Supply chain risks: an automotive case study

The supply chain is a complex system exchanging information, goods, material and money within enterprises, as well as between enterprises within the value chain. An effective supply chain management contributes to large corporate profits and it is therefore a valid path to reinforce the enterprises' competitiveness. However, supply chain is exposed to influences from undesirable factors both from the outside environment and the entities in the chain. Moreover, industrial trends towards lean production, increasing outsourcing, globalisation and reliance on supply networks capabilities and innovations, increase the complexity of the supply chain . Therefore, managers need to identify, and manage risks, as well as opportunities, from a more diverse range of sources and contexts. This paper contributes to identify and categorise supply chain risks based on a literature study and an automotive manufacturer’s viewpoint. The empirical results indicate suppliers and raw material prices as the major internal and external potential risks

Histopathologic Evaluation of Polymer Supports for Pintucci-Type Keratoprostheses: an Animal Study

Purpose: To report histopathological findings for different types of polymers proposed as support for a Pintucci-type keratoprosthesis. Methods: Six polymers, including three types of polyesters (#1-3), one type of polytetrafluoroethylene (PTFE, #4), polyethylene (#5), and expanded polytetrafluoroethylene (ePTFE, #6) were evaluated. Four samples of each material were placed under the orbicularis oculi muscles of 12 rabbits. After five weeks, the samples were removed and evaluated histopathologically. Fibrovascular tissue ingrowths were investigated in terms of tissue penetration depth into the materials (graded as none, mild, moderate, and intense) and fibrovascular ingrowth area at the ultimate level of tissue penetrance. ImageJ software was used to calculate fibrovascular tissue area between the material fibers, and the mean area values were compared between the materials. Results: Polyester materials #1 and #3 demonstrated intense fibrovascular tissue penetration with a large fibrovascular ingrowth area; no overt tissue ingrowth was observed into material #6. The mean area of penetrated fibrovascular tissues was significantly different between materials (P < 0.001). Materials #2, #4, and #5 showed moderate fibrovascular tissue ingrowth and the area of presented fibrovascular tissue at the paracentral parts of material #4 was significantly smaller than that of materials #1 (P = 0.02) and #3 (P = 0.01). Conclusion: Two polyester materials that had relatively large pore sizes demonstrated a deep and large area of fibrovascular ingrowth. Given that material #3 is thicker and more consistent than material #1, the former can be used as the appropriate material for supporting the Pintucci-type keratoprosthesis

Lectin Pathway Mediates Complement Activation by SARS-CoV-2 Proteins.

Early and persistent activation of complement is considered to play a key role in the pathogenesis of COVID-19. Complement activation products orchestrate a proinflammatory environment that might be critical for the induction and maintenance of a severe inflammatory response to SARS-CoV-2 by recruiting cells of the cellular immune system to the sites of infection and shifting their state of activation towards an inflammatory phenotype. It precedes pathophysiological milestone events like the cytokine storm, progressive endothelial injury triggering microangiopathy, and further complement activation, and causes an acute respiratory distress syndrome (ARDS). To date, the application of antiviral drugs and corticosteroids have shown efficacy in the early stages of SARS-CoV-2 infection, but failed to ameliorate disease severity in patients who progressed to severe COVID-19 pathology. This report demonstrates that lectin pathway (LP) recognition molecules of the complement system, such as MBL, FCN-2 and CL-11, bind to SARS-CoV-2 S- and N-proteins, with subsequent activation of LP-mediated C3b and C4b deposition. In addition, our results confirm and underline that the N-protein of SARS-CoV-2 binds directly to the LP- effector enzyme MASP-2 and activates complement. Inhibition of the LP using an inhibitory monoclonal antibody against MASP-2 effectively blocks LP-mediated complement activation. FACS analyses using transfected HEK-293 cells expressing SARS-CoV-2 S protein confirm a robust LP-dependent C3b deposition on the cell surface which is inhibited by the MASP-2 inhibitory antibody. In light of our present results, and the encouraging performance of our clinical candidate MASP-2 inhibitor Narsoplimab in recently published clinical trials, we suggest that the targeting of MASP-2 provides an unsurpassed window of therapeutic efficacy for the treatment of severe COVID-19

‘There was nothing, just absolute darkness’: Understanding the needs of those caring for children and young people with complex neurodisability in a diverse UK context: A qualitative exploration in the ENCOMPASS study

Background: Children and young people (CYP) with complex neurodisability experience multiple physical, communication, educational and social challenges, which require complex packages of multidisciplinary care. Part of the holistic care required includes supporting the families and parents/caregivers. The aim of the wider study was to introduce a new programme (‘Ubuntu’) to parents/caregivers and healthcare professionals (HCPs) in order to test the feasibility and acceptability of the concept and content, with the goal of potential adaptation for the UK in mind. Data collection and analysis uncovered rich data on caregiving journeys, navigation of health services, and perceived service gaps. This paper focuses solely on these topics. Further papers will report on the feasibility and adaptation data. Methods: Two rounds of semi-structured interviews were conducted with 12 caregivers of CYP with complex neurodisability and six HCPs from a variety of disciplines, recruited from a community child health service in London Borough of Newham, UK in 2020. The interviews included open-ended questions to explore caregiving journeys, experiences of navigating health services and perceived service gaps. Transcripts were analysed using a data-driven inductive thematic analysis. Results: Three themes were identified that related to the aim of understanding caregivers' experiences and unmet needs relating to current service provision. These were (1) Caregiver Mental Health, (2) The Information Gap and (3) The Need for Holistic Support. Mental health difficulties were reported, particularly around the period of diagnosis. Priority needs included the provision of clear information about the diagnosis and services offered, opportunities to forge peer support networks and for services across the community to collaborate. Conclusions: The delivery of health services for CYP with neurodisability should encompass the broad needs of the family as well as meeting the clinical needs of the CYP

Structuring Stress for Active Materials Control

Active materials are capable of converting free energy into mechanical work to produce autonomous motion, and exhibit striking collective dynamics that biology relies on for essential functions. Controlling those dynamics and transport in synthetic systems has been particularly challenging. Here, we introduce the concept of spatially structured activity as a means to control and manipulate transport in active nematic liquid crystals consisting of actin filaments and light-sensitive myosin motors. Simulations and experiments are used to demonstrate that topological defects can be generated at will, and then constrained to move along specified trajectories, by inducing local stresses in an otherwise passive material. These results provide a foundation for design of autonomous and reconfigurable microfluidic systems where transport is controlled by modulating activity with light

MEAD - A Platform for Multidocument Multilingual Text Summarization

This paper describes the functionality of MEAD, a comprehensive, public domain, open source, multidocument multilingual summarization environment that has been thus far downloaded by more than 500 organizations. MEAD has been used in a variety of summarization applications ranging from summarization for mobile devices to Web page summarization within a search engine and to novelty detection

Exploring the needs of children and caregivers to inform design of an artificial intelligence-enhanced social robot in the pediatric emergency department

Background and Objective: Socially assistive robots (SARs) are a promising tool to manage children’s pain and distress related to medical procedures, but current options lack autonomous adaptability. The aim of this study was to understand children’s and caregivers' perceptions surrounding the use of an artificial intelligence (AI)-enhanced SAR to provide personalized procedural support to children during intravenous insertion (IVI) to inform the design of such a system following a user-centric approach. Methods: This study presents a descriptive qualitative needs assessment of children and caregivers. Data were collected via semi-structured individual interviews and focus groups. Participants were recruited from two Canadian pediatric emergency departments (EDs) between April 2021 and January 2022. Results: Eleven caregivers and 19 children completed 27 individual interviews and one focus group. Three main themes were identified: A. Experience in the clinical setting, B. Acceptance of and concerns surrounding SARs, and C. Features that support child engagement with SARs. Most participants expressed comfort with robot technology, however, concerns were raised about sharing personal information, photographing/videotaping, and the possibility of technical failure. Suggestions for feature enhancements included increasing movement to engage a child’s attention and tailoring language to developmental age. To enhance the overall ED experience, participants also identified a role for the SAR in the waiting room. Conclusion: Artificial intelligence-enhanced SARs were perceived by children and caregivers as a promising tool for distraction during IVIs and to enhance the overall ED experience. Insights collected will be used to inform the design of an AI-enhanced SAR

Antibody predictors of mortality and lung function trends in myositis spectrum interstitial lung disease

Objectives: The impact of autoantibody profiles on the prognosis for idiopathic inflammatory myositis-associated interstitial lung disease (IIM-ILD) and myositis spectrum ILD with myositis-specific antibodies (MSAs) remains unclear. This retrospective cohort study examined whether serological profiles were associated with mortality or longitudinal lung function change. Methods: The baseline clinical/demographic characteristics and follow-up lung function data of consecutive adult patients with IIM-ILD or interstitial pneumonia with autoimmune features (IPAF) positive for MSAs (IPAF-MSA) were extracted from three hospitals. Univariate and multivariate Cox proportional hazards analyses were used to compare mortality between groups of patients with different autoantibodies. Regression models were used to analyse their lung function trends. Results: Of the 430 included patients, 81% met the IIM criteria, and the remaining 19% were diagnosed with IPAF-MSA. On univariate analysis, the risk factors associated with mortality included higher age, Charlson Comorbidity Index, and CRP; and lower BMI, baseline TLCO% and FEV1%. Compared with anti-MDA5 negativity, anti-MDA5 positivity (MDA5+) was associated with higher mortality in the first 3 months [hazard ratio (HR) 65.2, 95% CI 14.1, 302.0], while no significant difference was seen thereafter (HR 0.55, 95% CI 0.14, 2.28). On multivariate analysis, combined anti-synthetase antibodies were associated with a reduced risk of mortality (HR 0.63), although individually, mortality was reduced in patients with anti-Jo1+ (HR 0.61, 95% CI 0.4-0.87) and increased in patients with anti-PL7+ (HR 2.07, 95% CI 1.44-2.99). Anti-MDA5+ was associated with slow improvement in %FVC over the first 3 years, while anti-PL7+ was linked with a slow decline from 12 months onwards. Conclusion: Among the autoantibody profiles in myositis spectrum disorders, anti-MDA5+ and anti-PL7+ conferred higher mortality risks in patients with IIM-ILD. Survivors of an early peak of mortality in anti-MDA5+ disease appeared to have a favourable prognosis.Funding: No specific funding was received from any bodies in the public, commercial or not-for-profit sectors to carry out the work described in this article. Disclosure statement: J.H.: none declared, A.L.: none declared, J.M.: none declared, M.N.: none declared, S.S.A.: none declared, C.S.: none declared, C.O.: none declared, A.D.: consultant of: Boehringer Ingelhime, Brainomix, L.P.: none declared, S.A.: none declared, B.A.-M.: none declared, M.A.G.-G.: none declared, A.P.: none declared, A.W.: none declared, K.T.: none declared, H.R.: none declared, F.C.: none declared, V.K.: none declared, B.L.: none declared, A.V.W.: speakers bureau from Boehringer Ingelheim, Roche, and Veracyte, and consultant for: Boehringer Ingelheim, Roche, and Veracyte, S.N.: none declared, J.G.: none declared, E.A.R.: none declared, P.A.G.: speakers bureau from UCB, consultant for Eli Lilly, and Galapagos, and grant/research support from Corbus Pharmaceuticals. Acknowledgements: This work has previously been presented in abstract form at EULAR 2023. J.H. received personal support through grants from the King’s College Hospital Charity

A General Purpose Transpiler for Fully Homomorphic Encryption

Fully homomorphic encryption (FHE) is an encryption scheme which enables computation on encrypted data without revealing the underlying data. While there have been many advances in the field of FHE, developing programs using FHE still requires expertise in cryptography. In this white paper, we present a fully homomorphic encryption transpiler that allows developers to convert high-level code (e.g., C++) that works on unencrypted data into high-level code that operates on encrypted data. Thus, our transpiler makes transformations possible on encrypted data. Our transpiler builds on Google's open-source XLS SDK (https://github.com/google/xls) and uses an off-the-shelf FHE library, TFHE (https://tfhe.github.io/tfhe/), to perform low-level FHE operations. The transpiler design is modular, which means the underlying FHE library as well as the high-level input and output languages can vary. This modularity will help accelerate FHE research by providing an easy way to compare arbitrary programs in different FHE schemes side-by-side. We hope this lays the groundwork for eventual easy adoption of FHE by software developers. As a proof-of-concept, we are releasing an experimental transpiler (https://github.com/google/fully-homomorphic-encryption/tree/main/transpiler) as open-source software

Venus Observations at 40 and 90 GHz with CLASS

Using the Cosmology Large Angular Scale Surveyor, we measure the disk-averaged absolute Venus brightness temperature to be 432.3 $\pm$ 2.8 K and 355.6 $\pm$ 1.3 K in the Q and W frequency bands centered at 38.8 and 93.7 GHz, respectively. At both frequency bands, these are the most precise measurements to date. Furthermore, we observe no phase dependence of the measured temperature in either band. Our measurements are consistent with a CO$_2$-dominant atmospheric model that includes trace amounts of additional absorbers like SO$_2$ and H$_2$SO$_4$.Comment: 7 pages, 3 figures, published in PS