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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 ISCUSflex, 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 ISCUSflex, 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.

Following traumatic brain injury (TBI), raised cerebral lactate/pyruvate ratio (LPR) reflects impaired energy metabolism. Raised LPR correlates with poor outcome and mortality following TBI. We prospectively recruited patients with TBI requiring neurocritical care and multimodal monitoring, and utilised a tiered management protocol targeting LPR. We identified patients with persistent raised LPR despite adequate cerebral glucose and oxygen provision, which we clinically classified as cerebral 'mitochondrial dysfunction' (MD). In patients with TBI and MD, we administered disodium 2,3-13C2 succinate (12 mmol/L) by retrodialysis into the monitored region of the brain. We recovered 13C-labelled metabolites by microdialysis and utilised nuclear magnetic resonance spectroscopy (NMR) for identification and quantification.Of 33 patients with complete monitoring, 73% had MD at some point during monitoring. In 5 patients with multimodality-defined MD, succinate administration resulted in reduced LPR(-12%) and raised brain glucose(+17%). NMR of microdialysates demonstrated that the exogenous 13C-labelled succinate was metabolised intracellularly via the tricarboxylic acid cycle. By targeting LPR using a tiered clinical algorithm incorporating intracranial pressure, brain tissue oxygenation and microdialysis parameters, we identified MD in TBI patients requiring neurointensive care. In these, focal succinate administration improved energy metabolism, evidenced by reduction in LPR. Succinate merits further investigation for TBI therapy., The authors disclose receipt of the following financial support for the research, authorship, and/or publication of this article: Medical Research Council (Grant no.G1002277 ID98489) and National Institute for Health Research Biomedical Research Centre, Cambridge (Neuroscience Theme; Brain Injury and Repair Theme). Authors��� support: NMG���National Institute for Health Research; AA���Academy of Medical Sciences Newton Fellowship; MGS���National Institute for Health Research Biomedical Research Centre, Cambridge; IJ���Medical Research Council (Grant no.G1002277 ID 98489) and National Institute for Health Research Biomedical Research Centre, Cambridge; DKM���National Institute for Health Research Senior Investigator Awards; MJK���Cambridge Australia Oliphant Scholarship in partnership with the Cambridge Trust; PJH���National Institute for Health Research (Professorship, Biomedical Research Centre, Brain Injury MedTech Co-operative, Senior Investigator Award and the Royal College of Surgeons of England; KLHC���National Institute for Health Research Biomedical Research Centre, Cambridge (Neuroscience Theme; Brain Injury and Repair Theme); EPT���Swedish Brain Foundation (Hj��rnfonden), Swedish Medical Society (SLS) and Swedish Society for Medical Research (SSMF); AH���Medical Research Council/Royal College of Surgeons of England Clinical Research Training Fellowship (Grant no.G0802251), the NIHR Biomedical Research Centre and the NIHR Brain Injury MedTech Co-operative.

Using data received through the Freedom of Information Act, this observational study explores whether Army law enforcement personnel do not find probable cause in sexual assault cases at higher rates than in other serious crimes. The study compares sexual assaults, homicides, robberies, and assaults in the Army from 2008 to 2014 and July 2015 to 2017. For the first period, the study finds that the odds are 5.30 times greater that Army law enforcement will not find probable cause in a sexual assault case when compared to other crimes, and for the second period the odds are 4.39 times greater.

Objective Youth with early-onset mood or psychotic disorders are occasionally prescribed metformin to manage cardiometabolic risk. This retrospective study explores the demographic, clinical and metabolic factors associated with metformin prescription youth with mood or psychotic disorders. Method Participants included 72 youth with mood or psychotic disorders from a young adult mental health inpatient unit, of which 18 (33%) were newly prescribed metformin, and 54 (66%) were not prescribed metformin. Demographic and clinical information were extracted from the patients’ medical files along with body mass index (BMI), fasting serum bloods and calculated updated homeostatic model of insulin resistance assessment (HOMA2-IR) scores to compare profiles between groups. Results Of those prescribed metformin, 83% were overweight or obese and 72% had elevated HOMA2-IR scores. Of those not receiving metformin treatment, 41% were overweight or obese and 22% had elevated HOMA2-IR scores. Youth prescribed metformin had significantly higher BMI, and elevated markers of insulin resistance, but did not differ to those not prescribed metformin on other demographic, clinical or metabolic factors. Conclusions While metformin is prescribed to some youth with mood or psychotic disorders displaying markers of cardiometabolic disturbance, there is a need to develop clearer treatment guidelines for metformin in these youth.

The primary purpose of conducting a structured interview as part of a functional behavior assessment (FBA) is to assist teams in generating a hypothesis about the reason for a student’s problem behavior based on specific information. Although the use of an interview can be beneficial in identifying the function of a student’s behavior, it often only includes information provided by teachers, support staff, and family members and overlooks the student’s involvement. In this article, we discuss some of the barriers educators may encounter during the structured interview process and describe in detail possible solutions and adaptations educators can use to assist in planning and successfully conducting a student-involved structured interview as part of the FBA process.

This study examined my experience as a doctoral student following the death of my son. The focus of this research is on the interaction of paternal grief and adult learning in the context of higher education. The central emphasis seeks to offer existential bearing to the interplay between the narrative identities of adult learner and paternal griever that is seldom considered in combination for adult learning scholarship. I employed the reflexive process of autoethnography through free writing and review of personal journals. I used the analytical lens of a dialogical narrator who held two opposing I-positions of the self, adult learner and grieving father. This methodological approach allowed the pursuit of adult learning to emerge into a position that promoted reorganization of my grief, bridging the divergence of loss and gain. This study placed focus on the dialogical I-positions of self as a vector for growth. The novelty of this research is the placement of andragogical considerations in adult learning following paternal grief. These considerations have capacity to endorse the paternal griever I-position to begin understanding grief transition through pursuit of knowledge. Characterizing the embodied transition is central to the bereavement process. Bringing the transition into dialogue with adult learning can provide educators with enhanced instructional precision when planning and conducting learning activities in a grief environment.

Students with significant support needs (SSN) are often at an increased risk of demonstrating challenging behaviors compared with their peers without disabilities. As a result, students engaging in these behaviors typically experience fewer opportunities for inclusive education, strained relationships with educators, and increased likelihood of exposure to intrusive and harmful practices (e.g., restraint and seclusion), thus providing increased support for the use of effective behavioral interventions. Although research has shown that function-based interventions are more effective in addressing challenging behavior and these practices should be implemented for SSN who engage in challenging behavior, unfortunately these supports are often planned without involvement from the student. All students, including those with SSN, should have input in the selection and design of the supports they receive. Therefore, the purpose of this article is to provide educators with strategies for including student voice in the functional behavior assessment process and when developing a behavior support plan for students with SSN. We describe in detail methods for (a) gathering student input during the indirect assessment interview process, (b) administering direct preference assessments, and (c) increasing accessibility of these methods for students with SSN.

Introduction The ICH E9 addendum outlining the estimand framework for clinical trials was published in 2019 but provides limited guidance around how to handle intercurrent events for non-inferiority studies. Once an estimand is defined, it is also unclear how to deal with missing values using principled analyses for non-inferiority studies. Methods Using a tuberculosis clinical trial as a case study, we propose a primary estimand, and an additional estimand suitable for non-inferiority studies. For estimation, multiple imputation methods that align with the estimands for both primary and sensitivity analysis are proposed. We demonstrate estimation methods using the twofold fully conditional specification multiple imputation algorithm and then extend and use reference-based multiple imputation for a binary outcome to target the relevant estimands, proposing sensitivity analyses under each. We compare the results from using these multiple imputation methods with those from the original study. Results Consistent with the ICH E9 addendum, estimands can be constructed for a non-inferiority trial which improves on the per-protocol/intention-to-treat-type analysis population previously advocated, involving respectively a hypothetical or treatment policy strategy to handle relevant intercurrent events. Results from using the ‘twofold’ multiple imputation approach to estimate the primary hypothetical estimand, and using reference-based methods for an additional treatment policy estimand, including sensitivity analyses to handle the missing data, were consistent with the original study’s reported per-protocol and intention-to-treat analysis in failing to demonstrate non-inferiority. Conclusions Using carefully constructed estimands and appropriate primary and sensitivity estimators, using all the information available, results in a more principled and statistically rigorous approach to analysis. Doing so provides an accurate interpretation of the estimand.

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This review essay addresses the major themes of Ghanaian theologian Kwame Bediako’s thought, as presented in Tim Hartman, Kwame Bediako: African Theology for a World Christianity. Bediako advocated examining the traditional spirituality of African peoples, studying the Bible in vernacular languages, and asking how the person and work of Jesus Christ engage local cultures. He insisted that Western theology was not central and normative to the Christian faith, and that African theology provided a better model for the development of contextual theologies worldwide.

The COVID-19 pandemic commenced in March 2020. In May 2019, a new Medical Examiner system was introduced to scrutinise deaths of patients dying within acute National Health Service Trusts. The Coronavirus Act 2020 which came into force in March 2020 modified certification of death requirements. Newly formed Medical Examiner Services were advised they could suspend scrutiny during the pandemic. The Norfolk & Norwich University Hospital Medical Examiner Service (NNUH MES) continued to scrutinise patient deaths throughout. This study summarises the workload of the NNUH MES from 1st June 2020 to 31st May 2021 over which period 2856 deaths were recorded and 2687 scrutinised by the Medical Examiners.

This research seeks to identify newspapers’ contribution to the construction of the language describing the era now popularly termed the “gold rush.” We examine the early narratives of the first golden finds, tracing how these ignited a conflagration which would impact the whole world and examining the unique contribution made by the Hawai’ian Polynesian newspaper to spread the news to Australasia, the American East Coast, and even Great Britain. Employing text-mining tools offers a way of uncovering the language used in context and at source over the past two centuries, and to provide an overarching view of the language of the rush for gold. Text-mining tools and primary source newspapers are used to identify this contribution and the startling conclusion that the world experienced, not a rush for gold, but a fever, a mania, and even an excitement.

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.