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Although there is a plethora of cancer associated-factors that can ultimately culminate in death (cachexia, organ impairment, metastases, opportunistic infections, etc.), the focal element of every terminal malignancy is the failure of our natural defences to control unlimited cell proliferation. The reasons why our defences apparently lack efficiency is a complex question, potentially indicating that, under Darwinian terms, solutions other than preventing cancer progression are also important contributors. In analogy with host-parasite systems, we propose to call this latter option ‘tolerance’ to cancer. Here, we argue that the ubiquity of oncogenic processes among metazoans is at least partially attributable to both the limitations of resistance mechanisms and to the evolution of tolerance to cancer. Deciphering the ecological contexts of alternative responses to the cancer burden is not a semantic question, but rather a focal point in understanding the evolutionary ecology of host-tumour relationships, the evolution of our defences, as well as why and when certain cancers are likely to be detrimental for survival.
System software subsystems in an unmanned aircraft system share hardware resources due to space, weight, and power constraints. Such subsystems have different criticality, requirements, and failure rates, and can cause undesired interference when sharing the same hardware. A component with high failure rate can reduce the reliability of the system unless a fault containment mechanism is adopted.
This work proposes an asymmetric multiprocessor architecture to establish isolation at the hardware level for distributed implementation of safety-critical subsystems along with user defined payload subsystems on the same hardware with minimally reduced reliability of the system. To achieve that, subsystems are strategically segregated in separate processors, connected to an on-chip protective interconnect for inter-processor communications. A custom watchdog and reset mechanism are implemented to reset a specific processor without affecting the entire system if required. The architecture is demonstrated on a FPGA chip. In addition, an example of an optimised distribution is provided for a specific flight control system with five subsystems.
In this paper, prediction models are proposed which allow the mineralogical characterization of particle systems observed by X-ray micro tomography (XMT). The models are calibrated using 2D image data obtained by a combination of scanning electron microscopy and energy dispersive X-ray spectroscopy in a planar cross-section of the XMT data. To reliably distinguish between different minerals the models are based on multidimensional distributions of certain particle characteristics describing, for example, their size, shape, and texture. These multidimensional distributions are modeled using parametric Archimedean copulas which are able to describe the correlation structure of complex multidimensional distributions with only a few parameters. Furthermore, dimension reduction of the multidimensional vectors of particle characteristics is utilized to make non-parametric approaches such as the computation of distributions via kernel density estimation viable. With the help of such distributions the proposed prediction models are able to distinguish between different types of particles among the entire XMT image.
Late Quaternary landscapes of unglaciated Beringia were largely shaped by ice-wedge polygon tundra. Ice Complex (IC) strata preserve such ancient polygon formations. Here we report on the Yukagir IC from Bol'shoy Lyakhovsky Island in northeastern Siberia and suggest that new radioisotope disequilibria (230Th/U) dates of the Yukagir IC peat confirm its formation during the Marine Oxygen Isotope Stage (MIS) 7a–c interglacial period. The preservation of the ice-rich Yukagir IC proves its resilience to last interglacial and late glacial–Holocene warming. This study compares the Yukagir IC to IC strata of MIS 5, MIS 3, and MIS 2 ages exposed on Bol'shoy Lyakhovsky Island. Besides high intrasedimental ice content and syngenetic ice wedges intersecting silts, sandy silts, the Yukagir IC is characterized by high organic matter (OM) accumulation and low OM decomposition of a distinctive Drepanocladus moss-peat. The Yukagir IC pollen data reveal grass-shrub-moss tundra indicating rather wet summer conditions similar to modern ones. The stable isotope composition of Yukagir IC wedge ice is similar to those of the MIS 5 and MIS 3 ICs pointing to similar atmospheric moisture generation and transport patterns in winter. IC data from glacial and interglacial periods provide insights into permafrost and climate dynamics since about 200 ka.
In the 2015 review paper ‘Petawatt Class Lasers Worldwide’ a comprehensive overview of the current status of high-power facilities of
was presented. This was largely based on facility specifications, with some description of their uses, for instance in fundamental ultra-high-intensity interactions, secondary source generation, and inertial confinement fusion (ICF). With the 2018 Nobel Prize in Physics being awarded to Professors Donna Strickland and Gerard Mourou for the development of the technique of chirped pulse amplification (CPA), which made these lasers possible, we celebrate by providing a comprehensive update of the current status of ultra-high-power lasers and demonstrate how the technology has developed. We are now in the era of multi-petawatt facilities coming online, with 100 PW lasers being proposed and even under construction. In addition to this there is a pull towards development of industrial and multi-disciplinary applications, which demands much higher repetition rates, delivering high-average powers with higher efficiencies and the use of alternative wavelengths: mid-IR facilities. So apart from a comprehensive update of the current global status, we want to look at what technologies are to be deployed to get to these new regimes, and some of the critical issues facing their development.
Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder which frequently persists into adulthood. The primary goal of the current study was to (a) investigate attentional functions of stimulant medication-naïve adults with ADHD, and (b) investigate the effects of 6 weeks of methylphenidate treatment on these functions.
The study was a prospective, non-randomized, non-blinded, 6-week follow-up design with 42 stimulant medication-naïve adult patients with ADHD, and 42 age and parental education-matched healthy controls. Assessments included measures of visual attention, based on Bundesen's Theory of Visual Attention (TVA), which yields five precise measures of aspects of visual attention; general psychopathology; ADHD symptoms; dyslexia screening; and estimates of IQ.
At baseline, significant differences were found between patients and controls on three attentional parameters: visual short-term memory capacity, threshold of conscious perception, and to a lesser extent visual processing speed. Secondary analyses revealed no significant correlations between TVA parameter estimates and severity of ADHD symptomatology. At follow-up, significant improvements were found specifically for visual processing speed; this improvement had a large effect size, and remained when controlling for re-test effects, IQ, and dyslexia screen performance. There were no significant correlations between changes in visual processing speed and changes in ADHD symptomatology.
ADHD in adults may be associated with deficits in three distinct aspects of visual attention. Improvements after 6 weeks of medication are seen specifically in visual processing speed, which could represent an improvement in alertness. Clinical symptoms and visual attentional deficits may represent separate aspects of ADHD in adults.
We report the results of a laboratory experiment based on a
citizen–candidate model with private information about ideal points.
Inefficient political polarization is observed in all treatments;
that is, citizens with extreme ideal points enter as candidates more
often than moderate citizens. Second, less entry occurs, with even
greater polarization, when voters have directional information about
candidates’ ideal points, using ideological party labels.
Nonetheless, this directional information is welfare enhancing
because the inefficiency from greater polarization is outweighed by
lower entry expenses and better voter information. Third, entry
rates are decreasing in group size and the entry cost. These
findings are all implied by properties of the unique symmetric
Bayesian equilibrium cutpoint pair of the entry game.
Quantitatively, we observe too little (too much) entry when the
theoretical entry rates are high (low). This general pattern of
observed biases in entry rates is implied by logit quantal response
In this paper, three-dimensional (3D) image data of ore particle systems is investigated. By combining X-ray microtomography with scanning electron microscope (SEM)-based image analysis, additional information about the mineralogical composition from certain planar sections can be gained. For the analysis of tomographic images of particle systems the extraction of single particles is essential. This is performed with a marker-based watershed algorithm and a post-processing step utilizing a neural network to reduce oversegmentation. The results are validated by comparing the 3D particle-wise segmentation empirically with 2D SEM images, which have been obtained with a different imaging process and segmentation algorithm. Finally, a stereological application is shown, in which planar SEM images are embedded into the tomographic 3D image. This allows the estimation of local X-ray attenuation coefficients, which are material-specific quantities, in the entire tomographic image.
Innovation platforms are fast becoming part of the mantra of agricultural research for development projects and programmes. Their basic tenet is that stakeholders depend on one another to achieve agricultural development outcomes, and hence need a space where they can learn, negotiate and coordinate to overcome challenges and capture opportunities through a facilitated innovation process. Although much has been written on how to implement and facilitate innovation platforms efficiently, few studies support ex-ante appraisal of when and for what purpose innovation platforms provide an appropriate mechanism for achieving development outcomes, and what kinds of human and financial resource investments and enabling environments are required. Without these insights, innovation platforms run the risk of being promoted as a panacea for all problems in the agricultural sector. This study makes clear that not all constraints will require innovation platforms and, if there is a simpler and cheaper alternative, that should be considered first. Based on the review of critical design principles and plausible outcomes of innovation platforms, this study provides a decision support tool for research, development and funding agencies that can enhance more critical thinking about the purposes and conditions under which innovation platforms can contribute to achieving agricultural development outcomes.
Schizophrenia (SZ) and bipolar disorder (BP) are causes of severe disability worldwide and parents’ severe mental illness (SMI) is associated with childhood adversity, and socio-emotional and cognitive problems in children. Yet, how parental BP and SZ affect educational attainment in offspring is still unclear.
We included all children (N = 684.248) born and living in Denmark between 1986 and 1996 and their parents. Our follow-up lasted from 1986 until children's graduation in 2014. The main outcome variable was their school grades following their primary education. School outcomes were divided into four categories: not graduated, low-grade point average (GPA), medium GPA and high GPA. We then performed a multiple logistic regression with medium GPA as the reference category, with the children of parents without SZ or BP as the reference group.
Children of parents with SZ faced higher odds than their peers of not graduating primary education (OR 2.6), along with low GPA (odds ratios (OR) 1.6) and lower odds for a high GPA (OR 0.7). Moreover, it was the children of mothers rather than fathers with BP who had higher odds of not graduating primary education (OR 1.6). Lastly, child placement was associated with lower grades and lower graduation rates, and outcomes for children of parents with SMI were favorable compared with other children placed in care.
For children, parental SZ is associated with lower grades and lower chances for graduating primary education. In contrast, the children of parents with BP were indistinguishable from the reference group regarding school grades. This signifies that specificity of parental severe mental illness is important in relation to educational achievement of children.
Antipsychotics are associated with a polymorphic ventricular tachycardia, torsades de pointes, which, in the worst case, can lead to sudden cardiac death. The QT interval corrected for heart rate (QTc) is used as a clinical proxy for torsades de pointes. The QTc interval can be prolonged by antipsychotic monotherapy, but it is unknown if the QTc interval is prolonged further with antipsychotic polypharmaceutical treatment. Therefore, this study investigated the associations between QTc interval and antipsychotic monotherapy and antipsychotic polypharmaceutical treatment in schizophrenia, and measured the frequency of QTc prolongation among patients.
We carried out an observational cohort study of unselected patients with schizophrenia visiting outpatient facilities in the region of Central Jutland, Denmark. Patients were enrolled from January of 2013 to June of 2015, with follow-up until June of 2015. Data were collected from clinical interviews and clinical case records.
Electrocardiograms were available for 65 patients, and 6% had QTc prolongation. We observed no difference in average QTc interval for the whole sample of patients receiving no antipsychotics, antipsychotic monotherapy, or antipsychotic polypharmaceutical treatment (p=0.29). However, women presented with a longer QTc interval when receiving polypharmacy than when receiving monotherapy (p=0.01). A limitation of this study was its small sample size.
We recommend an increased focus on monitoring the QTc interval in women with schizophrenia receiving antipsychotics as polypharmacy.
The presence of interfaces and geometrical confinement can have a strong influence on the structure and morphology of thin films of semicrystalline polymers. Using surface-sensitive grazing incidence wide angle X-ray scattering and atomic force microscopy to investigate the vertical structure of thin films of poly(3-hexylthiophene) crystallized from the melt, we show that highly oriented crystallites are induced at the air/polymer interface and not as sometimes assumed at the interface to the substrate. These crystallites are oriented with their crystallographic a-axis perpendicular to the plane of the film. While the corresponding orientation dominates in thinner films, for sufficiently thick films (>60 nm) a layer containing unoriented crystals is present below the surface layer. Due to the anisotropic charge transport properties, the observed effects are expected to be of special relevance for potential applications of semiconductor polymers in the field of organic photovoltaics for which vertical transport in thicker films plays an important role.
We report on a target system supporting automated positioning of nano-targets with a precision resolution of
in three dimensions. It relies on a confocal distance sensor and a microscope. The system has been commissioned to position nanometer targets with 1 Hz repetition rate. Integrating our prototype into the table-top ATLAS 300 TW-laser system at the Laboratory for Extreme Photonics in Garching, we demonstrate the operation of a 0.5 Hz laser-driven proton source with a shot-to-shot variation of the maximum energy about 27% for a level of confidence of 0.95. The reason of laser shooting experiments operated at 0.5 Hz rather than 1 Hz is because the synchronization between the nano-foil target positioning system and the laser trigger needs to improve.
Right heart function is an important predictor of morbidity and mortality in pulmonary arterial hypertension and many CHD. We investigated whether treatment with the prostacyclin analogue treprostinil could prevent pressure overload-induced right ventricular hypertrophy and failure.
Male Wistar rats were randomised to severe pulmonary trunk banding with a 0.5-mm banding clip (n=41), moderate pulmonary trunk banding with a 0.6-mm banding clip (n=36), or sham procedure (n=10). The banded rats were randomised to 6 weeks of treatment with a moderate dose of treprostinil (300 ng/kg/minute), a high dose of treprostinil (900 ng/kg/minute), or vehicle.
Pulmonary trunk banding effectively induced hypertrophy, dilatation, and decreased right ventricular function. The severely banded animals presented with decompensated heart failure with extracardial manifestations. Treatment with treprostinil neither reduced right ventricular hypertrophy nor improved right ventricular function.
In the pulmonary trunk banding model of pressure overload-induced right ventricular hypertrophy and failure, moderate- and high-dose treatment with treprostinil did not improve right ventricular function neither in compensated nor in decompensated right heart failure.
We discuss the stellar halos of massive elliptical galaxies, as revealed by our ambitious integral-field spectroscopic survey MASSIVE. We show that metallicity drops smoothly as a function of radius out to ~ 2.5 Re, while the [α/Fe] abundance ratios stay flat. The stars in the outskirts likely formed rapidly (to explain the high ratio of alpha to Fe) but in a relatively shallow potential (to explain the low metallicities). This is consistent with expectations for a two-phase growth of massive galaxies, in which the second phase involves accretion of small satellites. We also show some preliminary study of the gas content of these most MASSIVE galaxies.
A connection between microscopic structure and macroscopic properties is expected for almost all material systems. High-resolution transmission electron microscopy is a technique offering insight into the atomic structure, but the analysis of large image series can be time consuming. The present work describes a method to automatically estimate the atomic structure in two-dimensional materials. As an example graphene is chosen, in which the positions of the carbon atoms are reconstructed. Lattice parameters are extracted in the frequency domain and an initial atom positioning is estimated. Next, a plausible neighborhood structure is estimated. Finally, atom positions are adjusted by simulation of a Markov random field model, integrating image evidence and the strong geometric prior. A pristine sample with high regularity and a sample with an induced hole are analyzed. False discovery rate-controlled large-scale simultaneous hypothesis testing is used as a statistical framework for interpretation of results. The first sample yields, as expected, a homogeneous distribution of carbon–carbon (C–C) bond lengths. The second sample exhibits regions of shorter C–C bond lengths with a preferred orientation, suggesting either strain in the structure or a buckling of the graphene sheet. The precision of the method is demonstrated on simulated model structures and by its application to multiple exposures of the two graphene samples.