Implementation of Time-Delay Interferometry for LISA

We discuss the baseline optical configuration for the Laser Interferometer Space Antenna (LISA) mission, in which the lasers are not free-running, but rather one of them is used as the main frequency reference generator (the {\it master}) and the remaining five as {\it slaves}, these being phase-locked to the master (the {\it master-slave configuration}). Under the condition that the frequency fluctuations due to the optical transponders can be made negligible with respect to the secondary LISA noise sources (mainly proof-mass and shot noises), we show that the entire space of interferometric combinations LISA can generate when operated with six independent lasers (the {\it one-way method}) can also be constructed with the {\it master-slave} system design. The corresponding hardware trade-off analysis for these two optical designs is presented, which indicates that the two sets of systems needed for implementing the {\it one-way method}, and the {\it master-slave configuration}, are essentially identical. Either operational mode could therefore be implemented without major implications on the hardware configuration. We then.......Comment: 39 pages, 6 figures, 2 table

ARIA 2016 Executive Summary Integrated care pathways for predictive medicine across the life cycle

The Allergic Rhinitis and its Impact on Asthma (ARIA) initiative commenced during a World Health Organization (WHO) workshop in 1999. The initial goals were (i) to propose a new allergic rhinitis classification, (ii) to promote the concept of multi-morbidity in asthma and rhinitis and (iii) to develop guidelines with all stakeholders for global use in all countries and populations. ARIA - disseminated and implemented in over 70 countries globally - is now focusing on the implementation of emerging technologies for individualized and predictive medicine. MASK (MACVIA (Contre les MAladies Chroniques pour un VIeillissement Actif)-ARIA Sentinel NetworK) uses mobile technology to develop care pathways in order to enable the management of rhinitis and asthma by a multi-disciplinary group or by patients themselves. An App (Android and iOS) is available in 20 countries and 15 languages. It uses a visual analogue scale to assess symptom  control and work productivity as well as a clinical decision support system. It is associated with an inter-operable tablet for physicians and other health care professionals. The scaling up strategy uses the recommendations of the European Innovation Partnership on Active and Healthy Ageing. The aim of the novel ARIA approach is to provide an active and healthy life to rhinitis sufferers, whatever their age, sex or socio-economic status, in order to reduce health and social inequalities incurred by the disease.Keywords: ARIA, rhinitis, ICT, EIP on AHA, mobile technology, AIRWAYS ICP

Dupilumab reduces systemic corticosteroid use and sinonasal surgery rate in CRSwNP

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a type 2 inflammatory disease with a high symptom burden and poor quality of life. Treatment options include recurrent surgeries and/or frequent systemic corticosteroids (SCS). Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin-4 and interleukin-13, key drivers of type 2-mediated inflammation. We report results of pooled analyses from 2 randomised, double-blind, placebo-controlled phase 3 studies (SINUS 24 [NCT02912468]; SINUS-52 [NCT02898454]) to evaluate dupilumab effect versus placebo in adults with CRSwNP with/without SCS use and sinonasal surgery. METHODOLOGY: SINUS-24 patients were randomised 1:1 to subcutaneous dupilumab 300 mg (n=143) or placebo (n=133) every 2 weeks (q2w) for 24 weeks. SINUS-52 patients were randomised 1:1:1 to 52 weeks of subcutaneous dupilumab 300 mg q2w (n=150), 24 weeks q2w followed by 28 weeks of dupilumab 300 mg every 4 weeks (n=145) or 52 weeks of placebo q2w (n=153). RESULTS: Dupilumab reduced the number of patients undergoing sinonasal surgery (82.6%), the need for in-study SCS use (73.9%), and SCS courses (75.3%). Significant improvements were observed with dupilumab vs placebo regardless of prior sinonasal surgery or SCS use in nasal polyp, nasal congestion, Lund-MacKay, and Sinonasal Outcome Test (22-items) scores, and the University of Pennsylvania Smell Identification Test. CONCLUSIONS: Dupilumab demonstrated significant improvements in disease signs and symptoms and reduced the need for sino-nasal surgery and SCS use versus placebo in patients with severe CRSwNP, regardless of SCS use in the previous 2 years, or prior sinonasal surgery

Impact of Rhinitis on Work Productivity : A Systematic Review

BACKGROUND: Allergic rhinitis (AR) is increasingly acknowledged as having a substantial socioeconomic impact associated with impaired work productivity, although available information remains fragmented. OBJECTIVE: This systematic review summarizes recently available information to provide a quantitative estimate of the burden of AR on work productivity including lost work time (ie, absenteeism) and reduced performance while working (ie, presenteeism). METHODS: A Medline search retrieved original studies from 2005 to 2015 pertaining to the impact of AR on work productivity. A pooled analysis of results was carried out with studies reporting data collected through the validated Work Productivity and Activity Impairment (WPAI) questionnaire. RESULTS: The search identified 19 observational surveys and 9 interventional studies. Six studies reported economic evaluations. Pooled analysis of WPAI-based studies found an estimated 3.6% (95% confidence interval [CI], 2.4; 4.8%) missed work time and 35.9% (95% CI, 29.7; 42.1%) had impairment in at-work performance due to AR. Economic evaluations indicated that indirect costs associated with lost work productivity are the principal contributor to the total AR costs and result mainly from impaired presenteeism. The severity of AR symptoms was the most consistent disease-related factor associated with a greater impact of AR on work productivity, although ocular symptoms and sleep disturbances may independently affect work productivity. Overall, the pharmacologic treatment of AR showed a beneficial effect on work productivity. CONCLUSIONS: This systematic review provides summary estimates of the magnitude of work productivity impairment due to AR and identifies its main determinant factors. This information may help guide both clinicians and health policy makers. (C) 2017 American Academy of Allergy, Asthma & ImmunologyPeer reviewe

Euforea treatment algorithm for allergic rhinitis

Non peer reviewe

Aligning the Good Practice MASK With the Objectives of the European Innovation Partnership on Active and Healthy Ageing

The reference sites of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) were renewed in 2019. The DG Sante good practice Mobile Airways Sentinel networK was reviewed to meet the objectives of the EIP on AHA. It included 1) Management of care process, 2) Blueprint of digital transformation, 3) EIP on AHA, innovation to market, 4) Community for monitoring and assessment framework, 5) Political, organizational, technological and financial readiness, 6) Contributing to European co-operation and transferability, 7) Delivering evidence of impact against the triple win approach, 8) Contribution to the European Digital Transformation of Health and Care and 9) scale of demonstration and deployment of innovation.Peer reviewe

ARIA 2016: Care pathways implementing emerging technologies for predictive medicine in rhinitis and asthma across the life cycle

The Allergic Rhinitis and its Impact on Asthma (ARIA) initiative commenced during a World Health Organization workshop in 1999. The initial goals were (1) to propose a new allergic rhinitis classification, (2) to promote the concept of multi-morbidity in asthma a

Biological conditions affecting chronic inflammation in upper airways in children.

A child's immune system cannot depend on a memory-type immune response and it also induces cytokine responses less efficiently. Biological conditions like allergy or cystic fibrosis, immune deficiency or gastrooesophageal reflux can induce and maintain background inflammation in children's upper airways, making newborns and children more susceptible to upper airway infections and inflammations. This paper will describe in brief how allergy, cystic fibrosis, immune deficiency, nasal and paranasal anatomical variants, and gastro-oesophageal reflux (GOR) can affect the immune and inflammatory responses in upper airways and how they could interfere with immunity development and maturation in children. Literature review. Chronic inflammation induced by infection, allergy, cystic fibrosis or immune deficiency is multifactorial in origin and is strongly influenced by physiological, immunological, anatomical, environmental and, above all, genetic parameters. Finally, the direct role played by nasal and paranasal anatomical variants and GOR is also discussed. These conditions should be screened systematically in all children presenting chronic clinical features of upper airway inflammation

SCUAD and chronic rhinosinusitis. Reinforcing hypothesis driven research in difficult cases

Background: Our objective is to present recent research findings on recalcitrant chronic rhinosinusitis (CRS) in relation to "Severe Chronic Upper Airway Disease" (SCUAD). Methodology: Literature review using Medline and Embase databases (search terms 'chronic rhinosinusitis", "chronic sinusitis" or "Severe Chronic Upper Airway Disease") limited to articles published in the English language. Results: Complex pathophysiological mechanisms characterize various forms of chronic rhinitis and rhinosinusitis (CRS), where inflammation persists in spite of adequate medical treatment. In these cases, a multifactorial etiology often underlies the development of sino-nasal inflammation. The interaction between chronic upper and lower airway inflammation via neurogenic and systemic pathways may complicate the therapy of these patients, and lead to insufficient symptom control. Conclusion: The recently introduced definition of "Severe Chronic Upper Airway Disease" (SCUAD) increases awareness of those patients with persistent inflammation and symptoms despite guideline-driven pharmacologic treatment. The concept of SCUAD may prove helpful in directing research towards clarifying the definition, diagnosis and pathophysiology of rhinitis and rhinosinusitis, their limits and overlap. In this review, a hypothesis on SCUAD immunopathology is also presented

Phenotypes and endotypes of rhinitis and their impact on management: A PRACTALL report

Rhinitis is an umbrella term that encompasses many different subtypes, several of which still elude complete characterization. The concept of phenotyping, being the definition of disease subtypes on the basis of clinical presentation, has been well established in the last decade. Classification of rhinitis entities on the basis of phenotypes has facilitated their characterization and has helped practicing clinicians to efficiently approach rhinitis patients. Recently, the concept of endotypes, that is, the definition of disease subtypes on the basis of underlying pathophysiology, has emerged. Phenotypes/endotypes are dynamic, overlapping, and may evolve into one another, thus rendering clear-cut definitions difficult. Nevertheless, a phenotype-/endotype-based classification approach could lead toward the application of stratified and personalized medicine in the rhinitis field. In this PRACTALL document, rhinitis phenotypes and endotypes are described, and rhinitis diagnosis and management approaches focusing on those phenotypes/endotypes are presented and discussed. We emphasize the concept of control-based management, which transcends all rhinitis subtypes. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd