Scale Shift Research Articles

Tenecteplase thrombolytic therapy for acute ischaemic stroke in China: a real-world, multicentre, retrospective, controlled study

Background and aimsTenecteplase (TNK) offers logistical advantages in stroke thrombolytic therapy with its single bolus administration compared with alteplase. We aim to investigate the real-world evidence regarding its safety and effectiveness in China.MethodsWe conducted a retrospective study on patients receiving alteplase or TNK for acute ischaemic stroke (AIS) within 4.5 hours of onset between 1 March 2019 and 1 October 2023, from 18 stroke centres in China. Using propensity score matching (PSM), TNK-treated patients were matched 1:1 with alteplase-treated patients. The primary outcome was the rate of symptomatic intracranial haemorrhage (sICH) within 72 hours post-thrombolysis. Secondary outcomes comprised the rate of parenchymal haemorrhage type 2, any intracranial haemorrhage, any systematic bleeding and mortality at 90 days, as well as 24-hour National Institutes of Health Stroke Scale (NIHSS), early neurological improvement at 24 hours, modified Rankin Scale (mRS) shift, percentage of mRS 0–1 and mRS 0–2 at 90 days.ResultsWe identified 1113 patients with AIS who received TNK and 2360 patients who received alteplase. Following PSM, 1113 TNK-treated patients with AIS were matched to 1113 patients treated with alteplase. No significant differences were observed in rates of sICH (1.8% vs 1.98%, p=0.864) or other safety outcomes. Moreover, TNK-treated patients demonstrated a lower rate of any intracranial haemorrhage (OR: 0.51, 95% CI: 0.31 to 0.86, p=0.012). A higher proportion of patients achieving early neurological improvement at 24 hours (OR: 1.76, 95% CI: 1.48 to 2.09, p=0.000), better 90-day mRS (OR: 0.67, 95% CI: 0.57 to 0.79, p=0.000) as well as higher percentages of 90-day mRS 0–1 (OR: 1.27, 95% CI: 1.05 to 1.54, p=0.012) and mRS 0–2 (OR: 1.41, 95% CI: 1.14 to 1.75, p=0.001) compared with alteplase.ConclusionsThrombolysis with TNK is not associated with an increased risk of sICH, and may result in better early neurological improvement and 90-day functional outcomes compared with alteplase in patients with AIS.

Outcomes of different anesthesia techniques in nonagenarians treated with mechanical thrombectomy for anterior circulation large vessel occlusion: An inverse probability weighting analysis.

There is a lack of evidence for the optimal type of anesthesia technique in patients ⩾ 90 years with acute ischemic stroke undergoing mechanical thrombectomy (MT) as this subgroup of patients was often excluded or under-represented in previous trials. We aimed to compare outcomes between general anesthesia (GA) and non-GA techniques in patients ⩾ 90 years with large vessel occlusion (LVO) undergoing MT. Our study included patients ⩾ 90 years with anterior circulation LVO, NIHSS ⩾ 6, ASPECTS ⩾ 5 consecutively treated with MT within 6 h after stroke onset in three thrombectomy capable centers between January 1st, 2016 and March 30th, 2023. Inverse probability weighting (IPW) was used to reduce bias by indication of the anesthesia type on study outcomes. We used a weighted ordinal robust logistic regression analysis to explore the primary outcome of modified Rankin Scale (mRS) shift at 90 days in GA versus non-GA treated patients. Secondary outcomes included 90-day mortality, symptomatic intracranial hemorrhage (sICH) and TICI score of 2b, 2c, or 3. We included 139 patients ⩾ 90 years treated with MT, 62 were in GA group and 77 in non-GA group. There was a significant shift for worse mRS scores at 90-day in non-GA treated patients (cOR 3.65, 95% CI 1.77-7.77, p = 0.001). The weighted logistic regression showed that non-GA technique was an independent predictor of 90-day mortality (OR 7.49, 95% CI 2.00-28.09; p = 0.003). Our study indicated that nonagenarians with acute ischemic stroke treated with MT without GA have a worse prognosis than their counterparts undergoing MT with GA. Further studies in larger cohorts are warranted to evaluate the optimal type of anesthesia in this patient population.

Predictors and Outcomes of Excellent Recanalization Versus Successful Recanalization After Thrombectomy in Proximal and Distal Medium Vessel Occlusion Strokes: A Multinational Study

BACKGROUND Acute ischemic stroke arising from medium vessel occlusions (MeVO) poses substantial challenges in treatment and management. This study aims to elucidate the outcomes and factors contributing to achieving excellent recanalization (modified Thrombolysis in Cerebral Infarction [mTICI] 2c–3) versus successful recanalization (mTICI 2b) in patients with MeVO stroke undergoing mechanical thrombectomy (MT). METHODS We conducted a multinational study analyzing data from the MAD‐MT (Multicenter Analysis of Distal Medium Vessel Occlusions: Effect of Mechanical Thrombectomy) registry, encompassing 37 centers across North America, Asia, and Europe, collected between September 2017 and July 2023. The study included acute ischemic stroke patients with MeVO treated with MT, with or without intravenous thrombolysis, who achieved mTICI 2b–3 post‐MT. RESULTS Among 1463 patients with successful recanalization (mTICI 2b–3), 523 achieved mTICI 2b recanalization, and 940 achieved mTICI 2c–3. Distal occlusions exhibited higher odds of excellent recanalization compared with proximal MeVO vessel occlusions (odds ratio, 1.58; 95% CI, 1.17–2.15; P = 0.003). Cardioembolic stroke pathogenesis was associated with a higher likelihood of excellent recanalization (1.67; 95% CI, 1.07–2.59; P = 0.018). Patients achieving mTICI 2c–3 recanalization demonstrated lower initial National Institutes of Health Stroke Scale scores, significant improvements in postprocedural National Institutes of Health Stroke Scale shift, and a higher percentage of favorable 90‐day outcomes compared with those with mTICI 2b. However, no significant difference in 90‐day mortality rates was observed. CONCLUSION This study underscores that among patients with MeVO stroke with successful recanalization (mTICI 2b–3) there is higher likelihood of achieving excellent recanalization (mTICI 2c–3) in distal occlusions and cardioembolic pathogenesis. mTICI 2c–3 scores post‐MT correlate with improved clinical outcomes compared with mTICI 2b, affirming the superiority of excellent recanalization over successful recanalization in patients with MeVO stroke. Further prospective studies and randomized controlled trials are warranted for validation.

Reconstructing the past environmental conditions of southwestern India using estuarine sediment core

Geological archives can be examined via multiple proxies to uncover significant information about historical environmental changes. In comparison to single proxy approach, the use of multiple proxies can provide better resolution of the paleoenvironmental record. Thus, in the present study, to understand the paleoenvironmental conditions in the Kali coast in southwestern India, sedimentological, geochemical and isotopic (210Pb, 137Cs) proxies were used. The findings demonstrated that, in previous decades, the sedimentation rate varied from 0.5 to 1.0 cm/year under conditions with relatively higher hydrodynamic energy that were more common and fluctuating, allowing for larger sand particle deposition. However, in more recent years, finer particle deposition towards the surface has been observed under conditions with lower and more stable hydrodynamic energy, with a sedimentation rate of 1.87 cm/year. Additionally, the finer fractions displayed a strong correlation with the metal distribution, which was mostly governed by Fe-Mn oxides. Furthermore, it can be revealed that the environment was warm, humid, and marine-like between 1995 and 2000 based on chemical weathering intensity values and Rb/K ratios. A subtle shift to a freshwater habitat with relatively less warm, less humid climate occurred between 2000 and 2020. Therefore, similar research with longer depositional histories coupled with multiple proxies can help predict the future climatic shifts in decadal time scales.

New Lepage-type control charts for joint monitoring of location and scale

This paper introduces two new Shewhart Lepage-type control charts for jointly monitoring the location and scale parameters of continuous processes. The first is based on the van der Waerden (VW) and Ansari-Bradley (AB) tests while the other is on the VW and Mood tests. Statistical performances, in terms of average run length (ARL), of these charts are evaluated numerically and compared with that of their two competitor charts in the existing literature under four distributional models for the process output, namely, the normal, lognormal, Laplace, and logistic. The numerical results show that irrespective of the process distribution, one of the proposed charts (based on VW and Mood tests) has the best performance among all the four charts in the detection of simultaneous shifts in both the parameters of all sizes as well as in the detection of shifts in the scale that have not been accompanied by shifts in the location (only-scale shifts) of all sizes. Moreover, the other proposed chart (based on VW and AB tests) performs better than one of the competitor charts in the existing literature for detecting simultaneous shifts as well as only-scale shifts of all sizes. In addition, it performs better than the other competitor chart for detecting the simultaneous shifts consisting of a large location shift and a small scale shift, however, performs worse than that for detecting the simultaneous shifts consisting of a small location shift and a scale shift of any size, as well as for detecting the only-scale shifts of all sizes. All the four charts perform almost similarly in the detection of only-location shifts of all sizes. Regression models are provided for the proposed charts, which facilitate their designs in practice. Finally, the practical implementation of the proposed charts is illustrated through a real-data example.

Estimating Non-Stationary Extreme-Value Probability Distribution Shifts and Their Parameters Under Climate Change Using L-Moments and L-Moment Ratio Diagrams: A Case Study of Hydrologic Drought in the Goat River Near Creston, British Columbia

Here, we investigate the use of rolling-windowed L-moments (RWLMs) and L-moment ratio diagrams (LMRDs) combined with a Multiple Linear Regression (MLR) machine learning algorithm to model non-stationary low-flow hydrological extremes with the potential to simultaneously understand time-variant shape, scale, location, and probability distribution (PD) shifts under climate change. By employing LMRDs, we analyse changes in PDs and their parameters over time, identifying key environmental predictors such as lagged precipitation for September 5-day low-flows. Our findings indicate a significant relationship between total August precipitation L-moment ratios (LMRs) and September 5-day low-flow LMRs (τ2-Precipitation and τ2-Discharge: R2 = 0.675, p-values < 0.001; τ3-Precipitation and τ3-Discharge: R2 = 0.925, p-value for slope < 0.001, intercept not significant with p = 0.451, assuming α = 0.05 and a 31-year RWLM), which we later refine and use for prediction within our MLR algorithm. The methodology, applied to the Goat River near Creston, British Columbia, aids in understanding the implications of climate change on water resources, particularly for the yaqan nuʔkiy First Nation. We find that future low-flows under climate change will be outside the Natural Range of Variability (NROV) simulated from historical records (assuming a constant PD). This study provides insights that may help in adaptive water management strategies necessary to help preserve Indigenous cultural rights and practices and to help sustain fish and fish habitat into the future.

Scalar induced gravity waves from ultra slow-roll galileon inflation

We consider the production of secondary gravity waves in Galileon inflation with an ultra-slow roll (USR) phase and show that the spectrum of scalar-induced gravitational waves (SIGWs) in this case is consistent with the recent NANOGrav 15-year data and with sensitivities of other ground and space-based missions, LISA, BBO, DECIGO, CE, ET, HLVK (consists of aLIGO, aVirgo, and KAGRA), and HLV(03). Thanks to the non-renormalization property of Galileon theory, the amplitude of the large fluctuation is controllable at the sharp transitions between SR and USR regions. We show that the behavior of the GW spectrum, when one-loop effects are included in the scalar power spectrum, is preserved under a shift of the sharp transition scale with peak amplitude ΩGWh2∼O(10−6), and hence it can cover a wide range of frequencies within O(10−9Hz−107Hz). An analysis of the allowed mass range for primordial black holes (PBHs) is also performed, where we find that mass values ranging from O(1M⊙−10−18M⊙) can be generated over the corresponding allowed range of low and high frequencies.

Space Games: Ecologies of Scale and Technologies of Hope in Taiwan's OPUS Game Trilogy

Extending ecocritical game studies to the Sinophone (or Chinese-speaking) world, this article offers a close playing of three OPUS-themed science fiction videogames produced between 2016 and 2021 by Taiwanese indie developer SIGONO, exploring the games’ function as environmental texts and their relationship to Taiwanese literary and cultural studies. By asking the player to engage in shifts in scale and perspective from human to nonhuman, life to death, past to present, and enclosed to boundless space, the OPUS games serve as an effective way of understanding ecological intervention that promotes multiscalar awareness and asks what still can be done and what hope can be found when all has already been lost. In doing so, they demonstrate the ecocritical potential of science fiction videogames that feature an in-game environment many millions of light-years away from our current earth-bound realities.

Subnational Environmental Policy: Trends and Issues

Policies relevant to many key sociological processes are often subnational, enacted at the regional, state/provincial, and/or local levels. This applies notably in the politics of the environmental state, where public and private subnational environmental policies (SNEPs) have major consequences for managing climate change, addressing environmental injustices, regulating land uses, greening energy markets, limiting pollution, and much more. While sociologists focus more on national policies, diverse sociological contributions emphasize the importance of SNEPs and their origins, diffusion, implementation, and sources of backlash. We begin by providing a typology of SNEPs. Next, we highlight not only environmental sociology (with its particular attention to climate change and energy) but also the sociologies of social movements, politics, the economy, science, risk, and organizations, which have each offered unique perspectives. Finally, we outline an agenda for how sociologists can further elaborate a distinctive perspective that highlights inequality, valuation, diffusion, scale shifts, and venue-shopping up to national and global policy systems.

Opportunities for achieving landscape scale conservation in England

The English countryside is set to undergo significant changes in the way it will be managed in the coming year. The incoming Environmental Land Management schemes represents a shift in scale and focus of public goods provisioning, with the Landscape Recovery scheme in particular now geared more in favour of a coordinated landscape scale delivery of these public goods. This also comes at a time when the countryside has been experiencing a diversification within the land management community, which are moving towards an increasingly heterogenous mix of values and motivations for occupying and managing land. This will have implication as to how effective these public goods can be delivered on a landscape scale. Further complicating this is that while the idea of landscape scale collaboration to deliver more meaningful outcomes towards conservation has been widely accepted in scientific circles, uncertainty about how to achieve this in practice remains. This prompts a growing need to better understand how willing these increasingly diverse range of landholders are in collaborating together.To address this, this paper explores how collaborations consisting of a heterogenous mix of stakeholders might function, and the drivers and interventions required for such collaboration to be sustained in the long term. Utilising Q-methodology, we establish various models of collaboration based around the range perspectives of different stakeholders. Our findings yield five models of collaboration: the “Traditional Farmer”, “Social Farmer”, “Hybrid Collaboration”, “Modern Collaborators” and “Pragmatic Collaborators”. While distinction between the groups are reflected by the aspects of collaboration they placed most importance to, several commonalities in views have emerged as well. This includes the trust required between conservation groups and landholders for effective conservation outcomes, and the opportunity to exchange knowledge and experience in collaborations. Ultimately, the models of collaboration suggest a need for future policies to think more directly about how different landholders might be grouped according to their perspective on collaboration and how they can be incentivised. This will facilitate more effective, and sustained, landholder collaborations that fulfils landscape scale ambitions of upcoming policies.

Research on Inter-Satellite Laser Ranging Scale Factor Estimation Methods for Next-Generation Gravity Satellites

The scale factor serves as a ruler for converting raw phase measurements into physical displacements and significantly impacts the preprocessing of data from the Laser Ranging Interferometer (LRI) in laser ranging systems. In the current GRACE Follow-On (GRACE-FO) mission for low–low tracking gravity satellites, most of the existing LRI scale factor estimation algorithms heavily rely on cross-calibration between instantaneous/biased ranges from the Ka-Band Ranging Interferometer (KBR) and the LRI. However, due to the nonlinearity of the objective function (which includes terms involving the product of scale and time shifts), the scale factor estimation may absorb errors from timing noise. Moreover, future gravity missions or gravity detection tasks may no longer incorporate KBR ranging instruments. To address these challenges, this paper proposes an energy-based method for scale factor estimation using inter-satellite baseline solutions. Comparative analysis indicates that the proposed method effectively disentangles two parameters in the objective function and can be applied in scenarios where KBR data are unavailable, demonstrating promising prospects for practical application. The experimental results show that when the KBR validation residuals are lower than 0.8 mm, the SYSU LRI1B V01 products exhibit residuals below the payload design accuracy thresholds in the frequency band of 2 mHz to 0.1 Hz. Additionally, the stability of the scale factors obtained from the baseline can reach 10−7. Although this is still below the required precision of better than 10−8 for the laser frequency stability in next-generation gravity satellites, advancements in orbit determination technology and the enhanced stability of GPS receivers offer potential for future precision improvements. Currently, this method appears suitable for roughly extracting the scale factor as a stochastic mean over several months or serving as a backup validation strategy for future missions, but it is not well suited to measure day-to-day variations.

Three modes of evolution?Remarks on rates of evolution and time scaling.

Rates of evolution get smaller when they are measured over longer time intervals. As first shown by Gingerich, rates of morphological change measured from fossil time series show a robust minus-one scaling with time span, implying that evolutionary changes are just as large when measured over a hundred years as when measured over a hundred-thousand years. On even longer time scales, however, the scaling shifts toward a minus-half exponent consistent with evolution behaving as Brownian motion, as commonly observed in phylogenetic comparative studies. Here, I discuss how such scaling patterns arise, and I derive the patterns expected from standard stochastic models of evolution. I argue that observed shifts cannot be easily explained by simple univariate models, but require shifts in mode of evolution as time scale is changing. To illustrate this idea, I present a hypothesis about three distinct, but connected, modes of evolution. I analyze the scaling patterns predicted from this, and use the results to discuss how rates of evolution should be measured and interpreted. I argue that distinct modes of evolution at different time scales act to decouple micro- and macroevolution, and criticize various attempts at extrapolating from one to the other.

Aspiration only versus stent retriever only thrombectomy in basilar artery occlusion: a propensity score-matched analysis of the German Stroke Registry

BackgroundEndovascular treatment has become the standard care for acute basilar artery occlusion (BAO). Uncertainty persists about the optimal thrombectomy technique.ObjectiveTo compare aspiration thrombectomy with stent retriever thrombectomy in patients with...

Outcomes of Bridging Intravenous Thrombolysis Versus Endovascular Therapy Alone in Late-Window Acute Ischemic Stroke.

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. 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. 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. 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. URL: https://www.clinicaltrials.gov; Unique identifier: NCT04096248.

Dynamics of scale shift: Contentious places and hybrid activism on social media

This article investigates the role of social media in scale shift of contention. Contentious politics research grapples with questions of scale shift, while digital activism explores connective potential of social media. Yet, the potential of social media is not fully explored in the scale shift processes. We conduct an explorative semantic network analysis to understand how activists create connections between contentious places to facilitate spatial and substantive scale shift. We define contentious places as places bearing demands and grievances on themselves, expressed with hashtags and connected via co-hashtagging practices. We employ the notion of hybridity to understand the role of online and offline dynamics in this process. Our results show that social media enables connections within and across borders, and across issues, hence expanding contention spatially and substantively.

ℏ2 Corrections to Semiclassical Transmission Coefficients.

The uniform semiclassical expression for the energy-dependent transmission probability through a barrier has been a staple of reaction rate theory for almost 90 years. Yet, when using the classical Euclidean action, the transmission probability is identical to 1/2 when the energy equals the barrier height since the Euclidean action vanishes at this energy. This result is generally incorrect. It also leads to an inaccurate estimate of the leading order term in an ℏ2n expansion of the thermal transmission coefficient. The central result of this paper is that adding an ℏ2 dependent correction to the uniform semiclassical expression, whether as a constant action or as a shift in the energy scale, not only corrects this inaccuracy but also leads to a theory that is more accurate than the previous one for almost any energy. Shifting the energy scale is a generalization of the vibrational perturbation theory 2 (VPT2) and is much more accurate than the "standard" VPT2 theory, especially when the potential is asymmetric. Shifting the action by a constant is a generalization of a result obtained by Yasumori and Fueki (YF) only for the Eckart barrier. The resulting modified VPT2 and YF semiclassical theories are applied to the symmetric and asymmetric Eckart barrier, a Gaussian barrier, and a tanh barrier. The one-dimensional theories are also generalized to many-dimensional systems. Their effect on the thermal instanton theory is discussed.

Hierarchical functional differences between gyri and sulci at different scales.

Gyri and sulci are 2 fundamental cortical folding patterns of the human brain. Recent studies have suggested that gyri and sulci may play different functional roles given their structural and functional heterogeneity. However, our understanding of the functional differences between gyri and sulci remains limited due to several factors. Firstly, previous studies have typically focused on either the spatial or temporal domain, neglecting the inherently spatiotemporal nature of brain functions. Secondly, analyses have often been restricted to either local or global scales, leaving the question of hierarchical functional differences unresolved. Lastly, there has been a lack of appropriate analytical tools for interpreting the hierarchical spatiotemporal features that could provide insights into these differences. To overcome these limitations, in this paper, we proposed a novel hierarchical interpretable autoencoder (HIAE) to explore the hierarchical functional difference between gyri and sulci. Central to our approach is its capability to extract hierarchical features via a deep convolutional autoencoder and then to map these features into an embedding vector using a carefully designed feature interpreter. This process transforms the features into interpretable spatiotemporal patterns, which are pivotal in investigating the functional disparities between gyri and sulci. We evaluate the proposed framework on Human Connectome Project task functional magnetic resonance imaging dataset. The experiments demonstrate that the HIAE model can effectively extract and interpret hierarchical spatiotemporal features that are neuroscientifically meaningful. The analyses based on the interpreted features suggest that gyri are more globally activated, whereas sulci are more locally activated, demonstrating a distinct transition in activation patterns as the scale shifts from local to global. Overall, our study provides novel insights into the brain's anatomy-function relationship.

Efficacy of Endovascular Thrombectomy in Acute Basilar Artery Occlusion with Low PC-ASPECTS: A Nationwide Prospective Registry-Based Study.

We evaluated the efficacy of endovascular thrombectomy (EVT) on the functional outcome of patients with acute basilar artery occlusion and low posterior circulation acute stroke prognosis early computed tomography score (PC-ASPECTS). We identified patients with acute ischemic stroke due to basilar artery occlusion and PC-ASPECTS of 6 or less, presenting within 24 h between August 2008 and April 2022. The primary outcome was a favorable functional outcome, defined as a modified Rankin Scale (mRS) score of 0-3 at 90 days. The secondary outcomes included an mRS score of 0-2, a favorable shift in the ordinal mRS scale, the occurrence of symptomatic intracranial hemorrhage (sICH), and mortality at 90 days. We compared the outcome of patients treated with EVT and those without EVT, using the inverse probability of treatment weighting methods. Out of 566 patients, 55.5% received EVT. In the EVT group, 106 (33.8%) achieved favorable outcomes, compared to 56 patients (22.2%) in the conservative group. EVT significantly increased the likelihood of achieving a favorable outcome compared to conservative treatment (relative risk [RR] 1.39, 95% confidence interval [CI], 1.11-1.74, p = 0.004). EVT was associated with a favorable shift in the mRS (RR 1.85, 95% CI, 1.49-2.29, p < 0.001) and reduced mortality without an increase in the risk of sICH. It did not have an impact on achieving an mRS score of 0-2. Patients with acute basilar artery occlusion and a PC-ASPECTS of 6 or less might benefit from EVT without an increasing sICH. ANN NEUROL 2024;95:788-799.

Superimposition of dental models to determine orthodontic tooth movements : Comparison of different superimposition methods in vitro and in vivo.

Using acommercial orthodontic treatment planning system, tooth movements were simulated to analyse how precise predefined movements can be determined by three different superimposition methods. Additionally, aretrospective analysis on clinical patient models before and after orthodontic treatment was performed to analyse possible differences in determination of clinical tooth movements with these methods. (1) A hexapod system was used to perform the tooth movements in physical maxillary dental models (N = 70). The initial and final situations were scanned, superimpositions executed, movements calculated, and their accuracy compared to the predefined movements was determined. (2) Digital three-dimensional (3D) maxillary dental models representing pre- and postorthodontic treatment situations (N = 100 patients) were superimposed. Selected tooth movements were calculated (N = 3600), and the results of the different superimposition methods were compared pairwise. (1) The experimental study delivered only small location and scale shifts. Furthermore, concordance correlation coefficients above 0.99 for all three methods. This verified that all methods deliver values corresponding well to the predefined movements. (2) The retrospective analysis of the clinically performed orthodontic tooth movements comparing pairwise the three different methods intraindividually also showed small location and scale shifts. Furthermore, concordance correlation coefficients between 0.68 and 0.98 were observed, with only three of them below 0.8. This verified that the applied superimposition methods delivered values sufficiently close to each other. As the experimental study showed very good agreement between the predefined and determined movements, and as the retrospective clinical study showed that the methods compared pairwise delivered values close to each other for the performed orthodontic tooth movements, it can be concluded that orthodontic tooth movements can be determined adequately correct by each of the examined methods.

Application of the Bayesian network theory in clinical trial data: Severity shift in spasticity numeric rating scale in patients with multiple sclerosis

BackgroundData digitization expands data collection opportunities, representing both a chance to understand interrelationships between variables and a challenge to identify the most appropriate clinical factors. Applications of causal inference techniques to clinical trial data is becoming very attractive, especially with the intent to provide insights into the relationships between baseline characteristics and outcomes. Graphical representations of model structures and conditional probabilities can be powerful tools to illustrate relationships in a high-dimensional data setting. MethodsWe review and apply Bayesian network theory to a clinical case study, presenting an analytical approach to investigating and visualizing causal relationships. We propose the use of the adherence score to compare data networks’ patterns based on different variables’ discretization. Data from adult patients with spasticity related to multiple sclerosis (MSS) from two randomized placebo-controlled clinical trials of nabiximols were used as analysis sets. The training and validation sets included 106 (53 treated, 53 placebo) and 155 (76 treated, 79 placebo) participants, respectively. The primary objective was to create a network and estimate the causal dependencies between participants’ characteristics, changes in MSS severity as reflected by shifts in the patient-reported numeric rating scale (NRS), and changes in symptoms, functional abilities, and quality of life factors. ResultsA causal network was identified between the key factors of assigned treatment, end of study spasticity NRS, and mental health/vitality subscales of the 36-Item Short Form Health Survey questionnaire (4 nodes and 3 edges; adherence score = 93%). In patients with mild spasticity, the impact of nabiximols on mental health or vitality subscales resulted in a probability ratio of 1.63. The decomposed mediation effect of spasticity NRS was observed through a mediation analysis between treatment and mental health (99.4%) or vitality (93.7%) subscales. ConclusionsThe use of innovative methods such as causal networks is highly encouraged to identify dependent relationships among key factors in clinical trial data and drive insights for additional research.