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Author Affiliations: Division of General Medicine, Department of Medicine, Beth Israel Deaconess Medical Center (Dr Weinstein), Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital (Drs Sesso, Lee, Rexrode, Cook, Manson, Buring, and Gaziano), and Department of Epidemiology, Harvard School of Public Health (Drs Lee, Manson, and Buring), Boston, Massachusetts.
Physical activity and body mass index (calculated as weight in kilograms divided by height in meters squared) independently alter the risk of coronary heart disease (CHD); however, their combined effect on CHD is not established. Our objective was to study the combined association of physical activity and body mass index on CHD.
Prospective cohort study of 38 987 women free of cardiovascular disease, cancer, and diabetes at baseline in the Women's Health Study, with 10.9 mean years of follow-up. Weight, height, and recreational activities were reported on entry. Body mass index was categorized as normal weight (<25), overweight (25 to <30), and obese (≥30). Active was defined as 1000 kilocalories or more expended on recreational activities weekly. Six joint body weight–physical activity categories were defined. The main outcome measure was the occurrence of incident CHD during follow-up, defined as a cardiovascular event including nonfatal myocardial infarction, coronary artery bypass graft, percutaneous transluminal coronary angioplasty, or CHD death.
A total of 948 cases of incident CHD occurred during follow-up. Higher body mass index and physical inactivity were individual predictors of CHD. In joint analyses, compared with active normal-weight individuals, the multivariate-adjusted hazard ratios (95% confidence intervals) were 1.54 (1.14-2.08) for overweight-active; 1.87 (1.29-2.71) for obese-active; 1.08 (0.84-1.39) for normal weight–inactive; 1.88 (1.46-2.42) for overweight-inactive; and 2.53 (1.94-3.30) for obese-inactive. Increasing levels of walking also resulted in significant reductions in CHD risk for overweight and obese individuals.
The risk of CHD associated with elevated body mass index is considerably reduced by increased physical activity levels. However, the risk is not completely eliminated, reinforcing the importance of being lean and physically active.
Both physical inactivity and obesity are modifiable risk factors that play significant roles in the development of coronary heart disease (CHD) and are thus major public health issues.1- 5 Obesity is recognized as a major public health issue owing to its dramatically rising prevalence and deleterious impact on many chronic diseases including CHD.6 In addition, the majority of Americans are inactive and not meeting the Surgeon General's goal for adequate physical activity.7- 9
There has been recent interest in studying the combined effect of physical activity and body weight on morbidity and mortality.10,11 Previous studies were often limited to secondary analyses.12,13 Some studies demonstrate that physical activity may be more important than body mass index (BMI) (calculated as weight in kilograms divided by height in meters squared) in the context of CHD prevention,14- 17 and others show a greater risk associated with BMI.18
Given the paucity of data and public health implications of distinguishing the impact of physical inactivity and elevated BMI on the risk of CHD, we investigated the combined relationship of total physical activity and walking with BMI to determine if physical activity reduces the adverse impact of elevated BMI (≥25) on CHD risk.
The Women's Health Study (WHS) is a recently completed, randomized, double-blind, clinical trial of low-dose aspirin and vitamin E in the primary prevention of cardiovascular disease (CVD) and cancer.19- 21 A total of 39 876 US female health professionals 45 years or older, reportedly free of CHD, CVD, and cancer, were enrolled and randomized beginning in 1992.22,23 Data were collected on sociodemographics, health habits, and medical history. For the present study, 889 participants were excluded because of missing data on physical activity or BMI or a history of myocardial infarction (MI), coronary artery bypass graft, percutaneous transluminal coronary angioplasty, or stroke, leaving 38 987 baseline subjects.
Body mass index was calculated with baseline self-reported height and weight. In the Nurses' Health Study, a similar cohort, recalled weight had a correlation of 0.96 with directly measured weight and recalled height had a correlation of 0.94, demonstrating high validity.24,25
Women were asked to estimate the average time per week spent during the past year on the following 8 groups of recreational activities: walking and hiking; jogging; running; bicycling; aerobic exercise, aerobic dance and exercise; swimming; tennis, squash, and racquetball; and lower-intensity exercise.12 The number of flights of stairs climbed daily was also reported. Based on the energy cost of each activity, a metabolic equivalent task (MET) score was assigned. One MET is approximately 1 kcal/kg of body weight per hour; thus, energy expenditure in kilocalories per week was estimated by multiplying the MET score by body weight and hours per week. This assessment of physical activity has been shown to be valid and reliable. The test-retest correlation over 2 years in a random sample of nurses was 0.59. Questionnaire estimates compared with 4 past-week physical activity recalls collected the year before the questionnaire was administered had a correlation of 0.79. Questionnaire estimates compared with activity diaries during the same year for 4 separate weeks had a correlation of 0.62.26
After the first 6 and 12 months and annually thereafter, subjects completed follow-up questionnaires that assessed their compliance in taking assigned treatment, potential adverse effects to treatment, risk factors for CHD, and study end points. Incident cases of CHD included MI, coronary artery bypass graft, percutaneous transluminal coronary angioplasty, and CHD death. Myocardial infarction was confirmed according to World Health Organization criteria.27 Coronary artery bypass graft and percutaneous transluminal coronary angioplasty were confirmed by hospital records. All CHD end points were determined by a blinded committee of physicians who deemed that there was convincing evidence of a cardiovascular mechanism from medical documentation, which included death certificates, autopsy reports, and medical records.
All analyses were conducted using SAS version 8 (SAS Institute Inc, Cary, North Carolina) statistical software. Body mass index and physical activity were categorized because we chose not to assume a linear relationship. Using the World Health Organization guidelines, we divided BMI into the following categories: normal weight (<25), overweight (25 to <30), and obese (≥30).28 Physical activity was first categorized as active (≥1000 kcal/wk) or inactive (<1000 kcal/wk), since 1000 kcal/wk approximates the Surgeon General's recommendations for physical activity (30 minutes of moderate-intensity activity for 5 d/wk or 20 minutes of vigorous-intensity activity on 3 d/wk).7- 9 Since kilocalories are determined by weight, we calculated the Spearman correlation coefficient of kilocalories per week and MET-hours per week score, a physical activity variable that is not dependent on weight. Because the correlation was high (0.99; P < .001), we chose to use kilocalories per week to facilitate the interpretation of the results.
Subjects were divided into a 6-group joint physical activity and BMI variable: normal weight–active, normal weight–inactive, overweight-active, overweight-inactive, obese-active, and obese-inactive. We also considered other definitions of total physical activity (in quartiles: <200, 200-599, 600-1499, and ≥1500 kcal/wk); and walking (time spent per week: no walking, <1, 1-1.5, 2-3, and ≥4 h/wk).
Cox proportional hazards models examined the independent association of both BMI and physical activity with CHD. Hazard ratios (HRs) and their 95% confidence intervals (CIs) were calculated using age + treatment– and multivariate-adjusted models. The primary multivariate model adjusted for age, parental history of MI before age 60 years (yes or no), alcohol use (rarely/never, 1-3 drinks/mo, 1-6 drinks/wk, or ≥1 drink/d), smoking status (never, past, or current), hormone therapy use (never, past, or current), dietary factors (saturated fat, fiber, vitamin E, folate, and fruit and vegetable intake calculated from a semiquantitative food frequency questionnaire), and randomized WHS treatments.29 Information on these variables was obtained by self-report at baseline. Though randomized active and placebo treatment assignments were evenly distributed across the groups, we controlled for randomized treatment to ensure that it had no influence on the results.
In secondary analyses, we controlled for the aforementioned covariates plus self-reported hypertension, high cholesterol level, and diabetes, which are likely intermediates in the causal pathway to the development of CHD and may reflect overadjustment. Hypertension was defined as self-reported high blood pressure diagnosed by a physician, self-reported systolic blood pressure of 140 mm Hg or higher, or diastolic blood pressure of 90 mm Hg or higher. In a small unpublished validation study in the WHS, the confirmation rate was 96% for self-reported hypertension. In another study, greater than 90% of WHS participants reporting no hypertension throughout follow-up were confirmed to be normotensive. High cholesterol level was defined as self-reported high cholesterol level diagnosed by a physician, self-reported total cholesterol of 240 mg/dL or greater (to convert to millimoles per liter, multiply by 0.0259), or use of cholesterol-lowering medications. In a recent study of the WHS, the Pearson and Spearman correlation coefficients were 0.54 and 0.57 (P < .001) for self-reported and measured total cholesterol, respectively. Self-reported high cholesterol level was a strong predictor of CVD.30 In validation studies using telephone interviews or supplemental questionnaires, the positive predictive value of diabetes was very high in the WHS (91%).31
Walking analyses adjusted for kilocalories per week on activities other than walking. Categorical variables containing each subgroup were entered into each model to calculate the test of trend. To test for overall effect modification, we tested an interaction term between the continuous BMI and physical activity (kilocalories per week) variables in both age + treatment– and multivariate-adjusted models.
Joint BMI and physical activity variables were entered into age + treatment– and multivariate-adjusted models to study their combined association with incident CHD. The normal-weight (BMI <25), most active (eg, ≥1000 kcal/wk) individuals were always considered the reference group. The assumption of proportional hazards was tested for each model and was not violated. To control for residual confounding due to body weight, interaction terms between BMI and the difference from the mean BMI for each strata were entered into each model. In secondary analyses, we limited analyses to the hard CHD end points, nonfatal and fatal MI. To test for effect modification in each joint analysis, an interaction term between BMI and each physical activity variable was entered into each model. P < .05 was considered statistically significant.
Of the 38 987 women at baseline, 948 developed CHD during 10.9 mean years of follow-up. At baseline, 34% of the women were considered physically active based on the Surgeon General's guidelines.7- 9 Median energy expenditure was 578 kcal/wk, and mean (SD) BMI was 26.0 (5.1). Of the women, 51% were considered normal weight; 31%, overweight; and 18%, obese. The Spearman correlation between MET score and kilocalories per week was 0.99 (P < .001).
Baseline characteristics of the subjects by the 6-category joint physical activity and BMI variable are given in Table 1. Elevated BMI was associated with hypertension, high cholesterol level, and diabetes and inversely associated with hormone therapy use, physical activity, and alcohol use. Inactive women were more likely to be current smokers.
In Table 2, as BMI increased, the risk of CHD increased even after adjusting for potential confounders (P < .001 for trend), with an HR of 1.64 for overweight women and 2.13 for obese women.Subjects who were physically active, as defined by the Surgeon General guidelines,7- 9 had a 31% reduction in risk with an age + treatment–adjusted HR of 0.69. When potential confounders were added, the HR was attenuated but remained significant (HR, 0.82; 95% CI, 0.70-0.96). For total physical activity and walking, there was a significant reduction in CHD risk even after adjusting for potential confounders. In additional analyses, we controlled for BMI in the physical activity models and for physical activity in the BMI models. Small changes in the HRs were found that did not alter the interpretation of the results.
There was no significant overall effect modification of physical activity (kilocalories per week) by BMI (P = .61); thus, BMI and physical activity remained independent predictors. No effect modification of physical activity by BMI status was found (P = .31-.84) in each joint model.
The joint effect of BMI and physical activity on CHD is shown in Figure 1. Compared with the normal weight–active group, CHD risk increased in overweight and obese subjects regardless of physical activity status in the multivariate model. As BMI increased in inactive women, there was an increase in the risk of CHD between each group (P value for normal weight–inactive vs overweight-inactive, <.001; P value for overweight–inactive vs obese-inactive, <.005). Among active women, there was a statistically significant difference between normal-weight women and overweight or obese women (P value for overweight-active vs normal weight–active, .005; P value for obese-active vs normal weight–active, .001); however, there was no statistically significant difference between overweight and obese groups (P = .32).
Hazard ratios of coronary heart disease in the joint body mass index (BMI) (calculated as weight in kilograms divided by height in meters squared) and physical activity model. P = .31 for interaction between the categorical BMI and physical activity variables. Adjusted for age, randomized treatment assignments, parental history of myocardial infarction, alcohol use, smoking, use of hormone therapy, and dietary factors. Ref indicates reference. Error bars represent 95% confidence intervals. * P < .05.
Similarly, when physical activity was delineated into quartiles of overall energy expenditure and jointly analyzed with BMI on CHD risk, increasing physical activity reduced the risk of CHD (Figure 2). As physical activity level increased, the difference in the risk of CHD between BMI strata decreased. Compared with normal-weight women, the HR remained significantly elevated (P < .01) in overweight and obese women irrespective of physical activity level, except for the overweight women who expended more than 1500 kcal/wk. Within each physical activity strata we found significant trends for increasing BMI (P values ranging from <.001 to .01). Within each BMI strata, trends were not significant for increasing physical activity level (P values ranging from .06 to .60).
Hazard ratios of coronary heart disease in the joint body mass index (BMI) and overall physical activity model. P = .84 for interaction between the categorical body mass index (BMI) (calculated as weight in kilograms divided by height in meters squared) and physical activity variables. Adjusted for age, randomized treatment assignments, parental history of myocardial infarction, alcohol use, smoking, use of hormone therapy, and dietary factors. Ref indicates reference. Error bars represent 95% confidence intervals. *P < .05.
In Table 3, increases in walking time reduced the risk of CHD, as did lower BMI levels. Similar to previous analyses, the risk of CHD decreased in each BMI strata as time spent walking increased. The greatest reduction in risk for each weight category occurred between no walking and 1.0 to 1.5 hours of walking per week. Among the overweight and obese, physical activity significantly reduced the risk of CHD; however, HRs remained elevated.
Adjustment for hypertension, high cholesterol level, and diabetes in each model considerably attenuated the risk of CHD; however, the trends across categories remained similar. The risk was reduced by approximately 16% in overweight women and by approximately 35% in obese women. When we excluded subjects with baseline and incident diabetes from our study population, the overall trends remained intact, but the magnitudes of the HRs were weakened by approximately 20% to 40%. Therefore, these 3 intermediate factors accounted for a moderate amount of attenuation of the overall associations of elevated BMI and physical inactivity with CHD and likely explain a modest portion of the mechanism by which overweight, obesity, and physical inactivity may contribute to CHD.
When we considered only nonfatal and fatal MI in the joint analyses, the results were similar but the magnitudes of effect were weakened. During the course of the study, 353 subjects developed MI. The overweight and obese active groups did not yield statistically significant results (P value for overweight-active vs normal weight–active, .27; P value for obese-active vs normal weight–active, .56); however, the pattern in the HRs was the same. The number of active individuals who developed these conditions was small; therefore, the lack of significance may reflect a lack of statistical power.
In this population of middle-aged and older women, both elevated BMI and reduced physical activity individually increased the risk of CHD, as in previous studies.1- 5 When the interrelationship of BMI and physical activity with CHD was evaluated, we found that physical activity attenuated the risk of CHD from elevated BMI (≥25). However, even high levels of physical activity did not eliminate the excess risk of CHD associated with overweight and obesity. Although there was no significant interaction between physical activity and BMI, this study improves our understanding of their interrelationship in the development of CHD.
Limited data are available on the combined relationship of physical activity and BMI, typically assessed as subgroup analyses within studies that were not specifically designed to comprehensively assess the joint effect.12 In an earlier subgroup analysis of the WHS, physical activity level and weight status appeared to have a comparable influence on the risk of CHD.12
Recent studies of the joint association of BMI and physical activity on CVD mortality and incidence are consistent with our findings. Joint studies have shown that fitness significantly reduced CVD mortality regardless of BMI level, suggesting that physical fitness had a greater impact than BMI.13,16,17 One joint study concluded that physical inactivity had a strong independent association with CVD risk; however, obesity was attenuated by risk factors, suggesting that obesity is a modifiable coronary risk factor.16 However, overweight individuals were not differentiated from normal-weight individuals, and the self-reported physical activity data were not as detailed. In this study, physical activity were defined as low (almost or completely inactive), moderate (some activity >4 h/wk) or high (vigorous activity >3 h/wk).
The Women's Ischemia Syndrome Evaluation study, which analyzed the joint relationship of physical fitness and BMI with CVD risk, suggested that obesity is a modifiable risk factor by physical fitness.14 Follow-up extended only 4 years, and only symptomatic individuals were evaluated; therefore, the effect on a healthy population is unclear. Although physical fitness has been used as a proxy for physical activity, it likely reflects a nonmodifiable genetic component, which may influence other protective pathways. Physical activity measures are more practical because they are modifiable, simpler to quantify, and easier to understand by the public, and they can be directly used to formulate public health guidelines. The Nurses' Health Study recently showed that obesity conferred greater risk than physical activity in joint analyses of BMI and physical activity on CHD risk.19 We were able to study high levels of physical activity that could not be evaluated in the Nurses' Health Study.
Our results can be explained by the current understanding of the pathophysiologic processes of CHD. Adipocytes release free fatty acids, interleukins, and cytokines that may have adverse effects on cardiac function by accelerating atherosclerosis and increasing endothelial dysfunction, coagulability, and inflammation.32,33 There is evidence that physical activity improves endothelial function and reduces vascular resistance.34 Physical activity also reduces fibrinogen and platelet aggregation and increases tissue plasminogen activator levels, which likely reduces the risk of thrombosis.34 The mechanism by which physical activity attenuates the negative effect of obesity on CHD remains unclear. We postulate that the beneficial effect of physical activity may directly reduce and combat the ill effect of the prothrombotic factors released by adipocytes.34
Limitations of our study include using self-reported physical activity data restricted to leisure-time physical activity. However, studies have shown that the self-reported physical activity questionnaire used is valid and reliable.26 While occupational physical activity was not reported, female health professionals would be expected to expend relatively little sustained occupational physical activity. Height and weight are limited by self-report, but high correlation with measured values has been demonstrated in a similar cohort.24,25 We did not account for changes in BMI and physical activity over time, which in a similar study of diabetes in the WHS did not affect our risk estimates.10 Weight gain tends to be linear over time; therefore, the difference between the groups is likely to remain constant even though weight may change. In addition, this cohort of female health professionals tends to be healthier than the general population35; however, the underlying biological mechanisms for physical activity and BMI affecting the development of CHD are unlikely to be different from the general population. In addition, the association between physical activity and CHD in normal-weight individuals remains unclear. Although the HRs trended downward with increasing activity levels, our study was underpowered to detect small differences in risk between the normal-weight individuals. As with any observational study, residual confounding is of concern; however, known major confounders have been comprehensively controlled for in our multivariate models. Percutaneous transluminal coronary angioplasty and coronary artery bypass graft may introduce bias, since they may be performed many years before an event would occur. Our analyses of nonfatal and fatal MI yielded similar results; however, they were underpowered. Additional analyses are needed to confirm these results.
In conclusion, both physical activity and BMI play an important role in the development of CHD. We observed that the risk associated with BMI in CHD is reduced considerably by physical activity. This suggests that regular physical activity reduces the risk of CHD in women and that further coronary benefits will accrue from maintaining a healthy weight. Our study strongly supports current physical activity guidelines recommending 30 minutes of moderate activity daily to reduce chronic disease. This level of activity improved CHD risk regardless of baseline BMI. Furthermore, this study suggests that more than 30 minutes of physical activity daily further reduces the risk. Even high quantities of physical activity are unlikely to fully reverse the risk of CHD in overweight and obese women without concurrent weight loss. Regardless of body weight, these data highlight the importance of counseling all women to participate in increasing amounts of regular physical activity and maintaining a healthy weight to reduce the risk of CHD.
Correspondence: Amy R. Weinstein, MD, MPH, Women's Health Center at Healthcare Associates, Beth Israel Deaconess Medical Center, 330 Brookline Ave, Shapiro 1, Atrium Suite, Boston, MA 02215 (firstname.lastname@example.com).
Accepted for Publication: November 5, 2007.
Author Contributions: Dr Weinstein had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Weinstein, Sesso, Lee, Manson, and Gaziano. Acquisition of data: Lee, Buring, and Gaziano. Analysis and interpretation of data: Weinstein, Sesso, Lee, Rexrode, Cook, Manson, and Gaziano. Drafting of the manuscript: Weinstein. Critical revision of the manuscript for important intellectual content: Weinstein, Sesso, Lee, Rexrode, Cook, Manson, Buring, and Gaziano. Statistical analysis: Weinstein, Sesso, Rexrode, Cook, and Gaziano. Obtained funding: Buring and Gaziano. Administrative, technical, and material support: Lee, Rexrode, Manson, Buring, and Gaziano. Study supervision: Sesso, Lee, Manson, and Gaziano.
Financial Disclosure: Dr Sesso has received investigator-initiated research funding as principal investigator from multiple not-for-profit entities including the National Institutes of Health (National Heart, Lung, and Blood Institute [NHLBI]), the American Heart Association, the American Cancer Society, and the California Strawberry Commission and has also received investigator-initiated research funding as principal investigator from for-profit entities including Roche Vitamins Inc (now DSM Pharmaceuticals). Dr Lee has received investigator-initiated research funding and support as principal investigator from the National Institutes of Health (NHLBI and National Cancer Institute [NCI]) and research support as coinvestigator from Dow Corning Corporation and also serves as a consultant to Virgin Life Care and sits on their Scientific Advisory Board. Dr Buring has received investigator-initiated research funding and support as principal investigator from the National Institutes of Health (NHLBI, NCI, and National Institute of Aging [NIA]) and Dow Corning Corporation; research support for pills and/or packaging from Bayer Health Care and the Natural Source Vitamin E Association for the completed Women's Health Study trial; and honoraria from Bayer for speaking engagements in 2005. Dr Gaziano has received investigator-initiated funding from the National Institutes of Health (NCI, NHLBI, NIA, and National Eye Institute) and the Department of Veterans Affairs (Cooperative Studies Program) and nonfederal investigator-initiated funding from McNeil Consumer Products, Amgen, and VeroScience; has received research support in the form of pills and/or packaging from BASF, DMS Pharmaceuticals, and Wyeth Pharmaceuticals; has received honoraria from Bayer and Pfizer for speaking engagements; has served as a consultant for McNeil Consumer Products, Wyeth Pharmaceuticals, and Bayer; and has served as an expert witness for Merck, Nutraquest, and GlaxoSmithKline.
Funding/Support: This work was supported by research grants CA-047988 and HL-080467 from the National Institutes of Health, Bethesda, Maryland.
Additional Contributions: We are grateful for the longstanding dedication and contributions from the 39 876 participants of the Women's Health Study.
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subset: commoncrawl


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BOWIE, Md. - The Curve's winning streak ended at eight Friday night, but not without a fight.
Altoona rallied to tie in the late going, only to see Bowie come right back with a big inning. Even then, however, the Curve had another rally but came up short, 7-5, at Prince George's Stadium.
The eight-game winning streak was the longest of the season and one of the longest in Curve history, falling just two shy of the team record. The club is now at the halfway point of the season and, thanks to the winning streak, has been able to improve its record substantially recently to a more respectable 33-38.
Altoona came back from a 3-0 deficit and pulled even at 3-3 in the seventh inning on an RBI single by Gift Ngoepe. Bowie answered with four runs in its half of the seventh inning off Curve starter Nick Kingham and Nate Baker for a 7-3 lead.
Back-to-back infield singles scored two runs that gave the Baysox a 5-3 lead, then Nolan Reimold drove home a pair with a single for a four-run cushion.
The Curve weren't about to let their winning streak end so easily, though, and threatened in their final two at-bats but couldn't come all the way. Jarek Cunningham's sacrifice fly scored Drew Maggi, and Carlos Paulino singled home Gregory Polanco in the eighth to pull Altoona back within 7-5.
Fact Box
Covering the bases
LEADING OFF: C Tony Sanchez became the 107th former Curve player to reach the major leagues when he was called up to the Pirates on Friday. Sanchez, the No. 4 overall pick in the 2009 draft, played for Altoona the past two years. He was hitting .305 with nine homers and 35 RBIs for Triple-A Indianapolis.
SAFE AT FIRST: 3B Adalberto Santos had quite a night Friday for the Curve. He not only went 4-for-5, but the one time he was retired came after a 15-pitch at-bat.
STEALING SECOND: Santos saw his average plummet from .345 to .231 in just a few weeks, but he's regrouped and raised the figure to .271 with his big game.
ROUNDING THIRD: The Curve are without manager Carlos Garcia for this series. He is home attending his son's high school graduation.
HEADING HOME: Despite playing in the same division, this weekend's series is the first time the Curve and Bowie are meeting this season. It didn't occur until Altoona's 71st game, the halfway point of the season.
-- Cory Giger
The Curve got a runner on in the ninth as Adalberto Santos singled to finish 4-for-5, but Bowie Oliver Drake retired Maggi and Polanco to earn his first save.
Kingham (1-1) allowed five runs in 6 1/3 innings to take the loss in his second Double-A start. He struck out six, walked one and allowed seven hits. Baker came on with two runners on and one out in the seventh and let both inherited runners score as Bowie took a 7-3 lead.
Baysox reliever Chris Petrini (2-3) retired only one batter in the seventh inning but was credited with the win.
SUBHD: Game recap
Key player: Curve 3B Adalberto Santos went 4-for-5 with an RBI in a losing effort.
Key play: LF Nolan Reimold delivered a big two-run single in the seventh to give Bowie a 7-3 lead.
Key stat: The Curve's eight-game winning streak was snapped.
SUBHD: How they scored
Bottom 3rd: Horton singled, scored on Romero groundout (0-1).
Bottom 4th: Urrutia singled, scored on Joseph two-run homer (0-3).
Top 5th: Vasquez singled, scored on Ngoepe groundout (1-3); Paulino walked, scored on Santos single (2-3).
Top 7th: Paulino singled, scored on Ngoepe single (3-3).
Bottom 7th: Rosa singled, scored on Kelly single (3-4); Pettit doubled, scored on Romero single (3-5); Reimold single scored Kelly and Romero (3-7).
Top 8th: Maggi walked, scored on Cunningham sacrifice fly (4-7); Polanco walked, scored on Paulino single (5-7).


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Two local residents have been elected to lead the student body at the University of South Carolina,
Chase Mizzell, a junior from Folly Beach, is student body president. He is majorig in international business and finance with a minor in Spanish.
Summerville sophomore Ryan Bailey has been named vice president of USC's student body. He is studying political science, emphasizing public administration and American government, and minoring in music.
Mizzell and Bailey both were in student council at Fort Dorchester High School. Fort Dorchester science teacher James Barton said this is the first time in his six years advising the student council that his former students have reached such positions.
"They were very motivated and driven to do a good job. They did a good job engaging other folks," Barton said. "I'm really proud of them."
Here is a look at the two student leaders:
Chase Mizzell
Parents: Jennifer and Steven Metts
Siblings: Mckenna Mizzell and Devin Metts
High School: Fort Dorchester
Involvement: University Ambassadors, EMPOWER Diversity Peer Leader, Dance Marathon, Omicron Delta Kappa Honors Society
Accomplishments as vice president last term: A University Neighborhood Association so that we can be more active citizens in our community. I continued work with the student body president to move forward an initiative to have free student legal services available on campus.
Duties as president: Preside over a cabinet of 27 student leaders; serve on the University Board of Trustees and guide the development of university policies that concern the student body.
Goals as president: Make visible meaningful changes for the campus and students, improve student government so that it will have a perennial place at the forefront of students' and administrators' minds and continue strengthening my personal relationships with the student body to a depth and breadth never achieved before.
Favorite things about Carolina: The historic Horseshoe. The light breeze and falling leaves of fall leave lasting memories of friendly conversations and picnics alike; the countless conversations with campus employees and students throughout the day and night that have contributed to my personal growth and development. Each member of our Gamecock family challenges me to be a better person and to make an impact on those around me. I would be remiss if I left out Gamecock athletics because nothing exemplifies the zeal and passion our community has for Carolina like a Saturday evening in fall in Williams-Brice (Stadium).
What do you miss the most about the Lowcountry: It may be too easy to focus on the simple joys of Charleston, but it's my family, the beach and good ol' Charleston cheese grits that I miss most.
What motivates you: Relentlessly pursuing my passion to get to know and impact everyone I meet.
Role model: My grandfather, Andaddy, who passed a couple of years ago, has always been an incredible role model of love and integrity.
Where do you see yourself in 10 years: I may travel abroad for a bit after school, attend graduate school or continue being an entrepreneur, but I'm sure that I'll continue what I'm doing now: getting to know every person I meet and striving to make a difference in their lives.
Ryan Bailey
Parents: Rob Bailey, Jennifer Bailey and stepmother Tracie (Massenburg) Bailey
Siblings: Ryan and Haley Massenburg
High School: Fort Dorchester
Involvement: Page in the S.C. Senate for Sen. Sean Bennett
Major accomplishments: As (USC) Senate Safety and Transportation chair: A safety pathway between campus and Five Points, which is series of call boxes along the three walking paths most traveled between campus and Five Points; making parking easier for students on campus with a metering system that will allow students to pay with a credit card, debit card, cash and via text message; research on bike racks on campus and how to better utilize our space. We are in the process of bringing a mobile blue light application to campus that will allow our students to always have a direct connection to the USCPD and Columbia Police Department from their smartphone.
Duties as vice president: President of the (USC) Senate, adviser to a great group of leaders on campus, implementing personal initiatives with my staff and several Senate committees and presidential initiatives.
Goals as vice president: I want to continue to work on student safety projects and see the Safety Pathway come all the way to fruition. I also want to continue to work with the parking services department to see pay-by-phone options for parking come to campus. I am looking forward to working with the Faculty Senate on creating an evaluation bank so that students can see exactly what they are getting into when signing up for classes; it will essentially be a rate my professor for USC students by USC students.
Favorite things about Carolina: I love the football games; there is nothing better than seeing your team dominate game after game. It is just such a good feeling being on campus; everybody here really feels like a family.
What do you miss most about the Lowcountry: I miss the beach and my family more than anything else in the world. All of my family, grandparents, aunts, uncles and cousins are all back in Charleston. I go home every chance I can to see them, and it is still never enough time.
What motivates you: I really just like helping people. If I can make a difference in only one student's life while I'm at Carolina, then I'd consider that a successful college career.
Role model: My dad. We do everything together. He is truly my best friend. I can't even imagine what my life would be like without him. We spend so much time talking about life and what it takes to accomplish goals. He really is the best person I know.
Where do you see yourself in 10 years: I would like to either be a JAG for the Marines or a piano teacher. I'm really not sure what the future holds. No matter what I decide to do, I want to have an impact on the people around me and I want to change things for the better. I'd like to live in Charleston. It's the best place in the world. Honestly, if I can wake up in the morning, have a cup of coffee on my front porch, and be excited about what I'm doing the rest of the day, I would be 100-percent satisfied.


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- Brand: Evergreen Enterprises
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A sub genre of grind core often sonically similar to pornogrind and goregrind; characterized by the "oompa oompa" sound created by chugging palm muted power chords and kick-snare-kick-snare drum beats
"Have you heard cemetery rapist? They're like porno, oompa oompa grind. Pretty sexy stuff"
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Mission Profile
NASA Ames Research Center and The Planetary Society are celebrating the Silver Anniversary of the launch of the Pioneer 10 Mission with an 25th Anniversary Conference to be held on Monday, March 3, 1997 from 9:00 AM TO 4:30 PM at NASA Headquarters Auditorium
Twenty five years ago on March 2, 1972, Pioneer 10 was launched (A 1.1M QuickTime Clip) from the launch pad at Cape Kennedy, carrying Earth's first space probe to an outer planet. To accomplish this feat, Pioneer 10 had to pass through what was initially feared to be an impenetrable asteroid belt.
After Pioneer 10 emerged through the asteroid belt, Pioneer 11, was launched on a similar trajectory. Pioneer 10 became the first spacecraft to encounter Jupiter. Launch Project Manager, Charlie Hall, (A 4.2M QuickTime Clip) describes mission control at the time of the Jupiter encounter in December, 1973. Pioneer 11 was the first at Saturn. The Pioneer missions paved the way for exploration of the outer solar system.
Now the most remote man-made object launched into the cosmos, Pioneer 10 is approaching nearly 7 billion miles from the Sun. It became the first artifact to "leave the Solar System" on June 13, 1983 when it passed beyond the farthest known planet. It is now searching for the heliopause, exploring the very edges of interstellar space as it drifts onward in mankind's first journey to the stars. (Click on this image for a larger version.)
Along with its sister ship Pioneer 11, Pioneer 10 carries a plaque with messages designed to make contact with possible alien civilizations. The late Dr. Carl Sagan helped devise the plaques that bear the illustration of a man and a woman as well as a diagram identifying earth's location in the galaxy. Like a message in a bottle, these plaques will journey out into interstellar space possibly to be found one day by an extraterrestrial civilization. Dr. Sagan, (A 5.7M QuickTime Clip) discussed the significance of the plaque placed in Pioneer 10 in this interview.
In a series of interviews to commemorate Pioneer 10 on its twenty- fifth anniversary. Dr. Larry Lasher, (A 3.4M QuickTime Clip) Pioneer Project Manager from the NASA Ames Research Center, relates some of the achievements of Pioneer 10. Dr. James Van Allen, (A 3.5M QuickTime Clip) Principal Investigator of the Geiger Tube Telescope instrument, talks about several of the scientific successes of Pioneer 10. The role of the Plasma Analyzer instrument in measuring the solar wind is discussed by its Principal Investigator, Dr. Aaron Barnes, (A 2.7M QuickTime Clip) from the NASA Ames Research Center. Dr. John Simpson, (A 2.9M QuickTime Clip) Principal Investigator of the Charged Particle instrument from the Enrico Fermi Institute of the University of Chicago, discourses on the boundary region of interstellar space.
Pioneer Mission Backgrounder:
Historical Significance: The Pioneer Project Office at NASA Ames Research Center and the Planetary Society are taking the occasion of March 3, 1997 to celebrate the twenty-fifth anniversary of a watershed event in space exploration history: the launch of Pioneer 10.
Some twenty five years ago on March 2, 1972, Pioneer 10 was launched on an Atlas/Centaur launch vehicle from Cape Kennedy carrying Earth's first space probe to an outer planet. To accomplish this feat, Pioneer 10 had to pass through what was feared to be a hazardous asteroid belt. Pioneer 10 demonstrated that this was not the case, thereby opening the door for all future outer planetary missions. After Pioneer 10 emerged from the asteroid belt, its follow-on companion, Pioneer 11, was launched on a similar trajectory. Its purpose was to serve as a backup had Pioneer 10 failed for any reason. After the first ever successful encounter with Jupiter by Pioneer 10, Pioneer 11 was retargeted mid-flight for an eventual encounter with Saturn following the second Jovian encounter in December, 1973
Pioneer 10 led the way for exploration of the outer solar system - paving the way for Pioneer 11, for the Voyagers, for Ulysses, and for the Cassini flight to Saturn in 1997. Pioneer 10 was the first ever to encounter Jupiter survive its intense radiation, and was the first probe to leave the realm of the planets and enter the edges of interstellar space for the first time in history! That major event occurred when Pioneer 10 became the first artifact to "leave the Solar System" on June 13, 1983 when it passed beyond the orbit of farthest known planet. Pioneer 10 is currently over 6 billion miles away with round-trip communications taking over 18 hours at the speed of light of 186,000 mile per second!
Pioneer 10 is now searching for the solar wind termination shock and the edge of interstellar space. It carries with it a plaque heralding a message of its origin to a possible extraterrestrial intelligence that may find it some day.
Extended Mission:
Heliospheric Boundary: The extended mission for Pioneer was to search for the heliopause. The heliopause is the meeting surface of the solar wind and the medium outside the solar environment where the region of interstellar space begins. The solar wind is a 1,600,000 km-per-hour (1,000,000 mph) flow of gases expelled by the sun consisting of protons, electrons, and other subatomic particles. The interstellar medium is of uncertain composition, but the interstellar winds are known to include energetic atomic nuclei whose cosmic flux is detected as far inward as the Earth. An artist's conception of the heliospheric boundaries, (click on the image to the right for a larger version) shows the other spacethat have joined Pioneer 10 and 11 in this search. We can see that only Pioneer 10 is moving in the opposite direction to the Sun's motion through the galaxy, shown here as the solar apex direction. The motion of the heliospheric boundary through the local interstellar medium may cause a bow wave upstream of the heliopause and a tail downstream. The flow of subatomic particles making up the solar wind is expected to undergo a shock transition from supersonic to subsonic before reaching the heliopause. This shock is called the solar-wind termination shock. Here termination refers to the end of supersonic flow and not the end of the solar wind, which occurs at the heliopause. Prior to Pioneers 10 and 11, the effect of the solar wind was thought to extend to the vicinity of Jupiter or perhaps a bit farther. The Pioneer scientists now predict the distance from the Sun at which the terminal shock may be encountered is from 60 to 100 astronomical units (AU) or more, where an AU is defined as the distance of the Earth from the sun ~ 150 million kilometers (~93,000 million miles). For reference, the distance to the outermost planet is ~ 40 AU's.
Star Encounters & Plaque: Several years from now the RTG power will degrade to a level that the signals to Earth will cease, and Pioneers 10 and 11 will coast silently through interstellar space forever.
Included on both spacecraft is the small gold-plated aluminum plaque which the figures of a man and a woman are shown to scale next to a line silhouette of the spacecraft. The bracketing bars on the far right are the representation of the number 8 in binary form (1000), where one is indicated above by the spin-flip radiation transition of a hydrogen atom from electron state spin up to state spin down that gives a characteristic radio wave length of 21 cm (8.3 inches). Therefore, the woman is 8 x 21 cm = 168 cm, or about 5' 6" tall. The bottom of the plaque shows schematically the path that Pioneers 10 and 11 took to escape the solar system - starting at the third planet from the Sun accelerating with a gravity assist from Jupiter out of the solar system. Also shown to help identify the origin of the spacecraft is a radial pattern etched on the plaque that represents the position of our Sun relative to 14 nearby pulsars (i.e., spinning neutron stars) and a line directed to the center of our Galaxy. The plaque may be considered as the cosmic equivalent to a message in a bottle cast into the sea. Sometime in the far distant future, perhaps billions of years from now, Pioneer may pass through a planetary system of a remote stellar neighbor, one of whose planets may have evolved intelligent life. If that life possesses the technical ability and curiosity, it may detect and pick up the spacecraft and inspect it. Then the plaque with its message from Earth may be found and deciphered. The late Dr. Carl Sagan, who helped design the plaque, discusses the significance of the plaque placed in Pioneer 10.
Articles and News Releases
January 28, 1997 NASA Press Release on a recent, successful targeting maneuver.
The November 4, 1996 Issue of: TIME Magazine has an excellent background
article on the Pioneer 10 mission and spacecraft.
Pioneer Homepage:
For additional information on Pioneer 10 & 11 and the current status of the missions, visit the Pioneer Project Home Page.
To download the Quicktime Player
(You will need to scroll past the software agreement.)
| Educational Resources | Conference Events | Virtual Conference |
This NASA K-12 Internet Initiative Web page


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After leaving one of the most successful rock bands of all time 16 years ago, Christine McVie is back – and her band mates couldn't be happier.
"We're thrilled," the band's co-founder and drummer, Mick Fleetwood, tells PEOPLE exclusively. "She's just the dearest of friends and we've remained that way always. We've always missed Chris. To have a key, key member return to the fold is huge. It's really not happened, to my knowledge in any shape or form, on this level."
McVie, 70, whose songs "Little Lies" and "Say You Love Me" were among Fleetwood Mac's biggest hits, tells PEOPLE exclusively, "I honestly could never in my wildest dreams have thought I could return to the band. It's just a dream come true. I go to bed going, 'This is so great. This is what I've been yearning for all these years and I didn't know it.' We're family. We're very lucky."
All five members of the band reunited this morning when McVie, along with her ex-husband, John McVie (who is "on the mend" after a cancer diagnosis last year, she says), Fleetwood, Lindsey Buckingham and Stevie Nicks appeared on Today to officially announce the return of the keyboardist and singer/songwriter.
Starting this fall, McVie will join Fleetwood Mac on its upcoming tour, On with the Show, and the band may release a new album "down the road," she says.
Fans, of course, are thrilled to have her back – and are wondering if there will be any drama, since the band was known as much for its mega-hits as for its feuds and, um, offstage fun.
"Us?" joked Fleetwood.
Says McVie, "Well, it wouldn't be Fleetwood Mac without a bit of drama, you know. Of course there will be some drama, but for the most part I have to say everyone is getting along really well. At the moment the drama is kind of the fun."
The British-American band was also notorious for its hookups – and breakups – which they wrote about in numerous songs. Nicks and Buckingham famously broke up, Fleetwood had an affair with Nicks, and the McVies divorced. Considering their history, do they foresee any more inter-band romances down the road?
"God knows we were probably overly open about all that stuff years ago," says Fleetwood, 66. "But that goose is cooked."
Why McVie Decided to Return
McVie joined the band in 1970, which her then-husband John McVie and Fleetwood founded three years earlier. In 1975, they were joined by Buckingham and then-girlfriend Nicks, becoming one of the most successful groups of all time, with best-selling albums including Fleetwood Mac, Rumours and Tusk.
Danny Clinch
While she released her last solo album in 2004, spending much of her time quietly in England, she says she had no intentions of returning to Fleetwood Mac.
"But then," she says, "two years ago I started to really miss playing. I was toying with the idea of playing with some little band or … I didn't know what, really. The truth of the matter is the only people I wanted to play with were the people I had played with all my life – these guys – Fleetwood Mac."
She overcame her fear of flying through therapy, boarding a plane for the first time in years in February 2013 with Fleetwood at her side, where she spent time in Maui with him and other friends, watching the Mick Fleetwood Blues Band rehearse for an upcoming show.
She did something else for the first time in 15 years during that Maui trip: She performed onstage at the Maui Arts & Cultural Center with Fleetwood – and Aerosmith front man Steven Tyler, a close friend and neighbor of Fleetwood's.
When Tyler asked McVie during rehearsals if she was going to join them onstage, she declined, which came as no surprise to Fleetwood, who promised he "would never ask her to play" since she would probably say no.
Still, says Fleetwood, "Chris called me the next morning and suddenly the ambient voice sounded quite small and she said, 'I was actually just thinking, would you like me to play at the gig?' I said, 'Are you kidding me? Of course!' And that was how we segued into Chris coming up and doing a few songs along with Steven Tyler and my little band."
The Dinner that Clinched It
Shortly after McVie performed with Fleetwood and Tyler in Maui, she had dinner at Locanda Portofino in Santa Monica, Calif., with the four remaining members of Fleetwood Mac, which convinced her to return to the band.
"Lindsey was saying, 'The chemistry around the table is so fantastic, you know?' " says McVie. "That was the start of it. I think I made overtures to Mick, saying, 'What would you think if I were to rejoin the band?' "
The four members talked it through, telling her they would love to have her back – as long as she meant it. "Lindsey was saying, 'If you really are serious, then you've got to commit.' It was sort of an epiphany in a way. I just knew that's what I wanted."
Preparing for Her Momentous Return
"I'd like to say it's like falling off a log but it's a little more complicated than that. My muscle memory needs to return," she says, explaining that she needs to brush up on the lyrics to the songs that made her famous. "But I also slipped back in to it as though I never left, in a sense. In fact, I actually feel stronger."
McVie – who wrote many of the band's most famous hits – is also writing new songs, which could turn up here or there during the tour or on an upcoming album.
"Lindsey has been trolling through some tapes and files I sent to him when I was in England," she says. "He took bits that I thought were useless and said, 'That's fantastic!' So he's made them into something that I didn't realize were really that good. I am going, 'God. I can't believe that I actually wrote that.' "
Full Circle
McVie says that she can't wait to start touring again. "It is a celebration and it is a really joyful time for the band. God must have been smiling on me because I feel like a different person. This has done nothing but wonders for me and I love my band so, so much."


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A TRANSLATOR is one who renders WRITTEN word from one language to another. An INTERPRETER is one who renders SPOKEN word from one language to another.
Interpretation is the oral rendering of oral messages, and may be done either simultaneously or consecutively. Simultaneous interpretation is by far the best known of these techniques. Here, the interpreter sits in a booth receiving the message to be interpreted through earphones; then, having understood the message, he or she delivers it in the target language into a microphone. In consecutive interpretation, the interpreter takes notes while a speaker delivers the message (in five to seven minute long sections), and then the interpreter delivers the message in the target language, employing special note-taking and memory improvement techniques to increase the amount of information that can be accurately interpreted.
Translation is the process whereby the meaning, style and information of a piece of written text in one human language is reproduced in another written human language. For example, an English document is translated into German so that it creates the same impression on, and communicates the same information to, the German reader as it did for the English reader.
Localization (L 10 N) is that process whereby an object (computer program, multimedia presentation, document, etc.) is not only translated, but also adapted to another culture. Such things as date formats, Metric/English measures, comma/decimal conventions etc. are considered in addition to the normal language issues. The idea is to make the product/service seem as though it originated in the target culture.
Computer Assisted Translation (CAT) is the label given to that category of computer program which supports humans who are performing translation tasks. The tools merely provide environments which enhance the ability of humans to provide timely translations of high quality in a cost effective manner. Examples are Sentence Memory (or Translation Memory), on-line dictionaries, bi-lingual editing systems, etc.
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At an event patronised by His Excellency Eng. Sultan Bin Saeed Al Mansoori, UAE Minister of Economy, the UAE Accountants and Auditors Association (AAA) and ACCA (the Association of Chartered Certified Accountants), the global body for professional accountants, signed a strategic partnership to develop the UAE chartered accountant certificate that supports the government's drive to promote the qualification of UAE nationals.
The strategic partnership, signed by Saif bin Abed Al Muhairi, Chairman of AAA and by ACCA President Martin Turner and witnessed by Mohammed Ahmed bin Abdul Aziz Al Shehhi, Undersecretary, UAEMinistry of Economy builds on a Memorandum of Understanding agreed in November 2013.
As part of this partnership, the ACCA Qualification will form the basis of the new national chartered accountant qualification, entitling those participating to an internationally-recognised qualification and eligibility for both AAA and ACCA memberships. The qualification will consist of exams, practical experience and ethics modules.
As part of the partnership, the AAA and ACCA will also run joint events and conferences to examine key issues for the accountancy and finance professions in the UAE, the wider region and internationally.
Mr. Saif bin Abed Al Muhairi, Chairman of AAA commented: 'We are confident that this partnership is a milestone for the accounting and finance profession in UAE. The global knowledge of ACCA, the local expertise and reach out of AAA and the country vision to excel in financial services are existing pillars of success.'
ACCA President Martin Turner said: 'ACCA is delighted to have signed this strategic partnership with AAA. We look forward to working closely with a professional body which we hold in the highest regard, to further enhance the accountancy profession in the UAE. There is a significant need for finance professionals in the UAE as the economy continues to grow and diversify and we are excited about supporting the development of the profession in the region.
'ACCA is proud that, through this agreement, it has an opportunity to support the UAE's vision to be the region's leading financial centre and to support the UAE government's focus to promote the qualification of UAE nationals, as part of the excellent Emiratisation initiative.'
Ahmad Darwish, Chairman of the Members' Advisory Committee for ACCA UAE and Head of Chartered Accountants Committee of AAA said: 'The excellent qualification that this partnership will develop will create new opportunities for future generations of Emiratis, enabling the UAE to further establish itself as a leading financial services hub with highly qualified, globally aware finance professionals.'
Bassel Nadim CEO of AAA said: 'We are well positioned to jointly drive this collaboration with ACCA and bring significant value to the finance sector in UAE.'


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When a man sticks a cube of chedar cheese inside a pregnant womans vagina and then as the woman is about to give birth he inserts his dick into the vagina therefore forcefully inserting the rounded cube of chese inside the childs mouth.
Hey babe, u want to do the Moldy Macaroni?
Beküldő: parkisonsexaddicts 2008. november 10.
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HOME Jacksonville Jaguars Gear Jacksonville Jaguars Mens Jacksonville Jaguars Mens Jerseys over $60 (1 items) Product ID: 845864
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- Fit: Nike Elite Jerseys are constructed of heavier-weight materials for on-field durability, and they do not fit or feel like a T-shirt.
- Fit: Nike Elite Jerseys have an athletic cut that fits snug in the chest and the shoulders.
- Flexible twill numbers
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- Laser-cut embossed jock tag
- Machine-washable
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- Officially licensed NFL product
- Player names cannot be printed on the team's jersey from which they retired
- Player names must match the current team rosters and the team for which they currently play
- TPU metallic-effect shield at collar
- Water-repelling fabric to help keep you stay lightweight and dry
- 88% Nylon/12% Spandex mesh
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Level: Intermediate
ISPE CEUs: 1.3
Type: Classroom Training Course
|This course is not currently scheduled, but may be offered at your company site. Please contact ISPE for more information.
This course uses the second edition of the ISPE Baseline® Guide: Sterile Product Manufacturing Facilities and the FDA's Guidance for Industry: Sterile Drug Products Produced by Aseptic Processing - Current Good Manufacturing Practice to provide an understanding of the key requirements and GMPs for sterile manufacturing facilities. The Guide provides valuable information on design, while the USFDA's Guidance helps professionals understand the regulatory context and expectations for sterile drug manufacturing.
Immediately apply the course learning objectives using the complimentary copy of the ISPE Baseline® Guide: Sterile Product Manufacturing Facilities (Second Edition)
Using the referenced documents, this course will cover regulatory philosophy, aseptic process and equipment considerations, aseptic clean room design and operation, differential pressure requirements, airlocks, basic utility systems, European HVAC considerations, and a brief introduction to barrier isolation technology. (Note: parts of Guidance for Industry: Sterile Drug Products Produced by Aseptic Processing - Current Good Manufacturing Practice that do not focus on facilities and equipment will not be discussed in detail.)
In addition, the course will include an exercise in the layout of an aseptic filling facility. In many cases, when a new facility is required within an existing or new building, the designer will begin by sketching a floor plan. This exercise will demonstrate how to use process flow diagrams and an accommodation schedule to thoroughly define facility requirements before advancing to the floor plan layout stage.
NOTE: Participants interested in commissioning and qualification should attend the Science and Risk-based Commissioning and Qualification - Applying the ISPE Good Practice Guide: Applied Risk Management for Commissioning and Qualification training course.
This training course is of particular interest to existing and future members of the ISPE Sterile Products Processing (COP).
ISPE will provide continuing education units (ISPE CEUs) for all North American and European courses. CEUs are nationally recognized units of achievement designed for those individuals continuing their education in their chosen field or profession. Verification of CEUs is based on attendance as well as satisfactory completion of all evaluation materials. Statements of credit will be available for download in your ISPE account within four weeks of the completion of training. Instruction for download will be sent when the CEUs are available. One hour of education programming equals 0.1 ISPE CEU credits.


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Are you a man...or a monster?
Challenging motocross racing at its best!
Become the team's Ice Hockey Hero!
Show off your best BMX freestyle tricks before time runs out!
Turbo Racing 2 hits the streets at high speed with a license to burn rubber
Assault Course 2 is serious about teaching you the basics.
Time to take the copter to war!
Drift downhill and speed past the other trikes!
Protect the town from the zombies with your meat cleaver!
Zombie kart racing at its best!
Get slam dunkin' with Basketball Jam!
Lead your team through the Beach Soccer tournament.
Pick up massive guns as you pile up defeated robots in your mission to build the tallest Kill Hill.
Take control of your Apache and take down the enemy forces!
Are you up the challenge of clearing all the bubbles?
Fight enemies in the much awaited sequel to Canyon Shooter.
Perform breathtaking tricks and win!
Can Commando free the world from the looming threat of world war 3?
Defend the Allies from the scourge of Europe.
You must defend your village with advanced war equipment!
Annihilate the alien infestation before it's too late!
Can you help Arnold the Cable Fitter escape the underground maze?
Pocket as many pool balls as you can before the time runs out!
How many touchdowns can you score?
Master the race tracks of the future as you tackle huge jumps.
Play 8 Ball Pool against other players online!
Defend the streets and free the bionic dinosaurs!
Bring home the Bacon, Hambo!
Help Joe to tear down buildings and evict the criminals.
You are on the run in Vegas, you must lose the cops and deliver the documents!
Navigate the obstacles in the quickest time possible!
Show us your moves!
Become the champion of World Rugby! Dodge, jump, tackle and pass your way to victory!
Extreme Snowboard tricks!
The missions of your H.A.D.E is to destroy all threatening life forms!
Defend against the Zombies migrating into your town!
Commando joins forces with his Allies to hold off the waves of enemies!
Do not let the classified documents get in the wrong hands!
Qualify in the races to reach the final! Choose your pit stop wisely, to replace tyres and fuel.
Help the robot hero to win the war against the evil robots!
Stop the express being taken by the Outlaws!
Your mission is to attack the enemy bases. Use the rivers to your advantage!
Compete to be the Soccer Star!
Compete over 8 crazy events to become Stunt Driver of the Year.
Serve Pizza for the superheros.
Take your team to the finals of the World Championship!
Our hero is on the defensive, take control of Commando's towers!
Throw the grenades and blow up your targets!
Eradicate this infested planet of all that walks its polluted surface.
Join in the saloon brawl and knock out the other cowboys!
Get rid of the cybertrash!
Use your sword and defeat all the stickmen attacking you.
The world has been consumed by darkness.
Trap, shoot, beat and blow up zombies in Zombie Trapper 2!
Devastate your enemies in Guns of Anarchy!
Complete action-packed missions on the Western Front!
Step up to the plate and go for the home run!
Only your skill and bravery can bring peace to the Kingdom of Avantia - it's time to become a hero in BEAST QUEST!


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On a wide natural road from Stuls to Runsolas, followed by a walking trail to Falein, and a descent to Filisur. Views across the villages in the upper Albula valley. "Zvieri" (salsiz, cheese, coffee) at the Heidi hut every Wednesday in summer. Bookings at Bergün Tourism. 3.5 hours towards Filisur, 4 hours in the opposite direction.
Tour Overview
3D hiking map Download GPX coordinates Download KMZ (GoogleEarth)
The careful planning of a tour will ensure that you also derive the maximum pleasure and enjoyment from it. Please take the time to contact the local information centre and enquire about route and weather conditions before setting off. Your intended trail may be fully or partially closed, depending on the time of year and weather conditions.


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See your CB40 team on Road to Lord's
Clydesdale Bank 40 cricket is back this week after the mid-season break as the teams battle it out on the Road to Lord's.
Don't miss the action. Get behind your county and buy your tickets now - full details on ecb.co.uk
The first matches this week are at Amstelveen and Edgbaston as pacesetters Netherlands take on winless Leicestershire, and Warwickshire welcome Sussex in a group-topping encounter.
There are then games on Thursday (Glamorgan v Somerset at The SWALEC Stadium), Friday (Northamptonshire v Derbyshire in Northampton) and Saturday (Leicestershire v Worcestershire at Grace Road) - before a Sunday programme of six matches.
Group games continue through July and August up to the climax on Bank Holiday Monday August 27 - with semi-finals September 1 deciding the Lord's finalists a fortnight later.


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Score a $2 BOOrito at Chipotle on Halloween IF you wear a costume
Start ironing those capes! You can score a $2 BOOrito (or a bowl, salad or an order of tacos) at Chipotle on Halloween from 4 p.m. to close if you arrive dressed in costume. And yes, this is the very same chain that our Leslie Brenner praised in the Impatient Palate, referring to the "mammoth burrito," in particular, as "by far the best I've ever had in a chain."
Also cool: The proceeds, up to $1 million, will benefit the Chipotle Cultivate foundation, a non-profit committed to creating a more sustainable and healthful food supply and raising awareness concerning food issues. And you can enter a costume contest by taking a photo of yourself inside or in front of a Chipotle restaurant on Halloween and submit it at chipotle.com/boorito by Nov. 2. Grand prize is $2,500, five runner ups will get $1,000 and 20 runner-ups will get a burrito party for ten at the Chipotle of your choice.


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on February 5, 2013 - 9:21 PM
, updated February 6, 2013 at 9:23 AM
A Niagara University alum gave an omen of things to come Sunday for the San Francisco 49ers – and was loved or vilified for doing so.
In Tide's 60-second "Miracle Stain" ad – one of the most praised commercials aired during the Super Bowl – sauce spilled on a football fan's jersey forms the image of fabled 49ers great Joe Montana and soon sends fans on a frenzied pilgrimage to his "Montana Land" home.
The buzz comes to a screeching halt when the man's wife, played by Carmen Ruby Floyd, a 2000 Niagara grad, informs him she has "inadvertently" washed the jersey because of the "stain." As he moans over the news, Floyd turns to the camera and says slyly, "Go Ravens."
"People hate me, people love me, it's fantastic. That's when you know you're a real celebrity, right? Isn't that the goal?" Floyd laughed.
"It's funny. Sports fans are really intense. They either blamed me for the loss or credited me for the win."
Floyd, 32, a Buffalo native who lives in Manhattan, said she had a lot of fun making the commercial in Los Angeles. "It was a blast. Marcus [Brown, her co-star] reminded me of my actual husband and he said I reminded him of his wife, so it was easy to role play. We basically laughed on set for the four days we shot it."
Floyd has done other commercial work and voice-overs. She was also the understudy last year for the role of Mariah in "Porgy and Bess" on Broadway, where she also has also appeared in "Avenue Q."
In 2011, Floyd appeared in an episode of "Law and Order: SVU," and sang "Creole Love Call" in "Cotton Club Parade" at City Center, prompting a New York Times critic to say her rendition had "an eerie, supernatural quality."
Floyd, who interrupted her Niagara education to perform in "The Lion King" in Toronto, credits the university for preparing her for a career in performance.
"There is obviously dance, vocal and acting, but they have you do stage management, costumes, lighting and sound," she said.
"It's a very well-rounded theater school, and my training has definitely paid off."
Eleanor Gayles Davis, Floyd's aunt and a Buffalo resident who has performed for decades in the Gayles Family Singers, which includes Floyd's mother, was "delighted" by the commercial.
"I was at a Super Bowl party, and we just applauded and were so happy," Davis said.
Floyd wasn't the only Niagara University graduate involved in some capacity with the Super Bowl.
Derek Zeller, who graduated last year with a degree in communications studies, photographed images of events in New Orleans leading up the to Super Bowl for a website affiliated with the NFL Players Association.
"It has been such a surreal experience – a dream come true," Zeller said in a statement, noting that he shook hands "with guys like Jerry Rice and Andre Reed."
Eleven students from NU's College of Hospitality and Tourism Management also went to New Orleans. They worked on Super Bowl Boulevard, helped at NFL Experience, the league's interactive theme park, and were involved in coordinating some postgame activities on the field.
On Monday, the Vincentian university students volunteered at that city's St. Vincent de Paul Society.
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Listening to Oprah Winfrey could be a step in the right direction for Lindsay Lohan.
Speaking on Tuesday's Good Morning America, Winfrey discussed her interview with Lohan, which will air Aug. 18 on OWN, saying that she advised Lohan to skip her trip to Europe.
"I just came from Europe, and Europe is the place to go when you want to feel really good and relax," Winfrey, 59, said. "It's hard to go to Capri and not have a Bellini."
Winfrey added that Lohan, who just completed three months of rehab at a Malibu treatment center, was hesitant because she had already paid for the trip, but eventually decided to cancel it.
When asked about her impression of Lohan's health, Oprah said she noticed a change from the last time the two had met.
"I thought that she's in the best place that I've ever seen her," said the media mogul. "I believe that she believes that she is now ready. And she admitted that there were other times when she was pretending to be ready and not quite sure. And sometimes resentful that she was being, you know, put in a position where she had to go to rehab. I think this is the first time I could see it really benefited her."
TV Watch Update
Oprah Winfrey Keeps Lindsay Lohan from Europe, Thinks She's Really Ready to Rehab
updated 08/06/2013 AT 12:40 PM EDT
•originally published 08/06/2013 AT 11:15 AM EDT


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Please enter a valid mileage
Based on 1706 Ratings for the 2005 - 2014 models.Review this car
By CC on Monday, December 29, 2014
I own this car - My approximate mileage is 4,500overall rating 10 of 10rating details
Pros: "Always fun to drive, reliable and efficient"
Cons: "A few dollars more would make it awesome"
Likely to recommend this car? (1-10): 9
"Strong performance combined with very good economy and a very thrift entry price. I have had zero mechanical or functional problems with this car. Overall gas mileage average for my car is 25.9mpg in mixed driving, mostly suburban city cycle. high points: HID headlights, steering feel and response / handling, very strong V6 engine, fuel economy, Seating position, very tight turning radius of size of car...Low points: shock tuning could be firmer without degrading ride, OEM tires perform poorly in snow and ice, better options exist for a performance all season solution Overall I am extremely satisfied with this car. The value to the price point is very good, and the S197 Mustang series 2005-2014 has proven to be a very mature and reliable product. The 3.7L V6 is a huge upgrade in power, economy and smoothness from the older 4.0L V6, and is a good substitute for the larger V8 for buyers on a budget. The V6 car is fast enough many drivers will never use the full power envelope of the engine. A very smooth and willing engine that never disappoints."
21 people out of 21 found this review helpful
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By Mu5t4ng0wn3r on Thursday, June 12, 2014
I own this car - My approximate mileage is 33,500overall rating 10 of 10rating details
Pros: "Performs excellently, great price, great mpgs"
Cons: "Needs a couple upgrades for top performance"
Likely to recommend this car? (1-10): 10
"This vehicle was the best possible value for what I needed; a performance car to throw around turns and suck me into the back of my seat, and something that I could not pour a bunch of money into the fuel tank with (if I can bring myself to drive normally...). Overall, paid about $25k for base model with performance package. 0-60 could best my classic camaro with a 350, suspension was tight enough to slalom the lines on the road with minimal roll, yet 30-32 highway mpg and 22-26 city (again, you have to shift at the recommended points in the manual to obtain the city mileage). The stock shifter was crummy (try to shift fast and you can miss the gate to 3rd and 5th) and had a long throw, so a replacement short throw took care of that. Also, it seems the suspension is a little too tight for the sway bar links; I messed up both front and back, and I didn't even abuse the thing. Not having independent rear suspension is noticeable too. Those features aside, this is the best car I've ever driven. I'm at the end of my factory warranty, and it still thrills me to get in it every morning. I got mine in performance white, so with the black 19" wheels and black side stripes, it still turns heads. Options to consider: -The stock stereo is what it is; bluetooth would be nice, but it wasn't worth the upgrade to the shaker system to me at the time. This option I constantly second guess. -Stone colored cloth seats are incredibly comfortable, but stain easy. Still glad I got them over the recaros, and it gives a sort of two-tone look to the interior. -Performance upgrades like forced air intake, exhaust, and a tune would make this quite the track car; 5.0 performance without the weight. -Bigger brakes would be excellent; the performance package upgrade was nearly unnoticeable. -It would look a whole lot meaner with a billet grille and some rear window louvers. Definitely consider this car if you're looking for muscle and daily driveability... so long as you don't mind having a tight suspension. Buying this car was the best decision I've ever made."
14 people out of 14 found this review helpful
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By Paulie-Oregon on Monday, November 5, 2007
overall rating 10 of 10rating details
"Once a month, I make the payment and frown. Everyday I drive it and smile..."
10 people out of 10 found this review helpful
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By SidVicious12 on Monday, December 12, 2011
I own this car - My approximate mileage is 10,500overall rating 10 of 10rating details
Pros: "Value, Power, Fun to Drive, Handling"
Cons: "Poor Cupholder Location"
Likely to recommend this car? (1-10): 10
"I bought my Mustang last year and I have enjoyed every minute of driving it. There is no better performance value for the money as far as I am concerned. 412 HP and a better power to weight ratio than anything offered by Chevy or Dodge...and all for a little over $29,000? Cannot be outdone. My kudos to Ford for making an outstanding car, throughout the Mustang range...unmatched. Well done! I absolutely recommend this car to anyone looking for performance, quality, value, and heritage wrapped into one great package! I have been converted...didnt used to like Mustangs...now, cant be pulled away!"
8 people out of 8 found this review helpful
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By Steve on Monday, April 7, 2008
overall rating 10 of 10rating details
"Ford nailed it with this car. I've had it for over 2yrs and still love it! Quality is up to par with cars costing far more and the fun and satisfaction level is off the scale. My car has had no defects or problems so far, and I can say the paint work is far better than that of my '03 Honda Accord. There is NO substitution for V8 rear wheel drive muscle. Every time I drive or look at this car it makes me smile."
6 people out of 6 found this review helpful
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on July 10, 2013 - 1:27 AM
, updated July 10, 2013 at 5:33 PM
Two appointments for teachers on special assignment drew criticism from several Holland School Board members Monday who questioned stipends for work performed during the day when those individuals also are receiving their full salaries as teachers.
New board member Brian Jones wanted to know why Allan Bett, director of health and physical education, was receiving a stipend for his role as dean of students when those duties are performed during the first period of his workday.
Meanwhile, Kelleen Kensey questioned a $6,500 stipend to Timothy Buckenmeyer, functioning as the district's new athletic director, when his predecessor got none.
"He's getting a full teacher's salary but not teaching full time. I believe the district got written up by auditors in the past for that," Kensey said. She said board members were under the impression the district had moved away from that kind of agreement.
Board member Judy Geer suggested they review the Holland teacher contract to determine if the district is locked into the special assignment stipend arrangement.
In another matter, interim Superintendent Sylvia Root bid farewell to the district at her final meeting. Root brought a conciliatory style of management to the district, which had become fractured in the months leading up to former Superintendent Dennis Johnson's early departure. New Superintendent Cathy Fabiatos was formally introduced.
Prior to the session, at the district's reorganization meeting, Steven Marom was elected president for the second consecutive year while Taina Armstrong-Hoffman accepted election as vice president. New board members Jenelle Nadler and Jones were sworn in.
The board also abolished small three-person subcommittees in favor of "committees-of-the-whole" with the full board in attendance.
"When we were working on the budget, our work sessions were very productive," Marom said.
The change will affect the Finance, Facilities, Audit and Policy committees.
The Negotiations Committee will remain a three-person subcommittee with Armstrong-Hoffman, Kelly and Geer the active members.
Work sessions will be called special meetings if the board anticipates action.


text:
Top Definition
weird, whacked out, messed up, not working for no definable reason. Usually applied to technology.
"Dude, you have the wonkiest computer in the world. I walked through the room and it crashed."
di Starla 09 luglio 2002
Trending Now
Can you define these popular missing words?
not right, odd
Jenni had a wonky eye, it was the source of all her self-esteem problems.
di ILoveThom'sChickenDance 16 ottobre 2003
Askew, non-intuitive, poorly designed, or not functioning as it should.
The UI on that site is kind of wonky.
My demo works, but when you start clicking around things get a little wonky.
My demo works, but when you start clicking around things get a little wonky.
di palousa 17 aprile 2003
Totally messed up; Strange and out of place; not working properly.
The printer's gone wonky.
di Jeremy 25 dicembre 2003
crazy,loony, not quite right, out of sorts. a mix of bonkers and wacky.
My computer keeps deleting my incoming mail,a nd being all wonky
di Loony Lovegood 29 maggio 2004
to not work properly, to be out of sorts
my computer went wonky today.
After drinking I felt a bit wonky
After drinking I felt a bit wonky
di Michael McGinty 06 marzo 2003
Another word for ketamine or the feeling of being ketimised
i should have done that bump before we even got in the club i am now wonky as fuck *proceeds to fall over*
di mandingo89 25 luglio 2009


text:
Wall Street Decline Takes Its Toll...
Developers of DTC Genetic Testing Are...
As Immunotherapy Revolutionizes the Cancer Treatment...
NSCLC is "Major Battlefield" as Merck,...
Lilly will transition diabetes drug to Amylin for global development and commercialization.[evgenyb - Fotolia.com]
Lilly and Amylin inked a deal with $250 million up front that will formally end their exenatide alliance and the outstanding legal wrangle that was instigated by Amylin back in May. Amylin's claimed that Lilly was in breach of its exenatide responsibilities and acting anticompetitively by using the same sales force to market both exenatide and Boehringer Ingelheim's competing diabetes drug, linagliptin.
Termination of the firms' decade-long exenatide partnership will see full responsibility for worldwide development and commercialization of exenatide passed to Amylin. Transition of the U.S. commercial operations from Lilly will be completed by the end of the month, and the firm will then transfer responsibility for commercializing the two exenatide drugs Byetta® and Bydureon® back to Amylin on a market-by-market basis in 2012 and 2013. The firm says it expects to work with one or more partners outside the U.S. to maximize the commercial potential of exenatide products.
Financially, the deal will involve Amylin making a $250 million up front payment to Lilly and future revenue-sharing payments equaling 15% of global net sales of exenatide products, up to $1.2 billion. If the EC-approved, once-weekly Bydureon formulation of exenatide doesn't receive FDA approval before June 30, 2014, Amylin's revenue-sharing obligations will be terminated, and the firm will instead pay Lilly 8% of global net sales of exenatide products. Amylin may also have to pay Lilly another $150 million milestone on FDA approval of a once-monthly suspension formulation of exenatide that is currently in Phase II development.
The GLP-1 receptor agonist Byetta was first launched in 2005, and the once-weekly formulation, Bydureon, was approved in the EU in June and is currently under review in the U.S. following a resubmission to FDA. A PDUFA data has been set for January 2012.
Amylin reported net U.S. Byetta sales of $128.1 million in the third quarter of 2011 (ending September 30), compared with $132.4 million in the equivalent period in 2010. Net U.S. sales of the drug in the nine months ending September 30, 2011, were $385.1 million compared with $422.9 million in 2010.
Until now Lilly has received a 50% share of Byetta's gross margin in the U.S. but has held on to 100% of Byetta and Bydureon sales outside the U.S. The firm reported total exenatide revenue of $106.7 million during the third quarter of 2011, up 4% on the same 2010 period. Worldwide exenatide sales were $171.0 million in the third quarter of 2011 (up 1%). The firm says that while U.S. sales of Byetta were down 4% (as reported by Amylin), primarily due to competitive pressures, sales of Byetta and Bydureon outside the U.S. increased 18% to $42.9 million.
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text:
Top Definition
A vibrator/dildo that is a falis with an extra clitoris stimulator. This extra part is made to lightly grab the clitoris while the vibrator/dildo is inside of the vagina.
Although she likes regular dildos, her favorite is her pearl panther.
door Jake Feldman 6 april 2005
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on October 5, 2012 - 3:37 PM
It's official - Buffalo's new federal courthouse will be named after former U.S. Supreme Court Justice Robert H. Jackson. President Obama signed legislation today that insures the $137 million building will carry the name of the Western New York native and Buffalo lawyer who went on to become solicitor general, attorney general, Supreme Court justice and later chief U.S. prosecutor at the Nuremberg trials. "I could not be more pleased that this majestic new building, located along the path that Justice Jackson himself walked each day from his home on Johnson Park to the firm in the Ellicott Square building where he practiced law, will bear the name of this man, who has left such a remarkable legacy on our nation's justice system," Rep. Brian Higgins, who helped sponsor the legislation, said in a statement. Jackson began his legal career in Jamestown but later moved his practice to Buffalo.


text:
Top Definition
Someone who comes in and takes over, they fill up a room and basically demand your attention , this person talks super fast and super loud and moves about so quickly and with so much energy sometimes leaving a mess in there path, can entertain or amuse a crowd for hours and seem to never stop moving or talking, and after hanging with a Hurricane Noelle you could feel worn out almost like you just weathered a storm!!
It's about to get loud and crazy cause Hurricane Noelle just got here!!!
de FortLaudypeeps 01 Aprilie 2010
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Main Content
Oh no, you just walked into a house party and spy your ex-boyfriend hanging out. Good thing you're wearing this flirty JJ tank top from Element. With the flowy fit and simple look, it'll definitely make him jealous; plus, this cute tank can also be worn with the extra fabric around your shoulders, giving you a cowl neckline. As all the other guys start chatting you up, he'll fume. Oh well, his loss!
- Tagless collar
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- Made in the USA
- Model shown is wearing size S
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TriStar Viper G2 LH Shotgun
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Chrome-lined chamber and barrel
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Product DescriptionThe Viper series G2 semi-automatic shotguns are gas-operated and interchangeably load 2.75" and 3" shells from the 3" chrome-lined chamber. These synthetic models feature Soft Touch textured gripping on stock and forend. The vent-rib barrel is threaded to accept the included Beretta-style choke tubes (IC, M, F), and is also chrome-lined. It has a matted sight plane and a fiber-optic front sight. The five-round magazine includes a shot plug and is equipped with a manual E-Z Load magazine cut-off allowing for quick unloading and safety. Left-handed shotgun.