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Supplemental material, sj-pdf-1-jcb-10.1177_0271678X231173584 for High-physiological and supra-physiological 1,2-13C2 glucose focal supplementation to the traumatised human brain by Matthew G Stovell, Duncan J Howe, Eric P Thelin, Ibrahim Jalloh, Adel Helmy, Mathew R Guilfoyle, Peter Grice, Andrew Mason, Susan Giorgi-Coll, Clare N Gallagher, Michael P Murphy, David K Menon, T Adrian Carpenter, Peter J Hutchinson and Keri LH Carpenter in Journal of Cerebral Blood Flow & Metabolism

Impaired cerebrovascular reactivity has emerged as an important associate with poor long-term outcome after moderate/severe traumatic brain injury (TBI). However, our understanding of what drives or modulates the degree of impaired cerebrovascular function remains poor. Age and biological sex remain important modifiers of cerebrovascular function in health and disease, yet their impact on cerebrovascular reactivity after TBI remains unclear. The aim of this study was to explore subgroup responses based on age and biological sex on cerebral physiology. Data from 283 TBI patients from the CAnadian High Resolution TBI (CAHR-TBI) Research Collaborative were evaluated. Cerebrovascular reactivity was determined using high-frequency cerebral physiology for the derivation of three intracranial pressure (ICP) based indices: (1). PRx - correlation between ICP and mean arterial pressure (MAP), (2). PAx - correlation between pulse amplitude of ICP (AMP) and MAP and (3). RAC - correlation between AMP and cerebral perfusion pressure (CPP). Insult burden (% time above clinically defined thresholds) were calculated for these indices. These cerebral physiology indices were studied for their relationship with age via linear regression, age trichotomization (< 40, 40 - 60, > 60) and decades of age (< 30, 30 - 39, 40 - 49, 50 - 59, 60 - 69, > 69) schemes. Similarly, differences based on biological sex were assessed. A statistically significant positive linear correlation was found between PAx, RAC and age. In corollary, a statistically significant relationship was found between increasing age on trichotomized and decades of age analysis with PAx and RAC measures. PRx failed to demonstrate such relationships to advancing age. There was no clear difference in cerebrovascular reactivity profiles between biological sex categories. These findings suggest that AMP-based cerebrovascular reactivity indices may be better positioned to detect impairment in TBI patients with advancing age. Further investigation into the utility of PAx and RAC is required, as they may prove useful for certain subgroups of patients.

The Policing and Crime Act 2017 (PACA) aims to promote integrity within policing via a reformed police complaints and discipline process that focuses on lesson learning. Integrity and lesson learning are virtuous aspirations, but this paper queries the degree to which the reforms deliver them. Importantly, the analysis here provides a novel contribution to debates about lesson learning within the police by distinguishing lesson learning directed towards street-level officers from the accountability of police professional standards departments (PSDs) for how that is delivered. Focusing on the latter and drawing on the findings of the Chapman Review and a detailed analysis of police complaints statistics, it concludes that true lesson learning (from which increased integrity within forces can develop) requires increased external scrutiny of PSDs. In contrast, the analysis demonstrates that the PACA significantly increases PSDs’ de facto autonomy over the police complaints and discipline process and incorporates a shift in how independent oversight of police complaints is conceived. The paper borrows from Valverde’s suggested analytical framework to probe the underlying logic of the reforms, considering also the techniques they employ and the scale at which they operate. This reveals that the lesson learning agenda reframes expressions by citizens of mistreatment at the hands of the police as data upon which future policy might be based. In doing so, far from working to improve integrity, it may instead be ushering in a concerning biopolitical conception of policing which has the potential to exacerbate the worst features of police operational culture.

In traumatic brain injury (TBI), future integration of multimodal monitoring of cerebral physiology and high-frequency signal processing techniques, with advanced neuroimaging, proteomic and genomic analysis, provides an opportunity to explore the molecular pathways involved in various aspects of cerebral physiologic dysfunctionin vivo. The main issue with early and rapid discovery in this field of personalized medicine is the expertise and complexity of data involved. This brief communication highlights the CAnadian High-Resolution Traumatic Brain Injury (CAHR-TBI) Research Collaborative, which has been formed from centers with specific expertise in the area of high-frequency physiologic monitoring/processing, and outlines its objectives.

How to optimise glucose metabolism in the traumatised human brain remains unclear, including whether injured brain can metabolise additional glucose when supplied. We studied the effect of microdialysis-delivered 1,2-13C2 glucose at 4 and 8 mmol/L on brain extracellular chemistry using bedside ISCUS flex, and the fate of the 13C label in the 8 mmol/L group using high-resolution NMR of recovered microdialysates, in 20 patients. Compared with unsupplemented perfusion, 4 mmol/L glucose increased extracellular concentrations of pyruvate (17%, p = 0.04) and lactate (19%, p = 0.01), with a small increase in lactate/pyruvate ratio (5%, p = 0.007). Perfusion with 8 mmol/L glucose did not significantly influence extracellular chemistry measured with ISCUS flex, compared to unsupplemented perfusion. These extracellular chemistry changes appeared influenced by the underlying metabolic states of patients’ traumatised brains, and the presence of relative neuroglycopaenia. Despite abundant 13C glucose supplementation, NMR revealed only 16.7% 13C enrichment of recovered extracellular lactate; the majority being glycolytic in origin. Furthermore, no 13C enrichment of TCA cycle-derived extracellular glutamine was detected. These findings indicate that a large proportion of extracellular lactate does not originate from local glucose metabolism, and taken together with our earlier studies, suggest that extracellular lactate is an important transitional step in the brain’s production of glutamine.

Pediatric glioblastoma multiforme (GBM) involving the spine is an aggressive tumor with a poor quality of life for patients. Despite this, there is only a limited number of reports describing the outcomes of pediatric spinal GBMs, both as primary spinal GBMs and metastases from an intracranial tumor. Here, we performed an individual patient meta-analysis to characterize factors affecting prognosis of pediatric spinal GBM. MEDLINE, Embase, and the Cochrane databases were searched for published studies on GBMs involving the spine in pediatric patients (age ≤ 21 years old). Factors associated with the survival were assessed with multi-factor ANOVAs, Cox hazard regression, and Kaplan-Meier analyses. We extracted data on 61 patients with spinal GBM from 40 studies that met inclusion criteria. Median survival was significantly longer in the primary spinal GBM compared that those with metastatic GBM (11 vs 3 months, p < 0.001). However, median survival of metastatic GBM patients was 10 months following diagnosis of their primary brain tumor, which was not different from that of primary spinal GBM patients (p = 0.457). Among primary spinal GBM patients, chemotherapy (hazard ratio (HR) = 0.255 [0.106–0.615], p = 0.013) and extent of resection (HR = 0.582 [0.374–0.905], p = 0.016) conferred a significant survival benefit. Younger age (less than 14 years) was associated with longer survival in patients treated with chemotherapy than those who did not undergo chemotherapy (β = − 1.12, 95% CI [− 2.20, − 0.03], p < 0.05). In conclusion, survival after presentation of metastases from intracranial GBM is poor in the pediatric population. In patients with metastatic GBM, chemotherapy may have provided the most benefit in young patients, and its efficacy might have an association with extent of surgical resection.

The shift from volume-based to value-based reimbursement has created a need for quantifying clinical performance of infectious diseases (ID) physicians. Nationally recognized ID specialty-specific quality measures will allow stakeholders, such as patients and payers, to determine the value of care provided by ID physicians and will promote clinical quality improvement. Few ID-specific measures have been developed; herein, we provide an overview of the importance of quality measurement for ID, discuss issues in quality measurement specific to ID, and describe standards by which candidate quality measures can be evaluated. If ID specialists recognize the need for quality measurement, then ID specialists can direct ID-related quality improvement, quantify the impact of ID physicians on patient outcomes, compare their performance to that of peers, and convey to stakeholders the value of the specialty.

During a midwinter cruise north of 80°N to Rijpfjorden, Svalbard, the composition and vertical distribution of the zooplankton community were studied using two different samplers 1) a vertically hauled multiple plankton sampler (MPS; mouth area 0.25 m2, mesh size 200 μm) and 2) a horizontally towed Methot Isaacs Kidd trawl (MIK; mouth area 3.14 m2, mesh size 1500 μm). Our results revealed substantially higher species diversity (49 taxa) than if a single sampler (MPS: 38 taxa, MIK: 28) had been used. The youngest stage present (CIII) of Calanus spp. (including C. finmarchicus and C. glacialis) was sampled exclusively by the MPS, and the frequency of CIV copepodites in MPS was double that than in MIK samples. In contrast, catches of the CV-CVI copepodites of Calanus spp. were substantially higher in the MIK samples (3-fold and 5-fold higher for adult males and females, respectively). The MIK sampling clearly showed that the highest abundances of all three Thysanoessa spp. were in the upper layers, although there was a tendency for the larger-sized euphausiids to occur deeper. Consistent patterns for the vertical distributions of the large zooplankters (e.g. ctenophores, euphausiids) collected by the MPS and MIK samplers provided more complete data on their abundances and sizes than obtained by the single net. Possible mechanisms contributing to the observed patterns of distribution, e.g. high abundances of both Calanus spp. and their predators (ctenophores and chaetognaths) in the upper water layers during midwinter are discussed.

Crossmodal correspondences are a feature of human perception in which two or more sensory dimensions are linked together; for example, high-pitched noises may be more readily linked with small than with large objects. However, no study has yet systematically examined the interaction between different visual-auditory crossmodal correspondences. We investigated how the visual dimensions of luminance, saturation, size, and vertical position can influence decisions when matching particular visual stimuli with high-pitched or low-pitched auditory stimuli. For multidimensional stimuli, we found a general pattern of summation of the individual crossmodal correspondences, with some exceptions that may be explained by Garner interference. These findings have applications for the design of sensory substitution systems, which convert information from one sensory modality to another.

Objective:To address whether to restart older patients on anticoagulants or antiplatelet agents in the setting of a chronic subdural hematoma (cSDH).Methods:This is an update of a previous review (searched until July 2012). Medline, EMBASE, ISI Web of Knowledge, Google Scholar, PLOS, and the Cochrane Register for Systematic Reviews databases were searched from January 2012 to December 2016. Studies included older adults (those over 65 years) experiencing traumatic subdural hematoma or cSDH who were on anticoagulation or antiplatelet agents.Results:Seven studies were included (mean age 72 years). Four out of 7 studies provided combined data on anticoagulants or antiplatelet use. Only one study found anticoagulant or antiplatelet agent use to be a significant factor for cSDH rebleeding. Two studies considered anticoagulant use only and both reported similar increased odds of rebleeding (odds ratio [OR] 1.75, 95% confidence interval [CI] 0.18–16.86; OR 2.7 95% CI 1.42–6.96). Antiplatelets were not found to be associated with rebleeding. Ideal timing to resume anticoagulants or antiplatelets was unclear.Conclusions:Anticoagulant medication was associated with increased rebleeding risk in older adults with cSDH. However, antiplatelet medication was not associated with increased risk of rebleeding.

Introduction Mild traumatic brain injury (mTBI) outcomes are variable, and 10–15% may suffer from prolonged symptoms beyond 3 months that impair the child's return to normal activities. Neurophysiological mechanisms of mTBI are incompletely understood, particularly in children, but alterations in cortical excitability have been proposed to underlie post-concussion syndrome. Improved understanding is required to advance interventions and improve outcomes. Objective/Hypothesis To determine if cortical excitability is altered in children with mTBI, and its association with clinical symptoms. Methods This was a cross-sectional controlled cohort study. School-aged children (8–18 years) with mTBI were compared to healthy controls. Cortical excitability was measured using multiple TMS paradigms in children with (symptomatic) and without (recovered) persistent symptoms one-month post-injury. Primary outcome was the cortical silent period (cSP), a potential neurophysiological biomarker of GABAergic inhibition. Secondary outcomes included additional TMS neurophysiology, safety and tolerability. Associations between neurophysiology parameters and clinical symptoms were evaluated. Results Fifty-three children with mTBI (55% male; mean age 14.1 SD: 2.4 years; 35 symptomatic and 27 asymptomatic participants) and 28 controls (46% male; mean age 14.3 SD: 3.1 years) were enrolled. cSP duration was similar between groups (F (2, 73) = 0.55, p = 0.582). Log 10 long interval intracortical inhibition (LICI) was reduced in symptomatic participants compared to healthy controls (F (2, 59) = 3.83, p = 0.027). Procedures were well tolerated with no serious adverse events. Conclusions TMS measures of cortical excitability are altered at one month in children with mTBI. Long interval cortical inhibition is decreased in children who remain symptomatic at one month post-injury.

Previous research has indicated a potential link between mental imagery and synaesthesia. However, these findings are mainly based on imagery self-report measures and recruitment of self-selected synaesthetes. To avoid issues of self-selection and demand effects, we recruited participants from the general population, rather than synaesthetes specifically, and used colour-picking consistency tests for letters and numbers to assess a ‘synaesthete-like’ experience. Mental imagery ability and mental rotation ability were assessed using both self-report measures and behavioural assessments. Consistency in colour-picking for letters (but not numbers) was predicted by performance on the visual mental imagery task but not by a mental rotation task or self-report measures. Using the consistency score as a proxy measure of grapheme-colour synaesthesia, we provide more evidence for the suggestion that synaesthetic experience is associated with enhanced mental imagery, even when participants are naive to the research topic. This article is part of a discussion meeting issue ‘Bridging senses: novel insights from synaesthesia’.

Background Time spent on the waiting list before liver transplantation (LT) provides an opportunity to optimize recipient fitness through prehabilitation, potentially reducing the physiological impact of major surgery. We assessed the feasibility and effectiveness of a 6-week exercise program in patients with cirrhotic liver disease awaiting LT. Methods This single-center, prospective cohort, feasibility study, enrolled patients awaiting LT to a 6-week period of thrice weekly, supervised exercise on a static bike. Cardiopulmonary exercise testing (CPET) was used to objectively assess cardiopulmonary fitness at baseline and after 6 weeks of exercise. A follow-up CPET was performed at 12 weeks. CPET-derived measures were used to guide prescription of the training program. A nonrandomized control cohort of LT patients were selected to match the exercise group based on specific demographic data. Allocation to study arms was primarily based on the distance participants lived from the hospital where training occurred. Both groups received structured nutritional advice. Results The exercise program was feasible, with 9 of 16 (56%) patients completing the full program of 6 weeks. Peak oxygen consumption (VO2peak) in the exercise group rose from a mean (SD) of 16.2 (±3.4) mL/kg/min at baseline to 18.5 (±4.6) mL/kg/min at week 6 (P = 0.02). In the control group, VO2peak decreased from a mean (SD) of 19.0 (±6.1) mL/kg/min to 17.1 (±6.0) at week 6 (P = 0.03). Conclusions We have demonstrated that it is feasible to engage patients awaiting LT in an intensive aerobic exercise program with a signal of improvement in fitness being detected.

The world is full of objects that can be perceived through multiple different senses to create an integrated understanding of our environment. Since each of us has different biological and psychological characteristics, different people may perceive the world in quite different ways. However, the questions of how and why our multisensory perceptions differ have not been explored in any great depth. This special issue, arising from a series of British Psychological Society-funded seminars, presents new research and opinions on the impacts of a variety of individual differences on multisensory perception. We hope that readers will enjoy this collection of eight papers on individual differences in multisensory perception arising from developmental changes, autism, Down syndrome, migraine, sensory loss and substitution, and personality.

Background: Understanding the epidemiology of traumatic brain injury (TBI) is essential to shape public health policy, implement prevention strategies, and justify allocation of resources toward research, education, and rehabilitation in TBI. There is not, to our knowledge, a systematic review of population-based studies addressing the epidemiology of TBI that includes all subtypes. We performed a comprehensive systematic review and meta-analysis of the worldwide incidence of TBI. Methods: A search was conducted on May 23, 2014, in Medline and EMBASE according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Abstracts were screened independently and in duplicate to identify original research. Study quality and ascertainment bias were assessed in duplicate using a previously published tool. Demographic data and incidence estimates from each study were recorded, along with stratification by age, gender, year of data collection, and severity. Results: The search strategy yielded 4944 citations. Two hundred and sixteen articles met criteria for full-text review; 144 were excluded. Hand searching resulted in ten additional articles. Eighty-two studies met all eligibility criteria. The pooled annual incidence proportion for all ages was 295 per 100,000 (95% confidence interval: 274-317). The pooled incidence rate for all ages was 349 (95% confidence interval: 96.2-1266) per 100,000 person-years. Incidence proportion and incidence rate were examined to see if associated with age, sex, country, or severity. Conclusions: We conclude that most TBIs are mild and most TBIs occur in males among the adult population. The incidence of TBI varies widely by ages and between countries. Despite being an important medical, economic, and social problem, the global epidemiology of TBI is still not well-characterized in the current literature. Understanding the incidence of TBI, particularly mild TBI, remains challenging because of nonstandardized reporting among neuroepidemiological studies.

An effective police complaints system is important in securing and maintaining police legitimacy. There is, however, a lack of clarity regarding the nature of the relationship between the two. What does it mean for the police complaints system to be effective and how does it contribute to the legitimacy of the police? Further, what does the way in which the complaints system operates reveal about how police legitimacy is conceived? This article argues that police legitimacy can be analysed by reference to two ideal types, organisational and constitutional legitimacy. In developing these ideas, it contends that reconceptualising the police complaints system as a key site where they become contested will enhance normative debate in this area. In addition, conceiving of the police complaints system in this broader sense also serves to highlight the importance of its function in providing the data that will make such debate meaningful.

BackgroundGuidelines recommend maintaining cerebral perfusion pressure (CPP) between 60 and 70mmHg in patients with severe traumatic brain injury (TBI), but acknowledge that optimal CPP may vary depending on cerebral blood flow autoregulation. Previous retrospective studies suggest that targeting CPP where the pressure reactivity index (PRx) is optimized (CPPopt) may be associated with improved recovery.MethodsWe performed a retrospective cohort study involving TBI patients who underwent PRx monitoring to assess issues of feasibility relevant to future interventional studies: (1) the proportion of time that CPPopt could be detected; (2) inter-observer variability in CPPopt determination; and (3) agreement between manual and automated CPPopt estimates. CPPopt was determined for consecutive 6-h epochs during the first week following TBI. Sixty PRx-CPP tracings were randomly selected and independently reviewed by six critical care professionals. We also assessed whether greater deviation between actual CPP and CPPopt (CPP) was associated with poor outcomes using multivariable models.ResultsIn 71 patients, CPPopt could be manually determined in 985 of 1173 (84%) epochs. Inter-observer agreement for detectability was moderate (kappa 0.46, 0.23-0.68). In cases where there was consensus that it could be determined, agreement for the specific CPPopt value was excellent (weighted kappa 0.96, 0.91-1.00). Automated CPPopt was within 5mmHg of manually determined CPPopt in 93% of epochs. Lower PRx was predictive of better recovery, but there was no association between CPP and outcome. Percentage time spent below CPPopt increased over time among patients with poor outcomes (p=0.03). This effect was magnified in patients with impaired autoregulation (defined as PRx>0.2; p=0.003).ConclusionProspective interventional clinical trials with regular determination of CPPopt and corresponding adjustment of CPP goals are feasible, but measures to maximize consistency in CPPopt determination are necessary. Although we could not confirm a clear association between CPP and outcome, time spent below CPPopt may be particularly harmful, especially when autoregulation is impaired.

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

We report on the rates of decomposition of a group of N-methylcarbamate (NMC) pesticides (carbaryl, carbofuran and propoxur) under pre-determined tropical field conditions. Rates of decomposition for three NMCs were determined at pH 7.08 and T = 20 °C and pH 7.70 and T = 33 °C respectively, as follows: carbaryl (78 days and 69 days); carbofuran (143 days and 83 days) and propoxur (116 days and 79 days). Investigation on methods for removal of NMCs and their phenolic decomposition products shows that activated charcoal outperforms zeolite, alumina, diatomaceous earth, cellulose and montmorillonite clay in the removal of both NMCs and phenols from aqueous solution. Furthermore, metal complexation studies on the NMCs and phenols showed that Fe (III) forms a complex with isopropoxyphenol (IPP) within which the Fe:IPP ratio is 1:3, indicative of the formation of a metal chelate complex with the formula Fe(IPP)

Metabolic abnormalities occur after traumatic brain injury (TBI). Glucose is conventionally regarded as the major energy substrate, although lactate can also be an energy source. We compared 3-13C lactate metabolism in TBI with “normal” control brain and muscle, measuring 13C-glutamine enrichment to assess tricarboxylic acid (TCA) cycle metabolism. Microdialysis catheters in brains of nine patients with severe TBI, five non-TBI brain surgical patients, and five resting muscle (non-TBI) patients were perfused (24 h in brain, 8 h in muscle) with 8 mmol/L sodium 3-13C lactate. Microdialysate analysis employed ISCUS and nuclear magnetic resonance. In TBI, with 3-13C lactate perfusion, microdialysate glucose concentration increased nonsignificantly (mean +11.9%, p = 0.463), with significant increases (p = 0.028) for lactate (+174%), pyruvate (+35.8%), and lactate/pyruvate ratio (+101.8%). Microdialysate 13C-glutamine fractional enrichments (median, interquartile range) were: for C4 5.1 (0–11.1) % in TBI and 5.7 (4.6–6.8) % in control brain, for C3 0 (0–5.0) % in TBI and 0 (0–0) % in control brain, and for C2 2.9 (0–5.7) % in TBI and 1.8 (0–3.4) % in control brain. 13C-enrichments were not statistically different between TBI and control brain, showing both metabolize 3-13C lactate via TCA cycle, in contrast to muscle. Several patients with TBI exhibited 13C-glutamine enrichment above the non-TBI control range, suggesting lactate oxidative metabolism as a TBI “emergency option.”