Judicial Review of European Administrative Procedure

Schwarze examines the requirements set down in the case law of the Court of Justice and the Court of First Instance that serve to guarantee a fair and impartial administrative process. He also considers whether improvements should be made to the design of the administrative process and, if so, what kind

Judicial Review of European Administrative Procedure

Schwarze examines the requirements set down in the case law of the Court of Justice and the Court of First Instance that serve to guarantee a fair and impartial administrative process. He also considers whether improvements should be made to the design of the administrative process and, if so, what kind

Assessment of proximal outcomes of self-management programs : translation and psychometric evaluation of a German version of the Health Education Impact Questionnaire (heiQtm)

Purpose This paper describes the translation, cultural adaption, and psychometric evaluation of a German version of the Health Education Impact Questionnaire (heiQ&trade;), a widely used generic instrument assessing a wide range of proximal outcomes of self-management programs.Methods The translation was carried out according to international standards and included forward and backward translations. Comprehensibility and content validity were tested using cognitive interviews with 10 rehabilitation inpatients. Psychometric properties were examined in rehabilitation inpatients (n = 1,202) with a range of chronic conditions. Factorial validity was assessed using confirmatory factor analysis; concurrent validity was explored by correlations with comparator scales.Results The items of the German heiQ&trade; were well understood by rehabilitation inpatients. The structure of the eight heiQ&trade; scales was replicated after minor adjustment. heiQ&trade; scales had higher correlations with comparator scales with similar constructs, particularly mental health concepts than with physical health. Moreover, all heiQ&trade; scales differentiated between individuals across different levels of depression.Conclusion The German heiQ&trade; is comprehensible for German-speaking patients suffering from different types of chronic conditions; it assesses relevant outcomes of self-management programs in a reliable and valid manner. Further studies involving its practical application are warranted.<br /

Helminth induced monocytosis conveys protection from respiratory syncytial virus infection in mice

Flow cytometry data were generated with support from the QMRI Flow Cytometry and cell sorting facility, University of Edinburgh. We acknowledge Alison Munro of HTPU Microarray Services at the Institute of Genetics and Cancer for their technical support. or the purpose of open access, the author has applied a Creative Commons Attribution (CC BY) licence to any Author Accepted Manuscript version arising from this submission. We thank Amy Buck (University of Edinburgh, United Kingdom) for providing H. polygyrus L3 larvae and Samanta Mariani (University of Edinburgh, United Kingdom) for advice on bone marrow Methocult assays.Peer reviewe

Helminth induced monocytosis conveys protection from respiratory syncytial virus infection in mice

Background: Respiratory syncytial virus (RSV) infection in infants is a major cause of viral bronchiolitis and hospitalisation. We have previously shown in a murine model that ongoing infection with the gut helminth Heligmosomoides polygyrus protects against RSV infection through type I interferon (IFN-I) dependent reduction of viral load. Yet, the cellular basis for this protection has remained elusive. Given that recruitment of mononuclear phagocytes to the lung is critical for early RSV infection control, we assessed their role in this coinfection model. Methods: Mice were infected by oral gavage with H. polygyrus. Myeloid immune cell populations were assessed by flow cytometry in lung, blood and bone marrow throughout infection and after secondary infection with RSV. Monocyte numbers were depleted by anti-CCR2 antibody or increased by intravenous transfer of enriched monocytes. Results: H. polygyrus infection induces bone marrow monopoiesis, increasing circulatory monocytes and lung mononuclear phagocytes in a IFN-I signalling dependent manner. This expansion causes enhanced lung mononuclear phagocyte counts early in RSV infection that may contribute to the reduction of RSV load. Depletion or supplementation of circulatory monocytes prior to RSV infection confirms that these are both necessary and sufficient for helminth induced antiviral protection. Conclusions: H. polygyrus infection induces systemic monocytosis contributing to elevated mononuclear phagocyte numbers in the lung. These cells are central to an anti-viral effect that reduces the peak viral load in RSV infection. Treatments to promote or modulate these cells may provide novel paths to control RSV infection in high risk individuals.</p

Helminth induced monocytosis conveys protection from respiratory syncytial virus infection in mice

Background: Respiratory syncytial virus (RSV) infection in infants is a major cause of viral bronchiolitis and hospitalisation. We have previously shown in a murine model that ongoing infection with the gut helminth Heligmosomoides polygyrus protects against RSV infection through type I interferon (IFN-I) dependent reduction of viral load. Yet, the cellular basis for this protection has remained elusive. Given that recruitment of mononuclear phagocytes to the lung is critical for early RSV infection control, we assessed their role in this coinfection model. Methods: Mice were infected by oral gavage with H. polygyrus. Myeloid immune cell populations were assessed by flow cytometry in lung, blood and bone marrow throughout infection and after secondary infection with RSV. Monocyte numbers were depleted by anti-CCR2 antibody or increased by intravenous transfer of enriched monocytes. Results: H. polygyrus infection induces bone marrow monopoiesis, increasing circulatory monocytes and lung mononuclear phagocytes in a IFN-I signalling dependent manner. This expansion causes enhanced lung mononuclear phagocyte counts early in RSV infection that may contribute to the reduction of RSV load. Depletion or supplementation of circulatory monocytes prior to RSV infection confirms that these are both necessary and sufficient for helminth induced antiviral protection. Conclusions: H. polygyrus infection induces systemic monocytosis contributing to elevated mononuclear phagocyte numbers in the lung. These cells are central to an anti-viral effect that reduces the peak viral load in RSV infection. Treatments to promote or modulate these cells may provide novel paths to control RSV infection in high risk individuals.</p

Community-based asthma assessment in young children: Adaptations for a multicentre longitudinal study in South Asia

Background: Systematic assessment of childhood asthma is challenging in low- and middle-income country (LMIC) settings due to the lack of standardised and validated methodologies. We describe the contextual challenges and adaptation strategies in the implementation of a community-based asthma assessment in four resource-constrained settings in Bangladesh, India, and Pakistan.Method: We followed a group of children of age 6-8 years for 12 months to record their respiratory health outcomes. The study participants were enrolled at four study sites of the \u27Aetiology of Neonatal Infection in South Asia (ANISA)\u27 study. We standardised the research methods for the sites, trained field staff for uniform data collection and provided a \u27Child Card\u27 to the caregiver to record the illness history of the participants. We visited the children on three different occasions to collect data on respiratory-related illnesses. The lung function of the children was assessed in the outreach clinics using portable spirometers before and after 6-minute exercise, and capillary blood was examined under light microscopes to determine eosinophil levels.Results: We enrolled 1512 children, 95.5% (1476/1512) of them completed the follow-up, and 81.5% (1232/1512) participants attended the lung function assessment tests. Pre- and post-exercise spirometry was performed successfully in 88.6% (1091/1232) and 85.7% (1056/1232) of children who attempted these tests. Limited access to health care services, shortage of skilled human resources, and cultural diversity were the main challenges in adopting uniform procedures across all sites. Designing the study implementation plan based on the local contexts and providing extensive training of the healthcare workers helped us to overcome these challenges.Conclusion: This study can be seen as a large-scale feasibility assessment of applying spirometry and exercise challenge tests in community settings of LMICs and provides confidence to build capacity to evaluate children\u27s respiratory outcomes in future translational research studies

Viral mimic poly-(I:C) attenuates airway epithelial T cell suppressive capacity; implications for asthma

In allergen-sensitised asthmatic individuals, allergen-specific type-2 T-helper cells proliferate and secrete type-2 cytokines (e.g. interleukin (IL)-4, -5 and -13), driving the airway inflammatory response that gives rise to the clinical symptoms of asthma. Both early-life sensitisation to aeroallergens and lower respiratory viral infections are important environmental risk factors for developing asthma. Additionally, respiratory viral infections are the most common trigger for asthma exacerbations. Of interest, many asthma susceptibility genes are expressed in the airway epithelium [1], which forms the first continuous line of defence against inhaled environmental insults, including viruses and aeroallergens. Impaired immune regulation and failure to maintain tolerance to allergens is thought to contribute to allergic sensitisation. Asthma epithelium may be deficient in its innate immune defence against viral infections, resulting in increased viral replication upon rhinovirus infection compared to nonasthma-derived epithelial cultures [2]. Furthermore, there is evidence for loss of the mucosal immune barrier in asthma, with disruption of epithelial integrity [1, 3]. This may lead not only to increased permeability, but also to the release of pro-inflammatory mediators, specifically of cytokines that drive type-2 responses [3, 4]. We recently observed that the ability of allergens to disrupt epithelial barrier function is related to the development of type-2-mediated inflammation in asthma [5, 6]. Furthermore, we demonstrated that healthy murine lung epithelium is a potent inhibitor of T-cell proliferation and that this inhibition is lost upon viral infection [7]. It is unknown if this immune regulatory effect is displayed by human epithelium and is dysregulated in asthma. We hypothesise that changes in this regulatory effect translate into aberrant regulation of T-cell responses in asthma. We studied the epithelial regulation of T-cell proliferation and cytokine responses upon epithelial stimulation with a viral mimic, using co-culture of human T-cells and primary bronchial epithelial cells (PBECs) from healthy controls and asthma patients