Lung inflammation and immunity : report from the 12th ERS Lung Science conference

The European Respiratory Society (ERS) seeks to alleviate suffering from respiratory diseases and promote lung health through research, dissemination of knowledge, and medical and public education. In support of this mission, the ERS organises the annual Lung Science Conference (LSC). This world-class research meeting brings together leading experts on topics that are of relevance to respiratory medicine. Furthermore, at the LSC, one of the main focuses is early-career physicians and scientists who are involved in respiratory research, as these are the future leaders of the field [1]. Inflammatory diseases of the lung are a major cause of morbidity and mortality. In March 2014, international experts met for the 12th LSC in Estoril, Portugal, to present and discuss novel findings in the field of “Lung Inflammation and Immunity”, recognising that inflammation is the main pathogenic process in many respiratory diseases, such as asthma and infection, and a significant contributor to many others [2, 3]. Old and recent anti-inflammatory and/or immunomodulating drugs are the main tools of our current treatment in many respiratory diseases, and new drugs targeting inflammatory pathways are being developed. This was discussed in an early evening session “The new drug discovery paradigm” by Tomas Mustelin (Respiratory, Inflammatory, and Autoimmune Diseases, MedImmune, Gaithersburg, MD, USA) and Robert Strieter (Novartis Institutes for BioMedical Research, Cambridge, MA, USA), who were both involved in academic respiratory research before joining pharmaceutical companies. Part of the 2014 LSC was focused on the mechanisms of allergy and asthma, but other fields of interest were discussed, particularly lung fibrosis, chronic obstructive pulmonary disease and emphysema, pulmonary hypertension, and lung transplantation

QJava: A Monadic Java Library for Quantum Programming

To help the understanding and development of quantum algorithms there is an effort focused on the investigation of new semantic models and programming languages for quantum computing. Researchers in computer science have the challenge of deve loping programming languages to support the creation, analysis, modeling and simulation of high level quantum algorithms. Based on previous works that use monads inside the programming language Haskell to elegantly explain the odd characteristics of quantum computation (like superposition and entanglement), in this work we present a monadic Java library for quantum programming. We use the extension of the programming language Java called BGGA Closure, that allow the manipulation of anonymous functions (closures) inside Java. We exemplify the use of the library with an implementation of the Toffoli quantum circuit

Análise probabilística do fator de segurança de taludes através do método de monte carlo

TCC (graduação) - Universidade Federal de Santa Catarina. Centro Tecnológico. Engenharia Civil.Nos estudos geotécnicos e geológicos, principalmente quando se analisa a segurança de taludes, é importante ter-se em mente a grande distinção de características que um solo pode apresentar, visto a alta variabilidade dos parâmetros característicos do solo, inclusive em uma camada relativamente homogênea. Dessa forma, faz-se cada vez mais necessária a utilização de métodos que garantam a confiabilidade das estruturas geotécnicas. É o caso dos métodos estatísticos que buscam, através da probabilidade, incorporar as incertezas relacionadas, complementando as análises determinísticas já existentes. Através deste trabalho, buscou-se inicialmente aplicar o método probabilístico de Monte Carlo sobre um talude finito de referência. Métodos clássicos de equilíbrio limite para taludes finitos, como por exemplo, Fellenius, também foram utilizados nesta análise. Sendo assim, foi estudada a variação aleatória de três parâmetros de alto grau de influência na análise de estabilidade de taludes, sendo eles coesão, ângulo de atrito e peso específico. Como resultado, além do Fator de Segurança (FS) calculado de forma determinística, calculou-se uma distribuição probabilística de soluções possíveis. Para o segundo caso de avaliação, agora para um talude de projeto de duplicação da BR 470, abrangeu-se a análise de estabilidade para um aterro sobre solos moles. Nesta etapa, a investigação de campo e de laboratório (SPT, CPTU, Palheta, Triaxial UU) delimitou a faixa de variação (valores médios e coeficientes de variação de acordo com a literatura) e os parâmetros a serem utilizados. Além dos já citados inclui-se a resistência não-drenada. O valor determinístico do FS foi diretamente comparado com o obtido pela análise probabilística, fornecendo maior abrangência sobre o comportamento real do talude em estudo. Somando-se a isso, foi determinada a probabilidade de ruptura para diversos casos de variação, mostrando que um FS > 1,0 não garante a estabilidade da estrutura. Portanto, o objetivo principal deste trabalho foi compreender a relevância de uma análise probabilística, tendo em conta os parâmetros geotécnicos, em complemento as análises determinísticas geralmente adotadas.In geotechnical and geological problems such as slope reliability analysis, it is important to bear in mind the great distinction of characteristics that can be presented by a soil, given the great variability of the soil’s parameters, even on a relatively homogeneous layer. In this way, the use of methods which can guarantee the reliability of geotechnical structures is increasingly necessary. That’s the case of statiscal methods, that seek to incorporate the associated uncertanties through probability, complementing the already existing deterministic analysis. In this context, the present work initially sought to apply the Monte Carlo probabilistic method in a finite slope, referred to as the reference section. Classical limit equilibrium methods for finite slopes, as Ordinary method (Fellenius) were also used in this analysis, which is structured to study the random variation of three parameters: cohesion, friction angle and specific weight. As an outcome, beyond the Safety factor (SF) calculated through deterministic analysis, a probabilistic distribution of possible results was also calculated. For the second assessment case, now for a slope of the BR 470 extension project, the stability analysis of a soft soil embankment was included. At this point, field and laboratory tests (SPT, CPTU, vane test, Triaxial UU) delimited the variation range (average values and variation coefficients) and the parameters to be used in the analysis. In addition to those already mentioned, it was include the undrained resistance. The deterministic value of the SF was directly compared with the one obtained through probabilistic analysis, providing greater comprehension over the real behaviour of the studied section. In addition, the probability of rupture was determined for several variation cases, showing that a SF > 1.0 does not guarantee the stability of the structure. Therefore, the main goal of this work was to understand the relevance of a probabilistic analysis, taking into account the geotechnical parameters, in complement to the results only obtained from deterministic analysis

Human lung fibroblasts may modulate dendritic cell phenotype and function: results from a pilot in vitro study

International audienceAbstractIn human lung fibrotic lesions, fibroblasts were shown to be closely associated with immature dendritic cell (DC) accumulation. The aim of the present pilot study was to characterize the role of pulmonary fibroblasts on DC phenotype and function, using co-culture of lung fibroblasts from patients with idiopathic pulmonary fibrosis (IPF) and from control patients, with a DC cell line MUTZ-3. We observed that co-culture of lung control and IPF fibroblasts with DCs reduced the expression of specific DC markers and down-regulated their T-cell stimulatory activity. This suggests that pulmonary fibroblasts might sustain chronic inflammation in the fibrotic lung by maintaining in situ a pool of immature DCs

Fibroblasts: the missing link between fibrotic lung diseases of different etiologies?

CommentaryInternational audienc

Safety, tolerability and appropriate use of nintedanib in idiopathic pulmonary fibrosis

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive disease characterised by dyspnea and loss of lung function. Methods: Using pooled data from the replicate, randomized, 52-week, placebo-controlled INPULSIS® trials, we characterized the safety and tolerability of nintedanib 150 mg twice daily in patients with IPF and described how adverse events were managed during these trials. Results: One thousand and sixty- one patients were treated (nintedanib 638; placebo 423). Higher proportions of patients in the nintedanib group than the placebo group had ≥1 dose reduction to 100 mg bid (27.9 % versus 3.8 %) or treatment interruption (23.7 % versus 9.9 %). Adverse events led to permanent treatment discontinuation in 19.3 % and 13.0 % of patients in the nintedanib and placebo groups, respectively. Diarrhea was the most frequent adverse event, reported in 62.4 % of patients in the nintedanib group versus 18.4 % in the placebo group; however, only 4.4 % of nintedanib-treated patients discontinued trial medication prematurely due to diarrhea. Monitoring of liver enzymes before and periodically during nintedanib treatment was recommended so that liver enzyme elevations could be managed through dose reduction or treatment interruption. Conclusion: Nintedanib had a manageable safety and tolerability profile in patients with IPF. Recommendations for adverse event management minimized permanent treatment discontinuations in the INPULSIS® trials. Trial registration: clinicaltrials.gov NCT01335464and NCT01335477.</p

Association between Vascular Remodelling and Necrotic Core in Coronary Arteries: Analysis by Intracoronary Ultrasound with Virtual Histology®

ABSTRACTBackgroundAnatomopathological studies suggest an association of positive vascular remodeling and vulnerable coronary plaques. The objective of this study was to verify whether there is a correlation between positive vascular remodeling and necrotic core in atherosclerotic coronary lesions.MethodsWe studied 270 cross sections obtained by Virtual Histology® in 30 patients who had positive remodeling in coronary artery segments with lesions > 50%, identified by coronary angiography. Seven cross sections were assessed per segment of coronary artery, including the cross section with the highest remodeling index, denominated cross section of interest (cross section 4).ResultsMean age was 60.8±8.8 years, 80% were male and 30% were diabetic. Unstable angina was the most frequent clinical presentation (56.6%) and the left anterior descending artery was the most analyzed vessel (43%). The vessel reference area was 15.5±4.9mm2 and the remodeling index in cross section 4 was 1.2±0.1. Repeated measures analysis of variance showed a higher percentage of necrotic core in the cross section of interest (P < 0.001). We observed a positive correlation of coronary artery remodeling and necrotic core (r = 0.79; P < 0.001).ConclusionsPositive coronary artery remodeling is associated to the presence of necrotic core, which characterizes vulnerable atherosclerotic plaques. The search for positive arterial remodeling may be a useful strategy for detecting vulnerable plaques before rupture

Effect of Nintedanib on Progression of Systemic Sclerosis-Associated Interstitial Lung Disease Over 100 Weeks: Data From a Randomized Controlled Trial

OBJECTIVE In the SENSCIS trial, participants with systemic sclerosis-associated interstitial lung disease (SSc-ILD) were randomized to receive nintedanib or placebo until the last participant reached week 52 but for 100 weeks or less. Nintedanib reduced the rate of decline in forced vital capacity (FVC) (ml/year) over 52 weeks by 44% (41 ml [95% confidence interval (95% CI): 2.9-79.0]) versus placebo. We investigated the effect of nintedanib over the whole SENSCIS trial. METHODS The annual rate of decline in FVC (ml/year) over the whole trial was assessed descriptively using 1) on-treatment data plus off-treatment data from participants who prematurely discontinued treatment (intent-to-treat analysis) and 2) only on-treatment data to assess the effect of nintedanib in participants who remained on treatment. RESULTS In the intent-to-treat analysis, the adjusted mean (SE) annual rate of decline in FVC over 100 weeks was -54.9 (11.1) and -88.8 (10.9) ml/year in the nintedanib (n = 287) and placebo (n = 288) groups, respectively (difference 34.0 ml/year [95% CI: 3.4-64.5]). In the on-treatment analysis, the adjusted mean (SE) annual rate of decline in FVC over 100 weeks was -55.1 (12.3) and -94.0 (11.7) ml/year in the nintedanib (n = 286) and placebo (n = 288) groups, respectively (difference 38.9 ml/year [95% CI: 5.6-72.1]). The adverse event profile of nintedanib over 100 weeks was consistent with that observed over 52 weeks. CONCLUSION Nintedanib provides a sustained benefit on slowing the progression of SSc-ILD over 100 weeks, with adverse events that are manageable for most patients

Anti-acid therapy in idiopathic pulmonary fibrosis: insights from the INPULSIS (R) trials

Background: The benefits and risks of anti-acid medication in patients with idiopathic pulmonary fibrosis (IPF) remain a topic of debate. We investigated whether use of anti-acid medication at baseline was associated with differences in the natural course of disease or influenced the treatment effect of nintedanib in patients with IPF. Methods: Post-hoc analyses of outcomes in patients receiving versus not receiving anti-acid medication (proton pump or histamine-2 receptor inhibitor) at baseline using pooled data from the two Phase III randomized placebo-controlled INPULSIS (R) trials of nintedanib in patients with IPF. Results: At baseline, 406 patients were receiving anti-acid medication (244 nintedanib;162 placebo) and 655 were not (394 nintedanib;261 placebo). In an analysis of the natural course of IPF by anti-acid medication use at baseline, the adjusted annual rate of decline in FVC was -252.9 mL/year in placebo-treated patients who were receiving anti-acid medication at baseline and -205.4 mL/year in placebo-treated patients who were not (difference of -47.5 mL/year [95% CI: -105.1, 10.1];p = 0.1057). In an analysis of the potential influence of anti-acid medication use on the treatment effect of nintedanib, the adjusted annual rates of decline in FVC were -124.4 mL/year in the nintedanib group and 252.9 mL/year in the placebo group (difference of 128.6 mL/year [95% CI: 74.9, 182.2]) in patients who were receiving anti-acid medication at baseline and -107.0 mL/year in the nintedanib group and -205.3 mL/year in the placebo group (difference of 98.3 mL/year [95% CI: 54.1, 142.5]) in patients who were not (treatment-by-time-by-subgroup interaction p = 0.3869). The proportions of patients who had >= 1 investigator-reported acute exacerbation were 11.7% and 5.0% in placebo-treated patients, and 4.9% and 4.8% of nintedanib-treated patients, among patients who were and were not receiving anti-acid medication at baseline, respectively. Conclusions: In post-hoc analyses of data from the INPULSIS (R) trials, anti-acid medication use at baseline was not associated with a more favorable course of disease, and did not impact the treatment effect of nintedanib, in patients with IPF