bluuebunny/crossref_metadata_2025 huggingface dataset:
Cost-effectiveness analysis of gene-based therapies for patients with spinal muscular atrophy type I in Australia
Authors: Wang Tianjiao , Scuffham Paul , Byrnes Joshua , Downes Martin
Published: August 2022

Introduction

Spinal muscular atrophy (SMA) is an inherited neuromuscular disorder and regarded as one of the most frequent genetic causes of infant mortality. The aim of this study is to develop a cost-effectiveness analysis of AVXS-101 (Onasemnogene Abeparvovec/Zolgensma®) and nusinersen (Spinraza®) for SMA to inform decision-making on reimbursement policies in Australia.

Methods

A Markov model was developed with five health states to evaluate the costs and effects for patients with SMA Type I from a healthcare system perspective over a time-horizon of 100 years. The model parameters were based on clinical trials, parametric distributions, published literature, and Australian registries. One-way and probabilistic sensitivity analysis were performed to appraise the uncertainties of the parameters in the model. A threshold analysis was conducted to estimate the cost of AVXS-101 of being cost-effective.

Results

The incremental cost-effectiveness ratio (ICER) of AVXS-101 was $1,808,471 per quality-adjusted life year (QALY) and that of nusinersen was $2,772,798 per QALY, compared to standard of care, respectively. The ICER of AVXS-101 was $1,238,288 per QALY compared to nusinersen. The key drivers influencing on ICERs were costs of using treatments and utility values of sitting and walking independently.

Conclusion

Both nusinersen and AVXS-101 resulted in health benefits, but they were not cost-effective with a commonly used willingness-to-pay (WTP) threshold of $50,000 per QALY. Developing high-quality clinical data and exploring appropriate WTP thresholds are critical for decision-making on reimbursement policies in the treatment of rare diseases.
Primary mitochondrial myopathy: 12-month follow-up results of an Italian cohort
Authors: Montano V. , Lopriore P. , Gruosso F. , Carelli V. , Comi G. P. , Filosto M. , Lamperti C. , Mongini T. , Musumeci O. , Servidei S. , Tonin P. , Toscano A. , Primiano G. , Valentino M. L. , Bortolani S. , Marchet S. , Ricci G. , Modenese A. , Cotti Piccinelli S. , Risi B. , Meneri M. , Arena I. G. , Siciliano G. , Mancuso Michelangelo
Published: August 2022

Objectives

To assess natural history and 12-month change of a series of scales and functional outcome measures in a cohort of 117 patients with primary mitochondrial myopathy (PMM).

Methods

Twelve months follow-up data of 117 patients with PMM were collected. We analysed the 6-min walk test (6MWT), timed up-and-go test (× 3) (3TUG), five-times sit-to-stand test (5XSST), timed water swallow test (TWST), and test of masticating and swallowing solids (TOMASS) as functional outcome measures; the Fatigue Severity Scale and West Haven-Yale Multidimensional pain inventory as patient-reported outcome measures. PMM patients were divided into three phenotypic categories: mitochondrial myopathy (MiMy) without extraocular muscles involvement, pure chronic progressive external ophthalmoplegia (PEO) and PEO&MiMy. As 6MWT is recognized to have significant test–retest variability, we calculated MCID (minimal clinically important difference) as one third of baseline 6 min walking distance (6MWD) standard deviation.

Results

At 12-month follow-up, 3TUG, 5XSST and FSS were stable, while TWST and the perceived pain severity (WHYMPI) worsened. 6MWD significantly increased in the entire cohort, especially in the higher percentiles and in PEO patients, while was substantially stable in the lower percentile (< 408 m) and MiMy patients. This increase in 6MWD was considered not significant, as inferior to MCID (33.3 m). NMDAS total score showed a slight but significant decline at 12 months (0.9 point). The perceived pain severity significantly worsened. Patients with PEO performed better in functional measures than patients with PEO&MiMy or MiMy, and had lower values of NMDAS.

Conclusions

PMM patients showed a slow global decline valued by NMDAS at 12 months; 6MWT was a more reliable measurement below 408 m, substantially stable at 12 months. PEO patients had better motor performance and lower NMDAS than PEO&MiMy and MiMy also at 12 months of follow-up.
Bayesian inference for random field parameters with a goal-oriented quality control of the PGD forward model’s accuracy
Authors: Coelho Lima Isabela , Robens-Radermacher Annika , Titscher Thomas , Kadoke Daniel , Koutsourelakis Phaedon-Stelios , Unger Jörg F.
Published: August 2022

Numerical models built as virtual-twins of a real structure (digital-twins) are considered the future of monitoring systems. Their setup requires the estimation of unknown parameters, which are not directly measurable. Stochastic model identification is then essential, which can be computationally costly and even unfeasible when it comes to real applications. Efficient surrogate models, such as reduced-order method, can be used to overcome this limitation and provide real time model identification. Since their numerical accuracy influences the identification process, the optimal surrogate not only has to be computationally efficient, but also accurate with respect to the identified parameters. This work aims at automatically controlling the Proper Generalized Decomposition (PGD) surrogate’s numerical accuracy for parameter identification. For this purpose, a sequence of Bayesian model identification problems, in which the surrogate’s accuracy is iteratively increased, is solved with a variational Bayesian inference procedure. The effect of the numerical accuracy on the resulting posteriors probability density functions is analyzed through two metrics, the Bayes Factor (BF) and a criterion based on the Kullback-Leibler (KL) divergence. The approach is demonstrated by a simple test example and by two structural problems. The latter aims to identify spatially distributed damage, modeled with a PGD surrogate extended for log-normal random fields, in two different structures: a truss with synthetic data and a small, reinforced bridge with real measurement data. For all examples, the evolution of the KL-based and BF criteria for increased accuracy is shown and their convergence indicates when model refinement no longer affects the identification results.
A walk in the black-box: 3D visualization of large neural networks in virtual reality
Authors: Linse Christoph , Alshazly Hammam , Martinetz Thomas
Published: August 2022

Within the last decade Deep Learning has become a tool for solving challenging problems like image recognition. Still, Convolutional Neural Networks (CNNs) are considered black-boxes, which are difficult to understand by humans. Hence, there is an urge to visualize CNN architectures, their internal processes and what they actually learn. Previously, virtual realityhas been successfully applied to display small CNNs in immersive 3D environments. In this work, we address the problem how to feasibly render large-scale CNNs, thereby enabling the visualization of popular architectures with ten thousands of feature maps and branches in the computational graph in 3D. Our software ”DeepVisionVR” enables the user to freely walk through the layered network, pick up and place images, move/scale layers for better readability, perform feature visualization and export the results. We also provide a novel Pytorch module to dynamically link PyTorch with Unity, which gives developers and researchers a convenient interface to visualize their own architectures. The visualization is directly created from the PyTorch class that defines the Pytorch model used for training and testing. This approach allows full access to the network’s internals and direct control over what exactly is visualized. In a use-case study, we apply the module to analyze models with different generalization abilities in order to understand how networks memorize images. We train two recent architectures, CovidResNet and CovidDenseNet on the Caltech101 and the SARS-CoV-2 datasets and find that bad generalization is driven by high-frequency features and the susceptibility to specific pixel arrangements, leading to implications for the practical application of CNNs. The code is available on Github https://github.com/Criscraft/DeepVisionVR.
Depression nach Schlaganfall
Authors: Ferrari Julia , Sachs Gabriele , Erfurth Andreas
Published: August 2022

Nach einem Schlaganfall treten häufig relevante depressive Symptome (poststroke depression, PSD) auf, die in der klinischen Praxis häufig übersehen oder unterschätzt werden. Die rasche Erkennung und angemessene Behandlung der PSD sind für die Rehabilitation und die Chance auf ein optimales funktionelles Ergebnis von entscheidender Bedeutung. Selektive Serotonin-Rückaufnahme-Inhibitoren (SSRI) sind sehr gut für die Behandlung der PSD untersucht, für die kognitiv-behaviorale Therapie gibt es gute Evidenz. Für eine regelhafte prophylaktische Verwendung eines SSRI nach jedem Schlaganfallereignis gibt es keine Empfehlung, in Einzelfällen sollte eine solche Prophylaxe diskutiert werden. Von Bedeutung ist die routinemäßige Erfassung kognitiver Dysfunktionen, da sowohl Schlaganfälle als auch depressive Störungen mit behandlungsbedürftigen kognitiven Störungen einhergehen können.
Direct 14C dating of equine products preserved in archaeological pottery vessels from Botai and Bestamak, Kazakhstan
Authors: Casanova Emmanuelle , Knowles Timothy D. J. , Outram Alan K. , Stear Natalie A. , Roffet-Salque Mélanie , Zaibert Viktor , Logvin Andrey , Shevnina Irina , Evershed Richard P.
Published: August 2022

Direct and accurate radiocarbon dating of lipid residues preserved in ceramics is a recently established method that allows direct dating of specific food products and their inception in human subsistence strategies. The method targets individual fatty acids originating from animal fats such as ruminant dairy, ruminant adipose, non-ruminant adipose and aquatic fats. Horse lipid residues found in Central Asian pottery vessels are also directly dateable using this new method. Here we present the identification of equine lipid residues preserved in two pottery assemblages from the Neolithic and Eneolithic in Kazakhstan and their direct 14C dating. The site of Botai, previously radiocarbon-dated to the 4th millennium BC, was used as a reference to evaluate the dates obtained directly on horse lipids. The direct dating of equine products extracted from Botai potsherds are shown to be compatible with previous 14C dates at the site. The site of Bestamak, lacking previous14C measurements, had been relatively dated to the Neolithic based on pottery typologies. The direct dating of equine residues made it possible to anchor the pottery assemblage of Bestamak in the 6th millennium BC confirming their Neolithic attribution. These findings demonstrate the potential for dating horse products through a compound-specific approach, while highlighting challenges in 14C dating individual fatty acids from lipid extracts in which their abundances differ substantially.
Diachronic forager mobility: untangling the Stone Age movement patterns at the sites Norje Sunnansund, Skateholm and Västerbjers through strontium isotope ratio analysis by laser ablation
Authors: Boethius Adam , Kjällquist Mathilda , Kielman-Schmitt Melanie , Ahlström Torbjörn , Larsson Lars
Published: August 2022

Strontium isotope ratios in human teeth from the three Swedish prehistoric Stone Age hunter-fisher-gathering societies Norje Sunnansund (Maglemose), Skateholm (Ertebølle) and Västerbjers (Pitted Ware Culture) were analysed with laser ablation to produce data on both individual movement patterns and societal mobility trends. The analyses of teeth from both Skateholm and Västerbjers displayed homogeneous ratios and corresponding mobility patterns, while the data from Norje Sunnansund showed larger variances with heterogenous strontium ratios and varied inter-individual mobility patterns. Correlation with the bioavailable baseline suggests that the size of the geographical areas, where human strontium ratios could have originated, was roughly comparable for all three sites. The teeth measurements were reflected within a 50-km radius of the surrounding landscape and the 25–75% data quartile matched with distances between 3 and 30 km from the sites, suggesting limited mobility ranges among aquatically dependent foragers from southernmost Sweden. By applying ethnographic analogies and site-specific contextual inferences, the results suggest that mobility ranges at Norje Sunnansund were likely not delimited by neighbouring group territories. This changed over time and an increasing territorialisation of the landscape may have influenced movement patterns and caused restrictions to the foraging activities at both Skateholm and Västerbjers.
Lymph node ratio predicts overall survival in patients with stage II non-small cell lung cancer: a population-based SEER analysis
Authors: Feng Nan , Wu Bo , Zhang Xiang , Chen Jianhui , Xiang Zhongtian , Wei Yiping , Zhang Wenxiong
Published: August 2022

Background

In non-small-cell lung cancer (NSCLC), there are many factors that affect prognosis, and the lymph node ratio (LNR) may play a significant role. Our study aimed to confirm the value of the LNR in the prognosis of patients with stage II NSCLC.

Methods

Patient data were obtained from the Surveillance, Epidemiology and End Results (SEER) database. The classification for the LNR was best determined using the X-tile method. The correlation between the LNR and overall survival (OS) was validated after the Kaplan–Meier analysis was performed. To determine the correlation between the LNR and survival, stratification and the Cox regression analysis were used.

Results

In our study, 14,183 stage II NSCLC patients were included. Among them, 8303 patients had N1 disease. According to the X-tile analysis, the optimal critical points for the LNR in N1 patients with NSCLC was 0.21 and 0.38. We categorized the cohorts as low (LNR-L ≤ 0.21; n = 5158, 62.1%), medium (0.21 < LNR-M ≤ 0.38; n = 1736, 20.9%), and high (LNR-H > 0.38; n = 1409, 17.0%). According to the Kaplan–Meier analysis, the patients with a high LNR were considerably worse than those with a medium or low LNR (P < 0.001), which was also proven by stratified and multivariate analyses. The value of the LNR was reflected in all the subgroup analyses, especially in patients ages < 60 years. The multivariate competing risks regression analysis revealed that younger age, female sex, T1 disease, adenocarcinoma and N0 disease was associated with a better prognosis after controlling for potential confounders (P < 0.001).

Conclusions

For patients with stage II NSCLC, the LNR is valuable for assessing prognosis. A higher LNR indicates a worse prognosis.
Use of a roving computer vision system to compare anomaly detection techniques for health monitoring of bridges
Authors: Lydon Darragh , Kromanis Rolands , Lydon Myra , Early Juliana , Taylor Su
Published: August 2022

Displacement measurements can provide valuable insights into structural conditions and in-service behaviour of bridges under operational and environmental loadings. Computer vision systems have been validated as a means of displacement estimation; the research developed here is intended to form the basis of a real-time damage detection system. This paper demonstrates a solution for detecting damage to a bridge from displacement measurements using a roving vision sensor-based approach. Displacements are measured using a synchronised multi-camera vision-based measurement system. The performance of the system is evaluated in a series of controlled laboratory tests. For damage detection, five unsupervised anomaly detection techniques: Autoencoder, K-Nearest Neighbours, Kernel Density, Local Outlier Factor and Isolation Forest, are compared. The results obtained for damage detection and localisation are promising, with an f1-Score of 0.96–0.97 obtained across various analysis scenarios. The approaches proposed in this research provide a means of detecting changes to bridges using low-cost technologies requiring minimal sensor installation and reducing sources of error and allowing for rating of bridge structures.
Experimental and Numerical Investigations of Using Nanoparticles in Groundwater Remediation
Authors: Okasha Ahmed S. , Abd-Elmegeed Mohamed A. , Hassan Ahmed E.
Published: August 2022

The efficiency of using zeolite nano-clay and silica sand in removing iron from groundwater is investigated experimentally as an application of in situ remediation technique using permeable reactive barrier (PRB). In the first stage of the study batch experiments were conducted on coarse silica sand and fine silica gravel to determine their iron removal efficiency from contaminated water. The results showed that the removal efficiency was about 51.90% for coarse silica sand while fine silica gravel failed to reduce the iron concentration in water. A mix of zeolite nano-clay and coarse silica sand with a ratio of 1:30 was tested. It was found that iron removal efficiency significantly increases to about 99.70%. The linear adsorption isotherm was found to be the most representative for the adsorption of iron onto coarse silica sand and the mix of nano-clay and coarse silica sand with distribution coefficients equal 0.0009 and 0.001, respectively. In the second stage a glass sand tank with coarse silica sand and a mix of zeolite nano-clay and coarse silica PRBs was constructed. The sand tank was used to investigate the effect of sampling time, head difference, iron concentration, nano-clay dosage, and thickness of permeable reactive barrier on the iron removal efficiency. The results indicated that increasing iron concentration and head difference decreases iron removal efficiency. The mix of zeolite nano-clay and coarse silica sand improves iron removal efficiency. Furthermore, increasing nano-clay dosage slightly increases the removal efficiency. However, increasing the thickness of filter layer (i.e., PRB) significantly improves the removal efficiency. Finally, the experimental model data were used to test the capability of a numerical contaminant transport model to predict the removal efficiency. The MT3DMS numerical model included within the Groundwater Modeling System (GMS) was used along with the different experimental data to obtain reaction rate values as calibration parameters for linear isotherm. Reaction rates that yield modeling results matching experimental data were obtained.
Supporting children’s mental health in primary schools: a qualitative exploration of educator perspectives
Authors: Giles-Kaye Alison , Quach Jon , Oberklaid Frank , O’Connor Meredith , Darling Simone , Dawson Georgia , Connolly Ann-Siobhan
Published: August 2022

Schools are often seen as a key setting for the provision of mental health support for children. This study aimed to explore the professional perspectives of primary school educators in Victoria, Australia, regarding how schools can support the mental health of their students. Semi-structured interviews and focus groups were conducted with 17 primary school educators, from four schools. Thematic analysis was used to generate themes from the data. This study indicates that educators report significant concerns about the complexities of their role and their capacity to support children’s mental health due to a lack of resources, overwhelming demands, and inadequate training. Educators highlighted the importance of partnership and communication with families and of a school culture that prioritises mental health. This study provides insights into external factors that can undermine effective support of children’s mental health within primary schools and indicates a need for a more integrated approach to supporting children’s mental health across education and healthcare.
Meckel-Gruber Syndrome in Twin Pregnancy: A Case Report
Authors: Atakir Kadir , Atakir Emine Aylin
Published: August 2022

Meckel-Gruber syndrome is a rare, OR-transitive and fatal disease. Prenatal diagnosis is important, especially in regions where consanguineous marriages are common. The classic triad of the disease is occipital meningoencephalocele, renal anomalies and postaxial polydactyly. The diagnosis is made by the presence of two of these three major features. Just over 200 cases have been reported in the world literature. The purpose of presenting our case is that all findings of the disease were detected in both fetuses in a twin pregnancy for the first time, which has not been reported in literature.
A Voronoi strain-based method for granular materials and continua
Authors: Frenning Göran
Published: August 2022

In a recent article (Frenning in Comp Part Mech 24:1–4, 2021), we demonstrated that a Delaunay-based strain estimate could be used as a starting point for the development of a particle-based method for continua. In this article, we argue that the Voronoi diagram, dual to the previously used Delaunay tetrahedralization, provides a more natural description of the underlying particulate system. For this reason, a Voronoi-based estimate of the deformation gradient is derived and used to the same effect. Although the gradient vectors cease to be antisymmetric, sums over nearest neighbors vanish, which results in a formulation that not only is linearly complete but also satisfies the patch test irrespective of initial particle placement. Pairwise forces, inferred from the local (nonaffine) deformation of each bond or contact, impart a physical stabilization. Forces are obtained from a discrete Lagrangian, thus ensuring that linear and angular momenta are conserved in the absence of external forces and torques. Methods to enforce different types of boundary conditions are described; these are exact for linear displacements, for constant stresses and for free surfaces. The performance of the method is assessed in a number of numerical tests.
Emergency Department Utilization Among Undocumented Latino Patients During the COVID-19 Pandemic
Authors: Ro Annie , Bruckner Tim A. , Huynh Michael Pham , Du Senxi , Young Andrew
Published: August 2022

Objective

To determine whether Latino undocumented immigrants had a steeper decline in Emergency Department (ED) utilization compared to Latino Medi-Cal patients in a Los Angeles safety-net hospital, March 13, 2020, to May 8, 2020.

Study Design

The data were extracted from patient medical records for ED visits at LAC + USC Medical Center from January 2018 to September 2020. We analyzed weekly ED encounters among undocumented Latino patients in the nine-week period after COVID was declared a national emergency. We applied time-series routines to identify and remove autocorrelation in ED encounters before examining its relation with the COVID-19 pandemic. We included Latino patients 18 years of age and older who were either on restricted or full-scope Medi-Cal (n = 230,195).

Results

All low-income Latino patients, regardless of immigration status, experienced a significant decline in ED utilization during the first nine weeks of the pandemic. Undocumented patients, however, experienced an even steeper decline. ED visits for this group fall below expected levels between March 13, 2020, and May 8, 2020 (coef. =  − 38.67; 95% CI =  − 71.71, − 5.63). When applied to the weekly mean of ED visits, this translates to a 10% reduction below expected levels in ED visits during this time period.

Conclusion

Undocumented immigrants’ health care utilization was influenced by external events that occurred early in the pandemic, such as strict stay-at-home orders and the public charge rule change. Health care institutions and local policy efforts could work to ensure that hospitals are safer spaces for undocumented immigrants to receive care without immigration concerns.
Health and environment from adaptation to adaptivity: a situated relational account
Authors: Menatti Laura , Bich Leonardo , Saborido Cristian
Published: August 2022

The definitions and conceptualizations of health, and the management of healthcare have been challenged by the current global scenarios (e.g., new diseases, new geographical distribution of diseases, effects of climate change on health, etc.) and by the ongoing scholarship in humanities and science. In this paper we question the mainstream definition of health adopted by the WHO—‘a state of complete physical, mental and social well-being and not merely the absence of disease or infirmity’ (WHO in Preamble to the constitution of the World Health Organization as adopted by the international health conference, The World Health Organization, 1948)—and its role in providing tools to understand what health is in the contemporary context. More specifically, we argue that this context requires to take into account the role of the environment both in medical theory and in the healthcare practice. To do so, we analyse WHO documents dated 1984 and 1986 which define health as ‘coping with the environment’. We develop the idea of ‘coping with the environment’, by focusing on two cardinal concepts: adaptation in public health and adaptivity in philosophy of biology. We argue that the notions of adaptation and adaptivity can be of major benefit for the characterization of health, and have practical implications. We explore some of these implications by discussing two recent case studies of adaptivity in public health, which can be valuable to further develop adaptive strategies in the current pandemic scenario: community-centred care and microbiologically healthier buildings.
Ongoing Commercialization of Gestational Surrogacy due to Globalization of the Reproductive Market before and after the Pandemic
Authors: Hibino Yuri
Published: August 2022

Surrogacy tourism in Asian countries has surged in recent decades due to affordable prices and favourable regulations. Although it has recently been banned in many countries, it is still carried out illegally across borders. With demand for surrogacy in developed countries increasing and economically vulnerable Asian women lured by lucrative compensation, there are efforts by guest countries to ease the strict surrogacy regulations in host countries. Despite a shift toward “altruistic surrogacy”, commercial surrogacy persists. Recent research carried out by international organizations that seek to establish a legal relationship between the commissioning parents and children in cross-border surrogacy arrangements, under the guise of the “best interests of the child,” appears to promote a resurgence of overseas commercial surrogacy rather than restrict it. Further commercialization of surrogacy should be prevented by carefully investigating the reality of the surrogacy process.
Mapping the potential for offshore aquaculture of salmonids in the Yellow Sea
Authors: Yu Shuang-En , Dong Shuang-Lin , Zhang Zhi-Xin , Zhang Yu-Yang , Sarà Gianluca , Wang Jie , Dong Yun-Wei
Published: August 2022

Mariculture has been one of the fastest-growing global food production sectors over the past three decades. With the congestion of space and deterioration of the environment in coastal regions, offshore aquaculture has gained increasing attention. Atlantic salmon (Salmo salar) and rainbow trout (Oncorhynchus mykiss) are two important aquaculture species and contribute to 6.1% of world aquaculture production of finfish. In the present study, we established species distribution models (SDMs) to identify the potential areas for offshore aquaculture of these two cold-water fish species considering the mesoscale spatio-temporal thermal heterogeneity of the Yellow Sea. The values of the area under the curve (AUC) and the true skill statistic (TSS) showed good model performance. The suitability index (SI), which was used in this study to quantitatively assess potential offshore aquaculture sites, was highly dynamic at the surface water layer. However, high SI values occurred throughout the year at deeper water layers. The potential aquaculture areas for S. salar and O. mykiss in the Yellow Sea were estimated as 52,270 ± 3275 (95% confidence interval, CI) and 146,831 ± 15,023 km2, respectively. Our results highlighted the use of SDMs in identifying potential aquaculture areas based on environmental variables. Considering the thermal heterogeneity of the environment, this study suggested that offshore aquaculture for Atlantic salmon and rainbow trout was feasible in the Yellow Sea by adopting new technologies (e.g., sinking cages into deep water) to avoid damage from high temperatures in summer.
A modular switched-capacitor multilevel inverter featuring voltage gain ability
Authors: Wang Yaoqiang , Ye Juncheng , Ku Ruohan , Shen Yuchen , Li Gen , Liang Jun
Published: August 2022

This article presents a modular switched-capacitor multilevel inverter which uses two capacitors and a single dc source to obtain triple voltage gain. It is worth noting that the inherent inversion capacity removes the H-bridge, which can efficaciously diminish the voltage stress of switches, and the maximum voltage stress (MVS) on devices is kept within 2Vdc. Additionally, the proposed topology is able to integrate inductive load, and the capacitor voltage self-balancing can be achieved. Moreover, the modular structure also has an expandable topology which can generate more levels and raise the voltage gain by using multiple switched-capacitor units, meanwhile the voltage stress on power switches can be kept within 2Vdc. Furthermore, comprehensive analysis and comparison with other multilevel inverters have been implemented to certify the superiority of the proposed topology. Finally, the steady-state and dynamic performance of the proposed topology is examined through a seven-level inverter prototype, the validity and practicability of the topology are verified by simulations and experiments.
Refocusing Rape Investigations: A Commentary on Research Supporting Operation Soteria Bluestone
Authors: Brown Jennifer
Published: August 2022

This paper presents a commentary on the academic research that was undertaken in support of a pilot project in Avon and Somerset Constabulary to develop a new rape investigation model, Operation Soteria Bluestone. A five-pillar approach re-oriented investigative practice towards suspect focussed case building whilst maintaining support for complainants. In addition, organisation enablers were developed to enhance specialist training, intelligent use of data, and promoting officer welfare and wellbeing. The empirical papers addressed various aspects of the five Pillars. Proof of concept, conduciveness of the political, economic, and social environment, and connectivity with other associated work were employed as appraisal criteria. There is much to commend in the proposed model but the absence of research on suspects and offenders, given their prominence in the model’s new direction, together with the lack of a strong implementation framework, are omissions that hopefully will be addressed in the future.
Opportunities in Critical Rare Earth Metal Recycling Value Chains for Economic Growth with Sustainable Technological Innovations
Authors: Patil Ajay B. , Struis Rudolf P. W. J. , Ludwig Christian
Published: August 2022

Rare earth elements (REEs) are often referred to as the industrial vitamins and the key drivers of the industry 4.0 revolution. The current global supply chain of REEs for green and high-tech applications with more than 220 metric kilotons per year involves a huge environmental impact (backpack) as well as the piling up of radioactive by-products to about 1.5 times the amount of REEs produced. E-wastes and municipal solid waste streams are attractive secondary resources. The current opinion paper discusses the recycling of rare earth metals along the value chain with the opportunities and challenges associated with it. The way to mitigate the economic constraints has been pointed out in terms of competitive quality and recovery of the REEs when compared with the mineral exploration options in the market. It is also emphasised that the technical complexity, capital expenditures and operating expenses need to fit the economic boundary conditions to make the recycling viable. In future, the appropriate REE-rich feedstocks such as fluorescent lamp e-waste powders and magnets can be potential secondary sources of the critical raw materials necessary for the green transition. The success of the viable recycling approaches and technologies will largely depend on the public–private partnerships based on hybrid financing models and local know-how generation to compete with quasi-monopoly in the REE supply chains. However, to break the monopolies, it will not be sufficient to only recycle the REEs; it will also be relevant to diversify the industries that produce REE-containing goods from recycled waste streams.
Hydrodynamic performance of slender swimmer: effect of travelling wavelength
Authors: Chao Li-Ming , Mahbub Alam Md. , Cheng Liang
Published: August 2022

The impact of Strouhal number St (= 0.1–1.0), Reynolds number Re (= 50–2000) and dimensionless wavelength λ (= 0.5–2.0) on the hydrodynamic performance of a travelling wavy foil of a constant length is extensively investigated. The relationship of time-mean thrust with St, Re and λ is presented, suggesting that the propulsive force increases with increasing St, Re and λ. As such, the drag–thrust boundary advances as these parameters increase. A shorter λ makes the thrust steadier while a longer λ enhances the maximum instantaneous thrust. The latter is beneficial for prey to escape from a predator. The fluid added mass caused by the foil oscillation increases with St and λ but declines with Re (<500). Seven types of wake structures produced by the foil are identified, discussed and connected to thrust generation, showing how St, Re and λ affect the fluid dynamics, wake transition, vortex strength, wake jet, velocity, added mass, added damping, power input, efficiency and pressure profiles. The outcome of this work renders a physical basis for understanding the swimming of aquatic animals.
Gromov–Wasserstein distances between Gaussian distributions
Authors: Delon Julie , Desolneux Agnes , Salmona Antoine
Published: August 2022

Gromov–Wasserstein distances were proposed a few years ago to compare distributions which do not lie in the same space. In particular, they offer an interesting alternative to the Wasserstein distances for comparing probability measures living on Euclidean spaces of different dimensions. We focus on the Gromov–Wasserstein distance with a ground cost defined as the squared Euclidean distance, and we study the form of the optimal plan between Gaussian distributions. We show that when the optimal plan is restricted to Gaussian distributions, the problem has a very simple linear solution, which is also a solution of the linear Gromov–Monge problem. We also study the problem without restriction on the optimal plan, and provide lower and upper bounds for the value of the Gromov–Wasserstein distance between Gaussian distributions.
The Face on the Turoe Stone
Authors: FOSTER JENNIFER , BATTEN MAGDALEN
Published: August 2022

Re-examination of the Turoe stone, Co. Galway, Ireland, a small granite pillar decorated with Celtic art, has revealed a possible, previously un-noticed, stylised boar’s head.
Spatiotemporal Distribution of Shallow Tremors Along the Nankai Trough, Southwest Japan, as Determined From Waveform Amplitudes and Cross‐Correlations
Authors: Tamaribuchi Koji , Ogiso Masashi , Noda Akemi
Published: August 2022

Shallow slow earthquakes in subduction zones are related to spatiotemporal variations of stress on the plate boundary adjacent to a megathrust earthquake. A dense network (DONET) of cabled ocean‐bottom seismometers (OBSs) deployed in the Nankai Trough seismogenic zone, southwest Japan, has enabled real‐time monitoring of tremors. Because the amplitudes of tremor signals are very low, even when recorded by OBSs, we developed a hybrid method that simultaneously uses traveltimes based on cross‐correlations and amplitudes of waveforms to determine tremor hypocenters. We applied our method to waveforms observed during five years of continuous DONET recording from April 2016 to September 2021 to detect more than 6,500 tremors, including three major episodes in 2016, 2018, and 2020–2021. The tremors of each episode were distributed over distances of >100 km along the trench axis in two regions, southeast of the Kii Peninsula and off Cape Muroto. We also estimated seismic energy rates and found that for the three major tremor episodes, energy rates increased gradually with time. The 2018 and 2020–2021 episodes began near a subducted seamount and a subducted ridge, respectively, and were likely related to fluid movements controlled by the topography of the downgoing plate. We showed that the tremors were spatiotemporally synchronized with slow slip events, and their spatial variations of energy rate corresponded to stress heterogeneity on the shallow plate boundary. Future real‐time monitoring of shallow tremors will contribute to our understanding of changes of stress state due to slow earthquakes at the shallow plate boundary.
The Role of Turbulence in Fueling the Subsurface Chlorophyll Maximum in Tidally Dominated Shelf Seas
Authors: Becherer Johannes , Burchard Hans , Carpenter Jeffrey R. , Graewe Ulf , Merckelbach Lucas M.
Published: August 2022

Glider observations show a subsurface chlorophyll maximum (SCM) at the base of the seasonal pycnocline in the North Sea during stable summer conditions. A colocated peak in the dissipation rate of turbulent kinetic energy suggests the presence of active turbulence that potentially generates a nutrient flux to fuel the SCM. A one‐dimensional turbulence closure model is used to investigate the dynamics behind this local maximum in turbulent dissipation at the base of the pycnocline (PCB) as well as its associated nutrient fluxes. Based on a number of increasingly idealized forcing setups of the model, we are able to draw the following conclusions: (a) only turbulence generated inside the stratified PCB is able to entrain a tracer (e.g., nutrients) from the bottom mixed layer into the SCM region; (b) surface wind forcing only plays a secondary role during stable summer conditions; (c) interfacial shear from the tide accounts for the majority of turbulence production at the PCB; (d) in stable summer conditions, the strength of the turbulent diapycnal fluxes at the PCB is set by the strength of the anticyclonic component of the tidal currents.
Ice Aggregation in Low‐Level Mixed‐Phase Clouds at a High Arctic Site: Enhanced by Dendritic Growth and Absent Close to the Melting Level
Authors: Chellini Giovanni , Gierens Rosa , Kneifel Stefan
Published: August 2022

Low‐level mixed‐phase clouds (MPCs) occur extensively in the Arctic, and are known to play a key role for the energy budget. While their characteristic structure is nowadays well understood, the significance of different precipitation‐formation processes, such as aggregation and riming, is still unclear. Using a 3‐year data set of vertically pointing W‐band cloud radar and K‐band Micro Rain Radar (MRR) observations from Ny‐Ålesund, Svalbard, we statistically assess the relevance of aggregation in Arctic low‐level MPCs. Combining radar observations with thermodynamic profiling, we find that larger snowflakes (mass median diameter larger than 1 mm) are predominantly produced in low‐level MPCs whose mixed‐phase layer is at temperatures between −15 and −10°C. This coincides with the temperature regime known for favoring aggregation due to growth and subsequent mechanical entanglement of dendritic crystals. Doppler velocity information confirms that these signatures are likely due to enhanced ice particle growth by aggregation. Signatures indicative of enhanced aggregation are however not distributed uniformly across the cloud deck, and only observed in limited regions, suggesting a link with dynamical effects. Low Doppler velocity values further indicate that significant riming of large particles is unlikely at temperatures colder than −5°C. Surprisingly, we find no evidence of enhanced aggregation at temperatures warmer than −5°C, as is typically observed in deeper cloud systems. Possible reasons are discussed, likely connected to the ice habits that form at temperatures warmer than −10°C, increased riming, and lack of particle populations characterized by broader size distributions precipitating from higher altitudes.
Estimating Drivers and Pathways for Hydroelectric Reservoir Methane Emissions Using a New Mechanistic Model
Authors: Delwiche Kyle B. , Harrison John A. , Maasakkers Joannes D. , Sulprizio Melissa P. , Worden John , Jacob Daniel J. , Sunderland Elsie M.
Published: August 2022

Hydroelectric reservoirs can emit significant quantities of methane, particularly through degassing at turbine outlets. Improved understanding of processes affecting hydroelectric reservoir CH4 emissions is thus important as the world economy transitions to renewable forms of energy production. Here we develop and evaluate a new mechanistic model of CH4 emissions: ResME ([Res]ervoir [M]ethane [E]missions), which estimates carbon inputs and methanogenesis to predict CH4 release via ebullition and diffusion, plant emissions, and downstream emissions. ResME results demonstrate that the relative importance of allochthonous and autochthonous carbon input to methane emissions varies by latitude, with allochthonous carbon contributions typically being higher in tropical reservoirs. Results also demonstrate that total reservoir emissions are highly dependent on turbine intake depths, which are not typically reported. Potential maximum degassing emissions from existing hydroelectric reservoirs are estimated as 11 ± 4 Tg C/yr, if all reservoirs had deep turbine intakes and stratified for 5 months per year. In comparison, the estimated diffusive, ebullitive, and plant CH4 emissions are estimated to be 2.8 ± 0.2 Tg C/yr (where the true uncertainty is much higher than the model standard error). Future work should focus on improving estimates of reservoir carbon inputs and decomposition rates, as well as surveying turbine intake depths. Satellite measurements from missions such as TROPOMI may also help constrain hydropower methane emissions.
Development of a spontaneous pain indicator based on brain cellular calcium using deep learning
Authors: Yoon Heera , Bak Myeong Seong , Kim Seung Ha , Lee Ji Hwan , Chung Geehoon , Kim Sang Jeong , Kim Sun Kwang
Published: August 2022

Chronic pain remains an intractable condition in millions of patients worldwide. Spontaneous ongoing pain is a major clinical problem of chronic pain and is extremely challenging to diagnose and treat compared to stimulus-evoked pain. Although extensive efforts have been made in preclinical studies, there still exists a mismatch in pain type between the animal model and humans (i.e., evoked vs. spontaneous), which obstructs the translation of knowledge from preclinical animal models into objective diagnosis and effective new treatments. Here, we developed a deep learning algorithm, designated AI-bRNN (Average training, Individual test-bidirectional Recurrent Neural Network), to detect spontaneous pain information from brain cellular Ca2+ activity recorded by two-photon microscopy imaging in awake, head-fixed mice. AI-bRNN robustly determines the intensity and time points of spontaneous pain even in chronic pain models and evaluates the efficacy of analgesics in real time. Furthermore, AI-bRNN can be applied to various cell types (neurons and glia), brain areas (cerebral cortex and cerebellum) and forms of somatosensory input (itch and pain), proving its versatile performance. These results suggest that our approach offers a clinically relevant, quantitative, real-time preclinical evaluation platform for pain medicine, thereby accelerating the development of new methods for diagnosing and treating human patients with chronic pain.
Inhibiting peripheral and central MAO-B ameliorates joint inflammation and cognitive impairment in rheumatoid arthritis
Authors: Won Woojin , Choi Hyun-Ji , Yoo Ji-Young , Kim Daeun , Kim Tai Young , Ju YeonHa , Park Ki Duk , Lee Hyunbeom , Jung Sang Youn , Lee C. Justin
Published: August 2022

Rheumatoid arthritis (RA) is an autoimmune disorder characterized by chronic inflammation and the destruction of joints and systemic organs. RA is commonly accompanied by neuropsychiatric complications, such as cognitive impairment and depression. However, the role of monoamine oxidase (MAO) and its inhibitors in controlling neurotransmitters associated with these complications in RA have not been clearly identified. Here, we report that peripheral and central MAO-B are highly associated with joint inflammation and cognitive impairment in RA, respectively. Ribonucleic acid (RNA) sequencing and protein expression quantification were used to show that MAO-B and related molecules, such as gamma aminobutyric acid (GABA), were elevated in the inflamed synovium of RA patients. In primary cultured fibroblast-like synoviocytes in the RA synovium, MAO-B expression was significantly increased by tumor necrosis factor (TNF)-α-induced autophagy, which produces putrescine, the polyamine substrate for GABA synthesis. We also observed that MAO-B-mediated aberrant astrocytic production of GABA was augmented by interleukin (IL)-1β and inhibited CA1-hippocampal pyramidal neurons, which are responsible for memory storage, in an animal model of RA. Moreover, a newly developed reversible inhibitor of MAO-B ameliorated joint inflammation by inhibiting cyclooxygenase (Cox)-2. Therefore, MAO-B can be an effective therapeutic target for joint inflammation and cognitive impairment in patients with RA.
FMRP modulates the Wnt signalling pathway in glioblastoma
Authors: Pedini Giorgia , Buccarelli Mariachiara , Bianchi Fabrizio , Pacini Laura , Cencelli Giulia , D’Alessandris Quintino Giorgio , Martini Maurizio , Giannetti Stefano , Sasso Franceschina , Melocchi Valentina , Farace Maria Giulia , Achsel Tilmann , Larocca Luigi M. , Ricci-Vitiani Lucia , Pallini Roberto , Bagni Claudia
Published: August 2022

Converging evidence indicates that the Fragile X Messenger Ribonucleoprotein (FMRP), which absent or mutated in Fragile X Syndrome (FXS), plays a role in many types of cancers. However, while FMRP roles in brain development and function have been extensively studied, its involvement in the biology of brain tumors remains largely unexplored. Here we show, in human glioblastoma (GBM) biopsies, that increased expression of FMRP directly correlates with a worse patient outcome. In contrast, reductions in FMRP correlate with a diminished tumor growth and proliferation of human GBM stem-like cells (GSCs) in vitro in a cell culture model and in vivo in mouse brain GSC xenografts. Consistently, increased FMRP levels promote GSC proliferation. To characterize the mechanism(s) by which FMRP regulates GSC proliferation, we performed GSC transcriptome analyses in GSCs expressing high levels of FMRP, and in these GSCs after knockdown of FMRP. We show that the WNT signalling is the most significantly enriched among the published FMRP target genes and genes involved in ASD. Consistently, we find that reductions in FMRP downregulate both the canonical WNT/β-Catenin and the non-canonical WNT-ERK1/2 signalling pathways, reducing the stability of several key transcription factors (i.e. β-Catenin, CREB and ETS1) previously implicated in the modulation of malignant features of glioma cells. Our findings support a key role for FMRP in GBM cancer progression, acting via regulation of WNT signalling.