Tunnel inspections may demand personnel to access hazardous environments soliciting the need for robotic operations to minimize human intervention. CERN, the European Organisation for Nuclear ...Research, has a number of tunnel infrastructures, including the tunnel hosting the Large Hadron Collider (LHC). A Train Inspection Monorail (TIM) was installed in the LHC tunnel to reduce personnel intervention. It gathers data from various sensors and captures images which, up till now, were only used for data record purposes. In this paper we present a computer vision system, TInspect, that uses a robust hybrid change detection algorithm to monitor changes on the LHC tunnel linings. The system achieves a high sensitivity of 83.5% and 82.8% precision, and an average accuracy of 81.4%. The proposed system is also configurable through different parameters to adapt to different scenarios, making it useable in other tunnel environments and therefore not exclusive to the LHC tunnel.
•The paper presents a novel vision-based change detection system for tunnel linings inspection.•It presents a pre-processing stage to mitigate the problem of low lighting and contrast in such environments.•It presents a registration solution to cater for the mobile platform that carries the camera.•It presents a new hybrid change detection system to improve the accuracy of detecting changes in the tunnel linings.
Summary Background Dupilumab, a fully human anti-interleukin-4 receptor α monoclonal antibody, inhibits interleukin-4 and interleukin-13 signalling, key drivers of type-2-mediated inflammation. ...Adults with uncontrolled persistent asthma who are receiving medium-to-high-dose inhaled corticosteroids plus a long-acting β2 agonist require additional treatment options as add-on therapy. We aimed to assess the efficacy and safety of dupilumab as add-on therapy in patients with uncontrolled persistent asthma on medium-to-high-dose inhaled corticosteroids plus a long-acting β2 agonist, irrespective of baseline eosinophil count. Methods We did this randomised, double-blind, placebo-controlled, parallel-group, pivotal phase 2b clinical trial at 174 study sites across 16 countries or regions. Adults (aged ≥18 years) with an asthma diagnosis for 12 months or more based on the Global Initiative for Asthma 2009 Guidelines receiving treatment with medium-to-high-dose inhaled corticosteroids plus a long-acting β2 agonist were eligible for participation. Patients were randomly assigned (1:1:1:1:1) to receive subcutaneous dupilumab 200 mg or 300 mg every 2 weeks or every 4 weeks, or placebo, over a 24-week period. The primary endpoint was change from baseline at week 12 in forced expiratory volume in 1 s (FEV1 in L) in patients with baseline blood eosinophil counts of at least 300 eosinophils per μL assessed in the intention-to-treat population. Safety outcomes were assessed in all patients that received at least one dose or part of a dose of study drug. This trial is registered at ClinicalTrials.gov , number NCT01854047 , and with the EU Clinical Trials Register, EudraCT number 2013-000856-16. Findings 769 patients (158 in the placebo group and 611 in the dupilumab groups) received at least one dose of study drug. In the subgroup with at least 300 eosinophils per μL, the greatest increases (200 mg every 2 weeks, p=0·0008; 300 mg every 2 weeks, p=0·0063) in FEV1 compared with placebo were observed at week 12 with doses every 2 weeks in the 300 mg group (mean change 0·39 L SE 0·05; mean difference 0·21 95% CI 0·06–0·36; p=0·0063) and in the 200 mg group (mean change 0·43 L SE 0·05; mean difference 0·26 0·11–0·40; p=0·0008) compared with placebo (0·18 L SE 0·05). Similar significant increases were observed in the overall population and in the fewer than 300 eosinophils per μL subgroup (overall population: 200 mg every 2 weeks, p<0·0001; 300 mg every 2 weeks, p<0·0001; <300 eosinophils per μL: 200 mg every 2 weeks, p=0·0034; 300 mg every 2 weeks, p=0·0086), and were maintained to week 24. Likewise, dupilumab every 2 weeks produced the greatest reductions in annualised rates of exacerbation in the overall population (70–70·5%), the subgroup with at least 300 eosinophils per μL (71·2–80·7%), and the subgroup with fewer than 300 eosinophils per μL (59·9–67·6%). The most common adverse events with dupilumab compared with placebo were upper respiratory tract infections (33–41% vs 35%) and injection-site reactions (13–26% vs 13%). Interpretation Dupilumab increased lung function and reduced severe exacerbations in patients with uncontrolled persistent asthma irrespective of baseline eosinophil count and had a favourable safety profile, and hence in addition to inhaled corticosteroids plus long-acting β2 -agonist therapy could improve the lives of patients with uncontrolled persistent asthma compared with standard therapy alone. Funding Sanofi-Genzyme and Regeneron Pharmaceuticals.
Phytoremediation is an attractive strategy for cleaning soils polluted with a wide spectrum of organic and inorganic toxic compounds. Among these pollutants, heavy metals have attracted global ...attention due to their negative effects on human health and terrestrial ecosystems. As a result of this, numerous studies have been carried out to elucidate the mechanisms involved in removal processes. These studies have employed many plant species that might be used for phytoremediation and the obtention of end bioproducts such as biofuels and biogas useful in combustion and heating. Phytotechnologies represent an attractive segment that is increasingly gaining attention worldwide due to their versatility, economic profitability, and environmental co-benefits such as erosion control and soil quality and functionality improvement. In this review, the process of valorizing biomass from phytoremediation is described; in addition, relevant experiments where polluted biomass is used as feedstock or bioenergy is produced via thermo- and biochemical conversion are analyzed. Besides, pretreatments of biomass to increase yields and treatments to control the transfer of metals to the environment are also mentioned. Finally, aspects related to the feasibility, benefits, risks, and gaps of converting toxic-metal-polluted biomass are discussed.
Elevated numbers of blood eosinophils are a risk factor for asthma exacerbations. Reslizumab is a humanised anti-interleukin 5 monoclonal antibody that disrupts eosinophil maturation and promotes ...programmed cell death. We aimed to assess the efficacy and safety of reslizumab in patients with inadequately controlled, moderate-to-severe asthma.
We did two duplicate, multicentre, double-blind, parallel-group, randomised, placebo-controlled phase 3 trials. Both trials enrolled patients with asthma aged 12-75 years (from 128 clinical research centres in study 1 and 104 centres in study 2) from Asia, Australia, North America, South America, South Africa, and Europe, whose asthma was inadequately controlled by medium-to-high doses of inhaled corticosteroid based therapy and who had blood eosinophils of 400 cells per μL or higher and one or more exacerbations in the previous year. Patients were randomly assigned (1:1) to receive either intravenous reslizumab (3·0 mg/kg) or placebo every 4 weeks for 1 year by computerised central randomisation. Patients and investigators were masked to treatment assignment during the study. Each patient received a specific volume of study drug (reslizumab or matching placebo) on the basis of the patient's body weight and randomly assigned treatment group. Additionally, the sponsor's clinical personnel involved in the study were masked to the study drug identity until the database was locked for analysis and the treatment assignment revealed. The primary outcome was the annual frequency of clinical asthma exacerbations and was analysed by intention to treat. We assessed safety outcomes in the patients who had received one or more dose of the drug. The trials have been completed and are registered with ClinicalTrials.gov, numbers NCT01287039 (study 1) and NCT01285323 (study 2).
Study 1 was done between April 12, 2011, and March 3, 2014 and study 2 between March 22, 2011, and April 9, 2014. Of 2597 patients screened, 953 were randomly assigned to receive either reslizumab (n=477 245 in study 1 and 232 in study 2) or placebo (n=476 244 and 232). In both studies, patients receiving reslizumab had a significant reduction in the frequency of asthma exacerbations (study 1: rate ratio RR 0·50 95% CI 0·37-0·67; study 2: 0·41 0·28-0·59; both p<0·0001) compared with those receiving placebo. Common adverse events on reslizumab were similar to placebo. The most common adverse events were worsening asthma symptoms (127 52% for placebo and 97 40% for reslizumab in study 1; 119 51% for placebo and 67 29% for reslizumab for study 2), upper respiratory tract infections (32 13% and 39 16%; 16 7% and eight 3%), and nasopharyngitis (33 14% and 28 11%; 56 24% and 45 19%). Two patients in the reslizumab group had anaphylactic reactions; both responded to standard treatment at the study centre and resolved, and the patients were withdrawn from the study.
These results support the use of reslizumab in patients with asthma and elevated blood eosinophil counts who are inadequately controlled on inhaled corticosteroid-based therapy.
Teva Branded Pharmaceutical Products R&D.
Background The development of asthma after respiratory syncytial virus (RSV) bronchiolitis has been demonstrated in case-control studies, although the determinants of post-RSV asthma remain ...undefined. Objectives We sought to evaluate the potential determinants of physician-diagnosed asthma after severe RSV bronchiolitis during infancy. Methods We enrolled 206 children during an initial episode of severe RSV bronchiolitis at 12 months of age or less in a prospective cohort study and followed these children for up to 6 years. In a subset of 81 children, we analyzed CCL5 (RANTES) mRNA expression in upper airway epithelial cells. Results Forty-eight percent of children had physician-diagnosed asthma before the seventh birthday. Independent determinants significantly associated with increased risk for physician-diagnosed asthma by the seventh birthday included maternal asthma (odds ratio OR, 5.2; 95% CI, 1.7-15.9; P = .004), exposure to high levels of dog allergen (OR, 3.2; 95% CI, 1.3-7.7; P = .012), aeroallergen sensitivity at age 3 years (OR, 10.7; 95% CI, 2.1-55.0; P = .005), recurrent wheezing during the first 3 years of life (OR, 7.3; 95% CI, 1.2-43.3; P = .028), and CCL5 expression in nasal epithelia during acute RSV infection (OR, 3.8; 95% CI, 1.2-2.4; P < .001). White children (OR, 0.19; 95% CI, 0.04-0.93; P = .041) and children attending day care (OR, 0.18; 95% CI, 0.04-0.84; P = .029) had a decreased risk of physician-diagnosed asthma. Conclusions Approximately 50% of children who experience severe RSV bronchiolitis have a subsequent asthma diagnosis. The presence of increased CCL5 levels in nasal epithelia at the time of bronchiolitis or the development of allergic sensitization by age 3 years are associated with increased likelihood of subsequent asthma.
Background Asthma in children is a heterogeneous disorder with many phenotypes. Although unsupervised cluster analysis is a useful tool for identifying phenotypes, it has not been applied to ...school-age children with persistent asthma across a wide range of severities. Objectives This study determined how children with severe asthma are distributed across a cluster analysis and how well these clusters conform to current definitions of asthma severity. Methods Cluster analysis was applied to 12 continuous and composite variables from 161 children at 5 centers enrolled in the Severe Asthma Research Program. Results Four clusters of asthma were identified. Children in cluster 1 (n = 48) had relatively normal lung function and less atopy. Children in cluster 2 (n = 52) had slightly lower lung function, more atopy, and increased symptoms and medication use. Cluster 3 (n = 32) had greater comorbidity, increased bronchial responsiveness, and lower lung function. Cluster 4 (n = 29) had the lowest lung function and the greatest symptoms and medication use. Predictors of cluster assignment were asthma duration, the number of asthma controller medications, and baseline lung function. Children with severe asthma were present in all clusters, and no cluster corresponded to definitions of asthma severity provided in asthma treatment guidelines. Conclusion Severe asthma in children is highly heterogeneous. Unique phenotypic clusters previously identified in adults can also be identified in children, but with important differences. Larger validation and longitudinal studies are needed to determine the baseline and predictive validity of these phenotypic clusters in the larger clinical setting.
Cross-sectional studies suggest an exacerbation-prone asthma (EPA) phenotype and the utility of blood eosinophils and plasma IL-6 as predictive biomarkers.
To prospectively test for EPA phenotype and ...utility of baseline blood measures of eosinophils and IL-6 as predictive biomarkers.
Three-year asthma exacerbation data were analyzed in 406 adults in the Severe Asthma Research Program-3. Transition models were used to assess uninformed and informed probabilities of exacerbation in year 3. Binomial regression models were used to assess eosinophils and IL-6 as predictive biomarkers.
Eighty-three participants (21%) had ≥1 exacerbation in each year (EPA) and 168 participants (41%) had no exacerbation in any year (exacerbation-resistant asthma). The uninformed probability of an exacerbation in Year 3 was 40%, but the informed probability increased to 63% with an exacerbation in Year 2 and 82% with an exacerbation in Years 1 and 2. The probability of a Year 3 exacerbation with no Year 1 or 2 exacerbations was 13%. Compared with exacerbation-resistant asthma, EPA was characterized by lower FEV
and a higher prevalence of obesity, hypertension, and diabetes. High-plasma IL-6 occurred in EPA, and the incident rate ratio for exacerbation increased 10% for each 1-pg/μl increase in baseline IL-6 level. Although high blood eosinophils did not occur in EPA, the incident rate ratio for exacerbations increased 9% for each 100-cell/μl increase in baseline eosinophil number.
Longitudinal analysis confirms an EPA phenotype characterized by features of metabolic dysfunction. Blood measures of IL-6, but not eosinophils, were significantly associated with EPA, and IL-6 and eosinophils predicted exacerbations in the sample as a whole.
Asthma outcomes: Composite scores of asthma control Cloutier, Michelle M., MD; Schatz, Michael, MD, MS; Castro, Mario, MD, MPH ...
Journal of allergy and clinical immunology,
03/2012, Letnik:
129, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Background Current asthma guidelines recommend assessing the level of a patient’s asthma control. Consequently, there is increasing use of asthma control as an outcome measure in clinical research ...studies. Several composite assessment instruments have been developed to measure asthma control. Objective National Institutes of Health institutes and federal agencies convened an expert group to propose the most appropriate standardized composite score of asthma control instruments to be used in future asthma studies. Methods We conducted a comprehensive search of PubMed using both the National Library of Medicine’s Medical Subject Headings and key terms to identify studies that attempted to develop and/or test composite score instruments for asthma control. We classified instruments as core (required in future studies), supplemental (used according to study aims and standardized), or emerging (requiring validation and standardization). This work was discussed at a National Institutes of Health–organized workshop convened in March 2010 and finalized in September 2011. Results We identified 17 composite score instruments with published validation information; all had comparable content. Eight instruments demonstrated responsiveness over time; 3 demonstrated responsiveness to treatment. A minimal clinically important difference has been established for 3 instruments. The instruments have demographic limitations; some are proprietary, and their use could be limited by cost. Conclusion Two asthma composite score instruments are sufficiently validated for use in adult populations, but additional research is necessary to validate their use in nonwhite populations. Gaps also exist in validating instruments for pediatric populations.
Background Studies of asthma phenotypes have identified obesity as a component of a group characterized by a high proportion of subjects with adult-onset asthma. However, whether age of asthma onset ...modifies the association between obesity and asthma is unknown. Objectives We sought to compare the associations between body mass index (BMI) categories with physiological, inflammatory, and clinical parameters across age of asthma onset phenotypes; and to compare the rate of BMI change in relation to asthma duration, by age of onset asthma phenotypes. Methods From the Severe Asthma Research Program, we defined age of asthma onset as early (<12 years of age) and late (≥12 years of age). Comparisons of BMI categories were done within age-of-onset groups, and obesity was also compared across these groups. Multivariable logistic regression analysis was done to evaluate the association between BMI categories with health care use and respiratory symptoms and multivariable linear regression for the association between duration of asthma and weight gain (BMI change per year). An interaction between obesity and age of asthma onset was included in the multivariable analyses. Results The study population consisted of 1049 subjects, and the median age for asthma onset was 10 years (interquartile range, 4-25 years); 48% had late-onset asthma (≥12 years of age), and 52% had early-onset asthma (<12 years of age). Compared with obese subjects with late-onset asthma, obese subjects with early-onset asthma had more airway obstruction, bronchial hyperresponsiveness, and higher odds ratios of ever having 3 or more previous oral steroid tapers per year or intensive care unit admissions for asthma per preceding year (interactions between obesity and age of asthma onset were P = .055 and P = .02, respectively). In subjects with early-onset asthma but not in subjects with late-onset asthma, there was a significant association between increasing BMI and duration of asthma after adjusting for confounders. The interaction between asthma duration and age of asthma onset was a P value of less than .01. Conclusion Asthmatic subjects are differentially affected by obesity based on whether they had asthma early (<12 years of age) or later in life. These results highlight the need to understand obesity as a comorbidity that affects specific clinical phenotypes and not all asthma subjects alike.
In this work, heterostructures formed by carbon nitride (CN) and hydroxyapatite (HAp) were successfully synthesized by the microwave-assisted hydrothermal method, varying the addition of CN in mass ...percentages (25–50%). Structural and spectroscopic analyses showed the formation of the CN/HAp heterostructure free from impurities with the presence of both phases, and morphological analyses showed the HAp nanorods together with the CN nanosheets. The obtained heterostructures enabled absorption in the visible region, with a band gap reduction from 5.43 eV (HAp) to 3.07 eV. The photocatalytic activity of the nanoparticles was evaluated under sunlight irradiation on the degradation of organic methylene blue (MB) and methyl orange (MO) dyes, and a mixture (MIX) of both. The heterostructure with 50% CN had degradation efficiency of up to 99% of MB and up to 81% of MO after 20 min. The reusability of the photocatalysts was tested in three cycles and showed improved photocatalytic activity of the heterostructure, maintaining its structural stability in the photodegradation of the dyes by at least 75%. Tests with inhibitors indicated that superoxide (O
2
−
) and hole (h
+
) are the active radicals, indicating that the obtained heterostructure is type I.