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from
Part II
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State space methods for clinical data
By
M. B. Westover, Massachusetts General Hospital,
S. Ching, Washington University at St Louis,
M. M. Shafi, Massachusetts General Hospital,
S. S. Cash, Massachusetts General Hospital,
E. N. Brown, Massachusetts Institute of Technology
Burst suppression – a discontinuous electroencephalographic (EEG) pattern in which flatline (suppression) and higher voltage (burst) periods alternate systematically but with variable burst and suppression durations (see Figure 14.1) – is a state of profound brain inactivation. Burst suppression is inducible by high doses of most anesthetics (Clark & Rosner 1973) or in profound hypothermia (e.g. used for cerebral protection in cardiac bypass surgeries) (Stecker et al. 2001); may occur pathologically in patients with coma after cardiac arrest or trauma as a manifestation of diffuse cortical hypoxicischemic injury (Young 2000), or in a form of early infantile encephalopathy (“Othahara syndrome”) (Ohtahara & Yamatogi 2006); and as a non-pathological finding in the EEGs of premature infants known as “trace alternant” or “trace discontinu.” The fact that these diverse etiologies produce similar brain activity have led to the current consensus view that (i) burst suppression reflects the operation of a low-order dynamic process which persists in the absence of higher-level brain activity, and (ii) there may be a common pathway to the state of brain inactivation.
Four cardinal phenomenological features of burst suppression have been established through a variety of EEG and neurophysiological studies (Akrawi et al. 1996; Amzica 2009; Ching et al. 2012). First, burst onsets are generally spatially synchronous (i.e., bursts begin and end nearly simultaneously across the entire scalp), except in cases of large-scale cortical deafferentation (Niedermeyer 2009), in which cases regional differences in blood supply and autoregulation may prevent the uniformity typically associated with burst suppression. A caveat here is related to recent evidence that suggests that, on a local circuit level, the onset of bursts may exhibit significant heterogeneity (Lewis et al. 2013). Second, the fraction of time spent in suppression– classically quantified using the burst suppression ratio (BSR) – increases monotonically with the level of brain inactivation. For example, the BSR increases with increasing doses of anesthetic or hypothermia, eventually reaching 100% as the EEG becomes isoelectric (flatline).
from
Part II
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State space methods for clinical data
By
L. H. Lehman, Massachusetts Institute of Technology,
M. J. Johnson, Massachusetts Institute of Technology,
S. Nemati, Harvard University,
R. P. Adams, Harvard University,
R. G. Mark, Massachusetts Institute of Technology
The time series of vital signs, such as heart rate (HR) and blood pressure (BP), can exhibit complex dynamic behaviors as a result of internally and externally induced changes in the state of the underlying control systems (Peng et al. 1995; Ivanov et al. 1999; Costa et al. 2002). For instance, time series of BP can exhibit oscillations on the order of seconds (e.g., due to the variations in sympathovagal balance), to minutes (e.g., as a consequence of fever, blood loss, or behavioral factors), to hours (e.g., due to humoral variations, sleep-wake cycle, or circadian effects) (Mancia 2012; Parati et al. 2013). A question of interest is whether “similar” dynamical patterns can be automatically identified across a heterogeneous patient cohort, and be used for prognosis of patients' health and progress.
In this work, we present a Bayesian nonparametric switching Markov processes framework with conditionally linear dynamics to learn phenotypic dynamic behaviors from vital sign time series of a patient cohort, and use the learned dynamics to characterize the changing physiological states of patients for critical-care bed-side monitoring (Lehman et al. 2012, 2013, 2014a; Nemati 2012). We assume that although the underlying dynamical system may be nonlinear and nonstationary and the stochastic noise components can be non-Gaussian, the dynamics can be approximated by a collection of linear dynamical systems (Nemati 2012; Nemati et al. 2012). Each such linear “dynamic” (or mode) is a time-dependent rule that describes how the future state of the system evolves from its current state, centered around a given system equilibrium point. Therefore, an ideal algorithm would be able to identify time series segments that follow a “similar” dynamic, and would switch to a different mode upon a change in the state of the underlying system.
We explore several variants of the Bayesian nonparametric approach to discovery of shared dynamics among patients via switching Markov processes: hierarchical Dirichlet process (HDP) autoregressive hidden Markov model (HDP-AR-HMM) (Teh et al. 2006; Fox et al. 2008), an explicit-duration HDP-based hidden semi-Markov model (HDP-AR-HSMM) (Johnson & Willsky 2013a), and the beta process autoregressive HMM (BP-AR-HMM) (Fox 2009; Fox et al. 2009, 2014).
In Achlioptas processes, starting from an empty graph, in each step two potential edges are chosen uniformly at random, and using some rule one of them is selected and added to the evolving graph. The evolution of the rescaled size of the largest component in such variations of the Erdős–Rényi random graph process has recently received considerable attention, in particular for Bollobás's ‘product rule’. In this paper we establish the following result for rules such as the product rule: the limit of the rescaled size of the ‘giant’ component exists and is continuous provided that a certain system of differential equations has a unique solution. In fact, our result applies to a very large class of Achlioptas-like processes.
Our proof relies on a general idea which relates the evolution of stochastic processes to an associated system of differential equations. Provided that the latter has a unique solution, our approach shows that certain discrete quantities converge (after appropriate rescaling) to this solution.
Algebraic coding theory has in recent years been increasingly applied to the study of combinatorial designs. This book gives an account of many of those applications together with a thorough general introduction to both design theory and coding theory - developing the relationship between the two areas. The first half of the book contains background material in design theory, including symmetric designs and designs from affine and projective geometry, and in coding theory, coverage of most of the important classes of linear codes. In particular, the authors provide a new treatment of the Reed-Muller and generalized Reed-Muller codes. The last three chapters treat the applications of coding theory to some important classes of designs, namely finite planes, Hadamard designs and Steiner systems, in particular the Witt systems. The book is aimed at mathematicians working in either coding theory or combinatorics - or related areas of algebra. The book is, however, designed to be used by non-specialists and can be used by those graduate students or computer scientists who may be working in these areas.
This authoritative work provides an in-depth treatment of state space methods, with a range of applications in neural and clinical data. Advanced and state-of-the-art research topics are detailed, including topics in state space analyses, maximum likelihood methods, variational Bayes, sequential Monte Carlo, Markov chain Monte Carlo, nonparametric Bayesian, and deep learning methods. Details are provided on practical applications in neural and clinical data, whether this is characterising time series data from neural spike trains recorded from the rat hippocampus, the primate motor cortex, or the human EEG, MEG or fMRI, or physiological measurements of heartbeats or blood pressures. With real-world case studies of neuroscience experiments and clinical data sets, and written by expert authors from across the field, this is an ideal resource for anyone working in neuroscience and physiological data analysis.
Let p1, p2, p3 be three noncollinear points in the plane, and let P be a set of n other points in the plane. We show that the number of distinct distances between p1, p2, p3 and the points of P is Ω(n6/11), improving the lower bound Ω(n0.502) of Elekes and Szabó [4] (and considerably simplifying the analysis).
In the tournament game two players, called Maker and Breaker, alternately take turns in claiming an unclaimed edge of the complete graph Kn and selecting one of the two possible orientations. Before the game starts, Breaker fixes an arbitrary tournament Tk on k vertices. Maker wins if, at the end of the game, her digraph contains a copy of Tk; otherwise Breaker wins. In our main result, we show that Maker has a winning strategy for k = (2 − o(1))log2n, improving the constant factor in previous results of Beck and the second author. This is asymptotically tight since it is known that for k = (2 − o(1))log2n Breaker can prevent the underlying graph of Maker's digraph from containing a k-clique. Moreover, the precise value of our lower bound differs from the upper bound only by an additive constant of 12.
We also discuss the question of whether the random graph intuition, which suggests that the threshold for k is asymptotically the same for the game played by two ‘clever’ players and the game played by two ‘random’ players, is supported by the tournament game. It will turn out that, while a straightforward application of this intuition fails, a more subtle version of it is still valid.
Finally, we consider the orientation game version of the tournament game, where Maker wins the game if the final digraph – also containing the edges directed by Breaker – possesses a copy of Tk. We prove that in that game Breaker has a winning strategy for k = (4 + o(1))log2n.
However, since the paper uses complex-valued representations, the integrand on the right here may not retain the absolute value of that on the left. Without this equality, the proof of Corollary 3 can no longer be reduced to an application of Lemma 2. However, it can be proved directly from Schur Orthogonality along very similar lines to the proof of Lemma 2.
A set A of positive integers is a Bh-set if all the sums of the form a1 + . . . + ah, with a1,. . .,ah ∈ A and a1 ⩽ . . . ⩽ ah, are distinct. We provide asymptotic bounds for the number of Bh-sets of a given cardinality contained in the interval [n] = {1,. . .,n}. As a consequence of our results, we address a problem of Cameron and Erdős (1990) in the context of Bh-sets. We also use these results to estimate the maximum size of a Bh-sets contained in a typical (random) subset of [n] with a given cardinality.
Concentration inequalities are fundamental tools in probabilistic combinatorics and theoretical computer science for proving that functions of random variables are typically near their means. Of particular importance is the case where f(X) is a function of independent random variables X = (X1, . . ., Xn). Here the well-known bounded differences inequality (also called McDiarmid's inequality or the Hoeffding–Azuma inequality) establishes sharp concentration if the function f does not depend too much on any of the variables. One attractive feature is that it relies on a very simple Lipschitz condition (L): it suffices to show that |f(X) − f(X′)| ⩽ ck whenever X, X′ differ only in Xk. While this is easy to check, the main disadvantage is that it considers worst-case changes ck, which often makes the resulting bounds too weak to be useful.
In this paper we prove a variant of the bounded differences inequality which can be used to establish concentration of functions f(X) where (i) the typical changes are small, although (ii) the worst case changes might be very large. One key aspect of this inequality is that it relies on a simple condition that (a) is easy to check and (b) coincides with heuristic considerations as to why concentration should hold. Indeed, given an event Γ that holds with very high probability, we essentially relax the Lipschitz condition (L) to situations where Γ occurs. The point is that the resulting typical changes ck are often much smaller than the worst case ones.
To illustrate its application we consider the reverse H-free process, where H is 2-balanced. We prove that the final number of edges in this process is concentrated, and also determine its likely value up to constant factors. This answers a question of Bollobás and Erdős.
A family of sets is called union-closed if whenever A and B are sets of the family, so is A ∪ B. The long-standing union-closed conjecture states that if a family of subsets of [n] is union-closed, some element appears in at least half the sets of the family. A natural weakening is that the union-closed conjecture holds for large families, that is, families consisting of at least p02n sets for some constant p0. The first result in this direction appears in a recent paper of Balla, Bollobás and Eccles [1], who showed that union-closed families of at least $\tfrac{2}{3}$2n sets satisfy the conjecture; they proved this by determining the minimum possible average size of a set in a union-closed family of given size. However, the methods used in that paper cannot prove a better constant than $\tfrac{2}{3}$. Here, we provide a stability result for the main theorem of [1], and as a consequence we prove the union-closed conjecture for families of at least ($\tfrac{2}{3}$ − c)2n sets, for a positive constant c.
We give an easy method for constructing containers for simple hypergraphs. The method also has consequences for non-simple hypergraphs. Some applications are given; in particular, a very transparent calculation is offered for the number of H-free hypergraphs, where H is some fixed uniform hypergraph.
Written for mathematicians working with the theory of graph spectra, this book explores more than 400 inequalities for eigenvalues of the six matrices associated with finite simple graphs: the adjacency matrix, Laplacian matrix, signless Laplacian matrix, normalized Laplacian matrix, Seidel matrix, and distance matrix. The book begins with a brief survey of the main results and selected applications to related topics, including chemistry, physics, biology, computer science, and control theory. The author then proceeds to detail proofs, discussions, comparisons, examples, and exercises. Each chapter ends with a brief survey of further results. The author also points to open problems and gives ideas for further reading.
We consider ‘unconstrained’ random k-XORSAT, which is a uniformly random system of m linear non-homogeneous equations in $\mathbb{F}$2 over n variables, each equation containing k ⩾ 3 variables, and also consider a ‘constrained’ model where every variable appears in at least two equations. Dubois and Mandler proved that m/n = 1 is a sharp threshold for satisfiability of constrained 3-XORSAT, and analysed the 2-core of a random 3-uniform hypergraph to extend this result to find the threshold for unconstrained 3-XORSAT.
We show that m/n = 1 remains a sharp threshold for satisfiability of constrained k-XORSAT for every k ⩾ 3, and we use standard results on the 2-core of a random k-uniform hypergraph to extend this result to find the threshold for unconstrained k-XORSAT. For constrained k-XORSAT we narrow the phase transition window, showing that m − n → −∞ implies almost-sure satisfiability, while m − n → +∞ implies almost-sure unsatisfiability.
We study 3-random-like graphs, that is, sequences of graphs in which the densities of triangles and anti-triangles converge to 1/8. Since the random graph $\mathcal{G}$n,1/2 is, in particular, 3-random-like, this can be viewed as a weak version of quasi-randomness. We first show that 3-random-like graphs are 4-universal, that is, they contain induced copies of all 4-vertex graphs. This settles a question of Linial and Morgenstern [10]. We then show that for larger subgraphs, 3-random-like sequences demonstrate completely different behaviour. We prove that for every graph H on n ⩾ 13 vertices there exist 3-random-like graphs without an induced copy of H. Moreover, we prove that for every ℓ there are 3-random-like graphs which are ℓ-universal but not m-universal when m is sufficiently large compared to ℓ.