Redefining Cut-Points for High Symptom Burden of the Global Initiative for Chronic Obstructive Lung Disease Classification in 18,577 Patients With Chronic Obstructive Pulmonary Disease.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) can be classified into groups A/C or B/D based on symptom intensity. Different threshold values for symptom questionnaires can result in misclassification and, in turn, different treatment recommendations. The primary aim was to find the best fitting cut-points for Global initiative for chronic Obstructive Lung Disease (GOLD) symptom measures, with an modified Medical Research Council dyspnea grade of 2 or higher as point of reference. METHODS: After a computerized search, data from 41 cohorts and whose authors agreed to provide data were pooled. COPD studies were eligible for analyses if they included, at least age, sex, postbronchodilator spirometry, modified Medical Research Council, and COPD Assessment Test (CAT) total scores. MAIN OUTCOMES: Receiver operating characteristic curves and the Youden index were used to determine the best calibration threshold for CAT, COPD Clinical Questionnaire, and St. Georges Respiratory Questionnaire total scores. Following, GOLD A/B/C/D frequencies were calculated based on current cut-points and the newly derived cut-points. FINDINGS: A total of 18,577 patients with COPD [72.0% male; mean age: 66.3 years (standard deviation 9.6)] were analyzed. Most patients had a moderate or severe degree of airflow limitation (GOLD spirometric grade 1, 10.9%; grade 2, 46.6%; grade 3, 32.4%; and grade 4, 10.3%). The best calibration threshold for CAT total score was 18 points, for COPD Clinical Questionnaire total score 1.9 points, and for St. Georges Respiratory Questionnaire total score 46.0 points. CONCLUSIONS: The application of these new cut-points would reclassify about one-third of the patients with COPD and, thus, would impact on individual disease management. Further validation in prospective studies of these new values are needed.

Common coding variant in SERPINA1 increases the risk for large artery stroke.

Large artery atherosclerotic stroke (LAS) shows substantial heritability not explained by previous genome-wide association studies. Here, we explore the role of coding variation in LAS by analyzing variants on the HumanExome BeadChip in a total of 3,127 cases and 9,778 controls from Europe, Australia, and South Asia. We report on a nonsynonymous single-nucleotide variant in serpin family A member 1 (SERPINA1) encoding alpha-1 antitrypsin [AAT; p.V213A; P = 5.99E-9, odds ratio (OR) = 1.22] and confirm histone deacetylase 9 (HDAC9) as a major risk gene for LAS with an association in the 3'-UTR (rs2023938; P = 7.76E-7, OR = 1.28). Using quantitative microscale thermophoresis, we show that M1 (A213) exhibits an almost twofold lower dissociation constant with its primary target human neutrophil elastase (NE) in lipoprotein-containing plasma, but not in lipid-free plasma. Hydrogen/deuterium exchange combined with mass spectrometry further revealed a significant difference in the global flexibility of the two variants. The observed stronger interaction with lipoproteins in plasma and reduced global flexibility of the Val-213 variant most likely improve its local availability and reduce the extent of proteolytic inactivation by other proteases in atherosclerotic plaques. Our results indicate that the interplay between AAT, NE, and lipoprotein particles is modulated by the gate region around position 213 in AAT, far away from the unaltered reactive center loop (357-360). Collectively, our findings point to a functionally relevant balance between lipoproteins, proteases, and AAT in atherosclerosis.

Confinement of dynamical chaos expansion in rotifer populations inhabiting heterogeneous environments: an effect of attractor size invariance.

We study the impact of inter-habitat interactions in rotifer populations with intrinsically different types of dynamics: chaotic and regular. For this purpose we use a modified version of the Consensus model. The Consensus model has been shown to be realistic enough to reproduce distinguishing features of the rotifer species dynamics. Being uncoupled, a habitat with chaotic dynamics and habitats with regular oscillations of the rotifer density do not affect each other. Migration of the rotifers between the habitats leads to the invasion of chaos into neighboring habitats, that is chaotic rotifer oscillations replace regular oscillations of the rotifer density in neighboring habitats. The invasion of chaos distorts spatial borders of the rotifer oscillations synchronization clusters. We show that the invasion of chaos is spatially confined. Invariance of the attractor size under transformation of regular oscillations into chaotic ones is demonstrated to be responsible for the chaos confinement.

Invasion of pests resistant to Bt toxins can lead to inherent non-uniqueness in genetically modified Bt-plant dynamics: mathematical modeling.

Genetically modified crops are effective pest management tools for worldwide growers. However, there is a concern that pests may develop resistance to Bt-toxins produced by genetically modified Bt-plants. We study the impact of the Bt-resistant pests on Bt-crops. Furthermore, the dynamics of the Bt-plant-Bt-susceptible insects-Bt-resistant insects system is analysed and it is shown that throughout the insect reproduction period the plant biomass dynamics resulting from invasion of Bt-resistant insects is non-unique. Namely, the chaotic attractor and the limit cycle, which are responsible for the plant and insect biomass dynamics, are shown to coexist. As a result, the Bt-plant-Bt-resistant insect system can manifest either chaotic or regular oscillations of plant and insect biomass depending on spatial patterns resulting from invasion of Bt resistant insects into the Bt plant-Bt susceptible insect system. We show that the non-uniqueness of the system dynamics under unfavorable environmental conditions, such as in the so-called zones of risky agriculture in many developing countries and industrialized countries, can lead to essential decrease in the plant biomass.

Visualization of blood microcirculation parameters in human tissues by time-integrated dynamic speckles analysis.

Statistical analysis of images of time-integrated non-stationary speckle patterns is a tool for diagnostics and imaging of in vivo dynamics of blood microcirculation in superficial layers of tissues and organs. The approach to monitoring blood microcirculation using the contrast analysis of time-averaged speckle images is known as the laser speckle contrast analysis (LASCA) technique. This paper presents a modified version of LASCA, based on the application of a localized light source in combination with the speckle contrast analysis of time-integrated dynamic speckle patterns. This method adds possibilities for the analysis of depth distributions of the blood microcirculation parameters. A theoretical background for the depth-resolved analysis of blood microcirculation parameters is considered here on the basis of the concept of effective optical path distributions for a multiply scattered probe light.