The use of Multiple Breath Washout for Assessing Cystic Fibrosis in Infants

INTRODUCTION: Lung Clearance Index, measured using the multiple breath washout (MBW) technique, may be a useful test in infants with Cystic Fibrosis (CF). However, the requirement for specialised equipment and a number of important technical and methodological considerations relevant to testing in infants have complicated matters, and to date prevented its widespread translatability in this age group. Areas covered: We review the current status of infant MBW testing in CF, focusing on Lung Clearance Index. This includes a review of recent developments in the field relevant to testing methodology in the infant population, use in evaluating lung disease in CF in infancy, and the associated challenges which remain. Expert commentary: The challenges of infant MBW are not limited to those associated with testing equipment, but also gaps in our understanding regarding the interpretation of MBW indices in infants. This includes their relationship to underlying physiology and pathology, and tracking over time. Recent advances in understanding and improving the infant MBW test set up (including both hardware and software) relevant to infants will greatly progress the field

The Elephant Trunk Nebula and the Trumpler 37 cluster: Contribution of triggered star formation to the total population of an HII region

Rich young stellar clusters produce HII regions whose expansion into the nearby molecular cloud is thought to trigger the formation of new stars. However, the importance of this mode of star formation is uncertain. This investigation seeks to quantify triggered star formation (TSF) in IC 1396A (a.k.a., the Elephant Trunk Nebula), a bright rimmed cloud (BRC) on the periphery of the nearby giant HII region IC 1396 produced by the Trumpler 37 cluster. X-ray selection of young stars from Chandra X-ray Observatory data is combined with existing optical and infrared surveys to give a more complete census of the TSF population. Over 250 young stars in and around IC 1396A are identified; this doubles the previously known population. A spatio-temporal gradient of stars from the IC 1396A cloud toward the primary ionizing star HD 206267 is found. We argue that the TSF mechanism in IC 1396A is the radiation-driven implosion process persisting over several million years. Analysis of the X-ray luminosity and initial mass functions indicates that >140 stars down to 0.1 Msun were formed by TSF. Considering other BRCs in the IC 1396 HII region, we estimate the TSF contribution for the entire HII region exceeds 14-25% today, and may be higher over the lifetime of the HII region. Such triggering on the periphery of HII regions may be a significant mode of star formation in the Galaxy.Comment: Accepted for publication in MNRAS; 28 pages, 18 figure

The bronchodilator response in preschool children: A systematic review

BACKGROUND: The bronchodilator response (BDR) is frequently used to support diagnostic and therapeutic decision-making for children who wheeze. However, there is little evidence-based guidance describing the role of BDR testing in preschool children and it is unclear whether published cut-off values, which are derived from adult data, can be applied to this population. METHODS: We searched MEDLINE, EMBASE, Web of Science, and Cochrane databases (inception-September 2015) for studies reporting response to a bronchodilator in healthy preschool children, response following placebo inhalation, and the diagnostic efficacy of BDR compared with a clinical diagnosis of asthma/recurrent wheezing. FINDINGS: We included 14 studies. Thirteen studies provided BDR data from healthy preschool children. Two studies reported response to placebo in preschool children with asthma/recurrent wheezing. Twelve studies compared BDR measurements from preschool children with asthma/recurrent wheeze to those from healthy children and seven of these studies reported diagnostic efficacy. Significant differences between the BDR measured in healthy preschool children compared with that in children with asthma/recurrent wheeze were demonstrated in some, but not all studies. Techniques such as interrupter resistance, oscillometry, and plethysmography were more consistently successfully completed than spirometry. Between study heterogeneity precluded determination of an optimum technique. INTERPRETATION: There is little evidence to suggest spirometry-based BDR can be used in the clinical assessment of preschool children who wheeze. Further evaluation of simple alternative techniques is required. Future studies should recruit children in whom airways disease is suspected and should evaluate the ability of BDR testing to predict treatment response

Testing effects of Lorentz invariance violation in the propagation of astroparticles with the Pierre Auger Observatory

The successful installation, commissioning, and operation of the Pierre Auger Observatory would not have been possible without the strong commitment and effort from the technical and administrative staff in Malargüe. We are very grateful to the following agencies and organizations for financial support: Argentina — Comisión Nacional de Energía Atómica; Agencia Nacional de Promoción Científica y Tecnológica (ANPCyT); Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET); Gobierno de la Provincia de Mendoza; Municipalidad de Malargüe; NDM Holdings and Valle Las Leñas; in gratitude for their continuing cooperation over land access; Australia — the Australian Research Council; Belgium — Fonds de la Recherche Scientifique (FNRS); Research Foundation Flanders (FWO); Brazil — Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq); Financiadora de Estudos e Projetos (FINEP); Fundação de Amparo à Pesquisa do Estado de Rio de Janeiro (FAPERJ); São Paulo Research Foundation (FAPESP) Grants No. 2019/10151-2, No. 2010/07359-6 and No. 1999/05404-3; Ministério da Ciência, Tecnologia, Inovações e Comunicações (MCTIC); Czech Republic — Grant No. MSMT CR LTT18004, LM2015038, LM2018102, CZ.02.1.01/0.0/0.0/16_013/0001402, CZ.02.1.01/0.0/0.0/18_046/0016010 and CZ.02.1.01/0.0/0.0/17_049/0008422; France — Centre de Calcul IN2P3/CNRS; Centre National de la Recherche Scientifique (CNRS); Conseil Régional Ile-de-France; Département Physique Nucléaire et Corpusculaire (PNC-IN2P3/CNRS); Département Sciences de l’Univers (SDU-INSU/CNRS); Institut Lagrange de Paris (ILP) Grant No. LABEX ANR-10-LABX-63 within the Investissements d’Avenir Programme Grant No. ANR-11-IDEX-0004-02; Germany — Bundesministerium für Bildung und Forschung (BMBF); Deutsche Forschungsgemeinschaft (DFG); Finanzministerium Baden-Württemberg; Helmholtz Alliance for Astroparticle Physics (HAP); Helmholtz-Gemeinschaft Deutscher Forschungszentren (HGF); Ministerium für Innovation, Wissenschaft und Forschung des Landes Nordrhein-Westfalen; Ministerium für Wissenschaft, Forschung und Kunst des Landes Baden-Württemberg; Italy — Istituto Nazionale di Fisica Nucleare (INFN); Istituto Nazionale di Astrofisica (INAF); Ministero dell’Istruzione, dell’Università e della Ricerca (MIUR); CETEMPS Center of Excellence; Ministero degli Affari Esteri (MAE); México — Consejo Nacional de Ciencia y Tecnología (CONACYT) No. 167733; Universidad Nacional Autónoma de México (UNAM); PAPIIT DGAPA-UNAM; The Netherlands — Ministry of Education, Culture and Science; Netherlands Organisation for Scientific Research (NWO); Dutch national e-infrastructure with the support of SURF Cooperative; Poland — Ministry of Education and Science, grant No. DIR/WK/2018/11; National Science Centre, Grants No. 2016/22/M/ST9/00198, 2016/23/B/ST9/01635, and 2020/39/B/ST9/01398; Portugal — Portuguese national funds and FEDER funds within Programa Operacional Factores de Competitividade through Fundação para a Ciência e a Tecnologia (COMPETE); Romania — Ministry of Research, Innovation and Digitization, CNCS/CCCDI — UEFISCDI, projects PN19150201/16N/2019, PN1906010, TE128 and PED289, within PNCDI III; Slovenia — Slovenian Research Agency, grants P1-0031, P1-0385, I0-0033, N1-0111; Spain — Ministerio de Economía, Industria y Competitividad (FPA2017-85114-P and PID2019-104676GB-C32), Xunta de Galicia (ED431C 2017/07), Junta de Andalucía (SOMM17/6104/UGR, P18-FR-4314) Feder Funds, RENATA Red Nacional Temática de Astropartículas (FPA2015-68783-REDT) and María de Maeztu Unit of Excellence (MDM-2016-0692); U.S.A. — Department of Energy, Contracts No. DE-AC02-07CH11359, No. DE-FR02-04ER41300, No. DE-FG02-99ER41107 and No. DE-SC0011689; National Science Foundation, Grant No. 0450696; The Grainger Foundation; Marie Curie-IRSES/EPLANET; European Particle Physics Latin American Network; and UNESCO.Lorentz invariance violation (LIV) is often described by dispersion relations of the form E i2 = m i2+p i2+δi,n E 2+n with delta different based on particle type i, with energy E, momentum p and rest mass m. Kinematics and energy thresholds of interactions are modified once the LIV terms become comparable to the squared masses of the particles involved. Thus, the strongest constraints on the LIV coefficients δi,n tend to come from the highest energies. At sufficiently high energies, photons produced by cosmic ray interactions as they propagate through the Universe could be subluminal and unattenuated over cosmological distances. Cosmic ray interactions can also be modified and lead to detectable fingerprints in the energy spectrum and mass composition observed on Earth. The data collected at the Pierre Auger Observatory are therefore possibly sensitive to both the electromagnetic and hadronic sectors of LIV. In this article, we explore these two sectors by comparing the energy spectrum and the composition of cosmic rays and the upper limits on the photon flux from the Pierre Auger Observatory with simulations including LIV. Constraints on LIV parameters depend strongly on the mass composition of cosmic rays at the highest energies. For the electromagnetic sector, while no constraints can be obtained in the absence of protons beyond 1019 eV, we obtain δγ,0 > -10-21, δγ,1 > -10-40 eV-1 and δγ,2 > -10-58 eV-2 in the case of a subdominant proton component up to 1020 eV. For the hadronic sector, we study the best description of the data as a function of LIV coefficients and we derive constraints in the hadronic sector such as δhad,0 < 10-19, δhad,1 < 10-38 eV-1 and δhad,2 < 10-57 eV-2 at 5σ CL.Argentina — Comisión Nacional de Energía AtómicaAgencia Nacional de Promoción Científica y Tecnológica (ANPCyT)Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)Gobierno de la Provincia de MendozaMunicipalidad de MalargüeNDM Holdings and Valle Las LeñasAustralia — the Australian Research CouncilBelgium — Fonds de la Recherche Scientifique (FNRS)Research Foundation Flanders (FWO)Brazil — Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Financiadora de Estudos e Projetos (FINEP)Fundação de Amparo à Pesquisa do Estado de Rio de Janeiro (FAPERJ)São Paulo Research Foundation (FAPESP) Grants No. 2019/10151-2, No. 2010/07359-6 and No. 1999/05404-3Ministério da Ciência, Tecnologia, Inovações e Comunicações (MCTIC)Czech Republic — Grant No. MSMT CR LTT18004, LM2015038, LM2018102, CZ.02.1.01/0.0/0.0/16_013/0001402, CZ.02.1.01/0.0/0.0/18_046/0016010 and CZ.02.1.01/0.0/0.0/17_049/0008422France — Centre de Calcul IN2P3/CNRSCentre National de la Recherche Scientifique (CNRS)Conseil Régional Ile-de-France; Département Physique Nucléaire et Corpusculaire (PNC-IN2P3/CNRS)Département Sciences de l’Univers (SDU-INSU/CNRS)Institut Lagrange de Paris (ILP) Grant No. LABEX ANR-10-LABX-63- Investissements d’Avenir Programme Grant No. ANR-11-IDEX-0004-02Germany — Bundesministerium für Bildung und Forschung (BMBF)GermanyDeutsche Forschungsgemeinschaft (DFG)Finanzministerium Baden-WürttembergHelmholtz Alliance for Astroparticle Physics (HAP)Helmholtz-Gemeinschaft Deutscher Forschungszentren (HGF)Ministerium für Innovation, Wissenschaft und Forschung des Landes Nordrhein-WestfalenMinisterium für Wissenschaft, Forschung und Kunst des Landes Baden-WürttembergItaly — Istituto Nazionale di Fisica Nucleare (INFN)Istituto Nazionale di Astrofisica (INAF)Ministero dell’Istruzione, dell’Università e della Ricerca (MIUR)CETEMPS Center of ExcellenceMinistero degli Affari Esteri (MAE)México — Consejo Nacional de Ciencia y Tecnología (CONACYT) No. 167733Universidad Nacional Autónoma de México (UNAM)PAPIIT DGAPA-UNAMThe Netherlands — Ministry of Education, Culture and ScienceNetherlands Organisation for Scientific Research (NWO)Dutch national e-infrastructure with the support of SURF Cooperative; Poland — Ministry of Education and Science, grant No. DIR/WK/2018/11National Science Centre, Grants No. 2016/22/M/ST9/00198, 2016/23/B/ST9/01635, and 2020/39/B/ST9/01398Portugal — Portuguese national funds and FEDER funds within Programa Operacional Factores de Competitividade through Fundação para a Ciência e a Tecnologia (COMPETE)Romania — Ministry of Research, Innovation and Digitization, CNCS/CCCDI — UEFISCDI, projects PN19150201/16N/2019, PN1906010, TE128 and PED289, within PNCDI IIISlovenia — Slovenian Research Agency, grants P1-0031, P1-0385, I0-0033, N1-0111Spain — Ministerio de Economía, Industria y Competitividad (FPA2017-85114-P and PID2019-104676GB-C32)Xunta de Galicia (ED431C 2017/07)Junta de Andalucía (SOMM17/6104/UGR, P18-FR-4314)Feder FundsRENATA Red Nacional Temática de Astropartículas (FPA2015-68783-REDT)María de Maeztu Unit of Excellence (MDM-2016-0692)U.S.A. — Department of Energy, Contracts No. DE-AC02-07CH11359, No. DE-FR02-04ER41300, No. DE-FG02-99ER41107 and No. DE-SC0011689National Science Foundation, Grant No. 0450696The Grainger FoundationMarie Curie-IRSES/EPLANETEuropean Particle Physics Latin American NetworkUNESC

In vitro assessment of tick-borne encephalitis vaccine:Suitable human cell platforms and potential biomarkers

Tick-borne encephalitis (TBE) virus causes a severe disease that can lead to permanent neurological complications. The whole inactivated TBE vaccine is highly effective, as proven by high seroconversion rates and near eradication of the disease in countries where vaccination programs have been implemented. TBE vaccine potency testing currently requires the use of in vivo methods that present issues of reproducibility as well as animal discomfort. As an alternative, public and private entities are currently exploring a batch-to-batch consistency approach which would demonstrate conformity of a newly produced vaccine batch with a batch with proven in vivo efficacy with respect to a range of in vitro measurable quality parameters. For the identification of a suitable cellular platform to be used in a panel of in vitro batch-to-batch assessments for the TBE vaccine, we exposed human cell-based systems, both of primary origin and cell line-derived, to vaccine formulations of high and low quality. Following stimulation, cell responses were evaluated by assessing the expression of selected genes by qPCR. Our findings show that the expression of interferon-stimulated genes differed after treatment with non-adjuvanted vaccine batches of different quality in peripheral blood mononuclear cells (PBMCs) and in monocyte-derived dendritic cells, but not in monocyte-free PBMC suspensions nor in cell line-derived immune cells. These results indicate suitable platforms and potential biomarkers for a cell-based assay that, together with other immunochemical analyses, could serve for batch-to-batch assessment of the TBE vaccine, reducing (and eventually replacing) in vivo methods for potency testing

Cooperation between expert knowledge and data mining discovered knowledge: Lessons learned

Expert systems are built from knowledge traditionally elicited from the human expert. It is precisely knowledge elicitation from the expert that is the bottleneck in expert system construction. On the other hand, a data mining system, which automatically extracts knowledge, needs expert guidance on the successive decisions to be made in each of the system phases. In this context, expert knowledge and data mining discovered knowledge can cooperate, maximizing their individual capabilities: data mining discovered knowledge can be used as a complementary source of knowledge for the expert system, whereas expert knowledge can be used to guide the data mining process. This article summarizes different examples of systems where there is cooperation between expert knowledge and data mining discovered knowledge and reports our experience of such cooperation gathered from a medical diagnosis project called Intelligent Interpretation of Isokinetics Data, which we developed. From that experience, a series of lessons were learned throughout project development. Some of these lessons are generally applicable and others pertain exclusively to certain project types

Chapter Quality of Information within Internet of Things Data

Due to the increasing number of IoT devices, the amount of data gathered nowadays is rather large and continuously growing. The availability of new sensors presented in IoT devices and open data platforms provides new possibilities for innovative applications and use-cases. However, the dependence on data for the provision of services creates the necessity of assuring the quality of data to ensure the viability of the services. In order to support the evaluation of the valuable information, this chapter shows the development of a series of metrics that have been defined as indicators of the quality of data in a quantifiable, fast, reliable, and human-understandable way. The metrics are based on sound statistical indicators. Statistical analysis, machine learning algorithms, and contextual information are some of the methods to create quality indicators. The developed framework is also suitable for deciding between different datasets that hold similar information, since until now with no way of rapidly discovering which one is best in terms of quality had been developed. These metrics have been applied to real scenarios which have been smart parking and environmental sensing for smart buildings, and in both cases, the methods have been representative for the quality of the data

Staging Anti-Inflammatory Therapy in Alzheimer's Disease

The use of non-steroidal anti-inflammatory drugs (NSAIDs) in Alzheimer's disease (AD) is controversial because conclusions from numerous epidemiological studies reporting delayed onset of AD in NSAID users have not been corroborated in clinical trials. The purpose of this personal view is to revise the case for NSAIDs in AD therapeutics in light of: (i) the last report from the only primary prevention trial in AD, ADAPT, which, although incomplete, points to significant protection in long-term naproxen users, and (ii) the recently proposed dynamic model of AD evolution. The model contends that there is a clinical silent phase in AD that can last up to 20 years, the duration depending on life style habits, genetic factors, or cognitive reserve. The failure of many purported disease-modifying drugs in AD clinical trials is forcing the view that treatments will only be efficacious if administered pre-clinically. Here we will argue that NSAIDs failed in clinical trials because they are disease-modifying drugs, and they should be administered in early stages of the disease. A complete prevention trial in cognitively normal individuals is thus called for. Further, the shift of anti-inflammatory treatment to early stages uncovers a knowledge void about the targets of NSAIDs in asymptomatic individuals. AD researchers have mostly relied on post-mortem analysis of Aβ plaque-laden brains from demented patients or animal models, thus drawing conclusions about AD pathogenesis based on late symptoms. We will discuss evidence in support that defective, not excessive, inflammation underlies AD pathogenesis, that NSAIDs are multifunctional drugs acting on inflammatory and non-inflammatory targets, and that astrocytes and microglia may play differing roles in disease progression, with an emphasis of ApoEε4 as a key, undervalued target of NSAIDs. According to a meta-analysis of epidemiological data, NSAIDs afford an average protection of 58%. If this figure is true, and translated into patient numbers, NSAID treatment may revive as a worth pursuing strategy to significantly reduce the socio-economical burden imposed by AD