Внутренние источники финансирования инвестиционной деятельности в Украине

В статье рассмотрены 4 основных источника финансирования инвестиционной деятельности, и проблемы связанные с их формированием и использованием. Учитывая непосредственное влияние внутренних источников инвестиций на экономический рост, и их минимальное использование в Украине, тема становится актуальной, требующей детальной проработки.У статті розглянуті 4 основні джерела фінансування інвестиційної діяльності та проблеми, пов'язані з їх формуванням та використанням. З огляду на безпосередній вплив внутрішніх джерел інвестицій на економічний зріст, та їх мінімальне використання в Україні, тема стає актуальною, потребуючою детального опрацювання.Four basic sources of financing investment activity as well as problems related to their forming and use are considered in the article. This theme is essential and needs detailed development under circumstances of direct impact of the internal sources of investment on economical growth and still minimum use in Ukraine

Low-dose CT measurements of airway dimensions and emphysema associated with airflow limitation in heavy smokers:a cross sectional study

Background: Increased airway wall thickness (AWT) and parenchymal lung destruction both contribute to airflow limitation. Advances in computed tomography (CT) post-processing imaging allow to quantify these features. The aim of this Dutch population study is to assess the relationships between AWT, lung function, emphysema and respiratory symptoms.Methods: AWT and emphysema were assessed by low-dose CT in 500 male heavy smokers, randomly selected from a lung cancer screening population. AWT was measured in each lung lobe in cross-sectionally reformatted images with an automated imaging program at locations with an internal diameter of 3.5 mm, and validated in smaller cohorts of patients. The 15th percentile method (Perc15) was used to assess the severity of emphysema. Information about respiratory symptoms and smoking behavior was collected by questionnaires and lung function by spirometry.Results: Median AWT in airways with an internal diameter of 3.5 mm (AWT(3.5)) was 0.57 (0.44 - 0.74) mm. Median AWT in subjects without symptoms was 0.52 (0.41-0.66) and in those with dyspnea and/or wheezing 0.65 (0.52-0.81) mm (pConclusions: Post processing standardization of airway wall measurements provides a reliable and useful method to assess airway wall thickness. Increased airway wall thickness contributes more to airflow limitation than emphysema in a smoking male population even after adjustment for smoking behavior.</p

The COVID HOME study research protocol: Prospective cohort study of non-hospitalised COVID-19 patients.

BACKGROUND: Guidelines on COVID-19 management are developed as we learn from this pandemic. However, most research has been done on hospitalised patients and the impact of the disease on non-hospitalised and their role in transmission are not yet well understood. The COVID HOME study conducts research among COVID-19 patients and their family members who were not hospitalised during acute disease, to guide patient care and inform public health guidelines for infection prevention and control in the community and household. METHODS: An ongoing prospective longitudinal observational study of COVID-19 outpatients was established in March 2020 at the beginning of the COVID-19 pandemic in the Netherlands. Laboratory confirmed SARS-CoV-2 infected individuals of all ages that did not merit hospitalisation, and their household (HH) members, were enrolled after written informed consent. Enrolled participants were visited at home within 48 hours after initial diagnosis, and then weekly on days 7, 14 and 21 to obtain clinical data, a blood sample for biochemical parameters/cytokines and serological determination; and a nasopharyngeal/throat swab plus urine, stool and sperm or vaginal secretion (if consenting) to test for SARS-CoV-2 by RT-PCR (viral shedding) and for viral culturing. Weekly nasopharyngeal/throat swabs and stool samples, plus a blood sample on days 0 and 21 were also taken from HH members to determine whether and when they became infected. All participants were invited to continue follow-up at 3-, 6-, 12- and 18-months post-infection to assess long-term sequelae and immunological status

Susceptibility to chronic mucus hypersecretion, a genome wide association study

Background: Chronic mucus hypersecretion (CMH) is associated with an increased frequency of respiratory infections, excess lung function decline, and increased hospitalisation and mortality rates in the general population. It is associated with smoking, but it is unknown why only a minority of smokers develops CMH. A plausible explanation for this phenomenon is a predisposing genetic constitution. Therefore, we performed a genome wide association (GWA) study of CMH in Caucasian populations.Methods: GWA analysis was performed in the NELSON-study using the Illumina 610 array, followed by replication and metaanalysis in 11 additional cohorts. In total 2,704 subjects with, and 7,624 subjects without CMH were included, all current or former heavy smokers (&gt;= 20 pack-years). Additional studies were performed to test the functional relevance of the most significant single nucleotide polymorphism (SNP).Results: A strong association with CMH, consistent across all cohorts, was observed with rs6577641 (p = 4.25610(-6), OR = 1.17), located in intron 9 of the special AT-rich sequence-binding protein 1 locus (SATB1) on chromosome 3. The risk allele (G) was associated with higher mRNA expression of SATB1 (4.3610 29) in lung tissue. Presence of CMH was associated with increased SATB1 mRNA expression in bronchial biopsies from COPD patients. SATB1 expression was induced during differentiation of primary human bronchial epithelial cells in culture.Conclusions: Our findings, that SNP rs6577641 is associated with CMH in multiple cohorts and is a cis-eQTL for SATB1, together with our additional observation that SATB1 expression increases during epithelial differentiation provide suggestive evidence that SATB1 is a gene that affects CMH.</p

Susceptibility to chronic mucus hypersecretion, a genome wide association study

Background: Chronic mucus hypersecretion (CMH) is associated with an increased frequency of respiratory infections, excess lung function decline, and increased hospitalisation and mortality rates in the general population. It is associated with smoking, but it is unknown why only a minority of smokers develops CMH. A plausible explanation for this phenomenon is a predisposing genetic constitution. Therefore, we performed a genome wide association (GWA) study of CMH in Caucasian populations. Methods: GWA analysis was performed in the NELSON-study using the Illumina 610 array, followed by replication and meta-analysis in 11 additional cohorts. In total 2,704 subjects with, and 7,624 subjects without CMH were included, all current or former heavy smokers (≥20 pack-years). Additional studies were performed to test the functional relevance of the most significant single nucleotide polymorphism (SNP). Results: A strong association with CMH, consistent across all cohorts, was observed with rs6577641 (p = 4.25x10-6, OR = 1.17), located in intron 9 of the special AT-rich sequence-binding protein 1 locus (SATB1) on chromosome 3. The risk allele (G) was associated with higher mRNA expression of SATB1 (4.3x10 -9) in lung tissue. Presence of CMH was associated with increased SATB1 mRNA expression in bronchial biopsies from COPD patients. SATB1 expression was induced during differentiation of primary human bronchial epithelial cells in culture. Conclusions: Our findings, that SNP rs6577641 is associated with CMH in multiple cohorts and is a cis-eQTL for SATB1, together with our additional observation that SATB1 expression increases during epithelial differentiation provide suggestive evidence that SATB1 is a gene that affects CMH

Chronic respiratory symptoms associated with airway wall thickening measured by thin-slice low-dose CT

OBJECTIVE: In lung cancer screening, the prevalence of chronic respiratory symptoms is high among heavy smokers. The purpose of this study was to compare CT-derived airway wall measurements between male smokers with and those without chronic respiratory symptoms. MATERIALS AND METHODS: Fifty male heavy smokers with chronic respiratory symptoms (cough, excessive mucus secretion, dyspnea, and wheezing) and 50 without any respiratory symptom were randomly selected from the Dutch-Belgian Randomized Lung Cancer Screening Trial. Thin-slice low-dose CT images were evaluated with dedicated software for airway measurements. Wall area percentage and airway wall thickness were measured from trachea to bronchi in five different pulmonary lobes of airways with a luminal diameter of 5 mm or greater. Association between airway wall measurements and respiratory symptoms was analyzed by multiple linear regression adjusted for age, body mass index, smoking status, emphysema, and pulmonary function. RESULTS: After adjustment for relevant factors, a significant positive association between airway wall measurements and respiratory symptoms was found in airways with a luminal diameter between 5 to 10 mm (p < 0.01), but not in airways measuring 10 mm or greater (p > 0.05). At the airway level between 5 to 10 mm, the mean wall area percentages were 51.5% ± 7.9%. Airway wall thicknesses were 1.54 ± 0.39 mm and 1.37 ± 0.35 mm (p < 0.001). CONCLUSION: Male heavy smokers with chronic respiratory symptoms in lung cancer screening, who are at high-risk of chronic bronchitis, have bronchial wall thickening in airways with a luminal diameter of 5-10 mm but not in larger airways

A pro-inflammatory role for the Frizzled-8 receptor in chronic bronchitis

Rationale We have previously shown increased expression of the Frizzled-8 receptor of the Wingless/integrase-1 (WNT) signalling pathway in COPD. Here, we investigated if the Frizzled-8 receptor has a functional role in airway inflammation associated with chronic bronchitis. Methods Acute cigarette-smoke-induced airway inflammation was studied in wild-type and Frizzled-8-deficient mice. Genetic association studies and lung expression quantitative trait loci (eQTL) analyses for Frizzled-8 were performed to evaluate polymorphisms in FZD8 and their relationship to tissue expression in chronic bronchitis. Primary human lung fibroblasts and primary human airway epithelial cells were used for in vitro studies. Results Cigarette-smoke-exposure induced airway inflammation in wild-type mice, which was prevented in Frizzled-8-deficient mice, suggesting a crucial role for Frizzled-8 in airway inflammation. Furthermore, we found a significant genetic association (p=0.009) between single nucleotide polymorphism (SNP) rs663700 in the FZD8 region and chronic mucus hypersecretion, a characteristic of chronic bronchitis, in a large cohort of smoking individuals. We found SNP rs663700 to be a cis-eQTL regulating Frizzled-8 expression in lung tissue. Functional data link mesenchymal Frizzled-8 expression to inflammation as its expression in COPD-derived lung fibroblasts was regulated by pro-inflammatory cytokines in a genotype-dependent manner. Moreover, Frizzled-8 regulates inflammatory cytokine secretion from human lung fibroblasts, which in turn promoted MUC5AC expression by differentiated human airway epithelium. Conclusions These findings indicate an important pro-inflammatory role for Frizzled-8 and suggest that its expression is related to chronic bronchitis. Furthermore, our findings indicate an unexpected role for fibroblasts in regulating airway inflammation in COPD

Risk factors for chronic mucus hypersecretion in individuals with and without COPD: influence of smoking and job exposure on CMH

BACKGROUND: Chronic mucus hypersecretion (CMH) is highly prevalent in smokers and associated with an accelerated lung function decline and chronic obstructive pulmonary disease (COPD). Several risk factors contribute to CMH and to COPD. It is, however, unknown if risk factors for CMH are similar in persons with and without COPD.\n\nMETHODS: 1479 persons with and 8529 without COPD, participating in the general population-based LifeLines cohort, completed questionnaires and underwent spirometry. Occupational exposure was assessed using the ALOHA+ job exposure matrix. Analyses were performed using multiple logistic regression models.\n\nRESULTS: In COPD, a significantly higher risk for CMH was associated with higher pack-years smoking (per 10 pack-years) (OR=1.28; 1.12 to 1.46) and environmental tobacco smoke (ETS) (OR=2.06; 1.33 to 3.19). In non-COPD; male gender (OR=1.91; 1.51 to 2.41), higher Body Mass Index (OR=1.04; 1.01 to 1.06), higher pack-years smoking (OR=1.28; 1.14 to 1.44), current smoking (OR=1.50; 1.04 to 2.18), low and high exposure to mineral dust (OR=1.39; 1.04 to 1.87 and OR=1.60; 1.02 to 2.52), high exposure to gases & fumes (OR=2.19; 1.49 to 3.22). Significant interactions were found between COPD and exposure to gases & fumes (p=0.018) and aromatic solvents (p=0.038).\n\nCONCLUSIONS: A higher risk for CMH was associated with higher pack-years smoking regardless of COPD status. However, a higher risk for CMH was associated with high occupational exposure to gases & fumes in individuals without COPD only

Susceptibility to chronic mucus hypersecretion, a genome wide association study

Background: Chronic mucus hypersecretion (CMH) is associated with an increased frequency of respiratory infections, excess lung function decline, and increased hospitalisation and mortality rates in the general population. It is associated with smoking, but it is unknown why only a minority of smokers develops CMH. A plausible explanation for this phenomenon is a predisposing genetic constitution. Therefore, we performed a genome wide association (GWA) study of CMH in Caucasian populations. Methods: GWA analysis was performed in the NELSON-study using the Illumina 610 array, followed by replication and metaanalysis in 11 additional cohorts. In total 2,704 subjects with, and 7,624 subjects without CMH were included, all current or former heavy smokers ($20 pack-years). Additional studies were performed to test the functional relevance of the most significant single nucleotide polymorphism (SNP). Results: A strong association with CMH, consistent across all cohorts, was observed with rs6577641 (p = 4.25x10⎺⁶, OR = 1.17), located in intron 9 of the special AT-rich sequence-binding protein 1 locus (SATB1) on chromosome 3. The risk allele (G) was associated with higher mRNA expression of SATB1 (4.3x10⎺⁹) in lung tissue. Presence of CMH was associated with increased SATB1 mRNA expression in bronchial biopsies from COPD patients. SATB1 expression was induced during differentiation of primary human bronchial epithelial cells in culture. Conclusions: Our findings, that SNP rs6577641 is associated with CMH in multiple cohorts and is a cis-eQTL for SATB1, together with our additional observation that SATB1 expression increases during epithelial differentiation provide suggestive evidence that SATB1 is a gene that affects CMH