Objective: Evaluate guselkumab efficacy, an anti-interleukin-23p19-subunit antibody, in patients with active psoriatic arthritis (PsA) and inadequate response to 1 or 2 tumour necrosis factor inhibitors (TNFi-IR), uti...
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Objective: Evaluate guselkumab efficacy, an anti-interleukin-23p19-subunit antibody, in patients with active psoriatic arthritis (PsA) and inadequate response to 1 or 2 tumour necrosis factor inhibitors (TNFi-IR), utilizing composite indices assessing disease activity across disease domains. Methods: In the Phase IIIb cosmos trial, 285 adults with TNFi-IR PsA were randomized (2:1) to receive guselkumab 100 mg or placebo at Week (W)0, W4, then every 8 weeks through W44. Patients receiving placebo crossed over to guselkumab at W24. In this post hoc analysis, composite indices evaluated included the Disease Activity Index for Psoriatic Arthritis (DAPSA), Disease Activity Score 28 (DAS28), Psoriatic Arthritis Response Criteria (PsARC), Psoriatic Arthritis Disease Activity Score (PASDAS), GRAPPA Composite score (GRACE), modified Composite Psoriatic Disease Activity Index (mCPDAI), minimal disease activity (MDA), and very low disease activity (VLDA). Through W24, treatment failure rules were applied. Through W48, non-responder imputation was used for missing data. Results: Greater proportions of guselkumabthan placebo-randomized patients achieved composite index endpoints relating to low disease activity (LDA;14.8-52.4% vs 3.1-28.1%) or remission (3.7-5.3% vs 0.0-2.1%) at W24. Among guselkumab-randomized patients, LDA rates increased to W48 (DAPSA, 44.4%;DAS28, 47.8%;PASDAS, 34.4%;GRACE, 33.3%;mCPDAI, 40.2%), and 27.0% and 64.0% achieved MDA and a PsARC response, respectively. In the placebo>guselkumab crossover group, W48 response rates were similar to the guselkumabrandomized group. Conclusion: Guselkumab treatment provided substantial benefits across multiple disease domains, with increasing proportions of patients achieving LDA/remission over 1 year, highlighting the effectiveness of guselkumab despite previous inadequate response to TNFi.
Purpose: Field-to-susceptibility inversion in quantitative susceptibility mapping (QSM) is ill-posed and needs numerical stabilization through either regularization or oversampling by acquiring data at three or more o...
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Purpose: Field-to-susceptibility inversion in quantitative susceptibility mapping (QSM) is ill-posed and needs numerical stabilization through either regularization or oversampling by acquiring data at three or more object orientations. Calculation Of Susceptibility through Multiple Orientations Sampling (cosmos) is an established oversampling approach and regarded as QSM gold standard. It achieves a well-conditioned inverse problem, requiring rotations by 0 degrees, 60 degrees and 120 degrees in the yz-plane. However, this is impractical in vivo, where head rotations are typically restricted to a range of +/- 25 degrees. Non-ideal sampling degrades the conditioning with residual streaking artifacts whose mitigation needs further regularization. Moreover, susceptibility anisotropy in white matter is not considered in the cosmos model, which may introduce additional bias. The current work presents a thorough investigation of these effects in primate brain. Methods: Gradient-recalled echo (GRE) data of an entire fixed chimpanzee brain were acquired at 7 T (350 mu m resolution, 10 orientations) including ideal cosmos sampling and realistic rotations in vivo. Comparisons of the results included ideal cosmos, in-vivo feasible acquisitions with 3-8 orientations and single-orientation iLSQR QSM. Results: In-vivo feasible and optimal cosmos yielded high-quality susceptibility maps with increased SNR resulting from averaging multiple acquisitions. cosmos reconstructions from non-ideal rotations about a single axis required additional L2-regularization to mitigate residual streaking artifacts. Conclusion: In view of unconsidered anisotropy effects, added complexity of the reconstruction, and the general challenge of multi-orientation acquisitions, advantages of sub-optimal cosmos schemes over regularized singleorientation QSM appear limited in in-vivo settings.
There is a tendency in recent Johannine scholarship to understand kappa o sigma mu omicron sigma in the majority of instances in the Gospel of John as 'humanity'. It is assumed that the meaning 'creation&#...
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There is a tendency in recent Johannine scholarship to understand kappa o sigma mu omicron sigma in the majority of instances in the Gospel of John as 'humanity'. It is assumed that the meaning 'creation' is appropriate only in a few occurrences. In this article, I want to challenge this consensus in three steps. First, a survey of the scholarship on the Johannine use of kappa o sigma mu omicron sigma will focus on the question of whether there is an anthropocentric bias in the history of reception. Second, a semantic analysis will explore the possible passages in which the kappa o sigma mu omicron sigma cannot be reduced to humanity but also includes nonhuman creation. Third, an eco-hermeneutical outlook will set the debate in the context of the ecological crisis and focus on the interdependence between humanity and the rest of the cosmos. Is it time to rethink the meaning of kappa o sigma mu omicron sigma in light of the climate crises? Does God only love humanity or does he care about his whole creation (3.16)? Is Jesus, according to 4.42, only the savior of humans or also of the 'more than human creation'? And if so, does doing the works of God (6.28) imply caring for the creation?
As private interests expand in space, what is the significance, if any, to social work? To answer this question, I present several implications of contemporary human activities in space and assess their relevance to e...
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As private interests expand in space, what is the significance, if any, to social work? To answer this question, I present several implications of contemporary human activities in space and assess their relevance to environmental and ecological justice. Specifically, I evaluate the connection between the profession and the commercialization and exploitation of space resources, human-generated cosmic "trash," and terrestrial challenges. I conclude that social work must "look to the stars" and help humanity navigate competing interests in a delicate space future. Nearly a quarter century ago, ecological consequences of human activity prompted social work to incorporate the natural environment into practice. In preparation for the realization of modern extraterrestrial objectives, I propose that social work expand its conceptualization of the natural environment from ecosphere to cosmos. In this uncharted context, I propose future directions and offer questions to which leaders, scholars, and practitioners might begin seeking answers.
In response to Yuk Hui's essay "For a Cosmotechnical Event," I argue that the cosmos can only be metaphysically apprehended through a deepening of its astrophysical understanding. This understanding make...
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In response to Yuk Hui's essay "For a Cosmotechnical Event," I argue that the cosmos can only be metaphysically apprehended through a deepening of its astrophysical understanding. This understanding makes the universe-and the Earth-a contingent, historical, and an-archic formation. Dasein is therefore under planetary condition, seeking to ensure that the Earth is finally able to recognize its strangeness. The technologies capable of accompanying an Earth traversed by the abyss of the universe should be able to express a resolutely a-modern, a-human, a-national, and ex-centric technique.
This paper explores how political ecology can advance existing understandings of China's Belt and Road Initiative (BRI) and its effects, and how the BRI can contribute to recent shifts in the study of political ec...
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This paper explores how political ecology can advance existing understandings of China's Belt and Road Initiative (BRI) and its effects, and how the BRI can contribute to recent shifts in the study of political ecology. It argues that the idea of infrastructural overlap can sensitize discourse to the ways in which the materializations of the BRI, as a series of infrastructural megaprojects, intersect with other infrastructural formations, such as the environment and religion. By focusing on the effects of the BRI on resource-dependent communities located between the 'commons' and the 'cosmos' we can appreciate the sense of existential crisis that is triggered and exacerbated by China's world-building agenda in Southeast Asia and beyond.
We outline our experience in organizing the 10th edition of the International Workshop on Astronomy and Relativistic Astrophysics: from Quarks to cosmos, IWARA2022, in hybrid format, combining virtual and face-to-face...
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We outline our experience in organizing the 10th edition of the International Workshop on Astronomy and Relativistic Astrophysics: from Quarks to cosmos, IWARA2022, in hybrid format, combining virtual and face-to-face sessions. The meeting was held from 05 to 09 September, 2022, in Antigua, Guatemala.
Norbert Wiener was the first to functionally define cybernetics as "the study of control and communication in the animal and the machine". Herein, it is shown that as a manifestation of physiology, cyberneti...
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Norbert Wiener was the first to functionally define cybernetics as "the study of control and communication in the animal and the machine". Herein, it is shown that as a manifestation of physiology, cybernetics can be further reduced to cell-cell signaling to maintain homeostasis, bridging Newtonian 3rd Order Cybernetics with Quantum Mechanical 4th Order Cybernetics as our `conversation with the cosmos' based on Quantum Entanglement, constrained by non-localization. As such, cybernetics can be scientifically tested in toto from the functional to the metaphysical, rendered physical as communication for the first time. If that is correct, then the sooner we begin operating based on Quantum Mechanical principles, the sooner we will function based on predictive algorithms.
Blockchains require deterministic execution in order to reach consensus. This is often guaranteed in languages designed to write smart contracts, such as Solidity. Application-specific blockchains or "appchains&q...
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ISBN:
(纸本)9798350317824
Blockchains require deterministic execution in order to reach consensus. This is often guaranteed in languages designed to write smart contracts, such as Solidity. Application-specific blockchains or "appchains" allow the blockchain application logic to be written using general-purpose programming languages, giving developers more flexibility but also additional responsibilities. In particular, developers must ensure that their blockchain application logic does not contain any sources of non-determinism. Any source of non-determinism may be a potential source of vulnerabilities. This paper focuses on the use of Static Application Security Testing (SAST) tools to detect such sources of non-determinism at development time. We focus on cosmos, a prominent open-source project that lets developers build interconnected networks of application-specific blockchains. cosmos provides a Software Development Kit (SDK) that allows these chains to be implemented in the Go programming language. We create a corpus of 11 representative cosmos-based appchains to analyze for sources of non-determinism in Go. As part of our study, we identified cosmos-sdk-codeql, a set of CodeQL code analysis rules for cosmos applications. We find that these rules generate many false positives and propose a refactored set of rules that more precisely detects sources of non-determinism only in code that runs as part of the blockchain logic. We demonstrate a significant increase in the precision of the rules, making the SAST tool more effective and hence potentially contributing to enhanced security for cosmos-based blockchains.
The cosmos uses an Inter-Blockchain Communication protocol (IBC), which achieves interoperability among heterogeneous blockchains, and horizontal scaling. In cosmos, inter-chain transactions show lower performance tha...
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ISBN:
(数字)9784885523397
ISBN:
(纸本)9784885523397
The cosmos uses an Inter-Blockchain Communication protocol (IBC), which achieves interoperability among heterogeneous blockchains, and horizontal scaling. In cosmos, inter-chain transactions show lower performance than intra-chain transactions. As the inter-chain transaction rate increases, the entire network's transaction processing speed per second (TPS) decreases. Detail performance evaluations on cosmos are essential for improving interoperability and designing with the trade-offs between scalability and compatibility. Therefore, this paper proposes a new approach to measure and analyze the inter-chain message relay time in cosmos. Our results focus on the performance of inter-chain in terms of communication between different chains.
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