Optical Control of Cell-Surface and Endomembrane-Exclusive ß-Adrenergic Receptor Signaling.

Beta-adrenergic receptors (ßARs) are G protein-coupled receptors (GPCRs) that mediate catecholamine hormone-induced stress responses, such as elevation of heart rate. Besides those that are plasma membrane-bound, endomembrane ßARs are also signaling competent. Dysregulation of ßAR pathways underlies severe pathological conditions. Emerging evidence indicates pathological molecular signatures in deeper endomembrane ßARs signaling, likely contributing to conditions such as cardiomyocyte hypertrophy and apoptosis. However, the lack of approaches to control endomembrane ß1ARs has impeded linking signaling with pathology. Informed by the ß1AR-catecholamine interactions, we engineered an efficient photo-labile pro-ligand (OptoIso) to trigger ßAR signaling exclusively in endomembrane regions using blue light stimulation. Not only does OptoIso undergo blue light deprotection in seconds, but also efficiently enters cells and allows examination of G protein heterotrimer activation exclusively at endomembranes. OptoIso also allows optical activation of plasma membrane ßAR signaling in selected single cells with native fidelity, which can be reversed by terminating blue light. Thus, OptoIso will be a valuable experimental tool to elicit spatial and temporal control of ßAR signaling in user-defined endomembrane or plasma membrane regions in unmodified cells with native fidelity.

Comparing First-Year Engineering Student Conceptions of Ethical Decision-Making to Performance on Standardized Assessments of Ethical Reasoning.

The Defining Issues Test 2 (DIT-2) and Engineering Ethical Reasoning Instrument (EERI) are designed to measure ethical reasoning of general (DIT-2) and engineering-student (EERI) populations. These tools-and the DIT-2 especially-have gained wide usage for assessing the ethical reasoning of undergraduate students. This paper reports on a research study in which the ethical reasoning of first-year undergraduate engineering students at multiple universities was assessed with both of these tools. In addition to these two instruments, students were also asked to create personal concept maps of the phrase "ethical decision-making." It was hypothesized that students whose instrument scores reflected more postconventional levels of moral development and more sophisticated ethical reasoning skills would likewise have richer, more detailed concept maps of ethical decision-making, reflecting their deeper levels of understanding of this topic and the complex of related concepts. In fact, there was no significant correlation between the instrument scores and concept map scoring, suggesting that the way first-year students conceptualize ethical decision making does not predict the way they behave when performing scenario-based ethical reasoning (perhaps more situated). This disparity indicates a need to more precisely quantify engineering ethical reasoning and decision making, if we wish to inform assessment outcomes using the results of such quantitative analyses.

Variability patterns in dual antiplatelet therapy following endovascular repair of intracranial aneurysms: Insight into regimen heterogeneity and the need for a consensus.

This comprehensive review delves into the evolving field of neurointervention for intracranial aneurysms, exploring the critical adjunct of Dual Antiplatelet Therapy (DAPT) to endovascular coiling, stent-assisted coiling (SAC), flow-diversion stents, and flow-disruption (intrasaccular) devices. Despite growing evidence supporting the success of DAPT in reducing thromboembolic events, the lack of consensus on optimal regimens, doses, and duration is evident. Factors contributing to this variability include genetic polymorphisms affecting treatment response and ongoing debates regarding the clinical significance of hemorrhagic complications associated with DAPT. This review analyzes pre- and post-procedural antiplatelet usage across various interventions. The imperative lies in ongoing research to define optimal DAPT durations, ensuring a nuanced approach to the delicate balance between thrombosis and hemorrhage in intracranial aneurysm management.

Embolization Prior to Radiosurgery in Treatment of Arteriovenous Malformations: Defining Radiosurgery Target Dose with Nidal Volume Reduction.

INTRODUCTION: Arteriovenous malformations (AVMs) can be treated with observation, surgery, embolization, stereotactic radiosurgery (SRS), or a combination of therapies. SRS has been used for AVMs that pose a high risk of surgery, such as in deep or eloquent anatomic locations. Smaller AVMs, <3 cm, have been shown to have higher rates of complete obliteration after SRS. For AVMs that are a larger size, embolization prior to SRS has been used to reduce the size of the AVM nidus. In this study we analyzed embolization prior to SRS to reduce nidal volume and describe imaging techniques to target for SRS post embolization. METHODS: We retrospectively reviewed all patients at a single academic institution treated with embolization prior to SRS for treatment of AVMs. We then used contrast enhanced magnetic resonance imaging (MRI) to contour AVM volumes based on pre-embolization imaging and compared to post-embolization imaging. Planned AVM volume prior to embolization was then compared to actual treated AVM volume. RESULTS: We identified 11 patients treated with embolization prior to SRS from 2011-2023. Median AVM nidal volume prior to embolization was 7.69 mL and post embolization was 3.61 ML (P < 0.01). There was a 45.5% obliteration rate at follow up in our series, with 2 minor complications related to radiosurgery. CONCLUSIONS: In our cohort, embolization prior to SRS resulted in a statistically significant reduction in AVM nidal volume. Therefore, embolization prior to SRS can result in dose reduction at time of SRS treatment allowing for decreased risk of SRS complications without higher embolization complication rates.

Equity in Clinical Care and Research Involving Persons with Disorders of Consciousness.

People with disorders of consciousness (DoC) are characteristically unable to synchronously participate in decision-making about clinical care or research. The inability to self-advocate exacerbates preexisting socioeconomic and geographic disparities, which include the wide variability observed across individuals, hospitals, and countries in access to acute care, expertise, and sophisticated diagnostic, prognostic, and therapeutic interventions. Concerns about equity for people with DoC are particularly notable when they lack a surrogate decision-maker (legally referred to as "unrepresented" or "unbefriended"). Decisions about both short-term and long-term life-sustaining treatment typically rely on neuroprognostication and individual patient preferences that carry additional ethical considerations for people with DoC, as even individuals with well thought out advance directives cannot anticipate every possible situation to guide such decisions. Further challenges exist with the inclusion of people with DoC in research because consent must be completed (in most circumstances) through a surrogate, which excludes those who are unrepresented and may discourage investigators from exploring questions related to this population. In this article, the Curing Coma Campaign Ethics Working Group reviews equity considerations in clinical care and research involving persons with DoC in the following domains: (1) access to acute care and expertise, (2) access to diagnostics and therapeutics, (3) neuroprognostication, (4) medical decision-making for unrepresented people, (5) end-of-life decision-making, (6) access to postacute rehabilitative care, (7) access to research, (8) inclusion of unrepresented people in research, and (9) remuneration and reciprocity for research participation. The goal of this discussion is to advance equitable, harmonized, guideline-directed, and goal-concordant care for people with DoC of all backgrounds worldwide, prioritizing the ethical standards of respect for autonomy, beneficence, and justice. Although the focus of this evaluation is on people with DoC, much of the discussion can be extrapolated to other critically ill persons worldwide.

Endothelial Progenitor Cells: A Review of Molecular Mechanisms in the Pathogenesis and Endovascular Treatment of Intracranial Aneurysms.

This comprehensive review explores the multifaceted role of endothelial progenitor cells (EPCs) in vascular diseases, focusing on their involvement in the pathogenesis and their contributions to enhancing the efficacy of endovascular treatments for intracranial aneurysms (IAs). Initially discovered as CD34+ bone marrow-derived cells implicated in angiogenesis, EPCs have been linked to vascular repair, vasculogenesis, and angiogenic microenvironments. The origin and differentiation of EPCs have been subject to debate, challenging the conventional notion of bone marrow origin. Quantification methods, including CD34+ , CD133+ , and various assays, reveal the influence of factors, like age, gender, and comorbidities on EPC levels. Cellular mechanisms highlight the interplay between bone marrow and angiogenic microenvironments, involving growth factors, matrix metalloproteinases, and signaling pathways, such as phosphatidylinositol-3-kinase (PI3K) and mitogen-activated protein kinase (MAPK). In the context of the pathogenesis of IAs, EPCs play a role in maintaining vascular integrity by replacing injured and dysfunctional endothelial cells. Recent research has also suggested the therapeutic potential of EPCs after coil embolization and flow diversion, and this has led the development of device surface modifications aimed to enhance endothelialization. The comprehensive insights underscore the importance of further research on EPCs as both therapeutic targets and biomarkers in IAs.

Thromboembolic Events After the Coverage of Anterior Cerebral Artery with Flow Diversion: A Single Institution Series and Systematic Review.

BACKGROUND: Advances in the use of flow diversion (FD) now extend to bifurcation aneurysms; herein, we compare thromboembolic events in patients with internal carotid artery (ICA) aneurysms treated with and without exclusion of the anterior cerebral artery (ACA). METHODS: Retrospective analysis of aneurysms in the terminal ICA treated with FD from 2013 to 2023 at a single-center study. Procedures were classified according to the coverage at the origin of the ACA and compared through bivariate-analysis. A review was also carried on PubMed, Web of Science, and EMBASE until April 2024, adhering to the PRISMA reporting guidelines. RESULTS: Ninety-five patients harboring 113 aneurysms treated in 102 procedures were evaluated. Fifty-eight were treated covering the ACA origin. Dual antiplatelet regimens included aspirin-clopidogrel (50%), aspirin-ticagrelor (44.1%), and aspirin-prasugrel (4.9%). Thromboembolic events occurred in 6 patients (5.9%), all of which presented with large vessel occlusion of the ICA, but without reaching statistical difference in the 2 treated cohorts (P = 0.46). At a median clinical follow-up of 5.95 months, there were no differences in the functional outcomes in the 2 groups (P = 0.22). Contralateral angiographic runs post-treatment after covering the ACA origin demonstrated increase in the A1 (median: 0.45 mm; IQR = 0.4-1.2) and ICA diameter (median: 0.55 mm; IQR = 0.1-1.2). After pooling data from literature and our cohort, complete side branch occlusion after the coverage of ACA was seen in 25% of branches (95%CI = 0.16-0.36), and thromboembolic events were observed after 3% (95%CI = 0.01-0.04) of procedures. CONCLUSIONS: Thromboembolic events can occur in distal ICA aneurysms treated with FD, but no significant association was seen with covering the ACA origin.

Thromboembolic Events in the Posterior Circulation After Flow Diversion-A Closer Look at Coverage of the Posterior Cerebral Artery.

BACKGROUND: Flow diversion for bifurcation aneurysms requires excluding one of the branches from the parent artery, raising concern for ischemic events. We evaluated thromboembolic events and their relationship with covering the origin of the posterior cerebral artery (PCA). METHODS: This retrospective analysis included patients with confirmed basilar and proximal PCA aneurysms treated with flow diversion between 2013 and 2023. Procedures were classified according to the coverage of the origin of the PCA. Thromboembolic events associated with the excluded PCA were evaluated. RESULTS: Of the total 28 aneurysms included, 7 were at the basilar tip, 16 in the basilar trunk, and 5 in the first segment of the PCA; 15 were treated by excluding one of the PCAs. Dual antiplatelet therapy included aspirin and ticagrelor (57.1%), aspirin and clopidogrel (35.7%), or aspirin and prasugrel (3.57%). Complete and near-complete aneurysm occlusion was achieved in 80.8% of the aneurysms treated at a median follow-up of 12.31 months. Thromboembolic complications occurred in 3 patients (2 with basilar perforator stroke and 1 with basilar in-stent thrombosis). However, the difference in these events was not statistically significant between patients with PCA coverage and those without (P = 0.46). Diminished flow and a lack of flow was seen in 8 and 7 of the covered vessels, respectively. A modified Rankin scale score of ≤2 was reported for 89.3% of patients at a median clinical follow-up of 5.5 months. CONCLUSIONS: The incidence of thromboembolic events is high in distal basilar and proximal PCA aneurysms; however, PCA coverage was not associated with their occurrence. There was no difference in postprocedural disability between patients whose aneurysms were treated by excluding one of the PCAs and those who were not.

Long-term exposure to ambient air pollution and measures of central hemodynamics and arterial stiffness among multiethnic Chicago residents.

OBJECTIVES: To examine whether long-term air pollution exposure is associated with central hemodynamic and brachial artery stiffness parameters. METHODS: We assessed central hemodynamic parameters including central blood pressure, cardiac parameters, systemic vascular compliance and resistance, and brachial artery stiffness measures [including brachial artery distensibility (BAD), compliance (BAC), and resistance (BAR)] using waveform analysis of the arterial pressure signals obtained from a standard cuff sphygmomanometer (DynaPulse2000A, San Diego, CA). The long-term exposures to particles with an aerodynamic diameter < 2.5 µm (PM2.5) and nitrogen dioxide (NO2) for the 3-year periods prior to enrollment were estimated at residential addresses using fine-scale intra-urban spatiotemporal models. Linear mixed models adjusted for potential confounders were used to examine associations between air pollution exposures and health outcomes. RESULTS: The cross-sectional study included 2,387 Chicago residents (76% African Americans) enrolled in the ChicagO Multiethnic Prevention And Surveillance Study (COMPASS) during 2013-2018 with validated address information, PM2.5 or NO2, key covariates, and hemodynamics measurements. We observed long-term concentrations of PM2.5 and NO2 to be positively associated with central systolic, pulse pressure and BAR, and negatively associated with BAD, and BAC after adjusting for relevant covariates. A 1-µg/m3 increment in preceding 3-year exposures to PM2.5 was associated with 1.8 mmHg higher central systolic (95% CI: 0.98, 4.16), 1.0 mmHg higher central pulse pressure (95% CI: 0.42, 2.87), a 0.56%mmHg lower BAD (95% CI: -0.81, -0.30), and a 0.009 mL/mmHg lower BAC (95% CI: -0.01, -0.01). CONCLUSION: This population-based study provides evidence that long-term exposures to PM2.5 and NO2 is related to central BP and arterial stiffness parameters, especially among African Americans.

Defining light transmission aggregometry cutoff values for clopidogrel and aspirin resistance in flow diversion treatment of intracranial aneurysms.

OBJECTIVE: Concern about thromboembolic events after flow diversion (FD) warrants dual antiplatelet therapy for 3 to 6 months. Platelet function tests are routinely performed prior to the procedure to detect clopidogrel responsiveness, as resistance is associated with CYP2C19 gene polymorphisms. This study aimed to identify optimal cutoff values in light transmission aggregometry (LTA) for clopidogrel and aspirin as predictive indicators of thromboembolic complications. METHODS: The authors conducted a retrospective analysis of aneurysms treated with FD between 2013 and 2023 at a single academic institution. Patients with LTA data for adenosine diphosphate (ADP) and arachidonic acid (ARA) were included, excluding those with aborted procedures. Receiver operating characteristic curves were plotted for ADP and ARA assays to determine optimal cutoff values. RESULTS: A total of 442 patients harboring 552 aneurysms treated in 485 procedures were selected for this analysis. Complete and near-complete aneurysm occlusion on the last radiological follow-up was achieved in 81.8% of aneurysms in a median last imaging follow-up of 13.9 months. A good functional outcome (modified Rankin Scale score ≤ 2) was achieved in 96.3% of patients on the last follow-up. Thromboembolic complications occurred in 4.9% of procedures, and intracranial hemorrhagic complications in 1.9%. For the ADP assay, a value ≥ 40% reached a sensitivity of 82.1% and a specificity of 42.9% with a positive likelihood ratio (LR) of 1.50. For the ARA assay, a value ≥ 13.5% reached a sensitivity of 82.1% and a specificity of 45.6% with a positive LR of 1.51. CONCLUSIONS: This study analyzed the largest FD-treated cohort in which optimal LTA platelet function thresholds for clopidogrel were evaluated and is the first to assess LTA values for aspirin. The authors found that values ≥ 40% for clopidogrel and ≥ 13.5% for aspirin were optimal for predicting thromboembolic complications after FD in treating aneurysms.

Clipping of a Ruptured Small Anterior Communicating Artery Aneurysm: Technical Video.

In recent years there has been a significant shift in the management of intracranial aneurysms, as most, both ruptured and unruptured, are being treated through an endovascular approach.1-3 However, there are still instances in which open surgical clipping is the best option for definitive management. Both patient factors, such as age and comorbidities, and aneurysm characteristics, such as size, morphology, and location, must be taken into consideration when treating aneurysms. This is especially true for anterior1 communicating artery aneurysms, as these have been treated successfully using multiple different techniques.4,5 There are no absolute guidelines indicating how a particular aneurysm should be treated and, therefore, one must be able to determine how to best manage a patient based on their own skill set, knowledge, and experience. We present a case of a 61-year-old woman who presented with a ruptured anterior communicating artery aneurysm. Initially she was brought to the angiography suite to undergo possible endovascular treatment of the aneurysm, but after reviewing the morphology and size of the aneurysm, we believed that this aneurysm could not be treated safely through an endovascular approach and surgical clipping was the better option. The patient consented to the procedure. In this operative video, we describe the technical aspects of the surgical procedure and the benefits of our approach (Video 1).

The impact of the Affordable Care Act Medicaid Expansion in Medicare beneficiaries with peripheral artery disease.

Background: In 2014, the Affordable Care Act Medicaid Expansion (ME) increased Medicaid eligibility for adults with an income level up to 138% of the federal poverty level. In this study, we examined the impact of ME on mortality and amputation in patients with peripheral artery disease (PAD). Methods: The 100% MedPAR and Part-B Carrier files from 2011 to 2018 were queried to identify all fee-for-service Medicare beneficiaries with PAD using International Classification of Diseases codes. Our primary exposure was whether a state had adopted the ME on January 1, 2014. Our primary outcomes were the change in all-cause 1-year mortality and leg amputation. We used a state-level difference-in-differences (DID) analysis to compare the rates of the primary outcomes among patients who were in states (including the District of Columbia) who adopted ME (n = 25) versus those who were in states that did not (n = 26). We performed a subanalysis stratifying by sex, race, region, and dual-eligibility status. Results: Over the 8-year period, we studied 37,743,929 patients. The average unadjusted 1-year mortality decreased from 2011 to 2018 in both non-ME (9.5% to 8.7%, p < 0.001) and ME (9.1% to 8.3%, p < 0.001) states. The average unadjusted 1-year amputation rate did not improve in either the non-ME (0.86% to 0.87%, p = 0.17) or ME (0.69% to 0.69%, p = 0.65) states. Across the entire cohort, the DID model revealed that ME did not lead to a significant change in mortality (p = 0.15) or amputation (p = 0.34). Conclusion: Medicaid Expansion was not associated with reduced mortality or leg amputation in Medicare beneficiaries with PAD.

Flow Diversion as a Definitive Treatment for Recurrently Ruptured A1-A2 Anterior Cerebral Artery Aneurysm Following Clipping and Coiling.

Even after clipping of intracranial aneurysms, patients may experience incomplete occlusion or the future recurrence of their treated aneurysm. This paper presents a distinctive case of a recurrent A1-A2 anterior cerebral artery aneurysm that underwent four interventions over 16 years. The aneurysm was treated with two clippings, subsequent coiling, and flow diversion for definitive treatment. The challenges encountered in managing bifurcation aneurysms are discussed, emphasizing the importance of considering hemodynamic factors, vessel geometry, and recurrence risk factors in treatment decisions. The case highlights the need for closer follow-up of ruptured bifurcation aneurysms due to the higher likelihood of recurrence. The role of flow diverters in reinforcing vessel anatomy and preventing recurrence is also highlighted.

Understanding Individual Subject Differences through Large Behavioral Datasets: Analytical and Statistical Considerations.

A core feature of behavior analysis is the single-subject design, in which each subject serves as its own control. This approach is powerful for identifying manipulations that are causal to behavioral changes but often fails to account for individual differences, particularly when coupled with a small sample size. It is more common for other subfields of psychology to use larger-N approaches; however, these designs also often fail to account for the individual by focusing on aggregate-level data only. Moving forward, it is important to study individual differences to identify subgroups of the population that may respond differently to interventions and to improve the generalizability and reproducibility of behavioral science. We propose that large-N datasets should be used in behavior analysis to better understand individual subject variability. First, we describe how individual differences have been historically treated and then outline practical reasons to study individual subject variability. Then, we describe various methods for analyzing large-N datasets while accounting for the individual, including correlational analyses, machine learning, mixed-effects models, clustering, and simulation. We provide relevant examples of these techniques from published behavioral literature and from a publicly available dataset compiled from five different rat experiments, which illustrates both group-level effects and heterogeneity across individual subjects. We encourage other behavior analysts to make use of the substantial advancements in online data sharing to compile large-N datasets and use statistical approaches to explore individual differences.

Long-Term Outcomes After Stereotactic Radiosurgery for Pediatric Brain Arteriovenous Malformations: A Systematic Review.

BACKGROUND: The long-term outcomes after stereotactic radiosurgery (SRS) for pediatric brain arteriovenous malformations (AVMs) remain poorly understood given the paucity of longitudinal studies. A systematic review was conducted to pool cumulative incidences for all outcomes. METHODS: PubMed, Embase, and Web of Science were queried to systematically extract potential references. The articles relating to AVMs treated via SRS were required to be written in English, involve pediatric patients (<18 years of age), and include a mean follow-up period of >5 years. Individual patient data were obtained to construct a pooled Kaplan-Meier plot on obliteration rates over time. RESULTS: Among the 6 studies involving 1315 pediatric patients averaging a follow-up period of 86.6 months (range, 6-276), AVM obliteration was observed in 66.1% with cumulative probabilities of 48.28% (95% confidence interval [CI], 41.89-54.68), 76.11% (95% CI, 67.50-84.72), 77.48% (95% CI, 66.37-88.59) over 3, 5, and 10 years, respectively. The cumulative incidence of post-SRS hemorrhage, tumors, cysts, and de novo seizures was 7.2%, 0.3%, 1.6%, and 1.5%, respectively. The cumulative incidence of radiation-induced necrosis, edema, radiologic radiation-induced changes (RICs), symptomatic RICs, and permanent RICs were 8.0%, 1.4%, 28.0%, 8.7%, and 4.9%, respectively. CONCLUSIONS: Studies assessing long-term outcomes after SRS are moderate in quality and retrospective. Thus, interpretation with caution is advised given the variable degree of loss to follow-up, which suggests that complication rates may be higher than the values stated in the literature. Future prospective studies are needed to validate these findings.

Methods, design, and initial results of an angiographic core lab from VOYAGER-PAD.

Background: Anatomy is critical in risk stratification and therapeutic decision making in coronary disease. The relationship between anatomy and outcomes is not well described in PAD. We sought to develop an angiographic core lab within the VOYAGER-PAD trial. The current report describes the methods of creating this core lab, its study population, and baseline anatomic variables. Methods: Patients undergoing lower-extremity revascularization for symptomatic PAD were randomized in VOYAGER-PAD. The median follow up was 2.25 years. Events were adjudicated by a blinded Clinical Endpoint Committee. Angiograms were collected from study participants; those with available angiograms formed this core lab cohort. Angiograms were scored for anatomic and flow characteristics by trained reviewers blinded to treatment. Ten percent of angiograms were evaluated independently by two reviewers; inter-rater agreement was assessed. Clinical characteristics and the treatment effect of rivaroxaban were compared between the core lab cohort and noncore lab participants. Anatomic data by segment were analyzed. Results: Of 6564 participants randomized in VOYAGER-PAD, catheter-based angiograms from 1666 patients were obtained for this core lab. Anatomic and flow characteristics were collected across 16 anatomic segments by 15 reviewers. Concordance between reviewers for anatomic and flow variables across segments was 90.5% (24,417/26,968). Clinical characteristics were similar between patients in the core lab and those not included. The effect of rivaroxaban on the primary efficacy and safety outcomes was also similar. Conclusions: The VOYAGER-PAD angiographic core lab provides an opportunity to correlate PAD anatomy with independently adjudicated outcomes and provide insights into therapy for PAD. (ClinicalTrials.gov Identifier: NCT02504216).

Biochemical Safety of SBRT to Multiple Intrahepatic Lesions for Hepatocellular Carcinoma.

Background: We aim to better characterize stereotactic body radiation therapy (SBRT)-related hepatic biochemical toxicity in patients with multiple intrahepatic lesions from hepatocellular carcinoma (HCC). Methods: We conducted a retrospective analysis of patients with HCC who underwent SBRT for 2 or more synchronous or metachronous liver lesions. We collected patient characteristics and dosimetric data (mean liver dose [MLD], cumulative effective volume [Veff], cumulative volume of liver receiving 15 Gy [V15Gy], and cumulative planning target volume [PTV]) along with liver-related toxicity (measured by albumin-bilirubin [ALBI] and Child-Pugh [CP] scores). A linear mixed-effects model was used to assess the effect of multi-target SBRT on changes in ALBI. Results: There were 25 patients and 56 lesions with median follow-up of 29 months. Eleven patients had synchronous lesions, and 14 had recurrent lesions treated with separate SBRT courses. Among those receiving multiple SBRT courses, there were 7 lesions with overlap of V15Gy (median V15Gy overlap: 35 mL, range: 0.5-388 mL). There was no association between cumulative MLD, Veff, V15Gy, or PTV and change in ALBI. Four of 25 patients experienced non-classic radiation-induced liver disease (RILD), due to an increase of CP score by ≥2 points 3 to 6 months after SBRT. Sixteen of 25 patients experienced an increase in ALBI grade by 1 or more points 3 to 6 months after SBRT. Comparing the groups that received SBRT in a single course versus multiple courses revealed no statistically significant differences in liver toxicity. Conclusion: Liver SBRT for multiple lesions in a single or in separate courses is feasible and with acceptable risk of hepatotoxicity. Prospective studies with a larger cohort are needed to better characterize safety in this population.

Applying the IEEE BRAIN neuroethics framework to intra-cortical brain-computer interfaces.

Objective. Brain-computer interfaces (BCIs) are neuroprosthetic devices that allow for direct interaction between brains and machines. These types of neurotechnologies have recently experienced a strong drive in research and development, given, in part, that they promise to restore motor and communication abilities in individuals experiencing severe paralysis. While a rich literature analyzes the ethical, legal, and sociocultural implications (ELSCI) of these novel neurotechnologies, engineers, clinicians and BCI practitioners often do not have enough exposure to these topics.Approach. Here, we present the IEEE Neuroethics Framework, an international, multiyear, iterative initiative aimed at developing a robust, accessible set of considerations for diverse stakeholders.Main results. Using the framework, we provide practical examples of ELSCI considerations for BCI neurotechnologies. We focus on invasive technologies, and in particular, devices that are implanted intra-cortically for medical research applications.Significance. We demonstrate the utility of our framework in exposing a wide range of implications across different intra-cortical BCI technology modalities and conclude with recommendations on how to utilize this knowledge in the development and application of ethical guidelines for BCI neurotechnologies.