Novel Post-Neurointensive Care Recovery Clinic: Design, Utilization, and Clinician Perspectives.

Background and Objectives: Despite increasing interest in post-intensive care unit (ICU) clinical care and management, there have been limited descriptions focused on the post-neurologic (neuro)-ICU population. Here, we describe the design of a post-neuro-ICU Neurorecovery Clinic (NRC) and present data collected regarding the clinic's population, referrals, visits, and clinician satisfaction. Methods: This is a single-institution experience with a NRC designed to provide an infrastructure for post-ICU care to patients recovering from acute neurologic disorders or systemic conditions with neurologic sequelae. The clinic offers 2 visit types with different frequencies: a weekly visit and a monthly multidisciplinary visit. This study assessed clinical utilization and clinician perspectives regarding the clinic. Data on clinic referrals, no-show frequency, visit types, and diagnoses for both weekly and monthly visits were collected. A survey was conducted to assess clinician satisfaction and perspectives. Qualitative thematic analysis was performed to identify major themes among survey free responses. Results: In a 2-year period, 225 patients were referred from the Massachusetts General Hospital neuro-ICU to the NRC. Of those, 105 (47%) were seen in clinic for at least one visit. The most common reasons for loss to follow-up were no shows (38%) and noncontracted insurance (21%). Twenty percent of visits were in-person (the rest were by telehealth). Forty-eight percent were new patients compared with return visits. The most common diagnoses were other (36%), ischemic stroke (26%), and traumatic brain injury (17%). An additional monthly multidisciplinary clinic has seen 14 patients with one no show. Clinicians found their experience in the NRC valuable. Identified benefits included interdisciplinary collaboration, being a more well-rounded and better clinician, improving effectiveness in managing post-ICU problems, and influencing ICU prognosis. Clinicians' greatest challenge was navigating resource limitations for patients. Discussion: A postneuro-ICU NRC is a feasible model of care delivery for patients after severe acute neurologic disorders. Patients with a broad variety of diagnoses were seen in a 2-year period. Providers valued their clinic time and experiences. Future studies should evaluate whether this model of care improves patients' postneuro-ICU outcomes.

Evaluating the safety and efficacy of medical management in extracranial pseudoaneurysms: a comparative study.

OBJECTIVE: As endovascular interventions become safer and their use more prevalent for treating extracranial pseudoaneurysms, fewer pseudoaneurysms are treated with medical therapy alone. This study aimed to assess the indications for intervention and the safety of medical management. METHODS: A dual-center retrospective analysis was conducted on patients diagnosed with extracranial carotid and vertebral pseudoaneurysms between December 2006 and June 2023. RESULTS: Of 145 pseudoaneurysms, 121 (83%) received medical therapy, 22 (15%) were treated endovascularly, and 2 (1.4%) were treated with open surgery. In the medical group, there were 2 (1.9%) complications, one unrelated to the pseudoaneurysm. In the intervention group, there were 3 (16%) complications, with 1 patient requiring two retreatments and sacrifice of the vessel. Major trauma (OR 4.0, 95% CI 1.3-14; p = 0.02), use of digital subtraction angiography as the initial imaging modality (OR 9.8, 95% CI 2.5-42; p < 0.01), and a maximum lesion diameter > 6 mm (OR 5.3, 95% CI 1.4-25; p = 0.03) proved to be significant in the decision to intervene. At a median follow-up of 18.1 months, 94.7% of the lesions treated with intervention healed completely compared with 19% of aneurysms in the medical group. Among those medically managed that did not resolve, the median change in diameter was -0.4 mm (IQR -1.8 to 0.4 mm). Age ≤ 50 years and aneurysm maximum diameter ≤ 6 mm predicted healing at follow-up in the medical group with 92% specificity and 65% sensitivity (area under the curve 0.87). At follow-up, 98% of patients were functionally independent (modified Rankin Scale score ≤ 2). CONCLUSIONS: Medical management alone is safe for most extracranial pseudoaneurysms, resulting in significantly fewer complications than endovascular intervention. Maximum diameter ≤ 6 mm and age ≤ 50 years were significant predictors of pseudoaneurysm resolution with medical therapy alone. Lesions that do not heal do not cause further symptoms or require additional intervention.

Characterizing Revascularization After Encephalo-Duro-Arterio-Synangiosis (EDAS) in Adult Patients With Moyamoya Disease Using the Orbital Grading System.

BACKGROUND: The Matsushima grade has traditionally been used to evaluate vessel ingrowth from the superficial temporal artery after encephalo-duro-arterio-synangiosis (EDAS) for Moyamoya disease (MMD) patients. However, this grading is subjective and prone to measurement variability. Herein, we propose the orbital grading system quantifying leptomeningeal and burr hole-related vessel-ingrowth from the superficial temporal artery and/or middle meningeal artery to the middle and anterior cerebral arteries post EDAS in MMD patients. METHODS: An anatomical classification was developed by reference to 2 parallel vertical lines from the bony landmarks of the orbit, categorized from Grade 0-3. Regression models were used to compare clinical and functional outcomes of our grading system with the Matsushima scale. RESULTS: Forty MMD patients, with median age of 48 years, mostly females (72.5%), underwent 56 EDAS procedures. Presentation included ischemic events (65.0%), hemorrhage (22.5%), and seizures (7.5%). Most patients were categorized as Suzuki ≥ IV (69.5%). Fifty EDAS (89.9%) had concurrent burr holes placed (parietal and frontal regions). At a median follow-up of 13.7 months, collateral growth was graded as follows: grade 0 (6; 10.8%), grade 1 (12; 21.4%), grade 2 (23; 41.1%), and grade 3 (15; 26.8%). Linear regression showed similarities in the distribution between the orbital grading system and Matsushima grading (r = 0.86; P < 0.01). Ischemic events were fewer in hemispheres categorized as grade 2-3 compared to grade 0-1 (P = 0.047) as well as in Matsushima grading A or B compared to C (P = 0.047). CONCLUSIONS: The orbital grading system demonstrated agreement in identifying postoperative ischemic events as the Matsushima grade and provides a more practical and objective evaluation of collateral vessel ingrowth after EDAS with and without burr holes.

The Supreme Court's Loper Bright Ruling: Implications for Clinical Testing, Innovation, and Public Health.

This Viewpoint explores the US Supreme Court's ruling in Loper Bright Enterprises v Raimondo and the implications the ruling could have on the regulation of laboratory-developed tests and public health.

Cost-effectiveness of platelet function testing in dual antiplatelet therapy decision-making after intracranial aneurysm treatment with flow diversion.

Dual antiplatelet therapy (DAPT) use is the standard of practice after flow diversion (FD) for intracranial aneurysms (IAs). Yet, no consensus exists in the literature regarding the optimal regimen. Certain institutions utilize various platelet function testing (PFT) to assess patient responsiveness to DAPT. Clopidogrel is the most commonly prescribed drug during DAPT; however, up to 52% of patients can be non-responders, justifying PFT use. Additionally, prices vary significantly among antiplatelet drugs, often further complicated by insurance restrictions. We aimed to determine the most cost-effective strategy for deciding DAPT regimens for patients after IA treatment. A decision tree with Monte Carlo simulations was performed to simulate patients undergoing various three-month postoperative DAPT regimens. Patients were either universally administered aspirin alongside clopidogrel, ticagrelor, or prasugrel without PFT, or administered one of the former thienopyridine medications based on platelet reactivity unit (PRU) results after clopidogrel. Input data for the model were extracted from the current literature, and the willingness-to-pay threshold (WTP) was defined as $100,000 per QALY as per standard practice in the US. The baseline comparison was with universal clopidogrel DAPT without any PFT. Probabilistic and deterministic sensitivity analyses were performed to evaluate the robustness of the model. Utilizing PFT and switching clopidogrel to prasugrel if resistance is documented was the most cost-effective regimen compared to universal clopidogrel, with a base-case incremental cost-effectiveness ratio (ICER) of $-35,255 (cost $2,336.67, effectiveness 0.85). Performing PFT and switching clopidogrel to ticagrelor (ICER $-4,671; cost $2,995.06, effectiveness 0.84), universal prasugrel (ICER $5,553; cost $3,097.30, effectiveness 0.84), or universal ticagrelor (ICER $75,969; cost $3,801.36, effectiveness 0.84) were all more cost-effective than treating patients with universal clopidogrel (cost $3,041.77, effectiveness 0.83). These conclusions remain robust in probabilistic and deterministic sensitivity analyses. The most cost-effective strategy guiding DAPT after FD for IAs is to perform PFTs and switch clopidogrel to prasugrel if resistance is documented, alongside aspirin. The cost of PFT is strongly justified and recommended when deciding patient-specific DAPT regimens.

Timing, type, and impact of thromboembolic events caused by flow diversion: a 10-year experience.

OBJECTIVE: Thromboembolic (TE) events are among the most feared complications after flow diversion (FD) and have been reported to occur even with adequate dual antiplatelet therapy. Herein, the authors characterize thrombotic and embolic events that developed after FD, focusing on the morbidity of each of these events and the predisposing factors associated with their development. METHODS: A retrospective analysis of aneurysms treated with FD at a single institution in the US between 2013 and 2023 was performed. The authors documented the emergence of intraprocedural and postoperative TE events. A survival analysis and a Cox regression model was conducted to identify predictors associated with these events. RESULTS: The authors included 651 procedures performed in 591 patients to treat 746 aneurysms. TE events occurred in 38 of the procedures performed (5.8%), causing permanent deficit in 20 patients and death in 4 patients. Eleven cases presented with acute stent thrombosis, 11 with large-vessel occlusion, and 9 with perforator strokes. At a median follow-up of 9.5 months, 73.0% of patients with an ischemic event had a modified Rankin Scale score ≤ 2. Three of the deaths were secondary to occlusion at the basilar trunk and vertebral artery. In patients with TE events in the anterior circulation, 7 of 11 patients with middle cerebral artery occlusion and 9 of 12 patients with internal carotid artery occlusion achieved independence. Time-to-event Cox regression analysis demonstrated that TE events were more frequent in patients exhibiting aspirin resistance (hazard ratio 2.66; 95% CI 1.10-6.70). CONCLUSIONS: TE events after FD result from multiple factors, including age, aneurysm characteristics, aneurysm location, antiplatelet resistance, and procedural factors. In our cohort, we found the highest morbidity for patients with TE events presenting with large-vessel occlusion at the middle cerebral artery, and vertebrobasilar system.

The evolution and future directions of bypass surgery.

Cerebral bypass surgery is one of the most complex and elegant procedures in neurosurgery. It involves several meticulous steps that test the skills of even the most prepared neurosurgeons. This surgery has transcended its traditional role in arterial stenosis and atherosclerosis, expanding its applications to include flow preservation techniques for complex conditions such as aneurysms, tumors, and vascular malformations. The decreased number of procedures performed across many hospitals reflects the development of newer endovascular therapies but is also due to the results of the extracranial-intracranial bypass study, the Carotid Occlusion Surgery Study, and the Carotid and Middle Cerebral Artery Occlusion Surgery Study, which have raised questions about the efficacy of cerebral bypass surgery for individuals with carotid artery occlusion who are prone to ischemic stroke. Despite this, there is still a potential benefit of bypass surgery for patients with hemodynamic impairment refractory to medical management. Also, revascularization in moyamoya vasculopathy is an effective strategy for preventing ischemic and hemorrhagic events in both children and adults. Additionally, innovations in the technique, such as the flow-regulated bypass and intraoperative flow assessment, aim to minimize perioperative morbidity. Despite bypass surgery being less performed in this current era, the teaching and development of these skills are still encouraged for future neurosurgeons, as a role for bypass will exist for the foreseeable future.

Anterior choroidal artery aneurysms: a systematic review and meta-analysis of outcomes and ischemic complications following surgical and endovascular treatment.

OBJECTIVE: Anterior choroidal artery (AChA) aneurysms account for 2%-5% of all intracranial aneurysms. Treatment considerations include microsurgical clipping, flow diversion, or coiling with or without adjunctive devices. AChA aneurysms pose challenges in treatment due to the origination of the aneurysm from the origin or proximal segment of the AChA. The AChA is particularly susceptible to vasospasm and occlusion during treatment with devastating neurological deficits, including hemiparesis, hemianesthesia, lethargy, neglect, and hemianopia. In this study, the authors performed a meta-analysis to quantify the outcomes and complication rates across treatment modalities for AChA aneurysms and to identify risk factors reported in the literature. METHODS: The authors performed a systematic review of AChA aneurysms treated with surgical clipping, endovascular coiling, or flow diversion and reported in the PubMed, Embase, Scopus, and Cochrane search databases. Single-arm meta-analyses of the selected outcomes were performed in RStudio. RESULTS: Literature review yielded 25 studies that met the inclusion criteria. In total, 1627 patients were included in the analysis, with 554 males, 1009 females, and 64 unspecified. The rate of any complication in the full cohort was 11.6%, with a rate of ischemic complications of 5.5% and a favorable recovery rate of 90.3% of all patients treated. In total, 1064 patients underwent surgical clipping, 443 were treated with coiling, and 120 patients with flow diversion. In clipped patients, the rate of total surgical complications was 17.6%, with an ischemic complication rate of 9.4%. The rate of good functional recovery, defined on the basis of a Glasgow Outcome Scale score of 4-5 or modified Rankin Scale score of 0-2, was 88.0%, and complete obliteration was achieved in 84.5% of surgically clipped aneurysms. The complication rate in coiled patients was 10.3%, with an ischemic complication rate of 3.0%. Good functional recovery was achieved in 88.6% of coiled patients and complete aneurysm obliteration in 74.1%. Flow diversion resulted in a complication rate of 1.3%, with 0.7% rate of ischemic complications. Good functional recovery was achieved in 98.4% of patients and complete aneurysm obliteration in 79.0% in the flow diversion group. Aneurysm morphological features that impacted the complication rate were also identified to augment quantitative data and to help guide treatment selection for AChA aneurysms. CONCLUSIONS: Flow diversion showed significantly lower total and ischemic complications and improved outcomes compared to clipping and coiling. There may be differences in outcomes between treatment types, especially when considering the varied patient presentations that guide treatment selection.

In-person learning during the pandemic: Student take-up and school-level effects of remote and hybrid instruction on student outcomes.

While studies have examined the effects of schools offering in-person learning during the pandemic, this study provides analysis of student enrollment decisions (remote versus in-person) in response to schools providing in-person learning opportunities. In Connecticut during the 2020-21 school year, we find that student take-up of in-person learning opportunities was low with students on average enrolled in-person for only half of the days offered, and take-up was even lower in schools with larger shares of disadvantaged students. The provision of in-person learning opportunities has been previously shown to mitigate pandemic learning losses. By exploiting data on actual enrollment, we show that the protective benefits of in-person learning are twice as large as previously estimated once we account for the low rates of student take-up. Finally, we provide evidence suggesting that a key mechanism behind the benefits of in-person learning is alleviating the burden faced by schools and teachers in delivering remote education. First, we show that the benefits to individual students of their in-person learning are substantially smaller than the overall benefits a student receives from their school average level of in-person enrollment. Second, we show that a combination of remote and in-person learning (hybrid) with a full-time on-line presence of students when at home was worse than hybrid learning with students never or only partially online. This second finding is consistent with qualitative evidence showing that teachers found hybrid learning especially challenging when having to manage both in-person and remote students for the entire class period.

Quantifying urban park use in the USA at scale: empirical estimates of realised park usage using smartphone location data.

BACKGROUND: A large body of evidence connects access to greenspace with substantial benefits to physical and mental health. In urban settings where access to greenspace can be limited, park access and use have been associated with higher levels of physical activity, improved physical health, and lower levels of markers of mental distress. Despite the potential health benefits of urban parks, little is known about how park usage varies across locations (between or within cities) or over time. METHODS: We estimated park usage among urban residents (identified as residents of urban census tracts) in 498 US cities from 2019 to 2021 from aggregated and anonymised opted-in smartphone location history data. We used descriptive statistics to quantify differences in park usage over time, between cities, and across census tracts within cities, and used generalised linear models to estimate the associations between park usage and census tract level descriptors. FINDINGS: In spring (March 1 to May 31) 2019, 18·9% of urban residents visited a park at least once per week, with average use higher in northwest and southwest USA, and lowest in the southeast. Park usage varied substantially both within and between cities; was unequally distributed across census tract-level markers of race, ethnicity, income, and social vulnerability; and was only moderately correlated with established markers of census tract greenspace. In spring 2019, a doubling of walking time to parks was associated with a 10·1% (95% CI 5·6-14·3) lower average weekly park usage, adjusting for city and social vulnerability index. The median decline in park usage from spring 2019 to spring 2020 was 38·0% (IQR 28·4-46·5), coincident with the onset of physical distancing policies across much of the country. We estimated that the COVID-19-related decline in park usage was more pronounced for those living further from a park and those living in areas of higher social vulnerability. INTERPRETATION: These estimates provide novel insights into the patterns and correlates of park use and could enable new studies of the health benefits of urban greenspace. In addition, the availability of an empirical park usage metric that varies over time could be a useful tool for assessing the effectiveness of policies intended to increase such activities. FUNDING: Google.

A Novel Scoring System Predicting Aneurysm Incomplete Occlusion After Flow Diversion: A 10-Year Experience.

BACKGROUND: Factors impacting the rate of aneurysm occlusion after flow diversion (FD) have been well described in the literature. In this article, we sought to evaluate those variables to develop and validate a scoring system predicting aneurysm incomplete occlusion after FD. METHODS: Retrospective review of patients with intracranial aneurysms treated with FD at a single institution between March 2013 and March 2023. Multivariable logistic regression model was developed using factors associated with aneurysm incomplete occlusion. The ABC scoring system consisted of: Age (<60 years old: 0, 60-69 years: 1, 70-79: 2, and ≥80: 3), Branch coming out of the aneurysm dome/neck (yes: 2, no: 0), and Cigarette smoking history (never smoker: 1, current or past smoker: 0). The scoring system performance was evaluated with receiver operating characteristic curve and calculating the area under the curve. RESULTS: A total of 449 patients with 563 aneurysms treated in 482 procedures were evaluated. Most cases were females (81.7%) with a median age of 59 years old. At a median follow-up of 13.2 months, 84.0% of aneurysms were completely or near-complete occluded. The scoring system had an area under the curve of 0.71. A value ≥ 2, reached a sensitivity of 74.4%, a specificity of 60.9%, a likelihood ratio+ of 1.90, and proved to be reliable in predicting the risk of incomplete occlusion (odds ratio = 4.53; 95% confidence interval: 2.73-7.54; P < 0.001). CONCLUSIONS: The proposed ABC scoring system can be used to evaluate the risk of aneurysm incomplete occlusion after treatment with FD, identifying patients who would benefit from adjunctive coiling or alternative treatment modalities.

Actual uptake pursuance analysis of certification examination among industrial engineers in the Philippines: A TPB-PVT approach.

The demand for Industrial Engineers across the globe is significantly increasing and professional certifications give advantage in the job marketplace. The Philippine Institute of Industrial Engineers (PIIE) - Industrial Engineering Certification Board facilitates the conferment of the Certified Industrial Engineer (CIE) in the Philippines. The goal of this study was to determine the factors affecting the intention IEs in the Philippines to take the CIE examination using an integration of the Perceived Value Theory and the Extended Theory of Planned Behavior. The research data were collected through an online distributed survey questionnaire to 690 graduating students and graduates from private and public universities across the Philippines. Employing a variance-based partial least squares structural equation modeling, the different significant variables and factors were assessed holistically. It was seen that attitude, perceived behavioral control, subjective norms, and understanding of the CIE examination have significant positive effects to intent to take the CIE examination and becoming a CIE. The perceived benefits and positive emotions brought by becoming a CIE significantly affects the attitude and behavior. This study also confirmed that the higher the perceived return on investment, the more the IEs will take the CIE examination. Moreover, demographic characteristics were identified to correlate and are significant among different variables. As a reflection, the findings and the integrated framework can be utilized in future studies related to development, career pathing, lifelong learning, and other related professional education.

The Neurovascular Disease Management Course: A Medical Student Opportunity for Early Exposure and Technical Development in Vascular Neurosurgery.

BACKGROUND: As endovascular neurosurgery techniques continue to evolve, medical students in the United States have widely varying exposures to the field, particularly with respect to opportunities for hands-on experiences. Current medical school curricula could benefit from a novel and adaptive course on vascular neurosurgery to increase student exposure earlier in their training. METHODS: We launched a yearly hands-on vascular neurosurgery course for medical students and residents. The day-long course is a combination of lectures focused on neurovascular disease and management accompanied by hands-on sessions where students practiced fundamental microsurgery and angiography techniques using real microscopes and angiography simulators. We surveyed the students before and after each of the 2 courses. The survey following the second annual course included quiz questions the students had not previously seen. RESULTS: Over 2 courses, we had 149 attendees, 71.8% of which were first and second-year medical students representing fifteen institutions. The average survey completion rate was 41.4% for the 4 surveys across the 2 courses. Attendees' interest in pursuing a surgical specialty (t = 1.815, P = 0.039) along with their comfort with neuroanatomy (t = 8.780, P ≤ 0.001) and neurosurgical disease (t = 6.133, P ≤ 0.001) was significantly elevated after the completion of the second course. Responses to the post-survey showed a good grasp of the fundamentals with 68% of attendees answering 70% of the quiz questions correctly. CONCLUSIONS: An interactive course on vascular neurosurgery may be an effective vehicle to provide medical students with exposure to the field and the opportunity to learn the fundamentals.

Endovascular Treatment of Basilar Apex Aneurysms: An Updated Systematic Review and Meta-Analysis in the Era of Flow Diversion.

BACKGROUND: Endovascular options for the treatment of basilar apex aneurysms (BAAs) are heterogeneous, and evidence is limited to retrospective cohorts and case series. We seek to evaluate the efficacy and complications associated with various endovascular treatment methods of BAAs. METHODS: Systematic review of PubMed, Embase, and Web of Science adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Retrospective and prospective studies evaluating endovascular treatment of BAAs between January 2010 and July 2024 were included. Relevant information including occlusion rates, aneurysm recurrence, retreatment rates, and complications were subjected to meta-analysis. RESULTS: Fifteen studies with 1049 BAAs were included. The median aneurysm diameter was 8.5 mm (range, 4.6-19.75), with a median follow-up of 33.7 months (range, 6.0-117.6). Residual aneurysm filling occurred in 24% after primary coiling (95% CI = 0.16-0.32), 25% after single stent-assisted coiling (s-SAC; 95% CI = 0.04-0.46), 25% after Y-stents (95% CI = 0.12-0.37), and 23% after flow diverter stent (FDS; 95% CI = 0.11-0.35). Recurrence rates were high for primary coiling (27%, 95% CI = 0.18-0.36) and s-SAC (19%, 95% CI = 0.13-0.26), but significantly lower for Y-stents (9%, 95% CI = 0.03-0.15) and FDS (4%, 95% CI = -0.04-0.11). Retreatment rates were 19% for primary coiling (95% CI = 0.12-0.26), 17% for s-SAC (95% CI = 0.07-0.27), 5% for Y-stents (95% CI = -0.03-0.12), and 13% for FDS (95% CI = -0.01-0.27). Meta-regression indicated larger aneurysms had higher complication rates (P = 0.02). Thromboembolic events were most frequent with FDS and Y-stents(12%). CONCLUSIONS: Occlusion rates were similar across treatments, but recurrence rates were significantly lower after Y-stents and FDS compared to primary coiling, although they carried a higher number of thromboembolic complications.

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.

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 photolabile proligand (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.

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.