Altered Innate Immune Responses in Neutrophils from Patients with Well- and Suboptimally Controlled Asthma

© 2015 Francesca S. M. Tang et al. Background. Respiratory infections are a major cause of asthma exacerbations where neutrophilic inflammation dominates and is associated with steroid refractory asthma. Structural airway cells in asthma differ from nonasthmatics; however it is unknown if neutrophils differ. We investigated neutrophil immune responses in patients who have good (AGood) and suboptimal (ASubopt) asthma symptom control. Methods. Peripheral blood neutrophils from AGood (ACQ 0.75, n=7), and healthy controls (HC) (n=9) were stimulated with bacterial (LPS (1 g/mL), fMLF (100 nM)), and viral (imiquimod (3 g/mL), R848 (1.5 g/mL), and poly I:C (10 g/mL)) surrogates or live rhinovirus (RV) 16 (MOI1). Cell-free supernatant was collected after 1 h for neutrophil elastase (NE) and matrix metalloproteinase- (MMP-) 9 measurements or after 24 h for CXCL8 release. Results. Constitutive NE was enhanced in AGood neutrophils compared to HC. fMLF stimulated neutrophils from ASubopt but not AGood produced 50% of HC levels. fMLF induced MMP-9 was impaired in ASubopt and AGood compared to HC. fMLF stimulated CXCL8 but not MMP-9 was positively correlated with FEV1 and FEV1/FVC. ASubopt and AGood responded similarly to other stimuli. Conclusions. Circulating neutrophils are different in asthma; however, this is likely to be related to airflow limitation rather than asthma control

Elastic-plastic solutions for expanding cavities embedded in two different cohesive-frictional materials

An analytical solution of cavity expansion in two different concentric regions of soil is developed and investigated in this paper. The cavity is embedded within a soil with finite radial dimension and surrounded by a second soil, which extends to infinity. Large-strain quasi-static expansion of both spherical and cylindrical cavities in elastic-plastic soils is considered. A non-associated Mohr–Coulomb yield criterion is used for both soils. Closed-form solutions are derived, which provide the stress and strain fields during the expansion of the cavity from an initial to a final radius. The analytical solution is validated against finite element simulations, and the effect of varying geometric and material parameters is studied. The influence of the two different soils during cavity expansion is discussed by using pressure–expansion curves and by studying the development of plastic regions within the soils. The analytical method may be applied to various geotechnical problems, which involve aspects of soil layering, such as cone penetration test interpretation, ground-freezing around shafts, tunnelling, and mining

Population genetics of trypanosoma brucei rhodesiense: clonality and diversity within and between foci

African trypanosomes are unusual among pathogenic protozoa in that they can undergo their complete morphological life cycle in the tsetse fly vector with mating as a non-obligatory part of this development. Trypanosoma brucei rhodesiense, which infects humans and livestock in East and Southern Africa, has classically been described as a host-range variant of the non-human infective Trypanosoma brucei that occurs as stable clonal lineages. We have examined T. b. rhodesiense populations from East (Uganda) and Southern (Malawi) Africa using a panel of microsatellite markers, incorporating both spatial and temporal analyses. Our data demonstrate that Ugandan T. b. rhodesiense existed as clonal populations, with a small number of highly related genotypes and substantial linkage disequilibrium between pairs of loci. However, these populations were not stable as the dominant genotypes changed and the genetic diversity also reduced over time. Thus these populations do not conform to one of the criteria for strict clonality, namely stability of predominant genotypes over time, and our results show that, in a period in the mid 1990s, the previously predominant genotypes were not detected but were replaced by a novel clonal population with limited genetic relationship to the original population present between 1970 and 1990. In contrast, the Malawi T. b. rhodesiense population demonstrated significantly greater diversity and evidence for frequent genetic exchange. Therefore, the population genetics of T. b. rhodesiense is more complex than previously described. This has important implications for the spread of the single copy T. b. rhodesiense gene that allows human infectivity, and therefore the epidemiology of the human disease, as well as suggesting that these parasites represent an important organism to study the influence of optional recombination upon population genetic dynamics

Human preferences for sexually dimorphic faces may be evolutionarily novel

This article has been made available through the Brunel Open Access Publishing Fund.A large literature proposes that preferences for exaggerated sex typicality in human faces (masculinity/femininity) reflect a long evolutionary history of sexual and social selection. This proposal implies that dimorphism was important to judgments of attractiveness and personality in ancestral environments. It is difficult to evaluate, however, because most available data come from largescale, industrialized, urban populations. Here, we report the results for 12 populations with very diverse levels of economic development. Surprisingly, preferences for exaggerated sex-specific traits are only found in the novel, highly developed environments. Similarly, perceptions that masculine males look aggressive increase strongly with development, specifically, urbanization. These data challenge the hypothesis that facial dimorphism was an important ancestral signal of heritable mate value. One possibility is that highly developed environments provide novel opportunities to discern relationships between facial traits and behavior by exposing individuals to large numbers of unfamiliar faces, revealing patterns too subtle to detect with smaller samples

Obesity Is A Modifier of Autonomic Cardiac Responses to Fine Metal Particulates

Background: Increasing evidence suggests that obesity may impart greater susceptibility to adverse effects of air pollution. Particulate matter, especially PM$_{2.5}$ (particulate matter with aero-dynamic diameter ≤2.5 μm), is associated with increased cardiac events and reduction of heart rate variability (HRV).Objectives Our goal was to investigate whether particle-mediated autonomic modulation is aggravated in obese individuals.Methods We examined PM$_{2.5}$-mediated acute effects on HRV and heart rate (HR) using 10 24-hr and 13 48-hr ambulatory electrocardiogram recordings collected from 18 boilermakers (39.5 ± 9.1 years of age) exposed to high levels of metal particulates. Average HR and 5-min HRV [SDNN: standard deviation of normal-to-normal intervals (NN); rMSSD: square-root of mean squared-differences of successive NN intervals; HF: high-frequency power 0.15–0.4 Hz] and personal PM$_{2.5}$ exposures were continuously monitored. Subjects with body mass index ≥ 30 kg/m$^2$ were classified as obese. Mixed-effect models were used for statistical analyses. Results: Half (50%) of the study subjects were obese. After adjustment for confounders, each 1-mg/m$^3$ increase in 4-hr moving average PM$_{2.5}$ was associated with HR increase of 5.9 bpm [95% confidence interval (CI), 4.2 to 7.7] and with 5-min HRV reduction by 6.5% (95% CI, 1.9 to 11.3%) for SDNN, 1.7% (95% CI, –4.9 to 8.4%) for rMSSD, and 8.8% (95% CI, –3.8 to 21.3%) for HF. Obese individuals had greater PM$_{2.5}$-mediated HRV reductions (2- to 3-fold differences) than nonobese individuals, and had more PM$_{2.5}$-mediated HR increases (9-bpm vs. 4-bpm increase in HR for each 1-mg/m$^3$ increase in PM$_{2.5}$; p < 0.001). Conclusions: Our study revealed greater autonomic cardiac responses to metal particulates in obese workers, supporting the hypothesis that obesity may impart greater susceptibility to acute cardiovascular effects of fine particles

Breastfeeding : a potential excretion route for mothers and implications for infant exposure to perfluoroalkyl acids

Background: The presence of perfluoroalkyl acids (PFAAs) in breast milk has been documented, but their lactational transfer has been rarely studied. Determination of the elimination rates of these chemicals during breastfeeding is important and critical for assessing exposure in mothers and infants. Objectives: We aimed to investigate the association between breastfeeding and maternal serum concentrations of perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorononanoic acid (PFNA), and perfluorohexane sulfonate (PFHxS). For a subset of the population, for whom we also have their infants’ measurements, we investigated associations of breastfeeding with infant serum PFAA concentrations. Methods: The present analysis included 633 women from the C8 Science Panel Study who had a child &lt; 3.5 years of age and who provided blood samples and reported detailed information on breastfeeding at the time of survey. PFAA serum concentrations were available for all mothers and 8% (n = 49) of the infants. Maternal and infant serum concentrations were regressed on duration of breastfeeding. Results: Each month of breastfeeding was associated with lower maternal serum concentrations of PFOA (–3%; 95% CI: –5, –2%), PFOS (–3%; 95% CI: –3, –2%), PFNA (–2%; 95% CI: –2, –1%), and PFHxS (–1%; 95% CI: –2, 0%). The infant PFOA and PFOS serum concentrations were 6% (95% CI: 1, 10%) and 4% (95% CI: 1, 7%) higher per month of breastfeeding. Conclusions: Breast milk is the optimal food for infants, but is also a PFAA excretion route for lactating mothers and exposure route for nursing infants

Heterogeneity of Paucigranulocytic Asthma: A Prospective Cohort Study with Hierarchical Cluster Analysis.

BACKGROUND: Asthma, a heterogeneous disease, can be divided into 4 inflammatory phenotypes using induced sputum cell counts-eosinophilic asthma (EA), neutrophilic asthma (NA), mixed granulocytic asthma, and paucigranulocytic asthma (PGA). Although research has focused on EA and NA, there is little known about PGA. OBJECTIVE: To study the heterogeneity of PGA and identify possible PGA clusters to guide clinical treatment. METHODS: Patients with PGA were grouped by hierarchical cluster analysis and enrolled into a prospective cohort study to validate the clusters, relative to future risk of asthma exacerbations in a real-world setting. Clusters were validated by tree analysis in a separate population. Finally, we explored PGA stability. RESULTS: Cluster analysis of 145 patients with PGA identified 3 clusters: cluster 1 (n = 110, 75.9%) was "mild PGA," cluster 2 (n = 20, 13.8%) was "PGA with psychological dysfunction and rhinoconjunctivitis and other allergic diseases," and cluster 3 (n = 15, 10.3%) was "smoking-associated PGA." Cluster 3 had significantly increased risk of severe exacerbation (relative risk [RR] = 6.43, P = .01), emergency visit (RR = 8.61, P = .03), and hospitalization (RR = 12.94, P < .01). Results of the cluster analysis were successfully validated in an independent PGA population classified using decision tree analysis. Although PGA can transform into or develop from other phenotypes, 70% were stable over time. CONCLUSIONS: Among 3 identified PGA clusters, cluster 3 had a higher risk of severe exacerbation. PGA heterogeneity indicates the requirement of novel targeted interventions

Telepresence and the Role of the Senses

The telepresence experience can be evoked in a number of ways. A well-known example is a player of videogames who reports about a telepresence experience, a subjective experience of being in one place or environment, even when physically situated in another place. In this paper we set the phenomenon of telepresence into a theoretical framework. As people react subjectively to stimuli from telepresence, empirical studies can give more evidence about the phenomenon. Thus, our contribution is to bridge the theoretical with the empirical. We discuss theories of perception with an emphasis on Heidegger, Merleau-Ponty and Gibson, the role of the senses and the Spinozian belief procedure. The aim is to contribute to our understanding of this phenomenon. A telepresence-study that included the affordance concept is used to empirically study how players report sense-reactions to virtual sightseeing in two cities. We investigate and explore the interplay of the philosophical and the empirical. The findings indicate that it is not only the visual sense that plays a role in this experience, but all senses