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To determine whether myocardial necrosis may occur during postischemic reperfusion, electron microscopy was used to identify morphological features of irreversible injury in myocardial samples taken from anesthetized dogs with 90-min ischemia and 0-, 5-, 90-, or 180-min reperfusion. In samples without detectable collateral blood flow, necrosis was almost complete, whether or not the myocardium was reperfused. In samples with collateral flow, necrosis was more frequent after 180-min reperfusion than in the absence of reperfusion, despite similar collateral flows in the two groups. Excess of necrosis after 180-min reperfusion was evident in endocardium (ischemia only: 4 of 13, 180-min reflow: 14 of 20; P = 0.03) and midwall (ischemia only: 9 of 25, 180-min reflow: 29 of 45;P = 0.02). Multiple logistic regression with variables of collateral flow and transmural position was used to determine risk of irreversible injury in 111 samples from ischemic myocardium without reperfusion (model predictive accuracy = 75%, P < 0.00001) and to predict risk of necrosis in myocardium reperfused for 180 min. Of 65 samples from endocardium and midwall with detectable collateral flow, the model predicted necrosis in 23 samples but necrosis was observed in 43 samples (P < 0.01). Reperfusion duration was a determinant of frequency of irreversible injury. Multiple logistic regression for 186 samples from myocardium reperfused for 5, 90, or 180 min showed that reperfusion duration was an independent predictor of irreversible injury (P = 0.0003) when collateral flow and transmural location were accounted for. These findings are consistent with the occurrence of necrosis during reperfusion in myocardium exposed to substantial, prolonged ischemia but with sufficient residual perfusion to avoid necrosis during the period of flow impairment.
- myocardium
- cell death
- electron microscopy
- blood flow
it is generally accepted that reperfusion can cause prolonged, but ultimately reversible, myocardial contractile dysfunction without necrosis ("stunned myocardium") (8) as well as potentially serious arrhythmias (26), but there is controversy over whether reperfusion results in further necrosis of ischemically injured myocytes. Although reperfusion is clearly beneficial in an overall sense, the occurrence of reperfusion injury may limit the maximum benefit obtained by reperfusion. Experimental studies show that reperfusion of ischemic myocardium causes major structural changes in injured myocytes (19, 23, 41, 46), whereas nonreperfused infarcts are characterized by relatively well-preserved myofibrils (35). Despite the apparent destructive effects of reperfusion on the structure of ischemic myocardium, it has been argued that these effects are confined to myocytes that are already irreversibly injured and that reperfusion does not result in necrosis of additional myocytes (9, 18, 22, 41).
This argument is challenged by numerous studies that showed that infarct size can be reduced by a therapeutic intervention administered shortly before, or at the time of, reperfusion. In particular, interventions directed against neutrophils were successful at limiting infarct size (24, 25, 29, 32, 43), but administration of oxygen free radical scavengers (2), adenosine (31), nitric oxide donors (42), and perfluorochemicals (5) were also successful. These intervention studies are not conclusive, however, because the evidence provided by these interventions for reperfusion-related necrosis is essentially indirect. Not all such studies were positive (13, 36, 45), and although methodological factors may account for negative results, these findings question the existence of additional myocardial necrosis occurring after reperfusion.
Conclusive proof of additional necrosis during reperfusion injury would require demonstration that a population of myocytes, which had suffered reversible injury but were viable at the end of the ischemic period, subsequently lost viability and developed irreversible structural damage during the reperfusion period. Unfortunately, such serial ultrastructural studies in the same population of myocytes are not presently possible. Nevertheless, some previous studies used histopathological methods serially in the same animals to address this issue and reported that necrosis may occur after blood flow is restored (14, 15). However, these conclusions have been questioned because of possible unreliability of the stains and tracers used to identify myocyte necrosis.
An alternate approach is to demonstrate in a group of animals that reperfused myocardium exhibits more necrosis than nonreperfused myocardium, after controlling for the severity of the preceding ischemia. In our study, we chose electron microscopy to identify necrotic myocytes because it represents the "gold standard" for such assessments. Electron microscopy is sensitive and equally applicable to nonreperfused and reperfused myocardium, and the morphological criteria for irreversible injury are well established (22, 23, 35, 39-41). The experiment was designed to account for the major determinants of ischemic necrosis (6, 27, 33, 37) and included a constant ischemia time of 90 min, several different durations of reperfusion (0–180 min), and a multivariate analysis that accounted for transmural progression of necrosis and collateral blood flow as well as duration of reperfusion. The results show that, in addition to collateral flow and transmural location, the duration of reperfusion is an important independent predictor of myocardial necrosis, confirming by a new and direct approach that myocyte necrosis may develop after restoration of blood flow.
Experimental protocol.
At Johns Hopkins University, adult mongrel dogs of either gender (25–30 kg) were anesthetized with intravenous sodium thiamylal (12.5 mg/kg) and intramuscular urethan (136 mg/kg) containing α-chloralose (14 mg/kg). The dogs were ventilated with room air at positive pressure. A catheter was inserted into the aorta for microsphere sampling. The heart was exposed through a left lateral thoracotomy, and a catheter was placed in the left atrium for microsphere injections. A black silk suture was placed loosely around the circumflex artery, proximal to any major marginal branches. The coronary artery was occluded by sliding a small plastic tube over the suture, and regional myocardial blood flow was measured after 85-min ischemia with radionuclide-labeled microspheres. The total duration of ischemia was 90 min in each dog. Dogs were randomly assigned to ischemia without reperfusion or ischemia with different durations of reperfusion before the start of each experiment. Reperfusion was effected by release of the coronary snare.
The frequency of irreversible injury was first compared between myocardial samples taken from ischemic myocardium without reperfusion (n = 12 dogs) and from myocardium reperfused for 180 min (n = 12 dogs). The effect of duration of reperfusion on frequency of irreversible injury was studied in myocardial samples from a further five dogs (5-min reperfusion: n = 2, 90-min reperfusion: n = 3). At the conclusion of each experiment, the heart was arrested with potassium chloride and immediately removed. The left ventricle was sectioned into five ∼1-cm-thick short-axis slices, and multiple transmural myocardial biopsies (2-mm wide and 2-mm deep) were rapidly excised from the apical surface of each slice. Most biopsies were taken from the ischemic myocardium in the circumflex territory, but control samples were also obtained from the nonischemic territory of the left anterior descending artery. Each transmural biopsy was divided into endocardial, midwall, and epicardial sections. Each of these samples was weighed (20–30 mg), immediately placed in plastic scintillation vials filled with cold 3% glutaraldehyde (in 0.1 M cacodylate buffer, pH 7.4), and subsequently counted in a gamma counter for calculation of regional myocardial blood flow. An average of 50 samples (range 30–75) were obtained from each heart. The number of samples taken depended on the size of the ischemic region.
Measurement of regional myocardial blood flow.
Regional myocardial blood flow was measured during coronary artery occlusion with 15-μm-diameter radionuclide-labeled microspheres (DuPont, North Billerica, MA). After vortex agitation ∼20 million microspheres were injected into the left atrium over 5–10 s, and a simultaneous reference blood sample was withdrawn from the femoral artery at a constant rate of 2.06 ml/min for 5 min. Blood and myocardial samples were counted in a gamma counter (Packard model 5986) at an appropriate energy window. Flow in each myocardial sample was calculated asQ˙s =Q˙r ×C s/C r, where Q˙s is sample flow, Q˙ris reference flow rate,C s is background-corrected sample counts per minute, andC r is background-corrected reference blood counts per minute.
Fixation and selection of samples for electron microscopy.
After myocardial samples were weighed and counted for radioactivity, they were kept in fixative at 4°C for 24 h, rinsed in cold 0.1 M cacodylate buffer (with saccharose added, pH 7.4), and stored at 4°C. The buffer was renewed daily until shipment by air express to the Max Planck Institute in Bad Nauheim, Germany, for electron microscopy. The glutaraldehyde-cacodylate buffer fixative was freshly prepared every 2 wk.
From each dog, 10–25 samples were selected for electron microscopy, according to the level of collateral blood flow to the sample during coronary occlusion. Samples with collateral flow >0.4 ml ⋅ min−1 ⋅ g−1were rejected because this level of flow does not usually result in myocyte necrosis during occlusion (37). About four samples from each heart were also selected from the anterior left ventricle to serve as a control for the tissue fixation and analysis procedure. Each sample was identified by an individual code number before shipment.
Microscopic analysis.
All samples were studied by light and electron microscopy by one of the authors (J. Schaper) without knowledge of sample location, regional blood flow, or duration of reperfusion. The tissue samples were embedded in Epon using a Wakura automatic tissue processor, after fixation in 2% osmic acid anhydride, dehydration in an ethanol series, and substitution by propylene oxide.
Semithin (1–2 μm) sections were prepared and stained with toluidine blue. Artifact-free areas were selected for preparation of thin sections (50–60 nm) for electron microscopy. These sections were attached to uncoated copper grids, stained with uranyl acetate and lead citrate, and viewed in a Philips EM 300 electron microscope. For each myocardial sample, 30–40 micrographs were examined for features of irreversible myocyte injury, according to previously published and validated criteria (Table 1; Refs. 39, 40). Irreversible injury was identified by the presence of amorphous densities, matrix clearing and/or cristae breakage in the mitochondria, clearing and shrinkage of nuclei, and/or disruption of the sarcolemma. The presence of contraction bands was not used as a criterion of irreversible injury. Each sample was deemed to have suffered irreversible injury if >90% of micrographs for that sample showed criteria for irreversible injury. In a few samples in which the micrographs revealed a heterogeneous appearance, additional sections were obtained and examined to resolve the issue for that sample.
Data analysis.
Because reperfusion is associated with tissue edema and an increase in tissue wet weight of ∼25% (34), the measured blood flows in each sample from reperfused myocardium were corrected for a 25% increase in wet weight during reperfusion and results are reported for corrected flows. Regional myocardial blood flows were compared between samples, grouped according to transmural location and duration of reperfusion, by analysis of variance (38). The frequency of samples meeting criteria for irreversible injury was compared by χ-square, with samples grouped according to collateral flow, transmural location, and duration of reperfusion. The relationships among the independent variables of collateral blood flow, transmural location, and duration of reperfusion and the dependent variable of risk of irreversible injury were determined for individual samples by multiple logistic regression (44a). All data are reported as means ± SD, and a P value <0.05 is considered significant.
Of 343 samples obtained from ischemic or reperfused myocardium, 176 (51%) were judged to predominantly contain irreversibly injured myocytes. Another 30 samples from the nonischemic control region were also examined, of which only 1 was considered to contain irreversibly injured myocytes. Examples of normal and reversibly injured myocardium are shown in Fig. 1. Mild to moderate chromatin clumping and clearing of the nucleus or limited mitochondrial changes with broken cristae were not considered evidence of irreversible injury. Representative examples meeting criteria for irreversible injury are shown in Fig. 2 for samples without reperfusion (Fig.2 A), after 5-min reperfusion (Fig.2 B), and after 180-min reperfusion (Fig. 2 C). In the absence of any reperfusion, irreversible injury was characterized by marked nuclear changes, amorphous densities in the mitochondria, and, sometimes, damage to the sarcolemma. Reperfusion for 5 min was associated with more severe morphological changes, including distortion of sarcomeres with formation of contraction bands and destruction of the sarcolemma. After 180-min reperfusion, irreversibly injured cells showed further structural deterioration, including contraction bands and destruction of mitochondria and the sarcolemma.
The mean collateral blood flow to the ischemic risk region was 0.08 ± 0.11 ml ⋅ min−1 ⋅ g−1in the 111 samples from myocardium that was not reperfused and 0.10 ± 0.12 ml ⋅ min−1 ⋅ g−1in 136 samples from myocardium reperfused for 180 min (P = not significant). Of the 42 samples reperfused for 5 min, mean collateral flow was 0.08 ± 0.09 ml ⋅ min−1 ⋅ g−1, and of the 54 samples reperfused for 90 min, mean collateral flow was 0.12 ± 0.13 ml ⋅ min−1 ⋅ g−1. There were no significant differences in mean collateral flow to the ischemic risk region between the samples without reperfusion and those samples with 5-, 90-, or 180-min reperfusion.
The frequency of irreversible injury is compared for samples from myocardium without reperfusion and those with 180-min reperfusion in Table 2. Data are shown for samples from 12 dogs in each group, and samples are grouped according to transmural location and the presence or absence of detectable collateral flow. Nearly all samples without detectable collateral flow had irreversible injury, whether or not the myocardium was reperfused. Among samples with detectable collateral flow, 24 of 74 samples from myocardium without reperfusion had irreversible injury. In contrast, 55 of 106 samples from myocardium reperfused for 180 min had irreversible injury. There was significantly more irreversible injury after 180-min reperfusion in both the endocardium and the midwall, despite similar collateral blood flows in the groups with and without reperfusion. The relationship between collateral blood flow and occurrence of irreversible injury in reperfused myocardium is further illustrated in Fig. 3. In the endocardial region, samples with collateral flow of 0.01–0.10 ml ⋅ min−1 ⋅ g−1had significantly more irreversible injury after 180-min reperfusion than did samples without reperfusion. Only a few samples with collateral flow >0.10 ml ⋅ min−1 ⋅ g−1had irreversible injury, even after 180-min reperfusion. The same pattern was evident in the midwall region, but irreversible injury was less frequent in the epicardial region. These grouped data, with samples matched for transmural location and collateral flow, indicate that irreversible injury is more frequent after 180-min reperfusion than in the absence of reperfusion.
The probability of irreversible injury occurring in individual samples was then examined by multiple logistic regression. A regression model (Table 3) was developed for 111 samples (n = 12 dogs) taken from ischemic myocardium in the absence of reperfusion, to describe the risk of irreversible injury occurring during ischemia alone. The predictive accuracy of the model was 75%, and collateral flow was identified as the main predictive variable. This model was then applied to the 136 individual samples from myocardium reperfused for 180 min. The comparison between the number of samples predicted to be necrotic from the regression model for ischemic injury and the number of samples observed to be necrotic after 180 min is shown in Table 4. For samples without detectable collateral flow, the model predicted that nearly all samples would have irreversible injury, and this was the observed result. For samples with detectable collateral flow, irreversible injury was observed more frequently than was predicted by the model. In 20 samples from the endocardial region, the model predicted irreversible injury in 4 samples, but 14 were found to have irreversible injury by electron microscopy (P = 0.002). Similarly, among 45 samples from the midwall region, 19 were predicted to be necrotic but 29 were found to have irreversible injury (P = 0.035).
The data in Table 4 were calculated using a 50% probability as the threshold for prediction of irreversible injury or otherwise in an individual sample. Because there is some error associated with the variable coefficients of the model (see Table 3), the use of a single threshold value for prediction of irreversible injury might be misleading. Therefore, the frequency of irreversible injury predicted by the model was compared with the observed frequency of irreversible injury for a wide range of probability thresholds in Fig.4. As the required probability for definition of irreversible injury increased, fewer myocardial samples were predicted to be injured (i.e., specificity increases but sensitivity decreases; Fig. 4 A). There was, however, no difference in the pattern of prediction of irreversible injury between samples from myocardium without reperfusion and samples with 180-min reperfusion. In contrast, the observed data show an excess proportion of irreversible injury after 180-min reperfusion. In samples predicted to be viable (absence of irreversible injury), an excess of irreversible injury (Fig.4 B) was evident across the whole range of probability thresholds for definition of irreversible injury.
The effect of the duration of ischemia on the frequency of irreversible injury was then examined. As shown previously, samples without detectable collateral flow nearly all had irreversible injury (10 of 11 samples with 5-min reperfusion, 6 of 6 samples with 90-min reperfusion, and 25 of 30 samples with 180-min reperfusion). Among samples with detectable collateral flow, irreversible injury was less frequent after 5-min reperfusion than after 90- or 180-min reperfusion (Table 5). This difference was evident in the endocardial, midwall, and epicardial regions of the myocardium. The role of the duration of reperfusion, as a determinant of risk of irreversible injury in individual samples, was examined by logistic regression for all 343 samples from ischemic and reperfused myocardium (Table 6, model A). The overall predictive accuracy of the model was 73%, and duration of reperfusion remained a significant and independent predictor when collateral flow and transmural position were included. The logistic regression was then repeated for the 186 samples from reperfused myocardium, which had detectable collateral flow (Table6, model B), and the duration of reperfusion was again found to be a significant predictor of irreversible injury. These findings show that reperfusion is associated with a greater frequency of irreversible injury than is ischemia without reperfusion, and the risk of irreversible injury appears to increase during the first 180 min of reperfusion.
The concept of myocardial reperfusion injury continues to be a source of controversy. The present study, which represents the first electron microscopic study to systematically address this issue, provides ultrastructural evidence of significant reperfusion-related irreversible myocyte injury. The results show that myocyte necrosis is associated with the duration of reperfusion, independent of collateral blood flow and transmural location, the two most important determinants of ischemic myocardial necrosis. Ours is one of the first studies to show that reperfusion necrosis occurs primarily in moderately ischemic myocardium but not in myocardium with critical ischemia (undetectable collateral flow), in which ischemic necrosis appears to predominate.
Because it is not possible to perform ultrastructural studies on the same myocardial sample at different time points, this study was designed to compare multiple samples after different durations of reperfusion in different animals. A critical requirement of this approach is that the major determinants of myocardial necrosis during the ischemic period be accounted for (6, 28, 33, 37). The duration of ischemia was held constant at 90 min, and all infarcts were studied in the circumflex territory. Collateral blood flow to, and transmural location of, each myocardial sample were included in the multivariate analysis. After these principal determinants of ischemic necrosis were controlled for, the duration of reperfusion remained as a significant and independent predictor of irreversible injury.
Electron microscopy was selected to identify the changes of irreversible myocardial injury in this study because the method is equally applicable to reperfused and nonreperfused myocardium and the ultrastructural criteria of irreversible injury are not difficult to identify and are well established in the literature (22, 23, 35,39-41). Although it is quite impractical to examine the entire ischemic risk region by electron microscopy, numerous samples were taken from the ischemic-reperfused region in each dog and multiple micrographs (n = 30–40) were examined for each sample before classification of injury. Functional criteria for loss of viability might appear preferable to morphological ones, but many criticisms can be offered against contractile function, metabolic activity, and perfusion, for example, as reliable indicators of viability, and practical issues limit the nondestructive serial application of most of these approaches to small samples of myocardium.
Schaper et al. (40) validated the ultrastructural criteria for irreversible injury in ischemic-reperfused canine hearts. Hearts undergoing ischemic arrest for 90 min developed marked contracture on reperfusion, associated with severely reduced myocardial ATP content (<0.5 μmol/g wet wt) and no subsequent return of contractile function or increase in myocardial ATP content. Serial biopsies from these irreversibly injured hearts consistently demonstrated certain ultrastructural features before reperfusion, including mitochondrial clearing and almost complete disappearance of the cristae, the presence of large, amorphous densities within the mitochondria, and severe nuclear swelling or pyknosis. After reperfusion, these morphological abnormalities became even more pronounced, with the appearance of sarcomere disruption, prominent contraction bands, marked edema, sarcolemmal breaks, and mitochondrial dense granules (22, 23, 35, 41). Shorter periods of ischemic arrest were associated with less severe ultrastructural abnormalities that often disappeared during reperfusion, and systolic function and myocardial ATP content recovered during the reperfusion period (39, 40). The point of transition from reversible to irreversible injury was marked by the appearance of mitochondrial amorphous densities, which probably represent complexes of insoluble proteins and lipids resulting from destruction of mitochondrial membranes (21).
This study required measurement of regional blood flow in small myocardial samples. The degree of spatial heterogeneity between small samples is such that extrapolation of flow measurements from large samples may not accurately reflect the level of collateral flow in individual samples (4, 11). Because the number of microspheres is reduced with small myocardial samples, we injected 20 million microspheres, which is ∼10 times the usual quantity for regional blood flow measurements. It is unlikely, however, that this large number of microspheres would contribute to ischemic myocardial injury, because it is estimated that <5% of capillaries would be occluded by these microspheres (47). Nonetheless, the stochastic error of microsphere flow measurements is increased in very small samples. If a 50-mg sample received only 50 microspheres at a flow of 0.1 ml ⋅ min−1 ⋅ g−1, the relative error in flow measurement would be 14% (3,10). When counting and weighing errors are included, the relative error in flow measurement for such a sample is probably 25%. As a result of these errors in flow measurement, some samples may have been incorrectly classified as having severe ischemia or vice versa. However, inaccuracies in blood flow measurement in small individual samples cannot explain our finding of greater irreversible injury with reperfusion, because stochastic or weighing errors would apply equally to samples from all groups. Tissue edema could increase during reperfusion, but we calculated corrected flows for each sample from reperfused myocardium, based on an estimated 25% increase in tissue wet weight during reperfusion (34). Statistical analyses of raw and corrected flow data revealed the same results.
Comparison to previous studies.
Several other groups have addressed the issue of reperfusion injury from a histopathological perspective. In a canine study, Hofmann et al. (20) occluded two coronary artery branches of approximately the same size in the same heart for either 3 or 6 h. Because one artery was reperfused for 60–90 min and the other was not, the duration of occlusion was made equal by staggering the onset of occlusion in the two arteries. These workers found no difference in infarct size between reperfused and nonreperfused territories, but collateral flow was not measured, and 6-h coronary occlusion usually results in extensive ischemic necrosis and large infarcts (33), precluding the possibility of further injury occurring during reperfusion.
Subsequently, Ganz and co-workers (16) were also unable to detect reperfusion injury in the canine heart. After occlusion of the left anterior descending artery for 90–240 min, the distal half of the risk region remained ischemic while the proximal half was reperfused for 5 min. The transmural extent of necrosis was similar in nonreperfused and reperfused regions. In a recent study by the same group (48), a similar result was found when the reperfusion period was extended to 3 h. In neither study, however, was collateral blood flow to the reperfused and nonreperfused regions measured in the hearts used for anatomic study. The relative severity of the ischemic episode in each region thus remains open to question. In both studies the extent of infarction was indexed by measuring the transmural extent of infarction on 2,3,5-triphenyltetrazolium chloride (TTC)-stained myocardial slices, but infarct edges in this model are very irregular, and therefore the measurement of transmural extent is subject to considerable variability. In addition, definition of necrotic myocardium by TTC in nonreperfused myocardium is less reliable than in reperfused myocardium (39, 40).
Three other studies have reported findings consistent with the occurrence of further necrosis during reperfusion. In rabbit hearts subjected to 30-min ischemia and up to 180-min reperfusion, Farb et al. (14) showed that infarct size, measured by tissue staining, increased from 45 ± 3% of the risk region at the onset of reperfusion to 60 ± 3% after 3 h (P = 0.0002). Infarct size immediately after reperfusion was measured using horseradish peroxidase, a protein that will only cross the sarcolemma of irreversibly injured myocytes. After 3-h reperfusion, infarct size was measured by TTC staining. In a canine study, Frame et al. (15) also found evidence of extension of infarction during reperfusion of ischemic myocardium. These workers used antimyosin F(ab)2 fragments to identify irreversibly injured myocytes. After 60-min coronary occlusion, radionuclide-labeled antimyosin antibodies were injected into the coronary circulation at the onset of reperfusion, and 45 min later, additional antimyosin antibodies with a different radionuclide label were administered. After each injection of antibodies, coronary sinus blood flow was temporarily diverted to prevent recirculation of the antibody. The binding of the antibody to the reperfused myocardium increased by 170% over the 45-min interval, suggesting progressive membrane damage and further myocyte necrosis.
Most recently, Matsumura et al. (27) demonstrated that, after 90-min ischemia in a canine model, as many as 65% of myocardial samples taken from the infarcted region (defined by TTC 4 h after reperfusion) were actually viable early after reperfusion. Viability in this study was defined metabolically by tissue 2-deoxy-d-glucose uptake. The amount of reperfusion-related necrosis was greatest for animals with moderate reductions of blood flow during ischemia and least for animals with very severe ischemia, similar to the results found in the current study.
Interpretation of findings.
Two different arguments can be advanced to account for our findings without invoking the concept of reperfusion-related necrosis. In the first instance, reperfusion might simply exacerbate the structural deterioration of myocytes that were already irreversibly injured. This process is known to occur within a few minutes of reperfusion and would already be manifest in samples taken after 5-min reperfusion. The time course of this explosive damage is too short to account for the observed differences in the extent of necrosis between myocardium reperfused for 5 and 90 or 180 min. This interpretation also implies that samples were misclassified by electron microscopy as reversibly injured during early reperfusion when the samples were actually already irreversibly damaged. This error is unlikely, in view of the previously established clear ultrastructural criteria of irreversible injury (22,23, 35, 39-41) that were used in this study. In addition, experimental studies show that myocardium with a pattern of reversible injury exhibits structural, metabolic, and functional recovery during reperfusion (23, 39, 41) rather than further deterioration. It is unlikely, therefore, that there was a population of nonviable myocytes, with the ultrastructural appearance of reversible injury, that survived ischemia and early reperfusion only to suffer major structural damage later during reperfusion.
Another interpretation of the present findings is that there is a population of myocytes that survive the ischemic period but are "programmed" by events during ischemia to undergo necrosis, irrespective of subsequent reperfusion. This is not reperfusion injury per se but, rather, a failure of reperfusion to salvage these myocytes. Although this interpretation may be consistent with the present findings, it is not consistent with the results of many intervention studies showing a reduction in infarct size by treatments given at the time of reperfusion. Studies from Buckberg's laboratory, for example, in canine surgical models, have reported that mitochondria remain surprisingly intact, both ultrastructurally and functionally, even after 6 h of ischemia (7) and that postischemic recovery can be enhanced by controlled reperfusion with substrate-enriched blood cardioplegic solution and left ventricular venting (1). These types of treatment studies suggest that cell death occurring during reperfusion is not inevitable but is amenable to therapeutic intervention, consistent with the hypothesis that reperfusion does cause necrosis of some myocytes.
Mechanism of reperfusion injury.
Although the present findings are consistent with the occurrence of necrosis during reperfusion, they do not provide direct information about the mechanism(s) responsible. Myocyte calcium overload, oxygen free radicals, microvascular obstruction, and neutrophil leukocytes have all been implicated. One feature of the present findings is that morphological changes of irreversible injury appear to increase in frequency between 5 and 90 or 180 min of reperfusion rather than occurring as a single event immediately on reperfusion. Neutrophils have been observed to accumulate progressively during the several hours after reperfusion (12, 17, 44), which would be consistent with the apparent time course of irreversible injury found in the present study.
The authors gratefully acknowledge the valuable technical assistance of Anthony DiPaula and of Christine G. Holzmueller and Susan E. Hayden in the preparation of this manuscript. Computational assistance was received through the General Clinical Research Center (GCRC) Computerized Data Management System.
Address for reprint requests and other correspondence: L. C. Becker, Johns Hopkins Hospital, 600 N. Wolfe St., Halsted 500, Baltimore MD 21287 (E-mail: lbecker{at}welchlink.welch.jhu.edu).
This work was supported by United States Public Health Service Grant 17655 (Specialized Center of Research in Ischemic Heart Disease) from the National Heart, Lung, and Blood Institute and by GCRC Grant M01-RR-00035. R. W. Jeremy was the recipient of an Overseas Research Fellowship of the National Heart Foundation of Australia and a Telectronics Travelling Fellowship from the Royal Australasian College of Physicians.
Present address of R. W. Jeremy: Dept. of Cardiology, Royal Prince Alfred Hospital, Missenden Rd., Camperdown, New South Wales 2050, Australia.
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.
- Copyright © 1999 the American Physiological Society


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Amumu Build Guide by
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Amumu Build
Ability Sequence
Not Updated For Current Season
The masteries shown here are not yet updated for the current season, the guide author needs to set up the new masteries. As such, they will be different than the masteries you see in-game.
Pros / Cons
-High AP ratios and base damage on all skills when ranked.
-A gap closer that stuns.
-Strong AoE burst and Sustained Damage.
-Two forms of crowd control, one that hits multiple targets
-A magic resist debuff on auto attacks to improve overall damage
-Two skills only work in melee Range
- Only chasing Ability is a skillshot.
-Long cooldowns.
-Heavy Mana costs, which take their toll in a drawn out fight.
-Weak early game/laning ability.
Skill Sequence
Regardless of how powerful Amumu's persistent AoE damage can be, I feel that maxing bandage toss first is more important. Of all his skills, it's the one that does the most damage to a single target. It lowers in cool down with ranks, and is his only form of crowd control barring his ultimate. This allows you to duel and chase down champions easier, which is one of Amumu's weaknesses. His Tantrum is maxed second due to the burst it provides, as a follow up to Bandage Toss. Despair is a nice one point wonder that is maxed last. Each point in his ultimate is crucial, so it is taken when available.
Starting Items:
Prospector's Ring + Boots + Red Potion x2
Catalyst + boots upgrade, typically treads.
Early Lead:
Rod of Ages
Glacial Shroud -> Revolver -> Deathcap -> Voidstaff -> Will of the Ancients
Armor: Frozen Heart -> Chain Vest -> Zhonya's Hourglass
Resist: Negatron Cloak -> Odyn's Veil/Abyssal Scepter/Quick Silver Sash
Health: Kindlegem -> Shurelia's Reverie/Hextech Sweeper
Sure, Sunfire is good, but you need different stats more:
-Resists are king until the enemy has %pen items.
-Sustain and landing your skills gives more overall health in most situations than stacking health items.
-Contrary to the above, you are melee. Some health is required just to survive.
-Mana is an issue that needs careful managing until you obtain catalyst and shroud.
-Cooldown Reduction is important in order for you to have your ultimate up fast and to keep your combo available.
-Don't squander money on potions. Health packs exist and are a short stop from important areas. Grab them along the way. The potions are there for the early game fights
Once you have those issues covered, stacking AP is an easy thing to do. The best part is your damage functions well just off the masteries, WotA, and a late void staff. Ability Power isn't a primary concern in the early game, but you want as much as you can squeeze in and not die with. Check the enemy's damage output after every death, and gauge what's important to itemize for based on that.
Summoner Spells
Flash and ghost cover two of your biggest weaknesses. Your reliance on being in melee range for your sustained damage, and using bandage toss to initiate onto an unfavorable target. Use flash to jump in, ult, then bandage the guy you want to hit. This allows you to take down an enemy squishy champion with ease in most cases, and chunk everyone else in the process. Ghost is obvious: Chase everyone! Your despair and occasional tantrums will deal all the damage you need in most cases.

subset: commoncrawl


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Helps you develop Internet sites without having to know HTML.
Just manipulating with webpage elements.
Has built-in image constructing instruments so you don`t need to exploit a other image tool.
Internet site images can be edited by various effects like glow, shadow, or opacity.
With Artistic Text you have character-level control over all content properties, including color, outline, and filling. It may be drawn with shadow and live effects, using any typeset that your computer has. To cut loading time for page users, the software optimizes pictures by eliminating unnecessary material. The optimization tool has simple interface and aids fast equate different graphic formats to create the smallest image.
Resolution-independent vector layers allow for quick creation pictures that may be resized without harm of quality. You can move and adjust its attributes over and over again when maintaining its original clarity and crispness with no touching another items in the artwork. Any layer may be drawn with many live distortions. Live effects are fully customizable. If you make any change to the layer, the result automatically updates. You may apply shadow to sprite, develop it flame, draw it with opacity and a lot more.
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For more data on the business and its services please visit its online site at http://jenniferyap.killer-technologies.com


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A rousing harmony of duelling fiddles drifts down the corridors of Cummins Area School.
The artists in residence have arrived.
The Fiddle Chicks are an Adelaide based musical duo, who have taken their strings out west, to bring the magic to the children of Cummins.
A class wanders into the school hall, and just before the scallywags can wrestle attention from the teacher, Emma Luker and Dee Trewartha energetically perform a special folk blend of traditional Celtic, meets blues and roots, with a twist of gypsy.
The class is spellbound.
It's the duo's original tune, Wind Up the Kilt, which you can hear on this video.
Albert Einstein famously said, "A table, a chair, a bowl of fruit and a violin; what else does a man need to be happy."
The experienced musicians are going to be at the school for a week each term and have planned the crescendo of their tenure to climax with a school musical extravaganza.
The stress of maths, spelling and grammar is lifted from the shoulders of the young students as they come up with simple dance moves to accompany the story of Tidderlick (the big green frog) - the traditional song that their class is performing at the concert.
All students have the chance to be a part of the choreography and everyone participates when it comes to the dancing.
When the siren signals that the class is over, the little ones drag their feet as they head back to the classroom and away from the fiddle.
Meet The Fiddle Chicks Emma and Dee, and see some of the action from their first week in Cummins, in the video above.
Thank you to Emma and Dee, the teenage jammers and to the junior primary class at Cummins Area School for letting me film you.
Please check your inbox and click on the link in this email within the next 2 days to complete your subscription.
If you don't find the confirmation email in your inbox, please look in your 'junk' mail folder (also sometimes called 'spam').
We love the Fiddle Chicks too. They were awesome! Come back soon!!
Good music, good fun!
A violin was one of the few ways the Sherlock Holmes would relax... says a lot about the fantastic joy that the instrument can bring.
Great video. Makes me want to dance with the kids.
I love the Fiddle Chicks!
Awesome video! I love the pace of the music... it just gave me a shot of energy to get through the rest of the afternoon. What a great thing for the kids to be able to take a participate in too.
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Disney Turns Profit Despite Sagging Movie Revenue10 May, 2006 By: Jessica Wolf
Tough video comparisons resulted in a shortfall in second-quarter revenue at The Walt Disney Co.'s studio segment, which includes theatrical and home video revenue.
Revenue in the segment fell 22%, to $1.8 billion, and operating income fell 39%, to $147 million, compared to the second-quarter 2005, which included sales from the March DVD release of The Incredibles.
The Chronicles of Narnia: The Lion, the Witch and the Wardrobe video sales are strong, executives said, but will mostly be realized in the third quarter, though continued theatrical performance of the fantasy flick helped prop up the lag in video sales for the second quarter.
"We knew we were going to have tough home video comparisons because we had The Incredibles last year," said CFO Thomas O. Staggs.
Disney expects theatrical and video revenue to ramp up in the final two quarters of the year with the release of Pixar's Cars and the adventure sequel Pirates of the Caribbean 2: Dead Man's Chest. The Pirates sequel represents Disney's increased focus on branded content lines, said president and CEO Bob Iger.
Company-wide net income increased 12%, to $733 million, for the quarter ended April 1. Income for the fiscal first half was up 9% to $1.5 billion over the prior year. Revenue for the company was up 3% to $8 billion for the quarter, and 2% to $16.9 billion for the mid-year point.
Executives expect 2006 to be the fourth consecutive year of double-digit growth.
Transitions in the wake of Disney's Pixar acquisition are going very smoothly, Iger said.
"Nothing is more important than creativity to Disney's success," Iger said, touting the studio's successful acquisition of creative powerhouse Pixar.
The Disney Co.'s recently announced offering of top ABC programs like "Lost" and "Desperate Housewives" for free on an advertiser-supported Web site ABC.com is an example of the company's future strategy, Iger said.
"Disney will continue to distribute its assets, or platform-specific content, to best take advantage of emerging platforms and consumer trends," he said.
Iger declined to give firm numbers on streaming activity on the ABC site, but said the advertisers are pleased, consumer feedback is great and that all signs indicate this kind of use of technology creates incremental consumption.
"This is not an experiment," he said. "We are in this for the long haul."
Iger did say that ABC and Disney shows have garnered 5 million downloads via iTunes since Disney released titles to that service in October 2005.


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Live 2
Part Two of Hosty's live performance on a 100 degree+ night in Oklahoma near the University of Oklahoma. Hosty plays guitar,drums,kazoo and harmonica all at the same time.
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No time to write about it — I still haven't packed for it — but I'm heading back down to Nicaragua in the morning. Here's one of my favorite photos from the last time or the time before.
More later, -jv
I'm having an odd sort of flashback.
I'm on a plane over Canada, flying up to Anchorage to address the Alaska Writers Conference. This plane is like many planes I've been on in my professional life, like any plane whisking me to Managua or Moscow or wherever. And, as usual, I have a laptop open on my tray table. I'm either working or not working. Knowing me, I've probably just finished playing a game, or just about to start. It's how I fly: I should be working, and sometimes I am, but often I'm not.
Usually on these gigs in wherever, I'm arriving as the expert from out of town, the consultant expected to teach and train writers (possibly even enlighten writers) but not necessarily to be a writer himself. And there have been many, many times in the past when I frittered away all the hours on the flight doing two things: not-writing, and feeling guilty about not-writing. I understood that, as a hard working and dedicated teacher and trainer, I had a pretty damn good excuse for not, at that moment, being a writer. Yet I felt guilty. Down deep in my heart, I felt like a fraud, and simultaneously loved and hated having a handy excuse for not advancing on my own writing front. And felt guilty. Like I was letting myself down, and really not living up to my reputation.
I recognize in this moment that this feeling of guilt is gone. I have finally, finally, written enough, achieved enough as an author, that I no longer feel like a fraud to me. No one can doubt my body of work. It's there. It exists. There's simply no way they can pin upon me the label of "those who can't do, teach." I do. I do plenty. I teach, too. So as I sit on this flight, monkeying with my next novel, I need not fear flying into a situation where someone asks, "What have you done for you lately?" I've done plenty for me. I still am. I'm the writer I always wanted to be. It's a pretty sweet feeling. It's nice to leave guilt behind.
I'm finally starting to fill the bottomless hole. It's not full, but it's not empty, either, and I, at last, seem to recognize that. I'm either growing up or growing old. From here at 35,000 feet, it's hard to tell which.
Anyway, Alaska. More writers to meet and teach, more pulp to push, more sights to see. I've never been to Alaska before. I hear they have moose.
More later, -jv
I've been having fun making up new words lately, sort of as a hobby or a mental exercise more fruitful than Sudoku. Some recent goodies…
Gagnostic. Someone who believes God's a joke.
Panticlimax. A dry hump.
Rantiquity. An old, old argument.
Hobotheosis. Elevation of the bum.
Wordsword. When you can't say anything nice, use this.
Not all of 'em are winners of course, but, to quote myself, "Is the point of the game to win? Or to have fun?" And I'm having fun, so much so that I'm contemplating giving myself the challenge of coining 1000 new words by Christmas. These I can then package, I suppose, and sell as a slender ebook, A THOUSAND NEW WORDS BY CHRISTMAS, VOLUME 1 (which would set me up for more of same mayhem next year, but whatever.) I think I may do it, for I'm like a dog with a bone with these things, but on the other hand, will I kill the fun of it when it becomes an obligation? Or maybe I'll just do as many as I can, and then package them as, say, 475 NEW WORDS BY CHRISTMAS. No one will know except me and both of you, my readers. So what do you say? All in favor of new words say, "Neologos!" The neologos have it. More later, -jv
Just found out that I was the number-two bestseller at Vroman's Bookstore this month:
by Ruby on April 4, 2011
Hardcover Fiction
Tiger's Wife, Tea Obreht
Albuquerque Turkey, John Vorhaus
Troubled Man, Henning Mankell
Lesson in Secrets, Jacqueline Winspear
Land of Painted Caves, Jean Auel
Saturday Big Tent Wedding Party, Alexander McCall Smith
Mystery, Jonathan Kellerman
Georgia Bottoms, Mark Childress
Pale King, David Foster Wallace
When the Killings Done, T C Boyle
Of course that may have had something to do with having done a big book launch event there that week, but still… it's the best bestselling I've done so far, so yay me.
(Me as I used to be)
More later, -jv
What a long yesterday. I got up at 4:00 a.m. to drive to San Diego to appear on a couple of morning talk shows, then had to kill the whole day down there before an in-store appearance at the Mysterious Galaxy Bookstore. Well, fortunately, there are card rooms in San Diego, so killing the day proved to be no problem. Even better, the TV appearances drove some traffic to the in-store, plus a whole bunch of other people came and it was just a fun, lively, wonderful evening of writers talking about writing, cracking jokes, eating cake and (me) selling a ton of books. Really one of those moments that makes the whole book launch thingie feel worthwhile.
One of the TV shows was kind enough to give me a recording of my appearance, and I've posted it to YouTube. If you want to see me working a completely lame version of the Hat Trick proposition bet, complete with bogus invisible magical straw, do please click here. If you want to do something else, do that instead. If you haven't yet ordered/bought/read/enjoyed The Albuquerque Turkey, what are you waiting for? It's the book that The Literate Kitty called "all-out satisfying feel-good fun," and while I don't generally take the word of cats, in this instance I believe I shall.
More later, -jv
I've been writing a novel set in 1969. There's no mystery about why: I'm stuck in that era; always have been. The music I listen to, the philosophies I believe in, the major discoveries I've made, the clothes I wear (I'm wearing an army jacket right now), my whole entire sense of self is rooted in the 1960s, and I do believe that the tragedy of my life — a thing that has haunted me from that day to this — is that I was just a little too young (and maybe a bit too scared) to be the hippie I wanted to be. So this novel I'm writing is nothing less than an emotional memoir, a wish-fulfilling journey down a path I might have walked. From time to time as I write it, I get very close to something I call "the bottom ache," which, for me, is where the writer's true emotions live. When I can get a bit of the bottom ache out of my heart and out of my head and onto the page with all its authentic sour sweetness, I feel like I've gotten somewhere with my work.
But there are unintended consequences of living in the past as I am. Melancholy frequently sweeps over me as I measure the distance between where I was and where I am. Rue slips in — damn, why didn't I take the road not taken? Frustration dogs me, for even when I successfully catch a snapshot of the '60s, I know it's only a snapshot, a dim reflection, not at all the real deal. And when I miss — when my details are lame and my dialogue flat — when I try to convey real emotion and real event on the page, and know that I'm not coming close, I'm not only burdened by the time gone by but also by the time I'm burning through now, trying and failing, trying and failing again.
Well, it's what writers do, one of the many things we do: We try; we fail; we try again. And when we succeed, we set harder targets for ourselves. That's part of the paradigm, and I understand it well. Writing is a "have more, need more" condition. No matter what goals we reach, real writers always need new goals and tougher ones. In this novel, my goal is to go deep and go back. In my dark days I fear I'm missing on both counts.
But I soldier on, because that's what real writers do, too. I feel like I'm participating in an experiment of a sort: how much melancholy can I stand to feel? At this moment, living in 2011 and trying so hard to live in 1969, I'm feeling it all, every single bit. I'm lost in the past. I put myself there, and now there's no way out of it except through it.
More later, -jv
She's been in and out of caves all week. Not spelunking, but… oh, hell, I'll let her tell you.
March 4: Aurangabad, India
Flew to Mumbai and then to Aurangabad – the first leg of my tour of India. Today's adventure was The Ellora Caves which are a mix of Buddhist, Hindu, and Jain cave temples that were built between the 6th and 10th Centuries AD near the ancient Indian village of Ellora.
The caves were carved out of the vertical face of the Charanandri hills at time when Buddhism was declining in India and Hinduism was beginning to assert itself. As time progressed to the 10th Century, local rulers switched allegiance from Shaivism (Hinduism devoted to Shiva) to the Digambara sect of Jainism.
The coexistence of structures from three different religions serve as a symbol of religious tolerance in India. The Ellora Caves were designated a UNESCO World Heritage Site in 1983.
More later, -jv (and Maxx)
Want to score a free copy of THE ALBUQUERQUE TURKEY? Just click below.
Giveaway ends February 23, 2011.
See the giveaway details
at Goodreads.
Self-produced in 1984 on the ironically vainglorious ONE STAR RECORDS label, Word Processor sold literally tens of copies before disappearing by the box-load into my basement. (more…)
First fact: Online poker is not the same as online gambling. If you put your money into play at www.joyofslots.com or www.casinofishie.com or any other online gambling site I might make up, one thing is for sure: You will not win. Not in the long run. (more…)


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More than 300 metal workers have formed a picket line outside Toyota's Altona plant in Melbourne to protest at the treatment of a fellow employee, the company said.
The strike began on Wednesday morning and involves trade employees from the Australian Manufacturing Workers' Union (AMWU) and the Electrical Trades Union (ETU).
Toyota branded the industrial action unlawful and said it was a result of an employee seeking preferential treatment over fellow workmates.
The company's public affairs manager Glenn Campbell said the employee wanted to continue working in the same position following Toyota's consolidation of its Port Melbourne operations with its Altona plant.
But he said although the company forged an agreement with staff four years ago that their positions would be retained in the consolidation, it did not apply to the employee in question because he joined the company later.
Mr Campbell said the employee's wage and conditions would remain the same as a result of his transfer from a production operations position to a trades role.
"We'll continue to keep working through the legal process to resolve this matter and strongly urge employees protesting to return to work," he said.
While the employee was welcomed to apply for a trades position when a vacancy arose, he also had the option to leave the company and redundancy would be offered, Mr Campbell said.
At this stage, the company said production at Altona was unaffected by the strike.
The consolidation of Toyota's Port Melbourne and Altona plants was announced in July 2002 and completed in May this year.
It involved hundreds of workers, many of whom were given the option of taking redundancies.
Comment was being sought from the AMWU and the ETU, which represent workers at the site.


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No GIA Report with this item.
company's comprehensive appraisal included.
Check out our diamond forum. Chat with others that love diamonds.
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Next Day Delivery | Click & Collect | Free UK Returns
Availability: Out of stock
Simple, chic necklace with an interlocking circle design in gold fill.
A cool, contemporary design that will work with lots of different outfits.
Handmade in NYC.
By Boe create one of a kind pieces from unique and vintage materials. A favourite brand of celebrities and fashion magazines.
Delivery Options
Click here to find out more about our Delivery Options.
Please note we do not ship large/heavy items/furniture/mirrors worldwide, this includes the Annie Sloan Paint & Wax.
While we hope that you will love your purchase, we understand that for whatever reason you may change you mind. If you would like to exchange or refund an item, simply fill out our returns form and post the item back to our store within 28 days. We will refund the amount minus any delivery costs.
Click here to find out more about our Returns & Refunds policy.
made by digital boutique


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The Queensberry Hotel
Absolute were tasked to refresh both The Queensberry Hotel and their restaurant's The Olive Tree's websites to ensure they are in line with technology and giving their visitors a new up to date look. The functionality was also reviewed to ensure this worked as simply and efficiently for the visitors, ensuring minimal click through, easy online booking and clear and concise information on their products and services. This work was done alongside Absolute's monthly management of their full online marketing, blog and social media posts.
Visit more at www.thequeensberry.co.uk and www.theolivetreebath.co.uk


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The dispute between Sona Heiden and SPB Charan has eventually been put to rest. The actress had filed a case against senior SPB's son accusing him of sexually assaulting her during a party being held at Vaibhavs place. This party was supposed to be a grand celebration for the success of Thala Ajiths Mankatha which saw the presence of the entire Mankatha team including director Venkat Prabhu.
Sona's claim-to-fame was soon to follow with her accusations of being mishandled by Charan. She had also provided an ultimatum of 10 days, which was casually ignored for reasons best known to Charan. On not receiving a written apology from Charan , an agitated Sona decided to get the support of the Jhansi Rani Women activists in order to stage a Mutrugai Porattam in front of Charans house. Howsoever with police interfering into the matter Sona was not allowed to take forward her protest march, throwing cold water on her plans of getting unwanted media attention. Now we hear that the spat is over between the two with their mutual friends successfully resolving the issue. Sona will soon leave to a foreign nation to avoid any more distracters. She was quoted saying, " Charan has always been a good friend and I wish him all the luck Thanks for all the support rendered by the media in highlighting the issue ".
Time to CHILLAX! for Sona. (Yeah… you did work hard to get some attention)


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Yes, Grandma I know - this is "a low down dirty shame." Especially when steam pipes are exploding in New York and bridges collapsing in Minnesota.
Washington Report, July 2006, pages 16-17
Congress Watch
By Shirl McArthur
Because of the uncertainties and ambiguities associated with U.S. aid to Israel, arriving at a precise figure for total direct U.S. aid to Israel probably is not possible. Parts of it are buried in the budgets of other government agencies—mostly the Defense Department (DOD)—or in a form not easily quantifiable—such as the early disbursement of aid, allowing Israel a direct gain and the U.S. Treasury a direct loss of interest on the unspent money. Given these caveats, the Washington Report on Middle East Affairs (WRMEA) conservatively estimates cumulative total direct U.S. aid to Israel at $107.961 billion.
For the complete report: http://www.uruknet.de/?p=m35020&hd=&size=1&l=e
Friday, August 3, 2007
U.S. Aid to Israel: $108 Billion - A Conservative Estimate
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€ 45.00
non E.U. price € 37.19
ex. import TAX & clearance costs
When Simone and his brothers were little boys, they took their rowing boat and headed for Capri...
They always made a speed contest around these limestone rocks, you cannot see them here, bacause they just left before the evening falls..
32 x 32 cm
100% linen handrolled made in Napels Italy
Collections: Accessories, All Products, Finamore, New Arrivals
Type: accessoires
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© 2017 Frans Boone Store.
All Pictures Copyright Frans Boone Store 2010-2016
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If Baywatch were to be made in India, Alia Bhatt & Sidharth Malhotra would be the potential leads. The statement is further proved by their latest photoshoot for Vogue. There might be many reasons for you to buy Vogue's March issue, but Alia & Sid would top all these reasons. And we are going to show you why.
Alia & Sid shot the cover for Vogue's latest issue in Maldives, and boy! were they hot! Alia is seen wearing boho print bikinis while Sid is bragging about his abs in his boxers.
These new kids of Bollywood just got better and bold. The cover is promising and fashionable. Alia's myriads outfits give us varieties of choices for the forthcoming summer, also stating that your beach fashion might overshadow your basic wardrobe.
Alia's hairstylist is Keiichiro Hirano, makeup artist Marco Antonio and stylist Anaita Shroff.
Let's take a look at this hot and sultry photoshoot:
Alia In Pia Pauro
Alia is wearing bikini top bySeafolly Australia and Sidharth's shorts are by Dolce & Gabbana
Alia In ONLY India Sweater
Alia is sporting a maxi printed dress by Sanchita Official and shorts byALL SAINTS.
Alia In Chanel
Everything Chanel is classy and now hot. Alia's shorts are by Sumarie Couture & Sidharth's Paul Smith Designs.
Alia In Dan and Dean Caten
Alia is sporting bikini top by Prism London and Sid is wearing Zegna shorts.


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Class Name :
1 Art and Science • DPRB181L04
Class Date :
September 06 - December 13
Meeting Times :
Wed 9am-noon (14 sessions)
Class Location :
Room 201
Instructor :
Guoliang Caji
Price :
About this Class:
1 Chinese Ink Brush Painting • DPGC173A10
Students will be introduced to the aesthetics of the Eastern art through the study of Chinese brush painting. The class leads students through learning and practicing various techniques of brush holding, ink usage, watercolor, and rice papers. Students will also be guided through their sketches and transferring them to a painting.
The 14 sessions are divided into four sections.
Section 1: Students will observe outstanding works of Chinese painting. The instructor will demonstrate the whole process and guide everyone through landscape painting (mountains, stones, clouds, water, trees, etc.).
Section 2: Controlling integration of water and ink, techniques on depicting the "weight" of an object, and getting familiar with rice paper.
Section 3: Copying artworks from others, sketching live scenery, and finding balance of Chinese painting.
Section 4: Application of color and finalizing artwork. Each student will create an artwork for a final project.
Supplies: All supplies will be provided by instructor. If individual students need extra rice paper that is beyond the scope of the class, students will be able to purchase more at a small cost.
No class Oct 11
Artwork by Guoliang Caji
Need a parking pass? Buy one here!


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Annual Flu. By: Emily Linn, Lucy Kurtz, and Makayla Claiborne. Symptoms. Fever Headache Sore Throat Fatigue Achy Muscles And other cold-like symptoms. Prevention and Treatment. Washing your hands Containing your coughs and sneezing in sleeve or tissue Avoid big crowds Vaccination
Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.
By: Emily Linn, Lucy Kurtz, and Makayla Claiborne


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MOVIE SYNOPSIS [ General Audiences ] With the film direction of Marisa Paniagua, Raphael leads the cast of this film of Spain, with script in Spanish (see subtitles), whose presentation to the public was scheduled for 2013. You can watch Raphael: Mi gran noche online on TV cable or theaters with original audio in Spanish at different dates. This film premiered in theaters in 2013.
Rating: 5 by 10 users./
Runtime: 92 minutes
Raphael, Coral Allegro, Sara Baras, Il Divo, Gloria Estefan, Dani Martín, Pastora Soler and Vega.
92-minute film (full movie) directed by Marisa Paniagua.
The original audio of Raphael: Mi gran noche has dialogues in or Spanish, it was produced in Spain.
It premiered in cinemas or television in 2013.
Screenplay written by Pedro Santos.
Chus Rubio and Toñi Prieto.
This film was produced and / or financed by Televisión Española (TVE).
Televisión Española (TVE).
Without commercial breaks, the full movie Raphael: Mi gran noche has a duration of 92 minutes; the official trailer can be watched in streaming on the Internet. You can watch this full movie free in English or Spanish in movie TV channels, renting the DVD or with VoD services (Video On Demand player, Hulu) and PPV (Pay Per View, Netflix).
See the page of this full movie, Raphael: Mi gran noche in FULLTV Movies.


text: I have been following Team Fiat for almost an year now and felt its high time to share my experience. It all started in the early 2007 when I was in UK driving a 98 Model Fiat Brava 1.6 petrol for more than 2 years. One day on my way to work I have seen two stunning puntos outside the Fiat showroom in East Ham near the community hall, I was very impressed and wanted to exchange my exisitng car for the punto. Couple of days later I went to the showroom and enquired about it. After the initial valuation of the Brava the difference amount was out of my affordability so the idea of owning the beauty is out of question. I moved back to India in 2008 and started using the spare car(Wagon R) we had at home. As my work place is 26 kms away from my home, idea of owning a Diesel car was always there. In Nov 2010 my wife got placed in to a new project and her office timings were different from mine, So finally I had to take a decision of buying a new car and gave the wagon R to my wife for her daily commute as she is used to it. After the decision was made the obvious choice was Punto Diesel which I wanted to buy when I was in UK though my parents were little worried about not seeing many puntos on road I was able to convince them. But the question was which variant, EMOTION was fitting my budget and with no second thought booked the HHBlack car from Tejaswi Motors near Hitech City on Dec 15th 2010. Sales Person Ms Nirosha was very courteous and helpful. I was promised delivery after 15 Days and I was ok with that. On Dec 22nd, 2010 I got a call from Ms Nirosha at around 5pm and she confirmed that the car has just arrived and they would be giving the delivery on 23rd itself. Took the delivery on 23rd at around 9pm as I was stuck at work due to some unplanned meeting. Let me tell you I havent done any PDI as I never knew that something like that exists and also I have not even taken the test drive and went with the previous experience of Brava. Till date I have clocked 22,000 Kms and I am very happy with the decision I have made. Issues Faced Till now: AC O ring gone within the very first week of taking the delivery and was fixed by Service Centre in a Day. Noise from Front and Rear window glasses. Complained every time I go to the SC will be ok for couple of days and will be back again. Living with it. Front Right Headlamp unit replaced under warrantly as there was some blackening. Proactively changed by SA. Long Drives Done: Total Distance: 1500 Kms Duration : 4 Days Route: Hyderabad - Tirupati - Kalhasti- Kanipakam - kanchi - Chengalpattu - Chennai - Vijaywada - Hyderbad. Total Distance: 3600 Kms Duration: 5 Days Route: Hyderabad - Viayawada - Visakhapatnam - Bherampur - Ramba - Bhubaneswar - Puri - Konark - Srikakulam - Simhachalam - Annavaram - Bhimavaram - Dwaraka Tirumala - Vijayawada - Hyderabad. During the Hyderabad - Bhubaneswar trip on the way back near Palakollu (40km away from Bhimavaram) at around 7:30pm drove thru a very big pot hole and engine guard was badly hit and started touching the gear box resulting in heavy noise. Stopped the car and called my Service Advisor Mr Joseph and he advised me to drive to the nearest town if there is no engine oil leak and if the temperature gauge remains normal. I drove to Bhimavaram and since I had already planned to stay that night in Bhimavaram I thought of calling the Fiat RSA next day morning. Next day morning I have called Fiat RSA and they confirmed that they have a mechanic available in Bhimavaram and told me I will have to bear the expenses for the repair as it was due to accident to which I agreed. In the next 30 mins mechanic came to my guest house and inspected the vehicle. He confirmed that due to the impact a dent was formed on the engine gaurd. Took the vehicle to his garage and fixed it. Whole thing was done in less than an hour and the charges were Rs 200/-. Before we went for the trip my father has booked a Dezire Vdi and after the trip he changed his decision and bought a Linea Active Diesel as he was very much impressed with the ride quality and the Fiat RSA. [TABLE="width: 239"] <TBODY> </TBODY>[/TABLE]


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Taking a cue from Zepster - will list all my PJ writing contest entries here...
Writing Contest #117 - http://www.penciljack.com/forum/show...=1#post1491824
Writing Contest #116 - http://www.penciljack.com/forum/show...=1#post1489845
Writing Contest #115 - a World of gods and Monsters - http://www.penciljack.com/forum/show...=1#post1488303
Updated 11-22-2017 at 03:20 AM by Chris2.0
Something ive been thinking about recently at night whislt at the drawing table and what probably is one of the biggest travestys in the art world is the lack of illustrated work on advertisments. Particulary for movie posters and book covers. I look back on the old Bond posters throughout the 60's, 70's ands 80's with a child like excitment. The amount of action, intriegue and of course the gorgously painted women still take my breath away and then i turn to what we have today. Really?
Following a detailed review of an abandoned newspaper I have identified a suitable position that will allow me virtually unrestricted access to the inner workings of a major commercial enterprise.
Also performed a service for the spot ridden teenage son next door ( Badger ). Assisted him in sorting out problems with their broadband connection. He was almost there, the plucky fellow, instructed him on the importance of encrypting their connection.
In my english class we are starting a poetry unit. We read a poem "You Bring Out the Mexican in Me" by Sandra Cisneros. We were assigned to write a poem in similar style. Here's what I wrote:
You bring out the artist in me
myself and I
The little kid, comic nerd
the yelling kid that's hardly heard.
You bring out the Pro in me
the inking man with pencils too
where would I be without you
Big erasers and small, small


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Be a Part of Our Success
Associate, Global Client Coverage
What is the opportunity?
Day to Day coverage to develop profitable new business for RBC I&TS and the wider RBC organisation with new institutional clients. Protect & retain NIAT/Revenue for I&TS' Coverage Relationships. Very strong value creation and NIAT production.
What will you do?
- Contribute to the maintenance of a detailed territory plan as part of the local Country Sales Strategy
- Build out bottom up territory plans by target client on those relationships
- Ensure focus is directed to 'on strategy' and strong NIAT generating opportunities
- Build out bottom up portfolio plans by existing client
- Manage the client portfolio through a 'Net' perspective ensuring profitable growth opportunities minimize any portfolio loss or re-pricing (including ManCo relationships, Boards, Offshore support)
- Seek/support revenue growth and cost reduction opportunities to enhance client NIAT
- Proactive calling ensuring RBC I&TS is the best connected and demonstrates best understanding of the clients business, strategic priorities, business challenges
- Profiling RBC strategically with clients well before clients conduct market review and issue Requests for Proposals
- Ensure broad deep connectivity at clients executive, management and operational levels
- Fully understand political landscape in the client organisation
- Metered engagement with client to explore for mutual value and test value proposition vs their value criteria
- Fully understand and leverage overall RBC enterprise connectivity to the client organisation
- Establishe and evolve a client specific value proposition and ensures it is unique and differentiating
- Spearhead the preparation and presentation to client of proposals and all client presentations. Owns the client strategy, and overall quality of the proposal and presentation is in conjunction with Deal Management.
- Draws on the expertise of the wider RBC organisation to fully leverage complementary solutions and intellectual capital for existing clients
What do you need to succeed?
- Emerging track record in Coverage/Relationship Management role (Ideally High/Medium Complex relationships/targets)
- Emerging ability of strategic planning and working with portfolio goals
- Emerging ability to sell/navigate to complex, multi-level organizations
- Emerging ability to engage senior business heads to support effective country strategies and product development
- Emerging negotiation/commercial skills
- Orientation towards disciplined strategic business development processes
- Refined interpersonal skills
- Proven Team Leader responsibilities
What's in it for you?
We thrive on the challenge to be our best, progressive thinking to keep growing, and working together to deliver trusted advice to help our clients thrive and communities prosper. We care about each other, reaching our potential, making a difference to our communities, and achieving success that is mutual.
About RBC
Royal Bank of Canada is Canada's largest bank, and one of the largest banks in the world, based on market capitalization. We are one of North America's leading diversified financial services companies, and provide personal and commercial banking, wealth management, insurance, investor services and capital markets products and services on a global basis. We have over 80,000 full- and part-time employees who serve more than 16 million personal, business, public sector and institutional clients through offices in Canada, the U.S. and 37 other countries. For more information, please visit rbc.com .
Inclusion and Equal Opportunity Employment
RBC is an equal opportunity employer committed to diversity and inclusion. We are pleased to consider all qualified applicants for employment without regard to race, color, religion, sex, sexual orientation, gender identity, national origin, age, disability, protected veterans status, Aboriginal/Native American status or any other legally-protected factors. Disability-related accommodations during the application process are available upon request.
City: City of London
Address: Riverbank House
Work Hours/Week: 35
Work Environment: Office
Employment Type: Permanent
Career Level: Experienced Hire/Professional
Pay Type: Salaried
Position Level: PL07
Required Travel(%): 0-25
Exempt/Non-Exempt: N/A
People Manager: No
Application Deadline: 2017-12-04
Req ID: 150117
Flexible Working Options Considered


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Urban Roots is a Japanese hair salon that is the go-to place for the city's sizable community of affluent Japanese housewives. The Japanese staff here specializes in executing immaculately done haircuts and coloring but the style here is on the safe side. If you're... Read more
Hair salon with brightly lit, white interiors and an internationally-trained staff of stylists and technicians. They offer color treatments, conditioning, perms, and styling. Cuts start at 150rmb. Read more
iBen Hair is both a boutique hair salon and a coffee shop, though most people going for the coffee are there for the hairstyling first. The salon offers haircuts, highlights, coloring, perms, and treatments from internationally trained, English-speaking stylists who... Read more
Zen offers an all-around experience where they pay special attention to little details. Expect a calm atmosphere, zen-like environment and small touches like fresh orchids, unique oils, to accompany their indulgent 4-hands massage (among other treatments they offer). Read more
Yuan Spa covers over 3,000 sqm of recreational and wellness space including 12 spa treatment rooms, a 24hour fitness centre, swimming pool, whirlpool, steam and sauna rooms, a beauty salon and a juice bar. Also has parent and baby swimming lessons. Read more
Located in Hongqiao, Shanghai United Family has a 24/7 emergency room that can handle acute surgical emergencies, neonatal intensive care, adult intensive care, and provide services like CAT scans, MRIs, Ultrasounds, and X-rays. They also specialize in prenatal care... Read more
Parkway is an expensive but entirely reliable way to see a doctor or a dentist in Shanghai. No waits, English-speaking, foreign-trained staff operate out of three or four locations in Shanghai. This is the one at the Portman Center. There's a doctors surgery that's... Read more
Western and Traditional Chinese Medicine Doctors using Chinese and Western medical practice for wide ranging treatments, including Gynecology, Psychology, Acupuncture and more. Read more
They say it's "only for members", but you're allowed to show up and "try it" for 150rmb during the week. That's meant to be a one-time deal, but who's going to know? On weekends it's members only. Membership gets you a year in the gym and use of the indoor and... Read more
Subconscious is a chain best known for its massages but also does facials, nails, body treatments, medical manual therapy, and waxing. They also house studios for classes like yoga, meditation, and even belly dancing. Service and amenities go above and beyond to set... Read more
One of Shanghai's biggest hospitals, Huashan is located in the center of the city on Wulumuqi Lu. They have 24/7 emergency services, specializing in neurological conditions, and English speaking staff. Anyone with emergencies should proceed directly to the local ER... Read more


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Photographers in Hungary
Here are the listings of Photographers for photography work in Hungary. Each photographer has its profile with portfolio of photography work, specialities and other details. You can use the filter facility on the left to exactly find an appropriate photographer in your area.
Free listings 12 Photographers in Hungary get listed here →
Gabriella Hidvegino portfolio
Attila Korbelyno portfolio
Digilabno portfolio
Montoni Photographyportfolio
Hungary, Budapest
Sebastian Bratescuno portfolio
Extravagance, personality and taste.
We make wedding photography a real experience to deliver the most out of it.
Daniel Illesno portfolio
Weigert Imagesportfolio
Zoltan Szabono portfolio
Northfotono portfolio
Daniel Horvathno portfolio
FOTOPno portfolio
Csaba Vighno portfolio
Hungary, Budapest
Why you should choose a photographer serving Hungary?
There are many reasons why someone would hire a professional Hungary photographer ... Some photographers offer video shooting as well. Hiring a Hungary photographer is an important decision that requires researching local photographers, learning a bit about photo equipment and style and finding the right personality. Be aware that some of the better photographers are booked up to 2 years in advance. Be sure that all of the details are clearly outlined in your contract with your Hungary photographer. By hiring a creative, experienced and reputable Hungary photographer, you can ensure that you'll get high-quality and professional photos.


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My job was boring until my boss introduced me to this new smoking hot employee. I could never really take my eyes off those bulging breasts. She has been seducing me for a while. She craves my big penis between her massive tits.
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- marcus
- : 6min 59sec
- : 2 Jan 2016
- Exclusive video


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This modern outdoor post light comes in a deep satin black finish with clear etched organic glass.More Details >
Add a chic, contemporary look to your home's exterior spaces with this Hinkley Lighting post mount light designed for outdoor use. The minimalist design is modern, and features a satin black finish over solid aluminum. Clear etched organic glass creates a waterfall effect when illuminated. Pole not included.


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SAN MATEO — With just a few weeks to go before a popular ice-skating rink closes to make room for one or more retail stores, dozens of supporters held a rally outside the venue, hoping to spur the city to take action to preserve it.
The sign-toting crowd outside the Ice Center on Saturday afternoon included youth hockey players and their families, coaches and Rawhide, the mascot of the San Francisco Bulls minor league hockey team. The center's hockey leagues are scrambling to find ice time at other crowded Bay Area rinks.
Fourteen-year-old Ben Frankel, of Palo Alto, who plays on a traveling team based at the rink, said he has "no idea" where his team will play in the fall. His mother, Marianne, said the Ice Center fosters a sense of community among players and their families — and provides a place where important lessons are learned.
"This is the place that teaches courage, teamwork, responsibility," she said.
The controversy stems from a decision by SPI Holdings, the owner of Bridgepointe Shopping Center, a complex of big-box stores near Foster City, not to renew the Ice Center's lease when it expires at the end of this month. SPI Holdings, which bought the shopping center in 2005, plans to convert the space to retail.
The master plan for the shopping center, however, requires an ice-skating rink or similar recreational use — the city extracted that concession as a condition for approving the plan in 1998. SPI submitted a pre-application in May of last year to amend the plan to allow the company to provide amenities elsewhere in the city instead, but the proposal stalled. The city held no hearings, and SPI withdrew the pre-application April 29.
The result is anger and confusion among hundreds of rink users, who wonder why the shopping center will be allowed to close the venue before the city approves an alternative that complies with the master plan. They want San Mateo to preserve the rink at Bridgepointe or help the operators find a new location.
The backlash comes on the heels of the city's 7-Eleven fiasco, when planners allowed a store to open last year in apparent violation of the city's zoning laws. The City Council overturned the decision, leading 7-Eleven to sue the city. The store is still operating.
Ron Munekawa, San Mateo's chief planner, said the city conferred with SPI in July and August as staffers prepared to hire a consultant to do a demographic study of rink users. The analysis would have helped the city come up with alternative uses that would serve a similar population. But SPI did not follow through on the city's request to fund the analysis, Munekawa said. Such studies typically cost $15,000 to $20,000, he added.
It was around that time that the proposal went "dormant," Munekawa said, and SPI dropped out of regular contact with the city. Munekawa said the city is researching whether SPI will be subject to any penalties come June for being out of compliance with the master plan. SPI's proposed amendment must be approved by the City Council.
David Satterfield, a spokesman for SPI, said the company intends to restart the pre-application process once it takes control of the rink June 1. The company has proposed several options for making recreational improvements, including a synthetic-turf playing field elsewhere in San Mateo and a bathroom at Mariner's Island Park.
"SPI is still working closely with the city in determining what that recreational use will be and where it will be — nothing has been nailed down yet," said Satterfield, adding that SPI has spent "tens of thousands of dollars" in recent years helping the Ice Center to find a new location.
Some Ice Center advocates don't think the company's proposals would make up for the loss of the rink.
"A toilet for the ice rink?" asked Julie McAuliffe, of San Mateo. "Give me a break."
Hockey players aren't the Ice Center's only patrons. There are people who simply drop in to get some exercise. Hundreds of young figure skaters practice there as well, said the rink's figure-skating director, Kim Delli-Gatti, who will be out of work when the facility closes.
Figure skater Kristi Yamaguchi, an Olympic gold medalist who grew up in Fremont, trained at the Ice Center for several years as a youth in the late 1980s. Supporters of the rink reached out to Yamaguchi and got a response.
"I'm saddened by the thought that a place where so many dreams are pursued and realized, including my own, is shutting its doors," Yamaguchi said in a statement provided by her husband, retired professional hockey player Bret Hedican. "I sincerely hope the city changes their mind."
Contact Aaron Kinney at 650-348-4357. Follow him at Twitter.com/kinneytimes.


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- Roger W. Elmore *a,
- Fred W. Roetha,
- Robert N. Kleinc,
- Stevan Z. Knezevicd,
- Alex Martinb,
- Lenis A. Nelsonb and
- Charles A. Shapirod
- a Univ. of Nebraska, South Central Res. and Ext. Center, Clay Center, NE 68933
c Univ. of Nebraska-Lincoln, West Central Res. and Ext. Center, North Platte, NE 69101
d Univ. of Nebraska, Northeast Res. and Ext. Center–Haskell Ag Lab, Concord, NE 68728
b Dep. of Agronomy, Univ. of Nebraska, Lincoln, NE 68583
Glyphosate (N-(phosphonomethyl) glycine)-resistant (GR) soybean [Glycine max (L.) Merr.] technology is gaining acceptance in U.S. cropping systems, yet potential yield suppression from either cultivar genetic differentials, the GR gene/gene insertion process, or glyphosate is a concern. Other work shows that the GR gene/gene insertion process may suppress soybean yield. No one has reported the effects of glyphosate on a diverse group of commercially available GR soybean cultivars. In this study we evaluated one of the potential sources of GR yield suppression—the effect of glyphosate on yield, growth, and development of GR cultivars. Field experiments were conducted at four Nebraska locations with12 GR cultivars in 1998 and 13 GR cultivars in 1999. Soybean response to glyphosate, ammonium sulfate (AMS), and water application at 21 and 42 d after soybean emergence was compared with control plots treated with AMS and water in 1998. An additional control, water alone, was added in 1999. Grain yield among cultivars differed as expected with a range of 3.44 to 3.96 Mg ha−1 in the 2-yr averages. Glyphosate did not affect the majority of the soybean growth and development characteristics measured. Grain yield of GR soybean was not affected by glyphosate at any location or when averaged over locations. Two-year average grain yield of cultivars treated with glyphosate, AMS, and water was 3.74 Mg ha−1; this was not different from 3.79 Mg ha−1 with AMS and water treatment.Please view the pdf by using the Full Text (PDF) link under 'View' to the left.
Copyright © 2001.


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Going Back Giving Back S01E01 WEB-DL x264-JIVEOct 4
As a nation, the UK is incredibly generous and presenter Aled Jones explores the personal history of incrdible individuals to see how they can positively change the life of another.
Season 01, Episode 01
In the first episode, Aled Jones is going back to the 1940s to hear the courageous story of one of the last remaining land girls in Great Britain, who worked the land and fields during World War Two. On her journey, she meets a modern-day veteran and his family who are still struggling with the effects of war. But can she give something back to them with a generous act that will change their lives?
Links: HOMEPAGE – TVDB
NFO – Torrent Search – NiTROFLARE – UPLOADED – RAPiDGATOR – UploadRocket


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Hawaii will become the first U.S. state to raise the legal smoking age to 21. How do you feel about this?
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I'm torn. While I know that brains are not fully developed until the mid-twenties, we let people register to vote, and enlist in the various branches of the service, at 18. Doesn't it seem strange that someone can fight and die for their country, yet is not allowed to smoke or drink?
I think we have to decide a definitive age that people become adults, and at that age, they should be allowed to make their own decisions about everything, including when to smoke and drink. Whether that means raising the age of majority, or not changing the smoking laws, I'm not sure.
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Smoking costs this country so much money. When we do recover, the money goes to lawyers and politicals and NOT lung cancer victims. Jack it up to 25 or more. If you are dumb enough to start when you are an adult, so be it. BUT, make it so the rest of us do not have to pay when they get sick from their choice.
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I don't think it will make much difference.
Teens who want to smoke will continue to smoke.
The irony in Hawaii is the legal age of consent to have sex is only 1i6.
Ultimately most "sin laws" don't prevent people from doing what they want to do. Marijuana laws never stopped anyone from getting pot.
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Why should smoking be legal in the first place.
The health risks are well known, and they have been known for a half a century.
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From what I've seen, many kids kind of bide their time until they're 18 (that "no-longer-a-minor" age), and once they get to 18 they, to one extent or another, get a little carried away with having passed that 18th birthday. Of course, kids who didn't give a hoot about what was legal or what their parents allowed don't always worry as much about getting to 18. I mean the ones who care, for the most part, about what their parents think and/or the law.
It was a long time ago, but when I was between mid-teens and mid-twenties it was common for many young people to smoke, say, when they were out with others who were smoking, or to have the occasional couple/few cigarettes but generally remain non-smokers the rest of the time and forever. Smoking doesn't become a habit unless someone allows it to be. Even then, though, it may not become a nicotine addiction unless it goes from easily managed (and "empty") habit/practice to something the person eventually relies on for "mood or stress reasons". That aside, I'm not sure how many people there are who found their first cigarette a pleasant experience.
In any case, considering what 18-year-olds are allowed/required to do, no, I don't think the age should be moved up. With the state-of-affairs with regard to what teens do these days; and with the state-of-affairs with regard to the numbers of people using all kinds of stuff that affects their ability to think straight, see straight, and/or operate machinery (including vehicles); I just think everyone has bigger fish to fry than worrying about who smokes at 17 versus 20 or 22.
Keep in mind that unless someone sets their house or the woods on fire through careless smoking; or, I suppose if they have a health condition that will immediately and drastically be made worse by smoking in one's teens/early twenties; health problems associated with smoking are nowhere near as immediate and/or life-ruining as some of the other things people decide to do when they're young, "young-at-mind", and/or just generally not very good at making the wisest choices.
Again, our whole culture has bigger, bigger, fish to fry than this particular issue. Besides, address the other sources of worry, horror, and stress and maybe a lot fewer people will even want/need to smoke in the first place.
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we can address those larger issues AND this. false dichotomy logical fallacy operates in your answer. having ten years taken off your life via an addiction is serious.
Yes, it's serious; but the question/my answer say nothing about who will/won't quit (for example, at age twenty-five, or even who starts at - whatever - fifteen, for example). It asks about 21 versus 18.
brains aren't fully developed until about age 25. before that, we all tend to be impulsive and not make the best decisions. getting the smoking age closer to maturity would allow some who can't sneak their parents' smokes to be able to make a more informed decision about something that would be likely to affect them financially and healthwise for many years.
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First off, Happy New Year! It is interesting that no one has taken up the argument of parental rights. At one time, any discussion of this nature would have involved a substantial group of people who would have believed that they knew their own kids better than the government did and that it should be left up to parents what or what not their kids could do, and at what ages. If there weren't so many terrible parents around, there is logic in this, since different kids develop at different rates. However I'm not a parent's rights advocate. If I can't be a good parent to my son ever, for whatever reason, I WANT the government or somebody to step in and take him away from me, please.
As everyone here is no doubt aware, being an adult doesn't mean making perfect decisions every time. it means making your own mistakes, dealing with the consequences, and hopefully learning those hard lessons the first time, instead of having to repeat them.
Anyhow, I'm with Lisa. Pick an age and call an adult an adult. 18 seems like a good balance between full brain development (which a healthy brain doesn't need to determine right from wrong) and puberty. My son is 16. He has had responsibilities, consequences, and practice in making his own decisions and living with them since he was wee. I feel confident that in two more years he won't be all that much worse at it, than he is right now.
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Few days ago I wrote a comment on the synopsis of the saifulislam's book "Aku Terima Nikahnya". Today, I came across the hacker's version of wedding proposal. It seems that sometimes a person worked hard, through his own way, to tie the knots. Kudos, anyway.
From matching gems to the perfect match
Hacker proposes to girlfriend
via casual puzzle game Bejeweled.
By Mike Smith
A hacker's
romantic gesture
You're probably accustomed to seeing big-screen proposals at
ball games, in crowded restaurants, and scrawled across the sky by aircraft. But
popping the question by hiding a message in your intended's favorite computer game is rather more unusual.
However, for computer programmer Bernie Peng, it obviously seemed like
the perfect idea. He spent a month reprogramming his girlfriend Tammy Liu's
favorite video game, gem-matching hit Bejeweled, so that it would display the
all-important message when she reached a certain score. As Peng told Newark's
Star-Ledger: "I thought it was pretty cool, in a nerdy way."


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Specialty Camps at J Camp
Our list of specialty camps is always growing and improving. Whether you're looking for one of our staples, like Art Camp or Theatre Camp, or you want to try something new, like Lego Camp, Triathlon Camp or Dance Camp, we've got the Camp for you!
In addition to their special focus, J specialty camps will provide your child with a unique camp experience including crafts, sports, songs, swimming and life-long friendships. J Camp is built on a foundation of Jewish values, which our trained Camp Staff instills in each camper: kindness, respect, responsibility and cooperation.
Art Camp: Entering 3rd-6th Grades
Culinary Camp: Entering 3rd-6th Grades
Dance Camp: Entering 1st-7th Grades
Engineering Camp: Entering 3rd-6th Grades
Lego Camp: Entering 1st-5th Grades
Next Level Advanced Sports Camp: Entering 3rd-7th Grades
Theatre Camps: Entering 3rd-8th Grades
Triathlon Camp: Entering 3rd-8th Grades


text: A picture is worth a thousand words. But so are reviews! We love our clients. And we like to think they love us too. Planning a wedding is a very personal undertaking and because of that, we take pride in the relationships we develop with our clients. We don't want to meet their expectations. We want to exceed them! Whether it's a small, intimate gathering of 40 or a grand, lavish event for 400, Birds of a Feather will be there to ensure your wedding is one for the record books. Check out some of the wonderful words and reviews our clients have to say about us