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December 12, 2000; 55 (11) Article
Early stroke treatment associated with better outcome
The NINDS rt-PA Stroke Study
J.R. Marler, B.C. Tilley, M. Lu, T.G. Brott, P.C. Lyden, J.C. Grotta, J.P. Broderick, S.R. Levine, M.P. Frankel, S.H. Horowitz, E.C. Haley, C.A. Lewandowski, T.P. Kwiatkowski, for the NINDS rt-PA Stroke Study Group
First published December 12, 2000,
J.R. Marler
From the National Institute of Neurological Disorders and Stroke, Rockville, MD.
B.C. Tilley
M. Lu
T.G. Brott
P.C. Lyden
J.C. Grotta
J.P. Broderick
S.R. Levine
M.P. Frankel
S.H. Horowitz
E.C. Haley Jr.
C.A. Lewandowski
T.P. Kwiatkowski
Neurology Dec 2000, 55 (11) 1649-1655;
Background: The National Institute of Neurological Disorders and Stroke (NINDS) rt-PA Stroke Study showed a similar percentage of intracranial hemorrhage and good outcome in patients 3 months after stroke treatment given 0 to 90 minutes and 91 to 180 minutes after stroke onset. At 24 hours after stroke onset more patients treated 0 to 90 compared to 91 to 180 minutes after stroke onset had improved by four or more points on the NIH Stroke Scale (NIHSS). The authors performed further analyses to characterize the relationship of onset-to-treatment time (OTT) to outcome at 3 months, early improvement at 24 hours, and intracranial hemorrhage within 36 hours.
Methods: Univariate analyses identified potentially confounding variables associated with OTT that could mask an OTT–treatment interaction. Tests for OTT–treatment interactions adjusting for potential masking confounders were performed. An OTT–treatment interaction was considered significant if p ≤ 0.10, implying that treatment effectiveness was related to OTT.
Results: For 24-hour improvement, there were no masking confounders identified and there was an OTT–treatment interaction (p = 0.08). For 3-month favorable outcome, the NIHSS met criteria for a masking confounder. After adjusting for NIHSS as a covariate, an OTT–treatment interaction was detected (p = 0.09): the adjusted OR (95% CI) for a favorable 3-month outcome associated with recombinant tissue-type plasminogen activator (rt-PA) was 2.11 (1.33 to 3.35) in the 0 to 90 minute stratum and 1.69 (1.09 to 2.62) in the 91 to 180 minute stratum. In the group treated with rt-PA, after adjusting for baseline NIHSS, an effect of OTT on the occurrence of intracranial hemorrhage was not detected.
Conclusions: If the NINDS rt-PA Stroke Trial treatment protocol is followed, this analysis suggests that patients treated 0 to 90 minutes from stroke onset with rt-PA have an increased odds of improvement at 24 hours and favorable 3-month outcome compared to patients treated later than 90 minutes. No effect of OTT on intracranial hemorrhage was detected within the group treated with rt-PA, possibly due to low power.
Both trials in the National Institute of Neurological Disorders and Stroke (NINDS) rt-PA Stroke Study1 demonstrated the effectiveness of recombinant tissue-type plasminogen activator (rt-PA) for the treatment of acute ischemic stroke when started within 3 hours of stroke onset. Because time from stroke onset to treatment was considered an important possible influence on subsequent outcome, randomization of patients in these two trials included stratification on time from stroke onset (0 to 90 minutes, 91 to 180 minutes). In the initial analysis of the results, there was little apparent observed difference between the two time strata in the number of favorable outcomes at 3 months or in the number of intracranial hemorrhages. The apparent lack of additional benefit for earlier treatment was unexpected because pilot studies2,3⇓ and laboratory research4 had shown reduced rates of hemorrhage and increased benefit with earlier treatment. A recent study has commented on the strength of the research data supporting the concept that earlier treatment would be expected to produce a better outcome.5 Although there appeared to be a difference between the two time strata in the proportion of patients showing either complete improvement or a four-point improvement in NIH Stroke Scale (NIHSS) at 24 hours, formal testing of an interaction was not conducted.
Seeking to understand the unexpected lack of difference between patient outcomes in the two time strata of these two trials, we proposed several explanations for the apparent lack of effect of time on patient outcome at 3 months: 1) patients treated sooner after stroke onset could have come to medical attention earlier because their presenting symptoms were more severe or noticeable; 2) patients starting treatment sooner after stroke onset may have come at a different time of day and received different care in the emergency department or intensive care unit; 3) patients treated earlier may have ischemic stroke subtypes less responsive to thrombolytic treatment; 4) for patients treated earlier compared to those treated later, baseline characteristics predicting better outcomes may have been distributed differently between the rt-PA and placebo groups.
After adjusting for patient baseline characteristics, as necessary, we performed further analyses of the data from the two trials in the NINDS rt-PA Stroke Study to determine if we could detect an onset-to-treatment time (OTT)–treatment interaction association with any of the outcomes of interest (24 hour improvement, 3 month favorable outcome, or hemorrhage in the first 36 hours). If an interaction was detected this would imply that treatment effect varied depending on OTT.
The NINDS rt-PA Stroke Study was performed in two parts, each of which was a separate trial conducted at eight centers using over 40 hospitals. The two parts differed only in the prospectively defined primary outcome. Data from both parts of the study were combined for the analyses reported here to obtain more statistical power and a more complete picture of the effect of OTT on patient outcomes.
Hypotheses.
The protocols in place before the start of both parts of the study specified testing the secondary hypotheses relating to treatment effectiveness within two OTT strata. The most powerful approach to testing these hypotheses is to test for an interaction between OTT by treatment interaction treating time as a continuum. Such an interaction, if present, implies that treatment effectiveness varies across OTT intervals and treatment effects within OTT strata should be assessed.
Definition of outcomes.
As described in the original report, rt-PA was considered to be effective 3 months after stroke if there was a consistent and persuasive difference in the proportions of rt-PA compared to placebo-treated patients with favorable outcome. A favorable outcome was defined as recovery with minimal or no deficit 3 months after treatment using four outcome measures: the Barthel Index6 ≥ 95, modified Rankin Scale7 ≤ 1, Glasgow Outcome Scale8 of 1, and NIHSS9 score ≤ 1.
A patient was considered to show improvement 24 hours after stroke if the patient had at least a four-point improvement from baseline in NIHSS score or a complete resolution of symptoms. For the analysis of hemorrhage, both symptomatic and asymptomatic intracranial hemorrhages occurring within 36 hours were included because the total number of symptomatic hemorrhages was so small. The definition of intracranial hemorrhage within 36 hours of treatment and methods for assessing hemorrhage are described elsewhere.10 More detail on the assessment of outcomes is given in the initial report on the NINDS trials.1
Determination of time of stroke onset.
Time of stroke onset was determined by interviewing patients and any available observers present when the stroke was first noticed. Physicians sought corroborating evidence (such as ambulance reports) and carefully screened for the possibility of onset during sleep. If the patient awoke with stroke symptoms, the time of onset was taken as the last time the patient was known to be awake and without any symptoms of stroke. If the onset time could not be established with confidence, the patient was not randomized. After randomization, the time of onset was re-reviewed using the emergency medical system logs and notes in the medical record. If discrepancies were found, corrections were made. It was through this review that two patients were identified who were randomized outside the 180-minute window. Audits of source records for all patients were performed to confirm consistency of stroke onset time and treatment start time determinations. The difference between these two times is referred to as the OTT.
Randomization and treatment.
In both the Part 1 and Part 2 trials, a permuted block randomization was used with varying block sizes stratified by clinical center and OTT (0 to 90 or 91 to 180 minutes). No other covariates were used as stratifying variables. To balance the number of patients treated in 0 to 90 minutes from stroke onset with those treated 91 to 180 minutes, no center was to randomize a patient at 91 to 180 minutes when they had already treated two more patients in the 91 to 180 minute group than in the 0 to 90 minute group. Patients received alteplase (Activase, an rt-PA manufactured by Genentech, South San Francisco) or placebo, 0.9 mg/kg (maximum 90 mg), with 10% given as a bolus followed by the remainder as a constant infusion over 60 minutes.
Patient selection.
A total of 624 patients were randomized to both trials in the study. The two patients inadvertently randomized outside the protocol-specified limit of 180 minutes were included in the original analyses based on the intention-to-treat principle. For one of these patients study treatment was started 195 minutes from stroke onset; for the second patient, treatment was started 24 hours after stroke onset. The focus of this report was treatment within 180 minutes of stroke onset. Whereas inclusion of these two patients did not change our results, we did not believe we should be extrapolating our results beyond 180 minutes based on data from two patients. Thus we excluded these two patients from the analysis. Data from the remaining 622 patients are included in the tables and analyses presented in this report.
Statistical analysis.
To understand more about OTT, we assessed the association between OTT and two other time-related variables (time of day and time from emergency department admission to treatment) using analyses of variance on the ranked data.
The primary objective was to determine if confounding variables could be masking the association of the OTT–treatment interaction with treatment outcomes; i.e., 3-month favorable outcome, 24-hour improvement, or hemorrhage within 36 hours. (In other reports on 3-month favorable outcome and hemorrhage, no baseline variable by treatment interactions had been detected, including interactions with OTT.10,11⇓) As a sufficient condition for a baseline variable to be a masking confounder for the OTT–treatment interaction, a variable must be associated with both the OTT–treatment interaction and the outcome of interest. As a necessary condition, leaving this variable out of the model testing the association of the interaction with treatment outcome would mask the association.12
Because the main effects for OTT and treatment would be in any regression model testing the baseline variable associations with the OTT–treatment interaction, we first tested for associations between the relevant baseline variables and OTT. OTT was uncategorized and we tested for associations by testing whether the Spearman's correlations were equal to zero. The baseline variables included in the analysis were those variables considered in previous reports to be associated with the outcomes of interest (3 months favorable outcome, 24-hour improvement, and hemorrhage)11 because these variables would be the only variables that could meet the sufficient condition above. We had previously tested for associations with treatment and found only associations with weight and aspirin. Neither variable was associated with outcome (sufficient condition).1
If potential confounding variables were not identified, we tested directly for OTT–treatment interactions using a logistic model (24 hours improvement and hemorrhage) or global test (3-month favorable outcome). More detail on the global analytical approach is published elsewhere.13 Where potential masking confounders were identified, we fit multivariable models to test for the OTT–treatment interactions, adjusting for the potential confounders again using the logistic regression or global tests depending on the outcome of interest. As noted above, in the models testing for OTT–treatment interactions, OTT and treatment main effects were included. Consistent with our previous work,10,11⇓ an interaction was considered significant if the p value was ≤ 0.10. We chose a significance level greater than 0.05, recognizing the limitations in power when testing for multiplicative interactions in multiplicative models. We also checked the underlying assumption of linearity in the log odds for the interaction terms and could not detect violations of this assumption. Where an interaction was detected, we present OTT stratified as 0 to 90 and 91 to 180 minutes from stroke onset, the strata used in randomization, along with odds ratios and 95% confidence limits. We present a graphic representation of the OTT–treatment interaction, with OTT uncategorized, to give a further illustration of the OTT–treatment interaction and its effect on treatment outcome. For the analysis considering NIHSS as a masking confounder where the outcome was hemorrhage, the baseline NIHSS was divided into five different groups (NIHSS <5, 6 to 10, 11 to 15, 16 to 20, and >20) to induce linearity in the associated log odds of hemorrhage. For all other analyses, the NIHSS was treated as a continuum. Because there were only 10 symptomatic and asymptomatic intracranial hemorrhages in the placebo group, analysis of the OTT hemorrhage association within the rt-PA treated group was planned regardless of the computed p value for the test of the interaction.
Analyses were repeated excluding 35 patients reported to have edema or mass effect on the initial CT scan.1 These patients might represent patients whose time of stroke onset was incorrectly classified and could have a longer time between stroke onset and treatment than reported.
Baseline characteristics. From January 1991 through October 1994, 624 patients were randomized in the two trials, Part 1 and Part 2. Excluding the two patients described in Methods, 302 patients were randomized in the 0 to 90 minute stratum and 320 in the 91 to 180 minute stratum. The clinical investigators were able to maintain the balance between the two OTT strata throughout the two trials. Based on the final determination of OTT, on 25 occasions (4% of randomizations) patients were randomized to the 91 to 180 minute strata at centers where there were already two more patients in the 91 to 180 minute stratum than the 0 to 90 minute stratum.
The distribution of OTT is shown in figure 1 for the combined Part 1 and Part 2 trial cohorts. OTT for the patients in the 0 to 90 minute stratum clustered close to the 90-minute limit. OTT for the patients in the 91 to 180 stratum was more evenly distributed across the time interval. Table 1 gives the distribution of time-related variables within the OTT strata and treatment categories. We detected no OTT strata or treatment group associations for time of day of stroke onset (p > 0.7). For time from emergency department admission to treatment there was no detectable association with treatment group (p > 0.63), but there was an association with OTT strata (p < 0.001). Delay from emergency department admission to start of treatment was 30 minutes longer for patients in the 91 to 180 minute strata (see table 1).
Figure 1. Histogram shows number of patients with time from stroke onset to start of treatment (onset-to-treatment time [OTT]) in intervals of 10 minutes. Total number of patients is 622 (excludes two patients randomized outside the 180-minute window).
Time from stroke onset (onset-to-treatment time [OTT]), delay after admission, and time of stroke onset
In order to compare differences in presenting signs, the components of the stroke scale are presented by treatment group and OTT strata in table 2. There are no apparent differences in the type of neurologic symptoms between OTT strata.
Similarity of baseline deficits: NIH Stroke Scale (NIHSS) components by stroke onset to treatment (onset-to-treatment time [OTT]) strata and treatment group
There was an association between OTT and baseline NIHSS whether or not the stroke scale was categorized (Spearman correlation p = 0.05, NIHSS as continuous variable; p = 0.04, NIHSS as categorical variable). We also noted that the mean and median NIHSS values at baseline were higher for the rt-PA–treated group compared to placebo group treated 0 to 90 minutes after onset and lower for the rt-PA compared to placebo groups treated at 91 to 180 minutes, confirmed by a significant OTT × treatment interaction with NIHSS as the outcome (table 3). Because of the presence of the interaction we tested the association within treatment group. Within the rt-PA group, the association between OTT and baseline NIHSS remained significant (Spearman correlation p = 0.04, NIHSS as continuous variable; p = 0.02, NIHSS as categorical variable), but there was no significant association detected in the placebo group (Spearman correlation p = 0.52, NIHSS as continuous variable; p = 0.60, NIHSS as categorical variable). Previous work10,11⇓ had also shown that there was a relationship between the NIHSS favorable outcome at 3 months (p < 0.001), and with hemorrhage within 36 hours (p < 0.001). Thus, NIHSS was a potential masking confounder. Because by chance the rt-PA treated patients in the 91 to 180 minute stratum had less severe strokes than the patients in the placebo group, the effect of rt-PA may have appeared to be greater than it actually was. In the 0 to 90 minute stratum the stroke severity was more equal between treatment groups. Comparison of the effects of rt-PA in the two strata may be misleading if the imbalance in stroke scales between the rt-PA and placebo groups is not taken into account.
Baseline NIH Stroke Scale (NIHSS) by time from stroke onset to treatment (onset-to-treatment time [OTT]) strata and treatment group
There was also an association between OTT and presumptive stroke subtype determined at baseline. Patients with small vessel strokes were treated later than patients with cardioembolic or large vessel strokes (p = 0.02). Stroke subtype was not associated with the 24-hour outcome and was not associated with 3-month favorable outcome or hemorrhage (all p values > 0.05) after adjusting for the NIHSS. Thus stroke subtype was not a potential masking confounder. There was no association detected (all p values > 0.05) between OTT and the other baseline variables considered.
Improvement from baseline at 24 hours.
For the 24-hour outcome (complete resolution of symptoms or a four or more point improvement in the NIHSS) an OTT–treatment interaction was detected (OR 0.992, 95% CI 0.98 to 1.00, p = 0.08) without adjustment for any baseline variables. Because we are considering a multiplicative interaction on a multiplicative scale, the interaction effect size appears small. To further represent the interaction, we categorized OTT into the two strata used for randomization.
The OR comparing rt-PA to placebo for patients treated within 0 to 90 minutes of stroke onset was 1.71 (95% CI 1.09 to 2.70, p = 0.02). An OR >1 indicates that the odds of a four or more point NIHSS improvement at 24 hours are greater in rt-PA treated patients compared to patients receiving placebo. The OR for patients treated between 91 and 180 minutes after stroke onset was 1.12 (95% CI 0.71 to 1.76, p = 0.62).
Favorable clinical outcome at 3 months.
In the model without covariates an OTT–treatment interaction was not detected (p = 0.31, OR 0.996, 95% CI 0.988 to 1.004). In the model including the NIHSS, an OTT–treatment interaction was detected (p = 0.09, interaction OR 0.993, 95% CI 0.983 to 1.001). The magnitude of the interaction is again small, given the use of the multiplicative model. To characterize the relationship of OTT to favorable outcome, figure 2 shows a graphical representation of the OTT–treatment interaction (with OTT as a continuum) in terms of the OR for a favorable outcome, after adjusting for NIHSS. As we did for 24-hour outcome, we also categorized OTT by the randomization strata. We then computed the OR (95% confidence limits) for a favorable outcome at 3 months, adjusting for baseline NIHSS. The adjusted OR for the rt-PA treated group as compared to placebo group was 2.11 (1.33 to 3.35), p = 0.002 for the 0 to 90 minute time strata. The adjusted OR was 1.69 (1.09 to 2.62), p = 0.02 for the 91 to 180 minute time strata.
Figure 2. Graph of model estimating OR for favorable outcome at 3 months in recombinant tissue-type plasminogen activator (rt-PA) treated patients compared to placebo treated patients by time from stroke onset to treatment (onset-to-treatment time [OTT]) with 95% confidence intervals, adjusting for the baseline NIH Stroke Scale. OR > 1 indicates greater odds that rt-PA treated patients will have a favorable outcome at 3 months compared to the placebo treated patients. Range of OTT was 58 to 180 minutes with mean (μ) of 119.7 minutes.
The OTT–treatment interaction remained significant, p = 0. 04, OR 0.991 (0.98 to 1.00), in a multivariable model of 3-month favorable outcome including the NIHSS and all other covariates identified in a previous report as being associated with 3-month favorable outcome.11 The adjusted OR (95% CI) for a favorable outcome at 3 months for the rt-PA treated group as compared to placebo group was 2.53 (1.53 to 4.19), p = 0.0003 for the 0 to 90 minute time strata. The adjusted OR was 1.61 (1.02 to 2.55), p = 0.04 for the 91 to 180 minute time strata.
Symptomatic and asymptomatic hemorrhage within 36 hours.
Because baseline NIHSS was associated with both intracranial hemorrhage within 36 hours and OTT, we tested for an interaction between treatment group and OTT adjusting for categorized NIHSS. No interaction was detected for all hemorrhages, p = 0.24, OR 0.99 (0.97 to 1.01), or for symptomatic hemorrhages, p = 0.74, OR 0.99 (0.95 to 1.03). Within the rt-PA group alone, after adjusting for baseline NIHSS, no OTT association with hemorrhage was detected (p > 0.76).
Exclusion of patients with midline shift and edema.
When the 35 patients with severe edema and midline shift at baseline were excluded, the results were similar to the analyses including these 35 patients presented above.
OTT was shown to be associated with a differential response to treatment both at 24 hours and 3 months after stroke. Due to chance, there was an imbalance in the NIHSS severity of stroke randomized in the two treatment groups at different OTT. Because baseline NIHSS is a good predictor of outcome, this imbalance in the treatment groups increased the number of favorable outcomes in the rt-PA group treated 91 to 180 minutes from stroke onset and reduced them in the group treated with rt-PA between 0 and 90 minutes. The imbalance obscured or confounded the increased response to treatment in the rt-PA group treated early compared to the rt-PA group treated later.
Before this analysis, the apparent similarity of the outcomes for the patients treated early and late could have encouraged the natural proclivity to delay treatment until the last possible minute. The clustering of patients in the 90 minute group (see figure 1) and the longer delay from emergency department admission to treatment in the 91 to 180 minute patient group demonstrates this tendency. The US Food and Drug Administration approval of rt-PA for use in all patients up to 3 hours from stroke onset could lead to clustering of treatment at 3 hours rather than 90 minutes. We observed a demonstration of this phenomenon in one of our clinical centers. In order to avoid turning away patients, investigators at this center did not open the 91 to 180 arm of the Part 1 trial at their center until there were 11 patients enrolled in the 0 to 90 minute stratum. Once they opened the 91 to 180 minute arm, time from admission to treatment increased from a median of 58 minutes to a median of 65 minutes and within 19 months the "surplus" of 0 to 90 minute patients was decreased to the two patient difference tolerated by the protocol.14 Whereas it is good to have some benefit to offer patients who come late for treatment with rt-PA, the results of our modeling suggest that the effort should be to treat each patient as early as possible before 3 hours. The fact that the models are consistent with our understanding of the pathophysiology of stroke and the mechanism of action of rt-PA adds to the significance of the findings reported here.
Before the initiation of the NINDS rt-PA Stroke Study, data from laboratory and pilot clinical studies with tissue plasminogen activator for ischemic stroke had suggested time was an important factor in determining outcome and the number of symptomatic hemorrhages.2,3⇓ Improved functional outcome in a laboratory model of multifocal ischemic brain injury is dose dependent.15 This is demonstrated by a graded response with reduced recovery rates as the delay between onset of ischemia and start of rt-PA infusion increases from 15 to 30, 45, and 60 minutes. In the 74-patient 0 to 90 minute open-label pilot study for the NINDS rt-PA Stroke Study, 46% of patients showed a four point improvement at 24 hours on the NIHSS and 4% had symptomatic intracranial hematoma. In a parallel 21-patient 91 to 180 minute pilot study, 15% of patients had a four-point improvement on the NIHSS at 24 hours and 10% had symptomatic intracranial hematoma rate. Comparison of these two open label studies suggested that there would be less benefit and more hemorrhages in patients treated after 90 minutes. An independent 93-patient open label study of angiographic patency16 showed a statistically significant difference in the number of intracerebral hemorrhages related to the time from stroke onset to treatment with tissue plasminogen activator. In that study patients who developed hemorrhagic transformation had a mean OTT of 6.1 ± 1.5 hours compared to 5.3 ± 1.7 hours for those who did not show evidence of hemorrhagic infarction.
The failure to detect the treatment × OTT interaction in the initial analyses of stroke outcome13 highlights a limitation of hierarchical modeling. In hierarchical modeling, the best set of three variables is chosen from the best set of two plus a new variable chosen from all variables not yet included. If we were truly looking for the best set of three variables, we would choose from among all sets of three variables, not just from the best set of two variables plus one. This limitation was acknowledged in the previous report. Best subset selection, used in traditional regression analyses,17 would have identified this OTT × treatment interaction, but this approach was not computationally feasible given the large number of variables and potential interactions, and the lengthy calculation required by the Generalized Estimating Equations (GEE) approach to developing a global test statistic. In the future, we expect that researchers will develop a computationally efficient approach to best subset selection that might be used in selecting subsets using GEE.
It is possible that, using a best subsets approach to data analysis, other confounding variables could be identified that would influence the OTT–treatment relationship. It is also possible that other unmeasured variables could influence the relationship. As another limitation, we initially analyzed OTT as a continuous variable (to increase our power) rather than as a categorized variable as specified in the protocol, and thus the analyses could be considered as post hoc. We also cannot draw conclusions regarding the OTT–treatment relationship beyond 180 minutes.
The investigators in the NINDS rt-PA Stroke Study urge continued efforts to treat patients eligible for rt-PA as quickly as possible, preferably within 60 minutes of emergency department arrival, but always within the currently required 3-hour time window using the NINDS protocol and the methods of the NINDS TPA Stroke Study Group.14,18,19⇓⇓ Even though the importance of early treatment was a prospectively defined hypothesis, the results reported here are the result of an exploratory analysis. It would be important to test whether the results of other trials of thrombolytic therapy confirm this result.
The following persons and institutions participated in the National Institute of Neurological Disorders and Stroke rt-PA Stroke Study. Participants are listed by their affiliation at the time the trial was conducted. Some of the investigators are now at other institutions.
Clinical centers: University of Cincinnati (150 patients)—Principal Investigator: T. Brott; Co-investigators: J. Broderick, R. Kothari, M. O'Donoghue, W. Barsan, T. Tomsick; Study Coordinators: J. Spilker, R. Miller, L. Sauerbeck; Affiliated sites: St. Elizabeth (South), J. Farrell, J. Kelly, T. Perkins, R. Miller, University Hospital, T. McDonald, Bethesda North Hospital, M. Rorick, C. Hickey, St. Luke (East), J. Armitage, C. Perry, Providence, K. Thalinger, R. Rhude, The Christ Hospital, J. Armitage, J. Schill, St. Luke (West), P.S. Becker, R.S. Heath, D. Adams, Good Samaritan Hospital, R. Reed, M. Klei, St. Francis/St. George, A. Hughes, R. Rhude, Bethesda Oak, J. Anthony, D. Baudendistel, St. Elizabeth (North), C. Zadicoff, R. Miller, St. Luke-Kansas City, M. Rymer, I. Bettinger, P. Laubinger, Jewish Hospital, M. Schmerler, G. Meirose.
University of California, San Diego (146)—Principal Investigator: P. Lyden; Co-investigators: J. Dunford, J. Zivin; Study Coordinators: K. Rapp, T. Babcock, P. Daum, D. Persona; Affiliated sites: UCSD, M. Brody, C. Jackson, S. Lewis, J. Liss, Z. Mahdavi, J. Rothrock, T. Tom, R. Zweifler, Sharp Memorial, R. Kobayashi, J. Kunin, J. Licht, R. Rowen, D. Stein, Mercy Hospital, J. Grisolia, F. Martin, Scripps Memorial, E. Chaplin, N. Kaplitz, J. Nelson, A. Neuren, D. Silver, Tri-City Medical Center, T. Chippendale, E. Diamond, M. Lobatz, D. Murphy, D. Rosenberg, T. Ruel, M. Sadoff, J. Schim, J. Schleimer, Mercy General, Sacramento, R. Atkinson, D. Wentworth, R. Cummings, R. Frink, P. Heublein.
University of Texas Medical School, Houston (104)—Principal Investigator: J.C. Grotta; Co-investigators: T. DeGraba, M. Fisher, A. Ramirez, S. Hanson, L. Morgenstern, C. Sills, W. Pasteur, F. Yatsu, K. Andrews, C. Villar-Cordova, P. Pepe; Study Coordinators: P. Bratina, L. Greenberg, S. Rozek, K. Simmons; Affiliated sites: Hermann Hospital, St. Lukes Episcopal Hospital, Lyndon Baines Johnson General Hospital, Memorial Northwest Hospital, Memorial Southwest Hospital, Heights Hospital, Park Plaza Hospital, Twelve Oaks Hospital.
Long Island Jewish Medical Center (72)—Principal Investigators: T.G. Kwiatkowski (6/92–), S.H. Horowitz (12/90–5/92); Co-investigators: R. Libman, R. Kanner, R. Silverman, J. LaMantia, C. Mealie, R. Duarte; Study Coordinators: R. Donnarumma, M. Okola, V. Cullin, E. Mitchell.
Henry Ford Hospital (62)—Principal Investigator: S.R. Levine; Co-investigators: C.A. Lewandowski, G. Tokarski, N.M. Ramadan, P. Mitsias, M. Gorman, B. Zarowitz, J. Kokkinos, J. Dayno, P. Verro, C. Gymnopoulos, R. Dafer, L. D'Olhaberriague; Study Coordinators: K. Sawaya, S. Daley, M. Mitchell.
Emory University School of Medicine (39)—Principal Investigator: M. Frankel (7/92–10/95), B. Mackay (11/90–6/92); Co-investigators: J. Weissman, J. Washington, B. Nguyen, A. Cook, H. Karp, M. Williams, T. Williamson; Study Coordinators: C. Barch, J. Braimah, B. Faherty, J. MacDonald, S. Sailor; Affiliated sites: Grady Memorial Hospital, Crawford Long Hospital, Emory University Hospital, South Fulton Hospital; M. Kozinn, L. Hellwick.
University of Virginia Health Sciences Center (37)—Principal Investigator: E.C. Haley, Jr.; Co-investigators: T.P. Bleck, W.S. Cail, G.H. Lindbeck, M.A. Granner, S.S. Wolf, M.W. Gwynn, R.W. Mettetal, Jr., C.W.J. Chang, N.J. Solenski, D.G. Brock, G.F. Ford; Study Coordinators: G.L. Kongable, K.N. Parks, S.S. Wilkinson, M.K. Davis; Affiliated sites: Winchester Medical Center, G.L. Sheppard, D.W. Zontine, K.H. Gustin, N.M. Crowe, S.L. Massey.
University of Tennessee (14)—Principal Investigator: M. Meyer (2/93–), K. Gaines (11/90–1/93); Study Coordinators: A. Payne, C. Bales, J. Malcolm, R. Barlow, M. Wilson; Affiliated sites: Baptist Memorial Hospital, C. Cape, Methodist Hospital Central, T. Bertorini, Jackson Madison County General Hospital, K. Misulis, University of Tennessee Medical Center, W. Paulsen, D. Shepard.
Coordinating center: Henry Ford Health Sciences Center—Principal Investigator: B.C. Tilley; Co-investigators: K.M.A. Welch, S.C. Fagan, M. Lu, S. Patel, E. Masha, J. Verter; Study Coordinators: J. Boura, J. Main, L. Gordon; Programmers: N. Maddy, T. Chociemski; CT Reading Centers: Part A–Henry Ford Health Sciences Center, J. Windham, H. Soltanian Zadeh; Part B–University of Virginia Medical Center, W. Alves, M.F. Keller, J.R. Wenzel; Central Laboratory: Henry Ford Hospital, N. Raman, L. Cantwell; Drug Distribution Center: A. Warren, K. Smith, E. Bailey.
Committees:Executive: K.M.A. Welch, B.C. Tilley, J.R. Marler; Steering: K.M.A. Welch (Chair), T. Brott, P. Lyden, J.C. Grotta, T.G. Kwiatkowski, S.R. Levine, M. Frankel, E.C. Haley, Jr., M. Meyer, B.C. Tilley, J.R. Marler; Genentech, Inc. Participants: J. Froehlich, J. Breed; Data And Safety Monitoring Committee: J.D. Easton (Chair), J.F. Hallenbeck, G. Lan, J.D. Marsh, M.D. Walker.
Project office: National Institute of Neurologic Disorders and Stroke, Project Officer: J.R. Marler.
Supported by the National Institute of Neurological Disorders and Stroke (NINDS) (N01-NS-02382, N01-NS-02374, N01-NS-02377, N01-NS-02381, N01-NS-02379, N01-NS-02373, N01-NS-02378, N01-NS-02376, N01-NS-02380). Genentech, Inc., South San Francisco, provided for supply and distribution of study drug (placebo and Activase, Alteplase) as well as clinical site monitoring.
↵*See the Appendix on page 1654 for a list of study participants.
Received October 21, 1998.
Accepted in final form August 24, 2000.
The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group.Tissue plasminogen activator for acute ischemic stroke.N Engl J Med . 1995;333:1581–1587.
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Haley EC Jr., Levy DE, Brott TG,et al.Urgent therapy for stroke II. Pilot study of tissue plasminogen activator administered within 90–180 minutes from onset.Stroke . 1992;23:641–645.
Zivin JA, Lyden PD, DeGirolami U,et al.Tissue plasminogen activator. Reduction of neurologic damage after experimental embolic stroke.Arch Neurol . 1988;45:387–391.
Zivin JA. Factors determining the therapeutic window for stroke.Neurology . 1998;50:599–603.
Mahoney FI, Barthel DW. Functional evaluation: The Barthel Index.Maryland State Med J . 1965;February
Van Sweiten JC, Koudstall PJ, Visser MC, Schouten HJA, van Ginn J. Interobserver agreement for the assessment of handicap in stroke patients.Stroke . 1987;19:604–607.
Teasdale G, Knill–Jones R, Vander J. Observer variability in assessing impaired consciousness and coma.J Neurol Neurosurg Psychiatry . 1978;41:603–610.
The American Nimodipine Study Group.Clinical Trial of Nimodipine in Acute Ischemic Stroke.Stroke . 1992;23:3–8.
The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group.Intracerebral hemorrhage after intravenous rt-PA therapy for ischemic stroke.Stroke . 1997;28:2109–2118.
The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group.Generalized efficacy of rt-PA for acute stroke: subgroup analysis of the NINDS rt-PA stroke trial.Stroke . 1997;28:2119–2125.
McNeil D. Epidemiological research methods. New York: John Wiley & Sons, 1977;349–381.
Tilley BC, Marler J, Geller NL,et al.Use of a global test for multiple outcomes in stroke trials with application to the National Institute of Neurological Disorders and Stroke rt-PA Trial.Stroke . 1996;27:2136–2142.
Tilley BC, Lyden PD, Brott TG, Lu M, Levine SR, Welch KMA. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. Total quality improvement method for reduction of delays between emergency department admission and treatment of acute ischemic stroke.Arch Neurol . 1997;54:1466–1474.
Zivin JA, Fisher M, DeGirolami U, Hemenway CC, Stashak JA. Tissue plasminogen activator reduces neurological damage after cerebral embolism.Science . 1985;230:1289–1292.
DelZoppo GJ, Poeck K, Pessin MS,et al.Recombinant tissue plasminogen activator in acute thrombotic and embolic stroke.Ann Neurol . 1992;32:78–86.
Seber GAF. Linear regression analysis. New York: John Wiley & Sons, 1977;349–381.
Marler JR, Emr M, Jones P, eds. Proceedings of the National Symposium on Rapid Identification and Treatment of Acute Stroke. The National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health, 1997. Available online at http:www.ninds.nih.gov (NINDS) and http:www.stroke-site.org (Brain Attack Coalition).
The National Institute of Neurological Disorders and Stroke (NINDS) rt-PA Stroke Study Group.A systems approach to immediate evaluation and management of hyperacute stroke. Experience at eight centers and implications for community practice and patient care.Stroke . 1997;28:1530–1540.


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Science Interviews
How do bees see flower iridescence?
Interview with
Alison Reed, University of Cambridge
Part of the show Supersenses: Extraordinary Animals
Bee_IRR2.jpg
Cambridge Department of Plant Sciences
PlayDownload
Recent studies have shown that bees can recognise iridescence. This is the rainbow pattern that you see on the shiny side of a CD and some plants use iridescence to give them their colour too. Kate Lamble headed over to Cambridge University's Bee Laboratory to speak to PhD student, Alison Reed about her research.
Alison - I'm particularly interested in looking at flower colour and the texture of a flower surface to see how bees and insect pollinate and interact with that surface.
Kate - Why do you think your research is important? How can it help us understand the natural world?
Alison - Well, because pollination and insect behaviour is so important and it's all around us, and it affects a lot of the things that we value including food production. That just a general understanding of how this process works is really valuable and it might feed on to other projects which might be able to benefit crop production and food production in the future.
Kate - So, how do bees see the world? Is it particularly different from what we see as humans?
Alison - Well, the colour spectrum that they see is very different to us. So, they can see UV wavelengths which we can't see and the colours that they see are quite different to what we see. And so, we need to look at things from the bee's point of view and do experiments to see if they can see colours that we can see basically. So, we're looking at iridescence in flowers because even though we can see it, bees may not be able to see it, so that's why we need to test it.
Kate - When I think of iridescence, I think of really shiny things like beetles or butterflies, but I don't necessarily think of flowers. Can you tell us a little bit more about how it works in plants?
Alison - It's very similar. A lot of the structures that animals use are also used by plants, but it wasn't really studied until very recently and that's why our lab is really interested in it. For example, we're mainly looking at flowers which have diffraction grating, so they have grooves, they're all folding at the cuticle on their petals, and that produces a diffraction grating which makes iridescence. I mean, that does happen in animals, but mostly, animals use multi-layers, but petals predominantly use diffraction gratings. It's fairly unique to flowers and we haven't found any flowers which have multi-layers on their petals.
Kate - If you want to test whether a bee can see these tiny folds on a flower, how do you go about testing that?
Alison - Well, the folds on a flower, very similar to the folds that you find on a CD. So, when you rotate a CD, you'll see the different colours and the iridescence, and that's exactly the same structure that we see on a flower. So sometimes to begin with, we wanted to see if they could see that CD iridescence because it's a perfecting grating. So, it produces a perfect iridescence. So, we first would test to see if they could see that and they could. And so then we followed that up by doing some experiments with flowers which had similar structures but not quite so perfect and they could also see those diffraction gratings in that iridescent effect.
Kate - Are there any particular flowers that you use that are particularly iridescent?
Alison - One of the first ones that we discovered was tulip flowers which have quite a good iridescence obviously and you could see that's why, one of the reasons why they're so shiny when you look at the surface of a tulip. And we've used those for most of our experiments because that's what's been used in the past, but over time, we're gradually finding more and more flowers that have got even better diffraction gratings and even better iridescence, so hopefully, we'll test them with those in the future.
Kate - If you're testing to see if a bee can see that iridescent effect, how do you physically go about it? Do you just show a bee your flower and see what happens?
Alison - Well, we can't really use real flowers because there are so many other things to consider like scent, so we make artificial flower in the lab out of plastic, and we do a differential conditioning experiment where you have two different flowers - one is iridescent and one isn't. Then with the non-iridescent flower, you provide a punishment which is a bitter quinine solution and with the iridescent one, you provide a reward which is a sugary sucrose solution. But if they can tell the difference between the two, they should learn not to go to the quinine and the horrible tasting flowers, but to go to the iridescent ones.
Kate - Could you show me a couple of those artificial flowers that you've got?
Alison - Yeah, of course. This is one made from a CD, so you have an impression of the CD and dental wax which makes a mould basically, a really fine structure mould and then you can make a plastic replica of the surface using resin.
Kate - So, it sort of looks like a small plastic coin with a hole in the middle.
Alison - It's basically like a miniature CD with a pigment in the plastic resin.
Kate - And why is there a hole in the middle? What's that used for?
Alison - That's used for putting a sucrose reward so the bees can feed from the middle, so it's basically replicating the structure of a flower.
Kate - It doesn't look particularly like a flower. I mean, if it was me, I'd make them to look like pretty petals.
Alison - The most important thing for us is that they're all the same so that they're comparable. I guess we could make them look like petals, but these bees have never seen flowers before so it wouldn't make much difference, I don't think.
Kate - If you've made that one from a CD, how would you go and make one from a flower?
Alison - It's very similar. You have to make sure that the petal that you're casting is very flat and you do the same thing basically. So, you go into the gardens and you find a flower that you're interested in testing and you make up the wax and you press the petal into the wax, and it dries within 10 minutes and then you've got your cast, your mould for making your discs.
Kate - So, what have you found out? Is there a difference between the CD ones that you've been using and the tulips?
Alison - It's very similar for CDs and for flowers, but bees move faster between the iridescent disks than they do between the non-iridescent ones. So, when you're using flower casts made from flowers with flat cells, that produces a very different result to flowers that have this diffraction grating on their surface.
Kate - So, do you think that flowers have evolved these tiny structures in order to attract insects like bees?
Alison - Sort of co-evolved I would've thought, insect vision and flower colours sort of co-evolved. I mean, it's important for the flower that it's unique in its environment so that it gets pollinated because obviously, it wants pollen from its own species to be transferred to another flower of the same species. So, it's really important that these flowers are unique and unusual. And that's one of the reasons probably why this is so helpful for flowers because it makes them unique.
Kate - Has there anything come up that you haven't expected?
Alison - How temperamental the bees are I think. You don't realise how much they're affected by the weather and by the conditions that you keep them in, and just what they feel like on a day to day basis I guess. So, sometimes you'll get bees that come and start an experiment, and then they'll go back to the colony and they won't appear for another few days and your experiment has been ruined. So, you have to start from the beginning again, but I guess that's all part of working with animals.
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redpajama_set_name: RedPajamaCommonCrawl


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Surprise, Surprise - Rep. Wilson, Democrats Call General Kelly "Racist"...
by Kurt
BREAKING: Quentin Tarantino KNEW About Horny Harvey Weinstein For DECADES...
BOOM: Congress Passes New Budget As Rand Pledges To Fight With Trump For Massive American Tax Cut!
Breaking News, Donald Trump, Economy, Featured, Media, News, Politics, Popular, Trending
by Kurt 3 years ago 3 years ago
Rand Paul, one of the most principled leaders in Washington, voted against the GOP budget despite his friendship with President Trump.
But on tax cuts? Rand is all-in.
The Republican senator tweeted to Trump this morning, pledging to help pass a massive tax reduction for the American people:
I'm all in for tax cuts @realDonaldTrump. The biggest, boldest cuts possible – and soon!
— Senator Rand Paul (@RandPaul) October 20, 2017
READ MORE: Steve Bannon Prepares For All-Out WAR Against RINO Republicans!
More from Reuters:
On Thursday, the Republican-controlled Senate approved the budget resolution for the 2018 fiscal year, with Paul casting the lone Republican vote against it. That approval paves the way for their tax-cut proposal that would add up to $1.5 trillion to the federal deficit over the next decade to pay for the cuts.
U.S. President Donald Trump on Friday signaled optimism for passage of the cuts, saying Paul would back the proposed tax measure when it comes up for a vote.
"The Budget passed late last night, 51 to 49. We got ZERO Democrat votes with only Rand Paul (he will vote for Tax Cuts) voting against," Trump wrote on Twitter. "This now allows for the passage of large scale Tax Cuts (and Reform), which will be the biggest in the history of our country!"
Paul responded with his own tweet, saying, "I'm all in for tax cuts @realDonaldTrump. The biggest, boldest cuts possible – and soon!"
The Kentucky Republican had said he would not vote for the budget measure unless it in kept in line with previously enacted federal budget spending caps.
Republicans are still hammering out their tax legislation after releasing an initial outline. The administration has said it would deliver up to $6 trillion in tax cuts to businesses and individuals.
Let's hear it for Rand and the GOP congress!
Wow, we haven't been able to cheer for congress in a long time!


text:
custom football sweatshirts
HomeI've had way more good games than bad ones, and I've played over 500 games online.. RB JERICK MC KINNON had 146 scrimmag
I've had way more good games than bad ones, and I've played over 500 games online.. RB JERICK MC KINNON had 146 scrimmag
I've had way more good games than bad ones, and I've played over 500 games online.. RB JERICK MC KINNON had 146 scrimmage yards (95 rush, 51 rec.) rush TD last week. Buccaneers notes: QB JAMEIS WINSTON passed for 334 yards TD for 86.7 rating last week. The meeting went poorly, by all accounts, and Harrison ended the season the NFL most heavily fined player in a single season, with $100,000 in levies.. Le chaleureux boui boui local fait assurment…
Some critics have argued that their issue with NFL players taking a knee is not so much the act of kneeling alone but do
Some critics have argued that their issue with NFL players taking a knee is not so much the act of kneeling alone but doing so during the national anthem. "He made me a better person, without a doubt. Pa [Paterno] is telling me there, he saying we played 1,000 games, we never had crowd noise called. All of the products are made in America, a key theme of the ad, the company noted. It had been only African Americans sitting…
Part of that is because of the shortcomings found in each prospect. New this year is the ability to watch with an Amazon
Part of that is because of the shortcomings found in each prospect. New this year is the ability to watch with an Amazon Prime or a CBS All Access subscription. You must be able to immerse yourself into a game, and not take your eyes off of it for even a moment. The difference between this game and the first meeting is the coach on the opposing sideline. David was inducted into the Comstock Athletic Hall of Fame in 2013…


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Mineplex — игровой сервер в игре Minecraft. Является одним из четырёх серверов, официально сотрудничающих со студией Mojang Studios, разработчиками игры Minecraft. Сервер был запущен 24 января 2013 года. По состоянию на середину 2016 года на Mineplex ежемесячно заходили миллионы уникальных игроков. На своем пике популярности сервер имел онлайн около 10 000 игроков почти в любое время, а 28 января 2015 года побил рекорд в Книге рекордов Гиннесса за то, что имел самый большой онлайн среди всех остальных серверов в Minecraft — 34 434 игроков.

История
Mineplex был основан и создан 24 января 2013 года Грегори Байлосом, известным в Minecraft как «Sterling_» и «Spu_». Mineplex является одним из старейших серверов Minecraft, которые работают и по сей день. Сервер получил большое увеличение количества игроков после того, как американский ютубер Джордан Марон (более известный под псевдонимом CaptainSparklez) опубликовал видеоролик с обзором на Mineplex. В 2016 году профессиональный баскетбольный клуб Даллас Маверикс совместно с сервером Mineplex создали мини-игру для сервера, под названием «Dallas Mavericks World». Согласно пресс-релизу команды, это позволяет игрокам соревноваться в строительных соревнованиях и играть в баскетбольную мини-игру в полномасштабной модели Американ Эйрлайнс-центра. Мини-игра была запущена на сервере летом 2016 года. В Книге рекордов Гиннесса 2016: Gamers Edition Mineplex был включен в список самых популярных серверов Minecraft, имея сразу 34 434 игрока на сервере 28 января 2015 года. Этот рекорд был потерян у сервера Hypixel в том же году. Популярность Mineplex снизилась с момента своего пика популярности, сейчас на нём играют в среднем около 500 игроков.

Обновления
С 2020 года у проекта Mineplex было 7 крупных обновлений, включая последнее, которое вышло 4 августа 2021 года.

Хронология обновлений
 Добавление нано-игр () — обновление, вышедшее в конце сентября 2020 года. В нём было исправлено много игровых багов, добавлены новые мини-игры (Bomber, Slimeball, Splash Down, Frenzy), а также были обновлены и удалены некоторые существующие.
 Обновление классических игр () вышло 10 октября 2020 года, после предыдущего обновления. Было разработано командой Bedrock Game Insights для версии Bedrock Edition. Были исправлены многие ошибки и были обновлены «классические» игры сервера (Dragons, Micro Battles, Turf Wars).
 На следующий день после выхода Classics Games Update вышло новое обновление под названием Halloween Update () приуроченное к Хэллоуину. Оно временно добавило на сервер соответствующую «жуткую» атмосферу и внесло изменения в игровой процесс классов сервера. Также были добавлены тематические карты.
 2 ноября 2020 года вышло ещё одно Halloween Update, но уже для Bedrock Edition. Разработчики исправили некоторые баги и добавили тематику Хэллоуина.
 11 декабря 2020 года вышло новогоднее обновление, добавившее рождественскую тематику и изменившее игровой процесс.
 В июле 2021 года вышло обновление для Bedrock Edition, которое ввело нововведения и изменения в игровой процесс.
 Большое патч-обновление вышло 4 августа 2021 года и исправило множество багов и ошибок, мини-игры также были обновлены.

Характеристики
Главной особенностью сервера Mineplex являются различные мини-игры, специально настроенные и сильно модифицированные многопользовательские карты с различными целями. Эти мини-игры обеспечивают выигрышную игровую механику для игры в песочницу. Они делятся на такие категории, как Классика, Аркада, Чемпионы, Кланы и Праздничные мини-игры. Чтобы заплатить за сервер и его разработку, сотрудники из Mineplex LLC продают игрокам внутриигровые косметические предметы и специальные функции.

Примечания

Ссылки
 Официальный сайт Mineplex

Программное обеспечение, разработанное в 2013 году
Серверы Minecraft

redpajama_set_name: RedPajamaWikipedia


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INTERVIEWS TELEVISION NEWS VIDEO
The Santa Clauses Video Interview with Tim Allen, Kal Penn, Elizabeth Mitchell, Jason Winer and Jack Burditt
Nov 28, 2022 DISNEY, ELIZABETH MITCHELL, KAL PENN, THE SANTA CLAUSES, TIM ALLEN
Struggling to find their rightful place in the world can be a challenge for anyone, even celebrated pop culture icons as Santa Claus. Even a man who has brought joy to countless families around the world for several decades can begin to realize that his own wife and children need to spend quality time with him, at home, as they get older. That's certainly the case for Tim Allen's incarnation of Santa Claus in the new Christmas mini-series, 'The Santa Clauses,' which is based on the hit 1990s-2000s film series of the same name.
Jack Burditt, who created the comedy-fantasy mini-series, worked as an executive producer and the showrunner on the project, as well. Allen and Jason Winer also served as executive producers on, and the latter also directed two episodes of, the comedy.
The first three episodes of the six-episode mini-series are now streaming on Disney+. The last remaining three episodes of 'The Santa Clauses' will premiere every Wednesday, with the last installment debuting on December 14.
In 'The Santa Clauses,' Scott Calvin (Allen) has been working as the titular Santa Claus for nearly 30 years. He's as jolly as ever, but as Christmas declines in popularity, so does his Santa magic. As a result, Scott struggles to keep up with the demands of the job, as well as being there for his family.
Upon discovering there's a way to retire from his post, Scott considers stepping down as Santa Claus. So he sets out to find a worthy successor so that he can become a better husband to his wife, Carol Calvin / Mrs. Claus (Elizabeth Mitchell), and father to their children, Buddy (Austin Kane) and Sandra (Elizabeth Allen-Dick).
Allen and Mitchell generously took the time recently to participate in a global virtual press conference to talk about starring on 'The Santa Clauses.' They were joined by fellow co-star Kal Penn, who plays Simon Choksi, a game inventor and product developer on the series, as well as Winer and Burditt.
Watch the video of 'The Santa Clauses' global virtual press conference above.
Disney's 'The Santa Clauses' stars Tim Allen as Scott Calvin and Elizabeth Mitchell as Carol Calvin. (Disney)
World Championship Race Scandal: Car Dealer Found Dead, Davies Investigates
Interview: Diego García Talks Causeway (Exclusive)


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1898, Castleford (Yorkshire) – 1986, Hadham (Hartfordshire)
Born at Castleford, Yorkshire, on 30th July
Attends elementary school in Castleford
Enlists in the Civil Service Rifles
Registers at the Sculpture department of Leeds College of Art as their first student.
Wins scholarship for the Royal College of Art, London
Instructor at the RCA Sculpture School
First solo exhibition at the Warren Gallery in London
Marriage to Irina Radetsky
Exhibits in the British Pavilion at the Venice Biennale
Becomes first head of sculpture at Chelsea School of Art
First solo exhibition abroad, at Buchholz Gallery, New York
Awarded Honorary Doctor of Literature, University of Leeds
Appointed member of the Royal Fine Arts Commission (1948-71)
First open space large scale sculpture "Family Group" in Stevenage
First retrospective at the Tate Gallery
Appointed Member of the Order of the Companions of Honour
Awared Order of Merit
Appointed member of the Arts Council of Great Britain
Received Honorary Doctorate, Royal College of Art, London
Elected Honorary Fellow of the Royal Institute of British Architects
Retrospective exhibition at Forte di Belvedere, Florence
Henry Moore Sculpture Centre opened at the Art Gallery of Ontario, Toronto
Inauguration of the Henry Moore Foundation at Much Hadham
Attends documenta 6 in Kassel
Exhibition at the Metropolitan Museum of Art, New York
Dies on 31st August in Perry Green, Hertfordshire


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universities in hague
The International Business School The Hague (IBSH) is an … Henley Business School, University of Reading. Leiden University College The Hague Leiden University College The Hague Leiden University College The Hague (LUC) is the international Honours College of Leiden University, offering an innovative and cutting edge Liberal Arts & Sciences programme to highly talented and motivated students from all over the world. In the Centre for Studies and Research, a select number of research will be supervised by experts in their field and will have access to the library in the Peace Palace.The Hague Academy of International Law Â, Leiden University College The Hague (LUC) is the international Honours College of Leiden University, offering an innovative and cutting edge Liberal Arts & Sciences programme to highly talented and motivated students from all over the world. 2501 EE The Hague . The Hague Academy is not only a unique experience for students: preparing and delivering lectures is an extraordinary experience for the professors, too. Clingendael 7 The Hague Masters Degrees in The Hague, Netherlands Higher education providers in The Hague include a number of universities of applied sciences as well as other specialist institutions. That it can develop distinctive curricula to help students function confidently in a global society that is changing faster every day. 2595 DG The Hague Most of them are four-year programmes, though some can be shortened to three years of study. Together with academics and fellow students from all over the world, you will actively address these challenges. Two brains are better than one. You will find that The Hague is a crossroads of cultures with well over one hundred nationalities represented, making your study abroad experience truly diverse. 2587 AH The Hague Read More, We are proud of the fact that Hotelschool The Hague is one of the last independent single sector Universities of Applied Sciences in The Netherlands. The University of Groningen offers a BSc degree in medicine in global health. ... Lange Voorhout 17 Together, we map out a learning path that suits you and your ambitions. Campus The Hague Alongside Leiden, Leiden University has a second hometown: The Hague. EPA TU Delft Campus The Hague Leiden University College, which is entirely English-speaking, offers an academic study programme that responds to today's global issues. Phone: +31 (0)70 315 47 77 Click on"Read more" for a detailed description of the university and an overview of the study programs offered.... On this page you can search for Universities, Colleges and Business schools in The Hague. With more than 65 Bachelor's programmes to choose from, you are sure to find the right programme for you at The Hague University of Applied Sciences. Â, The T.M.C. I was really keen on both universities, but thought the Hague should be more interesting. E-mail: info@asser.nl The strategic intent of KCN is to educate and equip its students with profound knowledge in Christian theology. Website: www.hotelschool.nl/en/ Leiden University - Campus The Hague Campus The Hague is a faculty of Leiden University, located in The Hague. Hotelschool The Hague was founded and funded by the hospitality industry. Trusted by students since 2002, ACADEMICCOURSES is your multilingual gateway to higher and continuing education close to home and around the world. We have over 65 bachelor's degree programmes which vary in type and length. That makes our university one of the most international universities of applied sciences in the Netherlands. The Hague Higher education is more than a college degree. Turfmarkt 99 (5th floor) See reviews, photos, directions, phone numbers and more for the best Colleges & Universities in Hague, NY. The Hague University of Applied Sciences (THU) is a university of applied sciences with a hands-on, vocational philosophy mixing both theory and practice. That's what The Hague University of Applied Sciences encourages everyone to do. Universities in The Hague (Den Haag) More than 30,000 students study in The Hague, a large share of which is international. You can immediately apply what you learn as a student in the international environment that The Hague offers. Hotelschool The Hague was founded and funded in 19 The main campus of the university is located in The Hague. E-mail: info@hotelschool.nl Website: www.thehagueacademy.com The knowledge and skills you develop here will benefit you for the rest of your life, regardless of the career path you choose! The University offers bachelors, masters and preparatory courses. Information is exploratory. Check out this overview of all educational institutions and programs in The Hague at the Study in The Hague website. Phone: +31 (0)70 324 53 84 Host University; Living Accommodations; Passport and Visa; About The Hague. Â, Campus The Hague is a faculty of Leiden University, located in The Hague. Students will be supervised by judges and other employees from institutions such as the International Court of Justice and the International Criminal Tribunal for the former Yugoslavia. HAC-T.M.C. . King's College of the Netherlands (KCN) as the name connotes, is a small educational institution driven with the goal of providing Christian theology as well as contemporary business education through teaching and research. Mekelweg 5 2517 KJ The Hague Website: https://www.koncon.nl/en/, The Royal Academy of Art (KABK) has been a leader in educating artists and designers since 1682. We have over 65 bachelor's degree programmes which vary in type and length. Universities in The Hague. Email: internationalcentre@denhaag.nl, https://www.tudelft.nl/onderwijs/opleidingen/masters/epa/msc-engineering-and-policy-analysis/. . Read More, Looking at the world around you with open eyes: at The Hague University of Applied Sciences that is simply the norm. We expect the same active, open-minded and critical attitude from you. MLU-OAS offers you a English Master of Science programme in Shipping and Transport at our location in Rotterdam, the Netherlands. 2511 DP The Hague Read More, Located right on The Hague University of Applied Sciences (THUAS) campus, The Hague Pathway College offers academic pathways in partnership with THUAS, which lead to globally recognized undergraduate The program in The Hague (Den Haag) offers the opportunity to enroll in a variety of disciplines at The Hague University of Applied Sciences European Studies Programme. Read More, If you're looking for a bachelor's degree programme, then you've come to the right place at THUAS. THU has more than 20,000 students who come from over 135 different countries. Research universities in the Netherlands are institutions of tertiary … What about the Hague? Campus The Hague offers bachelor and master programmes and teaching programmes for professionals working in the public sector, such as International Affairs, International Law or Security. Clingendael Netherlands Institute of International Relations Located right on The Hague University of Applied Sciences (THUAS) campus, The Hague Pathway College offers academic pathways in partnership with THUAS, which lead to globally recognized undergraduate degrees. Asser Institute organises a Summer Law Program in The Hague every year. Phone: +31 (0)70 800 95 00 Website: http://www.hagueacademy.nl, The Royal Conservatoire in The Hague is the oldest conservatoire in the Netherlands. The International Business School The Hague (IBSH) is an innovative school of business and management established in The Netherlands and is based in the city of The Hague. Website: www.lucthehague.nl Population: approx. Read More, The International Business School The Hague (IBSH) is an innovative school of business and management established in The Netherlands and is based in the city of The Hague. ACADEMICCOURSES is part of the Keystone Academic Solutions family of student-centered websites that help students and higher education institutions find each other online. ... Website: https://www.tudelft.nl/en/, The Hague International Centre Maastricht University has a similar programme in English. Educational institutions such as Hotelschool The Hague, the Royal Academy of Art and the Royal Conservatoire have a worldwide reputation. The University of Groningen (or RUG for short, known in Dutch as Rijksuniversiteit Groningen) is the second oldest university in the Netherlands, having been … ... Get all info about the various study options in The Hague and compare the tuition fees and length of study. USAC welcomes students interested in studying abroad in the Netherlands to study at The Hague University's Academy of European Studies! You will also be encouraged to conduct research in cooperation with eminent and enthusiastic scholars. All seven faculties are active at Campus The Hague and almost 20% of the total number of students at the university … Maastricht University, University College Maastricht (UCM) Maastricht University (UM) is the most international university in the Netherlands and, with 16,861 students and 4,300 employees, is still growing. The Hague University of Applied Sciences was founded in 1987, as a result of a merger of fourteen smaller institutions of higher professional education in the region. If you're looking for a bachelor's degree programme, then you've come to the right place at THUAS. A true international city, home to over 180 nationalities. The Hague is the political center of the Netherlands, and is a great location to pursue studies on Europe and its politics. Full list of The Hague colleges - Information about The Hague top schools, this complete listing of The Hague area universities and colleges and colleges near The Hague provides all the critical information. ... The first three years can be taught in English at Dutch universities but only two have this option and very few of the places are available to international students. ACADEMICCOURSES connects students with educators providing courses, preparatory years, short programs, certificates, diplomas, and more. Telephone: +31 (0)70 302 49 10 Since its foundation, the Hotelschool has become an international school specialised in hospitality management offering a 4-year Bachelor's degree in Hotel and Hospitality Management. Imperial College Business School. Prinsessegracht 4 We are proud of the fact that Hotelschool The Hague is one of the last independent single sector Universities of Applied Sciences in The Netherlands. E-mail: info@hagueacademy.nl Looking at the world around you with open eyes: at The Hague University of Applied Sciences that is simply the norm. Asser Instituut At Leiden University, the oldest university in the Netherlands, you can make a valuable contribution to tackling the various national and international challenges facing modern society. The by far largest institution is The Hague University of Applied Sciences (THUAS). Website: www.iss.nl Students are taught by leading international musicians and dancers.Royal Conservatoire The Hague offers a broad choice of appealing educational programmes in an international environment. The Hague University The Ivy League is an athletic conference composed of sports teams from eight private institutions of higher education in the Northeastern United States. Add to shortlist Compare. The Hague University of Applied Sciences consists of faculties, research groups and service departments. I've also been accepted in the Hague and Groningen, but didn't apply to Maastricht, because I didn't want to study European, but International Law. The Hague University. Are you curious, critical and involved in the world around you? Your Pathway to The Hague University … MLU-OAS is formerly known as Netherlands Maritime University. Start your pathway to one of 10 degrees taught in English. Anna van Buerenplein 301 We keep an open mind, do not shy away from difficult discussions and allow one another the space to disagree. Â, The Engineering and Policy Analysis program from TU Delft at the Faculty of Technology, Policy and Management combines engineering sciences with insights from the humanities and the social sciences. E-mail: info@tudelft.nl At Leiden University, the oldest university in the Netherlands, you can make a valuable contribution to tackling the various national an Website: www.clingendael.nl Phone: +31 (0)15 278 56 00 E-mail: info@koncon.nl Since, the university has increased the number of campuses, number of staff and students, and programmes offered. Website: http://www.asser.nl/ Website: www.campusdenhaag.leiden.edu Learn more about The Hague University of Applied Sciences (THUAS). And young professionals from countries all over the world choose to follow an advanced programme at the International Institute for Social Studies. After all, it is by keeping its eyes wide open that a university of applied sciences can claim its place at the centre of society. Presence Rank* Impact Rank* Openness Rank* Excellence Rank* 1: 60: Utrecht University / Universiteit Utrecht: 176: 96: 84: 43: 2 Luiss University. Website: https://www.kabk.nl/en/, Founded in 1929, the Hotelschool The Hague has become an international school specialised in hospitality management. 544,000; Distance from Amsterdam: 40 miles; Distance from Paris: 295 miles; The Hague lies on the North Sea and is a modern and sophisticated city, being one of four United Nation cities in the world. Netherlands School for Public Administration (NSOB) Leiden University - Campus The Hague Phone: +31 (0)70 3024242 Campus The Hague offers bachelor and master programmes and teaching programmes for professionals working in the public sector, such as International Affairs, International Law or Security. 2628 CC Delft E-mail: info@thehagueacademy.com Similar Universities. Email: info@nsob.nl Since, the university has increased the number of campuses, number of staff and students, and programmes offered. TU Delft has one of the largest university campuses in the world. Hotelschool The Hague was founded and funded in 1929 by the hospitality industry to create a central place where industry partners could gain and share new insight, skills and knowledge. Universidad Simón Bolívar (Colombia) The University of Sydney. Phone: +31 (0)70 315 15 15 Examples here include internships, graduation assignments, programme-specific projects and collaboration with our expertise centres. Leiden University College The Hague ... Brusselselaan 2 2502 LT The Hague University of the Arts, The Hague has garnered a reputation of a strong educational institution as it is among the top 30 universities of Netherlands. Website: www.nsob.nl The IBSH is unlike many othe Kortenaerkade 12 It is part of Erasmus University Rotterdam. The Hague has a large number of educational institutions which provide excellent study programmes in English. It counts as one of the best universities for engineering and technology worldwide, typically seen within the top 20. Website: https://www.tudelft.nl/onderwijs/opleidingen/masters/epa/msc-engineering-and-policy-analysis/ Research universities. 2517 JN The Hague University of the Arts, The Hague (KABK) - private higher education institution in Netherlands. You will easily find all information about the top ranked universities in The Hague. E-mail: post@kabk.nl You will easily find all information about the top ranked universities in The Hague. The courses offered by the Royal Academy of Art spell tradition, innovation and research. It is also an independent centre of applied research, critical thought and strategic advice about politics and governance. Email: info@clingendael.nl Hotelschool The Hague Highly skilled professional staff with international professional practices, guide and accompany students through their studies.Royal Academy of Art On this page you can search for Universities, Colleges and Business schools in The Hague. 2511 BT The Hague, Telephone: +31 70 353 50 43 The Hague University of Applied Sciences (Dutch: De Haagse Hogeschool), abbreviated THUAS, is a university of applied sciences with its campuses located in and around The Hague in the Randstad metropolitan region in the west of the Netherlands. Colleges Universities in Hague on YP.com. Also, many international conferences on these topics take place here. For accurate information, refer to the official website of the school. Email: info@iss.nl We want to change and improve the world we live in. Read More, King's College of the Netherlands (KCN) as the name connotes, is a small educational institution driven with the goal of providing Christian theology as well as contemporary business education through After all, it is by keeping its eyes wide open that a university of applied science It is an institute of music and dance where experiment and innovation go hand in hand with tradition and craftsmanship. ... 2500 GK The Hague Â, The Netherlands School of Public Administration (NSOB) is the country's premier provider of public sector executive education. Leiden University - Campus The Hague You can save time and contact universities in The Hague directly: fill out the"Request free information" form, which will put you in contact with the admissions office. Maritime & Logistics University of applied sciences (MLU-OAS) is a specialised educational institute. The Royal Academy of Art and Royal Conservatoire (KC) constitute the University of the Arts in The Hague. Â, Delft University of Technology - also known as TU Delft - is the largest and oldest Dutch public technological university. Phone: +31 (0)70 800 95 03 At the end of your journey, you'll be awarded a university of applied sciences diploma. Our modest community size in the historical cities of Leiden and The Hague creates a highly personal and committed atmosphere. Participants study important juridical topics that have a global reach. Phone: +31 (0)70 373 86 95 View the range of options! LUC is located in The Hague. The University has been located here for over 20 years. University of the Arts The Hague | Homepage Welcome to the website of the University of the Arts The Hague, the overarching organisation of the Royal Academy of Art and the Royal Conservatoire, The Hague. International Institute of Social Studies, ISS Here is an overview of universities in The Hague region. 2595 CA The Hague City Hall (Atrium) Spui 70 Â, The Hague Academy of International Law offer post-academic summer courses about public and private law. Juliana van Stolberglaan 1 Phone: +31 (0)15 27 89111 Leiden In The Hague, the international city of peace and justice, tens of thousands of people jointly pursue a more peaceful, just and secure world.For instance at the International Court of Justice and the International Criminal Court. You can attend guest lectures from highly respected experts and do an internship at one of the many institutions that help to shape our world. Phone: +31 (0)70 3420300 ... The Faculty's mission is to develop robust models and designs to solve the complex challenges of today's networked, urbanized knowledge society. . Seen within the top ranked universities in the international institute for Social Studies you can immediately what! 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Le Petit-duc de Mohéli (Otus moheliensis) est une espèce d'oiseaux de la famille des Strigidae.

Répartition
Cette espèce est endémique de l'île de Mohéli, aux Comores.

Annexes

Références taxinomiques

Liens externes

Strigidae
Faune endémique de Mohéli


Too many luxury hotels in China?
China may be facing a case of oversupply in its luxury hotel scene.
"When a new market opens up it is quite normal that you will see a lot of new supply go in," Clement Kwok, CEO of Hong Kong and Shanghai Hotels tells CNBC. "At the moment many people see great future prospects for China and they are building hotels in China." Hong Kong and Shanghai Hotels is the owner of the brand Peninsula with a total of nine hotels across the U.S. and Asia. The group has hotels in Beijing, Shanghai and Hong Kong, and is looking toward second-tier cities in China for future development.
According to the article, Shanghai alone has more than 1,000 luxury hotel rooms that were added to the market in 2013. "Definitely our room rates are lower than would be the case if there was less supply - that will always be the case," Kwok adds. "If there wasn't competition it would mean that the market we are operating in is not a desirable place."
Whether or not these hotels survive comes down to a matter of quality. Hoteliers often face the issue of balancing the necessity to invest in upgrades and renovations. Battling the competition is easy by keeping the product fresh while keeping margins under control.
"Who has the long-term staying power? We do not yet know," says Kwok. "We are still in the early stages of the game, and there's still a lot of the game to be played."


Book featuring Hadiach The main characters in Nikolai Gogol's story Ivan Fyodorovich Shponka and His Aunt are from Hadiach (Gadyach in the 1957 translation by David Magarshack). Residents Mykhailo Drahomanov (1841-1895), political theorist, economist, historian, philosopher, and ethnographer Olena Pchilka, mother of Lesya Ukrayinka and a sister of Drahomanov Gallery See also Treaty of Hadiach... Download Mirgorod and Its Inhabitants 1983 torrent YIFY full movie or via magnet. Based on the works of Nikolai Gogol - 'The Old World Landowners', 'The Tale of How Ivan Ivanovich Quarreled with Ivan Nikiforovich', 'Ivan Fyodorovich Shponka and His Aunt'.
Booktopia has The Diary of a Madman, The Government Inspector and Selected Stories, Penguin Classics by Nikolai Gogol . Buy a discounted Paperback of The Diary of a Madman, The Government Inspector and Selected Stories online from Australia's leading online bookstore.... Often rejected by women (a fate he bestowed upon Ivan Fyodorovich Shponka), Gogol never found a wife. His only comfort was in writing. His only comfort was in writing. Although Gogol received mixed reviews from critics, Pushkin and Turgenev admired and were influenced by his work.
25/10/2018�� 1- 3 Apr 10 02 Ivan Fyodorovich Shponka and His Aunt 4. 1- 4 Apr 17 02 The Nose 5. 1- 5 Apr 24 02 The Mysterious Portrait 6. 1- 6 May 1 02 The Diary of a Madman 1- 4 Apr 17 02 The Nose 5. 1- 5 Apr 24 02 The Mysterious Portrait 6.


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As Gaeilge Issue 3 Volume 15 | 09 January 2020
Welcome to the January edition of our Newsletter
2020 Visual Artists Workspace scheme recipients
Arts Council Collection
Irish-Language Writer-in-Residence 2020 in DCU
Aosdána General Assembly
Bring Your Own Lanyard on 14th February: Change Makers conference
ilDÁNA 2020 / 2021
Culture Night Conversations
Artist in Residence in Technology and Innovation
Public consultation for a new National Policy on Architecture
Launch of RAISE Phase 2 - call for expressions of interest
Deadline: Bursary Awards, Thursday, 30 January, 2020
Creative Schools/Scoileanna Ildánacha – Invite applications from schools across Ireland
Young Ensembles Scheme 2020
Deadline: Arts and Disability Connect scheme
Creative Europe Desk
Creative Europe in 2020
Cultural Cooperation Projects in the Western Balkans 2019
Equality, Human Rights, and Diversity
Equality, Human Rights and Diversity
ilDÁNA is designed to enhance the TG4 schedule by supporting the making of an ambitious and cinematic long-form documentary on the arts in Irish. A budget of €120,000 will be made available by the partners for this landmark documentary which will have a theatrical window before its broadcast in a primetime slot on TG4.
Applications must be made through TG4's E Comm E Coimisiún TG4 (HERE) no later than 17:00 on Friday, 31 January 2020.
Guidelines for ilDÁNA 2020:
Films commissioned for ilDÁNA will provide a definitive creative treatment of their arts subject. All artistic disciplines will be considered. Contemporary subjects are preferred but contemporary treatments of historical works/subjects may also be considered.
One film will be funded with a budget of up to €120,000. It will launch with a dedicated cinema screening and will have a theatrical window before broadcast to a primetime TG4 audience in 2020 / 2021.
TG4 will administer the commissioning process of ilDÁNA films, TG4 will issue contracts and TG4's 'Terms of Trade' will apply.
Representatives from TG4, the Arts Council/An Chomhairle Ealaíon and an independent assessor will make the selection for ilDÁNA.
Applications must be made through TG4's E Comm E Coimisiún TG4 (HERE) no later than 17:00 on Friday, 31 January 2020. Incomplete or late applications will not be accepted.
Film duration: feature length
Production Budget: Up to €120,000 per film
Format: HD with English subtitles
Language: Irish or bilingual
Applications for ilDÁNA must include the following:
A synopsis of the ilDÁNA film
A detailed treatment of the proposal
A description of the intended creative approach
An audience strategy that identifies the film's national TV audience plus any plan for theatrical exhibition (film festival/cinema) if applicable
A detailed production budget and budget summary (including music and subject
clearances, deliverables and marketing materials)
CVs of the creative team involved in the proposal including director, producer, writer, editor
Evidence of ownership to include copies of all option and writers' agreements entered in respect of story and script, if applicable to the project
Written confirmation in the form of clearances and permissions of key subject's willingness to participate, where applicable
Three excerpts of the director's work (not showreel) that inform the proposal
Any other relevant supporting materials that inform the creative approach for the proposal.
TG4 and the Arts Council/ An Chomhairle Ealaíon
encourage the employment of film practitioners working through the Irish language;
involve gender equality both in terms of contribution and production personnel;
require the provision of equitable conditions and fair remuneration for artists involved in the making of the ilDÁNA films.
ilDÁNA films will be selected based on:
the artistic vision of the applicant and his/her creative approach to the proposed subject
the feasibility of the proposal in the context of the objectives of IlDÁNA
the track record of the applicant
the extent to which the proposal promotes gender equality in terms of contribution and production personnel.
Additional funding (up to €5K per successful project) may be made available to support theatrical exhibition where a convincing audience strategy is proposed.
Shortlisted applicants will be invited to discuss their proposal towards the end of February 2020. The award for the series will be made by TG4 and standard commissioning terms will apply to the production agreement. It is expected that projects will be completed and available for broadcast on TG4 in 2020 / 2021.
Applicants must comply with all relevant statutory obligations.
All contracts will depend on provision of a Tax Clearance Certificate from the Revenue Commissioners.
Candidates are informed that the information provided may be disclosed to the public under the Freedom of Information Act.
There is no agreement – or any other type of contract – until a formal contract is written by or on behalf of TG4. Copyright for the film rests with the producer.


Madhya Pradesh Rajya Sahakari Bank Maryadit recently releases an employment notification to hire 03 eligible and capable aspirants for Consultant Posts. Candidates who are looking for govt jobs in Apex Bank can apply for this recruitment notification by submitting offline application form before the closing date i.e.(18th July 2018). Candidates can download format of application of through official website www.apexbank.in & fill all information into form and attach the copies of all the necessary documents with the application form Send the application to the address given below in the post along with the required documents.
Educational Qualifications For Apex Bank Jobs 2018: Candidates who have completed B.E or B.Tech/ LLB/ MBA or M.Com or CA/ Graduation with CAIIB from the recognized university or institution with required minimum marks can apply for Apex Bank jobs 2018.
The age of candidate who is willing to apply for Apex Bank should not be more than 62 Years As on 01-07-2018.
Contenders for Madhya Pradesh Rajya Sahakari Bank Maryadit Jobs 2018 are selected based on their performance in Personal Interview.
How to Apply for Apex Bank Vacancy?
First of all you have to logon to the Official website of organization that is www.apexbank.in.


text:
using System.Collections.Generic;

namespace Lette.ProjectEuler.Core.Runner
{
    public interface IProblemSuiteBuilder
    {
        IReadOnlyList<IProblem> CreateFromAssembly(string assemblyPath);
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}

redpajama_set_name: RedPajamaGithub