A Foundational Framework and Methodology for Personalized Early and Timely Diagnosis

Early diagnosis of diseases holds the potential for deep transformation in healthcare by enabling better treatment options, improving long-term survival and quality of life, and reducing overall cost. With the advent of medical big data, advances in diagnostic tests as well as in machine learning and statistics, early or timely diagnosis seems within reach. Early diagnosis research often neglects the potential for optimizing individual diagnostic paths. To enable personalized early diagnosis, a foundational framework is needed that delineates the diagnosis process and systematically identifies the time-dependent value of various diagnostic tests for an individual patient given their unique characteristics. Here, we propose the first foundational framework for early and timely diagnosis. It builds on decision-theoretic approaches to outline the diagnosis process and integrates machine learning and statistical methodology for estimating the optimal personalized diagnostic path. To describe the proposed framework as well as possibly other frameworks, we provide essential definitions. The development of a foundational framework is necessary for several reasons: 1) formalism provides clarity for the development of decision support tools; 2) observed information can be complemented with estimates of the future patient trajectory; 3) the net benefit of counterfactual diagnostic paths and associated uncertainties can be modeled for individuals 4) 'early' and 'timely' diagnosis can be clearly defined; 5) a mechanism emerges for assessing the value of technologies in terms of their impact on personalized early diagnosis, resulting health outcomes and incurred costs. Finally, we hope that this foundational framework will unlock the long-awaited potential of timely diagnosis and intervention, leading to improved outcomes for patients and higher cost-effectiveness for healthcare systems.Comment: 10 pages, 2 figure

Intravascular Palpography for Vulnerable Plaque Assessment

Palpography assesses the local mechanical properties of tissue using the deformation caused by the intraluminal pressure. The technique was validated in vitro using diseased human coronary and femoral arteries. Especially between fibrous and fatty tissue, a highly significant difference in strain (p = 0.0012) was found. Additionally, the predictive value to identify the vulnerable plaque was investigated. A high-strain region at the lumen vessel wall boundary has 88% sensitivity and 89% specificity for identifying these plaques. In vivo, the technique is validated in an atherosclerotic Yucatan minipig animal model. This study also revealed higher strain values in fatty than in fibrous plaques (p < 0.001). The presence of a high-strain region at the lumen-plaque interface has a high predictive value to identify macrophages. Patient studies revealed high strain values (1% to 2%) in noncalcified plaques. Calcified material showed low strain values (0% to 0.2%). With the development of three-dimensional palpography, identification of weak spots over the full length of a coronary artery becomes available. Patients with myocardial infarction or unstable angina have more high-strain spots in their coronary arteries than patients with stable angina. In conclusion, intravascular palpography is a unique tool to assess lesion composition and vulnerability. Three-dimensional palpography provides a technique that may develop into a clinically available tool for decision making to treat hemodynamically nonsignificant lesions by identifying vulnerable plaques. The clinical utility of this technique is yet to be determined, and more investigation is needed

Boundary Effective Field Theory and Trans-Planckian Perturbations: Astrophysical Implications

We contrast two approaches to calculating trans-Planckian corrections to the inflationary perturbation spectrum: the New Physics Hypersurface [NPH] model, in which modes are normalized when their physical wavelength first exceeds a critical value, and the Boundary Effective Field Theory [BEFT] approach, where the initial conditions for all modes are set at the same time, and modified by higher dimensional operators enumerated via an effective field theory calculation. We show that these two approaches -- as currently implemented -- lead to radically different expectations for the trans-Planckian corrections to the CMB and emphasize that in the BEFT formalism we expect the perturbation spectrum to be dominated by quantum gravity corrections for all scales shorter than some critical value. Conversely, in the NPH case the quantum effects only dominate the longest modes that are typically much larger than the present horizon size. Furthermore, the onset of the breakdown in the standard inflationary perturbation calculation predicted by the BEFT formalism is likely to be associated with a feature in the perturbation spectrum, and we discuss the observational signatures of this feature in both CMB and large scale structure observations. Finally, we discuss possible modifications to both calculational frameworks that would resolve the contradictions identified here.Comment: Reworded commentary, reference added (v2) References added (v3

Residential mobility and local housing-market differences

The authors extend previous literature on variations in mobility rates across local housing markets by examining the linkage of mobility rates at the household level to the structure of local housing markets. The results suggest that residential mobility rates differ widely across local housing markets, substantiating the view that residential relocation is intimately intertwined with conditions at the local level. Local housing-market conditions also have different effects on mobility rates for renters and owner-occupiers. The results suggest that variation in residential mobility rates across housing markets can be in part explained by level of urbanization, the tenure structure, the degree of government intervention, and the size of the housing market. Remarkably, these differences in local housing markets cannot be seen to be related to housing-market features only. The results suggest that these differences can also be attributed to the behavior or attitude of households with respect to housing

Contextual learning for unit commitment with renewable energy sources

In this paper, we study a unit commitment (UC) problem minimizing operating costs of the power system with renewable energy sources. We develop a contextual learning algorithm for UC (CLUC) which learns which UC schedule to choose based on the context information such as past load demand and weather condition. CLUC does not require any prior knowledge on the uncertainties such as the load demand and the renewable power outputs, and learns them over time using the context information. We characterize the performance of CLUC analytically, and prove its optimality in terms of the long-term average cost. Through the simulation results, we show the performance of CLUC and the effectiveness of utilizing the context information in the UC problem. © 2016 IEEE

Holographic multiverse and the measure problem

We discuss the duality, conjectured in earlier work, between the wave function of the multiverse and a 3D Euclidean theory on the future boundary of spacetime. In particular, we discuss the choice of the boundary metric and the relation between the UV cutoff scale xi on the boundary and the hypersurfaces Sigma on which the wave function is defined in the bulk. We propose that in the limit of xi going to 0 these hypersurfaces should be used as cutoff surfaces in the multiverse measure. Furthermore, we argue that in the inflating regions of spacetime with a slowly varying Hubble rate H the hypersurfaces Sigma are surfaces of constant comoving apparent horizon (CAH). Finally, we introduce a measure prescription (called CAH+) which appears to have no pathological features and coincides with the constant CAH cutoff in regions of slowly varying H.Comment: A minor change: the discussion of unitarity on p.9 is clarifie

Covariant description of inelastic electron--deuteron scattering:predictions of the relativistic impulse approximation

Using the covariant spectator theory and the transversity formalism, the unpolarized, coincidence cross section for deuteron electrodisintegration, $d(e,e'p)n$, is studied. The relativistic kinematics are reviewed, and simple theoretical formulae for the relativistic impulse approximation (RIA) are derived and discussed. Numerical predictions for the scattering in the high $Q^2$ region obtained from the RIA and five other approximations are presented and compared. We conclude that measurements of the unpolarized coincidence cross section and the asymmetry $A_\phi$, to an accuracy that will distinguish between different theoretical models, is feasible over most of the wide kinematic range accessible at Jefferson Lab.Comment: 54 pages and 24 figure

Immature Dengue Virus: A Veiled Pathogen?

Cells infected with dengue virus release a high proportion of immature prM-containing virions. In accordance, substantial levels of prM antibodies are found in sera of infected humans. Furthermore, it has been recently described that the rates of prM antibody responses are significantly higher in patients with secondary infection compared to those with primary infection. This suggests that immature dengue virus may play a role in disease pathogenesis. Interestingly, however, numerous functional studies have revealed that immature particles lack the ability to infect cells. In this report, we show that fully immature dengue particles become highly infectious upon interaction with prM antibodies. We demonstrate that prM antibodies facilitate efficient binding and cell entry of immature particles into Fc-receptor-expressing cells. In addition, enzymatic activity of furin is critical to render the internalized immature virus infectious. Together, these data suggest that during a secondary infection or primary infection of infants born to dengue-immune mothers, immature particles have the potential to be highly infectious and hence may contribute to the development of severe disease