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Brain tumor behavior is driven by aberrations in the genome and epigenome. Many of these changes, such as IDH mutations in diffuse low-grade glioma (DLGG), are common amongst the same class of tumour and can be incorporated into the diagnostic criteria. However, any given tumor may have other, less common genomic aberrations that are essential for its biological behavior and may inform on underlying aberrant cellular pathways, and potential therapeutic agents. Precision oncology is a genomics-based approach which profiles these alterations to better manage cancer patients and has established itself within the practice of oncology and is slowly making its way into neuro-oncology. The BC Cancer’s Personalized OncoGenomics (POG) program has profiled 16 adult tumours originating from the central nervous system using whole genome and transcriptome analysis (WGTA), for the first time, within a meaningful clinical timeframe/setting. As expected, primary genomic drivers were consistent with their respective diagnoses, though secondary drivers were found to be unique to each tumour. Although these analyses did not result in altered clinical management for these patients, primarily due to availability of drug or clinical trials, they highlight the heterogeneity of secondary drivers in cancers and provide clinicians with meaningful biological information. Lastly, the data generated by POG has highlighted the frequency and complexity of novel driver fusions which are predicted to behave similarly to canonical driver events in their respective tumours. The information available to clinicians through POG has provided paramount knowledge into the biology of each unique tumour.
Simulation models are used widely in pharmacology, epidemiology and health economics (HEs). However, there have been no attempts to incorporate models from these disciplines into a single integrated model. Accordingly, we explored this linkage to evaluate the epidemiological and economic impact of oseltamivir dose optimisation in supporting pandemic influenza planning in the USA. An HE decision analytic model was linked to a pharmacokinetic/pharmacodynamics (PK/PD) – dynamic transmission model simulating the impact of pandemic influenza with low virulence and low transmissibility and, high virulence and high transmissibility. The cost-utility analysis was from the payer and societal perspectives, comparing oseltamivir 75 and 150 mg twice daily (BID) to no treatment over a 1-year time horizon. Model parameters were derived from published studies. Outcomes were measured as cost per quality-adjusted life year (QALY) gained. Sensitivity analyses were performed to examine the integrated model's robustness. Under both pandemic scenarios, compared to no treatment, the use of oseltamivir 75 or 150 mg BID led to a significant reduction of influenza episodes and influenza-related deaths, translating to substantial savings of QALYs. Overall drug costs were offset by the reduction of both direct and indirect costs, making these two interventions cost-saving from both perspectives. The results were sensitive to the proportion of inpatient presentation at the emergency visit and patients’ quality of life. Integrating PK/PD–EPI/HE models is achievable. Whilst further refinement of this novel linkage model to more closely mimic the reality is needed, the current study has generated useful insights to support influenza pandemic planning.
Since Esping-Andersen classified the 18 Organization for Economic Co-operation and Development (OECD) countries into the “three worlds of welfare capitalism” in 1990, the comparative studies of welfare have been dominated by the responses to this study. This paper focuses on two of these responses. The first response is concerned with the gender insensitivity of Esping-Andersen's way of categorizing the welfare regimes. The second response is concerned with the issue that the East Asian countries are under-represented in the 18 OECD countries. To make contributions to these responses, two analytical tasks are conducted. First, we build new defamilisation typologies covering both East Asian countries and OECD countries. Second, we demonstrate that the evidence generated from the typologies suggest that some of the indispensable conditions for the development of a Confucian welfare regime do not exist.
To reduce nationwide door-to-balloon times (DTB) in patients presenting with acute ST-elevation myocardial infarction (STEMI) requiring primary percutaneous coronary intervention (PCI), by adoption of pre-hospital wireless 12-lead electrocardiogram (ECG) transmission by Singapore's national ambulance service.
A phased, prospective, before-after, interventional study of all patients who presented to the national ambulance service with the diagnosis of STEMI. In the ‘Before’ phase, chest pain patients only received 12-lead ECGs on arrival at the Emergency Departments (ED), where diagnosis of STEMI could be made. In the ‘After’ phase, 12-lead ECGs were performed in the field by ambulance crews and transmitted while en-route to the hospitals. Diagnoses of STEMI was made by on-duty emergency physicians (EP) prior to patients' arrival and PCI activated. Data was collected from ambulance run sheets, ECG transmission logs, EDs and cardiology units.
451 eligible patients from “Before” and 214 patients from “After” phase were included in the analysis. Median DTB time was 88 minutes in the “Before” and 52 minutes in the “After” phase (p = 0.0001). During office hours, median DTB times for ‘Before’ and ‘After’ phases were 84 minutes and 47 minutes, respectively (p = 0.0001). After office hours, median DTB times for ‘Before’ and ‘After’ phases were 95 minutes and 54 minutes, respectively (p = 0.0001). There were 11 false positive activations in “Before” phase and one in the “After” phase.
Pre-hospital ECG transmission resulted in significant reduction of DTB time; this effect occurred regardless of whether patients presented to the ED before or after office hours. No increase in false activations was found in the “After” phase. Pre-hospital ECG transmission should be adopted as “standard of care” for all STEMI cases meeting the criteria for PCI.
Layers that enhance light scattering and Raman-scattering-based spectral modification for solar cell applications were investigated. Titanium-oxide based rear diffuse reflector were found to increase the long wavelength response of crystalline solar cells. Also particle within the Titanium-oxide produce a far greater Stokes and anti-Stokes shift when compared to bulk crystal counterparts. The anti-Stokes to Stokes shift ratio in these particle systems is also greater and increased with increasing probe or bias light intensity. When applied to solar cells these layers extend the red response and thereby increase the overall performance.
A detailed analysis of photovoltaic front surface phosphor-based spectral modification and light scattering by hetero-structure was conducted. Phosphor based spectral downconversion is a well known laser technology. The analysis assumes that both sunlight energy and photovoltaic performance are at peak sunlight photon flux within the spectral range. Further, the analysis presented here indicates that parasitic losses and light scattering within the spectral range are large enough to offset any expected gains. For example, analysis of up-conversion phosphor-based approaches indicates that these are likely to suffer unexpectedly large losses in the peak spectral region due to parasitic absorption when attempting to down convert UV light.
Ruminant dung is a highly ephemeral, patchily distributed resource, which is used by a diverse community of invertebrate species. In such environments, high levels of insect aggregation may be important in facilitating stability and coexistence across patchily distributed populations. The aim of the present work was to quantify the aggregation of the insects colonising cow-dung in cattle pasture in southwest England and to test the hypothesis that the dung-pat community assemblage observed was the result of stochastic colonization. This was examined using batches of ten standardised, 1.5 kg, artificial cow pats placed out in cattle pastures in each of 24 weeks between May and October in 2001. Pats were left exposed in the field for seven days before being brought back to the laboratory, where any insect colonizers were collected and identified. Individual pats contained, on average, only half the number of insect taxa present in an entire batch put out at any one time. All larval coleopteran taxa, 20 of the 22 adult coleopteran taxa and 22 of the 23 dipteran taxa, showed significant aggregation, with the abundance of most taxa within pats approximating a negative binomial distribution. A simulation analysis was used to show that the observed relative frequency of taxa within pats did not differ from that expected by chance if colonisation is a random binomial event in which each species colonises a pat independently of all other species. Aggregated populations, of even highly abundant insects, may be more susceptible to the deleterious effects of insecticidal contaminants in dung than if they were evenly distributed, if by chance they colonize a pat containing insecticidal residues from a recently treated animal.
The optical and electrical properties of “tilted” and “spiral” indium tin oxide (ITO) thin films are reported. The influence of the flux incident angle on the optical and electrical properties is investigated. When the flux incident angle is increased, both the refractive index and extinction coefficient of the film are decreased, but the resistivity is increased. Thus, the physical properties of the film can be modified over a wide range by adjusting the flux incident angle and substrate rotation scheme. It is suggested that the oblique angle deposition technique provides ITO films with more application possibilities by allowing their optical and electrical properties to be tailored.
The seasonal abundance and reproductive output of two common, but little studied, dung-breeding flies, Neomyia cornicina and N. viridescens, were examined in artificial cow pats in pastures in southwest England in 2001 and 2004. In 2001, the numbers of both Neomyia species increased slowly over summer to show a sharp seasonal peak in late August and early September. There was no significant effect of mean temperature, mean relative humidity or dung water content on abundance or seasonally de-trended abundance. High levels of aggregation were seen between pats and, when present, greater numbers of N. cornicina emerged than N. viridescens. Neomyia cornicina was present in 13% of 240 artificial standardized pats put out in 2001, at a median of 19 adults per colonized pat; N. viridescens was present in 8% of artificial pats at a median of three adults per colonized pat. In 2004, N. cornicina emerged from 46% of the 94 artificial pats put out at a median of three adults per colonized pat, while N. viridescens emerged from only 12% of pats at a median of one adult per colonized pat. Flies were also collected in 2004, using sticky-traps and hand nets. Again, free-flying N. cornicina appeared to be more abundant in the field than N. viridescens; 162 N. cornicina were caught compared to 44 N. viridescens over the same sampling period. The size of each adult female was recorded and ovarian dissection was used to determine the numbers of eggs matured. Female N. viridescens were significantly larger than the N. cornicina and matured significantly higher numbers of eggs. Gravid N. viridescens matured a mean of 37.1 (±16.9) eggs, whereas gravid N. cornicina matured a mean of 28.8 (±13.2) eggs. The reasons why the larger, more fecund, N. viridescens adults are less abundant in the field or emerging from pats than N. cornicina are unknown. Further work is required to identify the nature and cause of the mortality experienced by the larvae of these species and the ecological differences and functional specialisation which allows co-existence to be maintained.
The rate of dung-pat degradation in cattle pastures in south west England was examined between May and September 2002, using batches of standardized, 1.5 kg, artificially-formed cow pats. In pats in which insects were allowed free access, the rate of disappearance, measured as ash-free dry weight, was faster in spring than summer and the loss of organic matter ranged between 0.69 and 1.99% per day, equating to an estimated time for complete disappearance of 57–78 and 88–111 days in spring and summer, respectively. To assess the role of colonizing insects on decomposition, six batches of pats were constructed and either left uncovered or, using fine mesh cages, were covered for 2, 7 or 14 days following deposition to exclude colonizing insects, after which they were uncovered. After 35 days all pats were then retrieved from the field, the composition of the invertebrate community within each pat was determined and the degree of degradation, measured as ash-free dry weight, was assessed. Covered pats had significantly higher rates of ash-free dry weight loss than uncovered pats. From the 180 pats that were recovered and searched, larvae of Aphodius (Coleoptera: Scarabaeidae) were the most numerous taxon collected (1435 individuals). Aphodius larvae were significantly more abundant in pats that remained uncovered or were covered for 2 days only, compared to pats that had been covered for 7 or 14 days. The results show that the exclusion of insects for as little as two days following deposition causes a significant reduction in both the insect population and the subsequent rate of pat degradation.
There are few reports of non-cryogenic preservation methods for marine invertebrates, so potable alcohol and acetone-based nail varnish remover (NVR) are for the first time evaluated against absolute ethanol as short-term preservatives of whole barnacles. Performance of ethanol and NVR-preserved material was comparable, but potable alcohol was significantly worse. These results are of practical importance for fieldwork in remote areas where laboratory chemicals are unattainable but potable alcohol or NVR are locally available. Of these, acetone-based NVR would be the solvent of preference.
We describe the next set of experiments proposed in the U.S. Heavy
Ion Fusion Virtual National Laboratory, the so-called Integrated Beam
Experiment (IBX). The purpose of IBX is to investigate in an integrated
manner the processes and manipulations necessary for a heavy ion fusion
induction accelerator. The IBX experiment will demonstrate injection,
acceleration, compression, bending, and final focus of a heavy ion beam
at significant line charge density. Preliminary conceptual designs are
presented and issues and trade-offs are discussed. Plans are also
described for the step after IBX, the Integrated Research Experiment
(IRE), which will carry out significant target experiments.
This article presents analytical and simulation studies of
intense heavy ion beam propagation, including the injection,
acceleration, transport and compression phases, and beam transport
and focusing in background plasma in the target chamber. Analytical
theory and simulations that support the High Current Experiment
(HCX), the Neutralized Transport Experiment (NTX), and the advanced
injector development program, are being used to provide a basic
understanding of the nonlinear beam dynamics and collective
processes, and to develop design concepts for the next-step
Integrated Beam Experiment (IBX), an Integrated Research Experiment
(IRE), and a heavy ion fusion driver. Three-dimensional nonlinear
perturbative simulations have been applied to collective
instabilities driven by beam temperature anisotropy, and to
two-stream interactions between the beam ions and any unwanted
background electrons; three-dimensional particle-in-cell
simulations of the 2-MV electrostatic quadrupole (ESQ) injector
have clarified the influence of pulse rise time; analytical
studies and simulations of the drift compression process have
been carried out; syntheses of a four-dimensional particle
distribution function from phase-space projections have been
developed; and studies of the generation and trapping of stray
electrons in the beam self-fields have been performed.
Particle-in-cell simulations, involving preformed plasma, are
being used to study the influence of charge and current
neutralization on the focusing of the ion beam in NTX and in
a fusion chamber.
Significant experimental and theoretical progress has been
made in the U.S. heavy ion fusion program on high-current sources,
transport, and focusing. Currents over 200 mA have been transported
through a matching section and 10 half-lattice periods with
electric quadrupoles. An experiment shows control of high-beam
current with an aperture, while avoiding secondary electrons.
New theory and simulations of the neutralization of intense
beam space charge with plasma in various focusing chamber
configurations predict that near-emittance-limited beam focal
spot sizes can be obtained even with beam perveance (ratio of
beam space potential to ion energy) >10× higher than
in earlier HIF focusing experiments. Progress in a new focusing
experiment with plasma neutralization up to 10−3
perveance, and designs for a next-step experiment to study beam
brightness evolution from source to target are described.
M-plane GaN(1100) is grown by plasma assisted molecular beam epitaxy on ZnO(1100) substrates. A low-temperature GaN buffer layer is found to be necessary to obtain good structural quality of the films. Well oriented (1100) GaN films are obtained, with a slate like surface morphology. On the GaN(1100) surfaces, reconstructions with symmetry of c(2×2) and approximate “4×5” are found under N- and Ga-rich conditions, respectively. We propose a model for Ga-rich conditions with the “4×5” structure consisting of ≥ 2 monolayers of Ga terminating the GaN surface.
We report soft X-ray spectra (4–18 nm) produced by the
interaction of 25–100-fs laser pulses at an intensity of up
to 7 × 1016 W/cm2 with a cryogenically
cooled Ar gas jet. New spectral lines from Ar8+,
Ar9+, and Ar10+ charge states appeared
with decreasing preexpansion gas temperature. A nonlinear increase
of X-ray line emission from Ar7+, Ar8+, and
Ar9+ was observed with cooling, which saturated below a
certain temperature. The drastic change in the spectrum is attributed
to efficient collisional heating and collisional ionization of growing,
small- to medium-sized (102–103 atoms) Ar
clusters from the cooled jet. When the laser pulse was extended from 25
to 100 fs we observed considerably stronger emission on lines from high
charge states, such as Ar8+, Ar9+, and
Ar10+, which suggests that the resonance absorption condition
could be reached for the 100-fs pulse.
Temperature programmed desorption (TPD) was performed on deuterated GaN(0001) surfaces which had been exposed to various doses of 90-eV electrons. TPD of the deuterated surface without electron exposure shows a broad D2 desorption feature with a peak desorption temperature at ∼400 °C. Electron exposure results in a decrease in intensity of the desorption peak which is attributed to removal of surface deuterium by electron stimulated desorption (ESD). This removal of deuterium by ESD produces no change in the peak desorption temperature indicating that recombinative desorption is first order in deuterium coverage.