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The participation of local communities in management decisions is critically important to the long-term salience and therefore, success, of protected areas. Engaging community members in meaningful ways requires knowledge of their behavior and its antecedents, particularly values. Understanding how learning influences cooperation in conservation initiatives is also fundamentally important for supporting decisions being made about public lands. However, there is little empirical evidence of how learning from different information sources works in conjunction with values that shape behavior. Using data from a household survey of residents living in the Denali region of Interior Alaska, U.S, we estimated a two-step structural equation model to understand the psychological reasons why stakeholders made decisions to collectively benefit the environment. Results showed that more diverse pathways by which learning occurred were instrumental in explaining why residents performed pro-environmental behaviors over the past year. Additionally, values that reflected the goals of eudaimonia influenced the transfer and negotiation of knowledge exchange among stakeholders as a correlate of behavior. Environmental concern and personal norms were positively associated with reported behaviors operationalized as social environmentalism and living in an environmentally conscientious manner, whereas environmental concern and willingness to pay for protected area management positively influenced civic engagement. We argue that broadening the range of learning spaces and considering a more diverse array of values in communities surrounding protected areas will encourage daily lifestyle changes, social interactions to support environmentalism, and more robust, pluralistic forms of public engagement in natural resource management.

This dissertation examines sermons delivered by Confessing Church pastors in the Nazi dictatorship. The approach of most historians has focused on the history of the Christian institutions, its leaders, and its persecution by the Nazi regime, leaving the most elemental task of the pastor – that is, preaching – largely unexamined. The question left unaddressed is how well did Confessing pastors fare in articulating their views of the Nazi regime and the persecution of the Jews through their sermons? To answer this question, I analyzed 910 sermons by Confessing Church pastors, all delivered or disseminated between 1933 and the end of World War II in Europe. I argue that new trends in preaching popular among Confessing Church pastors discouraged deviation from the biblical text in sermons, and thus one result was few criticisms concerning German politics and society. Nevertheless, a minority of pastors criticized the Nazi regime and its leaders for their racial ideology and claims of “Aryan” superiority, and also for unjust persecutions against Christians. They condemned Nazism as a morally corrupt ideology in contradiction to Christianity. Further, I argue that these sermons provide mixed messages about Jews and Judaism. While on the one hand, the sermons express admiration for Judaism as a foundation for Christianity and Jews as spiritual cousins; on the other hand, the sermons express religious prejudice in the form of anti-Judaic tropes that corroborated the Nazi ideology that portrayed Jews and Judaism as inferior. In the final section of the dissertation I explore the ministries of German pastors of Jewish descent and argue that they not only experienced persecution from the Nazi state, but also from their own congregations. Nevertheless, the themes of their sermons are consistent with those found in those of their colleagues.My research demonstrates that the German churches were in fact places to offer criticism of the Nazi regime, which was often veiled through biblical imagery and metaphor. Yet the messages reveal criticism from a position of obedience and subservience to the state, and at the same time the expose a confused ambiguity about the Jews and Judaism and their relation to Christians in Nazi Germany.

Perching in unmanned aerial vehicles (UAVs) offers the possibility of extending the range of aerial robots beyond the limits of their batteries. It has been a topic of intense study for multirotor UAVs. Perching in winged UAVs is harder because a kinetic energy balance has to be struck. Reducing too much energy results in the vehicle stalling and falling. Too much kinetic energy at touchdown could damage the vehicle. Most studies used dangerous pitch-up maneuvers to manage this balance. This work presents a system that eliminates the pitch-up maneuver by mechanically capturing and storing kinetic energy at impact. It is validated using a passive mechanical system consisting of a storage mechanism for energy recuperation and a claw for perching on a horizontal rod. The energy stored in the mechanism is then used to unperch. The mathematical model for the recuperation strategy is presented and perching success at various approach attitudes are characterized. The proof-of-concept claw recaptures 5% of the kinetic energy during perching. Experiments indicate that the device can successfully perch at a wide range of yaw angles, but requires more precision in roll. We show that our perching mechanism enables the fastest UAV perching to date (7.4 m s^−1).

Significance Natural carbon sinks can help mitigate climate change, but climate risks—like increased wildfire—threaten forests’ capacity to store carbon. California has recently set ambitious forest management goals to reduce these risks. However, management can incur carbon losses because wood residues are often burnt or left to decay. This study applies a systems approach to assess climate change mitigation potential and wildfire outcomes across forest management scenarios and several wood products. We find that innovative use of wood residues supports extensive wildfire hazard reduction and maximizes carbon benefits. Long-lived products that displace carbon-intensive alternatives have the greatest benefits, including wood building products. Our results suggest a low-cost pathway to reduce carbon emissions and support climate adaptation in temperate forests., Responsible stewardship of temperate forests can address key challenges posed by climate change through sequestering carbon, producing low-carbon products, and mitigating climate risks. Forest thinning and fuel reduction can mitigate climate-related risks like catastrophic wildfire. These treatments are often cost prohibitive, though, in part because of low demand for low-value wood “residues.” Where treatment occurs, this low-value wood is often burned or left to decay, releasing carbon. In this study, we demonstrate that innovative use of low-value wood, with improved potential revenues and carbon benefits, can support economical, carbon-beneficial forest management outcomes in California. With increased demand for wood residues, forest health–oriented thinning could produce up to 7.3 million (M) oven-dry tonnes of forest residues per year, an eightfold increase over current levels. Increased management and wood use could yield net climate benefits between 6.4 and 16.9 million tonnes of carbon dioxide equivalent (M tCO2e) per year when considering impacts from management, wildfire, carbon storage in products, and displacement of fossil carbon-intensive alternatives over a 40-y period. We find that products with durable carbon storage confer the greatest benefits, as well as products that reduce emissions in hard-to-decarbonize sectors like industrial heat. Concurrently, treatment could reduce wildfire hazard on 4.9 M ha (12.1 M ac), a quarter of which could experience stand-replacing effects without treatment. Our results suggest that innovative wood use can support widespread fire hazard mitigation and reduce net CO2 emissions in California.

The Nappi-Witten model is a Wess-Zumino-Witten model in which the target space is the nonreductive Heisenberg group $H_4$. We consider the representation theory underlying this conformal field theory. Specifically, we study the category of weight modules, with finite-dimensional weight spaces, over the associated affine vertex operator algebra $\mathsf{H}_4$. In particular, we classify the irreducible $\mathsf{H}_4$-modules in this category and compute their characters. We moreover observe that this category is nonsemisimple, suggesting that the Nappi-Witten model is a logarithmic conformal field theory., 21 pages; introduction expanded, references added, minor notation changes

Key Points Question What is the association of field position, career length, and playing era with risk of neurodegenerative disease in male former professional soccer players? Findings In this cohort study of 7676 Scottish male former professional soccer players and 23 028 general population control individuals matched by sex, year of birth, and area socioeconomic status, risk of neurodegenerative disease among former soccer players varied by field position and career length but was similar across era of participation. Meaning In this study, risk of neurodegenerative disease was higher among former professional soccer players with longer careers and among those in nongoalkeeper positions, indicating that factors associated with nongoalkeeper positions should be scrutinized to mitigate risk; meanwhile, strategies to reduce head impact exposure may be advisable to reduce negative outcomes in this population., This cohort study investigates the association of field position, professional career length, and playing era with risk of neurodegenerative disease among Scottish male former professional soccer players., Importance Neurodegenerative disease mortality is higher among former professional soccer players than general population controls. However, the factors contributing to increased neurodegenerative disease mortality in this population remain uncertain. Objective To investigate the association of field position, professional career length, and playing era with risk of neurodegenerative disease among male former professional soccer players. Design, Setting, and Participants This cohort study used population-based health record linkage in Scotland to evaluate risk among 7676 male former professional soccer players born between January 1, 1900, and January 1, 1977, and 23 028 general population control individuals matched by year of birth, sex, and area socioeconomic status providing 1 812 722 person-years of follow-up. Scottish Morbidity Record and death certification data were available from January 1, 1981, to December 31, 2016, and prescribing data were available from January 1, 2009, to December 31, 2016. Database interrogation was performed on December 10, 2018, and data were analyzed between April 2020 and May 2021. Exposures Participation in men’s soccer at a professional level. Main Outcomes and Measures Outcomes were obtained by individual-level record linkage to national electronic records of mental health and general hospital inpatient and day-case admissions as well as prescribing information and death certification. Risk of neurodegenerative disease was evaluated between former professional soccer players and matched general population control individuals. Results In this cohort study of 30 704 male individuals, 386 of 7676 former soccer players (5.0%) and 366 of 23 028 matched population control individuals (1.6%) were identified with a neurodegenerative disease diagnosis (hazard ratio [HR], 3.66; 95% CI, 2.88-4.65; P

BackgroundFatigue is one of the most commonly reported subjective symptoms following traumatic brain injury (TBI). The aims were to assess frequency of fatigue over the first 6 months after TBI, and examine whether fatigue changes could be predicted by demographic characteristics, injury severity and comorbidities.MethodsPatients with acute TBI admitted to 65 trauma centers were enrolled in the study Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI). Subjective fatigue was measured by single item on the Rivermead Post-Concussion Symptoms Questionnaire (RPQ), administered at baseline, three and 6 months postinjury. Patients were categorized by clinical care pathway: admitted to an emergency room (ER), a ward (ADM) or an intensive care unit (ICU). Injury severity, preinjury somatic- and psychiatric conditions, depressive and sleep problems were registered at baseline. For prediction of fatigue changes, descriptive statistics and mixed effect logistic regression analysis are reported.ResultsFatigue was experienced by 47% of patients at baseline, 48% at 3 months and 46% at 6 months. Patients admitted to ICU had a higher probability of experiencing fatigue than those in ER and ADM strata. Females and individuals with lower age, higher education, more severe intracranial injury, preinjury somatic and psychiatric conditions, sleep disturbance and feeling depressed postinjury had a higher probability of fatigue.ConclusionA high and stable frequency of fatigue was found during the first 6 months after TBI. Specific socio-demographic factors, comorbidities and injury severity characteristics were predictors of fatigue in this study.

The suspension of international student mobility programs has been common due to COVID-19. In the Republic of Korea, the successful management of the pandemic allowed borders to remain open and mobility to continue. In Spring 2020, however, the Korean government started requiring quarantine-upon-arrival for all inbound travel; the sudden announcement created confusion. The Fall semester would see students arrive with no knowledge of how quarantines would work or in what ways the isolation period might affect them. Student motivations for exchanges during a global pandemic with increased health risks, mobility obstacles, and stresses were unknown. This case study reports the arrival/quarantine experiences of 10 exchange students in Seoul, Korea. Students’ views and expectations of Korea as a safe study destination were juxtaposed with tumultuous arrival experiences. We discuss these findings in terms of the academic exchange life cycle and the importance of resource/service accessibility amid novel pandemic-based norms.

IDH wild-type glioblastoma (GBM) is the most prevalent malignant primary brain tumour in adults. GBM typically has a poor prognosis, mainly due to a lack of effective treatment options leading to tumour persistence or recurrence. Tackling this, we investigated the therapeutic potential of targeting anti-apoptotic BCL-2 proteins in GBM. Levels of anti- apoptotic BCL-xL and MCL-1 were consistently increased in GBM compared with non- malignant cells and tissue. Moreover, we found that relative to their differentiated counterparts, patient-derived GBM stem-like cells also displayed higher expression of anti- apoptotic BCL-2 family members. Surprisingly, high anti-apoptotic BCL-xL and MCL-1 expression correlated with heightened susceptibility of GBM to BCL-2 family protein- targeting BH3-mimetics. This is indicative of increased apoptotic priming. Indeed, GBM displayed an obligate requirement for MCL-1 expression in both tumour development and maintenance. Investigating this apoptotic sensitivity, we found that sequential inhibition of BCL-xL and MCL-1 led to robust anti-tumour responses in vivo, in the absence of overt toxicity. These data demonstrate that BCL-xL and MCL-1 pro-survival function is a fundamental prerequisite for GBM survival that can be therapeutically exploited by BH3- mimetics.

Background: The burden of traumatic brain injury (TBI) poses a large public health and societal problem, but the characteristics of patients and their care pathways in Europe are poorly understood. We aimed to characterise patient case-mix, care pathways, and outcomes of TBI. Methods: CENTER-TBI is a Europe-based, observational cohort study, consisting of a core study and a registry. Inclusion criteria for the core study were a clinical diagnosis of TBI, presentation fewer than 24 h after injury, and an indication for CT. Patients were differentiated by care pathway and assigned to the emergency room (ER) stratum (patients who were discharged from an emergency room), admission stratum (patients who were admitted to a hospital ward), or intensive care unit (ICU) stratum (patients who were admitted to the ICU). Neuroimages and biospecimens were stored in repositories and outcome was assessed at 6 months after injury. We used the IMPACT core model for estimating the expected mortality and proportion with unfavourable Glasgow Outcome Scale Extended (GOSE) outcomes in patients with moderate or severe TBI (Glasgow Coma Scale [GCS] score ≤12). The core study was registered with ClinicalTrials.gov, number NCT02210221, and with Resource Identification Portal (RRID: SCR_015582). Findings: Data from 4509 patients from 18 countries, collected between Dec 9, 2014, and Dec 17, 2017, were analysed in the core study and from 22 782 patients in the registry. In the core study, 848 (19%) patients were in the ER stratum, 1523 (34%) in the admission stratum, and 2138 (47%) in the ICU stratum. In the ICU stratum, 720 (36%) patients had mild TBI (GCS score 13–15). Compared with the core cohort, the registry had a higher proportion of patients in the ER (9839 [43%]) and admission (8571 [38%]) strata, with more than 95% of patients classified as having mild TBI. Patients in the core study were older than those in previous studies (median age 50 years [IQR 30–66], 1254 [28%] aged >65 years), 462 (11%) had serious comorbidities, 772 (18%) were taking anticoagulant or antiplatelet medication, and alcohol was contributory in 1054 (25%) TBIs. MRI and blood biomarker measurement enhanced characterisation of injury severity and type. Substantial inter-country differences existed in care pathways and practice. Incomplete recovery at 6 months (GOSE

Socioeconomic and racial-ethnic inequities in access to recreation settings are widely considered environmental justice (EJ) issues. Researchers in leisure, geography, urban planning, and other dis...

Increasing the capacity of communities on the rural-urban fringe to accommodate sustainable growth is a key concern among resource management agencies. Decisions about the future of these landscapes involve difficult tradeoffs that underscore the importance of incorporating diverse stakeholder values and preferences into planning efforts. We assessed residents’ preferences for exurban growth alternatives in two Midwestern U.S. counties – Jasper County, IA and Will County, IL – that have strong agrarian roots and lie at the fringe of rapidly-expanding metropolitan areas. Using a choice model, we identified how six landscape characteristics influenced respondents’ stated choices for growth scenarios. Informed by previous research, focus groups, and pilot testing, our final model evaluated preferences for residential growth, protected grasslands, recreation, agriculture, bison reintroduction, and unemployment. Results from a county-wide survey mailed to 3000 residents (final N = 889) indicated that five of the six landscape-scale attributes significantly influenced residents’ choices. Increased residential growth, more protected grasslands and agricultural lands, and greater access to recreation positively predicted choices for hypothetical growth scenarios while residents preferred future scenarios with low levels of unemployment. Further, the strength of preferences for these land use and economic conditions differed between Jasper and Will County residents. The study findings aid decision makers who face growth and urbanization pressures and provide insight on how to integrate preferences of current residents into planning decisions at a regional scale.

This study sought to explore the implications for individuals who experienced awe while in the presence of wildlife. A conceptual framework was adapted that integrated the theory of emotional learn...

Chronic traumatic encephalopathy (CTE) is reported at high prevalence in selected autopsy case series of former contact sports athletes. Nevertheless, the contribution of CTE pathology to clinical presentation and its interaction with co-morbid neurodegenerative pathologies remain unclear. To address these issues, we performed comprehensive neuropathology assessments on the brains of former athletes with dementia and considered these findings together with detailed clinical histories to derive an integrated clinicopathological diagnosis for each case. Consecutive, autopsy-acquired brains from former soccer and rugby players with dementia were assessed for neurodegenerative pathologies using established and preliminary consensus protocols. Thereafter, next of kin interviews were conducted to obtain detailed accounts of the patient's clinical presentation and course of disease to inform a final, integrated clinicopathological diagnosis. Neuropathologic change consistent with CTE (CTE-NC) was confirmed in five of seven former soccer and three of four former rugby players' brains, invariably in combination with mixed, often multiple neurodegenerative pathologies. However, in just three cases was the integrated dementia diagnosis consistent with CTE, the remainder having alternate diagnoses, with the most frequent integrated diagnosis Alzheimer's disease (AD) (four cases; one as mixed AD and vascular dementia). This consecutive autopsy series identifies neuropathologic change consistent with preliminary diagnostic criteria for CTE (CTE-NC) in a high proportion of former soccer and rugby players dying with dementia. However, in the majority, CTE-NC appears as a co-morbidity rather than the primary, dementia causing pathology. As such, we suggest that while CTE-NC might be common in former athletes with dementia, in many cases its clinical significance remains uncertain.

Cognitive behavioral therapy (CBT) is an evidence-based treatment for bulimia nervosa and binge-eating disorder and is regarded as the first-line treatment for both eating disorders. An enhanced version of the treatment (CBT-E) appears more effective in treating patients with severe comorbidity. There is less evidence that CBT is effective for the treatment of anorexia nervosa. Evidence suggests that CBT-E is no more effective than specialist care involving regular medical follow-up and supportive psychotherapy in the persistent adult form of anorexia nervosa (AN). Early studies suggest that CBT-E may be useful in treating the adolescent form of AN.

Urban vacancy is a pressing issue in many cities across the U.S. and globally. A variety of greening strategies have been proposed and implemented for repurposing vacant lots, and their success depends upon the extent to which greening goals address the social needs of residents. The primary contribution of this paper is to explore the relationship between place and community within the context of resident-led beautification of vacant lots. We queried new owners of vacant lots purchased in disenfranchised neighborhoods through the Chicago Large Lot Program in 2015. We used a mixed-methods design that included three focus groups (n = 25) and a mail/online survey (n = 197). Our work builds upon a relational place-making framework that casts the greening of vacant lots as acts of beautification with both physical and social expressions. Focus group findings indicated that resident-initiated beautification activities of cleaning, planting, and engaging with neighbors fulfilled personal goals in ownership while strengthening interpersonal relationships, which participants hoped could transform the community of their block. We examined these results in a path analysis of constructs developed from the survey. Results showed participants’ interest in beautifying their lot positively influenced social interaction with neighbors and individual investments in caring for a new lot. Social interaction was positively correlated with place attachment, which in turn predicted sense of community. Individual investments and neighborhood change did not influence place attachment or sense of community. Our work suggests that resident-led beautification of vacant lots can be an empowering way for communities to work for positive change.

Neurosurgical management of traumatic brain injury (TBI) is challenging, with only low-quality evidence. We aimed to explore differences in neurosurgical strategies for TBI across Europe.A survey was sent to 68 centers participating in the Collaborative European Neurotrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. The questionnaire contained 21 questions, including the decision when to operate (or not) on traumatic acute subdural hematoma (ASDH) and intracerebral hematoma (ICH), and when to perform a decompressive craniectomy (DC) in raised intracranial pressure (ICP).The survey was completed by 68 centers (100%). On average, 10 neurosurgeons work in each trauma center. In all centers, a neurosurgeon was available within 30 min. Forty percent of responders reported a thickness or volume threshold for evacuation of an ASDH. Most responders (78%) decide on a primary DC in evacuating an ASDH during the operation, when swelling is present. For ICH, 3% would perform an evacuation directly to prevent secondary deterioration and 66% only in case of clinical deterioration. Most respondents (91%) reported to consider a DC for refractory high ICP. The reported cut-off ICP for DC in refractory high ICP, however, differed: 60% uses 25 mmHg, 18% 30 mmHg, and 17% 20 mmHg. Treatment strategies varied substantially between regions, specifically for the threshold for ASDH surgery and DC for refractory raised ICP. Also within center variation was present: 31% reported variation within the hospital for inserting an ICP monitor and 43% for evacuating mass lesions.Despite a homogeneous organization, considerable practice variation exists of neurosurgical strategies for TBI in Europe. These results provide an incentive for comparative effectiveness research to determine elements of effective neurosurgical care.

Tau pathology associated with chronic traumatic encephalopathy has been documented in the brains of individuals with a history of repetitive mild traumatic brain injury (r-mTBI). At this stage, the pathobiological role of tau in r-mTBI has not been extensively explored in appropriate pre-clinical models. Here, we describe the acute and chronic behavioral and histopathological effects of single and repetitive mild TBI (five injuries given at 48 h intervals) in young adult (3 months old) hTau mice that express all six isoforms of hTau on a null murine tau background. Animals exposed to r-mTBI showed impaired visuospatial learning in the Barnes maze test that progressively worsened from two weeks to 12 months post-injury, which was also accompanied by significant deficits in visuospatial memory consolidation at 12 months post-injury. In contrast, only marginal changes were observed in visuospatial learning at six and 12 months after single mTBI. Histopathological analyses revealed that hTau mice developed axonal injury, thinning of the corpus callosum, microgliosis and astrogliosis in the white matter at acute and chronic time points after injury. Tau immunohistochemistry and enzyme-linked immunosorbent assay data suggest, however, only transient, injury-dependent increases in phosphorylated tau in the cerebral cortex beneath the impact site and in the CA1/CA3 subregion of the hippocampus after single or r-mTBI. This study implicates white matter degeneration as a prominent feature of survival from mTBI, while the role of tau pathology in the neuropathological sequelae of TBI remains elusive.

William Stewart, the Technical Director of Hermann’s Jazz Club in Victoria, Canada, discusses the technological solutions he devised to continue to present jazz concerts online during the pandemic.

Glioblastoma (GBM) is the most prevalent malignant primary brain tumour in adults. GBM typically has a poor prognosis, mainly due to a lack of effective treatment options leading to tumour persistence or recurrence. We investigated the therapeutic potential of targeting anti-apoptotic BCL-2 proteins in GBM. Levels of anti-apoptotic BCL-xL and MCL-1 were consistently increased in GBM compared with non-malignant cells and tissue. Moreover, we found that relative to their differentiated counterparts, patient-derived GBM stem-like cells also displayed higher expression of anti-apoptotic BCL-2 family members. High anti-apoptotic BCL-xL and MCL-1 expression correlated with heightened susceptibility of GBM to BCL-2 family protein-targeting BH3-mimetics. This is indicative of increased apoptotic priming. Indeed, GBM displayed an obligate requirement for MCL-1 expression in both tumour development and maintenance. Investigating this apoptotic sensitivity, we found that sequential inhibition of BCL-xL and MCL-1 led to robust anti-tumour responses in vivo, in the absence of overt toxicity. These data demonstrate that BCL-xL and MCL-1 pro-survival function is a fundamental prerequisite for GBM survival that can be therapeutically exploited by BH3-mimetics.

Key Points Question Do sex-associated differences exist in sport-related concussion (SRC) risk, mechanism, management, and recovery in adolescent soccer? Findings In this cohort study of a high school injury surveillance project, the risk of documented SRC was 1.88 times higher among adolescent girls than adolescent boys. Whereas boys most often sustained SRC from player contact (48.4%), documented SRCs in girls were most often from equipment contact (eg, ball or goalpost [41.9%]), and boys had 1.54 greater odds of immediate removal from play and returned to play 2 days sooner than girls. Meaning These findings suggest that concussion risk and outcome differences in adolescent soccer athletes might require sex-specific approaches to participation and concussion management in sport., Importance Because of the negative consequences of concussion, considerable research efforts have been directed toward understanding the risk factors for sport-related concussion (SRC) and its outcomes to better inform strategies for risk reduction. Girls are suggested to have an increased risk of concussion, warranting exploration into sex-dependent variations in concussion presentation and management, with the potential that this information might inform sex-specific rules directed toward risk reduction within sports. Objective To compare sex-associated differences in epidemiology and concussion management in adolescent soccer players within a prospective, longitudinal high school injury surveillance project. Design, Setting, and Participants This prospective, longitudinal cohort study assessed male and female soccer athletes from all high schools in the Michigan High School Athletic Association (MHSAA) during academic years 2016-2017 to 2018-2019. Exposures Sport-related concussion captured in the MHSAA Head Injury Reporting System. Main Outcomes and Measures Outcomes included details regarding each documented SRC event, including injury mechanism, immediate management, and return-to-play time. Multiple comparisons were made between male and female athletes regarding SRC risk, mechanism, short-term management, and outcomes. Results A total of 43 741 male and 39 637 female soccer athletes participated in MHSAA soccer during the 3 consecutive academic years of study (2016-2017: n = 751 schools; 2017-2018: n = 750 schools; and 2018-2019: n = 747 schools). During the 3 years of surveillance, 1507 of the 83 378 soccer athletes (1.8%) were reported to have SRC during soccer participation, including 557 boys (37.0%) and 950 girls (63.0%). Documented SRC risk in female soccer participants was greater than in male soccer participants (risk ratio, 1.88; 95% CI, 1.69-2.09; P, This cohort study compares sex-associated differences in epidemiologic factors and concussion management in adolescent soccer players within a high school injury surveillance project.

Efforts to characterize the late effects of traumatic brain injury (TBI) have been in progress for some time. In recent years much of this activity has been directed towards reporting of chronic traumatic encephalopathy (CTE) in former contact sports athletes and others exposed to repetitive head impacts. However, the association between TBI and dementia risk has long been acknowledged outside of contact sports. Further, growing experience suggests a complex of neurodegenerative pathologies in those surviving TBI, which extends beyond CTE. Nevertheless, despite extensive research, we have scant knowledge of the mechanisms underlying TBI-related neurodegeneration (TReND) and its link to dementia. In part, this is due to the limited number of human brain samples linked to robust demographic and clinical information available for research. Here we detail a National Institutes for Neurological Disease and Stroke Center Without Walls project, the COllaborative Neuropathology NEtwork Characterizing ouTcomes of TBI (CONNECT-TBI), designed to address current limitations in tissue and research access and to advance understanding of the neuropathologies of TReND. As an international, multidisciplinary collaboration CONNECT-TBI brings together multiple experts across 13 institutions. In so doing, CONNECT-TBI unites the existing, comprehensive clinical and neuropathological datasets of multiple established research brain archives in TBI, with survivals ranging minutes to many decades and spanning diverse injury exposures. These existing tissue specimens will be supplemented by prospective brain banking and contribute to a centralized route of access to human tissue for research for investigators. Importantly, each new case will be subject to consensus neuropathology review by the CONNECT-TBI Expert Pathology Group. Herein we set out the CONNECT-TBI program structure and aims and, by way of an illustrative case, the approach to consensus evaluation of new case donations.

There is continued interest in the association between exposure to traumatic brain injury (TBI) during contact sports participation and lifelong adverse health effects, including neurodegenerative disease, mental health disorders and suicide.1 In part, this is driven by reporting of a neurodegenerative pathology linked to TBI, chronic traumatic encephalopathy (CTE), in autopsy series of former athletes from multiple contact sports.1 However, while the number of cases with confirmed CTE neuropathological change grows, understanding of late clinical outcomes in ‘at risk’ populations remains challenged by acknowledged methodological limitations in many studies to date.1 2 In the paper by Brett et al 3, the authors address some of these limitations in providing …

This thesis was scanned from the print manuscript for digital preservation and is copyright the author. Researchers can access this thesis by asking their local university, institution or public library to make a request on their behalf. Monash staff and postgraduate students can use the link in the References field.

OBJECTIVE: The aim of this paper was to evaluate the prevalence of postconcussive symptoms and their relation to health-related quality of life (HRQOL) in pediatric and adolescent patients with mild traumatic brain injury (mTBI) who received head CT imaging during initial assessment. METHODS: Patients aged between 5 and 21 years with mTBI (Glasgow Coma Scale scores 13-15) and available Rivermead Post Concussion Questionnaire (RPQ) at 6 months of follow-up in the multicenter, prospectively collected CENTER-TBI (Collaborative European NeuroTrauma Effectiveness Research in TBI) study were included. The prevalence of postconcussive symptoms was assessed, and the occurrence of postconcussive syndrome (PSC) based on the ICD-10 criteria, was analyzed. HRQOL was compared in patients with and without PCS using the Quality of Life after Brain Injury (QOLIBRI) questionnaire. RESULTS: A total of 196 adolescent or pediatric mTBI patients requiring head CT imaging were included. High-energy trauma was prevalent in more than half of cases (54%), abnormalities on head CT scans were detected in 41%, and admission to the regular ward or intensive care unit was necessary in 78%. Six months postinjury, 36% of included patients had experienced at least one moderate or severe symptom on the RPQ. PCS was present in 13% of adolescents and children when considering symptoms of at least moderate severity, and those patients had significantly lower QOLIBRI total scores, indicating lower HRQOL, compared with young patients without PCS (57 vs 83 points, p < 0.001). CONCLUSIONS: Adolescent and pediatric mTBI patients requiring head CT imaging show signs of increased trauma severity. Postconcussive symptoms are present in up to one-third of those patients, and PCS can be diagnosed in 13% 6 months after injury. Moreover, PCS is significantly associated with decreased HRQOL., Funding Agencies: OneMind (USA) Hannelore Kohl Stiftung (Germany)

Contains fulltext : 238746.pdf (Publisher’s version ) (Closed access) Recent biomarker innovations hold potential for transforming diagnosis, prognostic modeling, and precision therapeutic targeting of traumatic brain injury (TBI). However, many biomarkers, including brain imaging, genomics, and proteomics, involve vast quantities of high-throughput and high-content data. Management, curation, analysis, and evidence synthesis of these data are not trivial tasks. In this review, we discuss data management concepts and statistical and data sharing strategies when dealing with biomarker data in the context of TBI research. We propose that application of biomarkers involves three distinct steps-discovery, evaluation, and evidence synthesis. First, complex/big data has to be reduced to useful data elements at the stage of biomarker discovery. Second, inferential statistical approaches must be applied to these biomarker data elements for assessment of biomarker clinical utility and validity. Last, synthesis of relevant research is required to support practice guidelines and enable health decisions informed by the highest quality, up-to-date evidence available. We focus our discussion around recent experiences from the International Traumatic Brain Injury Research (InTBIR) initiative, with a specific focus on four major clinical projects (Transforming Research and Clinical Knowledge in TBI, Collaborative European NeuroTrauma Effectiveness Research in TBI, Collaborative Research on Acute Traumatic Brain Injury in Intensive Care Medicine in Europe, and Approaches and Decisions in Acute Pediatric TBI Trial), which are currently enrolling subjects in North America and Europe. We discuss common data elements, data collection efforts, data-sharing opportunities, and challenges, as well as examine the statistical techniques required to realize successful adoption and use of biomarkers in the clinic as a foundation for precision medicine in TBI.

Surveys of a general population have been a mainstay of leisure and recreation research methods. This study assesses the impact of two different pre-incentives on eliciting a survey response. Two counties with large federal prairie restoration projects and active municipal and county park districts were the study sites. Results show that residents whose pre-incentive was two $1 bills had a significantly higher response rate than residents with a pre-incentive of one $2 bill. With park operations being responsive to needs and preferences of residents, the most accurate representation of the general population of constituents is an important goal in any research effort. Given that pre-incentives have become a standard and sizeable portion of a survey’s budget, maximizing the effectiveness of the pre-incentive investment is a small, yet critical, part of connecting research to practice. Subscribe to JPRA

Contains fulltext : 234957.pdf (Publisher’s version ) (Closed access) In medical research, missing data is common. In acute diseases, such as traumatic brain injury (TBI), even well-conducted prospective studies may suffer from missing data in baseline characteristics and outcomes. Statistical models may simply drop patients with any missing values, potentially leaving a selected subset of the original cohort. Imputation is widely accepted by methodologists as an appropriate way to deal with missing data. We aim to provide practical guidance on handling missing data for prediction modeling. We hereto propose a five-step approach, centered around single and multiple imputation: 1) explore the missing data patterns; 2) choose a method of imputation; 3) perform imputation; 4) assess diagnostics of the imputation; and 5) analyze the imputed data sets. We illustrate these five steps with the estimation and validation of the IMPACT (International Mission on Prognosis and Analysis of Clinical Trials in Traumatic Brain Injury) prognostic model in 1375 patients from the CENTER-TBI database, included in 53 centers across 17 countries, with moderate or severe TBI in the prospective European CENTER-TBI study. Future prediction modeling studies in acute diseases may benefit from following the suggested five steps for optimal statistical analysis and interpretation, after maximal effort has been made to minimize missing data.

The International Mission on Prognosis and Analysis of Clinical Trials in Traumatic Brain Injury (IMPACT) and Corticoid Randomisation After Significant Head injury (CRASH) prognostic models predict functional outcome after moderate and severe traumatic brain injury (TBI). We aimed to assess their performance in a contemporary cohort of patients across Europe. The Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) core study is a prospective, observational cohort study in patients presenting with TBI and an indication for brain computed tomography. The CENTER-TBI core cohort consists of 4509 TBI patients available for analyses from 59 centers in 18 countries across Europe and Israel. The IMPACT validation cohort included 1173 patients with GCS = 14, and 6-month Glasgow Outcome Scale-Extended (GOSE) available. The CRASH validation cohort contained 1742 patients with GCS = 16, and 14-day mortality or 6-month GOSE available. Performance of the three IMPACT and two CRASH model variants was assessed with discrimination (area under the receiver operating characteristic curve; AUC) and calibration (comparison of observed vs. predicted outcome rates). For IMPACT, model discrimination was good, with AUCs ranging between 0.77 and 0.85 in 1173 patients and between 0.80 and 0.88 in the broader CRASH selection (n = 1742). For CRASH, AUCs ranged between 0.82 and 0.88 in 1742 patients and between 0.66 and 0.80 in the stricter IMPACT selection (n = 1173). Calibration of the IMPACT and CRASH models was generally moderate, with calibration-in-the-large and calibration slopes ranging between -2.02 and 0.61 and between 0.48 and 1.39, respectively. The IMPACT and CRASH models adequately identify patients at high risk for mortality or unfavorable outcome, which supports their use in research settings and for benchmarking in the context of quality-of-care assessment.

Repeated exposure to mild TBI (mTBI) has been linked to an increased risk of Alzheimer’s disease (AD), chronic traumatic encephalopathy (CTE) and other neurodegenerative diseases. Some pathological features typically observed in AD have been found in postmortem brains of TBI and CTE, hence treatments tested for AD have a potential to be effective against r-mTBI outcomes. Neuroinflammation may present a possible answer due to its central role both in acute brain injury and in chronic degenerative-like disorders. Our previous studies have shown that drug nilvadipine, acting as an inhibitor of spleen tyrosine kinase (SYK), is effective at reducing inflammation, tau hyperphosphorylation and amyloid production in AD mouse models. To demonstrate the effect of nilvadipine in the absence of age-related variables, we introduced the same treatment to young r-mTBI mice. We further investigate therapeutic mechanisms of nilvadipine using its racemic properties. Both enantiomers, (+)-nilvadipine and (−)-nilvadipine, can lower SYK activity, whereas (+)-nilvadipine is also a potent L-type calcium channel blocker (CCB) and shown to be anti-hypertensive. All r-mTBI mice exhibited increased neuroinflammation and impaired cognitive performance and motor functions. Treatment with racemic nilvadipine mitigated the TBI-induced inflammatory response and significantly improved spatial memory, whereas (−)-enantiomer decreased microgliosis and improved spatial memory but failed to reduce the astroglial response to as much as the racemate. These results suggest the therapeutic potential of SYK inhibition that is enhanced when combined with the CCB effect, which indicate a therapeutic advantage of multi-action drugs for r-mTBI. Electronic supplementary material The online version of this article (10.1186/s40478-020-01045-x) contains supplementary material, which is available to authorized users.

Traumatic brain injury (TBI) is a significant cause of disability, but little is known about sex and gender differences after TBI. We aimed to analyze the association between sex/gender, and the broad range of care pathways, treatment characteristics, and outcomes following mild and moderate/severe TBI. We performed mixed-effects regression analyses in the prospective multi-center Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study, stratified for injury severity and age, and adjusted for baseline characteristics. Outcomes were various care pathway and treatment variables, and 6-month measures of functional outcome, health-related quality of life (HRQoL), post-concussion symptoms (PCS), and mental health symptoms. The study included 2862 adults (36% women) with mild (mTBI; Glasgow Coma Scale [GCS] score 13–15), and 1333 adults (26% women) with moderate/severe TBI (GCS score 3–12). Women were less likely to be admitted to the intensive care unit (ICU; odds ratios [OR] 0.6, 95% confidence interval [CI]: 0.4-0.8) following mTBI. Following moderate/severe TBI, women had a shorter median hospital stay (OR 0.7, 95% CI: 0.5-1.0). Following mTBI, women had poorer outcomes; lower Glasgow Outcome Scale Extended (GOSE; OR 1.4, 95% CI: 1.2-1.6), lower generic and disease-specific HRQoL, and more severe PCS, depression, and anxiety. Among them, women under age 45 and above age 65 years showed worse 6-month outcomes compared with men of the same age. Following moderate/severe TBI, there was no difference in GOSE (OR 0.9, 95% CI: 0.7-1.2), but women reported more severe PCS (OR 1.7, 95% CI: 1.1-2.6). Men and women differ in care pathways and outcomes following TBI. Women generally report worse 6-month outcomes, but the size of differences depend on TBI severity and age. Future studies should examine factors that explain these differences Ana Mikolic´ et al., 2020; Published by Mary Ann Liebert, Inc. This Open Access article is distributed under the terms of the Creative Commons License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.

PurposeEnrolling traumatic brain injury (TBI) patients with an inability to provide informed consent in research is challenging. Alternatives to patient consent are not sufficiently embedded in European and national legislation, which allows procedural variation and bias. We aimed to quantify variations in informed consent policy and practice.MethodsVariation was explored in the CENTER-TBI study. Policies were reported by using a questionnaire and national legislation. Data on used informed consent procedures were available for 4498 patients from 57 centres across 17 European countries.ResultsVariation in the use of informed consent procedures was found between and within EU member states. Proxy informed consent (N=1377;64%) was the most frequently used type of consent in the ICU, followed by patient informed consent (N=426;20%) and deferred consent (N=334;16%). Deferred consent was only actively used in 15 centres (26%), although it was considered valid in 47 centres (82%).ConclusionsAlternatives to patient consent are essential for TBI research. While there seems to be concordance amongst national legislations, there is regional variability in institutional practices with respect to the use of different informed consent procedures. Variation could be caused by several reasons, including inconsistencies in clear legislation or knowledge of such legislation amongst researchers.

Current diagnostic criteria for the neuropathological evaluation of the traumatic brain injury-associated neurodegeneration, chronic traumatic encephalopathy, define the pathognomonic lesion as hyperphosphorylated tau-immunoreactive neuronal and astroglial profiles in a patchy cortical distribution, clustered around small vessels and showing preferential localization to the depths of sulci. However, despite adoption into diagnostic criteria, there has been no formal assessment of the cortical distribution of the specific cellular components defining chronic traumatic encephalopathy neuropathologic change. To address this, we performed comprehensive mapping of hyperphosphorylated tau-immunoreactive neurofibrillary tangles and thorn-shaped astrocytes contributing to chronic traumatic encephalopathy neuropathologic change. From the Glasgow Traumatic Brain Injury Archive and the University of Pennsylvania Center for Neurodegenerative Disease Research Brain Bank, material was selected from patients with known chronic traumatic encephalopathy neuropathologic change, either following exposure to repetitive mild (athletes n = 17; non-athletes n = 1) or to single moderate or severe traumatic brain injury (n = 4), together with material from patients with previously confirmed Alzheimer’s disease neuropathologic changes (n = 6) and no known exposure to traumatic brain injury. Representative sections were stained for hyperphosphorylated or Alzheimer’s disease conformation-selective tau, after which stereotypical neurofibrillary tangles and thorn-shaped astrocytes were identified and mapped. Thorn-shaped astrocytes in chronic traumatic encephalopathy neuropathologic change were preferentially distributed towards sulcal depths [sulcal depth to gyral crest ratio of thorn-shaped astrocytes 12.84 ± 15.47 (mean ± standard deviation)], with this pathology more evident in material from patients with a history of survival from non-sport injury than those exposed to sport-associated traumatic brain injury (P = 0.009). In contrast, neurofibrillary tangles in chronic traumatic encephalopathy neuropathologic change showed a more uniform distribution across the cortex in sections stained for either hyperphosphorylated (sulcal depth to gyral crest ratio of neurofibrillary tangles 1.40 ± 0.74) or Alzheimer’s disease conformation tau (sulcal depth to gyral crest ratio 1.64 ± 1.05), which was comparable to that seen in material from patients with known Alzheimer’s disease neuropathologic changes (P = 0.82 and P = 0.91, respectively). Our data demonstrate that in chronic traumatic encephalopathy neuropathologic change the astroglial component alone shows preferential distribution to the depths of cortical sulci. In contrast, the neuronal pathology of chronic traumatic encephalopathy neuropathologic change is distributed more uniformly from gyral crest to sulcal depth and echoes that of Alzheimer’s disease. These observations provide new insight into the neuropathological features of chronic traumatic encephalopathy that distinguish it from other tau pathologies and suggest that current diagnostic criteria should perhaps be reviewed and refined., Mapping hyper-phosphorylated tau pathologies contributing to the pathognomonic cortical lesion of chronic traumatic encephalopathy neuropathologic change reveals immunoreactive astrocytes preferentially concentrate to sulcal depths. In contrast, neurofibrillary tangles show limited sulcal concentration, comparable with Alzheimer’s disease. These data provide new insight into the specific pathology of chronic traumatic encephalopathy., Graphical Abstract Graphical Abstract

Traumatic brain injury (TBI) is a risk factor for neurodegenerative disease, including chronic traumatic encephalopathy (CTE). Preliminary consensus criteria define the pathognomonic lesion of CTE as patchy tau pathology within neurons and astrocytes at the depths of cortical sulci. However, the specific tau isoform composition and post-translational modifications in CTE remain largely unexplored. Using immunohistochemistry, we performed tau phenotyping of CTE neuropathologies and compared this to a range of tau pathologies, including Alzheimer’s disease, primary age-related tauopathy, ageing-related tau astrogliopathy and multiple subtypes of frontotemporal lobar degeneration with tau inclusions. Cases satisfying preliminary consensus diagnostic criteria for CTE neuropathological change (CTE-NC) were identified (athletes, n = 10; long-term survivors of moderate or severe TBI, n = 4) from the Glasgow TBI Archive and Penn Neurodegenerative Disease Brain Bank. In addition, material from a range of autopsy-proven ageing-associated and primary tauopathies in which there was no known history of exposure to TBI was selected as non-injured controls (n = 32). Each case was then stained with a panel of tau antibodies specific for phospho-epitopes (PHF1, CP13, AT100, pS262), microtubule-binding repeat domains (3R, 4R), truncation (Tau-C3) or conformation (GT-7, GT-38) and the extent and distribution of staining assessed. Cell types were confirmed with double immunofluorescent labelling. Results demonstrate that astroglial tau pathology in CTE is composed of 4R-immunoreactive thorn-shaped astrocytes, echoing the morphology and immunophenotype of astrocytes encountered in ageing-related tau astrogliopathy. In contrast, neurofibrillary tangles of CTE contain both 3R and 4R tau, with post-translational modifications and conformations consistent with Alzheimer’s disease and primary age-related tauopathy. Our observations establish that the astroglial and neurofibrillary tau pathologies of CTE are phenotypically distinct from each other and recapitulate the tau immunophenotypes encountered in ageing and Alzheimer’s disease. As such, the immunohistochemical distinction of CTE neuropathology from other mixed 3R/4R tauopathies of Alzheimer’s disease and ageing may rest solely on the pattern and distribution of pathology.

Seventy-six FDA-approved oncology drugs and emerging therapeutics were evaluated in 25 multiple myeloma (MM) and 15 non-Hodgkin’s lymphoma cell lines and in 113 primary MM samples. Ex vivo drug sensitivities were mined for associations with clinical phenotype, cytogenetic, genetic mutation, and transcriptional profiles. In primary MM samples, proteasome inhibitors, dinaciclib, selinexor, venetoclax, auranofin, and histone deacetylating agents had the broadest cytotoxicity. Of interest, newly diagnosed patient samples were globally less sensitive especially to bromodomain inhibitors, inhibitors of receptor tyrosine kinases or non-receptor kinases, and DNA synthesis inhibitors. Clustering demonstrated six broad groupings of drug sensitivity linked with genomic biomarkers and clinical outcomes. For example, our findings mimic clinical observations of increased venetoclax responsiveness in t(11;14) patients but also identify an increased sensitivity profile in untreated patients, standard genetic risk, low plasma cell S-Phase, and in the absence of Gain(1q) and t(4;14). In contrast, increased ex vivo responsiveness to selinexor was associated with biomarkers of poor prognosis and later relapse patients. This “direct to drug” screening resource, paired with functional genomics, has the potential to successfully direct appropriate individualized therapeutic approaches in MM and to enrich clinical trials for likely responders.