The hidden burden of adult allergic rhinitis : UK healthcare resource utilisation survey

Funding Funding for this survey was provided by Meda Pharma.Peer reviewedPublisher PD

Genome-Wide Studies of Histone Demethylation Catalysed by the Fission Yeast Homologues of Mammalian LSD1

In order to gain a more global view of the activity of histone demethylases, we report here genome-wide studies of the fission yeast SWIRM and polyamine oxidase (PAO) domain homologues of mammalian LSD1. Consistent with previous work we find that the two S. pombe proteins, which we name Swm1 and Swm2 (after SWIRM1 and SWIRM2), associate together in a complex. However, we find that this complex specifically demethylates lysine 9 in histone H3 (H3K9) and both up- and down-regulates expression of different groups of genes. Using chromatin-immunoprecipitation, to isolate fragments of chromatin containing either H3K4me2 or H3K9me2, and DNA microarray analysis (ChIP-chip), we have studied genome-wide changes in patterns of histone methylation, and their correlation with gene expression, upon deletion of the swm1+ gene. Using hyper-geometric probability comparisons we uncover genetic links between lysine-specific demethylases, the histone deacetylase Clr6, and the chromatin remodeller Hrp1. The data presented here demonstrate that in fission yeast the SWIRM/PAO domain proteins Swm1 and Swm2 are associated in complexes that can remove methyl groups from lysine 9 methylated histone H3. In vitro, we show that bacterially expressed Swm1 also possesses lysine 9 demethylase activity. In vivo, loss of Swm1 increases the global levels of both H3K9me2 and H3K4me2. A significant accumulation of H3K4me2 is observed at genes that are up-regulated in a swm1 deletion strain. In addition, H3K9me2 accumulates at some genes known to be direct Swm1/2 targets that are down-regulated in the swm1¿ strain. The in vivo data indicate that Swm1 acts in concert with the HDAC Clr6 and the chromatin remodeller Hrp1 to repress gene expression. In addition, our in vitro analyses suggest that the H3K9 demethylase activity requires an unidentified post-translational modification to allow it to act. Thus, our results highlight complex interactions between histone demethylase, deacetylase and chromatin remodelling activities in the regulation of gene expression

Low reproductive performance and high sow mortality in a pig breeding herd: a case study

Sow performance is a key component of the productivity of commercial pig farms. Reproductive failure in the sow is common in pig production. For every 100 sows served, 89 should farrow. In absence of specific diseases such as porcine parvovirus, pseudo-rabies, swine fever, leptospirosis and brucellosis, management failures are the most important causes of loss. A syndrome associated with reproductive inefficiency, and post-service vaginal discharge and high sow mortality in a commercial pig farm is described. Pregnancy failures exceeded 20% and sow mortality exceeded 12% for two consecutive years. The abnormal post-service vaginal discharge rate was 1.7% during the period of investigation

Increasing condom use in heterosexual men: development of a theory-based interactive digital intervention

Increasing condom use to prevent sexually transmitted infections is a key public health goal. Interventions are more likely to be effective if they are theory- and evidence-based. The Behaviour Change Wheel (BCW) provides a framework for intervention development. To provide an example of how the BCW was used to develop an intervention to increase condom use in heterosexual men (the MenSS website), the steps of the BCW intervention development process were followed, incorporating evidence from the research literature and views of experts and the target population. Capability (e.g. knowledge) and motivation (e.g. beliefs about pleasure) were identified as important targets of the intervention. We devised ways to address each intervention target, including selecting interactive features and behaviour change techniques. The BCW provides a useful framework for integrating sources of evidence to inform intervention content and deciding which influences on behaviour to target

AXIOM: advanced X-ray imaging of the magnetosphere

Planetary plasma and magnetic field environments can be studied in two complementary ways—by in situ measurements, or by remote sensing. While the former provide precise information about plasma behaviour, instabilities and dynamics on local scales, the latter offers the global view necessary to understand the overall interaction of the magnetospheric plasma with the solar wind. Some parts of the Earth’s magnetosphere have been remotely sensed, but the majority remains unexplored by this type of measurements. Here we propose a novel and more elegant approach employing remote X-ray imaging techniques, which are now possible thanks to the relatively recent discovery of solar wind charge exchange X-ray emissions in the vicinity of the Earth’s magnetosphere. In this article we describe how an appropriately designed and located X-ray telescope, supported by simultaneous in situ measurements of the solar wind, can be used to image the dayside magnetosphere, magnetosheath and bow shock, with a temporal and spatial resolution sufficient to address several key outstanding questions concerning how the solar wind interacts with the Earth’s magnetosphere on a global level. Global images of the dayside magnetospheric boundaries require vantage points well outside the magnetosphere. Our studies have led us to propose ‘AXIOM: Advanced X-ray Imaging of the Magnetosphere’, a concept mission using a Vega launcher with a LISA Pathfinder-type Propulsion Module to place the spacecraft in a Lissajous orbit around the Earth–Moon L1 point. The model payload consists of an X-ray Wide Field Imager, capable of both imaging and spectroscopy, and an in situ plasma and magnetic field measurement package. This package comprises a Proton-Alpha Sensor, designed to measure the bulk properties of the solar wind, an Ion Composition Analyser, to characterise the minor ion populations in the solar wind that cause charge exchange emission, and a Magnetometer, designed to measure the strength and direction of the solar wind magnetic field. We also show simulations that demonstrate how the proposed X-ray telescope design is capable of imaging the predicted emission from the dayside magnetosphere with the sensitivity and cadence required to achieve the science goals of the mission

The ruptured Achilles tendon: operative and non-operative treatment options

The Achilles tendon is the strongest and thickest tendon in the human body. Like any other tendon in the body, however, it is susceptible to rupture. Many surgeons advocate early operative repair of the ruptured Achilles tendon, citing decreased re-rupture rates and improved functional outcome. Waiting for surgical repair for longer than one month may lead to inferior functional results postoperatively. Non-operative treatment has higher re-rupture rates as compared to surgically repaired tendons, but may be the treatment of choice in some patients. While for many years, patients were rigidly immobilized in a non-weightbearing cast for 6–8 weeks postoperatively, newer studies have shown excellent results with early weightbearing, and this is quickly becoming the standard of care amongst many physicians

The 10th Biennial Hatter Cardiovascular Institute workshop: cellular protection—evaluating new directions in the setting of myocardial infarction, ischaemic stroke, and cardio-oncology

Due to its poor capacity for regeneration, the heart is particularly sensitive to the loss of contractile cardiomyocytes. The onslaught of damage caused by ischaemia and reperfusion, occurring during an acute myocardial infarction and the subsequent reperfusion therapy, can wipe out upwards of a billion cardiomyocytes. A similar program of cell death can cause the irreversible loss of neurons in ischaemic stroke. Similar pathways of lethal cell injury can contribute to other pathologies such as left ventricular dysfunction and heart failure caused by cancer therapy. Consequently, strategies designed to protect the heart from lethal cell injury have the potential to be applicable across all three pathologies. The investigators meeting at the 10th Hatter Cardiovascular Institute workshop examined the parallels between ST-segment elevation myocardial infarction (STEMI), ischaemic stroke, and other pathologies that cause the loss of cardiomyocytes including cancer therapeutic cardiotoxicity. They examined the prospects for protection by remote ischaemic conditioning (RIC) in each scenario, and evaluated impasses and novel opportunities for cellular protection, with the future landscape for RIC in the clinical setting to be determined by the outcome of the large ERIC-PPCI/CONDI2 study. It was agreed that the way forward must include measures to improve experimental methodologies, such that they better reflect the clinical scenario and to judiciously select combinations of therapies targeting specific pathways of cellular death and injury

Lithic technological responses to Late Pleistocene glacial cycling at Pinnacle Point Site 5-6, South Africa

There are multiple hypotheses for human responses to glacial cycling in the Late Pleistocene, including changes in population size, interconnectedness, and mobility. Lithic technological analysis informs us of human responses to environmental change because lithic assemblage characteristics are a reflection of raw material transport, reduction, and discard behaviors that depend on hunter-gatherer social and economic decisions. Pinnacle Point Site 5-6 (PP5-6), Western Cape, South Africa is an ideal locality for examining the influence of glacial cycling on early modern human behaviors because it preserves a long sequence spanning marine isotope stages (MIS) 5, 4, and 3 and is associated with robust records of paleoenvironmental change. The analysis presented here addresses the question, what, if any, lithic assemblage traits at PP5-6 represent changing behavioral responses to the MIS 5-4-3 interglacial-glacial cycle? It statistically evaluates changes in 93 traits with no a priori assumptions about which traits may significantly associate with MIS. In contrast to other studies that claim that there is little relationship between broad-scale patterns of climate change and lithic technology, we identified the following characteristics that are associated with MIS 4: increased use of quartz, increased evidence for outcrop sources of quartzite and silcrete, increased evidence for earlier stages of reduction in silcrete, evidence for increased flaking efficiency in all raw material types, and changes in tool types and function for silcrete. Based on these results, we suggest that foragers responded to MIS 4 glacial environmental conditions at PP5-6 with increased population or group sizes, 'place provisioning', longer and/or more intense site occupations, and decreased residential mobility. Several other traits, including silcrete frequency, do not exhibit an association with MIS. Backed pieces, once they appear in the PP5-6 record during MIS 4, persist through MIS 3. Changing paleoenvironments explain some, but not all temporal technological variability at PP5-6.Social Science and Humanities Research Council of Canada; NORAM; American-Scandinavian Foundation; Fundacao para a Ciencia e Tecnologia [SFRH/BPD/73598/2010]; IGERT [DGE 0801634]; Hyde Family Foundations; Institute of Human Origins; National Science Foundation [BCS-9912465, BCS-0130713, BCS-0524087, BCS-1138073]; John Templeton Foundation to the Institute of Human Origins at Arizona State Universit