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Dantrolene Improves Survival After Ventricular Fibrillation by Mitigating Impaired Calcium Handling in Animal Models
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Background—Resistant ventricular fibrillation, refibrillation. and diminished myocardial contractility are important factors leading to poor survival after cardiac arrest. We hypothesized that dantrolene improves survival after ventricular fibrillation (VF) by rectifying the calcium dysregulation caused by VF.
Methods and Results—VF was induced in 26 Yorkshire pigs for 4 minutes. Cardiopulmonary resuscitation was then commenced for 3 minutes, and dantrolene or isotonic saline was infused at the onset of cardiopulmonary resuscitation. Animals were defibrillated and observed for 30 minutes. To study the effect of VF on calcium handling and its modulation by dantrolene, hearts from 14 New Zealand rabbits were Langendorff-perfused. The inducibility of VF after dantrolene administration was documented. Optical mapping was performed to evaluate diastolic spontaneous calcium elevations as a measure of cytosolic calcium leak. The sustained return of spontaneous circulation (systolic blood pressure ≥60 mm Hg) was achieved in 85% of the dantrolene group in comparison with 39% of controls (P=0.02). return of spontaneous circulation was achieved earlier in dantrolene-treated pigs after successful defibrillation (21±6 s versus 181±57 s in controls, P=0.005). The median number of refibrillation episodes was lower in the dantrolene group (0 versus 1, P=0.04). In isolated rabbit hearts, the successful induction of VF was achieved in 83% of attempts in controls versus 41% in dantrolene-treated hearts (P=0.007). VF caused diastolic calcium leaks in the form of spontaneous calcium elevations. Administration of 20 μmol/L dantrolene significantly decreased spontaneous calcium elevation amplitude versus controls. (0.024±0.013 versus 0.12±0.02 arbitrary unit [200-ms cycle length], P=0.001).
Conclusions—Dantrolene infusion during cardiopulmonary resuscitation facilitates successful defibrillation, improves hemodynamics postdefibrillation, decreases refibrillation, and thus improves survival after cardiac arrest. The effects are mediated through normalizing VF-induced dysfunctional calcium cycling.
- cardiopulmonary resuscitation
- death, sudden, cardiac
- ryanodine receptor calcium release channel
- ventricular fibrillation
Ventricular fibrillation (VF) is a major cause of sudden cardiac arrest and is the primary determinant of mortality from cardiovascular diseases. Nearly 83 000 cases of sudden cardiac death reported annually in United States are due to VF.1 Cardiopulmonary resuscitation (CPR) and defibrillation are the mainstays of immediate management; however, despite significant progress in CPR techniques in past decades, mortality from VF has remained unacceptably high,2,3 with 23.8% surviving to hospital admission and only 7.6% survival to hospital discharge.3 Shock-resistant VF, decreased cardiac contractility postdefibrillation (myocardial stunning), and the recurrence of VF (ventricular refibrillation) are the main challenges faced during CPR and they increase the morbidity and mortality.3,4
Editorial see p 834
Clinical Perspective on p 885
Studies of ion channel blockers have shown little or no benefit in experimental and clinical VF.2 However, VF is associated with significant impairment in cardiac calcium cycling and results in intracellular calcium ([Ca]2+i) overload.5–7 Dysfunction in [Ca]2+i handling and calcium overload during VF has been proposed to cause myocardial stunning postdefibrillation4,6 and trigger refibrillation by activating compensatory mechanisms such as the Na+/Ca2+ exchanger and causing after-depolarizations.8 Failed defibrillation or refibrillation leads to more ischemia, worsening the calcium overload. The stabilization of cardiac calcium cycling may be able to mitigate this vicious cycle, enhance defibrillation, and thus improve survival after VF.7
Ryanodine receptor-2 (RyR2) is the major calcium release channel expressed in the sarcoplasmic reticulum and plays a crucial role in cardiac contractility.9 Recently, it has been proposed that increased calcium leak from RyR2 results in the progression of heart failure and triggers VF.10 The stabilization of RyR2 function has been shown to be protective against cardiac arrhythmias in animal models of catecholaminergic polymorphic ventricular tachycardia.11 Stabilizing RyR2 function and restoring normal calcium cycling during VF might facilitate defibrillation, improve cardiac contractility, and improve survival in VF.
Dantrolene sodium, a stabilizer of skeletal muscle RyR1, has recently been shown to bind to RyR2, restore sarcoplasmic reticulum calcium reserve, improve cardiac function, and prevent arrhythmogenesis in various animal models of heart failure.11–13 We hypothesized that the administration of dantrolene during CPR improves survival in an in vivo swine model of sudden cardiac arrest due to VF by (1) enhancing defibrillation success and organizing VF, (2) improving hemodynamics after defibrillation, and (3) decreasing the incidence of refibrillation. We further hypothesized that these effects of dantrolene are mediated via its effects on stabilizing cardiac calcium cycling that results from VF-induced dysfunction of [Ca]2+i handling.
In Vivo Swine Model
Healthy 10- to 12-week-old Yorkshire pigs with weights ranging between 27 and 34 kg (n=26) were used. The protocol was approved by the Animal Care Committee of St. Michael's Hospital. A more detailed description of the experimental model and measurements are provided in the online-only Data Supplement Materials. After initial stabilization, VF was induced by burst pacing (10 V of 60-Hz current for 2 s) and left untreated for 4 minutes. Then, chest compression was started by using a pneumatic device (Lucas, Jolife AB, Lund, Sweden) at 100 compressions per minute and manual ventilation at 6 breaths per minute with 5 to 6 L/min of 100% O2 with an AMBU bag was performed. CPR was continued for 3 minutes with no interruption of chest compressions. At the onset of CPR, animals received either a bolus dose of dantrolene sodium (2 mg/kg) or isotonic saline. The dantrolene dose was determined based on previous studies on in vivo swine models of malignant hyperthermia14 and other animal models.15 After 7 minutes of VF, defibrillation was attempted at 150J. If defibrillation was unsuccessful, CPR was immediately restarted and defibrillation was again attempted at 200J after 2 minutes (with subsequent defibrillation attempts at 300J→360J→360J→360J→360J in case of the failure of the second or subsequent shocks). The energy level delivered is based on the front-panel–indicated energy values on the defibrillator. After successful defibrillation, animals were monitored for 30 minutes to assess the outcome and occurrence of refibrillations. Refibrillation was treated with the same energy level that defibrillated the initial VF. If animals could not be defibrillated during refibrillation, the energy level was increased in a stepwise fashion to up to 4 attempts at 360J.
Ex Vivo Rabbit Langendorff Model
New Zealand white rabbits with weight ranging from 2.4 to 4.5 kg were used (n=14). Details on the model and measurements are provided in the online-only Data Supplement Materials. VF was induced by burst pacing for 30 s at 60 Hz and 10 V, and hearts were continuously perfused during VF. At 1 minute of VF, a single dose of dantrolene (20 μmol/L) or isotonic saline was infused in the bubble trap. VF was monitored for 4 minutes and then defibrillated at 5J. Five more episodes of fibrillation-defibrillation were tried on each heart with 3 minutes of recovery time (in sinus rhythm) in between. VF duration for each VF episode was 4 minutes (or shorter in the case of self-termination) followed by defibrillation. Simultaneous optical mapping of calcium and voltage was performed during pacing to evaluate calcium amplitude alternans. Alternans was defined as the beat-to-beat difference of >10% in calcium wave amplitude. Alternans threshold was defined as the longest pacing cycle length (PCL) at which alternans emerged. Diastolic spontaneous [Ca]2+i elevation (SCaE) as a measure for diastolic calcium leak from RyR2 was evaluated in rabbit hearts. The protocol to measure SCaE amplitudes was adopted from Lee et al.16
Isolated Cardiomyocytes and Mathematical Modeling
A detailed description of the isolated cardiomyocyte study and mathematical modeling is provided in the online-only Data Supplement Materials. In brief, isolated cardiomyocytes were paced at 10 Hz to mimic the high activation during VF in the presence of 100 nmol/L of isoproterenol. The effect of dantrolene on ameliorating the pacing-induced rapid activation of cardiomyocytes was evaluated. In computer simulations, the role of dantrolene in suppressing the VF-induced automaticity and action potential duration (APD) formation in the Purkinje system and the whole heart was assessed.
Statistical Analysis
Time to return of spontaneous circulation (ROSC), time to successful defibrillation, and the onset of refibrillation were analyzed by using the log-rank test for survival analysis. SCaE amplitudes, alternans threshold, organization index of calcium and APD waves, regularity index of VF signals, and systolic and diastolic pressure at different time points and between groups were compared by using 2-way repeated-measures analysis of variance with pairwise analysis using Sidak correction for multiple comparisons. Comparison of ordinal variables (number of refibrillations, number of defibrillation attempts) and continuous variables in unpaired groups was performed with the use of the Wilcoxon Mann-Whitney test. The Wilcoxon signed rank test was used to compare variables in paired groups. Repeated-measures logistic regression was used to compare the incidence of consecutive induced and sustained VF episodes in the rabbit hearts. Categorical variables were compared with the use of the Fisher exact test. P≤0.05 was considered statistically significant. For repeated-measures analysis between groups, the P value for treatment and time interaction is provided unless otherwise stated. For pairwise comparisons, the adjusted P values for multiple comparisons are provided. All statistical analyses were performed with the use of Stata 11.1 (Stata Corp LP) and SPSS 17.
Dantrolene Increased Survival After VF
VF was successfully induced in all 26 animals. Pulsatile normal sinus rhythm immediately postdefibrillation (initial survival) was achieved in 85% (11/13) in the dantrolene group and 54% (7/13) in controls (P=0.1). At the end of the protocol, sustained ROSC was achieved in 85% (11/13) in the dantrolene group in comparison with 39% (5/13) in the controls (P=0.02; Table).
Dantrolene Organized VF Signals and Facilitated Defibrillation
VF signals recorded at time 0 (immediately after the induction of VF), before CPR (4 minutes of VF), and immediately before the first defibrillation attempt (7 minutes of VF) were compared between the dantrolene and control groups (Figure 1). VF was significantly more organized at 7 minutes of VF in the dantrolene group versus controls as measured by the Regularity Index (RI) of VF signals (0.69 versus 0.55, P=0.004). VF organization significantly deteriorated during 7 minutes of VF in controls in comparison with dantrolene-treated pigs. (ΔRI= −0.1±0.04 in dantrolene versus ΔRI= −0.24±0.02 in controls, P=0.006; Figure 1).
In all animals combined (survivors and nonsurvivors), the dominant frequency of VF at time 0 was 7.6±0.19 and 7.5±0.26 Hz in dantrolene and control groups, respectively (P=0.53). At 7 minutes of VF (3 minutes after the initiation of CPR), the dominant frequency increased to 8.7±0.62 and 9.9±0.59 Hz in dantrolene and control groups, respectively (P=0.19). In survivors, the dominant frequency after 7 minutes of VF was significantly (P=0.047) lower in dantrolene-treated pigs than in controls (9.2±0.62 Hz and 11.2±0.61 Hz, respectively).
Hemodynamic Outcomes After CPR
Although successful defibrillation was achieved significantly (P=0.006) earlier in dantrolene-treated pigs, the time to ROSC was also shorter in the dantrolene group. ROSC (systolic blood pressure [BP]≥60 mm Hg) was achieved after 21±6 s postdefibrillation in the dantrolene group versus 181±57 s in controls (Figure 2).
Systolic and diastolic BP during the postdefibrillation period in the dantrolene group were significantly higher than in controls (P=0.0014 and P=0.0017, respectively; Figure 2). By the end of the experiments, mean systolic BP and diastolic BP was 85 (95% confidence interval, 77–93) and 61 (95% confidence interval, 54–68) mm Hg in survivors in the dantrolene group and 66 (95% confidence interval, 53–79) and 46 (95% confidence interval, 37–55) mm Hg in controls, respectively.
To account for different total duration of VF in the 2 groups overall, we compared the hemodynamic outcomes in a subgroup of animals that were successfully defibrillated with the first defibrillation attempt. The total duration of VF in these cases was 7 minutes (n=8 in the dantrolene group and n=4 in controls). Time to achieving a systolic BP≥60 mm Hg was shorter in the dantrolene group (26±8 s versus 93±48 s in controls, P=0.06). Systolic and diastolic BPs were significantly higher in dantrolene-treated pigs than in their control peers during the 30 minutes postdefibrillation period (P=0.0016 and P=0.002 for the treatment effect).
Dantrolene Decreased Refibrillation and Improved Outcomes After Refibrillation
The median number of refibrillation episodes was significantly lower in the dantrolene group than in controls. Refibrillation occurred in 2 scenarios: when postdefibrillation rhythm was normal sinus rhythm with pulsatile rhythm (initial survivors) and when the postdefibrillation rhythm was either pulseless electric activity or asystole. Because the first scenario is more clinically relevant, we analyzed refibrillation in more detail in the initial survivors of the VF (Table). All refibrillations in the dantrolene group were terminated with the first defibrillation attempt and with no impact on hemodynamic parameters and survival afterward. Refibrillations were triggered by premature ventricular contractions in 96% of refibrillation episodes (24/25). Only in 1 case was refibrillation preceded by sustained ventricular tachycardia.
Dantrolene Did Not Alter Refractoriness
There was no significant difference in the postdefibrillation effective refractory period between dantrolene and controls (215±9 ms versus 206±4 ms, P=0.47). In the dantrolene group, the QT interval at baseline and postdefibrillation was 432±48 ms and 334±83 ms, but, in controls, the corresponding values were 442±50 ms and 325±6 ms, respectively. The change in postdefibrillation QT intervals versus baseline was not significant between control and dantrolene groups (P=0.35).
Ex Vivo Rabbit Protocol
Dantrolene-Treated Hearts Were Resistant to VF and Refibrillations
After the initial induction of 2 VF episodes, dantrolene-treated hearts were more resistant to refibrillation episodes. In controls, 20 (83%) of 24 attempts resulted in VF (VF lasting ≥10 s) in comparison with 41% (14/34 attempts) in dantrolene-treated hearts (P=0.007, repeated measures logistic regression). In several instances, VF episodes self-terminated into sinus rhythm or transitioned to monomorphic ventricular tachycardia in dantrolene-treated hearts. Additionally, spontaneous refibrillation occurred in 4 control hearts and in none of the dantrolene-treated hearts during experiments. The mean duration of all VF episodes combined was shorter in dantrolene-treated hearts (226.55±79.7 s versus 574.4±144.3 s, P=0.03). Sustained VF (VF lasting ≥60 s) was observed in 67% (16/24) of episodes in controls in comparison with 29% (10/34) in dantrolene-treated hearts (P=0.03, repeated measures logistic regression).
Dantrolene Increased Alternans Threshold and Decreased Diastolic Calcium Leak From RyR2 After VF
SCaE in diastole occurred after first or second VF episode (± isoproterenol [0.3 μmol/L]) in nontreated rabbit hearts detected as elevation in calcium fluorescence before the initiation of the first spontaneous beat after the termination of pacing (Figure 3). SCaE was either absent at baseline (before VF±isoproterenol) or was associated with short amplitude relative to the pacing beats in hearts in both groups (0.015±0.01 arbitrary unit at 200 ms PCL, 0.027±0.01 arbitrary unit at 180 ms PCL). SCaE amplitude significantly (P=0.0004) increased from baseline after 2 VF episodes in controls from 0.02±0.01 arbitrary unit to 0.12±0.02 arbitrary unit at 200 ms PCL. As shown in Figure 3, the administration of 20 μmol/L dantrolene almost prevented or significantly decreased the SCaE amplitude after VF.
With the subsequent induction of VF episodes, calcium alternans emerged at longer PCL in the control hearts. Calcium alternans emerged at shorter PCL in dantrolene-treated hearts with a 10% decrease from 195±9.5 ms PCL at baseline to 173±6.7 ms post-VF in comparison with an 11% increase in controls from 215±20 ms to 235±8 ms (P=0.05; Figure 3).
Increased Spatiotemporal Organization of Calcium Waves During VF in Dantrolene-Treated Hearts
Number of calcium wave fronts was analyzed as a surrogate for spatial organization of calcium waves during VF (ie, fewer wave fronts translates into higher organization of VF). Number of calcium wave fronts at 4 minutes of VF was significantly lower in dantrolene-treated hearts than in controls (2.2±0.06 versus 2.7±0.07 waves per frame, P=0.02). See details in Figure I in the online-only Data Supplement.
Mechanism of Antiarrhythmic Effect of Dantrolene on VF-Induced Arrhythmias
Rapid pacing (at 10 Hz) induced a large increase in the number of spontaneous sarcomere-shortening events per second on termination of pacing (pacing-induced rapid activation). Dantrolene treatment reduced the rate of spontaneous shortening observed after pacing cessation (P<0.0001; Figure 4), thereby enhancing the return of infrequent spontaneous activity observed in myocytes before pacing.
Mathematical Modeling of Purkinje Fibers
Consistent with the presence of delayed after-depolarizations in the isolated myocytes, delayed after-depolarizations were routinely observed in the myocardium of the rabbit heart in the model. These delayed after-depolarizations developed into action potentials, with several firing before spontaneously stopping as sarcoplasmic reticulum calcium became depleted. In the organ-scale model, delayed after-depolarizations arising in the myocardium were always subthreshold, a consequence of the electrotonic coupling of the tissue. Conversely, delayed after-depolarizations occurring in the Purkinje system did precipitate propagating action potentials, which were transmitted into the myocardium via anterograde activation. These observations were true for all stochastic distributions studied.
Setting the level of RyR2 block in the model was based on the rabbit experimental calcium measurements. With a 12% reduction in RyR2 conduction, the minimum pacing cycle length necessary for calcium alternans was reduced from 240 ms to 185 ms, consistent with the experimental measurements (from 195 to 173 ms; Figure 4). Adding dantrolene to the Purkinje cell ionic model completely abolished the appearance of ectopic action potentials after a pace-and-pause procedure. A 12% reduction in RyR2 conductance did not abolish delayed after-depolarizations developing into action potentials, but a 47% reduction did. In the ventricular model, dantrolene prevented the appearance of action potentials arising from delayed after-depolarizations. Even at a level insufficient to stop action potential formation in isolated ventricular myocytes, no action potentials spontaneously developed from the myocardium. Applying dantrolene to the Purkinje system alone was sufficient to inhibit delayed after-depolarization–induced action potentials.
We have demonstrated that, in an in vivo model of cardiac arrest due to VF and CPR, dantrolene significantly improves survival by mitigating the time-dependent increasing disorganization of VF, enhancing defibrillation success, enhancing the achievement of the return of spontaneous circulation, and preventing postdefibrillation hemodynamic compromise. Dantrolene also led to fewer refibrillations and, in addition, did not alter refractoriness. The drug also improved spatiotemporal organization of calcium waves during VF in ex vivo rabbit hearts. Most importantly, in rabbit hearts, dantrolene increased the calcium alternans threshold and significantly reduced RyR2-dependent diastolic calcium leak. Furthermore, dantrolene-treated rabbit hearts were more resistant to VF induction and refibrillation. Taken together, these findings suggest a potential novel strategy of using dantrolene for improving resuscitation outcomes by normalizing VF-induced calcium dysregulation.
Dantrolene has been safely used in clinical settings for years as a stabilizer of skeletal muscle RyR1. Recently, dantrolene was shown to bind to RyR2, which plays a crucial role in calcium cycling and cardiac contractility.12,13,17 Dantrolene has been shown to directly bind to domain 601 to 620 of RyR2 in failing cardiomyocytes and to stabilize the interdomain interaction within the channel and significantly improve the sarcoplasmic reticulum calcium reserve.12,13,17
Dantrolene Enhances Defibrillation Success
Dantrolene infusion during CPR was associated with earlier defibrillation success and shortened time to ROSC in this study. This can be related, in part, to the improved organization of VF after dantrolene infusion. In the control group, the organization of VF signals significantly decreased over time during VF. Dantrolene prevented the time-dependent disorganization of VF signals and enhanced defibrillation. Additionally, there was a significant increase in the organization of calcium wave fronts in isolated rabbit hearts after treatment with dantrolene in comparison with controls. Dantrolene-treated rabbit hearts were less susceptible to the induction of VF with most VF episodes resulting in self-termination of VF or the transformation of VF to ventricular tachycardia in <60 s.
VF is associated with [Ca]2+i overload and the derangement of cardiac calcium cycling.7 [Ca]2+i overload can contribute to sustaining VF and failed defibrillations.18,19 The long duration of calcium transients and the disorganized calcium cycling during VF has been proposed as a possible mechanism for long-duration VF.20 At 5 minutes of long-duration VF, calcium transients have been shown to become longer and more disorganized throughout the epicardium and endocardium with significant calcium alternans.20 It has also been demonstrated that [Ca]2+i, and the changes in calcium transient amplitude can indeed affect APD during VF and promote wave break.21 In fact, [Ca]2+i can act as both a driver and modulator for the wave break.22 Therefore, agents that modulate calcium cycling can potentially enhance defibrillation success.19 For example, administration of cariporide (a Na+/H+ exchanger blocker) is shown to improve myocardial electric and mechanical stability after VF and CPR by indirectly reducing the VF-induced [Ca]2+i overload.23
We observed a significant reduction in calcium wave fronts during VF after treatment with dantrolene, which translates to increased spatial organization of calcium waves during VF. This may further explain the transition of VF to ventricular tachycardia or self-termination of VF in several dantrolene-treated rabbit hearts. It has been proposed that non–voltage-gated calcium currents (mainly RyR2 and SERCA2 activity) contribute to the maintenance of VF.24 These local calcium release events during VF can change APD and promote wave breaks.24 Additionally, spontaneous calcium release and the formation of calcium sinkholes after defibrillation shocks have been proposed to decrease the chance of successful defibrillation shocks.25 The stabilization of RyR2 and the suppression of these local calcium release events during VF can potentially break the vicious cycle of long-duration VF and [Ca]2+i overload and enhance defibrillation success as proposed by other groups.5,24,25 Purkinje fiber activation is reported to be responsible for postshock arrhythmias and unsuccessful shocks after VF both in experimental25,26 and computer modeling27 studies. In our study, dantrolene suppressed after-depolarizations and triggered activity in Purkinje fibers (presumably by suppressing the afore-mentioned diastolic SCaEs) and, therefore, prevented APD formation and the propagation in Purkinje fibers after fast pacing and VF (Figure 4). Therefore, the suppression Purkinje fiber activation during VF by dantrolene can further explain the enhanced defibrillation success and reduced number of shock-resistant VFs in the dantrolene group in our in vivo study.
Dantrolene Improved Hemodynamic Outcomes Postdefibrillation
Among survivors of the in vivo pig experiments, dantrolene-treated pigs had significantly higher systolic and diastolic BP than controls. The rise in BP was specifically evident in the first 10 minutes postdefibrillation with a peak at 5 minutes. ROSC was achieved significantly earlier, and myocardial stunning was ameliorated in dantrolene-treated pigs.
This improvement in hemodynamics by dantrolene can be explained by 2 mechanisms: (1) the shorter time to defibrillation in dantrolene group, and (2) dantrolene's effect on cardiac calcium handling and the improvement in contractility by normalizing the VF-induced calcium dysregulation.
The rise in catecholamine levels postdefibrillation28 can result in significant stimulation of β-receptors in cardiomyocytes, impair calcium cycling by affecting ion channels such as RyR2, and result in diastolic calcium leak. Calcium leaks from sarcoplasmic reticulum in diastole will compromise the sarcoplasmic reticulum calcium reserve for subsequent beats resulting in a decrease in cardiac contractility.10,29 The same cascade of events can happen in VF and diminish cardiac contractility postdefibrillation. [Ca]2+i overload caused by VF and dysfunction in cardiac calcium cycling can diminish contractility.4,6 Similarly, we have shown that significant diastolic calcium leak from RyR2 develops after VF (+isoproterenol) in isolated rabbit hearts. These VF-induced calcium leaks from RyR2 coupled with the afore-mentioned rise in β-adrenergic stimulation postdefibrillation may underlie the lower pressure postdefibrillation in control pigs. Dantrolene infusion nearly abolished diastolic calcium leak in rabbit hearts post-VF and therefore can also explain the significant improvement of hemodynamics in the dantrolene group in comparison with controls.
Other studies have shown similar inotropic effects of dantrolene in the presence of adrenergic stimulation. Dantrolene was shown to improve the force frequency relationship in failing human myocardium by enhancing cardiac contractility in the presence of sympathetic stimulation.30 The effect was more pronounced in the presence of higher isoproterenol concentrations. The peak systolic [Ca]2+i was not different between the 2 groups, suggesting that the enhanced inotropic response to isoproterenol is due to the modulation of the diastolic concentration of cytosolic calcium by dantrolene.30
It was also reported that dantrolene protects cardiac tissue against injury induced by excess β-receptor stimulation.31 More recently, it was shown that dantrolene restores cardiac contractility by suppressing diastolic calcium leak from RyR2.13
Mechanism of Reduction of Refibrillations by Dantrolene
Dantrolene-treated pigs experienced fewer episodes of refibrillation. Additionally, the inducibility and sustainability of subsequent VF was significantly attenuated in dantrolene-treated rabbit hearts. To evaluate whether the restoration of cardiac calcium cycling by dantrolene attributed to the observed antiarrhythmic effect, we evaluated the effect of dantrolene on 2 mechanisms by which dysfunctional calcium cycling results in arrhythmias and refibrillation in particular: (1) diastolic calcium leak, delayed after-depolarizations, and triggered activity; and (2) calcium alternans and reentry.
Dantrolene infusion significantly reduced the pacing-induced rapid activation of isolated mice cardiomyocytes in the presence of isoproterenol, which demonstrates a direct effect of dantrolene as an antiarrhythmic agent. Based on our modeling of Purkinje cells, dantrolene specifically terminated delayed after-depolarizations arising from Purkinje fibers as a result of VF-like activation (fast pacing). Delayed after-depolarizations and triggered activity have been proposed as a possible mechanism of refibrillation. Where there is continuous calcium leak from sarcoplasmic reticulum either as a result of the hyperphosphorylation of calcium channels by Ca2+/calmodulin-dependent protein kinase II and protein kinase A activity (adrenergic stimulation) or genetic disorders of the channels, the resultant diastolic elevation in [Ca]2+i has been shown to activate compensatory mechanisms such as Na/Ca exchanger. Na/Ca exchanger activation during the repolarization phase can then induce delayed after-depolarizations that eventually leads to arrhythmias.8,29 The same concept can be applied to VF and refibrillation, because VF is associated with a significant increase in Ca2+/calmodulin-dependent protein kinase II activity (due to fast activation) and adrenergic stimulation.28,32
Previous studies have shown that these diastolic elevations in [Ca]2+i depend on RyR2 activity (leak) and can result in delayed after-depolarizations and triggered activity in the endocardium specifically in Purkinje fibers.16,26,33 Similarly, we found that VF-like activation promotes delayed after-depolarizations in our model in cardiomyocytes and Purkinje fibers, but only delayed after-depolarizations arising from Purkinje fibers could generate APDs propagating throughout the myocardium. Specifically in isolated myocytes, VF simulation resulted in spontaneous sarcomere shortenings. These sarcomere-shortening events are consistent with the appearance of delayed after-depolarizations, which are indicative of calcium overload. Dantrolene abolished these delayed after-depolarizations at the Purkinje level, which can be explained by the effect of dantrolene on the prevention, or at least the mitigation of diastolic SCaE as observed in our experimental rabbit study. These findings further support our hypothesis that rapid activation of the heart (whether cardiomyocytes or Purkinje fibers) results in excess activation of RyR2 and eventually leads to delayed after-depolarizations and refibrillations. The stabilization of RyR2 by dantrolene provided antiarrhythmic benefits and reduced refibrillation. Almost all refibrillations in the in vivo study were triggered by ectopic beats (triggered activity), which supports the theory that after-depolarizations cause refibrillation and that dantrolene reduces these refibrillations by modulating calcium cycling and suppressing delayed after-depolarizations at the Purkinje level.
The lower incidence of successfully induced or sustained refibrillation in dantrolene-treated rabbit hearts suggests that dantrolene directly plays a role in the regulation of calcium cycling during VF, and, by restoring RyR2 function, increased the calcium alternans threshold. It also prevented delayed after-depolarization formation at the Purkinje level after VF simulation. Refibrillations likely result from nonorganized spontaneous sarcoplasmic reticulum calcium release in the form of nonorganized calcium waves in the Purkinje system, and dantrolene provided antiarrhythmic benefits by suppressing these arrhythmogenic calcium waves in the Purkinje system.
Study Limitations
One of the limitations to this study is that healthy pigs with no underlying heart failure or coronary disease were studied. Although the evidence is strong for direct interaction of dantrolene with RyR1, RyR3, and RyR2, we cannot rule out the possible effect of dantrolene on other channels. However, we analyzed the changes in QT intervals and early repolarization pattern before and after VF as a surrogate for assessing the potassium channels involved in repolarization, and we found no impact.
We used an equivalent of the adult dose of defibrillation energy in the in vivo study, but the pigs weighed within the pediatric range (≈30 kg). Thoracic impedance of pigs and humans is different, and higher defibrillation energy levels are usually required for pigs in comparison with humans. However, the relatively high energy level might have had an impact in the defibrillation outcomes and should be taken into account.
Another limitation to this study is that different species were used for the in vivo and ex vivo studies. The interspecies variability in VF dynamics and defibrillation might affect the results and might limit the ability to extrapolate the findings from 1 model to the other.
Additionally, it is not clear whether the findings from these models would relate to resistant VF in humans. Therefore, the results should be interpreted cautiously in this context.
Dantrolene infusion during VF facilitates successful defibrillation, improves hemodynamics postdefibrillation, decreases refibrillation, and thus improves survival after cardiac arrest without promoting arrhythmias. The effects are mediated by enhancing calcium cycling and, at the Purkinje level, preventing arrhythmogenic calcium leak in diastole and suppressing triggered activity caused by rapid activation and sympathetic stimulation. Dantrolene might prove to be a useful adjunctive treatment for the management of sudden cardiac arrest due to VF.
We acknowledge Dr Wayne Chen for his invaluable feedback. We also thank John Asta, Chris Meyer, Sina Lahsaee, Lily Zou, and Gerhard Dashi for their contribution and efforts. We also thank Dr Joan Ivanov for her invaluable feedback and help with the statistical analysis of the data.
Sources of Funding
The project has been funded by an operating grant from the Canadian Institute of Health Research (CIHR) and by a career Investigator award to Dr Nanthakumar from the Heart and Stroke Foundation of Canada.
Despite decades of research in resuscitation, survival from sudden cardiac arrest due to ventricular fibrillation (VF) is still very low. The use of various antiarrhythmic agents has not resulted in the improvement in survival to discharge. Studying the molecular pathways and ion channels contributing to the maintenance of VF has become an area of interest in resuscitation research. In this study, we have demonstrated that targeting the VF-induced impairment of cardiac calcium cycling due to ryanodine receptor-2 dysfunction, by administration of dantrolene, significantly enhances defibrillation and facilitates the return of spontaneous circulation. The strategy also improved cardiac contractility postdefibrillation and reduced refibrillations. Modeling and computer simulations demonstrated that these effects of dantrolene are mostly mediated through its effects on Purkinje fibers. These findings suggest a novel therapeutic strategy in the management of sudden cardiac arrest due to VF. Dantrolene has been shown to be a safe drug and has been used in emergency settings such as malignant hyperthermia. Given its ease of delivery and rapid effect, dantrolene might prove to be an adjunctive treatment to cardiopulmonary resuscitation and defibrillation in sudden cardiac arrest due to VF.
The online-only Data Supplement is available with this article at http://circ.ahajournals.org/lookup/suppl/doi:10.1161/CIRCULATIONAHA.113.005443/-/DC1.
- Received August 5, 2013.
- Accepted November 21, 2013.
- © 2014 American Heart Association, Inc.
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Working conditions of criminal investigators are demanding, dangerous, and stressful. Sometimes you will have to work overtime or on holidays. Plus, being at crime scenes can be very mentally challenging because of the type of scenes you encounter. You must also be physically fit.
Criminal investigators have many responsibilities including:
collect and record evidence
interview suspects and witnesses
keep sketches
keep notes on autopsies
file paperwork
Working Conditions
What do you want to be when you grow up?
By: Nicole G.
To be a criminal investigator, you must have a four year science degree. Degrees in forensic science, psychology, or criminology is not required but helps your chance of getting the job. Only a few jobs require someone to have a high school deploma or GED.
You can become a criminal investigator through many processes of application like:
online application
structured interview
personal interview
You have to take a drug test and a medical exam to become a criminal investigator. You also have to take a background check and you must be able to handle firearms.
If you find out being a criminal investigator isn't right for you, you can always choose one of these similar jobs:
Police and detectives
financial advisors
private or federal investigators
computer forensics
The average yearly salary of a criminal investigator is $53k yearly, with the highest paid being $103k and the lowest being $31k. How much you get paid depends on how much experience you have.
What is a Criminal Investigator?
Crime investigators are the people who investigate and solve crimes, from burglaries to homicides. To do this they must find evidence like witnesses, records, and video surveilance.
"Become a Criminal Investigator." Become a Criminal Investigator. U.S Immigration and Customs Enforcement, n.d. Web. 28 May 2015.
Criminal investigator jobs are expected to increase 20% in the next five years according to the The United Stated Bureau for Labor Statistics. Competition for jobs in the federal and state will be higher than local governments.
"What Is a Criminal Investigator?" Legal Career Path. N.p., 12 Feb. 2013. Web. 28 May 2015.
Alliance, University. "Detective and Criminal Investigator Career and Salary Profile." Florida Tech Online. Bisk Education, 2015. Web. 28 May 2015.
High School Classes
Classes that will prepare you to become a criminal investigator include:
visual arts
civics and political science
physical education
Good Areas for Criminal Investigators
The best colleges to enroll in for a criminal degree are:
San Francisco State University
University of New Haven
University of Minnesota
West University of Florida
"Private Detectives and Investigators." United States Department of Labor. Bureau of Labor Statistics, 8 Jan. 2014. Web. 1 June 2015.
Career Path
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Bachelor's Degree
Fraud Investigator
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Security Director
Loss Prevention Investigator
Criminal Investigator
Detective or Investigator
Security Supervisor
Police Chief
The areas with the highest rate of employment are suburban areas. Texas has the highest rate of employment for criminal investigators, but California has the highest paid investigators.
"Detectives and Criminal Investigators." U.S. Bureau of Labor Statistics. U.S. Bureau of Labor Statistics, n.d. Web. 03 June 2015.
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LAST CALL! 50% OFF! Offered is a fancy and exciting vintage bolero. In a cream tone textured brocade, it served well in the '60's, but is equally stylish for today. We are showing this over a black vintage sheath, but picture it over a more modern top and skinny jeans--smashing. Adding a Hollywood touch is the pair of clear rhinestone studded buttons at the bottom as a means of closing the bolero (snaps serves as secure anchors). The bolero has a notched collar and crosses to the left. Details: 21" sleeves; 12" shoulder to waist; 37" bust; 31 1/4" bottom circumference; 14 1/2" across back. This lined in cream satin. We found no stains and no holes, but PLEASE NOTE: the left buttonhole which is the one that closes the jacket is frayed from use. This item has not been cleaned, but we note no unusual odor. Item 92146a
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Collectibles with a vintage sensibility; specialty in ladies hats and fashion accessories.
Any weekend finds me scouring auctions for fun "stuff". My finds are for your pleasure and mine.


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Archive for the 'Iran' Category
This article perfectly illustrates the foolishness of progressive foreign policy. As if we hadn't gotten too much of that during the Obama administration, we're getting another shot of it in this article.
In the article, it says "The move is also likely to isolate the U.S., cause confusion about its intentions, permit Iran to claim the high ground in any push to renegotiate, and provide both allies and adversaries with more evidence that the United States can't be trusted." Let's start with that last statement about the US not being able to be trusted. What's true is that the US can be trusted to correct its mistakes that left allies in the Middle East threatened by the developing Iranian hegemon.
There's a reason why the nations refused to attend President Obama's summit on the Middle East. Those nations flocked to President Trump's summit, though. That leads to the refutation that not certifying the Iran deal again will "likely isolate the US." Here's a question the author might want to ask himself: how can a man who gets 50+ Middle East and southwest Asia and north African nations to attend his summit on Iran and its proxies be isolated? Does this look isolated?
This isn't reassuring:
The 2015 deal lifted sanctions against Iran in exchange for limits on its nuclear program. Iran's compliance is being monitored by the United Nations, which has declared that the Islamic Republic is sticking by the letter of its obligations.
Getting the UN's word that Iran is living up to any agreement is like getting an arsonist's word that he won't play with matches anymore. In other words, it's worthless. As for the limits, they're temporary. President Trump is attempting to renegotiate more permanent limits, something the Obama administration didn't even attempt to do.
Iran still is developing a missile program and actively opposing U.S. policy in Syria, Iraq and plenty of other places. Trump, who has called the agreement "embarrassing" and much worse, can't really declare that Iran is violating its terms. Instead, he's likely to say Iran is not following its spirit, or that the deal is no longer in the U.S. national interest. The idea seems to be that decertifying will increase pressure on Iran to behave.
The point the Trump administration made last week is that the agreement was so limited in scope as to make it worthless. Getting Iran to limit some of its terrorist-supporting actions isn't securing our nation or our allies.
The Obama-Kerry foreign policy was built on the premise that appeasement works. It doesn't. That's why it's important for the US to reassert its leadership in the Middle East.
This article in the Pi-Press is disgusting in its dishonesty. In the article, the 'reporter' says that "Trump's highly controversial order suspends refugee admissions for 120 days and bars all immigration for 90 days of citizens from seven Muslim-majority countries with terrorism concerns: Iran, Iraq, Libya, Somalia, Sudan, Syria and Yemen. Those now being barred from the country include refugees who have already been thoroughly vetted by U.S. agencies."
Either this reporter is telling an outright lie or he's incredibly ignorant of the truth. Though Politifact attempts to sweep things under the carpet, the fact remains that FBI Director James Comey testified that "We can only query against that which we have collected, and so if someone has never made a ripple in the pond in Syria in a way that would get their identity or their interests reflected in our database, we can query our database till the cows come home, but … there'll be nothing show up, because we have no record on that person."
Politifact tried spinning things by saying "But did James Comey actually say the FBI "cannot properly vet" people coming from the Middle East? No, he didn't. Beruff is distorting a point Comey was making about a flaw in the vetting process, but he was reiterating the system in place was actually much better than it had been in the past."
Here's the real exchange:
Ranking member Rep. Bennie Thompson (D-Miss.) asked Comey, "Mr. Director, before this committee, [FBI] Assistant Director [Michael] Steinbach said that the concerns in Syria is that we don't have the systems in place on the ground to collect the information to vet. That would be the concern. Databases don't hold the information on these individuals. Is that still the position of the department?"
"Yes, I think that's the challenge we're all talking about, is that we can only query against that which we have collected, and so if someone has never made a ripple in the pond in Syria in a way that would get their identity or their interests reflected in our database, we can query our database till the cows come home, but we're not gonna—there'll be nothing show up, because we have no record on that person," said Comey. "That's what Assistant Director Steinbach was talking about," he added.
Not having verifiable data to compare against isn't "a flaw in the vetting process." That's admitting that it's impossible to vet people. Here's video of FBI Director Comey's testimony:
That's pretty open-and-shut testimony.
Technorati: Donald Trump, Executive Order, James Comey, Extreme Vetting, Refugee Resettlement Program, Syria, Iraq, Iran, Libya, Yemen, Somalia, Sudan, Barack Obama, Politifact, Spin
The dishonest media is doing its best to whip the nation into a frenzy by not reporting the contents of President Trump's EO accurately. Democrats are doing everything possible to keep the public misinformed. Kamala Harris, who replaced Barbara Boxer as the junior senator from California, is protesting President Trump's EO that temporarily bans Muslims from 7 specific nations known as terrorist hotbeds. Rather than doing the job that people expect them to do, which is to accurately inform people of what's happening in Washington, DC, the dishonest media is doing its best to mislead the public while telling people that President Trump is a racist and an Islamophobe.
William Jacobsen rightly said in this post that people "should actually read it". The important part of what President Trump's EO said actually cites the US law that permits him to act in our nation's national security interests. It says "Pursuant to section 212(f) of the INA, 8 U.S.C. 1182(f), I hereby proclaim that the entry of nationals of Syria as refugees is detrimental to the interests of the United States and thus suspend any such entry until such time as I have determined that sufficient changes have been made to the USRAP to ensure that admission of Syrian refugees is consistent with the national interest."
Not only is the dishonest media getting things wrong. It's badly misleading people to the point where it's difficult that this isn't intentional. Progressive activists aren't helping, either, by flocking to social media to complain about President Trump's EO, then aggregating them under the hashtag #MuslimBan. What the dishonest media and these progressive activists haven't explained is how the so-called #MuslimBan doesn't include the nation with the biggest Muslim population in the world (Indonesia) or how Muslim nations like Turkey, Jordan, Egypt and Saudi Arabia aren't on the list.
Then there's this:
The order bars all people hailing from Iraq, Syria, Iran, Libya, Somalia, Sudan and Yemen. Those countries were named in a 2016 law concerning immigration visas as "countries of concern."
If Trump is anti-Muslim for temporarily banning people from these countries, then former President Obama must be anti-Muslim, too, because he signed the bill into law. Thomas Lifson's article highlights the fact that Syria is the only nation named in President Trump's EO:
I read the order and Iraq, Iran, Libya, Somalia, Sudan and Yemen are not mentioned in it. Go back and read it again. Do a "ctrl-f" to find "Iraq." Where is "Iraq" in the order. It's not there. Only Syria is there. So where are the seven nations? Where is the "Muslim ban?" It turns out this was a form of fake news, or alternative facts. Trump didn't select seven "Muslim-majority" countries. US President Barack Obama's administration selected these seven Muslim-majority countries.
This is proof positive that President Trump is right in calling the dishonest media the opposition party. I'd go a step further. I'd argue that they're unindicted co-conspirators with dishonest Democratic Party politicians like Elizabeth Warren, Chuck Schumer, Kamala Harris, Dianne Feinstein and Nancy Pelosi.
If their collective dishonesty were political capital, that bunch would rule Washington, DC for decades. Thank God that isn't the case. They're just a bunch of dishonest progressive politicians that the nation rejected this past November. I'll leave you with this video:
It's video of a manipulative, dishonest politician. I never thought I'd say this but I think I'd prefer Harry Reid over this politician.
The opening paragraph of Thomas Friedman's latest column is proof positive that he's a blithering idiot. It's proof, too, that he's overpaid.
The opening paragraph of Friedman's column says "For those of you confused over the latest fight between President Obama and Prime Minister Bibi Netanyahu of Israel, let me make it simple: Barack Obama and John Kerry admire and want to preserve Israel as a Jewish and democratic state in the Land of Israel. I have covered this issue my entire adult life and have never met two U.S. leaders more committed to Israel as a Jewish democracy."
It's difficult to comment on such breathtaking stupidity. In the next paragraph, Friedman continues, saying "But they are convinced — rightly — that Netanyahu is a leader who is forever dog paddling in the middle of the Rubicon, never ready to cross it. He is unwilling to make any big, hard decision to advance or preserve a two-state solution if that decision in any way risks his leadership of Israel's right-wing coalition or forces him to confront the Jewish settlers, who relentlessly push Israel deeper and deeper into the West Bank."
Speaking of someone who "is unwilling to make any big, hard decision to advance or preserve a two-state solution if that decision in any way risks his leadership", this is who fits that description:
It's impossible to make a thoughtful argument that President Obama and John Kerry are pro-Israel. First, they sell out the entire Arab Peninsula, north Africa and Israel by negotiating a sweetheart nuclear proliferation deal with Iran, then giving the biggest state sponsor of terrorism $150,000,000,000 to spend on Hezbollah, Hamas and other anti-Israel proxies in the Middle East. Then, to 'prove' their loyalty to Israel, they ship systems to bolster Israel from the missiles that Iran's proxies will buy with the money they got from Mssrs. Obama and Kerry. Then there's this:
That is what precipitated this fight over Obama's decision not to block a U.N. resolution last week criticizing Israeli settlements in the West Bank. The settlers' goal is very clear, as Kerry put it on Wednesday: to strategically place settlements "in locations that make two states impossible," so that Israel will eventually annex all of the West Bank. Netanyahu knows this will bring huge problems, but his heart is with the settlers, and his passion is with holding power — at any cost.
I won't rebut that BS. Instead, I'll let Alan Dershowitz obliterate Friedman's BS:
Before June 4, 1967, Jews were forbidden from praying at the Western Wall, Judaism's holiest site. They were forbidden to attend classes at the Hebrew University at Mt. Scopus, which had been opened in 1925 and was supported by Albert Einstein. Jews could not seek medical care at the Hadassah Hospital on Mt. Scopus, which had treated Jews and Arabs alike since 1918. Jews could not live in the Jewish Quarter of Jerusalem, where their forbearers had built homes and synagogues for thousands of years. These Judenrein prohibitions were enacted by Jordan, which had captured by military force these Jewish areas during Israel's War of Independence, in 1948, and had illegally occupied the entire West Bank, which the United Nations had set aside for an Arab state. When the Jordanian government occupied these historic Jewish sites, they destroyed all the remnants of Judaism, including synagogues, schools, and cemeteries, whose headstones they used for urinals. Between 1948 and 1967 the UN did not offer a single resolution condemning this Jordanian occupation and cultural devastation.
What Friedman doesn't say is that this UNSCR, #2334, classifies these settlements as "territories being illegally occupied by Israel, and any building in these areas — including places for prayer at the Western Wall, access roads to Mt. Scopus, and synagogues in the historic Jewish Quarter — 'constitutes a flagrant violation under international law.'"
I'll finish by stating emphatically that Thomas Friedman isn't a journalist. He'd fit right in at Media Matters or Think Progress or other far left fever swamp websites.
Technorati: Thomas Friedman, Barack Obama, John Kerry, Hezbollah, Hamas, Democrats, Alan Dershowitz, Benjamin Netanyahu, West Bank, Jewish Settlements, Mt. Scopus, Temple Mount, United Nations, Iran
It isn't a secret that CAIR isn't a legitimate civil rights organization. They've supported terrorist groups like Hamas. They were funded by Hamas. Thursday night, Hassan Shibly, the "chief executive director of CAIR-Florida's chapter, attempted to shame Carl Higbie, a former Navy Seal and the spokesman for the pro-Trump Great America PAC. Wednesday night, Higbie was on Megyn Kelly's show when Higbie talked about a registry of immigrants from Muslim countries. Higbie said "To be perfectly honest, it's legal. It'll hold constitutional muster. I know the ACLU will challenge it but I think it'll pass. We did it with Iran back a while ago. We did it during WW II with the Japanese."
Thursday night, Higbie was Megyn's guest again. This time, he expanded on his statement of Wednesday night, saying "It was strictly a reference to the scrutiny of immigrants and registration of immigrants coming from places like Japan, Germany and Italy and places like that."
When it was Shibly's turn to speak, he immediately said to Higbie "To Carl, I say 'have you no sense of decency? Sir, America is a country based on freedom of religion. Freedom of religion is a fundamental principle that I have taken an oath and I'm sure that you have taken an oath to protect. It is ineffective to target people based solely on religion. Let's target criminals. Let's target terrorists…"
Here's the video of Thursday night's interview:
It isn't that religious freedom isn't a fundamental right in the United States. It's that protecting its citizens from Islamic terrorists is one of the federal government's primary responsibilities, too. There's judicial precedent stating that forcing people coming from terrorist nations to sign into a register before entering our nation is a reasonable thing. It's interesting that CAIR is ok with registering guns in the name of preventing attacks but it's protesting against registering people who might be violent terrorists.
It's foolish to think that sovereign nations don't have the right to protect its citizens from potentially violent immigrants. In fact, as commander-in-chief and as the chief law enforcement officer of the United States, the president has an affirmative responsibility to protect his citizens from violence.
Technorati: CAIR-Florida, Hassan Shibly, National Security Entry-Exit Registration System, NSEERS, Iran, Japan, Italy, Germany, Religious Liberty, National Security, Donald Trump, Terrorism, Carl Higbie, Navy Seals, Homeland Security, Republicans
According to this article, ISIS is taking credit for the stabbing spree at Crossroads Mall in St. Cloud.
This morning, they issued this statement, saying "The executor of the stabbing attacks in Minnesota yesterday was a soldier of the Islamic State and carried out the operation in response to calls to target the citizens of countries belonging to the crusader coalition."
ISIS wasn't the only person issuing a statement Sunday morning. US Sen. Klobuchar issued a statement, saying in part "Everyone should feel safe in their community, whether they're at school or a movie theater or a shopping mall. Last night that feeling of safety was greatly shaken when an assailant stabbed eight people at the Crossroads Center Mall in St. Cloud. I have visited the mall many times, and I can't imagine the horror experienced by those visiting and working there. My heart goes out to the victims and all those who were there last night."
Noticeably missing from Sen. Klobuchar's statement was a call for knife control legislation. Noticeably missing, too, from Sen. Klobuchar's statement was her admitting that she supported President Obama's Iran deal, which transferred $150,000,000,000 to the biggest state sponsor of terrorism.
It's fitting to care about those who were attacked at Crossroads Mall last night. I don't have a problem with that. I just wish she was as passionate about stopping terrorists before they commit acts of terrorism. I'd appreciate it, too, if Sen. Klobuchar wasn't intent on inviting more terrorists into Minnesota:
MONTAGNE: Now, in a letter to the president earlier this year, you joined 13 other senators and cited a number suggested for the U.S. by a major coalition of U.S. refugee groups, 65,000 Syrian refugees. That was their number. That would be a dramatic increase. Do you think that's a realistic number?
KLOBUCHAR: Well, the U.S., since we sent the letter, has agreed to increase from the around 1,000 mark to 5 to 8,000. And Senator Durbin and I, who led the letter, see this as a positive sign and a good beginning. We're talking about it over a period of time, the 65,000. And it is actually 50 percent of what the U.N. commission on refugees suggested that we take. That's usually the ballpark of what our country does.
What type of idiot invites more potential terrorists into Minnesota? Sen. Klobuchar later said that "we have a very intense screening process for these Syrian refugees."
I wrote here that "Nicholas Rasmussen, the head of the National Counterterrorism Center, admitted 'the intelligence that we have of this particular conflict zone is not as rich as we would like it to be.'"
Now that ISIS has infiltrated Minnesota and the United States, it would probably be wise to shut down the refugee resettlement program for at least a year.
Technorati: Crossroads Mall, Terrorist Attack, ISIS, Amy Klobuchar, Refugee Resettlement Program
When Hillary criticized Donald Trump for visiting Mexico, she said "You don't build a coalition by insulting our friends or acting like a loose cannon. You do it by putting in the slow, hard work of building relationships. Getting countries working together was my job every day as your Secretary of State. It's more than a photo op. It takes consistency and reliability. Actually, it's just like building personal relationships. People have got to know that they can count on you – that you won't say one thing one day and something totally different the next."
I'm sick of Hillary flapping her gums while pretending to have been a competent secretary of state. She wasn't competent. HRC said that people "have got to know that they can count on you", something that Christopher Stevens found out he couldn't do. HRC wasn't someone he could count on. He died while counting on HRC.
Next, Hillary said that diplomacy is about "putting in the slow, hard work of building relationships." Is she talking about the slow, hard work of building a relationship with Iran's mullahs? Or building the relationship with the Muslim Brotherhood in Egypt during the Arab Spring? Perhaps, she meant capitulating and appeasing Vladimir Putin in Russia? Which of those instances would HRC pick as shining examples of her competence?
Here's hoping Donald Trump hits back at HRC with questions about her incompetence as Secretary of State.
During his speech to the delegates attending the Democratic National Convention, Vice President Joe Biden was at his BSing best. At one point in his speech, Biden attacked Donald Trump, saying "lack of empathy and compassion can be summed up in a phrase I suspect he's most proud of having made famous, 'you're fired,'. How can there be pleasure in saying 'you're fired?' He's trying to tell us he cares about the middle class? Give me a break!" That's when Biden deployed "his own well-used tagline: "That's a bunch of malarkey!"
In another part of the speech, Biden praised Hillary, saying "Everybody knows she is smart. Everybody knows she is tough. But I know what she is passionate about. I know Hillary. Hillary understands. Hillary gets it."
When Biden praised President Obama, he went way overboard, saying that President Barack Obama was "the embodiment of honor, resolve and character, one of the finest presidents we have ever had." What a bunch of malarkey.
First, if Hillary is so smart, why did she expose her emails to Chinese, Iranian and Russian hackers? If Hillary's so smart, why did Russia experience a revival after Ronald Reagan killed it? Why did the Muslim Brotherhood take control of Egypt? If Hillary's so smart, how did Christopher Stevens not get the security he needed?
Next, saying that President Obama is "one of the finest presidents we've ever had" isn't just dishonest. It's verifiably false on issue after issue. Obamacare was supposedly President Obama's "signature accomplishment." Today, Americans were forced out of policies that they were satisfied with and into policies with ever-increasing premiums and skyrocketing deductibles.
President Obama's stimulus didn't revive the economy. It's been the most anemic economy since WWII. In June, 2012, the workforce participation rate was at a 30-year low of 64.3%. Four years later, the labor force participation rate dropped two-tenths of a point to 62.6 percent, near its 38-year low.
In terms of keeping Americans safe, President Obama is a failure. Police officers are getting assassinated, thanks in large part to President Obama's unwillingness to call out #BlackLivesMatter activists and Al Sharpton for the 'Hands up, don't shoot' hoax. In terms of preventing terrorist attacks and terrorist attacks increasing thanks in large part to President Obama's unseriousness in destroying ISIS, he's failed the US and the world.
If that's the resume of "one of the finest presidents we have ever had", I've got something to say to Vice President Biden: that's a bunch of malarkey.
Technorati: Joe Biden, Barack Obama, Hillary Clinton, Obamacare, Signature Achievement, Deductibles, National Security, Arab Spring, Reset Button, Christopher Stevens. Muslim Brotherhood, ISIS, Iran, Democratic National Convention, Election 2016
Donald Trump's ego got the better of him yesterday when he took credit for the Iran hostage release. Mr. Trump should've quit while he was behind. Later, in a totally bizarre change of direction, Mr. Trump criticized the terms of the swap.
In other words, Trump criticized the prisoner swap that he took credit for. Is that an example of New York values? I could certainly make an argument that wanting it both ways happens to lots of northeastern liberals. Hillary's certainly tried having it both ways. Chris Christie supported strict gun control laws and Sonia Sotomayor's appointment to the Supreme Court before categorically denying he'd supported either thing.
That's before talking about John Kerry's infamous "I actually voted for the $87 billion before I voted against it" episode:
Only in the northeast would a person think that there's nothing wrong with wanting things both ways. In fact, I'm betting that Trump would have a hissy fit if people called him on it. I'd bet the proverbial ranch on it, in fact.
It's important that we take 2 things away from this. First, Mr. Trump didn't actually do anything. His ego is too big, though, to admit that he didn't have anything to do with the swap. Next, and more importantly, Mr. Trump's behavior is, putting it charitably, unhinged. What type of people talk out of both sides of their mouth, then criticize people for when they call him on his manic behavior?
Mr. Trump is acting this way before a single vote's been cast. Why shouldn't people think that he'll crack if he's ever the president when he has real responsibilities? Right now, he's just a loudmouthed candidate and former reality TV celebrity. If he's that out to lunch now, why shouldn't we think he'd crack when he's given legitimate responsibilities?
CNBC's Larry Kudlow has earned the reputation of being pro-immigration reform. That's why Mr. Kudlow's NRO op-ed is startling. Mr. Kudlow admits that we're at war with Islamic terrorists and that "there should be no immigration or visa waivers until the U.S. adopts a completely new system to stop radical Islamic terrorists from entering the country." If that sounds like Trump's plan, it's because it's similar but it isn't the same.
Kudlow explains "Let me emphasize that my support for wartime immigration restrictions is not based on religion. I think Donald Trump made a big mistake here. Instead, I agree with this Rupert Murdoch tweet: 'Complete refugee pause to fix vetting makes sense.'"
That's the point I've made from the start. Let me outline the principles I'd use to prevent the next Paris or the next San Bernardino. First, I'd establish a tiered list of countries to accept refugees from. The first tier would be countries that we'd never accept refugees from. Basically, any nation whose government exists in name only would be on that list. Syria, Somalia, Mali, Libya and Yemen would be on that list.
I've nicknamed the second list the Procto list. Refugees from these countries would be given a full proctology examination. Each refugee would be given a full examination including everything up to the person's tonsils. Twice. I picture nations like Iraq, Iran, Pakistan, Afghanistan, Turkey and Greece on that list. It isn't that there are many Greek terrorists. It's that a bunch of ISIS terrorists stopped in Greece on their way to the west from Iraq and Syria. Pakistan, Iraq and Afghanistan are marginal allies but they're terrorist hotbeds, too.
I wrote this article to highlight the corruption within the Obama administration, especially in the State Department and the Department of Homeland Security. Tashfeen Malik, the terrorist bride, didn't "slip through the cracks" like the administration is spinning it. They all but rolled out the red carpet for her by shutting down a program that likely would've put her terrorist husband, Syed Farook, on the federal government's no-fly list because he attended a radicalized mosque.
FYI- That likely would've meant Malik's visa being rejected, too.
Larry Kudlow should be applauded for changing his very public stand. The late economist John Maynard Keynes was once asked why he'd changed his policy. His epic reply fits here:
When the facts change, I change my mind. What do you do, sir?"
Exactly right.


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204 Blake St, Lewiston, ME 04240Request info Add to list
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Mumbai: Kalbadevi martyr's son gets job with fire brigade
The Mumbai Fire Department has offered a junior engineer's job to Raj Rane, son of Sanjay Rane, the late assistant divisional fire officer who had succumbed to injuries suffered during the Gokul Niwas fire on May 9.
Municipal Commissioner Ajoy Mehta sanctioned the proposal to offer the job to Raj, who is currently pursuing his Bachelor of Electronics degree.
While Raj is slated to appear for his final exams soon, the authorities confirmed that he would be posted in the BMC's Disaster Management department.
A couple of days ago, CM Devendra Fadnavis had asked the BMC to ensure modernisation of the fire brigade.


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We're super excited to announce our partnership with Zoho Campaigns, a leading tool that helps you to engage with your customers across email, social and CRM solutions. This snappy integration allows you to quickly and easily add a SurveyMonkey survey to any email message you're delivering via Zoho Campaigns.
Find out more from your customer base–are they satisfied? What trends are they following? What do they think of your latest product release? The more information you have at your fingertips, the better your business will be.
Zoho Campaigns also offers a survey report that lets you view your survey's completion rates–how many people have finished, started or not yet started your survey–all within one location.
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Step 3: Choose from a selection of email templates, which will include a formatted "Give Feedback" button. Once they click the button, your email recipients will be able to complete your survey in a new web browser.
There you have it, folks. Simple. Fast. We love it and hope you will too.
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Tags: integration, partners, partnerships, SurveyMonkey, Zoho, Zoho Campaigns


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Veganmania.com ranks
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She mothers her two children; wifes her husband; pets her dog, 3 cats and 2 guinea pigs; writes a lot of adequate poetry, hosts blindfolded dinner parties, and rocks the apron. She is fond of both people, and non-people animals, and thinks planet Earth deserves a bit more of our attention. She does not enjoy oatmeal but asks that you help her keep this secret from Wilford Brimley, who frightens her, just a little. Christa's fondest wish is to become vegan baker to the stars. ...
Home Cooking Vegetarian Vegan who frightens her
Google Safe Browsing - Safe website. Clean from Viruses, Malicious Worms, Adwares, Trojans, Spywares and Suspicious Phishing Attacks.
81 - 13766 103 Ave, Surrey, BC - V3T 1R9, Canada. Phone: +1 778 908 5943, Fax: +1 519 473 3880 Email: christatrueman[AT]shaw.ca


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Get the newest updates.
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Just as you need rules when your paddling for waves out in the lineup, it is also necessary to apply proper etiquette when posting to the Swellinfo...
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what street works best with hightide?
some pics from today in Wrightsville
Why must some people paddle out and sit 5 feet away from me?I just don't get it.:confused:
So i'm at work and currently watching the billabong pro at J-Bay. I love the coverage online that they provide, but why cant we Televise this!!! I...
I saw a couple dudes taking shots in deal on saturday 7/10. Any of you on here?
So has anyone else noticed how much **** Adrianno de Souza and the judges got and are still getting for how he won the Rio Pro over Owen Wright's two...
For a SUMMER surf trip what are your opinions on Nicaragua , Costa Rica , panama
What are the pros and cons of these summer surf destinations
If you are gonna take part in this even the registration deadline in Aug 13.
Here is the link to sign up
im looking for an epoxy thruster around 6'0" preferrably with a bat tail or swallow tail, thumb might be ok too. around 18.5-19.5 in width preferred....
I went to the Channel Islands demo this weekend and want to have a board made based on one of their shapes. I'm in MD but wouldn't mind traveling to...
Going to CA next month, wondering if anyone has been and can recc. a good place to surf? I'll be in the LA, Santa Monica, and Venice Beach area. Are...
I'd like to see an overall view of projected surf conditions at all spots within a given region (Gulf Coast, Florida East Coast, etc).
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So I went surfing for the first time with my wife's girlfriend's Dad. I used his board...a 7' 10\" x 21 1/2 (I think), x 3 1/4\" Nolte fun board....
Can we please get something brewing in the Atlantic....just watching a hurricane's path is enough stoke for me right now... Tropics are awful quiet....
Pensacola Surf Report from Waterboyz is back on Swellinfo.
Here some: http://youtu.be/-s-HoqWrrAY
Now I must admit, it has been a while since I surfed in Delaware, but it just seems that there are no spots left that work on a 2-3 foot day. The...
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Kassidy Gaines
Volunteer Assistant
Kassidy Gaines enters his first year as an intercollegiate coach with the Beavers in 2017. Gaines, a former minor league prospect, joins BSU after competing in the United Shore Professional Baseball League (USPBL) during the 2016 season. Gaines, a Twin Falls, Idaho native, will join the Beavers with focus on pitchers and catchers.
In 2016, Gaines finished his first full season of minor-league baseball under his belt with the Utica Unicorns of the USPBL. He was among a league leader in several categories including finishing second in innings pitched (60.2) and second in wins (5), and he helped defeat the Birmingham-Bloomfield Beavers 5-0 to claim the USPBL championship. Gaines also had a short stint with the Lincoln Saltdogs of the American Association in 2015 and with the Florence Freedom of the Frontier League prior to his season in the USPBL.
Gaines served as an as assistant coach for the Aberdeen, S.D., American Legion team in 2015, taking over the responsibilities of renovating the pitching staff for the Smitty's, which included a significant drop in a team ERA from 9.6 in the prior season to a 6.12 ERA in the summer of 2015 season, and the first appearance at the South Dakota State American Legion Statement since winning the championship in 2009.
In the spring of 2015, Gaines graduated from Northern State University with a degree in marketing. He played three years for the Wolves via junior college transfer after his freshman year at Grays Harbor College in Aberdeen, Wash. Gaines spent the majority of his career as one of the starters in the Wolves rotation while also seeing innings from the bullpen as a setup/closer role. He also played for two summer leagues during his college career, the Kitsap BlueJackets of the West Coast League in 2011 and the SoCal Outlaws of the Southern California Collegiate League in 2013.


text: Oak Investment Partners is a multi-stage venture capital firm with a total of $8.4 billion in committed capital. The primary investment focus is on high growth opportunities in clean energy, communications, information technology, internet new media, financial services information technology, healthcare services and consumer retail. Over a 29-year history, Oak has achieved a strong track record as a stage-independent investor funding more than 435 companies at key points in their lifecycle. Oak has been involved in the formation of companies, funded spinouts of operating divisions and technology assets, and provided growth equity to mid- and late-stage private businesses and to public companies through PIPE investments.Oak has helped innovators exploit new business opportunities and anticipate trends through long-term relationships that endure the changing economic landscape. Their accomplishments can be best recognized through the success of their companies and the ability to deliver consistent performance over time.Â


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This sponsored post is produced in conjunction with ArcSoft.
You may not realize it, but there's a good chance you've used ArcSoft's software.
ArcSoft is one of the best kept secrets in Silicon Valley. Its imaging technology is included in 500 million Android devices, as well as many top digital SLR cameras. The company has been around for about 18 years.
The challenge, according to ArcSoft's Todd Peters, is keeping pace with the explosive increase in the number of cameras — and digital images — surrounding us.
Today, cameras are everywhere you go. Smartphones have improved the ease of taking pictures anywhere at any time. Yet the technology and software has not kept pace with the availability of cameras on these devices.
People post and take millions of photos every day, but too many of them are just of poor quality. Yet software — especially with the power available on a modern smartphone — can easily fix many common problems.
"Low light, out of focus, faces out of register, red-eye, people blinking or looking away — there's no need for that with today's technology," Peters says. "At ArcSoft, it is our belief that the software should provide for a better imaging experience as well as the management of those images after they've been captured."
Peters also thinks it should be easier to search, organize, and share your photos.
"You should be able to go through your own files and use your own verbal search cues, such as sunset, restaurant, pets, friends, and it should be able to find all pictures with that image based on the meta data in the image," Peters said. "We are working on a bunch of technologies that are cloud-based, so if you want to take 10,000 images and remove red-eye, we could provide you with that type of technology."
Video is the third area in which ArcSoft is focusing. Lots of people are shooting video with devices like GoPro cameras, but it's too hard to edit out the boring parts, add transitions, and make videos short and shareable — right on your smartphone.
"Intelligent imaging should focus on the minutes that matter and should be able to be done on a mobile device in the moment. With the proliferation of smartphones, we've gotten very careless," says Peters.
Watch the video below for his thoughts on the future of digital imaging.
Sponsored posts are content that has been produced by a company, which is either paying for the post or has a business relationship with VentureBeat, and they're always clearly marked. The content of news stories produced by our editorial team is never influenced by advertisers or sponsors in any way. For more information, contact firstname.lastname@example.com.


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What is the significance of the widow's offering and how does it inform our giving in the church today.
What is the significance of the widow's offering and how does it inform our giving in the church today.
The church is the body of Christ. He who does not have the church for his mother cannot have God for his father. As the body of Christ, every Christian is to be part of a local expression of the worldwide body of Christ, the church.
Jesus now asks the Jewish leaders a difficult question, "Whose Son is the Messiah?". This will give Jesus an opportunity to explain that the Messiah is much more than a descendant of David. He is God.
Jesus's teaching on the greatest commandment has much to teach us on God's love for us, our love for Him, our love for others, and the Christian life as a whole.
Jesus'surprising answer to the Pharisees' challenge about the legality of paying the Roman taxes and how we are to respect both government and God.
The only reasonable response to the faithfulness of God is a total allegiance to Him demonstrated by gratefulness and service from a humble heart.
Jesus tells the Parable of the Tenants, a very allegorical parable and prophecy detailing how the spiritual leaders of Israel have disregarded the prophets and will put Jesus to death later that week.
Our faith and willingness to obey are strengthened by reminding ourselves of the great deeds God has done for us.
A look at the importance of having faith in God, what faith is how to have faith and what to do to increase our faith.


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First Team News
Bony, Iheanacho and Mangala back for Newcastle
There appears to be light at the end of the tunnel regarding the injury troubles which have been plagued City in recent weeks.
Manuel Pellegrini has confirmed that three of his squad are back in contention to play against Newcastle United on Saturday afternoon.
Wilfried Bony, Kelechi Iheanacho and Eliaquim Mangala will all return to the squad list after missing the last few weeks.
However, there will still be five players missing for the home side in the final game before the October international break.
Pellegrini confirmed in his press conference: "Vincent Kompany, Clichy, Delph, Nasri and Toure are injured. Mangala is on the squad list and so are Kelechi and Bony.
"Kompany's calf is still injured – we'll see if he's fit after the international break.
"It's not been a normal situation to have so many injuries – against Sunderland we had 11 injured, then it's been seven or eight. I hope after this break, most of them will be fit.
"I never complain about the players who can't play. I don't think that one name can change the performance of this team. We also win a lot of games without Vincent.
"He's an important player for us of course – we hope we will play again soon of course."
City face a Newcastle side who are likely to be buoyed by their 2-2 draw against champions Chelsea last time out.
Manuel pointed to this performance, as well as the Magpies' goalless draw at Old Trafford, as evidence that his team will be in for a tough test at the Etihad Stadium.
"We always expect to win at home but away also," he said.
"We want to win everywhere. We have to play in the same way, in the same style.
"Tomorrow we have a tough game against Newcastle. They played very well against Chelsea and here in Manchester against United.
"We are not thinking of the top of the table at this moment – just to have a strong performance. It's important to be at the top in May.
"We know we are going to have eight or nine players defending so we have to create the space."
Finally, on the win over Borussia, Pellegrini stated his belief that the nature of the performance proved that City have the personality to succeed both at home and on the continent.
He added: "We have a strong team with strong character, in Europe and the Premier League.
"It was very important to win as it's difficult to qualify with no points from two games. Maybe we didn't deserve to lose against Juventus and maybe we only won against Borussia with a late goal.
"It's not easy to come from a goal down and play the way we did in the last 15 minutes."
Make sure you don't miss out on our next home match and buy your ticket now for City v Newcastle on Saturday 3rd October at 3pm. Tickets for this match are now extremely limited, with only single seats remaining.
Hospitality packages are also still available in the new Legends suite from £150 per person (plus VAT). You can enjoy your matchday with friends and family in this fantastic suite with great food and drink, as well as some of the best views of the pitch.
Call our dedicated sales team and book now on +44 (0)161 444 1894 (option 1, option 2).


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The following commentary does not necessarily reflect the views of AgWeb or Farm Journal Media. The opinions expressed below are the author's own.
The Global Farmer Network are farmers committed to inserting their voice and perspective in the global dialogue regarding food and nutritional security.
*Note - this week's column first appeared at The Huffington Post on Feb 3.
By Joni Kamiya-Rose: Kaneohe, Hawaii
No comments have been posted to this Blog Post


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Flowers are the most common thing that inspires an artist. A lot of abstract paintings too have been made based on flowers. The variation of colours itself are so stunning and beautiful that it is very easy to portray them on canvas. Abstract paintings can be made with normal wax crayons when made on paper. Water or oil painting colours can be used to make them on cloth canvas. The painting based on flowers are a mixture of beautiful and vibrant colours. The painter can use a mixture of random brush work to make these abstract art paintings.
Use of vibrant colours in the abstract art paintings based on flowers
Flowers in itself are very colourful. Colours and scent are the two things that come into our mind when we think about flowers. The common thing between all the paintings using flowers as the inspiration is the use of vibrant colours. It can range from splash of different colours to intricate designs based on the structure of flowers. Floral designs made from patches of colour is another common form of abstract art. The colour scheme is dominated by shades of red and yellow. But a lot of green is also seen as the leaves are a part of the paintings as well.
Use of floral designs
Abstract art basically does not follow any specific technique. The use of floral designs is such that it is a random array of colours that depicts flowers. The painter uses their imagination to draw from inspiration from the flowers. But the actual painting may not have the structural base of a flower. It might be just some random splashes of colours. A lot of things like sponges and corks are also used to make floral patterns. These things are dipped into paint and then scrubbed all over the canvas in no specific pattern.
Ideas for floral paintings
Abstract art having floral motifs are a visual treat for the eyes. A lot of different patterns can be used to make these paintings. These patterns can range from small circles or other geometric designs to big splashes of colour. Layering is a commonly used technique in making abstract art paintings with floral designs. The canvas is first painted in a single colour. Then another colour is added on top of that. The process goes on like this till the painter is happy with the outcome. A lot of different motifs can be used while making these paintings.
5 Best Flower Paintings of all times
Van Gogh
Vase with Pink Roses (1890)
National Gallery of Art, Washington DC
Sunflowers, irises and blazing cherry blossom: Vincent Van Gogh is more famous for these blooms, in all their painted variations. Even just to choose one of the sunflower pictures would have been hard enough. Here, instead, is a flower that lacks the brilliant colour he relished and which has such symbolic meaning (its pinks have faded to white) but which is just as stupendous: pale roses, incandescent against a light green wall. The flowers are in glorious, exuberant bloom, their furled forms animated by the ribbons of paint behind them. The surface feels still live with the artist's touch.
Henri Fantin-Latour
Roses (1894)
Private collection
Fantin-Latour is the great rose man. He painted roses from first to last, never tiring of their beauty. There is even a shrub rose named after him and it is (I think) right there at the centre of this bowl full of heavy, drowsy, scented blooms, in many shapes, colours and petal forms. Fantin-Latour is praised in Proust and sold almost every work as soon as it was finished, mainly to the English. This is a painting of summer roses that is for once as ravishing as the real thing.
Jan Brueghel the Elder
Flowers in a Vase (year unknown)
National Museum of Art, Bucharest
Lilies, tulips, fritillaries, daffodils, snowdrops, carnations, cornflowers, peonies, anemones, roses: this is an all-together-now bouquet and one of the largest and most luscious in art. But is it real? Could all these flowers have blossomed at the same time in 17th-century Holland without hothouses and chemical sprays? Possibly, but this is a vanitas painting, combining the real, the ideal and the symbolic. It would have given its wealthy patron a garden of flowers in a single vase, but it reminds him of his death as well. Some of the flowers are beginning to fade, others have already fallen.
Lilacs in a Vase (c 1882)
Nationalgalerie, Berlin
During his long final illness, Manet began to paint beautifully aphoristic pictures of flowers in crystal vases. His subjects were the posies friends brought to his Paris sickroom, in this case white lilac. Fascinated by the stems refracted through the silvery water, and by the flocculent green-in-white blossoms, he paints something closer to a portrait than a still life. You can feel the thick darkness – the darkness of late Goya, whom Manet admired from first to last – closing in around these lightsome white heads on their fragile stems. Flowers with the status of people
Georgia O'Keeffe
Oriental Poppies (1928)
Weisman Art Museum, Minneapolis
"If I could paint the flower exactly as I see it no one would see what I see because I would paint it small like the flower is small. So I said to myself – I'll paint it big… and they will be surprised." O'Keeffe's poppies are among her most famous works, the glossy red and orange flowers exploding on a canvas almost four feet wide. There is no background to distract from their sheer force of personality. Made in 1928, the painting is a vast close-up, pulling the eye into the dark heart of these flowers through the power of scale and colour.
Flowers are one of the best things from nature to draw inspiration from. They have a sense of subtle beauty around them. If the painter's imagination can attract that beauty and put it onto a canvas a beautiful painting can be created. Since abstract art does not follow any specific rule or technique it is solely based on the painter's imagination and his brush strokes. The use of multiple colours on one canvas makes the paintings very vibrant. They can tingle our senses and make us feel happy and warm from inside.


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software updates???
software updates???
I updated to 4.4 last week. I have not seen anything since then.
Yes, it did appear on the screen,with a small clock icon to either update now, or schedule for later. The one thing I noticed is that it did not tell which version it was. I only saw the version information after it succeeded. It also failed to update about four nights in a row. It complained the 12 volt battery was too low. We have a very cold April with lots of snow, so I just assumed the the cold whether was having an affect. It succeeded when the weather finally warmed up.
I had the 4.4 update last week, and I think it's been going out for about 2-3 weeks (I was not the first). Seems normal to me - they don't update everyone at the same time. I'm not sure anyone (other than Tesla) knows how they pick the order of cars to be updated either.
Once the update completes, you'll get a screen that will show the update version and a list of significant changes/features.
Four failed attempts to update software is not normal or related to the cold weather. You need to have the service center address the known 12 volt battery problem earlier rather than later. Once it goes it's been a real headache for owners. Use volkerize.com to search the forum for 12-volt battery issues for more information. In the interim, reduce your amperage while charging overnight i.e. lengthen your charging time to provide the longest trickle charge for the 12-volt battery until you can get it replaced. Good luck!


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Orthodoxy: The Way to Christ - Part 2
Expand Messages
- Orthodoxy: The Way to Christ - Part 2
by George Aramath
Humanity is created in the image of God and therefore all throughout life longs to return back to this image. As St. Augustine said, �our hearts are restless until they find their rest in Thee�. But in this fallen world, man gets sidetracked, chasing after other gods. The Church, the body of Christ, is instituted by God to continually bring back His children. Being the house of God, the Church is the place to which the prodigal son returns after his meaningless journey in life. The Holy, Universal, and Apostolic Church holds the map that leads to Christ.
To read more:- http://www.socdigest.org/articles/01oct07.html
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