Power Law versus Exponential State Transition Dynamics: Application to Sleep-Wake Architecture

BACKGROUND: Despite the common experience that interrupted sleep has a negative impact on waking function, the features of human sleep-wake architecture that best distinguish sleep continuity versus fragmentation remain elusive. In this regard, there is growing interest in characterizing sleep architecture using models of the temporal dynamics of sleep-wake stage transitions. In humans and other mammals, the state transitions defining sleep and wake bout durations have been described with exponential and power law models, respectively. However, sleep-wake stage distributions are often complex, and distinguishing between exponential and power law processes is not always straightforward. Although mono-exponential distributions are distinct from power law distributions, multi-exponential distributions may in fact resemble power laws by appearing linear on a log-log plot. METHODOLOGY/PRINCIPAL FINDINGS: To characterize the parameters that may allow these distributions to mimic one another, we systematically fitted multi-exponential-generated distributions with a power law model, and power law-generated distributions with multi-exponential models. We used the Kolmogorov-Smirnov method to investigate goodness of fit for the "incorrect" model over a range of parameters. The "zone of mimicry" of parameters that increased the risk of mistakenly accepting power law fitting resembled empiric time constants obtained in human sleep and wake bout distributions. CONCLUSIONS/SIGNIFICANCE: Recognizing this uncertainty in model distinction impacts interpretation of transition dynamics (self-organizing versus probabilistic), and the generation of predictive models for clinical classification of normal and pathological sleep architecture

The continuum of spreading depolarizations in acute cortical lesion development: Examining Leão's legacy.

A modern understanding of how cerebral cortical lesions develop after acute brain injury is based on Aristides Leão's historic discoveries of spreading depression and asphyxial/anoxic depolarization. Treated as separate entities for decades, we now appreciate that these events define a continuum of spreading mass depolarizations, a concept that is central to understanding their pathologic effects. Within minutes of acute severe ischemia, the onset of persistent depolarization triggers the breakdown of ion homeostasis and development of cytotoxic edema. These persistent changes are diagnosed as diffusion restriction in magnetic resonance imaging and define the ischemic core. In delayed lesion growth, transient spreading depolarizations arise spontaneously in the ischemic penumbra and induce further persistent depolarization and excitotoxic damage, progressively expanding the ischemic core. The causal role of these waves in lesion development has been proven by real-time monitoring of electrophysiology, blood flow, and cytotoxic edema. The spreading depolarization continuum further applies to other models of acute cortical lesions, suggesting that it is a universal principle of cortical lesion development. These pathophysiologic concepts establish a working hypothesis for translation to human disease, where complex patterns of depolarizations are observed in acute brain injury and appear to mediate and signal ongoing secondary damage

Guiding of relativistic electron beams in dense matter by laser-driven magnetostatic fields

Intense lasers interacting with dense targets accelerate relativistic electron beams, whichtransport part of the laser energy into the target depth. However, the overall laser-to-targetenergy coupling efficiency is impaired by the large divergence of the electron beam, intrinsicto the laser-plasma interaction. Here we demonstrate that an efficient guiding ofMeV electrons with about 30MA current in solid matter is obtained by imposing a laserdrivenlongitudinal magnetostatic field of 600 T. In the magnetized conditions the transportedenergy density and the peak background electron temperature at the 60-μm-thicktarget's rear surface rise by about a factor of five, as unfolded from benchmarked simulations.Such an improvement of energy-density flux through dense matter paves the ground foradvances in laser-driven intense sources of energetic particles and radiation, driving matter toextreme temperatures, reaching states relevant for planetary or stellar science as yet inaccessibleat the laboratory scale and achieving high-gain laser-driven thermonuclear fusion

Predicting protein linkages in bacteria: Which method is best depends on task

<p>Abstract</p> <p>Background</p> <p>Applications of computational methods for predicting protein functional linkages are increasing. In recent years, several bacteria-specific methods for predicting linkages have been developed. The four major genomic context methods are: Gene cluster, Gene neighbor, Rosetta Stone, and Phylogenetic profiles. These methods have been shown to be powerful tools and this paper provides guidelines for when each method is appropriate by exploring different features of each method and potential improvements offered by their combination. We also review many previous treatments of these prediction methods, use the latest available annotations, and offer a number of new observations.</p> <p>Results</p> <p>Using <it>Escherichia coli </it>K12 and <it>Bacillus subtilis</it>, linkage predictions made by each of these methods were evaluated against three benchmarks: functional categories defined by COG and KEGG, known pathways listed in EcoCyc, and known operons listed in RegulonDB. Each evaluated method had strengths and weaknesses, with no one method dominating all aspects of predictive ability studied. For functional categories, as previous studies have shown, the Rosetta Stone method was individually best at detecting linkages and predicting functions among proteins with shared KEGG categories while the Phylogenetic profile method was best for linkage detection and function prediction among proteins with common COG functions. Differences in performance under COG versus KEGG may be attributable to the presence of paralogs. Better function prediction was observed when using a weighted combination of linkages based on reliability versus using a simple unweighted union of the linkage sets. For pathway reconstruction, 99 complete metabolic pathways in <it>E. coli </it>K12 (out of the 209 known, non-trivial pathways) and 193 pathways with 50% of their proteins were covered by linkages from at least one method. Gene neighbor was most effective individually on pathway reconstruction, with 48 complete pathways reconstructed. For operon prediction, Gene cluster predicted completely 59% of the known operons in <it>E. coli </it>K12 and 88% (333/418)in <it>B. subtilis</it>. Comparing two versions of the <it>E. coli </it>K12 operon database, many of the unannotated predictions in the earlier version were updated to true predictions in the later version. Using only linkages found by both Gene Cluster and Gene Neighbor improved the precision of operon predictions. Additionally, as previous studies have shown, combining features based on intergenic region and protein function improved the specificity of operon prediction.</p> <p>Conclusion</p> <p>A common problem for computational methods is the generation of a large number of false positives that might be caused by an incomplete source of validation. By comparing two versions of a database, we demonstrated the dramatic differences on reported results. We used several benchmarks on which we have shown the comparative effectiveness of each prediction method, as well as provided guidelines as to which method is most appropriate for a given prediction task.</p

Causal inference as an emerging statistical approach in neurology: an example for epilepsy in the elderly

Lidia MVR Moura,1,2 M Brandon Westover,1,2 David Kwasnik,1 Andrew J Cole,1,2 John Hsu3&ndash;5 1Massachusetts General Hospital, Department of Neurology, Epilepsy Service, Boston, MA, USA; 2Harvard Medical School, Boston, MA, USA; 3Massachusetts General Hospital, Mongan Institute, Boston, MA, USA; 4Harvard Medical School, Department of Medicine, Boston, MA, USA; 5Harvard Medical School, Department of Health Care Policy, Boston, MA, USA Abstract: The elderly population faces an increasing number of cases of chronic neurological conditions, such as epilepsy and Alzheimer&rsquo;s disease. Because the elderly with epilepsy are commonly excluded from randomized controlled clinical trials, there are few rigorous studies to guide clinical practice. When the elderly are eligible for trials, they either rarely participate or frequently have poor adherence to therapy, thus limiting both generalizability and validity. In contrast, large observational data sets are increasingly available, but are susceptible to bias when using common analytic approaches. Recent developments in causal inference-analytic approaches also introduce the possibility of emulating randomized controlled trials to yield valid estimates. We provide a practical example of the application of the principles of causal inference to a large observational data set of patients with epilepsy. This review also provides a framework for comparative-effectiveness research in chronic neurological conditions. Keywords: epilepsy, epidemiology, neurostatistics, causal inferenc

K-alpha and bremsstrahlung x-ray radiation backlighter sources from short pulse laser driven silver targets as a function of laser pre-pulse energy

Measurements of silver K-shell and bremsstrahlung emission from thin-foil laser targets as a function of laser prepulse energy are presented. The silver targets were chosen as a potential 22 keV backlighter source for the National Ignition Facility Experiments. The targets were irradiated by the Titan laser with an intensity of 8 × 1017 W/cm2 with 40 ps pulse length. A secondary nanosecond timescale laser pulse with controlled, variable energy was used to emulate the laser prepulse. Results show a decrease in both Kα and bremsstrahlung yield with increasing artificial prepulse. Radiation hydrodynamic modeling of the prepulse interaction determined that the preplasma and intact target fraction were different in the three prepulse energies investigated. Interaction of the short pulse laser with the resulting preplasma and target was then modeled using a particle-in-cell code PSC which explained the experimental results. The relevance of this work to future Advanced Radiographic Capability laser x-ray backlighter sources is discussed. © 2014 AIP Publishing LLC

Communing with the Fictional Dead: Grave Tourism and the Sentimental Novel

From the 1770s onwards gravesites of characters from Laurence Sterne’s Life and Opinions of Tristram Shandy, Gentleman (1759–67), A Sentimental Journey through France and Italy (1768) and Susanna Rowson’s Charlotte Temple: A Tale of Truth (1791) appeared across Germany and in America as a unique form of literary afterlife. This essay argues that graves of literary heroines, Maria and Charlotte, were a means by which readers could express the heightened sensibility characteristic of the sentimental novel tradition through communing with favourite dead characters and—whether through sociable pilgrimage or simply in imagination—other sentimental readers. Considering the characteristically tragic outcomes for female protagonists of the sentimental novel, the practice of grave-visiting described here depends on while also unpacking narratives which explore female sexuality and its relationship with death. Graves to fictional characters therefore facilitated readers’ quixotic mourning while holding the potential to provoke collective criticism of sentimental literary culture’s framing of female sexuality, other than that which conveniently concludes with marriage, as traged