text:
Myeloperoxidase Inhibition Improves Ventricular Function and Remodeling After Experimental Myocardial Infarction
Author + information
- Received May 11, 2016
- Revision received September 12, 2016
- Accepted September 13, 2016
- Published online December 26, 2016.
Author Information
- Muhammad Ali, MDa,
- Benjamin Pulli, MDa,b,
- Gabriel Courties, PhDa,
- Benoit Tricot, MSca,
- Matthew Sebas, BSca,
- Yoshiko Iwamoto, BSca,
- Ingo Hilgendorf, MDa,
- Stefan Schob, MDa,
- Anping Dong, MD, PhDc,
- Wei Zheng, MDc,
- Athanasia Skoura, PhDc,
- Amit Kalgukar, PhDc,
- Christian Cortes, MScc,
- Roger Ruggeri, PhDc,
- Filip K. Swirski, PhDa,
- Matthias Nahrendorf, MD, PhDa,
- Leonard Buckbinder, PhDc and
- John W. Chen, MD, PhDa,b,∗ (jwchen{at}mgh.harvard.edu)
- aCenter for Systems Biology, and the Institute for Innovation in Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
- bDepartment of Radiology, Massachusetts General Hospital, Boston, Massachusetts
- cPfizer Worldwide Research & Development, Cardiovascular and Metabolic Diseases, Cambridge, Massachusetts
- ↵∗Reprint requests and correspondence:
Dr. John W. Chen, Massachusetts General Hospital, 185 Cambridge Street, Richard B. Simches Research Center, Boston, Massachusetts 02114.
Visual Abstract
• The inflammatory enzyme MPO is a potential therapeutic target in cardiovascular diseases.
• PF-1355 is an orally bioavailable mechanism-based inhibitor of MPO enzymatic activity. PF-1355 treatment successfully inhibited MPO in mouse models of myocardial infarction and ischemia reperfusion injury.
• Short duration oral drug treatment for 7 days attenuated inflammation and cardiac dilation during early infarct healing. However, MPO-containing cells persisted beyond 7 days.
• Prolonged 21-day treatment improved ejection fraction (∼44%) and decreased end-diastolic volume (∼53%) and left ventricular mass (∼33%) compared with untreated control subjects.
• Better therapeutic effect was also achieved when treatment was started early (at 1 h) after the initial ischemic insult.
PF-1355 is an oral myeloperoxidase (MPO) inhibitor that successfully decreased elevated MPO activity in mouse myocardial infarction models. Short duration PF-1355 treatment for 7 days decreased the number of inflammatory cells and attenuated left ventricular dilation. Cardiac function and remodeling improved when treatment was increased to 21 days. Better therapeutic effect was further achieved with early compared with delayed treatment initiation (1 h vs. 24 h after infarction). In conclusion, PF-1355 treatment protected a mouse heart from acute and chronic effects of MI, and this study paves the way for future translational studies investigating this class of drugs in cardiovascular diseases.
Myocardial infarction (MI) triggers an inflammatory cascade, where various local (ischemia, oxidative stress, endothelial, and myocardial dysfunction) and systemic factors (inflammatory cell recruitment, neuroendocrine disturbances) perform a complex interplay, which may lead to tissue fibrosis, ventricular dilation, and adverse remodeling (1), possibly culminating in sudden death or heart failure (2,3). Up to 24% (4,5) of patients after acute MI go on to develop heart failure accompanied with repeated hospitalizations, morbidity, and mortality. Successful interventional therapies have significantly improved the outcome after an acute coronary event (6) and are now a standard of care across the globe.
However, decreased mortality after acute MI has also skewed the patient population to an increased incidence of developing heart failure within both acute and chronic settings (5). Moreover, long-term survival in these patients with established therapies has not improved over the course of the last decade, and heart failure may even have slightly worsened according to a recent study (7). These factors underpin the importance of discovering new therapeutic drugs that complement current post-MI pharmacological treatment with a potential to improve left ventricular (LV) dilation, ventricular remodeling, and as a result, better long-term functional outcome (8).
Inflammation plays a central role in the evolution of pathological events after acute MI (9). Neutrophils followed by monocytes are recruited to the infarcted myocardium and deploy their inflammatory and proteolytic contents, including the enzyme myeloperoxidase (MPO), in the extracellular tissue environment (10). MPO, a highly abundant enzyme in neutrophils and inflammatory lymphocyte antigen 6C (Ly-6C)high monocytes (11), is capable of inducing tissue oxidative damage (12). In addition to its role in various stages of atherosclerotic plaque formation, MPO is linked with continuous activation and recruitment of leukocytes to infarcted tissue (13), further potentiating the downstream inflammatory cascade. At the same time, its oxidized products (hypochlorite) activate proteolytic enzymes (14) and break down extracellular matrix with resultant adverse ventricular remodeling.
Indeed, studies involving MPO knock out mice (MPO−/−) indicate that both the direct cytotoxic aldehyde products generated by MPO-mediated reactions (15) and leukocyte recruitment and proteolysis (13) are involved in adverse outcome after acute MI and heart ischemia reperfusion injury (IRI). As such MPO has been advocated as a prognostic and risk stratification marker in cardiovascular diseases (16). MPO plasma levels strongly predict coronary disease prevalence (17) associated with adverse outcome (18) and need of revascularization (19). These data also signify MPO as a potentially important therapeutic target (8). Thus, drugs that target MPO may help ameliorate degree of inflammation, oxidative damage, and ventricular remodeling after acute MI.
In this study, we investigated a novel MPO inhibitor, PF-1355 (2-[6-(2,5-dimethoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl]acetamide), in mouse models of MI and IRI. PF-1355 is a highly selective, mechanism-based, orally administered MPO inhibitor, which has been shown to be efficacious in a murine model of vasculitis with reduced disease severity, edema, neutrophil accumulation, and inflammation (20). PF-1355 is structurally related to a clinical candidate MPO inhibitor currently under development (21). We hypothesized that successful MPO inhibition with PF-1355 would result in decreased leukocyte recruitment and improved LV remodeling and function, and would provide insight to potential clinical applications leading to facilitate translation of this class of MPO inhibitors for cardiovascular diseases.
Methods detailing animal models, cardiac magnetic resonance (CMR) imaging, echocardiography, MPO enzymatic activity assays, histology, flow cytometry, and statistical analysis are provided in the Supplemental Appendix.
PF-1355 inhibits human and mouse MPO in vitro and ex vivo
We first tested the inhibitory potential of PF-1355 against purified human MPO and found the half-maximal inhibitory concentration of PF-1355 to be 0.56 μmol/l for MPO peroxidation activity (Supplemental Figure 1A). We then tested on mouse MPO extracted from MI and compared it with an intrinsic control without the drug. More than 80% of MPO control activity was reduced with a dose as little as 0.61 μmol/l (Supplemental Figure 1B). Mouse MPO obtained from bone marrow neutrophils was also inhibited with the similar potency (Supplemental Figure 1C).
Next, we determined the therapeutic efficacy of PF-1355 under biologically relevant conditions. For this purpose, mice received 50 mg/kg PF-1355 orally starting within 1 h post-surgery for 2 days, and hearts were processed to extract protein from extracellular fraction (ECF) and intracellular fraction (ICF) of the infarct tissue, as described previously (22). MPO activity was significantly reduced in both ECF and ICF as compared with vehicle-treated control subjects (p = 0.04 and p = 0.006, respectively) (Figure 1A). ECF MPO is important, as it is implicated in oxidative stress, host tissue damage (23,24), and neutrophilic extracellular trap formation (25). ICF MPO (lysosomal or intragranular MPO) was also inhibited, indicating that the agent may enter inflammatory cells. Note that the infarct fractions of vehicle-treated mice had similar MPO activity when compared with untreated infarcts (Supplemental Figure 1D), indicating that the vehicle treatment was inert. Moreover, PF-1355 plasma levels measured in animals with MI on day 2 showed that the average PF-1355 exposure was maintained above 3.1 μM (Supplemental Table 1), which exceeds the half-maximal effective concentration level in LPS-stimulated human blood (20).
PF-1355 inhibits MPO in vivo in mouse MI and IRI
MPO-Gd (bis-5-hydroxytryptamide-diethylenetriaminepentaacetate-gadolinium) is an activatable magnetic resonance imaging agent for reporting extracellular MPO activity (26,27). It has been validated for noninvasive MPO-specific imaging in MI and was shown to be able to follow therapeutic response to atorvastatin post-MI (10). To evaluate the effects of PF-1355 in vivo, we performed MPO-Gd magnetic resonance imaging in mice on day 2 after MI (Figure 1B), which corresponds to the acute inflammatory phase known to have high neutrophils and inflammatory monocyte numbers (10). As expected, the imaging metric lesion activation ratio (LAR) was elevated in the infarcted tissue. LAR reflects the amount of imaging agent activated by MPO over background, and was measured as a ratio of delayed enhancement at 60 min over nonspecific early enhancement at 15 min, as described previously (27). In the treated group, the LAR significantly decreased (p = 0.0003) (Figure 1C). In addition, absolute contrast to noise ratio (CNR) at 60 min was also reduced in the treated group (p = 0.04) (Figures 1C and 1D). These results were similar to the ex vivo ECF MPO inhibition with PF-1355 and confirmed the in vivo drug efficacy noninvasively. MPO-positive infarct areas were not significantly different between the two groups (p = 0.22) (Figures 1B and 1E).
To validate in vivo MPO inhibition by PF-1355 in reperfusion injury, mice were subjected to transient coronary ligation and then treated for 2 days until MPO-Gd imaging (n = 5 to 8/group) (Supplemental Figure 2A). Both LAR and absolute CNR at 60 min were decreased significantly in the treated groups compared with the vehicle-treated control subjects (p = 0.045 and p = 0.01, respectively) (Supplemental Figure 2B). MPO-positive infarct areas were again found to be similar in both groups (p = 0.6) (Supplemental Figure 2C). These results confirmed successful in vivo MPO inhibition after IRI by PF-1355. Moreover, when CNR values were plotted as a function of time course, we observed decreased enhancement at all time points in treated groups compared with vehicle control subjects, again confirming that PF-1355 decreased imaging agent activation and retention (Supplemental Figure 2D).
PF-1355 reduces inflammation at 7 days post-MI
To investigate the effects of PF-1355 on leukocyte recruitment and early infarct healing, immunoreactive staining was performed on heart infarcts harvested on day 7 and compared with vehicle-treated control subjects (n = 5/group). We found a significant decrease in MPO and CD11b-positive areas within infarcts in the treated group compared with the vehicle control subjects (p = 0.02 and p = 0.04, respectively) (Figure 2A). However, CD31 (angiogenesis) and collagen I−positive areas were not different between the groups (p > 0.05) (Figure 2B). To investigate the effect of PF-1355 on early myocardial remodeling on day 7, we measured myocardial thickness at the level of the midventricular slice containing infarct. Interestingly, infarcted walls were thicker in the treated mice as early as day 7 (p = 0.02) (Figure 2C).
Flow cytometry analysis of infarct tissue leukocytes from mice treated for 7 days revealed a trend toward moderately decreased neutrophils (relative to total leukocytes) compared with vehicle control subjects (p = 0.1) (Figure 2D). Interestingly, inflammatory Ly-6Chigh monocytes were significantly decreased in the treated group (p = 0.04) (Figure 2D). However, Ly-6Clow monocytes were not affected by the drug treatment (p = 0.14), indicating that PF-1355 acts through a decrease in recruitment of inflammatory Ly-6Chigh monocytes, but numbers of reparative Ly-6Clow monocytes were maintained or perhaps even increased.
MPO-positive myeloid cells are present in infarcts beyond day 7, during late infarct remodeling
Neutrophils followed by inflammatory Ly-6Chigh monocytes are the main source of MPO after infarction (10). Their numbers peak during the initial pro-inflammatory phase of infarct healing (from days 1 to 3) and start to decline afterwards (28). However, continuous MPO exposure and resultant cytotoxic aldehyde products potentially mediate long-term deleterious effects on ventricular remodeling, even during chronic healing phase (15). Therefore, we also evaluated if there were increased MPO and inflammatory cell subsets during the later phase of infarct remodeling (days 14 to 15) and compared with noninfarcted hearts. On histology, we found significantly more MPO-positive cells on both days 7 and 14, although there were approximately 45% less on day 14 compared with day 7 (p < 0.05) (Figures 3A and 3B). Similar results were observed for CD11b staining (p < 0.05) (Figures 3A and 3B).
On flow cytometry, significantly higher CD11b+ myeloid cell numbers were observed in the infarcted hearts on day 7 (p < 0.01) (Figure 3C). Interestingly, myeloid cells were still elevated on day 15 (neutrophils ∼4× and Ly6Chigh monocytes ∼3.5× elevated; p < 0.01 and p < 0.05, respectively) (Figure 3C) compared with noninfarcted hearts. Consistent with tissue repair, higher numbers of macrophages (p < 0.01) and Ly-6Clow monocytes (p < 0.05) were detected on day 15 (Supplemental Figure 3A). These results were corroborated by detection of increased neutrophils and Ly-6Chigh and Ly-6Clow monocytes in the blood of infarcted mice (p < 0.05, p = NS, and p < 0.05, respectively) (Supplemental Figure 3B).
Taken together, elevated neutrophils and Ly-6Chigh monocytes on flow cytometry combined with positive staining for MPO on histology indicated a continuous presence of MPO in the infarcted heart through days 14 to 15 (although less pronounced than on day 7). Concurrently, repair and healing had also been initiated, as evidenced by increased macrophages and Ly-6Clow cells.
Prolonged PF-1355 therapy improves cardiac function and remodeling
Oxidized products of MPO-catalyzed reactions have previously been implicated in late infarct remodeling observed on day 21 in mouse models of MI and IRI (13,15). Given our data that infarcted myocardium is continually exposed to MPO beyond the first week, we decided to investigate whether PF-1355 therapy should also be continued during the late remodeling phase. For this purpose, we divided infarcted mice into 2 treatment cohorts. In the first cohort, we treated mice for 7 days (early healing phase; n = 8) and then stopped treatment until day 21 to see whether this short treatment trial during the proinflammatory phase would benefit remodeling (Figures 4A and 4B). Indeed, we found significant improvement in end-diastolic volume (EDV) compared with untreated mice with MI (p < 0.05) (Figure 4E). However, we did not see significant differences in ejection fraction (EF) (Figure 4D) and LV mass (Figure 4F), although a trend toward improvement was noted between the control and 7-day treatment groups.
In the second cohort, mice were treated for the entire 21 days (n = 5) and compared with untreated mice with MI (Figures 4A and 4C). In contradistinction to the short-term treatment group, these mice not only had decreased EDV (p < 0.001) (Figure 4E), but also improved EF (p < 0.05) (Figure 4D) and LV mass compared with untreated control subjects (p < 0.001) (Figure 4F). Furthermore, when compared with the 7-day treatment cohort only, we observed a significant improvement in EDV and LV mass (p < 0.05) (Figures 4E and 4F), confirming that prolonged treatment is optimal for better structural outcome. Day 2 CMR was also performed to confirm the presence and extent of the infarct, which is shown in the Supplemental Appendix. Representative videos from day 2 and day 21 CMR (Supplemental Video 1) are also included.
Maximum therapeutic benefit is achieved with early treatment initiation
Plasma MPO has been identified as one of the earliest prognostic biomarkers in patients with acute coronary syndrome (18,19). Therefore, we investigated whether the time to initiate treatment has an effect on efficacy compared with vehicle-treated control subjects. PF-1355 treatment was initiated either at 1 h post-MI (early) or 24 h post-MI (delayed), and was then continued for 28 days. Cardiac function was evaluated by echocardiography at baseline and 28 days post-surgery (Figure 5A). At the end of the study, animals in both treatment groups showed better function as measured by improved LVEF, fractional shortening, and stroke volume compared with vehicle-treated MI control subjects (p < 0.0001, p < 0.001, and p < 0.01, respectively) (Figures 5B to 5D). Importantly, the early treatment initiation group showed significantly reduced cardiac remodeling with improved LV end-systolic volume (p < 0.05), whereas the delayed treatment-initiation group did not improve relative to controls (p = NS) (Figure 5E). Functional parameters like fractional shortening and EF were also significantly better with early compared with delayed treatment initiation (p < 0.05) (Figures 5B and 5C). These data indicate that the maximal therapeutic benefit for an MPO inhibitor was realized by initiating treatment as proximal to the event as possible.
In this study, we report that the MPO inhibitor PF-1355 efficiently inhibited human and mouse MPO both in vitro and in vivo in mouse models of MI and IRI. PF-1355 treatment for 7 days decreased myeloid cell recruitment and MPO presence. However, MPO-secreting neutrophils and Ly-6Chigh monocytes remained elevated beyond day 7 in untreated infarcts, and likely continued to promote a proinflammatory and oxidative environment that adversely affected healing. Indeed, prolonged (21+ days) MPO inhibition improved ejection fraction, end-diastolic/systolic volume and LV hypertrophy over short (7 days) treatment. In addition, initiating treatment immediately following MI provided greater therapeutic benefit than initiating treatment 24 h post-MI, consistent with early elevation of MPO in plasma.
Improved diastolic and systolic function with MPO inhibition is associated with a decrease in recruitment of myeloid cells, in particular inflammatory Ly-6Chigh monocytes, as shown by our data on day 7. As they are active during both inflammatory and reparative phases, excessive numbers of Ly-6Chigh monocytes have a detrimental role in the final outcome of infarct healing, and successful therapeutic strategies have been employed against these cells (29–31). Interestingly, when we treated the mice for the first 7 days only (early healing phase) and then stopped treatment until day 21 (reparative/late remodeling phase), there was less beneficial effect. This strongly suggests that MPO has a detrimental role during both early and late stages of infarct evolution. Although it is most abundant during the first week post-MI, we detected continued elevated MPO levels to at least day 15, when there is also evidence for a healing environment (concomitant presence of macrophages and Ly-6Clow monocytes). It is conceivable that during later stages of infarct remodeling, MPO inhibition may favorably tip the balance toward reparative cellular pathways, resulting in better chronic outcome.
When initial infarct areas were measured with magnetic resonance imaging on day 2, we did not observe significant differences between the control and treatment groups, both in MI and IRI. These findings were in line with studies on MPO knock-out mice, which indicated that MPO did not affect initial infarct size at day 3 post-IRI (15). However, MPO had a profound adverse effect on chronic LV remodeling and function that was thought to be mediated by MPO-oxidized aldehydes (15). Moreover, we found that MPO inhibition also decreased the recruitment of pro-inflammatory cells, suggesting another mechanism for MPO inhibition that may work in synergy with oxidative damage protection to improve long-term LV remodeling.
Plasma MPO levels elevate within h in patients with acute coronary syndrome (19) and predict early risk of MI and adverse outcome (18). Also, neutrophils mobilize quickly following ischemic insult, and their numbers already peak at 24 h post-MI (28), with concomitant accumulation of MPO-generated oxidants within the infarct (15). Therefore, early therapy commencement is also important to protect the myocardium from MPO released by infiltrating leukocytes. It is also noteworthy that neutrophils are important orchestrators of post-MI infarct evolution. A dramatic decrease in neutrophils with anti-Ly6G antibody pre-treatment has been shown to impair infarct remodeling, with increased fibrosis and αSMA immunostaining (32). PF-1355 only moderately decreased neutrophil recruitment to infarct at day 7 post-MI. It did not affect neutrophil survival, as blood neutrophils were still similar between groups (p = 0.66) (Supplemental Figure 4A). Concurrently, collagen I and αSMA positive areas on histology were similar between 2 experimental groups (αSMA: p = 0.35) (Supplemental Figures 4B and 4C), indicating that moderate neutrophil decrease did not adversely affect cardiac healing. Another important difference was that in our study, we administered PF-1355 after MI, but in the previous study, the anti-Ly6G antibody was administered 1 day before MI. Although the MPO molecule can attract neutrophils independent of its catalytic activity (33), this effect is not expected to be altered by PF-1355, which is an inhibitor of MPO's enzymatic activity and does not directly affect MPO concentration.
Percutaneous coronary intervention is the standard primary therapy in ST-segment elevation MI. However, sudden restoration of blood supply induces more oxidative stress to the already ischemic myocardium, and incoming leukocytes potentiate injury by releasing their granular contents containing MPO. Importantly, the ability of PF-1355 to inhibit MPO in a reperfusion injury model confers another potentially translatable clinical advantage: it may be used in conjunction with percutaneous coronary intervention and protect against reperfusion injury. Drug efficacy can also be monitored noninvasively with MPO molecular imaging.
In addition to MI, MPO and its oxidized products play an important role in a variety of cardiovascular diseases. During the development of atherosclerosis lesions, MPO confers its deleterious effects by causing endothelial dysfunction (34) and both low- (35) and high-density lipoprotein modification (36,37). It also contributes to vulnerable plaque formation and rupture, and acute thrombosis (12). Clinical studies predict that MPO is associated with both diastolic and systolic dysfunction as well as increased mortality (38,39). Due to these broad-spectrum detrimental effects, MPO has been increasingly considered an important therapeutic target for other cardiovascular diseases as well (40). Whether or not MPO inhibition has a protective role against various stages of atherogenesis is under investigation, and it will be very interesting to see the results of these studies.
Study limitations
It is important to mention that only young adult mice were used in the study. Old age is an important risk factor in cardiovascular diseases, and we do not know yet whether it affects PF-1355 therapy. Future studies utilizing older mice may shed more light upon this.
This study demonstrates that PF-1355 is a highly effective oral inhibitor of MPO enzymatic activity in vitro and in mouse models of MI and IRI. MPO inhibition for 7 days resulted in decreased MPO and CD11b expression, as well as inflammatory Ly-6Chigh monocytes. Because MPO is secreted beyond the early inflammatory phase, continuous MPO inhibition for 21+ days significantly improved ejection fraction, EDV/end-systolic volume, and LV mass on CMR. Our findings also support that MPO inhibitor treatment should be initiated soon after infarction to maximize therapeutic benefit. Upon successful translation, this class of drugs could be of great benefit to patients after an acute coronary event, both with and without percutaneous intervention.
COMPETENCY IN MEDICAL KNOWLEDGE: Due to its important pathophysiological role, MPO has long been advocated as an attractive therapeutic target in cardiovascular diseases. Preclinical evidence in this study indicated that the orally administered drug PF-1355 successfully inhibited MPO activity in mice infarcts. It also resulted in considerable structural and functional heart improvement, particularly when treatment was initiated early and continued during late ventricular remodeling.
TRANSLATIONAL OUTLOOK: Future experimental and translational studies are required to investigate if the pharmacological inhibition of MPO can be combined with angiotensin-converting enzyme inhibitors and/or beta-blockers and whether it improves mortality and the incidence of heart failure.
For an expanded Methods section as well as supplemental figures, a table, and a video, please see the online version of this article.
This work was supported by grants from the National Institutes of Health (R01-NS072167 and R01-NS070835) and a grant from Pfizer. All authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Abbreviations and Acronyms
- contrast to noise ratio
- end-diastolic volume
- ejection fraction
- ischemia reperfusion injury
- lesion activation ratio
- Ly-6C
- lymphocyte antigen 6C
- myocardial infarction
- myeloperoxidase
- myeloperoxidase knock out
- MPO-Gd
- bis-5-hydroxytryptamide-diethylenetriaminepentaacetate-gadolinium
- Received May 11, 2016.
- Revision received September 12, 2016.
- Accepted September 13, 2016.
- The Authors
- ↵
- Sutton M.G.,
- Sharpe N.
- ↵
- ↵
- Gerber Y.,
- Weston S.A.,
- Berardi C.,
- et al.
- ↵
- Velagaleti R.S.,
- Pencina M.J.,
- Murabito J.M.,
- et al.
- ↵
- ↵
- Chen J.,
- Hsieh A.F.-C.,
- Dharmarajan K.,
- Masoudi F.A.,
- Krumholz H.M.
- ↵
- Landmesser U.,
- Wollert K.C.,
- Drexler H.
- ↵
- Swirski F.K.,
- Nahrendorf M.
- ↵
- Nahrendorf M.,
- Sosnovik D.,
- Chen J.W.,
- et al.
- ↵
- ↵
- Nicholls S.J.,
- Hazen S.L.
- ↵
- Askari A.T.,
- Brennan M.L.,
- Zhou X.,
- et al.
- ↵
- Fu X.,
- Kassim S.Y.,
- Parks W.C.,
- Heinecke J.W.
- ↵
- Vasilyev N.,
- Williams T.,
- Brennan M.-L.,
- et al.
- ↵
- Schindhelm R.K.,
- van der Zwan L.P.,
- Teerlink T.,
- Scheffer P.G.
- ↵
- ↵
- Baldus S.,
- Heeschen C.,
- Meinertz T.,
- et al.
- ↵
- ↵
- Zheng W.,
- Warner R.,
- Ruggeri R.,
- et al.
- ↵
- Ruggeri R.B.,
- Buckbinder L.,
- Bagley S.W.,
- et al.
- ↵
- ↵
- Lefkowitz D.L.,
- Moné J.,
- Lefkowitz S.S.
- Klebanoff S.J.
- ↵
- Metzler K.D.,
- Fuchs T.A.,
- Nauseef W.M.,
- et al.
- ↵
- ↵
- Breckwoldt M.O.,
- Chen J.W.,
- Stangenberg L.,
- et al.
- ↵
- Nahrendorf M.,
- Swirski F.K.,
- Aikawa E.,
- et al.
- ↵
- Panizzi P.,
- Swirski F.K.,
- Figueiredo J.L.,
- et al.
- Hilgendorf I.,
- Gerhardt L.M.S.,
- Tan T.C.,
- et al.
- Kobzik L.,
- Swirski F.K.
- ↵
- Horckmans M.,
- Ring L.,
- Duchene J.,
- et al.
- ↵
- Klinke A.,
- Nussbaum C.,
- Kubala L.,
- et al.
- ↵
- Vita J.A.,
- Brennan M.L.,
- Gokce N.,
- et al.
- ↵
- ↵
- Bergt C.,
- Pennathur S.,
- Fu X.,
- et al.
- ↵
- Tang W.H.,
- Tong W.,
- Troughton R.W.,
- et al.
- ↵


text:
Programming competitions always attract programming geeks a lot. tough and tight they are. They test your skills, IQ and patience.
After participating many of such events, it can be concluded that PCs in karachi are good in number and in genaral well managed. As most of the PCs are managed by the students themselves so it is always very appreciable.
Organizers have a very tough responsibility. Apart from financial and other type of management responsibilities selecting the tasks is very critical part. The questions should be logical and should test every type of skills not just practice in programming.
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TechElite @ NED: Not behind in any terms. Organized by the energetic and dedicated students.
ITPromo @ KU: Had some nice features like Question section in which the number of students participating and getting rewarded is bigger.

subset: commoncrawl


text:
Petition against Benjamin Moore's e-store sign now
On Monday, February 1, 2010, Benjamin Moore launched their new e-store to sell Benjamin Moore products online. If you go to their homepage, they give you the option to buy all of your paint and painting supplies, shipped right to your front door. Presently, this site is available to US residents only but it is evident that in the near future it will be available to Canadians too. In fact, if you go to their site, you will see that where you enter your state, it shows a province and postal code option.
Retail stores are outraged by this because for as long as we have been in business, it has been Benjamin Moores promise to protect, support, maintain and respect the independent paint dealers. This has always been a comfort to us with the competition of the big box stores and technologies that have killed many small businesses. Not only did Benjamin Moore tell their retailers frequently about their promise but they also put it in writing on all opening pages of price lists and catalogues. It was titled, Declaration Of Policy and it reads:
To protect the Independent Paint Dealer by maintaining policies that afford opportunities for profit and business growth in a highly competitive market.
To support the efforts of the Independent Paint Dealer to increase paint sales to consumers, painting contractors and industry within the dealers service area.
To maintain product quality, service and price at levels competitively advantageous to the independent Paint Dealer.
To respect the Independent Pain Dealers rightful opportunity to operate without direct selling competition from the supplier.
Today thousands of Independent Paint Dealers selling Benjamin Moore & Co.s products in the United States and Canada know from experience that the companys strict adherence to these policies is the dealers assurance of a business relationship that fosters continuing growth and prosperity.
We havent seen this declaration on our documents in a while. This was a promise made before Benjamin Moore blossomed into the huge multi-million dollar company it is today. It is because of its thousands of independent paint dealers who have worked hard to give Benjamin Moore its prestigious reputation. Was this declaration of policy made just to appease the retailers mind for the time being? Now that Benjamin Moore made it where they are today and no longer need us, does the declaration no longer stand? We feel used, not protected, not supported and not respected to say the least.
We like your idea of a website to compliment our stores with great advice, ideas and product information. Wed love for you to do what you did in the past, which was to direct those customers from your site to our friendly, helpful and personalized retail stores.
We, the undersigned, call on Benjamin Moore Paints to refrain from becoming our competition and selling their products online. We have spent years selling and building your reputation and business, we refuse to let you kill ours. We have proven to be determined, dedicated individuals who have been successful. We will use this determination to make sure that Benjamin Moore does not continue to sell their products online.
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I support this petition
05 October 2015186. Bob A
According to Mr. Abrams, I have been successfully selling Benjamin Moore Paint to 4\% of the population. I am therefore, taking on two additional product lines in order to sell to the remaining 96\% of the population that can't afford Benjamin Moore Paint
29 September 2015185. Andrea B
I support this petition
09 September 2015184. Tom M
I support this petition
03 September 2015183. Thomas Addisonj
Independent Benjamin Moore dealers have a lot of skin in the game. Weve committed vast sums of time, energy and resources to selling and promoting the Benjamin Moore brand. For all our efforts which include investing in the Gennex platform and related inv
28 August 2015182. Rick C
I feel betrayed by the company who vowed to protec me against other competition that could hurt my business Business name Supreme Paint City & Province/State Redondo Beach, California Phone number 310-540-4456
29 July 2015181. A Hendrix
disgusting Business name a City & Province/State a Phone number a
24 July 2015180. Lee Annh
If Benjamin Moore wants to enter the online shopping world, then why don't they take that lovely web site that they want all of us to have and add an online store function so each dealer can sell paint online and keep the sales where they belong in our ha
11 July 2015179. Erik Y
Leave the retailing to us. If you want to do e-commerce, only make it available to people that don't live near an independent retailer. This is what Mythic Paint does. Business name Ace Hardware Weaverville City & Province/State Weaverville, NC Phone
10 July 2015178. Bill E
We do not allow certain employees from BM back into our store after we were treated with so little respect. We added another line of paint, PL three years ago. It was easy to sell. Business name Upstate Color Center City & Province/State Easley, SC P
02 July 2015177. Steve B
a take over of our independents Business name Paint Mart Inc City & Province/State MA
01 July 2015176. Tony C
I support this petition
20 June 2015175. Chris B
I support this petition
14 June 2015174. Donald P
Stand by your promise. Business name Bryant Tire & Appliance, Inc. City & Province/State Bartlett, TN Phone number (901)229-0545
Raul CooperBy:
Justice, rights and public orderIn:
Petition target:
Benjamin Moore & company
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text:
Oh my gosh, where can I start with my complaining about not having enough time to get everything done? I'm not gonna do it because I know that you all are in the same exact situation. It is what it is and we just deal with it the best we can. Its been so long since I have posted a blog that 'Blogger' has changed. The other day I had one of my customers/readers get on to me for not blogging enough and all I can say is that I totally agree. I finally got something finished yesterday. This frame has been sitting in our spare bedroom for a month or so but it had no fork, so yesterday I finally got it sprayed. The frame looks good and the fork looks good however I'm not so sure that they go good together. I mean its not bad but i'm not sure that they meld. I was gonna put a steel fork on this frame but then decide to put a carbon fork on to shave some weight and make it more raceworthy, racers tend to like lighter if you know what I mean. I tell you what, if you want a steel fork to go with this frame I can build it. Agreed. I also have another frame over at Paul's getting sprayed, hopefully this week, for Andy D. Thats actually the last frame I finished building and will be the last that I build until after the Texas Handmade Show thats coming up at the end of the month in Dallas. The 27th and 28th if you want to go. I have to get at least two more frames painted for the show and that is my priority between now and then. The weather is changing, a lot of rain and a little cooler and since I don't have a controlled climate painting booth that presents a problem for me. It has to be above 65 degrees and thats just to paint carbon, since steel is always about 10 degrees cooler than the temperature outside you need it closer to 75 to be painting steel and next week has a couple of days around that area and I just happen to be off. wish me luck. Anyway, luckily Ace said he would help me out even while he's working on his house. I've been priming everything so all he has to do is spray the base and the clear. He's saving me. The forecast shows a few warm days in the week ahead so I'm planning on knocking one or two out. Oh yeah, I just remembered that I also have to get Yancey's backup frame painted, thats three. Oh well, I went to church this morning and the preacher said that God has a plan for me already made out so hopefully I can ask you to just roll with me. Thanks.
Oh no, more of these shots!. Yeah, you know it. Hey, I'm an amatuer photographer and there is only so many areas/angles to shoot on a bicycle you know, unless someone is riding the bicycle and then the possibilities are endless. Cross season has arrived and I have some frames rolling around the courses in all four corners, so send me some pictures of you riding and racing and give me something to blog. I'd appreciate it.
I painted the brake bridge to contrast. Did I really need to tell you that? No, but I'm trying to make up for my lack of writing.
Jen-u-whine carbonified fiber chainstay 'slaption protector.' Ok, I'm inventing words now.
This is what threw me off. Enve's logo is just too cool to paint over so in an effort to let the world see it I left it unpainted. The black of the carbon fiber is not exactly the same color black as the MEECH logo so thats where I feel like they don't totally meld. However you know where they do meld? This frame and fork are built for one another and will roll beautifully with one another so these two shades of black are just gonna have to get along. Its all about the ride.
Overall I was pretty pleased with this paint job however I did have a couple of spots of overspray and this is one of them. Just when you think you have everything taped off frome even one paint particle getting through you peel all the paper and tape off to find that you left a small opening and you're gonna pay the toll. Its not gonna slow it down one bit. Black on yellow is a tough one and doesn't allow much room for error.
Not an exact match but it will work. Throw a white stem on it, perhaps a different colored saddle, some bar tape, maybe some wheels that have some white on them, one white spoke would be really cool, come on, use your imagination and you'd be surprised how good this frameset will look.
MEECH, handmade in Mountain Home, Arkansas. Come visit!
I think Dizzy may have outgrown his bed, it doesn't matter though because he's always sleeping in ours. He jacks the covers all up. Half the time I'm freezing with the corner of a sheet while he has the blankets, pillows, and all. Then he wakes up all fired up ready to go run. Dizzy consumes a little more time than I imagined but he's worth it, we love him.
Thanks for checking things out and I will try to be posting a little more frequently. Chao amigos, love ya!


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. . .FAME, I'm gonna live forever, I'm gonna learn how to fly FAME. . .
The song echoed in her mind as she sat down in front of the camera, as he pushed the record button.
He asked her The Question, "So what are you thinking?"
She didn't know how to respond, so she fidgeted, got flustered.
He asked her another question, "Do you really want to do this?"
She shook her head and mumbled a weak, "yeah". The word had no staying power, no passion behind it. But she could still hear the theme song from FAME in her head. She knew this was right even if she was scared enough to shit her pants.
She was also hearing something else below the FAME theme song. She was hearing her heart beat, her soul stir. "Yeah", she said, louder, stronger, more assured, "I really want to do this."
"You really want to know what I'm thinking? REALLY? I'm thinking you're an ass and no I'm not having your baby. I've already scheduled the appointment for an abortion. Oh and thanks for the Chlamydia. I gave it back to you right before I started my medication. The only thing you have left in the house is the camera recording this, as soon as you come out of shock, turn it off, pack it up and walk out the door."
She stood up, brushing past him and went into the bedroom, closing and locking the door. She knew he could kick it down if he really wanted. She hoped he didn't really want to.
She heard the soft, pouophh of the closing of the apartment door. Was he really gone? Did she dare step out of the room? Dammit she really hated wall to wall carpeting. Next week it was all getting ripped out, just like this child inside her tomorrow.
She had done it again, referred to it as a child. She wondered if she was getting cold feet. Wondered if maybe she really wanted to have a child, raise a child, love a child. Oh yeah they grow up. A child wasn't like the baby dolls she got when she was young. No, they grow up. You have to be responsible. You can't just leave them at your friends house. Plus they cry, a lot, all night sometimes. And if she kept it, HE would be around. He would be back and she never wanted to see him again.
After, waiting in the room for what seemed like hours, she slowly, carefully opened the bedroom door. She didn't see him, couldn't see him, all the lights were off. The glow from the full moon only partially illuminated the space. He could be hiding around any corner though, so she moved cautiously towards the light switch on the far wall.
Making it across the room and touching the cold plaster wall, she caught a reflection of the moon in the leaded glass vase to her right. It shimmered. She shivered and touched the switch.
The room was now bathed in soft flattering light when she noticed the DVD case on the console.
He left. He left her. She told him to leave and he left.
She thought about the door and ran towards it, to secure the slide bolt and engage the locks. The locksmith only changed one lock and hoped it was enough.
"Should I watch the DVD?", she questioned the empty apartment, padding towards the living room. "Yeah," she said again with conviction.
She grabbed the jewel case and located the remote. After pressing all the required buttons, she saw herself, heard her voice.
"God why didn't I put on any makeup? I look like a drug addict, dark circles under my eyes, sunken cheeks," she said to an empty room. No one answered. She was alone and the theme from FAME still echoed in her head along with her heartbeat.
Maybe, just maybe she'd finally hear her heart song.
Monday, April 13, 2009
Heart Beats, Soul Stirs | Fiction
Posted by Minna
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'Gaslighting is a form of manipulation that seeks to sow seeds of doubt in a targeted individual or in members of a targeted group, hoping to make them question their own memory, perception, and sanity. Using persistent denial, misdirection, contradiction, and lying, it attempts to destabilise the target and delegitimise the target's belief.'
As Aspies, I'm sure we're particularly prone to this. I know I am. My experience, too - with a sister-in-law who's a consummate narcissist - has caused me much grief and upset over the last 30 years. These were years when I not only didn't know that I was autistic, but I also didn't really know what her motivations were. I've found out so much more about it all since my diagnosis, and through having someone else who knows her tell me that she isn't just like it with me. For most of those years, I simply thought there was something wrong with me - and she was the one who, more than most, was at pains to keep reminding me. The damage this woman has done - not just to me, but to other members of my close family - is profound. Much of it is irreparable. But at least now I no longer have any reason to have any contact with her - notwithstanding the fact that she's married to my brother. I'm well rid of her. She's controlled and manipulated our family for far too long. My brother is her puppet. And so competent a puppeteer is she that he doesn't even realise he has strings! He's well and truly Stockholmed!
For years, I've been told I'm gullible, susceptible, credulous, naive, etc. I've had my leg pulled time after time, and been the butt-end of jokes. I've been taken for a ride, scammed, made to look ridiculous. But I take people at face value. If they tell me something, I tend to believe them. Why wouldn't I? Why would they lie to me? But people have, and do. It's why I detest gossip and won't have any part of it, because all it really is is manipulation and destabilisation, perpetuated by a group. Victimising the vulnerable. And it gives people a sense of 'belonging' to be onside in the gossip. If you're not happy with the way someone's behaving or performing - tell them! But no. Gossip is easier... and it's more fun. Huh!
Anyone else got any 'gaslight' tales to share?
Yes I have experienced this a lot in my life Tom.
I recall the first time I was conned at work when I was only maybe 20 years old. Someone I considered a friend persuaded a female working in the same organisation to pretend to be interested in meeting me for lunch in a local pub. It was a joke and of course I sat in the pub for half an hour and nobody showed up. When I returned to work he was all smiles and eventually confessed to the con. I have never forgotten the humiliation I felt and it affected my confidence significantly for many years.
I have experienced people approach me and tell me lies (gossip) to see if I would fall for the con and then be humiliated when the subject of the gossip was told I had believed the lie and came face to face with me to make it clear they knew what I had falsely believed.
Another incident occurred after I ended a relationship with a woman who persuaded me to go over for dinner and stay the night "for one last time" I declined but she was so persistent I eventually gave in. A few weeks later she called to tell me she was pregnant.
I believed her at the time but now realise it was in fact a lie to hurt me for ending our relationship.
One of the reasons I shy away from trying to socialise to this day.
Take care, Laddie.
I did an internet search on gaslighting and the answer is yes. I have had long term dealings with a gaslighter , who also happens to be a narcissist. And finally finishing with her was a great relief. ( She found a job abroad).
I haven't got time to go into details at this moment. But the experience could fill a book. Avoid getting involved with one.
Me too. Even at work, with people I feel reasonably confident around, I'm still wary. One woman in particular, who seems to like me and accept me for who I am, is quite a vindictive gossip. If she's got the knives out for someone, they go in. She took an instant dislike to another chap who started at the same time as I did. Yes, he was arrogant and a bit bullying in his manner - but I could get along with him. I thought he needed to grow up, and maybe ought to have the chance to. She whipped up all sorts of stuff against him, though. Eventually, last week, he was sacked. I'll admit I don't miss him - but I'm now much more wary around her.
Last week, our new manager got us together in a group and told us all - making it quite clear that 'this doesn't apply to most of you' - that we shouldn't be using mobile phones whilst working with clients. Fair enough - and I'm glad she said it and got it out in the open. It's been a bone of contention with me ever since I started there. And I certainly didn't feel it was directed at me, because I never use my phone at work.
Afterwards, I spoke to this colleague about it - and she was indignant. 'I don't think she should have generalised like that.' I pointed out that she actually hadn't generalised. She'd told all of us so that everyone knew, and she'd done it in a way that wasn't pointing a finger. 'No," she insisted. 'She did it wrong. She should just call people in the office individually and tell them - not generalise it and accuse everyone.'
I decided not to pursue it. If I'd been the manager, I'd have done the same. My colleague's now got a 'thing' about the manager - who really is a decent person and good at her job - so I wonder how long it will be before negativity will be building up against her. And how long before I start getting regarded as some sort of toady.
My experiences have filled a book! Yes... avoid at all costs. The only way to deal with a toxic person is to walk away and stop feeding them.
I see there is an article in the Guardian today about the equal pay row at the BBC where gaslighting is mentioned.
As has been pointed out to me previously when I joined this forum I suffered emotional deprivation as a child. I think this has made me a very needy person and so I sought a cure for this deprivation from other women as it was not available from my mother. I think this could have relevance to my naivity and gullability in later life. Constantly seeking love and affection missing from my childhood.
That would also explain why some people think I have behaved in a mysogenistic way towards women. My neediness making me too demanding in relationships with women. I may be wrong but it does seem to explain a lot. Is this gaslighting on my part?
Take care, Laddie
I'm not sure, Laddie. I mean, would you say your behaviour was deliberately manipulative and deceitful?
I've been accused of being abusive in a relationship - emotional and verbal abuse - but (without wishing to let myself off the hook over it - it isn't something I'm proud of) largely it's been in reaction to the behaviour of the other. My last partner definitely had narcissistic tendencies. She controlled most situations to her own advantage. And, at the end, she refused to accept that my outrages were in any way connected to her behaviour. Definitely a narcissistic trait.
I think, actually, there are crossovers with narcissistic behaviour and autistic behaviour. Obviously, though, the motivations are different.
No I would not say my behaviour was deliberately manipulative but I am also not sure if it wasn't deceitful at times. I was easily led astray and cheated once or twice when I should not have. I guess that's back to being too needy in relationships and hoping the grass is greener on the other side of the fence and not resisting the temptation to find out. But I have always confused sex with love anyway.
I have never been physically abusive with women but may have been derogatory with some of my comments.
I definitely have narcissistic traits. I seldom put others before myself but I never realised it at the time.
My ex wife did lose her temper with me once and physically attacked me. I think she was frustrated by my lack of empathy and that boiled over into violence. I think she knew from very early on I was autistic (she was a trained special needs teacher) and felt her efforts to "cure" me were not being appreciated.
So no I am fairly sure nothing in my behaviour has been deliberate.
Take care , Laddie
laddie49 said:But I have always confused sex with love anyway.
Me, too.
laddie49 said:I seldom put others before myself but I never realised it at the time.
Ah... I think this is the difference. A narcissist would realise it. They know precisely what they're doing.
Oh yes. As you know, I was in a 7 year relationship with a narcissist, so I have plenty of stories of gaslighting that I could tell.
But my recovery from that relationship, made me realise that the whole of society is gaslighting us and the manifestation of the relationship was simply a culmination of the whole of my life. I think this is why we're more susceptible to it, in its extreme form. Because we have been subjected to a less visibly extreme form of it all our lives, so we have built up a tolerance to it, were more accepting of it, it's seems more normal to us, because it is more normal to us.
When I did the recovery program, it was the beginning of me finding out who I was. I started the program just before Christmas in 2012, and it lead me on a remarkable journey of discovery, of who I was.
The first step was to take 100% responsibility for the relationship I was in, regardless of what part he played. When I was able to do that, I was able to take responsibility for the rest of my life. Which lead me to the discovery of autism, the discovery of who I was. I then found the freedom I had been searching for all my life, only to find that that doesn't exist either. Not in its purest sense. But by taking full responsibility, we are rewarded with as much freedom as we are ever going to have.
Meaning, we are all connected, we are all individual aspects of the one whole, so what I do to you, I do to me and visa versa. Whatever we do or don't do we have an effect on other people so our freedom comes in knowing who we are, that we are the creators of our lives and we use what we have and who we are, for the benefit of all. Which sounds like a tall order but it's easy when you know how.
And no, I don't gossip either. When I worked at a hotel bar when I lived in the Lake District. I noticed that the staff didn't come and talk to me like they did each other. Then I found out it was because they were gossiping, and knew I wouldn't join in.


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Selling your home for the first time can seem daunting. The market looks complex and you've probably heard horror stories about unqualified buyers, unsold homes and nightmare real estate agents who don't have your best interests at heart.
So, when it's time to sell your home you'll need sound advice and the right guidance so that you don't end up with your own bad story to tell. Keep in mind we are not just talking about financials. Selling your home can be an emotional time because of the deep sense of attachment to it. Chances are you've celebrated holidays and entertained friends and family and created great memories within its four walls.
So we've put together some advice that will help you confidently go forward with the sale of your home. Consider the following:
Change Your Perspective
Changing your perspective about your home is very important and should start to happen as soon as the decision is made to sell. Despite the emotional attachment you may have to your home, the distancing process has to begin because your home is now a financial asset. It's become something to be marketed to others. As hard as it is, try to put aside your emotions and concentrate your energy on selling your property. It helps to remind yourself that you will be moving somewhere else, to an even better place that you can call home.
The Price Has to Be Right
Pricing your home is not something you normally do without enlisting the help of a reputable listing agent. Refrain from choosing your cousin's sister-in-law, for example, who just dabbles in real estate as a side job. You'll fare much better if you select an experienced real estate agent who sells a fair number of listings, preferably in your neighbourhood.
Be Flexible with Showings
Showings are an integral part of selling property so you'll need to be flexible with times.
"If you're finding home showings to be an imposition, consider taking time off or going away on the weekend your home is put on the market."
It's true that it can feel a bit intrusive allowing strangers to walk through and "inspect" your home, but this is the best way to sell your home. Your presence is not needed and it's best to let the buyer tour the home, with the buyer's agent, in peace and quiet.
Find The Right Real Estate Agent
First of all, your home will not sell itself and in order to get the most money from the sale of your home, you'll need to rely on the professionals. Finding the right agent to guide you safely and comfortably is as essential as pricing your home correctly and making sure it's in good showing condition.
Stay Positive and Be Patient
At the end of the day, you cannot control the open market. So if you've taken care of the important elements to prepare your home to sell, try and relax and maintain your home's show-ready condition. If necessary you may need to consider making adjustments to the price or other terms if market conditions and feedback call for it.
But again, your real estate agent will help you understand what is the best course of action. Don't become too distraught if selling your home takes a little longer than you expected. Trust in yourself and your agent and you can be sure your home will sell!
If you're looking to sell your home, don't hesitate to contact us at Rego Realty and we'll help get you started!


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Does the idea of growing your portfolio sound appealing? We've surveyed the real estate investors at Memphis Invest and for most, it does! Real estate investors should be able to have a strategy for future growth and look forward to a flourishing, successful business. That said, there's a danger in growing too quickly. The best way to set yourself up for success in real estate investment is to maximize the efficiency of what you have, whether it's two properties or twenty.
When you have investing in real estate down to a fine art and everything is working as well as it can, then talk about adding more investment properties to the mix.


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Product Description
The RolDri Master Sponge Roller is the superior water removal product. The unit is constructed of stainless steel, including the hardware. The blue roller is constructed of PVA foam for increased durability. The handle and frame are reinforced so there is no wobbling and it makes it easy to push standing water off the surface. The unit also features a hook allowing it to be attached to the fence.


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My mental suffering, in part, is one of my own doing. When I'm at my lowest, I reach to folks I love the most. Often times, over the span of the last decade, I have seen those I love unconditionally have let me down tremendously. A couple of people have apologized for their inadequacies in providing friendship to me and others simply forget about me all together. These have come in the form of former friends and long term lovers. Now I have been asked how I can love someone that brings me down, worst yet, not there when I need them most. The simple answer is, my love for certain people is unwavering. I don't love because I am loved returned. I love because of a series of actions that have transpired over a period of time that opened up my senses to greatness. However, I'm learning slowly, that I can't be responsible for someone choosing to stop loving me based on their personal circumstances, etc. I am, however, responsible for how I allow it to affect me over a certain time period.
I have a best friend or lack thereof, just disappear without so much as a letter. I still love this individual, but I no longer expect a re-emergence in my life. This individual has passed away and I grieve accordingly. I have an old relationship that, unfortunately, I will have to put in this category as well. This is the process of cleaning house for the betterment of me.


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We are able to manufacture a huge range of FEFCO designs in multiple board specifications, offering unrivalled choice, flexibility and quality.READ MORE
Polystyrene is used to package and protect fragile or high value items. Available in various different qualities, being lightweight, able to withstand impact and having a huge design range, it is the perfect protective packaging.READ MORE
We are manufacturers of cut foam designed packaging. From our ranges of both Stratocell and Profile Foam, we are able to fulfil almost any design requirement without the need for expensive tooling charges.READ MORE
Our ability to understand your protective packaging requirements means we are able to design and manufacture multi-layered solutions using combined materials to create the perfect packaging option for your goods.READ MORE


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8/21/1944 - 4/20/2008
Born to Verion C. Day and Sharlie Wade. She is survived by her bothers and sisters, Zane (Gloria) Day, Jolene (Bob) Brouillette, Jay Day, Shona Day, Melanee Hupp, and many nieces and nephews. Preceded in death by her mother and father. She will be missed by all who knew and loved her.


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Shop 201-206, 2/F, Causeway Place, 2-10 Great George Street, Causeway Bay HK
When the craving for dessert hits, look no further than local family run cafe, HeSheEat. Satisfying those with a sweet tooth on both sides of the harbour, HeSheEat was the talk of the town when it first opened in Mong Kok in 2014. Expanding to a second location in Causeway Bay just one year later and extending its menu to include both savoury and sweet delights, HeSheEat continues to surprise and delight.
A chic minimalist haven, HeSheEat was founded by the three Lam brothers, Wai, Ken and Max. Wai is the culinary director, bringing to the table years of experience working in Michelin-starred kitchens including Hong Kong's L'Atelier de Joel Robuchon and 8 ½ Otto e Mezzo Bombana, as well as Melbourne's renowned Vue de Monde. Inspiration from Wai's travels is evident, from the friendly cafe vibe to the complex yet well-balanced flavours in the Western-oriented desserts.
The trendy cafe draws in everyone from university students popping in for a study break, to groups of friends looking for the perfect Instagram shot, with its cute décor and eye-catching presentations. Whether you're seated downstairs near the open cake display or upstairs in the more private alcove, the vibe is buzzy and infectious, crowded with millennials chatting and snapping away.
Often, the subject of their shots is the kitchen's piece de resistance: the salted caramel hotcake, a masterful creation that continues to make the rounds on social media. If you're ordering the signature creation, make sure you arrive hungry – the generous serving resembles a more traditional cake rather than a brunch offering.
Pierce the golden top with your fork so that as you pour over the decadent salted caramel sauce and maple syrup, the flavours soak into the very centre. Scoop it up with a scoop of vanilla ice cream for an icy-hot mouthful.
Other desserts are just as visually captivating, from the delicate blueberry cheesecake paired with a cloud of cheesecake foam, to the yoghurt panna cotta, built like a terrarium inside a glass with layers of mixed fruit, panna cotta and yoghurt sorbet.
While dessert is clearly the main attraction, a well rounded savoury selection makes HeSheEat a worthy stop for breakfast or lunch. The menu features lighter options such as crabmeat and avocado salad, and roasted Angus beef salad as well as guiltier indulgences such as barbecue pork ribs and deep-fried mushrooms sprinkled with parmesan cheese.
Drinks, meanwhile, are a category worth exploring on their own: there's a frothy toffee coffee frappucino, or a chestnut milkshake – served in a mason jar with a straw and a spoon to devour the thick, nutty concoction. If you're a coffee purist, enjoy a latte or espresso and explore the flavours of beans from Guatemala and Brazil.
Whether you're popping by to boost your sugar levels or your Instagram following, HeSheEat is a welcome paradise in the heart of the city's hustle and bustle. Offering something sweet for all, this reputable cafe is without a doubt here to stay.


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Heading off to the Yuma Symposium this weekend to have some fun, meet some people, see some old friends, and get inspired. When I get back I will have lots to share as I was also at a Bob Ebendorf workshop in Tucson last weekend. Hopefully I'll post soon, but my thesis show install is a week from tomorrow, so posting may have to wait!
Thursday, February 25, 2010
This weekend
Posted by Lynette at 8:23 AM
2 comments:
- Lucinda said...
All the best for your thesis show Lynette. I have been quietly following your blog for the past couple of years and really enjoy it! :)
- March 3, 2010 at 4:42 AM
- Lynette said...
Thanks Lucinda! I just checked out your blog, your work is amazing!
- March 3, 2010 at 10:02 AM
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text: On Sunday, I did a half marathon relay with Frank right here in our town. I've been doing the full, half marathon for a few years now but this year I wasn't ready for the 13.1 yet. It was a bit cool in the morning, but the sun was out- thank God, because later in…Read More


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US Marshals have arrested 29-year-old Jonathan Dewayne Viane, the prime suspect in the killing of a 23-year-old woman who was found dead in San Felipe, Zamabales, just over a month ago.
Marshals arrested Viane in the state of Iowa. He is currently being held there, his extradition status at this time is unknown.
Viane and a second cohort, Niño de la Cruz, were both charged with murder before a Zambales regional trial court for the death of Karie Ces Mojica.
De la Cruz was arrested on August 12 by members of the Special Action Force in Metro Manila.
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Chief OECD economist Jean Philippe Cotis wasn't only proferring recommendations to the Federal reserve yesterday. He was also not backward in coming forward with his opinions about future growth in the eurozone. Even if Cotis isn't exactly my favourite economist I feel here he may be a little nearer the truth.
The occasion for M. Cotis' observations was the official press briefing for an interim OECD assessment of the economic situation in Europe, the United States and Japan.
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Welcome to the Lab!
Research in my lab focuses on plant evolutionary biology, spanning population genetics to deep phylogeny. My main interest is in ferns (including Pteridium and Ceratopteris), but students in the lab are also working on flowering plants, including Eriogonum, Populus, Allenrolfea, Betula, and Boechera. The lab uses a wide array of tools, including next-generation genomic sequencing, RNA-seq, Rad-seq (GBS), single-gene Sanger sequencing, microsatellites, and AFLPs.
What Brings You to the Wolf Lab Today?
Latest News
February 2020
Sylvia's paper "Mothers of Pteridology" published in the American Fern Journal
Recent Publications
Marchant DB, EB Sessa, PG Wolf, K Heo, WB Barbazuk, PS Soltis, DE Soltis. 2019. The C-Fern (Ceratopteris richardii) genome: insights into plant genome evolution with the first partial homosporous fern genome assembly. Scientific Reports 9: 18181.
Wolf PG, Rowe CA, Kinosian SP, Der JP, Lockhart PJ, Shepherd LD, McLenachan PA, Thomson JA. 2019. Worldwide relationships in the fern genus Pteridium (bracken) based on nuclear genome markers. American Journal of Botany 106(10): 1365–1376
Rowe CA, PG Wolf, RW Lichvar. 2019. Do genetic differences explain the ability of an alkaline shrub to grow in both uplands and wetlands? Western North American Naturalist: 79: 260–269
Wolf, PG and MS Barker. 2019. Current status and future prospects for fern and lycophyte genomics: introduction to an American Fern Journal special issue. American Fern Journal 109 (3): 177-182


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Small Adventures Make for A Busy Week
This has been a week of small adventures – hilarious, joyful, tiresome, and sad ones. Between taking care of Appentin's infected eye, bucketing water at the house from the well to the standing tank, volunteer cooking day, and a sports day with the kids, it has been both a good and busy week.
After my little weekend getaway to the beach, my week started on Tuesday morning, bathing the babies. Five thirty came early, indeed after a weekend like that. The shenanigans began almost immediately. As I'm trying to get things together from the kitchen to serve breakfast, Augustine and Joshua decide to show me what they did while I was gone – catch a fish from a pond nearby. Not just point to the fish they had put in the large cooking pot in the kitchen, but take it out and really show me. They dropped it, of course, and had a fun time trying to pick the poor thing back up. I thought Joyce had killed it at one point when she tried pinning it down with her foot. Once it was caught and back in the pot, no harm done I suppose, Augustine told me he named it Cori.
Next, I noticed seven year old Appentin's left eye was swollen shut, along with a slight fever, a lump under his throat, and a bad cough. Usually he is a fully energetic kid, running around, wreaking havoc everywhere, but that morning he was barely awake. I took him back to the house, and quickly found out on the walk over, that the poor thing is afraid of anything that moves. With every goat, dog, chicken, or bird that passed by, he shuddered in absolute fear. It was a struggle trying not to laugh too much, which dragging him to the house. Once we got there, I cleaned his eye, fed him one of my egg sandwiches and some pineapple, and walked him back to school. He missed French class, but I don't think he was too heartbroken.
I was then immediately handed a baby. At the school now we have three 8 month old triplets living there and all three of them had some horrible flu, and were being treated for Malaria. The lovely family that had been doing an excellent job of giving them their medicine had gone into Accra for the day, so I was left with the task. I managed to get all three of them to take all of it, and only one threw up on me.
As I'm walking out of the school, I hear "Madame Cori, Madame Cori," coming from above me. Bernard and Evans had been instructed to find a pointer stick for the Class 2 teacher. I was thus enlisted to help them. I walk over to the stone wall in front of the tree just opposite the school yard and see thirteen year old Evans high up in the tree with a kitchen knife in his hand. Why these kids use a machete to cut their shoelaces, but a kitchen knife to cut tree branches down, I just don't know. So I swung myself up over the stone wall and into the tree where I was handed a kitchen knife to start hacking away at branches for a classroom pointer – resourcefulness at its finest. As soon as I swung myself though, I hear shouts of earnest and urgent concern below from the triplets' mother, absolutely horrified to see me climbing up in a tree, apparently. Between fits of laughter, I calmed her down and showed I was okay to help out, and began hacking at tree branches. We managed to get a few from the tree, but they told me to leave behind the largest one I cut, saying "That is big, Madame. That is big for a cane, not a pointer." Oops.
That evening the standing tank that makes the water flow through the taps went dry, again. So Patrick unfortunately sent all the kids to bucket water from the well to the standing tank. We of course helped in this process. Mostly, it was really just the older boys and girls doing the work and the little ones making things difficult for them – dropping buckets, splashing water, getting into arguments. But it was fun. Abednago took it upon himself to lead the team drawing water from the well, while Bernard lead the team on the standing tank, and Arnold the team up the ladder. Remarkably organized, these kids are. We spent a couple hours doing that until night fell and they headed back for dinner. I decided to go with them to help them carry back some things they had gathered from the garage. It was an adventure back to the school. Appentin, who had been afraid of everything two days before, decided he wanted to catch a fish from the pond like his big brother, and almost fell in. The girls decided they wanted me to push them in the wheelbarrow because I drive it so poorly they think it's fun. And six year old Elijah, usually always right close to a volunteer, hand in hand, was off somewhere catching birds and fireflies. We eventually all made it back unscathed for dinner.
The next day was more tiresome. Appentin's eye did not get any better, but worse even, so we decided he should go to the clinic. I elected to take him that morning and went into Kasoa with two of the medical volunteers. Appentin was a trooper with the first four hours, but grew incredibly tired and cranky in the afternoon, naturally. He loved the ride into Kasoa – they rarely get out of the vicinity of the school and house – and we arrived in the queue around 9:15am, where we were shuffled around before we saw the first doctor over two hours later, who we spent about thirty minutes with, waited another hour to see a second doctor, and finally another hour or so walking back and forth from the doctors to the pharmacy trying to get the medicine he needed. I was smart to have brought a coloring book, reading books, and a deck of cards to keep him occupied, though. He was alright until the last when he was just flat asleep in my lap, almost unable to wake up. Ultimately, they just gave him some medicated eye-drops, and an ointment I've had to fight with him four times each day to get in his eye. It's much better now, though!
The Kasoa clinic was impressive to me, though. It was hectic and overwhelmed with the number of people seeking help, but well-run. It seemed like they were giving generic prescriptions and treatment to everyone that came in, but also that they were all doing the best they could. It must have been a peculiar sight for everyone there to see me, a young Oburoni, with a small child. I got the question from everyone, "Is this your son?" To the people it mattered, I explained who he was and what I was doing in Ghana; to others I simply nodded, too tired myself to explain.
That day at the school was also "Volunteer Day." Once a month, the volunteers plan and cook three meals for the kids to eat, to give the cooks a day off and give the kids a little treat of having something new. It was mine and one other volunteer's job to do dessert. We decided to get them one of my favorite snacks: a bunch of bananas and a lot of ground-but paste (essentially peanut butter). It was hilarious giving these kids peanut butter and bananas. The majority of them looked incredibly confused, though delighted. Augustine refused to try it until all his friends said it was good. Kingsley asked for three before he even finished one. Gifty looked horrified when I put one in her hand, apparently grossed out by the texture of it in her hand, and immediately threw it back in the bowl, with a sharp "Madame, no!" All of the kids spent about an hour licking peanut butter from the roof of their mouths, though. I think they enjoyed it.
Friday was a particularly fun day. The kids had holiday off from school so we got to have a fun sports day with them. One volunteer brought with her a large set of mixed field games – badminton, baseball, that game with the Velcro balls and mitts, and a couple others. The family also had balloons to hand out to the kids. And of course, there was plenty of football. It was a fun time. I learned that Christiana and Abigail love to play baseball!
Friday night was peaceful, a good end to the week. I finally earned the trust of one of the newer little ones – Prince, age three. He lives very quietly in the shadow of his twin sister who never stops seeking attention, and his little sisters, the triplets, who need a lot of attention. But I finally got him to play with me some, and later he fell asleep in my arms. I could feel his little heart beating quickly against mine – and there are very few things in this world I love more than that feeling.


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16x20 Canvas
Vibrant Starry Night
About This Event
Please arrive 10-15 minutes early to get uncorked, smocked & in your seat! If you desire more time to unwind, and catch up with your friends, we invite you to arrive up to 30 minutes prior to start time.
We are a BYO, so bring your favorite snacks and drinks, but leave all your nice glassware at home! Finger foods are recommended and remember you are painting most of the time. We provide cups, plates, napkins, and bottle openers. We DO NOT provide ice, eating or serving utensils, so bring them with you.
SEATING REQUESTS: If you're coming with others, but making reservations separately, give us your group's name or point person in the special request box when you reserve online. We'll be sure to seat you together.
LOCATION: We are located in the heart of Richboro, at the corner of Almshouse Road and Second Street Pike. The building was formally known as The Spread Eagle Inn.
CANCELLATION/REFUND POLICY: Please note our policy to cancel applies to individuals in all public and private events.
• If you notify the studio at least 24 hours from your reservation time, studio credit will be issued for you to use towards a future class.
• If you notify the studio 24 hours or less, no refund or credit will be issued.
• If you chose not to show for your reserved class, studio credit will not be issued, and payment will be forfeited.
• Group of 3 or more must cancel 3 days prior with registering party requesting cancellation. Private Event Hosts follow the cancellation policy terms outlined in the Private Event Agreement signed by host.
**If, under unforseeable circumstance, that the class must be cancelled by management, class credit will be issued.
PAYMENT POLICY: Advanced payment online or via phone is required to guarantee your seat.
Age Policy
Ages 7 years old or older for Family or Kids Classes Adult Classes are 21 years and old. Under 21 must be with a responsible adult for all Adult Only Classes.
What to bring
Alcohol Policy
Wine, Beer, mixed drinks welcome (21 years old or older)
- Please bring your own ice
- Cups are provided
Painting Request
Can't make it to this event, but love the artwork? We will notify you the next time we schedule it! Just enter your email below. We will not use this email for any marketing purposes.
Customer Consent to Use Online Credit Card Payment for Purchase
In order to purchase Painting with a Twist products and services online or on your mobile device with a credit card, we need your consent. Your consent permits the charge to your credit card, and prevents disputes and chargebacks without just cause, in addition to mitigating the risk for fraudulent charges. This Painting with a Twist online credit card use consent applies to Painting with a Twist's mobile and online products and services, and all disclosures, notices, receipts, statements, and terms and conditions related to our products and services that you electronically access. You agree to provide us with true, accurate and complete email address and other contact information related to this purchase and your Painting with a Twist online account.
If you notify the studio at least 24 hours or more from your reservation time, Class Credit will be issued for you to use towards a future class. If you notify the studio 24 hours or less, no refund or credit will be issued. If you chose not to show for your reserved class, Class Credit will not be issued, and payment will be forfeited. Group of 3 or more must cancel 3 days prior with registering party requesting cancellation. Private Event Hosts follow the cancellation policy terms outlined in the Private Event Agreement signed by host. Bad Weather: Class will cancel if a weather emergency is declared or we determine the roads to be too unsafe to travel on, otherwise our cancellation policy is as stated above. In the rare case of a class cancelling due to poor weather conditions, Class Credit will be issued to all registered guests to be used towards a future class at our studio. **In rare occasion, if a Class must be cancelled, Class Credit will be issued towards a future class** Late Arrivals: If you arrive 15 minutes or more late you may not be allowed to paint and lose the registration fee. Please arrive no later than 10 minutes before the scheduled class time and we will have a blast!
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At Painting with a Twist, the fun is endless.
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Advertisement | Advertise Here
FRANKLIN TWP — Emergency crews responded to a garage fire around 4:40 p.m. Friday.
The building at 831 West Old Route 422, quickly was fully involved and is a total loss.
A home located near the structure did not catch fire.
The road is shut down from Dick Road to about M& B Truck Repair.
Fire departments from Prospect, Unionville, Portersville, Butler Township and Slippery Rock responded.
Other details were not immediately available.
This is a breaking news article — read a full article about the fire in Sunday's Butler Eagle.


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Small Enterprise Information
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Lately, starting a catering enterprise is all about discovering the fitting niche. Think along the lines of setting up a huge banquet table underneath the shade of a tree on an area farm and providing a improbable out of doors wine & dinner event for as much as, say, one hundred people at a time.
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Postgraduate Specialist in International Relations, Borders and Migrations in Europe
Información general
Nº de créditos: 36 créditos ECTS
Lugar de celebración: Campus de Cádiz
Fechas de celebración: del 11 de marzo al 30 de mayo de 2019
Fecha fin de preinscripción: 11/02/2019
Fecha inicio de matriculación: 19/02/2019
Fecha fin de matriculación: 27/02/2019
Días y horarios: de lunes a viernes, en horario de tarde
Precio de matrícula: 600€ Matrícula reducida: 400 € (Alumnos y egresados UCA, comunidad UCA, alumnos de Universidades socias, personas en situación acreditada de desempleo)
Lengua: 100 % inglés
The University of Cadiz offers this Postgraduate Diploma of 36 ECTS, which is a "Postgraduate Specialist in International Relations, Borders and Migrations in Europe".
This Specialist Diploma is linked to the 'Bilingual Master in International and European Studies: International Relations, EU, Migrations and Human Rights'. These Studies will be launched under the commitment between the University of Cadiz and the European Commission within the Framework of the Jean Monnet Centre of Excellence 'Migration and Human Rights in Europe's External Borders', of the European Commission. The fully-taught Courses in English are the essential part of the Specialist Diploma, completed with a complementary Course on Academic Writing and Presentation Skills in English, and a Final Dissertation before a Jury.
The cross curricular areas of the Specialist Diploma cover issues with great practical incidence, trying to give key knowledge about international relations and the European Union on one hand; and on the other policies on Migrations and Border Control, mainly focused to the european context: Visas, Schengen Area, Asylum Seekers or the Refugee Crisis. This Program was originally designed within the framework of the Jean Monnet Chair on Borders and Migrations (http://catedras.uca.es/jean-monnet).
** To train students with a key knowledge of the International Relations of a globalized and changing world, and the basic features of the European Union.
** To provide students insight into the migration realities, focusing International Borders and Migrations as one of the most controversial aspects of the European internal and external policies.
** Preparation and practical use of English in these subjects, providing the skills to have debates and use proper oral and written expression.
|Nº ECTS
|Introduction to International Relations and the EU
|Academic writing skills in English
|Intelligence ans Security for the XXI Century
|International Environmental Sustainability and the EU
|Expert Teaching in International Relations
|Introduction to International Migrations and Human Rights
|Academic Presentation Skills in English
|Alliens laws, Migration and Asylum in Internat. and European Law
|Foreigners in Europe;- consular and legal Issues
|Expert Teaching in Migrations and Human Rights
|Final Specialist Diploma Essay*
(Trabajo Fin de Título)


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People are having problems getting into the right treatment for their addiction. This is a broad issue that must be addressed if we are going to stem this opiate addiction crisis. People need long-term treatment in order to help them defeat their opiate addiction. There is no other way around it.
Addicts usually cannot recover by themselves. The opium drug chemical is simply far too powerful for anyone to conquer it on their own. Believe me, it has been tried many times and failure is the normal outcome.
As a matter of fact, even those who are receiving top treatment for opiate addiction usually end up relapsing. The stats show us that this is the case. 90% of all heroin addicts who enter rehab end up relapsing during the first week of treatment. That is 9 out of every 10 people!
What Does This Tell Us?
This tells us that treatment and recovery does NOT seem to be working. Something has to be changed in order to improve these numbers. People need to be able to detox, receive treatment and then recovery once and for all. It is difficult, but the first thing we need to do is make treatment more available for more people. No one should be denied from getting treatment.
Many people who have an opioid addiction don't enter treatment. Three-fourths of people who need help don't get it. There are many reasons for this failure. Listen to a group of people who have been dependent on opiates talk about their experiences finding the right help for them.
Its always wise to go straight to the source while investigating different issues and how to deal with them. Concerning Heroin & Opioid addiction, including the current epidemic this country is in…it is best to listen to recovering opiate addicts themselves describe this problem about treatment.
Below are the discussion points that will be covered in this PodCast. We wish to thank Gail Gabbert from "Opiate Support Group" for providing us these helpful & informative PodCasts. Listening to recovering addicts tell their story is the best way for us all to learn about these issues and figure out how to address them. Find the PodCast link below.
Discussion Guide:
- Did you have difficulty accessing treatment for your addiction?
- If you had problems finding the right treatment for you, where did it go wrong?
- Did the stigma about addiction and medication treatment keep you from seeking treatment?
- Was your physician knowledgeable about treatment resources and options?
- When you were ready to get help, was help immediately available or did you have to wait?
Supplemental Reading:
David Heitz, Opioid Addiction Epidemic: Most Users Are Not Getting Help, But Long-Term Recovery Is Their Best Hope, http://blackbearrehab.com/blog/opioid-addiction-epidemic-users-not-getting-help-long-term-recovery-best-hope/
SAMHSA Behavioral Health Treatment Services Locator https://www.findtreatment.samhsa.gov/
⇓ ⇓ (Click The Link Below To Listen To This PodCast) ⇓ ⇓
Having Problems Getting Into Treatment?
Please Share Our Site To Help Others.


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Harper's Bazaar is the worlds oldest fashion magazine. Their motto is 'thinking fashion'; the aim, to use fashion as a starting point to look at the ways it affects other parts of our lives. Picardie described Bazaar's approach as 'thoughtful', a magazine for "the well dressed woman with a well dressed mind."
Picardie believes fashion is about breaking rules. There is a common misconception that we should be following trends and focussing on uniformity but Harper's Bazaar encourages women to be confident in how they dress and in how they think.
Gabrielle Chanel used fashion as a tool to define herself and is the subject of Picardie's latest book 'Coco Chanel, The Legend and The Life'. It's easy to see why she would choose to focus on fashion's leading lady when you delve deeper into the way Chanel; the lady and the brand, perfectly embodies Bazaar's sentiment.
She broke rules by cropping her hair and wearing men's shirts. She took the colour black; commonly associated with mourning and turned it into a symbol of strength. She was the first person to use mens tailoring to give women a sense of sartorial its dignity.
We love Chanel, for the timeless elegance of their pieces. We love Harper's Bazaar for their forward thinking and innovative approach to fashion and what really matters to women.
Picardie, Harper's Bazaar and Chanel herself ultimately share the same ethos – to empower women and to break through boundaries imposed by others and by ourselves. We like to think we fit into that category too…At G&T we encourage our customers to stand outside of the lines and to express themselves in clothes that they love. We want customers to feel inspired, empowered and strong in the clothes they're wearing.
Fashion isn't the be all and end all, but it's a good place to start. In a world where so many things are completely out of our control, expressing ourselves through style is something we can all do.
Virginia Woolf said "clothes change our view of the world and the world's view of us" – remember that next time you're pounding the pavements of Bath's high street. Throw away the rule book, be brave and take risks with what you wear. Chanel did and she always looked fabulous – you will too.


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DW074-5 - Chen Tai Chi Straight Sword 陈氏太极拳小架系列-单剑 2 DVDs
- Availability: In Stock
- Product Code: DW074-5
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Chen Tai Chi Straight Sword 陈氏太极拳小架系列-单剑 2 DVDs
Tai Chi Single Sword is one of the short weapons of Chen Style Tai Chi system. It has 49 movements. Before practicing Tai Chi Straight Sword, you should have good foundation in Tai Chi combining extensive and elegant body form, agile and stable foot method, and with inflexibility and yielding, concealed and appeared, follow-up with sticking and attaching, in addition, the various changes, truly represents the features of Chen Style Tai Chi Sword that operates the sword with the whole body, continuously and roundly, combing hardness and softness, equaling stress the quickness and slowness, changing the crook and the stretch.
Format: DVD
Language: Chinese Mandarin with English Subtitle.


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You can download Summary Annual Report Template in your computer by clicking resolution image in Download by size:. Don't forget to rate and comment if you interest with this wallpaper.
Summary annual report template – Just your hard work won't be sufficient in getting promotion or increments. Your superiors should understand what you are doing. It's based on their reports on you the organization will decide on your future. To evaluate your performance, your superiors needed a work report from you. This demands one to send reports at regular intervals. Sometimes you may find it difficult to send reports on time as it requires a whole lot of time to have it typed and you may have several other tasks to be completed. Here the report templates will come for your aid.
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