bluuebunny/crossref_metadata_2025 huggingface dataset:
Explanatory factors of dynamic balance impairment in myotonic dystrophy type 1
Authors: Bélair Nicolas , Côté Isabelle , Gagnon Cynthia , Mathieu Jean , Duchesne Elise
Published: February 2022

Introduction/Aims

Myotonic dystrophy type 1 (DM1) is a neuromuscular disease affecting many systems and for which muscle weakness is one of the cardinal symptoms. People with DM1 also present with balance‐related impairments and high fall risk. The aim of this study was to explore explanatory factors of dynamic balance impairment in the DM1 population.

Methods

A secondary analysis of data collected as part of a larger study was performed. The Mini Balance Evaluation System Test (Mini‐BESTest) was used to assess dynamic balance. Age, sex, and CTG repeat length in blood were retrieved from medical records and research files. The maximal isometric muscle strength of five lower limb muscle groups (hip flexors and extensors, knee flexors and extensors, and ankle dorsiflexors) was quantitatively assessed as well as fatigue. Standard multiple regression analysis was used.

Results

Fifty‐two individuals (31 men) aged between 24 and 81 years were included. The final model explains 65.9% of the balance score; ankle dorsiflexor muscle strength was the strongest explanatory factor, followed by CTG repeat length, age and fatigue to a lesser extent.

Discussion

Dynamic balance is impaired in people with DM1. Results of this study suggest that rehabilitation interventions aimed at improving strength of the ankle dorsiflexors and managing fatigue could help to improve dynamic balance in this specific population.
Pins and needles: The neurological examination and electrodiagnosis in children
Authors: Karakis Ioannis
Published: February 2022

See article on pages 513–520 in this issue
Practice makes perfect? Inter‐analyst variation in the identification of fish remains from archaeological sites
Authors: Hawkins Alicia L. , Buckley Michael , Needs‐Howarth Suzanne , Orchard Trevor J.
Published: February 2022

Identification of faunal specimens based on a morphological comparison with known‐identity reference specimens is the standard methodology used in zooarchaeological analysis. However, the accuracy of identifications is rarely considered. In this paper, we report results of an experiment in which 13 analysts were asked to identify 50 fish skeletal elements from a reference collection and 50 fish skeletal elements from an archaeological collection in southern Ontario. The type and level of experience of the analysts and the amount of time they invested in the identification were controlled. The archaeological specimens were subsequently identified taxonomically using ZooMS. Our findings demonstrate that taxonomic and element identifications are far from perfect, both in the reference collection set and in the archaeological collection set. Probable contributing factors include the richness of taxonomic groups; distinctiveness of skeletal morphology; experience level of the analyst; and size of the individual specimens and whether the analyst had access to comprehensive, well‐labeled reference collections. We recommend emphasis be placed in training on the importance, for most species, of not making a taxonomic identification unless the element identification is certain; conservatism in identification of species in groups with many members; clear knowledge of the range of species possible within a region; and active involvement by the instructor or mentor to ensure that neophyte analysts are corrected.
X‐ray CT reveals 4D root system development and lateral root responses to nitrate in soil
Authors: Griffiths Marcus , Mellor Nathan , Sturrock Craig J. , Atkinson Brian S. , Johnson James , Mairhofer Stefan , York Larry M. , Atkinson Jonathan A. , Soltaninejad Mohammadreza , Foulkes John F. , Pound Michael P. , Mooney Sacha J. , Pridmore Tony P. , Bennett Malcolm J. , Wells Darren M.
Published: February 2022

The spatial arrangement of the root system, termed root system architecture, is important for resource acquisition as it directly affects the soil zone explored. Methods for phenotyping roots are mostly destructive, which prevents analysis of roots over time as they grow. Here, we used X‐ray microcomputed tomography (μCT) to non‐invasively characterize wheat (Triticum aestivum L.) seedling root development across time under high and low nitrate nutrition. Roots were imaged multiple times with the 3D models co‐aligned and timestamped in the architectural plant model OpenSimRoot for subsequent root growth and nitrate uptake simulations. Through 4D imaging, we found that lateral root traits were highly responsive to nitrate limitation in soil with greater lateral root length under low N. The root growth model using all μCT root scans was comparable to a parameterized model using only the final root scan in the series. In a second μCT experiment, root growth and nitrate uptake simulations of candidate wheat genotypes found significant root growth and uptake differences between lines. A high nitrate uptake wheat line selected from field data had a greater lateral root count and length at seedling growth stage compared with a low uptake line.
Redesign identification criteria for major hazard installation in Malaysia
Authors: Syed Muhammad Syed Malek , Harun Razif
Published: February 2022

Malaysia adopted the GHS through the CLASS Regulations of 2013. This new approach for chemical classification is inconsistent with the CIMAH Regulations of 1996 and has introduced new hazard categories, which are not included in the current major hazard identification criteria. For identifying MHI in Malaysia, the chemicals need to be reclassified. Therefore, this study aims to propose the indicative criteria for major hazard installation that are aligned with CLASS in order to simplify the process. The newly listed chemical threshold quantity, focusing on the acute toxicity group, was also identified. The steps involved include comparing major hazard legislation in the selected country, matching the criteria of CIMAH and CLASS, and reclassifying chemicals in Schedule Two of CIMAH. For estimation of TQ for nitric acid, dispersion modeling was selected. A guide for selecting suitable parameters was developed, ALOHA software was used to simulate the model, and the estimation result for nitric acid was 15.5 tonnes. This study provides the opportunity to improve CIMAH by applying CLASS hazard categories to identify major hazard installation. The guide to estimate TQ could be used for other acute toxicity chemicals as an option for regulators to negotiate and decide the TQ in CIMAH.
Recent Progress in Daytime Radiative Cooling: Advanced Material Designs and Applications
Authors: Zhang Qian , Wang Shuaihao , Wang Xueyang , Jiang Yi , Li Jinlei , Xu Weilin , Zhu Bin , Zhu Jia
Published: February 2022

Passive daytime radiative cooling (PDRC) is emerging as a promising cooling technology. Owing to the high, broadband solar reflectivity and high mid‐infrared emissivity, daytime radiative cooling materials can achieve passive net cooling power under direct sunlight. The zero‐energy‐consumption characteristic enables PDRC to reduce negative environmental issues compared with conventional cooling systems. In this review, the development of advanced daytime radiative cooling designs is summarized, recent progress is highlighted, and potential correlated applications, such as building cooling, photovoltaic cooling, and electricity generation, are introduced. The remaining challenges and opportunities of PDRCs are also indicated. It is expected that this review provides an overall picture of recent PDRC progress and inspires future research regarding the fundamental understanding and practical applications of PDRC.
Platinum Cluster/Carbon Quantum Dots Derived Graphene Heterostructured Carbon Nanofibers for Efficient and Durable Solar‐Driven Electrochemical Hydrogen Evolution
Authors: Wang Xiaohan , Zhang Yuanming , Li Junzhi , Liu Guiju , Gao Mingzhen , Ren Shihuan , Liu Bingxu , Zhang Lixue , Han Guangting , Yu Jianyong , Zhao Haiguang , Rosei Federico
Published: February 2022

Large scale solar‐driven hydrogen production is a crucial step toward decarbonizing society. However, the solar‐to‐hydrogen (STH) conversion efficiency, long‐term stability, and cost‐effectiveness in hydrogen evolution reaction (HER) still need to be improved. Herein, an efficient approach is demonstrated to produce low‐dimensional Pt/graphene‐carbon nanofibers (CNFs)‐based heterostructures for bias‐free, highly efficient, and durable HER. Carbon dots are used as efficient building blocks for the in situ formation of graphene along the CNFs surface. The presence of graphene enhances the electronic conductivity of CNFs to ≈3013.5 S m−1 and simultaneously supports the uniform Pt clusters growth and efficient electron transport during HER. The electrode with a low Pt loading amount (3.4 µg cm−2) exhibits a remarkable mass activity of HER in both acidic and alkaline media, which is significantly better than that of commercial Pt/C (31 µg cm−2 of Pt loading). In addition, using a luminescent solar concentrator‐coupled solar cell to provide voltage, the bias‐free water splitting system exhibits an STH efficiency of 0.22% upon one‐sun illumination. These results are promising toward using low‐dimensional heterostructured catalysts for future energy storage and conversion applications.
Influence of Large Steric Hinderance Substituent Position on Conformation and Charge Transfer Process for Non‐Fused Ring Acceptors
Authors: Li Jiayao , Li Hao , Ma Lijiao , Xu Ye , Cui Yong , Wang Jingwen , Ren Junzhen , Zhu Jincheng , Zhang Shaoqing , Hou Jianhui
Published: February 2022

To obtain stable and planar molecular geometry in non‐fused electron acceptors, A4T‐25 and A4T‐26 are designed and synthesized by introducing the bulk 2,4,6‐triisopropylphenyl side groups onto different positions of the central two thiophene units. A4T‐25 and A4T‐26 both show a narrow‐bandgap of 1.39 and 1.46 eV, with highest occupied molecular orbital/lowest unoccupied molecular orbital levels of −5.56/−3.81 and −5.65/−3.83 eV, respectively, and the electrostatic potential distributions imply that they have strong electron‐accepting capability. The single crystal structure analysis and the transfer integral calculation demonstrate that the much more compact π‐π stacking in A4T‐26 can promote efficient charge transportation compared to that in A4T‐25. Therefore, the electron mobility of A4T‐26 is obviously higher and more balanced than that of A4T‐25. When blending the two acceptors with the same polymer donor PBDB‐TF, the photovoltaic cell based on PBDB‐TF:A4T‐25 has an inadequate power conversion efficiency (PCE) of 7.83%, while the PBDB‐TF:A4T‐26‐based one yields an enhanced PCE of 12.1%. Overall, this study offers an insight into the relationship between the fine‐tuning of the molecular structure of non‐fused ring acceptors and the corresponding charge transfer process in organic solar cells.
Learning to think spatially through curricula that embed spatial training
Authors: Plummer Julia D. , Udomprasert Patricia , Vaishampayan Abha , Sunbury Susan , Cho Kyungjin , Houghton Harry , Johnson Erin , Wright Erika , Sadler Philip M. , Goodman Alyssa
Published: February 2022

Strong spatial skills are foundational in predicting students' performance in science, technology, engineering, and mathematics education. Decades of research have considered the relationship between thinking spatially and how scientists reason and solve problems. However, few studies have examined the factors that influence improvement in students' spatial thinking during their school science curricula. The present study investigates theThinkSpacecurricula—two middle school astronomy units designed to support students' ability to apply the spatial skill of perspective‐taking (PT) while learning to explain lunar phases (3 days) and the seasons (8 days). U.S. students in 6th and 8th grades (N = 877) across four districts participated in the study, completing assessments before and after theThinkSpacecurricula, along with an additional group of students in 6th and 7th grades (N = 172) who participated as a spatial control group. Data collection included multiple‐choice content assessments, PT skill assessments, and interviews (from a sub‐sample of 96 students), before and after instruction. After participating inThinkSpacecurricula, students demonstrated improved spatial thinking within the domain of astronomy, as measured by improved written content assessments, increased application of PT during conceptual interviews, and a general measurement of PT skill. Higher initial PT skill and higher gain in PT skill predicted greater improvement in students' astronomy understanding, even when accounting for their initial content knowledge. AlthoughThinkSpacestudents in all demographic groups improved PT skill post‐instruction, 8th graders (who were in districts with lower SES), and females were predicted to have smaller gains in their PT skill than the 6th graders (who were in districts with higher SES) and male students. These findings suggest that middle school students' spatial thinking in science can be improved during their middle school science curricula, but questions remain concerning how to reduce spatial‐learning gaps that are associated with gender and possibly SES.
Successful management of feline pemphigus foliaceus with pentoxifylline and topical hydrocortisone aceponate
Authors: Hobi Stefan , Beatty Julia A. , Sandy Jeanine R. , Barrs Vanessa R.
Published: February 2022

The treatment regimen for feline pemphigus foliaceus (PF), an autoimmune disease caused by auto‐antibodies against proteins of the desmosome junction, usually includes high doses of oral or parenteral immunosuppressive drugs, typically glucocorticoids. This case adds to a growing body of evidence that topical hydrocortisone aceponate is effective for the treatment of feline PF, and demonstrates the practical use of a non‐invasive diagnostic method for histopathology when owners refuse a biopsy to support a clinical diagnosis of PF. Finally, this case highlights an international trend of owner‐initiated treatment of feline infectious peritonitis (FIP) using unlicensed, unregistered drugs.
Modeling Splicing Variants Amenable to Antisense Therapy by Use of CRISPR-Cas9-Based Gene Editing in HepG2 Cells
Authors: López-Márquez Arístides , Martínez-Pizarro Ainhoa , Pérez Belén , Richard Eva , Desviat Lourdes R.
Published: February 2022

The field of splice modulating RNA therapy has gained new momentum with FDA approved antisense-based drugs for several rare diseases. In vitro splicing assays with minigenes or patient-derived cells are commonly employed for initial preclinical testing of antisense oligonucleotides aiming to modulate splicing. However, minigenes do not include the full genomic context of the exons under study and patients’ samples are not always available, especially if the gene is expressed solely in certain tissues (e.g. liver or brain). This is the case for specific inherited metabolic diseases such as phenylketonuria (PKU) caused by mutations in the liver-expressed PAH gene.

Herein we describe the generation of mutation-specific hepatic cellular models of PKU using CRISPR/Cas9 system, which is a versatile and easy-to-use gene editing tool. We describe in detail the selection of the appropriate cell line, guidelines for design of RNA guides and donor templates, transfection procedures and growth and selection of single-cell colonies with the desired variant, which should result in the accurate recapitulation of the splicing defect.
Establishment of In Vitro Brain Models for AON Delivery
Authors: Daoutsali Elena , Buijsen Ronald A. M.
Published: February 2022

Progress in stem cell biology has made it possible to generate human-induced pluripotent stem cells (hiPSC) that can be differentiated into complex, three-dimensional structures, where the cells are spatially organized. To study brain development, Lancaster and colleagues developed an hiPSC-derived three-dimensional organoid culture system, termed cerebral organoids, that develop various discrete, although interdependent, brain regions. Here we describe in detail the generation of cerebral organoids using a modified version of the culture protocol.
Considerations for Generating Humanized Mouse Models to Test Efficacy of Antisense Oligonucleotides
Authors: Vázquez-Domínguez Irene , Garanto Alejandro
Published: February 2022

Over the last decades, animal models have become increasingly important in therapeutic drug development and assessment. The use of these models, mainly mice and rats, allow evaluating drugs in the real-organism environment and context. However, several molecular therapeutic approaches are sequence-dependent, and therefore, the humanization of such models is required to assess the efficacy. The generation of genetically modified humanized mouse models is often an expensive and laborious process that may not always recapitulate the human molecular and/or physiological phenotype. In this chapter, we summarize basic aspects to consider before designing and generating humanized models, especially when they are aimed to test antisense-based therapies.
Generation of Humanized Zebrafish Models for the In Vivo Assessment of Antisense Oligonucleotide-Based Splice Modulation Therapies
Authors: Schellens Renske , de Vrieze Erik , Slijkerman Ralph , Kremer Hannie , van Wijk Erwin
Published: February 2022

Antisense oligonucleotide (AON)-based splice modulation is the most widely used therapeutic approach to redirect precursor messenger RNA (pre-mRNA) splicing. To study the functional effect of humanmutations affecting pre-mRNAsplicing for which AON-based splice redirection would be a potential therapeutic option, humanized knock-in animal models are pivotal. A major limitation of using humanized animal models for this purpose is the reported poor recognition of human splice sites by the splicing machineries of other species. To overcome this problem, we provide a detailed guideline for the generation of functional humanized knock-in zebrafish models to assess the effect of mutation-induced aberrant splicing and subsequent AON-based splice modulation therapy.
Use of Small Animal Models for Duchenne and Parameters to Assess Efficiency upon Antisense Treatment
Authors: Lu-Nguyen Ngoc , Malerba Alberto , Popplewell Linda
Published: February 2022

Duchenne muscular dystrophy (DMD) is a rare genetic disease affecting 1 in 5000 newborn boys. It is caused by mutations in the DMD gene with a consequent lack of dystrophin protein that leads to deterioration of myofibers and their replacement with fibro-adipogenic tissue. Using antisense oligonucleotides (AONs) to modify out-of-frame mutations in the DMD gene, named exon skipping, is currently considered among the most promising treatments for DMD patients. The development of this strategy is rapidly moving forward, and AONs designed to skip exons 51 and 53 have received accelerated approval in the USA. In preclinical setting, the mdx mouse model, carrying a point mutation in exon 23 of the murine Dmd gene that prevents production of dystrophin protein, has emerged as a valuable tool, and it is widely used to study in vivo therapeutic approaches for DMD. Here we describe the methodology for intravenous delivery of AONs targeting dystrophin through tail vein of mdx mice. Furthermore, the most relevant functional analyses to be performed in living mice, and the most informative histopathological and molecular assays to evaluate the effect of this treatment are detailed.
Delivery of Antisense Oligonucleotides to the Mouse Brain by Intracerebroventricular Injections
Authors: Metz Tom , Kuijper Elsa C. , van Roon-Mom Willeke M. C.
Published: February 2022

The use of antisense oligonucleotides (AONs) is a promising therapeutic strategy for central nervous system disorders. However, the delivery of AONs to the central nervous system is challenging because their size does not allow them to diffuse over the blood–brain barrier (BBB) when injected systemically. The BBB can be bypassed by administering directly into the brain. Here we describe a method to perform single and repeated intracerebroventricular injections into the lateral ventricle of the mouse brain.
Intrathecal Delivery of Therapeutic Oligonucleotides for Potent Modulation of Gene Expression in the Central Nervous System
Authors: Kennedy Zachary , Gilbert James W. , Godinho Bruno M. D. C.
Published: February 2022

Therapeutic oligonucleotides hold tremendous potential for treating central nervous system (CNS) disorders. The route of administration of oligonucleotides significantly impacts both distribution and silencing efficiency. Here, we describe a technically simple, clinically relevant method to administer oligonucleotide compounds into the CNS via direct intrathecal injections. This method achieves distribution throughout the CNS rapidly and permits high-throughput testing of oligonucleotide efficacy and potency in mammals.
Protocol for Isolation and Culture of Mouse Hepatocytes (HCs), Kupffer Cells (KCs), and Liver Sinusoidal Endothelial Cells (LSECs) in Analyses of Hepatic Drug Distribution
Authors: Elvevold Kjetil , Kyrrestad Ingelin , Smedsrød Bård
Published: February 2022

Development of the new generation of drugs (e.g., oligo- and polynucleotides administered intravascularly either as free compounds or as nano-formulations) frequently encounters major challenges such as lack of control of targeting and/or delivery. Uncontrolled or unwanted clearance by the liver is a well-known and particularly important hurdle in this respect. Hence, reliable techniques are needed to identify the type(s) of liver cells, receptors, and metabolic mechanisms that are responsible for unwanted clearance of these compounds.

We describe here a method for the isolation and culture of the major cell types from mouseliver: hepatocytes (HCs), Kupffer cells (KCs), and liver sinusoidal endothelial cells (LSECs). The presently described protocol employs perfusion of the liver with a collagenase-based enzyme preparation to effectively transform the intact liver to a single cell suspension. From this initial cell suspension HCs are isolated by specified centrifugation schemes, yielding highly pure HC preparations, and KCs and LSECs are isolated by employing magnetic-activated cell sorting (MACS). The MACS protocol makes use of magnetic microbeads conjugated with specific antibodies that bind unique surface antigens on either KCs or LSECs. In this way the two cell types are specifically and separately pulled out of the initial liver cell suspension by applying a magnetic field, resulting in high purity, yield, and viability of the two cell types, allowing functional studies of the cells.

If the drug compound in question is to be studied with respect to liver cell distribution of intravascularly administered drug compounds the isolated cells can be analyzed directly after isolation. Detailed studies of receptor-ligand interactions and/or dynamics of intracellular metabolism of the compound can be conducted in primary surface cultures of HCs, LSECs, and KCs established by seeding the isolated cells on specified growth substrates.
Patent Considerations When Embarking on New Antisense Drug Programs
Authors: Gainey Laurence D. S.
Published: February 2022

The aim of this chapter is to provide some key information on patents and the patent system to assist someone embarking on the design, development, and commercialization of new antisense drugs.

Here I outline certain key topics such as what is a patent? why patent? how do I protect my molecule with a patent? confidentiality, searching for the same or similar molecules in the prior art, data requirements, the patenting timeline and freedom to operate.
Design of Bifunctional Antisense Oligonucleotides for Exon Inclusion
Authors: Zhou Haiyan
Published: February 2022

Bifunctional antisense oligonucleotide (AON) is a specially designed AON to regulate pre-messenger RNA (pre-mRNA) splicing of a target gene. It is composed of two domains. The antisense domain contains sequences complementary to the target gene. The tail domain includes RNA sequences that recruit RNA binding proteins which may act positively or negatively in pre-mRNA splicing. This approach can be designed as targeted oligonucleotide enhancers of splicing, named TOES, for exon inclusion; or as targeted oligonucleotide silencers of splicing, named TOSS, for exon skipping. Here, we provide detailed methods for the design of TOES for exon inclusion, using SMN2 exon 7 splicing as an example. A number of annealing sites and the tail sequences previously published are listed. We also present methodology of assessing the effects of TOES on exon inclusion in fibroblasts cultured from a SMA patient. The effects of TOES on SMN2 exon 7 splicing were validated at RNA level by PCR and quantitative real-time PCR, and at protein level by western blotting.
Securitization, Emergency and the Rediscovery of Responsibility in Times of Pandemic: Analyzing Political Discourses from the European South
Authors: Boukala Salomi , Serafis Dimitris
Published: February 2022

This chapter intends to provide an argumentative perspective on the justification of securitization by Southern EU’s political leaders in times of a public health crisis and the COVID-19 pandemic by examining instances of public discourses, specifically addresses to the nation of four EU leaders with different ideological positioning, in different social settings of the European South. Based on the theory of securitization, we perceive public debate as a polylogical phenomenon where multiple actors, from multiple (ideological) positions, in multiple times and spaces interact, creating a complex network of public communication while expressing and supporting their claims. Through this prism, our aim is to shed light on argumentative polylogues by unveiling whether and how the state of emergency has been justified. We employ the frame of the Discourse-Historical Approach (DHA) to Critical Discourse Studies (CDS) (Reisigl & Wodak, 2016) to study the socio-historically conditions against which established endoxical premises are (re)constructed by the political leadership and how these interrelate with specific argumentation strategies (topoi) in the social settings under scrutiny. We then draw on the quasi-Y structure provided by the Argumentum Model of Topics (AMT) (Rigotti & Greco, 2019) to scrutinize the interplay of topical and endoxical premises in the development of single standpoint-argument couplings.
Staying Up to Date with Fact and Reason Checking: An Argumentative Analysis of Outdated News
Authors: Musi Elena , Rocci Andrea
Published: February 2022

This paper tackles outdated news about COVID-19 as a type of misinformation from an argumentative perspective, focusing on the fact-checker Snopes. In rapidly changing information environments the circulation of outdated news can be highly detrimental causing risky behaviors. Such type of misinformation is difficult to pin down through fact-checking since encompassing different types of contents, motivations and channels. To fully understand this phenomenon we deem necessary to move away from a naïve view of fact checking to an argumentative one. But what are the argumentative configurations of outdated statements in the context of the current information ecosystem? To answer this question we rely on the distinction between upstream and downstream argumentation to anchor the kind of issues put forward by outdated statements. We then take as a sample all the news that have been rated as “outdated” and “miscaptioned” by Snopes during the pandemic and analyse the type of source, the semantic type of news claim and the argumentative role played by the outdated information. We come up with an argumentative taxonomy of outdated news where the presence of multimodal information as well as the semantic-argumentative role played by outdated statements pattern with the spread of mis- and disinformation.
Good and Ought in Argumentation: COVID-19 as a Case Study
Authors: Soria-Ruiz Andrés , Maldonado Mora , Stojanovic Isidora
Published: February 2022

The present chapter concerns arguments whose conclusions take the form of a prescription such asyou ought to do such-and-such, which have driven much public discussion and policy since the beginning of the COVID-19 pandemic. We aim to tackle a hitherto under-explored characteristic of many such normative arguments, namely, the relationship between evaluative and deontic propositions, depending on whether they occur as premises or conclusions in such arguments. In order to investigate how willing people are to argue from what is good to what one ought to do, and the other way round, we conducted an Inferential Judgment Experiment. Participants were presented with arguments involving deontic and evaluative propositions, and had to judge whether they could infer conclusion from premise. The stimuli that we used are tightly related to the argumentation surrounding the pandemic, regarding the measures of preventing the spread of COVID-19. The results of the study show that there is a robust inferential connection between evaluatives and deontics, but at the same time, a significant asymmetry as well. We explore several theoretical approaches to the relationship between the deontic and the evaluative realm, and test their predictions against the results of our study.
Simulating Anisotropic Diffusion in Heterogeneous Brain Regions
Authors: Mardal Kent-André , Rognes Marie E. , Thompson Travis B. , Valnes Lars Magnus
Published: February 2022

In this chapter, we return to our model problem (1.1) and bring together the tools and techniques introduced in Chapters 3 to 5.
Concluding Remarks and Outlook
Authors: Mardal Kent-André , Rognes Marie E. , Thompson Travis B. , Valnes Lars Magnus
Published: February 2022

Physics-based modeling of brain mechanics, informed by multi-modal imaging data, is an exciting research area at the frontier of science.
Bypass and Other Engines
Authors: Decher Reiner
Published: February 2022

The modern fan engine has a propeller-like component whose aerodynamic performance differs from that of a propeller at the blade level but serves the same function. The blading aerodynamics differs from that of a compressor in notable ways.
Other Components of the Jet Engine
Authors: Decher Reiner
Published: February 2022

Thecompressor may be the challenging component of a gas turbine engine, a combustor and a turbine also must function efficiently. The design aspects of these two components are described here together with how the engine is configured and works as a system.
Pressure: The Bernoulli Principle and Flow Energy Conservation
Authors: Decher Reiner
Published: February 2022

The relation between descriptive variables of flowing air, pressure and the like, and the dynamic field, speeds or velocities, are often invoked for their understanding. Such relationships depend on whether the flow is compressible or not. When it is, physical work done by air elements on one another, become important. This chapter, virtually devoid of illuminating images, nevertheless sheds light on how to think about air flows in general and how to deduce the local pressures from knowledge of the flow field.
Pressure, Pressure, It’s All About Pressure!
Authors: Decher Reiner
Published: February 2022

The airplane or wing designer seeks to harness the pressure forces associated with the motion of air. These have important consequences for the operation of an airplane in flight because the forces on it must be balanced and flight should be stable. We examine the various descriptive pressures that are relevant and look at airfoil and wing data that is displayed as clean and compact. We introduce yet another consequence of the nature of vorticity associated with lift, namely drag that is associated with the trailing vortex system. The discussion is concluded with thoughts about how the pilot of an airplane thinks about speed.
Putting It All Together
Authors: Decher Reiner
Published: February 2022

We examine the lift and drag characteristics of wings as these are affected by the two physical aspects of flight: friction effects and for higher speed, air compressibility. We encounter the phenomenon of stall, shock waves, and visible condensation. These make flight phenomena interesting and challenging. Friction effects in supersonic flight are shown to be an almost negligibly small part of the heating of aircraft skin surfaces.
Propulsion for Flight: Power or Thrust?
Authors: Decher Reiner
Published: February 2022

An engine is required to provide the power necessary for overcoming the drag of flight. There are not many engine types available to perform that important function: they all have advantages and limitations. They share common features and are different in fundamental ways. The histories of their development paced the history of man’s ability to fly and the modern gas turbine engine is the climax of that progression toward today’s state of aviation. In this chapter we focus on the salient features of engines as they relate to flight.
A reverse Hölder inequality for the gradient of solutions to Trudinger’s equation
Authors: Saari Olli , Schwarzacher Sebastian
Published: February 2022

We provide a higher integrability result for the gradient of positive solutions to Trudinger’s equation (also known as the doubly non-linear equation) for the range $$p\in [2,\infty )$$

p
∈
[
2
,
∞
)

. The estimate is achieved by refining a construction of intrinsic cylinders from the vectorial setting by incorporating estimates that are only available in the scalar case.
Hand dominance and experience improve bimanual performance on arthroscopic simulator task
Authors: Feeley Aoife A. , Gibbons John P. , Feeley Iain H. , Fitzgerald Eilis , Merghani Khalid , Sheehan Eoin
Published: February 2022

Purpose

The aim of this study was to identify if experience in arthroscopy confers ambidexterity to the operator and the role of baseline characteristics in arthroscopic simulator performance.

Methods

A prospective comparative study was carried out across four regional Orthopaedic training centres. Participants were divided into novice, intermediate or experienced groups based on arthroscopic experience. Baseline demographics including age, sex, handedness, and gaming history were also collected. Following familiarisation with the procedure, participants were asked to complete a simulated task requiring bimanual control consisting of visualisation with camera control and manipulation of highlighted objects using a grasping instrument. One attempt using camera control and grasping accuracy per hand was performed by each participant, with scores for each hand collected for analysis. Performance scores for camera alignment, camera path length, grasper path length and grasping efficiency were collected. Time taken to completion was also noted for each attempt.

Results

Fifty-six participants were recruited to the study. A significant difference in grasping efficiency between groups in the dominant hand was demonstrated (p = 0.013). Novices demonstrated laterality with superior performance in grasping efficiency in the dominant hand (p = 0.001). No significant difference was noted between dominant and non-dominant hand performance in the experienced group.

Conclusion

Arthroscopic simulation-based training is a valuable learning tool for orthopaedic training. This study demonstrated that experienced orthopaedic surgeons have a greater degree of ambidexterity than intermediate or novice groups, hypothesised by authors to be conferred through conventional orthopaedic training. Dedicated bimanual control tasks to reduce laterality in trainees should be incorporated in simulated surgical curricula.

Level of evidence

III.
Interaction of childhood abuse and depressive symptoms on cortical thickness: a general population study
Authors: Voss Sara , Frenzel Stefan , Klinger-König Johanna , Janowitz Deborah , Wittfeld Katharina , Bülow Robin , Völzke Henry , Grabe Hans J.
Published: February 2022

Childhood abuse was inconsistently related to whole-brain cortical thickness in former studies. However, both childhood abuse and cortical thickness have been associated with depressive symptoms. We hypothesised that childhood abuse moderates the association between depressive symptoms and cortical thickness. In 1551 individuals of the general population, associations between whole-brain cortical thickness and the interaction of childhood abuse (emotional, physical, and sexual) and depressive symptoms were analysed using an ANCOVA. Linear regression analyses were used to estimate the same effect on the cortical thickness of 34 separate regions (Desikan-Killiany-atlas). A significant interaction effect of childhood abuse and depressive symptoms was observed for whole-brain cortical thickness (F(2, 1534) = 5.28, p = 0.007). A thinner cortex was associated with depressive symptoms in abused (t value = 2.78, p = 0.025) but not in non-abused participants (t value = − 1.50, p = 0.224). Focussing on non-depressed participants, a thicker whole-brain cortex was found in abused compared to non-abused participants (t value = − 2.79, p = 0.025). Similar interaction effects were observed in 12 out of 34 cortical regions. Our results suggest that childhood abuse is associated with reduced cortical thickness in subjects with depressive symptoms. In abused subjects without depressive symptoms, larger cortical thickness might act compensatory and thus reflect resilience against depressive symptoms.
Combining vestibular rehabilitation with noisy galvanic vestibular stimulation for treatment of bilateral vestibulopathy
Authors: Eder Josefine , Kellerer Silvy , Amberger Tamara , Keywan Aram , Dlugaiczyk Julia , Wuehr Max , Jahn Klaus
Published: February 2022

Objective

Noisy galvanic vestibular stimulation (nGVS) has been shown to partly restore vestibular function and to stabilize stance and gait in patients with incomplete bilateral vestibulopathy (BVP). Here, we examined potential synergistic effects of nGVS when combined with standardized vestibular rehabilitation training (VRT).

Methods

23 patients with confirmed BVP received a 30-min vestibular rehabilitation training (VRT) program three times a week for 2 weeks. The intervention group (n = 12) was stimulated with nGVS (at individually determined optimal amplitudes) during training, whereas the control group (n = 11) received zero-amplitude nGVS (sham stimulation) during training. Outcome measurements assessed at baseline, after 2 weeks of training, and at 2-week follow-up included quantitative posturography, instrumented gait analysis, Timed Up and Go Test (TUG), Functional Gait Assessment (FGA), and clinical scores related to quality of life and balance confidence.

Results

After 2 weeks of VRT, all patients showed moderate improvement in balance. Irrespective of nGVS treatment, performance improved in the TUG (p < 0.013), and in the FGA (p < 0.040). Furthermore, base of support when walking with closed eyes was reduced after 2-week training (p < 0.003). Postural sway did not change. There was no difference between groups and thereby no evidence for an additional influence of nGVS on the VRT treatment effects.

Conclusion

nGVS does not induce synergistic treatment effects in combination with VRT in patients with BVP when applied during treatment sessions. Hence, rather than being applied in parallel, nGVS and VRT might be complementary therapeutic options with nGVS being used during postural activities in daily life, e.g., walking.
UEG and EAES rapid guideline: Systematic review, meta-analysis, GRADE assessment and evidence-informed European recommendations on TaTME for rectal cancer
Authors: Milone Marco , Adamina Michel , Arezzo Alberto , Bejinariu Nona , Boni Luigi , Bouvy Nicole , de Lacy F Borja , Dresen Raphaëla , Ferentinos Konstantinos , Francis Nader K. , Mahaffey Joe , Penna Marta , Theodoropoulos George , Kontouli Katerina Maria , Mavridis Dimitris , Vandvik Per Olav , Antoniou Stavros A.
Published: February 2022

Background

Evidence and practice recommendations on the use of transanal total mesorectal excision (TaTME) for rectal cancer are conflicting.

Objective

We aimed to summarize best evidence and develop a rapid guideline using transparent, trustworthy, and standardized methodology.

Methods

We developed a rapid guideline in accordance with GRADE, G-I-N, and AGREE II standards. The steering group consisted of general surgeons, members of the EAES Research Committee/Guidelines Subcommittee with expertise and experience in guideline development, advanced medical statistics and evidence synthesis, biostatisticians, and a guideline methodologist. The guideline panel consisted of four general surgeons practicing colorectal surgery, a radiologist with expertise in rectal cancer, a radiation oncologist, a pathologist, and a patient representative. We conducted a systematic review and the results of evidence synthesis by means of meta-analyses were summarized in evidence tables. Recommendations were authored and published through an online authoring and publication platform (MAGICapp), with the guideline panel making use of an evidence-to-decision framework and a Delphi process to arrive at consensus.

Results

This rapid guideline provides a weak recommendation for the use of TaTME over laparoscopic or robotic TME for low rectal cancer when expertise is available. Furthermore, it details evidence gaps to be addressed by future research and discusses policy considerations. The guideline, with recommendations, evidence summaries, and decision aids in user-friendly formats can also be accessed in MAGICapp: https://app.magicapp.org/#/guideline/4494.

Conclusions

This rapid guideline provides evidence-informed trustworthy recommendations on the use of TaTME for rectal cancer.
Haben Patient*innen die moralische Pflicht, ihre klinischen Daten für Forschung bereitzustellen? Eine kritische Prüfung möglicher Gründe
Authors: Jungkunz Martin , Köngeter Anja , Mehlis Katja , Spitz Markus , Winkler Eva C. , Schickhardt Christoph
Published: February 2022

Die Sekundärnutzung klinischer Daten für Forschungs- und Lernaktivitäten hat das Potenzial, medizinisches Wissen und klinische Versorgung erheblich zu verbessern. Zur Realisierung dieses Potenzials bedarf es einer ethischen und rechtlichen Grundlage für die Datennutzung, vorzugsweise in Form der Einwilligung von Patient*innen. Damit stellt sich die grundsätzliche Frage: Haben Patient*innen eine moralische Pflicht, ihre klinischen Daten für Forschungs- und Lernaktivitäten zur Verfügung zu stellen?

Auf Basis eines ethischen Ansatzes, der als „sorgender Liberalismus“ bezeichnet werden kann, werden folgende Argumente zur Begründung einer Pflicht von Patient*innen zur Bereitstellung ihrer klinischen Daten für Forschungs- und Lernaktivitäten auf Plausibilität und moralisches Gewicht untersucht: die allgemeine Hilfspflicht; Solidarität; die Pflicht zu gemeinwohlförderlichem Handeln; das Trittbrettfahrerargument; transgenerationale Gerechtigkeit; das Prinzip des Zurückgebens; das Prinzip des Nicht-Schädigens; die Forschungsfreiheit und der Wert der Wissenschaft.

Die allgemeine Hilfspflicht und die Pflicht zu gemeinwohlförderlichem Handeln sind gewichtige Gründe für eine moralische Pflicht von Patient*innen zur Bereitstellung ihrer klinischen Daten für Forschungs- und Lernaktivitäten. Das Argument der transgenerationalen Gerechtigkeit und das Prinzip des Zurückgebens sind ethisch schwache Gründe für eine solche Pflicht, können jedoch eine motivationale Rolle spielen. Die anderen Gründe sind nicht geeignet, eine Pflicht zu begründen. Das Ergebnis ist in mehrfacher Hinsicht relevant: für Patient*innen, die um die Einwilligung in die Sekundärnutzung ihrer klinischen Daten gebeten werden; für die ethische Diskussion der Frage, ob und inwieweit Abstriche von der klassischen spezifischen Einwilligung unter bestimmten Bedingungen ethisch akzeptabel sind; für die rechtwissenschaftliche Diskussion der Bedingungen für eine juristisch verhältnismäßige Sekundärnutzung klinischer Daten für Forschungs- und Lernaktivitäten.
Being Overweight or Obese Is Associated with an Increased Platelet Reactivity Despite Dual Antiplatelet Therapy with Aspirin and Clopidogrel
Authors: Puccini Marianna , Rauch Christian , Jakobs Kai , Friebel Julian , Hassanein Adel , Landmesser Ulf , Rauch Ursula
Published: February 2022

Purpose

Obese patients exhibit an overall increased platelet reactivity and a reduced sensitivity to antiplatelet therapy. The aim of this study is to evaluate the platelet reactivity measured by impedance aggregometry in overweight and obese patients and chronic coronary syndrome (CCS) that were treated with dual antiplatelet therapy (DAPT).

Methods

Platelet aggregation was assessed by impedance aggregometry in patients with CCS receiving DAPT (aspirin plus clopidogrel). We compared the platelet reactivity in patients with a normal weight versus overweight or obese patients. Furthermore, the correlation between the body mass index (BMI) and adenosine diphosphate- (ADP-) or thrombin receptor-activating peptide- (TRAP-) dependent platelet aggregation was analyzed.

Results

64 patients were included in the study of which 35.9% were patients with normal weight. A higher ADP- and TRAP-dependent platelet reactivity was observed in overweight and obese patients (ADP: median 27 units (U) [IQR 13–39.5] vs. 7 U [6–15], p < 0.001 and TRAP: 97 U [73–118.5] vs. 85 U [36–103], p = 0.035). Significant positive correlations were observed between agonist-induced platelet reactivity and BMI.

Conclusion

Despite the use of DAPT, a higher platelet reactivity was found in overweight and obese patients with CCS. If these patients will benefit from treatment with more potent platelet inhibitors, it needs to be evaluated in future clinical trials.
Excess risk and clusters of symptoms after COVID-19 in a large Norwegian cohort
Authors: Caspersen Ida Henriette , Magnus Per , Trogstad Lill
Published: February 2022

Physical, psychological and cognitive symptoms have been reported as post-acute sequelae for COVID-19 patients but are also common in the general uninfected population. We aimed to calculate the excess risk and identify patterns of 22 symptoms up to 12 months after COVID-19. We followed more than 70,000 adult participants in an ongoing cohort study, the Norwegian Mother, Father and Child Cohort Study (MoBa) during the COVID-19 pandemic. Infected and non-infected participants registered presence of 22 different symptoms in March 2021. One year after infection, 13 of 22 symptoms were associated with SARS-CoV-2 infection, based on relative risks between infected and uninfected subjects. For instance, 17.4% of SARS-CoV-2 infected cohort participants reported fatigue that persist 12 months after infection, compared to new occurrence of fatigue that had lasted less than 12 months in 3.8% of non-infected subjects (excess risk 13.6%). The adjusted relative risk for fatigue was 4.8 (95% CI 3.5–6.7). Two main underlying factors explained 50% of the variance in the 13 symptoms. Brain fog, poor memory, dizziness, heart palpitations, and fatigue had high loadings on the first factor, while shortness-of breath and cough had high loadings on the second factor. Lack of taste and smell showed low to moderate correlation to other symptoms. Anxiety, depression and mood swings were not strongly related to COVID-19. Our results suggest that there are clusters of symptoms after COVID-19 due to different mechanisms and question whether it is meaningful to describe long COVID as one syndrome.