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Functional connectivity (FC) is a sensitive metric that provides a readout of whole cortex coordinate neural activity in a mouse model. We examine the impact of experimental SAH modeled through endovascular perforation, and the effectiveness of subsequent treatment on FC, through three key questions: 1) Does the endovascular perforation model of SAH induce deficits in FC; 2) Does exposure to hypoxic conditioning provide protection against these FC deficits and, if so, is this neurovascular protection SIRT1-mediated; and 3) does treatment with the SIRT1 activator resveratrol alone provide protection against these FC deficits? Cranial windows were adhered on skull-intact mice that were then subjected to either sham or SAH surgery and either left untreated or treated with hypoxic post-conditioning (with or without EX527) or resveratrol for 3 days. Mice were imaged 3 days post-SAH/sham surgery, temporally aligned with the onset of major SAH sequela in mice. Here we show that the endovascular perforation model of SAH induces global and network-specific deficits in FC by day 3, corresponding with the time frame of DCI in mice. Hypoxic conditioning provides SIRT1-mediated protection against these network-specific FC deficits post-SAH, as does treatment with resveratrol. Conditioning-based strategies provide multifaceted neurovascular protection in experimental SAH.

Diazaborines react slowly with H2O2 but rapidly with ONOO−, offering a new platform for discriminating between these two cellular ROS.

This chapter provides an introduction to the use of artificial intelligence (AI) at sentencing. It deals with the questions: What does it mean to talk about using artificial intelligence at sentencing? And why is it important to consider the ethical and penal theoretical aspects of the use of artificial intelligence in the determination of sentences? Furthermore, it provides an overview of the varied topics that are considered in the ensuing chapters of the book.

Proposals to incorporate AI into the sentencing process range from merely supporting judges, to replacing them entirely. This chapter discusses the appropriate role of AI at sentencing and explores some of its potential applications. We argue that the more ambitious proposals overlook several key characteristics of sentencing that render it an inherently human task. Nevertheless, AI is capable of making a much greater contribution to the sentencing process than at present. We discuss the benefits of what we term an Advisory Sentence—a sentence recommendation derived by an AI program based on past judicial practice. The Advisory Sentence has the potential to support and improve judicial decision-making, for example, by reducing discrimination at sentencing, detecting local sentencing anomalies, and facilitating appellate review. Lastly, the chapter touches on AI’s potential to shape and enhance existing sentencing guidelines.

In 2017, the Sentencing Council introduced a revised guideline for plea-based sentence reductions. The revisions were designed to provide greater certainty and to accelerate the timing of guilty pleas. Late pleas resulting in ‘cracked trials’ have long been a problem in the court system. The guideline was not intended to change the rate of defendants who plead guilty, but rather to increase the percentage of pleas entered early in the criminal process. This brief article reports findings from an analysis of data from the Crown Court before and after the introduction of the revised sentencing guideline. Findings reveal that the overall guilty plea remained stable over the period 2014–2019. The guideline appears to have had no effect on the timing of guilty pleas entered, and in fact the percentage of ‘cracked’ trials rose in the post-guideline period.

Sentencing for multiple offences poses many challenges and becomes even more complex when the crimes resulted in fatalities. This article uses the sentences imposed following convictions in the Essex lorry case to pose some general questions about the sentencing of multiple victim manslaughters. The four principal offenders were convicted of 39 counts of unlawful act manslaughter and conspiracy to facilitate unlawful immigration into the UK. The analysis identifies several ways in which the sentences ultimately imposed failed to adequately distinguish between offenders of very different levels of culpability. First, all four principal offenders were assigned to the same level of culpability in the manslaughter guideline. Second, although the court could have distinguished the offenders to reflect their different culpability levels, the same Starting Point sentence was imposed on all offenders. Third, the sentencing uplifts to reflect the multiple counts were similar across offenders of very different culpabilities. Fourth, the differential additional punishments for the conspiracy conviction — which would have separated the offenders’ time in custody further — were washed out by being made concurrent. As a result of these decisions, the final sentences failed to adequately distinguish between offenders of very different culpabilities. The article concludes with some lessons for sentencing in these cases, specifically with respect to the Sentencing Council’s guidelines.

Sleep curtailment and circadian misalignment disrupt energy sensing and eating behaviors, which can contribute to weight gain and obesity-related comorbidities. Herein, we review the effects of experimental manipulations of sleep duration and circadian alignment on circulating concentrations of appetite hormones, specifically leptin and ghrelin. Further, we focus on sex differences in hormonal and behavioral responses related to food intake. The studies reviewed suggest potential sex-specific effects of sleep curtailment on key hormones involved in the gut-brain axis, presumably leading to downstream effects on neural processes involved in food seeking and consumption behaviors. However, there is insufficient evidence to declare any sex-specific effects of circadian misalignment on appetite regulation. More research is needed to elucidate the complex sex-specific relationships between sleep, circadian rhythms, energy homeostasis, and appetite regulating mechanisms. Greater knowledge of these mechanisms would aid in the development of targeted methods to mitigate risk for obesity and related metabolic diseases.

Background and Purpose:Early brain injury may be a more significant contributor to poor outcome after aneurysmal subarachnoid hemorrhage (aSAH) than vasospasm and delayed cerebral ischemia. However, studying this process has been hampered by lack of a means of quantifying the spectrum of injury. Global cerebral edema (GCE) is the most widely accepted manifestation of early brain injury but is currently assessed only through subjective, qualitative or semi-quantitative means. Selective sulcal volume (SSV), the CSF volume above the lateral ventricles, has been proposed as a quantitative biomarker of GCE, but is time-consuming to measure manually. Here we implement an automated algorithm to extract SSV and evaluate the age-dependent relationship of reduced SSV on early outcomes after aSAH.Methods:We selected all adults with aSAH admitted to a single institution with imaging within 72 hours of ictus. Scans were assessed for qualitative presence of GCE. SSV was automatically segmented from serial CTs using a deep learning-based approach. Early SSV was the lowest SSV from all early scans. Modified Rankin Scale score of 4 to 6 at hospital discharge was classified as a poor outcome.Results:Two hundred forty-four patients with aSAH were included. Sixty-five (27%) had GCE on admission while 24 developed it subsequently within 72 hours. Median SSV on admission was 10.7 mL but frequently decreased, with minimum early SSV being 3.0 mL (interquartile range, 0.3–11.9). Early SSV below 5 mL was highly predictive of qualitative GCE (area under receiver-operating-characteristic curve, 0.90). Reduced early SSV was an independent predictor of poor outcome, with a stronger effect in younger patients.Conclusions:Automated assessment of SSV provides an objective biomarker of GCE that can be leveraged to quantify early brain injury and dissect its impact on outcomes after aSAH. Such quantitative analysis suggests that GCE may be more impactful to younger patients with SAH.

Little evidence supports acquisition of routine head imaging after uncomplicated elective neurosurgical procedures for patients with unchanged neurological examinations; however, imaging is still performed by some neurointerventionalists. We assessed the clinical utility of routine computed tomography of the head (CTH) following elective neuroendovascular interventions, including aneurysm coiling, aneurysm stent-assisted coiling, aneurysm flow diversion, arteriovenous malformation/fistula embolization, middle meningeal artery embolization for subdural hematoma, extracranial carotid artery stenting, and venous sinus stenting.Retrospective chart review identified patients undergoing neuroendovascular intervention from 2011 to 2021 at our institution. Demographic, clinical, and radiographic variables, including presenting signs and symptoms, antiplatelets and/or anticoagulant medications, intraprocedural complications, postprocedural CTH findings, and postprocedural neurological examinations, were recorded. Association of clinical variables with an abnormal postprocedural CTH was assessed with univariate analysis. Patients with ruptured vascular pathology, preoperative embolizations, and missing postprocedural CTH images and/or reports were excluded.Of 509 procedures identified, 354 were eligible for analysis; 4.8% of patients (17/354) had abnormal findings on postprocedural CTH. Nine patients had intraprocedural complications or new postprocedural neurological deficits that would have prompted imaging regardless of institutional practice. None of the remaining 8 (2.3%) patients required additional procedures. New postprocedural neurological deficit was the only significant predictor of abnormal postprocedural CTH (odds ratio = 6.79; 95% confidence interval, 2.01-20.32; P = 0.0009).In a large cohort of patients undergoing elective neuroendovascular intervention, no patients were identified for whom routine postprocedural CTH alone meaningfully altered their clinical care. Routine CTH is not necessary after uncomplicated elective neuroendovascular interventions performed with careful postprocedural neurological assessment.