RESPIRATORY RESPONSES TO ACUTE INTERMITTENT HYPOXIA AND HYPERCAPNIA IN AWAKE RATS

This article deals with the recognition of early changes in the breathing pattern, in response to acute intermittent stimuli in awake rats. Two different types of stimuli were given: 9% hypoxia in N 2 and 10% hypercapnia in O 2 . Animals were exposed to 3 consecutive cycles consisting of 3-min stimulus period separated by 8-min normoxic recovery intervals. Features of the breathing pattern, such as respiratory frequency, tidal volume, minute ventilation, inspiration and expiration times, peak inspiratory and expiratory flows, were measured by whole body plethysmography. The data were analyzed with the use of pattern recognition methods. We conclude that the overall respiratory changes were rather slight. However, computerized analysis using a k-nearest neighbor decision rule (k-NN) allowed for a good recognition of the respiratory responses to the stimuli. The misclassification rate (E r ) varied from 5 to 10%. After feature selection, E r decreased below 1%. The k-NN classifier differentiated correctly also the type of intermittent stimulus. Our experimental results demonstrate usefulness of pattern recognition algorithms in studying respiratory effects in biological models

Alpine altitude climate treatment for severe and uncontrolled asthma: An EAACI position paper

Currently available European Alpine Altitude Climate Treatment (AACT) programs combine the physical characteristics of altitude with the avoidance of environmental triggers in the alpine climate and a personalized multidisciplinary pulmonary rehabilitation approach. The reduced barometric pressure, oxygen pressure, and air density, the relatively low temperature and humidity, and the increased UV radiation at moderate altitude induce several physiological and immunological adaptation responses. The environmental characteristics of the alpine climate include reduced aeroallergens such as house dust mites (HDM), pollen, fungi, and less air pollution. These combined factors seem to have immunomodulatory effects controlling pathogenic inflammatory responses and favoring less neuro-immune stress in patients with different asthma phenotypes. The extensive multidisciplinary treatment program may further contribute to the observed clinical improvement by AACT in asthma control and quality of life, fewer exacerbations and hospitalizations, reduced need for oral corticosteroids (OCS), improved lung function, decreased airway hyperresponsiveness (AHR), improved exercise tolerance, and improved sinonasal outcomes. Based on observational studies and expert opinion, AACT represents a valuable therapy for those patients irrespective of their asthma phenotype, who cannot achieve optimal control of their complex condition despite all the advances in medical science and treatment according to guidelines, and therefore run the risk of falling into a downward spiral of loss of physical and mental health. In the light of the observed rapid decrease in inflammation and immunomodulatory effects, AACT can be considered as a natural treatment that targets biological pathways. Keywords: altitude; asthma; climate; environment; pulmonary rehabilitation

Searching for ß-delayed protons from 11 Be

ISOLDE Workshop and Usersmeeting. Wednesday 05 December - Friday 07 December 2018 .CERN ( ISOLDE User Support. PH Departmen - CERN/CH-1211 Geneve 23). --.https://indico.cern.ch/event/736872/contributions

Understanding first-year students’ curiosity and interest about physics : Lessons learned from the HOPE project

This paper focuses on results of an interview based survey of first-year university physics students, carried out within the EU Horizons in Physics Education (HOPE) project (http://hopenetwork.eu/). 94 interviews conducted in 13 universities have been analyzed to investigate the factors that inspire young people to study physics. In particular, the main motivational factor, which was proven to consist of personal interest and curiosity, was unfolded into different categories and detailed interest profiles were produced. The results are arguably useful to help academic curriculum developers and teaching personnel in physics departments to provide guidance to students in developing and focusing their interest towards specific sub-fields and/or to design targeted recruitment and outreach initiatives.Peer reviewe

Evaluation of polygenic risk scores for breast and ovarian cancer risk prediction in BRCA1 and BRCA2 mutation carriers

Background: Genome-wide association studies (GWAS) have identified 94 common single-nucleotide polymorphisms (SNPs) associated with breast cancer (BC) risk and 18 associated with ovarian cancer (OC) risk. Several of these are also associated with risk of BC or OC for women who carry a pathogenic mutation in the high-risk BC and OC genes BRCA1 or BRCA2. The combined effects of these variants on BC or OC risk for BRCA1 and BRCA2 mutation carriers have not yet been assessed while their clinical management could benefit from improved personalized risk estimates. Methods: We constructed polygenic risk scores (PRS) using BC and OC susceptibility SNPs identified through population-based GWAS: for BC (overall, estrogen receptor [ER]-positive, and ER-negative) and for OC. Using data from 15 252 female BRCA1 and 8211 BRCA2 carriers, the association of each PRS with BC or OC risk was evaluated using a weighted cohort approach, with time to diagnosis as the outcome and estimation of the hazard ratios (HRs) per standard deviation increase in the PRS. Results: The PRS for ER-negative BC displayed the strongest association with BC risk in BRCA1 carriers (HR = 1.27, 95% confidence interval [CI] = 1.23 to 1.31, P = 8.2 x 10(53)). In BRCA2 carriers, the strongest association with BC risk was seen for the overall BC PRS (HR = 1.22, 95% CI = 1.17 to 1.28, P = 7.2 x 10(-20)). The OC PRS was strongly associated with OC risk for both BRCA1 and BRCA2 carriers. These translate to differences in absolute risks (more than 10% in each case) between the top and bottom deciles of the PRS distribution; for example, the OC risk was 6% by age 80 years for BRCA2 carriers at the 10th percentile of the OC PRS compared with 19% risk for those at the 90th percentile of PRS. Conclusions: BC and OC PRS are predictive of cancer risk in BRCA1 and BRCA2 carriers. Incorporation of the PRS into risk prediction models has promise to better inform decisions on cancer risk management

Early Trauma and Increased Risk for Physical Aggression during Adulthood: The Moderating Role of MAOA Genotype

Previous research has reported that a functional polymorphism in the monoamine oxidase A (MAOA) gene promoter can moderate the association between early life adversity and increased risk for violence and antisocial behavior. In this study of a combined population of psychiatric outpatients and healthy volunteers (N = 235), we tested the hypothesis that MAOA genotype moderates the association between early traumatic life events (ETLE) experienced during the first 15 years of life and the display of physical aggression during adulthood, as assessed by the Aggression Questionnaire. An ANOVA model including gender, exposure to early trauma, and MAOA genotype as between-subjects factors showed significant MAOA×ETLE (F1,227 = 8.20, P = 0.005) and gender×MAOA×ETLE (F1,227 = 7.04, P = 0.009) interaction effects. Physical aggression scores were higher in men who had experienced early traumatic life events and who carried the low MAOA activity allele (MAOA-L). We repeated the analysis in the subgroup of healthy volunteers (N = 145) to exclude that the observed G×E interactions were due to the inclusion of psychiatric patients in our sample and were not generalizable to the population at large. The results for the subgroup of healthy volunteers were identical to those for the entire sample. The cumulative variance in the physical aggression score explained by the ANOVA effects involving the MAOA polymorphism was 6.6% in the entire sample and 12.1% in the sub-sample of healthy volunteers. Our results support the hypothesis that, when combined with exposure to early traumatic life events, low MAOA activity is a significant risk factor for aggressive behavior during adulthood and suggest that the use of dimensional measures focusing on behavioral aspects of aggression may increase the likelihood of detecting significant gene-by-environment interactions in studies of MAOA-related aggression

Alpine altitude climate treatment for severe and uncontrolled asthma: an EAACI position paper

Currently available European Alpine Altitude Climate Treatment (AACT) programs combine the physical characteristics of altitude with the avoidance of environmental triggers in the alpine climate and a personalized multidisciplinary pulmonary rehabilitation approach. The reduced barometric pressure, oxygen pressure, and air density, the relatively low temperature and humidity, and the increased UV radiation at moderate altitude induce several physiological and immunological adaptation responses. The environmental characteristics of the alpine climate include reduced aeroallergens such as house dust mites (HDM), pollen, fungi, and less air pollution. These combined factors seem to have immunomodulatory effects controlling pathogenic inflammatory responses and favoring less neuro-immune stress in patients with different asthma phenotypes. The extensive multidisciplinary treatment program may further contribute to the observed clinical improvement by AACT in asthma control and quality of life, fewer exacerbations and hospitalizations, reduced need for oral corticosteroids (OCS), improved lung function, decreased airway hyperresponsiveness (AHR), improved exercise tolerance, and improved sinonasal outcomes. Based on observational studies and expert opinion, AACT represents a valuable therapy for those patients irrespective of their asthma phenotype, who cannot achieve optimal control of their complex condition despite all the advances in medical science and treatment according to guidelines, and therefore run the risk of falling into a downward spiral of loss of physical and mental health. In the light of the observed rapid decrease in inflammation and immunomodulatory effects, AACT can be considered as a natural treatment that targets biological pathways

Detecting unilateral phrenic paralysis by acoustic respiratory analysis

The consequences of phrenic nerve paralysis vary from a considerable reduction in respiratory function to an apparently normal state. Acoustic analysis of lung sound intensity (LSI) could be an indirect non-invasive measurement of respiratory muscle function, comparing activity on the two sides of the thoracic cage. Lung sounds and airflow were recorded in ten males with unilateral phrenic paralysis and ten healthy subjects (5 men/5 women), during progressive increasing airflow maneuvers. Subjects were in sitting position and two acoustic sensors were placed on their back, on the left and right sides. LSI was determined from 1.2 to 2.4 L/s between 70 and 2000 Hz. LSI was significantly greater on the normal (19.3±4.0 dB) than the affected (5.7±3.5 dB) side in all patients (p = 0.0002), differences ranging from 9.9 to 21.3 dB (13.5±3.5 dB). In the healthy subjects, the LSI was similar on both left (15.1±6.3 dB) and right (17.4±5.7 dB) sides (p = 0.2730), differences ranging from 0.4 to 4.6 dB (2.3±1.6 dB). There was a positive linear relationship between the LSI and the airflow, with clear differences between the slope of patients (about 5 dB/L/s) and healthy subjects (about 10 dB/L/s). Furthermore, the LSI from the affected side of patients was close to the background noise level, at low airflows. As the airflow increases, the LSI from the affected side did also increase, but never reached the levels seen in healthy subjects. Moreover, the difference in LSI between healthy and paralyzed sides was higher in patients with lower FEV1 (%). The acoustic analysis of LSI is a relevant non-invasive technique to assess respiratory function. This method could reinforce the reliability of the diagnosis of unilateral phrenic paralysis, as well as the monitoring of these patients.Peer ReviewedPostprint (published version