Adult hypoglycaemia; a narrative review on forensic aspects

© 2021. Published by AME Publishing Company. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://jlpm.amegroups.com/article/view/5995/htmlForensic hypoglycaemia describes interactions between hypoglycaemia and the law. Hypoglycaemia, or more correctly the neuroglycopenia and associated temporary brain malfunction, may result in a state of automatism during which sufferers are absolved, in law, from responsibility for what would otherwise be a criminal offence. Courts consider hypoglycaemia beyond the experience of the layman and consequently require an expert to explain what it is and how it affects behaviour. Experts on hypoglycaemia are few reflecting the rarity with which hypoglycaemia occurs in all except patients with diabetes treated with hypoglycaemic agents. Experts on hypoglycaemia are drawn from a number of disciplines, toxicology, pharmacology, internal medicine, forensic pathology, endocrinology and clinical biochemistry of which the last three are the most important in the forensic context. Death from hypoglycaemia may be due either to natural underlying causes or from the hypoglycaemia. Hypoglycaemia is produced by accidental or malicious administration of hypoglycaemic agents of which insulin is the commonest. The purported victim may be alive or dead when first brought to medical attention. In the former, investigation is essentially the same as for any case of spontaneous hypoglycaemia. Investigation of suspected death from hypoglycaemia requires collaboration between a forensic pathologist and either a toxicologist or clinical biochemist. The post mortem measurement of blood glucose is of little or no value in the investigation of hypoglycaemia whereas detection and quantification of the pancreatic hormones insulin, C-peptide and proinsulin, preferably by liquid chromatography/mass-spectrometry (LC-MS), is essential. Vitreous humour is most useful fluid for analysis as all three hormones remain measurable for several days after death from insulin poisoning unlike in serum from peripheral blood. Biochemical and immunohistological analysis of tissue surrounding a suspected injection site, if identified, is also valuable.Published onlin

Ethanol consumption impairs vestibulo-ocular reflex function measured by the video head impulse test and dynamic visual acuity

Ethanol affects many parts of the nervous system, from the periphery to higher cognitive functions. Due to the established effects of ethanol on vestibular and oculomotor function, we wished to examine its effect on two new tests of the vestibulo-ocular reflex (VOR): the video head impulse test (vHIT) and dynamic visual acuity (DVA). We tested eight healthy subjects with no history of vestibular disease after consumption of standardized drinks of 40% ethanol. We used a repeated measures design to track vestibular function over multiple rounds of ethanol consumption up to a maximum breath alcohol concentration (BrAC) of 1.38‰. All tests were normal at baseline. VOR gain measured by vHIT decreased 25% by the highest BrAC level tested in each subject. Catch-up saccades were negligible at baseline and increased in number and size with increasing ethanol consumption (from 0.13° to 1.43° cumulative amplitude per trial). DVA scores increased by 86% indicating a deterioration of acuity, while static visual acuity (SVA) remained unchanged. Ethanol consumption systematically impaired the VOR evoked by high-acceleration head impulses and led to a functional loss of visual acuity during head movement.NHMR

Wavelet analysis of stratospheric gravity wave packets over Macquarie Island 2. Intermittency and mean-flow accelerations

We calculate the mean-flow accelerations due to gravity wave packets observed in the lower stratosphere over Macquarie Island (55°S, 159°E) between February 1994 and April 1995. The parameters of the wave packets were extracted from twice-daily radiosonde soundings using a wavelet-based analysis method introduced by Zink and Vincent [this issue]. The deduced wave parameters are used to directly compute momentum flux profiles in the lower stratosphere, and the shortcomings of this approach to assess mean-flow accelerations are discussed. We then use the observed wave packets as an input spectrum in a linear ray-tracing model. The vertical extent of the detected wave packets allows us to define an expression for wave intermittency, which enables us to compute zonal accelerations in the stratosphere and mesosphere. In the stratosphere the waves produce an acceleration of the mean flow, in accordance with predictions. In the mesosphere the inferred wave drag is 2–3 times larger than previous observational and theoretical estimates.Florian Zink and R. A. Vincen

Prevalence and clinical characteristics of serum neuronal cell surface antibodies in first-episode psychosis: a case-control study

$\textbf{Background}$ Psychosis is a common presenting feature in antibody-mediated encephalitis, for which prompt recognition and treatment usually leads to remission. We aimed to investigate whether people with circumscribed schizophrenia-like illnesses have such antibodies—especially antibodies against the N-methyl-D-aspartate receptor (NMDAR)—more commonly than do healthy controls. $\textbf{Methods}$ We recruited patients aged 14–35 years presenting to any of 35 mental health services sites across England with first-episode psychosis, less than 6 weeks of treatment with antipsychotic medication, and a score of 4 or more on at least one selected Positive and Negative Syndrome Scale (PANSS) item. Patients and controls provided venous blood samples. We completed standardised symptom rating scales (PANSS, ACE-III, GAF) at baseline, and tested serum samples for antibodies against NMDAR, LGI1, CASPR2, the GABAA receptor, and the AMPA receptor using live cell-based assays. Treating clinicians assessed outcomes of ICD diagnosis and functioning (GAF) at 6 months. We included healthy controls from the general population, recruited as part of another study in Cambridge, UK. $\textbf{Findings}$ Between Feb 1, 2013, and Aug 31, 2014, we enrolled 228 patients with first-episode psychosis and 105 healthy controls. 20 (9%) of 228 patients had serum antibodies against one or more of the neuronal cell surface antibodies compared with four (4%) of 105 controls (unadjusted odds ratio 2·4, 95% CI 0·8–7·3). These associations remained non-significant when adjusted for current cigarette smoking, alcohol consumption, and illicit drug use. Seven (3%) patients had NMDAR antibodies compared with no controls (p=0·0204). The other antibodies did not differ between groups. Antibody-positive patients had lower PANSS positive, PANSS total, and catatonia scores than did antibody-negative patients. Patients had comparable scores on other PANSS items, ACE-III, and GAF at baseline, with no difference in outcomes at 6 months. $\textbf{Interpretation}$ Some patients with first-episode psychosis had antibodies against NMDAR that might be relevant to their illness, but did not differ from patients without NMDAR antibodies in clinical characteristics. Our study suggests that the only way to detect patients with these potentially pathogenic antibodies is to screen all patients with first-episode psychosis at first presentation.Medical Research Counci

Dynamic CpG methylation delineates subregions within super-enhancers selectively decommissioned at the exit from naive pluripotency.

Clusters of enhancers, referred as to super-enhancers (SEs), control the expression of cell identity genes. The organisation of these clusters, and how they are remodelled upon developmental transitions remain poorly understood. Here, we report the existence of two types of enhancer units within SEs typified by distinctive CpG methylation dynamics in embryonic stem cells (ESCs). We find that these units are either prone for decommissioning or remain constitutively active in epiblast stem cells (EpiSCs), as further established in the peri-implantation epiblast in vivo. Mechanistically, we show a pivotal role for ESRRB in regulating the activity of ESC-specific enhancer units and propose that the developmentally regulated silencing of ESRRB triggers the selective inactivation of these units within SEs. Our study provides insights into the molecular events that follow the loss of ESRRB binding, and offers a mechanism by which the naive pluripotency transcriptional programme can be partially reset upon embryo implantation

20 questions on Adaptive Dynamics

Abstract Adaptive Dynamics is an approach to studying evolutionary change when fitness is density or frequency dependent. Modern papers identifying themselves as using this approach first appeared in the 1990s, and have greatly increased up to the present. However, because of the rather technical nature of many of the papers, the approach is not widely known or understood by evolutionary biologists. In this review we aim to remedy this situation by outlining the methodology and then examining its strengths and weaknesses. We carry this out by posing and answering 20 key questions on Adaptive Dynamics. We conclude that Adaptive Dynamics provides a set of useful approximations for studying various evolutionary questions. However, as with any approximate method, conclusions based on Adaptive Dynamics are valid only under some restrictions that we discuss