Pharmacological ablation of the airway smooth muscle layer—Mathematical predictions of functional improvement in asthma

Airway smooth muscle (ASM) plays a major role in acute airway narrowing and reducing ASM thickness is expected to attenuate airway hyper-responsiveness and disease burden. There are two therapeutic approaches to reduce ASM thickness: (a) a direct approach, targeting specific airways, best exemplified by bronchial thermoplasty (BT), which delivers radiofrequency energy to the airway via bronchoscope; and (b) a pharmacological approach, targeting airways more broadly. An example of the less well-established pharmacological approach is the calcium-channel blocker gallopamil which in a clinical trial effectively reduced ASM thickness; other agents may act similarly. In view of established anti-proliferative properties of the macrolide antibiotic azithromycin, we examined its effects in naive mice and report a reduction in ASM thickness of 29% (p <.01). We further considered the potential functional implications of this finding, if it were to extend to humans, by way of a mathematical model of lung function in asthmatic patients which has previously been used to understand the mechanistic action of BT. Predictions show that pharmacological reduction of ASM in all airways of this magnitude would reduce ventilation heterogeneity in asthma, and produce a therapeutic benefit similar to BT. Moreover there are differences in the expected response depending on disease severity, with the pharmacological approach exceeding the benefits provided by BT in more severe disease. Findings provide further proof of concept that pharmacological targeting of ASM thickness will be beneficial and may be facilitated by azithromycin, revealing a new mode of action of an existing agent in respiratory medicine

Use of vaccines and factors associated with their uptake variability in dogs, cats and rabbits attending a large sentinel network of veterinary practices across Great Britain

Vaccination remains a mainstay of companion animal population health. However, how vaccine use at a population level complies with existing guidelines is unknown. Here we use electronic health records to describe vaccination in dogs, cats and rabbits attending a large sentinel network of UK veterinary practices. In total, 77.9% (95% CI: 77.6-78.1) of animals had recorded vaccinations. The percentage of animals with recorded vaccinations was higher in dogs, neutered animals, in insured dogs and cats and in purebred dogs. Vaccination rates varied in different regions of Great Britain in all species. Dogs and cats belonging to owners living in less deprived areas of England and Scotland were more likely to be recorded as vaccinated. In the vaccinated population, cats received more core vaccines per year of life (0.86) than dogs (0.75), with feline leukaemia vaccines almost as frequent as core vaccines. In dogs, leptospira vaccines were more frequent than core vaccines. This descriptive study suggests a substantial proportion of animals are not benefiting from vaccine protection. For the first time, we identify potential factors associated with variations in recorded vaccination frequency, providing a critical baseline against which to monitor future changes in companion animal vaccination and evidence to inform future targeted health interventions

Mitochondrial haplotypes reveal low diversity and restricted connectivity of the critically endangered batoid population in a Marine Protected Area

Stability and long-term persistence of a species rely heavily on its genetic diversity, which is closely allied to its capacity for adaptation. In threatened species, population connectivity can play a major role in maintaining that diversity, and genetic assessments of their populations can be crucial for the design of effective spatial conservation management. Not only is it worth evaluating the amount of diversity in a candidate population for protection, but the magnitude of outgoing gene flow can provide insight into its potential to replenish others via emigrants. The critically endangered flapper skate Dipturus intermedius receives protection in the Loch Sunart to the Sound of Jura Marine Protected Area (MPA) in Scotland. However, there is insufficient knowledge of genetic diversity and connectivity across its range. Recent tagging studies in the MPA suggest the presence of animals with high levels of site fidelity and residency, as well as transient individuals, raising concerns of limited connectivity to populations beyond the MPA. In this study, a newly developed mitochondrial haplotype marker allowed use of DNA sourced from fin clips, mucus and egg cases to investigate population structure and mitochondrial variability across several sites around the British Isles, including the MPA. Unfortunately, results characterized the MPA as having particularly low haplotype diversity and significant population differentiation from other sample sites. More than a quarter of its individuals carry a haplotype rarely observed elsewhere, leaving outgoing gene flow questionable. The MPA appears unlikely to sustain the species{\textquoteright} existing mtDNA genetic diversity or act as an effective source population

Digital technology and governance in transition: The case of the British Library

Comment on the organizational consequences of the new information and communications technologies (ICTs) is pervaded by a powerful imagery of disaggregation and a tendency for ?virtual? forms of production to be seen as synonymous with the ?end? of bureaucracy. This paper questions the underlying assumptions of the ?virtual organization?, highlighting the historically enduring, diversified character of the bureaucratic form. The paper then presents case study findings on the web-based access to information resources now being provided by the British Library (BL). The case study evidence produces two main findings. First, radically decentralised virtual forms of service delivery are heavily dependent on new forms of capacity-building and information aggregation. Second, digital technology is embedded in an inherently contested and contradictory context of institutional change. Current developments in the management and control of digital rights are consistent with the commodification of the public sphere. However, the evidence also suggests that scholarly access to information resources is being significantly influenced by the ?information society? objectives of the BL and other institutional players within the network of UK research libraries

Massive binary black holes in galactic nuclei and their path to coalescence

Massive binary black holes form at the centre of galaxies that experience a merger episode. They are expected to coalesce into a larger black hole, following the emission of gravitational waves. Coalescing massive binary black holes are among the loudest sources of gravitational waves in the Universe, and the detection of these events is at the frontier of contemporary astrophysics. Understanding the black hole binary formation path and dynamics in galaxy mergers is therefore mandatory. A key question poses: during a merger, will the black holes descend over time on closer orbits, form a Keplerian binary and coalesce shortly after? Here we review progress on the fate of black holes in both major and minor mergers of galaxies, either gas-free or gas-rich, in smooth and clumpy circum-nuclear discs after a galactic merger, and in circum-binary discs present on the smallest scales inside the relic nucleus.Comment: Accepted for publication in Space Science Reviews. To appear in hard cover in the Space Sciences Series of ISSI "The Physics of Accretion onto Black Holes" (Springer Publisher

Quasielastic 12C(e,e'p) Reaction at High Momentum Transfer

We measured the 12C(e,e'p) cross section as a function of missing energy in parallel kinematics for (q,w) = (970 MeV/c, 330 MeV) and (990 MeV/c, 475 MeV). At w=475 MeV, at the maximum of the quasielastic peak, there is a large continuum (E_m > 50 MeV) cross section extending out to the deepest missing energy measured, amounting to almost 50% of the measured cross section. The ratio of data to DWIA calculation is 0.4 for both the p- and s-shells. At w=330 MeV, well below the maximum of the quasielastic peak, the continuum cross section is much smaller and the ratio of data to DWIA calculation is 0.85 for the p-shell and 1.0 for the s-shell. We infer that one or more mechanisms that increase with $\omega$ transform some of the single-nucleon-knockout into multinucleon knockout, decreasing the valence knockout cross section and increasing the continuum cross section.Comment: 14 pages, 7 figures, Revtex (multicol, prc and aps styles), to appear in Phys Rev

The Role of Color Neutrality in Nuclear Physics--Modifications of Nucleonic Wave Functions

The influence of the nuclear medium upon the internal structure of a composite nucleon is examined. The interaction with the medium is assumed to depend on the relative distances between the quarks in the nucleon consistent with the notion of color neutrality, and to be proportional to the nucleon density. In the resulting description the nucleon in matter is a superposition of the ground state (free nucleon) and radial excitations. The effects of the nuclear medium on the electromagnetic and weak nucleon form factors, and the nucleon structure function are computed using a light-front constituent quark model. Further experimental consequences are examined by considering the electromagnetic nuclear response functions. The effects of color neutrality supply small but significant corrections to predictions of observables.Comment: 37 pages, postscript figures available on request to [email protected]

Questioning ten common assumptions about peatlands

Peatlands have been widely studied in terms of their ecohydrology, carbon dynamics, ecosystem services and palaeoenvironmental archives. However, several assumptions are frequently made about peatlands in the academic literature, practitioner reports and the popular media which are either ambiguous or in some cases incorrect. Here we discuss the following ten common assumptions about peatlands: 1. the northern peatland carbon store will shrink under a warming climate; 2. peatlands are fragile ecosystems; 3. wet peatlands have greater rates of net carbon accumulation; 4. different rules apply to tropical peatlands; 5. peat is a single soil type; 6. peatlands behave like sponges; 7. Sphagnum is the main ‘ecosystem engineer’ in peatlands; 8. a single core provides a representative palaeo-archive from a peatland; 9. water-table reconstructions from peatlands provide direct records of past climate change; and 10. restoration of peatlands results in the re-establishment of their carbon sink function. In each case we consider the evidence supporting the assumption and, where appropriate, identify its shortcomings or ways in which it may be misleading