Dynamic laryngeal narrowing during exercise: a mechanism for generating intrinsic PEEP in COPD?

INTRODUCTION: Patients with COPD commonly exhibit pursed-lip breathing during exercise, a strategy that, by increasing intrinsic positive end-expiratory pressure, may optimise lung mechanics and exercise tolerance. A similar role for laryngeal narrowing in modulating exercise airways resistance and the respiratory cycle volume–time course is postulated, yet remains unstudied in COPD. The aim of this study was to assess the characteristics of laryngeal narrowing and its role in exercise intolerance and dynamic hyperinflation in COPD. METHODS: We studied 19 patients (n=8 mild–moderate; n=11 severe COPD) and healthy age and sex matched controls (n=11). Baseline physiological characteristics and clinical status were assessed prior to an incremental maximal cardiopulmonary exercise test with continuous laryngoscopy. Laryngeal narrowing measures were calculated at the glottic and supra-glottic aperture at rest and peak exercise. RESULTS: At rest, expiratory laryngeal narrowing was pronounced at the glottic level in patients and related to FEV(1) in the whole cohort (r=−0.71, p<0.001) and patients alone (r=−0.53, p=0.018). During exercise, glottic narrowing was inversely related to peak ventilation in all subjects (r=−0.55, p=0.0015) and patients (r=−0.71, p<0.001) and peak exercise tidal volume (r=−0.58, p=0.0062 and r=−0.55, p=0.0076, respectively). Exercise glottic narrowing was also inversely related to peak oxygen uptake (% predicted) in all subjects (r=−0.65, p<0.001) and patients considered alone (r=−0.58, p=0.014). Exercise inspiratory duty cycle was related to exercise glottic narrowing for all subjects (r=−0.69, p<0.001) and patients (r=−0.62, p<0.001). CONCLUSIONS: Dynamic laryngeal narrowing during expiration is prevalent in patients with COPD and is related to disease severity, respiratory duty cycle and exercise capacity

Spatially Resolved Magnetic Field Structure in the Disk of a T Tauri Star

Magnetic fields in accretion disks play a dominant role during the star formation process but have hitherto been observationally poorly constrained. Field strengths have been inferred on T Tauri stars themselves and possibly in the innermost part of the accretion disk, but the strength and morphology of the field in the bulk of the disk have not been observed. Unresolved measurements of polarized emission (arising from elongated dust grains aligned perpendicular to the field) imply average fields aligned with the disks. Theoretically, the fields are expected to be largely toroidal, poloidal, or a mixture of the two, which imply different mechanisms for transporting angular momentum in the disks of actively accreting young stars such as HL Tau. Here we report resolved measurements of the polarized 1.25 mm continuum emission from HL Tau's disk. The magnetic field on a scale of 80 AU is coincident with the major axis (~210 AU diameter) of the disk. From this we conclude that the magnetic field inside the disk at this scale cannot be dominated by a vertical component, though a purely toroidal field does not fit the data well either. The unexpected morphology suggests that the magnetic field's role for the accretion of a T Tauri star is more complex than the current theoretical understanding.Comment: Accepted for publication in Natur

Matrix theory origins of non-geometric fluxes

We explore the origins of non-geometric fluxes within the context of M theory described as a matrix model. Building upon compactifications of Matrix theory on non-commutative tori and twisted tori, we formulate the conditions which describe compactifications with non-geometric fluxes. These turn out to be related to certain deformations of tori with non-commutative and non-associative structures on their phase space. Quantization of flux appears as a natural consequence of the framework and leads to the resolution of non-associativity at the level of the unitary operators. The quantum-mechanical nature of the model bestows an important role on the phase space. In particular, the geometric and non-geometric fluxes exchange their properties when going from position space to momentum space thus providing a duality among the two. Moreover, the operations which connect solutions with different fluxes are described and their relation to T-duality is discussed. Finally, we provide some insights on the effective gauge theories obtained from these matrix compactifications.Comment: 1+31 pages, reference list update

Membrane Sigma-Models and Quantization of Non-Geometric Flux Backgrounds

We develop quantization techniques for describing the nonassociative geometry probed by closed strings in flat non-geometric R-flux backgrounds M. Starting from a suitable Courant sigma-model on an open membrane with target space M, regarded as a topological sector of closed string dynamics in R-space, we derive a twisted Poisson sigma-model on the boundary of the membrane whose target space is the cotangent bundle T^*M and whose quasi-Poisson structure coincides with those previously proposed. We argue that from the membrane perspective the path integral over multivalued closed string fields in Q-space is equivalent to integrating over open strings in R-space. The corresponding boundary correlation functions reproduce Kontsevich's deformation quantization formula for the twisted Poisson manifolds. For constant R-flux, we derive closed formulas for the corresponding nonassociative star product and its associator, and compare them with previous proposals for a 3-product of fields on R-space. We develop various versions of the Seiberg-Witten map which relate our nonassociative star products to associative ones and add fluctuations to the R-flux background. We show that the Kontsevich formula coincides with the star product obtained by quantizing the dual of a Lie 2-algebra via convolution in an integrating Lie 2-group associated to the T-dual doubled geometry, and hence clarify the relation to the twisted convolution products for topological nonassociative torus bundles. We further demonstrate how our approach leads to a consistent quantization of Nambu-Poisson 3-brackets.Comment: 52 pages; v2: references adde

Tree thinking cannot taken for granted: challenges for teaching phylogenetics

Tree thinking is an integral part of modern evolutionary biology, and a necessary precondition for phylogenetics and comparative analyses. Tree thinking has during the 20th century largely replaced group thinking, developmental thinking and anthropocentricism in biology. Unfortunately, however, this does not imply that tree thinking can be taken for granted. The findings reported here indicate that tree thinking is very much an acquired ability which needs extensive training. I tested a sample of undergraduate and graduate students of biology by means of questionnaires. Not a single student was able to correctly interpret a simple tree drawing. Several other findings demonstrate that tree thinking is virtually absent in students unless they are explicitly taught how to read evolutionary trees. Possible causes and implications of this mental bias are discussed. It seems that biological textbooks can be an important source of confusion for students. While group and developmental thinking have disappeared from most textual representations of evolution, they have survived in the evolutionary tree drawings of many textbooks. It is quite common for students to encounter anthropocentric trees and even trees containing stem groups and paraphyla. While these biases originate from the unconscious philosophical assumptions made by authors, the findings suggest that presenting unbiased evolutionary trees in biological publications is not merely a philosophical virtue but has also clear practical implications

Mobile Phone Radiation Induces Reactive Oxygen Species Production and DNA Damage in Human Spermatozoa In Vitro

Background: In recent times there has been some controversy over the impact of electromagnetic radiation on human health. The significance of mobile phone radiation on male reproduction is a key element of this debate since several studies have suggested a relationship between mobile phone use and semen quality. The potential mechanisms involved have not been established, however, human spermatozoa are known to be particularly vulnerable to oxidative stress by virtue of the abundant availability of substrates for free radical attack and the lack of cytoplasmic space to accommodate antioxidant enzymes. Moreover, the induction of oxidative stress in these cells not only perturbs their capacity for fertilization but also contributes to sperm DNA damage. The latter has, in turn, been linked with poor fertility, an increased incidence of miscarriage and morbidity in the offspring, including childhood cancer. In light of these associations, we have analyzed the influence of RF-EMR on the cell biology of human spermatozoa in vitro. Principal Findings: Purified human spermatozoa were exposed to radio-frequency electromagnetic radiation (RF-EMR) tuned to 1.8 GHz and covering a range of specific absorption rates (SAR) from 0.4 W/kg to 27.5 W/kg. In step with increasing SAR, motility and vitality were significantly reduced after RF-EMR exposure, while the mitochondrial generation of reactive oxygen species and DNA fragmentation were significantly elevated (P<0.001). Furthermore, we also observed highly significant relationships between SAR, the oxidative DNA damage bio-marker, 8-OH-dG, and DNA fragmentation after RF-EMRexposure. Conclusions: RF-EMR in both the power density and frequency range of mobile phones enhances mitochondrial reactive oxygen species generation by human spermatozoa, decreasing the motility and vitality of these cells while stimulating DNA base adduct formation and, ultimately DNA fragmentation. These findings have clear implications for the safety of extensive mobile phone use by males of reproductive age, potentially affecting both their fertility and the health and wellbeing of their offspring

Persistence and Availability of Web Services in Computational Biology

We have conducted a study on the long-term availability of bioinformatics Web services: an observation of 927 Web services published in the annual Nucleic Acids Research Web Server Issues between 2003 and 2009

How many mailouts? Could attempts to increase the response rate in the Iraq war cohort study be counterproductive?

<p>Abstract</p> <p>Background</p> <p>Low response and reporting errors are major concerns for survey epidemiologists. However, while nonresponse is commonly investigated, the effects of misclassification are often ignored, possibly because they are hard to quantify. We investigate both sources of bias in a recent study of the effects of deployment to the 2003 Iraq war on the health of UK military personnel, and attempt to determine whether improving response rates by multiple mailouts was associated with increased misclassification error and hence increased bias in the results.</p> <p>Methods</p> <p>Data for 17,162 UK military personnel were used to determine factors related to response and inverse probability weights were used to assess nonresponse bias. The percentages of inconsistent and missing answers to health questions from the 10,234 responders were used as measures of misclassification in a simulation of the 'true' relative risks that would have been observed if misclassification had not been present. Simulated and observed relative risks of multiple physical symptoms and post-traumatic stress disorder (PTSD) were compared across response waves (number of contact attempts).</p> <p>Results</p> <p>Age, rank, gender, ethnic group, enlistment type (regular/reservist) and contact address (military or civilian), but not fitness, were significantly related to response. Weighting for nonresponse had little effect on the relative risks. Of the respondents, 88% had responded by wave 2. Missing answers (total 3%) increased significantly (p < 0.001) between waves 1 and 4 from 2.4% to 7.3%, and the percentage with discrepant answers (total 14%) increased from 12.8% to 16.3% (p = 0.007). However, the adjusted relative risks decreased only slightly from 1.24 to 1.22 for multiple physical symptoms and from 1.12 to 1.09 for PTSD, and showed a similar pattern to those simulated.</p> <p>Conclusion</p> <p>Bias due to nonresponse appears to be small in this study, and increasing the response rates had little effect on the results. Although misclassification is difficult to assess, the results suggest that bias due to reporting errors could be greater than bias caused by nonresponse. Resources might be better spent on improving and validating the data, rather than on increasing the response rate.</p

Estimating the risk of rabies transmission to humans in the U.S.: a delphi analysis

<p>Abstract</p> <p>Background</p> <p>In the United States, the risk of rabies transmission to humans in most situations of possible exposure is unknown. Controlled studies on rabies are clearly not possible. Thus, the limited data on risk has led to the frequent administration of rabies post-exposure prophylaxis (PEP), often in inappropriate circumstances.</p> <p>Methods</p> <p>We used the Delphi method to obtain an expert group consensus estimate of the risk of rabies transmission to humans in seven scenarios of potential rabies exposure. We also surveyed and discussed the merits of recommending rabies PEP for each scenario.</p> <p>Results</p> <p>The median risk of rabies transmission without rabies PEP for a bite exposure by a skunk, bat, cat, and dog was estimated to be 0.05, 0.001, 0.001, and 0.00001, respectively. Rabies PEP was unanimously recommended in these scenarios. However, rabies PEP was overwhelmingly not recommended for non-bite exposures (e.g. dog licking hand but unavailable for subsequent testing), estimated to have less than 1 in 1,000,000 (0.000001) risk of transmission.</p> <p>Conclusions</p> <p>Our results suggest that there are many common situations in which the risk of rabies transmission is so low that rabies PEP should not be recommended. These risk estimates also provide a key parameter for cost-effective models of human rabies prevention and can be used to educate health professionals about situation-specific administration of rabies PEP.</p