Spatial Distribution of the Coefficient of Variation for the Paleo-Earthquakes in Japan

NASA Astrophysics Data System (ADS)

Nomura, S.; Ogata, Y.

2015-12-01

Renewal processes, point prccesses in which intervals between consecutive events are independently and identically distributed, are frequently used to describe this repeating earthquake mechanism and forecast the next earthquakes. However, one of the difficulties in applying recurrent earthquake models is the scarcity of the historical data. Most studied fault segments have few, or only one observed earthquake that often have poorly constrained historic and/or radiocarbon ages. The maximum likelihood estimate from such a small data set can have a large bias and error, which tends to yield high probability for the next event in a very short time span when the recurrence intervals have similar lengths. On the other hand, recurrence intervals at a fault depend on the long-term slip rate caused by the tectonic motion in average. In addition, recurrence times are also fluctuated by nearby earthquakes or fault activities which encourage or discourage surrounding seismicity. These factors have spatial trends due to the heterogeneity of tectonic motion and seismicity. Thus, this paper introduces a spatial structure on the key parameters of renewal processes for recurrent earthquakes and estimates it by using spatial statistics. Spatial variation of mean and variance parameters of recurrence times are estimated in Bayesian framework and the next earthquakes are forecasted by Bayesian predictive distributions. The proposal model is applied for recurrent earthquake catalog in Japan and its result is compared with the current forecast adopted by the Earthquake Research Committee of Japan.

Bayesian regression model for recurrent event data with event-varying covariate effects and event effect.

PubMed

Lin, Li-An; Luo, Sheng; Davis, Barry R

2018-01-01

In the course of hypertension, cardiovascular disease events (e.g., stroke, heart failure) occur frequently and recurrently. The scientific interest in such study may lie in the estimation of treatment effect while accounting for the correlation among event times. The correlation among recurrent event times come from two sources: subject-specific heterogeneity (e.g., varied lifestyles, genetic variations, and other unmeasurable effects) and event dependence (i.e., event incidences may change the risk of future recurrent events). Moreover, event incidences may change the disease progression so that there may exist event-varying covariate effects (the covariate effects may change after each event) and event effect (the effect of prior events on the future events). In this article, we propose a Bayesian regression model that not only accommodates correlation among recurrent events from both sources, but also explicitly characterizes the event-varying covariate effects and event effect. This model is especially useful in quantifying how the incidences of events change the effects of covariates and risk of future events. We compare the proposed model with several commonly used recurrent event models and apply our model to the motivating lipid-lowering trial (LLT) component of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) (ALLHAT-LLT).

Bayesian regression model for recurrent event data with event-varying covariate effects and event effect

PubMed Central

Lin, Li-An; Luo, Sheng; Davis, Barry R.

2017-01-01

In the course of hypertension, cardiovascular disease events (e.g., stroke, heart failure) occur frequently and recurrently. The scientific interest in such study may lie in the estimation of treatment effect while accounting for the correlation among event times. The correlation among recurrent event times come from two sources: subject-specific heterogeneity (e.g., varied lifestyles, genetic variations, and other unmeasurable effects) and event dependence (i.e., event incidences may change the risk of future recurrent events). Moreover, event incidences may change the disease progression so that there may exist event-varying covariate effects (the covariate effects may change after each event) and event effect (the effect of prior events on the future events). In this article, we propose a Bayesian regression model that not only accommodates correlation among recurrent events from both sources, but also explicitly characterizes the event-varying covariate effects and event effect. This model is especially useful in quantifying how the incidences of events change the effects of covariates and risk of future events. We compare the proposed model with several commonly used recurrent event models and apply our model to the motivating lipid-lowering trial (LLT) component of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) (ALLHAT-LLT). PMID:29755162

Constraining the Long-Term Average of Earthquake Recurrence Intervals From Paleo- and Historic Earthquakes by Assimilating Information From Instrumental Seismicity

NASA Astrophysics Data System (ADS)

Zoeller, G.

2017-12-01

Paleo- and historic earthquakes are the most important source of information for the estimationof long-term recurrence intervals in fault zones, because sequences of paleoearthquakes cover more than one seismic cycle. On the other hand, these events are often rare, dating uncertainties are enormous and the problem of missing or misinterpreted events leads to additional problems. Taking these shortcomings into account, long-term recurrence intervals are usually unstable as long as no additional information are included. In the present study, we assume that the time to the next major earthquake depends on the rate of small and intermediate events between the large ones in terms of a ``clock-change'' model that leads to a Brownian Passage Time distribution for recurrence intervals. We take advantage of an earlier finding that the aperiodicity of this distribution can be related to the Gutenberg-Richter-b-value, which is usually around one and can be estimated easily from instrumental seismicity in the region under consideration. This allows to reduce the uncertainties in the estimation of the mean recurrence interval significantly, especially for short paleoearthquake sequences and high dating uncertainties. We present illustrative case studies from Southern California and compare the method with the commonly used approach of exponentially distributed recurrence times assuming a stationary Poisson process.

Clustered mixed nonhomogeneous Poisson process spline models for the analysis of recurrent event panel data.

PubMed

Nielsen, J D; Dean, C B

2008-09-01

A flexible semiparametric model for analyzing longitudinal panel count data arising from mixtures is presented. Panel count data refers here to count data on recurrent events collected as the number of events that have occurred within specific follow-up periods. The model assumes that the counts for each subject are generated by mixtures of nonhomogeneous Poisson processes with smooth intensity functions modeled with penalized splines. Time-dependent covariate effects are also incorporated into the process intensity using splines. Discrete mixtures of these nonhomogeneous Poisson process spline models extract functional information from underlying clusters representing hidden subpopulations. The motivating application is an experiment to test the effectiveness of pheromones in disrupting the mating pattern of the cherry bark tortrix moth. Mature moths arise from hidden, but distinct, subpopulations and monitoring the subpopulation responses was of interest. Within-cluster random effects are used to account for correlation structures and heterogeneity common to this type of data. An estimating equation approach to inference requiring only low moment assumptions is developed and the finite sample properties of the proposed estimating functions are investigated empirically by simulation.

Comparison of Time-to-First Event and Recurrent Event Methods in Randomized Clinical Trials.

PubMed

Claggett, Brian; Pocock, Stuart; Wei, L J; Pfeffer, Marc A; McMurray, John J V; Solomon, Scott D

2018-03-27

Background -Most Phase-3 trials feature time-to-first event endpoints for their primary and/or secondary analyses. In chronic diseases where a clinical event can occur more than once, recurrent-event methods have been proposed to more fully capture disease burden and have been assumed to improve statistical precision and power compared to conventional "time-to-first" methods. Methods -To better characterize factors that influence statistical properties of recurrent-events and time-to-first methods in the evaluation of randomized therapy, we repeatedly simulated trials with 1:1 randomization of 4000 patients to active vs control therapy, with true patient-level risk reduction of 20% (i.e. RR=0.80). For patients who discontinued active therapy after a first event, we assumed their risk reverted subsequently to their original placebo-level risk. Through simulation, we varied a) the degree of between-patient heterogeneity of risk and b) the extent of treatment discontinuation. Findings were compared with those from actual randomized clinical trials. Results -As the degree of between-patient heterogeneity of risk was increased, both time-to-first and recurrent-events methods lost statistical power to detect a true risk reduction and confidence intervals widened. The recurrent-events analyses continued to estimate the true RR=0.80 as heterogeneity increased, while the Cox model produced estimates that were attenuated. The power of recurrent-events methods declined as the rate of study drug discontinuation post-event increased. Recurrent-events methods provided greater power than time-to-first methods in scenarios where drug discontinuation was ≤30% following a first event, lesser power with drug discontinuation rates of ≥60%, and comparable power otherwise. We confirmed in several actual trials in chronic heart failure that treatment effect estimates were attenuated when estimated via the Cox model and that increased statistical power from recurrent-events methods was most pronounced in trials with lower treatment discontinuation rates. Conclusions -We find that the statistical power of both recurrent-events and time-to-first methods are reduced by increasing heterogeneity of patient risk, a parameter not included in conventional power and sample size formulas. Data from real clinical trials are consistent with simulation studies, confirming that the greatest statistical gains from use of recurrent-events methods occur in the presence of high patient heterogeneity and low rates of study drug discontinuation.

Reinforced two-step-ahead weight adjustment technique for online training of recurrent neural networks.

PubMed

Chang, Li-Chiu; Chen, Pin-An; Chang, Fi-John

2012-08-01

A reliable forecast of future events possesses great value. The main purpose of this paper is to propose an innovative learning technique for reinforcing the accuracy of two-step-ahead (2SA) forecasts. The real-time recurrent learning (RTRL) algorithm for recurrent neural networks (RNNs) can effectively model the dynamics of complex processes and has been used successfully in one-step-ahead forecasts for various time series. A reinforced RTRL algorithm for 2SA forecasts using RNNs is proposed in this paper, and its performance is investigated by two famous benchmark time series and a streamflow during flood events in Taiwan. Results demonstrate that the proposed reinforced 2SA RTRL algorithm for RNNs can adequately forecast the benchmark (theoretical) time series, significantly improve the accuracy of flood forecasts, and effectively reduce time-lag effects.

Estimate variable importance for recurrent event outcomes with an application to identify hypoglycemia risk factors.

PubMed

Duan, Ran; Fu, Haoda

2015-08-30

Recurrent event data are an important data type for medical research. In particular, many safety endpoints are recurrent outcomes, such as hypoglycemic events. For such a situation, it is important to identify the factors causing these events and rank these factors by their importance. Traditional model selection methods are not able to provide variable importance in this context. Methods that are able to evaluate the variable importance, such as gradient boosting and random forest algorithms, cannot directly be applied to recurrent events data. In this paper, we propose a two-step method that enables us to evaluate the variable importance for recurrent events data. We evaluated the performance of our proposed method by simulations and applied it to a data set from a diabetes study. Copyright © 2015 John Wiley & Sons, Ltd.

Whole-Body MR Imaging Including Angiography: Predicting Recurrent Events in Diabetics.

PubMed

Bertheau, Robert C; Bamberg, Fabian; Lochner, Elena; Findeisen, Hannes M; Parhofer, Klaus G; Kauczor, Hans-Ulrich; Schoenberg, Stefan O; Weckbach, Sabine; Schlett, Christopher L

2016-05-01

Whether whole-body MRI can predict occurrence of recurrent events in patients with diabetes mellitus. Whole-body MRI was prospectively applied to 61 diabetics and assessed for arteriosclerosis and ischemic cerebral/myocardial changes. Occurrence of cardiocerebral events and diabetic comorbidites was determined. Patients were stratified whether no, a single or recurrent events arose. As a secondary endpoint, events were stratified into organ system-specific groups. During a median follow-up of 70 months, 26 diabetics developed a total of 39 events; 18 (30%) developed one, 8 (13%) recurrent events. Between diabetics with no, a single and recurrent events, a stepwise higher burden was observed for presence of left ventricular (LV) hypo-/akinesia (3/28/75%, p < 0.0001), myocardial delayed-contrast-enhancement (17/33/63%, p = 0.001), carotid artery stenosis (11/17/63%, p = 0.005), peripheral artery stenosis (26/56/88%, p = 0.0006) and vessel score (1.00/1.30/1.76, p < 0.0001). After adjusting for clinical characteristics, LV hypo-/akinesia (hazard rate ratio = 6.57, p < 0.0001) and vessel score (hazard rate ratio = 12.29, p < 0.0001) remained independently associated. Assessing organ system risk, cardiac and cerebral MR findings predicted more strongly events in their respective organ system. Vessel-score predicted both cardiac and cerebral, but not non-cardiocerebral, events. Whole-body MR findings predict occurrence of recurrent events in diabetics independent of clinical characteristics, and may concurrently provide organ system-specific risk. • Patients with long-standing diabetes mellitus are at high risk for recurrent events. • Whole-body MRI predicts occurrence of recurrent events independently of clinical characteristics. • The vessel score derived from whole-body angiography is a good general risk-marker. • Whole-body MRI may also provide organ-specific risk assessment. • Current findings may indicate benefits of whole-body MRI for risk stratification.

Are 12-lead ECG findings associated with the risk of cardiovascular events after ischemic stroke in young adults?

PubMed

Pirinen, Jani; Putaala, Jukka; Aarnio, Karoliina; Aro, Aapo L; Sinisalo, Juha; Kaste, Markku; Haapaniemi, Elena; Tatlisumak, Turgut; Lehto, Mika

2016-11-01

Ischemic stroke (IS) in a young patient is a disaster and recurrent cardiovascular events could add further impairment. Identifying patients with high risk of such events is therefore important. The prognostic relevance of ECG for this population is unknown. A total of 690 IS patients aged 15-49 years were included. A 12-lead ECG was obtained 1-14 d after the onset of stroke. We adjusted for demographic factors, comorbidities, and stroke characteristics, Cox regression models were used to identify independent ECG parameters associated with long-term risks of (1) any cardiovascular event, (2) cardiac events, and (3) recurrent stroke. Median follow-up time was 8.8 years. About 26.4% of patients experienced a cardiovascular event, 14.5% had cardiac events, and 14.6% recurrent strokes. ECG parameters associated with recurrent cardiovascular events were bundle branch blocks, P-terminal force, left ventricular hypertrophy, and a broader QRS complex. Furthermore, more leftward P-wave axis, prolonged QTc, and P-wave duration >120 ms were associated with increased risks of cardiac events. No ECG parameters were independently associated with recurrent stroke. A 12-lead ECG can be used for risk prediction of cardiovascular events but not for recurrent stroke in young IS patients. KEY MESSAGES ECG is an easy, inexpensive, and useful tool for identifying young ischemic stroke patients with a high risk for recurrent cardiovascular events and it has a statistically significant association with these events even after adjusting for confounding factors. Bundle branch blocks, P-terminal force, broader QRS complex, LVH according to Cornell voltage duration criteria, more leftward P-wave axis, prolonged QTc, and P-wave duration >120 ms are predictors for future cardiovascular or cardiac events in these patients. No ECG parameters were independently associated with recurrent stroke.

Variations in rupture process with recurrence interval in a repeated small earthquake

USGS Publications Warehouse

Vidale, J.E.; Ellsworth, W.L.; Cole, A.; Marone, Chris

1994-01-01

In theory and in laboratory experiments, friction on sliding surfaces such as rock, glass and metal increases with time since the previous episode of slip. This time dependence is a central pillar of the friction laws widely used to model earthquake phenomena. On natural faults, other properties, such as rupture velocity, porosity and fluid pressure, may also vary with the recurrence interval. Eighteen repetitions of the same small earthquake, separated by intervals ranging from a few days to several years, allow us to test these laboratory predictions in situ. The events with the longest time since the previous earthquake tend to have about 15% larger seismic moment than those with the shortest intervals, although this trend is weak. In addition, the rupture durations of the events with the longest recurrence intervals are more than a factor of two shorter than for the events with the shortest intervals. Both decreased duration and increased friction are consistent with progressive fault healing during the time of stationary contact.In theory and in laboratory experiments, friction on sliding surfaces such as rock, glass and metal increases with time since the previous episode of slip. This time dependence is a central pillar of the friction laws widely used to model earthquake phenomena. On natural faults, other properties, such as rupture velocity, porosity and fluid pressure, may also vary with the recurrence interval. Eighteen repetitions of the same small earthquake, separated by intervals ranging from a few days to several years, allow us to test these laboratory predictions in situ. The events with the longest time since the previous earthquake tend to have about 15% larger seismic moment than those with the shortest intervals, although this trend is weak. In addition, the rupture durations of the events with the longest recurrence intervals are more than a factor of two shorter than for the events with the shortest intervals. Both decreased duration and increased friction are consistent with progressive fault healing during the time of stationary contact.

Building Time-Dependent Earthquake Recurrence Models for Probabilistic Loss Computations

NASA Astrophysics Data System (ADS)

Fitzenz, D. D.; Nyst, M.

2013-12-01

We present a Risk Management perspective on earthquake recurrence on mature faults, and the ways that it can be modeled. The specificities of Risk Management relative to Probabilistic Seismic Hazard Assessment (PSHA), include the non-linearity of the exceedance probability curve for losses relative to the frequency of event occurrence, the fact that losses at all return periods are needed (and not at discrete values of the return period), and the set-up of financial models which sometimes require the modeling of realizations of the order in which events may occur (I.e., simulated event dates are important, whereas only average rates of occurrence are routinely used in PSHA). We use New Zealand as a case study and review the physical characteristics of several faulting environments, contrasting them against properties of three probability density functions (PDFs) widely used to characterize the inter-event time distributions in time-dependent recurrence models. We review the data available to help constrain both the priors and the recurrence process. And we propose that with the current level of knowledge, the best way to quantify the recurrence of large events on mature faults is to use a Bayesian combination of models, i.e., the decomposition of the inter-event time distribution into a linear combination of individual PDFs with their weight given by the posterior distribution. Finally we propose to the community : 1. A general debate on how best to incorporate our knowledge (e.g., from geology, geomorphology) on plausible models and model parameters, but also preserve the information on what we do not know; and 2. The creation and maintenance of a global database of priors, data, and model evidence, classified by tectonic region, special fluid characteristic (pH, compressibility, pressure), fault geometry, and other relevant properties so that we can monitor whether some trends emerge in terms of which model dominates in which conditions.

40 CFR 418.11 - Specialized definitions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... including precipitation runoff which, during manufacturing or processing, comes into incidental contact with...) Precipitation runoff; (2) accidental spills; (3) accidental leaks caused by the failure of process equipment and... shall mean the maximum 24-hour precipitation event with a probable recurrence interval of once in 10...

A Brownian model for recurrent earthquakes

USGS Publications Warehouse

Matthews, M.V.; Ellsworth, W.L.; Reasenberg, P.A.

2002-01-01

We construct a probability model for rupture times on a recurrent earthquake source. Adding Brownian perturbations to steady tectonic loading produces a stochastic load-state process. Rupture is assumed to occur when this process reaches a critical-failure threshold. An earthquake relaxes the load state to a characteristic ground level and begins a new failure cycle. The load-state process is a Brownian relaxation oscillator. Intervals between events have a Brownian passage-time distribution that may serve as a temporal model for time-dependent, long-term seismic forecasting. This distribution has the following noteworthy properties: (1) the probability of immediate rerupture is zero; (2) the hazard rate increases steadily from zero at t = 0 to a finite maximum near the mean recurrence time and then decreases asymptotically to a quasi-stationary level, in which the conditional probability of an event becomes time independent; and (3) the quasi-stationary failure rate is greater than, equal to, or less than the mean failure rate because the coefficient of variation is less than, equal to, or greater than 1/???2 ??? 0.707. In addition, the model provides expressions for the hazard rate and probability of rupture on faults for which only a bound can be placed on the time of the last rupture. The Brownian relaxation oscillator provides a connection between observable event times and a formal state variable that reflects the macromechanics of stress and strain accumulation. Analysis of this process reveals that the quasi-stationary distance to failure has a gamma distribution, and residual life has a related exponential distribution. It also enables calculation of "interaction" effects due to external perturbations to the state, such as stress-transfer effects from earthquakes outside the target source. The influence of interaction effects on recurrence times is transient and strongly dependent on when in the loading cycle step pertubations occur. Transient effects may be much stronger than would be predicted by the "clock change" method and characteristically decay inversely with elapsed time after the perturbation.

Chilean megathrust earthquake recurrence linked to frictional contrast at depth

NASA Astrophysics Data System (ADS)

Moreno, M.; Li, S.; Melnick, D.; Bedford, J. R.; Baez, J. C.; Motagh, M.; Metzger, S.; Vajedian, S.; Sippl, C.; Gutknecht, B. D.; Contreras-Reyes, E.; Deng, Z.; Tassara, A.; Oncken, O.

2018-04-01

Fundamental processes of the seismic cycle in subduction zones, including those controlling the recurrence and size of great earthquakes, are still poorly understood. Here, by studying the 2016 earthquake in southern Chile—the first large event within the rupture zone of the 1960 earthquake (moment magnitude (Mw) = 9.5)—we show that the frictional zonation of the plate interface fault at depth mechanically controls the timing of more frequent, moderate-size deep events (Mw < 8) and less frequent, tsunamigenic great shallow earthquakes (Mw > 8.5). We model the evolution of stress build-up for a seismogenic zone with heterogeneous friction to examine the link between the 2016 and 1960 earthquakes. Our results suggest that the deeper segments of the seismogenic megathrust are weaker and interseismically loaded by a more strongly coupled, shallower asperity. Deeper segments fail earlier ( 60 yr recurrence), producing moderate-size events that precede the failure of the shallower region, which fails in a great earthquake (recurrence >110 yr). We interpret the contrasting frictional strength and lag time between deeper and shallower earthquakes to be controlled by variations in pore fluid pressure. Our integrated analysis strengthens understanding of the mechanics and timing of great megathrust earthquakes, and therefore could aid in the seismic hazard assessment of other subduction zones.

LSTM-CRF | Informatics Technology for Cancer Research (ITCR)

Cancer.gov

LSTM-CRF uses Natural Language Processing methods for detecting Adverse Drug Events, Drugname, Indication and other medically relevant information from Electronic Health Records. It implements Recurrent Neural Networks using several CRF based inference methods.

The association between high on-treatment platelet reactivity and early recurrence of ischemic events after minor stroke or TIA.

PubMed

Rao, Zilong; Zheng, Huaguang; Wang, Fei; Wang, Anxin; Liu, Liping; Dong, Kehui; Zhao, Xingquan; Wang, Yilong; Cao, Yibin

2017-08-01

To evaluate the role of HTPR in predicting early recurrence of ischemic events in patients with minor ischemic stroke or high-risk TIA. From January 2014 to September 2014, a single center continuously enrolled patients with minor ischemic stroke or high-risk TIA and gave them antiplatelet therapy consisting of aspirin with clopidogrel. HTPR was assessed by TEG after 7 days of antiplatelet therapy and detected CYP2C19 genotype. The incidence of recurrent ischemic events was assessed 3 months after onset. The incidence of recurrent ischemic events was compared between the HTPR and NTPR groups with the Kaplan-Meier method, and multivariate Cox proportional hazards models were used to determine the risk factors associated with recurrent ischemic events. We enrolled 278 eligible patients with minor ischemic stroke or high-risk TIA. Through TEG testing, patients with HTPR were 22.7%, and carriers were not associated with HTPR to ADP by TEG-ADP(%) (p = 0.193). A total of 265 patients completed 3 months of follow-up, and Kaplan-Meier analysis showed that patients with HTPR had a higher percentage of recurrent ischemic events compared with patients with NTPR (p = 0.002). In multivariate Cox proportional hazards models, history of ischemic stroke or TIA (HR 4.45, 95% CI 1.77-11.16, p = 0.001) and HTPR (HR 3.34, 95% CI 1.41-7.91, p = 0.006) was independently associated with recurrent ischemic events. In patients with minor stroke or TIA, the prevalence of HTPR was 22.7%, and HTPR was independently associated with recurrent ischemic events.

Characterization of high-intensity, long-duration continuous auroral activity (HILDCAA) events using recurrence quantification analysis

NASA Astrophysics Data System (ADS)

Mendes, Odim; Oliveira Domingues, Margarete; Echer, Ezequiel; Hajra, Rajkumar; Everton Menconi, Varlei

2017-08-01

Considering the magnetic reconnection and the viscous interaction as the fundamental mechanisms for transfer particles and energy into the magnetosphere, we study the dynamical characteristics of auroral electrojet (AE) index during high-intensity, long-duration continuous auroral activity (HILDCAA) events, using a long-term geomagnetic database (1975-2012), and other distinct interplanetary conditions (geomagnetically quiet intervals, co-rotating interaction regions (CIRs)/high-speed streams (HSSs) not followed by HILDCAAs, and events of AE comprised in global intense geomagnetic disturbances). It is worth noting that we also study active but non-HILDCAA intervals. Examining the geomagnetic AE index, we apply a dynamics analysis composed of the phase space, the recurrence plot (RP), and the recurrence quantification analysis (RQA) methods. As a result, the quantification finds two distinct clusterings of the dynamical behaviours occurring in the interplanetary medium: one regarding a geomagnetically quiet condition regime and the other regarding an interplanetary activity regime. Furthermore, the HILDCAAs seem unique events regarding a visible, intense manifestations of interplanetary Alfvénic waves; however, they are similar to the other kinds of conditions regarding a dynamical signature (based on RQA), because it is involved in the same complex mechanism of generating geomagnetic disturbances. Also, by characterizing the proper conditions of transitions from quiescent conditions to weaker geomagnetic disturbances inside the magnetosphere and ionosphere system, the RQA method indicates clearly the two fundamental dynamics (geomagnetically quiet intervals and HILDCAA events) to be evaluated with magneto-hydrodynamics simulations to understand better the critical processes related to energy and particle transfer into the magnetosphere-ionosphere system. Finally, with this work, we have also reinforced the potential applicability of the RQA method for characterizing nonlinear geomagnetic processes related to the magnetic reconnection and the viscous interaction affecting the magnetosphere.

Periodic, chaotic, and doubled earthquake recurrence intervals on the deep San Andreas Fault

USGS Publications Warehouse

Shelly, David R.

2010-01-01

Earthquake recurrence histories may provide clues to the timing of future events, but long intervals between large events obscure full recurrence variability. In contrast, small earthquakes occur frequently, and recurrence intervals are quantifiable on a much shorter time scale. In this work, I examine an 8.5-year sequence of more than 900 recurring low-frequency earthquake bursts composing tremor beneath the San Andreas fault near Parkfield, California. These events exhibit tightly clustered recurrence intervals that, at times, oscillate between ~3 and ~6 days, but the patterns sometimes change abruptly. Although the environments of large and low-frequency earthquakes are different, these observations suggest that similar complexity might underlie sequences of large earthquakes.

Recurrence Interval and Event Age Data for Type A Faults

USGS Publications Warehouse

Dawson, Timothy E.; Weldon, Ray J.; Biasi, Glenn P.

2008-01-01

This appendix summarizes available recurrence interval, event age, and timing of most recent event data for Type A faults considered in the Earthquake Rate Model 2 (ERM 2) and used in the ERM 2 Appendix C analysis as well as Appendix N (time-dependent probabilities). These data have been compiled into an Excel workbook named Appendix B A-fault event ages_recurrence_V5.0 (herein referred to as the Appendix B workbook). For convenience, the Appendix B workbook is attached to the end of this document as a series of tables. The tables within the Appendix B workbook include site locations, event ages, and recurrence data, and in some cases, the interval of time between earthquakes is also reported. The Appendix B workbook is organized as individual worksheets, with each worksheet named by fault and paleoseismic site. Each worksheet contains the site location in latitude and longitude, as well as information on event ages, and a summary of recurrence data. Because the data has been compiled from different sources with different presentation styles, descriptions of the contents of each worksheet within the Appendix B spreadsheet are summarized.

Regression analysis of mixed recurrent-event and panel-count data with additive rate models.

PubMed

Zhu, Liang; Zhao, Hui; Sun, Jianguo; Leisenring, Wendy; Robison, Leslie L

2015-03-01

Event-history studies of recurrent events are often conducted in fields such as demography, epidemiology, medicine, and social sciences (Cook and Lawless, 2007, The Statistical Analysis of Recurrent Events. New York: Springer-Verlag; Zhao et al., 2011, Test 20, 1-42). For such analysis, two types of data have been extensively investigated: recurrent-event data and panel-count data. However, in practice, one may face a third type of data, mixed recurrent-event and panel-count data or mixed event-history data. Such data occur if some study subjects are monitored or observed continuously and thus provide recurrent-event data, while the others are observed only at discrete times and hence give only panel-count data. A more general situation is that each subject is observed continuously over certain time periods but only at discrete times over other time periods. There exists little literature on the analysis of such mixed data except that published by Zhu et al. (2013, Statistics in Medicine 32, 1954-1963). In this article, we consider the regression analysis of mixed data using the additive rate model and develop some estimating equation-based approaches to estimate the regression parameters of interest. Both finite sample and asymptotic properties of the resulting estimators are established, and the numerical studies suggest that the proposed methodology works well for practical situations. The approach is applied to a Childhood Cancer Survivor Study that motivated this study. © 2014, The International Biometric Society.

Periodontal Disease Associated with Aortic Arch Atheroma in Patients with Stroke or Transient Ischemic Attack.

PubMed

Sen, Souvik; Chung, Matthew; Duda, Viktoriya; Giamberardino, Lauren; Hinderliter, Alan; Offenbacher, Steven

2017-10-01

Periodontal disease (PD) is associated with recurrent vascular event in stroke or transient ischemic attack (TIA). In this study, we investigated whether PD is independently associated with aortic arch atheroma (AA). We also explored the relationship PD has with AA plaque thickness and other characteristics associated with atheroembolic risk among patients with stroke or TIA. Finally, we confirmed the association between AA and recurrent vascular event in patients with stroke or TIA. In this prospective longitudinal hospital-based cohort study, PD was assessed in patients with stroke and TIA. Patients with confirmed stroke and TIA (n = 106) were assessed by calibrated dental examiners to determine periodontal status and were followed over a median of 24 months for recurrent vascular events (stroke, myocardial infarction, and death). The extent of AA and other plaque characteristics was assessed by transesophageal echocardiography. Within our patient cohort, 27 of the 106 participants had recurrent vascular events (including 16 with stroke or TIA) over the median of 24-month follow-up. Severe PD was associated with increased AA plaque thickness and calcification. The results suggest that PD may be a risk factor for AA. In this cohort, we confirm the association of severe AA with recurrent vascular events. In patients with stroke or TIA, severe PD is associated with increased AA plaque thickness, a risk factor for recurrent events. Further studies are needed to confirm this finding and to determine whether treatment of PD can reduce the rate of AA plaque progression and recurrent vascular events. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Patterns of stroke recurrence according to subtype of first stroke event: the North East Melbourne Stroke Incidence Study (NEMESIS).

PubMed

Azarpazhooh, Mahmoud Reza; Nicol, Marcus B; Donnan, Geoffrey A; Dewey, Helen M; Sturm, Jonathan W; Macdonell, Richard A L; Pearce, Dora C; Thrift, Amanda G

2008-08-01

Specific information about the nature of recurrent events that occur after each subtype of index stroke may be useful for refining preventive therapies. We aimed to determine whether stroke recurrence rates, the pattern of subtype recurrence, and prescription of secondary prevention agents differed according to initial stroke subtype. Multiple overlapping sources were used to recruit all first-ever stroke patients from a geographically defined region of Melbourne, Australia over a 3-year period from 1996 to 1999. Potential stroke recurrences (fatal and nonfatal) occurring within 2 years of the initial event were identified following patient interview and follow up of death records. Subjects were classified into the different Oxfordshire groups and the type of first-ever stroke was compared with recurrent stroke events. One thousand, three hundred and sixteen first-ever strokes were registered during the 3-year period (mean age 74.4 years). A total of 103 first recurrent stroke events (fatal and nonfatal) occurred among those with a first-ever ischemic stroke or intracerebral hemorrhage (ICH) during the 2-year follow-up period. The recurrent stroke subtype was different to the index stroke subtype in most (78%) patients. People with partial anterior circulation infarct had the greatest proportion of recurrences (13%), with a third of these being the more severe total anterior circulation infarct subgroup. The relative risk of ICH after an index lacunar infarct (LACI) compared with an index non-LACI was 4.06 (95% CI 1.10-14.97, P=0.038). Prescription of secondary prevention agents was greater at 2 years after stroke than at hospital discharge, and was similar between ischemic stroke subtypes. Approximately 9% of people with first-ever stroke suffered a recurrent event, despite many being prescribed secondary prevention agents. This has implications for the uptake of current preventive strategies and the development of new strategies. The possibility that ICH is greater among index LACI cases needs to be confirmed.

Genomic analysis reveals secondary glioblastoma after radiotherapy in a subset of recurrent medulloblastomas.

PubMed

Phi, Ji Hoon; Park, Ae Kyung; Lee, Semin; Choi, Seung Ah; Baek, In-Pyo; Kim, Pora; Kim, Eun-Hye; Park, Hee Chul; Kim, Byung Chul; Bhak, Jong; Park, Sung-Hye; Lee, Ji Yeoun; Wang, Kyu-Chang; Kim, Dong-Seok; Shim, Kyu Won; Kim, Se Hoon; Kim, Chae-Yong; Kim, Seung-Ki

2018-06-01

Despite great advances in understanding of molecular pathogenesis and achievement of a high cure rate in medulloblastoma, recurrent medulloblastomas are still dismal. Additionally, misidentification of secondary malignancies due to histological ambiguity leads to misdiagnosis and eventually to inappropriate treatment. Nevertheless, the genomic characteristics of recurrent medulloblastomas are poorly understood, largely due to a lack of matched primary and recurrent tumor tissues. We performed a genomic analysis of recurrent tumors from 17 pediatric medulloblastoma patients. Whole transcriptome sequencing revealed that a subset of recurrent tumors initially diagnosed as locally recurrent medulloblastomas are secondary glioblastomas after radiotherapy, showing high similarity to the non-G-CIMP proneural subtype of glioblastoma. Further analysis, including whole exome sequencing, revealed missense mutations or complex gene fusion events in PDGFRA with augmented expression in the secondary glioblastomas after radiotherapy, implicating PDGFRA as a putative driver in the development of secondary glioblastomas after treatment exposure. This result provides insight into the possible application of PDGFRA-targeted therapy in these second malignancies. Furthermore, genomic alterations of TP53 including 17p loss or germline/somatic mutations were also found in most of the secondary glioblastomas after radiotherapy, indicating a crucial role of TP53 alteration in the process. On the other hand, analysis of recurrent medulloblastomas revealed that the most prevalent alterations are the loss of 17p region including TP53 and gain of 7q region containing EZH2 which already exist in primary tumors. The 7q gain events are frequently accompanied by high expression levels of EZH2 in both primary and recurrent medulloblastomas, which provides a clue to a new therapeutic target to prevent recurrence. Considering the fact that it is often challenging to differentiate between recurrent medulloblastomas and secondary glioblastomas after radiotherapy, our findings have major clinical implications both for correct diagnosis and for potential therapeutic interventions in these devastating diseases.

The role of life events and psychological factors in the onset of first and recurrent mood episodes in bipolar offspring: results from the Dutch Bipolar Offspring Study.

PubMed

Kemner, S M; Mesman, E; Nolen, W A; Eijckemans, M J C; Hillegers, M H J

2015-01-01

Life events are an established risk factor for the onset and recurrence of unipolar and bipolar mood episodes, especially in the presence of genetic vulnerability. The dynamic interplay between life events and psychological context, however, is less studied. In this study, we investigated the impact of life events on the onset and recurrence of mood episodes in bipolar offspring, as well as the effects of temperament, coping and parenting style on this association. Bipolar offspring (n = 108) were followed longitudinally from adolescence to adulthood. Mood disorders were assessed with: the Kiddie Schedule of Affective Disorders and Schizophrenia - Present and Lifetime Version or the Structured Clinical Interview for DSM-IV Axis I disorders; life events with the Life Events and Difficulties Schedule; and psychological measures using the Utrecht Coping List, Temperament and Character Inventory and short-EMBU (memories of upbringing instrument). Anderson-Gill models (an extension of the Cox proportional hazard model) were utilized. Life events were associated with an increased risk for first and, although less pronounced, subsequent mood episodes. There was a large confounding effect for the number of previous mood episodes; findings suggest a possible kindling effect. Passive coping style increased the risk of mood episode onset and recurrent episodes, but also altered the effect of life events on mood disorders. Harm avoidance temperament was associated with mood episode recurrence. Life events are especially a risk factor in the onset of mood disorders, though less so in recurrent episodes. Psychological features (passive coping and harm-avoidant temperament) contribute to the risk of an episode occurring, and also have a moderating effect on the association between life events and mood episodes. These findings create potential early intervention strategies for bipolar offspring.

Self-organized criticality in complex systems: Applicability to the interoccurrent and recurrent statistical behavior of earthquakes

NASA Astrophysics Data System (ADS)

Abaimov, Sergey G.

The concept of self-organized criticality is associated with scale-invariant, fractal behavior; this concept is also applicable to earthquake systems. It is known that the interoccurrent frequency-size distribution of earthquakes in a region is scale-invariant and obeys the Gutenberg-Richter power-law dependence. Also, the interoccurrent time-interval distribution is known to obey Poissonian statistics excluding aftershocks. However, to estimate the hazard risk for a region it is necessary to know also the recurrent behavior of earthquakes at a given point on a fault. This behavior has been investigated in the literature, however, major questions remain unresolved. The reason is the small number of earthquakes in observed sequences. To overcome this difficulty this research utilizes numerical simulations of a slider-block model and a sand-pile model. Also, experimental observations of creep events on the creeping section of the San Andreas fault are processed and sequences up to 100 events are studied. Then the recurrent behavior of earthquakes at a given point on a fault or at a given fault is investigated. It is shown that both the recurrent frequency-size and the time-interval behaviors of earthquakes obey the Weibull distribution.

Copeptin and Long-Term Risk of Recurrent Vascular Events After Transient Ischemic Attack and Ischemic Stroke: Population-Based Study.

PubMed

Greisenegger, Stefan; Segal, Helen C; Burgess, Annette I; Poole, Debbie L; Mehta, Ziyah; Rothwell, Peter M

2015-11-01

Copeptin, the c-terminal portion of provasopressin, is a useful prognostic marker in patients after myocardial infarction and heart failure. More recently, high levels of copeptin have also been associated with worse functional outcome and increased mortality within the first year after ischemic stroke and transient ischemic attack (TIA). However, to date, there are no published data on whether copeptin predicts long-term risk of vascular events after TIA and stroke. We measured copeptin levels in consecutive patients with TIA or ischemic stroke in a population-based study (Oxford Vascular Study) recruited from 2002 to 2007 and followed up to 2014. Associations with risk of recurrent vascular events were determined by Cox-regression. During ≈6000 patient-years in 1076 patients, there were 357 recurrent vascular events, including 174 ischemic strokes. After adjustment for age, sex, and risk factors, copeptin was predictive of recurrent vascular events (adjusted hazard ratio per SD, 1.47; 95% confidence interval, 1.31-1.64; P=0.0001), vascular death (1.85; 1.60-2.14; P<0.0001), all-cause death (1.75; 1.58-1.93; P<0.0001), and recurrent ischemic stroke (1.22; 1.04-1.44; P=0.017); and improved model-discrimination significantly: net reclassification improvement for recurrent vascular events (32%; P<0.0001), vascular death (55%; P<0.0001), death (66%; P<0.0001), and recurrent stroke (16%; P=0.044). The predictive value of copeptin was largest in patients with cardioembolic index events (adjusted hazard ratio, 1.84; 95% confidence interval, 1.53-2.20 versus 1.31, 1.14-1.50 in noncardioembolic stroke; P=0.0025). In patients with cardioembolic stroke, high copeptin levels were associated with a 4-fold increased risk of vascular events within the first year of follow-up (adjusted hazard ratio, 4.02; 95% confidence interval, 2.13-7.70). In patients with TIA and ischemic stroke, copeptin predicted recurrent vascular events and death, particularly after cardioembolic TIA/stroke. Further validation is required, in particular, in studies using more extensive cardiac evaluation. © 2015 American Heart Association, Inc.

Leveraging Long-term Seismic Catalogs for Automated Real-time Event Classification

NASA Astrophysics Data System (ADS)

Linville, L.; Draelos, T.; Pankow, K. L.; Young, C. J.; Alvarez, S.

2017-12-01

We investigate the use of labeled event types available through reviewed seismic catalogs to produce automated event labels on new incoming data from the crustal region spanned by the cataloged events. Using events cataloged by the University of Utah Seismograph Stations between October, 2012 and June, 2017, we calculate the spectrogram for a time window that spans the duration of each event as seen on individual stations, resulting in 110k event spectrograms (50% local earthquakes examples, 50% quarry blasts examples). Using 80% of the randomized example events ( 90k), a classifier is trained to distinguish between local earthquakes and quarry blasts. We explore variations of deep learning classifiers, incorporating elements of convolutional and recurrent neural networks. Using a single-layer Long Short Term Memory recurrent neural network, we achieve 92% accuracy on the classification task on the remaining 20K test examples. Leveraging the decisions from a group of stations that detected the same event by using the median of all classifications in the group increases the model accuracy to 96%. Additional data with equivalent processing from 500 more recently cataloged events (July, 2017), achieves the same accuracy as our test data on both single-station examples and multi-station medians, suggesting that the model can maintain accurate and stable classification rates on real-time automated events local to the University of Utah Seismograph Stations, with potentially minimal levels of re-training through time.

Social Rhythm Disrupting Events Increase the Risk of Recurrence among Individuals with Bipolar Disorder

PubMed Central

Levenson, Jessica C.; Wallace, Meredith L.; Anderson, Barbara P.; Kupfer, David J.; Frank, Ellen

2015-01-01

Objectives As outlined in the social zeitgeber hypothesis, social rhythm disrupting (SRD) life events begin a cascade of social and biological rhythm disruption that may lead to the onset of affective episodes in those vulnerable to bipolar disorder. Thus, the study of SRD events is particularly important in individuals with this chronic condition. The purpose of the current study was to evaluate 1) the extent to which social rhythm disrupting life events increased the risk of recurrence of a bipolar mood episode, and 2) whether the social rhythm disruption associated with the event conferred an increased risk of recurrence, after accounting for the level of threat associated with the life event. Methods We examined the effect of SRD events on recurrence during preventative treatment in a sample of 118 patients with bipolar disorder who achieved remission from an acute episode after receiving psychotherapy and pharmacotherapy. Life events were measured with the Bedford College Life Events and Difficulty Schedule and were rated for degree of SRD and threat. Results Time-dependent Cox proportional hazards models showed that that having a higher SRD rating was significantly associated with an increased risk of recurrence, even when accounting for the threat effect of a life event and psychosocial treatment (Hazard Rate = 1.33; 95% CI = 1.04, 1.70; p=0.023). However, this finding fell below conventional levels of statistical significance when accounting for other covariates. Conclusions Our findings lend partial support to the social zeitgeber hypothesis. PMID:26614534

Shallow repeating seismic events under an alpine glacier at Mount Rainier, Washington, USA

USGS Publications Warehouse

Thelen, Weston A.; Allstadt, Kate E.; De Angelis, Silvio; Malone, Stephen D.; Moran, Seth C.; Vidale, John

2013-01-01

We observed several swarms of repeating low-frequency (1–5 Hz) seismic events during a 3 week period in May–June 2010, near the summit of Mount Rainier, Washington, USA, that likely were a result of stick–slip motion at the base of alpine glaciers. The dominant set of repeating events ('multiplets') featured >4000 individual events and did not exhibit daytime variations in recurrence interval or amplitude. Volcanoes and glaciers around the world are known to produce seismic signals with great variability in both frequency content and size. The low-frequency character and periodic recurrence of the Mount Rainier multiplets mimic long-period seismicity often seen at volcanoes, particularly during periods of unrest. However, their near-surface location, lack of common spectral peaks across the recording network, rapid attenuation of amplitudes with distance, and temporal correlation with weather systems all indicate that ice-related source mechanisms are the most likely explanation. We interpret the low-frequency character of these multiplets to be the result of trapping of seismic energy under glacial ice as it propagates through the highly heterogeneous and attenuating volcanic material. The Mount Rainier multiplet sequences underscore the difficulties in differentiating low-frequency signals due to glacial processes from those caused by volcanic processes on glacier-clad volcanoes.

Bayesian Design of Superiority Clinical Trials for Recurrent Events Data with Applications to Bleeding and Transfusion Events in Myelodyplastic Syndrome

PubMed Central

Chen, Ming-Hui; Zeng, Donglin; Hu, Kuolung; Jia, Catherine

2014-01-01

Summary In many biomedical studies, patients may experience the same type of recurrent event repeatedly over time, such as bleeding, multiple infections and disease. In this article, we propose a Bayesian design to a pivotal clinical trial in which lower risk myelodysplastic syndromes (MDS) patients are treated with MDS disease modifying therapies. One of the key study objectives is to demonstrate the investigational product (treatment) effect on reduction of platelet transfusion and bleeding events while receiving MDS therapies. In this context, we propose a new Bayesian approach for the design of superiority clinical trials using recurrent events frailty regression models. Historical recurrent events data from an already completed phase 2 trial are incorporated into the Bayesian design via the partial borrowing power prior of Ibrahim et al. (2012, Biometrics 68, 578–586). An efficient Gibbs sampling algorithm, a predictive data generation algorithm, and a simulation-based algorithm are developed for sampling from the fitting posterior distribution, generating the predictive recurrent events data, and computing various design quantities such as the type I error rate and power, respectively. An extensive simulation study is conducted to compare the proposed method to the existing frequentist methods and to investigate various operating characteristics of the proposed design. PMID:25041037

Statistical analysis of mixed recurrent event data with application to cancer survivor study

PubMed Central

Zhu, Liang; Tong, Xingwei; Zhao, Hui; Sun, Jianguo; Srivastava, Deo Kumar; Leisenring, Wendy; Robison, Leslie L.

2014-01-01

Event history studies occur in many fields including economics, medical studies and social science. In such studies concerning some recurrent events, two types of data have been extensively discussed in the literature. One is recurrent event data that arise if study subjects are monitored or observed continuously. In this case, the observed information provides the times of all occurrences of the recurrent events of interest. The other is panel count data, which occur if the subjects are monitored or observed only periodically. This can happen if the continuous observation is too expensive or not practical and in this case, only the numbers of occurrences of the events between subsequent observation times are available. In this paper, we discuss a third type of data, which is a mixture of recurrent event and panel count data and for which there exists little literature. For regression analysis of such data, a marginal mean model is presented and we propose an estimating equation-based approach for estimation of regression parameters. A simulation study is conducted to assess the finite sample performance of the proposed methodology and indicates that it works well for practical situations. Finally it is applied to a motivating study on childhood cancer survivors. PMID:23139023

Estimating the effect of a rare time-dependent treatment on the recurrent event rate.

PubMed

Smith, Abigail R; Zhu, Danting; Goodrich, Nathan P; Merion, Robert M; Schaubel, Douglas E

2018-05-30

In many observational studies, the objective is to estimate the effect of treatment or state-change on the recurrent event rate. If treatment is assigned after the start of follow-up, traditional methods (eg, adjustment for baseline-only covariates or fully conditional adjustment for time-dependent covariates) may give biased results. We propose a two-stage modeling approach using the method of sequential stratification to accurately estimate the effect of a time-dependent treatment on the recurrent event rate. At the first stage, we estimate the pretreatment recurrent event trajectory using a proportional rates model censored at the time of treatment. Prognostic scores are estimated from the linear predictor of this model and used to match treated patients to as yet untreated controls based on prognostic score at the time of treatment for the index patient. The final model is stratified on matched sets and compares the posttreatment recurrent event rate to the recurrent event rate of the matched controls. We demonstrate through simulation that bias due to dependent censoring is negligible, provided the treatment frequency is low, and we investigate a threshold at which correction for dependent censoring is needed. The method is applied to liver transplant (LT), where we estimate the effect of development of post-LT End Stage Renal Disease (ESRD) on rate of days hospitalized. Copyright © 2018 John Wiley & Sons, Ltd.

Modelling volatility recurrence intervals in the Chinese commodity futures market

NASA Astrophysics Data System (ADS)

Zhou, Weijie; Wang, Zhengxin; Guo, Haiming

2016-09-01

The law of extreme event occurrence attracts much research. The volatility recurrence intervals of Chinese commodity futures market prices are studied: the results show that the probability distributions of the scaled volatility recurrence intervals have a uniform scaling curve for different thresholds q. So we can deduce the probability distribution of extreme events from normal events. The tail of a scaling curve can be well fitted by a Weibull form, which is significance-tested by KS measures. Both short-term and long-term memories are present in the recurrence intervals with different thresholds q, which denotes that the recurrence intervals can be predicted. In addition, similar to volatility, volatility recurrence intervals also have clustering features. Through Monte Carlo simulation, we artificially synthesise ARMA, GARCH-class sequences similar to the original data, and find out the reason behind the clustering. The larger the parameter d of the FIGARCH model, the stronger the clustering effect is. Finally, we use the Fractionally Integrated Autoregressive Conditional Duration model (FIACD) to analyse the recurrence interval characteristics. The results indicated that the FIACD model may provide a method to analyse volatility recurrence intervals.

Semiparametric temporal process regression of survival-out-of-hospital.

PubMed

Zhan, Tianyu; Schaubel, Douglas E

2018-05-23

The recurrent/terminal event data structure has undergone considerable methodological development in the last 10-15 years. An example of the data structure that has arisen with increasing frequency involves the recurrent event being hospitalization and the terminal event being death. We consider the response Survival-Out-of-Hospital, defined as a temporal process (indicator function) taking the value 1 when the subject is currently alive and not hospitalized, and 0 otherwise. Survival-Out-of-Hospital is a useful alternative strategy for the analysis of hospitalization/survival in the chronic disease setting, with the response variate representing a refinement to survival time through the incorporation of an objective quality-of-life component. The semiparametric model we consider assumes multiplicative covariate effects and leaves unspecified the baseline probability of being alive-and-out-of-hospital. Using zero-mean estimating equations, the proposed regression parameter estimator can be computed without estimating the unspecified baseline probability process, although baseline probabilities can subsequently be estimated for any time point within the support of the censoring distribution. We demonstrate that the regression parameter estimator is asymptotically normal, and that the baseline probability function estimator converges to a Gaussian process. Simulation studies are performed to show that our estimating procedures have satisfactory finite sample performances. The proposed methods are applied to the Dialysis Outcomes and Practice Patterns Study (DOPPS), an international end-stage renal disease study.

A class of Box-Cox transformation models for recurrent event data.

PubMed

Sun, Liuquan; Tong, Xingwei; Zhou, Xian

2011-04-01

In this article, we propose a class of Box-Cox transformation models for recurrent event data, which includes the proportional means models as special cases. The new model offers great flexibility in formulating the effects of covariates on the mean functions of counting processes while leaving the stochastic structure completely unspecified. For the inference on the proposed models, we apply a profile pseudo-partial likelihood method to estimate the model parameters via estimating equation approaches and establish large sample properties of the estimators and examine its performance in moderate-sized samples through simulation studies. In addition, some graphical and numerical procedures are presented for model checking. An example of application on a set of multiple-infection data taken from a clinic study on chronic granulomatous disease (CGD) is also illustrated.

Using Rapid Improvement Events for Disaster After-Action Reviews: Experience in a Hospital Information Technology Outage and Response.

PubMed

Little, Charles M; McStay, Christopher; Oeth, Justin; Koehler, April; Bookman, Kelly

2018-02-01

The use of after-action reviews (AARs) following major emergency events, such as a disaster, is common and mandated for hospitals and similar organizations. There is a recurrent challenge of identified problems not being resolved and repeated in subsequent events. A process improvement technique called a rapid improvement event (RIE) was used to conduct an AAR following a complete information technology (IT) outage at a large urban hospital. Using RIE methodology to conduct the AAR allowed for the rapid development and implementation of major process improvements to prepare for future IT downtime events. Thus, process improvement methodology, particularly the RIE, is suited for conducting AARs following disasters and holds promise for improving outcomes in emergency management. Little CM , McStay C , Oeth J , Koehler A , Bookman K . Using rapid improvement events for disaster after-action reviews: experience in a hospital information technology outage and response. Prehosp Disaster Med. 2018;33(1):98-100.

A POISSON PROCESS APPROACH FOR RECURRENT EVENT DATA WITH ENVIRONMENTAL COVARIATES. (R825266)

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

Recurrent Targeted Genes of Hepatitis B Virus in the Liver Cancer Genomes Identified by a Next-Generation Sequencing–Based Approach

PubMed Central

Ding, Dong; Lou, Xiaoyan; Hua, Dasong; Yu, Wei; Li, Lisha; Wang, Jun; Gao, Feng; Zhao, Na; Ren, Guoping; Li, Lanjuan; Lin, Biaoyang

2012-01-01

Integration of the viral DNA into host chromosomes was found in most of the hepatitis B virus (HBV)–related hepatocellular carcinomas (HCCs). Here we devised a massive anchored parallel sequencing (MAPS) method using next-generation sequencing to isolate and sequence HBV integrants. Applying MAPS to 40 pairs of HBV–related HCC tissues (cancer and adjacent tissues), we identified 296 HBV integration events corresponding to 286 unique integration sites (UISs) with precise HBV–Human DNA junctions. HBV integration favored chromosome 17 and preferentially integrated into human transcript units. HBV targeted genes were enriched in GO terms: cAMP metabolic processes, T cell differentiation and activation, TGF beta receptor pathway, ncRNA catabolic process, and dsRNA fragmentation and cellular response to dsRNA. The HBV targeted genes include 7 genes (PTPRJ, CNTN6, IL12B, MYOM1, FNDC3B, LRFN2, FN1) containing IPR003961 (Fibronectin, type III domain), 7 genes (NRG3, MASP2, NELL1, LRP1B, ADAM21, NRXN1, FN1) containing IPR013032 (EGF-like region, conserved site), and three genes (PDE7A, PDE4B, PDE11A) containing IPR002073 (3′, 5′-cyclic-nucleotide phosphodiesterase). Enriched pathways include hsa04512 (ECM-receptor interaction), hsa04510 (Focal adhesion), and hsa04012 (ErbB signaling pathway). Fewer integration events were found in cancers compared to cancer-adjacent tissues, suggesting a clonal expansion model in HCC development. Finally, we identified 8 genes that were recurrent target genes by HBV integration including fibronectin 1 (FN1) and telomerase reverse transcriptase (TERT1), two known recurrent target genes, and additional novel target genes such as SMAD family member 5 (SMAD5), phosphatase and actin regulator 4 (PHACTR4), and RNA binding protein fox-1 homolog (C. elegans) 1 (RBFOX1). Integrating analysis with recently published whole-genome sequencing analysis, we identified 14 additional recurrent HBV target genes, greatly expanding the HBV recurrent target list. This global survey of HBV integration events, together with recently published whole-genome sequencing analyses, furthered our understanding of the HBV–related HCC. PMID:23236287

Regression Analysis of Mixed Recurrent-Event and Panel-Count Data with Additive Rate Models

PubMed Central

Zhu, Liang; Zhao, Hui; Sun, Jianguo; Leisenring, Wendy; Robison, Leslie L.

2015-01-01

Summary Event-history studies of recurrent events are often conducted in fields such as demography, epidemiology, medicine, and social sciences (Cook and Lawless, 2007; Zhao et al., 2011). For such analysis, two types of data have been extensively investigated: recurrent-event data and panel-count data. However, in practice, one may face a third type of data, mixed recurrent-event and panel-count data or mixed event-history data. Such data occur if some study subjects are monitored or observed continuously and thus provide recurrent-event data, while the others are observed only at discrete times and hence give only panel-count data. A more general situation is that each subject is observed continuously over certain time periods but only at discrete times over other time periods. There exists little literature on the analysis of such mixed data except that published by Zhu et al. (2013). In this paper, we consider the regression analysis of mixed data using the additive rate model and develop some estimating equation-based approaches to estimate the regression parameters of interest. Both finite sample and asymptotic properties of the resulting estimators are established, and the numerical studies suggest that the proposed methodology works well for practical situations. The approach is applied to a Childhood Cancer Survivor Study that motivated this study. PMID:25345405

Retinal microvascular changes and subsequent vascular events after ischemic stroke.

PubMed

De Silva, D A; Manzano, J J F; Liu, E Y; Woon, F-P; Wong, W-X; Chang, H-M; Chen, C; Lindley, R I; Wang, J J; Mitchell, P; Wong, T-Y; Wong, M-C

2011-08-30

Retinal microvasculature changes are associated with vascular events including stroke in healthy populations. It is not known whether retinal microvascular changes predict recurrent vascular events after ischemic stroke. We examined the relationship between retinal microvascular signs and subsequent vascular events in a prospective cohort of 652 acute ischemic stroke patients admitted to a tertiary hospital in Singapore from 2005 to 2007. Retinal photographs taken within 1 week of stroke onset were assessed in a masked manner for quantitative and qualitative measures. Follow-up data over 2-4 years were obtained by standardized telephone interview and then were verified from medical records. Predictors of recurrent vascular events (cerebrovascular, coronary, vascular death, and composite vascular events) were determined using Cox regression models. Follow-up data over a median of 29 months were obtained for 89% (652 patients) of the cohort. After adjustment for covariates including traditional risk factors and index stroke etiology, patients with severe arteriovenous nicking (AVN) were more likely to have a recurrent cerebrovascular event (hazard ratio [HR] 2.28, 95% confidence interval [CI] 1.20-4.33) compared with those without AVN. Patients with severe focal arteriolar narrowing (FAN) were more likely to have a recurrent cerebrovascular event (HR 2.75, 95% CI 1.14-6.63) or subsequent composite vascular event (HR 2.77, 95% CI 1.31-5.86) compared to those without FAN. Retinal microvascular changes predicted subsequent vascular events after ischemic stroke, independent of traditional risk factors and stroke subtype. Thus, retinal imaging has a potential role in predicting the risk of recurrent vascular events after ischemic stroke and in understanding novel vascular risk factors.

An epigenetically derived monoclonal origin for recurrent respiratory papillomatosis.

PubMed

Stephen, Josena Kunjoonju; Vaught, Lori E; Chen, Kang Mei; Shah, Veena; Schweitzer, Vanessa G; Gardner, Glendon; Benninger, Michael S; Worsham, Maria J

2007-07-01

To investigate the contribution of promoter methylation-mediated epigenetic events in recurrent respiratory papillomatosis tumorigenesis. Archival tissue DNA, extracted from microdissected papilloma lesions, was interrogated for methylation status by means of the novel, multigene methylation-specific multiplex ligation-dependent probe amplification assay. Fifteen subjects with recurrent respiratory papillomatosis, 3 females and 12 males, all with adult onset of illness (age range, 23-73 years) except for 1 female patient with juvenile onset (1 year old). Promoter hypermethylation was recorded in 14 of 15 cases, and 19 of 22 unique methylation-prone cancer genes in the multigene panel had altered DNA methylation in at least 1 laryngeal papilloma biopsy specimen. Identical abnormally methylated genes were found in 5 of 15 recurrent cases, of which the CDKN2B gene was hypermethylated in all 5 cases. Dissimilar epigenetic events were noted in the remaining cases. A clonal origin was derived for 5 of 15 recurrent respiratory papillomatosis biopsy specimens based on identical epigenetic events. The high frequency of epigenetic events, characterized by consistent promoter hypermethylation of multiple tumor suppressor genes, points to the use of gene silencing mechanisms in the pathogenesis of recurrent respiratory papillomatosis.

Recurrence time statistics of landslide events simulated by a cellular automaton model

NASA Astrophysics Data System (ADS)

Piegari, Ester; Di Maio, Rosa; Avella, Adolfo

2014-05-01

The recurrence time statistics of a cellular automaton modelling landslide events is analyzed by performing a numerical analysis in the parameter space and estimating Fano factor behaviors. The model is an extended version of the OFC model, which is a paradigm for SOC in non-conserved systems, but it works differently from the original OFC model as a finite value of the driving rate is applied. By driving the system to instability with different rates, the model exhibits a smooth transition from a correlated to an uncorrelated regime as the effect of a change in predominant mechanisms to propagate instability. If the rate at which instability is approached is small, chain processes dominate the landslide dynamics, and power laws govern probability distributions. However, the power-law regime typical of SOC-like systems is found in a range of return intervals that becomes shorter and shorter by increasing the values of the driving rates. Indeed, if the rates at which instability is approached are large, domino processes are no longer active in propagating instability, and large events simply occur because a large number of cells simultaneously reach instability. Such a gradual loss of the effectiveness of the chain propagation mechanism causes the system gradually enter to an uncorrelated regime where recurrence time distributions are characterized by Weibull behaviors. Simulation results are qualitatively compared with those from a recent analysis performed by Witt et al.(Earth Surf. Process. Landforms, 35, 1138, 2010) for the first complete databases of landslide occurrences over a period as large as fifty years. From the comparison with the extensive landslide data set, the numerical analysis suggests that statistics of such landslide data seem to be described by a crossover region between a correlated regime and an uncorrelated regime, where recurrence time distributions are characterized by power-law and Weibull behaviors for short and long return times, respectively. Finally, in such a region of the parameter space, clear indications of temporal correlations and clustering by the Fano factor behaviors support, at least in part, the analysis performed by Witt et al. (2010).

Combining Major Life Events and Recurrent Hassles in the Assessment of Stress in Chinese Adolescents: Preliminary Evidence

ERIC Educational Resources Information Center

Cheng, Sheung-Tak; Li, Kin-Kit

2010-01-01

Major life events and hassles have been considered 2 distinct constructs in the measurement of stress. Research also shows that chronic events are more impactful than time-limited ones. This study reports a new approach to measuring stress in which major life events are combined with recurrent hassles to form a single index--the Adolescent Stress…

One-Year Outcomes After Minor Stroke or High-Risk Transient Ischemic Attack: Korean Multicenter Stroke Registry Analysis.

PubMed

Park, Hong-Kyun; Kim, Beom Joon; Han, Moon-Ku; Park, Jong-Moo; Kang, Kyusik; Lee, Soo Joo; Kim, Jae Guk; Cha, Jae-Kwan; Kim, Dae-Hyun; Nah, Hyun-Wook; Park, Tai Hwan; Park, Sang-Soon; Lee, Kyung Bok; Lee, Jun; Hong, Keun-Sik; Cho, Yong-Jin; Lee, Byung-Chul; Yu, Kyung-Ho; Oh, Mi-Sun; Kim, Joon-Tae; Choi, Kang-Ho; Kim, Dong-Eog; Ryu, Wi-Sun; Choi, Jay Chol; Johansson, Saga; Lee, Su Jin; Lee, Won Hee; Lee, Ji Sung; Lee, Juneyoung; Bae, Hee-Joon

2017-11-01

Patients with minor ischemic stroke or transient ischemic attack are at high risk of recurrent stroke and vascular events, which are potentially disabling or fatal. This study aimed to evaluate contemporary subsequent vascular event risk after minor ischemic stroke or transient ischemic attack in Korea. Patients with minor ischemic stroke or high-risk transient ischemic attack admitted within 7 days of symptom onset were identified from a Korean multicenter stroke registry database. We estimated 3-month and 1-year event rates of the primary outcome (composite of stroke recurrence, myocardial infarction, or all-cause death), stroke recurrence, a major vascular event (composite of stroke recurrence, myocardial infarction, or vascular death), and all-cause death and explored differences in clinical characteristics and event rates according to antithrombotic strategies at discharge. Of 9506 patients enrolled in this study, 93.8% underwent angiographic assessment and 72.7% underwent cardiac evaluations; 25.1% had symptomatic stenosis or occlusion of intracranial arteries. At discharge, 95.2% of patients received antithrombotics (antiplatelet polytherapy, 37.1%; anticoagulation, 15.3%) and 86.2% received statins. The 3-month cumulative event rate was 5.9% for the primary outcome, 4.3% for stroke recurrence, 4.6% for a major vascular event, and 2.0% for all-cause death. Corresponding values at 1 year were 9.3%, 6.1%, 6.7%, and 4.1%, respectively. Patients receiving nonaspirin antithrombotic strategies or no antithrombotic agent had higher baseline risk profiles and at least 1.5× higher event rates for clinical event outcomes than those with aspirin monotherapy. Contemporary secondary stroke prevention strategies based on thorough diagnostic evaluation may contribute to the low subsequent vascular event rates observed in real-world clinical practice in Korea. © 2017 American Heart Association, Inc.

How Travel Demand Affects Detection of Non-Recurrent Traffic Congestion on Urban Road Networks

NASA Astrophysics Data System (ADS)

Anbaroglu, B.; Heydecker, B.; Cheng, T.

2016-06-01

Occurrence of non-recurrent traffic congestion hinders the economic activity of a city, as travellers could miss appointments or be late for work or important meetings. Similarly, for shippers, unexpected delays may disrupt just-in-time delivery and manufacturing processes, which could lose them payment. Consequently, research on non-recurrent congestion detection on urban road networks has recently gained attention. By analysing large amounts of traffic data collected on a daily basis, traffic operation centres can improve their methods to detect non-recurrent congestion rapidly and then revise their existing plans to mitigate its effects. Space-time clusters of high link journey time estimates correspond to non-recurrent congestion events. Existing research, however, has not considered the effect of travel demand on the effectiveness of non-recurrent congestion detection methods. Therefore, this paper investigates how travel demand affects detection of non-recurrent traffic congestion detection on urban road networks. Travel demand has been classified into three categories as low, normal and high. The experiments are carried out on London's urban road network, and the results demonstrate the necessity to adjust the relative importance of the component evaluation criteria depending on the travel demand level.

[Validation of an adverse event reporting system in primary care].

PubMed

de Lourdes Rojas-Armadillo, María; Jiménez-Báez, María Valeria; Chávez-Hernández, María Margarita; González-Fondón, Araceli

2016-01-01

Patient safety is a priority issue in health systems, due to the damage costs, institutional weakening, lack of credibility, and frustration on those who committed an error that resulted in an adverse event. There is no standardized instrument for recording, reporting, and analyzing sentinel or adverse events (AE) in primary care. Our aim was to design and validate a surveillance system for recording sentinel events, adverse events and near miss incidents in primary care. We made a review of systems for recording and reporting adverse events in primary care. Then, we proposed an instrument to record these events, and register faults in the structure and process, in primary health care units in the Instituto Mexicano del Seguro Social. We showed VENCER-MF format to 35 subjects. Out of them, 100% identified a failure in care process, 90% recorded a sentinel event, 85% identified the cause of this event, 75% of them suggested some measures for avoiding the recurrence of adverse events. We used a Cronbach's alpha of 0.6, p=0.03. The instrument VENCER-MF has a good consistency for the identification of adverse events.

Prognostic value of trans-thoracic echocardiography in patients with acute stroke and atrial fibrillation: findings from the RAF study.

PubMed

Paciaroni, Maurizio; Agnelli, Giancarlo; Falocci, Nicola; Caso, Valeria; Becattini, Cecilia; Marcheselli, Simona; Rueckert, Christina; Pezzini, Alessandro; Poli, Loris; Padovani, Alessandro; Csiba, Laszló; Szabó, Lilla; Sohn, Sung-Il; Tassinari, Tiziana; Abdul-Rahim, Azmil H; Michel, Patrik; Cordier, Maria; Vanacker, Peter; Remillard, Suzette; Alberti, Andrea; Venti, Michele; Acciarresi, Monica; D'Amore, Cataldo; Mosconi, Maria Giulia; Scoditti, Umberto; Denti, Licia; Orlandi, Giovanni; Chiti, Alberto; Gialdini, Gino; Bovi, Paolo; Carletti, Monica; Rigatelli, Alberto; Putaala, Jukka; Tatlisumak, Turgut; Masotti, Luca; Lorenzini, Gianni; Tassi, Rossana; Guideri, Francesca; Martini, Giuseppe; Tsivgoulis, Georgios; Vadikolias, Kostantinos; Liantinioti, Chrissoula; Corea, Francesco; Del Sette, Massimo; Ageno, Walter; De Lodovici, Maria Luisa; Bono, Giorgio; Baldi, Antonio; D'Anna, Sebastiano; Sacco, Simona; Carolei, Antonio; Tiseo, Cindy; Imberti, Davide; Zabzuni, Dorjan; Doronin, Boris; Volodina, Vera; Consoli, Domenico; Galati, Franco; Pieroni, Alessio; Toni, Danilo; Monaco, Serena; Baronello, Mario Maimone; Barlinn, Kristian; Pallesen, Lars-Peder; Kepplinger, Jessica; Bodechtel, Ulf; Gerber, Johannes; Deleu, Dirk; Melikyan, Gayane; Ibrahim, Faisal; Akhtar, Naveed; Lees, Kennedy R

2016-02-01

Anticoagulant therapy is recommended for the secondary prevention of stroke in patients with atrial fibrillation (AF). T he identification of patients at high risk for early recurrence, which are potential candidates to prompt anticoagulation, is crucial to justify the risk of bleeding associated with early anticoagulant treatment. The aim of this study was to evaluate in patients with acute ischemic stroke and AF the association between findings at trans-thoracic echocardiography (TTE) and 90 days recurrence. In consecutive patients with acute ischemic stroke and AF, TTE was performed within 7 days from hospital admission. Study outcomes were recurrent ischemic cerebrovascular events (stroke or TIA) and systemic embolism. 854 patients (mean age 76.3 ± 9.5 years) underwent a TTE evaluation; 63 patients (7.4%) had at least a study outcome event. Left atrial thrombosis was present in 11 patients (1.3%) among whom 1 had recurrent ischemic event. Left atrial enlargement was present in 548 patients (64.2%) among whom 51 (9.3%) had recurrent ischemic events. The recurrence rate in the 197 patients with severe left atrial enlargement was 11.7%. On multivariate analysis, the presence of atrial enlargement (OR 2.13; 95% CI 1.06-4.29, p = 0.033) and CHA2DS2-VASc score (OR 1.22; 95% CI 1.04-1.45, p = 0.018, for each point increase) were correlated with ischemic recurrences. In patients with AF-associated acute stroke, left atrial enlargement is an independent marker of recurrent stroke and systemic embolism. The risk of recurrence is accounted for by severe atrial enlargement. TTE-detected left atrial thrombosis is relatively uncommon.

Revisit, Subsequent Hospitalization, Recurrent Fall, and Death Within 6 Months After a Fall Among Elderly Emergency Department Patients.

PubMed

Sri-On, Jiraporn; Tirrell, Gregory P; Bean, Jonathan F; Lipsitz, Lewis A; Liu, Shan W

2017-10-01

We seek to describe the risk during 6 months and specific risk factors for recurrent falls, emergency department (ED) revisits, subsequent hospitalizations, and death within 6 months after a fall-related ED presentation. This was a secondary analysis of a retrospective cohort of elderly fall patients who presented to the ED from one urban teaching hospital. We included patients aged 65 years and older who had an ED fall visit in 2012. We examined the frequency and risk factors of adverse events (composite of recurrent falls, ED revisits, subsequent hospitalization, and death, selected a priori) at 6 months. Our study included 350 older adults. Adverse events steadily increased, from 7.7% at 7 days, 21.4% at 30 days, and 50.3% at 6 months. Within 6 months, 22.6% of patients had at least one recurrent fall, 42.6% revisited the ED, 31.1% had subsequent hospitalizations, and 2.6% died. In multivariable logistic regression analysis, psychological or sedative drug use predicted recurrent falls, ED revisits, subsequent hospitalizations, and adverse events. More than half of fall patients had an adverse event within 6 months of presenting to the ED after a fall. The risk during 6 months of these adverse events increased with psychological or sedative drug use. Larger future studies should confirm this association and investigate methods to minimize recurrent falls through management of such medications. Copyright © 2017 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.

Recurrence risk after noncardioembolic mild ischemic stroke in a Japanese population.

PubMed

Kono, Yuji; Yamada, Sumio; Kamisaka, Kenta; Araki, Amane; Fujioka, Yusuke; Yasui, Keizo; Hasegawa, Yasuhiro; Koike, Yasuo

2011-01-01

This study aimed to identify the recurrence rate and risk factors or clinical variables predictive of vascular events after mild ischemic stroke (IS). From December 2006 to September 2007, patients with acute IS with a modified Rankin Scale of 0∼1 were consecutively enrolled in this study. Variables including sex, family history of vascular disease, age, height, weight, stroke subtype, blood pressure, lipid profile, fasting glucose, HbA1c, smoking, alcohol consumption, exercise habits, waist circumference, ankle-brachial pressure index, salt intake and physical activity were assessed. The primary outcome was stroke recurrence or other vascular events such as myocardial infarction, angina pectoris, and peripheral artery disease. Survival curves were calculated by Kaplan-Meier survival analysis, and hazard ratios for recurrence were determined by univariate and multivariate Cox proportional hazards regression models. A total of 102 mild IS patients (78 men and 24 women, mean age 64 years) were successfully followed for 3 years. Of those 102 patients, 25 (24.5%) had stroke recurrence, and 4 (3.9%) had a coronary event. Among the variables studied, abnormal ankle-brachial pressure index, metabolic syndrome, stroke subtypes, salt intake and poor lifestyle management were significant independent predictors of stroke recurrence or cardiovascular events. In mild IS patients within 3 years after onset, not only pathophysiological factors but also lifestyle factors can aid in the identification of patients at high risk for recurrence. Copyright © 2011 S. Karger AG, Basel.

Distinct Facial Processing Related Negative Cognitive Bias in First-Episode and Recurrent Major Depression: Evidence from the N170 ERP Component

PubMed Central

Chen, Jiu; Ma, Wentao; Zhang, Yan; Wu, Xingqu; Wei, Dunhong; Liu, Guangxiong; Deng, Zihe; Yang, Laiqi; Zhang, Zhijun

2014-01-01

Background States of depression are associated with increased sensitivity to negative events. For this novel study, we have assessed the relationship between the number of depressive episodes and the dysfunctional processing of emotional facial expressions. Methodology/Principal Findings We used a visual emotional oddball paradigm to manipulate the processing of emotional information while event-related brain potentials were recorded in 45 patients with first episode major depression (F-MD), 40 patients with recurrent major depression (R-MD), and 46 healthy controls (HC). Compared with the HC group, F-MD patients had lower N170 amplitudes when identifying happy, neutral, and sad faces; R-MD patients had lower N170 amplitudes when identifying happy and neutral faces, but higher N170 amplitudes when identifying sad faces. F-MD patients had longer N170 latencies when identifying happy, neutral, and sad faces relative to the HC group, and R-MD patients had longer N170 latencies when identifying happy and neutral faces, but shorter N170 latencies when identifying sad faces compared with F-MD patients. Interestingly, a negative relationship was observed between N170 amplitude and the depressive severity score for identification of happy faces in R-MD patients while N170 amplitude was positively correlated with the depressive severity score for identification of sad faces in F-MD and R-MD patients. Additionally, the deficits of N170 amplitude for sad faces positively correlated with the number of depressive episodes in R-MD patients. Conclusion/Significance These results provide new evidence that having more recurrent depressive episodes and serious depressive states are likely to aggravate the already abnormal processing of emotional facial expressions in patients with depression. Moreover, it further suggests that the impaired processing as indexed by N170 amplitude for positive face identification may be a potentially useful biomarker for predicting propagation of depression while N170 amplitude for negative face identification could be a potential biomarker for depression recurrence. PMID:25314024

Prognostic Value of C-Reactive Protein and Homocysteine in Large-Artery Atherosclerotic Stroke: a Prospective Observational Study.

PubMed

Ye, Zusen; Zhang, Zhizhong; Zhang, Hao; Hao, Yonggang; Zhang, Jun; Liu, Wenhua; Xu, Gelin; Liu, Xinfeng

2017-03-01

Our objective is to investigate whether C-reactive protein (CRP) and homocysteine (Hcy) levels in the acute phase of large-artery atherosclerotic stroke predict long-term functional disability and recurrent vascular events. Patients with first-ever large-artery atherosclerotic ischemic stroke were prospectively registered in the Nanjing Stroke Registry Program between January 2012 and June 2014. Venous blood samples were collected within 2 weeks after the index stroke. Patients were followed up for 1 year. The Kaplan-Meier method was performed in survival analysis. Multiple logistic regression analysis and Cox proportional hazard model were applied to identify predictors of functional disability and recurrent vascular events, respectively. A total of 625 eligible patients (458 males) were evaluated. During the 1-year follow-up period, 63 patients suffered recurrent vascular events. An elevated CRP level is an independent predictor of poor functional disability at 1 year (P for trend = .002), in both males (P for trend = .017) and females (P for trend = .042). Hcy showed no relationship with functional disability. No significant relationship between CRP and Hcy levels and recurrent vascular events was found in total patients in multiple models. Stratified by sex, high Hcy levels were associated with recurrent vascular events in females (P for trend = .036) but not in males. Elevated CRP levels are associated with poor functional disability in patients with large-artery atherosclerotic stroke at 1 year, and Hcy is a relatively moderate predictor of recurrent vascular events in female patients with large-artery atherosclerotic stroke at 1 year. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

An automatic microseismic or acoustic emission arrival identification scheme with deep recurrent neural networks

NASA Astrophysics Data System (ADS)

Zheng, Jing; Lu, Jiren; Peng, Suping; Jiang, Tianqi

2018-02-01

The conventional arrival pick-up algorithms cannot avoid the manual modification of the parameters for the simultaneous identification of multiple events under different signal-to-noise ratios (SNRs). Therefore, in order to automatically obtain the arrivals of multiple events with high precision under different SNRs, in this study an algorithm was proposed which had the ability to pick up the arrival of microseismic or acoustic emission events based on deep recurrent neural networks. The arrival identification was performed using two important steps, which included a training phase and a testing phase. The training process was mathematically modelled by deep recurrent neural networks using Long Short-Term Memory architecture. During the testing phase, the learned weights were utilized to identify the arrivals through the microseismic/acoustic emission data sets. The data sets were obtained by rock physics experiments of the acoustic emission. In order to obtain the data sets under different SNRs, this study added random noise to the raw experiments' data sets. The results showed that the outcome of the proposed method was able to attain an above 80 per cent hit-rate at SNR 0 dB, and an approximately 70 per cent hit-rate at SNR -5 dB, with an absolute error in 10 sampling points. These results indicated that the proposed method had high selection precision and robustness.

More than words: patients' views on apology and disclosure when things go wrong in cancer care.

PubMed

Mazor, Kathleen M; Greene, Sarah M; Roblin, Douglas; Lemay, Celeste A; Firneno, Cassandra L; Calvi, Josephine; Prouty, Carolyn D; Horner, Kathryn; Gallagher, Thomas H

2013-03-01

Guidelines on apology and disclosure after adverse events and errors have been in place for over 5 years. This study examines whether patients consider recommended responses to be appropriate and desirable, and whether clinicians' actions after adverse events are consistent with recommendations. Patients who believed that something had gone wrong during their cancer care were identified. During in-depth interviews, patients described the event, clinicians' responses, and their reactions. 78 patients were interviewed. Patients' valued apology and expressions of remorse, empathy and caring, explanation, acknowledgement of responsibility, and efforts to prevent recurrences, but these key elements were often missing. For many patients, actions and evidence of clinician learning were most important. Patients' reports of apology and disclosure when they believe something has gone wrong in their care suggest that clinicians' responses continue to fall short of expectations. Clinicians preparing to talk with patients after an adverse event or medical error should be aware that patients expect their actions to be congruent with their words of apology and caring. Healthcare systems need to support clinicians throughout the disclosure process, and facilitate both system and individual learning to prevent recurrences. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

More Than Words: Patients' Views on Apology and Disclosure When Things Go Wrong in Cancer Care

PubMed Central

Mazor, Kathleen M.; Greene, Sarah M.; Roblin, Douglas; Lemay, Celeste A.; Firneno, Cassandra L.; Calvi, Josephine; Prouty, Carolyn D.; Horner, Kathryn; Gallagher, Thomas H.

2011-01-01

Objective Guidelines on apology and disclosure after adverse events and errors have been in place for over five years. This study examines whether patients consider recommended responses to be appropriate and desirable, and whether clinicians' actions after adverse events are consistent with recommendations. Methods Patients who believed that something had gone wrong during their cancer care were identified. During in-depth interviews, patients described the event, clinicians' responses, and their reactions. Results 78 patients were interviewed. Patients' valued apology and expressions of remorse, empathy and caring, explanation, acknowledgement of responsibility, and efforts to prevent recurrences, but these key elements were often missing. For many patients, actions and evidence of clinician learning were most important. Conclusion Patients' reports of apology and disclosure when they believe something has gone wrong in their care suggest that clinicians' responses continue to fall short of expectations. Practice Implications Clinicians preparing to talk with patients after an adverse event or medical error should be aware that patients expect their actions to be congruent with their words of apology and caring. Healthcare systems need to support clinicians throughout the disclosure process, and facilitate both system and individual learning to prevent recurrences. PMID:21824739

Analyzing recurrent events when the history of previous episodes is unknown or not taken into account: proceed with caution.

PubMed

Navarro, Albert; Casanovas, Georgina; Alvarado, Sergio; Moriña, David

Researchers in public health are often interested in examining the effect of several exposures on the incidence of a recurrent event. The aim of the present study is to assess how well the common-baseline hazard models perform to estimate the effect of multiple exposures on the hazard of presenting an episode of a recurrent event, in presence of event dependence and when the history of prior-episodes is unknown or is not taken into account. Through a comprehensive simulation study, using specific-baseline hazard models as the reference, we evaluate the performance of common-baseline hazard models by means of several criteria: bias, mean squared error, coverage, confidence intervals mean length and compliance with the assumption of proportional hazards. Results indicate that the bias worsen as event dependence increases, leading to a considerable overestimation of the exposure effect; coverage levels and compliance with the proportional hazards assumption are low or extremely low, worsening with increasing event dependence, effects to be estimated, and sample sizes. Common-baseline hazard models cannot be recommended when we analyse recurrent events in the presence of event dependence. It is important to have access to the history of prior-episodes per subject, it can permit to obtain better estimations of the effects of the exposures. Copyright © 2016 SESPAS. Publicado por Elsevier España, S.L.U. All rights reserved.

Predictors of course in obsessive-compulsive disorder: logistic regression versus Cox regression for recurrent events.

PubMed

Kempe, P T; van Oppen, P; de Haan, E; Twisk, J W R; Sluis, A; Smit, J H; van Dyck, R; van Balkom, A J L M

2007-09-01

Two methods for predicting remissions in obsessive-compulsive disorder (OCD) treatment are evaluated. Y-BOCS measurements of 88 patients with a primary OCD (DSM-III-R) diagnosis were performed over a 16-week treatment period, and during three follow-ups. Remission at any measurement was defined as a Y-BOCS score lower than thirteen combined with a reduction of seven points when compared with baseline. Logistic regression models were compared with a Cox regression for recurrent events model. Logistic regression yielded different models at different evaluation times. The recurrent events model remained stable when fewer measurements were used. Higher baseline levels of neuroticism and more severe OCD symptoms were associated with a lower chance of remission, early age of onset and more depressive symptoms with a higher chance. Choice of outcome time affects logistic regression prediction models. Recurrent events analysis uses all information on remissions and relapses. Short- and long-term predictors for OCD remission show overlap.

Association of Progression of Carotid Artery Wall Volume and Recurrent Transient Ischemic Attack or Stroke: A Magnetic Resonance Imaging Study.

PubMed

Lu, Mingming; Peng, Peng; Cui, Yuanyuan; Qiao, Huiyu; Li, Dongye; Cai, Jianming; Zhao, Xihai

2018-03-01

This study aimed to investigate the association between carotid plaque progression and subsequent recurrent events using magnetic resonance imaging. Sixty-three symptomatic patients with ipsilateral carotid atherosclerotic stenosis (30%-69% stenosis) determined by ultrasound underwent first and second carotid artery magnetic resonance imaging for carotid artery at baseline and ≥6 months after the first scan, respectively. All the patients had clinical follow-up after the second magnetic resonance scan for ≤5 years until the onset of recurrent transient ischemic attack or stroke. Presence/absence of carotid plaque compositional features, particularly intraplaque hemorrhage and fibrous cap rupture was identified. The annual progression of carotid wall volume between 2 magnetic resonance scans was measured. Univariate and multivariate Cox regression was used to calculate the hazard ratio and corresponding 95% confidence interval of carotid plaque features in discriminating recurrent events. Receiver-operating-characteristic-curve analysis was conducted to determine the area-under-the-curve of carotid plaque features in predicting recurrent events. Sixty-three patients (mean age: 66.5±10.0 years old; 54 males) were eligible for final statistics analysis. During a mean follow-up duration of 55.1±13.6 months, 14.3% of patients (n=9) experienced ipsilateral recurrent transient ischemic attack/stroke. The annual progression of carotid wall volume was significantly associated with recurrent events before (hazard ratio, 1.14 per 10 mm 3 ; 95% confidence interval, 1.02-1.27; P =0.019) and after (hazard ratio, 1.19 per 10 mm3; 95% confidence interval, 1.03-1.37; P =0.022) adjusted for confounding factors. In discriminating the recurrence of transient ischemia attack/stroke, receiver-operator curve analysis indicated that combined with annual progression of wall volume, there was a significant incremental improvement in the area-under-the-curve of intraplaque hemorrhage (area-under-the-curve: 0.69-0.81) and fibrous cap rupture (area-under-the-curve: 0.73-0.84). The annual progression of carotid wall volume is independently associated with recurrent ischemic cerebrovascular events, and this measurement has added value for intraplaque hemorrhage and fibrous cap rupture in predicting future events. © 2018 American Heart Association, Inc.

Controls on the long term earthquake behavior of an intraplate fault revealed by U-Th and stable isotope analyses of syntectonic calcite veins

NASA Astrophysics Data System (ADS)

Williams, Randolph; Goodwin, Laurel; Sharp, Warren; Mozley, Peter

2017-04-01

U-Th dates on calcite precipitated in coseismic extension fractures in the Loma Blanca normal fault zone, Rio Grande rift, NM, USA, constrain earthquake recurrence intervals from 150-565 ka. This is the longest direct record of seismicity documented for a fault in any tectonic environment. Combined U-Th and stable isotope analyses of these calcite veins define 13 distinct earthquake events. These data show that for more than 400 ka the Loma Blanca fault produced earthquakes with a mean recurrence interval of 40 ± 7 ka. The coefficient of variation for these events is 0.40, indicating strongly periodic seismicity consistent with a time-dependent model of earthquake recurrence. Stochastic statistical analyses further validate the inference that earthquake behavior on the Loma Blanca was time-dependent. The time-dependent nature of these earthquakes suggests that the seismic cycle was fundamentally controlled by a stress renewal process. However, this periodic cycle was punctuated by an episode of clustered seismicity at 430 ka. Recurrence intervals within the earthquake cluster were as low as 5-11 ka. Breccia veins formed during this episode exhibit carbon isotope signatures consistent with having formed through pronounced degassing of a CO2 charged brine during post-failure, fault-localized fluid migration. The 40 ka periodicity of the long-term earthquake record of the Loma Blanca fault is similar in magnitude to recurrence intervals documented through paleoseismic studies of other normal faults in the Rio Grande rift and Basin and Range Province. We propose that it represents a background rate of failure in intraplate extension. The short-term, clustered seismicity that occurred on the fault records an interruption of the stress renewal process, likely by elevated fluid pressure in deeper structural levels of the fault, consistent with fault-valve behavior. The relationship between recurrence interval and inferred fluid degassing suggests that pore fluid pressure along the fault may have been driven by variations in CO2 content, thereby fundamentally affecting earthquake frequency. Thus, the Loma Blanca fault provides a record of "naturally induced" seismicity, with lessons for better understanding anthropogenic induced seismicity.

Intermittent tremor migrations beneath Guerrero, Mexico, and implications for fault healing within the slow slip zone

NASA Astrophysics Data System (ADS)

Peng, Yajun; Rubin, Allan M.

2017-01-01

Slow slip events exhibit significant complexity in slip evolution and variations in recurrence intervals. Behavior that varies systematically with recurrence interval is likely to reflect different extents of fault healing between these events. Here we use high-resolution tremor catalogs beneath Guerrero, Mexico, to investigate the mechanics of slow slip. We observe complex tremor propagation styles, including rapid tremor migrations propagating either along the main tremor front or backward, reminiscent of those in northern Cascadia. We also find many migrations that originate well behind the front and repeatedly occupy the same source region during a tremor episode, similar to those previously reported from Shikoku, Japan. These migrations could be driven by slow slip in the surrounding regions, with recurrence intervals possibly modulated by tides. The propagation speed of these migrations decreases systematically with time since the previous migration over the same source area. Tremor amplitudes seem consistent with changes in the propagation speeds being controlled primarily by changes in the slip speeds. One interpretation is that the high propagation speeds and inferred high slip speeds during the migrations with short recurrence intervals are caused by incomplete healing within the host rock adjacent to the shear zone, which could lead to high permeability and reduced dilatant strengthening of the fault gouge. Similar processes may operate in other slow slip source regions such as Cascadia.

Evidence for a twelfth large earthquake on the southern hayward fault in the past 1900 years

USGS Publications Warehouse

Lienkaemper, J.J.; Williams, P.L.; Guilderson, T.P.

2010-01-01

We present age and stratigraphic evidence for an additional paleoearthquake at the Tyson Lagoon site. The acquisition of 19 additional radiocarbon dates and the inclusion of this additional event has resolved a large age discrepancy in our earlier earthquake chronology. The age of event E10 was previously poorly constrained, thus increasing the uncertainty in the mean recurrence interval (RI), a critical factor in seismic hazard evaluation. Reinspection of many trench logs revealed substantial evidence suggesting that an additional earthquake occurred between E10 and E9 within unit u45. Strata in older u45 are faulted in the main fault zone and overlain by scarp colluviums in two locations.We conclude that an additional surfacerupturing event (E9.5) occurred between E9 and E10. Since 91 A.D. (??40 yr, 1??), 11 paleoearthquakes preceded the M 6:8 earthquake in 1868, yielding a mean RI of 161 ?? 65 yr (1??, standard deviation of recurrence intervals). However, the standard error of the mean (SEM) is well determined at ??10 yr. Since ~1300 A.D., the mean rate has increased slightly, but is indistinguishable from the overall rate within the uncertainties. Recurrence for the 12-event sequence seems fairly regular: the coefficient of variation is 0.40, and it yields a 30-yr earthquake probability of 29%. The apparent regularity in timing implied by this earthquake chronology lends support for the use of time-dependent renewal models rather than assuming a random process to forecast earthquakes, at least for the southern Hayward fault.

Intakes of meat, fish, poultry, and eggs and risk of prostate cancer progression.

PubMed

Richman, Erin L; Stampfer, Meir J; Paciorek, Alan; Broering, Jeanette M; Carroll, Peter R; Chan, June M

2010-03-01

Processed meat and fish have been shown to be associated with the risk of advanced prostate cancer, but few studies have examined diet after prostate cancer diagnosis and risk of its progression. We examined the association between postdiagnostic consumption of processed and unprocessed red meat, fish, poultry, and eggs and the risk of prostate cancer recurrence or progression. We conducted a prospective study in 1294 men with prostate cancer, without recurrence or progression as of 2004-2005, who were participating in the Cancer of the Prostate Strategic Urologic Research Endeavor and who were followed for an average of 2 y. We observed 127 events (prostate cancer death or metastases, elevated prostate-specific antigen concentration, or secondary treatment) during 2610 person-years. Intakes of processed and unprocessed red meat, fish, total poultry, and skinless poultry were not associated with prostate cancer recurrence or progression. Greater consumption of eggs and poultry with skin was associated with 2-fold increases in risk in a comparison of extreme quantiles: eggs [hazard ratio (HR): 2.02; 95% CI: 1.10, 3.72; P for trend = 0.05] and poultry with skin (HR: 2.26; 95% CI: 1.36, 3.76; P for trend = 0.003). An interaction was observed between prognostic risk at diagnosis and poultry. Men with high prognostic risk and a high poultry intake had a 4-fold increased risk of recurrence or progression compared with men with low/intermediate prognostic risk and a low poultry intake (P for interaction = 0.003). Our results suggest that the postdiagnostic consumption of processed or unprocessed red meat, fish, or skinless poultry is not associated with prostate cancer recurrence or progression, whereas consumption of eggs and poultry with skin may increase the risk.

Intakes of meat, fish, poultry, and eggs and risk of prostate cancer progression1234

PubMed Central

Richman, Erin L; Stampfer, Meir J; Paciorek, Alan; Broering, Jeanette M; Carroll, Peter R; Chan, June M

2010-01-01

Background: Processed meat and fish have been shown to be associated with the risk of advanced prostate cancer, but few studies have examined diet after prostate cancer diagnosis and risk of its progression. Objective: We examined the association between postdiagnostic consumption of processed and unprocessed red meat, fish, poultry, and eggs and the risk of prostate cancer recurrence or progression. Design: We conducted a prospective study in 1294 men with prostate cancer, without recurrence or progression as of 2004–2005, who were participating in the Cancer of the Prostate Strategic Urologic Research Endeavor and who were followed for an average of 2 y. Results: We observed 127 events (prostate cancer death or metastases, elevated prostate-specific antigen concentration, or secondary treatment) during 2610 person-years. Intakes of processed and unprocessed red meat, fish, total poultry, and skinless poultry were not associated with prostate cancer recurrence or progression. Greater consumption of eggs and poultry with skin was associated with 2-fold increases in risk in a comparison of extreme quantiles: eggs [hazard ratio (HR): 2.02; 95% CI: 1.10, 3.72; P for trend = 0.05] and poultry with skin (HR: 2.26; 95% CI: 1.36, 3.76; P for trend = 0.003). An interaction was observed between prognostic risk at diagnosis and poultry. Men with high prognostic risk and a high poultry intake had a 4-fold increased risk of recurrence or progression compared with men with low/intermediate prognostic risk and a low poultry intake (P for interaction = 0.003). Conclusions: Our results suggest that the postdiagnostic consumption of processed or unprocessed red meat, fish, or skinless poultry is not associated with prostate cancer recurrence or progression, whereas consumption of eggs and poultry with skin may increase the risk. PMID:20042525

Testing stress shadowing effects at the South American subduction zone

NASA Astrophysics Data System (ADS)

Roth, F.; Dahm, T.; Hainzl, S.

2017-11-01

The seismic gap hypothesis assumes that a characteristic earthquake is followed by a long period with a reduced occurrence probability for the next large event on the same fault segment, as a consequence of the induced stress shadow. The gap model is commonly accepted by geologists and is often used for time-dependent seismic hazard estimations. However, systematic and rigorous tests to verify the seismic gap model have often failed so far, which might be partially related to limited data and too tight model assumptions. In this study, we relax the assumption of a characteristic size and location of repeating earthquakes and analyse one of the best available data sets, namely the historical record of major earthquakes along a 3000 km long linear segment of the South American subduction zone. To test whether a stress shadow effect is observable, we compiled a comprehensive catalogue of mega-thrust earthquakes along this plate boundary from 1520 to 2015 containing 174 earthquakes with Mw > 6.5. In our new testing approach, we analyse the time span between an earthquake and the last event that ruptured the epicentre location, where we consider the impact of the uncertainties of epicentres and rupture extensions. Assuming uniform boundary conditions along the trench, we compare the distribution of these recurrence times with simple recurrence models. We find that the distribution is in all cases almost exponentially distributed corresponding to a random (Poissonian) process; despite some tendencies for clustering of the Mw ≥ 7 events and a weak quasi-periodicity of the Mw ≥ 8 earthquakes, respectively. To verify whether the absence of a clear stress shadow signal is related to physical assumptions or data uncertainties, we perform simulations of a physics-based stochastic earthquake model considering rate and state-dependent earthquake nucleation, which are adapted to the observations with regard to the number of events, spatial extend, size distribution and involved uncertainties. Our simulations show that the catalogue uncertainties lead to a significant blurring of the theoretically peaked distribution, but the distribution would be still distinguishable from the observed one for Mw ≥ 7 events. However, considering the stress transfer to adjacent fault segments and heterogeneous instead of constant stress drop within the rupture zone can explain the observed recurrence time distribution. We conclude that simplified recurrence models, ignoring the complexity of the underlying physical process, cannot be applied for forecasting the Mw ≥ 7 earthquake occurrence at this plate boundary.

[The development and effects of an integrated symptom management program for prevention of recurrent cardiac events after percutaneous coronary intervention].

PubMed

Son, Youn-Jung

2008-04-01

This study was conducted to develop and to determine the effects of an integrated symptom management program for prevention of recurrent cardiac events after percutaneous coronary intervention. Subjects consisted of 58 CAD patients (experimental group: 30, control group: 28). The experimental group participated in an integrated symptom management program for 6 months which was composed of tailored education, stress management, exercise, diet, deep breathing, music therapy, periodical telephone monitoring and a daily log. The control group received the usual care. The experimental group significantly decreased symptom experiences and the level of LDL compared to the control group. The experimental group significantly increased self care activity and quality of life compared to the control group. Although no significant difference was found in cardiac recurrence, the experimental group had fewer recurrences. These results suggest that an integrated symptom management program for prevention of recurrent cardiac events after percutaneous coronary intervention can improve symptom aggravation, recurrent rate, self care activity and quality of life. Nursing interventions are needed to maintain and further enhance the quality of life of these patients and the interventions should be implemented in the overall transition period.

The Effect of Subcritical Bone Loss and Exposure on Recurrent Instability After Arthroscopic Bankart Repair in Intercollegiate American Football.

PubMed

Dickens, Jonathan F; Owens, Brett D; Cameron, Kenneth L; DeBerardino, Thomas M; Masini, Brendan D; Peck, Karen Y; Svoboda, Steven J

2017-07-01

There is no consensus on the optimal method of stabilization (arthroscopic or open) in collision athletes with anterior shoulder instability. To examine the effect of "subcritical" bone loss and football-specific exposure on the rate of recurrent shoulder instability after arthroscopic stabilization in an intercollegiate American football population. Case-control study; Level of evidence, 3. Fifty intercollegiate football players underwent primary arthroscopic stabilization for anterior shoulder instability and returned to football for at least a single season. Preoperatively, 32 patients experienced recurrent subluxations, and 18 patients experienced a single or recurrent dislocation. Shoulders with glenoid bone loss >20%, an engaging Hill-Sachs lesion, an off-track lesion, and concomitant rotator cuff repair were excluded from the study. The primary outcome of interest was the ability to return to football without subsequent instability. Patients were followed for time to a subsequent instability event after return to play using days of exposure to football and total follow-up time after arthroscopic stabilization. Fifty consecutive patients returned to American football for a mean 1.5 seasons (range, 1-3) after arthroscopic stabilization. Three of 50 (6%; 95% CI, 1.3%-16.5%) patients experienced recurrent instability. There were no subsequent instability events after a mean 3.2 years of military service. All shoulders with glenoid bone loss >13.5% (n = 3) that underwent arthroscopic stabilization experienced recurrent instability upon returning to sport, while none of the shoulders with <13.5% glenoid bone loss (n = 47) sustained a recurrent instability event during football ( X 2 = 15.80, P < .001). Shoulders with >13.5% glenoid bone loss had an incidence rate of 5.31 cases of recurrent instability per 1000 athlete-exposures of football. In 72,000 athlete-exposures to football with <13.5% glenoid bone loss, there was no recurrent instability. Significantly more anchors were used during the primary arthroscopic stabilization procedure in patients who experienced multiple preoperative instability events ( P = .005), and lesions spanned significantly more extensive portions along the circumference of the glenoid ( P = .001) compared with shoulders having a single preoperative instability event before surgical stabilization. Arthroscopic stabilization of anterior shoulder instability in American football players with <13.5% glenoid bone loss provides reliable outcomes and low recurrence rates.

Recurrent persistent hypophosphatemia in a male-to-female transgender patient with anorexia nervosa: Case report.

PubMed

Beaty, L; Trees, N; Mehler, P

2017-05-01

Refeeding hypophosphatemia remains a serious and common complication during the early phases of nutritional rehabilitation and weight restoration for patients with anorexia nervosa. Typically, the risk of refeeding hypophosphatemia diminishes after the first 1-2 weeks of the refeeding process and thus, frequent monitoring serum phosphorus levels becomes less important as refeeding proceeds. Herein, we describe a case of persistent recurrent hypophosphatemia in a male-to-female transgender patient with severe anorexia nervosa. As transgender patients become increasingly seen in the realm of eating disorders, it is worth noting this phenomenon to mitigate adverse events. © 2017 Wiley Periodicals, Inc.

Associations between short-term exposure to particulate matter and ultrafine particles and myocardial infarction in Augsburg, Germany.

PubMed

Wolf, Kathrin; Schneider, Alexandra; Breitner, Susanne; Meisinger, Christa; Heier, Margit; Cyrys, Josef; Kuch, Bernhard; von Scheidt, Wolfgang; Peters, Annette

2015-08-01

Short-term exposure to increased particulate matter (PM) concentration has been reported to trigger myocardial infarction (MI). However, the association with ultrafine particles remains unclear. We aimed to assess the effects of short-term air pollution and especially ultrafine particles on registry-based MI events and coronary deaths in the area of Augsburg, Germany. Between 1995 and 2009, the MONICA/KORA myocardial infarction registry recorded 15,417 cases of MI and coronary deaths. Concentrations of PM<10μm (PM10), PM<2.5μm (PM2.5), particle number concentration (PNC) as indicator for ultrafine particles, and meteorological parameters were measured in the study region. Quasi-Poisson regression adjusting for time trend, temperature, season, and weekday was used to estimate immediate, delayed and cumulative effects of air pollutants on the occurrence of MI. The daily numbers of total MI, nonfatal and fatal events as well as incident and recurrent events were analysed. We observed a 1.3% risk increase (95%-confidence interval: [-0.9%; 3.6%]) for all events and a 4.4% [-0.4%; 9.4%] risk increase for recurrent events per 24.3μg/m(3) increase in same day PM10 concentrations. Nonfatal events indicated a risk increase of 3.1% [-0.1%; 6.5%] with previous day PM10. No association was seen for PM2.5 which was only available from 1999 on. PNC showed a risk increase of 6.0% [0.6%; 11.7%] for recurrent events per 5529 particles/cm(3) increase in 5-day average PNC. Our results suggested an association between short-term PM10 concentration and numbers of MI, especially for nonfatal and recurrent events. For ultrafine particles, risk increases were notably high for recurrent events. Thus, persons who already suffered a MI seemed to be more susceptible to air pollution. Copyright © 2015 Elsevier GmbH. All rights reserved.

Comparative hazard analysis of processes leading to remarkable flash floods (France, 1930-1999)

NASA Astrophysics Data System (ADS)

Boudou, M.; Lang, M.; Vinet, F.; Cœur, D.

2016-10-01

Flash flood events are responsible for large economic losses and lead to fatalities every year in France. This is especially the case in the Mediterranean and oversea territories/departments of France, characterized by extreme hydro-climatological features and with a large part of the population exposed to flood risks. The recurrence of remarkable flash flood events, associated with high hazard intensity, significant damage and socio-political consequences, therefore raises several issues for authorities and risk management policies. This study aims to improve our understanding of the hazard analysis process in the case of four remarkable flood events: March 1930, October 1940, January 1980 and November 1999. Firstly, we present the methodology used to define the remarkability score of a flood event. Then, to identify the factors leading to a remarkable flood event, we explore the main parameters of the hazard analysis process, such as the meteorological triggering conditions, the return period of the rainfall and peak discharge, as well as some additional factors (initial catchment state, flood chronology, cascade effects, etc.). The results contribute to understanding the complexity of the processes leading to flood hazard and highlight the importance for risk managers of taking additional factors into account.

Financial strain predicts recurrent events among women with coronary artery disease.

PubMed

Georgiades, Anastasia; Janszky, Imre; Blom, May; László, Krisztina D; Ahnve, Staffan

2009-06-26

Although a number of epidemiological studies have found an association between socioeconomic status (SES) indices such as income and education and coronary morbidity and mortality, few have looked at health consequences arising from actually experiencing financial shortcomings. The objective of the present study was to examine whether financial strain predicts recurrent coronary artery disease (CAD) events among women with established CAD. Two hundred two women (mean age 62+/-9 years) hospitalized for an acute coronary event were followed over a period of 3.5 years. Demographic, socioeconomic, lifestyle-related, psychosocial and biological characteristics were obtained by means of questionnaires and clinical examination. Data on recurrent cardiac events were collected from the Swedish discharge and death registers. Women experiencing financial strain over the past year had an increased risk for recurrent events, i.e. the combination of all-cause mortality, new acute myocardial infarction and unstable angina pectoris during the follow-up with an unadjusted hazard ratio (HR) of 3.2 (95% CI 1.6-6.6), and a HR of 2.76 (95% CI 1.02-7.50) after controlling for education, household income, age, cohabiting status, inclusion diagnosis and rehabilitation therapy. Adjustment for potential mediators, i.e. psychosocial factors, lipids, diabetes mellitus, smoking, body-mass index, blood pressure, physical activity, alcohol consumption, participation in other cardiac rehabilitation programs did not alter the results significantly. Financial strain was a predictor for recurrent events among women with CAD, independently of commonly used SES indicators such as education and household income. Future studies will have to explore the mechanism behind this association.

Platelet density per monocyte predicts adverse events in patients after percutaneous coronary intervention.

PubMed

Rutten, Bert; Roest, Mark; McClellan, Elizabeth A; Sels, Jan W; Stubbs, Andrew; Jukema, J Wouter; Doevendans, Pieter A; Waltenberger, Johannes; van Zonneveld, Anton-Jan; Pasterkamp, Gerard; De Groot, Philip G; Hoefer, Imo E

2016-01-01

Monocyte recruitment to damaged endothelium is enhanced by platelet binding to monocytes and contributes to vascular repair. Therefore, we studied whether the number of platelets per monocyte affects the recurrence of adverse events in patients after percutaneous coronary intervention (PCI). Platelet-monocytes complexes with high and low median fluorescence intensities (MFI) of the platelet marker CD42b were isolated using cell sorting. Microscopic analysis revealed that a high platelet marker MFI on monocytes corresponded with a high platelet density per monocyte while a low platelet marker MFI corresponded with a low platelet density per monocyte (3.4 ± 0.7 vs 1.4 ± 0.1 platelets per monocyte, P=0.01). Using real-time video microscopy, we observed increased recruitment of high platelet density monocytes to endothelial cells as compared with low platelet density monocytes (P=0.01). Next, we classified PCI scheduled patients (N=263) into groups with high, medium and low platelet densities per monocyte and assessed the recurrence of adverse events. After multivariate adjustment for potential confounders, we observed a 2.5-fold reduction in the recurrence of adverse events in patients with a high platelet density per monocyte as compared with a low platelet density per monocyte [hazard ratio=0.4 (95% confidence interval, 0.2-0.8), P=0.01]. We show that a high platelet density per monocyte increases monocyte recruitment to endothelial cells and predicts a reduction in the recurrence of adverse events in patients after PCI. These findings may imply that a high platelet density per monocyte protects against recurrence of adverse events.

Time-to-first-event versus recurrent-event analysis: points to consider for selecting a meaningful analysis strategy in clinical trials with composite endpoints.

PubMed

Rauch, Geraldine; Kieser, Meinhard; Binder, Harald; Bayes-Genis, Antoni; Jahn-Eimermacher, Antje

2018-05-01

Composite endpoints combining several event types of clinical interest often define the primary efficacy outcome in cardiologic trials. They are commonly evaluated as time-to-first-event, thereby following the recommendations of regulatory agencies. However, to assess the patient's full disease burden and to identify preventive factors or interventions, subsequent events following the first one should be considered as well. This is especially important in cohort studies and RCTs with a long follow-up leading to a higher number of observed events per patients. So far, there exist no recommendations which approach should be preferred. Recently, the Cardiovascular Round Table of the European Society of Cardiology indicated the need to investigate "how to interpret results if recurrent-event analysis results differ […] from time-to-first-event analysis" (Anker et al., Eur J Heart Fail 18:482-489, 2016). This work addresses this topic by means of a systematic simulation study. This paper compares two common analysis strategies for composite endpoints differing with respect to the incorporation of recurrent events for typical data scenarios motivated by a clinical trial. We show that the treatment effects estimated from a time-to-first-event analysis (Cox model) and a recurrent-event analysis (Andersen-Gill model) can systematically differ, particularly in cardiovascular trials. Moreover, we provide guidance on how to interpret these results and recommend points to consider for the choice of a meaningful analysis strategy. When planning trials with a composite endpoint, researchers, and regulatory agencies should be aware that the model choice affects the estimated treatment effect and its interpretation.

Nonparametric methods for analyzing recurrent gap time data with application to infections after hematopoietic cell transplant.

PubMed

Lee, Chi Hyun; Luo, Xianghua; Huang, Chiung-Yu; DeFor, Todd E; Brunstein, Claudio G; Weisdorf, Daniel J

2016-06-01

Infection is one of the most common complications after hematopoietic cell transplantation. Many patients experience infectious complications repeatedly after transplant. Existing statistical methods for recurrent gap time data typically assume that patients are enrolled due to the occurrence of an event of interest, and subsequently experience recurrent events of the same type; moreover, for one-sample estimation, the gap times between consecutive events are usually assumed to be identically distributed. Applying these methods to analyze the post-transplant infection data will inevitably lead to incorrect inferential results because the time from transplant to the first infection has a different biological meaning than the gap times between consecutive recurrent infections. Some unbiased yet inefficient methods include univariate survival analysis methods based on data from the first infection or bivariate serial event data methods based on the first and second infections. In this article, we propose a nonparametric estimator of the joint distribution of time from transplant to the first infection and the gap times between consecutive infections. The proposed estimator takes into account the potentially different distributions of the two types of gap times and better uses the recurrent infection data. Asymptotic properties of the proposed estimators are established. © 2015, The International Biometric Society.

Nonparametric methods for analyzing recurrent gap time data with application to infections after hematopoietic cell transplant

PubMed Central

Lee, Chi Hyun; Huang, Chiung-Yu; DeFor, Todd E.; Brunstein, Claudio G.; Weisdorf, Daniel J.

2015-01-01

Summary Infection is one of the most common complications after hematopoietic cell transplantation. Many patients experience infectious complications repeatedly after transplant. Existing statistical methods for recurrent gap time data typically assume that patients are enrolled due to the occurrence of an event of interest, and subsequently experience recurrent events of the same type; moreover, for one-sample estimation, the gap times between consecutive events are usually assumed to be identically distributed. Applying these methods to analyze the post-transplant infection data will inevitably lead to incorrect inferential results because the time from transplant to the first infection has a different biological meaning than the gap times between consecutive recurrent infections. Some unbiased yet inefficient methods include univariate survival analysis methods based on data from the first infection or bivariate serial event data methods based on the first and second infections. In this paper, we propose a nonparametric estimator of the joint distribution of time from transplant to the first infection and the gap times between consecutive infections. The proposed estimator takes into account the potentially different distributions of the two types of gap times and better uses the recurrent infection data. Asymptotic properties of the proposed estimators are established. PMID:26575402

Statistical modelling for recurrent events: an application to sports injuries

PubMed Central

Ullah, Shahid; Gabbett, Tim J; Finch, Caroline F

2014-01-01

Background Injuries are often recurrent, with subsequent injuries influenced by previous occurrences and hence correlation between events needs to be taken into account when analysing such data. Objective This paper compares five different survival models (Cox proportional hazards (CoxPH) model and the following generalisations to recurrent event data: Andersen-Gill (A-G), frailty, Wei-Lin-Weissfeld total time (WLW-TT) marginal, Prentice-Williams-Peterson gap time (PWP-GT) conditional models) for the analysis of recurrent injury data. Methods Empirical evaluation and comparison of different models were performed using model selection criteria and goodness-of-fit statistics. Simulation studies assessed the size and power of each model fit. Results The modelling approach is demonstrated through direct application to Australian National Rugby League recurrent injury data collected over the 2008 playing season. Of the 35 players analysed, 14 (40%) players had more than 1 injury and 47 contact injuries were sustained over 29 matches. The CoxPH model provided the poorest fit to the recurrent sports injury data. The fit was improved with the A-G and frailty models, compared to WLW-TT and PWP-GT models. Conclusions Despite little difference in model fit between the A-G and frailty models, in the interest of fewer statistical assumptions it is recommended that, where relevant, future studies involving modelling of recurrent sports injury data use the frailty model in preference to the CoxPH model or its other generalisations. The paper provides a rationale for future statistical modelling approaches for recurrent sports injury. PMID:22872683

An Integrated Approach Identifies Mediators of Local Recurrence in Head and Neck Squamous Carcinoma.

PubMed

Citron, Francesca; Armenia, Joshua; Franchin, Giovanni; Polesel, Jerry; Talamini, Renato; D'Andrea, Sara; Sulfaro, Sandro; Croce, Carlo M; Klement, William; Otasek, David; Pastrello, Chiara; Tokar, Tomas; Jurisica, Igor; French, Deborah; Bomben, Riccardo; Vaccher, Emanuela; Serraino, Diego; Belletti, Barbara; Vecchione, Andrea; Barzan, Luigi; Baldassarre, Gustavo

2017-07-15

Purpose: Head and neck squamous cell carcinomas (HNSCCs) cause more than 300,000 deaths worldwide each year. Locoregional and distant recurrences represent worse prognostic events and accepted surrogate markers of patients' overall survival. No valid biomarker and salvage therapy exist to identify and treat patients at high-risk of recurrence. We aimed to verify if selected miRNAs could be used as biomarkers of recurrence in HNSCC. Experimental Design: A NanoString array was used to identify miRNAs associated with locoregional recurrence in 44 patients with HNSCC. Bioinformatic approaches validated the signature and identified potential miRNA targets. Validation experiments were performed using an independent cohort of primary HNSCC samples and a panel of HNSCC cell lines. In vivo experiments validated the in vitro results. Results: Our data identified a four-miRNA signature that classified HNSCC patients at high- or low-risk of recurrence. These miRNAs collectively impinge on the epithelial-mesenchymal transition process. In silico and wet lab approaches showed that miR-9, expressed at high levels in recurrent HNSCC, targets SASH1 and KRT13, whereas miR-1, miR-133, and miR-150, expressed at low levels in recurrent HNSCC, collectively target SP1 and TGFβ pathways. A six-gene signature comprising these targets identified patients at high risk of recurrences, as well. Combined pharmacological inhibition of SP1 and TGFβ pathways induced HNSCC cell death and, when timely administered, prevented recurrence formation in a preclinical model of HNSCC recurrence. Conclusions: By integrating different experimental approaches and competences, we identified critical mediators of recurrence formation in HNSCC that may merit to be considered for future clinical development. Clin Cancer Res; 23(14); 3769-80. ©2017 AACR . ©2017 American Association for Cancer Research.

Atmospheric Rivers and floods in Southern California: Climate forcing of extreme weather events.

NASA Astrophysics Data System (ADS)

Hendy, I. L.; Heusser, L. E.; Napier, T.; Pak, D. K.

2016-12-01

Southern California has a Mediterranean type climate characterized by warm dry summers associated with the North Pacific High pressure system and cool, wet winters primarily associated in low pressure systems originating in the high latitude North Pacific. Extreme precipitation, however, is connected to strong zonal flow that brings warm, moist tropical across the Pacific (AKA atmospheric river). Here we present a revised record of flood events in Santa Barbara Basin that have been linked to atmospheric rivers focusing on events associated with transitions between known climate events using new radiocarbon chronology and detailed sediment composition. Flood events identified by homogenous grey layers are present throughout the Holocene with a recurrence every 110 years, but are particularly common (85 year recurrence) between 4,200 and 2,000 years BP. Interval between 6,500 and 4,500 commonly associated with dry conditions in California was associated with fewer flood events (recurrence interval increased to 176 years). Intervals of high lake levels in California associated with pluvials appear to be associated with more frequent extreme precipitation events. The longest recurrence interval (535 years) is associated with the Medieval Climate Anomaly. The season in which the atmospheric river occurs was estimated using the relative abundance of pollen within the flood deposit. The 735 and 1270 C.E. flood events are associated with May-June flowering vegetation, while the most recent events (1861-2 and 1761 C.E.) were associated with November to March flowering vegetation. This agrees with the December-January rainfall records of the historic 1861-62. We conclude the frequency of extreme precipitation events appears to increase as climate cools (e.g. the Little Ice Age).

The ARTICO study: identification of patients at high risk of vascular recurrence after a first non-cardioembolic stroke.

PubMed

Serena, Joaquín; Segura, Tomás; Roquer, Jaume; García-Gil, María; Castillo, José

2015-03-11

About 20% of patients with a first ischaemic stroke will experience a new vascular event within the first year. The atherosclerotic burden, an indicator of the extension of atherosclerosis in a patient, has been associated with the risk of new cardiovascular events in the general population. However, no predictive models reliably identify groups at a high risk of recurrence. The ARTICO study prospectively analysed the predictive value for the risk of recurrence of specific atherosclerotic markers. The multicentre ARTICO study included 620 consecutive independent patients older than 60 years suffering from a first non-cardioembolic stroke. We analysed classical stroke risk factors; duplex study of supraaortic trunk including intima-media thickness (IMT) measurement; quantification of internal carotid (ICA) stenosis; number, morphology and surface characteristics of carotid plaques; ankle brachial index (ABI); and the presence of microalbuminuria. Patients were followed up at 6 and 12 months after inclusion. The primary end-point was death or major cardiovascular events. Any vascular event or death at 12 months occurred in 78 (13.8%) patients. In 40 (7.1%) of these the vascular event was a stroke recurrence. Weight, history of diabetes mellitus, history of symptomatic PAD, ABI <0.9 and significant ICA stenosis (>50%) were associated with a higher risk of vascular events on follow-up in the bivariate analysis. In the final Cox regression analysis, body mass index (BMI), systolic blood pressure, history of diabetes mellitus, symptomatic PAD (HR, 2.76; 95% CI, 1.10-6.95; p=0.03), and particularly patients with both ICA stenosis >50% and PAD (HR 4.52; 95% CI, 2.14-9.53; p<0.001) were independently associated with an increased risk of vascular events. Neither isolated ICA stenosis >50% nor isolated abnormal ABI remained associated with an increased risk of recurrence in comparison with the whole population. Symptomatic PAD identifies a high risk group of vascular recurrence after a first non-cardioembolic stroke. The associated increased risk was particularly high in patients with both ICA stenosis and either symptomatic or asymptomatic PAD. Neither asymptomatic PAD alone nor isolated ICA stenosis >50% were associated with an increased risk of recurrence in this particularly high-risk group of non-cardioembolic stroke.

Reduction in recurrent cardiovascular events with prasugrel compared with clopidogrel in patients with acute coronary syndromes from the TRITON-TIMI 38 trial

PubMed Central

Murphy, Sabina A.; Antman, Elliott M.; Wiviott, Stephen D.; Weerakkody, Govinda; Morocutti, Giorgio; Huber, Kurt; Lopez-Sendon, Jose; McCabe, Carolyn H.; Braunwald, Eugene

2008-01-01

Aims In the TRITON-TIMI 38 trial, greater platelet inhibition with prasugrel reduced the first occurrence of the primary endpoint (cardiovascular death, MI, or stroke) compared with clopidogrel in patients with an acute coronary syndrome (ACS) undergoing planned percutaneous coronary intervention. We hypothesized that prasugrel would reduce not only first events but also recurrent primary endpoint events and therefore total events compared with clopidogrel. Methods and results Poisson regression analysis was performed to compare the number of occurrences of the primary endpoint between prasugrel and clopidogrel in TRITON-TIMI 38. Landmark analytic methods were used to evaluate the risk of a recurrent primary endpoint event following an initial non-fatal endpoint event. Among patients with an initial non-fatal event, second events were significantly reduced with prasugrel compared to clopidogrel (10.8 vs. 15.4%, HR 0.65, 95% CI 0.46–0.92; P = 0.016), as was CV death following the non-fatal event (3.7 vs. 7.1%, HR 0.46, 95% CI 0.25–0.82; P = 0.008). Overall there was a reduction of 195 total primary efficacy events with prasugrel vs. clopidogrel (rate ratio 0.79, 95% CI 0.71–0.87; P < 0.001). Recurrent bleeding events occurred infrequently (TIMI major non-CABG bleeds: four with prasugrel and two with clopidogrel). Study drug discontinuation was frequent following the initial major bleeding event (42% of patients discontinued study drug). Conclusion While standard statistical analytic techniques for clinical trials censor patients who experience a component of the primary composite endpoint, total cardiovascular events remain important to both patients and clinicians. Prasugrel, a more potent anti-platelet agent, reduced both first and subsequent cardiovascular events compared with clopidogrel in patients with ACS. PMID:18682445

A three-dimensional geometric morphometrics view of the cranial shape variation and population history in the New World.

PubMed

Galland, Manon; Friess, Martin

2016-09-10

Craniofacial variation in past and present Amerindians has been attributed to the effect of multiple founder events, or to one major migration followed by in situ differentiation and possibly recurrent contacts among Circum-Arctic groups. Our study aims to: (i) detect morphological differences that may indicate several migrations; (ii) test for the presence of genetic isolation; and (iii) test the correlation between shape data and competing settlement hypotheses by taking into account geography, chronology, climate effects, the presence of genetic isolation and recurrent gene flow. We analyzed a large sample of three-dimensional (3D) cranial surface scans (803 specimens) including past and modern groups from America and Australasia. Shape variation was investigated using geometric morphometrics. Differential external gene flow was evaluated by applying genetic concepts to morphometric data (Relethford-Blangero approach). Settlement hypotheses were tested using a matrix correlation approach (Mantel tests). Our results highlight the strong dichotomy between Circum-Arctic and continental Amerindians as well as the impact of climate adaptation, and possibly recurrent gene flow in the Circum-Arctic area. There is also evidence for the impact of genetic isolation on phenetic variation in Baja California. Several settlement hypotheses are correlated with our data. The three approaches used in this study highlight the importance of local processes especially in Baja California, and caution against the use of overly simplistic models when searching for the number of migration events. The results stress the complexity of the settlement of the Americas as well as the mosaic nature of the processes involved in this process. Am. J. Hum. Biol. 28:646-661, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Thromboembolic event rate in paroxysmal and persistent atrial fibrillation: Data from the GISSI-AF trial

PubMed Central

2013-01-01

Background Few data on the thromboembolic (TE) risk of paroxysmal and persistent atrial fibrillation (AF) are available. This study aimed to assess the incidence of TE events in paroxysmal and persistent AF. Methods We performed a subset post hoc analysis of 771 patients with paroxysmal and 463 with persistent AF enrolled in the multicenter, prospective, randomized, double-blind, placebo-controlled GISSI-AF trial - comparing the efficacy of valsartan versus placebo in preventing AF recurrences – where the choice of antithrombotic treatment was left to the judgment of the referring physician. TE and major outcome events were centrally validated. AF recurrences were detected by frequent clinic visits and a transtelephonic monitoring device with weekly and symptomatic transmissions. Results Eighty-five percent of patients had a history of hypertension, and the 7.7% had heart failure, left ventricular dysfunction, or both. The mean CHADS2 score was 1.41±0.84. TE and major bleeding events were observed at a low incidence among the overall population at 1-year follow-up (0.97% and 0.81%, respectively). The univariate and multivariable analyses revealed no statistically significant differences in the incidence of TE, major bleeding events or mortality in paroxysmal and persistent AF patients. TE events were more common among women than men (p=0.02). The follow-up examination showed under- or overtreatment with warfarin in many patients, according to guideline suggestions. Warfarin was more frequently prescribed to patients with persistent AF (p<0.0001) and patients with AF recurrences (p<0.0001). AF recurrences were noninvasively detected in 632 (51.2%) patients. In patients without AF recurrences, the TE event rate was 0.5% versus 1.74%, 1.28%, and 1.18% for those with only symptomatic, only asymptomatic or both symptomatic and asymptomatic AF recurrences, respectively, but the difference was not statistically significant, even after adjusting for warfarin treatment and the CHADS2 score (HR 2.93; CI 95%; 0.8-10.9; p=0.11). Conclusions TE and major bleeding events showed a very low incidence in the GISSI-AF trial population, despite under- or overtreatment with warfarin in many patients. TE events had a similar rate in paroxysmal and persistent AF. Trial registration Trial registration number: NCT00376272 PMID:23586654

Recurrent bridgehead effects accelerate global alien ant spread

Treesearch

Cleo Bertelsmeier; Sébastien Ollier; Andrew M. Liebhold; Eckehard G. Brockerhoff; Darren Ward; Laurent Keller

2018-01-01

Biological invasions are a major threat to biological diversity, agriculture, and human health. To predict and prevent new invasions, it is crucial to develop a better understanding of the drivers of the invasion process. The analysis of 4,533 border interception events revealed that at least 51 different alien ant species were intercepted at US ports over a period of...

Fixed recurrence and slip models better predict earthquake behavior than the time- and slip-predictable models 1: repeating earthquakes

USGS Publications Warehouse

Rubinstein, Justin L.; Ellsworth, William L.; Chen, Kate Huihsuan; Uchida, Naoki

2012-01-01

The behavior of individual events in repeating earthquake sequences in California, Taiwan and Japan is better predicted by a model with fixed inter-event time or fixed slip than it is by the time- and slip-predictable models for earthquake occurrence. Given that repeating earthquakes are highly regular in both inter-event time and seismic moment, the time- and slip-predictable models seem ideally suited to explain their behavior. Taken together with evidence from the companion manuscript that shows similar results for laboratory experiments we conclude that the short-term predictions of the time- and slip-predictable models should be rejected in favor of earthquake models that assume either fixed slip or fixed recurrence interval. This implies that the elastic rebound model underlying the time- and slip-predictable models offers no additional value in describing earthquake behavior in an event-to-event sense, but its value in a long-term sense cannot be determined. These models likely fail because they rely on assumptions that oversimplify the earthquake cycle. We note that the time and slip of these events is predicted quite well by fixed slip and fixed recurrence models, so in some sense they are time- and slip-predictable. While fixed recurrence and slip models better predict repeating earthquake behavior than the time- and slip-predictable models, we observe a correlation between slip and the preceding recurrence time for many repeating earthquake sequences in Parkfield, California. This correlation is not found in other regions, and the sequences with the correlative slip-predictable behavior are not distinguishable from nearby earthquake sequences that do not exhibit this behavior.

Economic burden of recurrent venous thromboembolism: analysis from a U.S. hospital perspective.

PubMed

Casciano, Julian P; Dotiwala, Zenobia; Kemp, Robert; Li, Chenghui; Cai, Jennifer; Preblick, Ronald

2015-02-15

An analysis of resource utilization and hospital costs associated with recurrent venous thromboembolism (VTE) is presented. A retrospective cohort analysis was conducted using a large U.S. hospital database. Patients with VTE-related hospitalization events during the period January-December 2010 were identified; data collection extended for up to 12 months after the index event. Postdischarge hospital resource use and total costs were compared in cohorts of patients with and without recurrent VTE. Regression analysis was performed to compare hospital costs and length of stay (LOS) during initial and subsequent VTE encounters. Among the study population of 43,734 patients, 4% had postdischarge VTE-related events during the data collection period. The median and mean ± S.D. times to VTE recurrence were 48 days and 98 ± 106 days, respectively. Patients with recurrent VTE had more all-cause hospitalizations than those without recurrent VTE (mean ± S.D., 1.07 ± 0.96 versus 0.15 ± 0.53; p < 0.0001), more all-cause emergency room visits (mean ± S.D., 0.31 ± 0.66 versus 0.05 ± 0.31; p < 0.0001), and greater total costs (mean ± S.D., $28,353 ± $39,624 versus $17,712 ± $33,461; p < 0.0001). Relative to initial VTE admissions, admissions for recurrent VTE were, on average, associated with a 14% longer LOS (p = 0.0002) and a 22% higher total cost (p < 0.001). Patients with recurrent VTE used more hospital resources than those without recurrent VTE. Readmissions for VTE were significantly longer and more costly than index encounters. Copyright © 2015 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

What is the contribution of different cognitive biases and stressful childhood events to the presence and number of previous depressive episodes?

PubMed

Vrijsen, Janna N; Becker, Eni S; Arias-Vásquez, Alejandro; van Dijk, Maarten K; Speckens, Anne; Oostrom, Iris van

2014-07-30

Negative cognitive biases as well as stressful childhood events are well-known risk factors for depression. Few studies have compared the association of different types of biases and events with depression. The current study examined whether different cognitive biases and stressful childhood events variables were associated with depression and recurrence. Three types of childhood events were assessed in 83 never-depressed and 337 formerly depressed individuals: trauma within the family, trauma outside the family, and adverse events. Furthermore, after a sad mood induction procedure, participants executed a Dot Probe task (selective attentional bias), an Emotional Stroop task (attentional interference bias) and an incidental learning task (memory bias). The association of these measures with case status and recurrence status (one or multiple past episodes) was examined. Negative memory bias and traumatic childhood events within the family were associated with case status, whereas none of the bias measures or childhood events variables were associated with recurrence status. The results indicate that memory bias as well as the experience of aggression and/or abuse within the family during childhood are independently associated with depression. Biases and stressful childhood events did not offer differentiation between individuals with one or multiple past episodes. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Repeating Earthquakes Following an Mw 4.4 Earthquake Near Luther, Oklahoma

NASA Astrophysics Data System (ADS)

Clements, T.; Keranen, K. M.; Savage, H. M.

2015-12-01

An Mw 4.4 earthquake on April 16, 2013 near Luther, OK was one of the earliest M4+ earthquakes in central Oklahoma, following the Prague sequence in 2011. A network of four local broadband seismometers deployed within a day of the Mw 4.4 event, along with six Oklahoma netquake stations, recorded more than 500 aftershocks in the two weeks following the Luther earthquake. Here we use HypoDD (Waldhauser & Ellsworth, 2000) and waveform cross-correlation to obtain precise aftershock locations. The location uncertainty, calculated using the SVD method in HypoDD, is ~15 m horizontally and ~ 35 m vertically. The earthquakes define a near vertical, NE-SW striking fault plane. Events occur at depths from 2 km to 3.5 km within the granitic basement, with a small fraction of events shallower, near the sediment-basement interface. Earthquakes occur within a zone of ~200 meters thickness on either side of the best-fitting fault surface. We use an equivalency class algorithm to identity clusters of repeating events, defined as event pairs with median three-component correlation > 0.97 across common stations (Aster & Scott, 1993). Repeating events occur as doublets of only two events in over 50% of cases; overall, 41% of earthquakes recorded occur as repeating events. The recurrence intervals for the repeating events range from minutes to days, with common recurrence intervals of less than two minutes. While clusters occur in tight dimensions, commonly of 80 m x 200 m, aftershocks occur in 3 distinct ~2km x 2km-sized patches along the fault. Our analysis suggests that with rapidly deployed local arrays, the plethora of ~Mw 4 earthquakes occurring in Oklahoma and Southern Kansas can be used to investigate the earthquake rupture process and the role of damage zones.

Recurrence of ICH after resumption of anticoagulation with VK antagonists: CHIRONE study.

PubMed

Poli, Daniela; Antonucci, Emilia; Dentali, Francesco; Erba, Nicoletta; Testa, Sophie; Tiraferri, Eros; Palareti, Gualtiero

2014-03-25

To evaluate the risk of recurrent intracranial hemorrhage (ICH) in patients on vitamin K antagonists (VKAs) after a first episode of ICH. The Cerebral Haemorrhage in patients Restarting Oral Anticoagulant Therapy (CHIRONE) Study collected data of patients eligible for the study from the database of 27 centers affiliated with the Italian Federation of Anticoagulation Clinics. We enrolled 267 patients (163 male, median age 73.9 years) who had received VKA anticoagulation after an ICH event. During the total period of follow-up (778 patient-years), ICH recurred in 20 patients (7.5%; rate 2.56 × 100 patient-years) at a median time of 16.5 months, and was fatal in 5 patients (25%; rate 0.4 × 100 patient-years). Male sex, hypertension, prosthetic valves, previous ischemic stroke, renal failure, cancer, and spontaneous events were associated with the risk of recurrence, though none of them in isolation reached statistical significance. More than one-third of spontaneous recurrences occurred in patients with a posttraumatic index event. Our results show that patients with a history of ICH carry a significant risk of recurrent ICH when treated with VKA anticoagulation. The risk is also present, though to a lower degree, in patients with previous posttraumatic events. All patients with a history of ICH require a careful evaluation of their thromboembolic risk to estimate the net clinical benefit of (re)starting anticoagulation with VKAs.

Aortic Arch Plaques and Risk of Recurrent Stroke and Death

PubMed Central

Di Tullio, Marco R.; Russo, Cesare; Jin, Zhezhen; Sacco, Ralph L.; Mohr, J.P.; Homma, Shunichi

2010-01-01

Background Aortic arch plaques are a risk factor for ischemic stroke. Although the stroke mechanism is conceivably thromboembolic, no randomized studies have evaluated the efficacy of antithrombotic therapies in preventing recurrent events. Methods and Results The relationship between arch plaques and recurrent events was studied in 516 patients with ischemic stroke, double–blindly randomized to treatment with warfarin or aspirin as part of the Patent Foramen Ovale in Cryptogenic Stroke Study (PICSS), based on the Warfarin-Aspirin Recurrent Stroke Study (WARSS). Plaque thickness and morphology was evaluated by transesophageal echocardiography. End-points were recurrent ischemic stroke or death over a 2-year follow-up. Large plaques (≥4mm) were present in 19.6% of patients, large complex plaques (those with ulcerations or mobile components) in 8.5 %. During follow-up, large plaques were associated with a significantly increased risk of events (adjusted Hazard Ratio 2.12, 95% Confidence Interval 1.04-4.32), especially those with complex morphology (HR 2.55, CI 1.10-5.89). The risk was highest among cryptogenic stroke patients, both for large plaques (HR 6.42, CI 1.62-25.46) and large-complex plaques (HR 9.50, CI 1.92-47.10). Event rates were similar in the warfarin and aspirin groups in the overall study population (16.4% vs. 15.8%; p=0.43). Conclusions In patients with stroke, and especially cryptogenic stroke, large aortic plaques remain associated with an increased risk of recurrent stroke and death at two years despite treatment with warfarin or aspirin. Complex plaque morphology confers a slight additional increase in risk. PMID:19380621

Paleoearthquake recurrence on the East Paradise fault zone, metropolitan Albuquerque, New Mexico

USGS Publications Warehouse

Personius, Stephen F.; Mahan, Shannon

2000-01-01

A fortuitous exposure of the East Paradise fault zone near Arroyo de las Calabacillas has helped us determine a post-middle Pleistocene history for a long-forgotten Quaternary fault in the City of Albuquerque, New Mexico. Mapping of two exposures of the fault zone allowed us to measure a total vertical offset of 2.75 m across middle Pleistocene fluvial and eolian deposits and to estimate individual surface-faulting events of about 1, 0.5, and 1.25 m. These measurements and several thermoluminescence ages allow us to calculate a long-term average slip rate of 0.01 ± 0.001 mm/yr and date two surface-faulting events to 208 ± 25 ka and 75 ± 7 ka. The youngest event probably occurred in the late Pleistocene, sometime after 75 ± 7 ka. These data yield a single recurrence interval of 133 ± 26 ka and an average recurrence interval of 90 ± 10 ka. However, recurrence intervals are highly variable because the two youngest events occurred in less than 75 ka. Offsets of 0.5-1.25 m and a fault length of 13-20 km indicate that surface-rupturing paleoearthquakes on the East Paradise fault zone had probable Ms or Mw magnitudes of 6.8-7.0. Although recurrence intervals are long on the East Paradise fault zone, these data are significant because they represent some of the first published slip rate, paleoearthquake magnitude, and recurrence information for any of the numerous Quaternary faults in the rapidly growing Albuquerque-Rio Rancho metropolitan area.

Laboratory constraints on models of earthquake recurrence

NASA Astrophysics Data System (ADS)

Beeler, N. M.; Tullis, Terry; Junger, Jenni; Kilgore, Brian; Goldsby, David

2014-12-01

In this study, rock friction "stick-slip" experiments are used to develop constraints on models of earthquake recurrence. Constant rate loading of bare rock surfaces in high-quality experiments produces stick-slip recurrence that is periodic at least to second order. When the loading rate is varied, recurrence is approximately inversely proportional to loading rate. These laboratory events initiate due to a slip-rate-dependent process that also determines the size of the stress drop and, as a consequence, stress drop varies weakly but systematically with loading rate. This is especially evident in experiments where the loading rate is changed by orders of magnitude, as is thought to be the loading condition of naturally occurring, small repeating earthquakes driven by afterslip, or low-frequency earthquakes loaded by episodic slip. The experimentally observed stress drops are well described by a logarithmic dependence on recurrence interval that can be cast as a nonlinear slip predictable model. The fault's rate dependence of strength is the key physical parameter. Additionally, even at constant loading rate the most reproducible laboratory recurrence is not exactly periodic, unlike existing friction recurrence models. We present example laboratory catalogs that document the variance and show that in large catalogs, even at constant loading rate, stress drop and recurrence covary systematically. The origin of this covariance is largely consistent with variability of the dependence of fault strength on slip rate. Laboratory catalogs show aspects of both slip and time predictability, and successive stress drops are strongly correlated indicating a "memory" of prior slip history that extends over at least one recurrence cycle.

Controversies concerning the antiphospholipid syndrome in obstetrics.

PubMed

Camarena Cabrera, Dulce María Albertina; Rodriguez-Jaimes, Claudia; Acevedo-Gallegos, Sandra; Gallardo-Gaona, Juan Manuel; Velazquez-Torres, Berenice; Ramírez-Calvo, José Antonio

Antiphospholipid antibody syndrome is a non-inflammatory autoimmune disease characterized by recurrent thrombotic events and/or obstetric complications associated with the presence of circulating antiphospholipid antibodies (anticardiolipin antibodies, anti-β 2 glycoprotein-i antibodies, and/or lupus anticoagulant. Antiphospholipid antibodies are a heterogeneous group of autoantibodies associated with recurrent miscarriage, stillbirth, fetal growth restriction and premature birth. The diversity of the features of the proposed placental antiphospholipid antibodies fingerprint suggests that several disease processes may occur in the placentae of women with antiphospholipid antibody syndrome in the form of immune responses: inflammatory events, complement activation, angiogenic imbalance and, less commonly, thrombosis and infarction. Because of the disparity between clinical and laboratory criteria, and the impact on perinatal outcome in patients starting treatment, we reviewed the aspects of antiphospholipid antibody syndrome related to obstetric complications and seronegative antiphospholipid antibody syndrome, and their treatment in obstetrics. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

Refining locations of the 2005 Mukacheve, West Ukraine, earthquakes based on similarity of their waveforms

NASA Astrophysics Data System (ADS)

Gnyp, Andriy

2009-06-01

Based on the results of application of correlation analysis to records of the 2005 Mukacheve group of recurrent events and their subsequent relocation relative to the reference event of 7 July 2005, a conclusion has been drawn that all the events had most likely occurred on the same rup-ture plane. Station terms have been estimated for seismic stations of the Transcarpathians, accounting for variation of seismic velocities beneath their locations as compared to the travel time tables used in the study. In methodical aspect, potentials and usefulness of correlation analysis of seismic records for a more detailed study of seismic processes, tectonics and geodynamics of the Carpathian region have been demonstrated.

High-grade extremity soft tissue sarcomas: factors predictive of local recurrence and its effect on morbidity and mortality.

PubMed

Eilber, Fritz C; Rosen, Gerald; Nelson, Scott D; Selch, Michael; Dorey, Frederick; Eckardt, Jeffery; Eilber, Frederick R

2003-02-01

To identify patient characteristics associated with the development of local recurrence and the effect of local recurrence on subsequent morbidity and mortality in patients with intermediate- to high-grade extremity soft tissue sarcomas. Numerous studies on extremity soft tissue sarcomas have consistently shown that presentation with locally recurrent disease is associated with the development of subsequent local recurrences and that large tumor size and high histologic grade are significant factors associated with decreased survival. However, the effect of local recurrence on patient survival remains unclear. From 1975 to 1997, 753 patients with intermediate- to high-grade extremity soft tissue sarcomas were treated at UCLA. Treatment outcomes and patient characteristics were analyzed to identify factors associated with both local recurrence and survival. Patients with locally recurrent disease were at a significantly increased risk of developing a subsequent local recurrence. Local recurrence was a morbid event requiring amputation in 38% of the cases. The development of a local recurrence was the most significant factor associated with decreased survival. Once a patient developed a local recurrence, he or she was about three times more likely to die of disease compared to similar patients who had not developed a local recurrence. Local recurrence in patients with intermediate- to high-grade extremity soft tissue sarcomas is associated with the development of subsequent local recurrences, a morbid event decreasing functional outcomes and the most significant factor associated with decreased survival. Although 85% to 90% of patients with high-grade extremity soft tissue sarcomas are treatable with a limb salvage approach, patients who develop a local recurrence need aggressive treatment and should be considered for trials of adjuvant systemic therapy.

Learning Orthographic Structure With Sequential Generative Neural Networks.

PubMed

Testolin, Alberto; Stoianov, Ivilin; Sperduti, Alessandro; Zorzi, Marco

2016-04-01

Learning the structure of event sequences is a ubiquitous problem in cognition and particularly in language. One possible solution is to learn a probabilistic generative model of sequences that allows making predictions about upcoming events. Though appealing from a neurobiological standpoint, this approach is typically not pursued in connectionist modeling. Here, we investigated a sequential version of the restricted Boltzmann machine (RBM), a stochastic recurrent neural network that extracts high-order structure from sensory data through unsupervised generative learning and can encode contextual information in the form of internal, distributed representations. We assessed whether this type of network can extract the orthographic structure of English monosyllables by learning a generative model of the letter sequences forming a word training corpus. We show that the network learned an accurate probabilistic model of English graphotactics, which can be used to make predictions about the letter following a given context as well as to autonomously generate high-quality pseudowords. The model was compared to an extended version of simple recurrent networks, augmented with a stochastic process that allows autonomous generation of sequences, and to non-connectionist probabilistic models (n-grams and hidden Markov models). We conclude that sequential RBMs and stochastic simple recurrent networks are promising candidates for modeling cognition in the temporal domain. Copyright © 2015 Cognitive Science Society, Inc.

Recurrence and death from breast cancer after complete treatments: an experience from hospitals in Northern Thailand.

PubMed

Chairat, Rungnapa; Puttisri, Adisom; Pamarapa, Asani; Wongrach, Nongnoot; Tawichasri, Chamaiporn; Patumanond, Jayanton; Tantraworasin, Apichat; Charoentum, Chaiyut

2014-09-01

To describe the pattern of disease progression and to describe locoregional recurrence, distant recurrence, and death rates in breast cancer patients after complete treatment. Medical records of women diagnosed with breast cancer at two university affiliated tertiary care hospitals in the Northern Thailand that had complete treatments between 2006 and 2010 were traced. Extracted key information included patient clinical profiles and documented recurrence of cancer The causes of death were verified from breast cancer case registration database, death certificates through The Ministry of Internal Affairs'civil registration, by direct telephone contact, or by distributed prepaid postcards. Medical records of 829 women diagnosed with breast cancer without prior evidence ofdistant metastasis, and had complete recommended treatment were included. Six hundred thirty seven women had not experienced any events up to the end of the follow-up (76.8%). The first occurring events were focused and categorized into three distinct types, locoregional recurrence (n = 83, median follow-up time = 34.2 months), distant recurrence (n = 78, median follow-up time = 35.4 months), and death without any evidences of locoregional or distant recurrences (n = 12, median follow-up time = 36.7 months). Distant recurrence after locoregional recurrence was reported (n = 33). There were 109 patient who had died (breast cancer related death) up to the end of the follow-up (13.2%). The three types of consecutively occurring deaths were death after locoregional recurrence without any distant recurrences (n = 15), death after distant recurrence with locoregional recurrence (n = 21), and death after documenited distant recurrence without any locoregional recurrences (n = 61). The trend was that the rate of the first occurring locoregional recurrence was slightly higher than that of distant recurrence, The death rate in patients without any recurrences was much lower than in those experiencing prior recurrences. The rates of disease progression from local recurrence to distant recurrence and to death were approximately 5 to 7 times faster in patients who had experienced earlierprogressions.

Regression Analysis of Mixed Panel Count Data with Dependent Terminal Events

PubMed Central

Yu, Guanglei; Zhu, Liang; Li, Yang; Sun, Jianguo; Robison, Leslie L.

2017-01-01

Event history studies are commonly conducted in many fields and a great deal of literature has been established for the analysis of the two types of data commonly arising from these studies: recurrent event data and panel count data. The former arises if all study subjects are followed continuously, while the latter means that each study subject is observed only at discrete time points. In reality, a third type of data, a mixture of the two types of the data above, may occur and furthermore, as with the first two types of the data, there may exist a dependent terminal event, which may preclude the occurrences of recurrent events of interest. This paper discusses regression analysis of mixed recurrent event and panel count data in the presence of a terminal event and an estimating equation-based approach is proposed for estimation of regression parameters of interest. In addition, the asymptotic properties of the proposed estimator are established and a simulation study conducted to assess the finite-sample performance of the proposed method suggests that it works well in practical situations. Finally the methodology is applied to a childhood cancer study that motivated this study. PMID:28098397

One-year adherence to warfarin treatment for venous thromboembolism in high-risk patients and its association with long-term risk of recurrent events.

PubMed

Chen, Shih-Yin; Wu, Ning; Gulseth, Michael; LaMori, Joyce; Bookhart, Brahim K; Boulanger, Luke; Fields, Larry; Schein, Jeff

2013-05-01

Warfarin is the predominant oral anticoagulant used for the prevention of recurrent venous thromboembolism (VTE) events. However, its long-term use is complicated by the need to manage the drug within a narrow therapeutic range and by possible food and drug interactions. To examine the association between 1-year adherence, measured through compliance with and persistence on warfarin treatment for VTE, and long-term risk of recurrent events among patients at high risk. Medical and pharmacy claims for patients with commercial or Medicare supplemental insurance in the Thomson Reuters MarketScan database were analyzed. Adult patients with medical claims with an associated VTE diagnosis between January 1, 2006, and March 31, 2008, were identified. The index date was defined as the date of the first observed VTE claim or the date of discharge if the index event was a hospital stay. High-risk patients (patients with cancer, or noncancer patients who did not have reversible risk factors during the 3-month period prior to the index date) who filled a warfarin prescription within 2 weeks of the index date were included. Persistence was evaluated in terms of discontinuation, defined as a 90-day gap in warfarin supply during a 1-year assessment period following the index date. Compliance was measured by the proportion of days covered (PDC) over the 1-year assessment period, with PDC less than 0.8 defined as noncompliance. Recurrent VTE events were identified as hospitalizations where VTE was the primary diagnosis after the 1-year assessment period and until patients were lost to follow-up. The association between adherence to warfarin therapy and VTE recurrence was evaluated descriptively via Kaplan-Meier curves and a Cox proportional hazards model, adjusted for patient demographic and clinical characteristics. A similar analysis using the medication possession ratio (MPR) as a measure of compliance was also performed in a subset of patients who had filled at least 2 warfarin prescriptions. The study included 8,040 VTE patients identified as being at high risk of recurrence (mean age 61 years, 59.4% male), of whom 76.9% were not compliant with warfarin therapy based on PDC, and 51.5% discontinued therapy. Among those with at least 2 warfarin prescriptions (n = 7612), 34.1% of high-risk patients were not compliant with warfarin therapy between the first and last refills based on MPR. Kaplan-Meier curves showed that patients who were compliant or continued warfarin therapy were less likely to experience a VTE event (all P less than 0.05). Noncompliant patients had a 3 times greater risk of VTE recurrence than compliant patients, based on PDC (hazard ratio [HR] = 3.01, 95% confidence interval [CI]: 1.28-4.97). Among the subpopulation who filled at least 2 warfarin prescriptions, noncompliant patients (based on MPR) were also found to be more likely to have recurrent VTE events, compared with compliant patients (HR = 1.60, 95% CI: 1.18-2.16). Patients who discontinued warfarin were more likely to have recurrent VTE events compared with patients who did not discontinue on warfarin treatment (HR = 1.48, 95% CI: 1.09-2.01). Adherence to a year of therapy was low in patients at high risk of recurrent VTE, even though long-term therapy should be considered in this population. Noncompliance and discontinuation of warfarin treatment over a 1-year period was associated with a higher risk of recurrent VTE. Future research should investigate and differentiate between patient and provider discontinuation to develop strategies to improve compliance and persistence with appropriate anticoagulation therapy that may potentially reduce recurrent VTE.

First and recurrent ischaemic heart disease events continue to decline in New Zealand, 2005-2015.

PubMed

Grey, Corina; Jackson, Rod; Wells, Susan; Wu, Billy; Poppe, Katrina; White, Harvey; Chan, Wing Cheuk; Kerr, Andrew J

2018-01-01

To examine recent trends in first and recurrent ischaemic heart disease (IHD) deaths and hospitalisations. Using anonymous patient-linkage of routinely collected data, all New Zealanders aged 35-84 years who experienced an International Statistical Classification of Diseases and Related Health Problems I(CD)-coded IHD hospitalisation and/or IHD death between 1 January 2005 and 31 December 2015 were identified. A 10-year look-back period was used to differentiate those experiencing first from recurrent events. Age-standardised hospitalisation and mortality rates were calculated for each calendar year and trends compared by sex and age. 160 109 people experienced at least one IHD event (259 678 hospitalisations and 35 548 deaths) over the 11-year study period, and there was a steady decline in numbers (from almost 24 000 in 2005 to just over 16 000 in 2015) and in age-standardised rates each year. With the exception of deaths in younger (35-64 years) women with prior IHD, there was a significant decline in IHD events in men and women of all ages, with and without a history of IHD. The decline in IHD mortality was greater for those experiencing a first rather than recurrent IHD event (3.8%-5.2% vs 0%-3.7% annually on average). In contrast, the decline in IHD hospitalisations was greater for those experiencing a recurrent compared with a first IHD event (5.6%-7.3% vs 3.2%-5.7% annually on average). The substantial decline in IHD hospitalisations and mortality observed in New Zealanders with and without prior IHD between 2005 and 2015 suggests that primary and secondary prevention efforts have been effective in reducing the occurrence of IHD events. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Recurrence and interoccurrence behavior of self-organized complex phenomena

NASA Astrophysics Data System (ADS)

Abaimov, S. G.; Turcotte, D. L.; Shcherbakov, R.; Rundle, J. B.

2007-08-01

The sandpile, forest-fire and slider-block models are said to exhibit self-organized criticality. Associated natural phenomena include landslides, wildfires, and earthquakes. In all cases the frequency-size distributions are well approximated by power laws (fractals). Another important aspect of both the models and natural phenomena is the statistics of interval times. These statistics are particularly important for earthquakes. For earthquakes it is important to make a distinction between interoccurrence and recurrence times. Interoccurrence times are the interval times between earthquakes on all faults in a region whereas recurrence times are interval times between earthquakes on a single fault or fault segment. In many, but not all cases, interoccurrence time statistics are exponential (Poissonian) and the events occur randomly. However, the distribution of recurrence times are often Weibull to a good approximation. In this paper we study the interval statistics of slip events using a slider-block model. The behavior of this model is sensitive to the stiffness α of the system, α=kC/kL where kC is the spring constant of the connector springs and kL is the spring constant of the loader plate springs. For a soft system (small α) there are no system-wide events and interoccurrence time statistics of the larger events are Poissonian. For a stiff system (large α), system-wide events dominate the energy dissipation and the statistics of the recurrence times between these system-wide events satisfy the Weibull distribution to a good approximation. We argue that this applicability of the Weibull distribution is due to the power-law (scale invariant) behavior of the hazard function, i.e. the probability that the next event will occur at a time t0 after the last event has a power-law dependence on t0. The Weibull distribution is the only distribution that has a scale invariant hazard function. We further show that the onset of system-wide events is a well defined critical point. We find that the number of system-wide events NSWE satisfies the scaling relation NSWE ∝(α-αC)δ where αC is the critical value of the stiffness. The system-wide events represent a new phase for the slider-block system.

Apixaban with antiplatelet therapy after acute coronary syndrome.

PubMed

Alexander, John H; Lopes, Renato D; James, Stefan; Kilaru, Rakhi; He, Yaohua; Mohan, Puneet; Bhatt, Deepak L; Goodman, Shaun; Verheugt, Freek W; Flather, Marcus; Huber, Kurt; Liaw, Danny; Husted, Steen E; Lopez-Sendon, Jose; De Caterina, Raffaele; Jansky, Petr; Darius, Harald; Vinereanu, Dragos; Cornel, Jan H; Cools, Frank; Atar, Dan; Leiva-Pons, Jose Luis; Keltai, Matyas; Ogawa, Hisao; Pais, Prem; Parkhomenko, Alexander; Ruzyllo, Witold; Diaz, Rafael; White, Harvey; Ruda, Mikhail; Geraldes, Margarida; Lawrence, Jack; Harrington, Robert A; Wallentin, Lars

2011-08-25

Apixaban, an oral, direct factor Xa inhibitor, may reduce the risk of recurrent ischemic events when added to antiplatelet therapy after an acute coronary syndrome. We conducted a randomized, double-blind, placebo-controlled clinical trial comparing apixaban, at a dose of 5 mg twice daily, with placebo, in addition to standard antiplatelet therapy, in patients with a recent acute coronary syndrome and at least two additional risk factors for recurrent ischemic events. The trial was terminated prematurely after recruitment of 7392 patients because of an increase in major bleeding events with apixaban in the absence of a counterbalancing reduction in recurrent ischemic events. With a median follow-up of 241 days, the primary outcome of cardiovascular death, myocardial infarction, or ischemic stroke occurred in 279 of the 3705 patients (7.5%) assigned to apixaban (13.2 events per 100 patient-years) and in 293 of the 3687 patients (7.9%) assigned to placebo (14.0 events per 100 patient-years) (hazard ratio with apixaban, 0.95; 95% confidence interval [CI], 0.80 to 1.11; P=0.51). The primary safety outcome of major bleeding according to the Thrombolysis in Myocardial Infarction (TIMI) definition occurred in 46 of the 3673 patients (1.3%) who received at least one dose of apixaban (2.4 events per 100 patient-years) and in 18 of the 3642 patients (0.5%) who received at least one dose of placebo (0.9 events per 100 patient-years) (hazard ratio with apixaban, 2.59; 95% CI, 1.50 to 4.46; P=0.001). A greater number of intracranial and fatal bleeding events occurred with apixaban than with placebo. The addition of apixaban, at a dose of 5 mg twice daily, to antiplatelet therapy in high-risk patients after an acute coronary syndrome increased the number of major bleeding events without a significant reduction in recurrent ischemic events. (Funded by Bristol-Myers Squibb and Pfizer; APPRAISE-2 ClinicalTrials.gov number, NCT00831441.).

Aspirin for the prevention of recurrent venous thromboembolism: the INSPIRE collaboration.

PubMed

Simes, John; Becattini, Cecilia; Agnelli, Giancarlo; Eikelboom, John W; Kirby, Adrienne C; Mister, Rebecca; Prandoni, Paolo; Brighton, Timothy A

2014-09-23

In patients with a first unprovoked venous thromboembolism (VTE) the risk of recurrent VTE remains high after anticoagulant treatment is discontinued. The Aspirin for the Prevention of Recurrent Venous Thromboembolism (the Warfarin and Aspirin [WARFASA]) and the Aspirin to Prevent Recurrent Venous Thromboembolism (ASPIRE) trials showed that aspirin reduces this risk, but they were not individually powered to detect treatment effects for particular outcomes or subgroups. An individual patient data analysis of these trials was planned, before their results were known, to assess the effect of aspirin versus placebo on recurrent VTE, major vascular events (recurrent VTE, myocardial infarction, stroke, and cardiovascular disease death) and bleeding, overall and within predefined subgroups. The primary analysis, for VTE, was by intention to treat using time-to-event data. Of 1224 patients, 193 had recurrent VTE over 30.4 months' median follow-up. Aspirin reduced recurrent VTE (7.5%/yr versus 5.1%/yr; hazard ratio [HR], 0.68; 95% confidence interval [CI], 0.51-0.90; P=0.008), including both deep-vein thrombosis (HR, 0.66; 95% CI, 0.47-0.92; P=0.01) and pulmonary embolism (HR, 0.66; 95% CI, 0.41-1.06; P=0.08). Aspirin reduced major vascular events (8.7%/yr versus 5.7%/yr; HR, 0.66; 95% CI, 0.50-0.86; P=0.002). The major bleeding rate was low (0.4%/yr for placebo and 0.5%/yr for aspirin). After adjustment for treatment adherence, recurrent VTE was reduced by 42% (HR, 0.58; 95% CI, 0.40-0.85; P=0.005). Prespecified subgroup analyses indicate similar relative, but larger absolute, risk reductions in men and older patients. Aspirin after anticoagulant treatment reduces the overall risk of recurrence by more than a third in a broad cross-section of patients with a first unprovoked VTE, without significantly increasing the risk of bleeding. www.anzctr.org.au. Unique identifier: ACTRN12611000684921. © 2014 American Heart Association, Inc.

Clinical presentation at first heart failure hospitalization does not predict recurrent heart failure admission.

PubMed

Kosztin, Annamaria; Costa, Jason; Moss, Arthur J; Biton, Yitschak; Nagy, Vivien Klaudia; Solomon, Scott D; Geller, Laszlo; McNitt, Scott; Polonsky, Bronislava; Merkely, Bela; Kutyifa, Valentina

2017-11-01

There are limited data on whether clinical presentation at first heart failure (HF) hospitalization predicts recurrent HF events. We aimed to assess predictors of recurrent HF hospitalizations in mild HF patients with an implantable cardioverter defibrillator or cardiac resynchronization therapy with defibrillator. Data on HF hospitalizations were prospectively collected for patients enrolled in MADIT-CRT. Predictors of recurrent HF hospitalization (HF2) after the first HF hospitalization were assessed using Cox proportional hazards regression models including baseline covariates and clinical presentation or management at first HF hospitalization. There were 193 patients with first HF hospitalization, and 156 patients with recurrent HF events. Recurrent HF rate after the first HF hospitalization was 43% at 1 year, 52% at 2 years, and 55% at 2.5 years. Clinical signs and symptoms, medical treatment, or clinical management of HF at first HF admission was not predictive for HF2. Baseline covariates predicting recurrent HF hospitalization included prior HF hospitalization (HR = 1.59, 95% CI: 1.15-2.20, P = 0.005), digitalis therapy (HR = 1.58, 95% CI: 1.13-2.20, P = 0.008), and left ventricular end-diastolic volume >240 mL (HR = 1.62, 95% CI: 1.17-2.25, P = 0.004). Recurrent HF events are frequent following the first HF hospitalization in patients with implanted implantable cardioverter defibrillator or cardiac resynchronization therapy with defibrillator. Neither clinical presentation nor clinical management during first HF admission was predictive of recurrent HF. Prior HF hospitalization, digitalis therapy, and left ventricular end-diastolic volume at enrolment predicted recurrent HF hospitalization, and these covariates could be used as surrogate markers for identifying a high-risk cohort. © 2017 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.

Brain responses to sound intensity changes dissociate depressed participants and healthy controls.

PubMed

Ruohonen, Elisa M; Astikainen, Piia

2017-07-01

Depression is associated with bias in emotional information processing, but less is known about the processing of neutral sensory stimuli. Of particular interest is processing of sound intensity which is suggested to indicate central serotonergic function. We tested weather event-related brain potentials (ERPs) to occasional changes in sound intensity can dissociate first-episode depressed, recurrent depressed and healthy control participants. The first-episode depressed showed larger N1 amplitude to deviant sounds compared to recurrent depression group and control participants. In addition, both depression groups, but not the control group, showed larger N1 amplitude to deviant than standard sounds. Whether these manifestations of sensory over-excitability in depression are directly related to the serotonergic neurotransmission requires further research. The method based on ERPs to sound intensity change is fast and low-cost way to objectively measure brain activation and holds promise as a future diagnostic tool. Copyright © 2017 Elsevier B.V. All rights reserved.

Increased Serum Alkaline Phosphatase and Serum Phosphate as Predictors of Mortality after Stroke

PubMed Central

S, Pratibha; JB, Agadi

2014-01-01

Context: Serum Alkaline phosphatase (ALP) & phosphate are considered to be indicators of vascular calcification. Link between bone metabolism, vascular calcification, cardiovascular events have been well studied in chronic kidney disease and ischemic heart disease. Aims: To determine that increased serum phosphate and alkaline phosphatase are predictors of mortality rates and recurrent vascular events in stroke. Materials and Methods: Sixty patients admitted with acute stroke (ischemic & haemorrhagic) were included in the study. Their baseline clinical characteristics and biochemical parameters including serum ALP and phosphate were noted. All patients were followed up for a period of one year. The all- cause mortality, the mortality due to cardiovascular events and recurrent vascular events without death were noted during the follow up. Statistical analyses were done to look for any correlation between mortality and baseline levels of serum ALP and phosphate. Results: Of the 60 patients, 8 (13.3%) patients were lost for follow up. Fourteen (26.9%) patients died; of which 12 deaths were due to vascular causes and 2 deaths were due to non vascular causes. Increasing levels of serum ALP and phosphate correlated with all cause mortality and recurrent vascular events without death Conclusion: Serum ALP and phosphate prove to be cost effective prognostic indicator of mortality and recurrent vascular events in stroke. This finding has to be confirmed with studies including larger population. Further research on ALP inhibitors, Vitamin D analogues and phosphate binders to improve mortality in stroke population can be encouraged. PMID:25300293

Increased serum alkaline phosphatase and serum phosphate as predictors of mortality after stroke.

PubMed

S, Pratibha; S, Praveen-Kumar; Jb, Agadi

2014-08-01

Serum Alkaline phosphatase (ALP) & phosphate are considered to be indicators of vascular calcification. Link between bone metabolism, vascular calcification, cardiovascular events have been well studied in chronic kidney disease and ischemic heart disease. To determine that increased serum phosphate and alkaline phosphatase are predictors of mortality rates and recurrent vascular events in stroke. Sixty patients admitted with acute stroke (ischemic & haemorrhagic) were included in the study. Their baseline clinical characteristics and biochemical parameters including serum ALP and phosphate were noted. All patients were followed up for a period of one year. The all- cause mortality, the mortality due to cardiovascular events and recurrent vascular events without death were noted during the follow up. Statistical analyses were done to look for any correlation between mortality and baseline levels of serum ALP and phosphate. Of the 60 patients, 8 (13.3%) patients were lost for follow up. Fourteen (26.9%) patients died; of which 12 deaths were due to vascular causes and 2 deaths were due to non vascular causes. Increasing levels of serum ALP and phosphate correlated with all cause mortality and recurrent vascular events without death Conclusion: Serum ALP and phosphate prove to be cost effective prognostic indicator of mortality and recurrent vascular events in stroke. This finding has to be confirmed with studies including larger population. Further research on ALP inhibitors, Vitamin D analogues and phosphate binders to improve mortality in stroke population can be encouraged.

SRSF2 mutations drive oncogenesis by activating a global program of aberrant alternative splicing in hematopoietic cells.

PubMed

Liang, Yang; Tebaldi, Toma; Rejeski, Kai; Joshi, Poorval; Stefani, Giovanni; Taylor, Ashley; Song, Yuanbin; Vasic, Radovan; Maziarz, Jamie; Balasubramanian, Kunthavai; Ardasheva, Anastasia; Ding, Alicia; Quattrone, Alessandro; Halene, Stephanie

2018-06-01

Recurrent mutations in the splicing factor SRSF2 are associated with poor clinical outcomes in myelodysplastic syndromes (MDS). Their high frequency suggests these mutations drive oncogenesis, yet the molecular explanation for this process is unclear. SRSF2 mutations could directly affect pre-mRNA splicing of a vital gene product; alternatively, a whole network of gene products could be affected. Here we determine how SRSF2 mutations globally affect RNA binding and splicing in vivo using HITS-CLIP. Remarkably, the majority of differential binding events do not translate into alternative splicing of exons with SRSF2 P95H binding sites. Alternative splice alterations appear to be dominated by indirect effects. Importantly, SRSF2 P95H targets are enriched in RNA processing and splicing genes, including several members of the hnRNP and SR families of proteins, suggesting a "splicing-cascade" phenotype wherein mutation of a single splicing factor leads to widespread modifications in multiple RNA processing and splicing proteins. We show that splice alteration of HNRNPA2B1, a splicing factor differentially bound and spliced by SRSF2 P95H , impairs hematopoietic differentiation in vivo. Our data suggests a model whereby the recurrent mutations in splicing factors set off a cascade of gene regulatory events that together affect hematopoiesis and drive cancer.

Invited review: Incidence, risk factors, and effects of clinical mastitis recurrence in dairy cows.

PubMed

Jamali, Hossein; Barkema, Herman W; Jacques, Mario; Lavallée-Bourget, Eve-Marie; Malouin, François; Saini, Vineet; Stryhn, Henrik; Dufour, Simon

2018-06-01

Clinical mastitis (CM) is one of the most frequent and costly diseases in dairy cows. A frustrating aspect of CM is its recurrent nature. This review was conducted to synthesize knowledge on risk of repeated cases of CM, effects of recurrent CM cases, and risk factors for CM recurrence. A systematic review methodology was used to identify articles for this narrative review. Searches were performed to identify relevant scientific literature published after 1989 in English or French from 2 databases (PubMed and CAB Abstracts) and 1 search platform (Web of Science). Fifty-seven manuscripts were selected for qualitative synthesis according to the inclusion criteria. Among the 57 manuscripts selected in this review, a description of CM recurrence, its risk factors, and effects were investigated and reported in 33, 37, and 19 selected manuscripts, respectively. Meta-analysis and meta-regression analyses were used to compute risk ratio comparing risk of CM in cows that already had 1 CM event in the current lactation with risk of CM in healthy cows. For these analyses, 9 manuscripts that reported the total number of lactations followed and the number of lactations with ≤1 and ≤2 CM cases were used. When summarizing results from studies requiring ≥5 d between CM events to consider a CM event as a new case, we observed no significant change in CM susceptibility following a first CM case (risk ratio: 0.99; 95% confidence interval: 0.86-1.14). However, for studies using a more liberal CM recurrence definition (i.e., only 24 h between CM events to consider new CM cases), we observed a 1.54 times greater CM risk (95% confidence interval: 1.20-1.97) for cows that already had 1 CM event in the current lactation compared with healthy cows. The most important risk factors for CM recurrence were parity (i.e., higher risk in older cows), a higher milk production, pathogen species involved in the preceding case, and whether a bacteriological cure was observed following the preceding case. The most important effects of recurrent CM were the milk yield reduction following a recurrent CM case, which was reported to be similar to that of the first CM case, and the increased risk of culling and mortality, which were reported to surpass those of first CM cases. Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Recurrence quantification analysis of global stock markets

NASA Astrophysics Data System (ADS)

Bastos, João A.; Caiado, Jorge

2011-04-01

This study investigates the presence of deterministic dependencies in international stock markets using recurrence plots and recurrence quantification analysis (RQA). The results are based on a large set of free float-adjusted market capitalization stock indices, covering a period of 15 years. The statistical tests suggest that the dynamics of stock prices in emerging markets is characterized by higher values of RQA measures when compared to their developed counterparts. The behavior of stock markets during critical financial events, such as the burst of the technology bubble, the Asian currency crisis, and the recent subprime mortgage crisis, is analyzed by performing RQA in sliding windows. It is shown that during these events stock markets exhibit a distinctive behavior that is characterized by temporary decreases in the fraction of recurrence points contained in diagonal and vertical structures.

Fully vs. partially covered selfexpandable metal stent for palliation of malignant esophageal strictures: a randomized trial (the COPAC study).

PubMed

Didden, Paul; Reijm, Agnes N; Erler, Nicole S; Wolters, Leonieke M M; Tang, Thjon J; Ter Borg, Pieter C J; Leeuwenburgh, Ivonne; Bruno, Marco J; Spaander, Manon C W

2018-06-12

 Covered esophageal self-expandable metal stents (SEMSs) are currently used for palliation of malignant dysphagia. The optimal extent of the covering to prevent recurrent obstruction is unknown. Therefore, we aimed to compare fully covered (FC) versus partially covered (PC) SEMSs in patients with incurable malignant esophageal stenosis.  In this multicenter randomized controlled trial, 98 incurable patients with dysphagia caused by a malignant stricture of the esophagus or cardia were randomized 1:1 to an FC-SEMS or PC-SEMS. The primary outcome was recurrent obstruction after endoscopic SEMS placement. Secondary outcomes were technical and clinical success, adverse events, and health-related quality of life (HRQoL). Patients were followed until 6 months after SEMS placement or to SEMS removal, second SEMS insertion, or death, whichever came first.  Recurrent obstruction after SEMS placement was similar for both types of stents: 19 % for FC-SEMSs and 22 % for PC-SEMSs ( P  = 0.65). The times to recurrent obstruction did not differ. The frequency of adverse events was similar between the two groups, with major adverse events occurring in 38 % and 47 % of patients for FC-SEMSs and PC-SEMSs, respectively ( P  = 0.34). No significant differences were seen in technical success, improvement of dysphagia, and HRQoL. Proximal esophageal stenosis and female sex were independently associated with recurrent obstruction and/or major adverse events.  Esophageal FC-SEMSs did not reveal a lower recurrent obstruction rate compared with PC-SEMSs in the palliative management of malignant dysphagia. © Georg Thieme Verlag KG Stuttgart · New York.

Does drought legacy alter the recovery of grassland carbon dynamics from drought?

NASA Astrophysics Data System (ADS)

Bahn, M.; Hasibeder, R.; Fuchslueger, L.; Ingrisch, J.; Ladreiter-Knauss, T.; Lair, G.; Reinthaler, D.; Richter, A.; Kaufmann, R.

2016-12-01

Climate projections suggest an increase in the frequency and the severity of extreme climatic events, such as droughts, with consequences for the carbon cycle and its feedbacks to the climate system. An important implication of increasing drought frequency is that possible legacies of previous droughts may increasingly affect ecosystem responses to new drought events, though this has been rarely tested. Based on a series of severe experimental droughts performed during nine subsequent years on a mountain grassland in the Austrian Alps, we present evidence of effects of drought legacies on the recovery of grassland carbon dynamics from drought and analyse the underlying mechanisms. Both single and recurrent droughts led to increased aboveground productivity during drought recovery relative to control plots, favoring the biomass production and leaf area of grass species more strongly than of forbs. Belowground productivity was significantly increased during recovery. This led to higher total root length, even though specific root length was strongly reduced during recovery, particularly after recurrent drought events. Following rewetting, the temperature dependence of soil respiration was increasingly diminished and the Birch effect declined with progressive recurrence of droughts. This was paralleled by a change in soil aggregate stability and soil porosity in plots repeatedly exposed to drought. Pulse-labelling experiments revealed effects of drought legacy on plant carbon uptake and belowground allocation and altered microbial turnover of recent plant-derived carbon during and after a subsequent drought. Shifts in tissue nitrogen concentration indicate that drought effects on soil nitrogen turnover and availability could play an important role in the recovery of grassland carbon dynamics following both single and recurrent droughts. In conclusion, drought legacies can alter the recovery of grassland carbon dynamics from drought, the effects increasing with increasing drought frequency and involving changes in both plant functional composition and soil structure and processes.

Does drought legacy alter the recovery of grassland carbon dynamics from drought?

NASA Astrophysics Data System (ADS)

Bahn, Michael; Hasibeder, Roland; Fuchslueger, Lucia; Ingrisch, Johannes; Ladreiter-Knauss, Thomas; Lair, Georg; Reinthaler, David; Richter, Andreas; Kaufmann, Rüdiger

2017-04-01

Climate projections suggest an increase in the frequency and the severity of extreme climatic events, such as droughts, with consequences for the carbon cycle and its feedbacks to the climate system. An important implication of increasing drought frequency is that possible legacies of previous droughts may increasingly affect ecosystem responses to new drought events, though this has been rarely tested. Based on a series of severe experimental droughts performed during nine subsequent years on a mountain grassland in the Austrian Alps, we present evidence of effects of drought legacies on the recovery of grassland carbon dynamics from drought and analyse the underlying mechanisms. Both single and recurrent droughts led to increased aboveground productivity during drought recovery relative to control plots, favoring the biomass production and leaf area of grass species more strongly than of forbs. Belowground productivity was significantly increased during recovery. This led to higher total root length, even though specific root length was strongly reduced during recovery, particularly after recurrent drought events. Following rewetting, the temperature dependence of soil respiration was increasingly diminished and the Birch effect declined with progressive recurrence of droughts. This was paralleled by a change in soil aggregate stability and soil porosity in plots repeatedly exposed to drought. Isotopic pulse-labelling experiments revealed effects of drought legacy on plant carbon uptake and belowground allocation and altered microbial turnover of recent plant-derived carbon during and after a subsequent drought. Shifts in tissue nitrogen concentration indicate that drought effects on soil nitrogen turnover and availability could play an important role in the recovery of grassland carbon dynamics following both single and recurrent droughts. In conclusion, drought legacies can alter the recovery of grassland carbon dynamics from drought, the effects increasing with increasing drought frequency and involving changes in both plant functional composition and soil structure and processes.

Plasminogen Activator Inhibitor-2 Polymorphism Associates with Recurrent Coronary Event Risk in Patients with High HDL and C-Reactive Protein Levels

PubMed Central

Corsetti, James P.; Salzman, Peter; Ryan, Dan; Moss, Arthur J.; Zareba, Wojciech; Sparks, Charles E.

2013-01-01

The objective of this work was to investigate whether fibrinolysis plays a role in establishing recurrent coronary event risk in a previously identified group of postinfarction patients. This group of patients was defined as having concurrently high levels of high-density lipoprotein cholesterol (HDL-C) and C-reactive protein (CRP) and was previously demonstrated to be at high-risk for recurrent coronary events. Potential risk associations of a genetic polymorphism of plasminogen activator inhibitor-2 (PAI-2) were probed as well as potential modulatory effects on such risk of a polymorphism of low-density lipoprotein receptor related protein (LRP-1), a scavenger receptor known to be involved in fibrinolysis in the context of cellular internalization of plasminogen activator/plansminogen activator inhibitor complexes. To this end, Cox multivariable modeling was performed as a function of genetic polymorphisms of PAI-2 (SERPINB, rs6095) and LRP-1 (LRP1, rs1800156) as well as a set of clinical parameters, blood biomarkers, and genetic polymorphisms previously demonstrated to be significantly and independently associated with risk in the study population including cholesteryl ester transfer protein (CETP, rs708272), p22phox (CYBA, rs4673), and thrombospondin-4 (THBS4, rs1866389). Risk association was demonstrated for the reference allele of the PAI-2 polymorphism (hazard ratio 0.41 per allele, 95% CI 0.20-0.84, p=0.014) along with continued significant risk associations for the p22phox and thrombospondin-4 polymorphisms. Additionally, further analysis revealed interaction of the LRP-1 and PAI-2 polymorphisms in generating differential risk that was illustrated using Kaplan-Meier survival analysis. We conclude from the study that fibrinolysis likely plays a role in establishing recurrent coronary risk in postinfarction patients with concurrently high levels of HDL-C and CRP as manifested by differential effects on risk by polymorphisms of several genes linked to key actions involved in the fibrinolytic process. PMID:23874812

Identifying Changes of Complex Flood Dynamics with Recurrence Analysis

NASA Astrophysics Data System (ADS)

Wendi, D.; Merz, B.; Marwan, N.

2016-12-01

Temporal changes in flood hazard system are known to be difficult to detect and attribute due to multiple drivers that include complex processes that are non-stationary and highly variable. These drivers, such as human-induced climate change, natural climate variability, implementation of flood defense, river training, or land use change, could impact variably on space-time scales and influence or mask each other. Flood time series may show complex behavior that vary at a range of time scales and may cluster in time. Moreover hydrological time series (i.e. discharge) are often subject to measurement errors, such as rating curve error especially in the case of extremes where observation are actually derived through extrapolation. This study focuses on the application of recurrence based data analysis techniques (recurrence plot) for understanding and quantifying spatio-temporal changes in flood hazard in Germany. The recurrence plot is known as an effective tool to visualize the dynamics of phase space trajectories i.e. constructed from a time series by using an embedding dimension and a time delay, and it is known to be effective in analyzing non-stationary and non-linear time series. Sensitivity of the common measurement errors and noise on recurrence analysis will also be analyzed and evaluated against conventional methods. The emphasis will be on the identification of characteristic recurrence properties that could associate typical dynamic to certain flood events.

Ischemic stroke and intracranial hemorrhage in patients with recurrent glioblastoma multiforme, treated with bevacizumab.

PubMed

Auer, Timo A; Renovanz, Mirjam; Marini, Federico; Brockmann, Marc A; Tanyildizi, Yasemin

2017-07-01

Bevacizumab (BVZ), a monoclonal antibody directed against vascular endothelial growth factor (VEGF), has been suspected to increase the incidence of ischemic stroke (IS) and intracranial hemorrhage (ICH) in GBM patients. Intracranial vascular events, such as IS and ICH, were retrospectively analyzed in 364 MRI scans of 82 patients with recurrent GBM (1st/2nd/3rd relapse). Out of these 82 patients, 40 were treated with BVZ (178 scans) in addition to basic treatment, whereas 42 patients matching for age and gender received basic treatment (186 scans). Distribution of typical vascular risk factors between both groups was analyzed retrospectively. In seven out of 82 patients (8%) vascular events were detected in MRI. Four vascular events were recorded in the BVZ-group (3 IS and 1 ICH), and 3 vascular events were found in the Control-group (1 IS and 2 ICH; p > 0.05 between both groups). Likewise, vascular risk factors (arterial hypertension, diabetes mellitus, obesity, former vascular event, hyperlipidemia, tobacco consumption and/or hypercholesterolemia) did not differ significantly between both groups. BVZ treatment does not seem to be associated with an increased risk for vascular events in patients with GBM in recurrence.

Universal Recurrence Time Statistics of Characteristic Earthquakes

NASA Astrophysics Data System (ADS)

Goltz, C.; Turcotte, D. L.; Abaimov, S.; Nadeau, R. M.

2006-12-01

Characteristic earthquakes are defined to occur quasi-periodically on major faults. Do recurrence time statistics of such earthquakes follow a particular statistical distribution? If so, which one? The answer is fundamental and has important implications for hazard assessment. The problem cannot be solved by comparing the goodness of statistical fits as the available sequences are too short. The Parkfield sequence of M ≍ 6 earthquakes, one of the most extensive reliable data sets available, has grown to merely seven events with the last earthquake in 2004, for example. Recently, however, advances in seismological monitoring and improved processing methods have unveiled so-called micro-repeaters, micro-earthquakes which recur exactly in the same location on a fault. It seems plausible to regard these earthquakes as a miniature version of the classic characteristic earthquakes. Micro-repeaters are much more frequent than major earthquakes, leading to longer sequences for analysis. Due to their recent discovery, however, available sequences contain less than 20 events at present. In this paper we present results for the analysis of recurrence times for several micro-repeater sequences from Parkfield and adjacent regions. To improve the statistical significance of our findings, we combine several sequences into one by rescaling the individual sets by their respective mean recurrence intervals and Weibull exponents. This novel approach of rescaled combination yields the most extensive data set possible. We find that the resulting statistics can be fitted well by an exponential distribution, confirming the universal applicability of the Weibull distribution to characteristic earthquakes. A similar result is obtained from rescaled combination, however, with regard to the lognormal distribution.

Work stress and the risk of recurrent coronary heart disease events: A systematic review and meta-analysis.

PubMed

Li, Jian; Zhang, Min; Loerbroks, Adrian; Angerer, Peter; Siegrist, Johannes

2015-01-01

Though much evidence indicates that work stress increases the risk of incident of coronary heart disease (CHD), little is known about the role of work stress in the development of recurrent CHD events. The objective of this study was to review and synthesize the existing epidemiological evidence on whether work stress increases the risk of recurrent CHD events in patients with the first CHD. A systematic literature search in the PubMed database (January 1990 - December 2013) for prospective studies was performed. Inclusion criteria included: peer-reviewed English papers with original data, studies with substantial follow-up (> 3 years), end points defined as cardiac death or nonfatal myocardial infarction, as well as work stress assessed with reliable and valid instruments. Meta-analysis using random-effects modeling was conducted in order to synthesize the observed effects across the studies. Five papers derived from 4 prospective studies conducted in Sweden and Canada were included in this systematic review. The measurement of work stress was based on the Demand- Control model (4 papers) or the Effort-Reward Imbalance model (1 paper). According to the estimation by meta-analysis based on 4 papers, a significant effect of work stress on the risk of recurrent CHD events (hazard ratio: 1.65, 95% confidence interval: 1.23-2.22) was observed. Our findings suggest that, in patients with the first CHD, work stress is associated with an increased relative risk of recurrent CHD events by 65%. Due to the limited literature, more well-designed prospective research is needed to examine this association, in particular, from other than western regions of the world. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.

The anticoagulant effects of warfarin and the bleeding risk associated with its use in patients with chronic thromboembolic pulmonary hypertension at a specialist center in Japan: a retrospective cohort study

PubMed Central

Jujo-Sanada, Takayuki; Tanabe, Nobuhiro; Sakao, Seiichiro; Sugiura, Toshihiko; Sekine, Ayumi; Nishimura, Rintaro; Suda, Rika; Naito, Akira; Miwa, Hideki; Yamamoto, Keiko; Sasaki, Akane; Matsumura, Akane; Ema, Ryogo; Kasai, Hajime; Kato, Fumiaki; Tatsumi, Koichiro

2017-01-01

Patients with chronic thromboembolic pulmonary hypertension (CTEPH) require lifelong anticoagulation therapy. However, the bleeding risk and recurrence of venous thromboembolism (VTE) in CTEPH patients who are administered warfarin have not been adequately evaluated. The purpose of this study was to evaluate the risk of clinically relevant bleeding, recurrent VTE, and clinical worsening in patients with CTEPH who were administered warfarin. The clinical records of 72 patients with CTEPH who regularly visited our institution and were administered warfarin were retrospectively reviewed between 1 January 2011 and 31 December 2015. We investigated the incidence of clinically relevant bleeding events, recurrent VTE, and hospitalization for the deterioration of pulmonary hypertension or right heart failure (RHF) during the observation period. The mean observation period for the 72 patients was 3.60 ± 1.60 person-years. Clinically relevant bleeding, RHF, and recurrent VTE occurred in 21 (29.2%), eight (11.1%), and three (4.2%) of 72 patients, respectively, and the incidence rates for these events were 8.1%/person-year, 3.1%/person-year, and 1.2%/person-year, respectively. The incidence rates for the major and non-major bleeding events were 5.0%/person-year and 3.9%/person-year, respectively. The incidence of clinically relevant bleeding events was 20.8%/person-year during medical treatment with a soluble guanylate cyclase stimulator. One of 35 patients (2.9%) during the post-pulmonary endarterectomy period experienced hemoptysis during observation period (> 6 months after pulmonary endarterectomy). No bleeding events occurred during the post-balloon pulmonary angioplasty period. In conclusion, warfarin effectively prevents VTE recurrence in CTEPH patients, but its effects may be associated with a considerable bleeding risk. PMID:28604280

Distribution and Characteristics of Repeating Earthquakes in Northern California

NASA Astrophysics Data System (ADS)

Waldhauser, F.; Schaff, D. P.; Zechar, J. D.; Shaw, B. E.

2012-12-01

Repeating earthquakes are playing an increasingly important role in the study of fault processes and behavior, and have the potential to improve hazard assessment, earthquake forecast, and seismic monitoring capabilities. These events rupture the same fault patch repeatedly, generating virtually identical seismograms. In California, repeating earthquakes have been found predominately along the creeping section of the central San Andreas Fault, where they are believed to represent failing asperities on an otherwise creeping fault. Here, we use the northern California double-difference catalog of 450,000 precisely located events (1984-2009) and associated database of 2 billion waveform cross-correlation measurements to systematically search for repeating earthquakes across various tectonic regions. An initial search for pairs of earthquakes with high-correlation coefficients and similar magnitudes resulted in 4,610 clusters including a total of over 26,000 earthquakes. A subsequent double-difference re-analysis of these clusters resulted in 1,879 sequences (8,640 events) where a common rupture area can be resolved to the precision of a few tens of meters or less. These repeating earthquake sequences (RES) include between 3 and 24 events with magnitudes up to ML=4. We compute precise relative magnitudes between events in each sequence from differential amplitude measurements. Differences between these and standard coda-duration magnitudes have a standard deviation of 0.09. The RES occur throughout northern California, but RES with 10 or more events (6%) only occur along the central San Andreas and Calaveras faults. We are establishing baseline characteristics for each sequence, such as recurrence intervals and their coefficient of variation (CV), in order to compare them across tectonic regions. CVs for these clusters range from 0.002 to 2.6, indicating a range of behavior between periodic occurrence (CV~0), random occurrence, and temporal clustering. 10% of the RES show burst-like behavior with mean recurrence times smaller than one month. 5% of the RES have mean recurrence times greater than one year and include more than 10 earthquakes. Earthquakes in the 50 most periodic sequences (CV<0.2) do not appear to be predictable by either time- or slip-predictable models, consistent with previous findings. We demonstrate that changes in recurrence intervals of repeating earthquakes can be routinely monitored. This is especially important for sequences with CV~0, as they may indicate changes in the loading rate. We also present results from retrospective forecast experiments based on near-real time hazard functions.

Laboratory constraints on models of earthquake recurrence

USGS Publications Warehouse

Beeler, Nicholas M.; Tullis, Terry; Junger, Jenni; Kilgore, Brian D.; Goldsby, David L.

2014-01-01

In this study, rock friction ‘stick-slip’ experiments are used to develop constraints on models of earthquake recurrence. Constant-rate loading of bare rock surfaces in high quality experiments produces stick-slip recurrence that is periodic at least to second order. When the loading rate is varied, recurrence is approximately inversely proportional to loading rate. These laboratory events initiate due to a slip rate-dependent process that also determines the size of the stress drop [Dieterich, 1979; Ruina, 1983] and as a consequence, stress drop varies weakly but systematically with loading rate [e.g., Gu and Wong, 1991; Karner and Marone, 2000; McLaskey et al., 2012]. This is especially evident in experiments where the loading rate is changed by orders of magnitude, as is thought to be the loading condition of naturally occurring, small repeating earthquakes driven by afterslip, or low-frequency earthquakes loaded by episodic slip. As follows from the previous studies referred to above, experimentally observed stress drops are well described by a logarithmic dependence on recurrence interval that can be cast as a non-linear slip-predictable model. The fault’s rate dependence of strength is the key physical parameter. Additionally, even at constant loading rate the most reproducible laboratory recurrence is not exactly periodic, unlike existing friction recurrence models. We present example laboratory catalogs that document the variance and show that in large catalogs, even at constant loading rate, stress drop and recurrence co-vary systematically. The origin of this covariance is largely consistent with variability of the dependence of fault strength on slip rate. Laboratory catalogs show aspects of both slip and time predictability and successive stress drops are strongly correlated indicating a ‘memory’ of prior slip history that extends over at least one recurrence cycle.

Stick-slip behavior in a continuum-granular experiment.

PubMed

Geller, Drew A; Ecke, Robert E; Dahmen, Karin A; Backhaus, Scott

2015-12-01

We report moment distribution results from a laboratory experiment, similar in character to an isolated strike-slip earthquake fault, consisting of sheared elastic plates separated by a narrow gap filled with a two-dimensional granular medium. Local measurement of strain displacements of the plates at 203 spatial points located adjacent to the gap allows direct determination of the event moments and their spatial and temporal distributions. We show that events consist of spatially coherent, larger motions and spatially extended (noncoherent), smaller events. The noncoherent events have a probability distribution of event moment consistent with an M(-3/2) power law scaling with Poisson-distributed recurrence times. Coherent events have a log-normal moment distribution and mean temporal recurrence. As the applied normal pressure increases, there are more coherent events and their log-normal distribution broadens and shifts to larger average moment.

Regression analysis of mixed panel count data with dependent terminal events.

PubMed

Yu, Guanglei; Zhu, Liang; Li, Yang; Sun, Jianguo; Robison, Leslie L

2017-05-10

Event history studies are commonly conducted in many fields, and a great deal of literature has been established for the analysis of the two types of data commonly arising from these studies: recurrent event data and panel count data. The former arises if all study subjects are followed continuously, while the latter means that each study subject is observed only at discrete time points. In reality, a third type of data, a mixture of the two types of the data earlier, may occur and furthermore, as with the first two types of the data, there may exist a dependent terminal event, which may preclude the occurrences of recurrent events of interest. This paper discusses regression analysis of mixed recurrent event and panel count data in the presence of a terminal event and an estimating equation-based approach is proposed for estimation of regression parameters of interest. In addition, the asymptotic properties of the proposed estimator are established, and a simulation study conducted to assess the finite-sample performance of the proposed method suggests that it works well in practical situations. Finally, the methodology is applied to a childhood cancer study that motivated this study. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Recurrent job loss and mental health among women.

PubMed

Nuttman-Shwartz, Orit; Gadot, Limor; Kacen, Lea

2009-06-01

Growing instability in the labor market has led to an increase in recurrent job loss, which primarily affects women (Tamir, 2007). Numerous studies have shown that job loss is a stressful, traumatic experience that has consequences for the individuals who are laid off. However, few studies have examined how recurrent job loss affects individuals. The present study of 134 Israeli women aged 30-45 years aimed to examine how recurrent job loss affected individual women's perceptions of the event and the extent to which it generated emotional stress and psychiatric symptoms. Most of the women perceived job loss as a challenging event and their assessments of job loss had a stronger impact on the development of mental health consequences than did the number of times they had actually been laid off. The more the women perceived job loss as threatening, the more they reported emotional stress and psychiatric symptoms. Conversely, the more they perceived job loss as challenging, the lower their levels of emotional stress. Never-married women were laid-off more, and they reported more mental health symptoms following recurrent job loss than did married women. The findings suggest that perception of job loss as a threatening event might cause mental health problems as results of lay-off.

Cross-sectional study on comorbidities and adverse events in patients with advanced and recurrent ovarian cancer in France.

PubMed

Le Saux, Olivia; Taylor, Aliki; Chia, Victoria; Pillas, Demetris; Kaur, Moninder; Freyer, Gilles

2015-01-01

The purpose of this study was to evaluate the prevalence of comorbidities and adverse events (AEs), and determine the treatment patterns according to platinum-sensitivity status in patients with advanced (stage IIIB-IV) or recurrent epithelial ovarian cancer (EOC). A cross-sectional study was carried out in France with patients over 18 years, diagnosed with advanced (stage IIIB-IV) or recurrent EOC between 2009 and 2012. A total of 23 physicians (oncologists and gynecologists) participated, contributing 127 patients. Data were abstracted by participating physicians into a case report form. Of the 127 patients included, 92 (72.4%) had advanced EOC and 35 (27.6%) had recurrent EOC. A total of 73 comorbidities were reported in 44 patients (34.6%). Vascular (10.2%), metabolic (7.1%), respiratory (5.5%), and psychiatric disorders (5.5%) were the most common types of comorbidities reported. Prevalence of AEs was 74.8%, of which 12.6% were classified as serious. The most common AEs were anemia (16.5%), hematologic events (12.6%), taste change (11.8%), and headache (7.1%). Throughout the follow-up period, twelve patient deaths were reported (six due to disease progression). Of 35 patients with recurrent disease, 16 were highly platinum sensitive (recurrence >12 months after stopping platinum-based therapy), eleven were partially platinum sensitive (recurrence 6-12 months after stopping platinum-based therapy), seven were platinum resistant (recurrence within 6 months of stopping platinum-based therapy or progression while receiving second- or later-line platinum-based therapy), and one was platinum refractory (recurrence within 6 months from the start of first-line platinum-based therapy). In this cross-sectional study of advanced and metastatic ovarian cancer patients, approximately one-third of patients were diagnosed with comorbidities, and approximately three-quarters were diagnosed with AEs (12.6% with severe AEs).

Catecholamines in Post-Traumatic Stress Disorder

DTIC Science & Technology

2012-07-01

could lead to memories that are too strong, contributing to the recurrent, intrusive retrieval of the traumatic events that occurs in PTSD. As a...emotionally arousing experiences are typically vivid and persistent. The recurrent, intrusive memories of traumatic events in post-traumatic stress disorder...signaling plays a critical role in the maintenance of waking and in the regulation of REM sleep. J Neurophysiol 92:2071–2082. Ouyang M, Zhang L, Zhu

Effective Measurement of Reliability of Repairable USAF Systems

DTIC Science & Technology

2012-09-01

Hansen presented a course, Concepts and Models for Repairable Systems Reliability, at the 2009 Centro de Investigacion en Mathematicas ( CIMAT ). The...recurrent event by calculating the mean quantity of recurrent events of the population of systems at risk at that point in time. The number of systems at... risk is the number of systems that are operating and providing information. [9] Information can be obscured by data censoring and truncation. One

Blood Pressure Reduction and Secondary Stroke Prevention: A Systematic Review and Metaregression Analysis of Randomized Clinical Trials.

PubMed

Katsanos, Aristeidis H; Filippatou, Angeliki; Manios, Efstathios; Deftereos, Spyridon; Parissis, John; Frogoudaki, Alexandra; Vrettou, Agathi-Rosa; Ikonomidis, Ignatios; Pikilidou, Maria; Kargiotis, Odysseas; Voumvourakis, Konstantinos; Alexandrov, Anne W; Alexandrov, Andrei V; Tsivgoulis, Georgios

2017-01-01

Current recommendations do not specifically address the optimal blood pressure (BP) reduction for secondary stroke prevention in patients with previous cerebrovascular events. We conducted a systematic review and metaregression analysis on the association of BP reduction with recurrent stroke and cardiovascular events using data from randomized controlled clinical trials of secondary stroke prevention. For all reported events during each eligible study period, we calculated the corresponding risk ratios to express the comparison of event occurrence risk between patients randomized to antihypertensive treatment and those randomized to placebo. On the basis of the reported BP values, we performed univariate metaregression analyses according to the achieved BP values under the random-effects model (Method of Moments) for those adverse events reported in ≥10 total subgroups of included randomized controlled clinical trials. In pairwise meta-analyses, antihypertensive treatment lowered the risk for recurrent stroke (risk ratio, 0.73; 95% confidence interval, 0.62-0.87; P<0.001), disabling or fatal stroke (risk ratio, 0.71; 95% confidence interval, 0.59-0.85; P<0.001), and cardiovascular death (risk ratio, 0.85; 95% confidence interval, 0.75-0.96; P=0.01). In metaregression analyses, systolic BP reduction was linearly related to the lower risk of recurrent stroke (P=0.049), myocardial infarction (P=0.024), death from any cause (P=0.001), and cardiovascular death (P<0.001). Similarly, diastolic BP reduction was linearly related to a lower risk of recurrent stroke (P=0.026) and all-cause mortality (P=0.009). Funnel plot inspection and Egger statistical test revealed no evidence of publication bias. The extent of BP reduction is linearly associated with the magnitude of risk reduction in recurrent cerebrovascular and cardiovascular events. Strict and aggressive BP control seems to be essential for effective secondary stroke prevention. © 2016 American Heart Association, Inc.

Recurrence-plot-based measures of complexity and their application to heart-rate-variability data.

PubMed

Marwan, Norbert; Wessel, Niels; Meyerfeldt, Udo; Schirdewan, Alexander; Kurths, Jürgen

2002-08-01

The knowledge of transitions between regular, laminar or chaotic behaviors is essential to understand the underlying mechanisms behind complex systems. While several linear approaches are often insufficient to describe such processes, there are several nonlinear methods that, however, require rather long time observations. To overcome these difficulties, we propose measures of complexity based on vertical structures in recurrence plots and apply them to the logistic map as well as to heart-rate-variability data. For the logistic map these measures enable us not only to detect transitions between chaotic and periodic states, but also to identify laminar states, i.e., chaos-chaos transitions. The traditional recurrence quantification analysis fails to detect the latter transitions. Applying our measures to the heart-rate-variability data, we are able to detect and quantify the laminar phases before a life-threatening cardiac arrhythmia occurs thereby facilitating a prediction of such an event. Our findings could be of importance for the therapy of malignant cardiac arrhythmias.

The safety of antiangiogenic agents and PARP inhibitors in platinum-sensitive recurrent ovarian cancer.

PubMed

Lorusso, Domenica; Fontanella, Caterina; Maltese, Giuseppa; Lepori, Stefano; Tripodi, Elisa; Bogani, Giorgio; Raspagliesi, Francesco

2017-06-01

Recurrence is a common event in endothelial ovarian cancer (EOC) patients, and the choice of the most appropriate treatment is driven by the platinum-free interval, molecular characteristics of the disease such as BRCA mutational status, previous treatments and toxicity. Areas covered: This review focuses on the main hematologic and non-hematologic toxicities correlated with the use of licensed antiangiogenic agents and PARP inhibitors in recurrent platinum-sensitive EOC, providing recommendations for their management. Expert opinion: The clinical research over the next years will be focused on a more precise characterization of molecular pathways underlying tumorigenesis of the five ovarian tumors, to improve the decision-making process in these rare diseases. For this purpose, new study designs and international collaborations will become mandatory. Immunotherapy, antiangiogenic agents and PARP inhibitors will be combined to build a treatment strategy algorithm which will allow patients to receive all the available treatment option, in the more appropriate sequence.

Lipoprotein(a) Levels and Recurrent Vascular Events After First Ischemic Stroke.

PubMed

Lange, Kristin S; Nave, Alexander H; Liman, Thomas G; Grittner, Ulrike; Endres, Matthias; Ebinger, Martin

2017-01-01

The association of elevated lipoprotein(a) (Lp(a)) levels and the incidence of cardiovascular disease, especially coronary heart disease and ischemic stroke, is well established. However, evidence on the association between Lp(a) levels and residual vascular risk in stroke survivors is lacking. We aimed to elucidate the risk for recurrent cardiovascular and cerebrovascular events in the patients with first-ever ischemic stroke with elevated Lp(a). All patients with acute ischemic stroke who participated in the prospective Berlin C&S study (Cream & Sugar) between January 2009 and August 2014 with available 12-month follow-up data and stored blood samples were eligible for inclusion. Lp(a) levels were determined in serum samples using an isoform-insensitive nephelometry assay. We assessed the risk for the composite vascular end point of ischemic stroke, transient ischemic attack, myocardial infarction, nonelective coronary revascularization, and cardiovascular death with elevated Lp(a) defined as >30 mg/dL using Cox regression analyses. Of 465 C&S study participants, 250 patients were included into this substudy with a median National Institutes of Health Stroke Scale score of 2 (1-4). Twenty-six patients (10%) experienced a recurrent vascular event during follow-up. Among patients with normal Lp(a) levels, 11 of 157 subjects (7%) experienced an event at a median time of 161 days (interquartile range, 19-196 days), whereas in patients with elevated Lp(a) levels, 15 of 93 subjects (16%) experienced an event at a median time of 48 days (interquartile range, 9-194 days; P=0.026). The risk for a recurrent event was significantly higher in patients with elevated Lp(a) levels after adjustment for potential confounders (hazard ratio, 2.60; 95% confidence interval, 1.19-5.67; P=0.016). Elevated Lp(a) levels are associated with a higher risk for combined vascular event recurrence in patients with acute, first-ever ischemic stroke. This finding should be validated in larger, multicenter trials. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01378468. © 2016 American Heart Association, Inc.

Effort-reward imbalance at work and recurrent coronary heart disease events: a 4-year prospective study of post-myocardial infarction patients.

PubMed

Aboa-Éboulé, Corine; Brisson, Chantal; Maunsell, Elizabeth; Bourbonnais, Renée; Vézina, Michel; Milot, Alain; Dagenais, Gilles R

2011-01-01

Prospective studies have shown that effort-reward imbalance (ERI) at work is associated with the incidence of a first coronary heart disease (CHD) event. However, it is unknown whether ERI at work increases the risk of recurrent CHD events. The objective of this study was to determine whether ERI at work and its components (effort and reward) increase the risk of recurrent CHD in post-myocardial infarction (post-MI) workers. We carried out a prospective cohort study of 669 men and 69 women who returned to work after a first MI. ERI at work was assessed by telephone interview using validated scales of reward and psychological demands. The outcome was a composite of fatal CHD, nonfatal MI, and unstable angina. CHD risk factors were documented in medical files and by interview. The participants were followed up for a mean period of 4.0 years (1998-2005). During the follow-up, 96 CHD events were documented. High ERI and low reward were associated with recurrent CHD (respective adjusted hazard ratios [HRs] = 1.75, 95% confidence interval [CI] = 0.99-3.08, and HR = 1.77, 95% CI = 1.16-2.71). There was a gender interaction showing stronger effects among women (respective adjusted HRs for high ERI and low reward: HR = 3.95, 95% CI = 0.93-16.79, and HR = 9.53, 95% CI = 1.15-78.68). Post-MI workers holding jobs that involved ERI or low reward had increased risk of recurrent CHD.

Recurrent decadal-scale dust events over Holocene western Africa and their control on canyon turbidite activity (Mauritania)

NASA Astrophysics Data System (ADS)

Hanebuth, Till J. J.; Henrich, Rüdiger

2009-02-01

Sediment records from continental shelves and slopes might provide paleoenvironmental information in the highest temporal resolution but are often hampered due to strong erosional and reworking processes. Here, we present a Holocene sedimentary record from an exceptional shelf mud belt depocenter off northern Mauritania, compared to a second sediment core located inside a large canyon system at the adjacent continental slope. Both records are of outstandingly continuous and highest temporal resolution (9 a/cm) and are investigated by sedimentological and geochemical methods. A series of sharply defined, recurrent dust peaks is preserved in the shelf archive. Each event has lasted for a single decade only and seems to coincide with an individual turbidite bed in the canyon. A joint mechanism should, thus, be responsible for both of these deposits and we suggest a regional atmospheric trigger. Only short-lasting Trade wind strengthening would cause such pronounced aridity over western Saharan Africa. The effect would be massive dust export to shelf and slope. Recently developed high resolution aridity and humidity records from western Africa support the existence of these events over the Holocene and identify them as being controlled by the Atlantic system as far south as 19°N.

Precipitation-Frequency and Discharge-Frequency Relations for Basins Less than 32 Square Miles in Kansas

USGS Publications Warehouse

Perry, Charles A.

2008-01-01

Precipitation-frequency and discharge-frequency relations for small drainage basins with areas less than 32 square miles in Kansas were evaluated to reduce the uncertainty of discharge-frequency estimates. Gaged-discharge records were used to develop discharge-frequency equations for the ratio of discharge to drainage area (Q/A) values using data from basins with variable soil permeability, channel slope, and mean annual precipitation. Soil permeability and mean annual precipitation are the dominant basin characteristics in the multiple linear regression analyses. In addition, 28 discharge measurements at ungaged sites by indirect surveying methods and by velocity meters also were used in this analysis to relate precipitation-recurrence interval to discharge-recurrence interval. Precipitation-recurrence interval for each of these discharge measurements were estimated from weather-radar estimates of precipitation and from nearby raingages. Time of concentration for each basin for each of the ungaged sites was computed and used to determine the precipitation-recurrence interval based on precipitation depth and duration. The ratio of discharge/drainage area (Q/A) value for each event was then assigned to that precipitation-recurrence interval. The relation between the ratio of discharge/drainage area (Q/A) and precipitation-recurrence interval for all 28 measured events resulted in a correlation coefficient of 0.79. Using basins less than 5.4 mi2 only, the correlation decreases to 0.74. However, when basins greater than 5.4 and less than 32 mi2 are examined the relation improves to a correlation coefficient of 0.95. There were a sufficient number of discharge and radar-measured precipitation events for both the 5-year (8 events) and the 100-year (11 events) recurrence intervals to examine the effect of basin characteristics on the Q/A values for basins less than 32 mi2. At the 5-year precipitation-/discharge-recurrence interval, channel slope was a significant predictor (r=0.99) of Q/A. Permeability (r=0.68) also had a significant effect on Q/A values for the 5-year recurrence interval. At the 100-year recurrence interval, permeability, channel slope, and mean annual precipitation did not have a significant effect on Q/A; however, time of concentration was a significant factor in determining Q/A for the 100-year events with greater times of concentration resulting in lower Q/A values. Additional high-recurrence interval (5-, 10-, 25-, 50-, and 100-year) precipitation/discharge data are needed to confirm these relations suggested above. Discharge data with attendant basin-wide precipitation data from precipitation-radar estimates provides a unique opportunity to study the effects of basin characteristics on the relation between precipitation recurrence interval and discharge-recurrence interval. Discharge-frequency values from the Q/A equations, the rational method, and the Kansas discharge-frequency equations (KFFE) were compared to 28 measured weather-radar precipitation-/discharge-frequency values. The association between precipitation frequency from weather-radar estimates and the frequency of the resulting discharge was shown in these comparisons. The measured and Q/A equation computed discharges displayed the best equality from low to high discharges of the three methods. Here the slope of the line was nearly 1:1 (y=0.9844x0.9677). Comparisons with the rational method produced a slope greater than 1:1 (y=0.0722x1.235), and the KFFE equations produced a slope less than 1:1 (y=5.9103x0.7475). The Q/A equation standard error of prediction averaged 0.1346 log units for the 5.4-to 32-square-mile group and 0.0944 log units for the less than 5.4-square mile group. The KFFE standard error averaged 0.2107 log units for the less-than-30-square-mile equations. Using the Q/A equations for determining discharge frequency values for ungaged sites thus appears to be a good alternative to the other two methods because of this s

Effects of long memory in the order submission process on the properties of recurrence intervals of large price fluctuations

NASA Astrophysics Data System (ADS)

Meng, Hao; Ren, Fei; Gu, Gao-Feng; Xiong, Xiong; Zhang, Yong-Jie; Zhou, Wei-Xing; Zhang, Wei

2012-05-01

Understanding the statistical properties of recurrence intervals (also termed return intervals in econophysics literature) of extreme events is crucial to risk assessment and management of complex systems. The probability distributions and correlations of recurrence intervals for many systems have been extensively investigated. However, the impacts of microscopic rules of a complex system on the macroscopic properties of its recurrence intervals are less studied. In this letter, we adopt an order-driven stock model to address this issue for stock returns. We find that the distributions of the scaled recurrence intervals of simulated returns have a power-law scaling with stretched exponential cutoff and the intervals possess multifractal nature, which are consistent with empirical results. We further investigate the effects of long memory in the directions (or signs) and relative prices of the order flow on the characteristic quantities of these properties. It is found that the long memory in the order directions (Hurst index Hs) has a negligible effect on the interval distributions and the multifractal nature. In contrast, the power-law exponent of the interval distribution increases linearly with respect to the Hurst index Hx of the relative prices, and the singularity width of the multifractal nature fluctuates around a constant value when Hx<0.7 and then increases with Hx. No evident effects of Hs and Hx are found on the long memory of the recurrence intervals. Our results indicate that the nontrivial properties of the recurrence intervals of returns are mainly caused by traders' behaviors of persistently placing new orders around the best bid and ask prices.

Viscoelasticity, postseismic slip, fault interactions, and the recurrence of large earthquakes

USGS Publications Warehouse

Michael, A.J.

2005-01-01

The Brownian Passage Time (BPT) model for earthquake recurrence is modified to include transient deformation due to either viscoelasticity or deep post seismic slip. Both of these processes act to increase the rate of loading on the seismogenic fault for some time after a large event. To approximate these effects, a decaying exponential term is added to the BPT model's uniform loading term. The resulting interevent time distributions remain approximately lognormal, but the balance between the level of noise (e.g., unknown fault interactions) and the coefficient of variability of the interevent time distribution changes depending on the shape of the loading function. For a given level of noise in the loading process, transient deformation has the effect of increasing the coefficient of variability of earthquake interevent times. Conversely, the level of noise needed to achieve a given level of variability is reduced when transient deformation is included. Using less noise would then increase the effect of known fault interactions modeled as stress or strain steps because they would be larger with respect to the noise. If we only seek to estimate the shape of the interevent time distribution from observed earthquake occurrences, then the use of a transient deformation model will not dramatically change the results of a probability study because a similar shaped distribution can be achieved with either uniform or transient loading functions. However, if the goal is to estimate earthquake probabilities based on our increasing understanding of the seismogenic process, including earthquake interactions, then including transient deformation is important to obtain accurate results. For example, a loading curve based on the 1906 earthquake, paleoseismic observations of prior events, and observations of recent deformation in the San Francisco Bay region produces a 40% greater variability in earthquake recurrence than a uniform loading model with the same noise level.

Recurrent flares in active region NOAA 11283

NASA Astrophysics Data System (ADS)

Romano, P.; Zuccarello, F.; Guglielmino, S. L.; Berrilli, F.; Bruno, R.; Carbone, V.; Consolini, G.; de Lauretis, M.; Del Moro, D.; Elmhamdi, A.; Ermolli, I.; Fineschi, S.; Francia, P.; Kordi, A. S.; Landi Degl'Innocenti, E.; Laurenza, M.; Lepreti, F.; Marcucci, M. F.; Pallocchia, G.; Pietropaolo, E.; Romoli, M.; Vecchio, A.; Vellante, M.; Villante, U.

2015-10-01

Context. Flares and coronal mass ejections (CMEs) are solar phenomena that are not yet fully understood. Several investigations have been performed to single out their related physical parameters that can be used as indices of the magnetic complexity leading to their occurrence. Aims: In order to shed light on the occurrence of recurrent flares and subsequent associated CMEs, we studied the active region NOAA 11283 where recurrent M and X GOES-class flares and CMEs occurred. Methods: We use vector magnetograms taken by HMI/SDO to calculate the horizontal velocity fields of the photospheric magnetic structures, the shear and the dip angles of the magnetic field, the magnetic helicity flux distribution, and the Poynting fluxes across the photosphere due to the emergence and the shearing of the magnetic field. Results: Although we do not observe consistent emerging magnetic flux through the photosphere during the observation time interval, we detected a monotonic increase of the magnetic helicity accumulated in the corona. We found that both the shear and the dip angles have high values along the main polarity inversion line (PIL) before and after all the events. We also note that before the main flare of X2.1 GOES class, the shearing motions seem to inject a more significant energy than the energy injected by the emergence of the magnetic field. Conclusions: We conclude that the very long duration (about 4 days) of the horizontal displacement of the main photospheric magnetic structures along the PIL has a primary role in the energy release during the recurrent flares. This peculiar horizontal velocity field also contributes to the monotonic injection of magnetic helicity into the corona. This process, coupled with the high shear and dip angles along the main PIL, appears to be responsible for the consecutive events of loss of equilibrium leading to the recurrent flares and CMEs. A movie associated to Fig. 4 is available in electronic form at http://www.aanda.org

Holocene Mass Transport Deposits in Western Norwegian fjords and lakes revealing prehistoric earthquake history of Scandinavia

NASA Astrophysics Data System (ADS)

Bellwald, B.; Hjelstuen, B. O.; Sejrup, H. P.; Kuvås, J.; Stokowy, T.

2016-12-01

The sensitivity of fjord sediments to seismic shaking makes fjord systems appropriate study sites when extending regional earthquake catalogs back in time and when estimating recurrence rates of prehistoric earthquakes in intraplate settings. In this study we compiled evidence of 140 postglacial mass movement events and their associated mass transport deposits (MTDs) from previously analyzed and new sediment cores and high-resolution seismic profiles from 22 fjord systems and six lakes in Western Norway. Evaluation of trigger mechanisms make us infer that most of these mass movement events were initiated by regional earthquakes, and that both climate-related processes and tsunamis most likely can be excluded as trigger mechanism for most of the events. A total of 33 individual earthquakes has been identified, which most likely outbalance the historically recorded events in magnitude, thus indicating magnitudes >6. Frequency plots of MTDs suggest high seismic activity in the early Holocene (11000-9700 cal. yrs BP), followed by seismic quiescence in the mid-Holocene before a seismic reactivation took place at 4000 cal. yrs BP. Coevally-triggered MTDs at 8100 cal. yrs BP are identified in all the archives, and are correlating with the age of the offshore Storegga slide. We estimate earthquake recurrence rates of 1/80 years directly after the last deglaciation of Western Norway (12800-11600 ca. yrs BP), 1/200 years for the early Holocene and 1/300 years for the last 4000 years. Our compilation suggests that the mid-Holocene is characterized by low seismic activity, suggesting recurrence rates of 1/1300 years. Comparisons of the Western Norwegian dataset with paleoseimologic studies of other previously glaciated intraplate settings indicate that both Scandinavia and the Alps show similar trends as Western Norway, whereas Eastern Canada is not correlating with the paleoseismologic trend of this study, which could be explained by different deglaciation histories.

Clinical Immunology Review Series: An approach too the patient with anaphylaxi

PubMed Central

El-Shanawany, T; Williams, P E; Jolles, S

2008-01-01

ARTICLES PUBLISHED IN THIS CLINICAL IMMUNOLOGY REVIEW SERIESallergy in childhood, allergy diagnosis by use of the clinical immunology laboratory, anaphylaxis, angioedema, management of pulmonary disease in primary antibody deficiency, recurrent infections in childhood, recurrent infections in adulthood, recurrent oro-genital ulceration, recurrent superficial abscesses, urticaria, vasculitis/CTD Anaphylaxis is a severe, life-threatening, generalized or systemic hypersensitivity reaction. While there is agreement as to this definition of anaphylaxis, the clinical presentation is often variable and it is not uncommon for there to be debate after the event as to whether anaphylaxis had actually occurred. The management of anaphylaxis falls into two distinct phases: (1) emergency treatment and resuscitation of a patient with acute anaphylaxis and (2) the search for a cause for the event and the formulation of a plan to prevent and treat possible further episodes of anaphylaxis. Both aspects are important in preventing death from anaphylaxis and are covered in this review. PMID:18577027

Divergent clonal selection dominates medulloblastoma at recurrence

PubMed Central

Morrissy, A. Sorana; Garzia, Livia; Shih, David J. H.; Zuyderduyn, Scott; Huang, Xi; Skowron, Patryk; Remke, Marc; Cavalli, Florence M. G.; Ramaswamy, Vijay; Lindsay, Patricia E.; Jelveh, Salomeh; Donovan, Laura K.; Wang, Xin; Luu, Betty; Zayne, Kory; Li, Yisu; Mayoh, Chelsea; Thiessen, Nina; Mercier, Eloi; Mungall, Karen L.; Ma, Yusanne; Tse, Kane; Zeng, Thomas; Shumansky, Karey; Roth, Andrew J. L.; Shah, Sohrab; Farooq, Hamza; Kijima, Noriyuki; Holgado, Borja L.; Lee, John J. Y.; Matan-Lithwick, Stuart; Liu, Jessica; Mack, Stephen C.; Manno, Alex; Michealraj, K. A.; Nor, Carolina; Peacock, John; Qin, Lei; Reimand, Juri; Rolider, Adi; Thompson, Yuan Y.; Wu, Xiaochong; Pugh, Trevor; Ally, Adrian; Bilenky, Mikhail; Butterfield, Yaron S. N.; Carlsen, Rebecca; Cheng, Young; Chuah, Eric; Corbett, Richard D.; Dhalla, Noreen; He, An; Lee, Darlene; Li, Haiyan I.; Long, William; Mayo, Michael; Plettner, Patrick; Qian, Jenny Q.; Schein, Jacqueline E.; Tam, Angela; Wong, Tina; Birol, Inanc; Zhao, Yongjun; Faria, Claudia C.; Pimentel, José; Nunes, Sofia; Shalaby, Tarek; Grotzer, Michael; Pollack, Ian F.; Hamilton, Ronald L.; Li, Xiao-Nan; Bendel, Anne E.; Fults, Daniel W.; Walter, Andrew W.; Kumabe, Toshihiro; Tominaga, Teiji; Collins, V. Peter; Cho, Yoon-Jae; Hoffman, Caitlin; Lyden, David; Wisoff, Jeffrey H.; Garvin, James H.; Stearns, Duncan S.; Massimi, Luca; Schüller, Ulrich; Sterba, Jaroslav; Zitterbart, Karel; Puget, Stephanie; Ayrault, Olivier; Dunn, Sandra E.; Tirapelli, Daniela P. C.; Carlotti, Carlos G.; Wheeler, Helen; Hallahan, Andrew R.; Ingram, Wendy; MacDonald, Tobey J.; Olson, Jeffrey J.; Van Meir, Erwin G.; Lee, Ji-Yeoun; Wang, Kyu-Chang; Kim, Seung-Ki; Cho, Byung-Kyu; Pietsch, Torsten; Fleischhack, Gudrun; Tippelt, Stephan; Ra, Young Shin; Bailey, Simon; Lindsey, Janet C.; Clifford, Steven C.; Eberhart, Charles G.; Cooper, Michael K.; Packer, Roger J.; Massimino, Maura; Garre, Maria Luisa; Bartels, Ute; Tabori, Uri; Hawkins, Cynthia E.; Dirks, Peter; Bouffet, Eric; Rutka, James T.; Wechsler-Reya, Robert J.; Weiss, William A.; Collier, Lara S.; Dupuy, Adam J.; Korshunov, Andrey; Jones, David T. W.; Kool, Marcel; Northcott, Paul A.; Pfister, Stefan M.; Largaespada, David A.; Mungall, Andrew J.; Moore, Richard A.; Jabado, Nada; Bader, Gary D.; Jones, Steven J. M.; Malkin, David; Marra, Marco A.; Taylor, Michael D.

2016-01-01

The development of targeted anti-cancer therapies through the study of cancer genomes is intended to increase survival rates and decrease treatment-related toxicity. We treated a transposon–driven, functional genomic mouse model of medulloblastoma with ‘humanized’ in vivo therapy (microneurosurgical tumour resection followed by multi-fractionated, image-guided radiotherapy). Genetic events in recurrent murine medulloblastoma exhibit a very poor overlap with those in matched murine diagnostic samples (<5%). Whole-genome sequencing of 33 pairs of human diagnostic and post-therapy medulloblastomas demonstrated substantial genetic divergence of the dominant clone after therapy (<12% diagnostic events were retained at recurrence). In both mice and humans, the dominant clone at recurrence arose through clonal selection of a pre-existing minor clone present at diagnosis. Targeted therapy is unlikely to be effective in the absence of the target, therefore our results offer a simple, proximal, and remediable explanation for the failure of prior clinical trials of targeted therapy. PMID:26760213

Enhancing Breast Cancer Recurrence Algorithms Through Selective Use of Medical Record Data.

PubMed

Kroenke, Candyce H; Chubak, Jessica; Johnson, Lisa; Castillo, Adrienne; Weltzien, Erin; Caan, Bette J

2016-03-01

The utility of data-based algorithms in research has been questioned because of errors in identification of cancer recurrences. We adapted previously published breast cancer recurrence algorithms, selectively using medical record (MR) data to improve classification. We evaluated second breast cancer event (SBCE) and recurrence-specific algorithms previously published by Chubak and colleagues in 1535 women from the Life After Cancer Epidemiology (LACE) and 225 women from the Women's Health Initiative cohorts and compared classification statistics to published values. We also sought to improve classification with minimal MR examination. We selected pairs of algorithms-one with high sensitivity/high positive predictive value (PPV) and another with high specificity/high PPV-using MR information to resolve discrepancies between algorithms, properly classifying events based on review; we called this "triangulation." Finally, in LACE, we compared associations between breast cancer survival risk factors and recurrence using MR data, single Chubak algorithms, and triangulation. The SBCE algorithms performed well in identifying SBCE and recurrences. Recurrence-specific algorithms performed more poorly than published except for the high-specificity/high-PPV algorithm, which performed well. The triangulation method (sensitivity = 81.3%, specificity = 99.7%, PPV = 98.1%, NPV = 96.5%) improved recurrence classification over two single algorithms (sensitivity = 57.1%, specificity = 95.5%, PPV = 71.3%, NPV = 91.9%; and sensitivity = 74.6%, specificity = 97.3%, PPV = 84.7%, NPV = 95.1%), with 10.6% MR review. Triangulation performed well in survival risk factor analyses vs analyses using MR-identified recurrences. Use of multiple recurrence algorithms in administrative data, in combination with selective examination of MR data, may improve recurrence data quality and reduce research costs. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Enhancing Breast Cancer Recurrence Algorithms Through Selective Use of Medical Record Data

PubMed Central

Chubak, Jessica; Johnson, Lisa; Castillo, Adrienne; Weltzien, Erin; Caan, Bette J.

2016-01-01

Abstract Background: The utility of data-based algorithms in research has been questioned because of errors in identification of cancer recurrences. We adapted previously published breast cancer recurrence algorithms, selectively using medical record (MR) data to improve classification. Methods: We evaluated second breast cancer event (SBCE) and recurrence-specific algorithms previously published by Chubak and colleagues in 1535 women from the Life After Cancer Epidemiology (LACE) and 225 women from the Women’s Health Initiative cohorts and compared classification statistics to published values. We also sought to improve classification with minimal MR examination. We selected pairs of algorithms—one with high sensitivity/high positive predictive value (PPV) and another with high specificity/high PPV—using MR information to resolve discrepancies between algorithms, properly classifying events based on review; we called this “triangulation.” Finally, in LACE, we compared associations between breast cancer survival risk factors and recurrence using MR data, single Chubak algorithms, and triangulation. Results: The SBCE algorithms performed well in identifying SBCE and recurrences. Recurrence-specific algorithms performed more poorly than published except for the high-specificity/high-PPV algorithm, which performed well. The triangulation method (sensitivity = 81.3%, specificity = 99.7%, PPV = 98.1%, NPV = 96.5%) improved recurrence classification over two single algorithms (sensitivity = 57.1%, specificity = 95.5%, PPV = 71.3%, NPV = 91.9%; and sensitivity = 74.6%, specificity = 97.3%, PPV = 84.7%, NPV = 95.1%), with 10.6% MR review. Triangulation performed well in survival risk factor analyses vs analyses using MR-identified recurrences. Conclusions: Use of multiple recurrence algorithms in administrative data, in combination with selective examination of MR data, may improve recurrence data quality and reduce research costs. PMID:26582243

Aspirin resistance are associated with long-term recurrent stroke events after ischaemic stroke.

PubMed

Zhang, Ning; Wang, Zhenhua; Zhou, Lihong

2017-09-01

To investigate the prevalent of aspirin resistance (AR) in stroke and its association with recurrent stroke in 214 patients with ischemic stroke who were receiving aspirin before the stroke onset. Two hundreds and fourteen acute stroke patients who previously received aspirin therapy (100mg/day for ≥7days) were enrolled. Whole blood samples were collected for platelet aggregation testing. The result is expressed in aspirin reaction units (ARU). A cutoff of 550 ARU was used to determine the presence of AR. A follow-up period of 1year was performed to record stroke recurrence events. In this study, the median age was 68 years (IQR, 60-77 years), and 118 (55.1%) were men. A total of 43 of 214 enrolled patients (20.1%) were AR. ARU levels were significantly higher in patients with recurrence than those without (514[IQR: 466-592] vs. 454[IQR: 411-499]; P <0.001). The stroke recurrence distribution across the ARU quartiles ranged between 7.41% (first quartile) to 40.74% (fourth quartile). In multivariate analyses, the 3th and 4th quartile of ARU was significantly associated with stroke recurrence during the observation period compared to the 1st quartile group, and the adjusted risk increased by 215% (OR=3.15 [95% CI 1.96-4.33], P=0.007) and 322% (4.22[2.56-7.16], P<0.001). In multivariate logistic regression analysis, AR was associated with a higher risk of stroke recurrence, and the adjusted risk increased by 365% (OR=4.65; 95% CI=2.99-8.16; P<0.001). In conclusion, AR is not uncommon in Chinese stroke patients who receive anti-platelet medications. Patients with AR may have a greater risk of suffering stroke recurrence events. Copyright © 2017 Elsevier Inc. All rights reserved.

Analysing recurrent hospitalizations in heart failure: a review of statistical methodology, with application to CHARM-Preserved.

PubMed

Rogers, Jennifer K; Pocock, Stuart J; McMurray, John J V; Granger, Christopher B; Michelson, Eric L; Östergren, Jan; Pfeffer, Marc A; Solomon, Scott D; Swedberg, Karl; Yusuf, Salim

2014-01-01

Heart failure is characterized by recurrent hospitalizations, but often only the first event is considered in clinical trial reports. In chronic diseases, such as heart failure, analysing all events gives a more complete picture of treatment benefit. We describe methods of analysing repeat hospitalizations, and illustrate their value in one major trial. The Candesartan in Heart failure Assessment of Reduction in Mortality and morbidity (CHARM)-Preserved study compared candesartan with placebo in 3023 patients with heart failure and preserved systolic function. The heart failure hospitalization rates were 12.5 and 8.9 per 100 patient-years in the placebo and candesartan groups, respectively. The repeat hospitalizations were analysed using the Andersen-Gill, Poisson, and negative binomial methods. Death was incorporated into analyses by treating it as an additional event. The win ratio method and a method that jointly models hospitalizations and mortality were also considered. Using repeat events gave larger treatment benefits than time to first event analysis. The negative binomial method for the composite of recurrent heart failure hospitalizations and cardiovascular death gave a rate ratio of 0.75 [95% confidence interval (CI) 0.62-0.91, P = 0.003], whereas the hazard ratio for time to first heart failure hospitalization or cardiovascular death was 0.86 (95% CI 0.74-1.00, P = 0.050). In patients with preserved EF, candesartan reduces the rate of admissions for worsening heart failure, to a greater extent than apparent from analysing only first hospitalizations. Recurrent events should be routinely incorporated into the analysis of future clinical trials in heart failure. © 2013 The Authors. European Journal of Heart Failure © 2013 European Society of Cardiology.

Recovery of self-rated health as a predictor of recurrent ischemic events after first myocardial infarction: a 13-year follow-up.

PubMed

Benyamini, Yael; Gerber, Yariv; Molshatzki, Noa; Goldbourt, Uri; Drory, Yaacov

2014-04-01

Following the trajectory hypothesis for the validity of self-rated health (SRH), we tested whether subjective recovery of health, that is, return to the same or higher level of SRH after a major health event, independently predicts better long-term prognosis. Participants were 640 patients (≤ 65 years) admitted to the eight medical centers in central Israel with incident MI in a 1-year period (mean age 54, 17% female). Baseline data were collected within days of the index MI. SRH in the preceding year was assessed at baseline, and current SRH was assessed 3-6 months later. Recurrent ischemic events (recurrent MI, hospitalization with unstable angina pectoris, or cardiac death) were recorded during a mean follow-up of 13 years. A reduced risk of recurrent events was associated with an upward change of one level (e.g., from 3 at T1 to 4 at T2) in SRH (HR = 0.76, 95%CI: 0.69-0.85), controlling for baseline retrospective SRH. Risk was still significantly lower for each unit of improvement after adjusting for sociodemographics, preevent comorbidity, cardiac risk factors, MI severity, and early post-MI events (HR = 0.85, 95% CI 0.75-0.95). Individuals who perceived themselves 3-6 months after a first MI to be healthier than they had been in the year preceding the MI were more likely to survive event-free throughout the next 13 years, controlling for baseline retrospective SRH and multiple cardiac risk factors. Failure to experience such subjective recovery of one's health is a serious risk factor, which indicates that SRH should be monitored regularly after a MI.

Recurrent Thrombotic Events after Discontinuation of Vitamin K Antagonist Treatment for Splanchnic Vein Thrombosis: A Multicenter Retrospective Cohort Study

PubMed Central

Riva, Nicoletta; Ageno, Walter; Poli, Daniela; Testa, Sophie; Rupoli, Serena; Santoro, Rita; Lerede, Teresa; Piana, Antonietta; Carpenedo, Monica; Nicolini, Alberto; Ferrini, Piera Maria; Martini, Giuliana; Mangione, Catello; Contino, Laura; Bonfanti, Carlo; Gresele, Paolo; Tosetto, Alberto

2015-01-01

It is generally recommended that patients with splanchnic vein thrombosis (SVT) should receive a minimum of 3 months of anticoagulant treatment. However, little information is available on the long-term risk of recurrent thrombotic events. The aim of this study was to evaluate the risk of venous and arterial thrombosis after discontinuation of vitamin K antagonist (VKA) in SVT patients. Retrospective information from a cohort of SVT patients treated with VKA and followed by 37 Italian Anticoagulation Clinics, up to June 2013, was collected. Only patients who discontinued VKA and did not receive any other anticoagulant drug were enrolled in this study. Thrombotic events during follow-up were centrally adjudicated. Ninety patients were included: 33 unprovoked SVT, 27 SVT secondary to transient risk factors, and 30 with permanent risk factors. During a median follow-up of 1.6 years, 6 venous and 1 arterial thrombosis were documented, for an incidence of 3.3/100 patient-years (pt-y). The recurrence rate was highest in the first year after VKA discontinuation (8.2/100'pt-y) and in patients with permanent risk factors (10.2/100'pt-y). Liver cirrhosis significantly increased the risk of recurrence. In conclusion, the rate of recurrent vascular complications after SVT is not negligible, at least in some patient subgroups. PMID:26508913

Recurrent Thrombotic Events after Discontinuation of Vitamin K Antagonist Treatment for Splanchnic Vein Thrombosis: A Multicenter Retrospective Cohort Study.

PubMed

Riva, Nicoletta; Ageno, Walter; Poli, Daniela; Testa, Sophie; Rupoli, Serena; Santoro, Rita; Lerede, Teresa; Piana, Antonietta; Carpenedo, Monica; Nicolini, Alberto; Ferrini, Piera Maria; Martini, Giuliana; Mangione, Catello; Contino, Laura; Bonfanti, Carlo; Gresele, Paolo; Tosetto, Alberto

2015-01-01

It is generally recommended that patients with splanchnic vein thrombosis (SVT) should receive a minimum of 3 months of anticoagulant treatment. However, little information is available on the long-term risk of recurrent thrombotic events. The aim of this study was to evaluate the risk of venous and arterial thrombosis after discontinuation of vitamin K antagonist (VKA) in SVT patients. Retrospective information from a cohort of SVT patients treated with VKA and followed by 37 Italian Anticoagulation Clinics, up to June 2013, was collected. Only patients who discontinued VKA and did not receive any other anticoagulant drug were enrolled in this study. Thrombotic events during follow-up were centrally adjudicated. Ninety patients were included: 33 unprovoked SVT, 27 SVT secondary to transient risk factors, and 30 with permanent risk factors. During a median follow-up of 1.6 years, 6 venous and 1 arterial thrombosis were documented, for an incidence of 3.3/100 patient-years (pt-y). The recurrence rate was highest in the first year after VKA discontinuation (8.2/100'pt-y) and in patients with permanent risk factors (10.2/100'pt-y). Liver cirrhosis significantly increased the risk of recurrence. In conclusion, the rate of recurrent vascular complications after SVT is not negligible, at least in some patient subgroups.

Large rock-slope failures impacting on lakes - Reconstruction of events and deciphering mobility processes at Lake Oeschinen (CH) and Lake Eibsee (D)

NASA Astrophysics Data System (ADS)

Knapp, Sibylle; Anselmetti, Flavio; Gilli, Adrian; Krautblatter, Michael; Hajdas, Irka

2017-04-01

Among single event landslide disasters large rock-slope failures account for 75% of disasters with more than 1000 casualties. The precise determination of recurrence rates and failure volumes combined with an improved understanding of mobility processes are essential to better constrain runout models and establish early warning systems. Here we present the data sets from the two alpine regions Lake Oeschinen (CH) and Lake Eibsee (D) to show how lake studies can help to decipher the multistage character of rock-slope failures and to improve the understanding of the processes related to rock avalanche runout dynamics. We focus on such that impacted on a (paleo-) lake for two main reasons. First, the lake background sedimentation acts as a natural chronometer, which enables the stratigraphic positioning of events and helps to reconstruct the event history. This way it becomes possible to (i) decipher the multistage character of the failure of a certain rock slope and maybe detect progressive failure, (ii) determine the recurrence rates of failures at that certain rock slope, and (iii) consider energies based on estimated failure volumes, fall heights and deposition patterns. Hence, the interactions between a rock-slope failure, the water reservoir and the altered rock-slope are better understood. Second, picturing a rock avalanche running through and beyond a lake, we assume the entrainment of water and slurry to be crucial for the subsequent flow dynamics. The entrainment consumes a large share of the total energy, and orchestrates the mobility leading to fluidization, a much higher flow velocity and a longer runout-path length than expected. At Lake Oeschinen (CH) we used lake sediment cores and reflection seismic profiles in order to reconstruct the 2.5 kyrs spanning rock-slope failure history including 10 events, six of which detached from the same mountain flank, and correlated them with (pre-) historical data. The Lake Eibsee records provide insights into the impact of the rock-slope failure at Mount Zugspitze on the presumed Eibsee paleolake 3.7 kyrs ago. We have been working on seismic profiles and sediment cores from the lake as well as on geoelectrical profiles and terrestrial sediments in the runout path aiming at the reconstruction of mobility processes related to the impact and leading to an extraordinarily long runout.

Risk of recurrent stroke in patients with silent brain infarction in the PRoFESS Imaging Substudy

PubMed Central

Weber, Ralph; Weimar, Christian; Wanke, Isabel; Möller-Hartmann, Claudia; Gizewski, Elke R.; Blatchford, Jon; Hermansson, Karin; Demchuk, Andrew M.; Forsting, Michael; Sacco, Ralph L.; Saver, Jeffrey L.; Warach, Steven; Diener, Hans Christoph; Diehl, Anke

2012-01-01

Background and Purpose Silent brain infarctions are associated with an increased risk of stroke in healthy individuals. Risk of recurrent stroke in patients with both symptomatic and silent brain infarction (SBI) has only been investigated in patients with cardioembolic stroke in the European Atrial Fibrillation Trial. We assessed whether patients with recent non-cardioembolic stroke and SBI detected on MRI are at increased risk for recurrent stroke, other cardiovascular events, and mortality. Methods The prevalence of SBI detected on MRI was assessed in 1014 patients enrolled in the imaging substudy of the Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) trial. The primary outcome was first recurrence of stroke in patients with both symptomatic stroke and SBI in comparison with age and sex matched stroke patients without SBI. Secondary outcomes were a combined vascular endpoint, other vascular events and mortality. The two groups were compared using conditional logistic regression. Results Silent brain infarction was detected in 207 (20.4%) patients of the 1014 patients. Twenty-seven (13.0%) patients with SBI and 19 (9.2%) without SBI had a recurrent stroke (odds ratio 1.42, 95% confidence interval 0.79 to 2.56; p=0.24) during a mean follow-op of 2.5 years. Similarly, there was no statistically significant difference for all secondary outcome parameters between patients with SBI and matched patients without SBI. Conclusion The presence of SBI in patients with recent mild non-cardioembolic ischemic stroke could not be shown to be an independent risk factor for recurrent stroke, other vascular events, or a higher mortality. PMID:22267825

Identification of vascular patients at very high risk for recurrent cardiovascular events: validation of the current ACC/AHA very high risk criteria.

PubMed

van den Berg, M Johanneke; Bhatt, Deepak L; Kappelle, L Jaap; de Borst, Gert J; Cramer, Maarten J; van der Graaf, Yolanda; Steg, Ph Gabriel; Visseren, Frank L J

2017-11-14

To validate and assess performance of the current ACC/AHA very high risk criteria in patients with clinically manifest arterial disease. Data were used from the SMART study (n = 7216) and REACH Registry (n = 48 322), two prospective cohorts of patients with manifest atherosclerotic arterial disease. Prevalence and incidence rates of recurrent major adverse cardiovascular events (MACE) were calculated, according to the ACC/AHA VHR criteria (cardiovascular disease combined with diabetes, smoking, dyslipidaemia, and/or recent recurrent coronary events). Performance of the ACC/AHA criteria was compared with single very high risk factors in terms of C-statistics and Net Reclassification Index. All patients were at VHR according to the ESC guidelines (incidence of recurrent MACE in SMART was 2.4/100PY, with 95% CI 2.3-2.5/100PY and in REACH 5.1/100PY with 95% CI 5.0-5.3/100PY). In SMART 57% of the patients were at VHR according to the ACC/AHA criteria (incidence of recurrent MACE 2.7/100PY, 95% CI 2.5-2.9/100PY) and in REACH this was 64% (5.9/100PY, 95% CI 5.7-6.1/100PY). The C-statistic for the ACC/AHA VHR criteria was 0.53 in REACH and 0.54 in SMART. Very high risk factors with comparable or slightly better performance were eGFR < 45, polyvascular disease and age >70 years. Around two third of the patients meeting the ACC/AHA VHR criteria had a predicted 10-year risk of recurrent MACE <30%. The ACC/AHA VHR criteria have limited discriminative power. Identifying patients with clinically manifest arterial disease at VHR for recurrent vascular events using eGFR <45, polyvascular disease, or age >70 years performs as well as the ACC/AHA VHR criteria. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

Optimized breeding strategies for multiple trait integration: II. Process efficiency in event pyramiding and trait fixation.

PubMed

Peng, Ting; Sun, Xiaochun; Mumm, Rita H

2014-01-01

Multiple trait integration (MTI) is a multi-step process of converting an elite variety/hybrid for value-added traits (e.g. transgenic events) through backcross breeding. From a breeding standpoint, MTI involves four steps: single event introgression, event pyramiding, trait fixation, and version testing. This study explores the feasibility of marker-aided backcross conversion of a target maize hybrid for 15 transgenic events in the light of the overall goal of MTI of recovering equivalent performance in the finished hybrid conversion along with reliable expression of the value-added traits. Using the results to optimize single event introgression (Peng et al. Optimized breeding strategies for multiple trait integration: I. Minimizing linkage drag in single event introgression. Mol Breed, 2013) which produced single event conversions of recurrent parents (RPs) with ≤8 cM of residual non-recurrent parent (NRP) germplasm with ~1 cM of NRP germplasm in the 20 cM regions flanking the event, this study focused on optimizing process efficiency in the second and third steps in MTI: event pyramiding and trait fixation. Using computer simulation and probability theory, we aimed to (1) fit an optimal breeding strategy for pyramiding of eight events into the female RP and seven in the male RP, and (2) identify optimal breeding strategies for trait fixation to create a 'finished' conversion of each RP homozygous for all events. In addition, next-generation seed needs were taken into account for a practical approach to process efficiency. Building on work by Ishii and Yonezawa (Optimization of the marker-based procedures for pyramiding genes from multiple donor lines: I. Schedule of crossing between the donor lines. Crop Sci 47:537-546, 2007a), a symmetric crossing schedule for event pyramiding was devised for stacking eight (seven) events in a given RP. Options for trait fixation breeding strategies considered selfing and doubled haploid approaches to achieve homozygosity as well as seed chipping and tissue sampling approaches to facilitate genotyping. With selfing approaches, two generations of selfing rather than one for trait fixation (i.e. 'F2 enrichment' as per Bonnett et al. in Strategies for efficient implementation of molecular markers in wheat breeding. Mol Breed 15:75-85, 2005) were utilized to eliminate bottlenecking due to extremely low frequencies of desired genotypes in the population. The efficiency indicators such as total number of plants grown across generations, total number of marker data points, total number of generations, number of seeds sampled by seed chipping, number of plants requiring tissue sampling, and number of pollinations (i.e. selfing and crossing) were considered in comparisons of breeding strategies. A breeding strategy involving seed chipping and a two-generation selfing approach (SC + SELF) was determined to be the most efficient breeding strategy in terms of time to market and resource requirements. Doubled haploidy may have limited utility in trait fixation for MTI under the defined breeding scenario. This outcome paves the way for optimizing the last step in the MTI process, version testing, which involves hybridization of female and male RP conversions to create versions of the converted hybrid for performance evaluation and possible commercial release.

Factors associated with time free of oral candidiasis in children living with HIV/AIDS, São Paulo, Brazil.

PubMed

Konstantyner, Thais Claudia Roma de Oliveira; Silva, Aline Medeiros da; Tanaka, Luana Fiengo; Marques, Heloísa Helena de Sousa; Latorre, Maria do Rosário Dias de Oliveira

2013-11-01

In clinical practice, recurrence of thrush is common in children living with HIV/AIDS. The aim of this study was to determine the factors associated with time spent free of oral candidiasis using survival analysis for recurrent events. A retrospective cohort study was carried out with 287 children treated between 1985 and 2009 at a reference center in the city of São Paulo, Brazil. The Prentice, Williams and Peterson model for recurrent events was used for the investigation of factors associated with the time free of oral candidiasis. The following factors were associated with the time patients were free of oral candidiasis: moderate immunodepression (HR = 2.5; p = 0.005), severe immunodepression (HR = 3.5; p < 0.001), anemia (HR = 3.3; p < 0.001), malnutrition (HR = 2.6; p = 0.004), hospitalization (HR = 2.2; p < 0.001), monotherapy (HR = 0.5; p = 0.006), dual therapy (HR = 0.3; p < 0.001) and triple therapy/highly active antiretroviral therapy (HR = 0.1; p < 0.001). The method analyzed in the present study proved useful for the investigation of recurrent events in patients living with HIV/AIDS.

C-reactive protein as a prognostic marker after lacunar stroke: levels of inflammatory markers in the treatment of stroke study.

PubMed

Elkind, Mitchell S V; Luna, Jorge M; McClure, Leslie A; Zhang, Yu; Coffey, Christopher S; Roldan, Ana; Del Brutto, Oscar H; Pretell, Edwin Javier; Pettigrew, L Creed; Meyer, Brett C; Tapia, Jorge; White, Carole; Benavente, Oscar R

2014-03-01

Inflammatory biomarkers predict incident and recurrent cardiac events, but their relationship to stroke prognosis is uncertain. We hypothesized that high-sensitivity C-reactive protein (hsCRP) predicts recurrent ischemic stroke after recent lacunar stroke. Levels of Inflammatory Markers in the Treatment of Stroke (LIMITS) was an international, multicenter, prospective ancillary biomarker study nested within Secondary Prevention of Small Subcortical Strokes (SPS3), a phase III trial in patients with recent lacunar stroke. Patients were assigned in factorial design to aspirin versus aspirin plus clopidogrel, and higher versus lower blood pressure targets. Patients had blood samples collected at enrollment and hsCRP measured using nephelometry at a central laboratory. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for recurrence risks before and after adjusting for demographics, comorbidities, and statin use. Among 1244 patients with lacunar stroke (mean age, 63.3±10.8 years), median hsCRP was 2.16 mg/L. There were 83 recurrent ischemic strokes (including 45 lacunes) and 115 major vascular events (stroke, myocardial infarction, and vascular death). Compared with the bottom quartile, those in the top quartile (hsCRP>4.86 mg/L) were at increased risk of recurrent ischemic stroke (unadjusted HR, 2.54; 95% CI, 1.30-4.96), even after adjusting for demographics and risk factors (adjusted HR, 2.32; 95% CI, 1.15-4.68). hsCRP predicted increased risk of major vascular events (top quartile adjusted HR, 2.04; 95% CI, 1.14-3.67). There was no interaction with randomized antiplatelet treatment. Among recent lacunar stroke patients, hsCRP levels predict the risk of recurrent strokes and other vascular events. hsCRP did not predict the response to dual antiplatelets. http://www.clinicaltrials.gov. Unique identifier: NCT00059306.

Risk of Cardiac Events Associated With Antidepressant Therapy in Patients With Long QT Syndrome.

PubMed

Wang, Meng; Szepietowska, Barbara; Polonsky, Bronislava; McNitt, Scott; Moss, Arthur J; Zareba, Wojciech; Auerbach, David S

2018-01-15

Patients with long QT syndrome (LQTS) are at a high risk of cardiac events. Many patients with LQTS are treated with antidepressant drugs (ADs). We investigated the LQTS genotype-specific risk of recurrent cardiac arrhythmic events (CAEs) associated with AD therapy. The study included 59 LQT1 and 72 LQT2 patients from the Rochester-based LQTS Registry with corrected QT (QT c ) prolongation and a history of AD therapy. Using multivariate Anderson-Gill models, we estimated the LQTS genotype-specific risk of recurrent CAEs (ventricular tachyarrhythmias, aborted cardiac arrest, or sudden cardiac death) associated with time-dependent ADs. Specifically, we examined the risk associated with all ADs, selective serotonin reuptake inhibitor (SSRI), and ADs classified on the CredibleMeds list (www.CredibleMeds.org) as "Conditional" or "Known risk of Torsades de pointes (TdP)." After adjusting for baseline QT c duration, sex, and time-dependent beta-blocker usage, there was an increased risk of recurrent CAEs associated with ADs in LQT1 patients (hazard ratio = 3.67, 95% confidence interval 1.98-6.82, p < 0.001) but not in LQT2 patients (hazard ratio = 0.89, 95% confidence interval 0.49-1.64, p = 0.716; LQT1 vs LQT2 interaction, p < 0.001). Similarly, LQT1 patients who were on SSRIs or ADs with "Known risk of TdP" had a higher risk of recurrent CAEs than those patients off all ADs, whereas there was no association in LQT2 patients. ADs with "Conditional risk of TdP" were not associated with the risk of recurrent CAEs in any of the groups. In conclusion, the risk of recurrent CAEs associated with time-dependent ADs is higher in LQT1 patients but not in LQT2 patients. Results suggest a LQTS genotype-specific effect of ADs on the risk of arrhythmic events. Copyright © 2017 Elsevier Inc. All rights reserved.

Cores Of Recurrent Events (CORE) | Informatics Technology for Cancer Research (ITCR)

Cancer.gov

CORE is a statistically supported computational method for finding recurrently targeted regions in massive collections of genomic intervals, such as those arising from DNA copy number analysis of single tumor cells or bulk tumor tissues.

Telmisartan to prevent recurrent stroke and cardiovascular events.

PubMed

Yusuf, Salim; Diener, Hans-Christoph; Sacco, Ralph L; Cotton, Daniel; Ounpuu, Stephanie; Lawton, William A; Palesch, Yuko; Martin, Reneé H; Albers, Gregory W; Bath, Philip; Bornstein, Natan; Chan, Bernard P L; Chen, Sien-Tsong; Cunha, Luis; Dahlöf, Björn; De Keyser, Jacques; Donnan, Geoffrey A; Estol, Conrado; Gorelick, Philip; Gu, Vivian; Hermansson, Karin; Hilbrich, Lutz; Kaste, Markku; Lu, Chuanzhen; Machnig, Thomas; Pais, Prem; Roberts, Robin; Skvortsova, Veronika; Teal, Philip; Toni, Danilo; VanderMaelen, Cam; Voigt, Thor; Weber, Michael; Yoon, Byung-Woo

2008-09-18

Prolonged lowering of blood pressure after a stroke reduces the risk of recurrent stroke. In addition, inhibition of the renin-angiotensin system in high-risk patients reduces the rate of subsequent cardiovascular events, including stroke. However, the effect of lowering of blood pressure with a renin-angiotensin system inhibitor soon after a stroke has not been clearly established. We evaluated the effects of therapy with an angiotensin-receptor blocker, telmisartan, initiated early after a stroke. In a multicenter trial involving 20,332 patients who recently had an ischemic stroke, we randomly assigned 10,146 to receive telmisartan (80 mg daily) and 10,186 to receive placebo. The primary outcome was recurrent stroke. Secondary outcomes were major cardiovascular events (death from cardiovascular causes, recurrent stroke, myocardial infarction, or new or worsening heart failure) and new-onset diabetes. The median interval from stroke to randomization was 15 days. During a mean follow-up of 2.5 years, the mean blood pressure was 3.8/2.0 mm Hg lower in the telmisartan group than in the placebo group. A total of 880 patients (8.7%) in the telmisartan group and 934 patients (9.2%) in the placebo group had a subsequent stroke (hazard ratio in the telmisartan group, 0.95; 95% confidence interval [CI], 0.86 to 1.04; P=0.23). Major cardiovascular events occurred in 1367 patients (13.5%) in the telmisartan group and 1463 patients (14.4%) in the placebo group (hazard ratio, 0.94; 95% CI, 0.87 to 1.01; P=0.11). New-onset diabetes occurred in 1.7% of the telmisartan group and 2.1% of the placebo group (hazard ratio, 0.82; 95% CI, 0.65 to 1.04; P=0.10). Therapy with telmisartan initiated soon after an ischemic stroke and continued for 2.5 years did not significantly lower the rate of recurrent stroke, major cardiovascular events, or diabetes. (ClinicalTrials.gov number, NCT00153062.) 2008 Massachusetts Medical Society

Exposure to hypoglycemia and risk of stroke.

PubMed

Smith, Logan; Chakraborty, Diya; Bhattacharya, Pallab; Sarmah, Deepaneeta; Koch, Sebastian; Dave, Kunjan R

2018-06-19

In the treatment of both type 1 and type 2 diabetes mellitus, maintaining a euglycemic state represents one of the key challenges. Improper dosing and administration of glucose-lowering drugs is associated with an increased risk of recurrent hypoglycemia episodes. In addition, the risk of adverse cardiovascular events in diabetic patients, particularly myocardial infarctions and strokes, is well established. Current research indicates a potential link between the baseline risk of cardio/cerebrovascular events in diabetic patients and exposure to hypoglycemia. In this review of the literature, we aim to determine if a relationship exists between recurrent hypoglycemia and adverse neurovascular events. © 2018 New York Academy of Sciences.

Markov chains and semi-Markov models in time-to-event analysis.

PubMed

Abner, Erin L; Charnigo, Richard J; Kryscio, Richard J

2013-10-25

A variety of statistical methods are available to investigators for analysis of time-to-event data, often referred to as survival analysis. Kaplan-Meier estimation and Cox proportional hazards regression are commonly employed tools but are not appropriate for all studies, particularly in the presence of competing risks and when multiple or recurrent outcomes are of interest. Markov chain models can accommodate censored data, competing risks (informative censoring), multiple outcomes, recurrent outcomes, frailty, and non-constant survival probabilities. Markov chain models, though often overlooked by investigators in time-to-event analysis, have long been used in clinical studies and have widespread application in other fields.

Markov chains and semi-Markov models in time-to-event analysis

PubMed Central

Abner, Erin L.; Charnigo, Richard J.; Kryscio, Richard J.

2014-01-01

A variety of statistical methods are available to investigators for analysis of time-to-event data, often referred to as survival analysis. Kaplan-Meier estimation and Cox proportional hazards regression are commonly employed tools but are not appropriate for all studies, particularly in the presence of competing risks and when multiple or recurrent outcomes are of interest. Markov chain models can accommodate censored data, competing risks (informative censoring), multiple outcomes, recurrent outcomes, frailty, and non-constant survival probabilities. Markov chain models, though often overlooked by investigators in time-to-event analysis, have long been used in clinical studies and have widespread application in other fields. PMID:24818062

Microalbuminuria could improve risk stratification in patients with TIA and minor stroke.

PubMed

Elyas, Salim; Shore, Angela C; Kingwell, Hayley; Keenan, Samantha; Boxall, Leigh; Stewart, Jane; James, Martin A; Strain, William David

2016-09-01

Transient ischemic attacks (TIA) and minor strokes are important risk factors for recurrent strokes. Current stroke risk prediction scores such as ABCD2, although widely used, lack optimal sensitivity and specificity. Elevated urinary albumin excretion predicts cardiovascular disease, stroke, and mortality. We explored the role of microalbuminuria (using albumin creatinine ratio (ACR)) in predicting recurrence risk in patients with TIA and minor stroke. Urinary ACR was measured on a spot sample in 150 patients attending a daily stroke clinic with TIA or minor stroke. Patients were followed up at day 7, 30, and 90 to determine recurrent stroke, cardiovascular events, or death. Eligible patients had a carotid ultrasound Doppler investigation. High-risk patients were defined as those who had an event within 90 days or had >50% internal carotid artery (ICA) stenosis. Fourteen (9.8%) recurrent events were reported by day 90 including two deaths. Fifteen patients had severe ICA stenosis. In total, 26 patients were identified as high risk. These patients had a higher frequency of previous stroke or hypercholesterolemia compared to low-risk patients (P = 0.04). ACR was higher in high-risk patients (3.4 [95% CI 2.2-5.2] vs. 1.7 [1.5-2.1] mg/mmol, P = 0.004), independent of age, sex, blood pressure, diabetes, and previous stroke. An ACR greater than 1.5 mg/mmol predicted high-risk patients (Cox proportional hazard ratio 3.5 (95% CI 1.3-9.5, P = 0.01). After TIA or minor stroke, a higher ACR predicted recurrent events and significant ICA stenosis. Incorporation of urinary ACR from a spot sample in the acute setting could improve risk stratification in patients with TIA and minor stroke.

Inflammation markers and prediction of post-stroke vascular disease recurrence: the MITICO study.

PubMed

Castillo, J; Alvarez-Sabín, J; Martínez-Vila, E; Montaner, J; Sobrino, T; Vivancos, J

2009-02-01

Vascular disease recurrence following stroke is the main cause of morbidity and mortality. The MITICO study was designed to assess the prognostic value of markers of inflammation in relation to the risk of recurrence of vascular disease. Multi-centered prospective observational study, in patients with ischemic stroke not receiving anti-coagulation therapy and who were recruited within 1-3 months from stroke onset. Blood samples were obtained at baseline and follow- up for the determination of high-sensitive C reactive protein (CRP), IL-6, IL-10, ICAM-1, VCAM- 1, MMP-9 and cellular fibronectin. Four follow-up visits within the first year were to rule out recurrence. Of 965 patients from 65 hospitals, 780 (aged 67.5+/-11.2 years, 33.6 % female) were valid for main analysis. One-hundred and three patients (13.2 %) had a new adverse vascular event and 116 patients (14.9 %) a vascular event or vascular death (66.4 % stroke, 21.5 % coronary and 12.1 % peripheral). Levels of IL-6 > 5 pg/mL and VCAM-1 > 1350 ng/mL (ROC curve analyses) were associated with vascular disease recurrence risk (OR: 28.7; 95 % CI: 14.2-58.0 vs. OR: 4.1; 95 % CI: 2.4-7.1, respectively) following adjustment for confounding variables. Risk of adverse vascular event or death from vascular disease were associated with IL-6 (OR: 21.2; 95 % CI: 11.6-38.7) and VCAM-1 (OR: 3.8; 95 % CI: 2.3-6.4). Baseline values of IL-6 > 5 pg/mL and VCAM-1 > 1350 ng/mL increase 21-fold and 4-fold, respectively, the risk of new vascular disease event or death from vascular disease in patients with ischemic stroke not receiving anti-coagulation treatment.

Prevalence and long-term clinical significance of intracranial atherosclerosis after ischaemic stroke or transient ischaemic attack: a cohort study.

PubMed

Ovesen, Christian; Abild, Annemette; Christensen, Anders Fogh; Rosenbaum, Sverre; Hansen, Christine Krarup; Havsteen, Inger; Nielsen, Jens Kellberg; Christensen, Hanne

2013-10-21

We investigated the prevalence and long-term risk associated with intracranial atherosclerosis identified during routine evaluation. This study presents data from a prospective cohort of patients admitted to our stroke unit for thrombolysis evaluation. We included 652 with a final diagnosis of ischaemic stroke or transient ischaemic attack (TIA) from April 2009 to December 2011. All patients were acutely evaluated with cerebral CT and CT angiography (CTA). Acute radiological examinations were screened for intracranial arterial stenosis (IAS) or intracranial arterial calcifications (IAC). Intracranial stenosis was grouped into 30-50%, 50-70% and >70% lumen reduction. The extent of IAC was graded as number of vessels affected. Patients were followed until July 2013. Recurrence of an ischaemic event (stroke, ischaemic heart disease (IHD) and TIA) was documented through the national chart system. Poor outcome was defined as death or recurrence of ischaemic event. 101 (15.5%) patients showed IAS (70: 30-50%, 29: 50-70% and 16: >70%). Two-hundred and fifteen (33%) patients had no IAC, 339 (52%) in 1-2 vessels and 102 (16%) in >2 vessels. During follow-up, 53 strokes, 20 TIA and 14 IHD occurred, and 95 patients died. The risk of poor outcome was significantly different among different extents of IAS as well as IAC (log-rank test p<0.01 for both). In unadjusted analysis IAS and IAC predicted poor outcome and recurrent ischaemic event. When adjusted, IAS and IAC independently increased the risk of a recurrent ischaemic event (IAS: HR 1.67; CI 1.04 to 2.64 and IAC: HR 1.22; CI 1.02 to 1.47). Intracranial atherosclerosis detected during acute evaluation predicts an increased risk of recurrent stroke.

Heterogeneous recurrence monitoring and control of nonlinear stochastic processes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, Hui, E-mail: huiyang@usf.edu; Chen, Yun

Recurrence is one of the most common phenomena in natural and engineering systems. Process monitoring of dynamic transitions in nonlinear and nonstationary systems is more concerned with aperiodic recurrences and recurrence variations. However, little has been done to investigate the heterogeneous recurrence variations and link with the objectives of process monitoring and anomaly detection. Notably, nonlinear recurrence methodologies are based on homogeneous recurrences, which treat all recurrence states in the same way as black dots, and non-recurrence is white in recurrence plots. Heterogeneous recurrences are more concerned about the variations of recurrence states in terms of state properties (e.g., valuesmore » and relative locations) and the evolving dynamics (e.g., sequential state transitions). This paper presents a novel approach of heterogeneous recurrence analysis that utilizes a new fractal representation to delineate heterogeneous recurrence states in multiple scales, including the recurrences of both single states and multi-state sequences. Further, we developed a new set of heterogeneous recurrence quantifiers that are extracted from fractal representation in the transformed space. To that end, we integrated multivariate statistical control charts with heterogeneous recurrence analysis to simultaneously monitor two or more related quantifiers. Experimental results on nonlinear stochastic processes show that the proposed approach not only captures heterogeneous recurrence patterns in the fractal representation but also effectively monitors the changes in the dynamics of a complex system.« less

Polyarterial clustered recurrence of cervical artery dissection seems to be the rule.

PubMed

Dittrich, R; Nassenstein, I; Bachmann, R; Maintz, D; Nabavi, D G; Heindel, W; Kuhlenbäumer, G; Ringelstein, E B

2007-07-10

Spontaneous cervical artery dissection (sCAD) in multiple neck arteries (polyarterial sCAD) is traditionally thought to represent a monophasic disorder suggesting nearly simultaneous occurrence of the various intramural hematomas. Its incidence ranges from 10 to 28%. The recurrence rate of sCAD in general over up to 8.6 years has been recorded to be 0 to 8%. To analyze more precisely the temporal and spatial neuroangiologic course of sCAD with particular focus on polyarterial manifestation. We prospectively investigated 36 consecutive patients with sCAD unexceptionally proven by MR imaging at 1.5 T. We reinvestigated these patients by two follow-up MR examinations. The first follow-up MR examination was performed after a mean of 16 +/- 13 days, and the last MR study after a mean of 7 +/- 2 months after the initial diagnosis. Systematic data evaluation of the 36 patients revealed the following phenomena of sCAD: 1) seemingly simultaneous polyarterial sCAD on the initial MRI scan (n = 2; 6%); 2) recurrent sCAD in one or several initially uninvolved cervical arteries during follow-up (n = 9; 25%). These latter sCAD occurred as an early polyarterial recurrent event within 1 to 4 weeks in 7 patients (19%), and as a delayed polyarterial recurrent event within 5 to 7 months in 2 patients (6%). Under a spatial perspective, sCAD recurrence took place in one additional cervical artery in 5 patients (14%), or in more than one previously uninvolved cervical artery in 4 patients (11%). All patients except one with sCAD recurrence remained asymptomatic or had local symptoms only. One patient experienced a significant clinical deterioration due to ischemic stroke with acute impairment of cerebral hemodynamics. During follow-up, patients received transient oral anticoagulation for at least 6 months with subsequent acetylsalicylic acid (ASA). More often than previously thought, the recurrence of spontaneous cervical artery dissection (sCAD) involves multiple cervical arteries in sequence. sCAD recurrence frequently appears to cluster within the first 2 months after the index event, rather than occurring steadily over time. The prognosis of recurring sCAD appears benign, particularly in patients already receiving antithrombotic therapy.

Treatment Options for Recurrent Mycosis Fungoides and the Sezary Syndrome

MedlinePlus

... Events Scientific Meetings & Lectures Conferences Advisory Board Meetings Social Media Events Cancer Currents Blog All Press Releases 2018 ... Events Scientific Meetings & Lectures Conferences Advisory Board Meetings Social Media Cancer Currents Blog About NCI NCI Overview History ...

Risk Factors for Stone Recurrence after Percutaneous Nephrolithotomy

NASA Astrophysics Data System (ADS)

Krambeck, Amy E.; Rangel, Laureano J.; LeRoy, Andrew J.; Patterson, David E.; Gettman, Matthew T.

2008-09-01

Recent studies have demonstrated more than 30% of percutaneous nephrolithotomy (PCNL) patients will experience a stone recurrence over a 20 year period. The goal of our study was to identify risk factors for stone recurrence after PCNL. Chart review identified 754 patients treated with PCNL for urolithiasis from March of 1983 to July 1984 at our institution. Of this cohort, 87 patients continued to receive medical care at our clinic and had been evaluated within the last 5 years. Of the 87 patients, 80 had recent radiographic imaging. Average follow-up was 19.2 years and 32 (40.0%) experienced at least 1 stone recurrence. There was no difference in preoperative BMI (p = 0.453) or change in BMI (p = 0.964) between patients that did and did not have a stone recurrence. Renal stone location (p = 0.605) and stone size (p = 0.238) were not predictive of recurrence. Patients with calcium oxalate monohydrate stones were less likely to recur (38.7% vs. 41.6%, p = 0.004) and those with calcium oxalate dihydrate (COD) were more likely to recur (31.1% vs. 19.6%, p = 0.006) compared to other compositions. Diabetes mellitus was not associated with recurrent stones (p = 0.810). Those patients with residual stones or fragments <3 mm were more likely to recur and to recur earlier than patients rendered entirely stone free at time of PCNL (p = 0.015). Stone recurrences were associated with the late development of renal insufficiency (25% vs. 2.1%, p = 0.002). In conclusion, stone composition, as well as the presence of residual fragments was associated with recurrent symptomatic stone events after PCNL. Recurrent stone events were significantly associated with the risk of developing renal insufficiency, further stressing the need for complete stone clearance at time of PCNL.

The nonalcoholic fatty liver disease (NAFLD) fibrosis score, cardiovascular risk stratification and a strategy for secondary prevention with ezetimibe.

PubMed

Simon, Tracey G; Corey, Kathleen E; Cannon, Christopher P; Blazing, Michael; Park, Jeong-Gun; O'Donoghue, Michelle L; Chung, Raymond T; Giugliano, Robert P

2018-05-26

The nonalcoholic fatty liver disease fibrosis score (NFS) is comprised of unique metabolic risk indicators that may accurately predict residual cardiovascular (CV) risk in patients with established coronary disease and metabolic dysfunction. We applied the NFS prospectively to 14,819 post-ACS patients randomized to ezetimibe/simvastatin (E/S) or placebo/simvastatin (P/S), in the IMPROVE-IT trial, using validated NFS cutoffs. The primary endpoint included CV death, myocardial infarction, unstable angina, revascularization or stroke. Outcomes were compared between NFS categories and treatment arms using frequency of events, KM rates and adjusted Cox proportional hazard models. The ability of the NFS to predict recurrent CV events was independently validated in 5395 placebo-treated patients enrolled in the SOLID-TIMI 52 trial. Among 14,819 patients enrolled in IMPROVE-IT, 14.2% (N = 2106) were high-risk (NFS > 0.67). The high-risk group had a 30% increased risk of recurrent major CV events, compared to the low-risk NFS group (HR 1.30 [1.19-1.43]; p < 0.001). Among high-risk patients, ezetimibe/simvastatin conferred a 3.7% absolute reduction in risk of recurrent CV events, compared to placebo/simvastatin (HR 0.85 [0.74-0.98]), translating to a number-needed-to-treat of 27. Similar benefit was not found in the low-risk group (HR ezetimibe/simvastatin vs. placebo/simvastatin, 1.01 [0.91-1.12]; p-interaction = 0.053). The relationship between NFS category and recurrent CV events was independently validated in patients enrolled in SOLID-TIMI 52 (HR for NFS > 0.67 vs. NFS < -1.455 = 1.55 [1.32-1.81]; p < 0.001). Stratification of cardiovascular risk by NFS identifies an independent population of patients who are at highest risk of recurrent events, and most likely to benefit from dual lipid-lowering therapy. Clinical trials.gov: NCT00202878. Copyright © 2017 Elsevier B.V. All rights reserved.

Electrophysiological evidence for phenomenal consciousness.

PubMed

Revonsuo, Antti; Koivisto, Mika

2010-09-01

Abstract Recent evidence from event-related brain potentials (ERPs) lends support to two central theses in Lamme's theory. The earliest ERP correlate of visual consciousness appears over posterior visual cortex around 100-200 ms after stimulus onset. Its scalp topography and time window are consistent with recurrent processing in the visual cortex. This electrophysiological correlate of visual consciousness is mostly independent of later ERPs reflecting selective attention and working memory functions. Overall, the ERP evidence supports the view that phenomenal consciousness of a visual stimulus emerges earlier than access consciousness, and that attention and awareness are served by distinct neural processes.

Patent foramen ovale transcatheter closure vs. medical therapy on recurrent vascular events: a systematic review and meta-analysis of randomized controlled trials.

PubMed

Rengifo-Moreno, Pablo; Palacios, Igor F; Junpaparp, Parichart; Witzke, Christian F; Morris, D Lynn; Romero-Corral, Abel

2013-11-01

In patients with cryptogenic stroke, transcatheter (TC) closure of a patent foramen ovale (PFO) has not been shown to better prevent recurrent vascular events than medical therapy. However, randomized controlled trials (RCT) to date have included few vascular events, and lack of power has been raised as an important concern. To conduct a systematic review and meta-analysis of existing RCT published studies assessing the recurrence of vascular events after TC PFO closure when compared to medical therapy. Using the search terms "patent foramen ovale", "PFO", "stroke", "percutaneous closure" and "transcatheter closure", Medline, Pubmed, Embase, and Cochrane databases were reviewed from inception through April 2013, with no language restrictions. Only studies in adult humans were considered. Additional references were obtained from the bibliographies of studies reviewed. The following criteria were used for study selection: 1) randomized controlled trial, 2) subjects were adult patients with cryptogenic stroke who were randomized to TC PFO closure or medical treatment (antiplatelet therapy and/or anticoagulation), and 3) reported outcomes included cardiac death, all death, stroke, transient ischemic attack, and peripheral embolism. Methodological and descriptive data, adverse events (including raw data and risk estimates), as well as procedural success and complications were abstracted in duplicate from each study independently, and agreement was tested. We followed rigorously the recommended guidelines for reporting and conducting and assessing quality of meta-analysis of RCT. The primary endpoints pre-specified in advance were recurrent vascular events, and composite endpoint of death, and recurrent vascular events. Three studies were identified as meeting selection criteria. These included a total of 2,303 patients, with 1,150 patients randomized to TC PFO closure and 1,153 patients randomized to medical therapy. Mean follow-up was 3.5 years. Baseline characteristics (age, sex, and cardiovascular risk factors) were similar across studies. Intention-to-treat analyses showed a statistically significant risk reduction in stroke and/or transient ischemic attack in the TC PFO closure group when compared to medical treatment, pooled HR = 0.59, 95%CI (0.36-0.97), P = 0.04. The combined outcome of death, and vascular events, showed a borderline statistically significant benefit for TC PFO closure when compared to medical treatment, pooled HR = 0.67, 95%CI (0.44-1.00), P = 0.05 Subjects with a substantial PFO shunt seem to benefit the most with TC PFO closure, pooled HR = 0.35, 95%CI (0.12-1.03), P = 0.06, however, it did not reach statistical significance. These results suggest that in patients with cryptogenic stroke, TC PFO closure may be beneficial in reducing the risk of recurrent vascular events when compared to medical treatment. The benefit of TC PFO closure may be greater in patients with a substantial shunt.

C-reactive protein gene C1444T polymorphism and risk of recurrent ischemic events in patients with symptomatic intracranial atherostenoses.

PubMed

Arenillas, Juan F; Massot, Andreu; Alvarez-Sabín, Jose; Fernandez-Cadenas, Israel; del Rio-Espinola, Albert; Chacon, Pilar; Quintana, Manuel; Molina, Carlos A; Rovira, Alex; Montaner, Joan

2009-01-01

High levels of C-reactive protein (CRP) are associated with an increased risk of further ischemic events in patients with symptomatic intracranial atherosclerotic disease (ICAD). It remains unknown to which extent this increased risk might be genetically predetermined. We aimed to investigate the relationship between a common genetic polymorphism of the CRP gene and the risk of recurrent ischemic events in symptomatic ICAD patients. We studied 75 consecutive patients with a first-ever cerebral ischemic event attributable to symptomatic ICAD. Blood samples were drawn 3 months after the qualifying event. Genomic DNA was isolated and the C1444T single nucleotide polymorphism (SNP) of the CRP gene was determined. The blood concentration of CRP was also measured. Patients underwent long-term clinical follow-up to detect the occurrence of further major ischemic events. During a median follow-up time of 23 months, 18 patients (24%) suffered a major ischemic event (10 ischemic strokes, 3 transient ischemic attacks and 5 myocardial infarctions). Raised CRP levels at baseline (p = 0.02) and the presence of the T allele within the CRP C1444T SNP were associated with a higher risk of recurrent ischemic events (p = 0.02). Kaplan-Meier and multivariable Cox regression analyses adjusted for age, sex, vascular risk factors and CRP level identified that the presence of the T allele in the studied polymorphism predicted the occurrence of further ischemic events (hazard ratio 3.6, 95% confidence interval 1.2-11.1; p = 0.025). The presence of the T allele within the CRP gene C1444T polymorphism may be associated with a higher risk of further ischemic events in symptomatic ICAD patients. (c) 2009 S. Karger AG, Basel.

Assessing the risk of recurrent venous thromboembolism--a practical approach.

PubMed

Fahrni, Jennifer; Husmann, Marc; Gretener, Silvia B; Keo, Hong H

2015-01-01

Recurrent venous thromboembolism (VTE) is associated with increased morbidity and mortality. This risk is lowered by anticoagulation, with a large effect in the initial phase following the venous thromboembolic event, and with a smaller effect in terms of secondary prevention of recurrence when extended anticoagulation is performed. On the other hand, extended anticoagulation is associated with an increased risk of major bleeding and thus leads to morbidity and mortality. Therefore, it is necessary to assess the risk of recurrence for VTE on an individual basis, and a recommendation for secondary prophylaxis should be specifically based on risk calculation of recurrence of VTE and bleeding. In this review, we provide a comprehensive summary of relevant risk factors for recurrent VTE and a practical approach for assessing the risk of recurrence in daily practice.

Integrated Molecular Characterization of Gastrointestinal Stromal Tumors (GIST) Harboring the Rare D842V Mutation in PDGFRA Gene

PubMed Central

Astolfi, Annalisa; Patterson, Janice; Nannini, Margherita; Saponara, Maristella; Gatto, Lidia; Santini, Donatella; do Valle, Italo F.; Castellani, Gastone; Fiorentino, Michelangelo; von Mehren, Margaret; Brandi, Giovanni; Biasco, Guido; Heinrich, Michael C.; Pantaleo, Maria Abbondanza

2018-01-01

Gastrointestinal stromal tumors (GIST) carrying the D842V activating mutation in the platelet-derived growth factor receptor alpha (PDGFRA) gene are a very rare subgroup of GIST (about 10%) known to be resistant to conventional tyrosine kinase inhibitors (TKIs) and to show an indolent behavior. In this study, we performed an integrated molecular characterization of D842V mutant GIST by whole-transcriptome and whole-exome sequencing coupled with protein–ligand interaction modelling to identify the molecular signature and any additional recurrent genomic event related to their clinical course. We found a very specific gene expression profile of D842V mutant tumors showing the activation of G-protein-coupled receptor (GPCR) signaling and a relative downregulation of cell cycle processes. Beyond D842V, no recurrently mutated genes were found in our cohort. Nevertheless, many private, clinically relevant alterations were found in each tumor (TP53, IDH1, FBXW7, SDH-complex). Molecular modeling of PDGFRA D842V suggests that the mutant protein binds imatinib with lower affinity with respect to wild-type structure, showing higher stability during the interaction with other type I TKIs (like crenolanib). D842V mutant GIST do not show any actionable recurrent molecular events of therapeutic significance, therefore this study supports the rationale of novel TKIs development that are currently being evaluated in clinical studies for the treatment of D842V mutant GIST. PMID:29510530

Fluctuations in Wikipedia access-rate and edit-event data

NASA Astrophysics Data System (ADS)

Kämpf, Mirko; Tismer, Sebastian; Kantelhardt, Jan W.; Muchnik, Lev

2012-12-01

Internet-based social networks often reflect extreme events in nature and society by drastic increases in user activity. We study and compare the dynamics of the two major complex processes necessary for information spread via the online encyclopedia ‘Wikipedia’, i.e., article editing (information upload) and article access (information viewing) based on article edit-event time series and (hourly) user access-rate time series for all articles. Daily and weekly activity patterns occur in addition to fluctuations and bursting activity. The bursts (i.e., significant increases in activity for an extended period of time) are characterized by a power-law distribution of durations of increases and decreases. For describing the recurrence and clustering of bursts we investigate the statistics of the return intervals between them. We find stretched exponential distributions of return intervals in access-rate time series, while edit-event time series yield simple exponential distributions. To characterize the fluctuation behavior we apply detrended fluctuation analysis (DFA), finding that most article access-rate time series are characterized by strong long-term correlations with fluctuation exponents α≈0.9. The results indicate significant differences in the dynamics of information upload and access and help in understanding the complex process of collecting, processing, validating, and distributing information in self-organized social networks.

Workup for Perinatal Stroke Does Not Predict Recurrence.

PubMed

Lehman, Laura L; Beaute, Jeanette; Kapur, Kush; Danehy, Amy R; Bernson-Leung, Miya E; Malkin, Hayley; Rivkin, Michael J; Trenor, Cameron C

2017-08-01

Perinatal stroke, including neonatal and presumed perinatal presentation, represents the age in childhood in which stroke occurs most frequently. The roles of thrombophilia, arteriopathy, and cardiac anomalies in perinatal ischemic stroke are currently unclear. We took a uniform approach to perinatal ischemic stroke evaluation to study these risk factors and their association with recurrent stroke. We reviewed records of perinatal stroke patients evaluated from August 2008 to February 2016 at a single referral center. Demographics, echocardiography, arterial imaging, and thrombophilia testing were collected. Statistical analysis was performed using Fisher exact test. Across 215 cases, the median follow-up was 3.17 years (1.49, 6.46). Females comprised 42.8% of cases. Age of presentation was neonatal (110, 51.2%) or presumed perinatal (105, 48.8%). The median age at diagnosis was 2.9 days (interquartile range, 2.0-9.9) for neonatal stroke and 12.9 months (interquartile range, 8.7-32.8) for presumed perinatal stroke. Strokes were classified as arterial (149, 69.3%), venous (60, 27.9%), both (4, 1.9%), or uncertain (2, 0.9%) by consensus imaging review. Of the 215 cases, there were 6 (2.8%) recurrent ischemic cerebrovascular events. Abnormal thrombophilia testing was not associated with recurrent stroke, except for a single patient with combined antithrombin deficiency and protein C deficiency. After excluding venous events, 155 patients were evaluated for arteriopathy and cardioembolic risk factors; neither was associated with recurrent stroke. Positive family history of thrombosis was not predictive of abnormal thrombophilia testing. Thrombophilia, arteriopathy, or cardioembolic risk factors were not predictive of recurrent events after perinatal stroke. Thrombophilia evaluation in perinatal stroke should only rarely be considered. © 2017 American Heart Association, Inc.

TIA triage in emergency department using acute MRI (TIA-TEAM): a feasibility and safety study.

PubMed

Vora, Nirali; Tung, Christie E; Mlynash, Michael; Garcia, Madelleine; Kemp, Stephanie; Kleinman, Jonathan; Zaharchuk, Greg; Albers, Gregory; Olivot, Jean-Marc

2015-04-01

Positive diffusion weighted imaging (DWI) on MRI is associated with increased recurrent stroke risk in TIA patients. Acute MRI aids in TIA risk stratification and diagnosis. To evaluate the feasibility and safety of TIA triage directly from the emergency department (ED) with acute MRI and neurological consultation. Consecutive ED TIA patients assessed by a neurologist underwent acute MRI/MRA of head/neck per protocol and were hospitalized if positive DWI, symptomatic vessel stenosis, or per clinical judgment. Stroke neurologist adjudicated the final TIA diagnosis as definite, possible, or not a cerebrovascular event. Stroke recurrence rates were calculated at 7, 90, 365 days and compared with predicted stroke rates derived from historical DWI and ABCD(2) score data. One hundred twenty-nine enrolled patients had a mean age of 69 years (± 17) and median ABCD(2) score of 3 (interquartile range [IQR] 3-4). During triage, 112 (87%) patients underwent acute MRI after a median of 16 h (IQR 10-23) from symptom onset. No patients experienced a recurrent event before imaging. Twenty-four (21%) had positive DWI and 8 (7%) had symptomatic vessel stenosis. Of the total cohort, 83 (64%) were discharged and 46 (36%) were hospitalized. By one-year follow-up, one patient in each group had experienced a stroke. Of 92 patients with MRI and index cerebrovascular event, recurrent stroke rates were 1.1% at 7 and 90 days. These were similar to predicted recurrence rates. TIA triage in the ED using a protocol with neurological consultation and acute MRI is feasible and safe. The majority of patients were discharged without hospitalization and rates of recurrent stroke were not higher than predicted. © 2014 World Stroke Organization.

Risk of recurrent stroke in patients with silent brain infarction in the Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) imaging substudy.

PubMed

Weber, Ralph; Weimar, Christian; Wanke, Isabel; Möller-Hartmann, Claudia; Gizewski, Elke R; Blatchford, Jon; Hermansson, Karin; Demchuk, Andrew M; Forsting, Michael; Sacco, Ralph L; Saver, Jeffrey L; Warach, Steven; Diener, Hans Christoph; Diehl, Anke

2012-02-01

Silent brain infarctions are associated with an increased risk of stroke in healthy individuals. Risk of recurrent stroke in patients with both symptomatic and silent brain infarction (SBI) has only been investigated in patients with cardioembolic stroke in the European Atrial Fibrillation Trial. We assessed whether patients with recent noncardioembolic stroke and SBI detected on MRI are at increased risk for recurrent stroke, other cardiovascular events, and mortality. The prevalence of SBI detected on MRI was assessed in 1014 patients enrolled in the imaging substudy of the Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) trial. The primary outcome was first recurrence of stroke in patients with both symptomatic stroke and SBI in comparison with age- and sex-matched patients with stroke without SBI. Secondary outcomes were a combined vascular end point, other vascular events, and mortality. The 2 groups were compared using conditional logistic regression. Silent brain infarction was detected in 207 (20.4%) of the 1014 patients. Twenty-seven (13.0%) patients with SBI and 19 (9.2%) without SBI had a recurrent stroke (OR, 1.42; 95% CI, 0.79-2.56; P=0.24) during a mean follow-up of 2.5 years. Similarly, there was no statistically significant difference for all secondary outcome parameters between patients with SBI and matched patients without SBI. The presence of SBI in patients with recent mild noncardioembolic ischemic stroke could not be shown to be an independent risk factor for recurrent stroke, other vascular events, or a higher mortality rate. URL: http://clinicaltrials.gov. Unique identifier: NCT00153062.

Our current approach to root cause analysis: is it contributing to our failure to improve patient safety?

PubMed

Kellogg, Kathryn M; Hettinger, Zach; Shah, Manish; Wears, Robert L; Sellers, Craig R; Squires, Melissa; Fairbanks, Rollin J

2017-05-01

Despite over a decade of efforts to reduce the adverse event rate in healthcare, the rate has remained relatively unchanged. Root cause analysis (RCA) is a process used by hospitals in an attempt to reduce adverse event rates; however, the outputs of this process have not been well studied in healthcare. This study aimed to examine the types of solutions proposed in RCAs over an 8-year period at a major academic medical institution. All state-reportable adverse events were gathered, and those for which an RCA was performed were analysed. A consensus rating process was used to determine a severity rating for each case. A qualitative approach was used to categorise the types of solutions proposed by the RCA team in each case and descriptive statistics were calculated. 302 RCAs were reviewed. The most common event types involved a procedure complication, followed by cardiopulmonary arrest, neurological deficit and retained foreign body. In 106 RCAs, solutions were proposed. A large proportion (38.7%) of RCAs with solutions proposed involved a patient death. Of the 731 proposed solutions, the most common solution types were training (20%), process change (19.6%) and policy reinforcement (15.2%). We found that multiple event types were repeated in the study period, despite repeated RCAs. This study found that the most commonly proposed solutions were weaker actions, which were less likely to decrease event recurrence. These findings support recent attempts to improve the RCA process and to develop guidance for the creation of effective and sustainable solutions to be used by RCA teams. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Genomic analysis of diffuse pediatric low-grade gliomas identifies recurrent oncogenic truncating rearrangements in the transcription factor MYBL1

PubMed Central

Ramkissoon, Lori A.; Horowitz, Peleg M.; Craig, Justin M.; Ramkissoon, Shakti H.; Rich, Benjamin E.; Schumacher, Steven E.; McKenna, Aaron; Lawrence, Michael S.; Bergthold, Guillaume; Brastianos, Priscilla K.; Tabak, Barbara; Ducar, Matthew D.; Van Hummelen, Paul; MacConaill, Laura E.; Pouissant-Young, Tina; Cho, Yoon-Jae; Taha, Hala; Mahmoud, Madeha; Bowers, Daniel C.; Margraf, Linda; Tabori, Uri; Hawkins, Cynthia; Packer, Roger J.; Hill, D. Ashley; Pomeroy, Scott L.; Eberhart, Charles G.; Dunn, Ian F.; Goumnerova, Liliana; Getz, Gad; Chan, Jennifer A.; Santagata, Sandro; Hahn, William C.; Stiles, Charles D.; Ligon, Azra H.; Kieran, Mark W.; Beroukhim, Rameen; Ligon, Keith L.

2013-01-01

Pediatric low-grade gliomas (PLGGs) are among the most common solid tumors in children but, apart from BRAF kinase mutations or duplications in specific subclasses, few genetic driver events are known. Diffuse PLGGs comprise a set of uncommon subtypes that exhibit invasive growth and are therefore especially challenging clinically. We performed high-resolution copy-number analysis on 44 formalin-fixed, paraffin-embedded diffuse PLGGs to identify recurrent alterations. Diffuse PLGGs exhibited fewer such alterations than adult low-grade gliomas, but we identified several significantly recurrent events. The most significant event, 8q13.1 gain, was observed in 28% of diffuse astrocytoma grade IIs and resulted in partial duplication of the transcription factor MYBL1 with truncation of its C-terminal negative-regulatory domain. A similar recurrent deletion-truncation breakpoint was identified in two angiocentric gliomas in the related gene v-myb avian myeloblastosis viral oncogene homolog (MYB) on 6q23.3. Whole-genome sequencing of a MYBL1-rearranged diffuse astrocytoma grade II demonstrated MYBL1 tandem duplication and few other events. Truncated MYBL1 transcripts identified in this tumor induced anchorage-independent growth in 3T3 cells and tumor formation in nude mice. Truncated transcripts were also expressed in two additional tumors with MYBL1 partial duplication. Our results define clinically relevant molecular subclasses of diffuse PLGGs and highlight a potential role for the MYB family in the biology of low-grade gliomas. PMID:23633565

Application of the aviation black box principle in pediatric cardiac surgery: tracking all failures in the pediatric cardiac operating room.

PubMed

Bowermaster, Rebecca; Miller, Megan; Ashcraft, Traci; Boyd, Michael; Brar, Anoop; Manning, Peter; Eghtesady, Pirooz

2015-02-01

Cardiac surgical procedures are complex and require the coordinated action of many. This creates the potential for small failures that could be the substrate for subsequent morbidity or mortality. High-reliability science suggests that preoccupation with small failures can lead to improved outcomes. Failures of all magnitudes (ie, events) were captured within the pediatric cardiac operating room starting with a single surgeon in April 2008. As the surgical team became more familiar with the process, failure recording was extended to all surgeons and all surgical procedures performed until the conclusion of the study in December 2010. New recording processes were developed and used on a rolling basis during this study. With systematic capture, event rates increased (from occurring within 20% to 50% of operative procedures). Although we identified 9 recurrent patterns, 2 categories (ie, Equipment and Patient Instability) accounted for almost half of the events (45%). The greatest number of events occurred during the prebypass period (40.2%), compared with bypass (20.1%) and postbypass (32.3%) periods. These events were mainly difficulties in access (31.8%), equipment (42.4%), and patient instability (33.3%) in each of the epochs, respectively. Of all events, 7.3% occurred during nonbypass cases, 30.6% of these were communication events. Implementation of this initiative led to recognition of major system-wide issues (eg, need for change in the blood-product acquisition process). Preoccupation with all failures in the operating room can reveal important information about the operating room and perioperative microenvironment that can prompt substantive process changes both locally and within the larger health system. Copyright © 2015 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

Occult cancer-related first venous thromboembolism is associated with an increased risk of recurrent venous thromboembolism.

PubMed

Gran, O V; Braekkan, S K; Paulsen, B; Skille, H; Rosendaal, F R; Hansen, J-B

2017-07-01

Essentials Recurrence risk after an occult cancer-related incident venous thromboembolism (VTE) is unknown. We compared the risk of VTE recurrence in occult-, overt- and non-cancer related first VTE. Patients with occult-cancer related first VTE had the highest risk of VTE recurrence. The high recurrence risk in occult cancer is likely due to the advanced cancers. Background Although venous thromboembolism (VTE) is associated with a high recurrence rate, the absolute recurrence rates for cancer-related VTE, particularly occult cancer, are not well known. Objectives To investigate the risk of VTE recurrence in patients with occult and overt cancer-related VTE. Methods Incident VTE events among participants of the first to sixth Tromsø surveys occurring in the period 1994-2012 were included. Occult cancer was defined as cancer diagnosed within a year following a VTE, and overt cancer was defined as cancer diagnosed within the 2 years before a VTE. Results Among 733 patients with incident VTE, 110 had overt cancer and 40 had occult cancer. There were 95 recurrent VTE events during a median of 3.2 years of follow-up. The 1-year cumulative incidence of VTE recurrence was 38.6% in subjects with occult cancer, 15.5% in subjects with overt cancer, and 3.8% in non-cancer subjects. The 1-year risk of recurrence was 12-fold (hazard ratio [HR] 12.4, 95% confidence interval [CI] 5.9-26.3) higher in subjects with occult cancer and four-fold (HR 4.3, 95% CI 2.0-9.2) higher in subjects with overt cancer than in non-cancer subjects. The occult cancers associated with VTE recurrence were typically located at prothrombotic sites (i.e. lung and gastrointestinal) and presented at advanced stages. The majority (69%) of recurrences in subjects with occult cancer occurred before or shortly after cancer diagnosis, and were therefore not treatment-related. Conclusion Our findings suggest that the increased risk of recurrence in patients with occult cancer is mainly attributable to the advanced cancers in these patients. © 2017 International Society on Thrombosis and Haemostasis.

Cancer stem cells in head and neck squamous cell carcinoma: a review.

PubMed

Satpute, Pranali Shirish; Hazarey, Vinay; Ahmed, Riyaz; Yadav, Lalita

2013-01-01

Research indicates that a small population of cancer cells is highly tumorigenic, endowed with the capacity for self-renewal, and has the ability to differentiate into cells that constitute the bulk of tumors. These cells are considered the "drivers" of the tumorigenic process in some tumor types, and have been named cancer stem cells (CSC). Epithelial-mesenchymal transition (EMT) appears to be involved in the process leading to the acquisition of stemness by epithelial tumor cells. Through this process, cells acquire an invasive phenotype that may contribute to tumor recurrence and metastasis. CSC have been identified in human head and neck squamous cell carcinomas (HNSCC) using markers such as CD133 and CD44 expression, and aldehyde dehydrogenase (ALDH) activity. Head and neck cancer stem cells reside primarily in perivascular niches in the invasive fronts where endothelial-cell initiated events contribute to their survival and function. Clinically, CSC enrichment has been shown to be enhanced in recurrent disease, treatment failure and metastasis. CSC represent a novel target of study given their slow growth and innate mechanisms conferring treatment resistance. Further understanding of their unique phenotype may reveal potential molecular targets to improve therapeutic and survival outcomes in patients with HNSCC. Here, we discuss the state-of-the-knowledge on the pathobiology of cancer stem cells, with a focus on the impact of these cells on head and neck tumor progression, metastasis and recurrence due to treatment failure.

Highly variable recurrence of tsunamis in the 7,400 years before the 2004 Indian Ocean tsunami

NASA Astrophysics Data System (ADS)

Horton, B.; Rubin, C. M.; Sieh, K.; Jessica, P.; Daly, P.; Ismail, N.; Parnell, A. C.

2017-12-01

The devastating 2004 Indian Ocean tsunami caught millions of coastal residents and the scientific community off-guard. Subsequent research in the Indian Ocean basin has identified prehistoric tsunamis, but the timing and recurrence intervals of such events are uncertain. Here, we identify coastal caves as a new depositional environment for reconstructing tsunami records and present a 5,000 year record of continuous tsunami deposits from a coastal cave in Sumatra, Indonesia which shows the irregular recurrence of 11 tsunamis between 7,400 and 2,900 years BP. The data demonstrates that the 2004 tsunami was just the latest in a sequence of devastating tsunamis stretching back to at least the early Holocene and suggests a high likelihood for future tsunamis in the Indian Ocean. The sedimentary record in the cave shows that ruptures of the Sunda megathrust vary between large (which generated the 2004 Indian Ocean tsunami) and smaller slip failures. The chronology of events suggests the recurrence of multiple smaller tsunamis within relatively short time periods, interrupted by long periods of strain accumulation followed by giant tsunamis. The average time period between tsunamis is about 450 years with intervals ranging from a long, dormant period of over 2,000 years, to multiple tsunamis within the span of a century. The very long dormant period suggests that the Sunda megathrust is capable of accumulating large slip deficits between earthquakes. Such a high slip rupture would produce a substantially larger earthquake than the 2004 event. Although there is evidence that the likelihood of another tsunamigenic earthquake in Aceh province is high, these variable recurrence intervals suggest that long dormant periods may follow Sunda Megathrust ruptures as large as that of 2004 Indian Ocean tsunami. The remarkable variability of recurrence suggests that regional hazard mitigation plans should be based upon the high likelihood of future destructive tsunami demonstrated by the cave record and other paleotsunami sites, rather than estimates of recurrence intervals.

Long-term antibiotics for prevention of recurrent urinary tract infection in older adults: systematic review and meta-analysis of randomised trials.

PubMed

Ahmed, Haroon; Davies, Freya; Francis, Nick; Farewell, Daniel; Butler, Christoper; Paranjothy, Shantini

2017-05-29

To address clinical uncertainties about the effectiveness and safety of long-term antibiotic therapy for preventing recurrent urinary tract infections (UTIs) in older adults. Systematic review andmeta-analysis of randomised trials. We searched Medline, Embase, The Cumulative Index to Nursing and Allied Health Literature( CINAHL), and the Cochrane Register of Controlled Trials from inception to August 2016. Eligible studies compared long-term antibiotic therapy with non-antibiotic therapy or placebo in men or women aged over 65, or in postmenopausal women, with recurrent UTIs. We did not identify any studies that included older men. Three randomised controlled trials compared long-term antibiotics with vaginal oestrogens (n=150), oral lactobacilli (n=238) and D-mannose powder (n=94) in postmenopausal women. Long-term antibiotics reduced the risk of UTI recurrence by 24% (three trials, n=482; pooled risk ratio (RR) 0.76; 95% CI 0.61 to 0.95, number needed to treat=8.5). There was no statistically significant increase in risk of adverse events (mild adverse events: pooled RR 1.52; 95% CI 0.76 to 3.03; serious adverse events: pooled RR 0.90, 95% CI 0.31 to 2.66). One trial showed 90% of urinary and faecal Escherichia coli isolates were resistant to trimethoprim-sulfamethoxazole after 1 month of prophylaxis. Findings from three small trials with relatively short follow-up periods suggest long-term antibiotic therapy reduces the risk of recurrence in postmenopausal women with recurrent UTI. We did not identify any evidence to inform several clinically important scenarios including, benefits and harms in older men or frail care home residents, optimal duration of prophylaxis, recurrence rates once prophylaxis stops and effects on urinary antibiotic resistance. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Aspirin and extended-release dipyridamole versus clopidogrel for recurrent stroke.

PubMed

Sacco, Ralph L; Diener, Hans-Christoph; Yusuf, Salim; Cotton, Daniel; Ounpuu, Stephanie; Lawton, William A; Palesch, Yuko; Martin, Reneé H; Albers, Gregory W; Bath, Philip; Bornstein, Natan; Chan, Bernard P L; Chen, Sien-Tsong; Cunha, Luis; Dahlöf, Björn; De Keyser, Jacques; Donnan, Geoffrey A; Estol, Conrado; Gorelick, Philip; Gu, Vivian; Hermansson, Karin; Hilbrich, Lutz; Kaste, Markku; Lu, Chuanzhen; Machnig, Thomas; Pais, Prem; Roberts, Robin; Skvortsova, Veronika; Teal, Philip; Toni, Danilo; Vandermaelen, Cam; Voigt, Thor; Weber, Michael; Yoon, Byung-Woo

2008-09-18

Recurrent stroke is a frequent, disabling event after ischemic stroke. This study compared the efficacy and safety of two antiplatelet regimens--aspirin plus extended-release dipyridamole (ASA-ERDP) versus clopidogrel. In this double-blind, 2-by-2 factorial trial, we randomly assigned patients to receive 25 mg of aspirin plus 200 mg of extended-release dipyridamole twice daily or to receive 75 mg of clopidogrel daily. The primary outcome was first recurrence of stroke. The secondary outcome was a composite of stroke, myocardial infarction, or death from vascular causes. Sequential statistical testing of noninferiority (margin of 1.075), followed by superiority testing, was planned. A total of 20,332 patients were followed for a mean of 2.5 years. Recurrent stroke occurred in 916 patients (9.0%) receiving ASA-ERDP and in 898 patients (8.8%) receiving clopidogrel (hazard ratio, 1.01; 95% confidence interval [CI], 0.92 to 1.11). The secondary outcome occurred in 1333 patients (13.1%) in each group (hazard ratio for ASA-ERDP, 0.99; 95% CI, 0.92 to 1.07). There were more major hemorrhagic events among ASA-ERDP recipients (419 [4.1%]) than among clopidogrel recipients (365 [3.6%]) (hazard ratio, 1.15; 95% CI, 1.00 to 1.32), including intracranial hemorrhage (hazard ratio, 1.42; 95% CI, 1.11 to 1.83). The net risk of recurrent stroke or major hemorrhagic event was similar in the two groups (1194 ASA-ERDP recipients [11.7%], vs. 1156 clopidogrel recipients [11.4%]; hazard ratio, 1.03; 95% CI, 0.95 to 1.11). The trial did not meet the predefined criteria for noninferiority but showed similar rates of recurrent stroke with ASA-ERDP and with clopidogrel. There is no evidence that either of the two treatments was superior to the other in the prevention of recurrent stroke. (ClinicalTrials.gov number, NCT00153062.) 2008 Massachusetts Medical Society

Value of the CHA2DS2-VASc score and Fabry-specific score for predicting new-onset or recurrent stroke/TIA in Fabry disease patients without atrial fibrillation.

PubMed

Liu, Dan; Hu, Kai; Schmidt, Marie; Müntze, Jonas; Maniuc, Octavian; Gensler, Daniel; Oder, Daniel; Salinger, Tim; Weidemann, Frank; Ertl, Georg; Frantz, Stefan; Wanner, Christoph; Nordbeck, Peter

2018-05-24

To evaluate potential risk factors for stroke or transient ischemic attacks (TIA) and to test the feasibility and efficacy of a Fabry-specific stroke risk score in Fabry disease (FD) patients without atrial fibrillation (AF). FD patients often experience cerebrovascular events (stroke/TIA) at young age. 159 genetically confirmed FD patients without AF (aged 40 ± 14 years, 42.1% male) were included, and risk factors for stroke/TIA events were determined. All patients were followed up over a median period of 60 (quartiles 35-90) months. The pre-defined primary outcomes included new-onset or recurrent stroke/TIA and all-cause death. Prior stroke/TIA (HR 19.97, P < .001), angiokeratoma (HR 4.06, P = .010), elevated creatinine (HR 3.74, P = .011), significant left ventricular hypertrophy (HR 4.07, P = .017), and reduced global systolic strain (GLS, HR 5.19, P = .002) remained as independent risk predictors of new-onset or recurrent stroke/TIA in FD patients without AF. A Fabry-specific score was established based on above defined risk factors, proving somehow superior to the CHA 2 DS 2 -VASc score in predicting new-onset or recurrent stroke/TIA in this cohort (AUC 0.87 vs. 0.75, P = .199). Prior stroke/TIA, angiokeratoma, renal dysfunction, left ventricular hypertrophy, and global systolic dysfunction are independent risk factors for new-onset or recurrent stroke/TIA in FD patients without AF. It is feasible to predict new or recurrent cerebral events with the Fabry-specific score based on the above defined risk factors. Future studies are warranted to test if FD patients with high risk for new-onset or recurrent stroke/TIA, as defined by the Fabry-specific score (≥ 2 points), might benefit from antithrombotic therapy. Clinical trial registration HEAL-FABRY (evaluation of HEArt invoLvement in patients with FABRY disease, NCT03362164).

Association Between Blood Pressure Control and Risk of Recurrent Intracerebral Hemorrhage.

PubMed

Biffi, Alessandro; Anderson, Christopher D; Battey, Thomas W K; Ayres, Alison M; Greenberg, Steven M; Viswanathan, Anand; Rosand, Jonathan

2015-09-01

Intracerebral hemorrhage (ICH) is the most severe form of stroke. Survivors are at high risk of recurrence, death, and worsening functional disability. To investigate the association between blood pressure (BP) after index ICH and risk of recurrent ICH. Single-site, tertiary care referral center observational study of 1145 of 2197 consecutive patients with ICH presenting from July 1994 to December 2013. A total of 1145 patients with ICH survived at least 90 days and were followed up through December 2013 (median follow-up of 36.8 months [minimum, 9.8 months]). Blood pressure measurements at 3, 6, 9, and 12 months, and every 6 months thereafter, obtained from medical personnel (inpatient hospital or outpatient clinic medical or nursing staff) or via patient self-report. Exposure was characterized in 3 ways: (1) recorded systolic and diastolic measurements; (2) classification as adequate or inadequate BP control based on American Heart Association/American Stroke Association recommendations; and (3) stage of hypertension based on Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure 7 criteria. Recurrent ICH and its location within the brain (lobar vs nonlobar). There were 102 recurrent ICH events among 505 survivors of lobar ICH and 44 recurrent ICH events among 640 survivors of nonlobar ICH. During follow-up adequate BP control was achieved on at least 1 measurement by 625 patients (54.6% of total [range, 49.2%-58.7%]) and consistently (ie, at all available time points) by 495 patients (43.2% of total [range, 34.5%-51.0%]). The event rate for lobar ICH was 84 per 1000 person-years among patients with inadequate BP control compared with 49 per 1000 person-years among patients with adequate BP control. For nonlobar ICH the event rate was 52 per 1000 person-years with inadequate BP control compared with 27 per 1000 person-years for patients with adequate BP control. In analyses modeling BP control as a time-varying variable, inadequate BP control was associated with higher risk of recurrence of both lobar ICH (hazard ratio [HR], 3.53 [95% CI, 1.65-7.54]) and nonlobar ICH (HR, 4.23 [95% CI, 1.02-17.52]). Systolic BP during follow-up was associated with increased risk of both lobar ICH recurrence (HR, 1.33 per 10-mm Hg increase [95% CI, 1.02-1.76]) and nonlobar ICH recurrence (HR, 1.54 [95% CI, 1.03-2.30]). Diastolic BP was associated with increased risk of nonlobar ICH recurrence (HR, 1.21 per 10-mm Hg increase [95% CI, 1.01-1.47]) but not with lobar ICH recurrence (HR, 1.36 [95% CI, 0.90-2.10]). In this observational single-center cohort study of ICH survivors, reported BP measurements suggesting inadequate BP control during follow-up were associated with higher risk of both lobar and nonlobar ICH recurrence. These data suggest that randomized clinical trials are needed to address the benefits and risks of stricter BP control in ICH survivors.

A long-recommended but seldom-used method of analysis for fall injuries found a unique pattern of risk factors in the youngest-old.

PubMed

Legrand, Helen; Pihlsgård, Mats; Nordell, Eva; Elmståhl, Sölve

2015-08-01

Few studies on fall risk factors use long-recommended methods for analysis of recurrent events. Previous falls are the biggest risk factor for future falls, but few fall studies focus on the youngest-old. This study's objective was to apply Cox regression for recurrent events to identify factors associated with injurious falls in the youngest-old. Participants were community-dwelling residents of southern Sweden (n = 1,133), aged 59-67 at baseline (median 61.2), from the youngest cohorts of the larger Good Aging in Skåne (GÅS) study. Exposure variable data were collected from baseline study visits and medical records. Injurious falls, defined as emergency, inpatient, or specialist visits associated with ICD-10 fall codes during the follow-up period (2001-2011), were gathered from national and regional registries. Analysis was conducted using time to event Cox Regression for recurrent events. A majority (77.1 %) of injurious falls caused serious injuries such as fractures and open wounds. Exposure to nervous system medications [hazard ratio (HR) 1.40, 95 % confidence interval (CI) 1.03-1.89], central nervous system disease (HR 1.79, CI 1.18-2.70), and previous injurious fall(s) (HR 2.00, CI 1.50-2.68) were associated with increased hazard of injurious fall. Regression for recurrent events is feasible with typical falls' study data. The association of certain exposures with increased hazard of injurious falls begins earlier than previously studied. Different patterns of risk factors by age can provide insight into the progression of frailty. Tailored fall prevention screening and intervention may be of value in populations younger than those traditionally screened.

The dusty ballerina skirt of Jupiter

NASA Astrophysics Data System (ADS)

Horanyi, M.; Morfill, G.; Gruen, E.

1993-12-01

We suggest a model to explain the unexpected recurrent dust events that were observed during the Jupiter encounter by the dust detector on board the Ulysses spacecraft. This model is based dust-magnetosphere interactions. Dust particles inside the Jovian magnetosphere collect electrostatic charges and their interaction with the magnetic and electric fields can lead to energization and subsequent ejection. We discuss the dusty regions (ring/halo, `gossamer' ring) and also Io as potential sources for the Ulysses events. This model favors Io as a source. The mass and velocity range of the escaping particles are compatible with the observations, and we also suggest internal periodicities to explain the recurrent nature of the Ulysses dust events.

Detection of Temporally and Spatially Limited Periodic Earthquake Recurrence in Synthetic Seismic Records

NASA Astrophysics Data System (ADS)

Zielke, O.; Arrowsmith, R. J.

2005-12-01

The nonlinear dynamics of fault behavior are dominated by complex interactions among the multiple processes controlling the system. For example, temporal and spatial variations in pore pressure, healing effects, and stress transfer cause significant heterogeneities in fault properties and the stress-field at the sub-fault level. Numerical and laboratory fault models show that the interaction of large systems of fault elements causes the entire system to develop into a state of self-organized criticality. Once in this state, small perturbations of the system may result in chain reactions (i.e., earthquakes) which can affect any number of fault segments. This sensitivity to small perturbations is strong evidence for chaotic fault behavior, which implies that exact event prediction is not possible. However, earthquake prediction with a useful accuracy is nevertheless possible. Studies of other natural chaotic systems have shown that they may enter states of metastability, in which the system's behavior is predictable. Applying this concept to earthquake faults, these windows of metastable behavior should be characterized by periodic earthquake recurrence. The observed periodicity of the Parkfield, CA (M= 6) events may resemble such a window of metastability. I am statistically analyzing numerically generated seismic records to study these phases of periodic behavior. In this preliminary study, seismic records were generated using a model introduced by Nakanishi [Phys. Rev. A, 43, 6613-6621, 1991]. It consists of a one-dimensional chain of blocks (interconnected by springs) with a relaxation function that mimics velocity-weakened frictional behavior. The earthquakes occurring in this model show generally a power-law frequency-size distribution. However, for large events the distribution has a shoulder where the frequency of events is higher than expected from the power law. I have analyzed time-series of single block motions within the system. These time-series include noticeable periodicity during certain intervals in an otherwise aperiodic record. The observed periodic signal is not equally distributed over the range of offsets but shows a multi-modal distribution with increased periodicity for the smallest events and for large events that show a specific offset. These large events also form a shoulder in the frequency-size distribution. Apparently, the model exhibits characteristic earthquakes (defined by similar coseismic slip) that occur more frequently than expected from a power law distribution, and also are significantly more periodic. The wavelength of the periodic signal generally equals the minimum loading time, which is related to the loading velocity and the amount of coseismic slip (i.e., stress drop). No significant event occurs between the characteristic events as long as the system stays in a window of periodic behavior. Within the windows of periodic behavior, earthquake prediction is straightforward. Therefore, recognition of these windows not only in synthetic data but also in real seismic records, may improve the intra-window forecast of earthquakes. Further studies will attempt to determine the characteristics of onset, duration, and end of these windows of periodic earthquake recurrence. Only the motion of a single block within a bigger system was analyzed so far. Going from a zero dimensional scenario to a two dimensional case where the offsets not only of a single block but the displacement patterns caused by a certain event are analyzed will increase the verisimilitude of the detection of periodic earthquake recurrence within an otherwise chaotic seismic record.

Prospective observational study of isoflavone and the risk of stroke recurrence: potential clinical implications beyond vascular function.

PubMed

Chan, Y-H; Lau, K-K; Yiu, K-H; Siu, C-W; Chan, H-T; Li, S-W; Tam, S; Lam, T-H; Lau, C-P; Tse, H-F

2012-04-01

Whether isoflavone has any effect on recurrent cardiovascular events is unknown. To investigate the relations between isoflavone intake and the risk of stroke recurrence. We recruited 127 consecutive patients with prior history of atherothrombotic/ hemorrhagic stroke (mean age: 67 ± 11 years, 69% male) and prospectively followed up for a mean duration of 30 months. Stroke recurrence and major adverse cardiovascular events (MACE) were documented. Brachial flow-mediated dilatation (FMD) was measured using high-resolution ultrasound. Isoflavone intake was estimated using a validated food frequency questionnaire. Median isoflavone intake was 6.9 (range: 2.1 - 14.5) mg/day. Isoflavone intake was independently associated with increased FMD (Pearson R=0.23, p=0.012). At 30 months, there were 10 stroke recurrence and 12 MACE. Kaplan-Meier analysis showed that patients with isoflavone intake higher than median value had significantly longer median stroke recurrence-free survival time (19.0 [range: 10.4 - 27.6] mth versus 5.0 [range: 4.1 - 5.9] mth, p=0.021) and MACE-free survival time (19.0 [range: 10.4 - 27.6] mth versus 4.0 [range: 2.4 - 5.6] mth, p=0.013). Using multivariate cox regression, higher isoflavone intake was an independent predictor for lower risk of stroke recurrence (hazards ratio 0.18 [95%CI: 0.03 - 0.95], risk reduction 82%, p=0.043) and MACE (hazards ratio 0.16 [95%CI: 0.03 - 0.84], risk reduction 84%, p=0.030). Higher isoflavone intake in stroke patients was associated with prolonged recurrence-free survival, and reduced risk of stroke recurrence and MACE independent of baseline vascular function. Whether isoflavone may confer clinically significant secondary protection in stroke patients should be further investigated in a randomized controlled trial.

Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes: the MIRACL study: a randomized controlled trial.

PubMed

Schwartz, G G; Olsson, A G; Ezekowitz, M D; Ganz, P; Oliver, M F; Waters, D; Zeiher, A; Chaitman, B R; Leslie, S; Stern, T

2001-04-04

Patients experience the highest rate of death and recurrent ischemic events during the early period after an acute coronary syndrome, but it is not known whether early initiation of treatment with a statin can reduce the occurrence of these early events. To determine whether treatment with atorvastatin, 80 mg/d, initiated 24 to 96 hours after an acute coronary syndrome, reduces death and nonfatal ischemic events. A randomized, double-blind trial conducted from May 1997 to September 1999, with follow-up through 16 weeks at 122 clinical centers in Europe, North America, South Africa, and Australasia. A total of 3086 adults aged 18 years or older with unstable angina or non-Q-wave acute myocardial infarction. Patients were stratified by center and randomly assigned to receive treatment with atorvastatin (80 mg/d) or matching placebo between 24 and 96 hours after hospital admission. Primary end point event defined as death, nonfatal acute myocardial infarction, cardiac arrest with resuscitation, or recurrent symptomatic myocardial ischemia with objective evidence and requiring emergency rehospitalization. A primary end point event occurred in 228 patients (14.8%) in the atorvastatin group and 269 patients (17.4%) in the placebo group (relative risk [RR], 0.84; 95% confidence interval [CI], 0.70-1.00; P =.048). There were no significant differences in risk of death, nonfatal myocardial infarction, or cardiac arrest between the atorvastatin group and the placebo group, although the atorvastatin group had a lower risk of symptomatic ischemia with objective evidence and requiring emergency rehospitalization (6.2% vs 8.4%; RR, 0.74; 95% CI, 0.57-0.95; P =.02). Likewise, there were no significant differences between the atorvastatin group and the placebo group in the incidence of secondary outcomes of coronary revascularization procedures, worsening heart failure, or worsening angina, although there were fewer strokes in the atorvastatin group than in the placebo group (12 vs 24 events; P =.045). In the atorvastatin group, mean low-density lipoprotein cholesterol level declined from 124 mg/dL (3.2 mmol/L) to 72 mg/dL (1.9 mmol/L). Abnormal liver transaminases (>3 times upper limit of normal) were more common in the atorvastatin group than in the placebo group (2.5% vs 0.6%; P<.001). For patients with acute coronary syndrome, lipid-lowering therapy with atorvastatin, 80 mg/d, reduces recurrent ischemic events in the first 16 weeks, mostly recurrent symptomatic ischemia requiring rehospitalization.

Assessing the risk of recurrent venous thromboembolism – a practical approach

PubMed Central

Fahrni, Jennifer; Husmann, Marc; Gretener, Silvia B; Keo, Hong H

2015-01-01

Recurrent venous thromboembolism (VTE) is associated with increased morbidity and mortality. This risk is lowered by anticoagulation, with a large effect in the initial phase following the venous thromboembolic event, and with a smaller effect in terms of secondary prevention of recurrence when extended anticoagulation is performed. On the other hand, extended anticoagulation is associated with an increased risk of major bleeding and thus leads to morbidity and mortality. Therefore, it is necessary to assess the risk of recurrence for VTE on an individual basis, and a recommendation for secondary prophylaxis should be specifically based on risk calculation of recurrence of VTE and bleeding. In this review, we provide a comprehensive summary of relevant risk factors for recurrent VTE and a practical approach for assessing the risk of recurrence in daily practice. PMID:26316770

Tremor reveals stress shadowing, deep postseismic creep, and depth-dependent slip recurrence on the lower-crustal San Andreas fault near Parkfield

USGS Publications Warehouse

Shelly, David R.; Johnson, Kaj M.

2011-01-01

The 2003 magnitude 6.5 San Simeon and the 2004 magnitude 6.0 Parkfield earthquakes induced small, but significant, static stress changes in the lower crust on the central San Andreas fault, where recently detected tectonic tremor sources provide new constraints on deep fault creep processes. We find that these earthquakes affect tremor rates very differently, consistent with their differing transferred static shear stresses. The San Simeon event appears to have cast a "stress shadow" north of Parkfield, where tremor activity was stifled for 3-6 weeks. In contrast, the 2004 Parkfield earthquake dramatically increased tremor activity rates both north and south of Parkfield, allowing us to track deep postseismic slip. Following this event, rates initially increased by up to two orders of magnitude for the relatively shallow tremor sources closest to the rupture, with activity in some sources persisting above background rates for more than a year. We also observe strong depth dependence in tremor recurrence patterns, with shallower sources generally exhibiting larger, less-frequent bursts, possibly signaling a transition toward steady creep with increasing temperature and depth. Copyright 2011 by the American Geophysical Union.

A new statistical time-dependent model of earthquake occurrence: failure processes driven by a self-correcting model

NASA Astrophysics Data System (ADS)

Rotondi, Renata; Varini, Elisa

2016-04-01

The long-term recurrence of strong earthquakes is often modelled by the stationary Poisson process for the sake of simplicity, although renewal and self-correcting point processes (with non-decreasing hazard functions) are more appropriate. Short-term models mainly fit earthquake clusters due to the tendency of an earthquake to trigger other earthquakes; in this case, self-exciting point processes with non-increasing hazard are especially suitable. In order to provide a unified framework for analyzing earthquake catalogs, Schoenberg and Bolt proposed the SELC (Short-term Exciting Long-term Correcting) model (BSSA, 2000) and Varini employed a state-space model for estimating the different phases of a seismic cycle (PhD Thesis, 2005). Both attempts are combinations of long- and short-term models, but results are not completely satisfactory, due to the different scales at which these models appear to operate. In this study, we split a seismic sequence in two groups: the leader events, whose magnitude exceeds a threshold magnitude, and the remaining ones considered as subordinate events. The leader events are assumed to follow a well-known self-correcting point process named stress release model (Vere-Jones, J. Phys. Earth, 1978; Bebbington & Harte, GJI, 2003, Varini & Rotondi, Env. Ecol. Stat., 2015). In the interval between two subsequent leader events, subordinate events are expected to cluster at the beginning (aftershocks) and at the end (foreshocks) of that interval; hence, they are modeled by a failure processes that allows bathtub-shaped hazard function. In particular, we have examined the generalized Weibull distributions, a large family that contains distributions with different bathtub-shaped hazard as well as the standard Weibull distribution (Lai, Springer, 2014). The model is fitted to a dataset of Italian historical earthquakes and the results of Bayesian inference are shown.

[Recurrent clinical mastitis in dairy cattle - importance and causes].

PubMed

Grieger, A-S; Zoche-Golob, V; Paduch, J-H; Hoedemaker, M; Krömker, V

2014-01-01

Clinical mastitis as a frequently recurrent event can cause substantive economic loss on dairy farms. The reason for recurrent mastitis can be either a persistent infection of the bovine mammary gland by a mastitis pathogen or a reinfection of a quarter or udder after bacteriological cure. The virulence properties of a mastitis pathogen and the cure odds of an individual cow determine the development of persistent infections. Clinical episodes may alternate with periods without symptoms in the course of persistent infections. Strategies to reduce cases of recurrent mastitis have to include improved treatment concepts and measures to decrease new infection rates. The present literature review summarises the knowledge of definitions, frequencies, causes and effects of recurrent mastitis.

One-year atherothrombotic vascular events rates in outpatients with recent non-cardioembolic ischemic stroke: the EVEREST (Effective Vascular Event REduction after STroke) registry.

PubMed

Suzuki, Norihiro; Sato, Motoki; Houkin, Kiyohiro; Terayama, Yasuo; Uchiyama, Shinichiro; Daida, Hiroyuki; Shigematsu, Hiroshi; Goto, Shinya; Tanaka, Kortaro; Origasa, Hideki; Miyamoto, Susumu; Minematsu, Kazuo; Matsumoto, Masayasu; Okada, Yasushi

2012-05-01

Patients with recent ischemic stroke may have higher risk of atherothrombosis than stable patients with established vascular events. Our aims were to investigate 1-year atherothrombotic vascular event rates and to assess the risk factors for recurrent ischemic stroke in this population. This prospective cohort study was conducted between January 2007 and July 2009 at 313 hospitals in Japan. Outpatients who were at least 45 years of age and who had received oral antiplatelet therapy were enrolled within 2 weeks to 6 months from the last onset of noncardioembolic ischemic stroke. At 12 ± 3 months after enrollment, data on presence/absence of atherothrombotic vascular events were collected. The primary endpoint was the occurrence of fatal or nonfatal ischemic stroke. A total of 3452 patients were enrolled, and 3411 patients who had baseline data were included in the analysis. The 1-year event rate was 3.81% (95% confidence interval 3.15-4.48%) for fatal or nonfatal ischemic stroke and 0.84% (95% confidence interval 0.52-1.15%) for all-cause mortality. The annual rate of recurrent ischemic stroke was significantly higher in patients who had ischemic stroke at least twice than in patients who had first-ever ischemic stroke (5.02% vs 3.59%; P = .0313). In the multivariable Cox regression analysis, recurrent ischemic stroke was significantly associated with age (P = .0033), the presence of diabetes (P = .0129), and waist circumference ≥80 cm (P = .0056). Patients with recent ischemic stroke have a higher risk of stroke recurrence than stable patients enrolled in the REduction of Atherothrombosis for Continued Health (REACH) registry even though they received antiplatelet therapy. The rigorous management of risk factors is needed. Copyright © 2012 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Predictors of long-term recurrent vascular events after ischemic stroke at young age: the Italian Project on Stroke in Young Adults.

PubMed

Pezzini, Alessandro; Grassi, Mario; Lodigiani, Corrado; Patella, Rosalba; Gandolfo, Carlo; Zini, Andrea; Delodovici, Maria Luisa; Paciaroni, Maurizio; Del Sette, Massimo; Toriello, Antonella; Musolino, Rossella; Calabrò, Rocco Salvatore; Bovi, Paolo; Adami, Alessandro; Silvestrelli, Giorgio; Sessa, Maria; Cavallini, Anna; Marcheselli, Simona; Bonifati, Domenico Marco; Checcarelli, Nicoletta; Tancredi, Lucia; Chiti, Alberto; Del Zotto, Elisabetta; Spalloni, Alessandra; Giossi, Alessia; Volonghi, Irene; Costa, Paolo; Giacalone, Giacomo; Ferrazzi, Paola; Poli, Loris; Morotti, Andrea; Rasura, Maurizia; Simone, Anna Maria; Gamba, Massimo; Cerrato, Paolo; Micieli, Giuseppe; Melis, Maurizio; Massucco, Davide; De Giuli, Valeria; Iacoviello, Licia; Padovani, Alessandro

2014-04-22

Data on long-term risk and predictors of recurrent thrombotic events after ischemic stroke at a young age are limited. We followed 1867 patients with first-ever ischemic stroke who were 18 to 45 years of age (mean age, 36.8±7.1 years; women, 49.0%), as part of the Italian Project on Stroke in Young Adults (IPSYS). Median follow-up was 40 months (25th to 75th percentile, 53). The primary end point was a composite of ischemic stroke, transient ischemic attack, myocardial infarction, or other arterial events. One hundred sixty-three patients had recurrent thrombotic events (average rate, 2.26 per 100 person-years at risk). At 10 years, cumulative risk was 14.7% (95% confidence interval, 12.2%-17.9%) for primary end point, 14.0% (95% confidence interval, 11.4%-17.1%) for brain ischemia, and 0.7% (95% confidence interval, 0.4%-1.3%) for myocardial infarction or other arterial events. Familial history of stroke, migraine with aura, circulating antiphospholipid antibodies, discontinuation of antiplatelet and antihypertensive medications, and any increase of 1 traditional vascular risk factor were independent predictors of the composite end point in multivariable Cox proportional hazards analysis. A point-scoring system for each variable was generated by their β-coefficients, and a predictive score (IPSYS score) was calculated as the sum of the weighted scores. The area under the receiver operating characteristic curve of the 0- to 5-year score was 0.66 (95% confidence interval, 0.61-0.71; mean, 10-fold internally cross-validated area under the receiver operating characteristic curve, 0.65). Among patients with ischemic stroke aged 18 to 45 years, the long-term risk of recurrent thrombotic events is associated with modifiable, age-specific risk factors. The IPSYS score may serve as a simple tool for risk estimation.

How do blockings relate to heavy precipitation events in Europe?

NASA Astrophysics Data System (ADS)

Lenggenhager, Sina; Romppainen, Olivia; Brönnimann, Stefan; Croci-Maspoli, Mischa

2017-04-01

Atmospheric blockings are quasi-stationary high pressure systems that persist for several days. Due to their longevity, blockings can be key features for extreme weather events. While several studies have shown their relevant role for temperatures extremes, the link between blockings and extreme precipitation and floods is still poorly understood. A case study of a Swiss lake flood event in the year 2000 reveals how different processes connected to blockings can favour the development of a flood. First upstream blocks helped to form strongly elongated troughs that are known to be associated with heavy precipitation events south of the Alps. Second recurrent precipitation events upstream of a block led to a moistening of the catchment and an increase of the lake level. Third the progression of the upstream weather systems was slowed and thereby the precipitation period over a catchment prolonged. Additionally, cloud diabatic processes in the flood region contributed to the establishment and maintenance of blocking anticyclones. Based on this case study we extend our analysis to all of Europe. Focusing on flood relevant precipitation events, i.e. extreme precipitation events that last for several days and affect larger areas, we show that different regions in Europe have very distinct seasonal precipitation patterns. Hence there is a strong seasonality in the occurrence of extreme events, depending on the geographical region. We further suggest that for different precipitation regimes, the preferred location of blockings varies strongly. Heavy precipitation events in southern France, for example, are often observed during Scandinavian blockings, while heavy precipitation events in south-eastern Europe coincide more often with eastern North-Atlantic blockings.

Risk of bleeding and repeated bleeding events in prasugrel-treated patients: a review of data from the Japanese PRASFIT studies.

PubMed

Nishikawa, Masakatsu; Isshiki, Takaaki; Kimura, Takeshi; Ogawa, Hisao; Yokoi, Hiroyoshi; Miyazaki, Shunichi; Ikeda, Yasuo; Nakamura, Masato; Tanaka, Yuko; Saito, Shigeru

2017-04-01

Prasugrel is a third-generation thienopyridine that achieves potent platelet inhibition with less pharmacological variability than other thienopyridines. However, clinical experience suggests that prasugrel may be associated with a higher risk of de novo and recurrent bleeding events compared with clopidogrel in Japanese patients undergoing percutaneous coronary intervention (PCI). In this review, we evaluate the risk of bleeding in Japanese patients treated with prasugrel at the doses (loading/maintenance doses: 20/3.75 mg) adjusted for Japanese patients, evaluate the risk factors for bleeding in Japanese patients, and examine whether patients with a bleeding event are at increased risk of recurrent bleeding. This review covers published data and new analyses of the PRASFIT (PRASugrel compared with clopidogrel For Japanese patIenTs) trials of patients undergoing PCI for acute coronary syndrome or elective reasons. The bleeding risk with prasugrel was similar to that observed with the standard dose of clopidogrel (300/75 mg), including when bleeding events were re-classified using the Bleeding Academic Research Consortium criteria. The pharmacodynamics of prasugrel was not associated with the risk of bleeding events. The main risk factors for bleeding events were female sex, low body weight, advanced age, and presence of diabetes mellitus. Use of a radial puncture site was associated with a lower risk of bleeding during PCI than a femoral puncture site. Finally, the frequency and severity of recurrent bleeding events during continued treatment were similar between prasugrel and clopidogrel. In summary, this review provides important insights into the risk and types of bleeding events in prasugrel-treated patients.Trial registration numbers: JapicCTI-101339 and JapicCTI-111550.

The morphometric and stratigraphic framework for estimates of debris flow incidence in the North Cascades foothills, Washington State, USA

NASA Astrophysics Data System (ADS)

Kovanen, Dori J.; Slaymaker, Olav

2008-07-01

Active debris flow fans in the North Cascade Foothills of Washington State constitute a natural hazard of importance to land managers, private property owners and personal security. In the absence of measurements of the sediment fluxes involved in debris flow events, a morphological-evolutionary systems approach, emphasizing stratigraphy, dating, fan morphology and debris flow basin morphometry, was used. Using the stratigraphic framework and 47 radiocarbon dates, frequency of occurrence and relative magnitudes of debris flow events have been estimated for three spatial scales of debris flow systems: the within-fan site scale (84 observations); the fan meso-scale (six observations) and the lumped fan, regional or macro-scale (one fan average and adjacent lake sediments). In order to characterize the morphometric framework, plots of basin area v. fan area, basin area v. fan gradient and the Melton ruggedness number v. fan gradient for the 12 debris flow basins were compared with those documented for semi-arid and paraglacial fans. Basin area to fan area ratios were generally consistent with the estimated level of debris flow activity during the Holocene as reported below. Terrain analysis of three of the most active debris flow basins revealed the variety of modes of slope failure and sediment production in the region. Micro-scale debris flow event systems indicated a range of recurrence intervals for large debris flows from 106-3645 years. The spatial variation of these rates across the fans was generally consistent with previously mapped hazard zones. At the fan meso-scale, the range of recurrence intervals for large debris flows was 273-1566 years and at the regional scale, the estimated recurrence interval of large debris flows was 874 years (with undetermined error bands) during the past 7290 years. Dated lake sediments from the adjacent Lake Whatcom gave recurrence intervals for large sediment producing events ranging from 481-557 years over the past 3900 years and clearly discernible sedimentation events in the lacustrine sediments had a recurrence interval of 67-78 years over that same period.

Detecting independent and recurrent copy number aberrations using interval graphs.

PubMed

Wu, Hsin-Ta; Hajirasouliha, Iman; Raphael, Benjamin J

2014-06-15

Somatic copy number aberrations SCNAS: are frequent in cancer genomes, but many of these are random, passenger events. A common strategy to distinguish functional aberrations from passengers is to identify those aberrations that are recurrent across multiple samples. However, the extensive variability in the length and position of SCNA: s makes the problem of identifying recurrent aberrations notoriously difficult. We introduce a combinatorial approach to the problem of identifying independent and recurrent SCNA: s, focusing on the key challenging of separating the overlaps in aberrations across individuals into independent events. We derive independent and recurrent SCNA: s as maximal cliques in an interval graph constructed from overlaps between aberrations. We efficiently enumerate all such cliques, and derive a dynamic programming algorithm to find an optimal selection of non-overlapping cliques, resulting in a very fast algorithm, which we call RAIG (Recurrent Aberrations from Interval Graphs). We show that RAIG outperforms other methods on simulated data and also performs well on data from three cancer types from The Cancer Genome Atlas (TCGA). In contrast to existing approaches that employ various heuristics to select independent aberrations, RAIG optimizes a well-defined objective function. We show that this allows RAIG to identify rare aberrations that are likely functional, but are obscured by overlaps with larger passenger aberrations. http://compbio.cs.brown.edu/software. © The Author 2014. Published by Oxford University Press.

Prevalence, risk factors and secondary prevention of stroke recurrence in eight countries from south, east and southeast asia: a scoping review.

PubMed

Chin, Y Y; Sakinah, H; Aryati, A; Hassan, B M

2018-04-01

In most Asian countries, stroke is one of the major causes of mortality. A stroke event is life-changing for stroke survivors, which results in either mortality or disability. Therefore, this study comprehensively focuses on prevalence, risk factors, and secondary prevention for stroke recurrence identified in South, East, and Southeast Asian countries. This scoping review uses the methodological framework of Arksey and O'Malley. A comprehensive search of academic journals (English) on this topic published from 2007 to 2017 was conducted. A total of 22 studies were selected from 585 studies screened from the electronic databases. First-year stroke recurrence rates are in the range of 2.2% to 25.4%. Besides that, modifiable risk factors are significantly associated with pathophysiological factors (hypertension, ankle-brachial pressure index, atherogenic dyslipidaemia, diabetes mellitus, metabolic syndrome, and atrial fibrillation) and lifestyle factors (obesity, smoking, physical inactivity, and high salt intake). Furthermore, age, previous history of cerebrovascular events, and stroke subtype are also significant influence risk factors for recurrence. A strategic secondary prevention method for recurrent stroke is health education along with managing risk factors through a combination of appropriate lifestyle intervention and pharmacological therapy. To prevent recurrent stroke, health intervention should be geared towards changing lifestyle to embody a healthier approach to life. This is of great importance to public health and stroke survivors' quality of life.

Coffee and tea consumption in relation to prostate cancer prognosis

PubMed Central

Geybels, Milan S.; Neuhouser, Marian L.; Wright, Jonathan L.; Stott-Miller, Marni; Stanford, Janet L.

2013-01-01

Background Bioactive compounds found in coffee and tea may delay the progression of prostate cancer. Methods We investigated associations of pre-diagnostic coffee and tea consumption with risk of prostate cancer recurrence/progression. Study participants were men diagnosed with prostate cancer in 2002–2005 in King County, Washington, USA. We assessed the usual pattern of coffee and tea consumption two years before diagnosis date. Prostate cancer outcome events were identified using a detailed follow-up survey. Multivariable Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results The analysis of coffee intake in relation to prostate cancer recurrence/progression included 630 patients with a median follow-up of 6.4 years, during which 140 prostate cancer recurrence/progression events were recorded. Approximately 61% of patients consumed at least one cup of coffee per day. Coffee consumption was associated with a reduced risk of prostate cancer recurrence/progression; the adjusted HR for ≥4 cups/day versus ≤1 cup/week was 0.41 (95% CI: 0.20, 0.81; P for trend = 0.01). Approximately 14% of patients consumed one or more cups of tea per day, and tea consumption was unrelated to prostate cancer recurrence/progression. Conclusion Results indicate that pre-diagnostic coffee consumption is associated with a lower risk of prostate cancer recurrence/progression. This finding will require replication in larger studies. PMID:23907772

Wasatch fault zone, Utah - segmentation and history of Holocene earthquakes

USGS Publications Warehouse

Machette, Michael N.; Personius, Stephen F.; Nelson, Alan R.; Schwartz, David P.; Lund, William R.

1991-01-01

The Wasatch fault zone (WFZ) forms the eastern boundary of the Basin and Range province and is the longest continuous, active normal fault (343 km) in the United States. It underlies an urban corridor of 1.6 million people (80% of Utah's population) representing the largest earthquake risk in the interior of the western United States. The authors have used paleoseismological data to identify 10 discrete segments of the WFZ. Five are active, medial segments with Holocene slip rates of 1-2 mm a-1, recurrence intervals of 2000-4000 years and average lengths of about 50 km. Five are less active, distal segments with mostly pre-Holocene surface ruptures, late Quaternary slip rates of <0.5 mm a-1, recurrence intervals of ???10,000 years and average lengths of about 20 km. Surface-faulting events on each of the medial segments of the WFZ formed 2-4-m-high scarps repeatedly during the Holocene. Paleoseismological records for the past 6000 years indicate that a major surface-rupturing earthquake has occurred along one of the medial segments about every 395 ?? 60 years. However, between about 400 and 1500 years ago, the WFZ experienced six major surface-rupturing events, an average of one event every 220 years, or about twice as often as expected from the 6000-year record. Evidence has been found that surface-rupturing events occurred on the WFZ during the past 400 years, a time period which is twice the average intracluster recurrence interval and equal to the average Holocene recurrence interval.

Flood of April 2007 in Southern Maine

USGS Publications Warehouse

Lombard, Pamela J.

2009-01-01

Up to 8.5 inches of rain fell from April 15 through 18, 2007, in southern Maine. The rain - in combination with up to an inch of water from snowmelt - resulted in extensive flooding. York County, Maine, was declared a presidential disaster area following the event. The U.S. Geological Survey, in cooperation with the Federal Emergency Management Agency (FEMA), determined peak streamflows and recurrence intervals at 24 locations and peak water-surface elevations at 63 sites following the April 2007 flood. Peak streamflows were determined with data from continuous-record streamflow-gaging stations where available and through hydraulic models where station data were not available. The flood resulted in peak streamflows with recurrence intervals greater than 100 years throughout most of York County, and recurrence intervals up to 50 years in Cumberland County. Peak flows for selected recurrence intervals varied from less than 10 percent to greater than 100 percent different than those in the current FEMA flood-insurance studies due to additional data or newer regression equations. Water-surface elevations observed during the April 2007 flood were bracketed by elevation profiles in FEMA flood-insurance studies with the same recurrence intervals as the recurrence intervals bracketing the observed peak streamflows at seven sites, with higher elevation-profile recurrence intervals than streamflow recurrence intervals at six sites, and with lower elevation-profile recurrence intervals than streamflow recurrence intervals at one site. The April 2007 flood resulted in higher peak flows and water-surface elevations than the flood of May 2006 in coastal locations in York County, and lower peak flows and water-surface elevations than the May 2006 flood further from the coast and in Cumberland County. The Mousam River watershed with over 13 dams and reservoirs was severely impacted by both events. Analyses indicate that the April 2007 peak streamflows in the Mousam River watershed occurred despite the fact that up to 287 million ft3 of runoff was stored by 13 dams and reservoirs.

Association of matrix metalloproteinase-3 gene 5A/6A polymorphism with the recurrence of ischemic stroke: A prospective observational study.

PubMed

Huang, Xiaoya; Ye, Qiang; Zhang, Zheng; Huang, Xiangdong; Zhu, Zhenguo; Chen, Yanyan; Li, Jia; Chen, Siyan; Xia, Niange; Mao, Xinlei; Han, Liya; Ye, Zusen

2017-11-01

Studies have demonstrated that matrix metalloproteinase-3 (MMP-3) is involved in the development and progression of atherosclerosis. However, there is no information available on the association of MMP-3 5A/6A polymorphism with recurrent ischemic stroke (IS) in different IS subtypes. We investigated the potential associations between MMP-3 serum level and -1171 5A/6A polymorphism and the recurrence of IS in a Chinese population. Consecutive acute first-ever IS patients were enrolled between August 2008 and October 2013. The genotypes of MMP-3 5A/6A polymorphism were determined using polymerase chain reaction-restriction fragment length polymorphism. IS recurrence was monitored after the index event and multivariate Cox proportional hazards model was constructed to identify factors related to future IS recurrence. A total of 1282 eligible patients were enrolled. During a 2-year follow-up period, 157 (12.25%) patients had recurrent events. MMP-3 level was significantly higher in patients with 5A/6A or 5A/5A genotype (22.72±7.29ng/ul) than in patients with 6A/6A genotype (20.48±7.58ng/ul), P<0.001. No interaction between MMP-3 5A/6A polymorphism and the risk of recurrence in total IS patients was found. The variant 5A/6A+5A/5A genotype and the 5A allele were significantly associated with a high risk of recurrence for large-artery atherosclerosis (LAA) (multivariate-adjusted, P=0.002, 0.001, respectively), but not for small-artery occlusion and cardioembolism. Our finding showed that MMP-3 5A/6A may be a useful biomarker for predicting recurrence for LAA stroke patients and 5A allele carrier may bear a higher risk of recurrence among patients with the subtype of LAA. Copyright © 2017. Published by Elsevier B.V.

Deciphering membrane-associated molecular processes in target tissue of autoimmune uveitis by label-free quantitative mass spectrometry.

PubMed

Hauck, Stefanie M; Dietter, Johannes; Kramer, Roxane L; Hofmaier, Florian; Zipplies, Johanna K; Amann, Barbara; Feuchtinger, Annette; Deeg, Cornelia A; Ueffing, Marius

2010-10-01

Autoimmune uveitis is a blinding disease presenting with autoantibodies against eye-specific proteins as well as autoagressive T cells invading and attacking the immune-privileged target tissue retina. The molecular events enabling T cells to invade and attack the tissue have remained elusive. Changes in membrane protein expression patterns between diseased and healthy stages are especially interesting because initiating events of disease will most likely occur at membranes. Since disease progression is accompanied with a break-down of the blood-retinal barrier, serum-derived proteins mask the potential target tissue-related changes. To overcome this limitation, we used membrane-enriched fractions derived from retinas of the only available spontaneous animal model for the disease equine recurrent uveitis, and compared expression levels by a label-free LC-MSMS-based strategy to healthy control samples. We could readily identify a total of 893 equine proteins with 57% attributed to the Gene Ontology project term "membrane." Of these, 179 proteins were found differentially expressed in equine recurrent uveitis tissue. Pathway enrichment analyses indicated an increase in proteins related to antigen processing and presentation, TNF receptor signaling, integrin cell surface interactions and focal adhesions. Additionally, loss of retina-specific proteins reflecting decrease of vision was observed as well as an increase in Müller glial cell-specific proteins indicating glial reactivity. Selected protein candidates (caveolin 1, integrin alpha 1 and focal adhesion kinase) were validated by immunohistochemistry and tissue staining pattern pointed to a significant increase of these proteins at the level of the outer limiting membrane which is part of the outer blood-retinal barrier. Taken together, the membrane enrichment in combination with LC-MSMS-based label-free quantification greatly increased the sensitivity of the comparative tissue profiling and resulted in detection of novel molecular pathways related to equine recurrent uveitis.

Percutaneous Occlusion of the Left Atrial Appendage with the Watchman Device in an Active Duty Sailor with Atrial Fibrillation and Recurrent Thromboembolism Despite Appropriate Use of Oral Anticoagulation.

PubMed

Cox, Justin M; Choi, Anthony J; Oakley, Luke S; Francisco, Gregory M; Nayak, Keshav R

2018-05-23

Atrial fibrillation is the most common significant cardiac arrhythmia and is associated with a five-fold increased risk of stroke from thromboembolism. Over 94% of these emboli arise from the left atrial appendage. Systemic embolic phenomena are rare, accounting for less than 1 out of 10 of all embolic events, but have a similar prevention strategy. Anticoagulation significantly reduces the risk of these events, and thus forms the cornerstone of therapy for most patients with atrial fibrillation. Left atrial appendage occlusion with the Watchman device is a recently approved alternative for stroke prevention in selected patients. We present a case of an active duty U.S. Navy sailor at low risk for thromboembolism who nonetheless suffered recurrent thromboembolic events despite appropriate anticoagulation, and thus underwent Watchman implantation. The therapy in this case will ideally provide a lifetime of protection from recurrent systemic embolization while allowing the patient to continue his active duty military career without restriction due to oral anticoagulation.

A CATALOG OF SOLAR X-RAY PLASMA EJECTIONS OBSERVED BY THE SOFT X-RAY TELESCOPE ON BOARD YOHKOH

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tomczak, M.; Chmielewska, E., E-mail: tomczak@astro.uni.wroc.pl, E-mail: chmielewska@astro.uni.wroc.pl

2012-03-01

A catalog of X-ray plasma ejections (XPEs) observed by the Soft X-ray Telescope on board the Yohkoh satellite has been recently developed in the Astronomical Institute of University of Wroclaw. The catalog contains records of 368 events observed in years 1991-2001 including movies and cross-references to associated events like flares and coronal mass ejections (CMEs). One hundred sixty-three XPEs out of 368 in the catalog were not reported until now. A new classification scheme of XPEs is proposed in which morphology, kinematics, and recurrence are considered. The relation between individual subclasses of XPEs and the associated events was investigated. Themore » results confirm that XPEs are strongly inhomogeneous, responding to different processes that occur in the solar corona. A subclass of erupting loop-like XPEs is a promising candidate to be a high-temperature precursor of CMEs.« less

Cost comparison of continued anticoagulation with rivaroxaban versus placebo based on the 1-year EINSTEIN-Extension trial efficacy and safety results.

PubMed

Wells, Philip S; Lensing, Anthonie W A; Haskell, Lloyd; Levitan, Bennett; Laliberté, François; Durkin, Michael; Ashton, Veronica; Xiao, Yongling; Crivera, Concetta; Lejeune, Dominique; Schein, Jeff; Lefebvre, Patrick

2018-06-01

The EINSTEIN-Extension trial (EINSTEIN-EXT) found that continued treatment with rivaroxaban for an additional 6 or 12 months (vs placebo) after 6-12 months of initial anticoagulation significantly reduced the risk of recurrent venous thromboembolism (VTE) with a small non-significant increased risk of major bleeding (none fatal or in critical site). This study aimed to compare total healthcare cost between rivaroxaban and placebo, based on the EINSTEIN-EXT event rates. Total healthcare cost was calculated as the sum of treatment and clinical event costs from a US managed care perspective. Treatment duration and event rates were obtained from the EINSTEIN-EXT study. Adjustment on treatment duration was made by assuming a 10% non-adherence rate. Drug costs were based on wholesale acquisition costs. Cost estimates for clinical events (i.e. recurrent deep vein thrombosis [DVT], recurrent pulmonary embolism, major bleeding, clinically relevant non-major bleeding) were determined from the literature. Results were examined over a ±20% range of each cost component and over 95% confidence intervals (CIs) of event rate differences in deterministic (one-way) and probabilistic sensitivity analyses (PSA). Total healthcare cost was $1,454 lower for rivaroxaban-treated (vs placebo-treated) patients in the base-case, with a lower clinical event cost fully offsetting drug cost. The cost savings of recurrent DVT alone (-$3,102) was greater than drug cost ($2,723). Total healthcare cost remained lower for rivaroxaban in the majority (73%) of PSA (cost difference [95% CI] = -$1,454 [-$2,396, $1,231]). This study was conducted over the 1-year observation period of the EINSTEIN-EXT trial, which limited "real-world" applicability and examination of long-term economic impact. Assumptions on drug and clinical event costs were US-based and, thus, not applicable to other healthcare systems. Total healthcare costs were estimated to be lower for patients continuing rivaroxaban therapy compared to those receiving placebo in VTE patients who had completed 6-12 months of VTE treatment.

Prognostic Significance of Blood Pressure Variability on Beat-to-Beat Monitoring After Transient Ischemic Attack and Stroke.

PubMed

Webb, Alastair J S; Mazzucco, Sara; Li, Linxin; Rothwell, Peter M

2018-01-01

Visit-to-visit and day-to-day blood pressure (BP) variability (BPV) predict an increased risk of cardiovascular events but only reflect 1 form of BPV. Beat-to-beat BPV can be rapidly assessed and might also be predictive. In consecutive patients within 6 weeks of transient ischemic attack or nondisabling stroke (Oxford Vascular Study), BPV (coefficient of variation) was measured beat-to-beat for 5 minutes (Finometer), day-to-day for 1 week on home monitoring (3 readings, 3× daily), and on awake ambulatory BP monitoring. BPV after 1-month standard treatment was related (Cox proportional hazards) to recurrent stroke and cardiovascular events for 2 to 5 years, adjusted for mean systolic BP. Among 520 patients, 26 had inadequate beat-to-beat recordings, and 22 patients were in atrial fibrillation. Four hundred five patients had all forms of monitoring. Beat-to-beat BPV predicted recurrent stroke and cardiovascular events independently of mean systolic BP (hazard ratio per group SD, stroke: 1.47 [1.12-1.91]; P =0.005; cardiovascular events: 1.41 [1.08-1.83]; P =0.01), including after adjustment for age and sex (stroke: 1.47 [1.12-1.92]; P =0.005) and all risk factors (1.40 [1.00-1.94]; P =0.047). Day-to-day BPV was less strongly associated with stroke (adjusted hazard ratio, 1.29 [0.97-1.71]; P =0.08) but similarly with cardiovascular events (1.41 [1.09-1.83]; P =0.009). BPV on awake ambulatory BP monitoring was nonpredictive (stroke: 0.89 [0.59-1.35]; P =0.59; cardiovascular events: 1.08 [0.77-1.52]; P =0.65). Despite a weak correlation ( r =0.119; P =0.02), beat-to-beat BPV was associated with risk of recurrent stroke independently of day-to-day BPV (1.41 [1.05-1.90]; P =0.02). Beat-to-beat BPV predicted recurrent stroke and cardiovascular events, independently of mean systolic BP and risk factors but short-term BPV on ambulatory BP monitoring did not. Beat-to-beat BPV may be a useful additional marker of cardiovascular risk. © 2017 The Authors.

A plate boundary earthquake record from a wetland adjacent to the Alpine fault in New Zealand refines hazard estimates

NASA Astrophysics Data System (ADS)

Cochran, U. A.; Clark, K. J.; Howarth, J. D.; Biasi, G. P.; Langridge, R. M.; Villamor, P.; Berryman, K. R.; Vandergoes, M. J.

2017-04-01

Discovery and investigation of millennial-scale geological records of past large earthquakes improve understanding of earthquake frequency, recurrence behaviour, and likelihood of future rupture of major active faults. Here we present a ∼2000 year-long, seven-event earthquake record from John O'Groats wetland adjacent to the Alpine fault in New Zealand, one of the most active strike-slip faults in the world. We linked this record with the 7000 year-long, 22-event earthquake record from Hokuri Creek (20 km along strike to the north) to refine estimates of earthquake frequency and recurrence behaviour for the South Westland section of the plate boundary fault. Eight cores from John O'Groats wetland revealed a sequence that alternated between organic-dominated and clastic-dominated sediment packages. Transitions from a thick organic unit to a thick clastic unit that were sharp, involved a significant change in depositional environment, and were basin-wide, were interpreted as evidence of past surface-rupturing earthquakes. Radiocarbon dates of short-lived organic fractions either side of these transitions were modelled to provide estimates for earthquake ages. Of the seven events recognised at the John O'Groats site, three post-date the most recent event at Hokuri Creek, two match events at Hokuri Creek, and two events at John O'Groats occurred in a long interval during which the Hokuri Creek site may not have been recording earthquakes clearly. The preferred John O'Groats-Hokuri Creek earthquake record consists of 27 events since ∼6000 BC for which we calculate a mean recurrence interval of 291 ± 23 years, shorter than previously estimated for the South Westland section of the fault and shorter than the current interseismic period. The revised 50-year conditional probability of a surface-rupturing earthquake on this fault section is 29%. The coefficient of variation is estimated at 0.41. We suggest the low recurrence variability is likely to be a feature of other strike-slip plate boundary faults similar to the Alpine fault.

RAG-mediated recombination is the predominant driver of oncogenic rearrangement in ETV6-RUNX1 acute lymphoblastic leukemia

PubMed Central

Papaemmanuil, Elli; Rapado, Inmaculada; Li, Yilong; Potter, Nicola E; Wedge, David C; Tubio, Jose; Alexandrov, Ludmil B; Van Loo, Peter; Cooke, Susanna L; Marshall, John; Martincorena, Inigo; Hinton, Jonathan; Gundem, Gunes; van Delft, Frederik W; Nik-Zainal, Serena; Jones, David R; Ramakrishna, Manasa; Titley, Ian; Stebbings, Lucy; Leroy, Catherine; Menzies, Andrew; Gamble, John; Robinson, Ben; Mudie, Laura; Raine, Keiran; O’Meara, Sarah; Teague, Jon W; Butler, Adam P; Cazzaniga, Giovanni; Biondi, Andrea; Zuna, Jan; Kempski, Helena; Muschen, Markus; Ford, Anthony M; Stratton, Michael R; Greaves, Mel; Campbell, Peter J

2014-01-01

The ETV6-RUNX1 fusion gene, found in 25% of childhood acute lymphoblastic leukemia (ALL), is acquired in utero but requires additional somatic mutations for overt leukemia. We used exome and low-coverage whole-genome sequencing to characterize secondary events associated with leukemic transformation. RAG-mediated deletions emerge as the dominant mutational process, characterized by recombination signal sequence motifs near the breakpoints; incorporation of non-templated sequence at the junction; ~30-fold enrichment at promoters and enhancers of genes actively transcribed in B-cell development and an unexpectedly high ratio of recurrent to non-recurrent structural variants. Single cell tracking shows that this mechanism is active throughout leukemic evolution with evidence of localized clustering and re-iterated deletions. Integration of point mutation and rearrangement data identifies ATF7IP and MGA as two new tumor suppressor genes in ALL. Thus, a remarkably parsimonious mutational process transforms ETV6-RUNX1 lymphoblasts, targeting the promoters, enhancers and first exons of genes that normally regulate B-cell differentiation. PMID:24413735

Impact of sex and traditional cardiovascular risk factors on the risk of recurrent venous thromboembolism: results from the German MAISTHRO Registry.

PubMed

Linnemann, Birgit; Zgouras, Dimitrios; Schindewolf, Marc; Schwonberg, Jan; Jarosch-Preusche, Marie; Lindhoff-Last, Edelgard

2008-03-01

As arterial and venous thrombosis share common risk factors, a link between arterial and venous thrombosis has been suggested recently. Therefore, we aimed to investigate the impact of established cardiovascular risk factors on the risk of recurrent venous thromboembolism (VTE). With a cross-sectional study design, we analyzed the data of 1006 patients (582 F, 424 M) consecutively treated in our outpatient department for VTE (i.e. lower extremity deep vein thrombosis and/or pulmonary embolism) and registered in the MAISTHRO (MAin-ISar-THROmbosis) database. Of the total cohort, 324 (32.2%) patients suffered a recurrent VTE. Compared with the patients with a single thromboembolic event, patients with recurrent VTE were more frequently male (39.4 vs. 27.0%, P < 0.001). In univariate analysis, the relative risk of recurrent VTE was 1.9 [95% confidence interval (CI) 1.53-2.39] for male sex and 1.6 (1.25-1.95) for age over 50 years (PAOD). After adjustments for age, sex, thrombophilia and other common VTE risk factors, male sex [hazard ratio (HR) = 1.7 (1.38-21.9)] and arterial hypertension [HR = 1.4 (1.05-1.78)] were independent risk factors of recurrent VTE. The higher risk in men than in women persisted even after the exclusion of women with transient hormonal risk factors [HR = 1.57 (1.19-2.07)]. In contrast, no association between the presence of diabetes, obesity, hypercholesterolemia or smoking and the risk of VTE recurrence was observed. Male sex and arterial hypertension are independently associated with an increased risk of recurrent VTE after termination of anticoagulant therapy for the first VTE event.

Poor Prognosis after Second Locoregional Recurrences in the CALOR Trial

PubMed Central

Wapnir, Irene L.; Gelber, Shari; Anderson, Stewart J.; Mamounas, Eleftherios P.; Robidoux, André; Martín, Miguel; Nortier, Johan W.R.; Geyer, Charles E.; Paterson, Alexander H.G.; Láng, István; Price, Karen N.; Coates, Alan S.; Gelber, Richard D.; Rastogi, Priya; Regan, Meredith M.; Wolmark, Norman; Aebi, Stefan

2016-01-01

Purpose Isolated locoregional recurrences (ILRR) of breast cancer confer a significant risk of developing distant metastasis. Management practices and second-ILRR events in the CALOR trial are investigated. Methods 162 patients with ILRR were randomly assigned to receive post-operative chemotherapy, or no chemotherapy. Descriptive statistics characterize outcomes according to local therapy and the influence of hormone receptor status on subsequent recurrences. Competing risk regression models, Kaplan-Meier estimates, and Cox proportional hazards models evaluate associations between treatment, site of second recurrence and outcome. Results The median follow-up was 4.9 years. Of the 98 patients who received breast-conserving primary surgery (BCS), 89 had an ipsilateral-breast tumor recurrence (IBTR); salvage mastectomy was performed in 73 and repeat lumpectomy in 16. Another 8 had nodal-ILRR and 1 chest wall-ILRR. Among 64 whose primary surgery was mastectomy, 52 had chest wall/skin-ILRR and 12 nodal-ILRR. Fifteen patients developed a second-ILRR at a median time from ILRR of 1.6 years (range: 0.08–4.8). All second-ILRR occurred in patients with PR-negative ILRR. Seven (47%) of 15 patients with second-ILRR, and 19 (51%) of 37 with a distant recurrence have died. On multivariable analysis, chemotherapy for the primary cancer (HR 3.55, 95% CI 1.15–10.9, p=0.03) and time interval (continuous) from primary surgery (HR 0.87 95% CI 0.75–1.00, p=0.05) were significant predictors of survival following either a second-ILRR or distant recurrence. Conclusions Second-ILRRs represented about one-third of all recurrence events after ILRR and all were PR negative. These second-ILRRs, as well as distant metastases, portend an unfavorable outcome. PMID:27663567

On the Bimodality of ENSO Cycle Extremes

NASA Technical Reports Server (NTRS)

Wilson, Robert M.

1999-01-01

On the basis of sea surface temperature in the Nino 3.4 region (5 deg N-5 deg S, 120 deg- 170 deg W) during the interval of 1950-1997, Kevin Trenberth previously has identified some 16 El Nino and 10 La Nina, these 26 events representing the extremes of the quasi-periodic El Nino-Southern Oscillation (ENSO) cycle. Runs testing shows that the duration and recurrence period associated with these extremes vary randomly, as does the sequencing of the extremes. Hence, the frequency of occurrence of these events during the 1990s, especially, for El Nino should not be construed as being significantly different from that of previous epochs. Additionally, the distribution of duration for both El Nino and La Nina looks bimodal, consisting of two preferred modes - about 8 and 16 months in length for El Nino and about 9 and 18 months in length for La Nina. Likewise, the distribution of recurrence period, especially, for El Nino looks bimodal, consisting of two preferred modes - about 21 and 50 months in length. Scatter plots of the recurrence period versus duration for El Nino strongly suggest preferential associations between them, linking shorter (longer) duration with shorter (longer) recurrence period. Because the last known onset of El Nino occurred in April 1997 and the event was of longer than average duration, one infers that the onset of the next expected El Nino will not occur until February 2000 or later.

Cure frailty models for survival data: application to recurrences for breast cancer and to hospital readmissions for colorectal cancer.

PubMed

Rondeau, Virginie; Schaffner, Emmanuel; Corbière, Fabien; Gonzalez, Juan R; Mathoulin-Pélissier, Simone

2013-06-01

Owing to the natural evolution of a disease, several events often arise after a first treatment for the same subject. For example, patients with a primary invasive breast cancer and treated with breast conserving surgery may experience breast cancer recurrences, metastases or death. A certain proportion of subjects in the population who are not expected to experience the events of interest are considered to be 'cured' or non-susceptible. To model correlated failure time data incorporating a surviving fraction, we compare several forms of cure rate frailty models. In the first model already proposed non-susceptible patients are those who are not expected to experience the event of interest over a sufficiently long period of time. The other proposed models account for the possibility of cure after each event. We illustrate the cure frailty models with two data sets. First to analyse time-dependent prognostic factors associated with breast cancer recurrences, metastases, new primary malignancy and death. Second to analyse successive rehospitalizations of patients diagnosed with colorectal cancer. Estimates were obtained by maximization of likelihood using SAS proc NLMIXED for a piecewise constant hazards model. As opposed to the simple frailty model, the proposed methods demonstrate great potential in modelling multivariate survival data with long-term survivors ('cured' individuals).

Recurrent secondary spontaneous pneumothorax in silicosis: a case report.

PubMed

Amanda, Gina; Taufik, Feni Fitriani

2016-01-01

Silicosis is an occupational lung disease which is caused by inhalation and accumulation of crystalline silica particles in the lung. It commonly occurs in workers involved in quarrying, mining, sandblasting, tunneling, foundry work, and ceramics. Pneumothorax is one of the complications of silicosis with pleural involvement. The occurrence of pneumothorax in a patient with silicosis is a rare event, but it may be fatal. The rate of pneumothorax recurrence in silicosis is usually low. We report a case of recurrent secondary spontaneous pneumothorax in silicosis.

Prevalence of epilepsy and seizure disorders as causes of apparent life- threatening event (ALTE) in children admitted to a tertiary hospital.

PubMed

Anjos, Alessandra Marques dos; Nunes, Magda Lahorgue

2009-09-01

To determine the prevalence and describe clinical characteristics of seizure disorders and epilepsy as causes of apparent life- threatening event (ALTE) in children admitted at the emergency and followed in a tertiary hospital. Cross-sectional study with prospective data collection using specific guidelines to determine the etiology of ALTE. During the study, 30 (4.2%) children admitted to the hospital had a diagnosis of ALTE. There was a predominance of males (73%) and term infants (70%). Neonatal neurological disorders and neuropsychomotor development delay were found respectively in 13.4% and 10% of the cases. Etiological investigation revealed that 50% of the cases were idiopathic, and 13.4% were caused by epilepsy or seizure disorders. Although all patients had recurrent ALTE events, epilepsy had not been previously suspected. Epilepsy should be included in the differential diagnosis of ALTE, particularly when events are recurrent.

A novel joint-processing adaptive nonlinear equalizer using a modular recurrent neural network for chaotic communication systems.

PubMed

Zhao, Haiquan; Zeng, Xiangping; Zhang, Jiashu; Liu, Yangguang; Wang, Xiaomin; Li, Tianrui

2011-01-01

To eliminate nonlinear channel distortion in chaotic communication systems, a novel joint-processing adaptive nonlinear equalizer based on a pipelined recurrent neural network (JPRNN) is proposed, using a modified real-time recurrent learning (RTRL) algorithm. Furthermore, an adaptive amplitude RTRL algorithm is adopted to overcome the deteriorating effect introduced by the nesting process. Computer simulations illustrate that the proposed equalizer outperforms the pipelined recurrent neural network (PRNN) and recurrent neural network (RNN) equalizers. Copyright © 2010 Elsevier Ltd. All rights reserved.

Paleoseismic Evidence for Recurrence of Earthquakes near Charleston, South Carolina

NASA Astrophysics Data System (ADS)

Talwani, Pradeep; Cox, John

1985-07-01

A destructive earthquake that occurred in 1886 near Charleston, South Carolina, was associated with widespread liquefaction of shallow sand structures and their extravasation to the surface. Several seismically induced paleoliquefaction structures preserved within the shallow sediments in the meizoseismal area of the 1886 event were identified. Field evidence and radiocarbon dates suggest that at least two earthquakes of magnitudes greater than 6.2 preceded the 1886 event in the past 3000 to 3700 years. The evidence yielded an initial estimate of about 1500 to 1800 years for the maximum recurrence of destructive, intraplate earthquakes in the Charleston region.

Central sleep apnea detection from ECG-derived respiratory signals. Application of multivariate recurrence plot analysis.

PubMed

Maier, C; Dickhaus, H

2010-01-01

This study examines the suitability of recurrence plot analysis for the problem of central sleep apnea (CSA) detection and delineation from ECG-derived respiratory (EDR) signals. A parameter describing the average length of vertical line structures in recurrence plots is calculated at a time resolution of 1 s as 'instantaneous trapping time'. Threshold comparison of this parameter is used to detect ongoing CSA. In data from 26 patients (duration 208 h) we assessed sensitivity for detection of CSA and mixed apnea (MSA) events by comparing the results obtained from 8-channel Holter ECGs to the annotations (860 CSA, 480 MSA) of simultaneously registered polysomnograms. Multivariate combination of the EDR from different ECG leads improved the detection accuracy significantly. When all eight leads were considered, an average instantaneous vertical line length above 5 correctly identified 1126 of the 1340 events (sensitivity 84%) with a total number of 1881 positive detections. We conclude that recurrence plot analysis is a promising tool for detection and delineation of CSA epochs from EDR signals with high time resolution. Moreover, the approach is likewise applicable to directly measured respiratory signals.

Phase II trial of CH5424802 (alectinib hydrochloride) for recurrent or refractory ALK-positive anaplastic large cell lymphoma: study protocol for a non-randomized non-controlled trial.

PubMed

Nagai, Hirokazu; Fukano, Reiji; Sekimizu, Masahiro; Kada, Akiko; M Saito, Akiko; Asada, Ryuta; Mori, Tetsuya

2017-08-01

Currently, a standard therapy has not been established for recurrent or refractory anaplastic lymphoma kinase-positive anaplastic large cell lymphoma. While there are many treatment options, such as hematopoietic stem cell transplantation, patients with resistant disease to conventional chemotherapies have particularly poor prognosis. There is urgent need to develop new drugs because of the lack of a standard therapy and poor prognoses. This phase II trial is designed for evaluating the efficacy and safety of alectinib hydrochloride for patients with recurrent or refractory anaplastic lymphoma kinase -positive anaplastic large cell lymphoma. The primary endpoint is the response rate according to the Revised Response Criteria for Malignant Lymphoma. The secondary endpoints are pharmacokinetics, safety in children, complete response rate, response duration, progression-free survival, event-free survival, overall survival, and adverse events. The results of this trial will be the pivotal data for the drug approval of alectinib hydrochloride for recurrent or refractory anaplastic lymphoma kinase-positive anaplastic large cell lymphoma.

Response of Jupiter's Aurora to Plasma Mass Loading Rate Monitored by the Hisaki Satellite During Volcanic Eruptions at Io

NASA Astrophysics Data System (ADS)

Kimura, T.; Hiraki, Y.; Tao, C.; Tsuchiya, F.; Delamere, P. A.; Yoshioka, K.; Murakami, G.; Yamazaki, A.; Kita, H.; Badman, S. V.; Fukazawa, K.; Yoshikawa, I.; Fujimoto, M.

2018-03-01

The production and transport of plasma mass are essential processes in the dynamics of planetary magnetospheres. At Jupiter, it is hypothesized that Io's volcanic plasma carried out of the plasma torus is transported radially outward in the rotating magnetosphere and is recurrently ejected as plasmoid via tail reconnection. The plasmoid ejection is likely associated with particle energization, radial plasma flow, and transient auroral emissions. However, it has not been demonstrated that plasmoid ejection is sensitive to mass loading because of the lack of simultaneous observations of both processes. We report the response of plasmoid ejection to mass loading during large volcanic eruptions at Io in 2015. Response of the transient aurora to the mass loading rate was investigated based on a combination of Hisaki satellite monitoring and a newly developed analytic model. We found that the transient aurora frequently recurred at a 2-6 day period in response to a mass loading increase from 0.3 to 0.5 t/s. In general, the recurrence of the transient aurora was not significantly correlated with the solar wind, although there was an exceptional event with a maximum emission power of 10 TW after the solar wind shock arrival. The recurrence of plasmoid ejection requires the precondition that an amount comparable to the total mass of magnetosphere, 1.5 Mt, is accumulated in the magnetosphere. A plasmoid mass of more than 0.1 Mt is necessary in case that the plasmoid ejection is the only process for mass release.

Spatial Distribution of the Coefficient of Variation and Bayesian Forecast for the Paleo-Earthquakes in Japan

NASA Astrophysics Data System (ADS)

Nomura, Shunichi; Ogata, Yosihiko

2016-04-01

We propose a Bayesian method of probability forecasting for recurrent earthquakes of inland active faults in Japan. Renewal processes with the Brownian Passage Time (BPT) distribution are applied for over a half of active faults in Japan by the Headquarters for Earthquake Research Promotion (HERP) of Japan. Long-term forecast with the BPT distribution needs two parameters; the mean and coefficient of variation (COV) for recurrence intervals. The HERP applies a common COV parameter for all of these faults because most of them have very few specified paleoseismic events, which is not enough to estimate reliable COV values for respective faults. However, different COV estimates are proposed for the same paleoseismic catalog by some related works. It can make critical difference in forecast to apply different COV estimates and so COV should be carefully selected for individual faults. Recurrence intervals on a fault are, on the average, determined by the long-term slip rate caused by the tectonic motion but fluctuated by nearby seismicities which influence surrounding stress field. The COVs of recurrence intervals depend on such stress perturbation and so have spatial trends due to the heterogeneity of tectonic motion and seismicity. Thus we introduce a spatial structure on its COV parameter by Bayesian modeling with a Gaussian process prior. The COVs on active faults are correlated and take similar values for closely located faults. It is found that the spatial trends in the estimated COV values coincide with the density of active faults in Japan. We also show Bayesian forecasts by the proposed model using Markov chain Monte Carlo method. Our forecasts are different from HERP's forecast especially on the active faults where HERP's forecasts are very high or low.

Thrombectomy for ischemic stroke: meta-analyses of recurrent strokes, vasospasms, and subarachnoid hemorrhages.

PubMed

Emprechtinger, Robert; Piso, Brigitte; Ringleb, Peter A

2017-03-01

Mechanical thrombectomy with stent retrievers is an effective treatment for patients with ischemic stroke. Results of recent meta-analyses report that the treatment is safe. However, the endpoints recurrent stroke, vasospasms, and subarachnoid hemorrhage have not been evaluated sufficiently. Hence, we extracted data on these outcomes from the five recent thrombectomy trials (MR CLEAN, ESCAPE, REVASCAT, SWIFT PRIME, and EXTEND IA published in 2015). Subsequently, we conducted meta-analyses for each outcome. We report the results of the fixed, as well as the random effects model. Three studies reported data on recurrent strokes. While the results did not reach statistical significance in the random effects model (despite a three times elevated risk), the fixed effects model revealed a significantly higher rate of recurrent strokes after thrombectomy. Four studies reported data on subarachnoid hemorrhage. The higher pooled rates in the intervention groups were statistically significant in both, the fixed and the random effects model. One study reported on vasospasms. We recorded 14 events in the intervention group and none in the control group. The efficacy of mechanical thrombectomy is not questioned, yet our results indicate an increased risk for recurrent strokes, subarachnoid hemorrhage, and vasospasms post-treatment. Therefore, we strongly recommend a thoroughly surveillance, concerning these adverse events in future clinical trials and routine registries.

Soluble CD40L Is a Useful Marker to Predict Future Strokes in Patients With Minor Stroke and Transient Ischemic Attack.

PubMed

Li, Jiejie; Wang, Yilong; Lin, Jinxi; Wang, David; Wang, Anxin; Zhao, Xingquan; Liu, Liping; Wang, Chunxue; Wang, Yongjun

2015-07-01

Elevated soluble CD40 ligand (sCD40L) was shown to be related to cardiovascular events, but the role of sCD40L in predicting recurrent stroke remains unclear. Baseline sCD40L levels were measured in 3044 consecutive patients with acute minor stroke and transient ischemic attack, who had previously been enrolled in the Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events (CHANCE) trial. Cox proportional-hazards model was used to assess the association of sCD40L with recurrent stroke. Patients in the top tertile of sCD40L levels had increased risk of recurrent stroke comparing with those in the bottom tertile, after adjusted for conventional confounding factors (hazard ratio, 1.49; 95% confidence interval, 1.11-2.00; P=0.008). The patients with elevated levels of both sCD40L and high-sensitive C-reactive protein also had increased risk of recurrent stroke (hazard ratio, 1.81; 95% confidence interval, 1.23-2.68; P=0.003). Elevated sCD40L levels independently predict recurrent stroke in patients with minor stroke and transient ischemic attack. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00979589. © 2015 American Heart Association, Inc.

A first-order seismotectonic regionalization of Mexico for seismic hazard and risk estimation

NASA Astrophysics Data System (ADS)

Zúñiga, F. Ramón; Suárez, Gerardo; Figueroa-Soto, Ángel; Mendoza, Avith

2017-11-01

The purpose of this work is to define a seismic regionalization of Mexico for seismic hazard and risk analyses. This seismic regionalization is based on seismic, geologic, and tectonic characteristics. To this end, a seismic catalog was compiled using the more reliable sources available. The catalog was made homogeneous in magnitude in order to avoid the differences in the way this parameter is reported by various agencies. Instead of using a linear regression to converts from m b and M d to M s or M w , using only events for which estimates of both magnitudes are available (i.e., paired data), we used the frequency-magnitude relations relying on the a and b values of the Gutenberg-Richter relation. The seismic regions are divided into three main categories: seismicity associated with the subduction process along the Pacific coast of Mexico, in-slab events within the down-going COC and RIV plates, and crustal seismicity associated to various geologic and tectonic regions. In total, 18 seismic regions were identified and delimited. For each, the a and b values of the Gutenberg-Richter relation were determined using a maximum likelihood estimation. The a and b parameters were repeatedly estimated as a function of time for each region, in order to confirm their reliability and stability. The recurrence times predicted by the resulting Gutenberg-Richter relations obtained are compared with the observed recurrence times of the larger events in each region of both historical and instrumental earthquakes.

A systematic comparison of recurrent event models for application to composite endpoints.

PubMed

Ozga, Ann-Kathrin; Kieser, Meinhard; Rauch, Geraldine

2018-01-04

Many clinical trials focus on the comparison of the treatment effect between two or more groups concerning a rarely occurring event. In this situation, showing a relevant effect with an acceptable power requires the observation of a large number of patients over a long period of time. For feasibility issues, it is therefore often considered to include several event types of interest, non-fatal or fatal, and to combine them within a composite endpoint. Commonly, a composite endpoint is analyzed with standard survival analysis techniques by assessing the time to the first occurring event. This approach neglects that an individual may experience more than one event which leads to a loss of information. As an alternative, composite endpoints could be analyzed by models for recurrent events. There exists a number of such models, e.g. regression models based on count data or Cox-based models such as the approaches of Andersen and Gill, Prentice, Williams and Peterson or, Wei, Lin and Weissfeld. Although some of the methods were already compared within the literature there exists no systematic investigation for the special requirements regarding composite endpoints. Within this work a simulation-based comparison of recurrent event models applied to composite endpoints is provided for different realistic clinical trial scenarios. We demonstrate that the Andersen-Gill model and the Prentice- Williams-Petersen models show similar results under various data scenarios whereas the Wei-Lin-Weissfeld model delivers effect estimators which can considerably deviate under commonly met data scenarios. Based on the conducted simulation study, this paper helps to understand the pros and cons of the investigated methods in the context of composite endpoints and provides therefore recommendations for an adequate statistical analysis strategy and a meaningful interpretation of results.

TRAF3 Epigenetic Regulation Is Associated With Vascular Recurrence in Patients With Ischemic Stroke.

PubMed

Gallego-Fabrega, Cristina; Carrera, Caty; Reny, Jean-Luc; Fontana, Pierre; Slowik, Agnieszka; Pera, Joanna; Pezzini, Alessandro; Serrano-Heras, Gemma; Segura, Tomás; Martí-Fàbregas, Joan; Muiño, Elena; Cullell, Natalia; Montaner, Joan; Krupinski, Jerzy; Fernandez-Cadenas, Israel

2016-05-01

Clopidogrel is one of the most used antiplatelet drugs in patients with cardiovascular disease. However, 16% to 50% of patients have a high on-clopidogrel platelet reactivity and an increased risk of ischemic events. The pathogenesis of high on-treatment platelet reactivity in patients with stroke is only partially explained by genetic variations. This study aims to find differentially methylated sites across the genome associated with vascular recurrence in ischemic stroke patients treated with clopidogrel. From a cohort of 1900 patients with ischemic stroke, we selected 42 patients treated with clopidogrel, including 21 with a recurrent vascular event and 21 without vascular recurrence during the first year of follow-up. Over 480 000 DNA methylation sites were analyzed across the genome. Differentially methylated CpG sites were identified by nonparametric testing using R. Replication analysis was performed in a new cohort of 191 subjects and results were correlated with platelet reactivity in a subset of 90 subjects using light transmission aggregometry. A total of 73 differentially methylated CpG sites (P<1×10(-05)) were identified; 3 of them were selected for further replication: cg03548645 (P=1.42×10(-05), TRAF3), cg09533145 (P=7.81×10(-06), ADAMTS2), and cg15107336 (P=1.89×10(-05), XRCC1). The cg03548645 CpG remained significant in the replication study (P=0.034), a deep analysis of this region revealed another methylation site associated with vascular recurrence, P=0.037. Lower cg03548645 (TRAF3) DNA methylation levels were correlated with an increased platelet aggregation (ρ=-0.29, P=0.0075). This study suggests for the first time that epigenetics may significantly contribute to the variability of clopidogrel response and recurrence of ischemic events in patients with stroke. © 2016 American Heart Association, Inc.

The association of statin therapy with the risk of recurrent venous thrombosis.

PubMed

Smith, N L; Harrington, L B; Blondon, M; Wiggins, K L; Floyd, J S; Sitlani, C M; McKnight, B; Larson, E B; Rosendaal, F R; Heckbert, S R; Psaty, B M

2016-07-01

Essentials A lowered risk of recurrent venous thrombosis (VT) with statin treatment is controversial. Among observational inception cohort of 2,798 adults with incident VT, 457 had recurrent VT. Time-to-event models with time-varying statin use and adjustment for potential confounders was used for analysis. Compared to nonuse, current statin use was associated with 26% lower risk of recurrent VT. Click to hear Prof. Büller's perspective on Anticoagulant Therapy in the Treatment of Venous Thromboembolism Background Meta-analyses of randomized controlled trials suggest that treatment with hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins) lowers the risk of incident venous thrombosis (VT), particularly among those without prevalent clinical cardiovascular disease (CVD). Whether this is true for the prevention of recurrent VT is debated. We used an observational inception cohort to estimate the association of current statin use with the risk of recurrent VT. Methods and Results The study setting was a large healthcare organization with detailed medical record and pharmacy information at cohort entry and throughout follow-up. We followed 2798 subjects 18-89 years of age who experienced a validated incident VT between January 1, 2002, and December 31, 2010, for a first recurrent VT, validated by medical record review. During follow-up, 457 (16%) developed a first recurrent VT. In time-to-event models incorporating time-varying statin use and adjusting for potential confounders, current statin use was associated with a 26% lower risk of recurrent VT: hazard ratio 0.74, 95% confidence interval 0.59-0.94. Among cohort members free of CVD (n = 2134), current statin use was also associated with a lower risk (38%) of recurrent VT: hazard ratio 0.62, 95% confidence interval 0.45-0.85. We found similar results when restricting to new users of statins and in subgroups of different statin types and doses. Conclusions In a population-based cohort of subjects who had experienced an incident VT, statin use, compared with nonuse, was associated with a clinically relevant lower risk of recurrent VT. These findings suggest a potential secondary benefit of statins among patients who have experienced an incident VT. © 2016 International Society on Thrombosis and Haemostasis.

Central San Juan caldera cluster: Regional volcanic framework

USGS Publications Warehouse

Lipman, Peter W.

2000-01-01

Eruption of at least 8800 km3 of dacitic-rhyolitic magma as 9 major ash-slow sheets (individually 150-5000 km3) was accompanied by recurrent caldera subsidence between 28.3 and about 26.5 Ma in the central San Juan Mountains, Colorado. Voluminous andesitic-decitic lavas and breccias were erupted from central volcanoes prior to the ash-flow eruptions, and similar lava eruptions continued within and adjacent to the calderas during the period of explosive volcanism, making the central San Juan caldera cluster an exceptional site for study of caldera-related volcanic processes. Exposed calderas vary in size from 10 to 75 km in maximum diameter, the largest calderas being associated with the most voluminous eruptions. After collapse of the giant La Garita caldera during eruption if the Fish Canyon Tuff at 17.6 Ma, seven additional explosive eruptions and calderas formed inside the La Garita depression within about 1 m.y. Because of the nested geometry, maximum loci of recurrently overlapping collapse events are inferred to have subsided as much as 10-17 km, far deeper than the roof of the composite subvolcanic batholith defined by gravity data, which represents solidified caldera-related magma bodies. Erosional dissection to depths of as much as 1.5 km, although insufficient to reach the subvolcanic batholith, has exposed diverse features of intracaldera ash-flow tuff and interleaved caldera-collapse landslide deposits that accumulated to multikilometer thickness within concurrently subsiding caldera structures. The calderas display a variety of postcollapse resurgent uplift structures, and caldera-forming events produced complex fault geometries that localized late mineralization, including the epithermal base- and precious-metal veins of the well-known Creede mining district. Most of the central San Juan calderas have been deeply eroded, and their identification is dependent on detailed geologic mapping. In contrast, the primary volcanic morphology of the symmetrically resurgent Creede caldera, the volcanic framework for Lake Creede, has been exceptionally preserved because of rapid infilling by moat sediments of the Creede Formation, which were preferentially eroded during the past few million years. The ash-flow tuffs and caldera of the central San Juan region have been widely recognized as exceptional sites for study of explosive volcanic processes, and the results reported here provide new insights into processes of pyroclastic eruption and emplacement, geometric interrelations between caldera subsidence and resurgence, the petrologic diversity of sequential ash-flow eruptions, recurrent eruption of intermediate-composition lavas after each caldera-forming event, associated regional fault development, volume relations between ash-flow eruptions and associated calderas, the emplacement of subvolcanic batholiths, and involvement of mantle-derived mafic phases in magma-generation processes.

Global warming and recurrent mass bleaching of corals

NASA Astrophysics Data System (ADS)

Hughes, Terry P.; Kerry, James T.; Álvarez-Noriega, Mariana; Álvarez-Romero, Jorge G.; Anderson, Kristen D.; Baird, Andrew H.; Babcock, Russell C.; Beger, Maria; Bellwood, David R.; Berkelmans, Ray; Bridge, Tom C.; Butler, Ian R.; Byrne, Maria; Cantin, Neal E.; Comeau, Steeve; Connolly, Sean R.; Cumming, Graeme S.; Dalton, Steven J.; Diaz-Pulido, Guillermo; Eakin, C. Mark; Figueira, Will F.; Gilmour, James P.; Harrison, Hugo B.; Heron, Scott F.; Hoey, Andrew S.; Hobbs, Jean-Paul A.; Hoogenboom, Mia O.; Kennedy, Emma V.; Kuo, Chao-Yang; Lough, Janice M.; Lowe, Ryan J.; Liu, Gang; McCulloch, Malcolm T.; Malcolm, Hamish A.; McWilliam, Michael J.; Pandolfi, John M.; Pears, Rachel J.; Pratchett, Morgan S.; Schoepf, Verena; Simpson, Tristan; Skirving, William J.; Sommer, Brigitte; Torda, Gergely; Wachenfeld, David R.; Willis, Bette L.; Wilson, Shaun K.

2017-03-01

During 2015-2016, record temperatures triggered a pan-tropical episode of coral bleaching, the third global-scale event since mass bleaching was first documented in the 1980s. Here we examine how and why the severity of recurrent major bleaching events has varied at multiple scales, using aerial and underwater surveys of Australian reefs combined with satellite-derived sea surface temperatures. The distinctive geographic footprints of recurrent bleaching on the Great Barrier Reef in 1998, 2002 and 2016 were determined by the spatial pattern of sea temperatures in each year. Water quality and fishing pressure had minimal effect on the unprecedented bleaching in 2016, suggesting that local protection of reefs affords little or no resistance to extreme heat. Similarly, past exposure to bleaching in 1998 and 2002 did not lessen the severity of bleaching in 2016. Consequently, immediate global action to curb future warming is essential to secure a future for coral reefs.

Global warming and recurrent mass bleaching of corals.

PubMed

Hughes, Terry P; Kerry, James T; Álvarez-Noriega, Mariana; Álvarez-Romero, Jorge G; Anderson, Kristen D; Baird, Andrew H; Babcock, Russell C; Beger, Maria; Bellwood, David R; Berkelmans, Ray; Bridge, Tom C; Butler, Ian R; Byrne, Maria; Cantin, Neal E; Comeau, Steeve; Connolly, Sean R; Cumming, Graeme S; Dalton, Steven J; Diaz-Pulido, Guillermo; Eakin, C Mark; Figueira, Will F; Gilmour, James P; Harrison, Hugo B; Heron, Scott F; Hoey, Andrew S; Hobbs, Jean-Paul A; Hoogenboom, Mia O; Kennedy, Emma V; Kuo, Chao-Yang; Lough, Janice M; Lowe, Ryan J; Liu, Gang; McCulloch, Malcolm T; Malcolm, Hamish A; McWilliam, Michael J; Pandolfi, John M; Pears, Rachel J; Pratchett, Morgan S; Schoepf, Verena; Simpson, Tristan; Skirving, William J; Sommer, Brigitte; Torda, Gergely; Wachenfeld, David R; Willis, Bette L; Wilson, Shaun K

2017-03-15

During 2015-2016, record temperatures triggered a pan-tropical episode of coral bleaching, the third global-scale event since mass bleaching was first documented in the 1980s. Here we examine how and why the severity of recurrent major bleaching events has varied at multiple scales, using aerial and underwater surveys of Australian reefs combined with satellite-derived sea surface temperatures. The distinctive geographic footprints of recurrent bleaching on the Great Barrier Reef in 1998, 2002 and 2016 were determined by the spatial pattern of sea temperatures in each year. Water quality and fishing pressure had minimal effect on the unprecedented bleaching in 2016, suggesting that local protection of reefs affords little or no resistance to extreme heat. Similarly, past exposure to bleaching in 1998 and 2002 did not lessen the severity of bleaching in 2016. Consequently, immediate global action to curb future warming is essential to secure a future for coral reefs.

Cost-effectiveness of Apixaban Versus Other Oral Anticoagulants for the Initial Treatment of Venous Thromboembolism and Prevention of Recurrence.

PubMed

Lanitis, Tereza; Leipold, Robert; Hamilton, Melissa; Rublee, Dale; Quon, Peter; Browne, Chantelle; Cohen, Alexander T

2016-03-01

To assess the cost-effectiveness of apixaban versus rivaroxaban, low-molecular-weight heparin (LMWH)/dabigatran, and LMWH/vitamin K antagonist (VKA) for the initial treatment and prevention of recurrent thromboembolic events in patients with venous thromboembolism (VTE). A Markov model was developed to evaluate the pharmacoeconomic effect of 6 months of treatment with apixaban versus other anticoagulants over a lifetime horizon. Network meta-analyses were conducted using the results of the Apixaban after the Initial Management of Pulmonary Embolism and Deep Vein Thrombosis with First-Line Therapy (AMPLIFY), EINSTEIN-pooled, and RE-COVER I and II trials for the following end points: recurrent VTE, major bleeds, clinically relevant non-major bleeds, and treatment discontinuations. The analysis was conducted from the perspective of the United Kingdom National Health Service. The outcomes evaluated were the number of events avoided in a 1000-patient cohort, total costs, life years, quality-adjusted life years (QALYs), and cost per QALY gained over a patient's lifetime. Treatment for 6 months with apixaban was projected to result in fewer recurrent VTE and bleeding events in comparison to rivaroxaban, LMWH/dabigatran, and LMWH/VKA. Apixaban was cost-effective compared with LMWH/VKA at an incremental cost-effectiveness ratio of £2520 per QALY gained and was a dominant (ie, lower costs and higher QALYs) alternative to either rivaroxaban or LMWH/dabigatran. Sensitivity analysis indicated that results were robust over a wide range of inputs. The assessment of the effects and costs of apixaban in this study predicted that apixaban is a dominant alternative to rivaroxaban and LMWH/dabigatran and a cost-effective alternative to LMWH/VKA for 6 months of treatment of VTE and the prevention of recurrence. Copyright © 2016 Elsevier HS Journals, Inc. All rights reserved.

Comparative Effectiveness of Blood Pressure-lowering Drugs in Patients who have Already Suffered From Stroke

PubMed Central

Wang, Wei-Ting; You, Li-Kai; Chiang, Chern-En; Sung, Shih-Hsien; Chuang, Shao-Yuan; Cheng, Hao-Min; Chen, Chen-Huan

2016-01-01

Abstract Hypertension is the most important risk factor for stroke and stroke recurrence. However, the preferred blood pressure (BP)-lowering drug class for patients who have suffered from a stroke has yet to be determined. To investigate the relative effects of BP-lowering therapies [angiotensin-converting enzyme inhibitor (ACEI), angiotensin receptor blockers (ARB), β blockers, calcium channel blockers (CCBs), diuretics, and combinations of these drugs] in patients with a prior stroke history, we performed a systematic review and meta-analysis using both traditional frequentist and Bayesian random-effects models and meta-regression of randomized controlled trials (RCTs) on the outcomes of recurrent stroke, coronary heart disease (CHD), and any major adverse cardiac and cerebrovascular events (MACCE). Trials were identified from searches of published hypertension guidelines, electronic databases, and previous systematic reviews. Fifteen RCTs composed of 39,329 participants with previous stroke were identified. Compared with the placebo, only ACEI along with diuretics significantly reduced recurrent stroke events [odds ratio (OR) = 0.54, 95% credibility interval (95% CI) 0.33–0.90]. On the basis of the distribution of posterior probabilities, the treatment ranking consistently identified ACEI along with diuretics as the preferred BP-lowering strategy for the reduction of recurrent stroke and CHD (31% and 35%, respectively). For preventing MACCE, diuretics appeared to be the preferred agent for stroke survivors (34%). Moreover, the meta-regression analysis failed to demonstrate a statistical significance between BP reduction and all outcomes (P = 0.1618 for total stroke, 0.4933 for CHD, and 0.2411 for MACCE). Evidence from RCTs supports the use of diuretics-based treatment, especially when combined with ACEI, for the secondary prevention of recurrent stroke and any vascular events in patients who have suffered from stroke. PMID:27082571

Utilization of Surveillance after Polypectomy in the Medicare Population – A Cohort Study

PubMed Central

Lansdorp-Vogelaar, Iris; Fedewa, Stacey; Lin, Chun Chieh; Virgo, Katherine S.; Jemal, Ahmedin

2014-01-01

Background Surveillance in patients with previous polypectomy was underused in the Medicare population in 1994. This study investigates whether expansion of Medicare reimbursement for colonoscopy screening in high-risk individuals has reduced the inappropriate use of surveillance. Methods We used Kaplan-Meier analysis to estimate time to surveillance and polyp recurrence rates for Medicare beneficiaries with a colonoscopy with polypectomy between 1998 and 2003 who were followed through 2008 for receipt of surveillance colonoscopy. Generalized Estimating Equations were used to estimate risk factors for: 1) failing to undergo surveillance and 2) polyp recurrence among these individuals. Analyses were stratified into three 2-year cohorts based on baseline colonoscopy date. Results Medicare beneficiaries undergoing a colonoscopy with polypectomy in the 1998–1999 (n = 4,136), 2000–2001 (n = 3,538) and 2002–2003 (n = 4,655) cohorts had respective probabilities of 30%, 26% and 20% (p<0.001) of subsequent surveillance events within 3 years. At the same time, 58%, 52% and 45% (p<0.001) of beneficiaries received a surveillance event within 5 years. Polyp recurrence rates after 5 years were 36%, 30% and 26% (p<0.001) respectively. Older age (≥ 70 years), female gender, later cohort (2000–2001 & 2002–2003), and severe comorbidity were the most important risk factors for failure to undergo a surveillance event. Male gender and early cohort (1998–1999) were the most important risk factors for polyp recurrence. Conclusions Expansion of Medicare reimbursement for colonoscopy screening in high-risk individuals has not reduced underutilization of surveillance in the Medicare population. It is important to take action now to improve this situation, because polyp recurrence is substantial in this population. PMID:25393312

Adverse events affect sorafenib efficacy in patients with recurrent hepatocellular carcinoma after liver transplantation: experience at a single center and review of the literature.

PubMed

Zavaglia, Claudio; Airoldi, Aldo; Mancuso, Andrea; Vangeli, Marcello; Viganò, Raffaella; Cordone, Gabriella; Gentiluomo, Maria; Belli, Luca Saverio

2013-02-01

The aim of this study was to assess the safety and efficacy of sorafenib, with or without everolimus, in the treatment of recurrent hepatocellular carcinoma (HCC) after an orthotopic liver transplantation (OLT). We reviewed the outcome of our consecutive cohort series of patients. Eleven patients (nine men) with recurrent HCC after OLT were treated. Four patients received cyclosporine plus sorafenib at a starting dose of 400 mg twice daily; seven received the combination of sorafenib (same dosage) and everolimus. Sorafenib was reduced or stopped according to the drug label. The median time to recurrence was 12 months (range 2-66). The mean age at the start of treatment was 57 ± 9 years. Sorafenib was withdrawn because of intolerance or side-effects in four (36%) patients. Dose reduction because of adverse events or intolerance was required in 91% of patients after 26 ± 11 days from the start of treatment. The average length of treatment was 68 days (range 15-444). One patient died because of a massive gastrointestinal bleeding while receiving sorafenib and everolimus. The most frequent adverse events were fatigue (54%), skin toxicity (45%), and hypophosphatemia (36%). Two patients (18%) showed a radiological partial response, one (9%) had a stable disease, and six (54%) showed a progressive disease. None of the patients achieved a complete response. Treatment response could not be assessed in two (18%) patients. The overall median survival since the start of treatment was 5 months. One-year survival was 18%. Sorafenib, with or without mammalian target of rapamycin inhibitors, is poorly tolerated and rarely effective in the treatment of recurrent HCC after OLT.

Survival and recurrent venous thromboembolism in patients with first proximal or isolated distal deep vein thrombosis and no pulmonary embolism.

PubMed

Barco, S; Corti, M; Trinchero, A; Picchi, C; Ambaglio, C; Konstantinides, S V; Dentali, F; Barone, M

2017-07-01

Essentials The long-term risk of recurrence and death after distal deep vein thrombosis (DVT) is uncertain. We included subjects with first proximal or isolated distal DVT (IDDVT) and no pulmonary embolism. The risk of symptomatic and asymptomatic recurrence is lower after IDDVT (vs. proximal). IDDVT may be associated with a lower long-term risk of death, especially after unprovoked DVT. Background A few studies have focused on the risk of recurrence after first acute isolated distal deep vein thrombosis (IDDVT) compared with proximal DVT (PDVT), whereas the incremental risk of death has never been explored beyond the first 3 years after acute event. Methods Our single-center cohort study included patients with first symptomatic acute PDVT or IDDVT. Patients were excluded if they had concomitant pulmonary embolism (PE) or prior venous thromboembolism. The primary outcomes were symptomatic objectively diagnosed recurrent PDVT or PE and all-cause death. Results In total, 4759 records were screened and 831 subjects included: 202 had symptomatic IDDVT and 629 had PDVT. The median age was 66 years and 50.5% were women. A total of 125 patients had recurrent PDVT or PE during 3175 patient-years of follow-up: 109 events occurred after PDVT (17.3%) and 16 after IDDVT (7.9%). Annual recurrence rates were 4.5% (95% confidence interval [CI], 3.7-5.4%) and 2.0% (95% CI, 1.1-3.2%), respectively, for an adjusted hazard ratio (aHR) for IDDVT patients of 0.32 (95% CI, 0.19-0.55). Death occurred in 263 patients (31.6% [95% CI, 28.6-34.9%]) during 5469 patient-years of follow-up for an overall annual incidence rate of 4.8% (95% CI, 4.2-5.4%). The mortality rate was 33.5% (n = 211) in PDVT patients and 25.7% (n = 52) in IDDVT patients. The long-term hazard of death appeared lower for IDDVT patients (aHR, 0.75 [95% CI, 0.55-1.02]), especially after unprovoked events (aHR, 0.58 [95% CI, 0.26-1.31]). Conclusions Compared with PDVT, IDDVT patients were at a lower risk of recurrent VTE. The risk of death appeared lower after IDDVT during a median follow-up of 7.6 years. © 2017 International Society on Thrombosis and Haemostasis.

Does high intelligence improve prognosis? The association of intelligence with recurrence and mortality among Swedish men with coronary heart disease.

PubMed

Sörberg Wallin, Alma; Falkstedt, Daniel; Allebeck, Peter; Melin, Bo; Janszky, Imre; Hemmingsson, Tomas

2015-04-01

Lower intelligence early in life is associated with increased risks for coronary heart disease (CHD) and mortality. Intelligence level might affect compliance to treatment but its prognostic importance in patients with CHD is unknown. A cohort of 1923 Swedish men with a measure of intelligence from mandatory military conscription in 1969-1970 at age 18-20, who were diagnosed with CHD 1991-2007, were followed to the end of 2008. recurrent CHD event. Secondary outcome: case fatality from the first event, cardiovascular and all-cause mortality. National registers provided information on CHD events, comorbidity, mortality and socioeconomic factors. The fully adjusted HRs for recurrent CHD for medium and low intelligence, compared with high intelligence, were 0.98, (95% CIs 0.83 to 1.16) and 1.09 (0.89 to 1.34), respectively. The risks were increased for cardiovascular and all-cause mortality with lower intelligence, but were attenuated in the fully adjusted models (fully adjusted HRs for cardiovascular mortality 1.92 (0.94 to 3.94) and 1.98 (0.89 to 4.37), respectively; for all-cause mortality 1.63 (1.00 to 2.65) and 1.62 (0.94 to 2.78), respectively). There was no increased risk for case-fatality at the first event (fully adjusted ORs 1.06 (0.73 to 1.55) and 0.97 (0.62 to 1.50), respectively). Although we found lower intelligence to be associated with increased mortality in middle-aged men with CHD, there was no evidence for its possible effect on recurrence in CHD. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Patent foramen ovale closure following cryptogenic stroke or transient ischaemic attack: Long-term follow-up of 301 cases.

PubMed

Mirzaali, Mikaeil; Dooley, Maureen; Wynne, Dylan; Cooter, Nina; Lee, Lorraine; Haworth, Peter; Saha, Romi; Gainsborough, Nicola; Hildick-Smith, David

2015-11-15

Patent foramen ovale has been identified as a conduit for paradoxical embolism resulting in cryptogenic stroke or transient ischemic attack (TIA). We aimed to establish rates of death, recurrent stroke or TIA among patients undergoing PFO closure for stroke or TIA at our unit. A retrospective analysis of all PFO closure patients was performed between May 2004 and January 2013. Follow up was performed by mortality tracing using the Medical Research Information Service of the Office of National Statistics. With regard to stroke or TIA recurrence, written consent forms and questionnaires were mailed with follow up telephone calls. Medical notes and imaging records were consulted where adverse events were noted. 301 patients aged 48.6 ± 11.0 years, 54.4% male, with ≥1 thromboembolic neurovascular event had percutaneous PFO closure with one of eight devices, with successful implantation in 99% of cases. Follow-up duration was 40.2 ± 26.2 months (range 1.3-105.3); complete in 301 patients for mortality (100%) and 283 patients (94.0%) for neurovascular events. Two patients died during follow-up (respiratory failure n = 1; road traffic accident n = 1). Recurrent stroke (MRI or CT confirmed) was observed in five patients (0.5%; 0.55 per 100 person-years) and TIA in 9 (1.1%; 0.98 per 100 person-years). Atrial fibrillation requiring treatment was documented in 14 patients (1.7%). Percutaneous PFO closure in patients with cryptogenic stroke or TIA is a safe treatment with a low incidence of procedural complications and recurrent neurovascular events. Registry data like these may help to demonstrate the utility of PFO closure in stroke. © 2015 Wiley Periodicals, Inc.

Risks of Bleeding Recurrence and Cardiovascular Events With Continued Aspirin Use After Lower Gastrointestinal Hemorrhage.

PubMed

Chan, Francis K L; Leung Ki, En-Ling; Wong, Grace L H; Ching, Jessica Y L; Tse, Yee Kit; Au, Kim W L; Wu, Justin C Y; Ng, Siew C

2016-08-01

It is not clear whether use of low-dose aspirin should be resumed after an episode of lower gastrointestinal (GI) bleeding. We assessed the long-term risks of recurrent lower GI bleeding and serious cardiovascular outcomes after aspirin-associated lower GI bleeding. We performed a retrospective study of patients diagnosed with lower GI bleeding (documented melena or hematochezia and absence of upper GI bleeding) from January 1, 2000 through December 31, 2007 at the Prince of Wales Hospital in Hong Kong. Using the hospital registry, we analyzed data from 295 patients on aspirin and determined their outcomes during a 5-year period. Outcomes included recurrent lower GI bleeding, serious cardiovascular events, and death from other causes, as determined by an independent, blinded adjudication committee. Outcomes were compared between patients assigned to the following groups based on cumulative duration of aspirin use: <20% of the follow-up period (121 nonusers) vs ≥50% of the observation period (174 aspirin users). Within 5 years, lower GI bleeding recurred in 18.9% of aspirin users (95% confidence interval [CI], 13.3%-25.3%) vs 6.9% of nonusers (95% CI, 3.2%-12.5%; P = .007). However, serious cardiovascular events occurred in 22.8% of aspirin users (95% CI, 16.6%-29.6%) vs 36.5% of nonusers (95% CI, 27.4%-45.6%; P = .017), and 8.2% of aspirin users died from other causes (95% CI, 4.6%-13.2%) vs 26.7% of nonusers (95% CI, 18.7%-35.4%; P = .001). Multivariable analysis showed that aspirin use was an independent predictor of rebleeding, but protected against cardiovascular events and death. Among aspirin users with a history of lower GI bleeding, continuation of aspirin is associated with an increased risk of recurrent lower GI bleeding, but reduced risk of serious cardiovascular events and death. Copyright © 2016. Published by Elsevier Inc.

Holocene forest dynamics in central and western Mediterranean: periodicity, spatio-temporal patterns and climate influence.

PubMed

Di Rita, Federico; Fletcher, William J; Aranbarri, Josu; Margaritelli, Giulia; Lirer, Fabrizio; Magri, Donatella

2018-06-12

It is well-known that the Holocene exhibits a millennial-scale climate variability. However, its periodicity, spatio-temporal patterns and underlying processes are not fully deciphered yet. Here we focus on the central and western Mediterranean. We show that recurrent forest declines from the Gulf of Gaeta (central Tyrrhenian Sea) reveal a 1860-yr periodicity, consistent with a ca. 1800-yr climate fluctuation induced by large-scale changes in climate modes, linked to solar activity and/or AMOC intensity. We show that recurrent forest declines and dry events are also recorded in several pollen and palaeohydrological proxy-records in the south-central Mediterranean. We found coeval events also in several palaeohydrological records from the south-western Mediterranean, which however show generally wet climate conditions, indicating a spatio-temporal hydrological pattern opposite to the south-central Mediterranean and suggesting that different expressions of climate modes occurred in the two regions at the same time. We propose that these opposite hydroclimate regimes point to a complex interplay of the prevailing or predominant phases of NAO-like circulation, East Atlantic pattern, and extension and location of the North African anticyclone. At a larger geographical scale, displacements of the ITCZ, modulated by solar activity and/or AMOC intensity, may have also indirectly influenced the observed pattern.

Recurrent Penile Fracture-Case Report and Alternative Surgical Approach.

PubMed

Nascimento, Bruno; Guglielmetti, Giuliano B; Miranda, Eduardo P; Ivanovic, Renato F; Batagello, Carlos A; Nahas, William C; Srougi, Miguel; Cury, José

2018-05-03

Penile refracture is an exceedingly rare event, with very few published studies. To the best of our knowledge, this is the first documented case in the literature of penile fracture with 3 same-site recurrences. To describe the case of a 25-year-old Caucasian man with recurrent penile fracture ultimately treated with resuture and patch reinforcement. Patient history (clinical and surgical) and literature review. After the 3rd same-site recurrence, patch reinforcement over the sutured area was performed. The patient had an uneventful recovery and no recurrences to date. There is no evidence indicating the superiority of non-absorbable sutures. Bovine pericardium reinforcement over the sutured area was used to minimize the chance of another recurrence. More studies are necessary to investigate its safety and efficacy in this scenario. Nascimento B, Guglielmetti GB, Miranda EP, et al. Recurrent Penile Fracture-Case Report and Alternative Surgical Approach. Sex Med 2018;X:XX-XX. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Prevention of post-operative recurrence of Crohn's disease.

PubMed

Vaughn, Byron Philip; Moss, Alan Colm

2014-02-07

Endoscopic and clinical recurrence of Crohn's disease (CD) is a common occurrence after surgical resection. Smokers, those with perforating disease, and those with myenteric plexitis are all at higher risk of recurrence. A number of medical therapies have been shown to reduce this risk in clinical trials. Metronidazole, thiopurines and anti-tumour necrosis factors (TNFs) are all effective in reducing the risk of endoscopic or clinical recurrence of CD. Since these are preventative agents, the benefits of prophylaxis need to be weighed-against the risk of adverse events from, and costs of, therapy. Patients who are high risk for post-operative recurrence should be considered for early medical prophylaxis with an anti-TNF. Patients who have few to no risk factors are likely best served by a three-month course of antibiotics followed by tailored therapy based on endoscopy at one year. Clinical recurrence rates are variable, and methods to stratify patients into high and low risk populations combined with prophylaxis tailored to endoscopic recurrence would be an effective strategy in treating these patients.

Amplitude and Recurrence Time of LP activity at Mt. Etna, Italy

NASA Astrophysics Data System (ADS)

Cauchie, Léna; Saccorotti, Gilberto; Bean, Christopher

2013-04-01

The manifestation of Long-Period (LP) activity is attested on many volcanoes worldwide and is thought to be associated with the resonant oscillations of subsurface, fluid-filled, cracks and conduits. Nonetheless the actual source mechanism that originates the resonance is still unclear. Different models have been proposed so far, including (i) fluid flow instabilities as periodic degassing and (ii) brittle failure in viscous magmas. Since LP activity usually precedes and accompanies volcanic eruption, the understanding of these sources is crucial for the hazard assessment and eruption early warning. The work is aimed at improving the understanding of the LP source mechanism through a statistical analysis of detailed LP catalogues. The behaviour of LP activity is compared with the empirical laws governing earthquakes recurrence (e.g., Gutenberg-Richter [GR] and Gamma-law distributions), in order to understand what relationships, if any, exist between these two apparently different earthquake classes. In particular, about 13000 events were detected on Mount Etna in August 2005 through a STA/LTA method. For this given period, the volcano does not present particular sign of unrest. The manifestation of the LP events is sustained in time over all the period of analysis. From the analysis of the directional properties, it turns out that the events of this first catalog propagate from 2 distinct sources . Furthermore, the events exhibit a high degree of waveform similarity, and provide a criterion for classification/source separation. The events were then grouped into families of comparable waveforms, resulting also in a separation for their source locations. We then used template signals of each family for a Matched-Filtering of the continuous data streams, in order to discriminate small-amplitude events previously undetected by the STA/LTA triggering method. This procedure allowed for a significant enrichment of the catalogues. The retrieved amplitude distributions, similar for both families, differ instead significantly from the Gutenberg-Richter law, and the inter-event times distributions don't follow a typical Gamma-law. In order to compare these results with a catalogue for which the source mechanism is well-established, we applied the same analysis procedure to a dataset from Stromboli Volcano, where LP activity is closely related to VLP (Very-Long-Period) pulses, in turn associated with the summit explosions. Again, catalogues of thousands of LP events were achieved over one month of seismic records (July 2011). Our results indicate a similar behaviour in terms of both amplitude and inter-event time distributions, with respect to what observed at Mt. Etna. This suggests that the Etna's LP data are likely related with a degassing process occurring at depth. Nonetheless, further studies are needed in order to quantify the time recurrence and amplitude distribution of brittle failure in viscous, stressed magmas. Hopefully, these steps will lead to an improved understanding of LP activity in different volcanic contexts, in turn clarifying its significance in terms of eruption forecasting.

Pre-Clinical Model to Study Recurrent Venous Thrombosis in the Inferior Vena Cava.

PubMed

Andraska, Elizabeth A; Luke, Catherine E; Elfline, Megan A; Henke, Samuel P; Madapoosi, Siddharth S; Metz, Allan K; Hoinville, Megan E; Wakefield, Thomas W; Henke, Peter K; Diaz, Jose A

2018-06-01

 Patients undergoing deep vein thrombosis (VT) have over 30% recurrence, directly increasing their risk of post-thrombotic syndrome. Current murine models of inferior vena cava (IVC) VT model host one thrombosis event.  We aimed to develop a murine model to study IVC recurrent VT in mice.  An initial VT was induced using the electrolytic IVC model (EIM) with constant blood flow. This approach takes advantage of the restored vein lumen 21 days after a single VT event in the EIM demonstrated by ultrasound. We then induced a second VT 21 days later, using either EIM or an IVC ligation model for comparison. The control groups were a sham surgery and, 21 days later, either EIM or IVC ligation. IVC wall and thrombus were harvested 2 days after the second insult and analysed for IVC and thrombus size, gene expression of fibrotic markers, histology for collagen and Western blot for citrullinated histone 3 (Cit-H3) and fibrin.  Ultrasound confirmed the first VT and its progressive resolution with an anatomical channel allowing room for the second thrombus by day 21. As compared with a primary VT, recurrent VT has heavier walls with significant up-regulation of transforming growth factor-β (TGF-β), elastin, interleukin (IL)-6, matrix metallopeptidase 9 (MMP9), MMP2 and a thrombus with high citrullinated histone-3 and fibrin content.  Experimental recurrent thrombi are structurally and compositionally different from the primary VT, with a greater pro-fibrotic remodelling vein wall profile. This work provides a VT recurrence IVC model that will help to improve the current understanding of the biological mechanisms and directed treatment of recurrent VT. Schattauer GmbH Stuttgart.

Estimating the ratio of multivariate recurrent event rates with application to a blood transfusion study.

PubMed

Ning, Jing; Rahbar, Mohammad H; Choi, Sangbum; Piao, Jin; Hong, Chuan; Del Junco, Deborah J; Rahbar, Elaheh; Fox, Erin E; Holcomb, John B; Wang, Mei-Cheng

2017-08-01

In comparative effectiveness studies of multicomponent, sequential interventions like blood product transfusion (plasma, platelets, red blood cells) for trauma and critical care patients, the timing and dynamics of treatment relative to the fragility of a patient's condition is often overlooked and underappreciated. While many hospitals have established massive transfusion protocols to ensure that physiologically optimal combinations of blood products are rapidly available, the period of time required to achieve a specified massive transfusion standard (e.g. a 1:1 or 1:2 ratio of plasma or platelets:red blood cells) has been ignored. To account for the time-varying characteristics of transfusions, we use semiparametric rate models for multivariate recurrent events to estimate blood product ratios. We use latent variables to account for multiple sources of informative censoring (early surgical or endovascular hemorrhage control procedures or death). The major advantage is that the distributions of latent variables and the dependence structure between the multivariate recurrent events and informative censoring need not be specified. Thus, our approach is robust to complex model assumptions. We establish asymptotic properties and evaluate finite sample performance through simulations, and apply the method to data from the PRospective Observational Multicenter Major Trauma Transfusion study.

Examining Fall Recurrence Risk of Homebound Hispanic Older Adults Receiving Home Care Services.

PubMed

Solis, Guillermina R; Champion, Jane Dimmitt

2017-03-01

Unintentional falls and injuries is a major problem among older adults and the fourth cause of death in the United States. A previous fall event doubles the risk of recurrence and lessens the person's quality of life. Hispanic older adults have higher rates of disability and lower independent functioning due to poor medical health and risk for fall recurrence. Most fall studies focus on fall risk with few studies on fall recurrence in older adults receiving home health care services unrelated to fall incident. A descriptive pilot study of 30 homebound Hispanic older adults receiving home care services who reported a fall within 3 months was conducted by a multidisciplinary team to evaluate risk of fall recurrence. A heightened risk for fall recurrence was identified with high number of chronic illnesses, high intake of medications, vision problems, and prevalence of urinary incontinence. Findings highlight significant number of intrinsic factors for fall risk recurrence and injuries in a Hispanic older adults population that is homebound and receiving home care services. A multidisciplinary evaluation and culturally appropriate interventions to lessen the risk of fall recurrence are recommended.

The Reappearance Hypothesis Revisited: Recurrent Involuntary Memories after Traumatic Events and in Everyday Life

PubMed Central

Berntsen, Dorthe; Rubin, David C.

2011-01-01

Recurrent involuntary memories are autobiographical memories that come to mind with no preceding retrieval attempt and that are subjectively experienced as being repetitive. Clinically, they are classified as a symptom of Posttraumatic Stress Disorder (PTSD). The present work is the first to systematically examine recurrent involuntary memories outside clinical settings. Study 1 examines recurrent involuntary memories among survivors of the tsunami catastrophe in Southeast Asia in 2004. Study 2 examines recurrent involuntary memories in a large general population. Study 3 examines whether the contents of recurrent involuntary memories recorded in a diary study are duplicates of, or differ from, one another. We show that recurrent involuntary memories are not limited to clinical populations or to emotionally negative experiences, that they typically do not come to mind in a fixed and unchangeable form, and that they show the same pattern regarding accessibility as autobiographical memories in general. We argue that recurrent involuntary memories after traumas and in everyday life can be explained in terms of general and well-established mechanisms of autobiographical memory. PMID:18426073

Recurrent Spontaneous Pneumothorax in a 42 Years Old Woman With Pulmonary Lymphangioleiomyomatosis: Insights and Pitfalls of the Surgical Treatment

PubMed Central

Spiliopoulos, Kyriakos; Tsantsaridou, Angeliki; Papamichali, Rodula; Kimpouri, Konstantina; Salemis, Nicolaos S.; Koukoulis, George K.; Tsilimingas, Nicolaos B.

2013-01-01

Lymphangioleiomyomatosis (LAM) is a rare disease that occurs predominantly in females between the ages of 30 and 50 years and is clinically characterized by progressive dyspnoea on exertion, recurrent pneumothoraces, abdominal and thoracic lymphadenopathy, as well tumors-like angiomyolipomas and lymphangiomyomas. We present the case of a 42-year-old woman, who developed recurrent pneumothoraces and was subsequently diagnosed with LAM. Although pneumothorax is a common complication of the disease, its optimal approach to treatment and prevention remains unclear. Chemical or surgical pleurodesis are often performed in order to prevent recurrence, but may predispose to perioperative complications in the event of future lung transplantation. PMID:23390481

Recurrent spontaneous pneumothorax in a 42 years old woman with pulmonary lymphangioleiomyomatosis: insights and pitfalls of the surgical treatment.

PubMed

Spiliopoulos, Kyriakos; Tsantsaridou, Angeliki; Papamichali, Rodula; Kimpouri, Konstantina; Salemis, Nicolaos S; Koukoulis, George K; Tsilimingas, Nicolaos B

2013-02-01

Lymphangioleiomyomatosis (LAM) is a rare disease that occurs predominantly in females between the ages of 30 and 50 years and is clinically characterized by progressive dyspnoea on exertion, recurrent pneumothoraces, abdominal and thoracic lymphadenopathy, as well tumors-like angiomyolipomas and lymphangiomyomas. We present the case of a 42-year-old woman, who developed recurrent pneumothoraces and was subsequently diagnosed with LAM. Although pneumothorax is a common complication of the disease, its optimal approach to treatment and prevention remains unclear. Chemical or surgical pleurodesis are often performed in order to prevent recurrence, but may predispose to perioperative complications in the event of future lung transplantation.

Controls on hillslope stability in a mountain river catchment

NASA Astrophysics Data System (ADS)

Golly, Antonius; Turowski, Jens; Hovius, Niels; Badoux, Alexandre

2015-04-01

Sediment transport in fluvial systems accounts for a large fraction of natural hazard damage costs in mountainous regions and is an important factor for risk mitigation, engineering and ecology. Although sediment transport in high-gradient channels gathered research interest over the last decades, sediment dynamics in steep streams are generally not well understood. For instance, the sourcing of the sediment and when and how it is actually mobilized is largely undescribed. In the Erlenbach, a mountain torrent in the Swiss Prealps, we study the mechanistic relations between in-channel hydrology, channel morphology, external climatic controls and the surrounding sediment sources to identify relevant process domains for sediment input and their characteristic scales. Here, we analyze the motion of a slow-moving landslide complex that was permanently monitored by time-lapse cameras over a period of 70 days at a 30 minutes interval. In addition, data sets for stream discharge, air temperature and precipitation rates are available. Apparent changes in the channel morphology, e.g. the destruction of channel-spanning bed forms, were manually determined from the time-lapse images and were treated as event marks in the time series. We identify five relevant types of sediment displacement processes emerging during the hillslope motion: concentrated mud flows, deep seated hillslope failure, catastrophic cavity failure, hillslope bank erosion and individual grain loss. Generally, sediment displacement occurs on a large range of temporal and spatial scales and sediment dynamics in steep streams not only depend on large floods with long recurrence intervals. We find that each type of displacement acts in a specific temporal and spatial domain with their characteristic scales. Different external climatic forcing (e.g. high-intensity vs. long-lasting precipitation events) promote different displacement processes. Stream morphology and the presence of boulders have a large effect on sediment input through deep seated failures and cavity failures while they have only minor impact on the other process types. In addition to large floods, which are generally recognized to produce huge amounts of sediment, we identify two relevant climatic regimes that play an important role for the sediment dynamics: a) long-lasting but low-intensity rainfall that explicitly trigger specific sediment displacement processes on the hillslopes and b) smaller discharge events with recurrence intervals of approximately one year that mobilize sediments from the hillslope's toes along the channel.

Tracking the Evolution of Non-Small-Cell Lung Cancer.

PubMed

Jamal-Hanjani, Mariam; Wilson, Gareth A; McGranahan, Nicholas; Birkbak, Nicolai J; Watkins, Thomas B K; Veeriah, Selvaraju; Shafi, Seema; Johnson, Diana H; Mitter, Richard; Rosenthal, Rachel; Salm, Max; Horswell, Stuart; Escudero, Mickael; Matthews, Nik; Rowan, Andrew; Chambers, Tim; Moore, David A; Turajlic, Samra; Xu, Hang; Lee, Siow-Ming; Forster, Martin D; Ahmad, Tanya; Hiley, Crispin T; Abbosh, Christopher; Falzon, Mary; Borg, Elaine; Marafioti, Teresa; Lawrence, David; Hayward, Martin; Kolvekar, Shyam; Panagiotopoulos, Nikolaos; Janes, Sam M; Thakrar, Ricky; Ahmed, Asia; Blackhall, Fiona; Summers, Yvonne; Shah, Rajesh; Joseph, Leena; Quinn, Anne M; Crosbie, Phil A; Naidu, Babu; Middleton, Gary; Langman, Gerald; Trotter, Simon; Nicolson, Marianne; Remmen, Hardy; Kerr, Keith; Chetty, Mahendran; Gomersall, Lesley; Fennell, Dean A; Nakas, Apostolos; Rathinam, Sridhar; Anand, Girija; Khan, Sajid; Russell, Peter; Ezhil, Veni; Ismail, Babikir; Irvin-Sellers, Melanie; Prakash, Vineet; Lester, Jason F; Kornaszewska, Malgorzata; Attanoos, Richard; Adams, Haydn; Davies, Helen; Dentro, Stefan; Taniere, Philippe; O'Sullivan, Brendan; Lowe, Helen L; Hartley, John A; Iles, Natasha; Bell, Harriet; Ngai, Yenting; Shaw, Jacqui A; Herrero, Javier; Szallasi, Zoltan; Schwarz, Roland F; Stewart, Aengus; Quezada, Sergio A; Le Quesne, John; Van Loo, Peter; Dive, Caroline; Hackshaw, Allan; Swanton, Charles

2017-06-01

Among patients with non-small-cell lung cancer (NSCLC), data on intratumor heterogeneity and cancer genome evolution have been limited to small retrospective cohorts. We wanted to prospectively investigate intratumor heterogeneity in relation to clinical outcome and to determine the clonal nature of driver events and evolutionary processes in early-stage NSCLC. In this prospective cohort study, we performed multiregion whole-exome sequencing on 100 early-stage NSCLC tumors that had been resected before systemic therapy. We sequenced and analyzed 327 tumor regions to define evolutionary histories, obtain a census of clonal and subclonal events, and assess the relationship between intratumor heterogeneity and recurrence-free survival. We observed widespread intratumor heterogeneity for both somatic copy-number alterations and mutations. Driver mutations in EGFR, MET, BRAF, and TP53 were almost always clonal. However, heterogeneous driver alterations that occurred later in evolution were found in more than 75% of the tumors and were common in PIK3CA and NF1 and in genes that are involved in chromatin modification and DNA damage response and repair. Genome doubling and ongoing dynamic chromosomal instability were associated with intratumor heterogeneity and resulted in parallel evolution of driver somatic copy-number alterations, including amplifications in CDK4, FOXA1, and BCL11A. Elevated copy-number heterogeneity was associated with an increased risk of recurrence or death (hazard ratio, 4.9; P=4.4×10 -4 ), which remained significant in multivariate analysis. Intratumor heterogeneity mediated through chromosome instability was associated with an increased risk of recurrence or death, a finding that supports the potential value of chromosome instability as a prognostic predictor. (Funded by Cancer Research UK and others; TRACERx ClinicalTrials.gov number, NCT01888601 .).

On my own: experiences of recovery from acute coronary syndrome for women living alone.

PubMed

Gallagher, Robyn; Marshall, Andrea P; Fisher, Murray J; Elliott, Doug

2008-01-01

Women who live alone are becoming an increasing proportion of our population, yet few studies have examined the experiences that these women have during recovery from an acute cardiac event. This study aims to describe women's experiences of recovering alone from acute coronary syndrome. Women attending cardiac rehabilitation were interviewed 3 to 9 months after acute coronary syndrome using a life history approach to address their personal/social background, professional life, and work-related processes, and to acquire an in-depth narrative of their recovery from illness in relation to this background. The sample included 11 women aged from 44 to 82 years who lived alone. "Being on my own" was the pervasive theme, with independence being both required and valued. One subtheme included the complexity of social support arrangements women needed for their recovery. This was particularly important because women felt vulnerable when they were alone, particularly if they had experienced a sudden cardiac event or recurrent symptoms. Recurrent cardiac symptoms were an important subtheme because of the pervasive influence on women's lives, including their ability to work and plan ahead. Finally, the work and financial issues subtheme was a central concern for women, first because work was an important source of income and enjoyment, and second because loss of work meant loss of income. For some women, this meant selling their home or moving to another house. Women who live alone are an increasing proportion of patients with cardiac disease. Although they share many similar issues with other women and men who live alone, they seem to have unique concerns related to vulnerability, recurrent cardiac symptoms, social support, work, and finances.

Transcriptome from circulating cells suggests dysregulated pathways associated with long-term recurrent events following first-time myocardial infarction.

PubMed

Suresh, Rahul; Li, Xing; Chiriac, Anca; Goel, Kashish; Terzic, Andre; Perez-Terzic, Carmen; Nelson, Timothy J

2014-09-01

Whole-genome gene expression analysis has been successfully utilized to diagnose, prognosticate, and identify potential therapeutic targets for high-risk cardiovascular diseases. However, the feasibility of this approach to identify outcome-related genes and dysregulated pathways following first-time myocardial infarction (AMI) remains unknown and may offer a novel strategy to detect affected expressome networks that predict long-term outcome. Whole-genome expression microarray on blood samples from normal cardiac function controls (n=21) and first-time AMI patients (n=31) within 48-hours post-MI revealed expected differential gene expression profiles enriched for inflammation and immune-response pathways. To determine molecular signatures at the time of AMI associated with long-term outcomes, transcriptional profiles from sub-groups of AMI patients with (n=5) or without (n=22) any recurrent events over an 18-month follow-up were compared. This analysis identified 559 differentially-expressed genes. Bioinformatic analysis of this differential gene-set for associated pathways revealed 1) increasing disease severity in AMI patients is associated with a decreased expression of genes involved in the developmental epithelial-to-mesenchymal transition pathway, and 2) modulation of cholesterol transport genes that include ABCA1, CETP, APOA1, and LDLR is associated with clinical outcome. Differentially regulated genes and modulated pathways were identified that were associated with recurrent cardiovascular outcomes in first-time AMI patients. This cell-based approach for risk stratification in AMI could represent a novel, non-invasive platform to anticipate modifiable pathways and therapeutic targets to optimize long-term outcome for AMI patients and warrants further study to determine the role of metabolic remodeling and regenerative processes required for optimal outcomes. Copyright © 2014 Elsevier Ltd. All rights reserved.

Bevacizumab in ovarian cancer: A critical review of phase III studies

PubMed Central

Rossi, Luigi; Verrico, Monica; Zaccarelli, Eleonora; Papa, Anselmo; Colonna, Maria; Strudel, Martina; Vici, Patrizia; Bianco, Vincenzo; Tomao, Federica

2017-01-01

Bevacizumab (BV) is a humanized monoclonal antibody targeting vascular endothelial growth factor and it is the first molecular-targeted agent to be used for the treatment of ovarian cancer (OC). Randomized Phase III trials evaluated the combination of BV plus standard chemotherapy for first-line treatment of advanced OC and for platinum-sensitive and platinum-resistant recurrent OC. These trials reported a statistically significant improvement in progression-free survival but not in overall survival. Furthermore, BV effectively improved the quality of life with regard to abdominal symptoms in recurrent OC patients. Bevacizumab is associated with adverse events such as hypertension, bleeding, thromboembolism, proteinuria, delayed wound healing, and gastrointestinal events. However, most of these events can be adequately managed. This review describes the latest evidence for BV treatment of OC and selection of patients for personalized treatment. PMID:27852039

Occurrence and Recurrence of Hepatocellular Carcinoma Were Not Rare Events during Phlebotomy in Older Hepatitis C Virus-Infected Patients

PubMed Central

Kanda, Tatsuo; Nakamoto, Shingo; Yasui, Shin; Nakamura, Masato; Miyamura, Tatsuo; Wu, Shuang; Jiang, Xia; Arai, Makoto; Imazeki, Fumio; Yokosuka, Osamu

2014-01-01

The use of phlebotomy is relatively common for ‘difficult-to-treat by antiviral therapies’ hepatitis C virus (HCV)-infected patients and for certain patients having chronic liver diseases with an iron overload of the liver. In the present study, we retrospectively analyzed patients treated with phlebotomy and their adverse events. We observed the occurrence and recurrence of hepatocellular carcinoma, and the appearance of ascites in some patients infected with HCV as well as the reduction of serum ferritin and alanine aminotransferase levels. Severe adverse events necessitating a cessation of phlebotomy occurred independently of α-fetoprotein (>10 ng/ml) in patients infected with HCV according to multivariate logistic regression analysis. These findings may serve as a basis for phlebotomy especially in older patients with chronic hepatitis C. PMID:24926259

Pharmacokinetic and Pharmacodynamic Responses to Clopidogrel: Evidences and Perspectives

PubMed Central

Zhang, Yan-Jiao; Li, Mu-Peng; Tang, Jie; Chen, Xiao-Ping

2017-01-01

Clopidogrel has significantly reduced the incidence of recurrent atherothrombotic events in patients with acute coronary syndrome (ACS) and in those undergoing percutaneous coronary intervention (PCI). However, recurrence events still remain, which may be partly due to inadequate platelet inhibition by standard clopidogrel therapy. Genetic polymorphisms involved in clopidogrel’s absorption, metabolism, and the P2Y12 receptor may interfere with its antiplatelet activity. Recent evidence indicated that epigenetic modification may also affect clopidogrel response. In addition, non-genetic factors such as demographics, disease complications, and drug-drug interactions can impair the antiplatelet effect of clopidogrel. The identification of factors contributing to the variation in clopidogrel response is needed to improve platelet inhibition and to reduce risk for cardiovascular events. This review encompasses the most recent updates on factors influencing pharmacokinetic and pharmacodynamic responses to clopidogrel. PMID:28335443

Two doses of rivaroxaban versus aspirin for prevention of recurrent venous thromboembolism. Rationale for and design of the EINSTEIN CHOICE study.

PubMed

Weitz, Jeffrey I; Bauersachs, Rupert; Beyer-Westendorf, Jan; Bounameaux, Henri; Brighton, Timothy A; Cohen, Alexander T; Davidson, Bruce L; Holberg, Gerlind; Kakkar, Ajay; Lensing, Anthonie W A; Prins, Martin; Haskell, Lloyd; van Bellen, Bonno; Verhamme, Peter; Wells, Philip S; Prandoni, Paolo

2015-08-31

Patients with unprovoked venous thromboembolism (VTE) are at high risk for recurrence. Although rivaroxaban is effective for extended VTE treatment at a dose of 20 mg once daily, use of the 10 mg dose may further improve its benefit-to-risk ratio. Low-dose aspirin also reduces rates of recurrent VTE, but has not been compared with anticoagulant therapy. The EINSTEIN CHOICE study is a multicentre, randomised, double-blind, active-controlled, event-driven study comparing the efficacy and safety of two once daily doses of rivaroxaban (20 and 10 mg) with aspirin (100 mg daily) for the prevention of recurrent VTE in patients who completed 6-12 months of anticoagulant therapy for their index acute VTE event. All treatments will be given for 12 months. The primary efficacy objective is to determine whether both doses of rivaroxaban are superior to aspirin for the prevention of symptomatic recurrent VTE, while the principal safety outcome is the incidence of major bleeding. The trial is anticipated to enrol 2,850 patients from 230 sites in 31 countries over a period of 27 months. In conclusion, the EINSTEIN CHOICE study will provide new insights into the optimal antithrombotic strategy for extended VTE treatment by comparing two doses of rivaroxaban with aspirin (clinicaltrials.gov NCT02064439).

Deep Recurrent Neural Network-Based Autoencoders for Acoustic Novelty Detection

PubMed Central

Vesperini, Fabio; Schuller, Björn

2017-01-01

In the emerging field of acoustic novelty detection, most research efforts are devoted to probabilistic approaches such as mixture models or state-space models. Only recent studies introduced (pseudo-)generative models for acoustic novelty detection with recurrent neural networks in the form of an autoencoder. In these approaches, auditory spectral features of the next short term frame are predicted from the previous frames by means of Long-Short Term Memory recurrent denoising autoencoders. The reconstruction error between the input and the output of the autoencoder is used as activation signal to detect novel events. There is no evidence of studies focused on comparing previous efforts to automatically recognize novel events from audio signals and giving a broad and in depth evaluation of recurrent neural network-based autoencoders. The present contribution aims to consistently evaluate our recent novel approaches to fill this white spot in the literature and provide insight by extensive evaluations carried out on three databases: A3Novelty, PASCAL CHiME, and PROMETHEUS. Besides providing an extensive analysis of novel and state-of-the-art methods, the article shows how RNN-based autoencoders outperform statistical approaches up to an absolute improvement of 16.4% average F-measure over the three databases. PMID:28182121

A High-yield Fall Risk and Adverse Events Screening Questions From the Stopping Elderly Accidents, Death, and Injuries (STEADI) Guideline for Older Emergency Department Fall Patients.

PubMed

Sri-On, Jiraporn; Tirrell, Gregory Philip; Kamsom, Anucha; Marill, Keith A; Shankar, Kalpana Narayan; Liu, Shan W

2018-03-25

The objectives were to examine whether responses to the Stopping Elderly Accidents, Death, and Injuries (STEADI) questions responses predicted adverse events after an older adult emergency department (ED) fall visits and to identify factors associated with such recurrent fall. We conducted a prospective study at two urban, teaching hospitals. We included patients aged ≥ 65 years who presented to the ED for an accidental fall. Data were gathered for fall-relevant comorbidities, high-risk medications for falls, and the responses to 12 questions from the STEADI guideline recommendation. Our outcomes were the number of 6-month adverse events that were defined as mortality, ED revisit, subsequent hospitalization, recurrent falls, and a composite outcome. There were 548 (86.3%) patients who completed follow-up and 243 (44.3%) patients experienced an adverse event after a fall within 6 months. In multivariate analysis, seven questions from the STEADI guideline predicted various outcomes. The question "Had previous fall" predicted recurrent falls (odds ratio [OR] = 2.45, 95% confidence interval [CI] = 1.52 to 3.97), the question "Feels unsteady when walking sometimes" (OR = 2.34, 95% CI = 1.44 to 3.81), and "Lost some feeling in their feet" predicted recurrent falls. In addition to recurrent falls risk, the supplemental questions "Use or have been advised to use a cane or walker," "Take medication that sometimes makes them feel light-headed or more tired than usual," "Take medication to help sleep or improve mood," and "Have to rush to a toilet" predicted other outcomes. A STEADI score of ≥4 did not predict adverse outcomes although seven individual questions from the STEADI guidelines were associated with increased adverse outcomes within 6 months. These may be organized into three categories (previous falls, physical activity, and high-risk medications) and may assist emergency physicians to evaluate and refer high-risk fall patients for a comprehensive falls evaluation. © 2018 by the Society for Academic Emergency Medicine.

Intraplaque stretch in carotid atherosclerotic plaque--an effective biomechanical predictor for subsequent cerebrovascular ischemic events.

PubMed

Teng, Zhongzhao; Sadat, Umar; Wang, Wenkai; Bahaei, Nasim S; Chen, Shengyong; Young, Victoria E; Graves, Martin J; Gillard, Jonathan H

2013-01-01

Stretch is a mechanical parameter, which has been proposed previously to affect the biological activities in different tissues. This study explored its utility in determining plaque vulnerability. One hundred and six patients with mild to moderate carotid stenosis were recruited in this study (53 symptomatic and 53 asymptomatic). High resolution, multi-sequence magnetic resonance (MR) imaging was performed to delineate various plaque components. Finite element method was used to predict high stretch concentration within the plaque. During a two-year follow-up, 11 patients in symptomatic group and 3 in asymptomatic group experienced recurrent cerebrovascular events. Plaque stretch at systole and stretch variation during one cardiac cycle was greater in symptomatic group than those in the asymptomatic. Within the symptomatic group, a similar trend was observed in patients with recurrent events compared to those without. Plaques with high stretch concentration and large stretch variation are associated with increased risk of future cerebrovascular events.

Implementing Extreme Value Analysis in a Geospatial Workflow for Storm Surge Hazard Assessment

NASA Astrophysics Data System (ADS)

Catelli, J.; Nong, S.

2014-12-01

Gridded data of 100-yr (1%) and 500-yr (0.2%) storm surge flood elevations for the United States, Gulf of Mexico, and East Coast are critical to understanding this natural hazard. Storm surge heights were calculated across the study area utilizing SLOSH (Sea, Lake, and Overland Surges from Hurricanes) model data for thousands of synthetic US landfalling hurricanes. Based on the results derived from SLOSH, a series of interpolations were performed using spatial analysis in a geographic information system (GIS) at both the SLOSH basin and the synthetic event levels. The result was a single grid of maximum flood elevations for each synthetic event. This project addresses the need to utilize extreme value theory in a geospatial environment to analyze coincident cells across multiple synthetic events. The results are 100-yr (1%) and 500-yr (0.2%) values for each grid cell in the study area. This talk details a geospatial approach to move raster data to SciPy's NumPy Array structure using the Python programming language. The data are then connected through a Python library to an outside statistical package like R to fit cell values to extreme value theory distributions and return values for specified recurrence intervals. While this is not a new process, the value behind this work is the ability to keep this process in a single geospatial environment and be able to easily replicate this process for other natural hazard applications and extreme event modeling.

Short-term outcomes of the transvaginal minimal mesh procedure for pelvic organ prolapse.

PubMed

Takazawa, Naoko; Fujisaki, Akiko; Yoshimura, Yasukuni; Tsujimura, Akira; Horie, Shigeo

2018-03-01

This study aimed to evaluate the clinical outcomes and complications of transvaginal minimal mesh repair without using commercially available kits for treatment of pelvic organ prolapse (POP). This retrospective cohort study involved 91 women who underwent surgical management of POP with originally designed small mesh between July 2014 and August 2015. This mesh is 56% smaller than the mesh widely used in Japan, and it has only two arms delivered into each right and left sacrospinous ligament. The main study outcome was the anatomic cure rate defined as recurrence of POP quantification (POP-Q) stage II or more. We also assessed changes in the overactive bladder symptom score (OABSS) and prolapse quality of life questionnaire (P-QOL) and evaluated adverse events. Finally, we compared patient backgrounds between the patients with and without recurrence. Prolapse recurred in 10 of 91 patients (11.0%), and all patients with recurrence were diagnosed as POP-Q stage II. As adverse events, only mesh erosion occurred in two (2.2%) and pelvic pain in one (1.1%) of the 91 patients. The OABSS and P-QOL were significantly improved by the operation. When we compared patient backgrounds between the patients with and without recurrence, body mass index was the only factor influencing affecting recurrence. Transvaginal minimal mesh repair resulted in successful outcomes with low mesh-related complications and anatomic recurrence at one year. Furthermore, significant improvement in QOL was offered by this procedure. Our minimal mesh technique should be considered as one treatment option for the management of POP.

Short-term outcomes of the transvaginal minimal mesh procedure for pelvic organ prolapse

PubMed Central

Takazawa, Naoko; Fujisaki, Akiko; Yoshimura, Yasukuni; Tsujimura, Akira

2018-01-01

Purpose This study aimed to evaluate the clinical outcomes and complications of transvaginal minimal mesh repair without using commercially available kits for treatment of pelvic organ prolapse (POP). Materials and Methods This retrospective cohort study involved 91 women who underwent surgical management of POP with originally designed small mesh between July 2014 and August 2015. This mesh is 56% smaller than the mesh widely used in Japan, and it has only two arms delivered into each right and left sacrospinous ligament. The main study outcome was the anatomic cure rate defined as recurrence of POP quantification (POP-Q) stage II or more. We also assessed changes in the overactive bladder symptom score (OABSS) and prolapse quality of life questionnaire (P-QOL) and evaluated adverse events. Finally, we compared patient backgrounds between the patients with and without recurrence. Results Prolapse recurred in 10 of 91 patients (11.0%), and all patients with recurrence were diagnosed as POP-Q stage II. As adverse events, only mesh erosion occurred in two (2.2%) and pelvic pain in one (1.1%) of the 91 patients. The OABSS and P-QOL were significantly improved by the operation. When we compared patient backgrounds between the patients with and without recurrence, body mass index was the only factor influencing affecting recurrence. Conclusions Transvaginal minimal mesh repair resulted in successful outcomes with low mesh-related complications and anatomic recurrence at one year. Furthermore, significant improvement in QOL was offered by this procedure. Our minimal mesh technique should be considered as one treatment option for the management of POP. PMID:29520390

STEREO/SEPT particle observations during the CIR event on 2011 August 9

NASA Astrophysics Data System (ADS)

Dresing, N.; Heber, B.; Klassen, A.; Kühl, P.; Boettcher, S. I.; Gomez-Herrero, R.; Wraase, S.

2017-12-01

Among others, shocks are known to be accelerators of energetic charged particles. However, many questions regarding the acceleration efficiency and the required conditions are not fully understood. In particular, the acceleration of electrons by shocks is often questioned. Recurrent energetic particle events are caused by the passage of Corotating Interaction Regions (CIRs) that have been extensively analysed by different instrumentation close to Earth. Measurements of the Solar Electron and Proton Telescope aboard the Solar TErrestrial RElations Observatory are utilized in the solar heliospheric community to investigate electron events. Due to its measurement principle, the magnet foil technique, ions can contribute to the electron channel. This effect is well known. During recurrent energetic particle events the averaged helium to proton ration is enhanced to more than 10%. The energy per nucleon spectra are nearly the same for protons and helium. Although the electron intensity profile is influenced by an ion contamination during the shock crossings it is not obvious that electrons are not enhanced during such periods. Computation using a GEANT4 simulation of the SEPT instrument resulted in response function for ions and electrons. These response functions have been utilzed to analyze the recurrent energetic particle event that was was measured by STEREO B on August 9, 2011. Assuming a constant helium to proton ratio and energy spectra described by a Band function we found that electron and ion measurement can be explained by the contribution of helium and protons with an helium to proton ratio of about 16%. Thus no electron enhancements are needed to explain the SEPT measurements.

Prospective study of single-stage repair of contaminated hernias using a biologic porcine tissue matrix: the RICH Study.

PubMed

Itani, Kamal M F; Rosen, Michael; Vargo, Daniel; Awad, Samir S; Denoto, George; Butler, Charles E

2012-09-01

In the presence of contamination, the repair of a ventral incisional hernia (VIH) is challenging. The presence of comorbidities poses an additional risk for postoperative wound events and hernia recurrence. To date, very few studies describe the outcomes of VIH repair in this high-risk population. A prospective, multicenter, single-arm, the Repair of Infected or Contaminated Hernias study was performed to study the clinical outcomes of open VIH repair of contaminated abdominal defects with a non-cross-linked, porcine, acellular dermal matrix, Strattice. Of 85 patients who consented to participate, 80 underwent open VIH repair with Strattice. Hernia defects were 'clean-contaminated' (n = 39), 'contaminated' (n = 39), or 'dirty' (n = 2), and the defects were classified as grade 3 (n = 60) or grade 4 (n = 20). The midline was restored, and primary closure was achieved in 64 patients; the defect was bridged in 16 patients. At 24 months, 53 patients (66%) experienced 95 wound events. There were 28 unique, infection-related events in 24 patients. Twenty-two patients experienced seromas, all but 5 of which were transient and required no intervention. No unanticipated adverse events occurred, and no tissue matrix required complete excision. There were 22 hernia (28%) recurrences by month 24. There was no correlation between infection-related events and hernia recurrence. The use of the intact, non-cross-linked, porcine, acellular dermal matrix, Strattice, in the repair of contaminated VIH in high-risk patients allowed for successful, single-stage reconstruction in >70% of patients followed for 24 months after repair. Published by Mosby, Inc.

Recurrence plots of discrete-time Gaussian stochastic processes

NASA Astrophysics Data System (ADS)

Ramdani, Sofiane; Bouchara, Frédéric; Lagarde, Julien; Lesne, Annick

2016-09-01

We investigate the statistical properties of recurrence plots (RPs) of data generated by discrete-time stationary Gaussian random processes. We analytically derive the theoretical values of the probabilities of occurrence of recurrence points and consecutive recurrence points forming diagonals in the RP, with an embedding dimension equal to 1. These results allow us to obtain theoretical values of three measures: (i) the recurrence rate (REC) (ii) the percent determinism (DET) and (iii) RP-based estimation of the ε-entropy κ(ε) in the sense of correlation entropy. We apply these results to two Gaussian processes, namely first order autoregressive processes and fractional Gaussian noise. For these processes, we simulate a number of realizations and compare the RP-based estimations of the three selected measures to their theoretical values. These comparisons provide useful information on the quality of the estimations, such as the minimum required data length and threshold radius used to construct the RP.

Circum-Pacific seismic potential: 1989-1999

USGS Publications Warehouse

Nishenko, S.P.

1991-01-01

The seismic potential for 96 segments of simple plate boundaries around the circum-Pacific region is presented in terms of the conditional probability for the occurrence of either large or great interplate earthquakes during the next 5, 10, and 20 years (i.e., 1989-1994, 1989-1999 and 1989-2009). This study represents the first probabilistic summary of seismic potential on this scale, and involves the comparison of plate boundary segments that exhibit varying recurrence times, magnitudes, and tectonic regimes. Presenting these data in a probabilistic framework provides a basis for the uniform comparison of seismic hazard between these differing fault segments, as well as accounting for individual variations in recurrence time along a specific fault segment, and uncertainties in the determination of the average recurrence time. The definition of specific segments along simple plate boundaries relies on the mapping of earthquake rupture zones as defined by the aftershock distributions of prior large and great earthquakes, and historic descriptions of felt intensities and damage areas. The 96 segments are chosen to represent areas likely to be ruptured by "characteristic" earthquakes of a specified size or magnitude. The term characteristic implies repeated breakage of a plate boundary segment by large or great earthquakes whose source dimensions are similar from cycle to cycle. This definition does not exclude the possibility that occasionally adjacent characteristic earthquake segments may break together in a single, larger event. Conversely, a segment may also break in a series of smaller ruptures. Estimates of recurrence times and conditional probabilities for characteristic earthquakes along segments of simple plate boundaries are based on 1) the historic and instrumental record of large and great earthquake occurrence; 2) paleoseismic evidence of recurrence from radiometric dating of Holocene features produced by earthquakes; 3) direct calculations of recurrence time from the size of the most recent characteristic event and the long-term rates of plate motion assuming the validity of the time-predictable model for earthquake recurrence; and 4) the application of a lognormal distribution for the recurrence times of large and great earthquakes. Time-dependent estimates of seismic potential are based on a physical model of earthquake occurrence which assumes that the probability for an earthquake is low immediately following the occurrence of a characteristic earthquake and increases with time as the stress on the fault segment recovers the stress drop of the event. This study updates earlier work on seismic gaps by explicitly including both recurrence time information and the temporal proximity to the next event as factors in describing earthquake hazards. Currently, 11 out of 96 regions have a high (i.e., ???50%) probability of recurrence during the next 10 years and are characterized by either fairly short (i.e., less than 30-40 years) recurrence times or long elapsed times relative to the average recurrence time. The majority of these segments are located in the southwest Pacific (Vanuatu, New Guinea, and Tonga). When a longer time window is considered (e.g., 20 years or 1989-2009), 30 out of 96 regions have a high potential. Many of these regions are located near areas of high population density. These determinations do not preclude rupture of other fault segments, with less than a 50% chance in 10 or 20 years, or large and great earthquakes in areas we have not studied in detail. While this study has summarized the seismic potential for a large number of regions around the circum-Pacific, there are still a number of geographic and seismotectonic regions that need to be considered, including Indonesia, the Philippines, New Zealand, and the countries that surround the Caribbean basin. ?? 1991 Birkha??user Verlag.

Source parameters of a M4.8 and its accompanying repeating earthquakes off Kamaishi, NE Japan: Implications for the hierarchical structure of asperities and earthquake cycle

USGS Publications Warehouse

Uchida, N.; Matsuzawa, T.; Ellsworth, W.L.; Imanishi, K.; Okada, T.; Hasegawa, A.

2007-01-01

We determine the source parameters of a M4.9 ?? 0.1 'characteristic earthquake' sequence and its accompanying microearthquakes at ???50 km depth on the subduction plate boundary offshore of Kamaishi, NE Japan. The microearthquakes tend to occur more frequently in the latter half of the recurrence intervals of the M4.9 ?? 0.1 events. Our results show that the microearthquakes are repeating events and they are located not only around but also within the slip area for the 2001 M4.8 event. From the hierarchical structure of slip areas and smaller stress drops for the microearthquakes compared to the M4.8 event, we infer the small repeating earthquakes rupture relatively weak patches in and around the slip area for the M4.8 event and their activity reflects a stress concentration process and/or change in frictional property (healing) at the area. We also infer the patches for the M4.9 ?? 0.1 and other repeating earthquakes undergo aseismic slip during their interseismic period. Copyright 2007 by the American Geophysical Union.

Closure of patent foramen ovale versus medical therapy after cryptogenic stroke.

PubMed

Carroll, John D; Saver, Jeffrey L; Thaler, David E; Smalling, Richard W; Berry, Scott; MacDonald, Lee A; Marks, David S; Tirschwell, David L

2013-03-21

Whether closure of a patent foramen ovale is effective in the prevention of recurrent ischemic stroke in patients who have had a cryptogenic stroke is unknown. We conducted a trial to evaluate whether closure is superior to medical therapy alone in preventing recurrent ischemic stroke or early death in patients 18 to 60 years of age. In this prospective, multicenter, randomized, event-driven trial, we randomly assigned patients, in a 1:1 ratio, to medical therapy alone or closure of the patent foramen ovale. The primary results of the trial were analyzed when the target of 25 primary end-point events had been observed and adjudicated. We enrolled 980 patients (mean age, 45.9 years) at 69 sites. The medical-therapy group received one or more antiplatelet medications (74.8%) or warfarin (25.2%). Treatment exposure between the two groups was unequal (1375 patient-years in the closure group vs. 1184 patient-years in the medical-therapy group, P=0.009) owing to a higher dropout rate in the medical-therapy group. In the intention-to-treat cohort, 9 patients in the closure group and 16 in the medical-therapy group had a recurrence of stroke (hazard ratio with closure, 0.49; 95% confidence interval [CI], 0.22 to 1.11; P=0.08). The between-group difference in the rate of recurrent stroke was significant in the prespecified per-protocol cohort (6 events in the closure group vs. 14 events in the medical-therapy group; hazard ratio, 0.37; 95% CI, 0.14 to 0.96; P=0.03) and in the as-treated cohort (5 events vs. 16 events; hazard ratio, 0.27; 95% CI, 0.10 to 0.75; P=0.007). Serious adverse events occurred in 23.0% of the patients in the closure group and in 21.6% in the medical-therapy group (P=0.65). Procedure-related or device-related serious adverse events occurred in 21 of 499 patients in the closure group (4.2%), but the rate of atrial fibrillation or device thrombus was not increased. In the primary intention-to-treat analysis, there was no significant benefit associated with closure of a patent foramen ovale in adults who had had a cryptogenic ischemic stroke. However, closure was superior to medical therapy alone in the prespecified per-protocol and as-treated analyses, with a low rate of associated risks. (Funded by St. Jude Medical; RESPECT ClinicalTrials.gov number, NCT00465270.).

Translocations in epithelial cancers

PubMed Central

Chad Brenner, J.; Chinnaiyan, Arul M.

2009-01-01

Genomic translocations leading to the expression of chimeric transcripts characterize several hematologic, mesenchymal and epithelial malignancies. While several gene fusions have been linked to essential molecular events in hematologic malignancies, the identification and characterization of recurrent chimeric transcripts in epithelial cancers has been limited. However, the recent discovery of the recurrent gene fusions in prostate cancer has sparked a revitalization of the quest to identify novel rearrangements in epithelial malignancies. Here, the molecular mechanisms of gene fusions that drive several epithelial cancers and the recent technological advances that increase the speed and reliability of recurrent gene fusion discovery are explored. PMID:19406209

Effectiveness and cost-effectiveness of mindfulness-based cognitive therapy compared with maintenance antidepressant treatment in the prevention of depressive relapse or recurrence (PREVENT): a randomised controlled trial.

PubMed

Kuyken, Willem; Hayes, Rachel; Barrett, Barbara; Byng, Richard; Dalgleish, Tim; Kessler, David; Lewis, Glyn; Watkins, Edward; Brejcha, Claire; Cardy, Jessica; Causley, Aaron; Cowderoy, Suzanne; Evans, Alison; Gradinger, Felix; Kaur, Surinder; Lanham, Paul; Morant, Nicola; Richards, Jonathan; Shah, Pooja; Sutton, Harry; Vicary, Rachael; Weaver, Alice; Wilks, Jenny; Williams, Matthew; Taylor, Rod S; Byford, Sarah

2015-07-04

Individuals with a history of recurrent depression have a high risk of repeated depressive relapse or recurrence. Maintenance antidepressants for at least 2 years is the current recommended treatment, but many individuals are interested in alternatives to medication. Mindfulness-based cognitive therapy (MBCT) has been shown to reduce risk of relapse or recurrence compared with usual care, but has not yet been compared with maintenance antidepressant treatment in a definitive trial. We aimed to see whether MBCT with support to taper or discontinue antidepressant treatment (MBCT-TS) was superior to maintenance antidepressants for prevention of depressive relapse or recurrence over 24 months. In this single-blind, parallel, group randomised controlled trial (PREVENT), we recruited adult patients with three or more previous major depressive episodes and on a therapeutic dose of maintenance antidepressants, from primary care general practices in urban and rural settings in the UK. Participants were randomly assigned to either MBCT-TS or maintenance antidepressants (in a 1:1 ratio) with a computer-generated random number sequence with stratification by centre and symptomatic status. Participants were aware of treatment allocation and research assessors were masked to treatment allocation. The primary outcome was time to relapse or recurrence of depression, with patients followed up at five separate intervals during the 24-month study period. The primary analysis was based on the principle of intention to treat. The trial is registered with Current Controlled Trials, ISRCTN26666654. Between March 23, 2010, and Oct 21, 2011, we assessed 2188 participants for eligibility and recruited 424 patients from 95 general practices. 212 patients were randomly assigned to MBCT-TS and 212 to maintenance antidepressants. The time to relapse or recurrence of depression did not differ between MBCT-TS and maintenance antidepressants over 24 months (hazard ratio 0·89, 95% CI 0·67-1·18; p=0·43), nor did the number of serious adverse events. Five adverse events were reported, including two deaths, in each of the MBCT-TS and maintenance antidepressants groups. No adverse events were attributable to the interventions or the trial. We found no evidence that MBCT-TS is superior to maintenance antidepressant treatment for the prevention of depressive relapse in individuals at risk for depressive relapse or recurrence. Both treatments were associated with enduring positive outcomes in terms of relapse or recurrence, residual depressive symptoms, and quality of life. National Institute for Health Research (NIHR) Health Technology Assessment (HTA) programme, and NIHR Collaboration for Leadership in Applied Health Research and Care South West Peninsula. Copyright © 2015 Kuyken et al. Open Access article distributed under the terms of CC BY. Published by Elsevier Ltd.. All rights reserved.

Event detection and localization for small mobile robots using reservoir computing.

PubMed

Antonelo, E A; Schrauwen, B; Stroobandt, D

2008-08-01

Reservoir Computing (RC) techniques use a fixed (usually randomly created) recurrent neural network, or more generally any dynamic system, which operates at the edge of stability, where only a linear static readout output layer is trained by standard linear regression methods. In this work, RC is used for detecting complex events in autonomous robot navigation. This can be extended to robot localization tasks which are solely based on a few low-range, high-noise sensory data. The robot thus builds an implicit map of the environment (after learning) that is used for efficient localization by simply processing the input stream of distance sensors. These techniques are demonstrated in both a simple simulation environment and in the physically realistic Webots simulation of the commercially available e-puck robot, using several complex and even dynamic environments.

Pancreatic Cancer in Pregnancy Presenting with Thromboembolic Events: Case Report and Review of the Literature.

PubMed

Wakefield, Brian W; Masterson, Crystal M C; Borges, Manuel T; Hurt, K Joseph

2018-06-08

Stroke and hepatic vein thrombosis are highly associated with neoplasia but are extremely rare events in young, pregnant women. Rare and recurrent thrombotic events in pregnancy increase the suspicion for occult malignancy. We describe the case of a healthy 31-year-old G2P1 who presented with visual changes and dysarthria during pregnancy. Imaging showed cerebral infarcts. Her thrombophilia evaluation was negative. During delivery, she was diagnosed with fulminant Budd-Chiari Syndrome. Hepatic ultrasound suggested malignancy or metastasis, and postpartum CT scan and biopsy confirmed the diagnosis of Stage IV pancreatic cancer. Although rare in pregnancy, a new diagnosis of malignancy should be considered in patients with recurrent unexplained hypercoagulable complications. We propose an evidence-based algorithm for evaluation of occult malignancy in pregnancy based upon this case and review of the literature. © 2018 S. Karger AG, Basel.

Hypothalamic-Pituitary-Adrenal Axis Programming after Recurrent Hypoglycemia during Development

PubMed Central

Rao, Raghavendra

2015-01-01

Permanent brain injury is a complication of recurrent hypoglycemia during development. Recurrent hypoglycemia also has adverse consequences on the neuroendocrine system. Hypoglycemia-associated autonomic failure, characterized by ineffective glucose counterregulation during hypoglycemia, is well described in children and adults on insulin therapy for diabetes mellitus. Whether recurrent hypoglycemia also has a programming effect on the hypothalamus-pituitary-adrenal cortex (HPA) axis has not been well studied. Hypoglycemia is a potent stress that leads to increased glucocorticoid secretion in all age groups, including the perinatal period. Other conditions associated with exposure to excess glucocorticoid in the perinatal period have a programming effect on the HPA axis activity. Limited animal data suggest the possibility of similar programming effect after recurrent hypoglycemia in the postnatal period. The age at exposure to hypoglycemia likely determines the HPA axis response in adulthood. Recurrent hypoglycemia in the early postnatal period likely leads to a hyperresponsive HPA axis, whereas recurrent hypoglycemia in the late postnatal period lead to a hyporesponsive HPA axis in adulthood. The age-specific programming effects may determine the neuroendocrine response during hypoglycemia and other stressful events in individuals with history of recurrent hypoglycemia during development. PMID:26343738

Hypothalamic-Pituitary-Adrenal Axis Programming after Recurrent Hypoglycemia during Development.

PubMed

Rao, Raghavendra

2015-08-28

Permanent brain injury is a complication of recurrent hypoglycemia during development. Recurrent hypoglycemia also has adverse consequences on the neuroendocrine system. Hypoglycemia-associated autonomic failure, characterized by ineffective glucose counterregulation during hypoglycemia, is well described in children and adults on insulin therapy for diabetes mellitus. Whether recurrent hypoglycemia also has a programming effect on the hypothalamus-pituitary-adrenal cortex (HPA) axis has not been well studied. Hypoglycemia is a potent stress that leads to increased glucocorticoid secretion in all age groups, including the perinatal period. Other conditions associated with exposure to excess glucocorticoid in the perinatal period have a programming effect on the HPA axis activity. Limited animal data suggest the possibility of similar programming effect after recurrent hypoglycemia in the postnatal period. The age at exposure to hypoglycemia likely determines the HPA axis response in adulthood. Recurrent hypoglycemia in the early postnatal period likely leads to a hyperresponsive HPA axis, whereas recurrent hypoglycemia in the late postnatal period lead to a hyporesponsive HPA axis in adulthood. The age-specific programming effects may determine the neuroendocrine response during hypoglycemia and other stressful events in individuals with history of recurrent hypoglycemia during development.

Identification of eight candidate target genes of the recurrent 3p12-p14 loss in cervical cancer by integrative genomic profiling.

PubMed

Lando, Malin; Wilting, Saskia M; Snipstad, Kristin; Clancy, Trevor; Bierkens, Mariska; Aarnes, Eva-Katrine; Holden, Marit; Stokke, Trond; Sundfør, Kolbein; Holm, Ruth; Kristensen, Gunnar B; Steenbergen, Renske D M; Lyng, Heidi

2013-05-01

The pathogenetic role, including its target genes, of the recurrent 3p12-p14 loss in cervical cancer has remained unclear. To determine the onset of the event during carcinogenesis, we used microarray techniques and found that the loss was the most frequent 3p event, occurring in 61% of 92 invasive carcinomas, in only 2% of 43 high-grade intraepithelial lesions (CIN2/3), and in 33% of 6 CIN3 lesions adjacent to invasive carcinomas, suggesting a role in acquisition of invasiveness or early during the invasive phase. We performed an integrative DNA copy number and expression analysis of 77 invasive carcinomas, where all genes within the recurrent region were included. We selected eight genes, THOC7, PSMD6, SLC25A26, TMF1, RYBP, SHQ1, EBLN2, and GBE1, which were highly down-regulated in cases with loss, as confirmed at the protein level for RYBP and TMF1 by immunohistochemistry. The eight genes were subjected to network analysis based on the expression profiles, revealing interaction partners of proteins encoded by the genes that were coordinately regulated in tumours with loss. Several partners were shared among the eight genes, indicating crosstalk in their signalling. Gene ontology analysis showed enrichment of biological processes such as apoptosis, proliferation, and stress response in the network and suggested a relationship between down-regulation of the eight genes and activation of tumourigenic pathways. Survival analysis showed prognostic impact of the eight-gene signature that was confirmed in a validation cohort of 74 patients and was independent of clinical parameters. These results support the role of the eight candidate genes as targets of the 3p12-p14 loss in cervical cancer and suggest that the strong selection advantage of the loss during carcinogenesis might be caused by a synergetic effect of several tumourigenic processes controlled by these targets. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Spatial recurrence analysis: A sensitive and fast detection tool in digital mammography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Prado, T. L.; Galuzio, P. P.; Lopes, S. R.

Efficient diagnostics of breast cancer requires fast digital mammographic image processing. Many breast lesions, both benign and malignant, are barely visible to the untrained eye and requires accurate and reliable methods of image processing. We propose a new method of digital mammographic image analysis that meets both needs. It uses the concept of spatial recurrence as the basis of a spatial recurrence quantification analysis, which is the spatial extension of the well-known time recurrence analysis. The recurrence-based quantifiers are able to evidence breast lesions in a way as good as the best standard image processing methods available, but with amore » better control over the spurious fragments in the image.« less

[Use of a new cobetalactamine in the therapy of acute and chronic odontogenic processes].

PubMed

De Siate, A

1979-01-01

Treatment of 70 patients with acute and chronic odontogenic processes for 5-35 days (mean 10.9 days) with a new cobetalactamine is reported. Rapid resolution was noted in nosological groups marked by the presence of acute infection. Particular interest is attached to the effect of the drug on chronicisting infections, such as apical granuloma, maxillary osteitis, and radicular cysts, since these forms displayed a high degree of vascular isolation, were often sustained by a mixed flora, and had been previously treated with other antibiotics. Follow-up four weeks after the conclusion of treatment showed a low incidence of recurrences that was in all events lower than in earlier experiments with chemical antibiotics. There were no instances of intolerance or allergy.

Butterfly, Recurrence, and Predictability in Lorenz Models

NASA Astrophysics Data System (ADS)

Shen, B. W.

2017-12-01

Over the span of 50 years, the original three-dimensional Lorenz model (3DLM; Lorenz,1963) and its high-dimensional versions (e.g., Shen 2014a and references therein) have been used for improving our understanding of the predictability of weather and climate with a focus on chaotic responses. Although the Lorenz studies focus on nonlinear processes and chaotic dynamics, people often apply a "linear" conceptual model to understand the nonlinear processes in the 3DLM. In this talk, we present examples to illustrate the common misunderstandings regarding butterfly effect and discuss the importance of solutions' recurrence and boundedness in the 3DLM and high-dimensional LMs. The first example is discussed with the following folklore that has been widely used as an analogy of the butterfly effect: "For want of a nail, the shoe was lost.For want of a shoe, the horse was lost.For want of a horse, the rider was lost.For want of a rider, the battle was lost.For want of a battle, the kingdom was lost.And all for the want of a horseshoe nail."However, in 2008, Prof. Lorenz stated that he did not feel that this verse described true chaos but that it better illustrated the simpler phenomenon of instability; and that the verse implicitly suggests that subsequent small events will not reverse the outcome (Lorenz, 2008). Lorenz's comments suggest that the verse neither describes negative (nonlinear) feedback nor indicates recurrence, the latter of which is required for the appearance of a butterfly pattern. The second example is to illustrate that the divergence of two nearby trajectories should be bounded and recurrent, as shown in Figure 1. Furthermore, we will discuss how high-dimensional LMs were derived to illustrate (1) negative nonlinear feedback that stabilizes the system within the five- and seven-dimensional LMs (5D and 7D LMs; Shen 2014a; 2015a; 2016); (2) positive nonlinear feedback that destabilizes the system within the 6D and 8D LMs (Shen 2015b; 2017); and (3) recurrence (e.g., quasi-periodic solutions) within non-dissipative LMs (Faghih-Naini and Shen, 2017; Shen and Faghih-Naini, 2017). http://bwshen.sdsu.edu/shen_agu17.html

Committee Opinion No. 681: Disclosure and Discussion of Adverse Events.

PubMed

2016-12-01

Adverse outcomes, preventable or otherwise, are a reality of medical care. Most importantly, adverse events affect patients, but they also affect health care practitioners. Disclosing information about adverse events has benefits for the patient and the physician and, ideally, strengthens the patient-physician relationship and promotes trust. Studies show that after an adverse outcome, patients expect and want timely and full disclosure of the event, an acknowledgment of responsibility, an understanding of what happened, expressions of sympathy, and a discussion of what is being done to prevent recurrence. Surveys have shown that patients are less likely to pursue litigation if they perceive that the event was honestly disclosed. Barriers to full disclosure are many and include fear of retribution for reporting an adverse event, lack of training, a culture of blame, and fear of lawsuits. To reduce these concerns, it is recommended that health care facilities establish a nonpunitive, blame-free culture that encourages staff to report adverse events and near misses (close calls) without fear of retaliation. Health care institutions should have written policies that address the management of adverse events. Having a responsive process to inform and aid the patient, loved ones, and practitioners is required. A commitment on the part of all health care practitioners and institutions to establish programs and develop the tools needed to help patients, families, health care practitioners, and staff members deal with adversity is essential.

Committee Opinion No. 681 Summary: Disclosure and Discussion of Adverse Events.

PubMed

2016-12-01

Adverse outcomes, preventable or otherwise, are a reality of medical care. Most importantly, adverse events affect patients, but they also affect health care practitioners. Disclosing information about adverse events has benefits for the patient and the physician and, ideally, strengthens the patient-physician relationship and promotes trust. Studies show that after an adverse outcome, patients expect and want timely and full disclosure of the event, an acknowledgment of responsibility, an understanding of what happened, expressions of sympathy, and a discussion of what is being done to prevent recurrence. Surveys have shown that patients are less likely to pursue litigation if they perceive that the event was honestly disclosed. Barriers to full disclosure are many and include fear of retribution for reporting an adverse event, lack of training, a culture of blame, and fear of lawsuits. To reduce these concerns, it is recommended that health care facilities establish a nonpunitive, blame-free culture that encourages staff to report adverse events and near misses (close calls) without fear of retaliation. Health care institutions should have written policies that address the management of adverse events. Having a responsive process to inform and aid the patient, loved ones, and practitioners is required. A commitment on the part of all health care practitioners and institutions to establish programs and develop the tools needed to help patients, families, health care practitioners, and staff members deal with adversity is essential.

Extreme and superextreme events in a loss-modulated CO2 laser: Nonlinear resonance route and precursors

NASA Astrophysics Data System (ADS)

Bonatto, Cristian; Endler, Antonio

2017-07-01

We investigate the occurrence of extreme and rare events, i.e., giant and rare light pulses, in a periodically modulated CO2 laser model. Due to nonlinear resonant processes, we show a scenario of interaction between chaotic bands of different orders, which may lead to the formation of extreme and rare events. We identify a crisis line in the modulation parameter space, and we show that, when the modulation amplitude increases, remaining in the vicinity of the crisis, some statistical properties of the laser pulses, such as the average and dispersion of amplitudes, do not change much, whereas the amplitude of extreme events grows enormously, giving rise to extreme events with much larger deviations than usually reported, with a significant probability of occurrence, i.e., with a long-tailed non-Gaussian distribution. We identify recurrent regular patterns, i.e., precursors, that anticipate the emergence of extreme and rare events, and we associate these regular patterns with unstable periodic orbits embedded in a chaotic attractor. We show that the precursors may or may not lead to the emergence of extreme events. Thus, we compute the probability of success or failure (false alarm) in the prediction of the extreme events, once a precursor is identified in the deterministic time series. We show that this probability depends on the accuracy with which the precursor is identified in the laser intensity time series.

Fixed recurrence and slip models better predict earthquake behavior than the time- and slip-predictable models: 2. Laboratory earthquakes

NASA Astrophysics Data System (ADS)

Rubinstein, Justin L.; Ellsworth, William L.; Beeler, Nicholas M.; Kilgore, Brian D.; Lockner, David A.; Savage, Heather M.

2012-02-01

The behavior of individual stick-slip events observed in three different laboratory experimental configurations is better explained by a "memoryless" earthquake model with fixed inter-event time or fixed slip than it is by the time- and slip-predictable models for earthquake occurrence. We make similar findings in the companion manuscript for the behavior of natural repeating earthquakes. Taken together, these results allow us to conclude that the predictions of a characteristic earthquake model that assumes either fixed slip or fixed recurrence interval should be preferred to the predictions of the time- and slip-predictable models for all earthquakes. Given that the fixed slip and recurrence models are the preferred models for all of the experiments we examine, we infer that in an event-to-event sense the elastic rebound model underlying the time- and slip-predictable models does not explain earthquake behavior. This does not indicate that the elastic rebound model should be rejected in a long-term-sense, but it should be rejected for short-term predictions. The time- and slip-predictable models likely offer worse predictions of earthquake behavior because they rely on assumptions that are too simple to explain the behavior of earthquakes. Specifically, the time-predictable model assumes a constant failure threshold and the slip-predictable model assumes that there is a constant minimum stress. There is experimental and field evidence that these assumptions are not valid for all earthquakes.

Salvage HDR Brachytherapy for Recurrent Prostate Cancer After Previous Definitive Radiation Therapy: 5-Year Outcomes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Chien Peter; Weinberg, Vivian; Shinohara, Katsuto

Purpose: Evaluate efficacy and toxicity of salvage high-dose-rate brachytherapy (HDRB) for locally recurrent prostate cancer after definitive radiation therapy (RT). Methods and Materials: We retrospectively analyzed 52 consecutively accrued patients undergoing salvage HDRB between 1998 and 2009 for locally recurrent prostate cancer after previous definitive RT. After pathologic confirmation of locally recurrent disease, patients received 36 Gy in 6 fractions. Twenty-four patients received neoadjuvant hormonal therapy before salvage, and no patients received adjuvant hormonal therapy. Determination of biochemical failure after salvage HDRB was based on the Phoenix definition. Overall survival (OS) and bF distributions were calculated using the Kaplan-Meier method.more » Univariate analyses were performed to identify predictors of biochemical control. Acute and late genitourinary (GU) and gastrointestinal (GI) toxicities, based on Common Terminology Criteria for Adverse Events (version 4), were documented. Results: Median follow-up after salvage HDRB was 59.6 months. The 5-year OS estimate was 92% (95% confidence interval [CI]: 80%-97%) with median survival not yet reached. Five-year biochemical control after salvage was 51% (95% CI: 34%-66%). Median PSA nadir postsalvage was 0.1 (range: 0-7.2) reached at a median of 10.2 months after completing HDRB. As for complications, acute and late grade 3 GU toxicities were observed in only 2% and 2%, respectively. No grade 2 or higher acute GI events and 4% grade 2 GI late events were observed. On univariate analysis, disease-free interval after initial definitive RT (P=.07), percent of positive cores at the time of diagnosis (P=.08), interval from first recurrence to salvage HDRB (P=.09), and pre-HDRB prostate-specific antigen (P=.07) were each of borderline significance in predicting biochemical control after salvage HDRB. Conclusions: Prostate HDRB is an effective salvage modality with relatively few long-term toxicities. We provide potential predictors of biochemical control for prostate salvage HDRB.« less

Octreotide LAR and Prednisone as Neoadjuvant Treatment in Patients with Primary or Locally Recurrent Unresectable Thymic Tumors: A Phase II Study

PubMed Central

Kirzinger, Lukas; Boy, Sandra; Marienhagen, Jörg; Schuierer, Gerhard; Neu, Reiner; Ried, Michael; Hofmann, Hans-Stefan; Wiebe, Karsten; Ströbel, Philipp; May, Christoph; Kleylein-Sohn, Julia; Baierlein, Claudia; Bogdahn, Ulrich; Marx, Alexander; Schalke, Berthold

2016-01-01

Therapeutic options to cure advanced, recurrent, and unresectable thymomas are limited. The most important factor for long-term survival of thymoma patients is complete resection (R0) of the tumor. We therefore evaluated the response to and the induction of resectability of primarily or locally recurrent unresectable thymomas and thymic carcinomas by octreotide Long-Acting Release (LAR) plus prednisone therapy in patients with positive octreotide scans. In this open label, single-arm phase II study, 17 patients with thymomas considered unresectable or locally recurrent thymoma (n = 15) and thymic carcinoma (n = 2) at Masaoka stage III were enrolled. Octreotide LAR (30 mg once every 2 weeks) was administered in combination with prednisone (0.6 mg/kg per day) for a maximum of 24 weeks (study design according to Fleming´s one sample multiple testing procedure for phase II clinical trials). Tumor size was evaluated by volumetric CT measurements, and a decrease in tumor volume of at least 20% at week 12 compared to baseline was considered as a response. We found that octreotide LAR plus prednisone elicited response in 15 of 17 patients (88%). Median reduction of tumor volume after 12 weeks of treatment was 51% (range 20%–86%). Subsequently, complete surgical resection was achieved in five (29%) and four patients (23%) after 12 and 24 weeks, respectively. Octreotide LAR plus prednisone treatment was discontinued in two patients before week 12 due to unsatisfactory therapeutic effects or adverse events. The most frequent adverse events were gastrointestinal (71%), infectious (65%), and hematological (41%) complications. In conclusion, octreotide LAR plus prednisone is efficacious in patients with primary or recurrent unresectable thymoma with respect to tumor regression. Octreotide LAR plus prednisone was well tolerated and adverse events were in line with the known safety profile of both agents. PMID:27992479

Glioblastoma adaptation traced through decline of an IDH1 clonal driver and macro-evolution of a double-minute chromosome

PubMed Central

Favero, F.; McGranahan, N.; Salm, M.; Birkbak, N. J.; Sanborn, J. Z.; Benz, S. C.; Becq, J.; Peden, J. F.; Kingsbury, Z.; Grocok, R. J.; Humphray, S.; Bentley, D.; Spencer-Dene, B.; Gutteridge, A.; Brada, M.; Roger, S.; Dietrich, P.-Y.; Forshew, T.; Gerlinger, M.; Rowan, A.; Stamp, G.; Eklund, A. C.; Szallasi, Z.; Swanton, C.

2015-01-01

Background Glioblastoma (GBM) is the most common malignant brain cancer occurring in adults, and is associated with dismal outcome and few therapeutic options. GBM has been shown to predominantly disrupt three core pathways through somatic aberrations, rendering it ideal for precision medicine approaches. Methods We describe a 35-year-old female patient with recurrent GBM following surgical removal of the primary tumour, adjuvant treatment with temozolomide and a 3-year disease-free period. Rapid whole-genome sequencing (WGS) of three separate tumour regions at recurrence was carried out and interpreted relative to WGS of two regions of the primary tumour. Results We found extensive mutational and copy-number heterogeneity within the primary tumour. We identified a TP53 mutation and two focal amplifications involving PDGFRA, KIT and CDK4, on chromosomes 4 and 12. A clonal IDH1 R132H mutation in the primary, a known GBM driver event, was detectable at only very low frequency in the recurrent tumour. After sub-clonal diversification, evidence was found for a whole-genome doubling event and a translocation between the amplified regions of PDGFRA, KIT and CDK4, encoded within a double-minute chromosome also incorporating miR26a-2. The WGS analysis uncovered progressive evolution of the double-minute chromosome converging on the KIT/PDGFRA/PI3K/mTOR axis, superseding the IDH1 mutation in dominance in a mutually exclusive manner at recurrence, consequently the patient was treated with imatinib. Despite rapid sequencing and cancer genome-guided therapy against amplified oncogenes, the disease progressed, and the patient died shortly after. Conclusion This case sheds light on the dynamic evolution of a GBM tumour, defining the origins of the lethal sub-clone, the macro-evolutionary genomic events dominating the disease at recurrence and the loss of a clonal driver. Even in the era of rapid WGS analysis, cases such as this illustrate the significant hurdles for precision medicine success. PMID:25732040

Efficacy of self-expandable metal stents in management of benign biliary strictures and comparison with multiple plastic stents: a meta-analysis.

PubMed

Khan, Muhammad Ali; Baron, Todd H; Kamal, Faisal; Ali, Bilal; Nollan, Richard; Ismail, Mohammad Kashif; Tombazzi, Claudio; Artifon, Everson L A; Repici, Alessandro; Khashab, Mouen A

2017-07-01

Background and study aims  There is burgeoning interest in the utilization of covered self-expandable metal stents (CSEMSs) for managing benign biliary stricture (BBS). This systematic review and meta-analysis evaluated cumulative stricture resolution and recurrence rates using CSEMSs and compared performance of CSEMSs and multiple plastic stents (MPS) in BBS management. Method  Searches in several databases identified studies including ≥ 10 patients that utilized CSEMSs for BBS treatment. Weighted pooled rates were calculated for stricture resolution and recurrence. Pooled risk ratios (RRs) comparing CSEMSs with MPS were calculated for stricture resolution, stricture recurrence, and adverse events. Pooled difference in means was calculated to compare number of endoscopic retrograde cholangiopancreatographies (ERCPs) in each group.  Results  The meta-analysis included 22 studies with 1298 patients. Weighted pooled rate for BBS resolution with CSEMS was 83 % (95 % confidence limits [95 %CLs] 78 %, 87 %; I 2  = 72 %). On meta-regression analysis, resolution in chronic pancreatitis patients and post-orthotopic liver transplant patients were significant predictors of heterogeneity. Weighted pooled rate for stricture recurrence with CSEMSs was 16 % (11 %, 22 %). Overall rate of adverse events requiring intervention and/or hospitalization was 15 %. Four randomized controlled trials with 213 patients compared CSEMSs with MPS: the pooled RRs for stricture resolution, recurrence, and adverse events were 1.07 (0.97, 1.18), 0.88 (0.48, 1.63), and 1.16 (0.71, 1.88), respectively with no heterogeneity. Pooled difference in means for number of ERCPs was - 1.71 ( - 2.33, - 1.09) in favor of CSEMS. Conclusions  CSEMSs appear to have excellent efficacy in BBS management. They are as effective as MPS but require fewer ERCPs to achieve clinical success. © Georg Thieme Verlag KG Stuttgart · New York.

Randomized, Double-Blind, Placebo-Controlled Trial of Asenapine Maintenance Therapy in Adults With an Acute Manic or Mixed Episode Associated With Bipolar I Disorder.

PubMed

Szegedi, Armin; Durgam, Suresh; Mackle, Mary; Yu, Sung Yun; Wu, Xiao; Mathews, Maju; Landbloom, Ronald P

2018-01-01

The authors determined the efficacy and safety of asenapine in preventing recurrence of any mood episode in adults with bipolar I disorder. Adults with an acute manic or mixed episode per DSM-IV-TR criteria were enrolled in this randomized, placebo-controlled trial consisting of an initial 12- to 16-week open-label period and a 26-week double-blind randomized withdrawal period. The target asenapine dosage was 10 mg b.i.d. in the open-label period but could be titrated down to 5 mg b.i.d. After completing the open-label period, subjects meeting stabilization/stable-responder criteria were randomized to asenapine or placebo treatment in the double-blind period. The primary efficacy endpoint was time to recurrence of any mood event during the double-blind period. Kaplan-Meier estimation was performed, and 95% confidence intervals were determined. Safety was assessed throughout. A total of 549 subjects entered the open-label period, of whom 253 enrolled in the double-blind randomized withdrawal period (127 in the placebo group; 126 in the asenapine group). Time to recurrence of any mood episode was statistically significantly longer for asenapine- than placebo-treated subjects. In post hoc analyses, significant differences in favor of asenapine over placebo were seen in time to recurrence of manic and depressive episodes. The most common treatment-emergent adverse events were somnolence (10.0%), akathisia (7.7%), and sedation (7.7%) in the open-label period and mania (11.9% of the placebo group compared with 4.0% of the asenapine group) and bipolar I disorder (6.3% compared with 1.6%) in the double-blind period. Long-term treatment with asenapine was more effective than placebo in preventing recurrence of mood events in adults with bipolar I disorder and was generally well-tolerated.

Identification of doctors at risk of recurrent complaints: a national study of healthcare complaints in Australia

PubMed Central

Bismark, Marie M; Spittal, Matthew J; Gurrin, Lyle C; Ward, Michael; Studdert, David M

2013-01-01

Objectives (1) To determine the distribution of formal patient complaints across Australia's medical workforce and (2) to identify characteristics of doctors at high risk of incurring recurrent complaints. Methods We assembled a national sample of all 18 907 formal patient complaints filed against doctors with health service ombudsmen (‘Commissions’) in Australia over an 11-year period. We analysed the distribution of complaints among practicing doctors. We then used recurrent-event survival analysis to identify characteristics of doctors at high risk of recurrent complaints, and to estimate each individual doctor's risk of incurring future complaints. Results The distribution of complaints among doctors was highly skewed: 3% of Australia's medical workforce accounted for 49% of complaints and 1% accounted for a quarter of complaints. Short-term risks of recurrence varied significantly among doctors: there was a strong dose-response relationship with number of previous complaints and significant differences by doctor specialty and sex. At the practitioner level, risks varied widely, from doctors with <10% risk of further complaints within 2 years to doctors with >80% risk. Conclusions A small group of doctors accounts for half of all patient complaints lodged with Australian Commissions. It is feasible to predict which doctors are at high risk of incurring more complaints in the near future. Widespread use of this approach to identify high-risk doctors and target quality improvement efforts coupled with effective interventions, could help reduce adverse events and patient dissatisfaction in health systems. PMID:23576774

Detailed longitudinal sampling of glioma stem cells in situ reveals Chr7 gain and Chr10 loss as repeated events in primary tumor formation and recurrence.

PubMed

Baysan, Mehmet; Woolard, Kevin; Cam, Margaret C; Zhang, Wei; Song, Hua; Kotliarova, Svetlana; Balamatsias, Demosthenes; Linkous, Amanda; Ahn, Susie; Walling, Jennifer; Belova, Galina I; Fine, Howard A

2017-11-15

Intratumoral heterogeneity at the genetic, epigenetic, transcriptomic, and morphologic levels is a commonly observed phenomenon in many aggressive cancer types. Clonal evolution during tumor formation and in response to therapeutic intervention can be predicted utilizing reverse engineering approaches on detailed genomic snapshots of heterogeneous patient tumor samples. In this study, we developed an extensive dataset for a GBM case via the generation of polyclonal and monoclonal glioma stem cell lines from initial diagnosis, and from multiple sections of distant tumor locations of the deceased patient's brain following tumor recurrence. Our analyses revealed the tissue-wide expansion of a new clone in the recurrent tumor and chromosome 7 gain and chromosome 10 loss as repeated genomic events in primary and recurrent disease. Moreover, chromosome 7 gain and chromosome 10 loss produced similar alterations in mRNA expression profiles in primary and recurrent tumors despite possessing other highly heterogeneous and divergent genomic alterations between the tumors. We identified ETV1 and CDK6 as putative candidate genes, and NFKB (complex), IL1B, IL6, Akt and VEGF as potential signaling regulators, as potentially central downstream effectors of chr7 gain and chr10 loss. Finally, the differences caused by the transcriptomic shift following gain of chromosome 7 and loss of chromosome 10 were consistent with those generally seen in GBM samples compared to normal brain in large-scale patient-tumor data sets. © 2017 UICC.

Recurrence intervals for the closure of the Dutch Maeslant surge barrier

NASA Astrophysics Data System (ADS)

van den Brink, Henk W.; de Goederen, Sacha

2017-09-01

The Dutch Maeslant Barrier, a movable surge barrier in the mouth of the river Rhine, closes when there is a surge in the North Sea and the water level in the river at Rotterdam exceeds 3 m above mean sea level. An important aspect of the failure probability is that the barrier might get damaged during a closure and that, within the time needed for repair, a second critical storm surge may occur. With an estimated closure frequency of once in 10 years, the question of how often the barrier has to be closed twice within one month arises.Instead of tackling this problem by the application of statistical models on the (short) observational series, we solve the problem by combining the surge model WAQUA/DCSMv5 with the output of all seasonal forecasts of the European Centre of Medium-Range Weather Forecasting (ECMWF) in the period 1981-2015, whose combination cumulates in a pseudo-observational series of more than 6000 years.We show that the Poisson process model leads to wrong results as it neglects the temporal correlations that are present on daily, weekly and monthly timescales.By counting the number of double events over a threshold of 2.5 m and assuming that the number of events is exponentially related to the threshold, it is found that two closures occur on average once in 150 years within a month, and once in 330 years within a week. The large uncertainty in these recurrence intervals of more than a factor of two is caused by the sensitivity of the results to the Gumbel parameters of the observed record, which are used for bias correction.Sea level rise has a significant impact on the recurrence time for both single and double closures. The recurrence time of single closures doubles with every 18 cm mean sea level rise (assuming that other influences remain unchanged) and double closures double with every 10 cm rise. This implies a 3-14 times higher probability of a double closure for a 15-40 cm sea level rise in 2050 (according to the KNMI climate scenarios).

Regularity of a renewal process estimated from binary data.

PubMed

Rice, John D; Strawderman, Robert L; Johnson, Brent A

2017-10-09

Assessment of the regularity of a sequence of events over time is important for clinical decision-making as well as informing public health policy. Our motivating example involves determining the effect of an intervention on the regularity of HIV self-testing behavior among high-risk individuals when exact self-testing times are not recorded. Assuming that these unobserved testing times follow a renewal process, the goals of this work are to develop suitable methods for estimating its distributional parameters when only the presence or absence of at least one event per subject in each of several observation windows is recorded. We propose two approaches to estimation and inference: a likelihood-based discrete survival model using only time to first event; and a potentially more efficient quasi-likelihood approach based on the forward recurrence time distribution using all available data. Regularity is quantified and estimated by the coefficient of variation (CV) of the interevent time distribution. Focusing on the gamma renewal process, where the shape parameter of the corresponding interevent time distribution has a monotone relationship with its CV, we conduct simulation studies to evaluate the performance of the proposed methods. We then apply them to our motivating example, concluding that the use of text message reminders significantly improves the regularity of self-testing, but not its frequency. A discussion on interesting directions for further research is provided. © 2017, The International Biometric Society.

Days to Return to Participation After a Hamstrings Strain Among American Collegiate Soccer Players

PubMed Central

Cross, Kevin M.; Saliba, Susan A.; Conaway, Mark; Gurka, Kelly K.; Hertel, Jay

2015-01-01

Context Among US collegiate soccer players, the incidence rate and the event characteristics of hamstrings strains differ between sexes, but comparisons in the return-to-participation (RTP) time have not been reported. Objective To compare the RTP time between male and female collegiate soccer players and analyze the influence of event characteristics on the RTP time for each sex. Design Descriptive epidemiology study. Setting Data were collected from collegiate teams that voluntarily participated in the National Collegiate Athletic Association Injury Surveillance System. Patients or Other Participants Collegiate soccer athletes who sustained 507 hamstrings strains (306 men, 201 women) during the 2004 through 2009 fall seasons. Main Outcome Measure(s) Nonparametric statistics were used to evaluate RTP time differences between sexes and among categories of each event characteristic (ie, time of season, practice or competition, player position). Negative binomial regression was used to model the RTP time for each sex. All analyses were performed separately for first-time and recurrent strains. Results We found no differences in the RTP time between sexes for first-time (median: men = 7.0 days, women = 6.0 days; P = .07) or recurrent (median: men = 11 days, women = 5.5 days; P = .06) hamstrings strains. For male players with first-time strains, RTP time was increased when the strain occurred during competition or the in-season/postseason and varied depending on the division of play. Among female players with first-time strains, we found no differences in RTP time within characteristics. For male players with recurrent hamstrings strains, the RTP time was longer when the injury occurred during the in-season/postseason. Among female players with recurrent strains, RTP time was longer for forwards than for midfielders or defenders. Conclusions Although we found no differences in the RTP time after hamstrings strains in male and female collegiate soccer players, each sex had unique event characteristics that influenced RTP time. PMID:25978100

Behavior in Oblivion: The Neurobiology of Subliminal Priming

PubMed Central

Jacobs, Christianne; Sack, Alexander T.

2012-01-01

Subliminal priming refers to behavioral modulation by an unconscious stimulus, and can thus be regarded as a form of unconscious visual processing. Theories on recurrent processing have suggested that the neural correlate of consciousness (NCC) comprises of the non-hierarchical transfer of stimulus-related information. According to these models, the neural correlate of subliminal priming (NCSP) corresponds to the visual processing within the feedforward sweep. Research from cognitive neuroscience on these two concepts and the relationship between them is discussed here. Evidence favoring the necessity of recurrent connectivity for visual awareness is accumulating, although some questions, such as the need for global versus local recurrent processing, are not clarified yet. However, this is not to say that recurrent processing is sufficient for consciousness, as a neural definition of consciousness in terms of recurrent connectivity would imply. We argue that the limited interest cognitive neuroscience currently has for the NCSP is undeserved, because the discovery of the NCSP can give insight into why people do (and do not) express certain behavior. PMID:24962773

Comparison of the low-density lipoprotein cholesterol target value and the preventive effect of statins in elderly patients and younger patients.

PubMed

Endo, Akihiro; Okada, Taiji; Pak, Misun; Kagawa, Yuzo; Ito, Shimpei; Sato, Hirotomo; Kageshima, Kenji; Yoshida, Yasuyuki; Tanabe, Kazuaki

2017-06-01

To assess whether the low-density lipoprotein cholesterol (LDL-C) target value and preventive effect of statins are different between elderly and younger patients. We investigated 304 patients with previous percutaneous coronary intervention who underwent coronary angiography from January 2007 to December 2016 for examination of recurrent ischemia beyond the early restenosis. Patients were classified into two groups: age ≥ 75 years (elderly group: n = 140) and < 75 years (younger group: n = 164). Relationships between the achieved LDL-C level, incidence of late coronary events, and the effectiveness of statins were evaluated. During follow-up, 179 patients underwent late coronary revascularization. Recurrent ischemia presenting as acute coronary syndrome (ACS) occurred in 83 cases. Kaplan-Meier curve analysis revealed that in the younger group, recurrent ACS was significantly lower in patients with LDL-C < 70 mg/dL than in those with LDL-C ranging from 70 to < 100 mg/dL ( P = 0.035); however, there was no difference between these in the elderly group ( P = 0.863). Instead, recurrent ACS was less frequent in patients with LDL-C ranging from 70 mg/dL to < 100 mg/dL than in those with LDL-C ≥ 100 mg/dL in the elderly group ( P = 0.033). Statin use was associated with decreased recurrent ACS ( P = 0.005); moreover, only using statins was an independent predictor in the elderly group (HR: 0.375; P = 0.007). Strict control of LDL-C to < 70 mg/dL was effective for reducing the incidence of recurrent ACS in younger patients. However, LDL-C < 100 mg/dL might be sufficient as the target value of LDL-C-lowering therapy for secondary prevention of ischemic events in Japanese elderly patients.

A GIS-based time-dependent seismic source modeling of Northern Iran

NASA Astrophysics Data System (ADS)

Hashemi, Mahdi; Alesheikh, Ali Asghar; Zolfaghari, Mohammad Reza

2017-01-01

The first step in any seismic hazard study is the definition of seismogenic sources and the estimation of magnitude-frequency relationships for each source. There is as yet no standard methodology for source modeling and many researchers have worked on this topic. This study is an effort to define linear and area seismic sources for Northern Iran. The linear or fault sources are developed based on tectonic features and characteristic earthquakes while the area sources are developed based on spatial distribution of small to moderate earthquakes. Time-dependent recurrence relationships are developed for fault sources using renewal approach while time-independent frequency-magnitude relationships are proposed for area sources based on Poisson process. GIS functionalities are used in this study to introduce and incorporate spatial-temporal and geostatistical indices in delineating area seismic sources. The proposed methodology is used to model seismic sources for an area of about 500 by 400 square kilometers around Tehran. Previous researches and reports are studied to compile an earthquake/fault catalog that is as complete as possible. All events are transformed to uniform magnitude scale; duplicate events and dependent shocks are removed. Completeness and time distribution of the compiled catalog is taken into account. The proposed area and linear seismic sources in conjunction with defined recurrence relationships can be used to develop time-dependent probabilistic seismic hazard analysis of Northern Iran.

Multi-state model for studying an intermediate event using time-dependent covariates: application to breast cancer.

PubMed

Meier-Hirmer, Carolina; Schumacher, Martin

2013-06-20

The aim of this article is to propose several methods that allow to investigate how and whether the shape of the hazard ratio after an intermediate event depends on the waiting time to occurrence of this event and/or the sojourn time in this state. A simple multi-state model, the illness-death model, is used as a framework to investigate the occurrence of this intermediate event. Several approaches are shown and their advantages and disadvantages are discussed. All these approaches are based on Cox regression. As different time-scales are used, these models go beyond Markov models. Different estimation methods for the transition hazards are presented. Additionally, time-varying covariates are included into the model using an approach based on fractional polynomials. The different methods of this article are then applied to a dataset consisting of four studies conducted by the German Breast Cancer Study Group (GBSG). The occurrence of the first isolated locoregional recurrence (ILRR) is studied. The results contribute to the debate on the role of the ILRR with respect to the course of the breast cancer disease and the resulting prognosis. We have investigated different modelling strategies for the transition hazard after ILRR or in general after an intermediate event. Including time-dependent structures altered the resulting hazard functions considerably and it was shown that this time-dependent structure has to be taken into account in the case of our breast cancer dataset. The results indicate that an early recurrence increases the risk of death. A late ILRR increases the hazard function much less and after the successful removal of the second tumour the risk of death is almost the same as before the recurrence. With respect to distant disease, the appearance of the ILRR only slightly increases the risk of death if the recurrence was treated successfully. It is important to realize that there are several modelling strategies for the intermediate event and that each of these strategies has restrictions and may lead to different results. Especially in the medical literature considering breast cancer development, the time-dependency is often neglected in the statistical analyses. We show that the time-varying variables cannot be neglected in the case of ILRR and that fractional polynomials are a useful tool for finding the functional form of these time-varying variables.

Using low-frequency earthquake families on the San Andreas fault as deep creepmeters

NASA Astrophysics Data System (ADS)

Thomas, A.; Beeler, N. M.; Bletery, Q.; Burgmann, R.; Shelly, D. R.

2017-12-01

The San Andreas fault hosts tectonic tremor and low-frequency earthquakes (LFEs) similar to those in subduction zone environments. These LFEs are grouped into families based on waveform similarity and locate between 16 and 29 km depth along a 150-km-long section of the fault centered on Parkfield, CA. ­Within individual LFE families event occurrence is not steady. In some families, bursts of a few events recur on timescales of days while in other families there are nearly quiescent periods that often last for months followed by episodes where hundreds of events occur over the course of a few days. These two different styles of LFE occurrence are called continuous and episodic respectively. LFEs are often assumed to reflect persistent regions that periodically fail during the aseismic shear of the surrounding fault allowing them to be used as creepmeters. We test this idea by formalizing the definition of a creepmeter (the LFE occurrence rate is proportional to the local fault slip rate), determining whether this definition is consistent with the observations, and over what timescale. We use the recurrence intervals of LFEs within individual families to create a catalog of LFE bursts. For the episodic families, we consider both longer duration (multiday) inferred creep episodes (dubbed long-timescale episodic) as well as the frequent short-term bursts of events that occur many times during inferred creep episodes (dubbed short-timescale episodic). We then use the recurrence intervals of LFE bursts to estimate the timing, duration, recurrence interval, slip, and slip rate associated with inferred slow slip events. We find that continuous families and the short-timescale episodic families appear to be inconsistent with our definition of a creepmeter (defined on the recurrence interval timescale) because their estimated durations are not physically meaningful. A straight-forward interpretation of the frequent short-term bursts of the continuous and short-timescale episodic families is that they do not represent individual creep events but rather are persistent asperities that are driven to failure by quasi-continuous creep on the surrounding fault. In contrast, episodic families likely define sections of the fault where slip is distinctly episodic in well-defined SSEs that slip at 15 times the long-term rate.

The Impact of Frictional Healing on Stick-Slip Recurrence Interval and Stress Drop: Implications for Earthquake Scaling

NASA Astrophysics Data System (ADS)

Im, Kyungjae; Elsworth, Derek; Marone, Chris; Leeman, John

2017-12-01

Interseismic frictional healing is an essential process in the seismic cycle. Observations of both natural and laboratory earthquakes demonstrate that the magnitude of stress drop scales with the logarithm of recurrence time, which is a cornerstone of the rate and state friction (RSF) laws. However, the origin of this log linear behavior and short time "cutoff" for small recurrence intervals remains poorly understood. Here we use RSF laws to demonstrate that the back-projected time of null-healing intrinsically scales with the initial frictional state θi. We explore this behavior and its implications for (1) the short-term cutoff time of frictional healing and (2) the connection between healing rates derived from stick-slip sliding versus slide-hold-slide tests. We use a novel, continuous solution of RSF for a one-dimensional spring-slider system with inertia. The numerical solution continuously traces frictional state evolution (and healing) and shows that stick-slip cutoff time also scales with frictional state at the conclusion of the dynamic slip process θi (=Dc/Vpeak). This numerical investigation on the origins of stick-slip response is verified by comparing laboratory data for a range of peak slip velocities. Slower slip motions yield lesser magnitude of friction drop at a given time due to higher frictional state at the end of each slip event. Our results provide insight on the origin of log linear stick-slip evolution and suggest an approach to estimating the critical slip distance on faults that exhibit gradual accelerations, such as for slow earthquakes.

Nonparametric analysis of bivariate gap time with competing risks.

PubMed

Huang, Chiung-Yu; Wang, Chenguang; Wang, Mei-Cheng

2016-09-01

This article considers nonparametric methods for studying recurrent disease and death with competing risks. We first point out that comparisons based on the well-known cumulative incidence function can be confounded by different prevalence rates of the competing events, and that comparisons of the conditional distribution of the survival time given the failure event type are more relevant for investigating the prognosis of different patterns of recurrence disease. We then propose nonparametric estimators for the conditional cumulative incidence function as well as the conditional bivariate cumulative incidence function for the bivariate gap times, that is, the time to disease recurrence and the residual lifetime after recurrence. To quantify the association between the two gap times in the competing risks setting, a modified Kendall's tau statistic is proposed. The proposed estimators for the conditional bivariate cumulative incidence distribution and the association measure account for the induced dependent censoring for the second gap time. Uniform consistency and weak convergence of the proposed estimators are established. Hypothesis testing procedures for two-sample comparisons are discussed. Numerical simulation studies with practical sample sizes are conducted to evaluate the performance of the proposed nonparametric estimators and tests. An application to data from a pancreatic cancer study is presented to illustrate the methods developed in this article. © 2016, The International Biometric Society.

Chaos in brake squeal noise

NASA Astrophysics Data System (ADS)

Oberst, S.; Lai, J. C. S.

2011-02-01

Brake squeal has become an increasing concern to the automotive industry because of warranty costs and the requirement for continued interior vehicle noise reduction. Most research has been directed to either analytical and experimental studies of brake squeal mechanisms or the prediction of brake squeal propensity using finite element methods. By comparison, there is a lack of systematic analysis of brake squeal data obtained from a noise dynamometer. It is well known that brake squeal is a nonlinear transient phenomenon and a number of studies using analytical and experimental models of brake systems (e.g., pin-on-disc) indicate that it could be treated as a chaotic phenomenon. Data obtained from a full brake system on a noise dynamometer were examined with nonlinear analysis techniques. The application of recurrence plots reveals chaotic structures even in noisy data from the squealing events. By separating the time series into different regimes, lower dimensional attractors are isolated and quantified by dynamic invariants such as correlation dimension estimates or Lyapunov exponents. Further analysis of the recurrence plot of squealing events by means of recurrence quantification analysis measures reveals different regimes of laminar and random behaviour, periodicity and chaos-forming recurrent transitions. These results help to classify brake squeal mechanisms and to enhance understanding of friction-related noise phenomena.

The link between heightened thrombogenicity and inflammation: pre-procedure characterization of the patient at high risk for recurrent events after stenting.

PubMed

Gurbel, Paul A; Bliden, Kevin P; Kreutz, Rolf P; Dichiara, Joseph; Antonino, Mark J; Tantry, Udaya S

2009-03-01

Heightened thrombogenicity and biomarker evidence of inflammation have been independently associated with ischemic risk in patients with coronary artery disease. However, a study examining their relation has not been reported. We analysed the relation between measurements of thrombogenicity and biomarkers in patients undergoing stenting and followed for 24 months recurrent ischemic events. In 84 consecutive patients undergoing stenting, pre-procedure thrombogenicity was measured by thrombelastography (TEG) and conventional aggregometry whereas biomarkers were measured by fluorokine multi-analyte profiling. Patients were stratified into quartiles based on platelet-fibrin clot strength (MA) by TEG and correlated with ischemic event occurrence. Patients in the highest MA quartile (high MA) had greater ADP-induced platelet aggregation (57.5 +/- 15.0% vs. 47.9 +/- 17.6%, p = 0.05), C-reactive protein (25.0 +/- 5.6 vs. 4.2 +/- 1.0 microg/mL, p = 0.006) and interleukin-8 (23.8 +/- 2.8 vs. 14.1 +/- 1.6 pg/mL, p < 0.001) than patients within the lowest MA quartile (low MA). Epidermal growth factor (7.7 +/- 2.2 vs. 1.2 +/- 0.3 pg/mL, p = 0.006) and vascular endothelial growth factor (296 +/- 35 vs. 190 +/- 10 pg/mL, p = 0.05) were also higher. Patients with high-MA had an ischemic event more often than patients with low-MA (48% vs. 13%, p = 0.02). Our study suggests that a link is present between inflammation and heightened thrombogenicity measured pre-procedurally in the patient at high risk for recurrent ischemic events after stenting. Larger studies are required to solidify these observations and their clinical relevance.

Magnetospheric State of Sawtooth Events

NASA Technical Reports Server (NTRS)

Fung, Shing F.; Tepper, Julia A.; Cai, Xia

2016-01-01

Magnetospheric sawtooth events, first identified in the early 1990s, are named for their characteristic appearance of multiple quasiperiodic intervals of slow decrease followed by sharp increase of proton differential energy fluxes in the geosynchronous region. The successive proton flux oscillations have been interpreted as recurrences of stretching and dipolarization of the nightside geomagnetic field. Due to their often extended intervals with 210 cycles, sawteeth occurrences are sometimes referred to as a magnetospheric mode. While studies of sawtooth events over the past two decades have yielded a wealth of information about such events, the magnetospheric state conditions for the occurrence of sawtooth events and how sawtooth oscillations may depend on the magnetospheric state conditions remain unclear. In this study, we investigate the characteristic magnetospheric state conditions (specified by Psw interplanetary magnetic field (IMF) Btot, IMF Bz Vsw, AE, Kp and Dst, all time shifted with respect to one another) associated with the intervals before, during, and after sawteeth occurrences. Applying a previously developed statistical technique, we have determined the most probable magnetospheric states propitious for the development and occurrence of sawtooth events, respectively. The statistically determined sawtooth magnetospheric state has also been validated by using out-of-sample events, confirming the notion that sawtooth intervals might represent a particular global state of the magnetosphere. We propose that the sawtooth state of the magnetosphere may be a state of marginal stability in which a slight enhancement in the loading rate of an otherwise continuous loading process can send the magnetosphere into the marginally unstable regime, causing it to shed limited amount of energy quickly and return to the marginally stable regime with the loading process continuing. Sawtooth oscillations result as the magnetosphere switches between the marginally stable (loading) and unstable (unloading) phases.

Deciphering ocean acidification from eutrophication events as the main cause of neritic carbonate factory collapse: Insight from a recurrently-perturbed Earth (Lower Jurassic, Morocco)

NASA Astrophysics Data System (ADS)

Bodin, S.; Krencker, F.; Suan, G.; Heimhofer, U.; Immenhauser, A.

2013-12-01

Shallow-marine carbonate ecosystems react sensitively to environmental changes and have often been documented as being early responders to climatic deteriorations. In extreme cases, such as pronounced global warming, ocean eutrophication or acidification events, the shallow-water carbonate community can collapse, leading to the so-called drowning events. However, deciphering the exact cause of carbonate platform demise in the geological record is not straightforward as the aforementioned mechanisms are intimately linked via feedback processes. The Upper Pliensbachian-Toarcian of Morocco presents an exceptional case study with regard to this question for several reasons: (1) It offers outstanding outcrops of carbonate ecosystem, that can be traced from shallow- to deep-water settings. (2) Over a period of ca. 15 Myrs, the Western Tethyan area was submitted to recurrent extreme environmental changes, linked to the long-lasting activity of the Karoo-Ferrar Large Igneous Province (LIP). During this period, the planet Earth has experienced several rapid changes between coldhouse and hothouse state, accompanied by massive injection of carbon into the ocean/atmosphere reservoirs. (3) The magnitude of change differs however from one event to another, with an oceanic acidification event only likely to have happened at the onset of the Toarcian Oceanic Anoxic Event (T-OAE), but not for the other events. In the High Atlas Basin of Morocco, a total of four successive events of carbonate factory demise can be documented during the Late Pliensbachian - Toarcian time interval. These events are contemporaneous with marine extinction events and can be linked to environmental deterioration consecutive to pulsed activity of the Karoo-Ferrar LIP. They all lead to a shutdown of carbonate accumulation. They however differ in their timing and unfolding. Of major interest are the demise events recorded at the Pliensbachian-Toarcian boundary (eT-E) and at the onset of the T-OAE. An intense sea-water eutrophication occurs during the first event, as documented by phosphorus analyses in deep-water setting and the disappearance of shallow-water oligotrophic hypercalcifiers (corals & lithiotids bivalves) to the benefit of siliciclastic sedimentation. Interestingly, the transition between the two sedimentation regimes is characterized by a swarming of echinoids. The oligotrophic hypercalcifiers are however quickly reappearing in the aftermath of the eT-e. The second demise event, associated with the T-OAE, where an ocean acidification event is suspected, is characterized by a dissolution surface and the long-lasting disappearance of the hypercalcifiers organisms. A clear differentiation is therefore documented between neritic carbonate factory demise linked to seawater eutrophication from those linked to ocean acidification.

Shock Wave Lithotripsy: Effects on the Pancreas and Recurrent Stone Disease

NASA Astrophysics Data System (ADS)

Krambeck, Amy E.; Rohlinger, Audrey L.; Lohse, Christine M.; Patterson, David E.; Gettman, Matthew T.

2007-04-01

Long-term effects of shockwave lithotripsy (SWL) are unknown; however, we recently found an association between SWL and diabetes mellitus in a population based case control cohort. To further study the association between SWL and diabetes mellitus, we determined the immediate impact of SWL on the pancreas as well as the long-term natural history of stone disease following treatment. Chart review identified 630 patients treated with SWL at our institution in 1985. Questionnaires focusing on recurrent stone episodes after SWL were sent to 578 patients alive in 2004. To further assess impact of SWL on the pancreas, pancreatic enzyme measurements were performed on 24 symptomatic stone patients treated in 2006 with ureteroscopy (n=12) and SWL (n=12). Serum amylase and lipase were evaluated pre and post SWL. A⩾5 U/L increase in either lab value was considered significant. Among patients in the long-term SWL treatment group, the questionnaire response rate was 58.9% (288/489). Recurrent stone events were noted in 154 (53.5%) of the survey respondents. Characteristics associated with stone recurrences were: gender (p=0.004), age at SWL (p=0.022), BMI (p=0.007), SWL complications (p=0.009), and lower pole SWL (p=0.025). Recurrent stone disease was also associated with the development of diabetes mellitus (p=0.020). In the contemporary group of treated stone patients, pancreatic enzyme analysis demonstrated an increase in serum amylase and lipase in 3 (25.0%) SWL patients and 1 (8.3%) ureteroscopy patient (p=0.273). In conclusion, over half of the patients treated with SWL will develop recurrent stone events. We found a strong association between recurrent stone disease and the development of diabetes mellitus at long-term follow-up. Although not statistically significant due to small number, data in a contemporary treatment cohort suggest the possibility that the pancreas can be adversely affected by SWL.

Optic neuromyelitis syndrome in Brazilian patients

PubMed Central

Papais-Alvarenga, R; Miranda-Santos, C; Puccioni-Sohler, M; de Almeida, A M V; Oliveira, S; De Oliveira, C A B.; Alvarenga, H; Poser, C

2002-01-01

Objectives: To report the clinical features and outcome of 24 Brazilian patients with optic neuromyelitis syndrome (ONM); discuss the underlying pathological events associated with the ONM syndrome; review the nosological situation of ONM in the group of inflammatory and demyelinating diseases of the central nervous system. Patients and Methods: Patients with ONM treated at the Hospital da Lagoa, Rio de Janeiro were studied. Demographic, clinical, magnetic resonance imaging, cerebrospinal fluid, and pathological data were analysed. Results: The study consisted of 20 women, four men of whom 10 were white and 14 Afro-Brazilians. Clinical course was recurrent in 22 cases and monophasic in two. Neurological manifestations at inclusion were: sensory impairment (66%), bilateral (41.6%) or unilateral blindness (20.8%), paraplegia or quadriplegia (37.5%). The EDSS was moderate/severe in 70.8%. The underlying pathological events were respectively pulmonary tuberculosis and upper respiratory infection in the two monophasic cases; in the 22 recurrent ONM patients: pulmonary tuberculosis (3), neurocysticercosis (1), polyarteritis nodosa (1), antinuclear antibody and rheumatoid factor (1), antiphospholipid antibody primary syndrome (1), diabetes mellitus (1), hypothyroidism (1), and amenorrhea-galactorrhea (4). Normal cerebrospinal fluid was found in 52% and an inflammatory profile in 48%. Only four recurrent ONM white patients had brain and spinal cord magnetic resonance imaging and cerebrospinal fluid findings compatible with the diagnosis of multiple sclerosis. Large lesions were seen in 62% of spinal magnetic resonance images. Six of 12 recurrent ONM Afro-Brazilian died. There were no statistical differences in the demographic data of the two ethnic groups. Afro-Brazilians were significantly more severely impaired and had a higher mortality rate than the white patients. Conclusion: These cases were classified as follows: two monophasic acute disseminated encephalomyelitis; one recurrent disseminated encephalomyelitis; three recurrent ONM associated with Hughes syndrome, autoantibodies and polyarteritis nodosa; six recurrent ONM with endocrinopathies; and finally, four muliple sclerosis cases. The remaining cases were not associated with any other condition. It would seem clear that ONM is a syndrome rather than a single disease. PMID:12235313

Work stress and patient safety: observer-rated work stressors as predictors of characteristics of safety-related events reported by young nurses.

PubMed

Elfering, A; Semmer, N K; Grebner, S

This study investigates the link between workplace stress and the 'non-singularity' of patient safety-related incidents in the hospital setting. Over a period of 2 working weeks 23 young nurses from 19 hospitals in Switzerland documented 314 daily stressful events using a self-observation method (pocket diaries); 62 events were related to patient safety. Familiarity of safety-related events and probability of recurrence, as indicators of non-singularity, were the dependent variables in multilevel regression analyses. Predictor variables were both situational (self-reported situational control, safety compliance) and chronic variables (job stressors such as time pressure, or concentration demands and job control). Chronic work characteristics were rated by trained observers. The most frequent safety-related stressful events included incomplete or incorrect documentation (40.3%), medication errors (near misses 21%), delays in delivery of patient care (9.7%), and violent patients (9.7%). Familiarity of events and probability of recurrence were significantly predicted by chronic job stressors and low job control in multilevel regression analyses. Job stressors and low job control were shown to be risk factors for patient safety. The results suggest that job redesign to enhance job control and decrease job stressors may be an important intervention to increase patient safety.

Recurrent Education in Yugoslavia.

ERIC Educational Resources Information Center

Soljan, Niksa Nikola, Ed.

These seven papers offer an insight into the different aspects of recurrent education in Yugoslavia. "Recurrent Education and Educational Changes" considers these three processes: the "de-etatization," the democratization, and the de-schooling of education. "The Unity of Education and Work and Recurrent Education"…

Ultra-Rapid serial visual presentation reveals dynamics of feedforward and feedback processes in the ventral visual pathway.

PubMed

Mohsenzadeh, Yalda; Qin, Sheng; Cichy, Radoslaw M; Pantazis, Dimitrios

2018-06-21

Human visual recognition activates a dense network of overlapping feedforward and recurrent neuronal processes, making it hard to disentangle processing in the feedforward from the feedback direction. Here, we used ultra-rapid serial visual presentation to suppress sustained activity that blurs the boundaries of processing steps, enabling us to resolve two distinct stages of processing with MEG multivariate pattern classification. The first processing stage was the rapid activation cascade of the bottom-up sweep, which terminated early as visual stimuli were presented at progressively faster rates. The second stage was the emergence of categorical information with peak latency that shifted later in time with progressively faster stimulus presentations, indexing time-consuming recurrent processing. Using MEG-fMRI fusion with representational similarity, we localized recurrent signals in early visual cortex. Together, our findings segregated an initial bottom-up sweep from subsequent feedback processing, and revealed the neural signature of increased recurrent processing demands for challenging viewing conditions. © 2018, Mohsenzadeh et al.

Post-disturbance sediment recovery: Implications for watershed resilience

NASA Astrophysics Data System (ADS)

Rathburn, Sara L.; Shahverdian, Scott M.; Ryan, Sandra E.

2018-03-01

Sediment recovery following disturbances is a measure of the time required to attain pre-disturbance sediment fluxes. Insight into the controls on recovery processes and pathways builds understanding of geomorphic resilience. We assess post-disturbance sediment recovery in three small (1.5-100 km2), largely unaltered watersheds within the northern Colorado Rocky Mountains affected by wildfires, floods, and debris flows. Disturbance regimes span 102 (floods, debris flows) to 103 years (wildfires). For all case studies, event sediment recovery followed a nonlinear pattern: initial high sediment flux during single precipitation events or high annual snowmelt runoff followed by decreasing sediment fluxes over time. Disturbance interactions were evaluated after a high-severity fire within the South Fork Cache la Poudre basin was followed by an extreme flood one year post-fire. This compound disturbance hastened suspended sediment recovery to pre-fire concentrations 3 years after the fire. Wildfires over the last 1900 YBP in the South Fork basin indicate fire recurrence intervals of 600 years. Debris flows within the upper Colorado River basin over the last two centuries have shifted the baseline of sediment recovery caused by anthropogenic activities that increased debris flow frequency. An extreme flood on North St. Vrain Creek with an impounding reservoir resulted in extreme sedimentation that led to a physical state change. We introduce an index of resilience as sediment recovery/disturbance recurrence interval, providing a relative comparison between sites. Sediment recovery and channel form resilience may be inversely related because of high or low physical complexity in streams. We propose management guidelines to enhance geomorphic resilience by promoting natural processes that maintain physical complexity. Finally, sediment connectivity within watersheds is an additional factor to consider when establishing restoration treatment priorities.

Critical role of canonical transient receptor potential channel 7 in initiation of seizures.

PubMed

Phelan, Kevin D; Shwe, U Thaung; Abramowitz, Joel; Birnbaumer, Lutz; Zheng, Fang

2014-08-05

Status epilepticus (SE) is a life-threatening disease that has been recognized since antiquity but still causes over 50,000 deaths annually in the United States. The prevailing view on the pathophysiology of SE is that it is sustained by a loss of normal inhibitory mechanisms of neuronal activity. However, the early process leading to the initiation of SE is not well understood. Here, we show that, as seen in electroencephalograms, SE induced by the muscarinic agonist pilocarpine in mice is preceded by a specific increase in the gamma wave, and genetic ablation of canonical transient receptor potential channel (TRPC) 7 significantly reduces this pilocarpine-induced increase of gamma wave activity, preventing the occurrence of SE. At the cellular level, TRPC7 plays a critical role in the generation of spontaneous epileptiform burst firing in cornu ammonis (CA) 3 pyramidal neurons in brain slices. At the synaptic level, TRPC7 plays a significant role in the long-term potentiation at the CA3 recurrent collateral synapses and Schaffer collateral-CA1 synapses, but not at the mossy fiber-CA3 synapses. Taken together, our data suggest that epileptiform burst firing generated in the CA3 region by activity-dependent enhancement of recurrent collateral synapses may be an early event in the initiation process of SE and that TRPC7 plays a critical role in this cellular event. Our findings reveal that TRPC7 is intimately involved in the initiation of seizures both in vitro and in vivo. To our knowledge, this contribution to initiation of seizures is the first identified functional role for the TRPC7 ion channel.

Software dependability in the Tandem GUARDIAN system

NASA Technical Reports Server (NTRS)

Lee, Inhwan; Iyer, Ravishankar K.

1995-01-01

Based on extensive field failure data for Tandem's GUARDIAN operating system this paper discusses evaluation of the dependability of operational software. Software faults considered are major defects that result in processor failures and invoke backup processes to take over. The paper categorizes the underlying causes of software failures and evaluates the effectiveness of the process pair technique in tolerating software faults. A model to describe the impact of software faults on the reliability of an overall system is proposed. The model is used to evaluate the significance of key factors that determine software dependability and to identify areas for improvement. An analysis of the data shows that about 77% of processor failures that are initially considered due to software are confirmed as software problems. The analysis shows that the use of process pairs to provide checkpointing and restart (originally intended for tolerating hardware faults) allows the system to tolerate about 75% of reported software faults that result in processor failures. The loose coupling between processors, which results in the backup execution (the processor state and the sequence of events) being different from the original execution, is a major reason for the measured software fault tolerance. Over two-thirds (72%) of measured software failures are recurrences of previously reported faults. Modeling, based on the data, shows that, in addition to reducing the number of software faults, software dependability can be enhanced by reducing the recurrence rate.

Importance of recurrence rating, morphology, hernial gap size, and risk factors in ventral and incisional hernia classification.

PubMed

Dietz, U A; Winkler, M S; Härtel, R W; Fleischhacker, A; Wiegering, A; Isbert, C; Jurowich, Ch; Heuschmann, P; Germer, C-T

2014-02-01

There is limited evidence on the natural course of ventral and incisional hernias and the results of hernia repair, what might partially be explained by the lack of an accepted classification system. The aim of the present study is to investigate the association of the criteria included in the Wuerzburg classification system of ventral and incisional hernias with postoperative complications and long-term recurrence. In a retrospective cohort study, the data on 330 consecutive patients who underwent surgery to repair ventral and incisional hernias were analyzed. The following four classification criteria were applied: (a) recurrence rating (ventral, incisional or incisional recurrent); (b) morphology (location); (c) size of the hernial gap; and (d) risk factors. The primary endpoint was the occurrence of a recurrence during follow-up. Secondary endpoints were incidence of postoperative complications. Independent association between classification criteria, type of surgical procedures and postoperative complications was calculated by multivariate logistic regression analysis and between classification criteria, type of surgical procedures and risk of long-term recurrence by Cox regression analysis. Follow-up lasted a mean 47.7 ± 23.53 months (median 45 months) or 3.9 ± 1.96 years. The criterion "recurrence rating" was found as predictive factor for postoperative complications in the multivariate analysis (OR 2.04; 95 % CI 1.09-3.84; incisional vs. ventral hernia). The criterion "morphology" had influence neither on the incidence of the critical event "recurrence during follow-up" nor on the incidence of postoperative complications. Hernial gap "width" predicted postoperative complications in the multivariate analysis (OR 1.98; 95 % CI 1.19-3.29; ≤5 vs. >5 cm). Length of the hernial gap was found to be an independent prognostic factor for the critical event "recurrence during follow-up" (HR 2.05; 95 % CI 1.25-3.37; ≤5 vs. >5 cm). The presence of 3 or more risk factors was a consistent predictor for "recurrence during follow-up" (HR 2.25; 95 % CI 1.28-9.92). Mesh repair was an independent protective factor for "recurrence during follow-up" compared to suture (HR 0.53; 95 % CI 0.32-0.86). The ventral and incisional hernia classification of Dietz et al. employs a clinically proven terminology and has an open classification structure. Hernial gap size and the number of risk factors are independent predictors for "recurrence during follow-up", whereas recurrence rating and hernial gap size correlated significantly with the incidence of postoperative complications. We propose the application of these criteria for future clinical research, as larger patient numbers will be needed to refine the results.

Physiological growth hormone replacement and rate of recurrence of craniopharyngioma: the Genentech National Cooperative Growth Study.

PubMed

Smith, Timothy R; Cote, David J; Jane, John A; Laws, Edward R

2016-10-01

OBJECTIVE The object of this study was to establish recurrence rates in patients with craniopharyngioma postoperatively treated with recombinant human growth hormone (rhGH) as a basis for determining the risk of rhGH therapy in the development of recurrent tumor. METHODS The study included 739 pediatric patients with craniopharyngioma who were naïve to GH upon entering the Genentech National Cooperative Growth Study (NCGS) for treatment. Reoperation for tumor recurrence was documented as an adverse event. Cox proportional-hazards regression models were developed for time to recurrence, using age as the outcome and enrollment date as the predictor. Patients without recurrence were treated as censored. Multivariate logistic regression was used to examine the incidence of recurrence with adjustment for the amount of time at risk. RESULTS Fifty recurrences in these 739 surgically treated patients were recorded. The overall craniopharyngioma recurrence rate in the NCGS was 6.8%, with a median follow-up time of 4.3 years (range 0.7-6.4 years.). Age at the time of study enrollment was statistically significant according to both Cox (p = 0.0032) and logistic (p < 0.001) models, with patients under 9 years of age more likely to suffer recurrence (30 patients [11.8%], 0.025 recurrences/yr of observation, p = 0.0097) than those ages 9-13 years (17 patients [6.0%], 0.17 recurrences/yr of observation) and children older than 13 years (3 patients [1.5%], 0.005 recurrences/yr of observation). CONCLUSIONS Physiological doses of GH do not appear to increase the recurrence rate of craniopharyngioma after surgery in children, but long-term follow-up of GH-treated patients is required to establish a true natural history in the GH treatment era.

Developing a post-fire flood chronology and recurrence probability from alluvial stratigraphy in the Buffalo Creek watershed, Colorado, USA

USGS Publications Warehouse

Elliott, J.G.; Parker, R.S.

2001-01-01

Stratigraphic and geomorphic evidence indicate floods that occur soon after forest fires have been intermittent but common events in many mountainous areas during the past several thousand years. The magnitude and recurrence of these post-fire flood events reflects the joint probability between the recurrence of fires and the recurrence of subsequent rainfall events of varying magnitude and intensity. Following the May 1996 Buffalo Creek, Colorado, forest fire, precipitation amounts and intensities that generated very little surface runoff outside of the burned area resulted in severe hillslope erosion, floods, and streambed sediment entrainment in the rugged, severely burned, 48 km2 area. These floods added sediment to many existing alluvial fans, while simultaneously incising other fans and alluvial deposits. Incision of older fans revealed multiple sequences of fluvially transported sandy gravel that grade upward into charcoal-rich, loamy horizons. We interpret these sequences to represent periods of high sediment transport and aggradation during floods, followed by intervals of quiescence and relative stability in the watershed until a subsequent fire occurred. An alluvial sequence near the mouth of a tributary draining a 0??82 km2 area indicated several previous post-fire flood cycles in the watershed. Dendrochronologic and radiocarbon ages of material in this deposit span approximately 2900 years, and define three aggradational periods. The three general aggradational periods are separated by intervals of approximately nine to ten centuries and reflect a 'millennium-scale' geomorphic response to a closely timed sequence of events: severe and intense, watershed-scale, stand-replacing fires and subsequent rainstorms and flooding. Millennium-scale aggradational units at the study site may have resulted from a scenario in which the initial runoff from the burned watershed transported and deposited large volumes of sediment on downstream alluvial surfaces and tributary fans. Subsequent storm runoff may have produced localized incision and channelization, preventing additional vertical aggradation on the sampled alluvial deposit for several centuries. Two of the millennium-scale aggradational periods at the study site consist of multiple gravel and loam sequences with similar radiocarbon ages. These closely dated sequences may reflect a 'multidecade-scale' geomorphic response to more frequent, but aerially limited and less severe fires, followed by rainstorms of relatively common recurrence. Published in 2001 by John Wiley and Sons, Ltd.

Killing wolves to prevent predation on livestock may protect one farm but harm neighbors.

PubMed

Santiago-Avila, Francisco J; Cornman, Ari M; Treves, Adrian

2018-01-01

Large carnivores, such as gray wolves, Canis lupus, are difficult to protect in mixed-use landscapes because some people perceive them as dangerous and because they sometimes threaten human property and safety. Governments may respond by killing carnivores in an effort to prevent repeated conflicts or threats, although the functional effectiveness of lethal methods has long been questioned. We evaluated two methods of government intervention following independent events of verified wolf predation on domestic animals (depredation) in the Upper Peninsula of Michigan, USA between 1998-2014, at three spatial scales. We evaluated two intervention methods using log-rank tests and conditional Cox recurrent event, gap time models based on retrospective analyses of the following quasi-experimental treatments: (1) selective killing of wolves by trapping near sites of verified depredation, and (2) advice to owners and haphazard use of non-lethal methods without wolf-killing. The government did not randomly assign treatments and used a pseudo-control (no removal of wolves was not a true control), but the federal permission to intervene lethally was granted and rescinded independent of events on the ground. Hazard ratios suggest lethal intervention was associated with an insignificant 27% lower risk of recurrence of events at trapping sites, but offset by an insignificant 22% increase in risk of recurrence at sites up to 5.42 km distant in the same year, compared to the non-lethal treatment. Our results do not support the hypothesis that Michigan's use of lethal intervention after wolf depredations was effective for reducing the future risk of recurrence in the vicinities of trapping sites. Examining only the sites of intervention is incomplete because neighbors near trapping sites may suffer the recurrence of depredations. We propose two new hypotheses for perceived effectiveness of lethal methods: (a) killing predators may be perceived as effective because of the benefits to a small minority of farmers, and (b) if neighbors experience side-effects of lethal intervention such as displaced depredations, they may perceive the problem growing and then demand more lethal intervention rather than detecting problems spreading from the first trapping site. Ethical wildlife management guided by the "best scientific and commercial data available" would suggest suspending the standard method of trapping wolves in favor of non-lethal methods (livestock guarding dogs or fladry) that have been proven effective in preventing livestock losses in Michigan and elsewhere.

Toxicity and quality of life after choline-PET/CT directed salvage lymph node dissection and adjuvant radiotherapy in nodal recurrent prostate cancer.

PubMed

Jilg, Cordula A; Leifert, Anja; Schnell, Daniel; Kirste, Simon; Volegova-Neher, Natalia; Schlager, Daniel; Wieser, Gesche; Henne, Karl; Schultze-Seemann, Wolfgang; Grosu, Anca-L; Rischke, Hans Christian

2014-08-12

In a previous study we demonstrated that, based on 11C/18 F-choline positron emission tomography-computerized-tomography as a diagnostic tool, salvage lymph node dissection (LND) plus adjuvant radiotherapy (ART) is feasible for treatment of pelvic/retroperitoneal nodal recurrence of prostate cancer (PCa). However, the toxicity of this combined treatment strategy has not been systematically investigated before. The aim of the current study was to evaluate the acute and late toxicity and quality of life of ART after LND in pelvic/retroperitoneal nodal recurrent PCa. 43 patients with nodal recurrent PCa were treated with 46 LND followed by ART (mean 49.6 Gy total dose) at the sites of nodal recurrence. Toxicity of ART was analysed by physically examination (31/43, 72.1%), by requesting 15 frequent items of adverse events from the Common-Terminology-Criteria for Adverse Events Version 4.0-catalogue and by review of medical records. QLQ-C30 (EORTC quality of life assessment) and PR25 (prostate cancer module) questionnaires were used to investigate quality of life. Toxicity was evaluated before starting of ART, during ART (acute toxicity), after ART (mean 2.3 months) and at end of follow up (mean 3.2 years after end of ART) reflecting late toxicity. 71.7% (33/46) of 46 ART were treatment of pelvic, 10.9% (5/46) of retroperitoneal only and 28.3% (13/46) of pelvic and retroperitoneal regions. Overall 52 symptoms representing toxicities were observed before ART, 107 during ART, 88 after end of ART and 52 at latest follow up. Leading toxicities during ART were diarrhoea (19%, 20/107), urinary incontinence (16%, 17/107) and fatigue (16%, 17/107). The spectrum of late toxicities was almost equal to those before beginning of ART. No grade 3 adverse events or chronic lymphedema at extremities were observed. We observed no clear correlation between localisation of treated regions, technique of ART and frequency or severity of toxicities. Mean quality of life at final evaluation was 74%. ART after extended LND in PCa relapse is justifiable with respect to adverse effects and toxicity. The side effects were circumscribed and well tolerated. The spectrum of adverse events at latest follow up was almost equal to those before start of ART.

Long-Term Outcomes of Patent Foramen Ovale Closure or Medical Therapy after Stroke.

PubMed

Saver, Jeffrey L; Carroll, John D; Thaler, David E; Smalling, Richard W; MacDonald, Lee A; Marks, David S; Tirschwell, David L

2017-09-14

Whether closure of a patent foramen ovale reduces the risk of recurrence of ischemic stroke in patients who have had a cryptogenic ischemic stroke is unknown. In a multicenter, randomized, open-label trial, with blinded adjudication of end-point events, we randomly assigned patients 18 to 60 years of age who had a patent foramen ovale (PFO) and had had a cryptogenic ischemic stroke to undergo closure of the PFO (PFO closure group) or to receive medical therapy alone (aspirin, warfarin, clopidogrel, or aspirin combined with extended-release dipyridamole; medical-therapy group). The primary efficacy end point was a composite of recurrent nonfatal ischemic stroke, fatal ischemic stroke, or early death after randomization. The results of the analysis of the primary outcome from the original trial period have been reported previously; the current analysis of data from the extended follow-up period was considered to be exploratory. We enrolled 980 patients (mean age, 45.9 years) at 69 sites. Patients were followed for a median of 5.9 years. Treatment exposure in the two groups was unequal (3141 patient-years in the PFO closure group vs. 2669 patient-years in the medical-therapy group), owing to a higher dropout rate in the medical-therapy group. In the intention-to-treat population, recurrent ischemic stroke occurred in 18 patients in the PFO closure group and in 28 patients in the medical-therapy group, resulting in rates of 0.58 events per 100 patient-years and 1.07 events per 100 patient-years, respectively (hazard ratio with PFO closure vs. medical therapy, 0.55; 95% confidence interval [CI], 0.31 to 0.999; P=0.046 by the log-rank test). Recurrent ischemic stroke of undetermined cause occurred in 10 patients in the PFO closure group and in 23 patients in the medical-therapy group (hazard ratio, 0.38; 95% CI, 0.18 to 0.79; P=0.007). Venous thromboembolism (which comprised events of pulmonary embolism and deep-vein thrombosis) was more common in the PFO closure group than in the medical-therapy group. Among adults who had had a cryptogenic ischemic stroke, closure of a PFO was associated with a lower rate of recurrent ischemic strokes than medical therapy alone during extended follow-up. (Funded by St. Jude Medical; RESPECT ClinicalTrials.gov number, NCT00465270 .).

Empirical recurrence rates for ground motion signals on planetary surfaces

NASA Astrophysics Data System (ADS)

Lorenz, Ralph D.; Panning, Mark

2018-03-01

We determine the recurrence rates of ground motion events as a function of sensed velocity amplitude at several terrestrial locations, and make a first interplanetary comparison with measurements on the Moon, Mars, Venus and Titan. This empirical approach gives an intuitive order-of-magnitude guide to the observed ground motion (including both tectonic and ocean- and atmosphere-forced signals) of these locations as a guide to instrument expectations on future missions, without invoking interior models and specific sources: for example a Venera-14 observation of possible ground motion indicates a microseismic environment mid-way between noisy and quiet terrestrial locations. Quiet terrestrial regions see a peak velocity amplitude in mm/s roughly equal to 0.3*N(-0.7), where N is the number of "events" (half-hour intervals in which a given peak ground motion is exceeded) observed per year. The Apollo data show endogenous seismic signals for a given recurrence rate that are typically about 10,000 times smaller in amplitude than a quiet site on Earth, although local thermally-induced moonquakes are much more common. Viking data masked for low-wind periods appear comparable with a quiet terrestrial site, whereas a Venera observation of microseisms suggests ground motion more similar to a more active terrestrial location. Recurrence rate plots from in-situ measurements provide a context for seismic instrumentation on future planetary missions, e.g. to guide formulation of data compression schemes. While even small geophones can discriminate terrestrial activity rates, observations with guidance accelerometers are typically too insensitive to provide meaningful constraints (i.e. a non-zero number of "events") on actual ground motion observations unless operated for very long periods.

Predictive Value of Pulse Pressure in Acute Ischemic Stroke for Future Major Vascular Events.

PubMed

Lee, Keon-Joo; Kim, Beom Joon; Han, Moon-Ku; Kim, Joon-Tae; Cho, Ki-Hyun; Shin, Dong-Ick; Yeo, Min-Ju; Cha, Jae-Kwan; Kim, Dae-Hyun; Nah, Hyun-Wook; Kim, Dong-Eog; Ryu, Wi-Sun; Park, Jong-Moo; Kang, Kyusik; Lee, Soo Joo; Oh, Mi-Sun; Yu, Kyung-Ho; Lee, Byung-Chul; Hong, Keun-Sik; Cho, Yong-Jin; Choi, Jay Chol; Sohn, Sung Il; Hong, Jeong-Ho; Park, Tai Hwan; Park, Sang-Soon; Kwon, Jee-Hyun; Kim, Wook-Joo; Lee, Jun; Lee, Ji Sung; Lee, Juneyoung; Gorelick, Philip B; Bae, Hee-Joon

2018-01-01

This study aimed to investigate whether pulse pressure (PP) obtained during the acute stage of ischemic stroke can be used as a predictor for future major vascular events. Using a multicenter prospective stroke registry database, patients who were hospitalized for ischemic stroke within 48 hours of onset were enrolled in this study. We analyzed blood pressure (BP) data measured during the first 3 days from onset. Primary and secondary outcomes were time to a composite of stroke recurrence, myocardial infarction, all-cause death, and time to stroke recurrence, respectively. Of 9840 patients, 4.3% experienced stroke recurrence, 0.2% myocardial infarction, and 7.3% death during a 1-year follow-up period. In Cox proportional hazards models including both linear and quadratic terms of PP, PP had a nonlinear J-shaped relationship with primary (for a quadratic term of PP, P =0.004) and secondary ( P <0.001) outcomes. The overall effects of PP and other BP parameters on primary and secondary outcomes were also significant ( P <0.05). When predictive power of BP parameters was compared using a statistic of -2 log-likelihood differences, PP was a stronger predictor than systolic BP (8.49 versus 5.91; 6.32 versus 4.56), diastolic BP (11.42 versus 11.05; 10.07 versus 4.56), and mean atrial pressure (8.75 versus 5.91; 7.03 versus 4.56) for the primary and secondary outcomes, respectively. Our study shows that PP when measured in the acute period of ischemic stroke has nonlinear J-shaped relationships with major vascular events and stroke recurrence, and may have a stronger predictive power than other commonly used BP parameters. © 2017 American Heart Association, Inc.

An Exercise Intervention During Chemotherapy for Women With Recurrent Ovarian Cancer: A Feasibility Study.

PubMed

Mizrahi, David; Broderick, Carolyn; Friedlander, Michael; Ryan, Mary; Harrison, Michelle; Pumpa, Kate; Naumann, Fiona

2015-07-01

The aim of this study was to determine the feasibility of a combined supervised and home-based exercise intervention during chemotherapy for women with recurrent ovarian cancer. Secondary aims were to determine the impact of physical activity on physical and psychological outcomes and on chemotherapy completion rates. Women with recurrent ovarian cancer were recruited from 3 oncology outpatient clinics in Sydney and Canberra, Australia. All participants received an individualized exercise program that consisted of 90 minutes or more of low to moderate aerobic, resistance, core stability, and balance exercise per week, for 12 weeks. Feasibility was determined by recruitment rate, retention rate, intervention adherence, and adverse events. Aerobic capacity, muscular strength, fatigue, sleep quality, quality of life, depression, and chemotherapy completion rates were assessed at weeks 0, 12, and 24. Thirty participants were recruited (recruitment rate, 63%), with a retention rate of 70%. Participants averaged 196 ± 138 min · wk of low to moderate physical activity throughout the intervention, with adherence to the program at 81%. There were no adverse events resulting from the exercise intervention. Participants who completed the study displayed significant improvements in quality of life (P = 0.017), fatigue (P = 0.004), mental health (P = 0.007), muscular strength (P = 0.001), and balance (P = 0.003) after the intervention. Participants completing the intervention had a higher relative dose intensity than noncompleters (P = 0.03). A program consisting of low to moderate exercise of 90 min · wk was achieved by two-thirds of women with recurrent ovarian cancer in this study, with no adverse events reported. Randomized control studies are required to confirm the benefits of exercise reported in this study.

Optimal timing of vitamin K antagonist resumption after upper gastrointestinal bleeding. A risk modelling analysis.

PubMed

Majeed, Ammar; Wallvik, Niklas; Eriksson, Joakim; Höijer, Jonas; Bottai, Matteo; Holmström, Margareta; Schulman, Sam

2017-02-28

The optimal timing of vitamin K antagonists (VKAs) resumption after an upper gastrointestinal (GI) bleeding, in patients with continued indication for oral anticoagulation, is uncertain. We included consecutive cases of VKA-associated upper GI bleeding from three hospitals retrospectively. Data on the bleeding location, timing of VKA resumption, recurrent GI bleeding and thromboembolic events were collected. A model was constructed to evaluate the 'total risk', based on the sum of the cumulative rates of recurrent GI bleeding and thromboembolic events, depending on the timing of VKA resumption. A total of 121 (58 %) of 207 patients with VKA-associated upper GI bleeding were restarted on anticoagulation after a median (interquartile range) of one (0.2-3.4) week after the index bleeding. Restarting VKAs was associated with a reduced risk of thromboembolism (HR 0.19; 95 % CI, 0.07-0.55) and death (HR 0.61; 95 % CI, 0.39-0.94), but with an increased risk of recurrent GI bleeding (HR 2.5; 95 % CI, 1.4-4.5). The composite risk obtained from the combined statistical model of recurrent GI bleeding, and thromboembolism decreased if VKAs were resumed after three weeks and reached a nadir at six weeks after the index GI bleeding. On this background we will discuss how the disutility of the outcomes may influence the decision regarding timing of resumption. In conclusion, the optimal timing of VKA resumption after VKA-associated upper GI bleeding appears to be between 3-6 weeks after the index bleeding event but has to take into account the degree of thromboembolic risk, patient values and preferences.

Association of black race with recurrent stroke risk.

PubMed

Park, Jong-Ho; Ovbiagele, Bruce

2016-06-15

The significantly higher risk of primary stroke in Black vs. Whites is very well established. However, very few studies have specifically examined the presence of this racial disparity in recurrent stroke risk. We conducted an analysis of a clinical trial dataset comprising 3470 recent non-cardioembolic stroke patients aged ≥35years and followed for 2years. Subjects were categorized by race into Whites and Blacks. Cox regression analysis was used to evaluate the associations between Black (vs. White) and ischemic stroke (primary outcome); and stroke/coronary heart disease (CHD)/vascular death as major vascular events (secondary outcome) with and without adjustment for comorbid conditions associated with stroke. Among participants (2925 Whites and 545 Blacks), a total of 287 (8.3%) incident stroke and 582 (16.8%) major vascular events occurred. Compared with Whites, Blacks had higher frequencies of prior stroke, hypertension, diabetes mellitus, and smoking; but were younger with lower prevalence of CHD. Frequency of stroke was higher in Blacks vs. Whites (11.4% vs. 7.7%; P=0.004), but there was no difference in major vascular events (16.9% vs. 16.8%). Compared with Whites, Blacks experienced a significantly higher risk of recurrent stroke (HR 1.58; 95% CI, 1.19-2.09), but the stroke risk was not significant after multivariable adjustment (1.13; 0.81-1.59). Blacks are ~60% more likely to experience a recurrent stroke within 2years than their Whites, but this risk is likely mediated via stroke risk factors. These results underscore a need to optimize and sustain risk factor control in Black stroke populations. Copyright © 2016 Elsevier B.V. All rights reserved.

Patent foramen ovale closure and medical treatments for secondary stroke prevention: a systematic review of observational and randomized evidence.

PubMed

Kitsios, Georgios D; Dahabreh, Issa J; Abu Dabrh, Abd Moain; Thaler, David E; Kent, David M

2012-02-01

Patients discovered to have a patent foramen ovale in the setting of a cryptogenic stroke may be treated with percutaneous closure, antiplatelet therapy, or anticoagulants. A recent randomized trial (CLOSURE I) did not detect any benefit of closure over medical treatment alone; the optimal medical therapy is also unknown. We synthesized the available evidence on secondary stroke prevention in patients with patent foramen ovale and cryptogenic stroke. A MEDLINE search was performed for finding longitudinal studies investigating medical treatment or closure, meta-analysis of incidence rates (IR), and IR ratios of recurrent cerebrovascular events. Fifty-two single-arm studies and 7 comparative nonrandomized studies and the CLOSURE I trial were reviewed. The summary IR of recurrent stroke was 0.36 events (95% confidence interval [CI], 0.24-0.56) per 100 person-years with closure versus 2.53 events (95% CI, 1.91-3.35) per 100 person-years with medical therapy. In comparative observational studies, closure was superior to medical therapy (IR ratio=0.19; 95% CI, 0.07-0.54). The IR for the closure arm of the CLOSURE I trial was higher than the summary estimate from observational studies; there was no significant benefit of closure over medical treatment (P=0.002 comparing efficacy estimates between observational studies and the trial). Observational and randomized data (9 studies) comparing medical therapies were consistent and suggested that anticoagulants are superior to antiplatelets for preventing stroke recurrence (IR ratio=0.42; 95% CI, 0.18-0.98). Although further randomized trial data are needed to precisely determine the effects of closure on stroke recurrence, the results of CLOSURE I challenge the credibility of a substantial body of observational evidence strongly favoring mechanical closure over medical therapy.

Detection of ATRX and IDH1-R132H immunohistochemistry in the progression of 211 paired gliomas

PubMed Central

Li, Qingbin; Wang, Zhiliang; Li, Guanzhang; Wang, Guangzhi; Yang, Pei; Li, Jianlong; Han, Bo; Jiang, Chuanlu; Sun, Ying; Jiang, Tao

2016-01-01

Recurrence and progression to higher grade lesions are key biological events and characteristic behaviors in the evolution process of glioma. A small residual population of cells always escapes surgery and chemoradiation, resulting in a typically fatal tumor recurrence or progression. IDH mutation (isocitrate dehydrogenase) and ATRX (alpha-thalassemia/mental retardation, X-linked) loss/mutation occur in association and may represent early genetic alterations in the development of gliomas. However, their prognostic value in the evolution of gliomas still needs further investigation. Two hundreds and eleven serial sampling of gliomas were included in our study. We used immunohistochemistry (IHC) to detect IDH1-R132H mutation and ATRX status and showed that the IDH1-R132H and (or) ATRX status could be necessary to provide the basic molecular information for the “integrated diagnosis” of gliomas. We illustrated an evaluation formula for the evolution of gliomas by IDH1-R132H combined with ATRX immunohistochemistry and identified the association of IDH1-R132H/ATRX loss accompanied by longer progression time interval of patients with gliomas. Furthermore, we observed that most recurrences had a consistent IDH1 and ATRX status with their matched primary tumors and demonstrated the progressive pattern of grade II astrocytoma/oligodendroglial tumors and anaplastic oligoastrocytoma with or without IDH1-R132H. Identification of IDH1-R132H and ATRX loss status in the primary-recurrent gliomas may aid in treatment strategy selection, therapeutic trial design, and clinical prognosis evaluation. PMID:26918938

Detection of ATRX and IDH1-R132H immunohistochemistry in the progression of 211 paired gliomas.

PubMed

Cai, Jinquan; Zhu, Ping; Zhang, Chuanbao; Li, Qingbin; Wang, Zhiliang; Li, Guanzhang; Wang, Guangzhi; Yang, Pei; Li, Jianlong; Han, Bo; Jiang, Chuanlu; Sun, Ying; Jiang, Tao

2016-03-29

Recurrence and progression to higher grade lesions are key biological events and characteristic behaviors in the evolution process of glioma. A small residual population of cells always escapes surgery and chemoradiation, resulting in a typically fatal tumor recurrence or progression. IDH mutation (isocitrate dehydrogenase) and ATRX (alpha-thalassemia/mental retardation, X-linked) loss/mutation occur in association and may represent early genetic alterations in the development of gliomas. However, their prognostic value in the evolution of gliomas still needs further investigation.Two hundreds and eleven serial sampling of gliomas were included in our study. We used immunohistochemistry (IHC) to detect IDH1-R132H mutation and ATRX status and showed that the IDH1-R132H and (or) ATRX status could be necessary to provide the basic molecular information for the "integrated diagnosis" of gliomas. We illustrated an evaluation formula for the evolution of gliomas by IDH1-R132H combined with ATRX immunohistochemistry and identified the association of IDH1-R132H/ATRX loss accompanied by longer progression time interval of patients with gliomas. Furthermore, we observed that most recurrences had a consistent IDH1 and ATRX status with their matched primary tumors and demonstrated the progressive pattern of grade II astrocytoma/oligodendroglial tumors and anaplastic oligoastrocytoma with or without IDH1-R132H. Identification of IDH1-R132H and ATRX loss status in the primary-recurrent gliomas may aid in treatment strategy selection, therapeutic trial design, and clinical prognosis evaluation.

Semitendinosus Tendon Transfer Associated With Distal Alignment for Patella Alta in a Patient With Recurrent Dislocations.

PubMed

Calderazzi, Filippo; Pellegrini, Andrea; Coviello, Gianluca; Groppi, Giulia; Ceccarelli, Francesco

2015-10-01

Patellofemoral instability is characterized by pain during normal daily activities and frequent dislocation events. In the reported case, an adolescent girl, aged 15 years, affected by left patellofemoral instability, underwent surgery with a double technique comprising tibial tubercle distalization and medial patellofemoral ligament reconstruction. In case of patella alta associated with patellofemoral instability, surgical treatment should focus on medial patellofemoral ligament repair and on recurrent instability prevention.

Dynamically triggered slip leading to sustained fault gouge weakening under laboratory shear conditions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Johnson, Paul Allan

We investigate dynamic wave-triggered slip under laboratory shear conditions. The experiment is composed of a three-block system containing two gouge layers composed of glass beads and held in place by a fixed load in a biaxial configuration. When the system is sheared under steady state conditions at a normal load of 4 MPa, we find that shear failure may be instantaneously triggered by a dynamic wave, corresponding to material weakening and softening if the system is in a critical shear stress state (near failure). Following triggering, the gouge material remains in a perturbed state over multiple slip cycles as evidencedmore » by the recovery of the material strength, shear modulus, and slip recurrence time. This work suggests that faults must be critically stressed to trigger under dynamic conditions and that the recovery process following a dynamically triggered event differs from the recovery following a spontaneous event.« less

Dynamically triggered slip leading to sustained fault gouge weakening under laboratory shear conditions

DOE PAGES

Johnson, Paul Allan

2016-02-28

We investigate dynamic wave-triggered slip under laboratory shear conditions. The experiment is composed of a three-block system containing two gouge layers composed of glass beads and held in place by a fixed load in a biaxial configuration. When the system is sheared under steady state conditions at a normal load of 4 MPa, we find that shear failure may be instantaneously triggered by a dynamic wave, corresponding to material weakening and softening if the system is in a critical shear stress state (near failure). Following triggering, the gouge material remains in a perturbed state over multiple slip cycles as evidencedmore » by the recovery of the material strength, shear modulus, and slip recurrence time. This work suggests that faults must be critically stressed to trigger under dynamic conditions and that the recovery process following a dynamically triggered event differs from the recovery following a spontaneous event.« less

Recurrent pericarditis: new and emerging therapeutic options.

PubMed

Imazio, Massimo; Lazaros, George; Brucato, Antonio; Gaita, Fiorenzo

2016-02-01

Recurrent pericarditis is one of the most common and troublesome complications after an episode of pericarditis, and affects 20-50% of patients treated for pericarditis. In most of these patients, the pericarditis remains idiopathic, although an immune-mediated (either autoimmune or autoinflammatory) pathogenesis is often presumed. The mainstay of therapy for recurrences is aspirin or NSAIDs, with the adjunct of colchicine. Corticosteroids are a second-line option to be considered for specific indications, such as connective tissue disease or pregnancy; contraindications or intolerance to aspirin, NSAIDs, and/or colchicine; or insufficient response to these medications. Furthermore, corticosteroids can be added to NSAIDs and colchicine in patients with persistent symptoms. In patients who do not respond adequately to any of these conventional therapies, alternative treatment options include azathioprine, intravenous human immunoglobulins, and anakinra. An improved understanding of how recurrent pericarditis develops after an initiating event is critical to prevent this complication, and further research is needed into the pathogenesis of recurrences. We discuss the aetiology and diagnosis of recurrent pericarditis, and extensively review the treatment options for this condition.

Sediment yield and runoff frequency of small drainage basins in the Mojave Desert, U.S.A

USGS Publications Warehouse

Griffiths, P.G.; Hereford, R.; Webb, R.H.

2006-01-01

Sediment yield from small arid basins, particularly in the Mojave Desert, is largely unknown owing to the ephemeral nature of these fluvial systems and long recurrence interval of flow events. We examined 27 reservoirs in the northern and eastern Mojave Desert that trapped sediment from small (< 1 km2) drainage basins on alluvial fans over the past 100 yr, calculated annual sediment yield, and estimated the average recurrence interval (RI) of sediment-depositing flow events. These reservoirs formed where railbeds crossed and blocked channels, causing sediment to be trapped and stored upslope. Deposits are temporally constrained by the date of railway construction (1906-1910), the presence of 137Cs in the reservoir profile (post-1952 sediment), and either 1993, when some basins breached during regional flooding, or 2000-2001, when stratigraphic analyses were performed. Reservoir deposits are well stratified at most sites and have distinct fining-upward couplets indicative of discrete episodes of sediment-bearing runoff. Average RI of runoff events for these basins ranges from 2.6 to 7.3 yr and reflects the incidence of either intense or prolonged rainfall; more than half the runoff events occurred before 1963. A period of above-normal precipitation, from 1905 to 1941, may have increased runoff frequency in these basins. Mean sediment yield (9 to 48 tons km-2 yr-1) is an order of magnitude smaller than sediment yields calculated elsewhere and may be limited by reduced storm intensity, the presence of desert pavement, and shallow gradient of fan surfaces. Sediment yield decreases as drainage area increases, a trend typical of much larger drainage basins where sediment-transport processes constrain sediment yield. Coarse substrate and low-angle slopes of these alluvial fan surfaces likely limit sediment transport capacity through transmission losses and channel storage. ?? 2005 Elsevier B.V. All rights reserved.

Multi-institutional Outcomes of Endoscopic Management of Stricture Recurrence after Bulbar Urethroplasty.

PubMed

Sukumar, Shyam; Elliott, Sean P; Myers, Jeremy B; Voelzke, Bryan B; Smith, Thomas G; Carolan, Alexandra Mc; Maidaa, Michael; Vanni, Alex J; Breyer, Benjamin N; Erickson, Bradley A

2018-05-03

Approximately 10-20% of patients will have a recurrence after urethroplasty. Initial management of these recurrences is often with urethral dilation (UD) or direct vision internal urethrotomy (DVIU). In the current study, we describe outcomes of endoscopic management of stricture recurrence after bulbar urethroplasty. We retrospectively reviewed bulbar urethroplasty data from 5 surgeons from the Trauma and Urologic Reconstruction Network of Surgeons. Men who underwent UD or DVIU for urethroplasty recurrence were identified. Recurrence was defined as inability to pass a 17Fr cystoscope through the area of reconstruction. The primary outcome was the success rate of recurrence management. Comparisons were made between UD and DVIU and then between endoscopic management of recurrences after excision and primary anastomosis urethroplasty (EPA) versus substitutional repairs using time-to-event statistics. There were 53 men with recurrence that were initially managed endoscopically. Median time to urethral stricture recurrence after urethroplasty was noted to be 5 months. At a median follow-up of 5 months, overall success was 42%. Success after UD (n=1/10, 10%) was significantly lower than after DVIU (n=21/43, 49%; p < 0.001) with a hazard ratio of failure of 3.15 (p=0.03). DVIU was more effective after substitutional failure than after EPA (53% vs.13%, P=0.005). DVIU is more successful than UD in the management of stricture recurrence after bulbar urethroplasty. DVIU is more successful for patients with a recurrence after a substitution urethroplasty compared to after EPA, perhaps indicating a different mechanism of recurrence for EPA (ischemic) versus substitution urethroplasty (non-ischemic). Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

[Clinical results of double versus single mammary artery myocardiac revascularization: 15 years of follow-up].

PubMed

López Rodríguez, F J; Voces, R; Lima, P; Reyes, G; Silva, J; Ruiz, M; Rico, M; González De Diego, F; Fortuny, R; Garrido, G; González Santos, J M; Albertos, J; Fernández Calella, D; Vallejo, J L

2001-07-01

Use of the left internal mammary artery to bypass the left anterior descending coronary artery reduces cardiac events and increases survival. However, there is some controversy as to the benefits of using both mammary arteries. To assess the long-term outcome of the use of both mammary arteries in comparison with the use of only one. A retrospective cohort study with a mean follow-up of 9.0 +/- 4.2 years was performed including 108 patients consecutively revascularized using both mammary arteries (II) and 108 patients randomly chosen in whom one mammary artery (I) was used for this purpose. Both groups were similar. There were no differences between the groups in operative morbidity or mortality. The survival at 10 years was similar (II: 84.61 +/- 4%; I: 85.18 +/- 3.8%), whereas recurrence of angina (II: 29.63 +/- 5.3%; I: 47.55 +/- 5.6%) (p = 0.012), the requirement for percutaneous angioplasty (II: 3.98 +/- 2%; I: 12.99 +/- 4.1%) (p = 0.009) and cardiologic events (II: 33.48 +/- 5.5%; I: 48.48 +/- 5.5%)(p = 0.022) were all lower in the group in which both mammary arteries were used. In the multivariate analysis, the use of both mammary arteries was an independent protective factor against angina recurrence (RR = 0.55), angioplasty (RR = 0.18) and cardiologic event (RR = 0.60). The use of both mammary arteries for revascularization does not increase operative morbidity. Since this procedure acts as an independent factor against angina recurrence, angioplasty and cardiologic event

The Effect of Earthquakes on Episodic Tremor and Slip Events on the Southern Cascadia Subduction Zone

NASA Astrophysics Data System (ADS)

Sainvil, A. K.; Schmidt, D. A.; Nuyen, C.

2017-12-01

The goal of this study is to explore how slow slip events on the southern Cascadia Subduction Zone respond to nearby, offshore earthquakes by examining GPS and tremor data. At intermediate depths on the plate interface ( 40 km), transient fault slip is observed in the form of Episodic Tremor and Slip (ETS) events. These ETS events occur regularly (every 10 months), and have a longer duration than normal earthquakes. Researchers have been documenting slow slip events through data obtained by continuously running GPS stations in the Pacific Northwest. Some studies have proposed that pore fluid may play a role in these ETS events by lowering the effective stress on the fault. The interaction of earthquakes and ETS can provide constraints on the strength of the fault and the level of stress needed to alter ETS behavior. Earthquakes can trigger ETS events, but the connection between these events and earthquake activity is less understood. We originally hypothesized that ETS events would be affected by earthquakes in southern Cascadia, and could result in a shift in the recurrence interval of ETS events. ETS events were cataloged using GPS time series provided by PANGA, in conjunction with tremor positions, in Southern Cascadia for stations YBHB and DDSN from 1997 to 2017. We looked for evidence of change from three offshore earthquakes that occurred near the Mendocino Triple Junction with moment magnitudes of 7.2 in 2005, 6.5 in 2010, and 6.8 in 2014. Our results showed that the recurrence interval of ETS for stations YBHB and DDSN was not altered by the three earthquake events. Future is needed to explore whether this lack of interaction is explained by the non-optimal orientation of the receiver fault for the earthquake focal mechanisms.

Drug-Induced by Systemic Lupus Erythematosus Presenting as Recurrent Pericardial Effusion After Mitral Valve Repair.

PubMed

Haydari, Aghigh; Sabzi, Feridoun; Dabiri, Samsam; Poormotaabed, Alireza

2017-09-01

We report a patient presented with recurrent pericardial effusion caused by drug-induced systemic lupus Erythematosus (SLE) following mitral valve repair. The surgery was complicated by hemiparesis and convulsion in early postoperative period. The patient had been received carbamazepine for a paroxysmal seizure that occurred following mitral valve repair. The post operative computed tomography showed embolic stroke and its sequel (seizure) that treated with carbamazepine. In the 3rd month of follow-up, however, hemiparesis recovered by physiotherapy but carbamazepine was not discontinued as by request of neurologist. In the 6th month of surgery, the patient admitted by dyspnea and massive pericardial effusion that treated by subxiphoid drainage. This event was re occurred in two times in a short time frame and each event treated by surgical approach. The serologic exam in the last admission revealed drug-induced lupus erythematosus. The carbamazepine as an anti convulsive drug has been described to cause LE like disease in multiple case reports. Laboratory exam exhibited the possibility of carbamazepine-induced lupus in our case, with the extremely rare presentation of recurrent massive pericardial effusion.

[A Case of Recurrent Gastric Cancer with Grade 3 Proteinuria Caused by Ramucirumab plus Paclitaxel Therapy].

PubMed

Kimura, Yutaka; Makari, Yoichi; Mikami, Jota; Hiraki, Yoko; Kato, Hiroaki; Iwama, Mitsuru; Shiraishi, Osamu; Yasuda, Atsushi; Shinkai, Masayuki; Imano, Motohiro; Imamoto, Haruhiko; Fujita, Junya; Furukawa, Hiroshi; Yasuda, Takushi

2017-11-01

Proteinuria is one of the characteristic adverse events by ramucirumab(RAM)plus paclitaxel(PTX)combination therapy for advanced gastric cancer. We reported a case of recurrent gastric cancer with grade(gr)3 proteinuria caused by RAM plus PTX therapy. 77-year-old woman was underwent distal gastrectomy in 76 years old for gastric cancer that was diagnosed mucinous adenocarcinoma, fStage III C(T4aN3H0P0CY0M0)and received adjuvant chemotherapy of S-1 for 1 year. She suffered from peritoneal recurrence with ascites after 1 year and 4 months of the operation and RAM(8mg/kg; day 1 and 15)plus PTX(80mg/m2; day 1, 8 and 15)therapy was administrated as second-line chemotherapy. After 1 course, weekly PTX has been continued for gr 3 proteinuria and the ascites disappeared after 4 courses. This successful case might indicate that it was important for patients with gr 3 proteinuria as adverse event to consider discontinuance of RAM and continuation of PTX according to the proper usage guide of RAM.

Memories of environmental change and local adaptations among molapo farming communities in the Okavango Delta, Botswana-A gender perspective.

PubMed

Ngwenya, B N; Thakadu, O T; Magole, L; Chimbari, M J

2017-11-01

This paper focuses on ways in which three riparian communities (Xobe, Shorobe and Tubu) practising flood recession (molapo) farming along the fringes of the Okavango Delta in Ngamiland District in north-western Botswana, present memories of experiential impacts of and adaptation to key environmental and anthropogenic change events. Participatory methodological tools were used to capture local knowledge of people who had resided in the Okavango wetlands for many years. Findings indicate that key environmental change events were characterized by intergenerational experiences of severe and frequent droughts, floods, and recurrent outbreaks of human and animal disease. These events had impacted livelihoods and well-being of communities. Community adaptation strategies were embedded in local institutions of governance, especially chieftainship and the Kgotla, as legitimate platforms for community re-organization against unpredictable environmental change. We concluded that policy/program formulation processes need to take cognisance of local communities' historical knowledge of environmental change and adaptation. In particular it emerged that men and women, and people of different ages have differentiated memories of historical events which are complementary and necessary in developing a comprehensive adaptation strategy. Copyright © 2016 Elsevier B.V. All rights reserved.

Search for Correlated Fluctuations in the Beta+ Decay of Na-22

NASA Astrophysics Data System (ADS)

Silverman, M. P.; Strange, W.

2008-10-01

Claims for a ``cosmogenic'' force that correlates otherwise independent stochastic events have been made for at least 10 years, based largely on visual inspection of time series of histograms whose shapes were interpreted as suggestive of recurrent patterns with semi-diurnal, diurnal, and monthly periods. Building on our earlier work to test randomness of different nuclear decay processes, we have searched for correlations in the time-series of coincident positron-electron annihilations deriving from beta+ decay of Na-22. Disintegrations were counted within a narrow time window over a period of 7 days, leading to a time series of more than 1 million events. Statistical tests were performed on the raw time series, its correlation function, and its Fourier transform to search for cyclic correlations indicative of quantum-mechanical violating deviations from Poisson statistics. The time series was then partitioned into a sequence of 167 ``bags'' each of 8192 events. A histogram was made of the events of each bag, where contiguous frequency classes differed by a single count. The chronological sequence of histograms was then tested for correlations within classes. In all cases the results of the tests were in accord with statistical control, giving no evidence of correlated fluctuations.

Use of oseltamivir after influenza infection is associated with reduced incidence of recurrent adverse cardiovascular outcomes among military health system beneficiaries with prior cardiovascular diseases.

PubMed

Casscells, S Ward; Granger, Elder; Kress, Amii M; Linton, Andrea; Madjid, Mohammad; Cottrell, Linda

2009-03-01

Influenza infection has been associated with increased risk of adverse cardiac and cerebral vascular outcomes. Oseltamivir, a treatment for influenza, has been shown to decrease the severity of an influenza episode, but few data exist regarding its potentially protective effect against recurrent vascular outcomes among influenza patients with a history of vascular disease. Electronic healthcare service and pharmacy records for 37,482 TRICARE beneficiaries, aged 18 and older, with a coded history of cardiovascular (CV) disease and a subsequent diagnosis of influenza from October 1, 2003, through September 30, 2007, were examined. Subjects were grouped according to whether they had filled a prescription for oseltamivir within 2 days of their influenza diagnosis. The incidence of recurrent CV events within 30 days after the influenza diagnosis among oseltavmivir-treated and untreated subjects was 8.5% and 21.2%, respectively (P<0.005). Subject age was a persistent and significant contributor to the likelihood of recurrent CV outcomes. After controlling for the differences in demographics among treated and untreated cohorts using a propensity-scored logistic regression model, a statistically significant protective effect was associated with oseltamivir treatment (odds ratio, 0.417; 95% CI, 0.349 to 0.498). Our findings suggests that oseltamivir treatment for influenza is associated with significant decrease in the risk of recurrent CV events in subjects with a history of CV disease. These findings merit confirmation in further prospective and controlled studies. Meanwhile, in patients with CV disease, strict adherence with current practice guidelines for prevention and treatment of influenza is recommended.

Modeling the Treatment of Glioblastoma Multiforme and Cancer Stem Cells with Ordinary Differential Equations.

PubMed

Abernathy, Kristen; Burke, Jeremy

2016-01-01

Despite improvements in cancer therapy and treatments, tumor recurrence is a common event in cancer patients. One explanation of recurrence is that cancer therapy focuses on treatment of tumor cells and does not eradicate cancer stem cells (CSCs). CSCs are postulated to behave similar to normal stem cells in that their role is to maintain homeostasis. That is, when the population of tumor cells is reduced or depleted by treatment, CSCs will repopulate the tumor, causing recurrence. In this paper, we study the application of the CSC Hypothesis to the treatment of glioblastoma multiforme by immunotherapy. We extend the work of Kogan et al. (2008) to incorporate the dynamics of CSCs, prove the existence of a recurrence state, and provide an analysis of possible cancerous states and their dependence on treatment levels.

Basic mechanisms in intracranial large-artery atherosclerosis: advances and challenges.

PubMed

Arenillas, Juan F; Alvarez-Sabín, José

2005-01-01

Intracranial large-artery atherosclerosis is a major cause of ischemic stroke worldwide. Patients affected by this disease are at a high risk of suffering recurrent ischemic events despite antithrombotic therapy. Progression and a greater extent of intracranial atherosclerosis imply a higher risk for recurrence. Studies performed by our group in patients with symptomatic intracranial large-artery atherosclerosis have shown that: (1) C-reactive protein predicts its progression and recurrence, suggesting that inflammation may play a deleterious role in this condition; (2) a high level of the anti-angiogenic endostatin is also associated with a progressive and recurrent intracranial atherosclerosis, which might support a beneficial role for angiogenesis in this group of patients; and (3) elevated lipoprotein(a) concentration and diabetes mellitus characterize those patients with a higher number of intracranial stenoses. 2005 S. Karger AG, Basel

Beyond Word Frequency: Bursts, Lulls, and Scaling in the Temporal Distributions of Words

PubMed Central

Altmann, Eduardo G.; Pierrehumbert, Janet B.; Motter, Adilson E.

2009-01-01

Background Zipf's discovery that word frequency distributions obey a power law established parallels between biological and physical processes, and language, laying the groundwork for a complex systems perspective on human communication. More recent research has also identified scaling regularities in the dynamics underlying the successive occurrences of events, suggesting the possibility of similar findings for language as well. Methodology/Principal Findings By considering frequent words in USENET discussion groups and in disparate databases where the language has different levels of formality, here we show that the distributions of distances between successive occurrences of the same word display bursty deviations from a Poisson process and are well characterized by a stretched exponential (Weibull) scaling. The extent of this deviation depends strongly on semantic type – a measure of the logicality of each word – and less strongly on frequency. We develop a generative model of this behavior that fully determines the dynamics of word usage. Conclusions/Significance Recurrence patterns of words are well described by a stretched exponential distribution of recurrence times, an empirical scaling that cannot be anticipated from Zipf's law. Because the use of words provides a uniquely precise and powerful lens on human thought and activity, our findings also have implications for other overt manifestations of collective human dynamics. PMID:19907645

Non-random nature of spontaneous mIPSCs in mouse auditory brainstem neurons revealed by recurrence quantification analysis

PubMed Central

Leao, Richardson N; Leao, Fabricio N; Walmsley, Bruce

2005-01-01

A change in the spontaneous release of neurotransmitter is a useful indicator of processes occurring within presynaptic terminals. Linear techniques (e.g. Fourier transform) have been used to analyse spontaneous synaptic events in previous studies, but such methods are inappropriate if the timing pattern is complex. We have investigated spontaneous glycinergic miniature synaptic currents (mIPSCs) in principal cells of the medial nucleus of the trapezoid body. The random versus deterministic (or periodic) nature of mIPSCs was assessed using recurrence quantification analysis. Nonlinear methods were then used to quantify any detected determinism in spontaneous release, and to test for chaotic or fractal patterns. Modelling demonstrated that this procedure is much more sensitive in detecting periodicities than conventional techniques. mIPSCs were found to exhibit periodicities that were abolished by blockade of internal calcium stores with ryanodine, suggesting calcium oscillations in the presynaptic inhibitory terminals. Analysis indicated that mIPSC occurrences were chaotic in nature. Furthermore, periodicities were less evident in congenitally deaf mice than in normal mice, indicating that appropriate neural activity during development is necessary for the expression of deterministic chaos in mIPSC patterns. We suggest that chaotic oscillations of mIPSC occurrences play a physiological role in signal processing in the auditory brainstem. PMID:16271982

Magnitude of virologic blips is associated with a higher risk for virologic rebound in HIV-infected individuals: a recurrent events analysis.

PubMed

Grennan, J Troy; Loutfy, Mona R; Su, DeSheng; Harrigan, P Richard; Cooper, Curtis; Klein, Marina; Machouf, Nima; Montaner, Julio S G; Rourke, Sean; Tsoukas, Christos; Hogg, Bob; Raboud, Janet

2012-04-15

The importance of human immunodeficiency virus (HIV) blip magnitude on virologic rebound has been raised in clinical guidelines relating to viral load assays. Antiretroviral-naive individuals initiating combination antiretroviral therapy (cART) after 1 January 2000 and achieving virologic suppression were studied. Negative binomial models were used to identify blip correlates. Recurrent event models were used to determine the association between blips and rebound by incorporating multiple periods of virologic suppression per individual. 3550 participants (82% male; median age, 40 years) were included. In a multivariable negative binomial regression model, the Amplicor assay was associated with a lower blip rate than branched DNA (rate ratio, 0.69; P < .01), controlling for age, sex, region, baseline HIV-1 RNA and CD4 count, AIDS-defining illnesses, year of cART initiation, cART type, and HIV-1 RNA testing frequency. In a multivariable recurrent event model controlling for age, sex, intravenous drug use, cART start year, cART type, assay type, and HIV-1 RNA testing frequency, blips of 500-999 copies/mL were associated with virologic rebound (hazard ratio, 2.70; P = .002), whereas blips of 50-499 were not. HIV-1 RNA assay was an important determinant of blip rates and should be considered in clinical guidelines. Blips ≥500 copies/mL were associated with increased rebound risk.

Activity and safety of bevacizumab plus fotemustine for recurrent malignant gliomas.

PubMed

Vaccaro, V; Fabi, A; Vidiri, A; Giannarelli, D; Metro, G; Telera, S; Vari, S; Piludu, F; Carosi, M A; Villani, V; Cognetti, F; Pompili, A; Marucci, L; Carapella, C M; Pace, A

2014-01-01

No established chemotherapeutic regimen exists for the treatment of recurrent malignant gliomas (rMGs). Herein, we report the activity and safety results of the bevacizumab (B) plus fotemustine (FTM) combination for the treatment of rMGs. An induction phase consisted of B 10 mg/kg days 1, 15 plus FTM 65 mg/m(2) days 1, 8, and 15. Nonprogressive patients entered the maintenance phase with B 10 mg/kg plus FTM 75 mg/m(2) every 3 weeks. The primary endpoint was response rate; secondary endpoints included safety, progression free survival (PFS), and overall survival (OS). Twenty-six patients affected by recurrent MGs (50% glioblastoma) were enrolled. Eight partial responses (31%) were observed. Median PFS and OS were 4 (95% C.I.: 2.8-5.1) and 6 months (95% C.I.: 4.2-7.8), respectively. Responses were significantly associated with both improved PFS and OS (P = 0.002 and P = 0.001, resp.). Treatment adverse events were mostly mild to moderate in intensity. Bevacizumab-related adverse events included grade 3 venous thromboembolic event (8%), grade 2 epistaxis (4%), hypertension (8%), and gastrointestinal perforation (4%). Bevacizumab plus FTM showed activity and good tolerability in pretreated MGs. Further investigations are needed in order to verify the benefits deriving from the addition of B to a cytotoxic in this clinical setting of patients.

Early Recurrence and Cerebral Bleeding in Patients With Acute Ischemic Stroke and Atrial Fibrillation: Effect of Anticoagulation and Its Timing: The RAF Study.

PubMed

Paciaroni, Maurizio; Agnelli, Giancarlo; Falocci, Nicola; Caso, Valeria; Becattini, Cecilia; Marcheselli, Simona; Rueckert, Christina; Pezzini, Alessandro; Poli, Loris; Padovani, Alessandro; Csiba, Laszló; Szabó, Lilla; Sohn, Sung-Il; Tassinari, Tiziana; Abdul-Rahim, Azmil H; Michel, Patrik; Cordier, Maria; Vanacker, Peter; Remillard, Suzette; Alberti, Andrea; Venti, Michele; Scoditti, Umberto; Denti, Licia; Orlandi, Giovanni; Chiti, Alberto; Gialdini, Gino; Bovi, Paolo; Carletti, Monica; Rigatelli, Alberto; Putaala, Jukka; Tatlisumak, Turgut; Masotti, Luca; Lorenzini, Gianni; Tassi, Rossana; Guideri, Francesca; Martini, Giuseppe; Tsivgoulis, Georgios; Vadikolias, Kostantinos; Liantinioti, Chrissoula; Corea, Francesco; Del Sette, Massimo; Ageno, Walter; De Lodovici, Maria Luisa; Bono, Giorgio; Baldi, Antonio; D'Anna, Sebastiano; Sacco, Simona; Carolei, Antonio; Tiseo, Cindy; Acciarresi, Monica; D'Amore, Cataldo; Imberti, Davide; Zabzuni, Dorjan; Doronin, Boris; Volodina, Vera; Consoli, Domenico; Galati, Franco; Pieroni, Alessio; Toni, Danilo; Monaco, Serena; Baronello, Mario Maimone; Barlinn, Kristian; Pallesen, Lars-Peder; Kepplinger, Jessica; Bodechtel, Ulf; Gerber, Johannes; Deleu, Dirk; Melikyan, Gayane; Ibrahim, Faisal; Akhtar, Naveed; Mosconi, Maria Giulia; Bubba, Valentina; Silvestri, Ilenia; Lees, Kennedy R

2015-08-01

The best time for administering anticoagulation therapy in acute cardioembolic stroke remains unclear. This prospective cohort study of patients with acute stroke and atrial fibrillation, evaluated (1) the risk of recurrent ischemic event and severe bleeding; (2) the risk factors for recurrence and bleeding; and (3) the risks of recurrence and bleeding associated with anticoagulant therapy and its starting time after the acute stroke. The primary outcome of this multicenter study was the composite of stroke, transient ischemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding and major extracranial bleeding within 90 days from acute stroke. Of the 1029 patients enrolled, 123 had 128 events (12.6%): 77 (7.6%) ischemic stroke or transient ischemic attack or systemic embolism, 37 (3.6%) symptomatic cerebral bleeding, and 14 (1.4%) major extracranial bleeding. At 90 days, 50% of the patients were either deceased or disabled (modified Rankin score ≥3), and 10.9% were deceased. High CHA2DS2-VASc score, high National Institutes of Health Stroke Scale, large ischemic lesion and type of anticoagulant were predictive factors for primary study outcome. At adjusted Cox regression analysis, initiating anticoagulants 4 to 14 days from stroke onset was associated with a significant reduction in primary study outcome, compared with initiating treatment before 4 or after 14 days: hazard ratio 0.53 (95% confidence interval 0.30-0.93). About 7% of the patients treated with oral anticoagulants alone had an outcome event compared with 16.8% and 12.3% of the patients treated with low molecular weight heparins alone or followed by oral anticoagulants, respectively (P=0.003). Acute stroke in atrial fibrillation patients is associated with high rates of ischemic recurrence and major bleeding at 90 days. This study has observed that high CHA2DS2-VASc score, high National Institutes of Health Stroke Scale, large ischemic lesions, and type of anticoagulant administered each independently led to a greater risk of recurrence and bleedings. Also, data showed that the best time for initiating anticoagulation treatment for secondary stroke prevention is 4 to 14 days from stroke onset. Moreover, patients treated with oral anticoagulants alone had better outcomes compared with patients treated with low molecular weight heparins alone or before oral anticoagulants. © 2015 American Heart Association, Inc.

Adjuvant Nivolumab versus Ipilimumab in Resected Stage III or IV Melanoma.

PubMed

Weber, Jeffrey; Mandala, Mario; Del Vecchio, Michele; Gogas, Helen J; Arance, Ana M; Cowey, C Lance; Dalle, Stéphane; Schenker, Michael; Chiarion-Sileni, Vanna; Marquez-Rodas, Ivan; Grob, Jean-Jacques; Butler, Marcus O; Middleton, Mark R; Maio, Michele; Atkinson, Victoria; Queirolo, Paola; Gonzalez, Rene; Kudchadkar, Ragini R; Smylie, Michael; Meyer, Nicolas; Mortier, Laurent; Atkins, Michael B; Long, Georgina V; Bhatia, Shailender; Lebbé, Celeste; Rutkowski, Piotr; Yokota, Kenji; Yamazaki, Naoya; Kim, Tae M; de Pril, Veerle; Sabater, Javier; Qureshi, Anila; Larkin, James; Ascierto, Paolo A

2017-11-09

Nivolumab and ipilimumab are immune checkpoint inhibitors that have been approved for the treatment of advanced melanoma. In the United States, ipilimumab has also been approved as adjuvant therapy for melanoma on the basis of recurrence-free and overall survival rates that were higher than those with placebo in a phase 3 trial. We wanted to determine the efficacy of nivolumab versus ipilimumab for adjuvant therapy in patients with resected advanced melanoma. In this randomized, double-blind, phase 3 trial, we randomly assigned 906 patients (≥15 years of age) who were undergoing complete resection of stage IIIB, IIIC, or IV melanoma to receive an intravenous infusion of either nivolumab at a dose of 3 mg per kilogram of body weight every 2 weeks (453 patients) or ipilimumab at a dose of 10 mg per kilogram every 3 weeks for four doses and then every 12 weeks (453 patients). The patients were treated for a period of up to 1 year or until disease recurrence, a report of unacceptable toxic effects, or withdrawal of consent. The primary end point was recurrence-free survival in the intention-to-treat population. At a minimum follow-up of 18 months, the 12-month rate of recurrence-free survival was 70.5% (95% confidence interval [CI], 66.1 to 74.5) in the nivolumab group and 60.8% (95% CI, 56.0 to 65.2) in the ipilimumab group (hazard ratio for disease recurrence or death, 0.65; 97.56% CI, 0.51 to 0.83; P<0.001). Treatment-related grade 3 or 4 adverse events were reported in 14.4% of the patients in the nivolumab group and in 45.9% of those in the ipilimumab group; treatment was discontinued because of any adverse event in 9.7% and 42.6% of the patients, respectively. Two deaths (0.4%) related to toxic effects were reported in the ipilimumab group more than 100 days after treatment. Among patients undergoing resection of stage IIIB, IIIC, or IV melanoma, adjuvant therapy with nivolumab resulted in significantly longer recurrence-free survival and a lower rate of grade 3 or 4 adverse events than adjuvant therapy with ipilimumab. (Funded by Bristol-Myers Squibb and Ono Pharmaceutical; CheckMate 238 ClinicalTrials.gov number, NCT02388906 ; Eudra-CT number, 2014-002351-26 .).

Probability Elicitation Under Severe Time Pressure: A Rank-Based Method.

PubMed

Jaspersen, Johannes G; Montibeller, Gilberto

2015-07-01

Probability elicitation protocols are used to assess and incorporate subjective probabilities in risk and decision analysis. While most of these protocols use methods that have focused on the precision of the elicited probabilities, the speed of the elicitation process has often been neglected. However, speed is also important, particularly when experts need to examine a large number of events on a recurrent basis. Furthermore, most existing elicitation methods are numerical in nature, but there are various reasons why an expert would refuse to give such precise ratio-scale estimates, even if highly numerate. This may occur, for instance, when there is lack of sufficient hard evidence, when assessing very uncertain events (such as emergent threats), or when dealing with politicized topics (such as terrorism or disease outbreaks). In this article, we adopt an ordinal ranking approach from multicriteria decision analysis to provide a fast and nonnumerical probability elicitation process. Probabilities are subsequently approximated from the ranking by an algorithm based on the principle of maximum entropy, a rule compatible with the ordinal information provided by the expert. The method can elicit probabilities for a wide range of different event types, including new ways of eliciting probabilities for stochastically independent events and low-probability events. We use a Monte Carlo simulation to test the accuracy of the approximated probabilities and try the method in practice, applying it to a real-world risk analysis recently conducted for DEFRA (the U.K. Department for the Environment, Farming and Rural Affairs): the prioritization of animal health threats. © 2015 Society for Risk Analysis.

El Niño impact on mollusk biomineralization-implications for trace element proxy reconstructions and the paleo-archeological record.

PubMed

Pérez-Huerta, Alberto; Etayo-Cadavid, Miguel F; Andrus, C Fred T; Jeffries, Teresa E; Watkins, Clifton; Street, Shane C; Sandweiss, Daniel H

2013-01-01

Marine macroinvertebrates are ideal sentinel organisms to monitor rapid environmental changes associated with climatic phenomena. These organisms build up protective exoskeletons incrementally by biologically-controlled mineralization, which is deeply rooted in long-term evolutionary processes. Recent studies relating potential rapid environmental fluctuations to climate change, such as ocean acidification, suggest modifications on carbonate biominerals of marine invertebrates. However, the influence of known, and recurrent, climatic events on these biological processes during active mineralization is still insufficiently understood. Analysis of Peruvian cockles from the 1982-83 large magnitude El Niño event shows significant alterations of the chemico-structure of carbonate biominerals. Here, we show that bivalves modify the main biomineralization mechanism during the event to continue shell secretion. As a result, magnesium content increases to stabilize amorphous calcium carbonate (ACC), inducing a rise in Mg/Ca unrelated to the associated increase in sea-surface temperature. Analysis of variations in Sr/Ca also suggests that this proxy should not be used in these bivalves to detect the temperature anomaly, while Ba/Ca peaks are recorded in shells in response to an increase in productivity, or dissolved barium in seawater, after the event. Presented data contribute to a better understanding of the effects of abrupt climate change on shell biomineralization, while also offering an alternative view of bivalve elemental proxy reconstructions. Furthermore, biomineralization changes in mollusk shells can be used as a novel potential proxy to provide a more nuanced historical record of El Niño and similar rapid environmental change events.

North Atlantic weather regimes: A synoptic study of phase space. M.S. Thesis

NASA Technical Reports Server (NTRS)

Orrhede, Anna Karin

1990-01-01

In the phase space of weather, low frequency variability (LFV) of the atmosphere can be captured in a large scale subspace, where a trajectory connects consecutive large scale weather maps, thus revealing flow changes and recurrences. Using this approach, Vautard applied the trajectory speed minimization method (Vautard and Legras) to atmospheric data. From 37 winters of 700 mb geopotential height anomalies over the North Atlantic and the adjacent land masses, four persistent and recurrent weather patterns, interpreted as weather regimes, were discernable: a blocking regime, a zonal regime, a Greenland anticyclone regime, and an Atlantic regime. These regimes are studied further in terms of maintenance and transitions. A regime survey unveils preferences regarding event durations and precursors for the onset or break of an event. The transition frequencies between regimes vary, and together with the transition times, suggest the existence of easier transition routes. These matters are more systematically studied using complete synoptic map sequences from a number of events.

Comparison of response rates on invitation mode of a web-based survey on influenza vaccine adverse events among healthcare workers: a pilot study.

PubMed

Tai, Xiaochen; Smith, Alanna M; McGeer, Allison J; Dubé, Eve; Holness, Dorothy Linn; Katz, Kevin; McGillis Hall, Linda; McNeil, Shelly A; Powis, Jeff; Coleman, Brenda L

2018-06-20

Web-based surveys have become increasingly popular but response rates are low and may be prone to selection bias. How people are invited to participate may impact response rates and needs further study as previous evidence is contradictory. The purpose of this study was to determine whether response to a web-based survey of healthcare workers would be higher with a posted or an emailed invitation. We also report results of the pilot study, which aims to estimate the percentage of adults vaccinated against influenza who report recurrent systemic adverse events (the same systemic adverse event occurring successively following receipt of influenza vaccines). The pilot study was conducted in November 2016 in Toronto, Canada. Members of a registry of adults (18 years and older and predominantly healthcare workers) who volunteered to receive information regarding future studies about influenza were randomly assigned to receive either an email or postal invitation to complete a web-based survey regarding influenza vaccinations. Non-respondents received one reminder using the same mode of contact as their original invitation. The overall response rate was higher for those sent the invitation by email (34.8%) than by post (25.8%; p < 0.001) and for older versus younger participants (p trend  < 0.001). Of those who responded, 387/401 had been vaccinated against influenza at least once since adulthood. Of those responding to the question, 70/386 (18.1%) reported a systemic adverse event after their most recent influenza vaccine including 22 (5.7%) who reported a recurring systemic event. Systemic adverse events were reported more often by males 18-49 years old than by other groups (p = 0.01). Recurrent systemic adverse events were similar by age and sex with muscle ache being the most commonly reported recurrent reaction. More respondents who reported only a local adverse event (93.1%) planned to be vaccinated again next year than those with a systemic adverse event (69.7%; p = 0.04). In this convenience sample of registry volunteers, response rates were generally low, but were higher for the emailed than posted invitations and for older than younger adults.

Transcriptomic Profiling and Functional Characterization of Fusion Genes in Recurrent Ovarian Cancer

DTIC Science & Technology

2017-09-01

the enhanced malignancy observed in recurrent disease. In the first year of this proposal we have assembled a cohort of 18 patient matched pairs of...significance and biologic function of prioritized RNA fusion events. 15. SUBJECT TERMS 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18 ...cellularity. 19 cases were identified (Table 1) but one was removed for quality control issues thus leaving a total of 18 cases. Table 1 shows the clinical

On the Bimodality of ENSO Cycle Extremes

NASA Technical Reports Server (NTRS)

Wilson, Robert M.

2000-01-01

On the basis of sea surface temperature in the El Nino 3.4 region (5 deg. N.,-5 deg. S., 120-170 deg. W.) during the interval of 1950-1997, Kevin Trenberth previously has identified some 16 El Nino and 10 La Nina, these 26 events representing the extremes of the quasi-periodic El Nino-Southern Oscillation (ENSO) cycle. Runs testing shows that the duration, recurrence period, and sequencing of these extremes vary randomly. Hence, the decade of the 1990's, especially for El Nino, is not significantly different from that of previous decadal epochs, at least, on the basis of the frequency of onsets of ENSO extremes. Additionally, the distribution of duration for both El Nino and La Nina looks strikingly bimodal, each consisting of two preferred modes, about 8- and 16-mo long for El Nino and about 9- and 18-mo long for La Nina, as does the distribution of the recurrence period for El Nino, consisting of two preferred modes about 21- and 50-mo long. Scatterplots of the recurrence period versus duration for El Nino are found to be statistically important, displaying preferential associations that link shorter (longer) duration with shorter (longer) recurrence periods. Because the last onset of El Nino occurred in April 1997 and the event was of longer than average duration, onset of the next anticipated El Nino is not expected until February 2000 or later.

On The Bimodality of ENSO Cycle Extremes

NASA Technical Reports Server (NTRS)

Wilson, Robert M.

2000-01-01

On the basis of sea surface temperature in the El Nino 3.4 region (5N.-5S., 120-170W.) during the interval of 1950-1997, Kevin Trenberth previously has identified some 16 El Nino and 10 La Nina, these 26 events representing the extremes of the quasi-periodic El Nino-Southern Oscillation (ENSO) cycle. Runs testing shows that the duration, recurrence period, and sequencing of these extremes vary randomly. Hence, the decade of the 1990's, especially for El Nino, is not significantly different from that of previous decadal epochs, at least, on the basis of the frequency of onsets of ENSO extremes. Additionally, the distribution of duration for both El Nino and La Nina looks strikingly bimodal, each consisting of two preferred modes, about 8- and 16-months long for El Nino and about 9- and 18-months long for La Nina, as does the distribution of the recurrence period for El Nino, consisting of two preferred modes about 21- and 50- mo long. Scatterplots of the recurrence period versus duration for El Nino are found to be statistically important, displaying preferential associations that link shorter (longer) duration with shorter (longer) recurrence periods. Because the last onset of El Nino occurred in April 1997 and the event was of longer than average duration, onset of the next anticipated El Nino is not expected until February 2000 or later.

Bezlotoxumab for Prevention of Recurrent Clostridium difficile Infection.

PubMed

Wilcox, Mark H; Gerding, Dale N; Poxton, Ian R; Kelly, Ciaran; Nathan, Richard; Birch, Thomas; Cornely, Oliver A; Rahav, Galia; Bouza, Emilio; Lee, Christine; Jenkin, Grant; Jensen, Werner; Kim, You-Sun; Yoshida, Junichi; Gabryelski, Lori; Pedley, Alison; Eves, Karen; Tipping, Robert; Guris, Dalya; Kartsonis, Nicholas; Dorr, Mary-Beth

2017-01-26

Clostridium difficile is the most common cause of infectious diarrhea in hospitalized patients. Recurrences are common after antibiotic therapy. Actoxumab and bezlotoxumab are human monoclonal antibodies against C. difficile toxins A and B, respectively. We conducted two double-blind, randomized, placebo-controlled, phase 3 trials, MODIFY I and MODIFY II, involving 2655 adults receiving oral standard-of-care antibiotics for primary or recurrent C. difficile infection. Participants received an infusion of bezlotoxumab (10 mg per kilogram of body weight), actoxumab plus bezlotoxumab (10 mg per kilogram each), or placebo; actoxumab alone (10 mg per kilogram) was given in MODIFY I but discontinued after a planned interim analysis. The primary end point was recurrent infection (new episode after initial clinical cure) within 12 weeks after infusion in the modified intention-to-treat population. In both trials, the rate of recurrent C. difficile infection was significantly lower with bezlotoxumab alone than with placebo (MODIFY I: 17% [67 of 386] vs. 28% [109 of 395]; adjusted difference, -10.1 percentage points; 95% confidence interval [CI], -15.9 to -4.3; P<0.001; MODIFY II: 16% [62 of 395] vs. 26% [97 of 378]; adjusted difference, -9.9 percentage points; 95% CI, -15.5 to -4.3; P<0.001) and was significantly lower with actoxumab plus bezlotoxumab than with placebo (MODIFY I: 16% [61 of 383] vs. 28% [109 of 395]; adjusted difference, -11.6 percentage points; 95% CI, -17.4 to -5.9; P<0.001; MODIFY II: 15% [58 of 390] vs. 26% [97 of 378]; adjusted difference, -10.7 percentage points; 95% CI, -16.4 to -5.1; P<0.001). In prespecified subgroup analyses (combined data set), rates of recurrent infection were lower in both groups that received bezlotoxumab than in the placebo group in subpopulations at high risk for recurrent infection or for an adverse outcome. The rates of initial clinical cure were 80% with bezlotoxumab alone, 73% with actoxumab plus bezlotoxumab, and 80% with placebo; the rates of sustained cure (initial clinical cure without recurrent infection in 12 weeks) were 64%, 58%, and 54%, respectively. The rates of adverse events were similar among these groups; the most common events were diarrhea and nausea. Among participants receiving antibiotic treatment for primary or recurrent C. difficile infection, bezlotoxumab was associated with a substantially lower rate of recurrent infection than placebo and had a safety profile similar to that of placebo. The addition of actoxumab did not improve efficacy. (Funded by Merck; MODIFY I and MODIFY II ClinicalTrials.gov numbers, NCT01241552 and NCT01513239 .).

On the role of fluids in stick-slip dynamics of saturated granular fault gouge using a coupled computational fluid dynamics-discrete element approach

NASA Astrophysics Data System (ADS)

Dorostkar, Omid; Guyer, Robert A.; Johnson, Paul A.; Marone, Chris; Carmeliet, Jan

2017-05-01

The presence of fault gouge has considerable influence on slip properties of tectonic faults and the physics of earthquake rupture. The presence of fluids within faults also plays a significant role in faulting and earthquake processes. In this paper, we present 3-D discrete element simulations of dry and fluid-saturated granular fault gouge and analyze the effect of fluids on stick-slip behavior. Fluid flow is modeled using computational fluid dynamics based on the Navier-Stokes equations for an incompressible fluid and modified to take into account the presence of particles. Analysis of a long time train of slip events shows that the (1) drop in shear stress, (2) compaction of granular layer, and (3) the kinetic energy release during slip all increase in magnitude in the presence of an incompressible fluid, compared to dry conditions. We also observe that on average, the recurrence interval between slip events is longer for fluid-saturated granular fault gouge compared to the dry case. This observation is consistent with the occurrence of larger events in the presence of fluid. It is found that the increase in kinetic energy during slip events for saturated conditions can be attributed to the increased fluid flow during slip. Our observations emphasize the important role that fluid flow and fluid-particle interactions play in tectonic fault zones and show in particular how discrete element method (DEM) models can help understand the hydromechanical processes that dictate fault slip.

Estimating the burden of recurrent events in the presence of competing risks: the method of mean cumulative count.

PubMed

Dong, Huiru; Robison, Leslie L; Leisenring, Wendy M; Martin, Leah J; Armstrong, Gregory T; Yasui, Yutaka

2015-04-01

Cumulative incidence has been widely used to estimate the cumulative probability of developing an event of interest by a given time, in the presence of competing risks. When it is of interest to measure the total burden of recurrent events in a population, however, the cumulative incidence method is not appropriate because it considers only the first occurrence of the event of interest for each individual in the analysis: Subsequent occurrences are not included. Here, we discuss a straightforward and intuitive method termed "mean cumulative count," which reflects a summarization of all events that occur in the population by a given time, not just the first event for each subject. We explore the mathematical relationship between mean cumulative count and cumulative incidence. Detailed calculation of mean cumulative count is described by using a simple hypothetical example, and the computation code with an illustrative example is provided. Using follow-up data from January 1975 to August 2009 collected in the Childhood Cancer Survivor Study, we show applications of mean cumulative count and cumulative incidence for the outcome of subsequent neoplasms to demonstrate different but complementary information obtained from the 2 approaches and the specific utility of the former. © The Author 2015. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Safety of Pregnancy After Cerebral Venous Thrombosis: Results of the ISCVT (International Study on Cerebral Vein and Dural Sinus Thrombosis)-2 PREGNANCY Study.

PubMed

Aguiar de Sousa, Diana; Canhão, Patrícia; Crassard, Isabelle; Coutinho, Jonathan; Arauz, Antonio; Conforto, Adriana; Béjot, Yannick; Giroud, Maurice; Ferro, José M

2017-11-01

Pregnancy is associated with increased risk of venous thrombotic events, including cerebral venous thrombosis. We aimed to study the complications and outcome of subsequent pregnancies in women with previous cerebral venous thrombosis. Follow-up study of women with acute cerebral venous thrombosis at childbearing age included in a previously described cohort (International Study of Cerebral Vein and Dural Sinus Thrombosis). Patients were interviewed by local neurologists to assess rate of venous thrombotic events, pregnancy outcomes, and antithrombotic prophylaxis during subsequent pregnancies. A total of 119 women were included, with a median follow-up of 14 years. Eighty-two new pregnancies occurred in 47 women. In 83% (68 of 82), some form of antithrombotic prophylaxis was given during at least 1 trimester of pregnancy or puerperium. Venous thrombotic events occurred in 3 pregnancies, including 1 recurrent cerebral venous thrombosis. Two of the 3 women were on prophylactic low-molecular-weight heparin at the time of the event. Outcomes of pregnancies were 51 full-term newborns, 9 preterm births, 2 stillbirths, and 20 abortions (14 spontaneous). In women with prior cerebral venous thrombosis, recurrent venous thrombotic events during subsequent pregnancies are infrequent. © 2017 American Heart Association, Inc.

Genetic Risk, Coronary Heart Disease Events, and the Clinical Benefit of Statin Therapy

PubMed Central

Smith, JG; Chasman, DI; Caulfield, M; Devlin, JJ; Nordio, F; Hyde, C; Cannon, CP; Sacks, F; Poulter, N; Sever, P; Ridker, PM; Braunwald, E; Melander, O

2015-01-01

Background Genetic variants have been associated with the risk of coronary heart disease (CHD). We tested whether a composite of these variants could identify the risk of both incident as well as recurrent CHD events and distinguish individuals who derived greater clinical benefit from statin therapy. Methods A community-based cohort and four randomized controlled trials of both primary (JUPITER and ASCOT) and secondary (CARE and PROVE IT-TIMI 22) prevention with statin therapy totaling 48,421 individuals and 3,477 events were included in these analyses. We examined the association of a genetic risk score based on 27 genetic variants with incident or recurrent CHD, adjusting for established clinical predictors. We then investigated the relative and absolute risk reductions in CHD events with statin therapy stratified by genetic risk. Data from studies were combined using meta-analysis. Findings When individuals were divided into low (quintile 1), intermediate (quintiles 2-4), and high (quintile 5) genetic risk categories, a significant gradient of risk for incident or recurrent CHD was demonstrated with the multivariable-adjusted HRs (95% CI) for CHD for the intermediate and high genetic risk categories vs. low genetic risk category being 1.32 (1.20-1.46, P<0.0001) and 1.71 (1.54-1.91, P<0.0001), respectively. In terms of the benefit of statin therapy in the four randomized trials, there was a significant gradient of increasing relative risk reduction across the low, intermediate, and high genetic risk categories (13%, 29%, and 48%, P=0.0277). Similarly, greater absolute risk reductions were seen in those individuals in higher genetic risk categories (P=0.0101), resulting in an approximate three-fold gradient in the number needed to treat (NNT) in the primary prevention trials. Specifically, in the primary prevention trials, the NNT to prevent one MACE over 10 years for the low, intermediate, and high GRS individuals was 66, 42, and 25 in JUPITER and 57, 47, and 20 in ASCOT. Interpretation A genetic risk score identified individuals at increased risk for both incident and recurrent CHD events. Individuals with the highest burden of genetic risk derived the largest relative and absolute clinical benefit with statin therapy. PMID:25748612

Analysis of Surgical Success in Preventing Recurrent Acute Exacerbations in Chronic Pancreatitis

PubMed Central

Nealon, William H.; Matin, Sina

2001-01-01

Objective To determine whether surgical intervention prevents recurrent acute exacerbations in chronic pancreatitis (CP). Summary Background Data The primary goal of surgical intervention in the treatment of CP has been relief of chronic unrelenting abdominal pain. A subset of patients with CP have intermittent acute exacerbations, often with increasing frequency and often unrelated to ongoing ethanol abuse. Little data exist regarding the effectiveness of surgery to prevent acute attacks. Methods From 1985 to 1999, all patients identified with a diagnosis of CP were recruited to participate in an ongoing program of serial clinic visits and functional and clinical evaluations. Patients were offered surgery using standard criteria. Data were gathered regarding ethanol abuse, pain, narcotic use, and recurrent acute exacerbations requiring hospital admission before and after surgery. Patients were broadly categorized as having severe unrelenting pain alone (group 1), severe pain with intermittent acute exacerbations (group 2), and intermittent acute exacerbations only (group 3). Results Two hundred fifty-nine patients were recruited. One hundred eighty-five patients underwent 199 surgical procedures (124 modified Puestow procedure [LPJ], 29 distal pancreatectomies [DP], and 46 pancreatic head resections [PHR; 14 performed after failure of LPJ]). There were no deaths. The complication rate was 4% for LPJ, 15% for DP, and 27% for PHR. Ethanol abuse was causative in 238 patients (92%). Mean follow-up was 81 months. There were 104 patients in group 1 (86 who underwent surgery), 71 patients in group 2 (64 who underwent surgery), and 84 in group 3 (49 who underwent surgery). No patient without surgery had spontaneous resolution of symptoms. Postoperative pain relief (freedom from narcotic analgesics) was achieved in 153 of 185 patients (83%) overall: 106 of 124 (86%) for LPJ, 19 of 29 (67%) for DP, and 42 of 46 (91%) for PHR. The mean rate of acute exacerbations was 6.3 ± 2.1 events per year before surgery in group 2 and 7.8 ± 1.8 events per year in group 3. After surgery, no acute exacerbations occurred in 42 of 64 (66%) group 2 patients and in 40 of 49 (82%) group 3 patients. The mean number of episodes of acute exacerbation after surgery was 1.6 ± 2.3 events in group 2 and 1.1 ± 1.9 events in group 3. Only four patients in group 2 and one patient in group 3 had an equal or increased frequency of attacks after surgery. Preventing attacks was most effective with LPJ (58/64, 91%) and least effective for DP (6/18, 33%). Conclusions Surgical intervention prevents recurrent acute exacerbations. The overall frequency of events was reduced in nearly all patients. Therefore, surgical intervention is indicated in patients with CP whose disease is characterized by recurrent acute exacerbations. PMID:11371738

Analysis of surgical success in preventing recurrent acute exacerbations in chronic pancreatitis.

PubMed

Nealon, W H; Matin, S

2001-06-01

To determine whether surgical intervention prevents recurrent acute exacerbations in chronic pancreatitis (CP). The primary goal of surgical intervention in the treatment of CP has been relief of chronic unrelenting abdominal pain. A subset of patients with CP have intermittent acute exacerbations, often with increasing frequency and often unrelated to ongoing ethanol abuse. Little data exist regarding the effectiveness of surgery to prevent acute attacks. From 1985 to 1999, all patients identified with a diagnosis of CP were recruited to participate in an ongoing program of serial clinic visits and functional and clinical evaluations. Patients were offered surgery using standard criteria. Data were gathered regarding ethanol abuse, pain, narcotic use, and recurrent acute exacerbations requiring hospital admission before and after surgery. Patients were broadly categorized as having severe unrelenting pain alone (group 1), severe pain with intermittent acute exacerbations (group 2), and intermittent acute exacerbations only (group 3). Two hundred fifty-nine patients were recruited. One hundred eighty-five patients underwent 199 surgical procedures (124 modified Puestow procedure [LPJ], 29 distal pancreatectomies [DP], and 46 pancreatic head resections [PHR; 14 performed after failure of LPJ]). There were no deaths. The complication rate was 4% for LPJ, 15% for DP, and 27% for PHR. Ethanol abuse was causative in 238 patients (92%). Mean follow-up was 81 months. There were 104 patients in group 1 (86 who underwent surgery), 71 patients in group 2 (64 who underwent surgery), and 84 in group 3 (49 who underwent surgery). No patient without surgery had spontaneous resolution of symptoms. Postoperative pain relief (freedom from narcotic analgesics) was achieved in 153 of 185 patients (83%) overall: 106 of 124 (86%) for LPJ, 19 of 29 (67%) for DP, and 42 of 46 (91%) for PHR. The mean rate of acute exacerbations was 6.3 +/- 2.1 events per year before surgery in group 2 and 7.8 +/- 1.8 events per year in group 3. After surgery, no acute exacerbations occurred in 42 of 64 (66%) group 2 patients and in 40 of 49 (82%) group 3 patients. The mean number of episodes of acute exacerbation after surgery was 1.6 +/- 2.3 events in group 2 and 1.1 +/- 1.9 events in group 3. Only four patients in group 2 and one patient in group 3 had an equal or increased frequency of attacks after surgery. Preventing attacks was most effective with LPJ (58/64, 91%) and least effective for DP (6/18, 33%). Surgical intervention prevents recurrent acute exacerbations. The overall frequency of events was reduced in nearly all patients. Therefore, surgical intervention is indicated in patients with CP whose disease is characterized by recurrent acute exacerbations.

Prognosis of Patients With Familial Hypercholesterolemia After Acute Coronary Syndromes.

PubMed

Nanchen, David; Gencer, Baris; Muller, Olivier; Auer, Reto; Aghlmandi, Soheila; Heg, Dik; Klingenberg, Roland; Räber, Lorenz; Carballo, David; Carballo, Sebastian; Matter, Christian M; Lüscher, Thomas F; Windecker, Stephan; Mach, François; Rodondi, Nicolas

2016-09-06

Patients with heterozygous familial hypercholesterolemia (FH) and coronary heart disease have high mortality rates. However, in an era of high-dose statin prescription after acute coronary syndrome (ACS), the risk of recurrent coronary and cardiovascular events associated with FH might be mitigated. We compared coronary event rates between patients with and without FH after ACS. We studied 4534 patients with ACS enrolled in a multicenter, prospective cohort study in Switzerland between 2009 and 2013 who were individually screened for FH on the basis of clinical criteria according to 3 definitions: the American Heart Association definition, the Simon Broome definition, and the Dutch Lipid Clinic definition. We used Cox proportional models to assess the 1-year risk of first recurrent coronary events defined as coronary death or myocardial infarction and adjusted for age, sex, body mass index, smoking, hypertension, diabetes mellitus, existing cardiovascular disease, high-dose statin at discharge, attendance at cardiac rehabilitation, and the GRACE (Global Registry of Acute Coronary Events) risk score for severity of ACS. At the 1-year follow-up, 153 patients (3.4%) had died, including 104 (2.3%) of fatal myocardial infarction. A further 113 patients (2.5%) experienced nonfatal myocardial infarction. The prevalence of FH was 2.5% with the American Heart Association definition, 5.5% with the Simon Broome definition, and 1.6% with the Dutch Lipid Clinic definition. Compared with patients without FH, the risk of coronary event recurrence after ACS was similar in patients with FH in unadjusted analyses, although patients with FH were >10 years younger. However, after multivariable adjustment including age, the risk was greater in patients with FH than without, with an adjusted hazard ratio of 2.46 (95% confidence interval, 1.07-5.65; P=0.034) for the American Heart Association definition, 2.73 (95% confidence interval, 1.46-5.11; P=0.002) for the Simon Broome definition, and 3.53 (95% confidence interval, 1.26-9.94; P=0.017) for the Dutch Lipid Clinic definition. Depending on which clinical definition of FH was used, between 94.5% and 99.1% of patients with FH were discharged on statins and between 74.0% and 82.3% on high-dose statins. Patients with FH and ACS have a >2-fold adjusted risk of coronary event recurrence within the first year after discharge than patients without FH despite the widespread use of high-intensity statins. © 2016 American Heart Association, Inc.

Using Natural Language Processing to Improve Efficiency of Manual Chart Abstraction in Research: The Case of Breast Cancer Recurrence

PubMed Central

Carrell, David S.; Halgrim, Scott; Tran, Diem-Thy; Buist, Diana S. M.; Chubak, Jessica; Chapman, Wendy W.; Savova, Guergana

2014-01-01

The increasing availability of electronic health records (EHRs) creates opportunities for automated extraction of information from clinical text. We hypothesized that natural language processing (NLP) could substantially reduce the burden of manual abstraction in studies examining outcomes, like cancer recurrence, that are documented in unstructured clinical text, such as progress notes, radiology reports, and pathology reports. We developed an NLP-based system using open-source software to process electronic clinical notes from 1995 to 2012 for women with early-stage incident breast cancers to identify whether and when recurrences were diagnosed. We developed and evaluated the system using clinical notes from 1,472 patients receiving EHR-documented care in an integrated health care system in the Pacific Northwest. A separate study provided the patient-level reference standard for recurrence status and date. The NLP-based system correctly identified 92% of recurrences and estimated diagnosis dates within 30 days for 88% of these. Specificity was 96%. The NLP-based system overlooked 5 of 65 recurrences, 4 because electronic documents were unavailable. The NLP-based system identified 5 other recurrences incorrectly classified as nonrecurrent in the reference standard. If used in similar cohorts, NLP could reduce by 90% the number of EHR charts abstracted to identify confirmed breast cancer recurrence cases at a rate comparable to traditional abstraction. PMID:24488511

Recurrent Neural Network Applications for Astronomical Time Series

NASA Astrophysics Data System (ADS)

Protopapas, Pavlos

2017-06-01

The benefits of good predictive models in astronomy lie in early event prediction systems and effective resource allocation. Current time series methods applicable to regular time series have not evolved to generalize for irregular time series. In this talk, I will describe two Recurrent Neural Network methods, Long Short-Term Memory (LSTM) and Echo State Networks (ESNs) for predicting irregular time series. Feature engineering along with a non-linear modeling proved to be an effective predictor. For noisy time series, the prediction is improved by training the network on error realizations using the error estimates from astronomical light curves. In addition to this, we propose a new neural network architecture to remove correlation from the residuals in order to improve prediction and compensate for the noisy data. Finally, I show how to set hyperparameters for a stable and performant solution correctly. In this work, we circumvent this obstacle by optimizing ESN hyperparameters using Bayesian optimization with Gaussian Process priors. This automates the tuning procedure, enabling users to employ the power of RNN without needing an in-depth understanding of the tuning procedure.

Glioblastoma adaptation traced through decline of an IDH1 clonal driver and macro-evolution of a double-minute chromosome.

PubMed

Favero, F; McGranahan, N; Salm, M; Birkbak, N J; Sanborn, J Z; Benz, S C; Becq, J; Peden, J F; Kingsbury, Z; Grocok, R J; Humphray, S; Bentley, D; Spencer-Dene, B; Gutteridge, A; Brada, M; Roger, S; Dietrich, P-Y; Forshew, T; Gerlinger, M; Rowan, A; Stamp, G; Eklund, A C; Szallasi, Z; Swanton, C

2015-05-01

Glioblastoma (GBM) is the most common malignant brain cancer occurring in adults, and is associated with dismal outcome and few therapeutic options. GBM has been shown to predominantly disrupt three core pathways through somatic aberrations, rendering it ideal for precision medicine approaches. We describe a 35-year-old female patient with recurrent GBM following surgical removal of the primary tumour, adjuvant treatment with temozolomide and a 3-year disease-free period. Rapid whole-genome sequencing (WGS) of three separate tumour regions at recurrence was carried out and interpreted relative to WGS of two regions of the primary tumour. We found extensive mutational and copy-number heterogeneity within the primary tumour. We identified a TP53 mutation and two focal amplifications involving PDGFRA, KIT and CDK4, on chromosomes 4 and 12. A clonal IDH1 R132H mutation in the primary, a known GBM driver event, was detectable at only very low frequency in the recurrent tumour. After sub-clonal diversification, evidence was found for a whole-genome doubling event and a translocation between the amplified regions of PDGFRA, KIT and CDK4, encoded within a double-minute chromosome also incorporating miR26a-2. The WGS analysis uncovered progressive evolution of the double-minute chromosome converging on the KIT/PDGFRA/PI3K/mTOR axis, superseding the IDH1 mutation in dominance in a mutually exclusive manner at recurrence, consequently the patient was treated with imatinib. Despite rapid sequencing and cancer genome-guided therapy against amplified oncogenes, the disease progressed, and the patient died shortly after. This case sheds light on the dynamic evolution of a GBM tumour, defining the origins of the lethal sub-clone, the macro-evolutionary genomic events dominating the disease at recurrence and the loss of a clonal driver. Even in the era of rapid WGS analysis, cases such as this illustrate the significant hurdles for precision medicine success. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology.

Hypouricemic and arthritis relapse-reducing effects of compound tufuling oral-liquid in intercritical and chronic gout

PubMed Central

Xie, Zhijun; Wu, Huaxiang; Jing, Xiaoqing; Li, Xiuyang; Li, Yasong; Han, Yongmei; Gao, Xiangfu; Tang, Xiaopo; Sun, Jing; Fan, Yongshen; Wen, Chengping

2017-01-01

Abstract Trial Design: In the double-blind, randomized, controlled trial, we aimed to evaluate the effects of compound tufuling oral liquid (CoTOL) on serum uric acid (sUA) levels and recurrence of acute gouty arthritis in intercritical and chronic gout treatment. Methods: A total of 210 patients with gout were screened from 8 hospitals to observe the sUA and acute gouty arthritis recurrence rate-reducing effects of CoTOL in intercritical and chronic gout during a 12-week treatment. We treated 139 and 71 patients with CoTOL and the placebo, respectively, and evaluated their sUA levels, acute gouty arthritis recurrence rate, and adverse events at week 0, 6, and 12. Results: Twenty-five and 12 patients in the treatment and control groups, respectively, had interrupted treatments, whereas 114 and 59 cases, respectively, completed their treatments. At the end of the 12-week treatment, the average decrease in sUA was 74.26 (95% confidence interval [CI]: 56.74–91.77 μmol/L) and 28.81 μmol/L (95% CI: 4.91–52.71 μmol/L) in the treatment and control groups, respectively (P = 0.004). The average decrease rate of sUA was 12.76% (95% CI: 9.82%–15.70%) and 4.57% (95% CI: 0.42%–8.71%) in the treatment and control groups, respectively (P = 0.004), and the gouty arthritis recurrence rate of the treatment group was lower than that of the control group (from week 6 to 12, 21.93% and 50.88% in the treatment and control group, respectively, P < 0.001; from baseline to week 12, 38.5% and 63.16%, respectively, P = 0.003). Severe adverse events were not observed in either groups, and fewer leucopenia incidences were observed in the treatment group than those in the control group (3/139 vs. 7/71, respectively, P = 0.033). Conclusion: CoTOL reduced sUA levels and effectively prevented acute arthritis recurrence in intercritical and chronic gout without serious adverse events. PMID:28296744

Statistical Frequency-Dependent Analysis of Trial-to-Trial Variability in Single Time Series by Recurrence Plots.

PubMed

Tošić, Tamara; Sellers, Kristin K; Fröhlich, Flavio; Fedotenkova, Mariia; Beim Graben, Peter; Hutt, Axel

2015-01-01

For decades, research in neuroscience has supported the hypothesis that brain dynamics exhibits recurrent metastable states connected by transients, which together encode fundamental neural information processing. To understand the system's dynamics it is important to detect such recurrence domains, but it is challenging to extract them from experimental neuroscience datasets due to the large trial-to-trial variability. The proposed methodology extracts recurrent metastable states in univariate time series by transforming datasets into their time-frequency representations and computing recurrence plots based on instantaneous spectral power values in various frequency bands. Additionally, a new statistical inference analysis compares different trial recurrence plots with corresponding surrogates to obtain statistically significant recurrent structures. This combination of methods is validated by applying it to two artificial datasets. In a final study of visually-evoked Local Field Potentials in partially anesthetized ferrets, the methodology is able to reveal recurrence structures of neural responses with trial-to-trial variability. Focusing on different frequency bands, the δ-band activity is much less recurrent than α-band activity. Moreover, α-activity is susceptible to pre-stimuli, while δ-activity is much less sensitive to pre-stimuli. This difference in recurrence structures in different frequency bands indicates diverse underlying information processing steps in the brain.

Statistical Frequency-Dependent Analysis of Trial-to-Trial Variability in Single Time Series by Recurrence Plots

PubMed Central

Tošić, Tamara; Sellers, Kristin K.; Fröhlich, Flavio; Fedotenkova, Mariia; beim Graben, Peter; Hutt, Axel

2016-01-01

For decades, research in neuroscience has supported the hypothesis that brain dynamics exhibits recurrent metastable states connected by transients, which together encode fundamental neural information processing. To understand the system's dynamics it is important to detect such recurrence domains, but it is challenging to extract them from experimental neuroscience datasets due to the large trial-to-trial variability. The proposed methodology extracts recurrent metastable states in univariate time series by transforming datasets into their time-frequency representations and computing recurrence plots based on instantaneous spectral power values in various frequency bands. Additionally, a new statistical inference analysis compares different trial recurrence plots with corresponding surrogates to obtain statistically significant recurrent structures. This combination of methods is validated by applying it to two artificial datasets. In a final study of visually-evoked Local Field Potentials in partially anesthetized ferrets, the methodology is able to reveal recurrence structures of neural responses with trial-to-trial variability. Focusing on different frequency bands, the δ-band activity is much less recurrent than α-band activity. Moreover, α-activity is susceptible to pre-stimuli, while δ-activity is much less sensitive to pre-stimuli. This difference in recurrence structures in different frequency bands indicates diverse underlying information processing steps in the brain. PMID:26834580

Life Events: A Complex Role In The Timing Of Suicidal Behavior Among Depressed Patients

PubMed Central

Oquendo, Maria A.; Perez-Rodriguez, M. Mercedes; Poh, Ernest; Sullivan, Gregory; Burke, Ainsley K.; Sublette, M. Elizabeth; Mann, J. John; Galfalvy, Hanga

2013-01-01

Suicidal behavior is often conceptualized as a response to overwhelming stress. Our model posits that given a propensity for acting on suicidal urges, stressors such as life events or major depressive episodes (MDEs) determine the timing of suicidal acts. Depressed patients (n=415) were assessed prospectively for suicide attempts and suicide, life events and MDE over 2 years. Longitudinal data was divided into 1-month intervals characterized by MDE (yes/no), suicidal behavior (yes/no), and life event scores. Marginal logistic regression models were fit, with suicidal behavior as the response variable and MDE and life event score in either the same or previous month, respectively, as time-varying covariates. Among 7843 person-months, 33% had MDE and 73% had life events. MDE increased risk for suicidal behavior (OR=4.83, p< 0.0001). Life event scores were unrelated to the timing of suicidal behavior (OR=1.06 per 100 point increase, p=0.32), even during an MDE (OR=1.12, p=0.15). However, among those without Borderline Personality Disorders (BPD), both health and work related life events were key precipitants, as was recurrent MDE, with a 13-fold effect. The relationship of life events to suicidal behavior among those with BPD was more complex. Recurrent MDE was a robust precipitant for suicidal behavior, regardless of BPD comorbidity. The specific nature of life events is key to understanding the timing of suicidal behavior. Given unanticipated results regarding the role of BPD and study limitations, these findings require replication. Of note, that MDE, a treatable risk factor, strongly predicts suicidal behaviors is cause for hope. PMID:24126928

Recurrent viral liver disease (hepatitis B and C) after liver transplantation.

PubMed

Olivera-Martínez, Marco Antonio; Gallegos-Orozco, Juan F

2007-08-01

Hepatitis C represents more than 35% of liver transplant candidates worldwide. Meanwhile, hepatitis B continues to be an important cause of end-stage liver disease and hepatocellular carcinoma in Asia and Africa. Recurrent viral liver disease is a significant event after liver transplantation and continues to be one of the main causes of graft dysfunction and loss in the middle and long-term follow-up. Mechanisms of liver reinfection and disease recurrence vary between these two viruses and pre-emptive as well as the therapeutic approaches are different. Hepatitis B patients can be managed with immune globulin immediately after liver transplant and various agents such as nucleotide and nucleoside analogues can be associated. As a result, disease recurrence has been delayed or prevented in these patients. Individuals transplanted for hepatitis C are known to have universal reinfection and a high rate of disease recurrence has been reported in the literature. Strategies to treat hepatitis C recurrence are limited to the use of pegylated interferon and ribavirin when disease is demonstrated histologically and biochemically, although other strategies have been described with limited or no success. We herein review the mechanisms of disease recurrence and the current as well as the future therapeutic approaches to prevent and to treat these diseases.

Surgery and proton pump inhibitors for treatment of vocal process granulomas.

PubMed

Hong-Gang, Duan; He-Juan, Jin; Chun-Quan, Zheng; Guo-Kang, Fan

2013-11-01

The aim of this study was to analyze the outcomes of vocal process granulomas treated with surgery and proton pump inhibitors and to specify related factors of recurrence. The medical records of patients with diagnosis of vocal process granuloma between 2000 and 2012 were reviewed. All patients were treated with surgery and proton pump inhibitors for at least 1 month. Forty-one patients were reviewed; mean follow-up time was 45 months. There was no recurrence among the patients who had a recent history of intubation. The recurrence rates of contact granuloma was 38.7 %, and significantly related to the frequency of surgery (P = 0.042), but was not significantly associated with the history of acid reflux (P = 0.676) and vocal abuse (P = 0.447), lesion size (P = 0.203) or surgical techniques (P = 0.331). Surgery combined with proton pump inhibitors was partially effective for the vocal process granulomas, especially with intubated patients. However, repeat surgery for recurrent contact granuloma should be preceded with caution due to high recurrence rates.

Forest operations, extreme flooding events, and considerations for hydrologic modeling in the Appalachians--A review

Treesearch

M.A. Eisenbies; W.M. Aust; J.A. Burger; M.B. Adams

2007-01-01

The connection between forests and water resources is well established, but the relationships among controlling factors are only partly understood. Concern over the effects of forestry operations, particularly harvesting, on extreme flooding events is a recurrent issue in forest and watershed management. Due to the complexity of the system, and the cost of installing...

Rate of duodenal-biliary reflux increases in patients with recurrent common bile duct stones: evidence from barium meal examination.

PubMed

Zhang, Rongchun; Luo, Hui; Pan, Yanglin; Zhao, Lina; Dong, Junqiang; Liu, Zhiguo; Wang, Xiangping; Tao, Qin; Lu, Guohua; Guo, Xuegang

2015-10-01

Stone recurrence is a common late adverse event after ERCP in patients with common bile duct stones (CBDS). Duodenal-biliary reflux (DBR) is considered a major cause of CBDS recurrence. However, specific evidence is still lacking. To investigate the DBR rate in patients with recurrent CBDS after ERCP. A prospective case-control study. A tertiary center. During follow-up, patients with a history of either recurrent CBDS (recurrence group) or nonrecurrent CBDS (control group) were invited to participate in the study. All patients had previously undergone successful CBDS removal by ERCP. Patients in the control group were matched with the recurrence group by age and gender in a 1:1 ratio. Patients with gallbladder stones, hepatolithiasis, remnant CBDS, CBD strictures, or stents were excluded. Standard barium meal examination, MRCP, and enhanced abdominal CT. DBR. Thirty-two patients with a history of recurrent CBDS and 32 matched control subjects were enrolled. Baseline characteristics and parameters regarding the first ERCP were comparable between the 2 groups. The DBR rate was significantly higher in the recurrent than in the control group (68.8% vs 15.6%, P < .001). Multivariate analysis indicated that DBR (OR, 9.59; 95% CI, 2.65-34.76) and acute distal CBD angulation (OR, 5.48; 95% CI, 1.52-19.78) were independent factors associated with CBDS recurrence. DBR rates in patients with no, single, or multiple recurrences were 15.6%, 60.9%, and 88.9%, respectively (P < .001). Intrahepatic bile duct reflux was more common in patients with multiple recurrences. Small sample size. DBR is correlated with CBDS recurrence in patients who had previously undergone ERCP. DBR and acute distal CBD angulation are 2 independent risk factors related to stone recurrence. ( NCT02329977.) Copyright © 2015 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

Genetic risk, coronary heart disease events, and the clinical benefit of statin therapy: an analysis of primary and secondary prevention trials.

PubMed

Mega, J L; Stitziel, N O; Smith, J G; Chasman, D I; Caulfield, M; Devlin, J J; Nordio, F; Hyde, C; Cannon, C P; Sacks, F; Poulter, N; Sever, P; Ridker, P M; Braunwald, E; Melander, O; Kathiresan, S; Sabatine, M S

2015-06-06

Genetic variants have been associated with the risk of coronary heart disease. In this study, we tested whether or not a composite of these variants could ascertain the risk of both incident and recurrent coronary heart disease events and identify those individuals who derive greater clinical benefit from statin therapy. A community-based cohort study (the Malmo Diet and Cancer Study) and four randomised controlled trials of both primary prevention (JUPITER and ASCOT) and secondary prevention (CARE and PROVE IT-TIMI 22) with statin therapy, comprising a total of 48,421 individuals and 3477 events, were included in these analyses. We studied the association of a genetic risk score based on 27 genetic variants with incident or recurrent coronary heart disease, adjusting for traditional clinical risk factors. We then investigated the relative and absolute risk reductions in coronary heart disease events with statin therapy stratified by genetic risk. We combined data from the different studies using a meta-analysis. When individuals were divided into low (quintile 1), intermediate (quintiles 2-4), and high (quintile 5) genetic risk categories, a significant gradient in risk for incident or recurrent coronary heart disease was shown. Compared with the low genetic risk category, the multivariable-adjusted hazard ratio for coronary heart disease for the intermediate genetic risk category was 1·34 (95% CI 1·22-1·47, p<0·0001) and that for the high genetic risk category was 1·72 (1·55-1·92, p<0·0001). In terms of the benefit of statin therapy in the four randomised trials, we noted a significant gradient (p=0·0277) of increasing relative risk reductions across the low (13%), intermediate (29%), and high (48%) genetic risk categories. Similarly, we noted greater absolute risk reductions in those individuals in higher genetic risk categories (p=0·0101), resulting in a roughly threefold decrease in the number needed to treat to prevent one coronary heart disease event in the primary prevention trials. Specifically, in the primary prevention trials, the number needed to treat to prevent one such event in 10 years was 66 in people at low genetic risk, 42 in those at intermediate genetic risk, and 25 in those at high genetic risk in JUPITER, and 57, 47, and 20, respectively, in ASCOT. A genetic risk score identified individuals at increased risk for both incident and recurrent coronary heart disease events. People with the highest burden of genetic risk derived the largest relative and absolute clinical benefit from statin therapy. National Institutes of Health. Copyright © 2015 Elsevier Ltd. All rights reserved.

Wrightwood and the earthquake cycle: What a long recurrence record tells us about how faults work

USGS Publications Warehouse

Weldon, R.; Scharer, K.; Fumal, T.; Biasi, G.

2004-01-01

The concept of the earthquake cycle is so well established that one often hears statements in the popular media like, "the Big One is overdue" and "the longer it waits, the bigger it will be." Surprisingly, data to critically test the variability in recurrence intervals, rupture displacements, and relationships between the two are almost nonexistent. To generate a long series of earthquake intervals and offsets, we have conducted paleoseismic investigations across the San Andreas fault near the town of Wrightwood, California, excavating 45 trenches over 18 years, and can now provide some answers to basic questions about recurrence behavior of large earthquakes. To date, we have characterized at least 30 prehistoric earthquakes in a 6000-yr-long record, complete for the past 1500 yr and for the interval 3000-1500 B.C. For the past 1500 yr, the mean recurrence interval is 105 yr (31-165 yr for individual intervals) and the mean slip is 3.2 m (0.7-7 m per event). The series is slightly more ordered than random and has a notable cluster of events, during which strain was released at 3 times the long-term average rate. Slip associated with an earthquake is not well predicted by the interval preceding it, and only the largest two earthquakes appear to affect the time interval to the next earthquake. Generally, short intervals tend to coincide with large displacements and long intervals with small displacements. The most significant correlation we find is that earthquakes are more frequent following periods of net strain accumulation spanning multiple seismic cycles. The extent of paleoearthquake ruptures may be inferred by correlating event ages between different sites along the San Andreas fault. Wrightwood and other nearby sites experience rupture that could be attributed to overlap of relatively independent segments that each behave in a more regular manner. However, the data are equally consistent with a model in which the irregular behavior seen at Wrightwood typifies the entire southern San Andreas fault; more long event series will be required to definitively outline prehistoric rupture extents.

The fundamental importance of smoking cessation in those with premature ST-segment elevation acute myocardial infarction.

PubMed

Rallidis, Loukianos S; Pavlakis, George

2016-09-01

Smoking is the most prevalent risk factor among young patients suffering acute myocardial infarction (AMI). In this review, we will present data on the detrimental consequences of continued smoking with regard to the recurrence of coronary events after an AMI at an early age. A prospective study with long-term follow-up of young survivors of AMI showed that continuation of smoking after a first episode of AMI was the strongest independent predictor of further cardiac events. In particular, persistent smokers had ∼2.5 times higher risk of a new coronary event when compared with nonsmokers. This emphasizes the fundamental importance of initiating smoking cessation treatment in all smokers with AMI during hospitalization. Extrapolating the results of previous studies showing the benefits of smoking cessation in middle-aged or elderly coronary patients, an even greater benefit should be expected in young patients because of their specific characteristics, which are presented in the current review. Young persistent smokers after a premature AMI constitute a high-risk subgroup for a recurrence of cardiac events. Therefore, smoking cessation is a key issue for improving their prognosis and all smokers should be offered effective antismoking treatment at the time of initial hospitalization.

Uranium/Thorium Dating and Growth Laminae Counting of Stalagmites Reveal a Record of Major Earthquakes in the Midwestern US

NASA Astrophysics Data System (ADS)

Zhang, Z.; Lundstrom, C.; Panno, S.; Hackley, K. C.; Fouke, B. W.; Curry, B.

2009-12-01

The recurrence interval of large New Madrid Seismic Zone (NMSZ) earthquakes is uncertain because of the limited number and likely incomplete nature of the record of dated seismic events. Data on paleoseismicity in this area is necessary for refining estimates of a recurrence interval for these earthquakes and for characterizing the geophysical nature of the NMSZ. Studies of the paleoseismic history of the NMSZ have previously used liquefaction features and flood plain deposits along the Mississippi River to estimate recurrence interval with considerable uncertainties. More precise estimates of the number and ages of paleoseismic events would enhance the ability of federal, state, and local agencies to make critical preparedness decisions. Initiation of new speleothems (cave deposits) has been shown in several localities to record large earthquake events. Our ongoing work in caves of southwestern Illinois, Missouri, Indiana and Arkansas has used both U/Th age dating techniques and growth laminae counting of actively growing stalagmites to determine the age of initiation of stalagmites in caves across the Midwestern U.S. These age initiations cluster around two known events, the great NMSZ earthquakes of 1811-1812 and the Missouri earthquake of 1917, suggesting that cave deposits in this region constitute a unique record of paleo-seismic history of the NMSZ. Furthermore, the U-Th disequilibria growth laminae ages of young, white stalagmites and of older stalagmites on which they grew, plus published Holocene stalagmite ages of initiation and regrowth from Missouri caves, are all coincident with suspected NMSZ earthquakes based on liquefaction and other paleoseimic techniques. We hypothesize that these speleothems were initiated by earthquake-induced opening/closing of fracture-controlled flowpaths in the ceilings of cave passages.

Effectiveness of Conservation Measures in Reducing Runoff and Soil Loss Under Different Magnitude-Frequency Storms at Plot and Catchment Scales in the Semi-arid Agricultural Landscape.

PubMed

Zhu, T X

2016-03-01

In this study, multi-year stormflow data collected at both catchment and plot scales on an event basis were used to evaluate the efficiency of conservation. At the catchment scale, soil loss from YDG, an agricultural catchment with no conservation measures, was compared with that from CZG, an agricultural catchment with an implementation of a range of conservation measures. With an increase of storm recurrence intervals in the order of <1, 1-2, 2-5, 5-10, 10-20, and >20 years, the mean event sediment yield was 639, 1721, 5779, 15191, 19627, and 47924 t/km(2) in YDG, and was 244, 767, 3077, 4679, 8388, and 15868 t/km(2) in CZG, which represented a reduction effectiveness of 61.8, 55.4, 46.7, 69.2, 57.2, and 66.8 %, respectively. Storm events with recurrence intervals greater than 2 years contributed about two-thirds of the total runoff and sediment in both YDG and CZG catchments. At the plot scale, soil loss from one cultivated slopeland was compared with that from five conservation plots. The mean event soil loss was 1622 t/km(2) on the cultivated slopeland, in comparison to 27.7 t/km(2) on the woodland plot, 213 t/km(2) on the grassland plot, 467 t/km(2) on the alfalfa plot, 236 t/km(2) on the terraceland plot, and 642 t/km(2) on the earthbank plot. Soil loss per unit area from all the plots was significantly less than that from the catchments for storms of all categories of recurrence intervals.

Association of Lp-PLA2-A and early recurrence of vascular events after TIA and minor stroke.

PubMed

Lin, Jinxi; Zheng, Hongwei; Cucchiara, Brett L; Li, Jiejie; Zhao, Xingquan; Liang, Xianhong; Wang, Chunxue; Li, Hao; Mullen, Michael T; Johnston, S Claiborne; Wang, Yilong; Wang, Yongjun

2015-11-03

To determine the association of lipoprotein-associated phospholipase A2 (Lp-PLA2) measured in the acute period and the short-term risk of recurrent vascular events in patients with TIA or minor stroke. We measured Lp-PLA2 activity (Lp-PLA2-A) in a subset of 3,201 participants enrolled in the CHANCE (Clopidogrel in High-Risk Patients with Acute Non-disabling Cerebrovascular Events) trial. Participants with TIA or minor stroke were enrolled within 24 hours of symptom onset and randomized to single or dual antiplatelet therapy. In the current analysis, the primary outcome was defined as the composite of ischemic stroke, myocardial infarction, or death within 90 days. The composite endpoint occurred in 299 of 3,021 participants (9.9%). The population average Lp-PLA2-A level was 209 ± 59 nmol/min/mL (95% confidence interval [CI] 207-211). Older age, male sex, and current smoking were associated with higher Lp-PLA2-A levels. Lp-PLA2-A was significantly associated with the primary endpoint (adjusted hazard ratio 1.07, 95% CI 1.01-1.13 for every 30 nmol/min/mL increase). Similar results were seen for ischemic stroke alone. Adjustment for low-density lipoprotein cholesterol attenuated the association between Lp-PLA2-A and the primary endpoint (adjusted hazard ratio 1.04, 95% CI 0.97-1.11 for every 30 nmol/min/mL increase). Higher levels of Lp-PLA2-A in the acute period are associated with increased short-term risk of recurrent vascular events. © 2015 American Academy of Neurology.

Closure versus medical therapy for preventing recurrent stroke in patients with patent foramen ovale and a history of cryptogenic stroke or transient ischemic attack.

PubMed

Li, Jie; Liu, Junfeng; Liu, Ming; Zhang, Shihong; Hao, Zilong; Zhang, Jing; Zhang, Canfei

2015-09-08

The optimal therapy for preventing recurrent stroke in people with cryptogenic stroke and patent foramen ovale (PFO) has not been defined. The choice between medical therapy (antithrombotic treatment with antiplatelet agents or anticoagulants) and transcatheter device closure has been the subject of intense debate over the past several years. Despite the lack of scientific evidence, a substantial number of people undergo transcatheter device closure (TDC) for secondary stroke prevention. To: 1) compare the safety and efficacy of TDC with best medical therapy alone for preventing recurrent stroke (fatal or non-fatal) or transient ischemic attacks (TIAs) in people with PFO and a history of cryptogenic stroke or TIA; 2) identify specific subgroups of people most likely to benefit from closure for secondary prevention; and 3) assess the cost-effectiveness of this strategy, if possible. We searched the Cochrane Stroke Group Trials Register (July 2014), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 2, 2014), MEDLINE (1950 to July 2014) and EMBASE (1980 to July 2014). In an effort to identify unpublished and ongoing trials we searched seven trials registers and checked reference lists. We included randomized controlled trials (RCTs), irrespective of blinding, publication status, and language, comparing the safety and efficacy of device closure with medical therapy for preventing recurrent stroke or TIA in people with PFO and a history of cryptogenic stroke or TIA. Two review authors independently selected trials for inclusion, assessed quality and risk of bias, and extracted data. The primary outcome measures of this analysis were the composite endpoint of ischemic stroke or TIA events as well as recurrent fatal or non-fatal ischemic stroke. Secondary endpoints included all-cause mortality, serious adverse events (atrial fibrillation, myocardial infarction, bleeding) and procedural success and effective closure. We used the Mantel-Haenszel method to obtain pooled risk ratios (RRs) using the random-effects model regardless of the level of heterogeneity. We pooled data for the primary outcome measure with the generic inverse variance method using the random-effects model, yielding risk estimates as pooled hazard ratio (HR), which accounts for time-to-event outcomes. We included three RCTs involving a total of 2303 participants: 1150 participants were randomized to receive TDC and 1153 participants were randomized to receive medical therapy. Overall, the risk of bias was regarded as high. The mean follow-up period of all three included trials was less than five years. Baseline characteristics (age, sex, and vascular risk factors) were similar across trials. Intention-to-treat analyses did not show a statistically significant risk reduction in the composite endpoint of recurrent stroke or TIA in the TDC group when compared with medical therapy (RR 0.73, 95% CI 0.45 to 1.17). A time-to-event analysis combining the results of two RCTs also failed to show a significant risk reduction with TDC (HR 0.69, 95% CI 0.43 to 1.13). When assessing stroke prevention alone, TDC still did not show a statistically significant benefit (RR 0.61, 95% CI 0.29 to 1.27) (HR 0.55, 95% CI 0.26 to 1.18). In a sensitivity analysis including the two studies using the Amplatzer PFO occluder, TDC showed a possible protective effect on recurrent stroke compared with medical therapy (HR 0.38, 95% CI 0.14 to 1.02); however, it did not reach statistical significance. Safety analysis found that the overall risks for all-cause mortality and adverse events were similar in both the TDC and medical therapy groups. However, TDC increased the risk of new-onset atrial fibrillation (RR 3.50, 95% CI 1.47 to 8.35) and may be associated with the type of device used. The combined data from recent RCTs have shown no statistically significant differences between TDC and medical therapy in the prevention of recurrent ischemic stroke. TDC closure was associated with an increased risk of atrial fibrillation but not with serious adverse events.

Validation study of genes with hypermethylated promoter regions associated with prostate cancer recurrence

PubMed Central

Stott-Miller, Marni; Zhao, Shanshan; Wright, Jonathan L.; Kolb, Suzanne; Bibikova, Marina; Klotzle, Brandy; Ostrander, Elaine A.; Fan, Jian-Bing; Feng, Ziding; Stanford, Janet L.

2014-01-01

Background One challenge in prostate cancer (PCa) is distinguishing indolent from aggressive disease at diagnosis. DNA promoter hypermethylation is a frequent epigenetic event in PCa, but few studies of DNA methylation in relation to features of more aggressive tumors or PCa recurrence have been completed. Methods We used the Infinium® HumanMethylation450 BeadChip to assess DNA methylation in tumor tissue from 407 patients with clinically localized PCa who underwent radical prostatectomy. Recurrence status was determined by follow-up patient surveys, medical record review, and linkage with the SEER registry. The methylation status of 14 genes for which promoter hypermethylation was previously correlated with advanced disease or biochemical recurrence was evaluated. Average methylation level for promoter region CpGs in patients who recurred compared to those with no evidence of recurrence was analyzed. For two genes with differential methylation, time to recurrence was examined. Results During an average follow-up of 11.7 years, 104 (26%) patients recurred. Significant promoter hypermethylation in at least 50% of CpG sites in two genes, ABHD9 and HOXD3, was found in tumors from patients who recurred compared to those without recurrence. Evidence was strongest for HOXD3 (lowest P = 9.46x10−6), with higher average methylation across promoter region CpGs associated with reduced recurrence-free survival (P = 2×10−4). DNA methylation profiles did not differ by recurrence status for the other genes. Conclusions These results validate the association between promoter hypermethylation of ADHB9 and HOXD3 and PCa recurrence. Impact Tumor DNA methylation profiling may help distinguish PCa patients at higher risk for disease recurrence. PMID:24718283

Earthquake Clustering on Normal Faults: Insight from Rate-and-State Friction Models

NASA Astrophysics Data System (ADS)

Biemiller, J.; Lavier, L. L.; Wallace, L.

2016-12-01

Temporal variations in slip rate on normal faults have been recognized in Hawaii and the Basin and Range. The recurrence intervals of these slip transients range from 2 years on the flanks of Kilauea, Hawaii to 10 kyr timescale earthquake clustering on the Wasatch Fault in the eastern Basin and Range. In addition to these longer recurrence transients in the Basin and Range, recent GPS results there also suggest elevated deformation rate events with recurrence intervals of 2-4 years. These observations suggest that some active normal fault systems are dominated by slip behaviors that fall between the end-members of steady aseismic creep and periodic, purely elastic, seismic-cycle deformation. Recent studies propose that 200 year to 50 kyr timescale supercycles may control the magnitude, timing, and frequency of seismic-cycle earthquakes in subduction zones, where aseismic slip transients are known to play an important role in total deformation. Seismic cycle deformation of normal faults may be similarly influenced by its timing within long-period supercycles. We present numerical models (based on rate-and-state friction) of normal faults such as the Wasatch Fault showing that realistic rate-and-state parameter distributions along an extensional fault zone can give rise to earthquake clusters separated by 500 yr - 5 kyr periods of aseismic slip transients on some portions of the fault. The recurrence intervals of events within each earthquake cluster range from 200 to 400 years. Our results support the importance of stress and strain history as controls on a normal fault's present and future slip behavior and on the characteristics of its current seismic cycle. These models suggest that long- to medium-term fault slip history may influence the temporal distribution, recurrence interval, and earthquake magnitudes for a given normal fault segment.

Recurrent Ischemic Lesions After Acute Atherothrombotic Stroke: Clopidogrel Plus Aspirin Versus Aspirin Alone.

PubMed

Hong, Keun-Sik; Lee, Seung-Hoon; Kim, Eung Gyu; Cho, Ki-Hyun; Chang, Dae Il; Rha, Joung-Ho; Bae, Hee-Joon; Lee, Kyung Bok; Kim, Dong Eog; Park, Jong-Moo; Kim, Hahn-Young; Cha, Jae-Kwan; Yu, Kyung-Ho; Lee, Yong-Seok; Lee, Soo Joo; Choi, Jay Chol; Cho, Yong-Jin; Kwon, Sun U; Kim, Gyeong-Moon; Sohn, Sung-Il; Park, Kwang-Yeol; Kang, Dong-Wha; Sohn, Chul-Ho; Lee, Jun; Yoon, Byung-Woo

2016-09-01

In patients with acute ischemic stroke caused by large artery atherosclerosis, clopidogrel plus aspirin versus aspirin alone might be more effective to prevent recurrent cerebral ischemia. However, there is no clear evidence. In this multicenter, double-blind, placebo-controlled trial, we randomized 358 patients with acute ischemic stroke of presumed large artery atherosclerosis origin within 48 hours of onset to clopidogrel (75 mg/d without loading dose) plus aspirin (300-mg loading followed by 100 mg/d) or to aspirin alone (300-mg loading followed by 100 mg/d) for 30 days. The primary outcome was new symptomatic or asymptomatic ischemic lesion on magnetic resonance imaging within 30 days. Secondary outcomes were 30-day functional disability, clinical stroke recurrence, and composite of major vascular events. Safety outcome was any bleeding. Of 358 patients enrolled, 334 (167 in each group) completed follow-up magnetic resonance imaging. The 30-day new ischemic lesion recurrence rate was comparable between the clopidogrel plus aspirin and the aspirin monotherapy groups (36.5% versus 35.9%; relative risk, 1.02; 95% confidence interval, 0.77-1.35; P=0.91). Of the recurrent ischemic lesions, 94.2% were clinically asymptomatic. There were no differences in secondary outcomes between the 2 groups. Any bleeding were more frequent in the combination group than in the aspirin monotherapy group, but the difference was not significant (16.7% versus 10.7%; P=0.11). One hemorrhagic stroke occurred in the clopidogrel plus aspirin group. Clopidogrel plus aspirin might not be superior to aspirin alone for preventing new ischemic lesion and clinical vascular events in patients with acute ischemic stroke caused by large artery atherosclerosis. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00814268. © 2016 American Heart Association, Inc.

A New Insight into the Earthquake Recurrence Studies from the Three-parameter Generalized Exponential Distributions

NASA Astrophysics Data System (ADS)

Pasari, S.; Kundu, D.; Dikshit, O.

2012-12-01

Earthquake recurrence interval is one of the important ingredients towards probabilistic seismic hazard assessment (PSHA) for any location. Exponential, gamma, Weibull and lognormal distributions are quite established probability models in this recurrence interval estimation. However, they have certain shortcomings too. Thus, it is imperative to search for some alternative sophisticated distributions. In this paper, we introduce a three-parameter (location, scale and shape) exponentiated exponential distribution and investigate the scope of this distribution as an alternative of the afore-mentioned distributions in earthquake recurrence studies. This distribution is a particular member of the exponentiated Weibull distribution. Despite of its complicated form, it is widely accepted in medical and biological applications. Furthermore, it shares many physical properties with gamma and Weibull family. Unlike gamma distribution, the hazard function of generalized exponential distribution can be easily computed even if the shape parameter is not an integer. To contemplate the plausibility of this model, a complete and homogeneous earthquake catalogue of 20 events (M ≥ 7.0) spanning for the period 1846 to 1995 from North-East Himalayan region (20-32 deg N and 87-100 deg E) has been used. The model parameters are estimated using maximum likelihood estimator (MLE) and method of moment estimator (MOME). No geological or geophysical evidences have been considered in this calculation. The estimated conditional probability reaches quite high after about a decade for an elapsed time of 17 years (i.e. 2012). Moreover, this study shows that the generalized exponential distribution fits the above data events more closely compared to the conventional models and hence it is tentatively concluded that generalized exponential distribution can be effectively considered in earthquake recurrence studies.

Efficacy of Antiarrhythmic Drugs Short-Term Use After Catheter Ablation for Atrial Fibrillation (EAST-AF) trial.

PubMed

Kaitani, Kazuaki; Inoue, Koichi; Kobori, Atsushi; Nakazawa, Yuko; Ozawa, Tomoya; Kurotobi, Toshiya; Morishima, Itsuro; Miura, Fumiharu; Watanabe, Tetsuya; Masuda, Masaharu; Naito, Masaki; Fujimoto, Hajime; Nishida, Taku; Furukawa, Yoshio; Shirayama, Takeshi; Tanaka, Mariko; Okajima, Katsunori; Yao, Takenori; Egami, Yasuyuki; Satomi, Kazuhiro; Noda, Takashi; Miyamoto, Koji; Haruna, Tetsuya; Kawaji, Tetsuma; Yoshizawa, Takashi; Toyota, Toshiaki; Yahata, Mitsuhiko; Nakai, Kentaro; Sugiyama, Hiroaki; Higashi, Yukei; Ito, Makoto; Horie, Minoru; Kusano, Kengo F; Shimizu, Wataru; Kamakura, Shiro; Morimoto, Takeshi; Kimura, Takeshi; Shizuta, Satoshi

2016-02-14

Substantial portion of early arrhythmia recurrence after catheter ablation for atrial fibrillation (AF) is considered to be due to irritability in left atrium (LA) from the ablation procedure. We sought to evaluate whether 90-day use of antiarrhythmic drug (AAD) following AF ablation could reduce the incidence of early arrhythmia recurrence and thereby promote reverse remodelling of LA, leading to improved long-term clinical outcomes. A total of 2038 patients who had undergone radiofrequency catheter ablation for paroxysmal, persistent, or long-lasting AF were randomly assigned to either 90-day use of Vaughan Williams class I or III AAD (1016 patients) or control (1022 patients) group. The primary endpoint was recurrent atrial tachyarrhythmias lasting for >30 s or those requiring repeat ablation, hospital admission, or usage of class I or III AAD at 1 year, following the treatment period of 90 days post ablation. Patients assigned to AAD were associated with significantly higher event-free rate from recurrent atrial tachyarrhythmias when compared with the control group during the treatment period of 90 days [59.0 and 52.1%, respectively; adjusted hazard ratio (HR) 0.84; 95% confidence interval (CI) 0.73-0.96; P = 0.01]. However, there was no significant difference in the 1-year event-free rates from the primary endpoint between the groups (69.5 and 67.8%, respectively; adjusted HR 0.93; 95% CI 0.79-1.09; P = 0.38). Short-term use of AAD for 90 days following AF ablation reduced the incidence of recurrent atrial tachyarrhythmias during the treatment period, but it did not lead to improved clinical outcomes at the later phase. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

Patent foramen ovale closure versus medical therapy after cryptogenic stroke: An updated meta-analysis of all randomized clinical trials.

PubMed

Kheiri, Babikir; Abdalla, Ahmed; Osman, Mohammed; Ahmed, Sahar; Hassan, Mustafa; Bachuwa, Ghassan

2018-03-07

Cryptogenic strokes can be attributed to paradoxical emboli through patent foramen ovale (PFO). However, the effectiveness of PFO closure in preventing recurrent stroke is uncertain and the results of previous randomized clinical trials (RCTs) have been inconclusive. Hence, this study provides an updated meta-analysis of all RCTs comparing PFO closure with medical therapy for secondary prevention of cryptogenic stroke. All RCTs were identified by a comprehensive literature search of PubMed, Embase, the Cochrane Collaboration Central Register of Controlled Trials, Scopus, and Clinicaltrials.gov. The primary outcome was recurrent ischemic stroke and secondary outcomes were transient ischemic attack (TIA), all-cause mortality, new-onset atrial fibrillation (AF), serious adverse events, and major bleeding. 5 RCTs with 3440 participants were included in the present study (1829 patients underwent PFO closure and 1611 were treated medically). Pooled analysis showed a statistically significant reduction in the rate of recurrent stroke with PFO closure in comparison to medical therapy (OR 0.41; 95% CI 0.19-0.90; p = 0.03). However, there were no statistically significant reductions of recurrent TIAs (OR 0.77; 95% CI 0.51-1.14; p = 0.19) or all-cause mortality (OR 0.76; 95% CI 0.35-1.65; p = 0.48). The risk of developing new-onset AF was increased significantly with PFO closure (OR 4.74; 95% CI 2.33-9.61; p < 0.0001), but no significant differences in terms of serious adverse events or major bleeding between both groups. Patent foramen ovale closure in adults with recent cryptogenic stroke was associated with a lower rate of recurrent strokes in comparison with medical therapy alone.

Posttraumatic stress disorder increases risk for suicide attempt in adults with recurrent major depression.

PubMed

Stevens, Daniel; Wilcox, Holly C; MacKinnon, Dean F; Mondimore, Francis M; Schweizer, Barbara; Jancic, Dunya; Coryell, William H; Weissman, Myrna M; Levinson, Douglas F; Potash, James B

2013-10-01

Genetics of Recurrent Early-Onset Depression study (GenRED II) data were used to examine the relationship between posttraumatic stress disorder (PTSD) and attempted suicide in a population of 1,433 individuals with recurrent early-onset major depressive disorder (MDD). We tested the hypothesis that PTSD resulting from assaultive trauma increases risk for attempted suicide among individuals with recurrent MDD. Data on lifetime trauma exposures and clinical symptoms were collected using the Diagnostic Interview for Genetic Studies version 3.0 and best estimate diagnoses of MDD, PTSD, and other DSM-IV Axis I disorders were reported with best estimated age of onset. The lifetime prevalence of suicide attempt in this sample was 28%. Lifetime PTSD was diagnosed in 205 (14.3%) participants. We used discrete time-survival analyses to take into account timing in the PTSD-suicide attempt relationship while adjusting for demographic variables (gender, race, age, and education level) and comorbid diagnoses prior to trauma exposure. PTSD was an independent predictor of subsequent suicide attempt (HR = 2.5, 95% CI: 1.6, 3.8; P < .0001). Neither assaultive nor nonassaultive trauma without PTSD significantly predicted subsequent suicide attempt after Bonferroni correction. The association between PTSD and subsequent suicide attempt was driven by traumatic events involving assaultive violence (HR = 1.7, 95% CI: 1.3, 2.2; P< .0001). Among those with recurrent MDD, PTSD appears to be a vulnerability marker of maladaptive responses to traumatic events and an independent risk factor for attempted suicide. Additional studies examining differences between those with and without PTSD on biological measures might shed light on this potential vulnerability. © 2013 Wiley Periodicals, Inc.

De novo Diagnosis of Fabry Disease among Italian Adults with Acute Ischemic Stroke or Transient Ischemic Attack.

PubMed

Romani, Ilaria; Borsini, Walter; Nencini, Patrizia; Morrone, Amelia; Ferri, Lorenzo; Frusconi, Sabrina; Donadio, Vincenzo Angelo; Liguori, Rocco; Donati, Maria Alice; Falconi, Serena; Pracucci, Giovanni; Inzitari, Domenico

2015-11-01

Cerebrovascular complications are often the first cause of hospitalization in patients with Fabry disease (FD). Screenings for FD among stroke patients have yielded discrepant results, likely as a result of heterogeneous or incomplete assessment. We designed a study to identify FD among adults 60 years of age or younger who were consecutively admitted for acute ischemic stroke or transient ischemic attack (TIA) to a stroke neurology service in Italy. Patients with first-ever or recurrent events were included, irrespective of gender, risk factors, or stroke type. We screened male patients using α-galactosidase A enzyme assay, and female patients using DNA sequencing. FD was eventually established after a broad multidisciplinary discussion. We screened 108 patients (61% males, median age: 48 years); 84% of these patients had stroke. De novo FD diagnosis was established in 3 patients (2.8%; 95% confidence interval, .57-8.18): a 59-year-old man with recurrent lacunar-like strokes and multiple risk factors; a 42-year-old woman with recurrent cryptogenic minor strokes; and a 32-year-old woman with recurrent strokes previously attributed to Behçet's disease. Screened patients were systematically asked for typical FD symptoms; each of the de novo patients reported one or more of the following: episodes of hand/foot pain during fever, angiokeratoma, and family history of heart disease. In all of the patients events were recurrent, and lacunar-like infarcts characterized their brain imaging. Prevalence of FD among nonselected adults 60 years of age or younger with acute ischemic stroke or TIA is not negligible. A systematic search for FD in a stroke setting, using a comprehensive clinical, biochemical, and genetic screening protocol, may be worthwhile. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Daptomycin Resistance in Clinical MRSA Strains Is Associated with a High Biological Fitness Cost

PubMed Central

Roch, Melanie; Gagetti, Paula; Davis, James; Ceriana, Paola; Errecalde, Laura; Corso, Alejandra; Rosato, Adriana E.

2017-01-01

Daptomycin remains as one of the main treatment options for Methicillin-Resistant Staphylococcus aureus (MRSA). Sporadic resistance cases reported in patients treated with either daptomycin or glycopeptides are a growing concern. In a previous study, we described a clinical case of a patient with a community-acquired MRSA infection resistant to daptomycin and with intermediate resistance to vancomycin who developed a recurrent infection with a susceptible isogenic strain. In the present work, we further investigated the sequential events to determine whether the switch from a daptomycin resistance to a susceptible phenotype was due to a phenomenon of resistance reversion or recurrent infection with a susceptible strain. Pairwise competition experiments showed that the susceptible clinical recurrent SA6850 strain had increased fitness when compared to the resistant counterpart SA6820 strain. In fact, although we have demonstrated that reversion of daptomycin resistance to daptomycin susceptible can occur in vitro after serial passages in drug-free media, phylogenetic analysis suggested that the in vivo process was the result of a recurrent infection with a previous susceptible isolate carried by the patient rather than a resistance reversion of the strain. Whole genome sequence of evolved strains showed that daptomycin resistance in MRSA is associated with a high fitness cost mediated by mutations in mprF gene, revealed as a key element of the biological cost. Moreover, we determined that daptomycin resistance-associated fitness cost was independent of vancomycin intermediate resistance phenotype, as demonstrated in additional clinical MRSA vancomycin susceptible strains. This study highlights important observations as, despite daptomycin offers a useful treatment option for the patients with persistent infections, it has to be carefully monitored. The high fitness cost associated to daptomycin resistance may explain the reduced dissemination of daptomycin resistance and the absence of daptomycin reported outbreaks. PMID:29259579

Daptomycin Resistance in Clinical MRSA Strains Is Associated with a High Biological Fitness Cost.

PubMed

Roch, Melanie; Gagetti, Paula; Davis, James; Ceriana, Paola; Errecalde, Laura; Corso, Alejandra; Rosato, Adriana E

2017-01-01

Daptomycin remains as one of the main treatment options for Methicillin-Resistant Staphylococcus aureus (MRSA). Sporadic resistance cases reported in patients treated with either daptomycin or glycopeptides are a growing concern. In a previous study, we described a clinical case of a patient with a community-acquired MRSA infection resistant to daptomycin and with intermediate resistance to vancomycin who developed a recurrent infection with a susceptible isogenic strain. In the present work, we further investigated the sequential events to determine whether the switch from a daptomycin resistance to a susceptible phenotype was due to a phenomenon of resistance reversion or recurrent infection with a susceptible strain. Pairwise competition experiments showed that the susceptible clinical recurrent SA6850 strain had increased fitness when compared to the resistant counterpart SA6820 strain. In fact, although we have demonstrated that reversion of daptomycin resistance to daptomycin susceptible can occur in vitro after serial passages in drug-free media, phylogenetic analysis suggested that the in vivo process was the result of a recurrent infection with a previous susceptible isolate carried by the patient rather than a resistance reversion of the strain. Whole genome sequence of evolved strains showed that daptomycin resistance in MRSA is associated with a high fitness cost mediated by mutations in mprF gene, revealed as a key element of the biological cost. Moreover, we determined that daptomycin resistance-associated fitness cost was independent of vancomycin intermediate resistance phenotype, as demonstrated in additional clinical MRSA vancomycin susceptible strains. This study highlights important observations as, despite daptomycin offers a useful treatment option for the patients with persistent infections, it has to be carefully monitored. The high fitness cost associated to daptomycin resistance may explain the reduced dissemination of daptomycin resistance and the absence of daptomycin reported outbreaks.

Optimized breeding strategies for multiple trait integration: I. Minimizing linkage drag in single event introgression.

PubMed

Peng, Ting; Sun, Xiaochun; Mumm, Rita H

2014-01-01

From a breeding standpoint, multiple trait integration (MTI) is a four-step process of converting an elite variety/hybrid for value-added traits (e.g. transgenic events) using backcross breeding, ultimately regaining the performance attributes of the target hybrid along with reliable expression of the value-added traits. In the light of the overarching goal of recovering equivalent performance in the finished conversion, this study focuses on the first step of MTI, single event introgression, exploring the feasibility of marker-aided backcross conversion of a target maize hybrid for 15 transgenic events, incorporating eight events into the female hybrid parent and seven into the male parent. Single event introgression is conducted in parallel streams to convert the recurrent parent (RP) for individual events, with the primary objective of minimizing residual non-recurrent parent (NRP) germplasm, especially in the chromosomal proximity to the event (i.e. linkage drag). In keeping with a defined lower limit of 96.66 % overall RP germplasm recovery (i.e. ≤120 cM NRP germplasm given a genome size of 1,788 cM), a breeding goal for each of the 15 single event conversions was developed: <8 cM of residual NRP germplasm across the genome with ~1 cM in the 20 cM region flanking the event. Using computer simulation, we aimed to identify optimal breeding strategies for single event introgression to achieve this breeding goal, measuring efficiency in terms of number of backcross generations required, marker data points needed, and total population size across generations. Various selection schemes classified as three-stage, modified two-stage, and combined selection conducted from BC1 through BC3, BC4, or BC5 were compared. The breeding goal was achieved with a selection scheme involving five generations of marker-aided backcrossing, with BC1 through BC3 selected for the event of interest and minimal linkage drag at population size of 600, and BC4 and BC5 selected for the event of interest and recovery of the RP germplasm across the genome at population size of 400, with selection intensity of 0.01 for all generations. In addition, strategies for choice of donor parent to facilitate conversion efficiency and quality were evaluated. Two essential criteria for choosing an optimal donor parent for a given RP were established: introgression history showing reduction of linkage drag to ~1 cM in the 20 cM region flanking the event and genetic similarity between the RP and potential donor parents. Computer simulation demonstrated that single event conversions with <8 cM residual NRP germplasm can be accomplished by BC5 with no genetic similarity, by BC4 with 30 % genetic similarity, and by BC3 with 86 % genetic similarity using previously converted RPs as event donors. This study indicates that MTI to produce a 'quality' 15-event-stacked hybrid conversion is achievable. Furthermore, it lays the groundwork for a comprehensive approach to MTI by outlining a pathway to produce appropriate starting materials with which to proceed with event pyramiding and trait fixation before version testing.

Recurrent stroke risk and cerebral microbleed burden in ischemic stroke and TIA

PubMed Central

Wilson, Duncan; Charidimou, Andreas; Ambler, Gareth; Fox, Zoe V.; Gregoire, Simone; Rayson, Phillip; Imaizumi, Toshio; Fluri, Felix; Naka, Hiromitsu; Horstmann, Solveig; Veltkamp, Roland; Rothwell, Peter M.; Kwa, Vincent I.H.; Thijs, Vincent; Lee, Yong-Seok; Kim, Young Dae; Huang, Yining; Wong, Ka Sing; Jäger, Hans Rolf

2016-01-01

Objective: To determine associations between cerebral microbleed (CMB) burden with recurrent ischemic stroke (IS) and intracerebral hemorrhage (ICH) risk after IS or TIA. Methods: We identified prospective studies of patients with IS or TIA that investigated CMBs and stroke (ICH and IS) risk during ≥3 months follow-up. Authors provided aggregate summary-level data on stroke outcomes, with CMBs categorized according to burden (single, 2–4, and ≥5 CMBs) and distribution. We calculated absolute event rates and pooled risk ratios (RR) using random-effects meta-analysis. Results: We included 5,068 patients from 15 studies. There were 115/1,284 (9.6%) recurrent IS events in patients with CMBs vs 212/3,781 (5.6%) in patients without CMBs (pooled RR 1.8 for CMBs vs no CMBs; 95% confidence interval [CI] 1.4–2.5). There were 49/1,142 (4.3%) ICH events in those with CMBs vs 17/2,912 (0.58%) in those without CMBs (pooled RR 6.3 for CMBs vs no CMBs; 95% CI 3.5–11.4). Increasing CMB burden increased the risk of IS (pooled RR [95% CI] 1.8 [1.0–3.1], 2.4 [1.3–4.4], and 2.7 [1.5–4.9] for 1 CMB, 2–4 CMBs, and ≥5 CMBs, respectively) and ICH (pooled RR [95% CI] 4.6 [1.9–10.7], 5.6 [2.4–13.3], and 14.1 [6.9–29.0] for 1 CMB, 2–4 CMBs, and ≥5 CMBs, respectively). Conclusions: CMBs are associated with increased stroke risk after IS or TIA. With increasing CMB burden (compared to no CMBs), the risk of ICH increases more steeply than that of IS. However, IS absolute event rates remain higher than ICH absolute event rates in all CMB burden categories. PMID:27590288

Eight Flurothyl-Induced Generalized Seizures Lead to the Rapid Evolution of Spontaneous Seizures in Mice: A Model of Epileptogenesis with Seizure Remission

PubMed Central

Kadiyala, Sridhar B.; Yannix, Joshua Q.; Nalwalk, Julia W.; Papandrea, Dominick; Beyer, Barbara S.; Herron, Bruce J.

2016-01-01

The occurrence of recurrent, unprovoked seizures is the hallmark of human epilepsy. Currently, only two-thirds of this patient population has adequate seizure control. New epilepsy models provide the potential for not only understanding the development of spontaneous seizures, but also for testing new strategies to treat this disorder. Here, we characterize a primary generalized seizure model of epilepsy following repeated exposure to the GABAA receptor antagonist, flurothyl, in which mice develop spontaneous seizures that remit within 1 month. In this model, we expose C57BL/6J mice to flurothyl until they experience a generalized seizure. Each of these generalized seizures typically lasts <30 s. We induce one seizure per day for 8 d followed by 24 h video-electroencephalographic recordings. Within 1 d following the last of eight flurothyl-induced seizures, ∼50% of mice have spontaneous seizures. Ninety-five percent of mice tested have seizures within the first week of the recording period. Of the spontaneous seizures recorded, the majority are generalized clonic seizures, with the remaining 7–12% comprising generalized clonic seizures that transition into brainstem seizures. Over the course of an 8 week recording period, spontaneous seizure episodes remit after ∼4 weeks. Overall, the repeated flurothyl paradigm is a model of epileptogenesis with spontaneous seizures that remit. This model provides an additional tool in our armamentarium for understanding the mechanisms underlying epileptogenesis and may provide insights into why spontaneous seizures remit without anticonvulsant treatment. Elucidating these processes could lead to the development of new epilepsy therapeutics. SIGNIFICANCE STATEMENT Epilepsy is a chronic disorder characterized by the occurrence of recurrent, unprovoked seizures in which the individual seizure–ictal events are self-limiting. Remission of recurrent, unprovoked seizures can be achieved in two-thirds of cases by treatment with anticonvulsant medication, surgical resection, and/or nerve/brain electrode stimulation. However, there are examples in humans of epilepsy with recurrent, unprovoked seizures remitting without any intervention. While elucidating how recurrent, unprovoked seizures develop is critical for understanding epileptogenesis, an understanding of how and why recurrent, unprovoked seizures remit may further our understanding and treatment of epilepsy. Here, we describe a new model of recurrent, unprovoked spontaneous seizures in which the occurrence of spontaneous seizures naturally remits over time without any therapeutic intervention. PMID:27413158

Practicing safe cell culture: applied process designs for minimizing virus contamination risk.

PubMed

Kiss, Robert D

2011-01-01

CONFERENCE PROCEEDING Proceedings of the PDA/FDA Adventitious Viruses in Biologics: Detection and Mitigation Strategies Workshop in Bethesda, MD, USA; December 1-3, 2010 Guest Editors: Arifa Khan (Bethesda, MD), Patricia Hughes (Bethesda, MD) and Michael Wiebe (San Francisco, CA) Genentech responded to a virus contamination in its biologics manufacturing facility by developing and implementing a series of barriers specifically designed to prevent recurrence of this significant and impactful event. The barriers included steps to inactivate or remove potential virus particles from the many raw materials used in cell culture processing. Additionally, analytical testing barriers provided protection of the downstream processing areas should a culture contamination occur, and robust virus clearance capability provided further assurance of virus safety should a low level contamination go undetected. This conference proceeding will review Genentech's approach, and lessons learned, in minimizing virus contamination risk in cell culture processes through multiple layers of targeted barriers designed to deliver biologics products with high success rates.

Killing wolves to prevent predation on livestock may protect one farm but harm neighbors

PubMed Central

Cornman, Ari M.; Treves, Adrian

2018-01-01

Large carnivores, such as gray wolves, Canis lupus, are difficult to protect in mixed-use landscapes because some people perceive them as dangerous and because they sometimes threaten human property and safety. Governments may respond by killing carnivores in an effort to prevent repeated conflicts or threats, although the functional effectiveness of lethal methods has long been questioned. We evaluated two methods of government intervention following independent events of verified wolf predation on domestic animals (depredation) in the Upper Peninsula of Michigan, USA between 1998–2014, at three spatial scales. We evaluated two intervention methods using log-rank tests and conditional Cox recurrent event, gap time models based on retrospective analyses of the following quasi-experimental treatments: (1) selective killing of wolves by trapping near sites of verified depredation, and (2) advice to owners and haphazard use of non-lethal methods without wolf-killing. The government did not randomly assign treatments and used a pseudo-control (no removal of wolves was not a true control), but the federal permission to intervene lethally was granted and rescinded independent of events on the ground. Hazard ratios suggest lethal intervention was associated with an insignificant 27% lower risk of recurrence of events at trapping sites, but offset by an insignificant 22% increase in risk of recurrence at sites up to 5.42 km distant in the same year, compared to the non-lethal treatment. Our results do not support the hypothesis that Michigan’s use of lethal intervention after wolf depredations was effective for reducing the future risk of recurrence in the vicinities of trapping sites. Examining only the sites of intervention is incomplete because neighbors near trapping sites may suffer the recurrence of depredations. We propose two new hypotheses for perceived effectiveness of lethal methods: (a) killing predators may be perceived as effective because of the benefits to a small minority of farmers, and (b) if neighbors experience side-effects of lethal intervention such as displaced depredations, they may perceive the problem growing and then demand more lethal intervention rather than detecting problems spreading from the first trapping site. Ethical wildlife management guided by the “best scientific and commercial data available” would suggest suspending the standard method of trapping wolves in favor of non-lethal methods (livestock guarding dogs or fladry) that have been proven effective in preventing livestock losses in Michigan and elsewhere. PMID:29320512

Marginal regression analysis of recurrent events with coarsened censoring times.

PubMed

Hu, X Joan; Rosychuk, Rhonda J

2016-12-01

Motivated by an ongoing pediatric mental health care (PMHC) study, this article presents weakly structured methods for analyzing doubly censored recurrent event data where only coarsened information on censoring is available. The study extracted administrative records of emergency department visits from provincial health administrative databases. The available information of each individual subject is limited to a subject-specific time window determined up to concealed data. To evaluate time-dependent effect of exposures, we adapt the local linear estimation with right censored survival times under the Cox regression model with time-varying coefficients (cf. Cai and Sun, Scandinavian Journal of Statistics 2003, 30, 93-111). We establish the pointwise consistency and asymptotic normality of the regression parameter estimator, and examine its performance by simulation. The PMHC study illustrates the proposed approach throughout the article. © 2016, The International Biometric Society.

The Adherence eValuation After Ischemic Stroke Longitudinal (AVAIL) registry: design, rationale, and baseline patient characteristics.

PubMed

Bushnell, Cheryl; Zimmer, Louise; Schwamm, Lee; Goldstein, Larry B; Clapp-Channing, Nancy; Harding, Tina; Drew, Laura; Zhao, Xin; Peterson, Eric

2009-03-01

Approximately one third of the 780,000 people in the United States who have a stroke each year have recurrent events. Although efficacious secondary prevention measures are available, levels of adherence to these strategies in patients who have had stroke are largely unknown. Understanding medication-taking behavior in this population is an important step to optimizing the appropriate use of proven secondary preventive therapies and reducing the risk of recurrent stroke. The Adherence eValuation After Ischemic Stroke Longitudinal (AVAIL) registry is a prospective study of adherence to stroke prevention medications from hospital discharge to 1 year in patients admitted with stroke or transient ischemic attack. The primary outcomes are medication usage as determined by patient interviews after 3 and 12 months. Potential patient-, provider-, and system-level barriers to persistence of medication use are also collected. Secondary outcomes include the rates of recurrent stroke or transient ischemic attack, vascular events, and rehospitalization and functional status as measured by the modified Rankin score. The AVAIL enrolled about 2,900 subjects from 106 hospitals from July 2006 through July 2008. The 12-month follow-up will be completed in August 2009. The AVAIL registry will document the current state of adherence and persistence to stroke prevention medications among a nationwide sample of patients. These data will be used to design interventions to improve the quality of care post acute hospitalization and reduce the risks of future stroke and cardiovascular events.

Relationship between risk factor control and vascular events in the SAMMPRIS trial.

PubMed

Turan, Tanya N; Nizam, Azhar; Lynn, Michael J; Egan, Brent M; Le, Ngoc-Anh; Lopes-Virella, Maria F; Hermayer, Kathie L; Harrell, Jamie; Derdeyn, Colin P; Fiorella, David; Janis, L Scott; Lane, Bethany; Montgomery, Jean; Chimowitz, Marc I

2017-01-24

The Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) study is the first stroke prevention trial to include protocol-driven intensive management of multiple risk factors. In this prespecified analysis, we aimed to investigate the relationship between risk factor control during follow-up and outcome of patients in the medical arm of SAMMPRIS. Data from SAMMPRIS participants in the medical arm (n = 227) were analyzed. Risk factors were recorded at baseline, 30 days, 4 months, and then every 4 months for a mean follow-up of 32 months. For each patient, values for all risk factor measures were averaged and dichotomized as in or out of target. Participants who were out of target for systolic blood pressure and physical activity, as well as those with higher mean low-density lipoprotein cholesterol and non-high-density lipoprotein, were more likely to have a recurrent vascular event (stroke, myocardial infarction, or vascular death) at 3 years compared to those who had good risk factor control. In the multivariable analysis, greater physical activity decreased the likelihood of a recurrent stroke, myocardial infarction, or vascular death (odds ratio 0.6, confidence interval 0.4-0.8). Raised blood pressure, cholesterol, and physical inactivity should be aggressively treated in patients with intracranial atherosclerosis to prevent future vascular events. Physical activity, which has not received attention in stroke prevention trials, was the strongest predictor of a good outcome in the medical arm in SAMMPRIS. NCT00576693. © 2016 American Academy of Neurology.

The cortisol awakening response predicts major depression: predictive stability over a 4-year follow-up and effect of depression history.

PubMed

Vrshek-Schallhorn, S; Doane, L D; Mineka, S; Zinbarg, R E; Craske, M G; Adam, E K

2013-03-01

The cortisol awakening response (CAR) has been shown to predict major depressive episodes (MDEs) over a 1-year period. It is unknown whether this effect: (a) is stable over longer periods of time; (b) is independent of prospective stressful life events; and (c) differentially predicts first onsets or recurrences of MDEs. A total of 270 older adolescents (mean age 17.06 years at cortisol measurement) from the larger prospective Northwestern-UCLA Youth Emotion Project completed baseline diagnostic and life stress interviews, questionnaires, and a 3-day cortisol sampling protocol measuring the CAR and diurnal rhythm, as well as up to four annual follow-up interviews of diagnoses and life stress. Non-proportional person-month survival analyses revealed that higher levels of the baseline CAR significantly predict MDEs for 2.5 years following cortisol measurement. However, the strength of prediction of depressive episodes significantly decays over time, with the CAR no longer significantly predicting MDEs after 2.5 years. Elevations in the CAR did not significantly increase vulnerability to prospective major stressful life events. They did, however, predict MDE recurrences more strongly than first onsets. These results suggest that a high CAR represents a time-limited risk factor for onsets of MDEs, which increases risk for depression independently of future major stressful life events. Possible explanations for the stronger effect of the CAR for predicting MDE recurrences than first onsets are discussed.

Long-term changes in regular and low-frequency earthquake inter-event times near Parkfield, CA

NASA Astrophysics Data System (ADS)

Wu, C.; Shelly, D. R.; Johnson, P. A.; Gomberg, J. S.; Peng, Z.

2012-12-01

The temporal evolution of earthquake inter-event time may provide important clues for the timing of future events and underlying physical mechanisms of earthquake nucleation. In this study, we examine inter-event times from 12-yr catalogs of ~50,000 earthquakes and ~730,000 LFEs in the vicinity of the Parkfield section of the San Andreas Fault. We focus on the long-term evolution of inter-event times after the 2003 Mw6.5 San Simeon and 2004 Mw6.0 Parkfield earthquakes. We find that inter-event times decrease by ~4 orders of magnitudes after the Parkfield and San Simeon earthquakes and are followed by a long-term recovery with time scales of ~3 years and more than 8 years for earthquakes along and to the southwest of the San Andreas fault, respectively. The differing long-term recovery of the earthquake inter-event times is likely a manifestation of different aftershock recovery time scales that reflect the different tectonic loading rates in the two regions. We also observe a possible decrease of LFE inter-event times in some LFE families, followed by a recovery with time scales of ~4 months to several years. The drop in the recurrence time of LFE after the Parkfield earthquake is likely caused by a combination of the dynamic and positive static stress induced by the Parkfield earthquake, and the long-term recovery in LFE recurrence time could be due to post-seismic relaxation or gradual recovery of the fault zone material properties. Our on-going work includes better constraining and understanding the physical mechanisms responsible for the observed long-term recovery in earthquake and LFE inter-event times.

Deep Recurrent Neural Networks for seizure detection and early seizure detection systems

DOE Office of Scientific and Technical Information (OSTI.GOV)

Talathi, S. S.

Epilepsy is common neurological diseases, affecting about 0.6-0.8 % of world population. Epileptic patients suffer from chronic unprovoked seizures, which can result in broad spectrum of debilitating medical and social consequences. Since seizures, in general, occur infrequently and are unpredictable, automated seizure detection systems are recommended to screen for seizures during long-term electroencephalogram (EEG) recordings. In addition, systems for early seizure detection can lead to the development of new types of intervention systems that are designed to control or shorten the duration of seizure events. In this article, we investigate the utility of recurrent neural networks (RNNs) in designing seizuremore » detection and early seizure detection systems. We propose a deep learning framework via the use of Gated Recurrent Unit (GRU) RNNs for seizure detection. We use publicly available data in order to evaluate our method and demonstrate very promising evaluation results with overall accuracy close to 100 %. We also systematically investigate the application of our method for early seizure warning systems. Our method can detect about 98% of seizure events within the first 5 seconds of the overall epileptic seizure duration.« less

Suicidal Ideation and Its Recurrence in Boys and Men from Early Adolescence to Early Adulthood: An Event History Analysis

PubMed Central

Kerr, David C. R.; Owen, Lee. D.; Capaldi, Deborah M.

2008-01-01

Occurrence and recurrences of suicidal ideation (SI) were modeled among boys/men assessed annually from ages 12 to 29 years. Multiple-spell discrete-time event history analyses permitted (a) determination of whether risk for SI escalates with prior experiences of SI (Spell effects), (b) while accounting for changes in risk with time (Period effects), and (c) controlling for vulnerability factors. Self-reported SI (presence/absence in past week), depressive symptoms, alcohol/substance use, and antisocial behavior, and official arrest records were collected annually from 205 boys recruited on the basis of community risk for delinquency. Parents’ self-reported psychopathology and SES were collected in childhood. Period effects supported decreasing risk for SI over time. Spell and time-varying, 1-year lagged substance use and depressive symptoms independently predicted increased risk for SI. Models involving SI with intent were explored. Consistent with interpersonal psychological theory, risk for young men’s SI increases with past experience of SI, even with key propensities controlled; however, risk also decays over time. Targeting conditions that confer risk for SI is essential. Preventing and delaying SI occurrence and recurrence may represent independent mechanisms by which prevention efforts operate. PMID:18729614

Assessing Landscape Change and Processes of Recurrence, Replacement, and Recovery in the Southeastern Coastal Plains, USA

NASA Astrophysics Data System (ADS)

Drummond, Mark A.; Stier, Michael P.; Auch, Roger F.; Taylor, Janis L.; Griffith, Glenn E.; Riegle, Jodi L.; Hester, David J.; Soulard, Christopher E.; McBeth, Jamie L.

2015-11-01

The processes of landscape change are complex, exhibiting spatial variability as well as linear, cyclical, and reversible characteristics. To better understand the various processes that cause transformation, a data aggregation, validation, and attribution approach was developed and applied to an analysis of the Southeastern Coastal Plains (SECP). The approach integrates information from available national land-use, natural disturbance, and land-cover data to efficiently assess spatially-specific changes and causes. Between 2001 and 2006, the processes of change affected 7.8 % of the SECP but varied across small-scale ecoregions. Processes were placed into a simple conceptual framework to explicitly identify the type and direction of change based on three general characteristics: replacement, recurrence, and recovery. Replacement processes, whereby a land use or cover is supplanted by a new land use, including urbanization and agricultural expansion, accounted for approximately 15 % of the extent of change. Recurrent processes that contribute to cyclical changes in land cover, including forest harvest/replanting and fire, accounted for 83 %. Most forest cover changes were recurrent, while the extents of recurrent silviculture and forest replacement processes such as urbanization far exceeded forest recovery processes. The total extent of landscape recovery, from prior land use to natural or semi-natural vegetation cover, accounted for less than 3 % of change. In a region of complex change, increases in transitory grassland and shrubland covers were caused by large-scale intensive plantation silviculture and small-scale activities including mining reclamation. Explicit identification of the process types and dynamics presented here may improve the understanding of land-cover change and landscape trajectory.

Assessing landscape change and processes of recurrence, replacement, and recovery in the Southeastern Coastal Plains, USA

USGS Publications Warehouse

Drummond, Mark A.; Stier, Michael P.; Auch, Roger F.; Taylor, Janis L.; Griffith, Glenn E.; Hester, David J.; Riegle, Jodi L.; Soulard, Christopher E.; McBeth, Jamie L.

2015-01-01

The processes of landscape change are complex, exhibiting spatial variability as well as linear, cyclical, and reversible characteristics. To better understand the various processes that cause transformation, a data aggregation, validation, and attribution approach was developed and applied to an analysis of the Southeastern Coastal Plains (SECP). The approach integrates information from available national land-use, natural disturbance, and land-cover data to efficiently assess spatially-specific changes and causes. Between 2001 and 2006, the processes of change affected 7.8 % of the SECP but varied across small-scale ecoregions. Processes were placed into a simple conceptual framework to explicitly identify the type and direction of change based on three general characteristics: replacement, recurrence, and recovery. Replacement processes, whereby a land use or cover is supplanted by a new land use, including urbanization and agricultural expansion, accounted for approximately 15 % of the extent of change. Recurrent processes that contribute to cyclical changes in land cover, including forest harvest/replanting and fire, accounted for 83 %. Most forest cover changes were recurrent, while the extents of recurrent silviculture and forest replacement processes such as urbanization far exceeded forest recovery processes. The total extent of landscape recovery, from prior land use to natural or semi-natural vegetation cover, accounted for less than 3 % of change. In a region of complex change, increases in transitory grassland and shrubland covers were caused by large-scale intensive plantation silviculture and small-scale activities including mining reclamation. Explicit identification of the process types and dynamics presented here may improve the understanding of land-cover change and landscape trajectory.

Assessing Landscape Change and Processes of Recurrence, Replacement, and Recovery in the Southeastern Coastal Plains, USA.

PubMed

Drummond, Mark A; Stier, Michael P; Auch, Roger F; Taylor, Janis L; Griffith, Glenn E; Riegle, Jodi L; Hester, David J; Soulard, Christopher E; McBeth, Jamie L

2015-11-01

The processes of landscape change are complex, exhibiting spatial variability as well as linear, cyclical, and reversible characteristics. To better understand the various processes that cause transformation, a data aggregation, validation, and attribution approach was developed and applied to an analysis of the Southeastern Coastal Plains (SECP). The approach integrates information from available national land-use, natural disturbance, and land-cover data to efficiently assess spatially-specific changes and causes. Between 2001 and 2006, the processes of change affected 7.8% of the SECP but varied across small-scale ecoregions. Processes were placed into a simple conceptual framework to explicitly identify the type and direction of change based on three general characteristics: replacement, recurrence, and recovery. Replacement processes, whereby a land use or cover is supplanted by a new land use, including urbanization and agricultural expansion, accounted for approximately 15% of the extent of change. Recurrent processes that contribute to cyclical changes in land cover, including forest harvest/replanting and fire, accounted for 83%. Most forest cover changes were recurrent, while the extents of recurrent silviculture and forest replacement processes such as urbanization far exceeded forest recovery processes. The total extent of landscape recovery, from prior land use to natural or semi-natural vegetation cover, accounted for less than 3% of change. In a region of complex change, increases in transitory grassland and shrubland covers were caused by large-scale intensive plantation silviculture and small-scale activities including mining reclamation. Explicit identification of the process types and dynamics presented here may improve the understanding of land-cover change and landscape trajectory.

Estimating interevent time distributions from finite observation periods in communication networks

NASA Astrophysics Data System (ADS)

Kivelä, Mikko; Porter, Mason A.

2015-11-01

A diverse variety of processes—including recurrent disease episodes, neuron firing, and communication patterns among humans—can be described using interevent time (IET) distributions. Many such processes are ongoing, although event sequences are only available during a finite observation window. Because the observation time window is more likely to begin or end during long IETs than during short ones, the analysis of such data is susceptible to a bias induced by the finite observation period. In this paper, we illustrate how this length bias is born and how it can be corrected without assuming any particular shape for the IET distribution. To do this, we model event sequences using stationary renewal processes, and we formulate simple heuristics for determining the severity of the bias. To illustrate our results, we focus on the example of empirical communication networks, which are temporal networks that are constructed from communication events. The IET distributions of such systems guide efforts to build models of human behavior, and the variance of IETs is very important for estimating the spreading rate of information in networks of temporal interactions. We analyze several well-known data sets from the literature, and we find that the resulting bias can lead to systematic underestimates of the variance in the IET distributions and that correcting for the bias can lead to qualitatively different results for the tails of the IET distributions.

Event Reports Promoting Root Cause Analysis.

PubMed

Pandit, Swananda; Gong, Yang

2016-01-01

Improving health is the sole objective of medical care. Unfortunately, mishaps or patient safety events happen during the care. If the safety events were collected effectively, they would help identify patterns, underlying causes, and ultimately generate proactive and remedial solutions for prevention of recurrence. Based on the AHRQ Common Formats, we examine the quality of patient safety incident reports and describe the initial data requirement that can support and accelerate effective root cause analysis. The ultimate goal is to develop a knowledge base of patient safety events and their common solutions which can be readily available for sharing and learning.

Awareness of antiplatelet resistance in patient with repeated episodes of thrombotic events

NASA Astrophysics Data System (ADS)

Dalimunthe, N. N.; Hamonangan, R.; Antono, D.; Prasetya, I.; Rusdi, L.

2018-03-01

Antiplatelet has been the cornerstones management of acute coronary syndrome. However, numbers of patients on these agents had episodes of adverse cardiovascular events. A 65-year-old woman post cardiac coronary bypass surgery on dual antiplatelet therapy, Aspirin, and Clopidogrel underwent several episodes of thrombotic events despite good adhered to thedailyantiplatelet regimen.These recurrent events had led to clinical suspicious of antiplatelet resistance. Platelet function test was performed which indicates a poor platelet response to Clopidogrel. Clopidogrelwas discontinued and Ticagrelor was prescribed together with Aspirin. During two months of follow up, there is no episode of chest discomfort.

Arrests, Recent Life Circumstances, and Recurrent Job Loss for At-Risk Young Men: An Event-History Analysis

ERIC Educational Resources Information Center

Wiesner, Margit; Capaldi, Deborah M.; Kim, Hyoun K.

2010-01-01

This study used longitudinal data from 202 at-risk young men to examine effects of arrests, prior risk factors, and recent life circumstances on job loss across a 7-year period in early adulthood. Repeated failure-time continuous event-history analysis indicated that occurrence of job loss was primarily related to prior mental health problems,…

Radiofrequency ablation of stage IA non-small cell lung cancer in medically inoperable patients: Results from the American College of Surgeons Oncology Group Z4033 (Alliance) trial.

PubMed

Dupuy, Damian E; Fernando, Hiran C; Hillman, Shauna; Ng, Thomas; Tan, Angelina D; Sharma, Amita; Rilling, William S; Hong, Kelvin; Putnam, Joe B

2015-10-01

This study evaluated the 2-year overall survival rate, adverse event rate, local control rate, and impact on pulmonary function tests for medically inoperable patients with stage IA non-small cell lung cancer (NSCLC) undergoing computed tomography (CT)-guided radiofrequency ablation (RFA) in a prospective, multicenter trial. Fifty-four patients (25 men and 29 women) with a median age of 76 years (range, 60-89 years) were enrolled from 16 US centers; 51 patients were eligible for evaluation (they had biopsy-proven stage IA NSCLC and were deemed medically inoperable by a board-certified thoracic surgeon). Pulmonary function tests were performed within the 60 days before RFA and 3 and 24 months after RFA. Adverse events were recorded and categorized. Patients were followed with CT and fludeoxyglucose positron emission tomography. Local control rate and recurrence patterns were analyzed. The overall survival rate was 86.3% at 1 year and 69.8% at 2 years. The local tumor recurrence-free rate was 68.9% at 1 year and 59.8% at 2 years and was worse for tumors > 2 cm. In the 19 patients with local recurrence, 11 were re-treated with RFA, 9 underwent radiation, and 3 underwent chemotherapy. There were 21 grade 3 adverse events, 2 grade 4 adverse events, and 1 grade 5 adverse event in 12 patients within the first 90 days after RFA. None of the grade 4 or 5 adverse events were attributable to RFA. There was no significant change in the forced expiratory volume in the first second of expiration or the diffusing capacity of lung for carbon monoxide after RFA. A tumor size less than 2.0 cm and a performance status of 0 or 1 were associated with statistically significant improved survival of 83% and 78%, respectively, at 2 years. RFA is a single, minimally invasive procedure that is well tolerated in medically inoperable patients, does not adversely affect pulmonary function tests, and provides a 2-year overall survival rate that is comparable to the rate reported after stereotactic body radiotherapy in similar patients. © 2015 American Cancer Society.

Adjuvant Sunitinib in High-Risk Renal-Cell Carcinoma after Nephrectomy.

PubMed

Ravaud, Alain; Motzer, Robert J; Pandha, Hardev S; George, Daniel J; Pantuck, Allan J; Patel, Anup; Chang, Yen-Hwa; Escudier, Bernard; Donskov, Frede; Magheli, Ahmed; Carteni, Giacomo; Laguerre, Brigitte; Tomczak, Piotr; Breza, Jan; Gerletti, Paola; Lechuga, Mariajose; Lin, Xun; Martini, Jean-Francois; Ramaswamy, Krishnan; Casey, Michelle; Staehler, Michael; Patard, Jean-Jacques

2016-12-08

Sunitinib, a vascular endothelial growth factor pathway inhibitor, is an effective treatment for metastatic renal-cell carcinoma. We sought to determine the efficacy and safety of sunitinib in patients with locoregional renal-cell carcinoma at high risk for tumor recurrence after nephrectomy. In this randomized, double-blind, phase 3 trial, we assigned 615 patients with locoregional, high-risk clear-cell renal-cell carcinoma to receive either sunitinib (50 mg per day) or placebo on a 4-weeks-on, 2-weeks-off schedule for 1 year or until disease recurrence, unacceptable toxicity, or consent withdrawal. The primary end point was disease-free survival, according to blinded independent central review. Secondary end points included investigator-assessed disease-free survival, overall survival, and safety. The median duration of disease-free survival was 6.8 years (95% confidence interval [CI], 5.8 to not reached) in the sunitinib group and 5.6 years (95% CI, 3.8 to 6.6) in the placebo group (hazard ratio, 0.76; 95% CI, 0.59 to 0.98; P=0.03). Overall survival data were not mature at the time of data cutoff. Dose reductions because of adverse events were more frequent in the sunitinib group than in the placebo group (34.3% vs. 2%), as were dose interruptions (46.4% vs. 13.2%) and discontinuations (28.1% vs. 5.6%). Grade 3 or 4 adverse events were more frequent in the sunitinib group (48.4% for grade 3 events and 12.1% for grade 4 events) than in the placebo group (15.8% and 3.6%, respectively). There was a similar incidence of serious adverse events in the two groups (21.9% for sunitinib vs. 17.1% for placebo); no deaths were attributed to toxic effects. Among patients with locoregional clear-cell renal-cell carcinoma at high risk for tumor recurrence after nephrectomy, the median duration of disease-free survival was significantly longer in the sunitinib group than in the placebo group, at a cost of a higher rate of toxic events. (Funded by Pfizer; S-TRAC ClinicalTrials.gov number, NCT00375674 .).

Prevention of venous thromboembolism in pregnant patients with a history of venous thromboembolic disease: A retrospective cohort study.

PubMed

Lazo-Langner, Alejandro; Al-Ani, Fatimah; Weisz, Sarah; Rozanski, Camilla; Louzada, Martha; Kovacs, Judy; Kovacs, Michael J

2018-05-05

Optimal prophylactic strategies in pregnant women with a history of venous thromboembolism (VTE) are unknown. We conducted a retrospective cohort study of consecutive pregnant patients with a previous VTE history. Patients were followed until 6 weeks postpartum. Patients with a previous unprovoked event (including antepartum VTE) received antenatal prophylaxis, mostly with low dose low molecular weight heparin (LMWH). All patients received prophylaxis for six weeks after delivery. We included a total of 199 pregnancies in 142 women. Of these, 147 pregnancies occurred in women with unprovoked or estrogen-related VTE history and 52 pregnancies in women with provoked VTE. There were 8 recurrences in 199 pregnancies (4%; 95%CI: 2.05-7.73), of which 5 were antepartum recurrences (2.5%; 95%CI 1.08-5.75) and 3 were postpartum (1.5%; 95% CI 0.51-4.34). In the unprovoked VTE group there were 7 recurrences (4.7%; 95%CI: 2.32-9.50), whereas in the provoked VTE group there was 1 (1.9%; 95%CI: 0.34-10.12). There was one major bleeding event in a patient not receiving LMWH secondary to placental abruption. This study suggests that the use of prophylactic doses of LMWH during pregnancy and puerperium, as described in this study, results in low occurrence of ante- and postpartum VTE recurrences in patients with previous VTE. Further studies are required to confirm this observation. Copyright © 2018 Elsevier Ltd. All rights reserved.

A GIS-Based Model for the analysis of an urban flash flood and its hydro-geomorphic response. The Valencia event of 1957

NASA Astrophysics Data System (ADS)

Portugués-Mollá, I.; Bonache-Felici, X.; Mateu-Bellés, J. F.; Marco-Segura, J. B.

2016-10-01

Flash floods are recurrent events around the Mediterranean region. Extreme episodes activate hydro-geomorphic high-intensity processes with low frequency. In urban environments, the complexity becomes higher due to the existence of very quick-response runoff. However, immediate recovery works remove the urban marks. After a short time both the significance and magnitude of the hydro-geomorphic event become completely unrecognizable. Nevertheless, these episodes generate extensive documentation which is testimony of the processes in almost real time. It is necessary to exploit this source typology in order to draw flood sketches when events far in time may lack a sufficiently rich database. This is particularly the case for the Valencia flash flood (October 1957), located in the lower Turia River basin (Eastern Spain). It left numerous pieces of hydro-geomorphic evidence, but its tracks were covered a short while after the flood. In any case, it remains part of a non-systematic legacy that has not yet been exploited, consisting of immediate aerial and oblique high resolution photography, pictures at street level, water marks and administrative records. Paradoxically, despite being considered a milestone in metropolitan territorial planning (the river was definitely diverted), an accurate reconstruction of the hydraulic behaviour was required from an integrated point of view. To this aim, the development of a GIS-Based Model enabled the utilisation of the above-mentioned materials. This non-conventional information was treated jointly from a new perspective. It provided database support through a vast amount of organised, structured and georeferenced information about the 1957 event. In a second stage, the GBM made it possible to characterise the Turia urban reach and interpret both the hydro-geomorphic (trenches along barrier beaches, erosion, deposition, etc.) and hydraulic (urban streams along the streets, flow directions, flood extent, levees breaks, overflows and inflows, etc.) processes mainly through photo-interpretation.

Illness perceptions or recurrence risk perceptions: What comes first? A longitudinal cross-lagged examination among cardiac patients.

PubMed

Peleg, Shira; Drori, Erga; Banai, Shmuel; Finkelstein, Ariel; Shiloh, Shoshana

2016-05-01

Previous research suggested that illness perceptions provide the basis for illness risk perceptions through an inductive reasoning process. This study aimed to assess the direction of relationships between illness and recurrence risk perceptions over time, among cardiac patients. A longitudinal study was conducted among 138 patients undergoing coronary angioplasty. Self-report questionnaires measured perceived recurrence risk and illness perceptions one day and one month after catheterisation. Cross-lagged Panel Model Analyses revealed that higher perceptions of timeline, consequences and emotional representations of illness at hospitalisation were associated with higher recurrence risk perceptions one month later. Perceived personal control was the only illness perception with bi-directional associations: higher perceived personal control at hospitalisation was associated with higher recurrence risk perceptions one month later; and higher recurrence risk perceptions at hospitalisation was associated with lower personal control one month later. The findings suggest that the associations between recurrence risk and illness perceptions can only partly be explained by inductive reasoning. Halo effects and defensive processes are suggested as complementary explanations for the observed associations between risk and illness perceptions.

Climate Change and Hydrological Extreme Events - Risks and Perspectives for Water Management in Bavaria and Québec

NASA Astrophysics Data System (ADS)

Ludwig, R.

2017-12-01

There is as yet no confirmed knowledge whether and how climate change contributes to the magnitude and frequency of hydrological extreme events and how regional water management could adapt to the corresponding risks. The ClimEx project (2015-2019) investigates the effects of climate change on the meteorological and hydrological extreme events and their implications for water management in Bavaria and Québec. High Performance Computing is employed to enable the complex simulations in a hydro-climatological model processing chain, resulting in a unique high-resolution and transient (1950-2100) dataset of climatological and meteorological forcing and hydrological response: (1) The climate module has developed a large ensemble of high resolution data (12km) of the CRCM5 RCM for Central Europe and North-Eastern North America, downscaled from 50 members of the CanESM2 GCM. The dataset is complemented by all available data from the Euro-CORDEX project to account for the assessment of both natural climate variability and climate change. The large ensemble with several thousand model years provides the potential to catch rare extreme events and thus improves the process understanding of extreme events with return periods of 1000+ years. (2) The hydrology module comprises process-based and spatially explicit model setups (e.g. WaSiM) for all major catchments in Bavaria and Southern Québec in high temporal (3h) and spatial (500m) resolution. The simulations form the basis for in depth analysis of hydrological extreme events based on the inputs from the large climate model dataset. The specific data situation enables to establish a new method for `virtual perfect prediction', which assesses climate change impacts on flood risk and water resources management by identifying patterns in the data which reveal preferential triggers of hydrological extreme events. The presentation will highlight first results from the analysis of the large scale ClimEx model ensemble, showing the current and future ratio of natural variability and climate change impacts on meteorological extreme events. Selected data from the ensemble is used to drive a hydrological model experiment to illustrate the capacity to better determine the recurrence periods of hydrological extreme events under conditions of climate change.

Atrial ectopy predicts late recurrence of atrial fibrillation after pulmonary vein isolation.

PubMed

Gang, Uffe J O; Nalliah, Chrishan J; Lim, Toon Wei; Thiagalingam, Aravinda; Kovoor, Pramesh; Ross, David L; Thomas, Stuart P

2015-06-01

Late recurrence of atrial fibrillation (AF) after radiofrequency ablation remains significant. Asymptomatic recurrence poses a difficult clinical problem as it is associated with an equally increased risk of stroke and death compared with symptomatic AF events. Meta-analyses reveal that no single preablation patient characteristic efficiently predicts these AF recurrences. This study aimed to evaluate the prognostic value of premature atrial complex (PAC) occurrence with regard to the risk of late AF recurrence after radiofrequency ablation. The study cohort consisted of 124 patients with 7-day Holter recordings at 6 months post radiofrequency ablation for AF. No patients had AF recurrence before this time. Patients were followed-up every 6 months. Holter-detected PACs were defined as any supraventricular complexes occurring >30% earlier than expected. During a median follow-up of 4.2 years (first quartile to third quartile [Q1-Q3]=1.6-4.5), 32 patients (26%) had late recurrences of AF at a median of 462 days (Q1-Q3=319-1026) post radiofrequency ablation. The number of PACs per 24 hours was 248 (Q1-Q3=62-1026) in patients with and 77 (Q1-Q3=24-448) in patients without recurrence of AF (P=0.02). Multivariate analysis of the risk of late AF recurrence found ≥142 PACs per 24 hours to have a hazard ratio 2.84 (confidence interval, 1.26-6.43), P=0.01. This study showed that occurrence of ≥142 PACs per day at 6 months after PVI was independently associated with a significantly increased risk of late AF recurrence. These results could have important clinical implications for the design of post-PVI follow-up. URL: http://www.anzctr.org.au. Unique identifier: ACRTN12606000467538. © 2015 American Heart Association, Inc.

Dilation or biodegradable stent placement for recurrent benign esophageal strictures: a randomized controlled trial.

PubMed

Walter, Daisy; van den Berg, Maarten W; Hirdes, Meike M; Vleggaar, Frank P; Repici, Alessandro; Deprez, Pierre H; Viedma, Bartolomé L; Lovat, Laurence B; Weusten, Bas L; Bisschops, Raf; Haidry, Rehan; Ferrara, Elisa; Sanborn, Keith J; O'Leary, Erin E; van Hooft, Jeanin E; Siersema, Peter D

2018-06-08

 Dilation is the standard of care for recurrent benign esophageal strictures (BES). Biodegradable stents may prolong the effect of dilation and reduce recurrences. Efficacy and safety of dilation and biodegradable stent placement early in the treatment algorithm of recurrent BES were compared.  This multicenter, randomized study enrolled patients with BES treated with previous dilations to ≥ 16 mm. The primary end point was number of repeat endoscopic dilations for recurrent stricture within 3 and 6 months. Secondary outcomes through 12 months included safety, time to first dilation for recurrent stricture, dysphagia, and level of activity.  At 3 months, the biodegradable stent group (n = 32) underwent significantly fewer endoscopic dilations for recurrent stricture compared with the dilation group (n = 34; P  < 0.001). By 6 months, the groups were similar. The number of patients experiencing adverse events was similar between the groups. Two patients in the biodegradable stent group died after developing tracheoesophageal fistulas at 95 and 96 days post-placement; no deaths were attributed to the stent. Median time to first dilation of recurrent stricture for the biodegradable stent group was significantly longer (106 vs. 41.5 days; P  = 0.003). Dysphagia scores improved for both groups. Patients in the biodegradable stent group had a significantly higher level of activity through 12 months ( P  < 0.001).  Biodegradable stent placement is associated with temporary reduction in number of repeat dilations and prolonged time to recurrent dysphagia compared with dilation. Additional studies are needed to better define the exact role of biodegradable stent placement to treat recurrent BES. © Georg Thieme Verlag KG Stuttgart · New York.

Prospective Study of Plasmodium vivax Malaria Recurrence after Radical Treatment with a Chloroquine-Primaquine Standard Regimen in Turbo, Colombia

PubMed Central

Blair, Silvia; Akinyi Okoth, Sheila; Udhayakumar, Venkatachalam; Marcet, Paula L.; Escalante, Ananias A.; Alexander, Neal; Rojas, Carlos

2016-01-01

Plasmodium vivax recurrences help maintain malaria transmission. They are caused by recrudescence, reinfection, or relapse, which are not easily differentiated. A longitudinal observational study took place in Turbo municipality, Colombia. Participants with uncomplicated P. vivax infection received supervised treatment concomitantly with 25 mg/kg chloroquine and 0.25 mg/kg/day primaquine for 14 days. Incidence of recurrence was assessed over 180 days. Samples were genotyped, and origins of recurrences were established. A total of 134 participants were enrolled between February 2012 and July 2013, and 87 were followed for 180 days, during which 29 recurrences were detected. The cumulative incidence of first recurrence was 24.1% (21/87) (95% confidence interval [CI], 14.6 to 33.7%), and 86% (18/21) of these events occurred between days 51 and 110. High genetic diversity of P. vivax strains was found, and 12.5% (16/128) of the infections were polyclonal. Among detected recurrences, 93.1% (27/29) of strains were genotyped as genetically identical to the strain from the previous infection episode, and 65.5% (19/29) of infections were classified as relapses. Our results indicate that there is a high incidence of P. vivax malaria recurrence after treatment in Turbo municipality, Colombia, and that a large majority of these episodes are likely relapses from the previous infection. We attribute this to the primaquine regimen currently used in Colombia, which may be insufficient to eliminate hypnozoites. PMID:27185794

Steroids for preventing recurrence of acute severe migraine headaches: a meta-analysis.

PubMed

Huang, Y; Cai, X; Song, X; Tang, H; Huang, Y; Xie, S; Hu, Y

2013-08-01

Recurrence of migraine headaches after treatment is common. The evidence regarding steroids for preventing migraine headache recurrence is controversial. This meta-analysis examined the effectiveness of steroids for prevention of recurrent headaches. Databases (PubMed, Embase and the Cochrane Library) and conference proceedings were searched for randomized controlled trials comparing steroids and placebo in the treatment of migraine headaches. Two independent reviewers assessed studies and extracted data. Relative risks (RRs) of headache recurrence and adverse events were calculated and reported with 95% confidence intervals (95% CIs). Eight studies with 905 patients were included. Pooled analysis showed that when steroids were added to standard abortive therapy they reduced the rate of moderate or severe headache recurrence after 24-72 h of follow-up evaluation (RR = 0.71; 95% CI = 0.59-0.86). There was no significant benefit of steroids compared with placebo in the proportion of totally resolved migraines (RR = 1.11; 95% CI = 0.94-1.32). The side effects of steroids are mild and not significant except for dizziness. Subgroup meta-analysis showed that parenteral dexamethasone tends to be more effective in reducing moderate or severe recurrent headaches (RR = 0.68; 95% CI = 0.55-0.84). However, no significant differences were found between oral administration and parenteral administration of steroids (P = 0.37). When steroids are added to standard abortive therapy for migraine headaches, they are effective and safe for preventing moderate or severe headache recurrence. © 2013 The Author(s) European Journal of Neurology © 2013 EFNS.

Clinical and economic benefits of extended treatment with apixaban for the treatment and prevention of recurrent venous thromboembolism in Canada.

PubMed

Quon, Peter; Le, Hoa H; Raymond, Vincent; Mtibaa, Mondher; Moshyk, Andriy

2016-06-01

Background and objective Venous thromboembolism (VTE) is associated with long-term clinical and economic burden. Clinical guidelines generally recommend at least 3 months of anticoagulation, but, in clinical practice, concerns over bleeding risk often limit extended treatment. Apixaban was studied for extended VTE treatment in the AMPLIFY-EXT trial, demonstrating superiority to placebo in VTE reduction without increasing risk of major bleeding. This study assessed the long-term clinical and economic benefits of extending treatment with apixaban when clinical equipoise exists compared to standard of care with enoxaparin/warfarin and other novel oral anti-coagulants (NOACs) for the treatment and prevention of recurrent VTE in Canada. Methods A Markov model was developed to follow patients with VTE over their lifetimes. Efficacy and safety for apixaban and enoxaparin/warfarin were based on AMPLIFY and AMPLIFY-EXT, while relative efficacy to other NOACs was synthesized by network meta-analysis (NMA). Dosages for NOACs and enoxaparin/warfarin were based on their respective trials and were given up to 18 months and up to 6 months, followed by no treatment, respectively. Patient quality adjusted life years (QALYs) were based on published studies, and costs for resource utilization were from a Ministry of Health perspective, expressed as 2014 CAD ($). Results Extended treatment with apixaban compared to enoxaparin/warfarin resulted in fewer recurrent VTEs, VTE-related deaths, and bleeding events, but at slightly increased cost. The incremental cost-effectiveness ratio was $4828 per QALY gained. Compared to other NOACs, apixaban had the fewest bleeding events, similar recurrent VTE events, and the lowest overall cost, which was driven by the strong bleeding profile. In scenario analyses of acute and lifetime treatments, apixaban was cost-effective against all strategies. Conclusions Extended treatment with apixaban can offer substantial clinical benefits and is a cost-effective alternative to enoxaparin/warfarin and other NOACs.

Modeling of cryoseismicity observed at the Fimbulisen Ice Shelf, East Antarctica

NASA Astrophysics Data System (ADS)

Hainzl, S.; Pirli, M.; Dahm, T.; Schweitzer, J.; Köhler, A.

2017-12-01

A source region of repetitive cryoseismic activity has been identified at the Fimbulisen ice shelf, in Dronning Maud Land, East Antarctica. The specific area is located at the outlet of the Jutulstraumen glacier, near the Kupol Moskovskij ice rise. A unique event catalog extending over 13 years, from 2003 to 2016 has been built based on waveform cross-correlation detectors and Hidden Markov Model classifiers. Phases of low seismicity rates are alternating with intense activity intervals that exhibit a strong tidal modulation. We performed a detailed analysis and modeling of the more than 2000 events recorded between July and October 2013. The observations are characterized by a number of very clear signals: (i) the event rate follows both the neap-spring and the semi-diurnal ocean-tide cycle; (ii) recurrences have a characteristic time of approximately 8 minutes; (iii) magnitudes vary systematically both on short and long time scales; and (iv) the events migrate within short-time clusters. We use these observations to constrain the dynamic processes at work at this particular region of the Fimbulisen ice shelf. Our model assumes a local grounding of the ice shelf, where stick-slip motion occurs. We show that the observations can be reproduced considering the modulation of the Coulomb-Failure stress by ocean tides.

Earthquake recurrence and risk assessment in circum-Pacific seismic gaps

USGS Publications Warehouse

Thatcher, W.

1989-01-01

THE development of the concept of seismic gaps, regions of low earthquake activity where large events are expected, has been one of the notable achievements of seismology and plate tectonics. Its application to long-term earthquake hazard assessment continues to be an active field of seismological research. Here I have surveyed well documented case histories of repeated rupture of the same segment of circum-Pacific plate boundary and characterized their general features. I find that variability in fault slip and spatial extent of great earthquakes rupturing the same plate boundary segment is typical rather than exceptional but sequences of major events fill identified seismic gaps with remarkable order. Earthquakes are concentrated late in the seismic cycle and occur with increasing size and magnitude. Furthermore, earthquake rup-ture starts near zones of concentrated moment release, suggesting that high-slip regions control the timing of recurrent events. The absence of major earthquakes early in the seismic cycle indicates a more complex behaviour for lower-slip regions, which may explain the observed cycle-to-cycle diversity of gap-filling sequences. ?? 1989 Nature Publishing Group.

A Randomized Controlled Phase III Trial of Recombinant Human Granulocyte Colony-Stimulating Factor (Filgrastim) for Treatment of Severe Chronic Neutropenia

PubMed Central

Dale, David C.; Bonilla, Mary Ann; Davis, Mark W.; Nakanishi, Arline M.; Hammond, William P.; Kurtzberg, Joanne; Wang, Winfred; Jakubowski, Ann; Winton, Elliott; Lalezari, Parviz; Robinson, William; Glaspy, John A.; Emerson, Steve; Gabrilove, Janice; Vincent, Martha; Boxer, Laurence A.

2014-01-01

Patients with idiopathic, cyclic, and congenital neutropenia have recurrent severe bacterial infections. One hundred twenty-three patients with recurrent infections and severe chronic neutropenia (absolute neutrophil count < 0.5 × 109/L) due to these diseases were enrolled in this multi-center phase III trial. They were randomized to either immediately beginning recombinant human granulocyte colony-stimulating factor (filgrastim) (3.45 to 11.50 μg/kg/d, subcutaneously) or entering a 4-month observation period followed by filgrastim administration. Blood neutrophil counts, bone marrow (BM) cell histology, and incidence and duration of infection-related events were monitored. Of the 123 patients enrolled, 120 received filgrastim. On therapy, 108 patients had a median absolute neutrophil count of ≥ 1.5 × 109/L. Examination of BM aspirates showed increased proportions of maturing neutrophils. Infection-related events were significantly decreased (P < .05) with approximately 50% reduction in the incidence and duration of infection-related events and almost 70% reduction in duration of antibiotic use. Asymptomatic splenic enlargement occurred frequently: adverse events frequently reported were bone pain, headache, and rash, which were generally mild and easily manageable. These data indicate that treatment of patients with severe chronic neutropenia with filgrastim results in a stimulation of BM production and maturation of neutrophils, an increase in circulating neutrophils, and a reduction in infection-related events. PMID:8490166

Effects of acoustic waves on stick-slip in granular media and implications for earthquakes

USGS Publications Warehouse

Johnson, P.A.; Savage, H.; Knuth, M.; Gomberg, J.; Marone, Chris

2008-01-01

It remains unknown how the small strains induced by seismic waves can trigger earthquakes at large distances, in some cases thousands of kilometres from the triggering earthquake, with failure often occurring long after the waves have passed. Earthquake nucleation is usually observed to take place at depths of 10-20 km, and so static overburden should be large enough to inhibit triggering by seismic-wave stress perturbations. To understand the physics of dynamic triggering better, as well as the influence of dynamic stressing on earthquake recurrence, we have conducted laboratory studies of stick-slip in granular media with and without applied acoustic vibration. Glass beads were used to simulate granular fault zone material, sheared under constant normal stress, and subject to transient or continuous perturbation by acoustic waves. Here we show that small-magnitude failure events, corresponding to triggered aftershocks, occur when applied sound-wave amplitudes exceed several microstrain. These events are frequently delayed or occur as part of a cascade of small events. Vibrations also cause large slip events to be disrupted in time relative to those without wave perturbation. The effects are observed for many large-event cycles after vibrations cease, indicating a strain memory in the granular material. Dynamic stressing of tectonic faults may play a similar role in determining the complexity of earthquake recurrence. ??2007 Nature Publishing Group.

Maastricht Delphi Consensus on Event Definitions for Classification of Recurrence in Breast Cancer Research

PubMed Central

van Roozendaal, Lori M.; Strobbe, Luc J. A.; Aebi, Stefan; Cameron, David A.; Dixon, J. Michael; Giuliano, Armando E.; Haffty, Bruce G.; Hickey, Brigid E.; Hudis, Clifford A.; Klimberg, V. Suzanne; Koczwara, Bogda; Kühn, Thorsten; Lippman, Marc E.; Lucci, Anthony; Piccart, Martine; Smith, Benjamin D.; Tjan-Heijnen, Vivianne C. G.; van de Velde, Cornelis J. H.; Van Zee, Kimberly J.; Vermorken, Jan B.; Viale, Giuseppe; Voogd, Adri C.; Wapnir, Irene L.; White, Julia R.; Smidt, Marjolein L.

2014-01-01

Background In breast cancer studies, many different endpoints are used. Definitions are often not provided or vary between studies. For instance, “local recurrence” may include different components in similar studies. This limits transparency and comparability of results. This project aimed to reach consensus on the definitions of local event, second primary breast cancer, regional and distant event for breast cancer studies. Methods The RAND-UCLA Appropriateness method (modified Delphi method) was used. A Consensus Group of international breast cancer experts was formed, including representatives of all involved clinical disciplines. Consensus was reached in two rounds of online questionnaires and one meeting. Results Twenty-four international breast cancer experts participated. Consensus was reached on 134 items in four categories. Local event is defined as any epithelial breast cancer or ductal carcinoma in situ (DCIS) in the ipsilateral breast, or skin and subcutaneous tissue on the ipsilateral thoracic wall. Second primary breast cancer is defined as epithelial breast cancer in the contralateral breast. Regional events are breast cancer in ipsilateral lymph nodes. A distant event is breast cancer in any other location. Therefore, this includes metastasis in contralateral lymph nodes and breast cancer involving the sternal bone. If feasible, tissue sampling of a first, solitary, lesion suspected for metastasis is highly recommended. Conclusion This project resulted in consensus-based event definitions for classification of recurrence in breast cancer research. Future breast cancer research projects should adopt these definitions to increase transparency. This should facilitate comparison of results and conducting reviews as well as meta-analysis. PMID:25381395

A Prospective Multi-center Trial of Escherichia coli Extract for the Prophylactic Treatment of Patients with Chronically Recurrent Cystitis

PubMed Central

Kim, Kun Suk; Kim, Ji-Yoon; Jeong, In Gab; Paick, Jae-Seung; Son, Hwancheol; Lim, Dae Jung; Shim, Hong Bang; Park, Won Hee; Jung, Hee Chang

2010-01-01

We have assessed the efficacy and safety of Escherichia coli extract (ECE; Uro-Vaxom®) which contains active immunostimulating fractions, in the prophylactic treatment of chronically recurrent cystitis. Forty-two patients with more than 2 episodes of cystitis in the proceeding 6 months were treated for 3 months with one capsule daily of ECE and observed for a further 6 months. The primary efficacy criterion was the number of episodes of recurrent cystitis during the 6 months after treatment compared to those during the 6 months before treatment. At the end of the 9-month trial, 34 patients (all women) were eligible for statistical analysis. Their mean age was 56.4 yr (range, 34-75 yr), and they had experienced recurrent urinary tract infections for 7.2±5.2 yr. The number of recurrences was significantly lower during the 6-month follow-up period than during the 6 months preceding the trial (0.35 vs. 4.26, P<0.001). During the follow-up, 28 (82.4%) patients had no recurrences and 4 (11.8%) had 1 each. In patients who relapsed, ECE alleviated cystitis symptoms, including painful voiding, frequency and urgency. There were no serious adverse events related to the study drug. Our study demonstrates the efficacy and safety of ECE in the prophylactic treatment of chronically recurrent cystitis. PMID:20191044

Risk factors for recurrence of venous thromboembolism associated with the use of oral contraceptives.

PubMed

Vaillant-Roussel, Hélène; Ouchchane, Lemlih; Dauphin, Claire; Philippe, Pierre; Ruivard, Marc

2011-11-01

Combined oral contraceptives (COC) increase the risk of venous thromboembolism (VTE), but the risk of recurrent VTE is not precisely determined. In this retrospective cohort study, we sought the risk factors for recurrence after a first VTE that occurred in women taking COC. Time-to-event analysis was done with Kaplan-Meier estimates. In total, 172 patients were included (43% with pulmonary embolism): 82% had no other clinical risk factor for VTE. Among the 160 patients who stopped anticoagulation, the cumulative incidence of recurrent VTE was 5.1% after 1 year and 14.2% after 5 years. Significant factors associated with recurrence were renewed use of COC [hazard ratio (HR)=8.2 (2.1-32.2)], antiphospholipid syndrome [HR=4.1 (1.3-12.5)] and protein C deficiency or factor II G20210A [HR=2.7 (1.1-7)]. Pure-progestin contraception [HR=1.3 (0.5-3.0)] or factor V Leiden [HR=1.3 (0.5-3.4)] did not increase recurrence. Postsurgical VTE had a lower risk of recurrence [HR=0.1 (0.0-0.9)]. Further studies are warranted to determine whether testing for antiphospholipid syndrome, protein C deficiency or the factor II G20210A could modify the duration of anticoagulation. This study confirms the safety of pure-progestin contraception. Copyright © 2011 Elsevier Inc. All rights reserved.

PPM1A Methylation Is Associated With Vascular Recurrence in Aspirin-Treated Patients.

PubMed

Gallego-Fabrega, Cristina; Carrera, Caty; Reny, Jean-Luc; Fontana, Pierre; Slowik, Agnieszka; Pera, Joanna; Pezzini, Alessandro; Serrano-Heras, Gemma; Segura, Tomás; Bin Dukhyil, Abdul-Aziz A; Martí-Fàbregas, Joan; Muiño, Elena; Cullell, Natalia; Montaner, Joan; Krupinski, Jerzy; Fernandez-Cadenas, Israel

2016-07-01

Despite great efforts by pharmacogenetic studies, the causes of aspirin failure to prevent the recurrence of ischemic events remain unclear. Our aim was to study whether epigenetics could be associated with the risk of vascular recurrence in aspirin-treated stroke patients. We performed an epigenetic joint analysis study in 327 patients treated with aspirin. In the discovery stage, we performed a nested case-control study in 38 matched ischemic stroke patients in whom 450 000 methylation sites were analyzed. Nineteen patients presented vascular recurrence after stroke, and 19 matched patients did not present vascular recurrence during the first year of follow-up. In a second stage, 289 new patients were analyzed by EpiTYPER. The following 3 differentially methylated candidate CpG sites, were identified in the discovery stage and analyzed in the second stage: cg26039762 (P=9.69×10(-06), RAF1), cg04985020 (P=3.47×10(-03), PPM1A), and cg08419850 (P=3.47×10(-03), KCNQ1). Joint analysis identified an epigenome-wide association for cg04985020 (PPM1A; P=1.78×10(-07)), with vascular recurrence in patients treated with aspirin. The pattern of differential methylation in PPM1A is associated with vascular recurrence in aspirin-treated stroke patients. © 2016 American Heart Association, Inc.

Mesalamine did not prevent recurrent diverticulitis in phase 3 controlled trials.

PubMed

Raskin, Jeffrey B; Kamm, Michael A; Jamal, M Mazen; Márquez, Juan; Melzer, Ehud; Schoen, Robert E; Szalóki, Tibor; Barrett, Karen; Streck, Paul

2014-10-01

No therapy has been proven to prevent the recurrence of diverticulitis. Mesalamine has shown efficacy in preventing relapse in inflammatory bowel disease, and there is preliminary evidence that it might be effective for diverticular disease. We investigated the efficacy of mesalamine in preventing recurrence of diverticulitis in 2 identical but separate phase 3, randomized, double-blind, placebo-controlled, multicenter trials (identical confirmatory trials were conducted for regulatory reasons). We evaluated the efficacy and safety of multimatrix mesalamine vs placebo in the prevention of recurrent diverticulitis in 590 (PREVENT1) and 592 (PREVENT2) adult patients with ≥1 episodes of acute diverticulitis in the previous 24 months that resolved without surgery. Patients received mesalamine (1.2 g, 2.4 g, or 4.8 g) or placebo once daily for 104 weeks. The primary end point was the proportion of recurrence-free patients at week 104. Diverticulitis recurrence was defined as surgical intervention at any time for diverticular disease or presence of computed tomography scan results demonstrating bowel wall thickening (>5 mm) and/or fat stranding consistent with diverticulitis. For a portion of the study, recurrence also required the presence of abdominal pain and an increase in white blood cells. Mesalamine did not reduce the rate of diverticulitis recurrence at week 104. Among patients in PREVENT1, 53%-63% did not have disease recurrence, compared with 65% of those given placebo. Among patients in PREVENT2, 59%-69% of patients did not have disease recurrence, compared with 68% of those given placebo. Mesalamine did not reduce time to recurrence, and the proportions of patients requiring surgery were comparable among treatment groups. No new adverse events were identified with mesalamine administration. Mesalamine was not superior to placebo in preventing recurrent diverticulitis. Mesalamine is not recommended for this indication. ClinicalTrials.gov ID: NCT00545740 and NCT00545103. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

Comparison of Holocene marine paleoseismic records of two sectors of the Algerian margin: what's the reason for different responses from turbidites?

NASA Astrophysics Data System (ADS)

Cattaneo, Antonio; Babonneau, Nathalie; Ratzov, Gueorgui; Yelles, Karim; Bracène, Rabah; Bachir, Roza Si; Déverchere, Jacques

2016-04-01

The Algerian margin is at the slow convergence (~3mm/yr) of the African and European plates and it is affected by seismic activity linked to the presence of faults located in the coastal region and/or offshore. The historical seismicity record includes earthquakes located all along the margin from the west (1954 Orléansville M6.7; 1980 El Asnam M7.3), to the central area offshore Algiers (2003 Boumerdès M6.9, and also earthquakes of 1847, 1716 et 1365 AD), to the eastern area (two events offshore Djidjelli in 1856). Thanks to recent work on the signature of earthquakes in the deep offshore domain inferred from the analysis of successions of alternating turbidites and hemipelagites, the record of earthquakes could be extended back in time over most of the Holocene, at least in two analysed sectors offshore Kramis and Algiers. Offshore Kramis, thirteen coastal paleoquakes over the last 8 ka support clusters of 3 to 6 events with mean recurrence intervals of ˜300-600 years, separated by two periods of quiescence of ˜1.7 ka without major events on any fault. They imply alternation of broad phases of strain loading and shorter phases of strain release along the fault network (Ratzov et al., 2015). Offshore Algiers, thirty-six events are identified along the Algiers margin segment over the last 9 kyr and are tentatively interpreted as seismically triggered, including the historical events of 2003, 1716 and 1365 AD. The recurrence interval of events varies from 50 to 900 years with three quiescence periods of 800, 1400 and 500 years (7-6.2 ka BP, 5.4-4 ka BP, and 1.5-1 ka BP), supporting an irregular earthquake cyclicity. Overall, the marine paleosesimicity record of the two study areas appears rather different. In particular, slope failures offshore Algiers could occur more frequently because of the proximity of lower magnitude earthquakes, explaining the high occurrence of turbiditic events, while the recurring interval of stronger earthquakes could be more easily comparable in the two margin sectors. Other possible explanations include: i) difference in the tectonic behavior of distinct margin sectors; (ii) temporal and spatial variability in sedimentary processes, possibly due to changes in sediment availability; (iii) different distance of the seismic sources from the areas of sediment destabilisation on the continental slope. Ref. 
Ratzov et al. (2015) Geology 43,4,331-334.

On the role of fluids in stick-slip dynamics of saturated granular fault gouge using a coupled computational fluid dynamics-discrete element approach: STICK-SLIP IN SATURATED FAULT GOUGE

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dorostkar, Omid; Guyer, Robert A.; Johnson, Paul A.

The presence of fault gouge has considerable influence on slip properties of tectonic faults and the physics of earthquake rupture. The presence of fluids within faults also plays a significant role in faulting and earthquake processes. In this study, we present 3-D discrete element simulations of dry and fluid-saturated granular fault gouge and analyze the effect of fluids on stick-slip behavior. Fluid flow is modeled using computational fluid dynamics based on the Navier-Stokes equations for an incompressible fluid and modified to take into account the presence of particles. Analysis of a long time train of slip events shows that themore » (1) drop in shear stress, (2) compaction of granular layer, and (3) the kinetic energy release during slip all increase in magnitude in the presence of an incompressible fluid, compared to dry conditions. We also observe that on average, the recurrence interval between slip events is longer for fluid-saturated granular fault gouge compared to the dry case. This observation is consistent with the occurrence of larger events in the presence of fluid. It is found that the increase in kinetic energy during slip events for saturated conditions can be attributed to the increased fluid flow during slip. Finally, our observations emphasize the important role that fluid flow and fluid-particle interactions play in tectonic fault zones and show in particular how discrete element method (DEM) models can help understand the hydromechanical processes that dictate fault slip.« less

On the role of fluids in stick-slip dynamics of saturated granular fault gouge using a coupled computational fluid dynamics-discrete element approach: STICK-SLIP IN SATURATED FAULT GOUGE

DOE PAGES

Dorostkar, Omid; Guyer, Robert A.; Johnson, Paul A.; ...

2017-05-01

The presence of fault gouge has considerable influence on slip properties of tectonic faults and the physics of earthquake rupture. The presence of fluids within faults also plays a significant role in faulting and earthquake processes. In this study, we present 3-D discrete element simulations of dry and fluid-saturated granular fault gouge and analyze the effect of fluids on stick-slip behavior. Fluid flow is modeled using computational fluid dynamics based on the Navier-Stokes equations for an incompressible fluid and modified to take into account the presence of particles. Analysis of a long time train of slip events shows that themore » (1) drop in shear stress, (2) compaction of granular layer, and (3) the kinetic energy release during slip all increase in magnitude in the presence of an incompressible fluid, compared to dry conditions. We also observe that on average, the recurrence interval between slip events is longer for fluid-saturated granular fault gouge compared to the dry case. This observation is consistent with the occurrence of larger events in the presence of fluid. It is found that the increase in kinetic energy during slip events for saturated conditions can be attributed to the increased fluid flow during slip. Finally, our observations emphasize the important role that fluid flow and fluid-particle interactions play in tectonic fault zones and show in particular how discrete element method (DEM) models can help understand the hydromechanical processes that dictate fault slip.« less

A novel process for introducing a new intraoperative program: a multidisciplinary paradigm for mitigating hazards and improving patient safety.

PubMed

Rodriguez-Paz, Jose M; Mark, Lynette J; Herzer, Kurt R; Michelson, James D; Grogan, Kelly L; Herman, Joseph; Hunt, David; Wardlow, Linda; Armour, Elwood P; Pronovost, Peter J

2009-01-01

Since the Institute of Medicine's report, To Err is Human, was published, numerous interventions have been designed and implemented to correct the defects that lead to medical errors and adverse events; however, most efforts were largely reactive. Safety, communication, team performance, and efficiency are areas of care that attract a great deal of attention, especially regarding the introduction of new technologies, techniques, and procedures. We describe a multidisciplinary process that was implemented at our hospital to identify and mitigate hazards before the introduction of a new technique: high-dose-rate intraoperative radiation therapy, (HDR-IORT). A multidisciplinary team of surgeons, anesthesiologists, radiation oncologists, physicists, nurses, hospital risk managers, and equipment specialists used a structured process that included in situ clinical simulation to uncover concerns among care providers and to prospectively identify and mitigate defects for patients who would undergo surgery using the HDR-IORT technique. We identified and corrected 20 defects in the simulated patient care process before application to actual patients. Subsequently, eight patients underwent surgery using the HDR-IORT technique with no recurrence of simulation-identified or unanticipated defects. Multiple benefits were derived from the use of this systematic process to introduce the HDR-IORT technique; namely, the safety and efficiency of care for this select patient population was optimized, and this process mitigated harmful or adverse events before the inclusion of actual patients. Further work is needed, but the process outlined in this paper can be universally applied to the introduction of any new technologies, treatments, or procedures.

Whole-exome sequencing reveals the spectrum of gene mutations and the clonal evolution patterns in paediatric acute myeloid leukaemia.

PubMed

Shiba, Norio; Yoshida, Kenichi; Shiraishi, Yuichi; Okuno, Yusuke; Yamato, Genki; Hara, Yusuke; Nagata, Yasunobu; Chiba, Kenichi; Tanaka, Hiroko; Terui, Kiminori; Kato, Motohiro; Park, Myoung-Ja; Ohki, Kentaro; Shimada, Akira; Takita, Junko; Tomizawa, Daisuke; Kudo, Kazuko; Arakawa, Hirokazu; Adachi, Souichi; Taga, Takashi; Tawa, Akio; Ito, Etsuro; Horibe, Keizo; Sanada, Masashi; Miyano, Satoru; Ogawa, Seishi; Hayashi, Yasuhide

2016-11-01

Acute myeloid leukaemia (AML) is a molecularly and clinically heterogeneous disease. Targeted sequencing efforts have identified several mutations with diagnostic and prognostic values in KIT, NPM1, CEBPA and FLT3 in both adult and paediatric AML. In addition, massively parallel sequencing enabled the discovery of recurrent mutations (i.e. IDH1/2 and DNMT3A) in adult AML. In this study, whole-exome sequencing (WES) of 22 paediatric AML patients revealed mutations in components of the cohesin complex (RAD21 and SMC3), BCORL1 and ASXL2 in addition to previously known gene mutations. We also revealed intratumoural heterogeneities in many patients, implicating multiple clonal evolution events in the development of AML. Furthermore, targeted deep sequencing in 182 paediatric AML patients identified three major categories of recurrently mutated genes: cohesion complex genes [STAG2, RAD21 and SMC3 in 17 patients (8·3%)], epigenetic regulators [ASXL1/ASXL2 in 17 patients (8·3%), BCOR/BCORL1 in 7 patients (3·4%)] and signalling molecules. We also performed WES in four patients with relapsed AML. Relapsed AML evolved from one of the subclones at the initial phase and was accompanied by many additional mutations, including common driver mutations that were absent or existed only with lower allele frequency in the diagnostic samples, indicating a multistep process causing leukaemia recurrence. © 2016 John Wiley & Sons Ltd.

Amplitude and recurrence time analysis of LP activity at Mount Etna, Italy

NASA Astrophysics Data System (ADS)

Cauchie, Léna; Saccorotti, Gilberto; Bean, Christopher J.

2015-09-01

The aim of this work is to improve our understanding of the long-period (LP) source mechanism at Mount Etna (Italy) through a statistical analysis of detailed LP catalogues. The behavior of LP activity is compared with the empirical laws governing earthquake recurrence, in order to investigate whether any relationships exist between these two apparently different earthquake classes. We analyzed a family of 8894 events detected during a temporary experiment in August 2005. For that time interval, the LP activity is sustained in time and the volcano did not exhibit any evident sign of unrest. The completeness threshold of the catalogue is established through a detection test based on synthetic waveforms. The retrieved amplitude distribution differs significantly from the Gutenberg-Richter law, and the interevent times distribution does not follow the typical γ law, expected for tectonic activity. In order to compare these results with a catalogue for which the source mechanism is well established, we applied the same procedure to a data set from Stromboli Volcano, where recurrent LP activity is closely related to very-long-period pulses, in turn associated with the summit explosions. Our results indicate that the two catalogues exhibit similar behavior in terms of amplitude and interevent time distributions. This suggests that the Etna's LP signals are most likely driven by stress changes caused by an intermittent degassing process occurring at depth, similar to that which drives the summit explosions at Stromboli Volcano.

Aspirin in venous leg ulcer study (ASPiVLU): study protocol for a randomised controlled trial.

PubMed

Weller, Carolina D; Barker, Anna; Darby, Ian; Haines, Terrence; Underwood, Martin; Ward, Stephanie; Aldons, Pat; Dapiran, Elizabeth; Madan, Jason J; Loveland, Paula; Sinha, Sankar; Vicaretti, Mauro; Wolfe, Rory; Woodward, Michael; McNeil, John

2016-04-11

Venous leg ulceration is a common and costly problem that is expected to worsen as the population ages. Current treatment is compression therapy; however, up to 50 % of ulcers remain unhealed after 2 years, and ulcer recurrence is common. New treatments are needed to address those wounds that are more challenging to heal. Targeting the inflammatory processes present in venous ulcers is a possible strategy. Limited evidence suggests that a daily dose of aspirin may be an effective adjunct to aid ulcer healing and reduce recurrence. The Aspirin in Venous Leg Ulcer study (ASPiVLU) will investigate whether 300-mg oral doses of aspirin improve time to healing. This randomised, double-blinded, multicentre, placebo-controlled, clinical trial will recruit participants with venous leg ulcers from community settings and hospital outpatient wound clinics across Australia. Two hundred sixty-eight participants with venous leg ulcers will be randomised to receive either aspirin or placebo, in addition to compression therapy, for 24 weeks. The primary outcome is time to healing within 12 weeks. Secondary outcomes are ulcer recurrence, wound pain, quality of life and wellbeing, adherence to study medication, adherence to compression therapy, serum inflammatory markers, hospitalisations, and adverse events at 24 weeks. The ASPiVLU trial will investigate the efficacy and safety of aspirin as an adjunct to compression therapy to treat venous leg ulcers. Study completion is anticipated to occur in December 2018. Australian New Zealand Clinical Trials Registry, ACTRN12614000293662.

Computer Game Play Reduces Intrusive Memories of Experimental Trauma via Reconsolidation-Update Mechanisms.

PubMed

James, Ella L; Bonsall, Michael B; Hoppitt, Laura; Tunbridge, Elizabeth M; Geddes, John R; Milton, Amy L; Holmes, Emily A

2015-08-01

Memory of a traumatic event becomes consolidated within hours. Intrusive memories can then flash back repeatedly into the mind's eye and cause distress. We investigated whether reconsolidation-the process during which memories become malleable when recalled-can be blocked using a cognitive task and whether such an approach can reduce these unbidden intrusions. We predicted that reconsolidation of a reactivated visual memory of experimental trauma could be disrupted by engaging in a visuospatial task that would compete for visual working memory resources. We showed that intrusive memories were virtually abolished by playing the computer game Tetris following a memory-reactivation task 24 hr after initial exposure to experimental trauma. Furthermore, both memory reactivation and playing Tetris were required to reduce subsequent intrusions (Experiment 2), consistent with reconsolidation-update mechanisms. A simple, noninvasive cognitive-task procedure administered after emotional memory has already consolidated (i.e., > 24 hours after exposure to experimental trauma) may prevent the recurrence of intrusive memories of those emotional events. © The Author(s) 2015.

The Mutational Landscape of Adenoid Cystic Carcinoma

PubMed Central

Ho, Allen S.; Kannan, Kasthuri; Roy, David M.; Morris, Luc G.T.; Ganly, Ian; Katabi, Nora; Ramaswami, Deepa; Walsh, Logan A.; Eng, Stephanie; Huse, Jason T.; Zhang, Jianan; Dolgalev, Igor; Huberman, Kety; Heguy, Adriana; Viale, Agnes; Drobnjak, Marija; Leversha, Margaret A.; Rice, Christine E.; Singh, Bhuvanesh; Iyer, N. Gopalakrishna; Leemans, C. Rene; Bloemena, Elisabeth; Ferris, Robert L.; Seethala, Raja R.; Gross, Benjamin E.; Liang, Yupu; Sinha, Rileen; Peng, Luke; Raphael, Benjamin J.; Turcan, Sevin; Gong, Yongxing; Schultz, Nikolaus; Kim, Seungwon; Chiosea, Simion; Shah, Jatin P.; Sander, Chris; Lee, William; Chan, Timothy A.

2013-01-01

Adenoid cystic carcinomas (ACCs) are among the most enigmatic of human malignancies. These aggressive salivary cancers frequently recur and metastasize despite definitive treatment, with no known effective chemotherapy regimen. Here, we determined the ACC mutational landscape and report the exome or whole genome sequences of 60 ACC tumor/normal pairs. These analyses revealed a low exonic somatic mutation rate (0.31 non-silent events/megabase) and wide mutational diversity. Interestingly, mutations selectively involved chromatin state regulators, such as SMARCA2, CREBBP, and KDM6A, suggesting aberrant epigenetic regulation in ACC oncogenesis. Mutations in genes central to DNA damage and protein kinase A signaling also implicate these processes. We observed MYB-NFIB translocations and somatic mutations in MYB-associated genes, solidifying these aberrations as critical events. Lastly, we identified recurrent mutations in the FGF/IGF/PI3K pathway that may potentially offer new avenues for therapy (30%). Collectively, our observations establish a molecular foundation for understanding and exploring new treatments for ACC. PMID:23685749

Computer Game Play Reduces Intrusive Memories of Experimental Trauma via Reconsolidation-Update Mechanisms

PubMed Central

James, Ella L.; Bonsall, Michael B.; Hoppitt, Laura; Tunbridge, Elizabeth M.; Geddes, John R.; Milton, Amy L.

2015-01-01

Memory of a traumatic event becomes consolidated within hours. Intrusive memories can then flash back repeatedly into the mind’s eye and cause distress. We investigated whether reconsolidation—the process during which memories become malleable when recalled—can be blocked using a cognitive task and whether such an approach can reduce these unbidden intrusions. We predicted that reconsolidation of a reactivated visual memory of experimental trauma could be disrupted by engaging in a visuospatial task that would compete for visual working memory resources. We showed that intrusive memories were virtually abolished by playing the computer game Tetris following a memory-reactivation task 24 hr after initial exposure to experimental trauma. Furthermore, both memory reactivation and playing Tetris were required to reduce subsequent intrusions (Experiment 2), consistent with reconsolidation-update mechanisms. A simple, noninvasive cognitive-task procedure administered after emotional memory has already consolidated (i.e., > 24 hours after exposure to experimental trauma) may prevent the recurrence of intrusive memories of those emotional events. PMID:26133572

Discordant 14C ages from buried tidal-marsh soils in the Cascadia subduction zone, southern Oregon coast

USGS Publications Warehouse

Nelson, A.R.

1992-01-01

Peaty, tidal-marsh soils interbedded with estuarine mud in late Holocene stratigraphic sequences near Coos Bay, Oregon, may have been submerged and buried during great (M > 8) subduction earthquakes, smaller localized earthquakes, or by nontectonic processes. Radiocarbon dating might help distinguish among these alternatives by showing that soils at different sites were submerged at different times along this part of the Cascadia subduction zone. But comparison of conventional 14C ages for different materials from the same buried soils shows that they contain materials that differ in age by many hundreds of years. Errors in calibrated soil ages represent about the same length of time as recurrence times for submergence events (150-500 yr)-this similarity precludes using conventional 14C ages to distinguish buried soils along the southern Oregon coast. Accelerator mass spectrometer 14C ages of carefully selected macrofossils from the tops of peaty soils should provide more precise estimates of the times of submergence events. ?? 1992.

Safety and efficacy of first-line bevacizumab-based therapy in advanced non-squamous non-small-cell lung cancer (SAiL, MO19390): a phase 4 study.

PubMed

Crinò, Lucio; Dansin, Eric; Garrido, Pilar; Griesinger, Frank; Laskin, Janessa; Pavlakis, Nick; Stroiakovski, Daniel; Thatcher, Nick; Tsai, Chun-Ming; Wu, Yi-long; Zhou, Caicun

2010-08-01

Results of two phase 3 trials have shown first-line bevacizumab in combination with chemotherapy improves clinical outcomes in patients with advanced or recurrent non-squamous non-small-cell lung cancer (NSCLC). The SAiL (MO19390) study was undertaken to assess the safety and efficacy of first-line bevacizumab combined with standard chemotherapy regimens in clinical practice. Between August, 2006, and June, 2008, patients with untreated locally advanced, metastatic, or recurrent non-squamous NSCLC were recruited to this open-label, single group, phase 4 study from centres in 40 countries. Eligible patients had histologically or cytologically documented inoperable, locally advanced, metastatic, or recurrent disease (stage IIIB-IV); an Eastern Cooperative Oncology Group performance status of 0-2; and adequate haematological, hepatic, and renal function. Patients received bevacizumab (7.5 or 15 mg/kg every 3 weeks) plus standard chemotherapy for up to six cycles, followed by single-agent bevacizumab until disease progression. The primary endpoint was safety; analysis was by intention to treat (ITT). This study is registered with ClinicalTrials.gov, number NCT00451906. At the final data cutoff (July 24, 2009), an ITT population of 2212 patients was assessed. The incidence of clinically significant (grade > or = 3) adverse events of special interest was generally low; thromboembolism occurred in 172 (8%) patients, hypertension in 125 (6%), bleeding in 80 (4%), proteinuria in 67 (3%), and pulmonary haemorrhage in 15 (1%). 57 (3%) patients died because of these adverse events, with thromboembolism (26 patients, 1%) and bleeding (17, 1%) as the most common causes. The most common grade 3 or higher serious adverse events deemed by investigators to be associated with bevacizumab were pulmonary embolism (28 patients; 1%) and epistaxis, neutropenia, febrile neutropenia, and deep vein thrombosis (all of which occurred in 13 patients [1%]). Bevacizumab was temporarily interrupted after 28 (2%) of 1347 bleeding events and 72 (7%) of 1025 hypertension events, and permanently discontinued after 110 (8%) bleeding events and 40 (4%) hypertension events. No new safety signals were reported. Our results confirm the manageable safety profile of first-line bevacizumab in combination with various standard chemotherapy regimens for treatment of advanced non-squamous NSCLC. F Hoffmann-La Roche Ltd. 2010 Elsevier Ltd. All rights reserved.

Biometrical issues in the analysis of adverse events within the benefit assessment of drugs.

PubMed

Bender, Ralf; Beckmann, Lars; Lange, Stefan

2016-07-01

The analysis of adverse events plays an important role in the benefit assessment of drugs. Consequently, results on adverse events are an integral part of reimbursement dossiers submitted by pharmaceutical companies to health policy decision-makers. Methods applied in the analysis of adverse events commonly include simple standard methods for contingency tables. However, the results produced may be misleading if observations are censored at the time of discontinuation due to treatment switching or noncompliance, resulting in unequal follow-up periods. In this paper, we present examples to show that the application of inadequate methods for the analysis of adverse events in the reimbursement dossier can lead to a downgrading of the evidence on a drug's benefit in the subsequent assessment, as greater harm from the drug cannot be excluded with sufficient certainty. Legal regulations on the benefit assessment of drugs in Germany are presented, in particular, with regard to the analysis of adverse events. Differences in safety considerations between the drug approval process and the benefit assessment are discussed. We show that the naive application of simple proportions in reimbursement dossiers frequently leads to uninterpretable results if observations are censored and the average follow-up periods differ between treatment groups. Likewise, the application of incidence rates may be misleading in the case of recurrent events and unequal follow-up periods. To allow for an appropriate benefit assessment of drugs, adequate survival time methods accounting for time dependencies and duration of follow-up are required, not only for time-to-event efficacy endpoints but also for adverse events. © 2016 The Authors. Pharmaceutical Statistics published by John Wiley & Sons Ltd. © 2016 The Authors. Pharmaceutical Statistics published by John Wiley & Sons Ltd.

Factors associated with occasional and recurrent falls in Mexican community-dwelling older people.

PubMed

Agudelo-Botero, Marcela; Giraldo-Rodríguez, Liliana; Murillo-González, Juana Catalina; Mino-León, Dolores; Cruz-Arenas, Esteban

2018-01-01

Falls are a frequent event among older adults that can cause wounds, disability, psychological disorders, and premature death. Although the large number of existing studies on the issue, few have been conducted in middle- and low-income countries. The objective of the present study is to identify the sociodemographic, medical, and functional performance factors associated with occasional and recurrent falls in Mexican older adults dwelling in community. Cross-sectional analysis of 9 598 adults ≥60 years old who participated in the fourth round (2015) of the Mexican Health and Aging Study. Bivariate tests were performed to evaluate the differences between covariates by distinct fall groups (no falls, occasional falls, and recurrent falls). Multiple logistic regressions with unadjusted and adjusted models were estimated. Approximately 46% of older adults had had at least one fall during the previous two years (one fall 16% and recurrent falls 30%). Occasional falls were only associated with being a woman; in addition to the sex, recurrent falls were strongly associated with advanced age, rural residence, bad and very bad self-perception of health status, activity-limiting pain, urinary incontinence, depression, arthritis, limitations in basic activities of daily living, and limitations in advanced activities of daily living. Falls, primarily recurrent falls, deserve to be addressed through multifactorial strategies that include different areas of intervention.

Up-regulation of CD44 in the development of metastasis, recurrence and drug resistance of ovarian cancer

PubMed Central

Gao, Yan; Foster, Rosemary; Yang, Xiaoqian; Feng, Yong; Shen, Jacson K.; Mankin, Henry J.; Hornicek, Francis J.; Amiji, Mansoor M.; Duan, Zhenfeng

2015-01-01

The clinical significance of Cluster of Differentiation 44 (CD44) remains controversial in human ovarian cancer. The aim of this study is to evaluate the clinical significance of CD44 expression by using a unique tissue microarray, and then to determine the biological functions of CD44 in ovarian cancer. In this study, a unique ovarian cancer tissue microarray (TMA) was constructed with paired primary, metastatic, and recurrent tumor tissues from 26 individual patients. CD44 expression in TMA was assessed by immunohistochemistry. Both the metastatic and recurrent ovarian cancer tissues expressed higher level of CD44 than the patient-matched primary tumor. A significant association has been shown between CD44 expression and both the disease free survival and overall survival. A strong increase of CD44 was found in the tumor recurrence of mouse model. Finally, when CD44 was knocked down, proliferation, migration/invasion activity, and spheroid formation were significantly suppressed, while drug sensitivity was enhanced. Thus, up-regulation of CD44 represents a crucial event in the development of metastasis, recurrence, and drug resistance to current treatments in ovarian cancer. Developing strategies to target CD44 may prevent metastasis, recurrence, and drug resistance in ovarian cancer. PMID:25823654

Preeclampsia: Reflections on How to Counsel About Preventing Recurrence.

PubMed

Costa, Maria Laura

2015-10-01

Preeclampsia is one of the most challenging diseases of pregnancy, with unclear etiology, no specific marker for prediction, and no precise treatment besides delivery of the placenta. Many risk factors have been identified, and diagnostic and management tools have improved in recent years. However, this disease remains one of the leading causes of maternal morbidity and mortality worldwide, especially in under-resourced settings. A history of previous preeclampsia is a known risk factor for a new event in a future pregnancy, with recurrence rates varying from less than 10% to 65%, depending on the population or methodology considered. A recent review that performed an individual participant data meta-analysis on the recurrence of hypertensive disorders of pregnancy in over 99 000 women showed an overall recurrence rate of 20.7%; when specifically considering preeclampsia, it was 13.8%, with milder disease upon recurrence. Prevention of recurrent preeclampsia has been attempted by changes in lifestyle, dietary supplementation, antihypertensive drugs, antithrombotic agents, and others, with much uncertainty about benefit. It is always challenging to treat and counsel a woman with a previous history of preeclampsia; this review will be based on hypothetical clinical cases, using common scenarios in obstetrical practice to consider the available evidence on how to counsel each woman during pre-conception and prenatal consultations.

Manuka honey as an effective treatment for chronic pilonidal sinus wounds.

PubMed

Thomas, M; Hamdan, M; Hailes, S; Walker, M

2011-11-01

A retrospective study to investigate the effectiveness of topical manuka honey in the treatment of chronic or recurrent pilonidal sinus disease (PSD), assessing the ability of this simple dressing technique to achieve complete wound healing, the time taken to achieve healing and the recurrence rate. All patients who received manuka honey dressing therapy following surgical intervention for chronic or recurrent PSD were identified over a 4-year period. In a retrospective review of case notes, data were collected on patient sex, age, nature of surgical procedures performed, time to achieve complete wound healing, and recurrences after completion of honey therapy. Seventeen patients were eligible for inclusion in the study. Mean time to commence honey therapy post-surgery was 93 days (5-517 days; median 33 days); 15 patients achieved complete wound healing, in a mean time of 65 days (14-264 days; median 49 days). Honey was discontinued in one patient due to an adverse event, and two patients experienced recurrence several months after completing honey therapy. Manuka honey dressing therapy provides an effective topical treatment for chronic/recurrent PSD. Further research is necessary to determine the optimum dressing protocol. The authors have no conflicts of interest to declare. There were no external sources of funding for this study.

Up-regulation of CD44 in the development of metastasis, recurrence and drug resistance of ovarian cancer.

PubMed

Gao, Yan; Foster, Rosemary; Yang, Xiaoqian; Feng, Yong; Shen, Jacson K; Mankin, Henry J; Hornicek, Francis J; Amiji, Mansoor M; Duan, Zhenfeng

2015-04-20

The clinical significance of Cluster of Differentiation 44 (CD44) remains controversial in human ovarian cancer. The aim of this study is to evaluate the clinical significance of CD44 expression by using a unique tissue microarray, and then to determine the biological functions of CD44 in ovarian cancer. In this study, a unique ovarian cancer tissue microarray (TMA) was constructed with paired primary, metastatic, and recurrent tumor tissues from 26 individual patients. CD44 expression in TMA was assessed by immunohistochemistry. Both the metastatic and recurrent ovarian cancer tissues expressed higher level of CD44 than the patient-matched primary tumor. A significant association has been shown between CD44 expression and both the disease free survival and overall survival. A strong increase of CD44 was found in the tumor recurrence of mouse model. Finally, when CD44 was knocked down, proliferation, migration/invasion activity, and spheroid formation were significantly suppressed, while drug sensitivity was enhanced. Thus, up-regulation of CD44 represents a crucial event in the development of metastasis, recurrence, and drug resistance to current treatments in ovarian cancer. Developing strategies to target CD44 may prevent metastasis, recurrence, and drug resistance in ovarian cancer.

Outcomes Associated With Resuming Warfarin Treatment After Hemorrhagic Stroke or Traumatic Intracranial Hemorrhage in Patients With Atrial Fibrillation.

PubMed

Nielsen, Peter Brønnum; Larsen, Torben Bjerregaard; Skjøth, Flemming; Lip, Gregory Y H

2017-04-01

The increase in the risk for bleeding associated with antithrombotic therapy causes a dilemma in patients with atrial fibrillation (AF) who sustain an intracranial hemorrhage (ICH). A thrombotic risk is present; however, a risk for serious harm associated with resumption of anticoagulation therapy also exists. To investigate the prognosis associated with resuming warfarin treatment stratified by the type of ICH (hemorrhagic stroke or traumatic ICH). This nationwide observational cohort study included patients with AF who sustained an incident ICH event during warfarin treatment from January 1, 1998, through February 28, 2016. Follow-up was completed April 30, 2016. Resumption of warfarin treatment was evaluated after hospital discharge. No oral anticoagulant treatment or resumption of warfarin treatment, included as a time-dependent exposure. One-year observed event rates per 100 person-years were calculated, and treatment strategies were compared using time-dependent Cox proportional hazards regression models with adjustment for age, sex, length of hospital stay, comorbidities, and concomitant medication use. A total of 2415 patients with AF in this cohort (1481 men [61.3%] and 934 women [38.7%]; mean [SD] age, 77.1 years [9.1 years]) sustained an ICH event. Of these events, 1325 were attributable to hemorrhagic stroke and 1090 were secondary to trauma. During the first year, 305 patients with a hemorrhagic stroke (23.0%) died, whereas 210 in the traumatic ICH group (19.3%) died. Among patients with hemorrhagic stroke, resuming warfarin therapy was associated with a lower rate of ischemic stroke or systemic embolism (SE) (adjusted hazard ratio [AHR], 0.49; 95% CI, 0.24-1.02) and an increased rate of recurrent ICH (AHR, 1.31; 95% CI, 0.68-2.50) compared with not resuming warfarin therapy, but these differences did not reach statistical significance. For patients with traumatic ICH, resuming warfarin therapy also was associated with a lower rate of ischemic stroke or SE (AHR, 0.40; 95% CI, 0.15-1.11); however, in contrast to patients with hemorrhagic stroke, therapy resumption was associated with a significantly lower rate of recurrent ICH (AHR, 0.45; 95% CI, 0.26-0.76). A reduction in mortality was associated with resuming warfarin therapy among patients with hemorrhagic stroke (AHR, 0.51; 95% CI, 0.37-0.71) and those with traumatic ICH (AHR, 0.35; 95% CI, 0.23-0.52). Resumption of warfarin therapy after spontaneous hemorrhagic stroke in patients with AF was associated with a lower rate of ischemic events and a higher rate of recurrent ICH. Among patients with a traumatic ICH, a similar lower rate of ischemic events was found; however, a lower relative risk for recurrent ICH despite resuming warfarin treatment was also revealed.

Context-dependent memory following recurrent hypoglycaemia in non-diabetic rats is mediated via glucocorticoid signalling in the dorsal hippocampus.

PubMed

Osborne, Danielle M; O'Leary, Kelsey E; Fitzgerald, Dennis P; George, Alvin J; Vidal, Michael M; Anderson, Brian M; McNay, Ewan C

2017-01-01

Recurrent hypoglycaemia is primarily caused by repeated over-administration of insulin to patients with diabetes. Although cognition is impaired during hypoglycaemia, restoration of euglycaemia after recurrent hypoglycaemia is associated with improved hippocampally mediated memory. Recurrent hypoglycaemia alters glucocorticoid secretion in response to hypoglycaemia; glucocorticoids are well established to regulate hippocampal processes, suggesting a possible mechanism for recurrent hypoglycaemia modulation of subsequent cognition. We tested the hypothesis that glucocorticoids within the dorsal hippocampus might mediate the impact of recurrent hypoglycaemia on hippocampal cognitive processes. We characterised changes in the dorsal hippocampus at several time points to identify specific mechanisms affected by recurrent hypoglycaemia, using a well-validated 3 day model of recurrent hypoglycaemia either alone or with intrahippocampal delivery of glucocorticoid (mifepristone) and mineralocorticoid (spironolactone) receptor antagonists prior to each hypoglycaemic episode. Recurrent hypoglycaemia enhanced learning and also increased hippocampal expression of glucocorticoid receptors, serum/glucocorticoid-regulated kinase 1, cyclic AMP response element binding (CREB) phosphorylation, and plasma membrane levels of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartic acid (NMDA) receptors. Both hippocampus-dependent memory enhancement and the molecular changes were reversed by glucocorticoid receptor antagonist treatment. These results indicate that increased glucocorticoid signalling during recurrent hypoglycaemia produces several changes in the dorsal hippocampus that are conducive to enhanced hippocampus-dependent contextual learning. These changes appear to be adaptive, and in addition to supporting cognition may reduce damage otherwise caused by repeated exposure to severe hypoglycaemia.

Investigation of freeway operations in metro Detroit.

DOT National Transportation Integrated Search

2011-10-01

Traffic incidents are the primary cause of non-recurrent congestion in urban areas, resulting in : reductions in roadway capacity due to crashes, vehicle breakdowns, and other events. In addition to : contributing to congestion and delay, incidents c...

Recurrent Otitis Media and Attachment Security: A Path Model.

ERIC Educational Resources Information Center

McCallum, Michelle S.; McKim, Margaret K.

1999-01-01

Used regular telephone interviews over six months to examine processes through which recurrent episodes of otitis media influence children's attachment security. Found that recurrent otitis media negatively affected attachment security by increasing mothers' perceptions of their children as behaving more negatively. Parenting stress was not…

A statistical framework for evaluating neural networks to predict recurrent events in breast cancer

NASA Astrophysics Data System (ADS)

Gorunescu, Florin; Gorunescu, Marina; El-Darzi, Elia; Gorunescu, Smaranda

2010-07-01

Breast cancer is the second leading cause of cancer deaths in women today. Sometimes, breast cancer can return after primary treatment. A medical diagnosis of recurrent cancer is often a more challenging task than the initial one. In this paper, we investigate the potential contribution of neural networks (NNs) to support health professionals in diagnosing such events. The NN algorithms are tested and applied to two different datasets. An extensive statistical analysis has been performed to verify our experiments. The results show that a simple network structure for both the multi-layer perceptron and radial basis function can produce equally good results, not all attributes are needed to train these algorithms and, finally, the classification performances of all algorithms are statistically robust. Moreover, we have shown that the best performing algorithm will strongly depend on the features of the datasets, and hence, there is not necessarily a single best classifier.

Time-decreasing hazard and increasing time until the next earthquake

DOE Office of Scientific and Technical Information (OSTI.GOV)

Corral, Alvaro

2005-01-01

The existence of a slowly always decreasing probability density for the recurrence times of earthquakes in the stationary case implies that the occurrence of an event at a given instant becomes more unlikely as time since the previous event increases. Consequently, the expected waiting time to the next earthquake increases with the elapsed time, that is, the event moves away fast to the future. We have found direct empirical evidence of this counterintuitive behavior in two worldwide catalogs as well as in diverse regional catalogs. Universal scaling functions describe the phenomenon well.

Field-Analytical approach of land-sea records for elucidating the Younger Dryas Boundary syndrome

NASA Astrophysics Data System (ADS)

Ge, T.; Courty, M. M.; Guichard, F.

2009-12-01

Linking lonsdaleite crystals, carbon spherules and diamond polymorphs from the North American dark layers at 12.9 cal yr B.P. to a cosmic event has questioned the nature and timing of the related impact processes. A global signal should trace the invoked airshocks and/or surface impacts from a swarm of comets or carbonaceous chondrites. Here we report on the contextual analytical study of debris fall events from three reference sequences of the Younger Dyras period (11-13 ka cal BP) : (1) sand dune fields along the French Atlantic coast at the Audenge site; (2) A 10 m record of detrital/bioorganic accumulation in the southern basin of the Caspian Sea with regular sedimentation rate (0.1 to 3 mm per year) from 14 to 2-ka BP cal; (3) the Paijan sequence (Peruvian coastal desert) offering fossiliferous fluvial layers with the last large mammals and aquatic fauna at 13 ka BP sealed by abiotic sand dunes. The three sequences display one remarkable layer of exogenous air-transported microdebris that is part of a complex time series of recurrent fine dust/wildfire events. The sharp debris-rich microfacies and its association to ashes derived from calcination of the local vegetation suggest instantaneous deposition synchronous to a high intensity wildfire. The debris assemblage comprises microtektite-like glassy spherules, partly devitrified glass shards, unmelted to partly melted sedimentary and igneous clasts, terrestrial native metals, and carbonaceous components. The later occur as grape-clustered polymers, vitrified graphitic carbon, amorphous carbon spherules with a honeycomb pattern, and green carbon fibres with recrystallized quartz and metal blebs. Evidence for high temperature formation from a heterogeneous melt with solid debris and volatile components derived from carbonaceous precursors supports an impact origin from an ejecta plume. The association of debris deposition to total firing would trace a high energy airburst with surface effects of the fireball. In contrast, microfacies and debris composition of the recurrent fine dust/wildfire events would trace a series of a low energy airburst. Their record is expressed in the Audenge sequence by a series of water-laid laminae of charred pine residues formed of carbonaceous spherules wrapped by carbonaceous polymers that includes lonsdaleite crystals as detected by high resolution in situ micro-Raman analysis. This association suggests recurrent flash forest wildfires ignited by hot spray of carbon-rich debris, followed by heavy snow falls. The record from the Peruvian desert suggests a possible linkage between the repeated debris fall/wildfires during the Younger Dryas and the following irreversible aridity along the Peruvian cost. In contrast the Caspian record of the Younger Dryas period indicates more gradual changes, possibly buffered by the hydrological functioning of the Caspian sea in a complex region. The Audenge context offers the amplified signal needed to understand at local to global scales the spatio-temporal pattern of impact-airburst events.

Care for women with prior preterm birth.

PubMed

Iams, Jay D; Berghella, Vincenzo

2010-08-01

Women who have delivered an infant between 16 and 36 weeks' gestation have an increased risk of preterm birth in subsequent pregnancies. The risk increases with more than 1 preterm birth and is inversely proportional to the gestational age of the previous preterm birth. African American women have rates of recurrent preterm birth that are nearly twice that of women of other backgrounds. An approximate risk of recurrent preterm birth can be estimated by a comprehensive reproductive history, with emphasis on maternal race, the number and gestational age of prior births, and the sequence of events preceding the index preterm birth. Interventions including smoking cessation, eradication of asymptomatic bacteriuria, progestational agents, and cervical cerclage can reduce the risk of recurrent preterm birth when employed appropriately. Copyright (c) 2010 Mosby, Inc. All rights reserved.

A geodetic matched-filter search for slow slip with application to the Mexico subduction zone

NASA Astrophysics Data System (ADS)

Rousset, B.; Campillo, M.; Lasserre, C.; Frank, W.; Cotte, N.; Walpersdorf, A.; Socquet, A.; Kostoglodov, V.

2017-12-01

Since the discovery of slow slip events, many methods have been successfully applied to model obvious transient events in geodetic time series, such as the widely used network strain filter. Independent seismological observations of tremors or low frequency earthquakes and repeating earthquakes provide evidence of low amplitude slow deformation but do not always coincide with clear occurrences of transient signals in geodetic time series. Here, we aim to extract the signal corresponding to slow slips hidden in the noise of GPS time series, without using information from independent datasets. We first build a library of synthetic slow slip event templates by assembling a source function with Green's functions for a discretized fault. We then correlate the templates with post-processed GPS time series. Once the events have been detected in time, we estimate their duration T and magnitude Mw by modelling a weighted stack of GPS time series. An analysis of synthetic time series shows that this method is able to resolve the correct timing, location, T and Mw of events larger than Mw 6.0 in the context of the Mexico subduction zone. Applied on a real data set of 29 GPS time series in the Guerrero area from 2005 to 2014, this technique allows us to detect 28 transient events from Mw 6.3 to 7.2 with durations that range from 3 to 39 days. These events have a dominant recurrence time of 40 days and are mainly located at the down dip edges of the Mw > 7.5 SSEs.

Management of recurrent inflammatory choroidal neovascular membrane secondary to Vogt-Koyanagi-Harada syndrome, using combined intravitreal injection of bevacizumab and triamcinolone acetate.

PubMed

Pai, Sivakami A; Hebri, Sudhira P; Lootah, Afra M

2012-01-01

The purpose of this report is to evaluate the efficacy and safety of combined intravitreal injection of bevacizumab and intravitreal triamcinolone acetonide (IVTA) for recurrent inflammatory choroidal neovascular membrane (CNVM). It was a prospective interventional study of a young female, who was a known case of Vogt-Koyanagi-Harada syndrome. She presented with an inflammatory choroidal neovascualar membrane and signs of panuveitis in the right eye. She underwent a complete ophthalmic examination. She was given intravitreal injection of bevacizumab and IVTA at different sites. There was complete regression of CNVM and ocular inflammation within a week. After six months, she had recurrence of CNVM in the same eye, which was treated similarly. There was a complete resolution of CNVM and ocular inflammation after the combination therapy and systemic steroids, until one year of follow-up. No serious systemic or ocular adverse events were noted. Combination therapy appears to be an effective and safe method in the management of recurrent inflammatory CNVM.

The Nazca-South American convergence rate and the recurrence of the great 1960 Chilean earthquake

NASA Technical Reports Server (NTRS)

Stein, S.; Engeln, J. F.; Demets, C.; Gordon, R. G.; Woods, D.

1986-01-01

The seismic slip rate along the Chile Trench estimated from the slip in the great 1960 earthquake and the recurrence history of major earthquakes has been interpreted as consistent with the subduction rate of the Nazca plate beneath South America. The convergence rate, estimated from global relative plate motion models, depends significantly on closure of the Nazca - Antarctica - South America circuit. NUVEL-1, a new plate motion model which incorporates recently determined spreading rates on the Chile Rise, shows that the average convergence rate over the last three million years is slower than previously estimated. If this time-averaged convergence rate provides an appropriate upper bound for the seismic slip rate, either the characteristic Chilean subduction earthquake is smaller than the 1960 event, the average recurrence interval is greater than observed in the last 400 years, or both. These observations bear out the nonuniformity of plate motions on various time scales, the variability in characteristic subduction zone earthquake size, and the limitations of recurrence time estimates.

Phase I trial of a Lactobacillus crispatus vaginal suppository for prevention of recurrent urinary tract infection in women.

PubMed

Czaja, Christopher A; Stapleton, Ann E; Yarova-Yarovaya, Yuliya; Stamm, Walter E

2007-01-01

We performed a phase I trial to assess the safety and tolerance of a Lactobacillus vaginal suppository for prevention of recurrent UTI. Premenopausal women with a history of recurrent UTI were randomized to use L. crispatus CTV-05 or placebo vaginal suppositories daily for five days. 30 women were randomized (15 to L. crispatus CTV-05). No severe adverse events occurred. Mild to moderate vaginal discharge and genital irritation were reported by women in both study arms. Seven women randomized to L. crispatus CTV-05 developed pyuria without associated symptoms. Most women had high concentrations of vaginal H202-producing lactobacilli before randomization. L. crispatus, L. jensenii, and L. gasseri were the most common Lactobacillus species identified, with stable prevalence over time. L. crispatus CTV-05 can be given as a vaginal suppository with minimal sideeffects to healthy women with a history of recurrent UTI. Mild inflammation of the urinary tract was noted in some women.

Phase I Trial of a Lactobacillus crispatus Vaginal Suppository for Prevention of Recurrent Urinary Tract Infection in Women

PubMed Central

Czaja, Christopher A.; Stapleton, Ann E.; Yarova-Yarovaya, Yuliya; Stamm, Walter E.

2007-01-01

Objectives: We performed a phase I trial to assess the safety and tolerance of a Lactobacillus vaginal suppository for prevention of recurrent UTI. Methods: Premenopausal women with a history of recurrent UTI were randomized to use L. crispatus CTV-05 or placebo vaginal suppositories daily for five days. Results: 30 women were randomized (15 to L. crispatus CTV-05). No severe adverse events occurred. Mild to moderate vaginal discharge and genital irritation were reported by women in both study arms. Seven women randomized to L. crispatus CTV-05 developed pyuria without associated symptoms. Most women had high concentrations of vaginal H202-producing lactobacilli before randomization. L. crispatus, L. jensenii, and L. gasseri were the most common Lactobacillus species identified, with stable prevalence over time. Conclusions: L. crispatus CTV-05 can be given as a vaginal suppository with minimal sideeffects to healthy women with a history of recurrent UTI. Mild inflammation of the urinary tract was noted in some women. PMID:18288237

Definitive fractionated re-irradiation for local recurrence following stereotactic body radiotherapy for primary lung cancer.

PubMed

Yoshitake, Tadamasa; Shioyama, Yoshiyuki; Nakamura, Katsumasa; Sasaki, Tomonari; Ohga, Saiji; Shinoto, Makoto; Terashima, Kotaro; Asai, Kaori; Matsumoto, Keiji; Hirata, Hideki; Honda, Hiroshi

2013-12-01

To retrospectively evaluate the efficacy and safety of definitive fractionated re-irradiation for local recurrence following stereotactic body radiotherapy (SBRT) for primary lung cancer. Between April 2003 and December 2011, 398 patients with primary lung tumor underwent SBRT at the Kyushu University Hospital, and 46 out of these developed local recurrence after SBRT. Definitive fractionated re-irradiation was performed for 17 out of the 46 patients. The median dose of re-irradiation was 60 Gy/ 30 fractions. Concurrent chemotherapy was given to four patients. The median follow-up duration was 12.6 months. At one year post-re-irradiation, local progression-free survival was 33.8%; progression-free survival, 30.9%; cause-specific survival, 79.3%; and overall survival, 74.7%. No severe adverse events were observed during the follow-up. Definitive fractionated re-irradiation is thought to be a safe alternative therapy for local recurrence following SBRT, although its efficacy may be not entirely satisfactory.

Influence of movement regime of stick-slip process on the size distribution of accompanying acoustic emission characteristics

NASA Astrophysics Data System (ADS)

Matcharashvili, Teimuraz; Chelidze, Tamaz; Zhukova, Natalia; Mepharidze, Ekaterine; Sborshchikov, Alexander

2010-05-01

Many scientific works on dynamics of earthquake generation are devoted to qualitative and quantitative reproduction of behavior of seismic faults. Number of theoretical, numerical or physical models are already designed for this purpose. Main assumption of these works is that the correct model must be capable to reproduce power law type relation for event sizes with magnitudes greater than or equal to a some threshold value, similar to Gutenberg-Richter (GR) law for the size distribution of earthquakes. To model behavior of a seismic faults in laboratory conditions spring-block experimental systems are often used. They enable to generate stick-slip movement, intermittent behavior occurring when two solids in contact slide relative to each other driven at a constant velocity. Wide interest to such spring-block models is caused by the fact that stick-slip is recognized as a basic process underlying earthquakes generation along pre-existing faults. It is worth to mention, that in stick slip experiments reproduction of power law, in slip events size distribution, with b values close or equal to the one found for natural seismicity is possible. Stick-slip process observed in these experimental models is accompanied by a transient elastic waves propagation generated during the rapid release of stress energy in spring-block system. Oscillations of stress energy can be detected as a characteristic acoustic emission (AE). Accompanying stick slip AE is the subject of intense investigation, but many aspects of this process are still unclear. In the present research we aimed to investigate dynamics of stick slip AE in order to find whether its distributional properties obey power law. Experiments have been carried out on spring-block system consisting of fixed and sliding plates of roughly finished basalt samples. The sliding block was driven with a constant velocity. Experiments have been carried out for five different stiffness of pulling spring. Thus five different regimes of stick slip movement has been maintained. The AE accompanying the elementary slip events of stick-slip process were recorded on a PC sound card. The sensor for the AE was a lead circonate-titanate with a natural frequency of 100 KHz. In order to ensure standard conditions in each experiment, sliding surfaces were sanded up by sandpaper and cleaned of a dust. AE data analysis consisted of signal conditioning, filtering, and correct wave trains separation. Onset time of AE was determined at a minimun of Akaike Information Criterion. Afterwards time series of AE characteristics such as: recurrence times between consecutive AE bursts as well as time intervals between their maximums, duration of AE bursts, energy and power of AE, max by modulus of AE wave train amplitudes, etc. have been compiled. Cumulative probability distributions for all these data sets have been constructed and tested on the subject of GR type power law relation. It was found that characteristics of AE of stick slip process are strongly depending on the movement regime. Number of registered AE essentially increased for stiffer spring. At the same time recurrence times and emitted AE energy decreases. Power law type relation have not been observed for all AE characteristics and not for all considered regimes of movement. Power law relation, close to observed for real seismicity, was found for power of AE time series at stiffer springs. It is interesting that recurrence times between maximums of consecutive AE bursts and duration of AE bursts, reveal b in the range of 0.6-1.65. These results point that experimental conditions of stick slip process including movement regimes should be selected with care to ensure similarity between model and natural seismicity distributional characteristics.

Dupuytren Contracture Recurrence Following Treatment With Collagenase Clostridium histolyticum (CORDLESS [Collagenase Option for Reduction of Dupuytren Long-Term Evaluation of Safety Study]): 5-Year Data.

PubMed

Peimer, Clayton A; Blazar, Philip; Coleman, Stephen; Kaplan, F Thomas D; Smith, Ted; Lindau, Tommy

2015-08-01

Collagenase Option for Reduction of Dupuytren Long-Term Evaluation of Safety Study was a 5-year noninterventional follow-up study to determine long-term efficacy and safety of collagenase clostridium histolyticum (CCH) treatment for Dupuytren contracture. Patients from previous CCH clinical studies were eligible. Enrolled patients were evaluated annually for contracture and safety at 2, 3, 4, and 5 years after their first injection (0.58 mg) of CCH. In successfully treated joints (≤ 5° contracture following CCH treatment), recurrence was defined as 20° or greater worsening (relative to day 30 after the last injection) with a palpable cord or any medical/surgical intervention to correct new/worsening contracture. A post hoc analysis was also conducted using a less stringent threshold (≥ 30° worsening) for comparison with criteria historically used to assess surgical treatment. Of 950 eligible patients, 644 enrolled (1,081 treated joints). At year 5, 47% (291 of 623) of successfully treated joints had recurrence (≥ 20° worsening)-39% (178 of 451) of metacarpophalangeal and 66% (113 of 172) of proximal interphalangeal joints. At year 5, 32% (198 of 623) of successfully treated joints had 30° or greater worsening (metacarpophalangeal 26% [119 of 451] and proximal interphalangeal 46% [79 of 172] joints). Of 105 secondary interventions performed in the successfully treated joints, 47% (49 of 105) received fasciectomy, 30% (32 of 105) received additional CCH, and 23% (24 of 105) received other interventions. One mild adverse event was attributed to CCH treatment (skin atrophy [decreased ring finger circumference from thinning of Dupuytren tissue]). Antibodies to clostridial type I and/or II collagenase were found in 93% of patients, but over the 5 years of follow-up, this did not correspond to any reported clinical adverse events. Five years after successful CCH treatment, the overall recurrence rate of 47% was comparable with published recurrence rates after surgical treatments, with one reported long-term treatment-related adverse event. Collagenase clostridium histolyticum injection proved to be an effective and safe treatment for Dupuytren contracture. For those receiving treatment during follow-up, both CCH and fasciectomy were elected options. Therapeutic II. Copyright © 2015 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

Cost-effectiveness of apixaban versus low molecular weight heparin/vitamin k antagonist for the treatment of venous thromboembolism and the prevention of recurrences.

PubMed

Lanitis, Tereza; Leipold, Robert; Hamilton, Melissa; Rublee, Dale; Quon, Peter; Browne, Chantelle; Cohen, Alexander T

2017-01-23

Prior analyses beyond clinical trials are yet to evaluate the projected lifetime benefit of apixaban treatment compared to low-molecular-weight heparin (LMWH)/vitamin K antagonist (VKA) for treatment of venous thromboembolism (VTE) and prevention of recurrences. The objective of this study is to assess the cost-effectiveness of initial plus extended treatment with apixaban versus LMWH/VKA for either initial treatment only or initial plus extended treatment. A Markov cohort model was developed to evaluate the lifetime clinical and economic impact of treatment of VTE and prevention of recurrences with apixaban (starting at 10 mg BID for 1 week, then 5 mg BID for 6 months, then 2.5 mg BID for an additional 12 months) versus LMWH/VKA for 6 months and either no further treatment or extended treatment with VKA for an additional 12 months. Clinical event rates to inform the model were taken from the AMPLIFY and AMPLIFY-EXT trials and a network meta-analysis. Background mortality rates, costs, and utilities were obtained from published sources. The analysis was conducted from the perspective of the United Kingdom National Health Service. The evaluated outcomes included the number of events avoided in a 1000-patient cohort, total costs, life-years, quality-adjusted life-years (QALYs), and cost per QALY gained. Initial plus extended treatment with apixaban was superior to both treatment durations of LMWH/VKA in reducing the number of bleeding events, and was superior to initial LMWH/VKA for 6 months followed by no therapy, in reducing VTE recurrences. Apixaban treatment was cost-effective compared to 6-month treatment with LMWH/VKA at an incremental cost-effectiveness ratio (ICER) of £6692 per QALY. When initial LMWH/VKA was followed by further VKA therapy for an additional 12 months (i.e., total treatment duration of 18 months), apixaban was cost-effective at an ICER of £8528 per QALY gained. Sensitivity analysis suggested these findings were robust over a wide range of inputs and scenarios for the model. In the UK, initial plus extended treatment with apixaban for treatment of VTE and prevention of recurrences appears to be economical and a clinically effective alternative to LMWH/VKA, whether used for initial or initial plus extended treatment.

Relationship between risk factor control and vascular events in the SAMMPRIS trial

PubMed Central

Nizam, Azhar; Lynn, Michael J.; Egan, Brent M.; Le, Ngoc-Anh; Lopes-Virella, Maria F.; Hermayer, Kathie L.; Harrell, Jamie; Derdeyn, Colin P.; Fiorella, David; Janis, L. Scott; Lane, Bethany; Montgomery, Jean; Chimowitz, Marc I.

2017-01-01

Objective: The Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) study is the first stroke prevention trial to include protocol-driven intensive management of multiple risk factors. In this prespecified analysis, we aimed to investigate the relationship between risk factor control during follow-up and outcome of patients in the medical arm of SAMMPRIS. Methods: Data from SAMMPRIS participants in the medical arm (n = 227) were analyzed. Risk factors were recorded at baseline, 30 days, 4 months, and then every 4 months for a mean follow-up of 32 months. For each patient, values for all risk factor measures were averaged and dichotomized as in or out of target. Results: Participants who were out of target for systolic blood pressure and physical activity, as well as those with higher mean low-density lipoprotein cholesterol and non–high-density lipoprotein, were more likely to have a recurrent vascular event (stroke, myocardial infarction, or vascular death) at 3 years compared to those who had good risk factor control. In the multivariable analysis, greater physical activity decreased the likelihood of a recurrent stroke, myocardial infarction, or vascular death (odds ratio 0.6, confidence interval 0.4–0.8). Conclusions: Raised blood pressure, cholesterol, and physical inactivity should be aggressively treated in patients with intracranial atherosclerosis to prevent future vascular events. Physical activity, which has not received attention in stroke prevention trials, was the strongest predictor of a good outcome in the medical arm in SAMMPRIS. ClinicalTrials.gov identifier: NCT00576693. PMID:28003500

PREDICTORS OF BIOCHEMICAL REMISSION AND RECURRENCE AFTER SURGICAL AND RADIATION TREATMENTS OF CUSHING DISEASE: A SYSTEMATIC REVIEW AND META-ANALYSIS.

PubMed

Abu Dabrh, Abd Moain Abu; Singh Ospina, Naykky M; Al Nofal, Alaa; Farah, Wigdan H; Barrionuevo, Patricia; Sarigianni, Maria; Mohabbat, Arya B; Benkhadra, Khalid; Carranza Leon, Barbara G; Gionfriddo, Michael R; Wang, Zhen; Mohammed, Khaled; Ahmed, Ahmed T; Elraiyah, Tarig A; Haydour, Qusay; Alahdab, Fares; Prokop, Larry J; Murad, Mohammad Hassan

2016-04-01

We conducted a systematic review and meta-analysis to synthesize the evidence about predictors that may affect biochemical remission and recurrence after transsphenoidal surgery (TSS), radiosurgery (RS), and radiotherapy (RT) in Cushing disease. We searched multiple databases through December 2014 including original controlled and uncontrolled studies that enrolled patients with Cushing disease who received TSS (first-line), RS, or RT. We extracted data independently, in duplicates. Outcomes of interest were biochemical remission and recurrence. A meta-analysis was conducted using the random-effects model to estimate event rates with 95% confidence intervals (CIs). First-line TSS was associated with high remission (76% [95% CI, 72 to 79%]) and low recurrence rates (10% [95% CI, 6 to 16%]). Remission after TSS was higher in patients with microadenomas or positive-adrenocorticotropic hormone tumor histology. RT was associated with a high remission rate (RS, 68% [95% CI, 61 to 77%]; RT, 66% [95% CI, 58 to 75%]) but also with a high recurrence rate (RS, 32% [95% CI, 16 to 60%]; RT, 26% [95% CI, 14 to 48%]). Remission after RS was higher at short-term follow-up (≤2 years) and with high-dose radiation, while recurrence was higher in women and with lower-dose radiation. Remission was after RT in adults who received TSS prior to RT, and with lower radiation doses. There was heterogeneity (nonstandardization) in the criteria and cutoff points used to define biochemical remission and recurrence. First-line TSS is associated with high remission and low recurrence, while RS and RT are associated with reasonable remission rates but important recurrence rates. The current evidence warrants low confidence due to the noncomparative nature of the studies, high heterogeneity, and imprecision.

Rate of recurrent anaphylaxis and associated risk factors among Olmsted County, Minnesota, residents: A population-based study.

PubMed

Lee, Sangil; Bashore, Curtis; Lohse, Christine M; Bellolio, M Fernanda; Chamberlain, Alanna; Yuki, Kumi; Hess, Erik P; Campbell, Ronna L

2016-12-01

The rate and risk factors for recurrence of anaphylaxis are not well known. To measure the rate and risk factors for recurrent anaphylaxis in a population-based cohort in Olmsted County, Minnesota. We conducted a population-based cohort study using the Rochester Epidemiology Project, a comprehensive medical records linkage system, to obtain records of patients who presented to medical centers within the Olmsted County area with anaphylaxis from January 1, 2001, through December 31, 2010. We evaluated the rate and associations of risk factors with anaphylaxis recurrence. Among the 611 patients with anaphylaxis, 50 (8%) experienced a total of 60 recurrences within the 10-year period, resulting in a recurrence rate of 2.6 per 100 person-years. A history of atopic dermatitis (hazard ratio [HR], 5.6; 95% confidence interval [CI], 2.0-16.1; P = .001), presenting symptoms of cough (HR, 4.7; 95% CI, 2.1-10.7; P < .001) oral pruritus (HR, 9.9; 95% CI, 4.3-23.2; P < .001), and receiving corticosteroids (HR, 5.2; 95% CI, 2.3-11.7; P < .001) were associated with an increased risk of recurrence. The cardiovascular symptom of chest pain (HR, 0.24; 95% CI, 0.07-0.79; P = .02) was associated with a decreased risk of recurrence. In this epidemiologic study, the rate of recurrence was 8% during the 10-year study period (recurrence rate of 2.6 per 100 person-years). Those with atopic dermatitis and mucocutaneous or respiratory symptoms were more likely to have a recurrent anaphylactic event. Our findings underscore the importance of early patient access to self-injectable epinephrine and referral to an allergist/immunologist for additional testing and education. Copyright © 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Conscious and Nonconscious Processes:Distinct Forms of Evidence Accumulation?

NASA Astrophysics Data System (ADS)

Dehaene, Stanislas

Among the many brain events evoked by a visual stimulus, which ones are associated specifically with conscious perception, and which merely reflect nonconscious processing? Understanding the neuronal mechanisms of consciousness is a major challenge for cognitive neuroscience. Recently, progress has been achieved by contrasting behavior and brain activation in minimally different experimental conditions, one of which leads to conscious perception whereas the other does not. This chapter reviews briefly this line of research and speculates on its theoretical interpretation. I propose to draw links between evidence accumulation models, which are highly successful in capturing elementary psychophysical decisions, and the conscious/nonconscious dichotomy. In this framework, conscious access would correspond to the crossing of a threshold in evidence accumulation within a distributed global workspace, a set of recurrently connected neurons with long axons that is able to integrate and broadcast back evidence from multiple brain processors. During nonconscious processing, evidence would be accumulated locally within specialized subcircuits, but would fail to reach the threshold needed for global ignition and, therefore, conscious reportability.

Neutral Community Dynamics and the Evolution of Species Interactions.

PubMed

Coelho, Marco Túlio P; Rangel, Thiago F

2018-04-01

A contemporary goal in ecology is to determine the ecological and evolutionary processes that generate recurring structural patterns in mutualistic networks. One of the great challenges is testing the capacity of neutral processes to replicate observed patterns in ecological networks, since the original formulation of the neutral theory lacks trophic interactions. Here, we develop a stochastic-simulation neutral model adding trophic interactions to the neutral theory of biodiversity. Without invoking ecological differences among individuals of different species, and assuming that ecological interactions emerge randomly, we demonstrate that a spatially explicit multitrophic neutral model is able to capture the recurrent structural patterns of mutualistic networks (i.e., degree distribution, connectance, nestedness, and phylogenetic signal of species interactions). Nonrandom species distribution, caused by probabilistic events of migration and speciation, create nonrandom network patterns. These findings have broad implications for the interpretation of niche-based processes as drivers of ecological networks, as well as for the integration of network structures with demographic stochasticity.

Surgical outcome of mesh and suture repair in primary umbilical hernia: postoperative complications and recurrence.

PubMed

Winsnes, A; Haapamäki, M M; Gunnarsson, U; Strigård, K

2016-08-01

To compare recurrence and surgical complications following two dominating techniques: the use of suture and mesh in umbilical hernia repair. 379 consecutive umbilical hernia repair procedures performed between 1 January 2005 and 14 March 2014 in a university setting were included. Gathering was made using International Classification of Diseases codes for both procedure and diagnosis. Each patient record was scrutinized with respect to 45 variables, and the results entered in a database. Exclusion <18 years-of-age (32), non-primary umbilical hernia (25), wrong diagnosis (7), concomitant major abdominal surgery (5), double registration (3) and pregnancy (1) left 306 patients eligible for analysis. Gender distribution was 97 women and 209 men. There was no difference between mesh and suture with regard to the primary outcome variable, cumulative recurrence rate, 8.4 %. Recurrence was both self-reported and found on clinical revisit and defined as recurrence when verified by a clinician and/or radiologist. Results presented as odds ratio (OR) with 95 % confidence interval (CI) show a significantly higher risk for recurrence in patients with a coexisting hernia OR 2.84, 95 % CI 1.24-6.48. Secondary outcome, postoperative surgical complication (n = 51 occurrences), included an array of postoperative surgical events commencing within 30 days after surgery. Complication rate was significantly higher in patients receiving mesh repair OR 6.63, 95 % CI 2.29-20.38. Suture repair decreases the risk for surgical complications, especially infection without an increase in recurrence rate. The risk for recurrence is increased in patients with a history of another hernia.

Acne inversa complicated by Actinomyces neuii.

PubMed

Nedomansky, Jakob; Weiss, Doris; Willinger, Birgit; Nickl, Stefanie; Steininger, Christoph

2016-04-01

Acne inversa (AI) is a chronic and recurrent inflammatory skin disease. It occurs in intertriginous areas of the skin and causes pain, drainage, malodor and scar formation. While supposedly caused by an autoimmune reaction, bacterial superinfection is a secondary event in the disease process. A unique case of a 43-year-old male patient suffering from a recurring AI lesion in the left axilla was retrospectively analysed. A swab revealed Actinomyces neuii as the only agent growing in the lesion. The patient was then treated with Amoxicillin/Clavulanic Acid 3 × 1 g until he was cleared for surgical excision. The intraoperative swab was negative for A. neuii. Antibiotics were prescribed for another 4 weeks and the patient has remained relapse free for more than 12 months now. Primary cutaneous Actinomycosis is a rare entity and the combination of AI and Actinomycosis has never been reported before. Failure to detect superinfections of AI lesions with slow-growing pathogens like Actinomyces spp. might contribute to high recurrence rates after immunosuppressive therapy of AI. The present case underlines the potentially multifactorial pathogenesis of the disease and the importance of considering and treating potential infections before initiating immunosuppressive regimens for AI patients.

What Controls Subduction Earthquake Size and Occurrence?

NASA Astrophysics Data System (ADS)

Ruff, L. J.

2008-12-01

There is a long history of observational studies on the size and recurrence intervals of the large underthrusting earthquakes in subduction zones. In parallel with this documentation of the variability in both recurrence times and earthquake sizes -- both within and amongst subduction zones -- there have been numerous suggestions for what controls size and occurrence. In addition to the intrinsic scientific interest in these issues, there are direct applications to hazards mitigation. In this overview presentation, I review past progress, consider current paradigms, and look toward future studies that offer some resolution of long- standing questions. Given the definition of seismic moment, earthquake size is the product of overall static stress drop, down-dip fault width, and along-strike fault length. The long-standing consensus viewpoint is that for the largest earthquakes in a subduction zone: stress-drop is constant, fault width is the down-dip extent of the seismogenic portion of the plate boundary, but that along-strike fault length can vary from one large earthquake to the next. While there may be semi-permanent segments along a subduction zone, successive large earthquakes can rupture different combinations of segments. Many investigations emphasize the role of asperities within the segments, rather than segment edges. Thus, the question of earthquake size is translated into: "What controls the along-strike segmentation, and what determines which segments will rupture in a particular earthquake cycle?" There is no consensus response to these questions. Over the years, the suggestions for segmentation control include physical features in the subducted plate, physical features in the over-lying plate, and more obscure -- and possibly ever-changing -- properties of the plate interface such as the hydrologic conditions. It seems that the full global answer requires either some unforeseen breakthrough, or the long-term hard work of falsifying all candidate hypotheses except one. This falsification process requires both concentrated multidisciplinary efforts and patience. Large earthquake recurrence intervals in the same subduction zone segment display a significant, and therefore unfortunate, variability. Over the years, many of us have devised simple models to explain this variability. Of course, there are also more complicated explanations with many additional model parameters. While there has been important observational progress as both historical and paleo-seismological studies continue to add more data pairs of fault length and recurrence intervals, there has been a frustrating lack of progress in elimination of candidate models or processes that explain recurrence time variability. Some of the simple models for recurrence times offer a probabilistic or even deterministic prediction of future recurrence times - and have been used for hazards evaluation. It is important to know if these models are correct. Since we do not have the patience to wait for a strict statistical test, we must find other ways to test these ideas. For example, some of the simple deterministic models for along-strike segment interaction make predictions for variation in tectonic stress state that can be tested during the inter-seismic period. We have seen how some observational discoveries in the past decade (e.g., the episodic creep events down-dip of the seismogenic zone) give us additional insight into the physical processes in subduction zones; perhaps multi-disciplinary studies of subduction zones will discover a new way to reliably infer large-scale shear stresses on the plate interface?

Outcomes of treatment with daclatasvir and asunaprevir for recurrent hepatitis C after liver transplantation.

PubMed

Honda, Masaki; Sugawara, Yasuhiko; Watanabe, Takehisa; Tateyama, Masakuni; Tanaka, Motohiko; Uchida, Koushi; Kawabata, Seiichi; Yoshii, Daiki; Miura, Kouhei; Isono, Kaori; Hayashida, Shintaro; Ohya, Yuki; Yamamoto, Hidekazu; Sasaki, Yutaka; Inomata, Yukihiro

2017-10-01

The development of direct-acting oral agents has dramatically changed the treatment strategy of hepatitis C virus (HCV) infection. Here we aimed to reveal the efficacy and safety of daclatasvir (DCV) and asunaprevir (ASV) for recurrent HCV genotype 1 infection after liver transplantation (LT). A retrospective study was undertaken on nine patients who underwent a 24-week DCV/ASV treatment regimen for recurrent HCV genotype 1 infection. Five of the patients were men; four had failed treatment with pegylated interferon (Peg-IFN)/ribavirin, two had failed simeprevir/Peg-IFN/ribavirin, one had the resistance-associated variant Y93H in the NS5A region, and one underwent maintenance dialysis. Median time to treatment initiation following LT was 70 months. Of the nine patients treated with DCV/ASV, eight (88.9%) achieved a sustained viral response 12 weeks after completion of therapy (SVR12). The patient with virologic failure had failed simeprevir/Peg-interferon/ribavirin therapy 4 months before undergoing the DCV/ASV treatment regimen. In addition, a resistance-associated variant D168E in the NS3 region was detected in the patient after discontinuation of the DCV/ASV regimen. The trough level of tacrolimus tended to decrease, and renal function showed no significant changes during treatment. Adverse events occurred in two patients (22.2%), but no severe adverse events occurred during treatment. The DCV/ASV regimen was well tolerated, resulting in high rates of sustained viral response 12 weeks after completion of therapy for LT patients with recurrent HCV genotype 1 infection. © 2016 The Japan Society of Hepatology.

Recurrent specialization on a toxic fruit in an island Drosophila population

PubMed Central

Yassin, Amir; Debat, Vincent; Bastide, Héloïse; Gidaszewski, Nelly; David, Jean R.; Pool, John E.

2016-01-01

Recurrent specialization on similar host plants offers a unique opportunity to unravel the evolutionary and genetic mechanisms underlying dietary shifts. Recent studies have focused on ecological races belonging to the same species, but it is hard in many cases to untangle the role of adaptive introgression versus distinct mutations in facilitating recurrent evolution. We discovered on the island of Mayotte a population of the generalist fly Drosophila yakuba that is strictly associated with noni (Morinda citrifolia). This case strongly resembles Drosophila sechellia, a genetically isolated insular relative of D. yakuba whose intensely studied specialization on toxic noni fruits has always been considered a unique event in insect evolution. Experiments revealed that unlike mainland D. yakuba strains, Mayotte flies showed strong olfactory attraction and significant toxin tolerance to noni. Island females strongly discriminated against mainland males, suggesting that dietary adaptation has been accompanied by partial reproductive isolation. Population genomic analysis indicated a recent colonization (∼29 kya), at a time when year-round noni fruits may have presented a predictable resource on the small island, with ongoing migration after colonization. This relatively recent time scale allowed us to search for putatively adaptive loci based on genetic variation. Strong signals of genetic differentiation were found for several detoxification genes, including a major toxin tolerance locus in D. sechellia. Our results suggest that recurrent evolution on a toxic resource can involve similar historical events and common genetic bases, and they establish an important genetic system for the study of early stages of ecological specialization and speciation. PMID:27044093

The 1993 Mississippi river flood: A one hundred or a one thousand year event?

USGS Publications Warehouse

Malamud, B.D.; Turcotte, D.L.; Barton, C.C.

1996-01-01

Power-law (fractal) extreme-value statistics are applicable to many natural phenomena under a wide variety of circumstances. Data from a hydrologic station in Keokuk, Iowa, shows the great flood of the Mississippi River in 1993 has a recurrence interval on the order of 100 years using power-law statistics applied to partial-duration flood series and on the order of 1,000 years using a log-Pearson type 3 (LP3) distribution applied to annual series. The LP3 analysis is the federally adopted probability distribution for flood-frequency estimation of extreme events. We suggest that power-law statistics are preferable to LP3 analysis. As a further test of the power-law approach we consider paleoflood data from the Colorado River. We compare power-law and LP3 extrapolations of historical data with these paleo-floods. The results are remarkably similar to those obtained for the Mississippi River: Recurrence intervals from power-law statistics applied to Lees Ferry discharge data are generally consistent with inferred 100- and 1,000-year paleofloods, whereas LP3 analysis gives recurrence intervals that are orders of magnitude longer. For both the Keokuk and Lees Ferry gauges, the use of an annual series introduces an artificial curvature in log-log space that leads to an underestimate of severe floods. Power-law statistics are predicting much shorter recurrence intervals than the federally adopted LP3 statistics. We suggest that if power-law behavior is applicable, then the likelihood of severe floods is much higher. More conservative dam designs and land-use restrictions Nay be required.

NAHR-mediated copy-number variants in a clinical population: mechanistic insights into both genomic disorders and Mendelizing traits.

PubMed

Dittwald, Piotr; Gambin, Tomasz; Szafranski, Przemyslaw; Li, Jian; Amato, Stephen; Divon, Michael Y; Rodríguez Rojas, Lisa Ximena; Elton, Lindsay E; Scott, Daryl A; Schaaf, Christian P; Torres-Martinez, Wilfredo; Stevens, Abby K; Rosenfeld, Jill A; Agadi, Satish; Francis, David; Kang, Sung-Hae L; Breman, Amy; Lalani, Seema R; Bacino, Carlos A; Bi, Weimin; Milosavljevic, Aleksandar; Beaudet, Arthur L; Patel, Ankita; Shaw, Chad A; Lupski, James R; Gambin, Anna; Cheung, Sau Wai; Stankiewicz, Pawel

2013-09-01

We delineated and analyzed directly oriented paralogous low-copy repeats (DP-LCRs) in the most recent version of the human haploid reference genome. The computationally defined DP-LCRs were cross-referenced with our chromosomal microarray analysis (CMA) database of 25,144 patients subjected to genome-wide assays. This computationally guided approach to the empirically derived large data set allowed us to investigate genomic rearrangement relative frequencies and identify new loci for recurrent nonallelic homologous recombination (NAHR)-mediated copy-number variants (CNVs). The most commonly observed recurrent CNVs were NPHP1 duplications (233), CHRNA7 duplications (175), and 22q11.21 deletions (DiGeorge/velocardiofacial syndrome, 166). In the ∼25% of CMA cases for which parental studies were available, we identified 190 de novo recurrent CNVs. In this group, the most frequently observed events were deletions of 22q11.21 (48), 16p11.2 (autism, 34), and 7q11.23 (Williams-Beuren syndrome, 11). Several features of DP-LCRs, including length, distance between NAHR substrate elements, DNA sequence identity (fraction matching), GC content, and concentration of the homologous recombination (HR) hot spot motif 5'-CCNCCNTNNCCNC-3', correlate with the frequencies of the recurrent CNVs events. Four novel adjacent DP-LCR-flanked and NAHR-prone regions, involving 2q12.2q13, were elucidated in association with novel genomic disorders. Our study quantitates genome architectural features responsible for NAHR-mediated genomic instability and further elucidates the role of NAHR in human disease.

Reoperations after tricuspid valve repair: re-repair versus replacement

PubMed Central

Hwang, Ho Young; Kim, Kyung-Hwan; Kim, Ki-Bong

2016-01-01

Background Data demonstrating results of reoperation after initial tricuspid valve repair are scarce. We evaluated outcomes of tricuspid reoperations after tricuspid valve repair and compared the results of tricuspid re-repair with those of tricuspid valve replacement (TVR). Methods From 1994 to 2012, 53 patients (56±15 years, male:female =14:39) underwent tricuspid reoperations due to recurrent tricuspid regurgitation (TR) after initial repair. Twenty-two patients underwent tricuspid re-repair (TAP group) and 31 patients underwent TVR (TVR group). Results Early mortality occurred in 6 patients (11%). Early mortality and incidence of postoperative complications were similar between the 2 groups. There were 14 cases of late mortality including 9 cardiac deaths. Five- and 10-year free from cardiac death rates were 82% and 67%, respectively, without any intergroup difference. Recurrent TR (> moderate) developed in 6 TAP group patients and structural valve deterioration occurred in 1 TVR group patient (P=0.002). Isolated tricuspid valve surgery (P=0.044) and presence of atrial fibrillation during the follow-up (P=0.051) were associated with recurrent TR after re-repair. However, the overall tricuspid valve-related event rates were similar between the 2 groups with 5- and 10-year rates of 61% and 41%, respectively. Conclusions Tricuspid valve reoperation after initial repair resulted in high rates of operative mortality and complications. Long-term event-free rate was similar regardless of the type of surgery. However, great care might be needed when performing re-repair in patients with atrial fibrillation and those who had isolated tricuspid valve disease due to high recurrence of TR after re-repair. PMID:26904221

Unusual geologic evidence of coeval seismic shaking and tsunamis shows variability in earthquake size and recurrence in the area of the giant 1960 Chile earthquake

USGS Publications Warehouse

Cisternas, M.; Garrett, E; Wesson, Robert L.; Dura, T.; Ely, L. L

2017-01-01

An uncommon coastal sedimentary record combines evidence for seismic shaking and coincident tsunami inundation since AD 1000 in the region of the largest earthquake recorded instrumentally: the giant 1960 southern Chile earthquake (Mw 9.5). The record reveals significant variability in the size and recurrence of megathrust earthquakes and ensuing tsunamis along this part of the Nazca-South American plate boundary. A 500-m long coastal outcrop on Isla Chiloé, midway along the 1960 rupture, provides continuous exposure of soil horizons buried locally by debris-flow diamicts and extensively by tsunami sand sheets. The diamicts flattened plants that yield geologically precise ages to correlate with well-dated evidence elsewhere. The 1960 event was preceded by three earthquakes that probably resembled it in their effects, in AD 898 - 1128, 1300 - 1398 and 1575, and by five relatively smaller intervening earthquakes. Earthquakes and tsunamis recurred exceptionally often between AD 1300 and 1575. Their average recurrence interval of 85 years only slightly exceeds the time already elapsed since 1960. This inference is of serious concern because no earthquake has been anticipated in the region so soon after the 1960 event, and current plate locking suggests that some segments of the boundary are already capable of producing large earthquakes. This long-term earthquake and tsunami history of one of the world's most seismically active subduction zones provides an example of variable rupture mode, in which earthquake size and recurrence interval vary from one earthquake to the next.

Paleoseismology under sea: First evidence for irregular seismic cycles during Holocene off Algeria from turbidites

NASA Astrophysics Data System (ADS)

Ratzov, Gueorgui; Cattaneo, Antonio; Babonneau, Nathalie; Déverchere, Jacques; Yelles, Karim; Bracene, Rabah

2013-04-01

According to simple models, stress build-up along a given fault is proportional to the time elapsed since the previous earthquake. Although the resulting « seismic gap » hypothesis suits well for moderate magnitude earthquake (Mw 4-5), large events (Mw>6) are hardly predictable and show great variation in recurrence intervals. Thus, models based on stress transfer and interactions between faults suggest that an earthquake may haste or delay the occurrence of next earthquake on adjacent fault by increasing or lowering the level of static stress. Here, we show that meaningful information of large earthquakes recurrence intervals over several seismic cycles may be obtained using turbidite record offshore the Algerian margin (Mediterranean Sea), an area prone to relatively large (M~7) earthquakes in historical times. Indeed, as evidenced on the Cascadia subduction zone, synchroneous turbidites over a large area and originated from independent sources, are most likely triggered by an earthquake. To test the method on this slowly convergent margin, we analysed turbidites in 3 sediment cores collected off the area shaken by the 1980 Ms 7.3 El Asnam and 1954 M6.7 Orléansville earthquakes. We used X-ray radioscopy, XRF major elements counter, magnetic susceptibility, and grain-size distribution to accurately discriminate turbidites (~instantaneous deposit) from hemipelagites (continuous background sedimentation). We dated turbidites by calculating hemipelagic sedimentation rates obtained with AMS radiocarbon ages, and applied the rates between turbidites. Finally, the age of events was compared to the only paleoseismic investigation available onland. We found that 10 to 25 turbidites deposited as single or multiple pulses over the last ~8ka. Once correlated from site to site, they support 14 seismic events. Most events are correlated with the paleoseismic record of the El Asnam fault, but uncorrelated events support that other faults were active. Only the first of the two major events of 1954 and 1980 triggered a turbidity current, implying that the sediment buffer on the continental shelf could not be reloaded in 26 years thus giving information on the minimum time resolution of our method. The new paleoseismic catalog shows a recurrence interval of 300-700 years for most events, but also a great interval of >1200 years without any major earthquake. This result suggest that the level of static stress may have drastically dropped as a result of three main events occurring within the 800 years prior the quiescence period. The quiescent period also supports a stress transfer and interaction between neighbouring faults.