Resonance as the Mechanism of Daytime Periodic Breathing in Patients with Heart Failure

Rationale: In patients with chronic heart failure, daytime oscillatory breathing at rest is associated with a high risk of mortality. Experimental evidence, including exaggerated ventilatory responses to CO2 and prolonged circulation time, implicates the ventilatory control system and suggests feedback instability (loop gain > 1) is responsible. However, daytime oscillatory patterns often appear remarkably irregular versus classic instability (Cheyne-Stokes respiration), suggesting our mechanistic understanding is limited. Objectives: We propose that daytime ventilatory oscillations generally result from a chemoreflex resonance, in which spontaneous biological variations in ventilatory drive repeatedly induce temporary and irregular ringing effects. Importantly, the ease with which spontaneous biological variations induce irregular oscillations (resonance “strength”) rises profoundly as loop gain rises toward 1. We tested this hypothesis through a comparison of mathematical predictions against actual measurements in patients with heart failure and healthy control subjects. Methods: In 25 patients with chronic heart failure and 25 control subjects, we examined spontaneous oscillations in ventilation and separately quantified loop gain using dynamic inspired CO2 stimulation. Measurements and Main Results: Resonance was detected in 24 of 25 patients with heart failure and 18 of 25 control subjects. With increased loop gain—consequent to increased chemosensitivity and delay—the strength of spontaneous oscillations increased precipitously as predicted (r = 0.88), yielding larger (r = 0.78) and more regular (interpeak interval SD, r = −0.68) oscillations (P < 0.001 for all, both groups combined). Conclusions: Our study elucidates the mechanism underlying daytime ventilatory oscillations in heart failure and provides a means to measure and interpret these oscillations to reveal the underlying chemoreflex hypersensitivity and reduced stability that foretells mortality in this population

Children and older adults exhibit distinct sub-optimal cost-benefit functions when preparing to move their eyes and hands

"© 2015 Gonzalez et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited"Numerous activities require an individual to respond quickly to the correct stimulus. The provision of advance information allows response priming but heightened responses can cause errors (responding too early or reacting to the wrong stimulus). Thus, a balance is required between the online cognitive mechanisms (inhibitory and anticipatory) used to prepare and execute a motor response at the appropriate time. We investigated the use of advance information in 71 participants across four different age groups: (i) children, (ii) young adults, (iii) middle-aged adults, and (iv) older adults. We implemented 'cued' and 'non-cued' conditions to assess age-related changes in saccadic and touch responses to targets in three movement conditions: (a) Eyes only; (b) Hands only; (c) Eyes and Hand. Children made less saccade errors compared to young adults, but they also exhibited longer response times in cued versus non-cued conditions. In contrast, older adults showed faster responses in cued conditions but exhibited more errors. The results indicate that young adults (18 -25 years) achieve an optimal balance between anticipation and execution. In contrast, children show benefits (few errors) and costs (slow responses) of good inhibition when preparing a motor response based on advance information; whilst older adults show the benefits and costs associated with a prospective response strategy (i.e., good anticipation)

Homozygosity for a missense mutation in the 67 kDa isoform of glutamate decarboxylase in a family with autosomal recessive spastic cerebral palsy: parallels with Stiff-Person Syndrome and other movement disorders

Background Cerebral palsy (CP) is an heterogeneous group of neurological disorders of movement and/or posture, with an estimated incidence of 1 in 1000 live births. Non-progressive forms of symmetrical, spastic CP have been identified, which show a Mendelian autosomal recessive pattern of inheritance. We recently described the mapping of a recessive spastic CP locus to a 5 cM chromosomal region located at 2q24-31.1, in rare consanguineous families. Methods Here we present data that refine this locus to a 0.5 cM region, flanked by the microsatellite markers D2S2345 and D2S326. The minimal region contains the candidate gene GAD1, which encodes a glutamate decarboxylase isoform (GAD67), involved in conversion of the amino acid and excitatory neurotransmitter glutamate to the inhibitory neurotransmitter γ-aminobutyric acid (GABA). Results A novel amino acid mis-sense mutation in GAD67 was detected, which segregated with CP in affected individuals. Conclusions This result is interesting because auto-antibodies to GAD67 and the more widely studied GAD65 homologue encoded by the GAD2 gene, are described in patients with Stiff-Person Syndrome (SPS), epilepsy, cerebellar ataxia and Batten disease. Further investigation seems merited of the possibility that variation in the GAD1 sequence, potentially affecting glutamate/GABA ratios, may underlie this form of spastic CP, given the presence of anti-GAD antibodies in SPS and the recognised excitotoxicity of glutamate in various contexts

Gravitational Microlensing Evidence for a Planet Orbiting a Binary Star System

The study of extra-solar planetary systems has emerged as a new discipline of observational astronomy in the past few years with the discovery of a number of extra-solar planets. The properties of most of these extra-solar planets were not anticipated by theoretical work on the formation of planetary systems. Here we report observations and light curve modeling of gravitational microlensing event MACHO-97-BLG-41, which indicates that the lens system consists of a planet orbiting a binary star system. According to this model, the mass ratio of the binary star system is 3.8:1 and the stars are most likely to be a late K dwarf and an M dwarf with a separation of about 1.8 AU. A planet of about 3 Jupiter masses orbits this system at a distance of about 7 AU. If our interpretation of this light curve is correct, it represents the first discovery of a planet orbiting a binary star system and the first detection of a Jovian planet via the gravitational microlensing technique. It suggests that giant planets may be common in short period binary star systems.Comment: 11 pages, with 1 color and 2 b/w Figures included (published version

Spatial capital as a tool for planning practice

This purpose of this article is to look at the potential benefit to planning practice of engaging with spatial capital – a concept derived from the social theory of Bourdieu. Doubt is expressed about the theoretical basis for spatial capital; nevertheless, it is argued that it may have merit as a trope for planning practitioners. Spatial capital has a strong empirical basis, making it accessible to planning practice and offering a new means for interpreting and communicating the combined effects of a range of individual urban events such as the gating of communities, differing mobilities and schooling tactics. By focussing on the interplay of social positioning within place, it emphasises the joined-up nature of disadvantage and highlights the limits of environmental determinism. However, its use is not without possible drawbacks. Here, the experience of social capital is informative, as this has been appropriated by groups with quite different readings of its implications for policy

Nebuliser therapy in the intensive care unit

The relationship between identity, lived experience, sexual practices and the language through which these are conveyed has been widely debated in sexuality literature. For example, ‘coming out’ has famously been conceptualised as a ‘speech act’ (Sedgwick 1990) and as a collective narrative (Plummer 1995), while a growing concern for individuals’ diverse identifications in relations to their sexual and gender practices has produced interesting research focusing on linguistic practices among LGBT-identified individuals (Leap 1995; Kulick 2000; Cameron and Kulick 2006; Farqhar 2000). While an explicit focus on language remains marginal to literature on sexualities (Kulick 2000), issue of language use and translation are seldom explicitly addressed in the growing literature on intersectionality. Yet intersectional perspectives ‘reject the separability of analytical and identity categories’ (McCall 2005:1771), and therefore have an implicit stake in the ‘vernacular’ language of the researched, in the ‘scientific’ language of the researcher and in the relationship of continuity between the two. Drawing on literature within gay and lesbian/queer studies and cross-cultural studies, this chapter revisits debates on sexuality, language and intersectionality. I argue for the importance of giving careful consideration to the language we choose to use as researchers to collectively define the people whose experiences we try to capture. I also propose that language itself can be investigated as a productive way to foreground how individual and collective identifications are discursively constructed, and to unpack the diversity of lived experience. I address intersectional complexity as a methodological issue, where methodology is understood not only as the methods and practicalities of doing research, but more broadly as ‘a coherent set of ideas about the philosophy, methods and data that underlie the research process and the production of knowledge’ (McCall 2005:1774). My points are illustrated with examples drawn from my ethnographic study on ‘lesbian’ identity in urban Russia, interspersed with insights from existing literature. In particular, I aim to show that an explicit focus on language can be a productive way to explore the intersections between the global, the national and the local in cross-cultural research on sexuality, while also addressing issues of positionality and accountability to the communities researched

Sensitivity of projected long-term CO 2 emissions across the Shared Socioeconomic Pathways

Scenarios showing future greenhouse gas emissions are needed to estimate climate impacts and the mitigation efforts required for climate stabilization. Recently, the Shared Socioeconomic Pathways (SSPs) have been introduced to describe alternative social, economic and technical narratives, spanning a wide range of plausible futures in terms of challenges to mitigation and adaptation. Thus far the key drivers of the uncertainty in emissions projections have not been robustly disentangled. Here we assess the sensitivities of future CO 2 emissions to key drivers characterizing the SSPs. We use six state-of-the-art integrated assessment models with different structural characteristics, and study the impact of five families of parameters, related to population, income, energy efficiency, fossil fuel availability, and low-carbon energy technology development. A recently developed sensitivity analysis algorithm allows us to parsimoniously compute both the direct and interaction effects of each of these drivers on cumulative emissions. The study reveals that the SSP assumptions about energy intensity and economic growth are the most important determinants of future CO 2 emissions from energy combustion, both with and without a climate policy. Interaction terms between parameters are shown to be important determinants of the total sensitivities

To respond or not to respond - a personal perspective of intestinal tolerance

For many years, the intestine was one of the poor relations of the immunology world, being a realm inhabited mostly by specialists and those interested in unusual phenomena. However, this has changed dramatically in recent years with the realization of how important the microbiota is in shaping immune function throughout the body, and almost every major immunology institution now includes the intestine as an area of interest. One of the most important aspects of the intestinal immune system is how it discriminates carefully between harmless and harmful antigens, in particular, its ability to generate active tolerance to materials such as commensal bacteria and food proteins. This phenomenon has been recognized for more than 100 years, and it is essential for preventing inflammatory disease in the intestine, but its basis remains enigmatic. Here, I discuss the progress that has been made in understanding oral tolerance during my 40 years in the field and highlight the topics that will be the focus of future research

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente