2,407 research outputs found
Sensitive and specific multi-cancer detection and localization using methylation signatures in cell-free DNA
Background:
Early cancer detection could identify tumors at a time when outcomes are superior and treatment is less morbid. This prospective case-control sub-study (from NCT02889978 and NCT03085888) assessed the performance of targeted methylation analysis of circulating cell-free DNA (cfDNA) to detect and localize multiple cancer types across all stages at high specificity.
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Participants and methods:
The 6689 participants [2482 cancer (>50 cancer types), 4207 non-cancer] were divided into training and validation sets. Plasma cfDNA underwent bisulfite sequencing targeting a panel of >100 000 informative methylation regions. A classifier was developed and validated for cancer detection and tissue of origin (TOO) localization.
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Results:
Performance was consistent in training and validation sets. In validation, specificity was 99.3% [95% confidence interval (CI): 98.3% to 99.8%; 0.7% false-positive rate (FPR)]. Stage IâIII sensitivity was 67.3% (CI: 60.7% to 73.3%) in a pre-specified set of 12 cancer types (anus, bladder, colon/rectum, esophagus, head and neck, liver/bile-duct, lung, lymphoma, ovary, pancreas, plasma cell neoplasm, stomach), which account for âŒ63% of US cancer deaths annually, and was 43.9% (CI: 39.4% to 48.5%) in all cancer types. Detection increased with increasing stage: in the pre-specified cancer types sensitivity was 39% (CI: 27% to 52%) in stage I, 69% (CI: 56% to 80%) in stage II, 83% (CI: 75% to 90%) in stage III, and 92% (CI: 86% to 96%) in stage IV. In all cancer types sensitivity was 18% (CI: 13% to 25%) in stage I, 43% (CI: 35% to 51%) in stage II, 81% (CI: 73% to 87%) in stage III, and 93% (CI: 87% to 96%) in stage IV. TOO was predicted in 96% of samples with cancer-like signal; of those, the TOO localization was accurate in 93%.
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Conclusions:
cfDNA sequencing leveraging informative methylation patterns detected more than 50 cancer types across stages. Considering the potential value of early detection in deadly malignancies, further evaluation of this test is justified in prospective population-level studies
The gradient of potential vorticity, quaternions and an orthonormal frame for fluid particles
The gradient of potential vorticity (PV) is an important quantity because of
the way PV (denoted as ) tends to accumulate locally in the oceans and
atmospheres. Recent analysis by the authors has shown that the vector quantity
\bdB = \bnabla q\times \bnabla\theta for the three-dimensional incompressible
rotating Euler equations evolves according to the same stretching equation as
for \bom the vorticity and \bB, the magnetic field in magnetohydrodynamics
(MHD). The \bdB-vector therefore acts like the vorticity \bom in Euler's
equations and the \bB-field in MHD. For example, it allows various analogies,
such as stretching dynamics, helicity, superhelicity and cross helicity. In
addition, using quaternionic analysis, the dynamics of the \bdB-vector
naturally allow the construction of an orthonormal frame attached to fluid
particles\,; this is designated as a quaternion frame. The alignment dynamics
of this frame are particularly relevant to the three-axis rotations that
particles undergo as they traverse regions of a flow when the PV gradient
\bnabla q is large.Comment: Dedicated to Raymond Hide on the occasion of his 80th birthda
precision mathematics and approximation mathematics the conceptual and educational role of their comparison
The relationship between applied and pure mathematics is of utmost concern for Klein. Examples from Volume III of his "Elementarmathematik" illustrate how, starting from an intuitive and sometimes practical approach, Klein develops abstract concepts working in rich "mathematical environments". The examples concern the concept of empirical function and its comparison with an idealised curve, point sets obtained through circular inversion that lead to compare rational numbers and real numbers, and the "continuous" transformation of curves with the help of a point moving in space
Chiral tunneling and the Klein paradox in graphene
The so-called Klein paradox - unimpeded penetration of relativistic particles
through high and wide potential barriers - is one of the most exotic and
counterintuitive consequences of quantum electrodynamics (QED). The phenomenon
is discussed in many contexts in particle, nuclear and astro- physics but
direct tests of the Klein paradox using elementary particles have so far proved
impossible. Here we show that the effect can be tested in a conceptually simple
condensed-matter experiment by using electrostatic barriers in single- and
bi-layer graphene. Due to the chiral nature of their quasiparticles, quantum
tunneling in these materials becomes highly anisotropic, qualitatively
different from the case of normal, nonrelativistic electrons. Massless Dirac
fermions in graphene allow a close realization of Klein's gedanken experiment
whereas massive chiral fermions in bilayer graphene offer an interesting
complementary system that elucidates the basic physics involved.Comment: 15 pages, 4 figure
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Linking farmer and beekeeper preferences with ecological knowledge to improve crop pollination
1. Pollination by insects is a key input into many crops, with managed honeybees often being hired to support pollination services. Despite substantial research into pollination management, no European studies have yet explored how and why farmers managed pollination services and few have explored why beekeepers use certain crops.
2. Using paired surveys of beekeepers and farmers in 10 European countries, this study examines beekeeper and farmer perceptions and motivations surrounding crop pollination.
3. Almost half of the farmers surveyed believed they had pollination service deficits in one or more of their crops.
4. Less than a third of farmers hired managed pollinators, however most undertook at least one form of agri-environment management known to benefit pollinators, although few did so to promote pollinators.
5. Beekeepers were ambivalent towards many mass flowering crops, with some beekeepers using crops for their honey that other beekeepers avoid because of perceived pesticide risks.
6. The findings highlight a number of largely overlooked knowledge gaps that will affect knowledge exchange and co-operation between the two groups
Long-range transfer of electron-phonon coupling in oxide superlattices
The electron-phonon interaction is of central importance for the electrical
and thermal properties of solids, and its influence on superconductivity,
colossal magnetoresistance, and other many-body phenomena in
correlated-electron materials is currently the subject of intense research.
However, the non-local nature of the interactions between valence electrons and
lattice ions, often compounded by a plethora of vibrational modes, present
formidable challenges for attempts to experimentally control and theoretically
describe the physical properties of complex materials. Here we report a Raman
scattering study of the lattice dynamics in superlattices of the
high-temperature superconductor and the
colossal-magnetoresistance compound that suggests
a new approach to this problem. We find that a rotational mode of the MnO
octahedra in experiences pronounced
superconductivity-induced lineshape anomalies, which scale linearly with the
thickness of the layers over a remarkably long range of
several tens of nanometers. The transfer of the electron-phonon coupling
between superlattice layers can be understood as a consequence of long-range
Coulomb forces in conjunction with an orbital reconstruction at the interface.
The superlattice geometry thus provides new opportunities for controlled
modification of the electron-phonon interaction in complex materials.Comment: 13 pages, 4 figures. Revised version to be published in Nature
Material
Two Energy Scales and two Quasiparticle Dynamics in the Superconducting State of Underdoped Cuprates
The superconducting state of underdoped cuprates is often described in terms
of a single energy-scale, associated with the maximum of the (d-wave) gap.
Here, we report on electronic Raman scattering results, which show that the gap
function in the underdoped regime is characterized by two energy scales,
depending on doping in opposite manners. Their ratios to the maximum critical
temperature are found to be universal in cuprates. Our experimental results
also reveal two different quasiparticle dynamics in the underdoped
superconducting state, associated with two regions of momentum space: nodal
regions near the zeros of the superconducting gap and antinodal regions. While
antinodal quasiparticles quickly loose coherence as doping is reduced, coherent
nodal quasiparticles persist down to low doping levels. A theoretical analysis
using a new sum-rule allows us to relate the low-frequency-dependence of the
Raman response to the temperature-dependence of the superfluid density, both
controlled by nodal excitations.Comment: 16 pages, 5 figure
Shaping bursting by electrical coupling and noise
Gap-junctional coupling is an important way of communication between neurons
and other excitable cells. Strong electrical coupling synchronizes activity
across cell ensembles. Surprisingly, in the presence of noise synchronous
oscillations generated by an electrically coupled network may differ
qualitatively from the oscillations produced by uncoupled individual cells
forming the network. A prominent example of such behavior is the synchronized
bursting in islets of Langerhans formed by pancreatic \beta-cells, which in
isolation are known to exhibit irregular spiking. At the heart of this
intriguing phenomenon lies denoising, a remarkable ability of electrical
coupling to diminish the effects of noise acting on individual cells.
In this paper, we derive quantitative estimates characterizing denoising in
electrically coupled networks of conductance-based models of square wave
bursting cells. Our analysis reveals the interplay of the intrinsic properties
of the individual cells and network topology and their respective contributions
to this important effect. In particular, we show that networks on graphs with
large algebraic connectivity or small total effective resistance are better
equipped for implementing denoising. As a by-product of the analysis of
denoising, we analytically estimate the rate with which trajectories converge
to the synchronization subspace and the stability of the latter to random
perturbations. These estimates reveal the role of the network topology in
synchronization. The analysis is complemented by numerical simulations of
electrically coupled conductance-based networks. Taken together, these results
explain the mechanisms underlying synchronization and denoising in an important
class of biological models
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Mediterranean Sea response to climate change in an ensemble of twenty first century scenarios
The Mediterranean climate is expected to become warmer and drier during the twenty-first century. Mediterranean Sea response to climate change could be modulated by the choice of the socio-economic scenario as well as the choice of the boundary conditions mainly the Atlantic hydrography, the river runoff and the atmospheric fluxes. To assess and quantify the sensitivity of the Mediterranean Sea to the twenty-first century climate change, a set of numerical experiments was carried out with the regional ocean model NEMOMED8 set up for the Mediterranean Sea. The model is forced by airâsea fluxes derived from the regional climate model ARPEGE-Climate at a 50-km horizontal resolution. Historical simulations representing the climate of the period 1961â2000 were run to obtain a reference state. From this baseline, various sensitivity experiments were performed for the period 2001â2099, following different socio-economic scenarios based on the Special Report on Emissions Scenarios. For the A2 scenario, the main three boundary forcings (river runoff, near-Atlantic water hydrography and airâsea fluxes) were changed one by one to better identify the role of each forcing in the way the ocean responds to climate change. In two additional simulations (A1B, B1), the scenario is changed, allowing to quantify the socio-economic uncertainty. Our 6-member scenario simulations display a warming and saltening of the Mediterranean. For the 2070â2099 period compared to 1961â1990, the sea surface temperature anomalies range from +1.73 to +2.97 °C and the SSS anomalies spread from +0.48 to +0.89. In most of the cases, we found that the future Mediterranean thermohaline circulation (MTHC) tends to reach a situation similar to the eastern Mediterranean Transient. However, this response is varying depending on the chosen boundary conditions and socio-economic scenarios. Our numerical experiments suggest that the choice of the near-Atlantic surface water evolution, which is very uncertain in General Circulation Models, has the largest impact on the evolution of the Mediterranean water masses, followed by the choice of the socio-economic scenario. The choice of river runoff and atmospheric forcing both have a smaller impact. The state of the MTHC during the historical period is found to have a large influence on the transfer of surface anomalies toward depth. Besides, subsurface currents are substantially modified in the Ionian Sea and the Balearic region. Finally, the response of thermosteric sea level ranges from +34 to +49 cm (2070â2099 vs. 1961â1990), mainly depending on the Atlantic forcing
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