Increasing prevalence of asthma diagnosis and symptoms in children is confined to mild symptoms

BACKGROUND: The prevalence of childhood asthma is increasing but few studies have investigated trends in asthma severity. We investigated trends in asthma diagnosis and symptom morbidity between an eight year time period in a paired prevalence study. METHODS: All children in one single school year aged 8-9 years in the city of Sheffield were given a parent respondent questionnaire in 1991 and 1999 based on questions from the International Survey of Asthma and Allergy in Children (ISAAC). Data were obtained regarding the prevalence of asthma and wheeze and current (12 month) prevalences of wheeze attacks, speech limiting wheeze, nocturnal cough and wheeze, and exertional symptoms. RESULTS: The response rates in 1991 and 1999 were 4580/5321 (85.3%) and 5011/6021 (83.2%), respectively. There were significant increases between the two surveys in the prevalence of asthma ever (19.9% v 29.7%, mean difference 11.9%, 95% confidence interval (CI) 10.16 to 13.57, p<0.001), current asthma (10.3% v 13.0%, mean difference 2.7%, 95% CI 1.44 to 4.03, p<0.001), wheeze ever (30.3% v 35.8%, mean difference 5.7%, 95% CI 3.76 to 7.56, p<0.001), wheeze in the previous 12 months (17.0% v 19.4%, mean difference 2.5, 95% CI 0.95 to 4.07, p<0.01), and reporting of medication use (16.9% v 20%, mean difference 3.0%, 95% CI 1.46 to 4.62, p<0.001). There were also significant increases in reported hayfever and eczema diagnoses. CONCLUSIONS: Diagnostic labelling of asthma and lifetime prevalence of wheeze has increased. The current 12 month point prevalence of wheeze has increased but this is confined to occasional symptoms. The increased medication rate may be responsible for the static prevalence of severe asthma symptoms. The significant proportion of children receiving medication but reporting no asthma symptoms identified from our 1999 survey suggests that some children are being inappropriately treated or overtreated

Theory and simulations of a gyrotron backward wave oscillator using a helical interaction waveguide

A gyrotron backward wave oscillator (gyro-BWO) with a helically corrugated interaction waveguide demonstrated its potential as a powerful microwave source with high efficiency and a wide frequency tuning range. This letter presents the theory describing the dispersion properties of such a waveguide and the linear beam-wave interaction. Numerical simulation results using the PIC code MAGIC were found to be in excellent agreement with the output measured from a gyro-BWO experiment

A cardinal role for cathepsin D in co-ordinating the host-mediated apoptosis of macrophages and killing of pneumococci

The bactericidal function of macrophages against pneumococci is enhanced by their apoptotic demise, which is controlled by the anti-apoptotic protein Mcl-1. Here, we show that lysosomal membrane permeabilization (LMP) and cytosolic translocation of activated cathepsin D occur prior to activation of a mitochondrial pathway of macrophage apoptosis. Pharmacological inhibition or knockout of cathepsin D during pneumococcal infection blocked macrophage apoptosis. As a result of cathepsin D activation, Mcl-1 interacted with its ubiquitin ligase Mule and expression declined. Inhibition of cathepsin D had no effect on early bacterial killing but inhibited the late phase of apoptosis-associated killing of pneumococci in vitro. Mice bearing a cathepsin D-/- hematopoietic system demonstrated reduced macrophage apoptosis in vivo, with decreased clearance of pneumococci and enhanced recruitment of neutrophils to control pulmonary infection. These findings establish an unexpected role for a cathepsin D-mediated lysosomal pathway of apoptosis in pulmonary host defense and underscore the importance of apoptosis-associated microbial killing to macrophage function

Simulated holographic three-dimensional intensity shaping of evanescent-wave fields

The size of bright structures in traveling-wave light fields is limited by diffraction. This in turn limits a number of technologies, for example, optical trapping. One way to beat the diffraction limit is to use evanescent waves instead of traveling waves. Here we apply a holographic algorithm, direct search, to the shaping of complex evanescent-wave fields. We simulate three-dimensional intensity shaping of evanescent-wave fields using this approach, and we investigate some of its limitations. (c) 2008 Optical Society of America.</p

A cusp electron gun for millimeter wave gyrodevices

The experimental results of a thermionic cusp electron gun, to drive millimeter and submillimeter wave harmonic gyrodevices, are reported in this paper. Using a "smooth" magnetic field reversal formed by two coils this gun generated an annular-shaped, axis-encircling electron beam with 1.5 A current, and an adjustable velocity ratio alpha of up to 1.56 at a beam voltage of 40 kV. The beam cross-sectional shape and transported beam current were measured by a witness plate technique and Faraday cup, respectively. These measured results were found to be in excellent agreement with the simulated results using the three-dimensional code MAGIC

Optimising Bowel Cancer Screening Phase 1: Optimising the cost effectiveness of repeated FIT screening and screening strategies combining bowel scope and FIT screening

ScHARR has been commissioned by the UK National Screening Committee (NSC) to consider the costeffectiveness and endoscopy capacity requirements of a variety of different screening options incorporating faecal immunochemical testing (FIT) and bowel scope (BS) within the Bowel Cancer Screening Programme (BCSP). An existing cost-effectiveness model was used. The model was refined considerably, new data included and model validation was undertaken. All FIT thresholds between 20 and 180 µg/ml were modelled. Analyses were undertaken to determine which screening strategies involving repeated FIT screening and/or bowel scope are most cost-effective given endoscopy constraints. Note that the conclusions reached are based on optimising cost-effectiveness where effectiveness is measured in terms of QALYs gained. If the aim was to optimise QALY gains or CRC incidence/mortality reduction then conclusions would be different. The analysis without endoscopy constraints indicates that the most cost effective screening strategy is the one which delivers the most intensive screening. Regardless of capacity constraints the current screening strategies (gFOBT 2-yearly 60-74 with or without bowel scope age 55) are dominated by a FIT screening strategy (i.e. a FIT strategy exists which is more effective and less expensive). For repeated FIT screening it is recommended that the screening interval is kept to 2-yearly screening. However, increased benefits may be obtained by re-inviting non-attenders after a 1 year interval. The optimal starting age for a repeated FIT screening strategy is 50 or 51 hence it is suggested that the screening start age is reduced compared to what is currently used in the BCSP. The optimal upper screening age varies between 65 and 74, depending on the capacity constraint used. The optimal FIT threshold depends on the available capacity for screening referral colonoscopies. With 50,000 screening referral colonoscopies (current capacity) then we recommend a strategy of 2-yearly, age 51-65, FIT161 (8 screens). With 70,000 screening referral colonoscopies (current capacity) then we recommend a strategy of: 2-yearly, age 50-70, FIT153 (11 screens). If 90,000 screening referral colonoscopies is considered feasible to achieve in the future then we recommend a strategy of 2-yearly, age 50-74, FIT124 (13 screens). In terms of bowel scope screening the model found uncertainty in whether it is cost effective to replace one FIT screen with a one-off bowel scope at age 58/59. However, a repeated FIT screening strategy requiring 125k screening referral colonoscopies annually would be far more effective and cost effective than a one-off bowel scope at age 59. Such strategies could be considered to have equivalent ‘endoscopy capacity’ (assuming that 10 bowel scopes and 4 screening referral colonoscopies are equivalent ).Hence, if bowel scope capacity could be used for undertaking screening referral colonoscopies this would result in higher effectiveness and cost-effectiveness

The Madison plasma dynamo experiment: a facility for studying laboratory plasma astrophysics

The Madison plasma dynamo experiment (MPDX) is a novel, versatile, basic plasma research device designed to investigate flow driven magnetohydrodynamic (MHD) instabilities and other high-$\beta$ phenomena with astrophysically relevant parameters. A 3 m diameter vacuum vessel is lined with 36 rings of alternately oriented 4000 G samarium cobalt magnets which create an axisymmetric multicusp that contains $\sim$14 m$^{3}$ of nearly magnetic field free plasma that is well confined and highly ionized $(>50\%)$. At present, 8 lanthanum hexaboride (LaB$_6$) cathodes and 10 molybdenum anodes are inserted into the vessel and biased up to 500 V, drawing 40 A each cathode, ionizing a low pressure Ar or He fill gas and heating it. Up to 100 kW of electron cyclotron heating (ECH) power is planned for additional electron heating. The LaB$_6$ cathodes are positioned in the magnetized edge to drive toroidal rotation through ${\bf J}\times{\bf B}$ torques that propagate into the unmagnetized core plasma. Dynamo studies on MPDX require a high magnetic Reynolds number $Rm > 1000$, and an adjustable fluid Reynolds number $10< Re <1000$, in the regime where the kinetic energy of the flow exceeds the magnetic energy ($M_A^2=($v$/$v$_A)^2 > 1$). Initial results from MPDX are presented along with a 0-dimensional power and particle balance model to predict the viscosity and resistivity to achieve dynamo action.Comment: 14 pages, 13 figure

Linking urban design to sustainability : formal indicators of social urban sustainability field research in Perth, Western Australia

The making of a livable urban community is a complex endeavor. For much of the 20th Century plannersand engineers believed that modern and rational decision-making would create successful cities. Today, political leaders across the globe are considering ways to promote sustainable development and the concepts of New Urbanism are making their way from the drawing board to the ground. While much has changed in the world, the creation of a successful street is as much of an art today as it was in the 1960s.Our work seeks to investigate 'street life' in cities as a crucial factor towards community success. What arethe components of the neighborhood and street form that contributes to the richness of street life? To answer this question we rely on the literature. The aim of the Formal Indicators of Social Urban Sustainability studyis to measure the formal components of a neighborhood and street that theorists have stated important in promoting sustainability. This paper will describe how this concept helps to bridge urban design and sustainability. It will describe the tool and show how this was applied in a comparative assessment of Joondalup and Fremantle, two urban centers in the Perth metropolitan area

Modelling the cost-effectiveness of public awareness campaigns for the early detection of non-small-cell lung cancer

Background: Survival rates in lung cancer in England are significantly lower than in many similar countries. A range of Be Clear on Cancer (BCOC) campaigns have been conducted targeting lung cancer and found to improve the proportion of diagnoses at the early stage of disease. This paper considers the cost-effectiveness of such campaigns, evaluating the effect of both the regional and national BCOC campaigns on the stage distribution of non-small-cell lung cancer (NSCLC) at diagnosis. Methods: A natural history model of NSCLC was developed using incidence data, data elicited from clinical experts and model calibration techniques. This structure is used to consider the lifetime cost and quality-adjusted survival implications of the early awareness campaigns. Incremental cost-effectiveness ratios (ICERs) in terms of additional costs per quality-adjusted life-years (QALYs) gained are presented. Two scenario analyses were conducted to investigate the role of changes in the ‘worried-well’ population and the route of diagnosis that might occur as a result of the campaigns. Results: The base-case theoretical model found the regional and national early awareness campaigns to be associated with QALY gains of 289 and 178 QALYs and ICERs of d13 660 and d18 173 per QALY gained, respectively. The scenarios found that increases in the ‘worried-well’ population may impact the cost-effectiveness conclusions. Conclusions: Subject to the available evidence, the analysis suggests that early awareness campaigns in lung cancer have the potential to be cost-effective. However, significant additional research is required to address many of the limitations of this study. In addition, the estimated natural history model presents previously unavailable estimates of the prevalence and rate of disease progression in the undiagnosed population