Toward Rare-Earth-Free Permanent Magnets: A Combinatorial Approach Exploiting the Possibilities of Modeling, Shape Anisotropy in Elongated Nanoparticles, and Combinatorial Thin-Film Approach

The objective of the rare-earth free permanent magnets (REFREEPM) project is to develop a new generation of high-performance permanent magnets (PMs) without rare earths. Our approach is based on modeling using a combinatorial approach together with micromagnetic modeling and the realization of the modeled systems (I) by using a novel production of high-aspect-ratio (>5) nanostructrures (nanowires, nanorods, and nanoflakes) by exploiting the magnetic shape anisotropy of the constituents that can be produced via chemical nanosynthesis polyol process or electrodeposition, which can be consolidated with novel processes for a new generation of rare-earth free PMs with energy product in the range of 60 kJ/m3 < (BH)max < 160 kJ/m3 at room temperature, and (II) by using a high-throughput thin-film synthesis and high-throughput characterization approach to identify promising candidate materials that can be stabilized in a tetragonal or hexagonal structure by epitaxial growth on selected substrates, under various conditions of pressure, stoichiometry, and temperature. In this article, we report the progress so far in selected phases.This work is supported by European Commission (REFREEPERMAG project) grant number GA-NMP3-SL-2012-280670

Genetics of Sputum Gene Expression in Chronic Obstructive Pulmonary Disease

Previous expression quantitative trait loci (eQTL) studies have performed genetic association studies for gene expression, but most of these studies examined lymphoblastoid cell lines from non-diseased individuals. We examined the genetics of gene expression in a relevant disease tissue from chronic obstructive pulmonary disease (COPD) patients to identify functional effects of known susceptibility genes and to find novel disease genes. By combining gene expression profiling on induced sputum samples from 131 COPD cases from the ECLIPSE Study with genomewide single nucleotide polymorphism (SNP) data, we found 4315 significant cis-eQTL SNP-probe set associations (3309 unique SNPs). The 3309 SNPs were tested for association with COPD in a genomewide association study (GWAS) dataset, which included 2940 COPD cases and 1380 controls. Adjusting for 3309 tests (p<1.5e-5), the two SNPs which were significantly associated with COPD were located in two separate genes in a known COPD locus on chromosome 15: CHRNA5 and IREB2. Detailed analysis of chromosome 15 demonstrated additional eQTLs for IREB2 mapping to that gene. eQTL SNPs for CHRNA5 mapped to multiple linkage disequilibrium (LD) bins. The eQTLs for IREB2 and CHRNA5 were not in LD. Seventy-four additional eQTL SNPs were associated with COPD at p<0.01. These were genotyped in two COPD populations, finding replicated associations with a SNP in PSORS1C1, in the HLA-C region on chromosome 6. Integrative analysis of GWAS and gene expression data from relevant tissue from diseased subjects has located potential functional variants in two known COPD genes and has identified a novel COPD susceptibility locus

The disease-specific clinical trial network for primary ciliary dyskinesia: PCD-CTN

Primary ciliary dyskinesia (PCD) is a rare genetic disorder characterised by impaired mucociliary clearance leading to irreversible lung damage. In contrast to other rare lung diseases like cystic fibrosis (CF), there are only few clinical trials and limited evidence-based treatments. Management is mainly based on expert opinions and treatment is challenging due to a wide range of clinical manifestations and disease severity. To improve clinical and translational research and facilitate development of new treatments, the clinical trial network for PCD (PCD-CTN) was founded in 2020 under the framework of the European Reference Network (ERN)-LUNG PCD Core. Applications from European PCD sites interested in participating in the PCD-CTN were requested. Inclusion criteria consisted of patient numbers, membership of ERN-LUNG PCD Core, use of associated standards of care, experience in PCD and/or CF clinical research, resources to run clinical trials, good clinical practice (GCP) certifications and institutional support. So far, applications from 22 trial sites in 18 European countries have been approved, including >1400 adult and >1600 paediatric individuals with PCD. The PCD-CTN is headed by a coordinating centre and consists of a steering and executive committee, a data safety monitoring board and committees for protocol review, training and standardisation. A strong association with patient organisations and industrial companies are further cornerstones. All participating trial sites agreed on a code of conduct. As CTNs from other diseases have demonstrated successfully, this newly formed PCD-CTN operates to establish evidence-based treatments for this orphan disease and to bring new personalised treatment approaches to patients

Prevalence of Chronic Obstructive Pulmonary Disease in Cyprus: A Population-Based Study

Background: The prevalence of Chronic Obstructive Pulmonary Disease (COPD) in Cyprus is largely unknown. The aim of the study was to estimate the prevalence of COPD in Cyprus through a spirometry population-based program and to identify certain disease characteristics in the Cypriot population. Methods: The study was performed in 1,233 randomly selected individuals covering representative urban and rural areas. Inclusion criteria were: age >= 35 years old and lifetime smoking history of at least 100 cigarettes. Participants answered a detailed questionnaire and underwent spirometry before and after the inhalation of 200 mu g of salbutamol. COPD diagnosis and severity were based on criteria developed by the Global Initiative for Chronic Obstructive Lung Diseases. Results: The overall prevalence of spirometry diagnosed COPD subjects was 4.9% (5.1% in men vs 3.5% in women). Mild COPD was found in 33.3% of COPD individuals, moderate in 45%, severe and very severe COPD was found in 20% and 1.7%, respectively. Physician diagnosis was reported in 48.3% of spirometry diagnosed COPD subjects, whereas 55.9% were asymptomatic. Age (p = 0.000), increased tobacco consumption (p = 0.001) and cough with phlegm (p = 0.048) were found to have a synergistic effect on the diagnosis of COPD. Conclusions: Results suggest that COPD is an important health problem in Cyprus. Programs that raise public awareness focusing on prevention, early detection and treatment are needed. Under-diagnosis of COPD raises the need for spirometry screening programs in high risk individuals and guideline implementation for the management of the disease

Viral epidemiology of acute exacerbations of chronic obstructive pulmonary disease

The role of viruses in Acute Exacerbations of Chronic Obstructive Pulmonary Disease (AECOPD) needs further elucidation. The aim of the present study was to evaluate the molecular epidemiology of viral pathogens in AECOPD.Patients presenting to the Emergency Room with AECOPD needing hospitalization were recruited. Oropharyngeal and sputum samples were collected in order to perform microarrays-based viral testing for the detection of respiratory viruses.A total of 200 (100%) patients were analyzed and from them in 107 (53.5%) a virus was detected. The commonest identified viruses were the human Respiratory Syncytial Virus (subtypes A and B) (40.5%), influenza virus (subtypes A, B, C) (11%), rhinovirus (8%) and human Parainfluenza Virus (subtypes A and B) (7.5%). A bacterial pathogen was isolated in 27 (14%) patients and a dual infection due to a bacterial and a viral pathogen was recognised in 14/107 patients. Patients with AECOPD and a viral infection had a lengthier hospital stay (9.2±4.6 vs 7.6±4.3, p&lt;0.01) while the severity of the disease was no related with significant differences among the groups of the study population.In conclusion, the isolation of a virus was strongly associated with AECOPD in the examined population. The stage of COPD appeared to have no relation with the frequency of the isolated viruses while dual infection with a viral and a bacterial pathogen was not rare. © 2011

Viral profile of COPD exacerbations according to patients

Background: To compare the differences between elderly and non-elderly patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) due to viral infections. Methods: Patients with chronic obstructive pulmonary disease (COPD) exacerbation were recruited and classified as elderly (&gt;65 years) and non-elderly (≤ 65 years). Sputum and oropharyngeal samples were assessed, PCR for respiratory viruses and cultures for common pathogens were performed. Results: 247 patients (median age: 69.3±9.5 years) were recruited and categorized into group A: non-elderly patients [n=81 (32.8%), median age 58±5.99] and group B: elderly patients [n=166 (67.2%), median age 74.8±4.8] years. In 133 (53.8%) patients a viral infection was identified and in 34 (13.8%) a bacterial pathogen was isolated from cultures. In 18 (7.3%) patients a double infection (bacterial+viral) was identified. In group B, the presence of cardiac failure (46.6% vs 28.3%, p&lt;0.001), renal failure (10.5% vs 4%, p=0.03), bacterial co-infection (13.8% vs 7.4%, p=0.04), influenza vaccination rates (45.5% vs 215, p&lt;0.001), and longer hospital stay (8.4±4.4 vs 7.5±3.2 days, p=0.02) were higher than group A. The overall rate of viral infections did not differ according to age. A trend to higher rates of infection with parainfluenza 3 [19 (20%) patients in group B vs3 (7.5%) patients in group A, p=0.04] was observed in older patients. Conclusion: No differences on the rate and type of viral infections were noted for elderly vs non elderly patients. However, they tended to have more bacterial co-infections that led to AECOPD and longer hospitalization stays compared to non-elderly patients. © Dimopoulos et al

Variability of Tidal Breathing Parameters in Preterm Infants and Associations with Respiratory Morbidity during Infancy: A Cohort Study

Objective: To test whether low variability of tidal volume (V T ) and capnographic indices are predictive of subsequent respiratory morbidity in preterm infants. Study design: In a birth cohort of 133 preterm infants, lung function was performed at 44 weeks postmenstrual age. Associations between the coefficient of variation (CV) of V T (CV VT ) and of expired CO 2 volume per breath (CV VE,CO2 ) with rehospitalization, wheeze, and inhalation therapy during infancy were assessed using logistic regression. Area under the curve (AUC) analysis was used to assess whether outcome prediction using bronchopulmonary dysplasia (BPD) classification was enhanced by CV VT or CV VE,CO2 . Results: For each IQR decrease in CV VT (range, 4%-35%) and CV VE , CO2 (range, 5%-40%), the OR for rehospitalization increased by 2.25 (95% CI, 1.21-4.20) and 2.31 (95% CI, 1.20-4.45), respectively. The predictive value of BPD for rehospitalization was improved when CV VT or CV VE,CO2 was added to the model, with the AUC increasing from 0.56 to 0.66 in both models. No association was found for the other outcomes. Conclusions: Compared with BPD classification alone, including near-term variability of tidal breathing parameters improves the prediction of rehospitalization in infancy. These findings may inform parent counseling and monitoring strategies in preterm infants