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We study the synchronization properties in a network of leaky integrate-and-fire oscillators with nonlocal connectivity under probabilistic small-world rewiring. We demonstrate that the random links lead to the emergence of chimera-like states where the coherent regions are interrupted by scattered, short-lived solitaries; these are termed "shooting solitaries." Moreover, we provide evidence that random links enhance the appearance of chimera-like states for values of the parameter space that otherwise support synchronization. This last effect is counter-intuitive because by adding random links to the synchronous state, the system locally organizes into coherent and incoherent domains.

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One of the most important subduction zones in the world is located in the Mexican Pacific Coast, where the Cocos plate inserts beneath the North American plate. One part of it is located in the Mexican Pacific Coast, where the Cocos plate inserts beneath the North American plate with different dip angles, showing important seismicity. Under the central Mexican area, such a dip angle becomes practically horizontal and such an area is known as flat slab. An earthquake of magnitude M7.1 occurred on 19 September 2017, the epicenter of which was located in this flat slab. It caused important human and material losses of urban communities including a large area of Mexico City. The seismicity recorded in the flat slab region is analyzed here in natural time from 1995 until the occurrence of this M7.1 earthquake in 2017 by studying the entropy change under time reversal and the variability ß of the order parameter of seismicity as well as characterize the risk of an impending earthquake by applying the nowcasting method. The entropy change ΔS under time reversal minimizes on 21 June 2017 that is almost one week after the observation of such a minimum in the Chiapas region where a magnitude M8.2 earthquake took place on 7 September 2017 being Mexico's largest quake in more than a century. A minimum of ß was also observed during the period February-March 2017. Moreover, we show that, after the minimum of ΔS, the order parameter of seismicity starts diminishing, thus approaching gradually the critical value 0.070 around the end of August and the beginning of September 2017, which signals that a strong earthquake is anticipated shortly in the flat slab.

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It has been recently shown [N. V. Sarlis, Phys. Rev. E 84, 022101 (2011) and N. V. Sarlis and S.-R. G. Christopoulos, Chaos 22, 023123 (2012)] that earthquakes of magnitude M greater or equal to 7 are globally correlated. Such correlations were identified by studying the variance κ1 of natural time which has been proposed as an order parameter for seismicity. Here, we study the fluctuations of this order parameter using the Global Centroid Moment Tensor catalog for a magnitude threshold Mthres = 5.0 and focus on its behavior before major earthquakes. Natural time analysis reveals that distinct minima of the fluctuations of the order parameter of seismicity appear within almost five and a half months on average before all major earthquakes of magnitude larger than 8.4. This phenomenon corroborates the recent finding [N. V. Sarlis et al., Proc. Natl. Acad. Sci. U.S.A. 110, 13734 (2013)] that similar minima of the seismicity order parameter fluctuations had preceded all major shallow earthquakes in Japan. Moreover, on the basis of these minima a statistically significant binary prediction method for earthquakes of magnitude larger than 8.4 with hit rate 100% and false alarm rate 6.67% is suggested.

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We study the threshold distribution function of the coherent-noise model for the case of infinite number of agents. This function is piecewise constant with a finite number of steps n. The latter exhibits a 1/f behavior as a function of the order of occurrence of an avalanche and hence versus natural time. An analytic expression of the expectation value E(S) for the size S of the next avalanche is obtained and used for the prediction of the next avalanche. Apart from E(S), the number of steps n can also serve for this purpose. This enables the construction of a similar prediction scheme which can be applied to real earthquake aftershock data.

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By using the most recent version (1900-2007) of the Centennial Earthquake Catalog, we examine the properties of the global seismicity. Natural time analysis reveals that the fluctuations of the order parameter κ(1) of seismicity exhibit for at least three orders of magnitude a characteristic feature similar to that of the order parameter for other equilibrium or non-equilibrium critical systems-including self-organized critical systems. Moreover, we find non-trivial magnitude correlations for earthquakes of magnitude greater than or equal to 7.

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BACKGROUND: Tumor lysis syndrome (TLS) is a life-threatening disorder characterized by hyperuricemia and metabolic derangements. The efficacy of rasburicase, administered daily for 5 days, has been well established. However, the optimal duration of therapy is unknown in adults. PATIENTS AND METHODS: We evaluated the efficacy of rasburicase (0.15 mg/kg) administered as single dose followed by as needed dosing (maximum five doses) versus daily dosing for 5 days in adult patients at risk for TLS. RESULTS: Eighty of the 82 patients enrolled received rasburicase; 40 high risk [median uric acid (UA) 8.5 mg/dl; range, 1.5-19.7] and 40 potential risk (UA = 5.6 mg/dl; range, 2.4-7.4). Seventy-nine patients (99%) experienced normalization in their UA within 4 h after the first dose; 84% to an undetectable level (<0.7 mg/dl). Thirty-nine of 40 (98%) patients in the daily-dose arm and 34 of 40 (85%) patients in single-dose arm showed sustained UA response. Six high-risk patients within the single-dose arm required second dose for UA >7.5 mg/dl. Rasburicase was well tolerated; one patient with glucose-6-phosphate dehydrogenase deficiency developed methemoglobinemia and hemolysis. CONCLUSIONS: Rasburicase is highly effective for prevention and management of hyperuricemia in adults at risk for TLS. Single-dose rasburicase was effective in most patients; only a subset of high-risk patients required a second dose.

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By employing natural time analysis, we analyze the worldwide seismicity and study the existence of correlations between earthquake magnitudes. We find that global seismicity exhibits nontrivial magnitude correlations for earthquake magnitudes greater than M(w) 6.5.

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BACKGROUND: The association between human papillomavirus (HPV) and overall survival (OS) in oropharynx cancer (OPC) was retrospectively examined in TAX 324, a phase III trial of sequential therapy for locally advanced head and neck cancer. METHODS: Accrual for TAX 324 was completed in 2003 and data updated through 2008. Pretherapy tumor biopsies were studied by PCR for human papillomavirus type 16 and linked to OS, progression-free survival (PFS) and demographics. RESULTS: Of 264 patients with OPC, 111 (42%) had evaluable biopsies; 56 (50%) were HPV+ and 55 (50%) were HPV-. HPV+ patients were significantly younger (54 versus 58 years, P = 0.02), had T1/T2 primary cancers (49% versus 20%, P = 0.001), and had a performance status of zero (77% versus 49%, P = 0.003). OS and PFS were better for HPV+ patients (OS, hazard ratio = 0.20, P < 0.0001). Local-regional failure was less in HPV+ patients (13% versus 42%, P = 0.0006); at 5 years, 82% of HPV+ patients were alive compared with 35% of HPV- patients (P < 0.0001). CONCLUSIONS: HPV+ OPC has a different biology compared with HPV- OPC; 5-year OS, PFS, and local-regional control are unprecedented. These results support the possibility of selectively reducing therapy and long-term morbidity in HPV+ OPC while preserving survival and approaching HPV- disease with more aggressive treatment.

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Electric field variations that appear before rupture have been recently studied by employing the detrended fluctuation analysis (DFA) to quantify their long-range temporal correlations. These studies revealed that seismic electric signal (SES) activities exhibit a scale invariant feature with an exponent αDFA≈1 over all scales investigated (around five orders of magnitude). Here, we study what happens upon significant data loss, which is a question of primary practical importance, and show that the DFA applied to the natural time representation of the remaining data still reveals for SES activities an exponent close to 1.0, which markedly exceeds the exponent found in artificial (man-made) noises. This enables the identification of a SES activity with probability of 75% even after a significant (70%) data loss. The probability increases to 90% or larger for 50% data loss.

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Nonextensive statistical mechanics, pioneered by Tsallis, has recently achieved a generalization of the Gutenberg-Richter law for earthquakes. This remarkable generalization is combined here with natural time analysis, which enables the distinction of two origins of self-similarity, i.e., the process' memory and the process' increments infinite variance. By using also detrended fluctuation analysis for the detection of long-range temporal correlations, we demonstrate the existence of both temporal and magnitude correlations in real seismic data of California and Japan. Natural time analysis reveals that the nonextensivity parameter q , in contrast to some published claims, cannot be considered as a measure of temporal organization, but the Tsallis formulation does achieve a satisfactory description of real seismic data for Japan for q=1.66 when supplemented by long-range temporal correlations.

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Hypercalcemia is the most common life-threatening metabolic disorder associated with cancer, occurring in approximately 10-30% of all patients with neoplastic disease, although it occurs much less often in the pediatric setting. Hypercalcemia can emerge in hematologic malignancies, particularly multiple myeloma, as well as assorted solid tumors, primarily lung and breast cancers, and can even dominate the clinical picture in select patients. Early diagnosis and treatment with fluids and drugs that lower calcium levels in the blood can improve symptoms in a few days, ameliorate the quality of life of these patients, and avoid delays in the implementation of further anticancer treatments. Occasionally, the symptoms of hypercalcemia can appear gradually, and may be non-specific, resembling symptoms of many cancers and other comorbidities, especially in the elderly, thus resulting in an underestimated incidence of hypercalcemia in cancer patients. Of note, there is an increasing number of antineoplastic compounds that can interfere with calcium metabolism. Taking into consideration both the severity of hypercalcemia and the tumor status, health care providers should determine and apply appropriate treatment measures. We provide a comprehensive subjective synthesis of peer-reviewed evidence on the pathophysiology and treatment of hypercalcemia in cancer patients.

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Natural time chi enables the distinction of two origins of self-similarity, i.e., the process memory and the process increments infinite variance. Employing multiplicative cascades in natural time, the most probable value of the variance kappa(1)(is identical to chi(2)-chi(2))is explicitly related with the parameter b of the Gutenberg-Richter law of randomly shuffled earthquake data. Moreover, the existence of temporal and magnitude correlations is studied in the original earthquake data. Magnitude correlations are larger for closer in time earthquakes, when the maximum interoccurrence time varies from half a day to 1 min.

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Magnetic field variations are detected before rupture in the form of "spikes" of alternating sign. The distinction of these spikes from random noise is of major practical importance since it is easier to conduct magnetic field measurements than electric field ones. Applying detrended fluctuation analysis (DFA), these spikes look to be random at short time lags. On the other hand, long-range correlations prevail at time lags larger than the average time interval between consecutive spikes with a scaling exponent alpha around 0.9. In addition, DFA is applied to recent preseismic electric field variations in long duration (several hours to a couple of days) and reveals a scale invariant feature with an exponent alpha approximately 1 over all scales available (around five orders of magnitude).

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The behavior of seismicity in the area candidate to suffer a main shock is investigated after the observation of the Seismic Electric Signal activity until the impending main shock. This is based on the view that the occurrence of earthquakes is a critical phenomenon to which statistical dynamics may be applied. In the present work, analysing the time series of small earthquakes, the concept of natural time chi was used and the results revealed that the approach to criticality itself can be manifested by the probability density function (PDF) of kappa(1) calculated over an appropriate statistical ensemble. Here, kappa(1) is the variance kappa(1)(=-(2)) resulting from the power spectrum of a function defined as Phi(omega)= summation operator(k=1)(N) p(k) exp(iomegachi(k)), where p(k) is the normalized energy of the k-th small earthquake and omega the natural frequency. This PDF exhibits a maximum at kappa(1) asymptotically equal to 0.070 a few days before the main shock. Examples are presented, referring to the magnitude 6 approximately 7 class earthquakes that occurred in Greece.

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Self-similarity may originate from two origins: i.e., the process memory and the process' increments "infinite" variance. A distinction is attempted by employing the natural time chi . Concerning the first origin, we analyze recent data on seismic electric signals, which support the view that they exhibit infinitely ranged temporal correlations. Concerning the second, slowly driven systems that emit bursts of various energies E obeying the power-law distribution--i.e., P(E) approximately E(-gamma)--are studied. An interrelation between the exponent gamma and the variance kappa1(identical with - ) is obtained for the shuffled (randomized) data. For real earthquake data, the most probable value of kappa1 of the shuffled data is found to be approximately equal to that of the original data, the difference most likely arising from temporal correlation. Finally, it is found that the differential entropy associated with the probability P(kappa1) maximizes for gamma around gamma approximately 1.6-1.7 , which is comparable to the value determined experimentally in diverse phenomena: e.g., solar flares, icequakes, dislocation glide in stressed single crystals of ice, etc. It also agrees with the b value in the Gutenberg-Richter law of earthquakes. In addition, the case of multiplicative cascades is studied in the natural time domain.

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Electric signals have been recently recorded at the Earth's surface with amplitudes appreciably larger than those hitherto reported. Their entropy in natural time is smaller than that of a "uniform" distribution. The same holds for their entropy upon time reversal. Such a behavior, which is also found by numerical simulations in fractional Brownian motion time series and in an on-off intermittency model, stems from infinitely ranged long range temporal correlations and hence these signals are probably seismic electric signal activities (critical dynamics). This classification is strikingly confirmed since three strong nearby earthquakes occurred (which is an extremely unusual fact) after the original submission of the present paper. The entropy fluctuations are found to increase upon approaching bursting, which is reminiscent of the behavior identifying sudden cardiac death individuals when analyzing their electrocardiograms.

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In this paper, we use quantum-mechanical formalism to describe the time evolution of a classical dynamical system with fluctuating parameters. By appropriate choice of "interaction picture representation," and the use of the Baker-Campbell-Hausdorff formula in the chronological time ordered evolution, we have obtained analytical expressions for the Lyapunov exponent of the energy evolution of the dynamical system. Our approach proved to be very powerful in handling either stochastic or highly correlated processes. The approach lends itself to generalizations for use in a wide field of applications.

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We report a similarity of fluctuations in equilibrium critical phenomena and nonequilibrium systems, which is based on the concept of natural time. The worldwide seismicity as well as that of the San Andreas fault system and Japan are analyzed. An order parameter is chosen and its fluctuations relative to the standard deviation of the distribution are studied. We find that the scaled distributions fall on the same curve, which interestingly exhibits, over four orders of magnitude, features similar to those in several equilibrium critical phenomena (e.g., two-dimensional Ising model) as well as in nonequilibrium systems (e.g., three-dimensional turbulent flow).

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Cytochrome P450 (CYP) is a group of enzymes that metabolize drugs to a more water-soluble form, rendering them available for renal excretion. The major site of CYP expression is the liver. Nearly 50% of all medications currently on the market are metabolized by the enzyme CYP3A4, while metabolism of another 35-40% occurs through enzymes CYP1A2, CYP2C19, CYP2D6, CYP3A5 CYP3A6, and CYP3A7. Here, we summarize the current knowledge of the effects of hormones on the CYP family. The term "hormone" is used in its broad sense and includes products of the major endocrine glands (i.e., thyroid, adrenals, gonads, pancreas) and compounds that are not classically considered hormones, such as neurogenic amines, cytokines, interleukins, and eicosanoids. In addition, we comment on the effects on CYP expression of states associated with profound hormonal changes, such as pregnancy, malnutrition, obesity, diabetes mellitus, systemic inflammation, and conditions of altered extracellular fluid volume or osmolality. Available data are limited and are derived primarily from in vitro and animal studies. Moreover, the picture is obscured by conflicting results among studies and the complexity of the regulation of the expression and activity of elements of the CYP system. While the clinical significance of hormonal effects on the CYP system remains to be determined, we anticipate that such effects will be most pertinent to drugs with a narrow therapeutic range. Further research is needed to determine the scope and significance of these effects in view of rapid advances in the field of pharmacogenomics and the ever-increasing number of drugs available for therapeutic use.

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We show that the entropy S , defined as S identical with chi ln chi - chi ln chi [Phys. Rev. E 68, 031106 (2003)] where chi stands for the natural time [Phys. Rev. E 66, 011902 (2002)], exhibits positivity and concavity as well as stability or experimental robustness. Furthermore, the distinction between the seismic electric signal activities and "artificial" noises, based on the classification of their S values, is lost when studying the time-reversed signals. This reveals the profound importance of considering the (true) time arrow.