Hypoxaemia in patients with pulmonary arterial hypertension during simulated air travel

SummaryBackgroundRecent air travel recommendations suggest patients with precapillary pulmonary hypertension (PCPH) in New York Heart Association (NYHA) functional class 3 and 4 should have in-flight oxygen without the need for pre-flight testing. However it remains unclear as to how best to determine patients fitness to fly.MethodsThis study (i) investigates the effect of hypoxic challenge testing (HCT) on the arterial oxygen levels in a cohort of 36 patients with PCPH and (ii) compares the relative frequency with which FC and HCT predict the requirement for in-flight oxygen.ResultsThe degree of arterial hypoxaemia induced by HCT (fall in partial pressure of oxygen in arterial blood (PaO2) 2.36 kPa, 95% CI 2.06–2.66 kPa) was similar to the drop observed in other published studies of chronic respiratory diseases.Following current air travel recommendations based on FC, 25 patients of the cohort would require in-flight oxygen whilst 10 subjects failed the HCT. Fourteen subjects had flown post-diagnosis. Of these, nine subjects should have had in-flight oxygen based on FC but were asymptomatic without. Also one who passed the HCT had developed symptoms during the flight whilst three who failed the HCT were asymptomatic flying without in-flight oxygen.ConclusionsHypoxaemia induced by simulated air travel in patients with PCPH is similar to that seen in published studies of patients with other chronic respiratory diseases. HCT failed to predict correctly who had developed symptoms during an aircraft flight in a significant minority of the study subjects. Similarly guidelines based on functional class result in a major increase in the proportion of patients being advised to use oxygen, many of whom had been asymptomatic on previous flights without it. More work is required to improve prediction of need for in-flight oxygen in patients with PCPH

Probing Supersymmetry With Third-Generation Cascade Decays

The chiral structure of supersymmetric particle couplings involving third generation Standard Model fermions depends on left-right squark and slepton mixings as well as gaugino-higgsino mixings. The shapes and intercorrelations of invariant mass distributions of a first or second generation lepton with bottoms and taus arising from adjacent branches of SUSY cascade decays are shown to be a sensitive probe of this chiral structure. All possible cascade decays that can give rise to such correlations within the MSSM are considered. For bottom-lepton correlations the distinctive structure of the invariant mass distributions distinguishes between decays originating from stop or sbottom squarks through either an intermediate chargino or neutralino. For decay through a chargino the spins of the stop and chargino are established by the form of the distribution. When the bottom charge is signed through soft muon tagging, the structure of the same-sign and opposite-sign invariant mass distributions depends on a set function of left-right and gaugino-higgsino mixings, as well as establishes the spins of all the superpartners in the sequential two-body cascade decay. Tau-lepton and tau-tau invariant mass distributions arising from MSSM cascade decays are likewise systematically considered with particular attention to their dependence on tau polarization. All possible tau-lepton and tau-tau distributions are plotted using a semi-analytic model for hadronic one-prong taus. Algorithms for fitting tau-tau and tau-lepton distributions to data are suggested.Comment: 35 pages, 17 .eps figure

The most creative organization in the world? The BBC, 'creativity' and managerial style

The managerial styles of two BBC directors-general, John Birt and Greg Dyke, have often been contrasted but not so far analysed from the perspective of their different views of 'creative management'. This article first addresses the orthodox reading of 'Birtism'; second, it locates Dyke's 'creative' turn in the wider context of fashionable neo-management theory and UK government creative industries policy; third, it details Dyke's drive to change the BBC's culture; and finally, it concludes with some reflections on the uncertainties inherent in managing a creative organisation

Evaluating Baculovirus as a Vector for Human Prostate Cancer Gene Therapy

Gene therapy represents an attractive strategy for the non-invasive treatment of prostate cancer, where current clinical interventions show limited efficacy. Here, we evaluate the use of the insect virus, baculovirus (BV), as a novel vector for human prostate cancer gene therapy. Since prostate tumours represent a heterogeneous environment, a therapeutic approach that achieves long-term regression must be capable of targeting multiple transformed cell populations. Furthermore, discrimination in the targeting of malignant compared to non-malignant cells would have value in minimising side effects. We employed a number of prostate cancer models to analyse the potential for BV to achieve these goals. In vitro, both traditional prostate cell lines as well as primary epithelial or stromal cells derived from patient prostate biopsies, in two- or three-dimensional cultures, were used. We also evaluated BV in vivo in murine prostate cancer xenograft models. BV was capable of preferentially transducing invasive malignant prostate cancer cell lines compared to early stage cancers and non-malignant samples, a restriction that was not a function of nuclear import. Of more clinical relevance, primary patient-derived prostate cancer cells were also efficiently transduced by BV, with robust rates observed in epithelial cells of basal phenotype, which expressed BV-encoded transgenes faster than epithelial cells of a more differentiated, luminal phenotype. Maximum transduction capacity was observed in stromal cells. BV was able to penetrate through three-dimensional structures, including in vitro spheroids and in vivo orthotopic xenografts. BV vectors containing a nitroreductase transgene in a gene-directed enzyme pro-drug therapy approach were capable of efficiently killing malignant prostate targets following administration of the pro-drug, CB1954. Thus, BV is capable of transducing a large proportion of prostate cell types within a heterogeneous 3-D prostate tumour, can facilitate cell death using a pro-drug approach, and shows promise as a vector for the treatment of prostate cancer

Fire and the relative roles of weather, climate and landscape characteristics in the Great Lakes-St. Lawrence forest of Canada

Question: In deciduous-dominated forest landscapes, what are the relative roles of fire weather, climate, human and biophysical landscape characteristics for explaining variation in large fire occurrence and area burned? Location: The Great Lakes-St. Lawrence forest of Canada. Methods: We characterized the recent (1959-1999) regime of large (≥ 200 ha) fires in 26 deciduous-dominated landscapes and analysed these data in an information-theoretic framework to compare six hypotheses that related fire occurrence and area burned to fire weather severity, climate normals, population and road densities, and enduring landscape characteristics such as surficial deposits and large lakes. Results: 392 large fires burned 833 698 ha during the study period, annually burning on average 0.07% ± 0.42% of forested area in each landscape. Fire activity was strongly seasonal, with most fires and area burned occurring in May and June. A combination of antecedent-winter precipitation, fire season precipitation deficit/surplus and percent of landscape covered by well-drained surficial deposits best explained fire occurrence and area burned. Fire occurrence varied only as a function of fire weather and climate variables, whereas area burned was also explained by percent cover of aspen and pine stands, human population density and two enduring characteristics: percent cover of large water bodies and glaciofluvial deposits. Conclusion: Understanding the relative role of these variables may help design adaptation strategies for forecasted increases in fire weather severity by allowing (1) prioritization of landscapes according to enduring characteristics and (2) management of their composition so that substantially increased fire activity would be necessary to transform landscape structure and composition

A model independent spin analysis of fundamental particles using azimuthal asymmetries

Exploiting the azimuthal angle dependence of the density matrices we construct observables that directly measure the spin of a heavy unstable particle. A novelty of the approach is that the analysis of the azimuthal angle dependence in a frame other than the usual helicity frame offers an independent cross-check on the extraction of the spin. Moreover, in some instances when the transverse polarisation tensor of highest rank is vanishing, for an accidental or dynamical reason, the standard azimuthal asymmetries vanish and would lead to a measurement with a wrong spin assignment. In a frame such as the one we construct, the correct spin assignment would however still be possible. The method gives direct information about the spin of the particle under consideration and the same event sample can be used to identify the spins of each particle in a decay chain. A drawback of the method is that it is instrumental only when the momenta of the test particle can be reconstructed. However we hope that it might still be of use in situations with only partial reconstruction. We also derive the conditions on the production and decay mechanisms for the spins, and hence the polarisations, to be measured at a collider experiment. As an example for the use of the method we consider the simultaneous reconstruction, at the partonic level, of the spin of both the top and the $W$ in top pair production in $e^+ e^-$ in the semi-leptonic channel.Comment: 42 pages, 7 figures, 4 table

Loss of β Epithelial Sodium Channel Function in Meibomian Glands Produces Pseudohypoaldosteronism 1–Like Ocular Disease in Mice

Human subjects with pseudohypoaldosteronism-1 because of loss-of-function mutations in epithelial sodium channel (ENaC) subunits exhibit meibomian gland (MG) dysfunction. A conditional βENaC MG knockout (KO) mouse model was generated to elucidate the pathogenesis of absent ENaC function in the MG and associated ocular surface disease. βENaC MG KO mice exhibited a striking age-dependent, female-predominant MG dysfunction phenotype, with white toothpaste–like secretions observed obstructing MG orifices at 7 weeks of age. There were compensatory increases in tear production but higher tear sodium and indexes of mucin concentration in βENaC MG KO mice. Histologically, MG acinar atrophy was observed with ductal enlargement and ductal epithelial hyperstratification. Inflammatory cell infiltration was observed in both MG and conjunctiva of βENaC MG KO mice. In older βENaC MG KO mice (5 to 11 months), significant ocular surface pathologies were noted, including corneal opacification, ulceration, neovascularization, and ectasia. Inflammation in MG and conjunctiva was confirmed by increased cytokine gene and protein expression and positive Ly-6B.2 immunostaining. Cell proliferation assays revealed lower proliferation rates of MG cells derived from βENaC MG KO than control mice, suggesting that βENaC plays a role in cell renewal of mouse MG. Loss of βENaC function resulted in MG disease and severe ocular surface damage that phenocopied aspects of human pseudohypoaldosteronism-1 MG disease and was sex dependent

Origin and Evolution of Saturn's Ring System

The origin and long-term evolution of Saturn's rings is still an unsolved problem in modern planetary science. In this chapter we review the current state of our knowledge on this long-standing question for the main rings (A, Cassini Division, B, C), the F Ring, and the diffuse rings (E and G). During the Voyager era, models of evolutionary processes affecting the rings on long time scales (erosion, viscous spreading, accretion, ballistic transport, etc.) had suggested that Saturn's rings are not older than 100 My. In addition, Saturn's large system of diffuse rings has been thought to be the result of material loss from one or more of Saturn's satellites. In the Cassini era, high spatial and spectral resolution data have allowed progress to be made on some of these questions. Discoveries such as the ''propellers'' in the A ring, the shape of ring-embedded moonlets, the clumps in the F Ring, and Enceladus' plume provide new constraints on evolutionary processes in Saturn's rings. At the same time, advances in numerical simulations over the last 20 years have opened the way to realistic models of the rings's fine scale structure, and progress in our understanding of the formation of the Solar System provides a better-defined historical context in which to understand ring formation. All these elements have important implications for the origin and long-term evolution of Saturn's rings. They strengthen the idea that Saturn's rings are very dynamical and rapidly evolving, while new arguments suggest that the rings could be older than previously believed, provided that they are regularly renewed. Key evolutionary processes, timescales and possible scenarios for the rings's origin are reviewed in the light of tComment: Chapter 17 of the book ''Saturn After Cassini-Huygens'' Saturn from Cassini-Huygens, Dougherty, M.K.; Esposito, L.W.; Krimigis, S.M. (Ed.) (2009) 537-57

White paper on guidelines concerning enteric nervous system stem cell therapy for enteric neuropathies.

Over the last 20 years, there has been increasing focus on the development of novel stem cell based therapies for the treatment of disorders and diseases affecting the enteric nervous system (ENS) of the gastrointestinal tract (so-called enteric neuropathies). Here, the idea is that ENS progenitor/stem cells could be transplanted into the gut wall to replace the damaged or absent neurons and glia of the ENS. This White Paper sets out experts' views on the commonly used methods and approaches to identify, isolate, purify, expand and optimize ENS stem cells, transplant them into the bowel, and assess transplant success, including restoration of gut function. We also highlight obstacles that must be overcome in order to progress from successful preclinical studies in animal models to ENS stem cell therapies in the clinic