS), AO/Global Neuro and the NIHR Global Health Research Group on Neurotrauma. Discussions and voting were organised around six pre-specified themes: (1) primary DC for mass lesions, (2) secondary DC for intracranial hypertension, (3) peri-operative care, (4) surgical technique, (5) cranial reconstruction and (6) DC in low- and middle-income countries.ResultsThe invited participants discussed existing published evidence and proposed consensus statements. Statements required an agreement threshold of more than 70% by blinded voting for approval.ConclusionsIn this manuscript, we present the final consensus-based recommendations. We have also identified areas of uncertainty, where further research is required, including the role of primary DC, the role of hinge craniotomy and the optimal timing and material for skull reconstruction.