Complexity measure in natural time analysis identifying the accumulation of stresses before major earthquakes.

Here, we suggest a procedure through which one can identify when the accumulation of stresses before major earthquakes (EQs) (of magnitude M 8.2 or larger) occurs. Analyzing the seismicity in natural time, which is a new concept of time, we study the evolution of the fluctuations of the entropy change of seismicity under time reversal for various scales of different length i (number of events).

Phase I Study of a Multivalent WT1 Peptide Vaccine (Galinpepimut-S) in Combination with Nivolumab in Patients with WT1-Expressing Ovarian Cancer in Second or Third Remission.

We examined the safety and immunogenicity of sequential administration of a tetravalent, non-HLA (human leukocyte antigen) restricted, heteroclitic Wilms' Tumor 1 (WT1) peptide vaccine (galinpepimut-S) with anti-PD-1 (programmed cell death protein 1) nivolumab. This open-label, non-randomized phase I study enrolled patients with WT1-expressing ovarian cancer in second or third remission from June 2016 to July 2017. Therapy included six (every two weeks) subcutaneous inoculations of galinpepimut-S vaccine adjuvanted with Montanide, low-dose subcutaneous sargramostim at the injection site, with intravenous nivolumab over 12 weeks, and up to six additional doses until disease progression or toxicity.

Earthquake Nowcasting: Retrospective Testing in Greece.

Earthquake nowcasting (EN) is a modern method of estimating seismic risk by evaluating the progress of the earthquake (EQ) cycle in fault systems. EN evaluation is based on a new concept of time, termed 'natural time'. EN employs natural time, and uniquely estimates seismic risk by means of the earthquake potential score (EPS), which has been found to have useful applications both regionally and globally.

Estimating the Epicenter of a Future Strong Earthquake in Southern California, Mexico, and Central America by Means of Natural Time Analysis and Earthquake Nowcasting.

It has recently been shown in the Eastern Mediterranean that by combining natural time analysis of seismicity with earthquake networks based on similar activity patterns and earthquake nowcasting, an estimate of the epicenter location of a future strong earthquake can be obtained. This is based on the construction of average earthquake potential score maps. Here, we propose a method of obtaining such estimates for a highly seismically active area that includes Southern California, Mexico and part of Central America, i.

Nowcasting Avalanches as Earthquakes and the Predictability of Strong Avalanches in the Olami-Feder-Christensen Model.

Nowcasting earthquakes, suggested recently as a method to estimate the state of a fault and hence the seismic risk, is based on the concept of natural time. Here, we generalize nowcasting to a prediction method the merits of which are evaluated by means of the receiver operating characteristics. This new prediction method is applied to a simple (toy) model for the waiting (natural) time of the stronger earthquakes, real seismicity, and the Olami-Feder-Christensen earthquake model with interesting results revealing acceptable to excellent or even outstanding performance.

Natural Time Analysis: The Area under the Receiver Operating Characteristic Curve of the Order Parameter Fluctuations Minima Preceding Major Earthquakes.

It has been reported that major earthquakes are preceded by Seismic Electric Signals (SES). Observations show that in the natural time analysis of an earthquake (EQ) catalog, an SES activity starts when the fluctuations of the order parameter of seismicity exhibit a minimum. Fifteen distinct minima-observed simultaneously at two different natural time scales and deeper than a certain threshold-are found on analyzing the seismicity of Japan from 1 January 1984 to 11 March 2011 (the time of the M9 Tohoku EQ occurrence) 1 to 3 months before large EQs.

Identifying the Occurrence Time of the Deadly Mexico M8.2 Earthquake on 7 September 2017.

It has been shown that some dynamic features hidden in the time series of complex systems can be unveiled if we analyze them in a time domain termed natural time. In this analysis, we can identify when a system approaches a critical point (dynamic phase transition). Here, based on natural time analysis, which enables the introduction of an order parameter for seismicity, we discuss a procedure through which we could achieve the identification of the occurrence time of the M8.

Study in Natural Time of Geoelectric Field and Seismicity Changes Preceding the M6.8 Earthquake on 25 October 2018 in Greece.

A strong earthquake of magnitude M w 6.8 struck Western Greece on 25 October 2018 with an epicenter at 37.515 ∘ N 20.

Tsallis Entropy Index and the Complexity Measure of Seismicity in Natural Time under Time Reversal before the M9 Tohoku Earthquake in 2011.

The observed earthquake scaling laws indicate the existence of phenomena closely associated with the proximity of the system to a critical point. Taking this view that earthquakes are critical phenomena (dynamic phase transitions), here we investigate whether in this case the Lifshitz-Slyozov-Wagner (LSW) theory for phase transitions showing that the characteristic size of the minority phase droplets grows with time as t 1 / 3 is applicable. To achieve this goal, we analyzed the Japanese seismic data in a new time domain termed natural time and find that an LSW behavior is actually obeyed by a precursory change of seismicity and in particular by the fluctuations of the entropy change of seismicity under time reversal before the Tohoku earthquake of magnitude 9.

Statistical Significance of Earth's Electric and Magnetic Field Variations Preceding Earthquakes in Greece and Japan Revisited.

By analyzing the seismicity in a new time domain, termed natural time, we recently found that the change of the entropy under time reversal (, , 625-634) and the relevant complexity measures (, , 477) exhibit pronounced variations before the occurrence of the M8.2 earthquake in Mexico on 7 September 2017. Here, the statistical significance of precursory phenomena associated with other physical properties and in particular the anomalous variations observed in the Earth's electric and magnetic fields before earthquakes in different regions of the world and in particular in Greece since 1980s and Japan during 2001-2010 are revisited (the latter, i.

The Complexity Measures Associated with the Fluctuations of the Entropy in Natural Time before the Deadly México M8.2 Earthquake on 7 September 2017.

We analyse seismicity during the 6-year period 2012-2017 in the new time domain termed natural time in the Chiapas region where the M8.2 earthquake occurred, Mexico's largest earthquake in more than a century, in order to study the complexity measures associated with fluctuations of entropy as well as with entropy change under time reversal. We find that almost three months before the M8.

Micro-scale, mid-scale, and macro-scale in global seismicity identified by empirical mode decomposition and their multifractal characteristics.

The magnitude time-series of the global seismicity is analyzed by the empirical mode decomposition giving rise to 14 intrinsic mode functions (IMF) and a trend. Using Hurst analysis one can identify three different sums of these IMFs and the trend which exhibit distinct multifractal behaviour and correspond to micro-, mid- and macro-scales. Their multifractal detrended fluctuation analysis reveals that the micro-scale time-series exhibits anticorrelated behaviour in contrast to the mid-scale one which is long-range correlated.

Phase 2 trial of a multivalent WT1 peptide vaccine (galinpepimut-S) in acute myeloid leukemia.

A National Cancer Institute consensus study on prioritization of cancer antigens ranked the Wilms tumor 1 (WT1) protein as the top immunotherapy target in cancer. We previously reported a pilot study of a multivalent WT1 peptide vaccine (galinpepimut-S) in acute myeloid leukemia (AML) patients. We have now conducted a phase 2 study investigating this vaccine in adults with AML in first complete remission (CR1).

Estimating the Compressibility of Osmium from Recent Measurements of Ir-Os Alloys under High Pressure.

Several fcc- and hcp-structured Ir-Os alloys have been recently studied up to 30 GPa at room temperature by means of synchrotron-based X-ray powder diffraction in diamond anvil cells. Using their bulk moduli, which increase with increasing osmium content, showing a deviation from linearity, and after employing a thermodynamical model, it was concluded that the bulk modulus for osmium is slightly smaller than that for diamond. Here, a similar conclusion is obtained upon employing an alternative model, thus strengthening the conclusion that osmium is the densest but not the most incompressible element.

Patterns of hydroxyurea use and clinical outcomes among patients with polycythemia vera in real-world clinical practice: a chart review.

Background: Hydroxyurea (HU) is among the most commonly used cytoreductive treatments for polycythemia vera (PV), but previous research and clinical experience suggest that not all patients respond optimally, consistently, or durably to HU treatment. This study investigated patterns of HU use and impact on disease control among patients with PV in real-world clinical practice in the United States.

Methods: Oncologists and hematologists recruited between April and July 2014 reported data from patient charts.

A pooled analysis of overall survival in COMFORT-I and COMFORT-II, 2 randomized phase III trials of ruxolitinib for the treatment of myelofibrosis.

Ruxolitinib, a potent Janus kinase 1/2 inhibitor, resulted in rapid and durable improvements in splenomegaly and disease-related symptoms in the 2 phase III COMFORT studies. In addition, ruxolitinib was associated with prolonged survival compared with placebo (COMFORT-I) and best available therapy (COMFORT-II). We present a pooled analysis of overall survival in the COMFORT studies using an intent-to-treat analysis and an analysis correcting for crossover in the control arms.

Endothelial growth factor receptor inhibitors in recurrent metastatic cancer of the head and neck.

Targeted therapy has become an important new class of therapeutic agents used in squamous cell carcinoma of the head and neck (SCCHN). Among them epidermal growth factor receptor (EGFR) inhibitors have been studied the most. Today, two classes of EGFR inhibitors are routinely used in the clinic; anti-EGFR monoclonal antibodies and small-molecule inhibitors of the EGFR tyrosine kinase activity.

Spatiotemporal variations of seismicity before major earthquakes in the Japanese area and their relation with the epicentral locations.

Using the Japan Meteorological Agency earthquake catalog, we investigate the seismicity variations before major earthquakes in the Japanese region. We apply natural time, the new time frame, for calculating the fluctuations, termed β, of a certain parameter of seismicity, termed κ1. In an earlier study, we found that β calculated for the entire Japanese region showed a minimum a few months before the shallow major earthquakes (magnitude larger than 7.

Myelofibrosis-associated complications: pathogenesis, clinical manifestations, and effects on outcomes.

Myelofibrosis (MF) is a rare chronic BCR-ABL1 (breakpoint cluster region-Abelson murine leukemia viral oncogene homologue 1)-negative myeloproliferative neoplasm characterized by progressive bone marrow fibrosis, inefficient hematopoiesis, and shortened survival. The clinical manifestations of MF include splenomegaly, consequent to extramedullary hematopoiesis, cytopenias, and an array of potentially debilitating abdominal and constitutional symptoms. Dysregulated Janus kinase (JAK)-signal transducer and activator of transcription signaling underlies secondary disease-associated effects in MF, such as myeloproliferation, bone marrow fibrosis, constitutional symptoms, and cachexia.

Symptom burden and splenomegaly in patients with myelofibrosis in the United States: a retrospective medical record review.

Myelofibrosis (MF) is a clonal hematopoietic malignancy characterized by constitutional and localized symptoms, progressive splenomegaly, bone marrow fibrosis, and cytopenias. Although MF is well studied, few studies exist regarding its symptomatic burden in routine clinical practice. This study aimed to characterize symptoms and other clinical features of MF among patients in the United States.

Management of cytopenias in patients with myelofibrosis treated with ruxolitinib and effect of dose modifications on efficacy outcomes.

Purpose: Ruxolitinib is an oral Janus kinase (JAK) 1/JAK2 inhibitor approved in the US for the treatment of intermediate-or high-risk myelofibrosis (MF). Because thrombopoietin and erythropoietin signal through JAK2, dose-dependent cytopenias are expected with treatment. In the COMFORT-I (COntrolled Myelofibrosis study with ORal JAK inhibitor Treatment I) trial, these cytopenias were effectively managed with dose adjustments.

On the recent seismic activity in North-Eastern Aegean Sea including the M(w)5.8 earthquake on 8 January 2013.

In the last week of November 2012, we announced that a strong electrotelluric disturbance, which we judged to be a Seismic Electric Signal (SES) activity, was recorded at station Assiros located in Northern Greece. This disturbance was actually followed by an Mw5.8 earthquake on 8 January 2013 in North-Eastern Aegean Sea.

Minimum of the order parameter fluctuations of seismicity before major earthquakes in Japan.

It has been shown that some dynamic features hidden in the time series of complex systems can be uncovered if we analyze them in a time domain called natural time χ. The order parameter of seismicity introduced in this time domain is the variance of χ weighted for normalized energy of each earthquake. Here, we analyze the Japan seismic catalog in natural time from January 1, 1984 to March 11, 2011, the day of the M9 Tohoku earthquake, by considering a sliding natural time window of fixed length comprised of the number of events that would occur in a few months.

Acetylated tubulin (AT) as a prognostic marker in squamous cell carcinoma of the head and neck.

Acetylated tubulin (AT) expression has been proposed as a marker for sensitivity to taxane chemotherapy. We wanted to explore AT as a prognostic marker in squamous cell carcinoma of the head and neck (SCCHN). We assessed AT expression in archival tissue from our institutional tissue bank of primary SCCHN specimens.

Progressive burden of myelofibrosis in untreated patients: assessment of patient-reported outcomes in patients randomized to placebo in the COMFORT-I study.

Patient-reported outcomes (PROs) and spleen size in patients not receiving therapy (N=154) in COMFORT-I, a randomized, double-blind study of the JAK1/JAK2 inhibitor ruxolitinib in patients with intermediate-2 or high-risk myelofibrosis were evaluated. Baseline PROs indicated considerable disease burden. European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 scores, modified Myelofibrosis Symptom Assessment Form v2.