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1.
Proc Natl Acad Sci U S A ; 120(45): e2205463120, 2023 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-37917793

RESUMO

Zero-knowledge proof (ZKP) is a fundamental cryptographic primitive that allows a prover to convince a verifier of the validity of a statement without leaking any further information. As an efficient variant of ZKP, noninteractive zero-knowledge proof (NIZKP) adopting the Fiat-Shamir heuristic is essential to a wide spectrum of applications, such as federated learning, blockchain, and social networks. However, the heuristic is typically built upon the random oracle model that makes ideal assumptions about hash functions, which does not hold in reality and thus undermines the security of the protocol. Here, we present a quantum solution to the problem. Instead of resorting to a random oracle model, we implement a quantum randomness service. This service generates random numbers certified by the loophole-free Bell test and delivers them with postquantum cryptography (PQC) authentication. By employing this service, we conceive and implement NIZKP of the three-coloring problem. By bridging together three prominent research themes, quantum nonlocality, PQC, and ZKP, we anticipate this work to inspire more innovative applications that combine quantum information science and the cryptography field.

2.
Eur Heart J ; 45(20): 1804-1815, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38583086

RESUMO

BACKGROUND AND AIMS: In patients with three-vessel disease and/or left main disease, selecting revascularization strategy based on coronary computed tomography angiography (CCTA) has a high level of virtual agreement with treatment decisions based on invasive coronary angiography (ICA). METHODS: In this study, coronary artery bypass grafting (CABG) procedures were planned based on CCTA without knowledge of ICA. The CABG strategy was recommended by a central core laboratory assessing the anatomy and functionality of the coronary circulation. The primary feasibility endpoint was the percentage of operations performed without access to the ICA. The primary safety endpoint was graft patency on 30-day follow-up CCTA. Secondary endpoints included topographical adequacy of grafting, major adverse cardiac and cerebrovascular (MACCE), and major bleeding events at 30 days. The study was considered positive if the lower boundary of confidence intervals (CI) for feasibility was ≥75% (NCT04142021). RESULTS: The study enrolled 114 patients with a mean (standard deviation) anatomical SYNTAX score and Society of Thoracic Surgery score of 43.6 (15.3) and 0.81 (0.63), respectively. Unblinding ICA was required in one case yielding a feasibility of 99.1% (95% CI 95.2%-100%). The concordance and agreement in revascularization planning between the ICA- and CCTA-Heart Teams was 82.9% with a moderate kappa of 0.58 (95% CI 0.50-0.66) and between the CCTA-Heart Team and actual treatment was 83.7% with a substantial kappa of 0.61 (95% CI 0.53-0.68). The 30-day follow-up CCTA in 102 patients (91.9%) showed an anastomosis patency rate of 92.6%, whilst MACCE was 7.2% and major bleeding 2.7%. CONCLUSIONS: CABG guided by CCTA is feasible and has an acceptable safety profile in a selected population of complex coronary artery disease.


Assuntos
Angiografia por Tomografia Computadorizada , Angiografia Coronária , Ponte de Artéria Coronária , Doença da Artéria Coronariana , Estudos de Viabilidade , Humanos , Ponte de Artéria Coronária/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Doença da Artéria Coronariana/cirurgia , Doença da Artéria Coronariana/diagnóstico por imagem , Idoso , Angiografia por Tomografia Computadorizada/métodos , Angiografia Coronária/métodos , Estudos Prospectivos , Grau de Desobstrução Vascular/fisiologia
3.
Small ; : e2403249, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38934358

RESUMO

Sweat passive-cooling textiles with asymmetric wettabilities on different sides offer an effective and low-energy consumption solution to personal thermal management in extreme thermal environments. However, the sweat-wicking and the cooling abilities decrease when the textile is contaminated by low-surface tension oily liquid fouling. The integration of anti-oily liquid fouling and sweat-wicking abilities on textile involves resolving the contradiction between hydrophilic and oleophobic properties and seeking eco-friendly short-chain fluorides to reduce the surface energy. Herein, a sustainable oily liquid-proof passive cooling (SOC) textile for personal thermal management is proposed. The SOC textile is obtained by applying a fluoride-free hydrophobic coating layer to one side of the high thermal conductive superoleophobic/superhydrophilic basal textile, which is fabricated using eco-friendly short-chain fluoride. The SOC textile preserves the anti-oily liquid fouling property even after 2000 abrasion cycles. Experimental test revealed that the SOC textile exhibits a cooling effect of ≈5 °C compared with the cotton textile, and the up to 70% reduction in sweating rate under the constant metabolic heat production rates. The configuration of the SOC textile would inspire the future design of intelligent textiles for personal thermal management, and the proposed strategy have implications for fabrication of eco-friendly oil-water separation materials.

4.
Osteoarthritis Cartilage ; 32(3): 310-318, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38043857

RESUMO

OBJECTIVE: To create a scalable and feasible retrospective consecutive knee osteoarthritis (OA) radiographic database with limited human labor using commercial and custom-built artificial intelligence (AI) tools. METHODS: We applied four AI tools, two commercially available and two custom-built tools, to analyze 6 years of clinical consecutive knee radiographs from patients aged 35-79 at the University of Copenhagen Hospital, Bispebjerg-Frederiksberg Hospital, Denmark. The tools provided Kellgren-Lawrence (KL) grades, joint space widths, patella osteophyte detection, radiographic view detection, knee joint implant detection, and radiographic marker detection. RESULTS: In total, 25,778 knee radiographs from 8575 patients were included in the database after excluding inapplicable radiographs, and 92.5% of the knees had a complete OA dataset. Using the four AI tools, we saved about 800 hours of radiologist reading time and only manually reviewed 16.0% of the images in the database. CONCLUSIONS: This study shows that clinical knee OA databases can be built using AI with limited human reading time for uniform grading and measurements. The concept is scalable temporally and across geographic regions and could help diversify further OA research by efficiently including radiographic knee OA data from different populations globally. We can prevent data dredging and overfitting OA theories on existing trite cohorts by including various gene pools and continuous expansion of new clinical cohorts. Furthermore, the suggested tools and applied approaches provide an ability to retest previous hypotheses and test new hypotheses on real-life clinical data with current disease prevalence and trends.


Assuntos
Osteoartrite do Joelho , Humanos , Osteoartrite do Joelho/diagnóstico por imagem , Osteoartrite do Joelho/epidemiologia , Articulação do Joelho/diagnóstico por imagem , Estudos Retrospectivos , Inteligência Artificial , Joelho
5.
Stat Med ; 43(1): 173-183, 2024 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-37937591

RESUMO

Existing phase II clinical trial designs focus on a single scalar endpoint, such as a binary, continuous, or survival endpoint. In some clinical trials, such as pain management studies, the efficacy endpoint of interest is measured longitudinally. We propose a Bayesian phase II design for such clinical trials. We model the longitudinal measurement process using Bayesian hierarchical model, where subject-specific trajectory shrinks toward the population trajectory to borrow information across subjects. The Bayesian penalized spline is used to model subject-specific and population trajectories without making strong parametric assumption on their shapes. We use the area under the curve of the trajectory as the summary of the treatment effect over time. The design takes a group sequential approach and takes into account both statistical significance and clinical relevance. Bayesian criteria is proposed to make interim and final decisions based on the evidence of statistical significance and clinical relevance. The proposed design is highly flexible and can accommodate trials with one or multiple longitudinal endpoints, as well as a longitudinal primary endpoint with a secondary endpoint. Simulation study shows that the proposed design is robust with desirable operating characteristics.


Assuntos
Projetos de Pesquisa , Humanos , Teorema de Bayes , Simulação por Computador
6.
Environ Res ; 252(Pt 1): 118798, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38555086

RESUMO

Blockchain technology, the backbone of cryptocurrency, is under scrutiny due to the environmental and health hazards linked to its energy-consuming Proof-of-Work (PoW) mining process. This review study provides a comprehensive analysis of the global health implications of PoW mining and cryptocurrency, with a focus on environmental sustainability and human health. The research utilized both traditional databases (PubMed and Web of Science) and additional primary sources. The study underscores the high energy consumption and carbon emissions of Bitcoin mining, despite ongoing debates comparing cryptocurrency to conventional finance. The review calls for immediate interventions, including the exploration of renewable energy sources and a transition from PoW to more sustainable consensus mechanisms. A case study on China's carbon policies highlights the necessity for effective regulatory measures. The findings reiterate the environmental and health risks associated with PoW cryptocurrency mining, including its resource-intensive procedures, reliance on non-renewable energy, and emission of air pollutants. The review emphasizes the urgent need for global regulation and a transition to more sustainable consensus mechanisms, such as Proof-of-Stake (PoS), to reduce the industry's impact on climate and human health.


Assuntos
Mineração , Humanos , Meio Ambiente
7.
Network ; 35(3): 300-318, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38293964

RESUMO

This research introduces an innovative solution addressing the challenge of user authentication in cloud-based systems, emphasizing heightened security and privacy. The proposed system integrates multimodal biometrics, deep learning (Instance-based learning-based DetectNet-(IL-DN), privacy-preserving techniques, and blockchain technology. Motivated by the escalating need for robust authentication methods in the face of evolving cyber threats, the research aims to overcome the struggle between accuracy and user privacy inherent in current authentication methods. The proposed system swiftly and accurately identifies users using multimodal biometric data through IL-DN. To address privacy concerns, advanced techniques are employed to encode biometric data, ensuring user privacy. Additionally, the system utilizes blockchain technology to establish a decentralized, tamper-proof, and transparent authentication system. This is reinforced by smart contracts and an enhanced Proof of Work (PoW) mechanism. The research rigorously evaluates performance metrics, encompassing authentication accuracy, privacy preservation, security, and resource utilization, offering a comprehensive solution for secure and privacy-enhanced user authentication in cloud-based environments. This work significantly contributes to filling the existing research gap in this critical domain.


Assuntos
Identificação Biométrica , Blockchain , Computação em Nuvem , Segurança Computacional , Aprendizado Profundo , Privacidade , Humanos , Identificação Biométrica/métodos
8.
Surg Endosc ; 2024 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-39266756

RESUMO

BACKGROUND: The role of gastroesophageal reflux in progressive lung damage is increasingly recognized. We have proposed, based on our work with lung transplant recipients, a novel immune mechanism of pulmonary injury after aspiration of gastric contents, during which higher levels of normally sequestered lung self-antigens (SAgs) collagen V (Col-V) and K-alpha-1 tubulin (Kα1T) in circulating small extracellular vesicles (EVs) induce the production of self-antibodies (SAbs) anti-Col-V and anti-Kα1T. Thus, we aimed to determine whether levels of SAbs or SAgs increased in an animal model of aspiration-induced lung damage in a nontransplant setting. METHODS: We created a murine model of repetitive lung aspiration using C57BL/6J mice. Mice were aspirated weekly with 1 mL/kg of hydrochloric acid (n = 9), human gastric contents (n = 9), or combined (1:1) fluid (n = 9) once, three, or six times (n = 3 in each subgroup; control group, n = 9). Blood samples were periodically obtained, and all animals were sacrificed at day 90 for pathological assessment. SAbs were measured using an enzyme-linked immunosorbent assay; SAgs and NF-κB contained in small EVs were assessed by western blot. RESULTS: Aspirated mice weighed significantly less than controls throughout the study and had histological evidence of pulmonary injury at day 90. Overall, aspirated mice developed higher concentrations of anti-Col-V at day 28 (53.9 ± 28.7 vs. 29.9 ± 4.5 ng/mL, p < 0.01), day 35 (42.6 ± 19.8 vs. 28.6 ± 7.2 ng/mL, p = 0.038), and day 90 (59.7 ± 27.7 vs. 34.1 ± 3.2 ng/mL, p = 0.014) than the control group. Circulating small EVs isolated from aspirated mice on day 90 contained higher levels of Col-V (0.7 ± 0.56 vs. 0.18 ± 0.6 m.o.d., p = 0.009) and NF-κB (0.42 ± 0.27 vs. 0.27 ± 0.09 m.o.d., p = 0.095) than those from controls. CONCLUSIONS: This experimental study supports the theory that gastroesophageal reflux leads to the development of lung damage and an increase of humoral markers that may serve as noninvasive biomarkers to detect asymptomatic lung injury among patients with gastroesophageal reflux disease.

9.
Arch Toxicol ; 98(10): 3209-3214, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39017690

RESUMO

Are all food ingredients, dietary supplement ingredients and even foods, required to meet the same safety standards? Are they all equally safe? If so, then why do the various categories have different expressions describing their safety, such as "reasonable certainty of no harm" for food ingredients and "reasonable expectation of no harm" for dietary supplement ingredients? The basis for these different expressions is that they are not standards of safety, but standards of proof of safety. Just as in criminal vs. civil courts, the threshold for proving guilt or fault is different, so too are there differences between various categories of consumer products regulated by the US Food and Drug Administration. This manuscript describes the threshold requirements for each standard, as well as to the identity of the decision makers on what is safe, their credentials as decision makers and the databases mandated for their use.


Assuntos
Qualidade de Produtos para o Consumidor , United States Food and Drug Administration , Estados Unidos , United States Food and Drug Administration/normas , Humanos , Qualidade de Produtos para o Consumidor/normas , Qualidade de Produtos para o Consumidor/legislação & jurisprudência , Suplementos Nutricionais/normas , Suplementos Nutricionais/efeitos adversos , Inocuidade dos Alimentos , Animais , Medição de Risco
10.
J Biopharm Stat ; : 1-15, 2024 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-39127994

RESUMO

Dose optimization is a critical challenge in drug development. Historically, dose determination in oncology has followed a divergent path from other non-oncology therapeutic areas due to the unique characteristics and requirements in Oncology. However, with the emergence of new drug modalities and mechanisms of drugs in oncology, such as immune therapies, radiopharmaceuticals, targeted therapies, cytostatic agents, and others, the dose-response relationship for efficacy and toxicity could be vastly varied compared to the cytotoxic chemotherapies. The doses below the MTD may demonstrate similar efficacy to the MTD with an improved tolerability profile, resembling what is commonly observed in non-oncology treatments. Hence, alternate strategies for dose optimization are required for new modalities in oncology drug development. This paper delves into the historical evolution of dose finding methods from non-oncology to oncology, highlighting examples and summarizing the underlying drivers of change. Subsequently, a practical framework and guidance are provided to illustrate how dose optimization can be incorporated into various stages of the development program. We provide the following general recommendations: 1) The objective for phase I is to identify a dose range rather than a single MTD dose for subsequent development to better characterize the safety and tolerability profile within the dose range. 2) At least two doses separable by PK are recommended for dose optimization in phase II. 3) Ideally, dose optimization should be performed before launching the confirmatory study. Nevertheless, innovative designs such as seamless II/III design can be implemented for dose selection and may accelerate the drug development program.

11.
J Biopharm Stat ; : 1-14, 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38335371

RESUMO

Combination therapies with multiple mechanisms of action can offer improved efficacy and/or safety profiles when compared to a single therapy with one mechanism of action. Consequently, the number of combination therapy studies have increased multi-fold, both in oncology and non-oncology indications. However, identifying the optimal doses of each drug in a combination therapy can require a large sample size and prolong study timelines, especially when full factorial designs are used. In this paper, we extend the MCP-Mod design of Bretz, Pinheiro, and Branson to a three-dimensional space to model the dose-response surface of a two-drug combination under the framework of Combination (Comb) MCP-Mod. The resulting model yields a set of dosages for each drug in the combination that elicits the target response so that an optimal dose for the combination can be selected for pivotal studies. We construct three-dimensional dose-response models for the combination and formulate the contrast test statistic to select the best model, which can then be used to select the optimal dose. Guidance to calculate power and sample size calculations are provided to assist study design. Simulation studies show that Comb MCP-Mod performs as well as the conventional multiple comparisons approach in controlling the family-wise error rate at the desired alpha level. However, Comb MCP-Mod is more powerful than the classical multiple comparisons approach in detecting dose-response relationships when treatment is non-null. The probability of correctly identifying the underlying dose-response relationship is generally higher when using Comb MCP-Mod than when using the multiple comparisons approach.

12.
Drug Resist Updat ; 66: 100890, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36455341

RESUMO

Drug resistance is well-defined as a serious problem in our living world. To survive, microbes develop defense strategies against antimicrobial drugs. Drugs exhibit less or no effective results against microbes after the emergence of resistance because they are unable to cross the microbial membrane, in order to alter enzymatic systems, and/or upregulate efflux pumps, etc. Drug resistance issues can be addressed effectively if a "Resistance-Proof" or "Resistance-Resistant" antimicrobial agent is developed. This article discusses first the need for resistance-proof drugs, the imminent properties of resistance-proof drugs, current and future research progress in the discovery of resistance-proof antimicrobials, the inherent challenges, and opportunities. A molecule having imminent resistance-proof properties could target microbes efficiently, increase potency, and rule out the possibility of early resistance. This review triggers the scientific community to think about how an upsurge in drug resistance can be averted and emphasizes the discussion on the development of next-generation antimicrobials that will provide a novel effective solution to combat the global problem of drug resistance. Hence, resistance-proof drug development is not just a requirement but rather a compulsion in the drug discovery field so that resistance can be battled effectively. We discuss several properties of resistance-proof drugs which could initiate new ways of thinking about next-generation antimicrobials to resolve the drug resistance problem. This article sheds light on the issues of drug resistance and discusses solutions in terms of the resistance-proof properties of a molecule. In summary, the article is a foundation to break new ground in the development of resistance-proof therapeutics in the field of infection biology.


Assuntos
Antibacterianos , Anti-Infecciosos , Humanos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana , Anti-Infecciosos/farmacologia , Anti-Infecciosos/uso terapêutico , Resistência a Medicamentos , Descoberta de Drogas/métodos
13.
J Med Internet Res ; 26: e46556, 2024 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-39320943

RESUMO

BACKGROUND: Telehealth played a critical role during the COVID-19 pandemic and continues to function as an essential component of health care. Existing platforms cannot ensure privacy and prevent cyberattacks. OBJECTIVE: The main objectives of this study are to understand existing cybersecurity issues in identity management and trustworthy communication processes in telehealth platforms and to design a software architecture integrated with blockchain to improve security and trustworthiness with acceptable performance. METHODS: We improved personal information security in existing telehealth platforms by adopting an innovative interdisciplinary approach combining design science, social science, and computer science in the health care domain, with prototype implementation. We used the design science research methodology to implement our overall design. We innovated over existing telehealth platforms with blockchain integration that improves health care delivery services in terms of security, privacy, and efficiency. We adopted a user-centric design approach and started with user requirement collection, followed by system functionality development. Overall system implementation facilitates user requirements, thus promoting user behavior for the adoption of the telehealth platform with decentralized identity management and an access control mechanism. RESULTS: Our investigation identified key challenges to identity management and trustworthy communication processes in telehealth platforms used in the current health care domain. By adopting distributed ledger technology, we proposed a decentralized telehealth platform to support identity management and a trustworthy communication process. Our design and prototype implementation using a smart contract-driven telehealth platform to provide decentralized identity management and trustworthy communication with token-based access control addressed several security challenges. This was substantiated by testing with 10,000 simulated transactions across 5 peers in the Rahasak blockchain network. The proposed design provides resistance to common attacks while maintaining a linear time overhead, demonstrating improved security and efficiency in telehealth services. We evaluated the performance in terms of transaction throughput, smart contract execution time, and block generation time. To create a block with 10,000 transactions, it takes 8 seconds on average, which is an acceptable overhead for blockchain-based applications. CONCLUSIONS: We identified technical limitations in current telehealth platforms. We presented several design innovations using blockchain to prototype a system. We also presented the implementation details of a unique distributed architecture for a trustworthy communication system. We illustrated how this design can overcome privacy, security, and scalability limitations. Moreover, we illustrated how improving these factors sets the stage for improving and standardizing the application and for the wide adoption of blockchain-enabled telehealth platforms.


Assuntos
Blockchain , COVID-19 , Segurança Computacional , Pandemias , SARS-CoV-2 , Telemedicina , Humanos , Confiança , Confidencialidade , Comunicação Interdisciplinar
14.
J Shoulder Elbow Surg ; 33(2): 291-299, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37479177

RESUMO

BACKGROUND: Shoulder internal rotation contracture and subluxation in the first year of life has long been recognized in some patients with brachial plexus birth injury (BPBI). Surgical management of shoulder pathology has traditionally been undertaken following nerve reconstruction as necessary. In some patients; however, shoulder pathology may impair or obscure functional neuromuscular recovery of the upper extremity. As a proof of concept, we report a highly selected subset of patients with BPBI in whom shoulder surgery undertaken before one year of age obviated the need for neuroma resection and nerve grafting. METHODS: A retrospective review was performed of all patients with upper trunk BPBI who underwent shoulder surgery before one year of age from 2015 to 2018. Upper extremity motor function was evaluated with preoperative and postoperative Active Movement Scale scores, Cookie tests, and the requirement for subsequent neuroma resection and nerve grafting. RESULTS: Fifteen patients with BPBI meeting the inclusion criteria underwent shoulder surgery (including a subscapularis slide and tendon transfers of the teres major and latissimus dorsi muscles) before 1 year of age. Preoperatively, no patients of the appropriate age passed the Cookie test for elbow flexion. Thirteen patients either passed the Cookie test or scored Active Movement Scale score 7 for elbow flexion at or before the last available follow-up undertaken at a median age of 3.4 [1.4, 5.2] years. One of those 13 patients underwent single fascicular distal nerve transfer to improve elbow flexion before subsequently passing the Cookie test. Two patients did not have sufficient follow-up to assess elbow flexion. CONCLUSION: Although the exact role of shoulder surgery in infancy for BPBI remains to be defined, the findings from this study provide proof of concept that early, targeted surgical treatment of the shoulder may obviate the need for brachial plexus nerve reconstruction in a highly selected group of infants with BPBI.


Assuntos
Traumatismos do Nascimento , Neuropatias do Plexo Braquial , Plexo Braquial , Contratura , Neuroma , Lactente , Humanos , Neuropatias do Plexo Braquial/cirurgia , Plexo Braquial/lesões , Neuroma/cirurgia , Amplitude de Movimento Articular , Resultado do Tratamento
15.
Sensors (Basel) ; 24(3)2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38339751

RESUMO

To address the complexities, inflexibility, and security concerns in traditional data sharing models of the Industrial Internet of Things (IIoT), we propose a blockchain-based data sharing and privacy protection (BBDSPP) scheme for IIoT. Initially, we characterize and assign values to attributes, and employ a weighted threshold secret sharing scheme to refine the data sharing approach. This enables flexible combinations of permissions, ensuring the adaptability of data sharing. Subsequently, based on non-interactive zero-knowledge proof technology, we design a lightweight identity proof protocol using attribute values. This protocol pre-verifies the identity of data accessors, ensuring that only legitimate terminal members can access data within the system, while also protecting the privacy of the members. Finally, we utilize the InterPlanetary File System (IPFS) to store encrypted shared resources, effectively addressing the issue of low storage efficiency in traditional blockchain systems. Theoretical analysis and testing of the computational overhead of our scheme demonstrate that, while ensuring performance, our scheme has the smallest total computational load compared to the other five schemes. Experimental results indicate that our scheme effectively addresses the shortcomings of existing solutions in areas such as identity authentication, privacy protection, and flexible combination of permissions, demonstrating a good performance and strong feasibility.

16.
Pharm Stat ; 23(1): 20-30, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37691560

RESUMO

Adaptive seamless trial designs, combining the learning and confirming cycles of drug development in a single trial, have gained popularity in recent years. Adaptations may include dose selection, sample size re-estimation and enrichment of the study population. Despite methodological advances and recognition of the potential efficiency gains such designs offer, their implementation, including how to enable efficient decision making on the adaptations in interim analyzes, remains a key challenge in their adoption. This manuscript uses a case study of an adaptive seamless proof-of-concept (Phase 2a)/dose-finding (Phase 2b) to showcase potential adaptive features that can be implemented in trial designs at earlier development stages and the role of simulations in assessing the design operating characteristics and specifying the decision rules for the adaptations. It further outlines the elements needed to support successful interim analysis decision making on the adaptations while safeguarding study integrity, including the role of different stakeholders, interactive simulation-based tools to facilitate decision making and operational aspects requiring preplanning. The benefits of the adaptive Phase 2a/2b design chosen compared to following the traditional two separate studies (2a and 2b) paradigm are discussed. With careful planning and appreciation of their complexity and components needed for their implementation, seamless adaptive designs have the potential to yield significant savings both in terms of time and resources.


Assuntos
Nefropatias , Projetos de Pesquisa , Humanos , Simulação por Computador , Tomada de Decisões , Tamanho da Amostra , Ensaios Clínicos como Assunto
17.
Sensors (Basel) ; 24(12)2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38931812

RESUMO

In this study, we have developed an electrostatically suspended accelerometer (ESA) specifically designed for ground use. To ensure sufficient overload capacity and minimize noise resulting from high suspension voltage, we introduced a proof mass design featuring a hollow, thin-walled cylinder with a thin flange fixed at the center, offering the highest surface-area-to-mass ratio compared to various typical proof mass structures. Preload voltage is directly applied to the proof mass via a golden wire, effectively reducing the maximum supply voltage for suspension. The arrangement of suspension electrodes, offering five degrees of freedom and minimizing cross-talk, was designed to prioritize simplicity and maximize the utilization of electrode area for suspension purposes. The displacement detection and electrostatic suspension force were accurately modeled based on the structure. A controller incorporating an inverse winding mechanism was developed and simulated using Simulink. The simulation results unequivocally demonstrate the successful completion of the stable initial levitation process and suspension under ±1g overload.

18.
Sensors (Basel) ; 24(17)2024 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-39275749

RESUMO

UAVs are increasingly being used in various domains, from personal and commercial applications to military operations. Ensuring the security and trustworthiness of UAV communications is crucial, and blockchain technology has been explored as a solution. However, privacy remains a challenge, especially in public blockchains. In this work, we propose a novel approach utilizing zero-knowledge proof techniques, specifically zk-SNARKs, which are non-interactive cryptographic proofs. This approach allows UAVs to prove their authenticity or location without disclosing sensitive information. We generated zk-SNARK proofs using the Zokrates tool on a Raspberry Pi, simulating a drone environment, and analyzed power consumption and CPU utilization. The results are promising, especially in the case of larger drones with higher battery capacities. Ethereum was chosen as the public blockchain platform, with smart contracts developed in Solidity and tested on the Sepolia testnet using Remix IDE. This novel proposed approach paves the way for a new path of research in the UAV area.

19.
Sensors (Basel) ; 24(7)2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38610426

RESUMO

Decentralized Identifiers have recently expanded into Internet of Things devices and are crucial in securing users' digital identities and data. However, Decentralized Identifiers face challenges in scenarios necessitating authority delegation and anonymity, such as when dealing with legal guardianship for minors, device loss or damage, and specific medical contexts involving patient information. This paper aims to strengthen data sovereignty within the Decentralized Identifier system by implementing a secure authority delegation and anonymity scheme. It suggests optimizing verifiable presentations by utilizing a sequential aggregate signature, a Non-Interactive Zero-Knowledge Proof, and a Merkle tree to prevent against linkage and Sybil attacks while facilitating delegation. This strategy mitigates security risks related to delegation and anonymity, efficiently reduces the computational and verification efforts for signatures, and reduces the size of verifiable presentations by about 1.2 to 2 times.

20.
Sensors (Basel) ; 24(3)2024 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-38339482

RESUMO

This treatise studies a microoptoelectromechanical accelerometer (MOEMA) with an optical measuring transducer built according to the optical tunneling principle (evanescent coupling). The work discusses the design of the accelerometer's microelectromechanical sensing element (MSE) and states the requirements for the design to achieve a sensitivity threshold of 1 µg m/s2 at a calculated eigenvalue of the MSE. The studies cover the selection of the dimensions, mass, eigenfrequency and corresponding stiffness of the spring suspension, gravity-induced cross-displacements. The authors propose and experimentally test an optical transducer positioning system represented by a capacitive actuator. This approach allows avoiding the restrictions in the fabrication of the transducer conditioned by the extremely high aspect ratio of deep silicon etching (more than 100). The designed MOEMA is tested on three manufactured prototypes. The experiments show that the sensitivity threshold of the accelerometers is 2 µg. For the dynamic range from minus 0.01 g to plus 0.01 g, the average nonlinearity of the accelerometers' characteristics ranges from 0.7% to 1.62%. For the maximum dynamic range from minus 0.015 g to plus 0.05 g, the nonlinearity ranges from 2.34% to 2.9%, having the maximum deviation at the edges of the regions. The power gain of the three prototypes of accelerometers varies from 12.321 mW/g to 26.472 mW/g. The results provide broad prospects for the application of the proposed solutions in integrated inertial devices.

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