Multidisciplinary design of a more electric regional aircraft including certification constraints

The use of electrified on-board systems is increasingly more required to reduce aircraft complexity, polluting emissions, and its life cycle cost. However, the more and all-electric aircraft configurations are still uncommon in the civil aviation context and their certifiability has yet to be proven in some aircraft segments. The aim of the present paper is to define a multidisciplinary design problem which includes some disciplines pertaining to the certification domain. In particular, the study is focused on the preliminary design of a 19 passengers small regional turboprop aircraft. Different on-board systems architectures with increasing electrification levels are considered. These architectures imply the use of bleedless technologies including electrified ice protection and environmental control systems. The use of electric actuators for secondary surfaces and landing gear are also considered. The aircraft design, which includes aerodynamic, structural, systems and propulsion domains, is then assessed by some certification disciplines. In particular, minimum performance, external noise and safety assessments are included in the workflow giving some insights on the aircraft certifiability. The results show a reduction of 3% of MTOM and 3% of fuel mass depending on the systems architecture selected. From the certification side, the design has proven to be certifiable and the margins with the certification constraint can be controlled to improve the overall design

Web of venom: exploration of big data resources in animal toxin research

Research on animal venoms and their components spans multiple disciplines, including biology, biochemistry, bioinformatics, pharmacology, medicine, and more. Manipulating and analyzing the diverse array of data required for venom research can be challenging, and relevant tools and resources are often dispersed across different online platforms, making them less accessible to nonexperts. In this article, we address the multifaceted needs of the scientific community involved in venom and toxin-related research by identifying and discussing web resources, databases, and tools commonly used in this field. We have compiled these resources into a comprehensive table available on the VenomZone website (https://venomzone.expasy.org/10897). Furthermore, we highlight the challenges currently faced by researchers in accessing and using these resources and emphasize the importance of community-driven interdisciplinary approaches. We conclude by underscoring the significance of enhancing standards, promoting interoperability, and encouraging data and method sharing within the venom research community

MBSE Certification-Driven Design of a UAV MALE Configuration in the AGILE 4.0 Design Environment

This paper presents a certification-driven design process for an Unmanned Medium-Altitude- Long-Endurance (UAV MALE) air vehicle, including on-board system design and placements, electro-magnetic compatibility analysis, and thermal risk assessments. In literature, the preliminary aircraft design phase is mainly driven by mission performances and structural integrity aspects. However, the inclusion of other disciplines, like on-board system design or electro-magnetic compatibility, or thermal analysis, can lead to more efficient and cost- effective solutions and becomes paramount for non-conventional configurations like unmanned vehicles or highly electrified platforms. In the EC-funded AGILE 4.0 project (2019-2022), the traditional scope of the preliminary aircraft design is extended by including domains that are usually considered only in later design phases, such as certification, production and maintenance. In this paper, the AGILE 4.0 design environment supports the definition and execution of a certification-driven design process of a UAV MALE configuration, using a Model-Based Systems Engineering (MBSE) approach

ArachnoServer 2.0, an updated online resource for spider toxin sequences and structures

ArachnoServer (www.arachnoserver.org) is a manually curated database providing information on the sequence, structure and biological activity of protein toxins from spider venoms. These proteins are of interest to a wide range of biologists due to their diverse applications in medicine, neuroscience, pharmacology, drug discovery and agriculture. ArachnoServer currently manages 1078 protein sequences, 759 nucleic acid sequences and 56 protein structures. Key features of ArachnoServer include a molecular target ontology designed specifically for venom toxins, current and historic taxonomic information and a powerful advanced search interface. The following significant improvements have been implemented in version 2.0: (i) the average and monoisotopic molecular masses of both the reduced and oxidized form of each mature toxin are provided; (ii) the advanced search feature now enables searches on the basis of toxin mass, external database accession numbers and publication date in ArachnoServer; (iii) toxins can now be browsed on the basis of their phyletic specificity; (iv) rapid BLAST searches based on the mature toxin sequence can be performed directly from the toxin card; (v) private silos can be requested from research groups engaged in venoms-based research, enabling them to easily manage and securely store data during the process of toxin discovery; and (vi) a detailed user manual is now available

ATDB: a uni-database platform for animal toxins

Venomous animals possess an arsenal of toxins for predation and defense. These toxins have great diversity in function and structure as well as evolution and therefore are of value in both basic and applied research. Recently, toxinomics researches using cDNA library sequencing and proteomics profiling have revealed a large number of new toxins. Although several previous groups have attempted to manage these data, most of them are restricted to certain taxonomic groups and/or lack effective systems for data query and access. In addition, the description of the function and the classification of toxins is rather inconsistent resulting in a barrier against exchanging and comparing the data. Here, we report the ATDB database and website which contains more than 3235 animal toxins from UniProtKB/Swiss-Prot and TrEMBL and related toxin databases as well as published literature. A new ontology (Toxin Ontology) was constructed to standardize the toxin annotations, which includes 745 distinct terms within four term spaces. Furthermore, more than 8423 TO terms have been manually assigned to 2132 toxins by trained biologists. Queries to the database can be conducted via a user-friendly web interface at http://protchem.hunnu.edu.cn/toxin

The Infrared Array Camera (IRAC) for the Spitzer Space Telescope

The Infrared Array Camera (IRAC) is one of three focal plane instruments in the Spitzer Space Telescope. IRAC is a four-channel camera that obtains simultaneous broad-band images at 3.6, 4.5, 5.8, and 8.0 microns. Two nearly adjacent 5.2x5.2 arcmin fields of view in the focal plane are viewed by the four channels in pairs (3.6 and 5.8 microns; 4.5 and 8 microns). All four detector arrays in the camera are 256x256 pixels in size, with the two shorter wavelength channels using InSb and the two longer wavelength channels using Si:As IBC detectors. IRAC is a powerful survey instrument because of its high sensitivity, large field of view, and four-color imaging. This paper summarizes the in-flight scientific, technical, and operational performance of IRAC.Comment: 7 pages, 3 figures. Accepted for publication in the ApJS. A higher resolution version is at http://cfa-www.harvard.edu/irac/publication

Measurement properties of EQ-5D-3L and EQ-5D-5L in recording self-reported health status in older patients with substantial multimorbidity and polypharmacy

Background The EQ-5D-3L and EQ-5D-5L are two generic health-related quality of life measures, which may be used in clinical and health economic research. They measure impairment in 5 aspects of health: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The aim of this study was to assess the performance of the EQ-5D-3L and EQ-5D-5L in measuring the self-reported health status of older patients with substantial multimorbidity and associated polypharmacy. Methods Between 2017 and 2019, we administered EQ-5D-3L and EQ-5D-5L to a subset of patients participating in the OPERAM trial at 6 months and 12 months after enrolment. The OPERAM trial is a two-arm multinational cluster randomised controlled trial of structured medication review assisted by a software-based decision support system versus usual pharmaceutical care, for older people (aged ≥ 70 years) with multimorbidity and polypharmacy. In the psychometric analyses, we only included participants who completed the measures in full at 6 and 12 months. We assessed whether responses to the measures were consistent by assessing the proportion of EQ-5D-5L responses, which were 2 or more levels away from that person’s EQ-5D-3L response. We also compared the measures in terms of informativity, and discriminant validity and responsiveness relative to the Barthel Index, which measures independence in activities of daily living. Results 224 patients (mean age of 77 years; 56% male) were included in the psychometric analyses. Ceiling effects reported with the EQ-5D-5L (22%) were lower than with the EQ-5D-3L (29%). For the mobility item, the EQ-5D-5L demonstrated better informativity (Shannon’s evenness index score of 0.86) than the EQ-5D-3L (Shannon’s evenness index score of 0.69). Both the 3L and 5L versions of EQ-5D demonstrated good performance in terms of discriminant validity, i.e. (out of all items of the EQ-5D-3L and EQ-5D-5L, the pain/discomfort and anxiety/depression items had the weakest correlation with the Barthel Index. Both the 3L and 5L versions of EQ-5D demonstrated good responsiveness to changes in the Barthel Index. Conclusion Both EQ-5D-3L and EQ-5D-5L demonstrated validity and responsiveness when administered to older adults with substantial multimorbidity and polypharmacy who were able to complete the measures

Detectability of Medication Errors With a STOPP/START-Based Medication Review in Older People Prior to a Potentially Preventable Drug-Related Hospital Admission.

INTRODUCTION Multimorbidity and polypharmacy are risk factors for drug-related hospital admissions (DRAs) in the ageing population. DRAs caused by medication errors (MEs) are considered potentially preventable. The STOPP/START criteria were developed to detect potential MEs in older people. OBJECTIVE The aim of this study was to assess the detectability of MEs with a STOPP/START-based in-hospital medication review in older people with polypharmacy and multimorbidity prior to a potentially preventable DRA. METHODS Hospitalised older patients (n = 963) with polypharmacy and multimorbidity from the intervention arm of the OPERAM trial received a STOPP/START-based in-hospital medication review by a pharmacotherapy team. Readmissions within 1 year after the in-hospital medication review were adjudicated for drug-relatedness. A retrospective assessment was performed to determine whether MEs identified at the first DRA were detectable during the in-hospital medication review. RESULTS In total, 84 of 963 OPERAM intervention patients (8.7%) were readmitted with a potentially preventable DRA, of which 72 patients (n = 77 MEs) were eligible for analysis. About half (48%, n = 37/77) of the MEs were not present during the in-hospital medication review and therefore were not detectable at that time. The pharmacotherapy team recommended a change in medication regimen in 50% (n = 20/40) of present MEs, which corresponds to 26% (n = 20/77) of the total identified MEs at readmission. However, these recommendations were not implemented. CONCLUSION MEs identified at readmission were not addressed by a prior single in-hospital medication review because either these MEs occurred after the medication review (~50%), or no recommendation was given during the medication review (~25%), or the recommendation was not implemented (~25%). Future research should focus on optimisation of the timing and frequency of medication review and the implementation of proposed medication recommendations. REGISTRATION ClinicalTrials.gov identifier: NCT02986425. December 8, 2016. FUNDING European Union HORIZON 2020, Swiss State Secretariat for Education, Research and Innovation (SERI), Swiss National Science Foundation (SNSF)

Thyroid antibodies and levothyroxine effects in subclinical hypothyroidism: A pooled analysis of two randomized controlled trials

Background: Antithyroid antibodies increase the likelihood of developing overt hypothyroidism, but their clinical utility remains unclear. No large randomized controlled trial (RCT) has assessed whether older adults with subclinical hypothyroidism (SHypo) caused by autoimmune thyroid disease derive more benefits from levothyroxine treatment (LT4). Objective: To determine whether older adults with SHypo and positive antibodies derive more clinical benefits from LT4 than those with negative antibodies. Methods: We pooled individual participant data from two RCTs, Thyroid Hormone Replacement for Untreated Older Adults with Subclinical Hypothyroidism and IEMO 80+. Participants with persistent SHypo were randomly assigned to receive LT4 or placebo. We compared the effects of LT4 versus placebo in participants with and without anti–thyroid peroxidase (TPO) at baseline. The two primary outcomes were 1-year change in Hypothyroid Symptoms and Tiredness scores on the Thyroid-Related Quality-of-Life Patient-Reported Outcome Questionnaire. Results: Among 660 participants (54% women) ≥65 years, 188 (28.5%) had positive anti-TPO. LT4 versus placebo on Hypothyroid Symptoms lead to an adjusted between-group difference of −2.07 (95% confidence interval: −6.04 to 1.90) for positive antibodies versus 0.89 (−1.76 to 3.54) for negative antibodies (p for interaction = 0.31). Similarly, there was no treatment effect modification by baseline antibody status for Tiredness scores—adjusted between-group difference 1.75 (−3.60 to 7.09) for positive antibodies versus 1.14 (−1.90 to 4.19) for negative antibodies (p for interaction = 0.98). Positive anti-TPO were not associated with better quality of life, improvement in handgrip strength, or fewer cardiovascular outcomes with levothyroxine treatment. Conclusions: Among older adults with SHypo, positive antithyroid antibodies are not associated with more benefits on clinical outcomes with LT4

Collaborative annotation of genes and proteins between UniProtKB/Swiss-Prot and dictyBase

UniProtKB/Swiss-Prot, a curated protein database, and dictyBase, the Model Organism Database for Dictyostelium discoideum, have established a collaboration to improve data sharing. One of the major steps in this effort was the ‘Dicty annotation marathon’, a week-long exercise with 30 annotators aimed at achieving a major increase in the number of D. discoideum proteins represented in UniProtKB/Swiss-Prot. The marathon led to the annotation of over 1000 D. discoideum proteins in UniProtKB/Swiss-Prot. Concomitantly, there were a large number of updates in dictyBase concerning gene symbols, protein names and gene models. This exercise demonstrates how UniProtKB/Swiss-Prot can work in very close cooperation with model organism databases and how the annotation of proteins can be accelerated through those collaborations