Effects of increasing tidal volume and end-expiratory lung volume on induced bronchoconstriction in healthy humans

Background: Increasing functional residual capacity (FRC) or tidal volume (VT) reduces airway resistance and attenuates the response to bronchoconstrictor stimuli in animals and humans. What is unknown is which one of the above mechanisms is more effective in modulating airway caliber and whether their combination yields additive or synergistic effects. To address this question, we investigated the effects of increased FRC and increased VT in attenuating the bronchoconstriction induced by inhaled methacholine (MCh) in healthy humans. Methods: Nineteen healthy volunteers were challenged with a single-dose of MCh and forced oscillation was used to measure inspiratory resistance at 5 and 19 Hz (R5 and R19), their difference (R5-19), and reactance at 5 Hz (X5) during spontaneous breathing and during imposed breathing patterns with increased FRC, or VT, or both. Importantly, in our experimental design we held the product of VT and breathing frequency (BF), i.e, minute ventilation (VE) fixed so as to better isolate the effects of changes in VT alone. Results: Tripling VT from baseline FRC significantly attenuated the effects of MCh on R5, R19, R5-19 and X5. Doubling VT while halving BF had insignificant effects. Increasing FRC by either one or two VT significantly attenuated the effects of MCh on R5, R19, R5-19 and X5. Increasing both VT and FRC had additive effects on R5, R19, R5-19 and X5, but the effect of increasing FRC was more consistent than increasing VT thus suggesting larger bronchodilation. When compared at iso-volume, there were no differences among breathing patterns with the exception of when VT was three times larger than during spontaneous breathing. Conclusions: These data show that increasing FRC and VT can attenuate induced bronchoconstriction in healthy humans by additive effects that are mainly related to an increase of mean operational lung volume. We suggest that static stretching as with increasing FRC is more effective than tidal stretching at constant VE, possibly through a combination of effects on airway geometry and airway smooth muscle dynamics.</p

The edge of the periphery: situating the ≠Khomani San of the Southern Kalahari in the political economy of Southern Africa

This is an Accepted Manuscript of an article published by Taylor & Francis in African Identities on 14/04/16, available online: http://www.tandfonline.com/10.1080/14725843.2016.1154813In this article, we situate the Southern Kalahari San within the political economy of Southern Africa and within the world system. Here we draw on and critique modernization theory as a model of explanation for the lack of development found locally. In the Southern Kalahari, the ≠Khomani San won a massive land claim that should have empowered and enabled local development. Yet they remain largely impoverished, while seeking out a meaningful life on the edge of the capitalist world system. Within states, contradictions remain as local diversity continues to be reproduced and modernity itself is reproduced as local diversity. The research is premised on empirical fieldwork conducted in the Southern Kalahari in 2013 and supported by a series of earlier field research over the previous five years. The San of the Southern Kalahari are not resisting modernity but drawing on aspects of it selectively for their own vision of meaningful development

Radial Migration in Galactic Thick Discs

We present a study of the extent to which the Sellwood & Binney radial migration of stars is affected by their vertical motion about the midplane. We use both controlled simulations in which only a single spiral mode is excited, as well as slightly more realistic cases with multiple spiral patterns and a bar. We find that rms angular momentum changes are reduced by vertical motion, but rather gradually, and the maximum changes are almost as large for thick disc stars as for those in a thin disc. We find that particles in simulations in which a bar forms suffer slightly larger angular momentum changes than in comparable cases with no bar, but the cumulative effect of multiple spiral events still dominates. We have determined that vertical action, and not vertical energy, is conserved on average during radial migration.Comment: 23 pages, 25 figures, accepted to appear in MNRA

Fas-positive T cells regulate the resolution of airway inflammation in a murine model of asthma

Persistent airway inflammation, mucus production, and airway hyperreactivity are the major contributors to the frequency and severity of asthma. Why lung inflammation persists in asthmatics remains unclear. It has been proposed that Fas-mediated apoptosis of inflammatory cells is a fundamental mechanism involved in the resolution of eosinophilic airway inflammation. Because infiltrating eosinophils are highly sensitive to Fas-mediated apoptosis, it has been presumed that direct ligation of Fas on eosinophils is involved. Here, we utilize adoptive transfers of T cells to demonstrate that the delayed resolution of eosinophilia in Fas-deficient mice is a downstream effect of Fas deficiency on T cells, not eosinophils. Interestingly, the mice that received Fas-deficient T cells, but not the controls, developed a persistent phase of inflammation that failed to resolve even 6 wk after the last challenge. This persistent phase correlated with decreased interferon (IFN)γ production by Fas-deficient T cells and could be reproduced with adoptive transfer of IFNγ-deficient T cells. These data demonstrate that Fas deficiency on T cells is sufficient for the development of long-term allergic airway disease in mice and implies that deregulation of death receptors such as Fas on human T cells could be an important factor in the development and/or chronic nature of asthma

Thick disk kinematics from RAVE and the solar motion

Radial velocity surveys such as the Radial Velocity Experiment (RAVE) provide us with measurements of hundreds of thousands of nearby stars most of which belong to the Galactic thin, thick disk or halo. Ideally, to study the Galactic disks (both thin and thick) one should make use of the multi-dimensional phase-space and the whole pattern of chemical abundances of their stellar populations. In this paper, with the aid of the RAVE Survey, we study the thin and thick disks of the Milky Way, focusing on the latter. We present a technique to disentangle the stellar content of the two disks based on the kinematics and other stellar parameters such as the surface gravity of the stars. Using the Padova Galaxy Model, we checked the ability of our method to correctly isolate the thick disk component from the Galaxy mixture of stellar populations. We introduce selection criteria in order to clean the observed radial velocities from the Galactic differential rotation and to take into account the partial sky coverage of RAVE. We developed a numerical technique to statistically disentangle thin and thick disks from their mixture. We deduce the components of the solar motion relative to the Local Standard of Rest (LSR) in the radial and vertical direction, the rotational lag of the thick disk component relative to the LSR, and the square root of the absolute value of the velocity dispersion tensor for the thick disk alone. The analysis of the thin disk is presented in another paper. We find good agreement with previous independent parameter determinations. In our analysis we used photometrically determined distances. In the Appendix we show that similar values can be found for the thick disk alone as derived in the main sections of our paper even without the knowledge of photometric distances.Comment: accepted on A&A, please see companion paper "THIN disk kinem...

Direct recordings of grid-like neuronal activity in human spatial navigation

Grid cells in the entorhinal cortex appear to represent spatial location via a triangular coordinate system. Such cells, which have been identified in rats, bats and monkeys, are believed to support a wide range of spatial behaviors. Recording neuronal activity from neurosurgical patients performing a virtual-navigation task, we identified cells exhibiting grid-like spiking patterns in the human brain, suggesting that humans and simpler animals rely on homologous spatial-coding schemes

Functioning of patients with chronic idiopathic axonal polyneuropathy (CIAP)

Although patients with Chronic Idiopathic Axonal Polyneuropathy (CIAP) report a slow deterioration of sensory and motor functions, the impact of this deterioration on daily functioning has not yet been investigated in detail. The first aim of this crosssectional study involving 56 patients with CIAP was, therefore, to assess patients’ functioning with use of the International Classification of Functioning, Disability and Health (ICF). The second aim was to find determinants of walking ability, dexterity, and autonomy. Fatigue and limited walking ability were present in most patients and differed considerably. In regression models, age, muscle strength, and fatigue together explained 63% of the variance in walking ability, which by itself explained almost 50% of the variance in patients’ autonomy indoors and outdoors (42% and 49%, respectively). Muscle strength and sensory function scores together explained 30% of the variance in dexterity scores, which in turn explained only 13% of the variance in autonomy indoors. The diminished autonomy of patients with CIAP might be improved by reducing fatigue, by means of training, and by improving walking ability