bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effects of a Perindopril-Based Regimen in Relation to Statin Use on the Outcomes of Patients with Vascular Disease: a Combined Analysis of the ADVANCE, EUROPA, and PROGRESS Trials
Authors: Radhoe S. P. , Boersma E. , Bertrand M. , Remme W. , Ferrari R. , Fox K. , MacMahon S. , Chalmers J. , Simoons M. L. , Brugts J. J.
Published: October 2022

Purpose

To study the effects of a perindopril-based regimen on cardiovascular (CV) outcomes in patients with vascular disease in relation to background statin therapy.

Methods

A pooled analysis of the randomized ADVANCE, EUROPA, and PROGRESS trials was performed to evaluate CV outcomes in 29,463 patients with vascular disease treated with perindopril-based regimens versus placebo. The primary endpoint was a composite of CV mortality, nonfatal myocardial infarction, and stroke. Multivariable Cox regression analyses were performed to assess the effects of a perindopril-based regimen versus placebo in relation to statin use.

Results

At randomization, 39.5% of the overall combined study population used statins. After a mean follow-up of 4.0 years (SD 1.0), the cumulative event-free survival was highest in the statin/perindopril group and lowest in the no statin/placebo group (91.2% vs. 85.6%, respectively, log-rank p < 0.001). In statin users (adjusted hazard ratio [aHR] 0.87, 95% confidence interval [CI] 0.77–0.98) and non-statin users (aHR 0.80, 95% CI 0.74–0.87), a perindopril-based regimen was associated with a significantly lower risk of the primary endpoint when compared to placebo. The additional treatment effect appeared numerically greater in non-statin users, but the observed difference was statistically nonsignificant.

Conclusion

Our data suggest that the treatment benefits of a perindopril-based regimen in patients with vascular disease are independent of statin use.
Social Memory in the Mekong’s Changing Floodscapes: Narratives of Agrarian Communities’ Adaptation
Authors: Tran Thong Anh , Rigg Jonathan , Taylor David , Miller Michelle Ann , Pittock Jamie , Le Phong Thanh
Published: October 2022

Rural adaptation encompasses place-based perceptions, behaviors, livelihoods, and traditional ways of life associated with local environments. These perceptions, norms, and practices are disturbed by coupled environment-development externalities. This study employs the Vietnamese Mekong floodplains as an exemplary case to illustrate how floods impact agrarian communities and how they have experienced flood alterations driven by hydropower development and climate change in recent years. Drawing on thematic and narrative analyses of qualitative data (focus group discussions and interviews) collected in three agrarian communities in the Vietnamese Mekong floodplains, sources drawn from various news outlets, and academic materials, we argue that disrupted flood environments in the floodplains have triggered affective flood reminiscences, catalysing shifts to incremental and transformative adaptation to achieve resilience. We build a nuanced understanding of how social memory helps to enhance human–environment relationships in response to highly complex hydrological dynamics in the delta.
Cost-based Optimization of Multistore Query Plans
Authors: Forresi Chiara , Francia Matteo , Gallinucci Enrico , Golfarelli Matteo
Published: October 2022

Multistores are data management systems that enable query processing across different and heterogeneous databases; besides the distribution of data, complexity factors like schema heterogeneity and data replication must be resolved through integration and data fusion activities. Our multistore solution relies on a dataspace to provide the user with an integrated view of the available data and enables the formulation and execution of GPSJ queries. In this paper, we propose a technique to optimize the execution of GPSJ queries by formulating and evaluating different execution plans on the multistore. In particular, we outline different strategies to carry out joins and data fusion by relying on different schema representations; then, a self-learning black-box cost model is used to estimate execution times and select the most efficient plan. The experiments assess the effectiveness of the cost model in choosing the best execution plan for the given queries and exploit multiple multistore benchmarks to investigate the factors that influence the performance of different plans.
ANFIS for risk estimation in risk-based access control model for smart homes
Authors: Atlam Hany F. , Wills Gary B.
Published: October 2022

The risk-based access control model is one of the dynamic models that use the security risk as a criterion to decide the access decision for each access request. This model permits or denies access requests dynamically based on the estimated risk value. The essential stage of implementing this model is the risk estimation process. This process is based on estimating the possibility of information leakage and the value of that information. Several researchers utilized different methods for risk estimation but most of these methods were based on qualitative measures, which cannot suit the access control context that needs numeric and precise risk values to decide either granting or denying access. Therefore, this paper presents a novel Adaptive Neuro-Fuzzy Inference System (ANFIS) model for risk estimation in the risk-based access control model for the Internet of Things (IoT). The proposed ANFIS model was implemented and evaluated against access control scenarios of smart homes. The results demonstrated that the proposed ANFIS model provides an efficient and accurate risk estimation technique that can adapt to the changing conditions of the IoT environment. To validate the applicability and effectiveness of the proposed ANFIS model in smart homes, ten IoT security experts were interviewed. The results of the interviews illustrated that all experts confirmed that the proposed ANFIS model provides accurate and realistic results with a 0.713 in Cronbach’s alpha coefficient which indicates that the results are consistent and reliable. Compared to existing work, the proposed ANFIS model provides an efficient processing time as it reduces the processing time from 57.385 to 10.875 Sec per 1000 access requests, which demonstrates that the proposed model provides effective and accurate risk evaluation in a timely manner.
Stakeholder and Equity Data-Driven Implementation: a Mixed Methods Pilot Feasibility Study
Authors: Aschbrenner Kelly A. , Kruse Gina , Emmons Karen M. , Singh Deepinder , Barber-Dubois Marjanna E. , Miller Angela M. , Thomas Annette N. , Bartels Stephen J.
Published: October 2022

We conducted a mixed methods pilot feasibility study of a Stakeholder and Equity Data-Driven Implementation (SEDDI) process to facilitate using healthcare data to identify patient groups experiencing gaps in the use of evidence-based interventions (EBIs) and rapidly adapt EBIs to achieve greater access and equitable outcomes. We evaluated the feasibility and acceptability of SEDDI in a pilot hybrid type 2 effectiveness-implementation trial of a paired colorectal cancer (CRC) and social needs screening intervention at four federally qualified community health centers (CHCs). An external facilitator partnered with CHC teams to support initial implementation, followed by the SEDDI phase focused on advancing health equity. Facilitation sessions were delivered over 8 months. Preliminary evaluation of SEDDI involved convergent mixed methods with quantitative survey and focus group data. CHCs used data to identify gaps in outreach and completion of CRC screening with respect to race/ethnicity, gender, age, and language. Adaptations to improve access and use of the intervention included cultural, linguistic, and health literacy tailoring. CHC teams reported that facilitation and systematic review of data were helpful in identifying and prioritizing gaps. None of the four CHCs completed rapid cycle testing of adaptations largely due to competing priorities during the COVID-19 response. SEDDI has the potential for advancing chronic disease prevention and management by providing a stakeholder and data-driven approach to identify and prioritize health equity targets and guide adaptations to improve health equity. ClinicalTrials.gov Identifier: NCT04585919.
Diamonds are not forever: Adam Smith and Carl Menger on value and relative status
Authors: Hurtado Jimena , Paganelli Maria Pia
Published: October 2022

The differences on value between Smith and Menger may be other from previously alleged if status is included as a need satisfied only by truly scarce goods. Given our innate desire to distinguish ourselves and be admired, Smith tells us that scarcity is what generates value. So, our desire for distinction is what drives our demand for “diamonds” and gives them value. But when “diamonds” become as abundant as “knitted stockings”, new forms of scarce status goods must be found. For Menger, value is also a dynamic, evolving “institution” that cannot be understood in a static analysis dealing only with supply and demand at a given moment. But abundance, for Menger, would simply allow us to fulfill higher-level needs. Thus, Smith, but not necessarily Menger, could explain why, as diamond rings, Prada shoes, and Gucci bags can be easily mass produced in identical but “fake” copies, irreproducible goods, such as charity donations and claims on digital art, are taking their place to indicate status in society.
Points to consider in seeking biosafety approval for research, testing, and environmental release of experimental genetically modified biocontrol products during research and development
Authors: Tonui W. K. , Ahuja V. , Beech C. J. , Connolly J. B. , Dass B. , Glandorf D. C. M. , James S. , Muchiri J. N. , Mugoya C. F. , Okoree E. A. , Quemada H. , Romeis J.
Published: October 2022

Novel genetically modified biological control products (referred to as “GM biocontrol products”) are being considered to address a range of complex problems in public health, conservation, and agriculture, including preventing the transmission of vector-borne parasitic and viral diseases as well as the spread of invasive plant and animal species. These interventions involve release of genetically modified organisms (GMOs) into the environment, sometimes with intentional dissemination of the modification within the local population of the targeted species, which presents new challenges and opportunities for regulatory review and decision-making. Practices developed for GMOs, primarily applied to date for GM crops may need to be adapted to accommodate different types of organisms, such as insects, and different technologies, such as gene drive. Developers of new GM biocontrol products would benefit from an early understanding of safety data and information that are likely to be required within the regulatory dossier for regulatory evaluation and decision making. Here a generalizable tool drawing from existing GM crop dossier requirements, forms, and relevant experience is proposed to assist researchers and developers organize and plan their research and trialing. This tool requires considering specifics of each investigational product, their intended use, and country specific requirements at various phases of potential product development, from laboratory research through contained field testing and experimental release into the environment. This may also be helpful to risk assessors and regulators in supporting their systematic and rigorous evaluation of new biocontrol products.
Schmerztherapie mit „eye movement desensitization and reprocessing“ (EMDR): eine Pilotstudie zur Verbesserung der Lebensqualität
Authors: Weiß Katharina , Kohls Niko
Published: October 2022

Hintergrund

Ein effektives Schmerzmanagement mit langandauernder Wirkung bei Menschen mit chronischen Schmerzen ist noch immer eine Herausforderung.

Ziel der Arbeit

Ziel der Arbeit ist die Untersuchung der Effekte einer gesundheitsförderlichen Intervention mit EMDR („eye movement desensitization and reprocessing“) bei Personen mit chronischen Schmerzen und eine mögliche Verbesserung ihrer Lebensqualität.

Methodik

Mit Hilfe einer Paper-pencil-Befragung wurden 30 Schmerzpatient:innen zu zwei Messzeitpunkten (MZP) mit Subskalen des Deutschen Schmerzfragebogens (DSF), dem Pain Disability Index (PDI) und der WHO Quality of Life-Kurzversion (WHOQOL-BREF) befragt. Zwischen den MZP wurden die Personen der Interventionsgruppe mit EMDR behandelt.

Ergebnisse

Einige signifikante Ergebnisse deuten darauf hin, dass durch die Intervention mit EMDR zur Behandlung chronischer Schmerzen die Lebensqualität verbessert wird. So verbesserte sich in der Interventionsgruppe die Lebensqualität in den Domänen physische, psychische und globale Lebensqualität signifikant im Vergleich beider MZP.

Schlussfolgerung

Da die erhobenen Befunde aufgrund des explorativen Studiencharakters nur unter Vorbehalt interpretiert werden können, sollten in Zukunft Langzeitstudien mit größeren Stichproben und Follow-up-Erhebungen durchgeführt werden, um eindeutige Aussagen über die Wirksamkeit und die Langzeiteffekte von EMDR zur Behandlung chronischer Schmerzen treffen zu können. In der Behandlungsmethode dürfte großes Potenzial liegen und es scheint vielversprechend zu sein, EMDR zu einem festen Bestandteil einer multimodalen, interdisziplinären Schmerztherapie werden zu lassen.
A compactness result for the div-curl system with inhomogeneous mixed boundary conditions for bounded Lipschitz domains and some applications
Authors: Pauly Dirk , Skrepek Nathanael
Published: October 2022

For a bounded Lipschitz domain with Lipschitz interface we show the following compactness theorem: Any $$\mathsf {L}_{}^{2}$$

L

2

-bounded sequence of vector fields with $$\mathsf {L}_{}^{2}$$

L

2

-bounded rotations and $$\mathsf {L}_{}^{2}$$

L

2

-bounded divergences as well as $$\mathsf {L}_{}^{2}$$

L

2

-bounded tangential traces on one part of the boundary and $$\mathsf {L}_{}^{2}$$

L

2

-bounded normal traces on the other part of the boundary, contains a strongly $$\mathsf {L}_{}^{2}$$

L

2

-convergent subsequence. This generalises recent results for homogeneous mixed boundary conditions in Bauer et al. (SIAM J Math Anal 48(4):2912-2943, 2016) Bauer et al. (in: Maxwell’s Equations: Analysis and Numerics (Radon Series on Computational and Applied Mathematics 24), De Gruyter, pp. 77-104, 2019). As applications we present a related Friedrichs/Poincaré type estimate, a div-curl lemma, and show that the Maxwell operator with mixed tangential and impedance boundary conditions (Robin type boundary conditions) has compact resolvents.
Overview of Moving Particle Semi-implicit Techniques for Hydrodynamic Problems in Ocean Engineering
Authors: Xie Fengze , Zhao Weiwen , Wan Decheng
Published: October 2022

With the significant development of computer hardware, many advanced numerical techniques have been proposed to investigate complex hydrodynamic problems. This article aims to provide a detailed review of moving particle semi-implicit (MPS) techniques and their application in ocean and coastal engineering. The achievements of the MPS method in stability and accuracy, boundary conditions, and acceleration techniques are discussed. The applications of the MPS method, which are classified into two main categories, namely, multiphase flows and fluid-structure interactions, are introduced. Finally, the prospects and conclusions are highlighted. The MPS method has the potential to solve practical problems.
Numerical Investigation on the Deformation of the Free Interface During Water Entry and Exit of a Circular Cylinder by Using the Immersed Boundary-Multiphase Lattice Boltzmann Flux Solver
Authors: Zhang Guiyong , Yan Haoran , Song Hong , Wang Heng , Hui Da
Published: October 2022

In this work, the deformation of free interface during water entry and exit of a circular cylinder is investigated numerically by using the two-dimensional (2D) immersed boundary-multiphase lattice Boltzmann flux solver (IB-MLBFS). The fluid domain is discretized by finite volume discretization, and the flux on the grid interface is evaluated by lattice Boltzmann equations. Both the implicit velocity correction and the surface flux correction are implemented by using the immersed boundary-method to consider the fluid-structure interaction and the contact interface between the multiphase fluids and the structure. First, the water entry of a circular cylinder is simulated and the results are compared with the experiment, which considered the length-diameter ratio of the circular cylinder. The reliability of 2D simulation is verified and the deformation of the free interface is well investigated. Afterward, the water exit of a circular cylinder with constant velocity is simulated, which is less researched. In addition, the results show the advantage of present IB-MLBFS to some extent. Finally, the water exit and re-entry of a circular cylinder are presented, and the results present the complex deformation of the free interface and the dynamic response of the moving structure. Based on the numerical results, the free interface of the multiphase fluids is well captured, and the contact interface on the boundary of the moving structure is accurately presented by the IB-MLBFS.
Clinical impact of amyloid PET using 18F-florbetapir in patients with cognitive impairment and suspected Alzheimer’s disease: a multicenter study
Authors: Matsuda Hiroshi , Okita Kyoji , Motoi Yumiko , Mizuno Toshiki , Ikeda Manabu , Sanjo Nobuo , Murakami Koji , Kambe Taiki , Takayama Toshiki , Yamada Kei , Suehiro Takashi , Matsunaga Keiko , Yokota Takanori , Tateishi Ukihide , Shigemoto Yoko , Kimura Yukio , Chiba Emiko , Kawashima Takahiro , Tomo Yui , Tachimori Hisateru , Kimura Yuichi , Sato Noriko
Published: October 2022

Objective

Amyloid positron emission tomography (PET) can reliably detect senile plaques and fluorinated ligands are approved for clinical use. However, the clinical impact of amyloid PET imaging is still under investigation. The aim of this study was to evaluate the diagnostic impact and clinical utility in patient management of amyloid PET using 18F-florbetapir in patients with cognitive impairment and suspected Alzheimer’s disease (AD). We also aimed to determine the cutoffs for amyloid positivity for quantitative measures by investigating the agreement between quantitative and visual assessments.

Methods

Ninety-nine patients suspected of having AD underwent 18F-florbetapir PET at five institutions. Site-specialized physicians provided a diagnosis of AD or non-AD with a percentage estimate of their confidence and their plan for patient management in terms of medication, prescription dosage, additional diagnostic tests, and care planning both before and after receiving the amyloid imaging results. A PET image for each patient was visually assessed and dichotomously rated as either amyloid-positive or amyloid-negative by four board-certified nuclear medicine physicians. The PET images were also quantitatively analyzed using the standardized uptake value ratio (SUVR) and Centiloid (CL) scale.

Results

Visual interpretation obtained 48 positive and 51 negative PET scans. The amyloid PET results changed the AD and non-AD diagnosis in 39 of 99 patients (39.3%). The change rates of 26 of the 54 patients (48.1%) with a pre-scan AD diagnosis were significantly higher than those of 13 of the 45 patients with a pre-scan non-AD diagnosis (χ2 = 5.334, p = 0.0209). Amyloid PET results also resulted in at least one change to the patient management plan in 42 patients (42%), mainly medication (20 patients, 20%) and care planning (25 patients, 25%). Receiver-operating characteristic analysis determined the best agreement of the quantitative assessments and visual interpretation of PET scans to have an area under the curve of 0.993 at an SUVR of 1.19 and CL of 25.9.

Conclusion

Amyloid PET using 18F-florbetapir PET had a substantial clinical impact on AD and non-AD diagnosis and on patient management by enhancing diagnostic confidence. In addition, the quantitative measures may improve the visual interpretation of amyloid positivity.
Assessing the Mycotoxin-related Health Impact of Shifting from Meat-based Diets to Soy-based Meat Analogues in a Model Scenario Based on Italian Consumption Data
Authors: Mihalache Octavian Augustin , Dellafiora Luca , Dall’Asta Chiara
Published: October 2022

The aim of this study was to assess the risk of replacing meat with plant-based analogues with respect to mycotoxin exposure, as a proof of concept to demonstrate the need for a proper regulatory framework for mycotoxins in meat imitates. Hence, we considered a full replacement of meat consumption with soy-based meat analogues and we evaluated the exposure to AFB1 and OTA, based on the Italian National Food Consumption Survey INRAN-SCAI 2005–2006 and the European Food Safety Authority occurrence data. The overall health impact from soy-based food consumption and a meat-free diet was quantified in terms of Disability-Adjusted Life Years (DALYs) in three different contamination and consumption scenarios. The substitution of meat products with soy-based imitates would prevent up to 406.2 colorectal cancer cases/year/country associated with 532 healthy years of life. However, we also determined an increased risk of liver cancer and loss of healthy life-years due to AFB1 exposure and a potential risk of renal cancer as due to an increased intake of OTA, leading up to 1208 extra cancer cases associated with the loss of 12,080 healthy life-years/country. Shifting to a plant-based diet actually eliminates a cancer risk factor such as processed meat, however, higher and unexpected risks could arise if mycotoxins are not properly regulated in plant-based meat alternatives. Taking into account the ubiquitous occurrence of mycotoxins, also in the light of climate change, and the growing trend toward plant-based meat analogues, greater importance should be given to actual food consumption trends and correlated with updated natural toxins regulations and risk assessments.

Graphical abstract
Long noncoding RNA SNHG1 alleviates high glucose-induced vascular smooth muscle cells calcification/senescence by post-transcriptionally regulating Bhlhe40 and autophagy via Atg10
Authors: Li Shuang , Ni Yuqing , Li Chen , Xiang Qunyan , Zhao Yan , Xu Hui , Huang Wu , Wang Yanjiao , Wang Yi , Zhan Junkun , Liu Youshuo
Published: October 2022

Long noncoding RNAs (lncRNAs) are emerging regulators of vascular diseases, yet their role in diabetic vascular calcification/aging remains poorly understood. In this study, we identified a down-expressed lncRNA SNHG1 in high glucose (HG)-induced vascular smooth muscle cells (HA-VSMCs), which induced excessive autophagy and promoted HA-VSMCs calcification/senescence. Overexpression of SNHG1 alleviated HG-induced HA-VSMCs calcification/senescence. The molecular mechanisms of SNHG1 in HA-VSMCs calcification/senescence were explored by RNA pull-down, RNA immunoprecipitation, RNA stability assay, luciferase reporter assay, immunoprecipitation and Western blot assays. In one mechanism, SNHG1 directly interacted with Bhlhe40 mRNA 3′-untranslated region and increased Bhlhe40 mRNA stability and expression. In another mechanism, SNHG1 enhanced Bhlhe40 protein SUMOylation by serving as a scaffold to facilitate the binding of SUMO E3 ligase PIAS3 and Bhlhe40 protein, resulting in increased nuclear translocation of Bhlhe40 protein. Moreover, Bhlhe40 suppressed the expression of Atg10, which is involved in the process of autophagosome formation. Collectively, the protective effect of SNHG1 on HG-induced HA-VSMCs calcification/senescence is accomplished by stabilizing Bhlhe40 mRNA and promoting the nuclear translocation of Bhlhe40 protein. Our study could provide a novel approach for diabetic vascular calcification/aging.
Multiperiod Equitable and Efficient Allocation Strategy of Emergency Resources Under Uncertainty
Authors: Wang Yanyan , Sun Baiqing
Published: October 2022

Equitable and efficient allocation of emergency resources is critical to ensure the success of relief efforts. The challenge comes largely from two aspects: the resources available for allocation are usually limited in quantity, especially in the early period of emergency response; and a large amount of uncertain information in the relief process affects the decision making of resource allocation. A multiperiod allocation model of emergency resources that takes into account both efficiency and equity based on uncertain disaster information is proposed. Interval number and triangular fuzzy number are introduced to describe the different sources of uncertainty (for example, demand, transportation time, and maximum transport amount), and the loss caused by unmet demand is used to quantify equity. Then, the deterministic transformation method of uncertain parameters is designed and the linear weighted sum method is applied to solve the proposed model. Finally, a computational case based on the 2017 Jiuzhaigou earthquake in Sichuan Province, China was conducted to validate the proposed model. The results show that the proposed model is feasible in the multiperiod allocation of emergency resources among multi-disaster sites, and the findings can help emergency managers to allocate emergency resources more scientifically, equitably, and effectively under uncertainty.
A derivative-free Milstein type approximation method for SPDEs covering the non-commutative noise case
Authors: von Hallern Claudine , Rößler Andreas
Published: October 2022

We propose a derivative-free Milstein type scheme to approximate the mild solution of stochastic partial differential equations (SPDEs) that do not need to fulfill a commutativity condition for the noise term. The newly developed derivative-free Milstein type scheme differs significantly from schemes that are appropriate for the case of commutative noise. As a key result, the new derivative-free Milstein type scheme needs only two stages that are specifically tailored based on a technique that, compared to the original Milstein scheme, allows for a reduction of the computational complexity by one order of magnitude. Moreover, the proposed derivative-free Milstein scheme can flexibly be combined with some approximation method for the involved iterated stochastic integrals. As the main result, we prove the strong $$L^2$$

L
2

-convergence of the introduced derivative-free Milstein type scheme, especially if it is combined with any suitable approximation algorithm for the necessary iterated stochastic integrals. We carry out a rigorous analysis of the error versus computational cost and derive the effective order of convergence for the derivative-free Milstein type scheme in the case that the truncated Fourier series algorithm for the approximation of the iterated stochastic integrals is applied. As a further novelty, we show that the use of approximations of iterated stochastic integrals based on truncated Fourier series together with the proposed derivative-free Milstein type scheme improves the effective order of convergence compared to that of the Euler scheme and the original Milstein scheme. This result is contrary to well known results in the finite dimensional SDE case where the use of merely truncated Fourier series does not improve the effective order of convergence in the $$L^2$$

L
2

-sense compared to that of the Euler scheme.
The Intertwined Histories of Artificial Intelligence and Education
Authors: Doroudi Shayan
Published: October 2022

In this paper, I argue that the fields of artificial intelligence (AI) and education have been deeply intertwined since the early days of AI. Specifically, I show that many of the early pioneers of AI were cognitive scientists who also made pioneering and impactful contributions to the field of education. These researchers saw AI as a tool for thinking about human learning and used their understanding of how people learn to further AI. Furthermore, I trace two distinct approaches to thinking about cognition and learning that pervade the early histories of AI and education. Despite their differences, researchers from both strands were united in their quest to simultaneously understand and improve human and machine cognition. Today, this perspective is neither prevalent in AI nor the learning sciences. I conclude with some thoughts on how the artificial intelligence in education and learning sciences communities might reinvigorate this lost perspective.
A long-term alternative formula for a stochastic stock price model
Authors: Okabe Takuya , Yoshimura Jin
Published: October 2022

This study presents a long-term alternative formula for stock price variation described by a geometric Brownian motion on the basis of median instead of mean or expected values. The proposed method is motivated by the observation made in remote fields, where optimalizty of bet-hedging or diversification strategies is explained based on a measure different from expected value, like geometric mean. When the probability distribution of possible outcomes is significantly skewed, it is generally known that expected value leads to an erroneous picture owing to its sensitivity to outliers, extreme values of rare occurrence. Since geometric mean, or its counterpart median for the log-normal distribution, does not suffer from this drawback, it provides us with a more appropriate measure especially for evaluating long-term outcomes dominated by outliers. Thus, the present formula makes a more realistic prediction for long-term outcomes of a large volatility, for which the probability distribution becomes conspicuously heavy-tailed.
Numerical calculation and finite element analysis for anisotropic elastic properties of carbon fibers: dependence of integration subinterval and mesh size on indentation-derived elastic modulus
Authors: Goto Kenta , Naito Kimiyoshi , Shirasu Keiichi , Watanabe Ikumu
Published: October 2022

The elastic modulus measured by indentation of carbon fibers with various anisotropic elasticity is calculated by two numerical approaches, the Vlassak–Nix model and finite element analysis, to reveal the acceptable calculation condition for highly anisotropic materials. Five commercially available carbon fibers that varied in anisotropy index in the range of 0.5–7.9 are used (either polyacrylonitrile- or pitch-based). The numerical error in the calculated modulus increases with the decrease in fiber angle and with the increase in the anisotropy index under the same mesh condition, indicating finer mesh is required for a highly anisotropic material. The acceptable mesh size linearly increases with anisotropic index. The Vlassak–Nix model overestimates the elastic modulus at a small tilt angle if few integration subintervals are used. Conversely, finite element analysis of the Hertz contact problem with coarse mesh underestimates the modulus at a small tilt angle, and a maximum modulus is observed when the fiber is tilted a few degrees against the indentation axis. These findings are expected to assist the future determination of ideal calculation conditions for materials with large anisotropic elasticity including fibers and composites.
Navigating Medical Device Certification: A Qualitative Exploration of Barriers and Enablers Amongst Innovators, Notified Bodies and Other Stakeholders
Authors: Baines Rebecca , Hoogendoorn Petra , Stevens Sebastian , Chatterjee Arunangsu , Ashall-Payne Liz , Andrews Tim , Leigh Simon
Published: October 2022

Background

Medical device certification has undergone significant changes in recent years. However, exploration of stakeholder experiences remains relatively limited, particularly in the context of software as a medical device. This study sought to explore stakeholder experiences of medical device certification across both the UK and EU.

Methods

Semi-structured interviews (n = 22) analysed using inductive-thematic analysis, synthesised using activity theory.

Results

Innovators, consultants and notified bodies share more similarities than differences when discussing barriers and enablers to achieving medical device certification. Systemic tensions between existing rules, tools, community understanding and division of labour currently undermine the intended aim of certification processes. Existing rules are considered complex, with small and medium-sized enterprises considered disproportionality affected, resulting in several unintended outcomes including the perceived ‘killing’ of innovation. Existing certification processes are described as unfit for purpose, unethical and unsustainable.

Conclusion

Stakeholder experiences suggest that the intention of establishing a robust and sustainable regulatory framework capable of ensuring a high level of safety whilst also supporting innovation is not yet being realised. Failure to enact desired changes may further jeopardise future innovations, outcomes and care quality.
NEGATIVE RESULTS ON PRECIPITOUS IDEALS ON
Authors: SARGSYAN GRIGOR
Published: October 2022

We show that in many extender models, e.g., the minimal one with infinitely many Woodin cardinals or the minimal with a Woodin cardinal that is a limit of Woodin cardinals, there are no generic embeddings with critical point
$\omega _1$
that resemble the stationary tower at the second Woodin cardinal. The meaning of “resemble” is made precise in the paper (see Definition 0.3).
The ugly truth behind transitional justice in the post-revolution phase: A constitutional law and economics analysis
Authors: Rashwan Eman Muhammad
Published: October 2022

This article explores the transitional justice (TJ) dilemmas after revolutions have overthrown autocratic regimes through developing a model that uses a law and economics methodology. The article seeks to answer two questions: Why do post-revolution regimes resort to or ignore TJ policies towards former autocratic regimes? And why is it difficult to adopt and apply welfare-enhancing TJ mechanisms in practice, including popular suggestions within the TJ literature to portray the civil society organizations as the key solution to TJ dilemmas? To answer these questions, the article provides a theoretical positive analysis of the scenarios and dilemmas of TJ. It argues that TJ should function both as an internalization mechanism of negative externalities of the violations of the past-regime, and a form of constitutional arrangements as anex anteincentives structure to prevent the repetition of these violations. However, due to asymmetric information problems, behavioural biases and the constitutional nature of TJ, the ‘TJ momentum’ precludes most of the traditional solutions for this principal–agent problem.
The Civic Option? Using Experiments to Estimate the Effects of Consuming Information in Local Elections
Authors: Boudreau Cheryl , Elmendorf Christopher S. , MacKenzie Scott A.
Published: October 2022

Political parties and civic organizations disseminate information to improve citizen decision making in local elections. Do citizens choose to consume such information and, if so, how does it affect their decisions? We conduct a survey experiment during a real-world local election that randomly assigns 1) political party endorsements, 2) a voter guide, 3) no information, or 4) a choice among these options. Respondents assigned to receive party endorsements and a voter guide are more likely than respondents receiving no information to choose candidates who share their policy views. When given a choice, a majority opts to receive information (including many with low levels of political interest), with most respondents preferring a voter guide. Using an instrumental variable approach, we show that the effect of information on those who choose to receive it is substantial. These results offer hope that voter education efforts can succeed despite widespread political disinterest.
The Chicxulub Impact Produced a Powerful Global Tsunami
Authors: Range Molly M. , Arbic Brian K. , Johnson Brandon C. , Moore Theodore C. , Titov Vasily , Adcroft Alistair J. , Ansong Joseph K. , Hollis Christopher J. , Ritsema Jeroen , Scotese Christopher R. , Wang He
Published: October 2022

The Chicxulub crater is the site of an asteroid impact linked with the Cretaceous‐Paleogene (K‐Pg) mass extinction at ∼66 Ma. This asteroid struck in shallow water and caused a large tsunami. Here we present the first global simulation of the Chicxulub impact tsunami from initial contact of the projectile to global propagation. We use a hydrocode to model the displacement of water, sediment, and crust over the first 10 min, and a shallow‐water ocean model from that point onwards. The impact tsunami was up to 30,000 times more energetic than the 26 December 2004 Indian Ocean tsunami, one of the largest tsunamis in the modern record. Flow velocities exceeded 20 cm/s along shorelines worldwide, as well as in open‐ocean regions in the North Atlantic, equatorial South Atlantic, southern Pacific and the Central American Seaway, and therefore likely scoured the seafloor and disturbed sediments over 10,000 km from the impact origin. The distribution of erosion and hiatuses in the uppermost Cretaceous marine sediments are consistent with model results.
Critical Role of Groundwater Inflow in Sustaining Lake Water Balance on the Western Tibetan Plateau
Authors: Lei Yanbin , Yang Kun , Immerzeel Walter W. , Song Peiping , Bird Broxton W. , He Jiankun , Zhao Huabiao , Li Zhiguo
Published: October 2022

It is difficult to quantify the amount of groundwater inflow on the Tibetan Plateau (TP), yet it can be critically important for sustaining lake water balance. Here we show that most endorheic lakes on the western TP exhibited considerable water level increase during the ice‐covered period, which contrasts with lakes in other regions of the TP. An analysis of lake water balance attributes this water surplus to significant groundwater inflow, which is estimated to be about 59%–66% of total inflow into lakes. The groundwater inflow occurred after the 2000s, which is consistent with the rapid lake expansion and significant increase in precipitation. We suggest that the groundwater inflow is mainly related to large‐scale active faults in the limestone bedrock and sufficient meltwater from high elevations. Our results imply that groundwater may be deeply involved in the water cycle and modify the seasonal and inter‐annual lake variations on the western TP.
Drought Conditions Enhance Groundwater Table Fluctuations Caused by Hydropower Plant Management
Authors: Basilio Hazas M. , Marcolini G. , Castagna M. , Galli M. , Singh T. , Wohlmuth B. , Chiogna G.
Published: October 2022

Management of hydropower plants strongly influences streamflow dynamics and hence the interaction between surface water and groundwater. As dam operations cause variations in river stages, these can result in changes in the groundwater level at multiple temporal scales. In this work, we study the case of an Alpine aquifer, where weekly fluctuations are particularly pronounced. We consider an area with four river reaches differently impacted by reservoir operations and investigate the influence of these rivers on the common aquifer. Using continuous wavelet transform and wavelet coherence analysis, we show that weekly fluctuations in the groundwater table are particularly pronounced in dry years, in particular in the winter season, although the area of the aquifer impacted by dam operations remains almost unchanged. We thus observe that in Alpine catchments, surface water‐groundwater interaction is sensitive to the conditions determined by a specific hydrological year. We also investigate the influences of the river‐aquifer water fluxes and show that under dry conditions hydropeaking mainly affects their temporal dynamics. Our observations have significant consequences for predicting nutrient and temperature dynamics/regimes in river‐aquifer systems impacted by hydropower plant management.
Mitochondrial dysfunction and impaired growth of glioblastoma cell lines caused by antimicrobial agents inducing ferroptosis under glucose starvation
Authors: Miki Kenji , Yagi Mikako , Yoshimoto Koji , Kang Dongchon , Uchiumi Takeshi
Published: October 2022

Glioblastoma is a difficult-to-cure disease owing to its malignancy. Under normal circumstances, cancer is dependent on the glycolytic system for growth, and mitochondrial oxidative phosphorylation (OXPHOS) is not well utilized. Here, we investigated the efficacy of mitochondria-targeted glioblastoma therapy in cell lines including U87MG, LN229, U373, T98G, and two patient-derived stem-like cells. When glioblastoma cells were exposed to a glucose-starved condition (100 mg/l), they rely on mitochondrial OXPHOS for growth, and mitochondrial translation product production is enhanced. Under these circumstances, drugs that inhibit mitochondrial translation, called antimicrobial agents, can cause mitochondrial dysfunction and thus can serve as a therapeutic option for glioblastoma. Antimicrobial agents activated the nuclear factor erythroid 2-related factor 2–Kelch-like ECH-associated protein 1 pathway, resulting in increased expression of heme oxygenase-1. Accumulation of lipid peroxides resulted from the accumulation of divalent iron, and cell death occurred via ferroptosis. In conclusion, mitochondrial OXPHOS is upregulated in glioblastoma upon glucose starvation. Under this condition, antimicrobial agents cause cell death via ferroptosis. The findings hold promise for the treatment of glioblastoma.
Oxytocin and orexin systems bidirectionally regulate the ability of opioid cues to bias reward seeking
Authors: Giannotti Giuseppe , Mottarlini Francesca , Heinsbroek Jasper A. , Mandel Mitchel R. , James Morgan H. , Peters Jamie
Published: October 2022

As opioid-related fatalities continue to rise, the need for novel opioid use disorder (OUD) treatments could not be more urgent. Two separate hypothalamic neuropeptide systems have shown promise in preclinical OUD models. The oxytocin system, originating in the paraventricular nucleus (PVN), may protect against OUD severity. By contrast, the orexin system, originating in the lateral hypothalamus (LH), may exacerbate OUD severity. Thus, activating the oxytocin system or inhibiting the orexin system are potential therapeutic strategies. The specific role of these systems with regard to specific OUD outcomes, however, is not fully understood. Here, we probed the therapeutic efficacy of pharmacological interventions targeting the orexin or oxytocin system on two distinct metrics of OUD severity in rats—heroin choice (versus choice for natural reward, i.e., food) and cued reward seeking. Using a preclinical model that generates approximately equal choice between heroin and food reward, we examined the impact of exogenously administered oxytocin, an oxytocin receptor antagonist (L-368,899), and a dual orexin receptor antagonist (DORA-12) on opioid choice. Whereas these agents did not alter heroin choice when rewards (heroin and food) were available, oxytocin and DORA-12 each significantly reduced heroin seeking in the presence of competing reward cues when no rewards were available. In addition, the number of LH orexin neurons and PVN oxytocin neurons correlated with specific behavioral economic variables indicative of heroin versus food motivation. These data identify a novel bidirectional role of the oxytocin and orexin systems in the ability of opioid-related cues to bias reward seeking.
A high hematopoietic cell transplantation comorbidity Index (HCT-CI) does not impair outcomes after non-myeloablative allogeneic stem cell transplantation in acute myeloid leukemia patients 60 years or older
Authors: Backhaus Donata , Brauer Dominic , Pointner Rosmarie , Bischof Lara , Vucinic Vladan , Franke Georg-Nikolaus , Niederwieser Dietger , Platzbecker Uwe , Jentzsch Madlen , Schwind Sebastian
Published: October 2022

For most acute myeloid leukemia (AML) patients an allogeneic hematopoietic stem cell transplantation (HSCT) offers the highest chance of cure. The introduction of less toxic non-myeloablative conditioning (NMA) regimes enabled older and/or comorbid patients to be consolidated with an allogeneic HSCT. While the hematopoietic cell transplantation comorbidity index (HCT-CI) predicted outcomes in many younger patient cohorts its impact in older AML patients receiving NMA-HSCT remains unknown. Here we analyzed 289 AML patients 60 years or older (median age 66, range 60-77 years) undergoing NMA-HSCT (2 or 3 Gray total body irradiation and 3 days of fludarabine 30 mg/m2). HCT-CI risk was low, intermediate, or high in 36%, 31%, and 33% of patients, respectively. Non-relapse mortality (NRM), cumulative incidence of relapse (CIR), and overall survival (OS) did not differ between HCT-CI groups. The HCT-CI also did not impact outcomes when considering the European LeukemiaNet 2017 risk at diagnosis or the measurable residual disease (MRD) status at HSCT. Notably, MRD-negative older NMA-transplanted AML patients had a beneficial OS of 49% after 5 years. Since a higher HCT-CI did not impair outcomes, age or comorbidities per se should not impede NMA-HSCT, presenting a feasible consolidation option for this group of AML patients.
Harnessing TRAIL-induced cell death for cancer therapy: a long walk with thrilling discoveries
Authors: Montinaro Antonella , Walczak Henning
Published: October 2022

Tumor necrosis factor (TNF)-related apoptosis inducing ligand (TRAIL) can induce apoptosis in a wide variety of cancer cells, both in vitro and in vivo, importantly without killing any essential normal cells. These findings formed the basis for the development of TRAIL-receptor agonists (TRAs) for cancer therapy. However, clinical trials conducted with different types of TRAs have, thus far, afforded only limited therapeutic benefit, as either the respectively chosen agonist showed insufficient anticancer activity or signs of toxicity, or the right TRAIL-comprising combination therapy was not employed. Therefore, in this review we will discuss molecular determinants of TRAIL resistance, the most promising TRAIL-sensitizing agents discovered to date and, importantly, whether any of these could also prove therapeutically efficacious upon cancer relapse following conventional first-line therapies. We will also discuss the more recent progress made with regards to the clinical development of highly active non-immunogenic next generation TRAs. Based thereupon, we next propose how TRAIL resistance might be successfully overcome, leading to the possible future development of highly potent, cancer-selective combination therapies that are based on our current understanding of biology TRAIL-induced cell death. It is possible that such therapies may offer the opportunity to tackle one of the major current obstacles to effective cancer therapy, namely overcoming chemo- and/or targeted-therapy resistance. Even if this were achievable only for certain types of therapy resistance and only for particular types of cancer, this would be a significant and meaningful achievement.