Corrigendum to: ATRI EDC: a novel cloud-native remote data capture system for large multicenter Alzheimer's disease and Alzheimer's disease-related dementias clinical trials.

[This corrects the article DOI: 10.1093/jamiaopen/ooab119.].

ATRI EDC: a novel cloud-native remote data capture system for large multicenter Alzheimer's disease and Alzheimer's disease-related dementias clinical trails.

OBJECTIVE: The Alzheimer's Therapeutic Research Institute (ATRI) developed a novel clinical data management system, the ATRI electronic data capture system (ATRI EDC), to address the complex regulatory, operational, and data requirements that arise in the conduct of multicenter Alzheimer's disease and Alzheimer's disease-related dementias (AD/ADRDs) clinical trials. We describe the system, its utility, and the broader implications for the field of clinical trials and clinical research informatics. MATERIALS AND METHODS: The ATRI EDC system was developed, tested, and validated using community-based agile software development methods and cloud-native single-page application design principles. It offers an increasing number of application modules, supports a high degree of study-specific configuration, and empowers study teams to effectively communicate and collaborate on the accurate and timely completion of study activities. RESULTS: To date, the ATRI EDC system supports 10 clinical studies, collecting study data for 4596 participants. Three case descriptions further illustrate how the system's capabilities support diverse study-specific requirements. DISCUSSION: The ATRI EDC system has several advantages: its modular capabilities can accommodate rapidly evolving research designs and technologies; its community-based agile development approach and community-friendly licensing model encourage collaboration per the principles of open science; finally, with continued development and community building efforts, the system has the potential to facilitate the effective conduct of clinical studies beyond the field of AD/ADRD. CONCLUSION: By effectively addressing the requirements of multicenter AD/ADRD studies, the ATRI EDC system supports ATRI's scientific mission of rigorously testing new AD/ADRD therapies and facilitating the effective conduct of multicenter clinical studies.

Turning of Additively Manufactured Ti6Al4V: Effect of the Highly Oriented Microstructure on the Surface Integrity.

Additive manufacturing processes induce a high orientation in the microstructure of the printed part due to the strong thermal gradients developed during the process caused by the highly concentrated heat source that is used to melt the metal powder layer-by-layer. The resulting microstructural anisotropy may have an effect on the post-processing operations such as machining ones. This paper investigates the influence of the anisotropy in turning operations carried out on laser powder bed fused Ti6Al4V parts manufactured with different scanning strategies. The machinability under both transverse and cylindrical turning operations was assessed in terms of surface integrity, considering both surface and sub-surface aspects. The effect of the different cooling conditions, that is flood and cryogenic ones, was studied as well. The outcomes showed that the microstructural anisotropy had a remarkable effect on the machining operations and that the cryogenic cooling enhanced the effect of the anisotropy in determining the surface integrity.

The Effect of Direct Electric Current on the Plastic Behavior of AA7075 Aluminum Alloy in Different States of Hardening.

Electrically-Assisted Forming (EAF) techniques are interesting and promising for the automotive industry. Electrically-assisted tensile tests were carried out on specimens of AA7075 aluminum alloy in different states of hardening, namely T6 (the as-received state) and the supersaturated solid solution state. All the tests were carried out in quasi-static conditions under the application of direct electric current (DC) in the range of 90 to 540 A. The experimental results showed that with a DC density of 10 A/mm2 the uniform strain and strain at fracture increased when the AA7075 was in the supersaturated solid solution state. A correlation between the mechanical results and microstructural features analysed through transmission electron microscopy was assessed. An explanation of the investigated phenomena based on the electron wind theory, heterogeneous microscale Joule heating and the Portevin-Le Chatelier (PLC) effect was finally proposed.

Search algorithms as a framework for the optimization of drug combinations.

Combination therapies are often needed for effective clinical outcomes in the management of complex diseases, but presently they are generally based on empirical clinical experience. Here we suggest a novel application of search algorithms -- originally developed for digital communication -- modified to optimize combinations of therapeutic interventions. In biological experiments measuring the restoration of the decline with age in heart function and exercise capacity in Drosophila melanogaster, we found that search algorithms correctly identified optimal combinations of four drugs using only one-third of the tests performed in a fully factorial search. In experiments identifying combinations of three doses of up to six drugs for selective killing of human cancer cells, search algorithms resulted in a highly significant enrichment of selective combinations compared with random searches. In simulations using a network model of cell death, we found that the search algorithms identified the optimal combinations of 6-9 interventions in 80-90% of tests, compared with 15-30% for an equivalent random search. These findings suggest that modified search algorithms from information theory have the potential to enhance the discovery of novel therapeutic drug combinations. This report also helps to frame a biomedical problem that will benefit from an interdisciplinary effort and suggests a general strategy for its solution.