Suchergebnisse

Study objective - This study examined the impact on children's respiratory health of a government air quality intervention that restricted the sulphur content of fuels to 0.5% from July 1990 onwards. Design/setting/participants - This study examined the changes, one and two years after the introduction of the intervention, in airway hyperreactivity of non-asthmatic and non-wheezing, primary 4, 5, and 6, school children aged 9-12 years living in a polluted district compared with those in a less polluted district. Bronchial hyperreactivity (BHR) (a 20% decrease in FEV, provoked by a cumulative dose of histamine less than 7.8 μmol) and bronchial reactivity slope (BR slope) (percentage change in logarithmic scale in FEV, per unit dose of histamine) were used to estimate responses to a histamine challenge. The between districts differences after the intervention were studied to assess the effectiveness of the intervention. Main results - In cohorts, comparing measurements made before the intervention and one year afterwards, both BHR and BR slope declined from 29% to 16% (p = 0.026) and from 48 to 39 (p = 0.075) respectively in the polluted district; and from 21% to 10% (p = 0.001) and 42 to 36 (p > 0.100) in the less polluted district. Comparing measurements made in 1991 (one year after intervention) with those in 1992 (two years after intervention), only the polluted district showed a significant decline from 28% to 12% (p = 0.016) and from 46 to 35 (p = 0.014), for BHR and BR slope respectively, with a greater decline in both responses (p = 0.018 and 0.073) than in the less polluted district. Conclusion - Bronchial hyperresponsiveness tests can be used to support the evaluation of an air quality intervention. The demonstrated reduction in bronchial hyperresponsiveness is an indication of the effectiveness of the intervention. ; published_or_final_version

Spin manipulation is one of the most critical challenges to realize spin-based logic devices and spintronic circuits. Graphene has been heralded as an ideal material to achieve spin manipulation, but so far new paradigms and demonstrators are limited. Here we show that certain impurities such as fluorine adatoms, which locally break sublattice symmetry without the formation of strong magnetic moment, could result in a remarkable variability of spin transport characteristics. The impurity resonance level is found to be associated with a long-range sublattice pseudospin polarization, which by locally decoupling spin and pseudospin dynamics provokes a huge spin lifetime electron-hole asymmetry. In the dilute impurity limit, spin lifetimes could be tuned electrostatically from 100 ps to several nanoseconds, providing a protocol to chemically engineer an unprecedented spin device functionality. ; This work has received funding from the European Union Seventh Framework Programme under Grant Agreement No. 604391 Graphene Flagship. S. R. acknowledges the Spanish Ministry of Economy and Competitiveness for funding (MAT2012-33911), the Secretaria de Universidades e Investigacion del Departamento de Economia y Conocimiento de la Generalidad de Cataluña, and the Severo Ochoa Program (MINECO SEV-2013-0295). ; Peer Reviewed

The mechanical interlocking of molecular components can lead to the appearance of novel and unconventional properties and processes, with potential relevance for applications in nanoscience, sensing, catalysis, and materials science. We describe a [3]rotaxane in which the number of recognition sites available on the axle component can be changed by acid-base inputs, encompassing cases in which this number is larger, equal to, or smaller than the number of interlocked macrocycles. These species exhibit very different properties and give rise to a unique network of acid-base reactions that leads to a fine p K a tuning of chemically equivalent acidic sites. The rotaxane where only one station is available for two rings exhibits a rich coconformational dynamics, unveiled by an integrated experimental and computational approach. In this compound, the two crown ethers compete for the sole recognition site, but can also come together to share it, driven by the need to minimize free energy without evident inter-ring interactions. ; This work was supported by the European Union's H2020 Research and Innovation Program (ERC Advanced Grant n.692981), the Italian Ministry of University and Research (FARE R16S9XXKX3 and PRIN 20173L7W8K), and FAR2019 Uninsubria, and L.C. and E.F. acknowledge the King Abdullah University of Science and Technology (KAUST) and the KAUST Supercomputing Laboratory (KSL) for support and for providing computational resources on the Shaheen II HPC system (project K1438).

Recent theoretical considerations have demonstrated that free-standing graphene doped with alkali metals (ACx) supports strong Dirac and weak acoustic plasmons. Here we show that when ACx is deposited on a metal surface the effective Coulomb screening produced by the substrate can completely wash out these collective modes. However, even tiny detachment of the ACx layer from the metal surface recovers the ACx plasmonic properties. Especially the acoustic plasmon intensity is strongly enhanced in comparison to a free-standing case. We further provide the physical background of these intriguing phenomena. The studied systems consist of lithium- and cesium-doped graphene layers deposited on the Ir(111) surface. ; V.D. acknowledges support from the QuantiXLie Center of Excellence, a project cofinanced by the Croatian Government and European Union through the European Regional Development Fund within the Competitiveness and Cohesion Operational Programme (Grant No. KK.01.1.1.01.0004). V.D. is also grateful to Donostia International Physics Center (DIPC) for hospitality during various stages of this work. D.N. acknowledges financial support from the European Regional Development Fund for the "Center of Excellence for Advanced Materials and Sensing Devices" (Grant No. KK.01.1.1.01.0001). I.L. acknowledges support from the European Union through the European Regional Development Fund within the Competitiveness and Cohesion Operational Programme (Grant No. KK.01.1.1.06). V.M.S. acknowledges partial support from the Spanish Ministry of Economy and Competitiveness MINECO Grant No. FIS2016-76617-P and from Project No. PI2017-30 of the Departamento de Educación, Política Lingüística y Cultura of the Basque government. Computational resources were provided by the DIPC Computing Center

The genus Capripoxvirus of the family Poxviridae consists of the species lumpy skin disease virus, sheeppox virus and goatpox virus that affect cattle, sheep and goats, respectively. Whereas lumpy skin disease virus (LSDV) is transmitted mainly mechanically via blood-feeding insects and possibly hard ticks, the major transmission routes of sheeppox virus (SPPV) and goatpox virus (GTPV) are via direct contact and aerosols. Affected animals develop fever and display clinical signs such as ocular and nasal discharge, lymphadenopathy and characteristic lesions of the skin. Severe clinical course, especially in combination with respiratory signs, can result in the death of the affected animals. In endemic regions, mortality of capripox virus-induced diseases is low (1-10%). However, mortalities of up to 75% have been reported for LSDV and up to 100% for SPPV and GTPV in exotic breeds and high-producing dairy or beef animals. The loss of quality of the leather, reduced weight gain and milk yield as well as complete loss of affected animals have severe impact on national and global economies. Therefore, capripox virus-induced diseases have significant impact on both the affected individual animal as well as on the existence of small-scale farmers and large agricultural enterprises. However, until now, only live attenuated vaccines are commercially available. These attenuated vaccines are not authorized in the European Union and their administration would comprise the disease-free status of the respective country. Thus, reliable diagnostic tools for the detection and characterization of capripox viruses as well as safe and efficient control measures are of high importance. The objectives of the present thesis were the development, validation and comparison of diagnostic tools, the establishment of challenge infection models and the performance of pathogenesis studies for all three capripox virus species, and the development and testing of different inactivated prototype vaccine candidates against LSDV. First, new real-time quantitative polymerase chain reaction (qPCR) assays for robust detection and differentiation of LSDV field strains, LSDV vaccine strains, SPPV and GTPV were developed and extensively validated. In the following, two single assays were combined to duplex assays, one for the differentiation between LSDV field strains and LSDV vaccine strains, and the second for discrimination of SPPV and GTPV. Finally, a diagnostic workflow based on these new duplex assays in combination with already published methods was established. This workflow enables time-saving, robust and reliable detection, species-specific identification and genetic and phylogenetic characterization of all three capripox virus species. In addition, already existing serological examination methods (serum neutralization assay and commercial enzyme-linked immunosorbent assay) were compared regarding their sensitivity and specificity. Furthermore, pathogenesis studies with different capripox virus isolates were performed in the respective target species, and the suitability of selected virus isolates as challenge viruses for future vaccine studies was analyzed. Pathogenesis studies with isolates GTPV-"V/103" and LSDV-"Macedonia2016" revealed that both are proper candidates for challenge models. Finally, three different SPPV isolates (SPPV-"V/104", SPPV-"India/2013/Surankote" and SPPV-"Egypt/2018") were tested in sheep regarding their virulence to find a suitable challenge model for SPPV, and SPPV-"India/2013/Surankote" was chosen for future vaccine studies. Once appropriate challenge models were established, different inactivated prototype vaccines against LSDV were developed, and vaccine safety as well as vaccine efficacy were tested in cattle. Eventually, a Polygen-adjuvanted inactivated LSDV-vaccine candidate was selected that is able to fully prevent cattle from any LSDV-related clinical signs after severe challenge infection. Furthermore, molecular and serological data indicate that this inactivated prototype vaccine is even able to induce a kind of "sterile immunity" against LSDV in those cattle. It has to be mentioned that a commercially available vaccine similar to this prototype vaccine would be a great advance for the control of LSDV. In the future, additional studies addressing diagnostics and optimized control of capripox viruses should be performed. Firstly, probe-based real-time qPCR assays for the differentiation of SPPV and GTPV vaccine strains from their respective virulent field strains should be developed and included into the diagnostic workflow. Secondly, further tests of the inactivated prototype vaccine, e.g. determination of the minimum protective dose and the possibility of cross-protection in sheep and goats against SPPV and GTPV, respectively, should be performed. ; Die Gattung Capripoxvirus beinhaltet das Virus der Lumpy-Skin-Krankheit (LSDV), das Schafpockenvirus (SPPV) und das Ziegenpockenvirus (GTPV), die hauptsächlich Rinder bzw. Schafe und Ziegen infizieren. Während LSDV vorwiegend mechanisch über blutsaugende Vektoren und möglicherweise über Schildzecken übertragen wird, sind der direkte Kontakt sowie die Aerosoltransmission als Hauptübertragungsrouten für SPPV und GTPV beschrieben. Betroffene Tiere entwickeln Fieber und zeigen klinische Anzeichen wie z.B. okularen und nasalen Ausfluss, Lymphadenopathie und charakteristische Hautläsionen. Schwere Krankheitsverläufe, insbesondere in Verbindung mit respiratorischen Symptomen, können für die infizierten Tiere zum Tod führen. In endemischen Gebieten ist die Mortalität Capripockenvirus-induzierter Erkrankungen relativ gering (1-10%). In exotischen Rassen oder in Tieren, die auf Hochleistung (zum Beispiel Milch- oder Fleischrassen) gezüchtet wurden, kann die Mortalität von LSDV bis zu 75% und die Mortalität von SPPV und GTPV bis zu 100% betragen. Der aus den Hautläsionen resultierende Qualitätsverlust des Leders, reduzierte Gewichtszunahme und reduzierte Milchleistung sowie der Verlust betroffener Tiere führen zu Umsatzeinbußen und beeinflussen dadurch sowohl die nationale als auch die globale Wirtschaft. Dadurch haben Capripockenvirus-induzierte Erkrankungen nicht nur einen erheblichen Einfluss auf das infizierte Einzeltier, sondern auch auf kleine Familienunternehmen und landwirtschaftliche Großbetriebe. Derzeit sind zur Prophylaxe lediglich attenuierte Lebendvakzinen kommerziell erhältlich. Diese sind in der Europäischen Union jedoch nicht zugelassen, da ihr Einsatz den Verlust des Status "Capripocken-frei" für das jeweilige Land bedeutet. Aus diesen Gründen werden dringend sowohl zuverlässige und zeitsparende Diagnostikmethoden für die Detektion und Charakterisierung von Capripocken, als auch sichere und effiziente Kontrollmaßnahmen benötigt. Ziele dieser Arbeit waren die Entwicklung, Validierung und vergleichende Analyse verschiedener diagnostischer Methoden, die Durchführung von Pathogenesestudien zur Etablierung von Infektionsmodellen für alle drei Capripockenviren und die Entwicklung und Testung verschiedener inaktivierter Prototypvakzinen gegen das LSDV. Im Laufe dieser Arbeit wurden neue real-time quantitative Polymerasekettenreaktion (qPCR)-Assays für eine robuste Detektion und Differenzierung zwischen LSDV-Feldstämmen, LSDV-Vakzinestämmen, SPPV und GTPV entwickelt und umfassend validiert. Im Anschluss wurden jeweils zwei dieser Einzelassays zu sogenannten Duplex-Assays kombiniert. Der erste Duplex-Assay ist in der Lage, zwischen LSDV-Feldstämmen und LSDV-Vakzinestämmen zu unterschieden, der zweite Duplex-Assay erlaubt die Differenzierung zwischen SPPV und GTPV. Schließlich wurde ein diagnostischer Workflow basierend auf den beiden neuen Duplex-Assays in Kombination mit bereits publizierten Methoden etabliert. Dieser ermöglicht eine zeitsparende, robuste und zuverlässige Detektion, Spezies-spezifische Identifizierung und genetische sowie phylogenetische Charakterisierung der drei Capripockenvirusspezies. Zudem wurden bereits vorhandene serologische Diagnostikmethoden (der Serumneutralisationstest und ein kommerziell erhältlicher ELISA) hinsichtlich ihrer Sensitivität und ihrer Spezifität verglichen. Des Weiteren wurden Pathogenesestudien mit verschiedenen Capripockenvirusisolaten in der jeweiligen Zieltierart durchgeführt, mit dem Ziel, geeignete Infektionsmodelle für zukünftige Vakzinestudien zu etablieren. Die Pathogenesestudien mit den Isolaten GTPV-"V/103" und LSDV-"Macedonia2016" zeigten, dass beide Virusisolate gute Kandidaten für Infektionsmodelle mit GTPV und LSDV darstellen. Um ein geeignetes Infektionsmodell für SPPV zu finden, war die Testung von drei verschiedenen SPPV-Isolaten (SPPV-"V/104", SPPV-"India/2013/Surankote" und SPPV-"Egypt/2018") notwendig. Letztendlich stellte sich das virulente SPPV-"India/2013/Surankote"-Isolat als geeignetster Kandidat heraus. Abschließend wurden verschiedene Prototypen einer inaktivierten LSDV-Vakzine entwickelt und hinsichtlich Abwehrreaktionen und Schutzwirkung im Rind getestet. Der entwickelte Vakzinekandidat induzierte einen vollständigen klinischen Schutz in Rindern und erwies sich damit als sehr vielversprechend. Molekulare und serologische Daten weisen zudem darauf hin, dass mit dieser Prototypvakzine eine sterile Immunität in den Rindern erzielt werden konnte. Eine kommerzielle Vakzine mit diesen Eigenschaften würde einen bedeutenden Fortschritt in der Kontrolle von LSDV darstellen. Weitere Studien mit dem Ziel, die Diagnostik und Kontrolle von Capripockenviren weiter zu verbessern, sind auch in Zukunft noch notwendig. Dieses betrifft beispielsweise die Entwicklung Sonden-basierter real-time qPCR-Assays zur Unterscheidung von SPPV- und GTPV-Feld- und Vakzinestämmen, die den diagnostischen Workflow komplettieren würden. Von Bedeutung sind außerdem weiterführende Tests der inaktivierten Prototypvakzine hinsichtlich der minimalen protektiven Dosis und einer möglichen Kreuzprotektion in Schafen und Ziegen gegen SPPV und GTPV.

Bronchial challenge is a powerful measure for C O P D differential diagnostics, treatment quality estimation, and action efficacy of various medications. Recently, many estimation ways are proposed and standardised for each bronchial challenge technique. The standard advances strict demand s to the choice of estimation criterias and methodically defined protocol fulfilment. That provides the comparability of test results. However, the current standard restricts the method ability by evidence of bronchial hyperreactivity in patients.Two year experience of routine evaluation of bronchial hyperreactivity in called for military service and exploration experience of new drugs were the basis of proposed ways to estimation of bronchial challenge results. The new ways allow to extend diagnostic abilities of the method by means of information about current impairment pathogenesis and to open wider the action mechanism of antiasthmatic medications.The short description of the currently acted standard of nonspecific bronchial challenge method with dosed aerosoles is presented in the article. New estimation parameters are proposed, analysed, and grounded. Advances of new method modifications are illustrated. Practical advices for use are given. The authors hope, that the article will be helpful for physician s and scientists dealt with bronchial hyperreactivity problem and new drug testing. ; Провокационное тестирование является мощным средством дифференциальной диагностики ХНЗЛ, оценки качества лечения и эффективности действия целого ряда препаратов. На сегодняшний день для каждой методики проведения провокационны х тестов предложены и стандартизированы способы оценки их результатов. Стандарт предъявляет жесткие требования к выбору оценочных показателей и выполнению предусмотренного методикой протокола исследования. Это обеспечивает сравнимость результатов тестирования. Однако действующий стандарт ограничивает возможности метода установлением факта наличия у пациента гиперреактивности бронхиального дерева.Двухлетний опыт ...

The definition of a primary care facility is the site where the first patient contact occurs. In developing countries, primary healthcare (PHC) facilities are officially healthcare centers, hosting World Health Organization (WHO) programs for tuberculosis and chronic respiratory diseases. In addition, there are many other providers of PHC services, which include emergency departments, general outpatient clinics in public hospitals. Asthma patients may present for treatment in any of these primary care facilities. An international study achieved by the Union showed that 51% of asthma patients in Syria are treated in emergency departments only, many developing countries like Sudan, Algeria, and some African countries had the same use of ER. There are questions about the quality of care provided in these clinics with regard to their adherence to Global Initiatives for Asthma (GINA) guidelines. Evidence suggests that there may be over prescribing of oral corticosteroids and antibiotics and under-prescription of inhaled corticosteroids, so there is a need to improve practice bringing it more into alignment to international guidelines. It may be considered by many that it is not possible to follow guidelines in developing countries and those that have economic and political pressures. However, a pilot program to test the feasibility of a providing systematic follow-up of uncontrolled asthma patients in a general free of charge hospital in Syria showed that it is possible to achieve asthma control following to GINA guidelines even in very deprived community. The same was mentioned by the Union in an international survey for other developing African and Mediterranean countries. WHO launched programs for non-communicable disease including chronic respiratory disease: Practical Approach to lung Health (PAL) and Package of essential no communicable (PEN) disease interventions for primary health care in low-resource settings. The IPCRG also worked on how to improve implementation of guidelines. We will provide the results and following evidence-based recommendations from our field surveys in developing countries, as well comment on international programs. Although much progress has been realized in the diagnosis and management of asthma in developed nations, progress in one variant of asthma, inner city asthma, has been slow. Inner city asthma is that variant of the disease which afflicts residents of urban environments with low socioeconomic conditions, poor housing, and rampant environmental risks. This variant of asthma appears to be more severe, associated with increased psychological burden as well as morbidity and mortality, has a diverse array of predisposing factors, and poses significant challenges in management and treatment. One important aspect of treatment is education which leads to the participation of the patient and the families in the care resulting in a more favorable outcome.

Organ injuries caused by environmental chemical exposures or use of pharmaceutical drugs pose a serious health risk that may be difficult to assess because of a lack of non‐invasive diagnostic tests. Mapping chemical injuries to organ‐specific histopathology outcomes via biomarkers will provide a foundation for designing precise and robust diagnostic tests. We identified co‐expressed genes (modules) specific to injury endpoints using the Open Toxicogenomics Project‐Genomics Assisted Toxicity Evaluation System (TG‐GATEs) – a toxicogenomics database containing organ‐specific gene expression data matched to dose‐ and time‐dependent chemical exposures and adverse histopathology assessments in Sprague–Dawley rats. We proposed a protocol for selecting gene modules associated with chemical‐induced injuries that classify 11 liver and eight kidney histopathology endpoints based on dose‐dependent activation of the identified modules. We showed that the activation of the modules for a particular chemical exposure condition, i.e., chemical‐time‐dose combination, correlated with the severity of histopathological damage in a dose‐dependent manner. Furthermore, the modules could distinguish different types of injuries caused by chemical exposures as well as determine whether the injury module activation was specific to the tissue of origin (liver and kidney). The generated modules provide a link between toxic chemical exposures, different molecular initiating events among underlying molecular pathways and resultant organ damage. Published 2016. This article is a U.S. Government work and is in the public domain in the USA. Journal of Applied Toxicology published by John Wiley & Sons, Ltd.