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Considerations for Observational Research Using Large Data Sets in Radiation Oncology

The radiation oncology community has witnessed growing interest in observational research conducted using large-scale data sources such as registries and claims-based data sets. With the growing emphasis on observational analyses in health care, the radiation oncology community must possess a sophisticated understanding of the methodological considerations of such studies in order to evaluate evidence appropriately to guide practice and policy. Because observational research has unique features that distinguish it from clinical trials and other forms of traditional radiation oncology research, the International Journal of Radiation Oncology, Biology, Physics assembled a panel of experts in health services research to provide a concise and well-referenced review, intended to be informative for the lay reader, as well as for scholars who wish to embark on such research without prior experience. This review begins by discussing the types of research questions relevant to radiation oncology that large-scale databases may help illuminate. It then describes major potential data sources for such endeavors, including information regarding access and insights regarding the strengths and limitations of each. Finally, it provides guidance regarding the analytical challenges that observational studies must confront, along with discussion of the techniques that have been developed to help minimize the impact of certain common analytical issues in observational analysis. Features characterizing a well-designed observational study include clearly defined research questions, careful selection of an appropriate data source, consultation with investigators with relevant methodological expertise, inclusion of sensitivity analyses, caution not to overinterpret small but significant differences, and recognition of limitations when trying to evaluate causality. This review concludes that carefully designed and executed studies using observational data that possess these qualities hold substantial promise for advancing our understanding of many unanswered questions of importance to the field of radiation oncology.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Force-controlled absorption in a fully-nonlinear numerical wave tank

An active control methodology for the absorption of water waves in a numerical wave tank is introduced. This methodology is based upon a force-feedback technique which has previously been shown to be very effective in physical wave tanks. Unlike other methods, an a-priori knowledge of the wave conditions in the tank is not required; the absorption controller being designed to automatically respond to a wide range of wave conditions. In comparison to numerical sponge layers, effective wave absorption is achieved on the boundary, thereby minimising the spatial extent of the numerical wave tank. In contrast to the imposition of radiation conditions, the scheme is inherently capable of absorbing irregular waves. Most importantly, simultaneous generation and absorption can be achieved. This is an important advance when considering inclusion of reflective bodies within the numerical wave tank. In designing the absorption controller, an infinite impulse response filter is adopted, thereby eliminating the problem of non-causality in the controller optimisation. Two alternative controllers are considered, both implemented in a fully-nonlinear wave tank based on a multiple-flux boundary element scheme. To simplify the problem under consideration, the present analysis is limited to water waves propagating in a two-dimensional domain. The paper presents an extensive numerical validation which demonstrates the success of the method for a wide range of wave conditions including regular, focused and random waves. The numerical investigation also highlights some of the limitations of the method, particularly in simultaneously generating and absorbing large amplitude or highly-nonlinear waves. The findings of the present numerical study are directly applicable to related fields where optimum absorption is sought; these include physical wavemaking, wave power absorption and a wide range of numerical wave tank schemes.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗

Power generation forecasting for solar plants based on Dynamic Bayesian networks by fusing multi-source information

A Dynamic Bayesian network (DBN) model for solar power generation forecasting in solar plants is proposed in this paper. The key idea is to fuse sensor data, operational indicators, meteorological data, lagged output power information, and model errors for more accurate short-term (e.g., hours) and mid-term (e.g., days to weeks) power generation forecasting. The proposed DBN augments automated data-driven structure learning with expert knowledge encoding using continuous and categorical data given constraints to represent causal relationships within a solar inverter system. Additionally, an error compensation mechanism is proposed to capture temporal fluctuation. The effectiveness of the DBN on solar power generation forecasting was evaluated by rolling window analysis with one-year testing data collected from a local solar plant. The proposed DBN is compared with four state-of-art methods including support-vector regression (SVR), k-nearest neighbors (kNN), artificial neural network (ANN), and long short-term memory (LSTM) models. The result show that the proposed DBN achieves better accuracy in general, and it is not as data-hungry as some neural network-based models. The proposed DBN is also shown to have robust and consistent forecasting power with different forecasting horizons. The accuracy is 92% - 95% from one hour to one week ahead forecasting.

14 SOLAR ENERGY↗

Overexpression of soluble ADAM33 promotes a hypercontractile phenotype of the airway smooth muscle cell in rat

A disintegrin and metalloproteinase 33 (ADAM33) has been identified as a susceptibility gene for asthma, but details of the causality are not fully understood. We hypothesize that soluble ADAM33 (sADAM33) overexpression can alter the mechanical behaviors of airway smooth muscle cells (ASMCs) via regulation of the cell's contractile phenotype, and thus contributes to airway hyperresponsiveness (AHR) in asthma. To test this hypothesis, we either overexpressed or knocked down the sADAM33 in rat ASMCs by transfecting the cells with sADAM33 coding sequence or a small interfering RNA (siRNA) that specifically targets the ADAM33 disintegrin domain, and subsequently assessed the cells for stiffness, contractility and traction force, together with the expression level of contractile and proliferative phenotype markers. We also investigated whether these changes were dependent on Rho/ROCK pathway by culturing the ASMCs either in the absence or presence of ROCK inhibitor (H1152). The results showed that the ASMCs with sADAM33 overexpression were stiffer and more contractile, generated greater traction force, exhibited increased expression levels of contractile phenotype markers and markedly enhanced Rho activation. Furthermore these changes were largely attenuated when the cells were cultured in the presence of H-1152. However, the knock-down of ADAM33 seemed insufficient to influence majority of the mechanical behaviors of the ASMCs. Taken together, we demonstrated that sADAM33 overexpression altered the mechanical behaviors of ASMCs in vitro, which was most likely by promoting a hypercontractile phenotype transition of ASMCs through Rho/ROCK pathway. This revelation may establish the previously missing link between ADAM33 expression and AHR, and also provide useful insight for targeting sADAM33 in asthma prevention and therapy. - Highlights: • sADAM33 overexpression enhances the stiffness, traction force and contractility of ASMCs. • sADAM33 overexpression promotes a hypercontractile phenotype of ASMCs. • The hypercontractile phenotype transition was largely mediated via Rho/ROCK pathway. • ADAM33 knock-down had little effect on the stiffness, traction force and contractility of ASMCs.

60 APPLIED LIFE SCIENCES↗

Dynamic Life-Cycle Analysis of Fast Pyrolysis Biorefineries: Impacts of Feedstock Moisture Content and Particle Size

The commercialization of biorefineries has been met with significant obstacles due to the technical difficulties of handling solid biomass feedstocks, which are highly variable in physical properties and chemical compositions. An understanding of the principles of unit operations along the supply chain is key to the success of the biofuel industry. This study applies a dynamic life-cycle analysis (DLCA) methodology by developing quantitative relationships between the inputs and outputs for each unit operation based on scientific understanding of the causal effects. Using the DLCA, we assessed system sustainability of drop-in fuel production from fast pyrolysis of pine residues followed by hydro-processing. Life-cycle greenhouse gas (GHG) emissions were calculated for 4641 runs involving two key feedstock parameters: moisture content after field drying and particle size of the feed to pyrolyzer. Moisture contents varied between 25% and 35%, while particle sizes varied between 0.5 and 5 mm in these runs. The life-cycle GHG emissions of these cases vary from 22 to 40 g/MJ. Close examination of each unit operation's contribution to the total GHG emissions reveals that low moisture content after field drying produces savings in energy consumption during feedstock transportation and on-site drying. However, although small particle size leads to overall higher fuel yield, it also requires a significant amount of energy for feedstock size reduction and fuel production. The energy penalty outweighs the benefit of increased fuel yields, especially when fine particles (<1 mm) are used for pyrolysis; thus, small particle size leads to increased GHG emissions overall. The results highlight the trade-offs between the energy demand for preprocessing and the conversion yields, which can be addressed with DLCA.

09 BIOMASS FUELS↗

Pushing the frontiers in climate modelling and analysis with machine learning

Climate modelling and analysis are facing new demands to enhance projections and climate information. Here, in this study, we argue that now is the time to push the frontiers of machine learning beyond state-of-the-art approaches, not only by developing machine-learning-based Earth system models with greater fidelity, but also by providing new capabilities through emulators for extreme event projections with large ensembles, enhanced detection and attribution methods for extreme events, and advanced climate model analysis and benchmarking. Utilizing this potential requires key machine learning challenges to be addressed, in particular generalization, uncertainty quantification, explainable artificial intelligence and causality. This interdisciplinary effort requires bringing together machine learning and climate scientists, while also leveraging the private sector, to accelerate progress towards actionable climate science.

54 ENVIRONMENTAL SCIENCES↗

Delayed choice experiments, the arrow of time, and quantum measurement

By a radical modification of statistical mechanics the measurement process of quantum mechanics can be described in terms of pure, unitary time evolution, with no wave function collapse or many-world ideas. The key notion is 'special states', rare microscopic states of a complex system. Recovering the standard probabilities requires of this theory the appearance of Cauchy-distributed noise in some measurement processes. This article treats experimental situations where such noise might be detected and correlated with the need or absence of need for special states. Included in this possibility are 'delayed choice' experiments, in which the correlation contravenes conventional ideas on causality. Background material on all topics is provided.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗

Generalized mutual information and Tsirelson's bound

We introduce a generalization of the quantum mutual information between a classical system and a quantum system into the mutual information between a classical system and a system described by general probabilistic theories. We apply this generalized mutual information (GMI) to a derivation of Tsirelson's bound from information causality, and prove that Tsirelson's bound can be derived from the chain rule of the GMI. By using the GMI, we formulate the 'no-supersignalling condition' (NSS), that the assistance of correlations does not enhance the capability of classical communication. We prove that NSS is never violated in any no-signalling theory.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗

Introduction to neutron stars

Neutron stars contain the densest form of matter in the present universe. General relativity and causality set important constraints to their compactness. In addition, analytic GR solutions are useful in understanding the relationships that exist among the maximum mass, radii, moments of inertia, and tidal Love numbers of neutron stars, all of which are accessible to observation. Some of these relations are independent of the underlying dense matter equation of state, while others are very sensitive to the equation of state. Recent observations of neutron stars from pulsar timing, quiescent X-ray emission from binaries, and Type I X-ray bursts can set important constraints on the structure of neutron stars and the underlying equation of state. In addition, measurements of thermal radiation from neutron stars has uncovered the possible existence of neutron and proton superfluidity/superconductivity in the core of a neutron star, as well as offering powerful evidence that typical neutron stars have significant crusts. These observations impose constraints on the existence of strange quark matter stars, and limit the possibility that abundant deconfined quark matter or hyperons exist in the cores of neutron stars.

79 ASTRONOMY AND ASTROPHYSICS↗

On the no-signaling approach to quantum nonlocality

The no-signaling approach to nonlocality deals with separable and inseparable multiparty correlations in the same set of probability states without conflicting causality. The set of half-spaces describing the polytope of no-signaling probability states that are admitted by the most general class of Bell scenarios is formulated in full detail. An algorithm for determining the skeleton that solves the no-signaling description is developed upon a new strategy that is partially pivoting and partially incremental. The algorithm is formulated rigorously and its implementation is shown to be effective to deal with the highly degenerate no-signaling descriptions. Several applications of the algorithm as a tool for the study of quantum nonlocality are mentioned. Applied to a large set of bipartite Bell scenarios, we found that the corresponding no-signaling polytopes have a striking high degeneracy that grows up exponentially with the size of the Bell scenario.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗

Differentiability of correlations in realistic quantum mechanics

We prove a version of Bell’s theorem in which the locality assumption is weakened. We start by assuming theoretical quantum mechanics and weak forms of relativistic causality and of realism (essentially the fact that observable values are well defined independently of whether or not they are measured). Under these hypotheses, we show that only one of the correlation functions that can be formulated in the framework of the usual Bell theorem is unknown. We prove that this unknown function must be differentiable at certain angular configuration points that include the origin. We also prove that, if this correlation is assumed to be twice differentiable at the origin, then we arrive at a version of Bell’s theorem. On the one hand, we are showing that any realistic theory of quantum mechanics which incorporates the kinematic aspects of relativity must lead to this type of rough correlation function that is once but not twice differentiable. On the other hand, this study brings us a single degree of differentiability away from a relativistic von Neumann no hidden variables theorem.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗

Two-dimensional hybrid simulations of kinetic plasma turbulence: Current and vorticity vs proton temperature

Proton temperature anisotropies between the directions parallel and perpendicular to the mean magnetic field are usually observed in the solar wind plasma. Here, we employ a high-resolution hybrid particle-in-cell simulation in order to investigate the relation between spatial properties of the proton temperature and the peaks in the current density and in the flow vorticity. Our results indicate that, although regions where the proton temperature is enhanced and temperature anisotropies are larger correspond approximately to regions where many thin current sheets form, no firm quantitative evidence supports the idea of a direct causality between the two phenomena. On the other hand, quite a clear correlation between the behavior of the proton temperature and the out-of-plane vorticity is obtained.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗

GYRO-ORBIT SIZE, BRIGHTNESS TEMPERATURE LIMIT, AND IMPLAUSIBILITY OF COHERENT EMISSION BY BUNCHING IN SYNCHROTRON RADIO SOURCES

We show that an upper limit on the maximum brightness temperature for a self-absorbed incoherent synchrotron radio source is obtained from the size of its gyro orbits, which in turn must lie well within the confines of the total source extent. These temperature limits are obtained without recourse to inverse Compton effects or the condition of equipartition of energy between magnetic fields and relativistic particles. For radio variables, the intra-day variability implies brightness temperatures {approx}10{sup 19} K in the comoving rest frame of the source. This, if interpreted purely due to an incoherent synchrotron emission, would imply gyroradii >10{sup 28} cm, the size of the universe, while from the causality arguments the inferred maximum size of the source in such a case is {approx}< 10{sup 15} cm. Such high brightness temperatures are sometimes modeled in the literature as some coherent emission process where bunches of non-thermal particles are somehow formed that radiate in phase. We show that, unlike in the case of curvature radiation models proposed in pulsars, in the synchrotron radiation mechanism the oppositely charged particles would contribute together to the coherent phenomenon without the need to form separate bunches of the opposite charges. At the same time we show that bunches would disperse over dimensions larger than a wavelength in time shorter than the gyro orbital period ({approx}< 0.1 s). Therefore, a coherent emission by bunches cannot be a plausible explanation of the high brightness temperatures inferred in extragalactic radio sources showing variability over a few hours or longer.

79 ASTRONOMY AND ASTROPHYSICS↗

Neutron star masses and radii from quiescent low-mass x-ray binaries

We perform a systematic analysis of neutron star radius constraints from five quiescent low-mass X-ray binaries and examine how they depend on measurements of their distances and amounts of intervening absorbing material, as well as their assumed atmospheric compositions. We construct and calibrate to published results a semi-analytic model of the neutron star atmosphere which approximates these effects for the predicted masses and radii. Starting from mass and radius probability distributions established from hydrogen-atmosphere spectral fits of quiescent sources, we apply this model to compute alternate sets of probability distributions. We perform Bayesian analyses to estimate neutron star mass-radius curves and equation of state (EOS) parameters that best-fit each set of distributions, assuming the existence of a known low-density neutron star crustal EOS, a simple model for the high-density EOS, causality, and the observation that the neutron star maximum mass exceeds 2 M {sub ☉}. We compute the posterior probabilities for each set of distance measurements and assumptions about absorption and composition. We find that, within the context of our assumptions and our parameterized EOS models, some absorption models are disfavored. We find that neutron stars composed of hadrons are favored relative to those with exotic matter with strong phase transitions. In addition, models in which all five stars have hydrogen atmospheres are found to be weakly disfavored. Our most likely models predict neutron star radii that are consistent with current experimental results concerning the nature of the nucleon-nucleon interaction near the nuclear saturation density.

79 ASTRONOMY AND ASTROPHYSICS↗

The Helmholtz Hierarchy: phase space statistics of cold dark matter

We present a new formalism to study large-scale structure in the universe. The result is a hierarchy (which we call the ''Helmholtz Hierarchy'') of equations describing the phase space statistics of cold dark matter (CDM). The hierarchy features a physical ordering parameter which interpolates between the Zel'dovich approximation and fully-fledged gravitational interactions. The results incorporate the effects of stream crossing. We show that the Helmholtz hierarchy is self-consistent and obeys causality to all orders. We present an interpretation of the hierarchy in terms of effective particle trajectories.

79 ASTRONOMY AND ASTROPHYSICS↗

Chronology protection in Galileon models and massive gravity

Galileon models are a class of effective field theories that have recently received much attention. They arise in the decoupling limit of theories of massive gravity, and in some cases they have been treated in their own right as scalar field theories with a specific nonlinearly realized global symmetry (Galilean transformation). It is well known that in the presence of a source, these Galileon theories admit superluminal propagating solutions, implying that as quantum field theories they must admit a different notion of causality than standard local Lorentz invariant theories. We show that in these theories it is easy to construct closed timelike curves (CTCs) within the naive regime of validity of the effective field theory. However, on closer inspection we see that the CTCs could never arise since the Galileon inevitably becomes infinitely strongly coupled at the onset of the formation of a CTC. This implies an infinite amount of backreaction, first on the background for the Galileon field, signaling the break down of the effective field theory, and subsequently on the spacetime geometry, forbidding the formation of the CTC. Furthermore the background solution required to create CTCs becomes unstable with an arbitrarily fast decay time. Thus Galileon theories satisfy a direct analogue of Hawking's chronology protection conjecture.

79 ASTRONOMY AND ASTROPHYSICS↗

Consistent perturbations in an imperfect fluid

We present a new prescription for analysing cosmological perturbations in a more-general class of scalar-field dark-energy models where the energy-momentum tensor has an imperfect-fluid form. This class includes Brans-Dicke models, f(R) gravity, theories with kinetic gravity braiding and generalised galileons. We employ the intuitive language of fluids, allowing us to explicitly maintain a dependence on physical and potentially measurable properties. We demonstrate that hydrodynamics is not always a valid description for describing cosmological perturbations in general scalar-field theories and present a consistent alternative that nonetheless utilises the fluid language. We apply this approach explicitly to a worked example: k-essence non-minimally coupled to gravity. This is the simplest case which captures the essential new features of these imperfect-fluid models. We demonstrate the generic existence of a new scale separating regimes where the fluid is perfect and imperfect. We obtain the equations for the evolution of dark-energy density perturbations in both these regimes. The model also features two other known scales: the Compton scale related to the breaking of shift symmetry and the Jeans scale which we show is determined by the speed of propagation of small scalar-field perturbations, i.e. causality, as opposed to the frequently used definition of the ratio of the pressure and energy-density perturbations.

79 ASTRONOMY AND ASTROPHYSICS↗

Consistency relation in power law G-inflation

In the standard inflationary scenario based on a minimally coupled scalar field, canonical or non-canonical, the subluminal propagation of speed of scalar perturbations ensures the following consistency relation: r ≤ −8n{sub T}, where r is the tensor-to-scalar-ratio and n{sub T} is the spectral index for tensor perturbations. However, recently, it has been demonstrated that this consistency relation could be violated in Galilean inflation models even in the absence of superluminal propagation of scalar perturbations. It is therefore interesting to investigate whether the subluminal propagation of scalar field perturbations impose any bound on the ratio r/|n{sub T}| in G-inflation models. In this paper, we derive the consistency relation for a class of G-inflation models that lead to power law inflation. Within these class of models, it turns out that one can have r > −8n{sub T} or r ≤ −8n{sub T} depending on the model parameters. However, the subluminal propagation of speed of scalar field perturbations, as required by causality, restricts r ≤ −(32/3) n{sub T}.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗