AbstractObjectiveTo determine whether coronary computed tomography angiography (CTA) should be performed in patients with any clinical probability of coronary artery disease (CAD), and whether the ...diagnostic performance differs between subgroups of patients.DesignProspectively designed meta-analysis of individual patient data from prospective diagnostic accuracy studies.Data sourcesMedline, Embase, and Web of Science for published studies. Unpublished studies were identified via direct contact with participating investigators.Eligibility criteria for selecting studiesProspective diagnostic accuracy studies that compared coronary CTA with coronary angiography as the reference standard, using at least a 50% diameter reduction as a cutoff value for obstructive CAD. All patients needed to have a clinical indication for coronary angiography due to suspected CAD, and both tests had to be performed in all patients. Results had to be provided using 2×2 or 3×2 cross tabulations for the comparison of CTA with coronary angiography. Primary outcomes were the positive and negative predictive values of CTA as a function of clinical pretest probability of obstructive CAD, analysed by a generalised linear mixed model; calculations were performed including and excluding non-diagnostic CTA results. The no-treat/treat threshold model was used to determine the range of appropriate pretest probabilities for CTA. The threshold model was based on obtained post-test probabilities of less than 15% in case of negative CTA and above 50% in case of positive CTA. Sex, angina pectoris type, age, and number of computed tomography detector rows were used as clinical variables to analyse the diagnostic performance in relevant subgroups.ResultsIndividual patient data from 5332 patients from 65 prospective diagnostic accuracy studies were retrieved. For a pretest probability range of 7-67%, the treat threshold of more than 50% and the no-treat threshold of less than 15% post-test probability were obtained using CTA. At a pretest probability of 7%, the positive predictive value of CTA was 50.9% (95% confidence interval 43.3% to 57.7%) and the negative predictive value of CTA was 97.8% (96.4% to 98.7%); corresponding values at a pretest probability of 67% were 82.7% (78.3% to 86.2%) and 85.0% (80.2% to 88.9%), respectively. The overall sensitivity of CTA was 95.2% (92.6% to 96.9%) and the specificity was 79.2% (74.9% to 82.9%). CTA using more than 64 detector rows was associated with a higher empirical sensitivity than CTA using up to 64 rows (93.4% v 86.5%, P=0.002) and specificity (84.4% v 72.6%, P<0.001). The area under the receiver-operating-characteristic curve for CTA was 0.897 (0.889 to 0.906), and the diagnostic performance of CTA was slightly lower in women than in with men (area under the curve 0.874 (0.858 to 0.890) v 0.907 (0.897 to 0.916), P<0.001). The diagnostic performance of CTA was slightly lower in patients older than 75 (0.864 (0.834 to 0.894), P=0.018 v all other age groups) and was not significantly influenced by angina pectoris type (typical angina 0.895 (0.873 to 0.917), atypical angina 0.898 (0.884 to 0.913), non-anginal chest pain 0.884 (0.870 to 0.899), other chest discomfort 0.915 (0.897 to 0.934)).ConclusionsIn a no-treat/treat threshold model, the diagnosis of obstructive CAD using coronary CTA in patients with stable chest pain was most accurate when the clinical pretest probability was between 7% and 67%. Performance of CTA was not influenced by the angina pectoris type and was slightly higher in men and lower in older patients.Systematic review registrationPROSPERO CRD42012002780.
Alloying of metals provides a vast parameter space for tuning of material, chemical, and mechanical properties, impacting disciplines ranging from photonics and catalysis to aerospace. From an ...optical point-of-view, pure thin metal films yield enhanced light absorption due to their cavity effects. However, an ideal metal–semiconductor photodetector requires not only high absorption, but also long hot carrier attenuation lengths in order to efficiently collect excited carriers. Here we demonstrate that Ag-Au alloys provide an ideal model system for controlling the optical and electrical responses in nanoscale thin metal films for hot carrier photodetectors with improved performance. While pure Ag and Au have long hot carrier attenuation lengths >20 nm, their optical absorption is insufficient for high efficiency devices. Instead, we find that alloying Ag and Au enhances the absorption by ∼50% while maintaining attenuation lengths >15 nm, currently limited by grain boundary scattering, although the electron attenuation length of pure Au outperforms pure Ag as well as all of the alloys investigated here. Further, our density functional theory analysis shows that the addition of small amounts of Au to the Ag lattice significantly enhances the hot hole generation rate. Combined, these findings suggest a route to high efficiency hot carrier devices based on metallic alloying with potential applications ranging from photodetectors and sensors to improved catalytic materials.
Plants and vegetation play a critical-but largely unpredictable-role in global environmental changes due to the multitude of contributing processes at widely different spatial and temporal scales. In ...this Perspective, we explore approaches to master this complexity and improve our ability to predict vegetation dynamics by explicitly taking account of principles that constrain plant and ecosystem behaviour: natural selection, self-organization and entropy maximization. These ideas are increasingly being used in vegetation models, but we argue that their full potential has yet to be realized. We demonstrate the power of natural selection-based optimality principles to predict photosynthetic and carbon allocation responses to multiple environmental drivers, as well as how individual plasticity leads to the predictable self-organization of forest canopies. We show how models of natural selection acting on a few key traits can generate realistic plant communities and how entropy maximization can identify the most probable outcomes of community dynamics in space- and time-varying environments. Finally, we present a roadmap indicating how these principles could be combined in a new generation of models with stronger theoretical foundations and an improved capacity to predict complex vegetation responses to environmental change.
HTLV-1 infection is a neglected disease, despite infecting 10-15 million people worldwide and severe illnesses develop in 10% of carriers lifelong. Acknowledging a greater risk for developing HTLV-1 ...associated illnesses due to immunosuppression, screening is being widely considered in the transplantation setting. Herein, we report the experience with universal HTLV testing of donors and recipients of solid organ transplants in a survey conducted in Spain.
All hospitals belonging to the Spanish HTLV network were invited to participate in the study. Briefly, HTLV antibody screening was performed retrospectively in all specimens collected from solid organ donors and recipients attended since the year 2008.
A total of 5751 individuals were tested for HTLV antibodies at 8 sites. Donors represented 2312 (42.2%), of whom 17 (0.3%) were living kidney donors. The remaining 3439 (59.8%) were recipients. Spaniards represented nearly 80%. Overall, 9 individuals (0.16%) were initially reactive for HTLV antibodies. Six were donors and 3 were recipients. Using confirmatory tests, HTLV-1 could be confirmed in only two donors, one Spaniard and another from Colombia. Both kidneys of the Spaniard were inadvertently transplanted. Subacute myelopathy developed within 1 year in one recipient. The second recipient seroconverted for HTLV-1 but the kidney had to be removed soon due to rejection. Immunosuppression was stopped and 3 years later the patient remains in dialysis but otherwise asymptomatic.
The rate of HTLV-1 is low but not negligible in donors/recipients of solid organ transplants in Spain. Universal HTLV screening should be recommended in all donor and recipients of solid organ transplantation in Spain. Evidence is overwhelming for very high virus transmission and increased risk along with the rapid development of subacute myelopathy.
There is an increasing interest in exploring the opportunities for competitive advantage that arise from reinforcing core competencies and innovative capabilities of the individual companies, and by ...forming integrated supply networks. In complex and dynamic environments such as the automotive and semiconductor industries, managing and co-ordinating the procurement of materials, their transformation into intermediate and finished products, and the distribution to the final customers, are very demanding tasks in terms of information systems. In general, current available software packages do not provide the full support needed for networked and distributed organizations, and are clearly insufficient in what concerns the planning and coordination activities needed in these heterogeneous environments. In order to adequately tackle these problems, this work proposes a multi-agent system architecture for real-time customer-order planning in distributed manufacturing enterprises, addressing the requirements of a make-to-order environment. The present research work resulted from the Co-OPERATE European Project. Enhanced visibility of information, early warning of disturbances, synchronized production and collaborative planning in the supply chain are the general goals of the project. In particular, for aggregate planning and order promising, a distributed and decentralized information system, based on an architecture of agents and extensively using the internet, was designed and implemented. This system aims at responding to the basic requirements of cooperativeness, integration and configurability, and at providing new and more powerful decision support.
Summary Background In September, 2015, the UN General Assembly established the Sustainable Development Goals (SDGs). The SDGs specify 17 universal goals, 169 targets, and 230 indicators leading up to ...2030. We provide an analysis of 33 health-related SDG indicators based on the Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015). Methods We applied statistical methods to systematically compiled data to estimate the performance of 33 health-related SDG indicators for 188 countries from 1990 to 2015. We rescaled each indicator on a scale from 0 (worst observed value between 1990 and 2015) to 100 (best observed). Indices representing all 33 health-related SDG indicators (health-related SDG index), health-related SDG indicators included in the Millennium Development Goals (MDG index), and health-related indicators not included in the MDGs (non-MDG index) were computed as the geometric mean of the rescaled indicators by SDG target. We used spline regressions to examine the relations between the Socio-demographic Index (SDI, a summary measure based on average income per person, educational attainment, and total fertility rate) and each of the health-related SDG indicators and indices. Findings In 2015, the median health-related SDG index was 59·3 (95% uncertainty interval 56·8–61·8) and varied widely by country, ranging from 85·5 (84·2–86·5) in Iceland to 20·4 (15·4–24·9) in Central African Republic. SDI was a good predictor of the health-related SDG index ( r2 =0·88) and the MDG index ( r2 =0·92), whereas the non-MDG index had a weaker relation with SDI ( r2 =0·79). Between 2000 and 2015, the health-related SDG index improved by a median of 7·9 (IQR 5·0–10·4), and gains on the MDG index (a median change of 10·0 6·7–13·1) exceeded that of the non-MDG index (a median change of 5·5 2·1–8·9). Since 2000, pronounced progress occurred for indicators such as met need with modern contraception, under-5 mortality, and neonatal mortality, as well as the indicator for universal health coverage tracer interventions. Moderate improvements were found for indicators such as HIV and tuberculosis incidence, minimal changes for hepatitis B incidence took place, and childhood overweight considerably worsened. Interpretation GBD provides an independent, comparable avenue for monitoring progress towards the health-related SDGs. Our analysis not only highlights the importance of income, education, and fertility as drivers of health improvement but also emphasises that investments in these areas alone will not be sufficient. Although considerable progress on the health-related MDG indicators has been made, these gains will need to be sustained and, in many cases, accelerated to achieve the ambitious SDG targets. The minimal improvement in or worsening of health-related indicators beyond the MDGs highlight the need for additional resources to effectively address the expanded scope of the health-related SDGs. Funding Bill & Melinda Gates Foundation.
We present results of a large-scale, multiepoch optical survey of the Orion OB1 association, carried out with the QUEST camera at the Venezuela National Astronomical Observatory. We identify for the ...first time the widely spread low-mass, young population in the Ori OB1a and OB1b subassociations. Candidate members were picked up by their variability in the V band and position in color-magnitude diagrams. We obtained spectra to confirm membership. In a region spanning ~68 deg2, we found 197 new young stars; of these, 56 are located in the Ori OB1a subassociation and 141 in Ori OB1b. The spatial distribution of the low-mass young stars is spatially coincident with that of the high-mass members but suggests a much sharper edge to the association. Comparison with the spatial extent of molecular gas and extinction maps indicates that the subassociation Ori OB1b is concentrated within a ringlike structure of radius ~2°(~15 pc at 440 pc), centered roughly on the star Ori in the Orion belt. The ring is apparent in 13CO and corresponds to a region with an extinction AV >= 1. The stars exhibiting strong Ha emission, an indicator of active accretion, are found along this ring, whereas the center is populated with weak Ha-emitting stars. In contrast, Ori OB1a is located in a region devoid of gas and dust. We identify a grouping of stars within a ~3 deg2 area located in Ori OB1a, roughly clustered around the B2 star 25 Ori. The Herbig Ae/Be star V346 Ori is also associated with this grouping, which could be an older analog of s Ori. Using several sets of evolutionary tracks, we find an age of 7-10 Myr for Ori OB1a and of ~4-6 Myr for Ori OB1b, consistent with previous estimates from OB stars. Indicators such as the equivalent width of Ha and near-IR excesses show that the number of accreting low-mass stars decreases sharply between Ori OB1b and Ori OB1a. These results indicate that although a substantial fraction of accreting disks remain at ages ~5 Myr, inner disks are essentially dissipated by 10 Myr.
The transatlantic slave trade was the largest forced migration in world history. However, the origins of the enslaved Africans and their admixture dynamics remain unclear. To investigate the ...demographic history of African-descendant Marron populations, we generated genome-wide data (4.3 million markers) from 107 individuals from three African-descendant populations in South America, as well as 124 individuals from six west African populations. Throughout the Americas, thousands of enslaved Africans managed to escape captivity and establish lasting communities, such as the Noir Marron. We find that this population has the highest proportion of African ancestry (∼98%) of any African-descendant population analyzed to date, presumably because of centuries of genetic isolation. By contrast, African-descendant populations in Brazil and Colombia harbor substantially more European and Native American ancestry as a result of their complex admixture histories. Using ancestry tract-length analysis, we detect different dates for the European admixture events in the African-Colombian (1749 CE; confidence interval CI: 1737–1764) and African-Brazilian (1796 CE; CI: 1789–1804) populations in our dataset, consistent with the historically attested earlier influx of Africans into Colombia. Furthermore, we find evidence for sex-specific admixture patterns, resulting from predominantly European paternal gene flow. Finally, we detect strong genetic links between the African-descendant populations and specific source populations in Africa on the basis of haplotype sharing patterns. Although the Noir Marron and African-Colombians show stronger affinities with African populations from the Bight of Benin and the Gold Coast, the African-Brazilian population from Rio de Janeiro has greater genetic affinity with Bantu-speaking populations from the Bight of Biafra and west central Africa.
RAS is a signaling protein associated with the cell membrane that is mutated in up to 30% of human cancers. RAS signaling has been proposed to be regulated by dynamic heterogeneity of the cell ...membrane. Investigating such a mechanism requires near-atomistic detail at macroscopic temporal and spatial scales, which is not possible with conventional computational or experimental techniques. We demonstrate here a multiscale simulation infrastructure that uses machine learning to create a scale-bridging ensemble of over 100,000 simulations of active wild-type KRAS on a complex, asymmetric membrane. Initialized and validated with experimental data (including a new structure of active wild-type KRAS), these simulations represent a substantial advance in the ability to characterize RAS-membrane biology. We report distinctive patterns of local lipid composition that correlate with interfacially promiscuous RAS multimerization. These lipid fingerprints are coupled to RAS dynamics, predicted to influence effector binding, and therefore may be a mechanism for regulating cell signaling cascades.
PDF
