bluuebunny/crossref_metadata_2025 huggingface dataset:
Motor unit distribution and recruitment in spastic and non-spastic bilateral biceps brachii muscles of chronic stroke survivors
Authors: Liu Yang , Chen Yen-Ting , Zhang Chuan , Zhou Ping , Li Sheng , Zhang Yingchun
Published: August 2022

Objective. This study aims to characterize the motor units (MUs) distribution and recruitment pattern in the spastic and non-spastic bilateral biceps brachii muscles (BBMs) of chronic stroke survivors. Approach. High-density surface electromyography (HD-sEMG) signals were collected from both spastic and non-spastic BBMs of fourteen chronic stroke subjects during isometric elbow flexion at 10%, 30%, 50% and 100% maximal voluntary contractions (MVCs). By combining HD-sEMG decomposition and bioelectrical source imaging, MU innervation zones (MUIZs) of the decomposed MUs were first localized in the 3D space of spastic and non-spastic BBMs. The MU depth defined as the distance between the localized MUIZ and its normal projection on the skin surface was then normalized to the arm radius of each subject and averaged at given contraction level. The averaged MU depth at different contraction levels on a specific arm side (intra-side) and the bilateral depths under a specific contraction level (inter-side) were compared. Main results. The average depth of decomposed MUs increased with the contraction force and significant differences observed between 10% vs 50% (p < 0.0001), 10% vs 100% (p < 0.0001) and 30% vs 100% MVC (p = 0.0017) on the non-spastic side, indicating that larger MUs with higher recruitment threshold locate in deeper muscle regions. In contrast, no force-related difference in MU depth was observed on the spastic side, suggesting a disruption of orderly recruitment of MUs with increase of force level, or the MU denervation and the subsequent collateral reinnervation secondary to upper motor neuron lesions. Inter-side comparison demonstrated significant MU depth difference at 10% (p= 0.0048) and 100% force effort (p= 0.0026). Significance. This study represents the first effort to non-invasively characterize the MU distribution inside spastic and non-spastic bilateral BBM of chronic stroke patients by combining HD-sEMG recording, EMG signal decomposition and bioelectrical source imaging. The findings of this study advances our understanding regarding the neurophysiology of human muscles and the neuromuscular alterations following stroke. It may also offer important MU depth information for botulinum toxin injection in clinical post-stroke spasticity management.
A quantitative analysis of a generalized Hopfield model that stores and retrieves mismatched memory patterns
Authors: Leuzzi Luca , Patti Alberto , Ricci-Tersenghi Federico
Published: August 2022

We study a class of Hopfield models where the memories are represented by a mixture of Gaussian and binary variables and the neurons are Ising spins. We study the properties of this family of models as the relative weight of the two kinds of variables in the patterns varies. We quantitatively determine how the retrieval phase squeezes toward zero as the memory patterns contain a larger fraction of mismatched variables. As the memory is purely Gaussian retrieval is lost for any positive storage capacity. It is shown that this comes about because of the spherical symmetry of the free energy in the Gaussian case. Introducing two different memory pattern overlaps between spin configurations and each contribution to the pattern from the two kinds of variables one can observe that the Gaussian parts of the patterns act as a noise, making retrieval more difficult. The basins of attraction of the states, the accuracy of the retrieval and the storage capacity are studied by means of Monte Carlo numerical simulations. We uncover that even in the limit where the network capacity shrinks to zero, the (few) retrieval states maintain a large basin of attraction and large overlaps with the mismatched patterns. So the network can be used for retrieval, but with a very small capacity.
Walking characteristics and collision avoidance strategy in bidirectional pedestrian flow: a study focused on the influence of social groups
Authors: Zhang Bosi , Gao Youmei , Han Yong , Liang Siyi , Chen Qiaolin , Yu Zhihong
Published: August 2022

The walking characteristics and collision avoidance strategies in bidirectional pedestrian flow with both individuals and groups under three different pedestrian densities were investigated experimentally in the present study. The results showed that pedestrians formed lanes in bidirectional flow, and the lane number basically increased with pedestrian density. In addition, the lane number was positively related to the number of groups in the first row of the two opposite crowds. Compared with the no-group experiments, the walking speed of pedestrians showed less difference in the experiments with groups. The fundamental diagram of the bidirectional pedestrian flow with groups under different pedestrian density conditions was calculated. Three types of collision avoidance strategies, detouring around conflicting pedestrians, passing through the conflicting group in the middle, and group splitting, were summarised based on the experimental results. The statistical results of the three collision avoidance strategies adopted by different size groups under the low, medium, and high pedestrian density conditions were obtained. It was found that the large group was more likely to split into subgroups when they encountered conflicting pedestrians, while the small group was more likely to detour around the conflicting pedestrians. For the same group size, the larger the pedestrian density, the higher the proportion of groups that would choose to split into subgroups during the collision avoidance process.
Addressing digitalization though out a prototyping framework for agile smart services development: the case of Livorno Port
Authors: Tardo A , Pagano P , Antonelli S , Rao S
Published: August 2022

One of the crucial challenges of maritime transport is digitalization through the implementation of proper IT solutions. Development and deployment of such solutions allows seaports to increase their overall efficiency, to lower costs and improve performance times of the intra-terminal operations, to improve information flow and decision-making and to decrease the environmental footprint by addressing the sustainability. Nevertheless, the digitalization levels are heterogeneous and depend on different factors, such as seaport size, cargo volumes and type, stakeholders’ needs, business models and investments. We propose a prototyping framework for agile smart service development relying on a set of standard and open-source technologies. The proposed framework is validated at The Port Network Authority of the Northern Tyrrhenian Sea (Port of Livorno) and the transferability of research results is assessed against the Port of Singapore, the most important hub of the Asian region.
Experimental study on smoke flow behaviour under ships’ deck structures in early stages of fire
Authors: Kimura Arata , Oka Yasushi , Oka Hideyuki , Ota Susumu
Published: August 2022

In ships’ cargo spaces carrying vehicles, so called “vehicle spaces”, fire has sometimes taken place and safety measures against such fire is under discussion at the International Maritime Organization (IMO). Early detection of fire is one of the essential elements of such safety measures. Location of fire detectors affects swiftness of detection of fire, and in onshore buildings, fire detectors are generally installed directly on ceilings because there are no obstacles under ceilings and smoke spreads along the ceilings. On the other hand, structures below ceilings, i.e., decks, of vehicle spaces are quite different from those of onshore buildings due to strength members below a deck, such as stiffeners and web beams. The appropriate positions of smoke detectors in a vehicle space, including vertical positions of detectors from a ceiling, has not been well-understood, while the maximum coverage of a detector is determined by an international regulation. In this study, the effect of structures below the ceilings of vehicle spaces on detection of fire has been investigated and the appropriate positions of smoke detectors including vertical positions have been considered, in particular, for smouldering fire sources. For this purpose, a one-sixth scaled deck model was prepared to simulate a part of a vehicle space and fire experiments were conducted using a small-scaled fire source. The effect of the structure on a smoke flow beneath the ceiling was experimentally investigated under the condition that the flow had a weak driving force in a smouldering fire or an early stage of fire. In the experiment, the flow was visualized using a laser and the smoke density expressed with the extinction coefficient was also measured. In addition, a small flaming fire source was used during the experiment, to further investigate a possibility of detection in an early stage of fire. The vertical profiles of smoke density were measured using the laser transmissometer. Furthermore, a smoke flow was visualized using continuous wave laser. As the results, it is concluded that it is appropriate to install smoke detectors at the lower end of the longitudinal stiffener, instead of installing on the ceilings in vehicle spaces.
Standardization of Risk Assessment in Navigation
Authors: Froese Jens
Published: August 2022

Marine traffic safety assessed by quantitative instead of qualitative methods is increasingly required. There are mature methods available to conduct a quantitative risk assessment such as IWRAP [1], resulting in collision and grounding probabilities. There is, however, the difficulty to determine the so-called causation factor having an impact on the results but there is currently no reliable method to fix it. To globally collect relevant empirical data to allow a statical determination could make risk analysis results less questionable but comparable.
Wave-field prediction based on radar snapshots taken on a moving vessel
Authors: Law Yun Zhi , Santo Harrif , Chua Kie Hian
Published: August 2022

This paper presents a framework that is capable of producing phase-resolved wave-field prediction in real-time based on radar measurements taken off a moving vessel. Phase-resolved wave prediction capability is essential in providing the operating environment that an autonomous vessel would encounter in order to plan for maneuvering and pathway. We use Higher Order Spectral (HOS) method to generate synthetic short-crested wave-field. Based on the snapshots of wave-field as would be obtained by an X-band radar mounted on a moving vessel, we perform wave-field reconstruction and propagation using a predictive model based on linear wave theory to produce predictions of encountered wave-field in real-time. Comparisons are made between the predicted encountered wave-field and the underlying synthetic wave-field, and reasonably good agreement can be achieved considering the use of low-order model. The wave prediction capability can be further evolved into the prediction of vessel motion and structural response.
From captain to button-presser: operators’ perspectives on navigating highly automated ferries
Authors: Veitch Erik , Christensen Kim Alexander , Log Markus , Valestrand Erik Thule , Lundheim Sigurd Hilmo , Nesse Martin , Alsos Ole Andreas , Steinert Martin
Published: August 2022

Teaming with Artificial Intelligence (AI) is changing the way seafarers work. We show that a new kind of seafaring is emerging, characterized by cooperation with AI systems. In this format of seafaring, navigation tasks are controlled automatically while human operators manage the automation, always “in the loop” and ready to take over control if necessary. Ideally, this arrangement sees improvements in overall system performance and safety. However, little is known today about how this format of work will unfold in real-world operations. We investigate this topic by interviewing operators (n = 5) on ferries recently outfitted with state-of-the-art automated navigation technology. We used a mixed-methods approach to analyze the case study interviews, combining quantitative text analysis with Grounded Theory qualitative analysis techniques. The results show that operators perceived a shift towards a backup role coincident with increasing agency of machine autonomy. This role shift was characterized by “button-pressing” to start the machine autonomy and subsequently intervening to stop it when things go wrong. We observed that this shift led to boredom, deskilling, stretched resources, and compromised organizational harmony – effects running counter to the intention of improved system performance and safety. Synthesizing the findings, we present (1) effects across three operational dimensions: (i) tasks, (ii) human-computer interaction, (iii) organization; and (2) a definition of collaborative (human-AI) seafaring. By identifying issues in the early implementation of highly automated ship navigation, we hope to guide designers of Maritime Autonomous Surface Ships (MASSs) away from potential pitfalls and towards development more in tune with real-world demands of collaborative work.
Abatement of GHG emissions onboard mobile offshore units
Authors: Ng Chunwee , Li Jizhao , Mishra Rakesh , Fagan Conn
Published: August 2022

The International Maritime Organisation (IMO) is setting clear and ambitious goals for the decarbonisation of the shipping industry through the introduction of new regulations like the Energy Efficiency Design Index (EEDI), Energy Efficiency Existing Ship Index (EEXI) and Carbon Intensity Indicator (CII). However, these new regulations do not cover mobile offshore units like the Floating Production Storage and Offloading (FPSO) units that fall under the same maritime regime. To embrace sustainability in their corporate strategies and improve their public image, it is in the interest of existing oil and gas companies and operators to embark on a program of abating Greenhouse Gas (GHG) emissions through careful measurement and analysis. This paper is aimed at providing an overview of the typical FPSO’s GHG emissions that originates from sources such as power generation, flaring, leakages and tank venting. The paper goes in-depth concerning some potential abatement measures that can be taken to reduce such emissions. This is followed by a case study of an FPSO assessed for the voluntary DNV class notation, Abate, to discuss how a competent third-party like DNV can play a significant role in helping offshore oil and gas companies demonstrate and achieve abatement in GHG emissions from their assets.
Numerical visualisation on applying a five-stage multi-scaled square turbulence-generating grid to generating turbulence
Authors: Suzuki Hiroki
Published: August 2022

This study presents the numerical visualisation of turbulence generated by a five-stage square-type multi-scale turbulence grid. The present study applies a turbulence grid with an increased number of stages to five, in contrast to previous studies using multi-scale turbulence grids with four stages. For the present numerical visualisation, direct numerical analysis is used in this analysis. This analysis uses the high-order central difference schemes and the third-order Runge-Kutta scheme. In addition to the multi-scale turbulence grid with five stages, the present study also covers two turbulence grids with four stages for reference. By using the external force term in the governing equations, the present multi-scale turbulence grids were formed numerically in the computational domain. The spatial homogeneity of the downstream turbulence field is approached in this work. The turbulence generated by the turbulence grids with four stages is characterised by a flow structure with a doughnut-like instantaneous velocity figure in the downstream region. By examining contour diagrams of the streamwise instantaneous velocity, the present study can see that the spatial homogeneity of the turbulence field downstream is improved by increasing the number of stages for the turbulence grid.
Uncertainty analysis of velocity field calibration in wind tunnels based on GUM and MCM
Authors: Du Yufeng , Xiong Neng , Lin Jun
Published: August 2022

The flow quality of wind tunnel is an important index to judge the performance of the wind tunnel, and it directly determines whether the aircraft can obtain high-quality test data, and directly relates to the ability of the wind tunnel to be applied to basic aerodynamic research. Velocity field calibration is necessary in flow field calibration and an important prerequisite for the accurate simulation of Mach number in wind tunnel tests. In this paper, the GUM method and the MCM method are used to compare and analyze the uncertainty of velocity field calibration of the high-speed wind tunnel, and the uncertainty of the Mach number in the range of 0.6 to 4 is solved. The uncertainty evaluation results of the two methods are basically the same, and are equivalent to the wind tunnel Mach number control accuracy value, which verifies the correctness of the evaluation results of the velocity field calibration uncertainty of high-speed wind tunnel, and the MCM method results verify the direct applicability of the GUM method for uncertainty evaluation in similar application scenarios.
Anticorrosive behavior assessment of electrodeposited zinc salicylate coating on carbon steel
Authors: Yuan Ronghui , Li Yan , Ye Xiangyu , Liu Furong , Tian Qiping , Wu Qiwang
Published: August 2022

The study focuses on the evaluation of a novel composite coating obtained from zinc salicylate (ZnSal). Ion distributions of salicylic acid and zinc(II) were surveyed at various acidities, and pH 9.5 was selected for the direct current electrodeposition of ZnSal/K2SO4 on carbon steel substrate. The surface morpholgy of the ZnSal-steel coating was revealed by scanning electron microscopy, and compact deposited films with dendrite structures (specific surface area 247 m2 g−1, type-H3 BET hysteresis loop at relative pressures from 0.4 to 1.0) could be formed within 25-min plating time. NSST was conducted, and the test duration was 120 h. Preliminary assays were employed to assess its anticorrosive performance in salt spray, and the corrosion rate of the steel plates exhibited a nonlinear relationship with the exposure time. The results showed that the ZnSal-steel had a low corrosion rate <0.11 μm h−1, thereby increasing the potential of ZnSal composites on actual carbon steel for anticorrosive coatings.
GHz-pulsed source of entangled photons for reconfigurable quantum networks
Authors: Cabrejo-Ponce Meritxell , Spiess Christopher , Marques Muniz André Luiz , Ancsin Philippe , Steinlechner Fabian
Published: August 2022

Entanglement is a universal resource in quantum networks, yet entangled photon sources are typically custom-made for a specific use case. Versatility, both in terms of state modulation and tunability of the temporal properties of the photons, is the key to flexible network architectures and cryptographic primitives that go beyond quantum key distribution. Here, we report on a flexible source design that produces high-quality entanglement in continuous-wave and GHz-rate-pulsed operation modes. Utilizing off-the-shelf optical components, our approach uses a fiber-based Sagnac loop to generate polarization-entangled photons at telecom wavelength with high efficiency and fidelities above 0.99. Phase modulation up to GHz before entangled state generation is also possible for fast entangled state switching. We show phase modulation at 100 MHz with an average fidelity of 0.95. Furthermore, the source 60 nm spectral bandwidth is entirely compatible with fully reconfigurable wavelength-multiplexed quantum networks.
Optimal finite-time processes in weakly driven overdamped Brownian motion
Authors: Nazé Pierre , Deffner Sebastian , Bonança Marcus V S
Published: August 2022

The complete physical understanding of the optimization of the thermodynamic work still is an important open problem in stochastic thermodynamics. We address this issue using the Hamiltonian approach of linear response theory in finite time and weak processes. We derive the Euler–Lagrange equation associated and discuss its main features, illustrating them using the paradigmatic example of driven Brownian motion in overdamped regime. We show that the optimal protocols obtained either coincide, in the appropriate limit, with the exact solutions by stochastic thermodynamics or can be even identical to them, presenting the well-known jumps. However, our approach reveals that jumps at the extremities of the process are a good optimization strategy in the regime of fast but weak processes for any driven system. Additionally, we show that fast-but-weak optimal protocols are time-reversal symmetric, a property that has until now remained hidden in the exact solutions far from equilibrium.
On Katznelson’s Question for skew-product systems
Authors: Glasscock Daniel , Koutsogiannis Andreas , Richter Florian
Published: August 2022

Katznelson’s Question is a long-standing open question concerning recurrence in topological dynamics with strong historical and mathematical ties to open problems in combinatorics and harmonic analysis. In this article, we give a positive answer to Katznelson’s Question for certain towers of skew-product extensions of equicontinuous systems, including systems of the form

(
x
,
t
)
↦
(
x
+
α
,
t
+
h
(
x
)
)

(x,t) \mapsto (x + \alpha , t + h(x))

. We describe which frequencies must be controlled for in order to ensure recurrence in such systems, and we derive combinatorial corollaries concerning the difference sets of syndetic subsets of the natural numbers.
Secondary motor areas for response inhibition: an epicortical recording and stimulation study
Authors: Takeyama Hirofumi , Matsumoto Riki , Usami Kiyohide , Nakae Takuro , Shimotake Akihiro , Kikuchi Takayuki , Yoshida Kazumichi , Kunieda Takeharu , Miyamoto Susumu , Takahashi Ryosuke , Ikeda Akio
Published: August 2022

The areas that directly inhibit motor responses in the human brain remain not fully clarified, although the pre-supplementary motor area and lateral premotor areas have been implicated. The objective of the present study was to delineate the critical areas for response inhibition and the associated functional organization of the executive action control system in the frontal lobe. The subjects were eight intractable focal epilepsy patients with chronic subdural or depth electrode implantation for presurgical evaluation covering the frontal lobe (five for left hemisphere, three for right). We recorded event-related potentials to a Go/No-Go task. We then applied a brief 50 Hz electrical stimulation to investigate the effect of the intervention on the task. Brief stimulation was given to the cortical areas generating discrete event-related potentials specific for the No-Go trials (1–3 stimulation sites/patient, a total of 12 stimulation sites). We compared the locations of event-related potentials with the results of electrical cortical stimulation for clinical mapping. We also compared the behavioural changes induced by another brief stimulation with electrical cortical stimulation mapping. As the results, anatomically, No-Go-specific event-related potentials with relatively high amplitude, named ‘large No-Go event-related potentials’, were observed predominantly in the secondary motor areas, made up of the supplementary motor area proper, the pre-supplementary motor area, and the lateral premotor areas. Functionally, large No-Go event-related potentials in the frontal lobe were located at or around the negative motor areas or language-related areas. Brief stimulation prolonged Go reaction time at most stimulation sites (66.7%) [P < 0.0001, effect size (d) = 0.30, Wilcoxon rank sum test], and increased No-Go error at some stimulation sites (25.0%: left posterior middle frontal gyrus and left pre-supplementary motor area). The stimulation sites we adopted for brief stimulation were most frequently labelled ‘negative motor area’ (63.6%), followed by ‘language-related area’ (18.2%) by the electrical cortical stimulation mapping. The stimulation sites where the brief stimulation increased No-Go errors tended to be labelled ‘language-related area’ more frequently than ‘negative motor area’ [P = 0.0833, Fisher’s exact test (two-sided)] and were located more anteriorly than were those without a No-Go error increase. By integrating the methods of different modality, namely, event-related potentials combined with brief stimulation and clinical electrical cortical stimulation mapping, we conducted a novel neuroscientific approach, providing direct evidence that secondary motor areas, especially the pre-supplementary motor area and posterior middle frontal gyrus, play an important role in response inhibition.
Malek’s Programmatic Secularism? A Dissent
Authors: Moyse Ashley
Published: August 2022

Programmatic secularism aims to secure public reason from rival rationalities, notably those from religious experience and education. The gathering of knowledge in clinical ethics into a concrete array of consensus claims and consensus-derived principles are thought by Janet Malek to secure such public reason—an essential tool for clinical ethics consultants to execute their professional role. The author compares this gathering of knowledge to an understanding of what technology is. Accordingly, the following interrogates Malek’s programmatic secularism, which is a moral technique (technology) that not only homogenizes moral dialogue but also dehumanizes persons as it tyrannizes the creative freedom for moral conversation and genuine encounter. Thus, the reader is encouraged to dissent of such a vision for delimiting the role of clinical ethics consultants according to the rule and measure of technology, the ontology of our age.
Rethinking sustainability: recalibrating the global SDGs to align with local principles for Buen Vivir
Authors: Chassagne Natasha
Published: August 2022

The Sustainable Development Goals (SDGs) were developed as a post-2015 response to growing global climate change and social justice issues, but the little progress made has been thrown off course by the COVID-19 pandemic. To achieve environmental and social transformation, we must recalibrate the global approach to include a contextual, bottom-up and wellbeing-oriented alternative to development that embraces holistic visions of wellbeing. This article advocates Buen Vivir as a localized approach to social and environmental wellbeing, but one that can plurally cooperate with other knowledges and frameworks such as the SDGs. It examines how the global SDGs can align with locally implemented principles for Buen Vivir to achieve effective and timely transformative change for communities and nature.
British Society for Immunology and United Kingdom Primary Immunodeficiency Network (UKPIN) consensus guideline for the management of immunoglobulin replacement therapy
Authors: Grigoriadou S , Clubbe R , Garcez T , Huissoon A , Grosse-Kreul D , Jolles S , Henderson K , Edmonds J , Lowe D , Bethune C
Published: August 2022

Currently, there is no guideline to support the use of immunoglobulin replacement therapy (IgRT) in primary and secondary immunodeficiency disorders in UK. The UK Primary Immunodeficiency Network (UK-PIN) and the British Society of Immunology (BSI) joined forces to address this need. Given the paucity of evidence, a modified Delphi approach was used covering statements for the initiation, monitoring, discontinuation of IgRT as well as home therapy programme. A group of six consultant immunologists and three nurse specialists created the statements, reviewed responses and feedback and agreed on final recommendations. This guideline includes 22 statements for initiation, 22 statements for monitoring, 11 statement for home therapy, and 19 statements for discontinuation of IgRT. Further areas of research are proposed to improve future delivery of care.
Adalimumab Is Associated With Lower Healthcare Resource and Steroid Use Versus Vedolizumab in Biologic-Naive Crohn’s Disease: A Retrospective Claims Database Analysis
Authors: Ungaro Ryan C , Griffith Jenny , Garcia-Horton Viviana , Wang Aolin , Cross Raymond K
Published: August 2022

Background

We compared real-world healthcare resource utilization (HRU), Crohn’s disease (CD)-related complications, and time to systemic corticosteroid discontinuation between patients with CD treated with adalimumab versus vedolizumab as initial biologic.

Methods

Biologic-naïve adults with CD and ≥2 claims between 05/20/2014 and 09/30/2019 for adalimumab or vedolizumab were identified in the IBM MarketScan research database. Patient characteristics were assessed during the 6-month baseline period before biologic initiation (index date). Adalimumab- and vedolizumab-treated patients were propensity score-matched 1:1 on demographics, disease characteristics, and comorbidities with ≥10% prevalence that differed significantly between groups. Categorical, continuous, and time-to-event outcomes between groups during the 12-month follow-up on/after index were compared with chi-square tests, Wilcoxon rank-sum tests, and Kaplan–Meier analyses, respectively.

Results

Adalimumab- and vedolizumab-treated patients were matched (n = 461 per group) and baseline characteristics balanced. Significantly fewer adalimumab- versus vedolizumab-treated patients had a CD-related emergency room visit (12-month proportion: 14.5% vs 21.0%; log-rank P < 0.01) or inpatient admission (14.9% vs 20.2%; log-rank P < 0.05). Rates of CD-related surgeries were similar (9.3% vs 11.5%; log-rank P = 0.282). Among patients without internal/perianal abscess or fistula or intestinal stricture at baseline (NADA = 360, NVDZ = 364), numerically but not significantly fewer adalimumab- versus vedolizumab-treated patients had CD-related complications at 12 months (18.3% vs 22.3%; P = 0.171). Among patients with corticosteroid use at index (NADA = 143, NVDZ = 139), significantly more adalimumab- versus vedolizumab-treated patients discontinued corticosteroids (12-month proportion: 90.2% vs 76.3%; log-rank P < 0.001).

Conclusions

Patients with CD treated with adalimumab as their first biologic experienced significantly lower CD-related HRU and were more likely to discontinue corticosteroids compared to vedolizumab-treated patients.
WTO Rulings and the Veil of Anonymity
Authors: Pauwelyn Joost , Pelc Krzysztof
Published: August 2022

Despite a general push for greater transparency, opacity continues to play an important function in international tribunals. The World Trade Organization (WTO) is a case in point. While it has done much to increase its openness, the very design of its dispute settlement body is premised on anonymity in some essential respects. We examine two such instances, each dealing with the authorship of dispute rulings. First, we use text analysis tools to demonstrate that the WTO’s panel reports appear to be largely drafted by WTO Secretariat staff rather than the panellists themselves. This appears especially true for the WTO’s most systemically important disputes. Second, we show that the formal anonymity of dissenting opinions, which is required by the WTO’s rules, is a thin veil. Using the most recent Appellate Body’s dissent for demonstration, we use text analysis to pinpoint its likely author. In both these instances, we argue that anonymity exists by design: it serves to strike a balance between judicial autonomy and political control. Yet, in both settings, due to increased scrutiny and widespread access to text analysis tools, the equilibrium relying on anonymity is likely to be upset, with implications for the institution’s future design. We argue that the ultimate result may be a beneficial one and offer a menu of reform options.
Geomagnetic field behaviour during the early Cretaceous Normal Superchron from palaeomagnetic analysis of the Ramon Volcanics, Israel
Authors: Dembo Neta , Kraus Erez , Seliverstov Irina , Weissman Gal , Granot Roi
Published: August 2022

Unravelling the long-term behaviour of the geomagnetic field is crucial for understanding the dynamics of the deep Earth. Yet, obtaining an accurate measure of geomagnetic palaeosecular variations (PSV) is difficult, partly because of tectonically induced rotations that overprint the original palaeomagnetic signal. We present a detailed palaeomagnetic investigation based on 99 sampling sites collected from the 119 to 112.6 Ma Ramon Volcanics exposed near the dormant Ramon Fault, southern Israel. These basaltic rocks were emplaced at equatorial palaeolatitudes during the beginning of the Cretaceous Normal Superchron (CNS; 123.4–83.6 Ma), during which there were no polarity reversals. Structurally corrected remanence directions consistently vary across the investigated area, whereby the sites found near a sharp bend of the Ramon Fault are clockwise rotated, whereas the other sites show no obvious rotational pattern. Elasto-plastic modelling suggests that the rotations were induced by up to 1.5 km of dextral horizontal slip accommodated by the fault, consistent with previous geological and geophysical estimations. Considering the remanence directions obtained from sites that were not influenced by the fault, we calculated an SB value of $13.3_{ - 1.3}^{ + 1.9 \circ }$ (95 percent confidence, 46 sites), which corresponds to previous SB estimations from pre- and early-CNS volcanic bodies emplaced at low palaeolatitudes (λ < 20°). This observation suggests that the emergence of the superchron was not accompanied by a change in the behaviour of the geomagnetic PSV. Finally, our results, together with previous palaeo-equatorial observations, show that the middle part of the superchron had lower angular dispersion (i.e. lower SB) compared to the scatter that prevailed during the beginning of the superchron. This observation suggests that the geomagnetic field transitioned into a more axial dipole dominance state towards the middle part of the superchron. Altogether, our analysis indicates that the superchron cannot be treated as a period characterized by a steady-state field behaviour.
N-glycolylated carbohydrates in nature
Authors: Awofiranye Adeola E , Dhar Chirag , He Peng , Varki Ajit , Koffas Mattheos A G , Linhardt Robert J
Published: August 2022

N-glycolylated carbohydrates are amino sugars with an N-glycolyl amide group. These glycans have not been well studied due to their surprising rarity in nature in comparison with N-acetylated carbohydrates. Recently, however, there has been increasing interest in N-glycolylated sugars because the non-human sialic acid N-glycolylneuraminic acid (Neu5Gc), apparently the only source of all N-glycolylated sugars in deuterostomes, appears to be involved in xenosialitis (inflammation associated with consumption of Neu5Gc-rich red meats). Xenosialitis has been implicated in cancers as well as other diseases including atherosclerosis. Furthermore, metabolites of Neu5Gc have been shown to be incorporated into glycosaminoglycans (GAGs), resulting in N-glycolylated GAGs. These N-glycolylated GAGs have important potential applications, such as dating the loss of the Neu5Gc-generating CMAH gene in humans and being explored as a xenosialitis biomarker and/or estimate of the body burden of diet-derived Neu5Gc, to understand the risks associated with the consumption of red meats. This review explores N-glycolylated carbohydrates, how they are metabolized to N-glycolylglucosamine and N-glycolylgalactosamine, and how these metabolites can be incorporated into N-glycolylated GAGs in human tissues. We also discuss other sources of N-glycolylated sugars, such as recombinant production from microorganisms using metabolic engineering as well as chemical synthesis.
2. How Did We Get Here?
Authors: Dinan Desmond
Published: August 2022

This chapter focuses on the historical development of the EU. The history of the EU began when European governments responded to a series of domestic, regional, and global challenges after World War II by establishing new transnational institutions in order to accelerate political and economic integration. These challenges ranged from postwar reconstruction to the Cold War, and then to globalization. Driven largely by mutually compatible national interests, Franco-German bargains, and American influence, politicians responded by establishing the EC in the 1950s and the EU in the 1990s. The chapter examines the Schuman Plan, the European Defence Community, the European Community, the Economic and Monetary Union (EMU), enlargement, Constitution-building, and the Eurozone crisis.
7. Internal Policies of the EU
Authors: Dimitrakopoulos Dionyssis G. , Kenealy Daniel
Published: August 2022

This chapter examines some of the EU’s key internal policies. The chapter begins by considering the different kinds of power that the EU possesses, and how that differs from national governments, before considering the EU’s reliance on member states to implement many of its policies. The chapter explores three types of internal policy. First, it discusses policies designed to build and expand the internal market, which remains the foundation of the project of European integration. Second, it explores policies designed to cushion, or correct, the impact of the internal market. Finally, it discusses policies that have taken the EU into new realms, beyond the original vision of constructing an internal market—realms that are associated with core state powers such as money, borders, and internal security.
A genome-wide association study for rheumatoid arthritis replicates previous HLA and non-HLA associations in a cohort from South Africa
Authors: Mathebula Evans M , Sengupta Dhriti , Govind Nimmisha , Laufer Vincent A , Bridges Jr S Louis , Tikly Mohammed , Ramsay Michèle , Choudhury Ananyo
Published: August 2022

The complex pathogenesis of rheumatoid arthritis (RA) is not fully understood, with few studies exploring the genomic contribution to RA in patients from Africa. We report a genome-wide association study (GWAS) of South-Eastern Bantu-Speaking South Africans (SEBSSAs) with seropositive RA (n = 531) and population controls (n = 2653). Association testing was performed using PLINK (logistic regression assuming an additive model) with sex, age, smoking and the first three principal components as covariates. The strong association with the Human Leukocyte Antigen (HLA) region, indexed by rs602457 (near HLA-DRB1), was replicated. An additional independent signal in the HLA region represented by the lead SNP rs2523593 (near the HLA-B gene; Conditional P-value = 6.4 × 10−10) was detected. Although none of the non-HLA signals reached genome-wide significance (P < 5 × 10−8), 17 genomic regions showed suggestive association (P < 5 × 10−6). The GWAS replicated two known non-HLA associations with MMEL1 (rs2843401) and ANKRD55 (rs7731626) at a threshold of P < 5 × 10−3 providing, for the first time, evidence for replication of non-HLA signals for RA in sub-Saharan African populations. Meta-analysis with summary statistics from an African-American cohort (CLEAR study) replicated three additional non-HLA signals (rs11571302, rs2558210 and rs2422345 around KRT18P39-NPM1P33, CTLA4-ICOS and AL645568.1, respectively). Analysis based on genomic regions (200 kb windows) further replicated previously reported non-HLA signals around PADI4, CD28 and LIMK1. Although allele frequencies were overall strongly correlated between the SEBSSA and the CLEAR cohort, we observed some differences in effect size estimates for associated loci. The study highlights the need for conducting larger association studies across diverse African populations to inform precision medicine-based approaches for RA in Africa.
Nesprin-1 LINC complexes recruit microtubule cytoskeleton proteins and drive pathology inLmna-mutant striated muscle
Authors: Leong Ei Leen , Khaing Nyein Thet , Cadot Bruno , Hong Wei Liang , Kozlov Serguei , Werner Hendrikje , Wong Esther Sook Miin , Stewart Colin L , Burke Brian , Lee Yin Loon
Published: August 2022

Mutations in LMNA, the gene encoding A-type lamins, cause laminopathies—diseases of striated muscle and other tissues. The aetiology of laminopathies has been attributed to perturbation of chromatin organization or structural weakening of the nuclear envelope (NE) such that the nucleus becomes more prone to mechanical damage. The latter model requires a conduit for force transmission to the nucleus. NE-associated Linker of Nucleoskeleton and Cytoskeleton (LINC) complexes are one such pathway. Using clustered regularly interspaced short palindromic repeats to disrupt the Nesprin-1 KASH (Klarsicht, ANC-1, Syne Homology) domain, we identified this LINC complex protein as the predominant NE anchor for microtubule cytoskeleton components, including nucleation activities and motor complexes, in mouse cardiomyocytes. Loss of Nesprin-1 LINC complexes resulted in loss of microtubule cytoskeleton proteins at the nucleus and changes in nuclear morphology and positioning in striated muscle cells, but with no overt physiological defects. Disrupting the KASH domain of Nesprin-1 suppresses Lmna-linked cardiac pathology, likely by reducing microtubule cytoskeleton activities at the nucleus. Nesprin-1 LINC complexes thus represent a potential therapeutic target for striated muscle laminopathies.
DNA methylation dynamics during stress response in woodland strawberry (Fragaria vesca)
Authors: López María-Estefanía , Roquis David , Becker Claude , Denoyes Béatrice , Bucher Etienne
Published: August 2022

Environmental stresses can result in a wide range of physiological and molecular responses in plants. These responses can also impact epigenetic information in genomes, especially at the level of DNA methylation (5-methylcytosine). DNA methylation is the hallmark heritable epigenetic modification and plays a key role in silencing transposable elements (TEs). Although DNA methylation is an essential epigenetic mechanism, fundamental aspects of its contribution to stress responses and adaptation remain obscure.

We investigated epigenome dynamics of wild strawberry (Fragaria vesca) in response to variable ecologically relevant environmental conditions at the DNA methylation level. F. vesca methylome responded with great plasticity to ecologically relevant abiotic and hormonal stresses. Thermal stress resulted in substantial genome-wide loss of DNA methylation. Notably, all tested stress conditions resulted in marked hot spots of differential DNA methylation near centromeric or pericentromeric regions, particularly in the non-symmetrical DNA methylation context. Additionally, we identified differentially methylated regions (DMRs) within promoter regions of transcription factor (TF) superfamilies involved in plant stress-response and assessed the effects of these changes on gene expression.

These findings improve our understanding on stress-response at the epigenome level by highlighting the correlation between DNA methylation, TEs and gene expression regulation in plants subjected to a broad range of environmental stresses.
The high-quality genome of pummelo provides insights into the tissue-specific regulation of citric acid and anthocyanin during domestication
Authors: Lu Zhihao , Huang Yue , Mao Sangyin , Wu Fangfang , Liu Yong , Mao Xiangqing , Adhikari Prakash Babu , Xu Yuantao , Wang Lun , Zuo Hao , Rao Muhammad Junaid , Xu Qiang
Published: August 2022

Citric acid and anthocyanin contents were co-selected during Citrus domestication. Pummelo is a founding species in the Citrus genus, but the domestication of pummelo has not been well studied. Here, we compared the citric acid and anthocyanin contents of a low citric acid pummelo (Citrus maxima LCA) and its high citric acid variety (HCA) from the same cultivation area in China. Our study revealed that, unlike the LCA type, the HCA variety accumulated anthocyanin in the pericarp early in fruit development. To investigate the genetic basis of acid and anthocyanin enrichment in HCA pulp and pericarp, respectively, we generated a chromosome-scale HCA genome using long-read sequence reads and Hi-C sequencing data. Transcriptome analysis and transient overexpression assays showed that the accumulation of citric acid and anthocyanin was associated with high expression of CgANTHOCYANIN1 (CgAN1), and two different MYBs transcription factors (CgPH4 and CgRuby1), respectively. Moreover, the CgAN1 promoter was more methylated in the LCA pulp than in the HCA pulp. Treatment with a DNA methylation inhibitor, 5-azacytidine, alleviated the CgAN1 promoter hypermethylation in the LCA pulp, leading to increased CgAN1 expression and citric acid content. This study provides a new high-quality pummelo genome and insight into the molecular mechanism behind the change in tissue-specific citric acid and anthocyanin accumulation during pummelo domestication and provides a conceptual basis for precise genetic manipulation in fruit flavor breeding.
Social inequalities in all-cause mortality among adults with multimorbidity: a 10-year prospective study of 0.5 million Chinese adults
Authors: Zou Siyu , Wang Zhicheng , Tang Kun
Published: August 2022

Background

Chinese individuals face an increase in multimorbidity, but little is known about the mortality gradients of multimorbid people in different socio-economic groups. This study measures relative and absolute socio-economic inequality in mortality among multimorbid Chinese.

Methods

For this study, the prospective China Kadoorie Biobank (CKB) enrolled 512 712 participants ages 30–79 y from 10 areas of China between 25 June 2004 and 15 July 2008. All-cause mortality was accessed with a mean follow-up period of 10 y (to 31 December 2016). Associations between multimorbidity and mortality were assessed using Cox proportional hazards models, with the relative index of inequality (RII) and slope index of inequality (SII) in mortality calculated to measure disparities.

Results

Mortality risk was highest for those who had not attended formal school and with four or more long-term conditions (LTCs) (hazard ratio 3.11 [95% confidence interval {CI} 2.75 to 3.51]). Relative educational inequality was lower in participants with four or more LTCs (RII 1.92 [95% CI 1.60 to 2.30]), especially in rural areas. Absolute disparities were greater in adults with more LTCs (SII 0.18 [95% CI 0.14 to 0.21] for rural participants with three LTCs).

Conclusions

Whereas the relative inequality in all-cause mortality was lower among multimorbid people, absolute inequality was greater among multimorbid men, especially in rural areas.
Population pharmacokinetics and clinical outcomes of polymyxin B in paediatric patients with multidrug-resistant Gram-negative bacterial infections
Authors: Wang Pei-Le , Liu Peng , Zhang Qi-Wen , Yuan Wen-Hua , Wang Dao , Zhang Xiao-Jian , Yang Jing
Published: August 2022

Background

Current polymyxin B dosing in children relies on scant data.

Objectives

To build a population pharmacokinetic (PK) model for polymyxin B in paediatric patients and assess the likely appropriateness of different dosages.

Methods

A total of 19 paediatric patients were enrolled to receive intravenous polymyxin B (1.33–2.53 mg/kg/day), and the median age was 12.5 (range 3.2–17.8) years. Serial plasma samples were collected at steady-state and modelled by population PK analysis. Clinical efficacy and nephrotoxicity of polymyxin B treatment were also assessed.

Results

PK data were adequately described by a two-compartment model with first-order elimination, and weight was a significant covariate of polymyxin B clearance. Clinical success occurred in 14 of 19 patients (73.7%) and only one patient developed acute kidney injury. The 28 day mortality was 10.5% (2/19). The steady-state polymyxin B exposure was 36.97 ± 9.84 mg·h/L, lower than the therapeutic exposure of 50–100 mg·h/L. With the AUC24h/MIC target of 50, the dosage of 1.5–3.0 mg/kg/day had a probability of target attainments over 90% when MICs were <0.5 mg/L.

Conclusions

Dose adjustment of polymyxin B needs to consider the MIC of infecting pathogens. Current polymyxin B dosing for paediatric patients may be acceptable when MICs are <0.5 mg/L.