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1.
Neurology ; 102(10): e209324, 2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38709999

RESUMEN

BACKGROUND AND OBJECTIVES: There is uncertainty whether patients with large vessel occlusion (LVO) presenting in the late 6-hour to 24-hour time window can be selected for endovascular therapy (EVT) by noncontrast CT (NCCT) and CT angiography (CTA) for LVO detection. We evaluated the clinical outcomes of patients selected for EVT by NCCT compared with those medically managed in the extended time window. METHODS: This multinational cohort study was conducted at 66 sites across 10 countries. Consecutive patients with proximal anterior LVO stroke selected for EVT by NCCT or medically managed and presenting within 6-24 hours of time last seen well (TSLW) from January 2014 to May 2022 were included. The primary end point was the 90-day ordinal shift in the modified Rankin Scale (mRS) score. Inverse probability treatment weighting (IPTW) and multivariable methods were used. RESULTS: Of 5,098 patients screened, 839 patients were included, with a median (interquartile range) age of 75 (64-83) years; 455 (54.2%) were women. There were 616 patients selected to undergo EVT by NCCT (73.4%) and 223 (26.6%) who were medically managed. In IPTW analyses, there was a more favorable 90-day ordinal mRS shift in patients selected by NCCT to EVT vs those who were medically managed (odds ratio [OR] 1.99, 95% CI 1.53-2.59; p < 0.001). There were higher rates of 90-day functional independence (mRS 0-2) in the EVT group (40.1% vs 18.4%, OR 3.31, 95% CI 2.11-5.20; p < 0.001). sICH was nonsignificantly higher in the EVT group (8.5% vs 1.4%, OR 3.77, 95% CI 0.72-19.7, p = 0.12). Mortality at 90 days was lower in the EVT vs MM group (23.9% vs 32.3%, OR 0.61, 95% CI 0.45-0.83, p = 0.002). DISCUSSION: In patients with proximal anterior LVO in the extended time window, there was a lower rate of disability and mortality in patients selected with NCCT and CTA to EVT compared with those who were medically managed. These findings support the use of NCCT as a simpler and more inclusive approach to patient selection in the extended window. TRIAL REGISTRATION INFORMATION: This study was registered at ClinicalTrials.gov under NCT04096248. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for patients with proximal anterior circulation occlusion presenting with ischemic stroke from 6 to 24 hours, compared with medical management, those undergoing thrombectomy based on NCCT have reduced disability and mortality at 90 days.


Asunto(s)
Procedimientos Endovasculares , Trombectomía , Humanos , Femenino , Anciano , Masculino , Trombectomía/métodos , Anciano de 80 o más Años , Persona de Mediana Edad , Procedimientos Endovasculares/métodos , Angiografía por Tomografía Computarizada , Tomografía Computarizada por Rayos X , Estudios de Cohortes , Tiempo de Tratamiento , Resultado del Tratamiento , Angiografía Cerebral
2.
Stroke ; 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38748598

RESUMEN

BACKGROUND: Studies comparing bridging intravenous thrombolysis (IVT) with direct endovascular therapy (EVT) in patients with acute ischemic stroke who present late are limited. We aimed to compare the clinical outcomes and safety of bridging IVT in patients with acute ischemic stroke due to anterior circulation large vessel occlusion who underwent EVT 6 to 24 hours after time last known well. METHODS: We enrolled patients with anterior circulation large vessel occlusion stroke and a National Institutes of Health Stroke Scale score of ≥6 from 20 centers across 10 countries in the multicenter retrospective CLEAR study (CT for Late Endovascular Reperfusion) between January 2014 and May 2022. We used inverse probability of treatment weighting modeling adjusted for clinical and imaging confounders to compare functional outcomes, reperfusion success, symptomatic intracranial hemorrhage, and mortality between EVT patients with and without prior IVT. RESULTS: Of 5098 patients screened for eligibility, we included 2749 patients, of whom 549 received bridging IVT before EVT. The timing of IVT was not recorded. Witnessed stroke onset and transfer rates were higher in the bridging IVT group (25% versus 12% and 77% versus 55%, respectively, P value for both <0.0001), and time intervals between stroke onset and treatment were shorter (time last known well-start of EVT median 560 minutes [interquartile range, 432-791] versus 724 minutes [interquartile range, 544-912]; P<0.0001). After adjustment for confounders, there was no difference in functional outcome at 3 months (adjusted common odds ratio for modified Rankin Scale shift, 1.03 [95% CI, 0.89-1.19]; P=0.72) or successful reperfusion (adjusted odds ratio, 1.19 [95% CI, 0.81-1.75]; P=0.39). There were no safety concerns associated with bridging IVT versus direct EVT (symptomatic intracranial hemorrhage: adjusted odds ratio, 0.75 [95% CI, 0.38-1.48]; P=0.40; mortality: adjusted odds ratio, 1.14 [95% CI, 0.89-1.46]; P=0.31). Results were unchanged when the analysis was limited to patients who received IVT >6 hours after last known well. CONCLUSIONS: In patients with an anterior circulation large vessel occlusion stroke who underwent EVT 6 to 24 hours from last known well, bridging IVT was not associated with a difference in outcomes compared with direct EVT. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04096248.

3.
Stroke ; 2024 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-38753954

RESUMEN

Background: Acute ischemic stroke (AIS) with isolated posterior cerebral artery occlusion (iPCAO) lacks management evidence from randomized trials. We aimed to evaluate whether the association between endovascular treatment (EVT) and outcomes in iPCAO-AIS is modified by initial stroke severity (baseline NIHSS) and arterial occlusion site. Methods: Based on the multicenter, retrospective, case-control study of consecutive iPCAO-AIS patients (PLATO study), we assessed the heterogeneity of EVT outcomes compared to medical management (MM) for iPCAO, according to baseline NIHSS (≤6 vs. >6) and occlusion site (P1 vs. P2), using multivariable regression modelling with interaction terms. The primary outcome was the favorable shift of 3-month mRS. Secondary outcomes included excellent outcome (mRS 0-1), functional independence (mRS 0-2), symptomatic intracranial hemorrhage (sICH) and mortality. Results: From 1344 patients assessed for eligibility, 1,059 were included (median age 74 years, 43.7% women, 41.3% had intravenous thrombolysis), 364 receiving EVT and 695 MM. Baseline stroke severity did not modify the association of EVT with 3-month mRS distribution (pint=0.312), but did with functional independence (pint=0.010), with a similar trend on excellent outcome (pint=0.069). EVT was associated with more favorable outcomes than MM in patients with baseline NIHSS>6 (mRS 0-1: 30.6% vs. 17.7%, aOR=2.01, 95%CI=1.22-3.31; mRS 0-2: 46.1% vs. 31.9%, aOR=1.64, 95%CI=1.08-2.51), but not in those with NIHSS≤6 (mRS 0-1: 43.8% vs. 46.3%, aOR=0.90, 95%CI=0.49-1.64; mRS 0-2: 65.3% vs. 74.3%, aOR=0.55, 95%CI=0.30-1.0). EVT was associated with more sICH regardless of baseline NIHSS (pint=0.467), while the mortality increase was more pronounced in patients with NIHSS≤6 (pint=0.044, NIHSS≤6: aOR=7.95,95%CI=3.11-20.28, NIHSS>6: aOR=1.98,95%CI=1.08-3.65). Arterial occlusion site did not modify the association of EVT with outcomes compared to MM. Conclusion: Baseline clinical stroke severity, rather than the occlusion site, may be an important modifier of the association between EVT and outcomes in iPCAO. Only severely affected patients with iPCAO (NIHSS>6) had more favorable disability outcomes with EVT than MM, despite increased mortality and sICH.

4.
Eur Stroke J ; : 23969873241249406, 2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38757713

RESUMEN

INTRODUCTION: The benefit of endovascular therapy (EVT) among stroke patients with large ischemic core (ASPECTS 0-5) in the extended time window outside of trial settings remains unclear. We analyzed the effect of EVT among these stroke patients in real-world settings. PATIENTS AND METHODS: The CT for Late Endovascular Reperfusion (CLEAR) study recruited patients from 66 centers in 10 countries between 01/2014 and 05/2022. The extended time-window was defined as 6-24 h from last-seen-well to treatment. The primary outcome was shift of the 3-month modified Rankin scale (mRS) score. Safety outcomes included symptomatic intracranial hemorrhage (sICH) and mortality. Outcomes were analyzed with ordinal and logistic regressions. RESULTS: Among 5098 screened patients, 2451 were included in the analysis (median age 73, 55% women). Of patients with ASPECTS 0-5 (n = 310), receiving EVT (n = 209/310) was associated with lower 3-month mRS when compared to medical management (median 4 IQR 3-6 vs 6 IQR 4-6; aOR 0.4, 95% CI 0.2-0.7). Patients undergoing EVT had higher sICH (11.2% vs 4.0%; aOR 4.1, 95% CI 1.2-18.8) and lower mortality (31.6% vs 58.4%, aOR 0.4; 95% CI 0.2-0.9) compared to medically managed patients. The relative benefit of EVT was comparable between patients with ASPECTS 0 and 5 and 6-10 in the extended time window (interaction aOR 0.9; 95% CI 0.5-1.7). CONCLUSION: In the extended time window, patients with ASPECTS 0-5 may have preserved relative treatment benefit of EVT compared to patients with ASPECTS 6-10. These findings are in line with recent trials showing benefit of EVT among real-world patients with large ischemic core in the extended time window. TRIAL REGISTRATION NUMBER: clinicaltrials.gov; Unique identifier: NCT04096248.

5.
J Neurointerv Surg ; 2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38760168

RESUMEN

BACKGROUND: Neurointerventional devices, particularly laser-cut thin-strut stents made of self-expanding nickel-titanium alloy, are increasingly utilized for endovascular applications in intracranial arteries and dural venous sinuses. Preventing thrombosis and stroke necessitates systemic anticoagulant and antiplatelet therapies with the risk of bleeding complications. Antithrombotic coatings present a promising solution. METHODS: In this study, we investigated the potential of hydrogels composed of four-armed poly(ethylene glycol) (starPEG) and heparin, with or without coagulation-responsive heparin release, as coatings for neurovascular devices to mitigate blood clot formation. We evaluated the feasibility and efficacy of these coatings on neurovascular devices through in vitro Chandler-Loop assays and implantation experiments in the supra-aortic arteries of rabbits. RESULTS: Stable and coagulation-responsive starPEG-heparin hydrogel coatings exhibited antithrombotic efficacy in vitro, although with a slightly reduced thromboprotection observed in vivo. Furthermore, the hydrogel coatings demonstrated robustness against shear forces encountered during deployment and elicited only marginal humoral and cellular inflammatory responses compared with the reference standards. CONCLUSION: Heparin hydrogel coatings offer promising benefits for enhancing the hemocompatibility of neurointerventional devices made of self-expanding nickel-titanium alloy. The variance in performance between in vitro and in vivo settings may be attributed to differences in low- and high-shear blood flow conditions inherent to these models. These models may represent the differences in venous and arterial systems. Further optimization is warranted to tailor the hydrogel coatings for improved efficacy in arterial applications.

6.
J Am Chem Soc ; 146(20): 13914-13923, 2024 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-38741029

RESUMEN

Although simple γ-lactones and γ-lactams have received considerable attention from the synthetic community, particularly due to their relevance in biological and medicinal contexts, stereoselective synthetic approaches to more densely substituted derivatives remain scarce. The in-depth study presented herein, showcasing a straightforward method for the stereocontrolled synthesis of γ-lactones and γ-lactams, builds on and considerably expands the stereodivergent synthesis of 1,4-dicarbonyl compounds by a ynamide/vinyl sulfoxide coupling. A full mechanistic and computational study of the rearrangement was conducted, uncovering the role of all of the reaction components and providing a rationale for stereoselection. The broad applicability of the developed tools to streamlining synthesis is demonstrated by concise enantioselective total syntheses of (+)-nephrosteranic acid, (+)-rocellaric acid, and (+)-nephromopsinic acid.

7.
J Am Heart Assoc ; 13(9): e031816, 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38639365

RESUMEN

BACKGROUND: Data on impact of COVID-19 vaccination and outcomes of patients with COVID-19 and acute ischemic stroke undergoing mechanical thrombectomy are scarce. Addressing this subject, we report our multicenter experience. METHODS AND RESULTS: This was a retrospective analysis of patients with COVID-19 and known vaccination status treated with mechanical thrombectomy for acute ischemic stroke at 20 tertiary care centers between January 2020 and January 2023. Baseline demographics, angiographic outcome, and clinical outcome evaluated by the modified Rankin Scale score at discharge were noted. A multivariate analysis was conducted to test whether these variables were associated with an unfavorable outcome, defined as modified Rankin Scale score >3. A total of 137 patients with acute ischemic stroke (48 vaccinated and 89 unvaccinated) with acute or subsided COVID-19 infection who underwent mechanical thrombectomy attributable to vessel occlusion were included in the study. Angiographic outcomes between vaccinated and unvaccinated patients were similar (modified Thrombolysis in Cerebral Infarction ≥2b: 85.4% in vaccinated patients versus 86.5% in unvaccinated patients; P=0.859). The rate of functional independence (modified Rankin Scale score, ≤2) was 23.3% in the vaccinated group and 20.9% in the unvaccinated group (P=0.763). The mortality rate was 30% in both groups. In the multivariable analysis, vaccination status was not a significant predictor for an unfavorable outcome (P=0.957). However, acute COVID-19 infection remained significant (odds ratio, 1.197 [95% CI, 1.007-1.417]; P=0.041). CONCLUSIONS: Our study demonstrated no impact of COVID-19 vaccination on angiographic or clinical outcome of COVID-19-positive patients with acute ischemic stroke undergoing mechanical thrombectomy, whereas worsening attributable to COVID-19 was confirmed.


Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , Accidente Cerebrovascular Isquémico , Trombectomía , Vacunación , Humanos , COVID-19/complicaciones , COVID-19/terapia , COVID-19/mortalidad , Masculino , Femenino , Accidente Cerebrovascular Isquémico/mortalidad , Accidente Cerebrovascular Isquémico/cirugía , Estudios Retrospectivos , Anciano , Persona de Mediana Edad , Resultado del Tratamiento , Vacunas contra la COVID-19/efectos adversos , SARS-CoV-2 , Anciano de 80 o más Años
8.
JACS Au ; 4(3): 1166-1183, 2024 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-38559722

RESUMEN

Cobalt complexes with multiproton- and multielectron-responsive ligands are of interest for challenging catalytic transformations. The chemical and redox noninnocence of pentane-2,4-dione bis(S-methylisothiosemicarbazone) (PBIT) in a series of cobalt complexes has been studied by a range of methods, including spectroscopy [UV-vis, NMR, electron paramagnetic resonance (EPR), X-ray absorption spectroscopy (XAS)], cyclic voltammetry, X-ray diffraction, and density functional theory (DFT) calculations. Two complexes [CoIII(H2LSMe)I]I and [CoIII(LSMe)I2] were found to act as precatalysts in a Wacker-type oxidation of olefins using phenylsilane, the role of which was elucidated through isotopic labeling. Insights into the mechanism of the catalytic transformation as well as the substrate scope of this selective reaction are described, and the essential role of phenylsilane and the noninnocence of PBIT are disclosed. Among the several relevant species characterized was an unprecedented Co(III) complex with a dianionic diradical PBIT ligand ([CoIII(LSMe••)I]).

9.
Phys Rev E ; 109(2-1): 024313, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38491583

RESUMEN

Multiplex networks are collections of networks with identical nodes but distinct layers of edges. They are genuine representations of a large variety of real systems whose elements interact in multiple fashions or flavors. However, multiplex networks are not always simple to observe in the real world; often, only partial information on the layer structure of the networks is available, whereas the remaining information is in the form of aggregated, single-layer networks. Recent works have proposed solutions to the problem of reconstructing the hidden multiplexity of single-layer networks using tools proper for network science. Here, we develop a machine-learning framework that takes advantage of graph embeddings, i.e., representations of networks in geometric space. We validate the framework in systematic experiments aimed at the reconstruction of synthetic and real-world multiplex networks, providing evidence that our proposed framework not only accomplishes its intended task, but often outperforms existing reconstruction techniques.

11.
Sci Adv ; 10(9): eadi9294, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38427730

RESUMEN

Previous research shows that the beauty of natural images is already determined during perceptual analysis. However, it is unclear which perceptual computations give rise to the perception of beauty. Here, we tested whether perceived beauty is predicted by spatial integration across an image, a perceptual computation that reduces processing demands by aggregating image parts into more efficient representations of the whole. We quantified integrative processing in an artificial deep neural network model, where the degree of integration was determined by the amount of deviation between activations for the whole image and its constituent parts. This quantification of integration predicted beauty ratings for natural images across four studies with different stimuli and designs. In a complementary functional magnetic resonance imaging study, we show that integrative processing in human visual cortex similarly predicts perceived beauty. Together, our results establish integration as a computational principle that facilitates perceptual analysis and thereby mediates the perception of beauty.


Asunto(s)
Corteza Visual , Percepción Visual , Humanos , Visión Ocular , Corteza Visual/diagnóstico por imagen , Imagen por Resonancia Magnética , Juicio , Mapeo Encefálico
12.
J Am Heart Assoc ; 13(6): e031854, 2024 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-38456409

RESUMEN

BACKGROUND: We studied the association of bridging intravenous thrombolysis (IVT) before thrombectomy for anterior circulation large-vessel occlusion and functional outcome and scrutinized its dependence on grade of reperfusion and distal thrombus migration. METHODS AND RESULTS: We included consecutive patients with anterior circulation large-vessel occlusion from our prospective registry of thrombectomy-eligible patients treated from January 1, 2017 to January 1, 2023 at a tertiary stroke center in Germany in this retrospective cohort study. To evaluate the association of bridging IVT and functional outcome quantified via modified Rankin Scale score at 90 days we used multivariable logistic and lasso regression including interaction terms with grade of reperfusion quantified via modified Thrombolysis in Cerebral Infarction (mTICI) scale and distal thrombus migration adjusted for demographic and cardiovascular risk profiles, clinical and imaging stroke characteristics, onset-to-recanalization time and distal thrombus migration. We performed sensitivity analysis using propensity score matching. In our study population of 1000 thrombectomy-eligible patients (513 women; median age, 77 years [interquartile range, 67-84]), IVT emerged as a predictor of favorable functional outcome (modified Rankin Scale score, 0-2) independent of modified mTICI score (adjusted odds ratio, 0.49 [95% CI, 0.32-0.75]; P=0.001). In those who underwent thrombectomy (n=812), the association of IVT and favorable functional outcome was reproduced (adjusted odds ratio, 0.49 [95% CI, 0.31-0.74]; P=0.001) and was further confirmed on propensity score analysis, where IVT led to a 0.35-point decrease in 90-day modified Rankin Scale score (ß=-0.35 [95 CI%, -0.68 to 0.01]; P=0.04). The additive benefit of IVT remained independent of modified mTICI score (ß=-1.79 [95% CI, -3.43 to -0.15]; P=0.03) and distal thrombus migration (ß=-0.41 [95% CI, -0.69 to -0.13]; P=0.004) on interaction analysis. Consequently, IVT showed an additive association with functional outcome in the subpopulation of patients undergoing thrombectomy who achieved successful reperfusion (mTICI ≥2b; ß=-0.46 [95% CI, -0.74 to -0.17]; P=0.002) and remained beneficial in those with unsuccessful reperfusion (mTICI ≤2a; ß=-0.47 [95% CI, -0.96 to 0.01]; P=0.05). CONCLUSIONS: In thrombectomy-eligible patients with anterior circulation large-vessel occlusion, IVT improves functional outcome independent of grade of reperfusion and distal thrombus migration.


Asunto(s)
Isquemia Encefálica , Procedimientos Endovasculares , Accidente Cerebrovascular , Trombosis , Humanos , Femenino , Anciano , Fibrinolíticos/efectos adversos , Estudios Retrospectivos , Isquemia Encefálica/terapia , Resultado del Tratamiento , Accidente Cerebrovascular/etiología , Trombectomía/efectos adversos , Trombectomía/métodos , Infarto Cerebral/etiología , Reperfusión , Terapia Trombolítica/efectos adversos , Terapia Trombolítica/métodos , Trombosis/etiología , Procedimientos Endovasculares/métodos
13.
Sci Rep ; 14(1): 6933, 2024 Mar 23.
Artículo en Inglés | MEDLINE | ID: mdl-38521798

RESUMEN

The hypergraph community detection problem seeks to identify groups of related vertices in hypergraph data. We propose an information-theoretic hypergraph community detection algorithm which compresses the observed data in terms of community labels and community-edge intersections. This algorithm can also be viewed as maximum-likelihood inference in a degree-corrected microcanonical stochastic blockmodel. We perform the compression/inference step via simulated annealing. Unlike several recent algorithms based on canonical models, our microcanonical algorithm does not require inference of statistical parameters such as vertex degrees or pairwise group connection rates. Through synthetic experiments, we find that our algorithm succeeds down to recently-conjectured thresholds for sparse random hypergraphs. We also find competitive performance in cluster recovery tasks on several hypergraph data sets.

14.
J Cogn Neurosci ; : 1-13, 2024 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-38527070

RESUMEN

Models of human cortex propose the existence of neuroanatomical pathways specialized for different behavioral functions. These pathways include a ventral pathway for object recognition, a dorsal pathway for performing visually guided physical actions, and a recently proposed third pathway for social perception. In the current study, we tested the hypothesis that different categories of moving stimuli are differentially processed across the dorsal and third pathways according to their behavioral implications. Human participants (n = 30) were scanned with fMRI while viewing moving and static stimuli from four categories (faces, bodies, scenes, and objects). A whole-brain group analysis showed that moving bodies and moving objects increased neural responses in the bilateral posterior parietal cortex, parts of the dorsal pathway. By contrast, moving faces and moving bodies increased neural responses, the superior temporal sulcus, part of the third pathway. This pattern of results was also supported by a separate ROI analysis showing that moving stimuli produced more robust neural responses for all visual object categories, particularly in lateral and dorsal brain areas. Our results suggest that dynamic naturalistic stimuli from different categories are routed in specific visual pathways that process dissociable behavioral functions.

15.
J Neurophysiol ; 131(4): 619-625, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38416707

RESUMEN

To create coherent visual experiences, the brain spatially integrates the complex and dynamic information it receives from the environment. We previously demonstrated that feedback-related alpha activity carries stimulus-specific information when two spatially and temporally coherent naturalistic inputs can be integrated into a unified percept. In this study, we sought to determine whether such integration-related alpha dynamics are triggered by categorical coherence in visual inputs. In an EEG experiment, we manipulated the degree of coherence by presenting pairs of videos from the same or different categories through two apertures in the left and right visual hemifields. Critically, video pairs could be video-level coherent (i.e., stem from the same video), coherent in their basic-level category, coherent in their superordinate category, or incoherent (i.e., stem from videos from two entirely different categories). We conducted multivariate classification analyses on rhythmic EEG responses to decode between the video stimuli in each condition. As the key result, we significantly decoded the video-level coherent and basic-level coherent stimuli, but not the superordinate coherent and incoherent stimuli, from cortical alpha rhythms. This suggests that alpha dynamics play a critical role in integrating information across space, and that cortical integration processes are flexible enough to accommodate information from different exemplars of the same basic-level category.NEW & NOTEWORTHY Our brain integrates dynamic inputs across the visual field to create coherent visual experiences. Such integration processes have previously been linked to cortical alpha dynamics. In this study, the integration-related alpha activity was observed not only when snippets from the same video were presented, but also when different video snippets from the same basic-level category were presented, highlighting the flexibility of neural integration processes.


Asunto(s)
Corteza Visual , Campos Visuales , Corteza Visual/fisiología , Ritmo alfa , Encéfalo , Mapeo Encefálico
16.
Can J Neurol Sci ; : 1-8, 2024 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-38403588

RESUMEN

BACKGROUND AND PURPOSE: To assess cost-effectiveness of late time-window endovascular treatment (EVT) in a clinical trial setting and a "real-world" setting. METHODS: Data are from the randomized ESCAPE trial and a prospective cohort study (ESCAPE-LATE). Anterior circulation large vessel occlusion patients presenting > 6 hours from last-known-well were included, whereby collateral status was an inclusion criterion for ESCAPE but not ESCAPE-LATE. A Markov state transition model was built to estimate lifetime costs and quality-adjusted life-years (QALYs) for EVT in addition to best medical care vs. best medical care only in a clinical trial setting (comparing ESCAPE-EVT to ESCAPE control arm patients) and a "real-world" setting (comparing ESCAPE-LATE to ESCAPE control arm patients). We performed an unadjusted analysis, using 90-day modified Rankin Scale(mRS) scores as model input and analysis adjusted for baseline factors. Acceptability of EVT was calculated using upper/lower willingness-to-pay thresholds of 100,000 USD/50,000 USD/QALY. RESULTS: Two-hundred and forty-nine patients were included (ESCAPE-LATE:n = 200, ESCAPE EVT-arm:n = 29, ESCAPE control-arm:n = 20). Late EVT in addition to best medical care was cost effective in the unadjusted analysis both in the clinical trial and real-world setting, with acceptability 96.6%-99.0%. After adjusting for differences in baseline variables between the groups, late EVT was marginally cost effective in the clinical trial setting (acceptability:49.9%-61.6%), but not the "real-world" setting (acceptability:32.9%-42.6%). CONCLUSION: EVT for LVO-patients presenting beyond 6 hours was cost effective in the clinical trial setting and "real-world" setting, although this was largely related to baseline patient differences favoring the "real-world" EVT group. After adjusting for these, EVT benefit was reduced in the trial setting, and absent in the real-world setting.

17.
Nature ; 626(7997): 92-97, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38297174

RESUMEN

Alkenes are indispensable feedstocks in chemistry. Functionalization at both carbons of the alkene-1,2-difunctionalization-is part of chemistry curricula worldwide1. Although difunctionalization at distal positions has been reported2-4, it typically relies on designer substrates featuring directing groups and/or stabilizing features, all of which determine the ultimate site of bond formation5-7. Here we introduce a method for the direct 1,3-difunctionalization of alkenes, based on a concept termed 'charge relocation', which enables stereodivergent access to 1,3-difunctionalized products of either syn- or anti-configuration from unactivated alkenes, without the need for directing groups or stabilizing features. The usefulness of the approach is demonstrated in the synthesis of the pulmonary toxin 4-ipomeanol and its derivatives.

18.
19.
Angew Chem Int Ed Engl ; 63(9): e202316579, 2024 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-38179790

RESUMEN

Sulfenyl imidinium salts are a virtually unexplored class of intermediates in organic chemistry. Herein, we demonstrate how sulfonium rearrangements can be deployed to access these versatile synthetic intermediates, bearing three contiguous (and congested) stereogenic centers, with high levels of selectivity. The synthetic value of the scaffold was unraveled by selective transformations into a range of building blocks, including 1,4-dicarbonyl derivatives and sulfonolactones.

20.
Cognition ; 245: 105723, 2024 04.
Artículo en Inglés | MEDLINE | ID: mdl-38262271

RESUMEN

According to predictive processing theories, vision is facilitated by predictions derived from our internal models of what the world should look like. However, the contents of these models and how they vary across people remains unclear. Here, we use drawing as a behavioral readout of the contents of the internal models in individual participants. Participants were first asked to draw typical versions of scene categories, as descriptors of their internal models. These drawings were converted into standardized 3d renders, which we used as stimuli in subsequent scene categorization experiments. Across two experiments, participants' scene categorization was more accurate for renders tailored to their own drawings compared to renders based on others' drawings or copies of scene photographs, suggesting that scene perception is determined by a match with idiosyncratic internal models. Using a deep neural network to computationally evaluate similarities between scene renders, we further demonstrate that graded similarity to the render based on participants' own typical drawings (and thus to their internal model) predicts categorization performance across a range of candidate scenes. Together, our results showcase the potential of a new method for understanding individual differences - starting from participants' personal expectations about the structure of real-world scenes.


Asunto(s)
Individualidad , Reconocimiento Visual de Modelos , Humanos , Redes Neurales de la Computación , Percepción Visual , Estimulación Luminosa/métodos
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