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Abstract Perching with winged Unmanned Aerial Vehicles has often been solved by means of complex control or intricate appendages. Here, we present a method that relies on passive wing morphing for crash-landing on trees and other types of vertical poles. Inspired by the adaptability of animals’ and bats’ limbs in gripping and holding onto trees, we design dual-purpose wings that enable both aerial gliding and perching on poles. With an upturned nose design, the robot can passively reorient from horizontal flight to vertical upon a head-on crash with a pole, followed by hugging with its wings to perch. We characterize the performance of reorientation and perching in terms of impact speed and angle, pole material, and size. The robot robustly reorients at impact angles above 15° and speeds of 3 m ⋅ s−1 to 9 m ⋅ s−1, and can hold onto various pole types larger than 28% of its wingspan in diameter. We demonstrate crash-perching on tree trunks with an overall success rate of 73%. The method opens up new possibilities for the use of aerial robots in applications such as inspection, maintenance, and biodiversity conservation.

Summary: Background: Traumatic brain injury is conventionally categorised as mild, moderate, or severe on the Glasgow Coma Scale (GCS). Recently developed biomarkers can provide more objective and nuanced measures of the extent of brain injury. Methods: Exposure–response relationships were investigated in 2479 patients aged ≥16 enrolled in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) prospective observational cohort study. Neurofilament protein-light (NFL), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), and glial fibrillary acidic protein (GFAP) were assayed from serum sampled in the first 24 h; concentrations were divided into quintiles within GCS severity groups. Relationships with the Glasgow Outcome Scale-Extended were examined using modified Poisson regression including age, sex, major extracranial injury, time to sample, and log biomarker concentration as covariates. Findings: Within severity groups there were associations between biomarkers and outcomes after adjustment for covariates: GCS 13–15 and negative CT imaging (relative risks [RRs] from 1.28 to 3.72), GCS 13–15 and positive CT (1.21–2.81), GCS 9–12 (1.16–2.02), GCS 3–8 (1.09–1.94). RRs were associated with clinically important differences in expectations of prognosis. In patients with GCS 3 (RRs 1.51–1.80) percentages of unfavourable outcome were 37–51% in the lowest quintiles of biomarker levels and reached 90–94% in the highest quintiles. Similarly, for GCS 15 (RRs 1.83–3.79), the percentages were 2–4% and 19–28% in the lowest and highest biomarker quintiles, respectively. Interpretation: Conventional TBI severity classification is inadequate and underestimates heterogeneity of brain injury and associated outcomes. The adoption of circulating biomarkers can add to clinical assessment of injury severity. Funding: European Union 7th Framework program (EC grant 602150), Hannelore Kohl Stiftung, One Mind, Integra LifeSciences, Neuro-Trauma Sciences, NIHR Rosetrees Trust.

Objective: Common femoral artery (CFA) access is commonly used for endovascular interventions. Access site complications contribute to significant morbidity and mortality. This study characterizes the radiographic variability in the relationship of the femoral head, the inguinal ligament, and the CFA bifurcation, to identify the zone of optimal CFA access. Methods: Human cadaver dissection of the inguinal ligament and CFA bifurcation was performed. The inguinal ligament and CFA bifurcation were marked with radiopaque pins and plain anteroposterior radiographs were obtained. Radiographic measurements of the femoral head length, the distance of the top of the femoral head to the inguinal ligament, and to the CFA bifurcation were obtained. Results were reported as percentage of femoral head covered by the inguinal ligament or the CFA bifurcation relative to the top of the femoral head. A heatmap was derived to determine a safe access zone between the inguinal ligament and CFA bifurcation. Results: Forty-five groin dissections (male, n = 20; female, n = 25) were performed in 26 cadavers. The mean overlap of the inguinal ligament with the femoral head was 11.2 mm (range, −19.4 to 27.4 mm). There were no age (25% overlap. In 11.1%, there was an overlap between the lower one-third of the femoral head and the CFA bifurcation. Cumulatively, heatmap analysis depicted a >80% likelihood of avoiding the inguinal ligament and CFA bifurcation below the midpoint of the femoral head. Conclusions: Significant variability exists in the relationship between the inguinal ligament, CFA bifurcation, and the femoral head, suggesting the lack of a consistently safe access zone. The safest access zone in >80% of patients lies below the radiographic midpoint of the femoral head and the inferior aspect of the femoral head. : Clinical Relevance: The primary site of access for percutaneous endovascular arterial interventions across multiple specialties remains the common femoral artery. Although femoral artery access is most commonly safe, access-related complications such as retroperitoneal hemorrhage, pseudoaneurysms, or arteriovenous fistulae can contribute to significant morbidity and mortality. Through cadaver dissection, this study highlights significant variability in the relationship between the inguinal ligament, the femoral head, and the common femoral artery bifurcation. The optimal zone of access overlies the lower one-half of the femoral head in most cases.

Friedrich Schleiermacher emerged as a prominent advocate for German nationalism in the Wars of Liberation from Napoleonic domination in the early nineteenth century. Alongside his work as a pastor and theologian in Berlin, and also as the co-founder of the University of Berlin, Schleiermacher developed German nationalism from a distinctly Protestant perspective, one that sought the preservation of Protestantism in the German lands under Napoleonic domination. While it would be an overstatement to suggest that Schleiermacher’s nationalism was anti-Catholic, he certainly sought to preserve and maintain Protestantism in the German lands. His vision of the German nation-state emphasized Germany’s role as a divine instrument of God’s will in the world. He assumed the cultural unity of the peoples in German lands, that is, an area of land in which the peoples are bound together by the common use of the German language. In his distinct role as a pastor, theologian, and academic, he was devoted to the cultivation of German national consciousness and the establishment of a German nation-state. Schleiermacher’s work would help to provide a cultural foundation for the emergence of the German nation-state more than half a century before the establishment of the German empire.

Summary: Background: Limited evidence existed on the comparative effectiveness of decompressive craniectomy (DC) versus craniotomy for evacuation of traumatic acute subdural hematoma (ASDH) until the recently published randomised clinical trial RESCUE-ASDH. In this study, that ran concurrently, we aimed to determine current practice patterns and compare outcomes of primary DC versus craniotomy. Methods: We conducted an analysis of centre treatment preference within the prospective, multicentre, observational Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (known as CENTER-TBI) and NeuroTraumatology Quality Registry (known as Net-QuRe) studies, which enrolled patients throughout Europe and Israel (2014–2020). We included patients with an ASDH who underwent acute neurosurgical evacuation. Patients with severe pre-existing neurological disorders were excluded. In an instrumental variable analysis, we compared outcomes between centres according to treatment preference, measured by the case-mix adjusted proportion DC per centre. The primary outcome was functional outcome rated by the 6-months Glasgow Outcome Scale Extended, estimated with ordinal regression as a common odds ratio (OR), adjusted for prespecified confounders. Variation in centre preference was quantified with the median odds ratio (MOR). CENTER-TBI is registered with ClinicalTrials.gov, number NCT02210221, and the Resource Identification Portal (Research Resource Identifier SCR_015582). Findings: Between December 19, 2014 and December 17, 2017, 4559 patients with traumatic brain injury were enrolled in CENTER-TBI of whom 336 (7%) underwent acute surgery for ASDH evacuation; 91 (27%) underwent DC and 245 (63%) craniotomy. The proportion primary DC within total acute surgery cases ranged from 6 to 67% with an interquartile range (IQR) of 12–26% among 46 centres; the odds of receiving a DC for prognostically similar patients in one centre versus another randomly selected centre were trebled (adjusted median odds ratio 2.7, p

Background It is estimated that by 2050 the global incidence of dementia will have exceeded 152 million. At present, there are no effective therapies for dementia, with a focus in research now turning to strategies for disease prevention. Traumatic brain injury (TBI) is recognised as a major risk factor for dementia; estimated to be responsible for at least 3% of cases in the community. However, adverse health outcomes after TBI are not restricted to dementia. A wide range of conditions are documented among TBI survivors, many of which also increase dementia risk. ‘HEalth And Dementia outcomes following Traumatic Brain Injury’ is a study aiming to explore the hypothesis that increased dementia risk following TBI reflects both the direct effect of the injury on the brain and the indirect effects of wider, adverse health outcomes associated with TBI which, in turn, increase dementia risk.Methods and analysis Comprehensive electronic medical and death certification records will be analysed for individuals with a documented history of TBI, compared with those of a matched general population control cohort with no documented TBI exposure. Cox proportional hazard regression models will be run to compare outcomes. Furthermore, existing diagnostic imaging and radiological reports for the cohort will be analysed to identify evidence of specific white matter abnormalities in TBI exposed individuals and their controls, and establish their potential diagnostic utility.Ethics and dissemination Approvals for the study have been obtained from the University of Glasgow College of Medical, Veterinary, and Life Sciences Research Ethics Committee (project number 200220038) and from National Health Service Scotland’s Public Benefits and Privacy Panel (application 2122-0224). As results emerge, these will be presented at appropriate multidisciplinary research conferences and made available through open access platforms where possible.

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).

Intense winds are a challenge for vertical take‐off and landing drones with wings. In particular, in the hovering regime, wings are sensitive to wind currents that can be detrimental to their operational and energetic performances. Tail‐sitters are particularly prone to those wind currents because their wings are perpendicular to the incoming wind during hovering. This wind generates a large amount of drag and can displace and destabilize the vehicle, possibly leading to catastrophic failures. Herein, our morphing strategy demonstrates in a custom‐built 1.8 kg tail‐sitter with morphing wings that can actively resist winds and leverage them to increase its aerodynamic efficiency. It is shown that adaptive wing morphing during hovering in adverse wind conditions can reduce normalized energy consumption up to 85%, increase attitude and positional stability, and leverage wind energy to increase its yaw angular rate up to 200% while decreasing motor saturation levels.

Abstract Traumatic brain injury (TBI) is associated with the development of a range of neurodegenerative pathologies, including chronic traumatic encephalopathy (CTE). Current consensus diagnostic criteria define the pathognomonic cortical lesion of CTE neuropathologic change (CTE-NC) as a patchy deposition of hyperphosphorylated tau in neurons, with or without glial tau in thorn-shaped astrocytes, typically towards the depths of sulci and clustered around small blood vessels. Nevertheless, although incorporated into consensus diagnostic criteria, the contribution of the individual cellular components to identification of CTE-NC has not been formally evaluated. To address this, from the Glasgow TBI Archive, cortical tissue blocks were selected from consecutive brain donations from contact sports athletes in which there was known to be either CTE-NC (n = 12) or Alzheimer’s disease neuropathologic change (n = 4). From these tissue blocks, adjacent tissue sections were stained for tau antibodies selected to reveal either solely neuronal pathology (3R tau; GT-38) or mixed neuronal and astroglial pathologies (4R tau; PHF-1). These stained sections were then randomised and independently assessed by a panel of expert neuropathologists, blind to patient clinical history and primary antibody applied to each section, who were asked to record whether CTE-NC was present. Results demonstrate that, in sections stained for either 4R tau or PHF-1, consensus recognition of CTE-NC was high. In contrast, recognition of CTE-NC in sections stained for 3R tau or GT-38 was poor; in the former no better than chance. Our observations demonstrate that the presence of both neuronal and astroglial tau pathologies facilitates detection of CTE-NC, with its detection less consistent when neuronal tau pathology alone is visible. The combination of both glial and neuronal pathologies, therefore, may be required for detection of CTE-NC.

The interrelated concepts of place attachment and place meaning are antecedents to pro-environmental behavior and essential for supporting decisions that foster relationships between people and places. Previous research has argued that affect is instrumental in conceptualizing place-related phenomena but has not yet been considered in terms of discrete emotions. We disentangled the empirical relationships between concepts of place and the emotions of pride and guilt to understand how they collectively contributed to individuals’ decisions about environmental sustainability. Specifically, we conducted an online survey of residents living in the Midwestern US and asked questions about their attachments to places and their place-related behavior. We then tested a latent variable path model with first- and second-order factors that shaped the behavioral intentions of survey respondents, as well as evaluated the psychometric properties of a place meaning scale, to uncover the range of reasons why human-nature relationships were formed. Our findings show that multiple place meanings predicted place attachment, which in turn predicted the discrete emotions of pride and guilt. Place attachment, pride, and guilt positively correlated with pro-environmental behavior. We also observed that the relationships between multi-dimensional conceptualizations of place attachment and behavioral intentions were partially mediated by pride but not guilt, as hypothesized in response to the broaden and build theory of positive emotions. This study develops theoretical insights to clarify how cognitive-emotional bonding can lead people to behave in more environmentally friendly ways.

Abstract Background Previous cohort studies have investigated the relationship between self-reported physical activity (PA) and dementia. Evidence from objective device-measured PA data is lacking. This study aimed to explore the association of device-measured PA with the risk of dementia incidence and common subtypes (Alzheimer’s disease [AD] and vascular dementia) using the UK Biobank study. Methods 84,854 participants (55.8% women), invited to participate in the device-measured PA between 2013 and 2015, were included in this prospective cohort study. Wrist accelerometers were used to measure light, moderate, vigorous, moderate-to-vigorous PA (MVPA) and total PA intensity and duration (MET/min/week). Incident dementia (fatal and non-fatal) was extracted from hospital episodes records for incidence and death register for mortality. Incidence follow-up was carried out until the end of March 2021in England and Scotland and the end of March 2018 in Wales. Mortality data were available until February 2021. Nonlinear associations were first investigated using penalised cubic splines fitted in the Cox proportional hazard models. In addition, using MVPA, five categories were created. Associations of these categories with the outcomes were investigated using Cox proportional hazard models. Analyses were adjusted for sociodemographic, lifestyle and health-related factors. Results After a median follow-up of 6.3 years, 678 individuals were diagnosed with dementia. Evidence of nonlinearity was observed for all PA modes and all-cause dementia. For categories of MVPA, there was a significant trend towards a low risk of overall dementia when higher levels of MVPA were achieved (HRtrend 0.66 [95% CI 0.62 to 0.70]. The lowest risk was identified in individuals who performed more than 1200 MET/min/week, those who had 84% (95% CI 0.12 to 0.21) lower risk of incident dementia compared to those who performed

ObjectiveSpine injury is highly prevalent in patients with poly-trauma, but data on the co-occurrence of spine trauma in patients with traumatic brain injury (TBI) are scarce. In this study, we used the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) database to assess the prevalence, characteristics, and outcomes of patients with TBI and a concurrent traumatic spinal injury (TSI).MethodsData from the European multi-center CENTER-TBI study were analyzed. Adult patients with TBI (≥18 years) presenting with a concomitant, isolated TSI of at least serious severity (Abbreviated Injury Scale; AIS ≥3) were included. For outcome analysis, comparison groups of TBI patients with TSI and systemic injuries (non-isolated TSI) and without TSI were created using propensity score matching. Rates of mortality, unfavorable outcomes (Glasgow Outcome Scale Extended; GOSe < 5), and full recovery (GOSe 7–8) of all patients and separately for patients with only mild TBI (mTBI) were compared between groups at 6-month follow-up.ResultsA total of 164 (4%) of the 4,254 CENTER-TBI core study patients suffered from a concomitant isolated TSI. The median age was 53 [interquartile range (IQR): 37–66] years and 71% of patients were men. mTBI was documented in 62% of cases, followed by severe TBI (26%), and spine injuries were mostly cervical (63%) or thoracic (31%). Surgical spine stabilization was performed in 19% of cases and 57% of patients were admitted to the ICU. Mortality at 6 months was 11% and only 36% of patients regained full recovery. There were no significant differences in the 6-month rates of mortality, unfavorable outcomes, or full recovery between TBI patients with and without concomitant isolated TSI. However, concomitant non-isolated TSI was associated with an unfavorable outcome and a higher mortality. In patients with mTBI, a negative association with full recovery could be observed for both concomitant isolated and non-isolated TSI.ConclusionRates of mortality, unfavorable outcomes, and full recovery in TBI patients with and without concomitant, isolated TSIs were comparable after 6 months. However, in patients with mTBI, concomitant TSI was a negative predictor for a full recovery. These findings might indicate that patients with moderate to severe TBI do not necessarily exhibit worse outcomes when having a concomitant TSI, whereas patients with mTBI might be more affected.

Abstract Many Northeast (NE) Pacific fishes and invertebrates survived Pleistocene glaciations in northern refugia, but the extent that kelps survived in northern areas is uncertain. Here, we test the hypothesis that populations of sugar kelp (Saccharina latissima) persisted in the Gulf of Alaska during ice‐age maxima when the western margin of the Cordilleran ice sheet covered coastal areas around the NE Pacific Ocean. We estimated genetic diversities within and phylogeographical relationships among 14 populations along 2,800 km in the NE Pacific and Bering Sea with partial sequences of mitochondrial DNA 5′‐cytochrome oxidase subunit I (COI, bp = 624, n = 543), chloroplast DNA ribulose‐1,5‐bisphosphate carboxylase large subunit‐3′ (rbcL, bp = 735, n = 514), and 11 microsatellite loci. Concatenated sequences of rbcL and COI showed moderate levels of within‐population genetic diversity (mean h = 0.200) but substantial differences among populations (ΦST = 0.834, p

Abstract 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.

Much has been written on Martin Buber’s public response to Mahatma Gandhi’s article “The Jews”, which had been published in the newspaper Harijan in 1938, just after the Nazi pogrom against the Jews known as “Kristallnacht”. I wish to examine more closely Buber’s conception of God’s command to the Jewish people to settle the land of Palestine in a manner that expresses love for their Arab neighbors, seeks harmony and peace in the land, and serves not only the common good among Jews and Arabs but the good of the land itself—that it would be fruitful for all. Central to Buber’s conception of the state of Israel in Palestine—and Jewish settlement more generally—was God’s ancient command that the Jews must establish a just society. The Jews must be faithful, Buber contended, to build a community and state that obeys God’s calling and aligns with their mission to reflect God’s justice in the world. Thus, understanding and harmony between the Jews and Arabs must be integral to the Jews’ approach to Arabs in Palestine, not peripheral to their mission. Buber’s response demonstrates his desire to relate directly and personally to Gandhi, to reveal falsehoods and misunderstandings, and to facilitate a greater awareness of the richness of the Jewish tradition that may be used to benefit the land of Palestine and its peoples. This vision for the Jewish mission deserves more attention in the historiography.

Abstract 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.

Introduction: Neurocognitive problems associated with posttraumatic stress disorder (PTSD) can interact with impairment resulting from traumatic brain injury (TBI). Research question: We aimed to identify neurocognitive problems associated with probable PTSD following TBI in a civilian sample. Material and methods: The study is part of the CENTER-TBI project (Collaborative European Neurotrauma Effectiveness Research) that aims to better characterize TBI. For this cross-sectional study, we included patients of all severities aged over 15, and a Glasgow Outcome Score Extended (GOSE) above 3. Participants were assessed at six months post-injury on the PTSD Checklist-5 (PCL-5), the Trail Making Test (TMT), the Rey Auditory Verbal Learning Test (RAVLT) and the Cambridge Neuropsychological Test Automated Battery (CANTAB). Primary analysis was a complete case analysis. Regression analyses were performed to investigate the association between the PCL-5 and cognition. Results: Of the 1134 participants included in the complete case analysis, 13.5% screened positive for PTSD. Probable PTSD was significantly associated with higher TMT-(B-A) (OR ​= ​1.35, 95% CI: 1.14–1.60, p ​

While Jägerstätter’s life and courageous stand against Hitler and National Socialism are well known and documented, the connections between his reading of scripture, his understanding of the way of the cross, and his conscientious objection have not been sufficiently explored by scholars. In his letters and writings, Jägerstätter repeatedly appealed to scripture’s call for the Christian to bear his or her cross and endure suffering, which he then used to support his stand as a conscientious objector to the Nazi regime. In one form or another, he refers to bearing the cross dozens of times in his letters and writings to emphasize the Christian’s call to obedience and discipleship to the glory of God. This article will examine his understanding of the cruciform life in the Greater German Reich, as one who conscientiously traveled the way of the cross. Jägerstätter used scripture as authoritative above other sources of knowledge or guidance—such as church hierarchy or tradition, experience, and feeling—to see the evil of National Socialism with clarity of vision; to prioritize his responsibilities to God, family, community, and the state; and to refine his conscience as a subject of the Greater German Reich. In these ways, Jägerstätter stood as a steadfast and committed man of faith and a model for the virtues of conscientious objection in the Christian tradition.

Abstract Clinical studies indicate that systemic infections accelerate cognitive decline in Alzheimer’s disease. Animal models suggest that this may be due to enhanced pro-inflammatory changes in the brain. We have performed a post-mortem human study to determine whether systemic infection modifies the neuropathology and in particular, neuroinflammation, in the late-stage of the disease. Sections of cerebral cortex and underlying white matter from controls and Alzheimer's patients who died with or without a terminal systemic infection were immunolabelled and quantified for: (i) Αβ and phosphorylated-tau; (ii) the inflammation-related proteins Iba1, CD68, HLA-DR, FcγRs (CD64, CD32a, CD32b, CD16), CHIL3L1, IL4R and CCR2; and (iii) T-cell marker CD3. In Alzheimer's disease, the synaptic proteins synaptophysin and PSD-95 were quantified by ELISA, and the inflammatory proteins and mRNAs by MesoScale Discovery Multiplex Assays and qPCR, respectively. Systemic infection in Alzheimer's disease was associated with decreased CD16 (p = 0.027, grey matter) and CD68 (p = 0.015, white matter); increased CD64 (p = 0.017, white matter) as well as increased protein expression of IL6 (p = 0.047) and decreased IL5 (p = 0.007), IL7 (p = 0.002), IL12/IL23p40 (p = 0.001), IL15 (p = 0.008), IL16 (p

Abstract According to the World Heritage Convention, rural landscapes are evolving cultural landscapes and their heritage and management is a major international concern. The proposal of UNESCO World Heritage Sustainable Tourism (WH+ST)’ has enlightened different arguments about protection and utilisation of the value of rural landscape heritage. The Outstanding Universal Value (OUV) of rural landscapes results from the interaction of nature and humankind. Local community residents are critical for the sustainable tourism development of rural landscape heritage. Landscapes would lose their authenticity and integrity without participation of community residents. At the same time tourism is promoting the economic development of communities, tourism will affect its natural environment and social culture in varying extents. Because of such impacts, rural landscapes are subject to the risk of becoming overly commercialised. In this sense, the discussion will focus on how to achieve balance among the various forces stemming from protection of the OUV of rural heritage, economic development and sustainable community-based tourism. This paper is based on field research at the World Heritage Hani Rice Terraces at Azheke Village (Yunnan Province, China). At this site, the agricultural landscape, architectural design, rural culture, and social traditions have confronted challenges because of the rapid development of the tourism industry soon after designation as a World Heritage Site in 2013. The planning was carried out in respect of three key problems: (1) How to motivate community residents’ sense of recognition and honour of the heritage value? (2) How to create the manner and approach for the community residents to participate in rural sustainable tourism? and (3) How to improve the social residents’ interests in the course of developing rural heritage tourism? Specific planning measures and suggestions have also been proposed in hopes that community residents take the initiative to protect, utilise and undertake the OUV of the Hani Rice Terraces.

Introduction: There is growing concern around the effects of concussion and sub-concussive impacts in sport. Routine game-play in soccer involves intentional and repeated head impacts through ball heading. Although heading is frequently cited as a risk to brain health, little data exist regarding the consequences of this activity. This study aims to assess the immediate outcomes of routine football heading using direct and sensitive measures of brain function. Methods: Nineteen amateur football players (5 females; age 22 ± 3 y) headed machine-projected soccer balls at standardized speeds, modelling routine soccer practice. The primary outcome measure of corticomotor inhibition measured using transcranial magnetic stimulation, was assessed prior to heading and repeated immediately, 24 h, 48 h and 2 weeks post-heading. Secondary outcome measures were cortical excitability, postural control, and cognitive function. Results: Immediately following heading an increase in corticomotor inhibition was detected; further to these electrophysiological alterations, measurable reduction memory function were also found. These acute changes appear transient, with values normalizing 24 h post-heading. Discussion: Sub-concussive head impacts routine in soccer heading are associated with immediate, measurable electrophysiological and cognitive impairments. Although these changes in brain function were transient, these effects may signal direct consequences of routine soccer heading on (long-term) brain health which requires further study.

Traumatic brain injury (TBI) is a serious public health concern which strikes someone every 15 s on average in the US. Even mild TBI, which comprise as many as 75% of all TBI cases, carries long term consequences. The effects of age and sex on long term outcome from TBI is not fully understood, but due to the increased risk for neurodegenerative diseases after TBI it is important to understand how these factors influence the outcome from TBI. This study examined the neurobehavioral and neuropathological effects of age and sex on the outcome 15 days following repetitive mild traumatic brain injury (r-mTBI) in mice transgenic for human tau (hTau). These mice express the six human isoforms of tau but do not express endogenous murine tau and they develop tau pathology and memory impairment in an age-dependent manner. After 5 mild impacts, aged female mice showed motor impairments that were absent in aged male mice, as well as younger animals. Conversely, aged female sham mice outperformed all other groups of aged mice in a Barnes maze spatial memory test. Pathologically, increases in IBA-1 and GFAP staining typically seen in this model of r-mTBI showed the expected increases with both injury and age, but phosphorylated tau stained with CP13 in the hippocampus (reduced in female sham mice compared to males) and PHF1 in the cortex (reduced in female TBI mice compared to male TBI mice) showed the only histological signs of sex-dependent differences in these mice.

In traditionally managed Howard walnut orchards, trees are pruned annually during the orchard development phase, an expensive operation in terms of labor and prunings disposal costs. Our observations and some prior research by others had suggested that pruning may not be necessary in walnut. In a trial of pruned and unpruned hedgerow trees over 8 years, beginning a year after planting, we documented canopy growth, tree height, yield and nut quality characteristics and also the effects of fruit removal. Pruning altered canopy shape but did not lead to increases in canopy development, yield or nut quality. Although fruit removal stimulated more vegetative growth in both the pruned and unpruned treatments, fruit removal did not result in an increase in midday canopy photosynthetically active radiation interception or cumulative yield when fruit removal was stopped after year 4. After 8 years, there were no significant differences in tree height, nut quality or cumulative yield among any of the treatments, which suggests that not pruning young Howard orchards could provide a net benefit to growers.

As part of California's strategy to reduce greenhouse gas emissions, private forest landowners are now required to address carbon sequestration as a management goal when submitting timber harvest plans. Using public data on forests and forest products, we developed a calculator that tracks the carbon sequestration benefits related to live trees, wood used for bioenergy and wood going into products. The calculator is adapted for different forest types, forest management techniques and time frames. Based on current best practices used in California, we estimate that harvested and regenerated forests will provide approximately 30% more total carbon sequestration benefits than forests left to grow for an equal time. More than half of the total benefits relate to harvested wood substituting for fossil fuels and fossil fuel–intensive materials such as cement and steel. With relatively efficient management practices, harvesting a ton of wood provides more sequestration benefits than leaving that ton growing in the forest.

Single-cell responses are shaped by the geometry of signalling kinetic trajectories carved in a multidimensional space spanned by signalling protein abundances. It is, however, challenging to assay a large number (more than 3) of signalling species in live-cell imaging, which makes it difficult to probe single-cell signalling kinetic trajectories in large dimensions. Flow and mass cytometry techniques can measure a large number (4 to more than 40) of signalling species but are unable to track single cells. Thus, cytometry experiments provide detailed time-stamped snapshots of single-cell signalling kinetics. Is it possible to use the time-stamped cytometry data to reconstruct single-cell signalling trajectories? Borrowing concepts of conserved and slow variables from non-equilibrium statistical physics we develop an approach to reconstruct signalling trajectories using snapshot data by creating new variables that remain invariant or vary slowly during the signalling kinetics. We apply this approach to reconstruct trajectories using snapshot data obtained from in silico simulations, live-cell imaging measurements, and, synthetic flow cytometry datasets. The application of invariants and slow variables to reconstruct trajectories provides a radically different way to track objects using snapshot data. The approach is likely to have implications for solving matching problems in a wide range of disciplines.

The parasite Cryptosporidium parvum represents a threat to livestock health and production, water quality and public health. Cattle are known to be significant reservoirs of C. parvum, but transmission routes are complex and recent studies have implicated the potential role of wildlife in parasite transmission to cattle and water sources. On the Orkney Isles, high densities of Greylag geese (Anser anser) cause widespread faecal contamination of cattle pastures, where cryptosporidiosis is known to be the main cause of neonatal calf diarrhoea and Cryptosporidium contamination frequently occurs in two reservoirs supplying Mainland Orkney’s public water. This study aimed to determine the Cryptosporidium species and subtypes present in geese and calves co-grazing on four farms surrounding two reservoirs on Mainland Orkney. Results indicated a high level of C. parvum prevalence in calves, geese and water samples. gp60 analysis illustrated that higher genotypic diversity was present in the goose population compared with calves, but did not yield sequence results for any of the water samples. It can be concluded that the high levels of C. parvum evident in calves, geese and water samples tested represents a significant risk to water quality and public health.

Forests play a central role in addressing climate change, and accurate estimates of forest carbon are critical for the development of actions that reduce emissions from forests and that maximize sequestration by forests. Methodological challenges persist regarding how best to estimate forest carbon stocks and flux at regulatory-relevant scales. Using California, USA as a case study, we compare two approaches to stock-difference forest carbon estimation for aboveground live trees: one based on ground inventories and one on land cover classification of remotely-sensed data. Previous work using ground inventory data from the Forest Inventory and Analysis Program (FIA) showed net aboveground carbon (AGC) sequestration by live trees in California forests, while estimates using land cover classification from the Landscape Fire and Resource Management Planning Tools (Landfire) showed net reductions in live tree AGC over a similar time period. We examined the discrepancy by re-analyzing the FIA inventory data through the lens of a category-change analysis based on Landfire. This analysis showed more than 50% of the live tree AGC in fewer than 4% of Landfire-equivalent categories and that the overwhelming majority (>80%) of forest area did not change height category between measurement periods. Despite the lack of categorical change, the majority of FIA plots increased in both 95th percentile tree height and in live tree AGC. These findings suggest that an approach based on observing categorical changes risks undercounting AGC sequestration resulting from growth and thus overstating the relative importance of AGC reductions that result from disturbances. This would bias AGC flux estimates downward, leading us to validate the conclusion that live trees in California were a net sink of aboveground carbon in the decade ending in 2016. Our findings suggest an inventory-based or hybrid approach is preferable to methods that depend on categorical bins for estimating AGC in disturbance-prone forest ecosystems.

Background: TAVR has emerged as an attractive alternative for treatment of severe aortic stenosis in high risk surgical patients. Despite several large multicenter registries, only one randomized trial (PARTNER) has been published. Objective: We aimed to compare the outcomes obtained using multicenter registries and the PARTNER trial. Methods: Standard MEDLINE search strategy was used to find multicenter registries, reporting clinical outcomes following TAVR. Meta-analytic techniques were utilized to calculate pooled outcomes across multicenter registries and compare them to outcomes in PARTNER trial. Results: Pooled 30-day mortality rate from the registries was 9.2%, which was significantly higher than that in the PARTNER trial (3.8%). Medium-term mortality rates were similar between the PARTNER trial and the multicenter registries. Pooled 30-day and 1-year stroke rates in multicenter registries were 2.6% and 3.8%, respectively. On the other hand, the corresponding rates in PARTNER trial were 5.2% and 7.6%, respectively. In the registry-related cohorts, pooled 30-day and 1-year mortality rates were 6.8% and 20.8% in the transfemoral group and 12.2% and 32.2% in the transapical group. In the PARTNER trial, the pooled incidence of 30-day and 1-year mortality rates were 3.9% and 26.2% in the transfemoral group and 3.8% and 29.0% in the transapical group. Conclusions: Short-term results in PARTNER were better than those reported in the registries, which may be due to better patient selection and aggressive bailout techniques. Similarity of medium-term outcomes between registries and PARTNER highlights that patient selection for TAVR is critical due to considerable risk of mortality in the first year even after the successful procedure.

Abstract Observed patterns of genetic variability among marine populations are shaped not only by contemporary levels of gene flow, but also by divergences during historical isolations. We examined variability at 15 SNP loci and in mtDNA sequences (COI, 665 bp) in red king crab from 17 localities in the North Pacific. These markers define three geographically distinct evolutionary lineages (SNPs, FCT = 0.054; mtDNA ΦCT = 0.222): (i) Okhotsk Sea–Norton Sound–Aleutian Islands, (ii) southeastern Bering Sea–western Gulf of Alaska, and (iii) Southeast Alaska. Populations in the Bering Sea and in Southeast Alaska are genetically heterogeneous, but populations in the center of the range are homogeneous. Mitochondrial DNA diversity drops from h = 0.91 in the northwestern Pacific to h = 0.24 in the Southeast Alaska. Bayesian skyline plots (BSPs) indicate postglacial population expansions, presumably from ice‐age refugia. BSPs of sequences simulated under a demographic model defined by late Pleistocene temperatures failed to detect demographic variability before the last glacial maximum. These results sound a note of caution for the interpretation of BSPs. Population fragmentation in the Bering Sea and in Southeast Alaskan waters requires population management on a small geographic scale, and deep evolutionary partitions between the three geographic groups mandate regional conservation measures.

BackgroundThe aim of this study was to compare left ventricular (LV) remodeling using myocardial strain between patients with severe aortic stenosis (AS) treated with transcatheter aortic valve replacement (TAVR) with and without prosthesis‐patient mismatch (PPM). Methods and ResultsIn a retrospective study, speckle‐tracking echocardiography was used to measure global longitudinal strain (GLS) and strain rate (GLSR), circumferential strain, and rotation before and at mid‐term follow‐up post‐TAVR. Moderate and severe PPM were defined as an effective orifice area ≤0.85 and

The sustained exploitation of marine populations requires an understanding of a species' adaptive seascape so that populations can track environmental changes from short- and long-term climate cycles and from human development. The analysis of the distributions of genetic markers among populations, together with correlates of life-history and environmental variability, can provide insights into the extent of adaptive variation. Here, we examined genetic variability among populations of mature European anchovies (n = 531) in the Adriatic (13 samples) and Tyrrhenian seas (2 samples) with neutral and putative non-neutral microsatellite loci. These genetic markers failed to confirm the occurrence of two anchovy species in the Adriatic Sea, as previously postulated. However, we found fine-scale population structure in the Adriatic, especially in northern areas, that was associated with four of the 13 environmental variables tested. Geographic gradients in sea temperature, salinity and dissolved oxygen appear to drive adaptive differences in spawning time and early larval development among populations. Resolving adaptive seascapes in Adriatic anchovies provides a means to understand mechanisms underpinning local adaptation and a basis for optimizing exploitation strategies for sustainable harvests.

Forty-two percent of California's forests and rangelands are privately owned (34 million acres). These lands provide important ecosystem services such as carbon sequestration, pollination and wildlife habitat, but little is known about the people who own and manage them. We surveyed forest and rangeland owners in California and found that these long-time landowners value their properties for their natural amenities and as a financial investment. Owners of large properties (500 or more acres) were significantly more likely to use their land for income production than owners of smaller properties, and they were also more likely to carry out or be interested in environmental improvements. Many forest and rangeland owners reported they had been previously approached to sell their land for development. Only about one-third had participated in conservation programs; few had conservation easements. This survey can help guide outreach and education efforts, and the development of information, policies, programs and financial incentives for landowners.

The extent of wildfires in the western United States is increasing, but how land ownership, firefighting, and reserve status influence fire probability is unclear. California serves as a unique natural experiment to estimate the impact of these factors, as ownership is split equally between federal and non-federal landowners; there is a relatively large proportion of reserved lands where extractive uses are prohibited and fire suppression is limited; and land ownership and firefighting responsibility are purposefully not always aligned. Panel Poisson regression techniques and pre-regression matching were used to model changes in annual fire probability from 1950–2015 on reserve and non-reserve lands on federal and non-federal ownerships across four vegetation types: forests, rangelands, shrublands, and forests without commercial species. Fire probability was found to have increased over time across all 32 categories. A marginal effects analysis showed that federal ownership and firefighting was associated with increased fire probability, and that the difference in fire probability on federal versus non-federal lands is increasing over time. Ownership, firefighting, and reserve status, played roughly equal roles in determining fire probability, and were found to have much greater influence than average maximum temperature (°C) during summer months (June, July, August), average annual precipitation (cm), and average annual topsoil moisture content by volume, demonstrating the critical role these factors play in western fire regimes and the importance of including them in future analysis focused on understanding and predicting wildfire in the Western United States.

An analysis by Sterman et al (2018 Environ. Res. Lett. 13 015007) suggests that use of wood for bioenergy production results in a worse climate outcome than from using coal. However, many of the assumptions on which their primary wood bioenergy scenario is based are not realistic and therefore are not informative. Assumptions of uncharacteristically long rotations for southern pine plantations, no utilization of wood for longer-duration products, and a single harvest over 100 years understate the carbon performance of current forest management practices. We provide references that support realistic modeling of forest carbon dynamics that are reflective of current practice and therefore more informative.

A plant-based regulated deficit irrigation (RDI) experiment in the northern Sacramento Valley determined that crop consumptive water use and irrigation could be reduced without significant detrimental effects on almond production. Tree stress was measured by recording midday stem water potential, a direct measure of tree water stress. With a water stress level of -14 to -18 bars during the hull-split period, average annual water savings were about 5 inches. Over 5 years, no significant yield reductions were observed, although average kernel weight was slightly lower. The results suggest that water savings can be achieved without affecting yield, even in soils with low water-holding capacity.

This is a semester-long study of the development of first-person biofunctional understanding in educational psychology for teacher education majors. We defined biofunctional under-standing as a spontaneous intellectual capacity. To reach its deep biological levels, sculpted by countless evolutionary millennia, students identified and dwelled in writing on their biggest idea of every week for a semester. They stated the idea in a simple sentence and followed by writing a concise paragraph to contemplate on it. Control sections equated their biggest idea with one most important to learn through the conventional learning-testing cycle of deliberate knowledge internalization or construction. Experimental sections fought the learning-testing-cycle urge and sought by hindsight the biggest idea of the most striking revelation (MSR) delivered to their awareness spontaneously by the biofunctional<>psycho-logyical spiral of their intuition>revelation<>reflection cycle. Results showed that experimental condition outperformed the control in the development of their insightful understanding measured by a Levels of Revelatory Strikingness Scale (LRSS) suggesting that learners change their understanding as a function of their 1st-person revelations than 2nd/3rd-person evidence

Meta-analyses of genome-wide association studies (GWAS) have improved our understanding of the genetic foundations of a number of diseases, including diabetes. However, SNPs that are identified by GWAS, especially those that fall outside of gene regions, do not always clearly link to the underlying biology. Despite this, these SNPs have often been validated through re-sequencing efforts as not just tag SNPs, but as causative SNPs, and so must play a role in disease development or progression. In this study, we show how the 3D genome (spatial connections) and trans-expression Quantitative Trait Loci (trans-eQTL) connect diabetes loci from different GWAS meta-analyses, informing the backbone of regulatory networks. Our findings include a three-way functional-spatial connection between the TM6SF2, CTRB1-BCAR1, and CELSR2-PSRC1 loci (rs201189528, rs7202844, and rs7202844, respectively) connected through the KCNIP3 and BCAR1/BCAR3 loci, respectively. These spatial hubs serve as an example of how loci in genes with little biological connection to disease come together to contribute to the diabetes phenotype.

Genome wide association studies are central to the evolution of personalized medicine. However, the propensity for SNPs to fall outside of genes means that understanding how these polymorphisms alter cellular function requires an expanded view of human genetics. Integrating the study of genome structure (chromosome conformation capture) into its function opens up new avenues of exploration. Changes in the epigenome associated with SNPs in gene deserts will allow us to define complex diseases in a much clearer manner, and usher in a new era of disease pathway exploration.

Intracranial metastases from liposarcoma are rare and almost always preceded by the development of systemic tumour spread. We report here a case of liposarcoma with spread to the cranial nervous system 23 years after treatment of the primary tumour. The literature on brain metastases from soft tissue sarcoma is also reviewed.

ObjectiveThis exploratory study is the first to examine family-based treatment (FBT) adherence and association to treatment outcome in the context of a large-scale, multi-centre study for the treatment of adolescents with anorexia nervosa.MethodOne hundred and ninety recorded FBT sessions from 68 adolescents with anorexia nervosa and their families were recruited across multiple sites (N = 6). Each site provided 1-4 tapes per family over four treatment time points, and each was independently rated for therapist adherence.ResultsThere were differences in adherence scores within and between sites. ANOVA produced a main effect for site, F(5, 46) = 8.6, p

Friedrich Schleiermacher emerged as a prominent advocate for German nationalism in the Wars of Liberation from Napoleonic domination in the early nineteenth century. Alongside his work as a pastor and theologian in Berlin, and also as the co-founder of the University of Berlin, Schleiermacher developed German nationalism from a distinctly Protestant perspective, one that sought the preservation of Protestantism in the German lands under Napoleonic domination. While it would be an overstatement to suggest that Schleiermacher's nationalism was anti-Catholic, he certainly sought to preserve and maintain Protestantism in the German lands. His vision of the German nation-state emphasized Germany's role as a divine instrument of God's will in the world. He assumed the cultural unity of the peoples in German lands, that is, an area of land in which the peoples are bound together by the common use of the German language. In his distinct role as a pastor, theologian, and academic, he was devoted to the cultivation of German national consciousness and the establishment of a German nation-state. Schleiermacher's work would help to provide a cultural foundation for the emergence of the German nation-state more than half a century before the establishment of the German empire. [ABSTRACT FROM AUTHOR]