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THE NEW ZEALAND MEDICAL JOURNAL Journal of the New Zealand Medical Association NZMJ 13 May 2011, Vol 124 No 1334; ISSN 1175 8716 URL: http://www.nzma.org.nz/journal/124-1334/4660/ Page 21 ©NZMA Sociodemographic differences in prevalence of diagnosed coronary heart disease in New Zealand estimated from linked national health records Simon Thornley, Wing Cheuk Chan, Sue Crengle, Tania Riddell, Shanthi Ameratunga, Suneela Mehta, Dudley Gentles, Sue Wells, Roger Marshall, Rod Jackson Abstract Aim To estimate sociodemographic differences in the prevalence of coronary heart disease (CHD) in New Zealand from linked health records. Methods We combined records of hospital treatment for CHD, dispensing of selected anti-anginal drugs and mortality to estimate the national point prevalence of coronary heart disease in New Zealand in December 2008. Stratified estimates are presented by gender; age; Māori, Pacific, Indian and 'Other'(mainly New Zealand European) ethnic groups; and socioeconomic status. Results Among a "health contact" population of adults (≥15 years), about one in twenty (6.5% of men and 4.1% of women) had indicators of a past diagnosis or treatment for CHD or both. Substantial differences in prevalence occurred by gender, ethnic group and socioeconomic status. For example, among New Zealanders aged 35 to 74 years, Indian men had the highest age-adjusted prevalence (7.78%; 95%CI 7.43 to 8.15), almost double the prevalence of 'Other' males. Among women, Māori had the highest adjusted prevalence (4.03%; 95%CI 3.89 to 4.17), just over twice that of 'Others.' Conclusion Major sociodemographic disparities in the national burden of CHD persist. Our results are similar to previous studies of ethnic disparities in CHD incidence, but also confirm concerns about the emerging CHD burden among South Asians. Indian males have the highest CHD prevalence of any gender-specific ethnic group. Of equal concern, Māori women have a similar prevalence to European males. Coronary heart disease (CHD) caused almost 6000 deaths in New Zealand in 2006,1 over twice that from stroke, the second highest disease-specific cause of death.2 Given that half of these deaths occur in people with prevalent CHD,3 timely and accurate estimates of prevalence are required to allocate resources to the health sector and also to monitor the effect of prevention programmes. Annual CHD mortality data are readily available from routine data collections and provide one indicator of the population burden of CHD, but prevalence, which is a better indicator of the current burden of disease, is, to date, not well documented. We sought to describe and compare the prevalence of coronary heart disease in New Zealand among different sociodemographic groups.
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NZMJ 13 May 2011, Vol 124 No 1334; ISSN 1175 8716 URL: http://www.nzma.org.nz/journal/124-1334/4660/ Page 22 ©NZMA Methods Denominator population—We linked routine national datasets to estimate the point prevalence of CHD in New Zealand residents. Every New Zealander now has a unique identifying code, the National Health Index (NHI) that is linked to most national health databases. The coverage of this indicator has increased substantially in recent years to over 94% from 2005. People with diagnosed CHD were identified from a denominator population, derived from linked, multiple, national health datasets (see below) to identify a 'health contact population' for New Zealand in 2008. This group became the denominator for all subsequent calculations. This method was preferred over using census population counts because variables for both numerator and denominator are derived from the same source, which avoids potential "numerator denominator bias". In New Zealand health datasets, a number of sociodemographic variables may be linked to individuals. Gender, age, ethnicity, and socioeconomic status of each participant were obtained as follows: ethnic group was taken from the 2nd quarter 2007 Primary Health Organisation (PHO) enrolment, using a prioritized method in the following order—Māori, Pacific, Indian and Other. Due to protocols of ethnicity data, other South Asian groups, such as Sri Lankans, Pakistanis and Bangladeshis cannot be accurately identified and are most likely to be recorded in the "Other" category (the majority of whom are New Zealand Europeans). NZDep2006, an area-based, decile measure of socioeconomic deprivation, was drawn from the meshblock recorded in PHO enrolment data, or if unavailable, taken from hospital discharge records (which represented a larger area measure – census area unit). Gender and age were recorded in the hospital discharge diagnosis dataset. People coded with overseas addresses were removed from the analysis. Appearance during 2008 in any of the following datasets defined the health contact, denominator population: • general medical subsidy (from visit to a GP) • last GP consultation • hospital discharge • pharmaceutical dispensing • laboratory claims • mental health service contact • immunisation register • PHO enrolment People who died during this year were removed to simulate a point prevalence survey carried out on the last day of 2008. Individuals were therefore assumed to be alive on the 31st of December 2008. The health contact population included between 89% and 94% of the census derived population estimate for the years 2005 to 2008.4 The variation was likely to be due to differences in the recording of people from different datasets in different years, with some recording, such as PHO enrolment only done at three yearly intervals. Numerator—Although much coronary artery disease is subclinical, and escapes medical attention, we focused on identifying individuals who had a clinical manifestation of their disease. From the "health contact" population, people were identified with diagnosed CHD if they had one or more of the following records indicating that they had received health care for this disorder: • Hospital discharge diagnosis of coronary artery disease (in years 1991–2008 with diagnostic ICD 10 or corresponding ICD 9 codes presented in Table 1) • One or more dispensing episodes for any of the following drugs used to treat CHD between 2007 and 2008: o glyceryl trinitrate o isosorbide dinitrate o isosorbide mononitrate o o nicorandil perhexiline
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NZMJ 13 May 2011, Vol 124 No 1334; ISSN 1175 8716 URL: http://www.nzma.org.nz/journal/124-1334/4660/ Page 23 ©NZMA These two treatment records are referred to by "hospital diagnosis" and "drug dispensing" in what follows. Table 1. ICD – 9/10 codes used to identify people with coronary artery disease Diagnosis or procedure description Coronary heart disease 410x to 414x Coronary angioplasty or stent or Percutaneous coronary intervention CABG ( including re-do procedures) 36.1x to 36.2x ICD 9 ICD 10 I20x to I25x 36.0x 3530400 to 3530501, 3531000 to 3531005 3849700 to 3850304, 9020100 to 9020103 3863700, 3845619, 3865308, 3850500 'x' refers to all next level subcodes Statistical analysis—Sociodemographic variables, including age, gender, ethnicity and NZDep06, were treated as categorical predictors (age was stratified into 5-year intervals). We used logistic regression to adjust for the effects of these variables and derive comparable estimates using R software.5 Scaled rectangle diagrams, which are like scaled Venn diagrams, depicted the relative size and degree overlap between datasets.6 Results The health contact population, in 2008, was equivalent to 90% (3,842,402/4,268,900) of the estimated intercensus population.4 Our analyses were restricted to people over the age of 15 years, and comprised a total of 2,985,877 people (88% of the equivalent intercensus estimate of 3,385,550). The overall prevalence of CHD in our cohort was 5.8% (174,399/2,985,877). A scaled rectangle diagram illustrates how people with CHD were identified (Figure 1). The smaller, higher, square is proportional to the number identified by drug dispensing, with the larger square representing cases selected by hospital diagnosis. Figure 1. Scaled rectangle diagram, showing overlap between databases used to identify people with CHD (by Drug-community dispensing; Diagnosi-discharge diagnoses)
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NZMJ 13 May 2011, Vol 124 No 1334; ISSN 1175 8716 URL: http://www.nzma.org.nz/journal/124-1334/4660/ Page 24 ©NZMA Most of the CHD population was found by hospital diagnosis, with drug dispensing capturing an additional 22% (38,905/174,399) of the total. About one in three people identified with CHD (36%; 63,147/174,399) were located in both sources. Table 2. Numbers and prevalence of people with CHD, by sociodemographic variables Characteristic Total Female Male Age category 15 to 19 20 to 24 25 to 29 30 to 34 35 to 39 40 to 44 45 to 49 50 to 54 55 to 59 60 to 64 65 to 69 70 to 74 75 to 79 80 to 84 85 plus Ethnic group Māori Pacific Indian Other NZDep06# 1 and 2 3 and 4 5 and 6 7 and 8 9 and 10 Missing CHD* counts (column %) 174399 77194 (44.3) 97205 (55.7) 112 (0.064) 166 (0.10) 209 (0.12) 395 (0.23) 1088 (0.62) 2779 (1.6) 5979 (3.4) 10042 (5.8) 14827 (8.5) 20438 (11.7) 23354 (13.4) 24757 (14.2) 26007 (14.9) 23273 (13.3) 20973 (12.0) 13143 (8.4) 5004 (3.2) 2962 (1.9) 134625 (86.4) 25460 (14.6) 29232 (16.8) 37206 (21.3) 44519 (25.5) 37202 (21.3) 780 (0.45) Denominator counts (column %) 2985887 1623254 (54.4) 1362633 (45.6) 271915 (9.1) 241430 (8.1) 221941 (7.4) 230813 (7.7) 271827 (9.1) 271986 (9.1) 281474 (9.4) 247884 (8.3) 223096 (7.5) 200806 (6.7) 159935 (5.4) 122970 (4.1) 101091 (3.4) 75968 (2.5) 62751 (2.1) 348222 (11.7) 175047 (5.9) 75604 (2.5) 2387014 (79.9) 552025 (18.5) 541858 (18.1) 599491 (20.1) 650945 (21.8) 623386 (20.9) 18182 (0.6) Crude CHD prevalence (%) 5.8 4.1 6.5 0.041 0.069 0.094 0.17 0.40 1.0 2.1 4.1 6.6 10.2 14.6 20.1 25.7 30.6 33.4 4.2 3.2 4.5 6.3 4.6 5.4 6.2 6.8 6.0 4.3 *CHD – coronary heart disease; #NZDep06 – an area based measure of socioeconomic status. The study population and crude prevalence estimates are summarised in Table 2. As expected, very few people developed CHD before the age of 35, and the proportion with CHD increases with age to one in three people aged over 85 years. As prevalence proportions by gender, ethnic group and socioeconomic status (NZdep06) are hard to interpret due to their different age structures, we present such data, by age group, in a series of figures (Figs 2–5).
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NZMJ 13 May 2011, Vol 124 No 1334; ISSN 1175 8716 URL: http://www.nzma.org.nz/journal/124-1334/4660/ Page 25 ©NZMA Figure 2. Age-specific prevalence of cardiovascular disease, by gender. F-female; M-male. Diagnosed CHD prevalence increased with advancing age up to age 80 to 84 years, and was higher in males than females in all age groups (Figure 2). At age 50-54 years CHD prevalence in males was just over 5% and in females was about 2.5%. By age 75 to 79 years this had increased to 30% in males and 22% in females. CHD prevalence increased with higher deprivation across all age groups up to ages 75 to 79 years (Figure 3). From age 80 years prevalence levelled off or fell slightly in the most deprived quintile.
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NZMJ 13 May 2011, Vol 124 No 1334; ISSN 1175 8716 URL: http://www.nzma.org.nz/journal/124-1334/4660/ Page 26 ©NZMA Figure 3. Age-specific CHD prevalence by socioeconomic status; lowess smoothed Age categoryProportion0.000.050.100.188.8.131.520.3525 to 29 30 to 34 35 to 39 40 to 44 45 to 49 50 to 54 55 to 59 60 to 64 65 to 69 70 to 74 75 to 79 80 to 84 85 plusNZdep061 and 2 least deprived3 and 45 and 67 and 89 and 10 most deprivedMissing
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NZMJ 13 May 2011, Vol 124 No 1334; ISSN 1175 8716 URL: http://www.nzma.org.nz/journal/124-1334/4660/ Page 27 ©NZMA Figure 4. Age-specific CHD prevalence by ethnic group (males); lowess smoothed CHD prevalence was highest in Indian males in all age groups (Figure 4). Māori males had the next highest prevalence up to age 74 years. Pacific men had the third highest CHD prevalence up to age 64 years after which 'Other' men (mainly New Zealand Europeans) had the third highest prevalence. Over age 75 years the prevalence of CHD in 'Other' men was higher than Māori men. While CHD prevalence continued to increase almost exponentially in Indian and 'Other' men throughout the age range examined, it began to flatten out in Pacific men after about age 55 to 65 years and a similar pattern was observed in Māori men after age 65 to 75 years.
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NZMJ 13 May 2011, Vol 124 No 1334; ISSN 1175 8716 URL: http://www.nzma.org.nz/journal/124-1334/4660/ Page 28 ©NZMA Figure 5. Age-specific CHD prevalence by ethnic group (females); lowess smoothed Among women (Figure 5), Māori had the highest CHD prevalence at all ages. Pacific women had the next highest prevalence up to age 55 years, when they were overtaken by Indian women. 'Other' women had the lowest CHD prevalence up to age 70 to 74 years, after which, they overtook Pacific women. The ethnic-specific prevalence patterns in women over the age of 80 years were unstable, although as with men, Pacific women aged over 85 years had the lowest CHD prevalence. Of note, Māori women had somewhat similar prevalence patterns to 'Other' men.
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NZMJ 13 May 2011, Vol 124 No 1334; ISSN 1175 8716 URL: http://www.nzma.org.nz/journal/124-1334/4660/ Page 29 ©NZMA Figure 6. Age-specific CHD prevalence by selected ethnic group and socioeconomic status combinations; lowess smoothed Figure 6 shows CHD prevalence in the highest and lowest socioeconomic quintiles for Māori and the 'Other' ethnic groups. Prevalence is higher among the least deprived quintile of Māori when compared to the most deprived 'Other' ethnic group, although this pattern is not observed after the age of 75 years. We also estimated prevalence by ethnic group using logistic regression, and adjusting for age, in one analysis, and both age and deprivation in another (Table 3). In these analyses the substantial age differences in prevalence observed in Figures 2-6 are effectively averaged. The age-adjusted differences in prevalence between ethnic groups was attenuated after adjustment for socioeconomic status (Figure 3).
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NZMJ 13 May 2011, Vol 124 No 1334; ISSN 1175 8716 URL: http://www.nzma.org.nz/journal/124-1334/4660/ Page 30 ©NZMA Table 3. Age and age & deprivation adjusted prevalences (logistic models) of CHD by gender and ethnic group, age 35 to 74 years Gender Ethnic group Age-adjusted prevalence (95%CI) 6.21 (6.05–6.38) 5.04 (4.84–5.24) 7.78 (7.43–8.15) 4.20 (4.14–4.27) 4.03 (3.89–4.17) 2.42 (2.29–2.55) 2.60 (2.41–2.81) 1.70 (1.66–1.74) Age & deprivation-adjusted prevalence (95%CI) 5.68 (5.53–5.84) 4.49 (4.31–4.68) 7.51 (7.17–7.87) 4.28 (4.22–4.35) 3.48 (3.35–3.60) 2.01 (1.90–2.13) 2.47 (2.29–2.67) 1.75 (1.71–1.79) Males Māori Pacific Indian Other Māori Pacific Indian Other Females Discussion We present the first direct (not modelled from life tables7) national estimates of diagnosed CHD prevalence, by sociodemographic status, undertaken in New Zealand. Such analyses were only possible because almost all New Zealanders now have a unique health identifier that can be anonymously and accurately linked to multiple health datasets. As expected, CHD prevalence differed by age group with 6 to 7-fold increases in prevalence between ages 50 to 54 years and 75 to 79 years. Also, as expected, males had 1.5 to 3 times the CHD prevalence as females of the same ethnic group, with Indians experiencing the greatest gender difference. Of note, Indian males had the highest prevalence of CHD in all age groups. Māori males had the second highest CHD prevalence, and of particular concern, in some age groups, Māori females had higher CHD prevalence than Pacific and 'Other' males. Similar to international studies, CHD prevalence was highest among people residing in more deprived areas. This effect would probably have been more marked if an individual (rather than the area based measure used here) marker of socioeconomic status was used. Part of the effect of ethnic group on CHD status is likely to be mediated through adverse effects on an individual's socioeconomic position. Therefore, as we observed, controlling for area-based deprivation reduced, but did not fully account for, between-ethnic group differences in CHD prevalence. Our results are strengthened by comprehensive coverage of routinely collected health data in New Zealand, which has improved substantially over the last three years. The method of estimating prevalence that we used obviates some of the limitations of community surveys. As a result of the low cost of data acquisition and near complete capture of health events, the analysis does not suffer from random error due to small numbers, or from responder bias common with health surveys (for example, the response rate of the latest New Zealand Health Survey was only 69%).8 Our health contact population was defined by at least one record of health-related care during 2008 which excludes about 10% of the census estimated population. The omitted 10% may not require healthcare due to excellent health status, or alternatively, do not access healthcare (except in dire circumstances). Using the health contact population denominator, however, will reduce the potential for other bias, if
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NZMJ 13 May 2011, Vol 124 No 1334; ISSN 1175 8716 URL: http://www.nzma.org.nz/journal/124-1334/4660/ Page 31 ©NZMA for example, individuals may be recorded in the denominator, but due to overseas travel or other reasons, are not able to be included in the disease (numerator) class if such an event occurs. Moreover, this approach prevents numerator-denominator bias related to ethnicity or deprivation classification as these variables were derived from the same, NHI linked, dataset for both the numerator and denominator in all calculations. The prevalences that we have estimated are, however, defined as those in the "health contact" population, and need to be regarded as such. As the health contact population undercounts the actual census count population by about 10%, the prevalences among the entire population will be correspondingly lower, if the numerator captures all cases of CHD. Limitations of the study include the lack of validity testing of our method. Whilst CHD diagnostic codes are likely to be reasonably accurate, our method of using drug dispensing, as an indicator of diagnosis, may result in some measurement error because some patients may be taking anti-anginal (particularly nitrate) drugs for either a therapeutic trial, when the diagnosis is not securely made; or for other indications, such as end stage liver disease. This group contributes <25% to the total estimate (Figure 1). If we apply a more strict criterion for CHD diagnosis, based on at least two anti-anginal dispensing episodes, the total prevalence of CHD reduces to 5.2% in people aged over 15 years (about 25,000 fewer cases). Also, with routinely collected data, important clinical and behavioural characteristics are not captured, such as smoking status and blood pressure. Such data would considerably assist untangling why such inequalities exist. From experience in other health care datasets, recording of diagnosis information is less likely to be accurate in older age groups,9 and this phenomenon may partly explain the large variation in prevalence at this end of the age range. Māori, in particular, have lower than expected prevalence in older age groups. Several explanations are possible. Firstly, fewer Māori and Pacific people may receive nitrate treatment, and, in support of this hypothesis, a separate analysis of the Counties Manukau population data showed no drop-off for Māori males when nitrates were excluded from the prevalence definition. Alternatively, higher case-fatality among Māori and Pacific people, as has been previously documented,3 may lead to this lower than expected prevalence. Such an issue will be studied in a future paper. Due to the protocols which determine the way ethnicity data is collected in New Zealand, in our analysis, non-Indian South Asian groups (Sri Lankan, Bangladeshi, Pakistani) were unable to be distinguished from several ethnic groups likely to have lower prevalence of CHD, such as Japanese and Korean people (all classified as "Other Asian"). This poor classification of Asian ethnicity would have led to an under-estimate of the prevalence of CHD in South Asians if all Asians were included as South Asians. Therefore we limited our analyses of South Asians to the "Indian" ethnic group (which includes Fijian Indians). A similar study, undertaken in 2007, documented the prevalence of a larger cluster of diagnoses - cardiovascular disease (CVD) - using a similar technique which combined historic hospital diagnoses and pharmaceutical use.10 This study reported CVD
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NZMJ 13 May 2011, Vol 124 No 1334; ISSN 1175 8716 URL: http://www.nzma.org.nz/journal/124-1334/4660/ Page 32 ©NZMA prevalence that was about 20% higher than our CHD estimates in older age groups. In addition, Māori – non Māori disparities in CVD burden were greater than for CHD burden. In our study, Indian males had the highest age-adjusted CHD prevalence, whereas Māori men had the highest ethnic-specific CVD prevalence. In both the CVD and CHD analyses, Māori had the highest prevalence in women. Gender and deprivation effects appeared similar in the two studies when examined by age category. The last published estimate of CHD prevalence was reported by Tobias and colleagues who analysed 2001-03 data and estimated CHD prevalence using multi-state lifetable modelling.7 In this study, incidence (from hospital diagnosis data) of CHD and mortality rates were used to mathematically derive prevalence. They reported overall male and female case numbers, that when combined with historic census data from 2003, gave a significantly lower overall CHD prevalence in the over 15 age group, compared to our calculations (Tobias male 3.8% and female 2.5%; compared to our male 6.5% and female 4.1%). The modelling approach may have underestimated CHD prevalence or our approach over-estimated it, however, the difference could not be accounted for entirely by our definition of prevalence using the health contact population as a denominator. In the former paper, only people with primary discharge codes of CHD were included, while our study used both primary and secondary codes. In addition, we included people who were dispensed anti-anginal agents but without CHD-coded hospital discharge records, which accounted for about 22% of CHD cases in our analyses. While our analyses are likely to better describe the current overall prevalence of CHD, both methods can be used to monitor change over time. Moreover the more restrictive approach taken by Tobias and colleagues is not prone to biases caused by changes in prescribing practice. Our most important findings were variations found by ethnic group and gender on CHD prevalence. Differences in smoking prevalence may account for some of these observed patterns. Smoking prevalence among Māori was higher in women (50.3%) than men (42.5%) in 2006 census data8 while estimates of Asian smoking show much higher prevalence in males (16.3% male; 3.4% female). The high prevalence of smoking among Māori is also likely to increase their case-fatality rate, which would tend to reduce prevalence but increase incidence. In addition to such risk factors, drug based primary prevention may differ between ethnic groups. For example, in the early 2000s, Māori were less likely to be screened for diabetes, and Māori people with diabetes were less likely to be treated with drugs that reduce the incidence of CHD events, such as statins and ACE-inhibitors, compared to other ethnic groups.11 Our analyses have accounted for differences in socioeconomic deprivation, but we did not include the other data required to determine if the standard risk factors (e.g. blood pressure, lipids, diabetes, smoking status) explain the ethnic prevalence differences. The reason for the high rates of CHD found in Indian men deserves further investigation, with attention to issues that may vary based on country of origin, migrant status and time in New Zealand. Similar, relatively high, rates of disease in South Asians living in Britain have been recorded, which have been attributed to their
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NZMJ 13 May 2011, Vol 124 No 1334; ISSN 1175 8716 URL: http://www.nzma.org.nz/journal/124-1334/4660/ Page 33 ©NZMA high prevalence of: diabetes, insulin resistance and raised serum triglycerides.12 Differences in diet may explain much of these high levels of risk factors, although exploring which nutritional element is responsible for these dramatic ethnic disparities in disease prevalence remains to be investigated. From a public health perspective, our findings highlight the considerable burden of CHD in the community, particularly among people over 50 years of age; and in Māori, Pacific and Indian men and women. From a clinical perspective, this prevalence information supports the use of a risk adjuster for Māori, Pacific and Indian peoples in New Zealand guidelines for the enrolment, assessment and management of CVD risk.13 Future work is planned to more fully explore the clinical and policy implications of this study. From an equity viewpoint, our analyses highlight where limited cardiovascular health resources require allocation and primary prevention strategies should be targeted. Competing interests: None. Author information: Simon Thornley, Research Fellow and Lecturer, Section of Epidemiology and Biostatistics, University of Auckland; Wing-Cheuk Chan, Public Health Physician, Counties Manukau District Health Board, Manukau City; Sue Crengle, Senior Lecturer, Te Kupenga Hauora Māori, School of Population Health, Tamaki Campus, University of Auckland; Tania Riddell, Research Fellow, Section of Epidemiology and Biostatistics, University of Auckland; Shanthi Ameratunga, Professor of Epidemiology, Section of Epidemiology and Biostatistics, University of Auckland; Suneela Mehta, Public Health Medicine Registrar, Section of Epidemiology and Biostatistics, University of Auckland; Dudley Gentles, Biostatistician, Section of Epidemiology and Biostatistics, University of Auckland; Sue Wells, Senior Lecturer, Section of Epidemiology and Biostatistics, University of Auckland; Roger Marshall, Associate-Professor of Biostatistics, Section of Epidemiology and Biostatistics, University of Auckland; Rod Jackson, Professor of Epidemiology, Section of Epidemiology and Biostatistics, University of Auckland Acknowledgements: This work was funded, in full, by a National Heart Foundation of New Zealand research grant. We also thank Dean Papa for assistance with data extraction. Correspondence: Simon Thornley, Research Fellow/Lecturer, Section of Epidemiology and Biostatistics, School of Population Health, Tamaki Campus, University of Auckland, Private Bag 92019, Auckland, New Zealand. Fax: +64 (0)9 2629501; email: firstname.lastname@example.com References: 1. Ministry of Health. Mortality and Demographic Data 2006. Wellington: Ministry of Health, 2009. 2. Tobias M, Turley M. Causes of death classified by risk and condition, New Zealand 1997. Aust N Z J Public Health. 2005;29(1):5–12. 3. Bullen C, Beaglehole R. Ethnic differences in coronary heart disease case fatality rates in Auckland. Aust N Z J Public Health. 1997;21(7):688–93. 4. Statistics New Zealand. 2006 Census. Wellington: Statistics New Zealand, 2010. 5. R Development Core Team. R: A language and environment for statistical computing. Vienna: R Foundation for Statistical Computing, 2007.
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NZMJ 13 May 2011, Vol 124 No 1334; ISSN 1175 8716 URL: http://www.nzma.org.nz/journal/124-1334/4660/ Page 34 ©NZMA 6. Marshall RJ. Scaled rectangle diagrams can be used to visualize clinical and epidemiological data. J Clin Epidemiol. 2005;58(10):974–81. 7. Tobias M, Chan W, Wright C, et al. Can the incidence and prevalence of coronary heart disease be determined from routinely collected national data? Population-based estimates for New Zealand in 2001-03. Aust N Z J Public Health. 2008;32(1):24–7. 8. Ministry of Health. A Portrait of Health: Key Results of the 2006/07 New Zealand Health Survey. Wellington: Ministry of Health, 2008. 9. Rosen M, Hakulinen T. Use of Disease Registers. In: Ahrens W, Pigeot I, editors. Handbook of Epidemiology. Berlin: Springer-Verlag, 2005. 10. Chan WC, Wright C, Riddell T, et al. Ethnic and socioeconomic disparities in the prevalence of cardiovascular disease in New Zealand. N Z Med J. 2008;121(1285):11–20. 11. Dawson S. Diabetes in New Zealand. Wellington: Ministry of Health, 2003. 12. Cappuccio FP. Ethnicity and cardiovascular risk: variations in people of African ancestry and South Asian origin. J Hum Hypertens. 1997;11(9):571–6. 13. New Zealand Guidelines Group. The assessment and management of cardiovascular risk. Wellington: New Zealand Guidelines Group, 2003.
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The Dutch education ministry wants to ban universities from investing in derivatives, Times Higher Education reported. Derivatives have become a popular financial strategy for many Dutch universities, but the government fears that twists in the economy could leave the universities in a highly vulnerable position because of the reliance on these investments.
Historian in Britain tries to remind students why they shouldn't skip his classes.
Japan's Education Ministry is preparing to allow universities to use a quarter system in addition to the traditional semester system, The Yomiuri Shimbun reported. In the current system, students take up to 10 courses a semester but the courses meet only once a week, and critics say that there is not enough focus on anything. Under a quarter system, students would take fewer courses but they would meet twice a week.
The National College of the Arts in Lahore, Pakistan's leading art college, is under heavy criticism from Islamic traditionalists over its journal, which published homoerotic images that also depicted Muslim clerics, the Associated Press reported. The college has shut down the journal, pulled all copies of the journal from bookstores and dissolved the journal's editorial board, the AP reported. But those actions have not stopped the controversy. A court is considering blasphemy charges against the journal's editorial board and the head of the college.
A New York Times article examines the potential for conflict of interest in Quacquarelli Symonds (known as QS) operating an international rankings system for universities and also a "ratings" system -- with the latter open to those who pay for an audit. The article notes that institutions that do poorly in international rankings (which tend to give the highest marks to research universities known around the world) are evaluated on different criteria, and are then awarded stars that they can use to boast and to recruit students. Two universities in Ireland are cited as examples of institutions that paid QS and now boast five-star ratings. Several international education experts are quoted expressing skepticism about whether the stars are meaningful. But the universities say that if they attract more students, their payments to QS will be worth it.
Indian President Pranab Mukherjee on Friday gave a speech calling for better standards and an enhanced private-sector role in higher education, Outlook India reported.
Mukherjee said that while ancient India had universities that were considered world leaders, many Indians today feel that they must leave the country to obtain the best possible higher education. He said that the country's top universities need to be able to compete in the top levels of international rankings, where their absence is the subject of much discussion in the country. "We must change the reality of our universities not figuring in the list of top universities of the world. Indian universities should aim at becoming top educational institutions in the world with global standards of research, teaching and learning," he said.
Further, he said that the country need more than its public universities. "It is important that the private sector also contributes its best to the provision of higher education in India," he said. "The private sector has played a key role in higher education in other countries across the world. Many top universities including Harvard, Yale and Stanford are the result of efforts of the private sector. There is no reason why Indian private sector cannot achieve similar results."
Israeli authorities on Monday granted full university status to the Ariel University Center, a higher education center on the West Bank whose future has become a hotly debated issue in Israeli academic and political circles, The Jerusalem Post reported. Advocates for Israeli settlements on the West Bank have pushed for the center to be given the same status as other Israeli universities. But many Israeli academics -- professors and administrators alike -- have opposed the idea. Some have argued that the move will link Israeli higher education to the government's policies supporting greater West Bank settlement -- policies that many Israel academics abhor. Other academics have offered more practical criticism, arguing that there isn't enough money for the country to support an eighth full-fledged university. An editorial in the Israeli newspaper Haaretz said that the move undercut the independence of Israeli higher education.
Seeking to block Monday's decision, the Council of Presidents of Israeli Universities on Tuesday asked the High Court of Justice to block the elevation of Ariel. On Wednesday, the court rejected a request for an injunction to block the change in status.
Sector's stratospheric enrollment growth flattens, in wake of policy changes that restricted flow of public funds to students at private institutions.
Scientists in Spain have been holding protests all week over cuts to research budgets, Nature reported. Government spending on science has been cut by 39 percent since 2009. In Madrid, scientists released balloons to symbolize the departure of talent from the country.
Cabinet member in charge of higher education policy says wealthy donors "buy a place" for offspring at elite American institutions.
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Editor's Note: Yes, it's that time of year again – the time for us to settle back into our protective bubble where the Chicago Cubs are destined for greatness, and[Read More…]
Editor's Note: Yes, it's that time of year again – the time for us to settle back into our protective bubble where the Chicago Cubs are destined for greatness, and[Read More…]
The Chicago Cubs dabbled in the Kiko Calero trade for many a week this offseason, eventually off-put by his past shoulder problems and demands for a multi-year deal. So it's[Read More…]
Editor's Note: Yes, it's that time of year again – the time for us to settle back into our protective bubble where the Chicago Cubs are destined for greatness, and[Read More…]
The Chicago Cubs have announced their broadcast schedule for the 2010 season, and it will feature the lowest number of games on WGN in a long, long time – just[Read More…]
Sports Illustrated's Jon Heyman threw together a list of the eight most disappointing offseasons in Major League Baseball this year, and – no surprise – the Chicago Cubs made the[Read More…]
Free agent starter Ben Sheets threw for several teams including the Chicago Cubs on Tuesday. Fortunately or unfortunately, depending on your perspective, the session was widely well-received. Sheets' fastball hung[Read More…]
Get ready to be overloaded with "addition by subtraction" type optimism pieces as we gear up for the 2010 Chicago Cubs season. The Cubs, apparently, are going to win eight[Read More…]
The market for starting pitcher Joel Pineiro has been both slow to develop and seemingly thin. It's hard to figure, given that his tremendous 2009 season was not necessarily an[Read More…]
Two weeks ago, it looked like the St. Louis Cardinals were going to lose Mark DeRosa, Joel Pineiro, John Smoltz, and Matt Holliday this offseason. Things were looking up for[Read More…]
Is he or isn't he? That's what the Cublogoverse is trying to figure out today about Chicago Cubs' ace (yes, he is an ace) Carlos Zambrano's availability. A few days[Read More…]
With Mark DeRosa leaving and Joel Pineiro set to leave, the St. Louis Cardinals were poised to be significantly worse (on paper) in 2010 than they were at the close[Read More…]
When the New York Mets signed Jason Bay on Tuesday, they conceivably shrunk the outfield market for the Chicago Cubs (by making Jacoby Ellsbury slightly less likely to be traded).[Read More…]
Mini-update, as it relates to the Chicago Cubs: With Bay going to the New York Mets, that's one fewer outfielder who could take a spot in the Boston Red Sox[Read More…]
It may shock you, but trading Milton Bradley for "pitcher" Carlos Silva was not the Chicago Cubs' idea of the perfect trade. The Cubs actually almost participated in a four-team[Read More…]
The Chicago Cubs were among approximately one thousand teams on hand to scout Cuban hurler Aroldis Chapman yesterday. Chapman, 21, recently defected from the socialist paradise down south, and is[Read More…]
Apparently, when Jim Hendry traded Aaron Heilman earlier this offseason to the Diamondbacks, it wasn't purely a salary dump or a dealing from a position of surplus. Silly us, we[Read More…]
Although sending Milton Bradley to Tampa for Pat Burrell remains the far most likely scenario, the Chicago Cubs are working to increase the possible destinations for Bradley. Meanwhile, the Cubs[Read More…]
Joel Sherman of the New York Post has tweeted that, if the Cubs are able to swing a Milton Bradley / Pat Burrell swap, the Mets are interested in a[Read More…]
There's been so much smoke surrounding the Chicago Cubs' efforts to swing a deal with Tampa Bay involving Milton Bradley and Pat Burrell that we're all choking on it. Still[Read More…]
As if signing reliever John Grabow to a two year $7 million contract was not enough indignity for a team approaching its budget limitations and with needs in the infield,[Read More…]
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24" Combination Microwave Single Electric Wall Oven with 1.34 cu. ft. Convection Oven, Digital Programming Controls and 6 Cooking Modes
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24" Single Electric Wall Oven with 3.1 cu. ft. Capacity, 3600 Watt Broil Element, Dual Interior Lighting, Delay Cook Setting, Sabbath Mode and Keep Warm Setting
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Latest News
Return to the Forbidden Planet Auditions
The biggest rock 'n' roll show is coming your way soon!
Join Captain Tempest and his crew on an epic voyage along with green monsters, a roller skating robot and insane scientist to boot.
All your favourite rock 'n' roll hits will be featured in this hot feature from Riverside Players coming to you in summer 2016 so buckle up, suit up and get ready for an intergalactic voyage into hyperspace… and beyond!
Be a part of that by auditioning for Return for the Forbidden Planet on October 4th at Anthony Roper School at 2pm.
All assets are available to download at the bottom of this post
The Crew
Captain Tempest – Male 28-40
The Captain of the Albatross, Tempest needs to have the authority to command the crew. He is the all American hero, with a pipe in one hand and apple pie in the other. He is stern but good natured and will always try to do the right thing.
Bosun –Male/Female, any age
The Bosun is Tempest's right hand man, a senior officer but not officer class. Coarser than his Captain, he is nevertheless fiercely loyal – but perhaps a little too eager in some cases.
Science Officer / Gloria – Female, 34+
The "new science officer" who dramatically is revealsed to be the ex-wife of Prospero. She is a cold, calculating, smart and sassy space woman. She's the only woman to get this far in the Space Core – and she didn't sleep her way to the top.
Cookie – Male, 18-25
The youngest (and least respected) member of the crew. He is a young, impressionable and easily led young man. Falls in love with Miranda and then plots revenge when it isn't returned.
Navigation Officer – Male/Female, Any Age
The person driving this damn tub! The Navigation Officer keeps the ship on course, with a few choice lines and some nice solo lines in the songs.
Crew – Any Sex, Any Age
Due to the needs of the show, there will be a few roles for musicians without given names in the script. There are a few lines that are up for grabs, but mainly they'll need to help make the music slick as well as making the ship look busy when necessary. If you're a musician that would rather rock out without too many Shakespearean lines to learn, this is the part for you!
The Outsiders
Doctor Prospero – Male, 39+
The Mad Scientist who is father to Miranda and ex-husband to Gloria. He feels maligned by the world, despite his obvious genius. He is a very protective father, but he is clearly someone who holds a grudge. Knows he is smarter than everyone else.
Miranda – Female, 15 – 21
The sweet, innocent daughter of Prospero and Gloria. She has never met anyone but her father and Ariel – making everything strange and exciting.
Ariel – Any Gender, Any Age
The robot created by Prospero to do his bidding. A wonder to behold – guardian of Miranda and bound to Prospero.
Audition Assets
Jack and the Beanstalk 2016 Auditions
Dear Lords and Ladies of Pantoland,
Yes it's that time again! (Oh no it isn't etc.) As I invite you all to attend auditions for the January 2016 production of Jack and the Beanstalk.
READTHROUGH DATE Monday 21st September, 8pm, EVH
AUDITION DATE Sunday 27th September 1pm, EVH
(Please do let me know at the earliest possible date if you cannot attend and I will arrange another audition with you BEFORE this date).
This story takes you to the once lovely land of Eynsinham (see what I did there). Unfortunately, the land has been over run by the evil Giant Blunderbore who claims taxes and riches off the Eynsigham's residents through his evil henchman Fleshcreep. Surely somebody is brave enough to stop this torment…? Cue Jack Trott, a brave, young, courageous boy who believes he can make a difference.
Of course, Jack is not alone….
Jack and the Beanstalk (J&B), has always been one of my favorite pantomime stories. It's got so much potential for an exciting family story with lots of fun loving characters to be involved.
I'm very excited about this new project, as I embark on directing my very first pantomime. Quite frankly, if the gags aren't funny, I've got nobody to blame but myself, as I also wrote the script!
I've already got an amazing production team working on this already and I now need those darling 'luvvies'.
Any problems or questions please contact me on 07507837931 or email@example.com
It will be fun, it will be cheesy and it will be one big spectacular adventure.
See you there,
|Playing Details
|Spoken Audition Piece
|Singing Audition Piece
|Jack Trott
|Male/Female 18-30
|The hero of the story. Although Jack is technically labeled as, the 'principal boy', I do not see him as a 'Prince Charming' type character, who goes out to seek the girl. He is poor boy (though not common) who wants to bring freedom to those he loves so dear and will do whatever it takes to do so. He loves Tamara. Jack has a fight scene.
|Jack and FleshcreepJack, Billy and Tamara
|I'll be there for you
|Princess Tamara
|Female 16-28
|The princess of the land who captures Jack's heart. She, like Jack, is kind and determined to bring freedom to the land and its people. She is not scared of Fleshcreep and she is one of the only characters brave enough to stand up to him. She loves Jack.
|Jack, Billy and TamaraFleshcreep and Tamara
|Holding Out for a Hero
|Dame Trott
|Male 30+
|Jack and Billy's mother, who provides much of the comedy for this pantomime. The Dame considers herself to be very sexy, much to the audience's disbelief! Uses several pet names for her two sons. She is always on the hunt for a new man.
|Dame TrottDame and Billy
|I'll be there for you
|Silly Billy
|Male any age
|The comic of the story. Partnered with Dame Trott for the majority of his stage time. Billy is probably the character with the most interaction with the audience so a high level energy performance is required. Billy does have a very messy slapstick scene with Dame Trott, which the audience should hopefully find very comical.
|Dame and BillyJack, Billy and Tamara
|I'll be there for you
|Male 30+
|The giant's representative on the land. Fleshcreep is mean and nasty towards everybody with the exception of his master (the Giant). He will go out of his way to make everybody's life a misery, as that is what makes him happy. A very menacing performance is required. Fleshcreep has a fight scene.
|Fleshcreep and TamaraJack and Fleshcreep
|I'll be there for you
|Fairy Flora
|Female any age
|This character is kind and not scary
She is the very lovely vegetable fairy
She is very caring and wants to help Jack
To bring freedom and everyone's happiness back
But one thing you may notice, which she does all the time
Oh yes, indeed, she is forever talking in fancy rhyme
|Fairy Flora
|Let It Go
|King Alan Cremer XXXXIIII
|Male 45+
|Yes that's King Alan Cremer the 44th. I didn't need a lot of inspiration for this character's name!
He is Tamara's father and a very run down king indeed. He is the loveable character that tries to use his status to take charge of the situation, but he is really just as silly as the rest.
|King, Dave and Chas
|I'll be there for you
|Dave and Chas
|Male or Female 25+
|The king's idiotic henchmen. These two characters are very fun loving, full of life and have many gags between them. These roles require a strong comic duo that can work well together and are able to bounce of one another.
|King, Dave and ChasDave and Chas
|I'll be there for you
|Giant Blunderbore
|Male 30+
|The antagonist of the story, even though we actually don't see the Giant until very late into the second half his booming, menacing voice is heard throughout. Must exaggerate gestures, as this character will be in a skin like costume. The giant has a fight scene.
|I'll be there for you
|Daisy The Cow
|Male or Female any age
|Is what she is, a beautiful cow and the darling of the story. I need two (or potentially more) Daisy operators as it were. Even though the cow has no lines (apart from moo) I have no doubt that the audience will fall in love with her and she will steal the show. Must exaggerate gestures, as this character will be in a skin costume. THERE IS NO SPECIFIC AUDITION FOR THIS PART (if you are interested, please state on audition form)…you can show me your best 'mooing' impression if you please!
|All genders, all ages
|Lots of fun cameo parts and lots of cheesy numbers to dance and sing to. There is also a chance to not only be human characters, but ghosts and ghouls too. Like any show like this, I need a fun loving and enthusiastic chorus. Must have the ability to smile and have lots of energy.
|I'll be there for you
Jack and the Beanstalk 2016
Directed and Written by Lawrence Watling
This story takes you to the once lovely land of Eynsinham (see what I did there). Unfortunately, the land has been over run by the evil Giant Blunderbore who claims taxes and riches off the Eynsigham's residents through his evil henchman Fleshcreep. Surely somebody is brave enough to stop this torment…? Cue Jack Trott, a brave, young, courageous boy who believes he can make a difference.
Of course, Jack is not alone….
Jack and the Beanstalk (J&B), has always been one of my favorite pantomime stories. It's got so much potential for an exciting family story with lots of fun loving characters to be involved.
Audition Pieces here
Friday 22nd & 29th January 7:45pm
Saturday 23rd & 30th January 2pm and 7:45pm
Sunday 24th January 12:30pm and 4pm
Tickets on sale soon…
Updates from Committee Meeting Aug 15
The committee met on August the 4th and amongst the copious amounts of snacks and pizza, we also made some headway with the upcoming season.
October 15 Slot
The next show for October will be 'My Brilliant Divorce' directed by Julie Lovelock; a one woman show of which has recently had acclaim when Dawn French played the main character.
Outdoor Production Proposals
The slot for the outdoor production in summer 17 has now had a deadline set on it due to the planning required to do so. This has been set to the end of August and any directors wishing submit a proposal should send at least an outlined proposal by this date to be considered. Proposals should be sent to email@example.com
Spring 16 Slot Proposals
We were overwhelmed by the amount of support from directors and budding directors to put on a show in the October slot and we have taken a couple forward to be considered for the Spring 16 slot. This of course is still open to the entire group to propose something and any proposals should be submitted by the end of September and sent to firstname.lastname@example.com
Return to the Forbidden Planet, Summer 16
The date for auditions has been set to be in October, more on this coming very soon.
If any member of riverside players wishes to view the minutes to the Committee Meetings, they are available upon request by emailing firstname.lastname@example.com
House of Dracula
The youth group extravaganza coming at you on the 14th of November 2015 will be House of Dracula written by Martin Downing and directed by Naomi Wolfe and Amy Barclay.
This is an exciting production for the Youth Group, not only are the two groups coming back together to put on this show, but it also debuts Amy Barclay's fantastic writing capabilities with complimentary scenes along with a more adventurous set.
Tickets can be booked directly through Naomi:
07427 607003


text:
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The Northpoint Christian Trojans girls basketball team won Tuesday's home conference game against Lausanne Collegiate by a score of 53-52.
(January 11, 2011: Southaven, MS 38672) The Lausanne Collegiate Lynx basketball team (Memphis, TN), was nudged 53-52 in Tuesday's league battle with the host Southern Baptist Trojans (Southaven, MS)
The Trojans now possess a 8-6 record. They play next when they travel to Harding Academy for a Division II-A - West battle on Friday, January 14. Southern Baptist will battle a Lions team coming off a 50-24 league win over Bishop Byrne (Memphis, TN). The Lions record now stands at 8-5.
The Lynx (0-9) will now prepare for their battle against First Assembly Christian (Cordova, TN). The Crusaders come into the Division II-A - West battle with a 5-5 record.


text:
Internet and Catalog Retail
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Our data partners will research the update request and update the information on this page if necessary. Research and follow-up could take several weeks. If you have questions, you can contact them at email@example.com.


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Calandra Racing Concepts Hard Anodized Side Link Balls (4) (Low Roll Center)
This is a set of four CRC Hard Anodized Low Roll Center Side Link Balls. These side link balls are now finished in a hard anodized coating, which is smoother and longer lasting than the conventional colored anodizing.
This product was added to our catalog on September 29, 2009.
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Comments about Bunn 1.9 L Thermal Pitcher:
This carafe is great, we are very pleased with it and we use it everyday at the office.
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Weekend watch: NFL players with Utah ties in this weekend's preseason action
School: Utah State
Davis, a third-round pick by the Dolphins in this year's draft, is listed fourth on the depth chart, along with fellow draftee Jamar Taylor of Boise State.
- Oldest first
- Newest first
- Most recommended
Utah (center), Utah State (CB), byU (long snapper), Utah (LB*), Utah(DE), Utah
(DT*), Utah(CB).
That about sums it up!
Go Utes!!
- 3:27 p.m. Aug. 1, 2013
- Like (4)
- Report abuse
5 utes. 1 aggie. 1 cougar
That is about the average in the NFL as a whole
I love my Pac 12 membership and real athletes!
- 3:29 p.m. Aug. 1, 2013
- Like (1)
- Report abuse
dosent miami stink or something. now the ravens that's a team. if it wasn't for an unavoidable injury who would have been tabbed the best TE in the nfl?
- 8:58 p.m. Aug. 1, 2013
- Like
- Report abuse
RE: Chris B.
"5 utes. 1 aggie. 1 cougar. That is about the average in the NFL as a whole."
No need to exaggerate on this one, Chris. I give the Utes full props for getting players in the NFL. The number they place ranks favorably in the PAC 12 (middle of the pack, 6th I believe) and is probably ranked around 30th in the league while BYU has only as many as USU and probably ranks around 80-100. But let's not read too much into that… Cal places more in the NFL (44) than Texas, Alabama, and Oregon. Iowa (35) places more than Michigan, Wisconsin, and Nebraska. Fresno State (24) places more than Oregon State, Arizona, and Washington. I'm thrilled Utah has had so much success in getting players to the league, and I'm even more excited to see what they can do on the field in six weeks.
- 11:00 a.m. Aug. 2, 2013
- Like (3)
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text:
In response to Andrys Basten's photo, "Stolen but found Parthenope and Metiochus ( Metiokhos )":
What a nice find that ceramic piece must be! Glad you found this page if it helps. Unfortunately, Gaziantep is currently in the danger zone for visitors due to terrorist activity. Glad we were able to see it back in 2004, and we were lucky at the time to get in at the last minute.
posted by Andrys Basten
In response to Andrys Basten's Istanbul - Sultanahmet photos gallery:
You have to continue, I like it
posted by gazon
In response to Andrys Basten's photo, "One talks, the other listens. #0858":
Thanks to illustrator Mark Simmons --http://bit.ly/mark-simmons_oakland-zoo-elephants --I can say that these are probably Lisa (37 in 2014), on the left, and Donna (35 in 2014) on the right, whom the Oakland Zoo pages say are closely bonded and sleep together at night.... The zoo also says that Donna, the dominant elephant in the group of 4 is the most playful,and Lisa is called "water baby" because she loves her pool.... Here's Lisa enjoying a bath in her water pool: http://bit.ly/lisa-in-poolat the 8-acre area they can roam.
posted by Andrys Basten


text:
Located in in the charming neighborhood of Carouge, the Qu'importe is a renowned wine bar serving a large selection of wines by the glass as well as tapas.
Listed as a historic building, the Brunswick Monument is surprising in its architecture and history. This neo-Gothic-style mausoleum is a historical replica of the Scaligeri family tomb in Verona dating from the fourteenth century and built at the request of the Duke of Brunswick.


text:
|Publication number
|Publication type
|Application number
|Publication date
|May 30, 2006
|Filing date
|Mar 6, 2003
|Priority date
|Mar 6, 2003
|Fee status
|Publication number
|Sarath P. Gunasekera, Ross E. Longley, Amy E. Wright, John K. Reed
|Original Assignee
|Harbor Branch Oceanographic Institution, Inc.
|Export Citation
|BiBTeX, EndNote, RefMan
|Patent Citations (9), Non-Patent Citations (10), Classifications (12), Legal Events (5)
|External Links: USPTO, USPTO Assignment, Espacenet
This invention relates to lactone compounds and compositions which have useful therapeutic properties. More particularly, the invention provides compounds having antitumor activities, pharmaceutical compositions comprising such compounds, methods for the preparation of the compounds, and compositions and methods of their use.
Various tumor and cancer related diseases afflict man and animals. The term "tumor" refers to abnormal masses of new tissue growth which is discordant with the economy of the tissue of origin or of the host's body as a whole. Tumors inflict mammals and man with a variety of disorders and conditions, including various forms of cancer. The seriousness of cancer is well known, e.g. cancer is second only to heart and vascular diseases as a cause of death in man. Tumors are common in a variety of mammals, and the prevention and control of the growth and regression of tumors in mammals is important to man.
Considerable research and resources have been devoted to oncology and antitumor measures, including chemotherapy. While certain methods and chemical compositions have been developed which aid in inhibiting, remitting, or controlling the growth of tumors and other forms of cancer, further antitumor methods and chemical compositions are needed.
It has been found that some natural products and organisms are potential sources for chemical molecules having useful biological activities. For example, the diterpene commonly known as taxol, isolated from several species of yew trees, is a mitotic spindle poison that stabilizes microtubules and inhibits their depolymerization to free tubulin (Fuchs, D. A., R. K. Johnson [1978] Cancer Treat. Rep. 62:1219–1222; Schiff, P. B., J. Fant, S. B. Horwitz [1979] Nature (London) 22:665–667). Taxol is also known to have antitumor activity and has undergone a number of clinical trials which have shown it to be effective in the treatment of a wide range of cancers (Rowinski, E. K. R. C. Donehower [1995] N. Engl. J. Med. 332:1004–1014). See also, e.g., U.S. Pat. Nos. 5,157,049; 4,960,790; and 4,206,221.
Marine life has been the source for the discovery of compounds having varied biological activities. Some of the United States patents which have issued for such inventions are as follows: U.S. Pat. No. 4,548,814 for didemnins, having antiviral activity, were isolated from a marine tunicate; U.S. Pat. No. 4,729,996 discloses compounds, having antitumor properties, that were isolated from marine sponges Teichaxinella morchella and Ptilocaulis walpersi; U.S. Pat. No. 4,808,590 discloses compounds, having antiviral, antitumor, and antifungal properties, isolated from the marine sponge Theonella sp.; and U.S. Pat. No. 4,737,510 discloses compounds, having antiviral and antibacterial properties, isolated from the Caribbean sponge Agelas coniferin.
A number of publications disclose organic compounds derived from marine sponges including Scheuer, P. J. (ed.) Marine Natural Products, Chemical and Biological Perspectives, Academic Press, New York, 1978–1983, Vol. I–V; Uemura, D., K. Takahashi, T. Yamamoto, C. Katayama, J. Tanaka, Y. Okumura, Y. Hirata (1985) J. Am. Chem. Soc. 107:4796–4798; Minale, L. et al. (1976) Fortschr. Chem. org. Naturst. 33:1–72; Faulkner, D. J. (1998) Natural Products Reports 15:113–158; and Gunasekera, S. P., M. Gunasekera, R. E. Longley and G. K. Schulte (1990) "Discodermolide: A new bioactive polyhydroxy lactone from the marine sponge Discodermia dissoluta" J. Org. Chem., 55:4912–4915 [correction (1991) J. Org. Chem. 56:1346]. U.S. Pat. No. 4,808,590 discloses compounds, having antiviral, antitumor, and antifungal properties, isolated from the marine sponge Theonella sp. (International Patent Application No. WO 9824429; Kowalski, R. J., P. Giannakakou, S. P. Gunasekera et al. (1997) Mol. Pharmacol 52:613–622; ter Haar, E., R. J. Kowalski, E. Hamel et al. (1996) Biochemistry 35:243–250; Stafford, J. A. and M. M. Mehrotra (1995) Chemtract: Org. Chem. 8:41–47; and U.S. Pat. No. 5,789,605.
The subject invention provides novel lactone compounds having advantageous biological activities. Specifically, in one embodiment, the lactone compounds and compositions of the subject invention can be used in the treatment of an animal (including humans) hosting cancer cells, including, for example, inhibiting the growth of tumor cells in a mammalian host. More particularly, the subject compounds can be used for inhibiting in a human the growth of tumor cells, including cancer cells of the pancreas, breast, colon, CNS, ovarian, renal, prostrate, lung, leukemia and melanoma cells. Specifically exemplified is plakolide A and its analogs.
Also provided according to the subject invention are compositions containing the biologically active lactone compounds, as well as methods for the preparation and use of the compounds and compositions.
Other advantages and further scope of applicability of the present invention will become apparent from the detailed descriptions given herein; it should be understood, however, that the detailed descriptions, while indicating preferred embodiments of the invention, are given by way of illustration only, since various changes and modifications within the spirit and scope of the invention will become apparent from such descriptions.
The subject invention pertains, in part, to novel lactone compounds and the use of these compounds to prevent pathological cellular proliferation. In a specific embodiment, the subject invention pertains to a novel compound known as plakolide A, as well as its analogs. The compounds of the subject invention can be formulated into pharmaceutical compositions and can be used to treat tumors and others forms of pathological cellular proliferation.
The compounds described are useful as antitumor agents. The compositions and methods of the subject invention can be used in the treatment of an animal (including humans) hosting cancer cells, including, for example, inhibiting the growth of tumor cells in a mammalian host. More particularly, the subject compounds can be used for inhibiting in a human the growth of tumor cells, including cancer cells of the pancreas, breast, colon, CNS, ovarian, renal, prostate, lung, leukemia and melanoma cells.
The present invention, utilizing sponges as a source material, provides the art with new biologically active compounds and new pharmaceutical compositions useful as antitumor agents. The present invention has added to the arsenal of pharmaceutical compounds by the discovery of novel compounds isolatable from extracts of marine sponges of the family Plakinidae.
Collection and Taxonomy. The sponge sample was collected by scuba, from the wall of a cave at a depth of 3.3 m, near La Palma, Canary Islands (Latitude 28� 41.75′ N; Longitude 17� 58.00′ W). This sponge most closely fits the genus Plakortis Schulz, 1880 (class Demospongia, order Homosclerophorida, family Plakinidae), but can not be ascribed to a known species at this time. The specimen was encrusting on the rock surface of a cave wall. It was ˜15 cm diameter and ˜1 cm thick, with a smooth ectosome. The color in situ was light brown. The spicule skeleton consists of diods and occasional triods. A museum voucher specimen preserved in EtOH has been deposited at the Harbor Branch Oceanographic Museum, catalog number 003:00976 and is available for taxonomic evaluation.
Extraction and Isolation. The sponge was extracted in EtOH (3�300 mL) and concentrated to give 9.3 g of the EtOH extract. The EtOH extract was partitioned between EtOAc and H2O. The EtOAc-soluble fraction (1.8 g) was chromatographed on a column of Si gel (230–400 mesh) using a CH2Cl2-MeOH step gradient, and the fractions were monitored for cytotoxic activity. The cytotoxic fraction that eluted with CH2Cl2 was rechromatographed over Si gel using a hexane-CH2Cl2 step gradient and the fractions were monitored again for cytotoxic activity. The active fraction (0.037 g) that eluted with 25% hexane-CH2Cl2 was further purified by HPLC (Phenomenex, SiO2, 5 μm, 250�10 mm) with hexane-EtOAc gradient (95:5 to 80:20 in 16 min, 3 mL/min) gave plakolide A (1) as a colorless gum (3.4 mg, 0.015% of wet wt).
Compounds useful according to the subject invention can be isolated by various fractionation and chromatographic techniques from the extracts obtained as disclosed herein. Preferred isolation procedures include various chromatography techniques, such as countercurrent chromatography, with suitable columns including multi-layer planetary coil columns. A variety of solvents are available for use as single or mixed eluents, such as tetrahydrofuran, methanol, ethyl acetate, acetonitrile, n-propanol, n-butanol, water, and equivalent solvents. Further purifications using such procedures may also be carried out on the recovered extractions. Preferred isolation techniques for further purifications include chromatographic operations such as high-pressure liquid chromatography (HPLC) with suitable columns and suitable solvents.
Plakolide A, is an α-exomethylene-γ-disubstituted-γ-lactone. These chiral unusually functionalized γ-lactones are uncommon among natural products and this is the first report from a marine organism. The αβ and γδ trans diene dodecane side chain that is attached to the γ position of the lactone ring is accountable for the liphophilicity of the compound. The unusual substitution pattern in the γ-lactone ring may be contributing to the biological activity of the compound.
Included within the scope of the subject invention are analogs (equivalents) of the compounds. As used in this application, the term "analogs" refers to compounds which are substantially the same as another compound but which may have been modified by, for example, adding side groups. Salts are also within the scope of the present invention. Analogs of the exemplified compounds can be readily prepared using commonly known, standard reactions. These standard reactions include, but are not limited to, hydrogenation, methylation, acetylation, and acidification reactions.
Thus, the subject invention pertains, in part, to plakolide A (1) having the following structure and characteristics:
Plakolide A (1): [α]24 D −31� (c 0.1, CH3OH); UV (MeOH) λmax 208 (logε4.36), 230 (4.47) nm; IR (NaCl disc) νmax 2934, 2858, 1768, 1457, 1380, 1269, 1208, 1108, 1051, 993, 941 cm−1; 1H NMR (500 MHz, CDCl3 referenced at δ 7.24) δ 6.21 (1H, dd, J=15.4, 10.4 Hz, H-6), 6.20 (1H, t, J=2.4 Hz, H-17), 5.97 (1H, dd, J=15.0, 10.4 Hz, H-7), 5.73 (1H, dt, J=15.0, 6.9 Hz, H-8), 5.58 (1H, d, J=15.4 Hz, H-5), 5.57 (1H, t, J=2.4 Hz, H-17), 2.89 (1H, dt, J=16.5, 2.4 Hz, H-3), ), 2.77 (1H, dt, J=16.5, 2.4 Hz, H-3), 2.05 (2H, dt, J=7.2, 6.9 Hz, H-9), 1.50 (3H, s, H-18), 1.33 (2H, m, H-10), 1.15 (10H, m, H11–H15), 0.85 (3H, t, J=7.2 Hz, H-16); 13C NMR (125.7 MHz, CDCl3 referenced at δ 77.0) δ 169.8 (s, C-1), 137.4 (d, C-8), 135.4 (s, C-2), 132.2 (d, C-5), 129.7 (d, C-6), 128.7 (d, C-7), 122.2 (t, C-17), 82.4 (s, C-4), 40.8 (t, C-3), 32.7 (t, C-9), 31.9 (t, C-14), 29.4, 29.3, 29.2, 29.1 (t, C-10–C13), 27.1 (q, C-18), 22.7 (t, C-15), 14.1 (q, C-16); HRFABMS (thioglycerol) m/z 277.2116, Δ 5 mmu for C18H29O2 [M+H]+.
Additional preferred embodiments include 5,7-tetrahydroplakolide A (2) and 5,7, (2–17)-hexahydroplakolide A (3)
Further preferred embodiments include:
The chiral compounds of the subject invention can be administered as a racemic mixture or in their single enantiomer forms. For the administration of a single enantiomer, the isolated enantiomeric forms of the compounds of the invention are substantially free from one another (i.e., in enantiomeric excess). In other words, the "R" forms of the compounds are substantially free from the "S" forms of the compounds and are, thus, in enantiomeric excess of the "S" forms. Conversely, "S" forms of the compounds are substantially free of "R" forms of the compounds and are, thus, in enantiomeric excess of the "R" forms. In one embodiment of the invention, the isolated enantiomeric compounds are at least about in 80% enantiomeric excess. In a preferred embodiment, the compounds are in at least about 90% enantiomeric excess. In a more preferred embodiment, the compounds are in at least about 95% enantiomeric excess. In an even more preferred embodiment, the compounds are in at least about 97.5% enantiomeric excess. In a most preferred embodiment, the compounds are in at least about 99% enantiomeric excess.
As described herein, the invention also comprises the use of the new compounds of the subject invention for inhibiting unwanted cellular proliferation and, in a preferred embodiment, for the inhibition of tumor growth. Thus, one aspect of the subject invention is a method for the antitumor treatment of a human in need of such treatment, i.e., a human hosting cancer cells, including breast, colon, or lung tumor cells, leukemia cells, CNS cancer cell lines, melanoma cell lines, ovarian cancer cell lines, renal cancer cell lines, and prostate cancer cell lines.
In accordance with the invention, methods for inhibiting tumors in a host comprise contacting tumor cells with an effective amount of the new pharmaceutical compositions of the invention. The tumor cells inhibited by the invention are those which are susceptible to the subject compounds described herein or compositions comprising those compounds.
A more complete understanding of the invention can be obtained by reference to preferred embodiments of the invention which are illustrated by the following specific examples of compounds, compositions, and methods of the invention. It will be apparent to those skilled in the art that the examples involve use of materials and reagents that are commercially available from known sources, e.g., chemical supply houses, so no details are given respecting them.
Following are examples which illustrate procedures for practicing the invention. These examples should not be construed as limiting. All percentages are by weight and all solvent mixture proportions are by volume unless otherwise noted.
Extracts and compounds were analyzed as to their effects on proliferation of A549 human adenocarcinoma, PANC-1 human pancreatic and P388 murine leukemia cell lines. P388 cells were obtained from Dr. R. Camalier, National Cancer Institute, Bethesda, Md., and A549 and PANC-1 cells were obtained from American Type Culture Collection, Rockville, Md. All cell lines were maintained in Roswell Park Memorial Institute (RPMI) medium 1640 supplemented with 10% fetal bovine serum. All cell lines are cultured in plastic tissue culture flasks and kept in an incubator at 37� C. in humidified air containing 5% CO2. Prior to testing, antibiotic-free stock cultures of each of the cell lines were subcultured to 106 cells/ml by dilution in fresh growth medium at 2 to 3 day intervals.
To assess the antiproliferative effects of extracts and compounds against the P388 cell line, 200 μl cultures (96-well tissue culture plates, Nunc, Denmark) are established at 1�105 cells/ml in drug-free medium or medium containing the test agent at 10.0, 1.0, 0.10 and 0.010 μg/ml. Solvent for all dilutions ethanol. All experimental cultures are initiated in medium containing Gentamycin sulfate (50 μg/ml; Schering Corporation, Kenilworth, N.J.). After 48-h exposures, P388 cells are enumerated using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) as described below (M. C. Alley, et al., Cancer Res. 48:589, 1988).
Similar procedures are utilized for A549 and PANC-1 cells which require an additional 48 hr exposure prior to MTT addition. Results are expressed as percent inhibition compared to the negative (no drug) control. Positive drug controls are included to monitor drug sensitivity of each of the cell lines. These include varying dilutions of 5-fluorouracil and adriamycin.
To quantitate the effects of pure compounds on cell proliferation and resulting IC50 values, 75 μl of warm growth media containing 5 mg/ml MTT is added to each well, cultures returned to the incubator, and left undisturbed for 90 minutes. To spectrophotometrically quantitate formation of reduced formazan, plates are centrifuged (900�g, 5 minutes), culture fluids removed by aspiration, and 200 μl of acidified isopropanol (2 ml concentrated HC1/liter isopropanol) added per well. The absorbance of the resulting solutions is measured at 570 nm with a plate reader (TECAN Spectra II Plate Reader, TECAN U.S., Research Triangle Park, N.C.). The absorbance of tests wells is divided by the absorbance of drug-free wells, and the concentration of agent that results in 50% of the absorbance of untreated cultures (IC50) is determined by linear regression of logit-transformed data (D. J. Finney, Statistical Method in Biological Assay, third ed., pp. 316–348, Charles Griffin Co., London, 1978). A linear relationship between tumor cell number and formazan production has been routinely observed over the range of cell densities observed in these experiments. The two standard drug controls (indicated above) are included in each assay as a check to monitor the drug sensitivity of each of the cell lines and IC50 values are determined for each drug-cell combination. Table 1 summarizes the activities determined for plakolide A.
Activity (IC50 μg/ml)
1.09 μg/ml
5.0 μg/ml
3.78 μg/ml
Therapeutic and prophylactic application of the lactone compounds, and compositions comprising them, can be accomplished by any suitable method and technique presently or prospectively known to those skilled in the art. Further, the compounds of the invention have use as starting materials or intermediates for the preparation of other useful compounds and compositions. The compounds of the invention are useful for various non-therapeutic and therapeutic purposes.
In one embodiment, the compounds of the subject invention are effective for inhibiting cell growth. Because of the antiproliferative properties of the compounds, they are useful to prevent unwanted cell growth in a wide variety of settings including in vitro uses. They are also useful as standards and for teaching demonstrations. They can also be used as ultraviolet screeners in the plastics industry since they effectively absorb UV rays. As disclosed herein, they are also useful prophylactically and therapeutically for treating cancer cells in animals and humans.
The dosage administration to a host in the above indications will be dependent upon the identity of the cancer cells, the type of host involved, its age, weight, health, kind of concurrent treatment, if any, frequency of treatment, and therapeutic ratio.
The compounds of the subject invention can be formulated according to known methods for preparing pharmaceutically useful compositions. Formulations are described in detail in a number of sources which are well known and readily available to those skilled in the art. For example, Remington's Pharmaceutical Science by E. W. Martin describes formulations which can be used in connection with the subject invention. In general, the compositions of the subject invention will be formulated such that an effective amount of the bioactive compound(s) is combined with a suitable carrier in order to facilitate effective administration of the composition.
In accordance with the invention, pharmaceutical compositions comprising, as an active ingredient, an effective amount of one or more of the new compounds and one or more non-toxic, pharmaceutically acceptable carrier or diluent. Examples of such carriers for use in the invention include ethanol, dimethyl sulfoxide, glycerol, silica, alumina, starch, and equivalent carriers and diluents.
To provide for the administration of such dosages for the desired therapeutic treatment, new pharmaceutical compositions of the invention will advantageously comprise between about 0.1% and 45%, and especially, 1 and 15%, by weight of the total of one or more of the new compounds based on the weight of the total composition including carrier or diluent. Illustratively, dosage levels of the administered active ingredients can be: intravenous, 0.01 to about 20 mg/kg; intraperitoneal, 0.01 to about 100 mg/kg; subcutaneous, 0.01 to about 100 mg/kg; intramuscular, 0.01 to about 100 mg/kg; orally 0.01 to about 200 mg/kg, and preferably about 1 to 100 mg/kg; intranasal instillation, 0.01 to about 20 mg/kg; and aerosol, 0.01 to about 20 mg/kg of animal (body) weight.
The compositions of the invention are advantageously used in a variety of forms, e.g., tablets, ointments, capsules, pills, powders, aerosols, granules, and oral solutions or suspensions and the like containing the indicated suitable quantities of the active ingredient. Such compositions are referred to herein and in the accompanying claims generically as "pharmaceutical compositions." Typically, they can be in unit dosage form, namely, in physically discrete units suitable as unitary dosages for human or animal subjects, each unit containing a predetermined quantity of active ingredient calculated to produce the desired therapeutic or prophylactic effect in association with one or more pharmaceutically acceptable other ingredients, e.g., diluent or carrier.
Where the pharmaceutical compositions are aerosols, the active ingredients can be packaged in pressurized aerosol containers with a propellant, e.g., carbon dioxide, nitrogen, propane, etc. with the usual adjuvants such as cosolvents, wetting agents, etc.
Where the pharmaceutical compositions are ointments, the active ingredient can be mixed with a diluent vehicle such as cocoa butter, viscous polyethylene glycols, hydrogenated oils, and such mixtures can be emulsified if desired.
All patents, patent applications, provisional applications, and publications referred to or cited herein are incorporated by reference in their entirety, including all figures and tables, to the extent they are not inconsistent with the explicit teachings of this specification.
It should be understood that the examples and embodiments described herein are for illustrative purposes only and that various modifications or changes in light thereof will be suggested to persons skilled in the art and are to be included within the spirit and purview of this application.
|Cited Patent
|Filing date
|Publication date
|Jan 3, 1979
|Jun 3, 1980
|The United States Of America As Represented By The Secretary Of Agriculture
|Cephalomannine and its use in treating leukemic tumors
|Sep 8, 1981
|Oct 22, 1985
|The Board Of Trustees Of The University Of Illinois
|Composition of matter and process
|May 29, 1986
|Mar 8, 1988
|Harbor Branch Oceanographic Institution, Inc.
|Antitumor compositions and their methods of use
|Sep 30, 1986
|Apr 12, 1988
|The Board Of Trustees Of The University Of Illinois
|Bioactive metabolites from the caribbean sponge agelas coniferin
|Jul 15, 1988
|Feb 28, 1989
|Harbor Branch Oceanographic Institution, Inc.
|Antiviral, antitumor and antifungal compositions and their methods of use
|Mar 9, 1989
|Oct 2, 1990
|University Of Kansas
|Derivatives of taxol, pharmaceutical compositions thereof and methods for the preparation thereof
|Oct 31, 1991
|Oct 20, 1992
|The United States Of America As Represented By The Department Of Health & Human Services
|Method of treating cancers sensitive to treatment with water soluble derivatives of taxol
|Dec 3, 1996
|Aug 4, 1998
|Trustees Of The University Of Pennsylvania
|Synthetic techniques and intermediates for polyhydroxy, dienyl lactones and mimics thereof
|Dec 1, 1997
|Jun 11, 1998
|Univ Pennsylvania
|Synthetic techniques and intermediates for polyhydroxy, dienyllactones and mimics thereof
|Faulkner, D.J. "Marine Natural Products" Natural Products Reports 1998, vol. 15, pp. 113-158.
|Fuchs, D.A. Johnson, R.K. "Cytologic evidence that taxol, an antineoplastic agent from Taxus brevifolia, acts as a mitotic spindle poison" Cancer Treat. Rep. 1978, vol. 62, pp. 1219-1222.
|Gunasekera, S.P. et al. "Discodermolide: A new bioactive polyhydroxy lactone from the marine sponge Discodermia dissolute" J. Org. Chem. 1990, vol. 55, pp. 4912-4915 [correction J. Org. Chem. 1991, vol. 56, p. 1346.]
|Kowalski et al. "The microtubule-stabilizing agent discodermolide competitively inhibits the binding of paclitaxel (Taxol) to tubulin polymers, enhances tubulin nucleation reactions more potently than paclitaxel, and inhibits the growth of paclitaxel-resistant cells" Mol. Pharmacol. 1997, vol. 52, pp. 613-622.
|Minale, L. et al. "Natural products from porifera" Fortschr. Chem. Org. Naturst. 1976, vol. 33, pp. 1-72.
|Rowinski, E.K., Donehower, R.C. "Paclitaxel (Taxol)" N. Engl. J. Med. 1995, vol. 332, pp. 1004-1014.
|Scheuer, P.J. (ed.) Marine Natural Products, Chemical and Biological Perspectives, Academic Press, New York, 1978-1983, vol. I-V.
|Schiff, P.B et al. "Promotion of microtubule assembly in vitro by taxol" Nature 1979, vol. 22, pp. 665-667.
|Ter Haar et al. "Discodermolide, a cytotoxic marine agent that stabilizes microtubules more potently than taxol" Biochemistry 1996, vol. 35, pp. 243-250.
|Uemura, D. et al. "Norhalichondrin A: An Antitumor Polyether Macrolide from a Marine Sponge" J. Am. Chem. Soc. 1985, vol. 107, pp. 4796-4798.
|U.S. Classification
|514/473, 549/295
|International Classification
|Cooperative Classification
|European Classification
|Jun 4, 2003
Owner name: HARBOR BRANCH OCEANOGRAPHIC INSTITUTION, INC., FLO
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|Oct 28, 2009
|Fee payment
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text:
Just remember those nice rubber mats are dust magnets, which may or may not be good. If you clean them outside the darkroom regularly then they will suck up the dust from your feet as you move about. If not they become an unrelenting source of tiny little spots on your pictures.
I forget, are you creating a positive pressure ventilation system in the darkroom? Works better than anything to keep exterior dust out.


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The latest content from Facebook, Twitter, YouTube, Tumblr, Vine, Instagram, plus exclusive backstage and paparazzi content, so you'll never miss a moment. You'll start by selecting your Favorites, so you can see their pics, vids, Fanpics and chats. You can even create your own Collections, or post your Fanpics to Fan Walls, or chat with fellow fans. Participate a lot and you might find yourself atop the Fan Rankings!
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Kershaw County Council will reconsider the Fiscal Year 2014 budget, which it passed on third and final reading on June 25.
Now that the town of Bethune no longer has a police department to fund, it will have a $29,557 surplus on hand for the 2014 fiscal year that started July 1. Bethune Town Council passed third and final reading of the budget at a special June 27 meeting.
Kershaw County has a new assessor.
A practice known as "Chinese overtime" will continue at the Kershaw County Sheriff's Office (KCSO) for the foreseeable future. As part of its vote on the county's Fiscal Year 2014 budget Tuesday, Kershaw County Council declined to provide the KCSO with additional funding to end the practice of paying deputies approximately half-time for each hour of overtime they work."
This camp is offered for girls ages 7 - 13. Camp dates are July 8-12 and will be at the CHS softball field from 9 a.m. to Noon. Learn fundamental skills of fast pitch softball or improve your skills in the camp. Daily sessions will include defensive play, base running and hitting. Instructing the camp will be Camden High Softball Coach, Lynn Looney along with other CHS coaches and local players assisting. The cost is $60. Pre-registration is required by July 3.
Joe Eason, director of the Florence County Parks and Recreation Department, will become the new director of the Kershaw County Recreation Department. Kershaw County Administrator Vic Carpenter made the announcement earlier this month at Kershaw County Council's June 11 meeting.
A new fence under construction is part of security upgrades being made at the Kershaw County Courthouse. According to Kershaw County Administrator Vic Carpenter, the upgrades are being made due to pressure from South Carolina Chief Justice Jean H. Toal and a review of the state's courthouses. He said upgrades being made at the Kershaw County Courthouse are a result of recommendations by a panel that includes those who use courthouses, such as judges. Carpenter said findings showed that the courthouse is deficient in terms of safety, with security methods dating back to the 1960s.
Kershaw County Council will discuss the Kershaw County School District's (KCSD) recent millage request during its meeting Tuesday. According to its agenda, council will discuss the request after third and final reading of the county's proposed 2013-14 fiscal year budget. KCSD is requesting an additional 3.5 mills from the county.
Kershaw County recently purchased several homes and the lots they sit on as part of an effort to expand the Kershaw County Airport's safety zone at Woodward Field.
Kershaw County's insurance carrier will pay former Kershaw County Sheriff Steve McCaskill $75,000 to settle his defamation lawsuit against the Kershaw County Sheriff's Office (KCSO). The lawsuit and four others were originally directed against current Kershaw County Sheriff Jim Matthews as an individual over comments he made soon after taking office in 2011. However, Matthews has maintained he was speaking as a county official, so all the lawsuits were redirected against the KCSO.
At a public hearing and regular Bethune Town Council meeting Thursday, council invited citizens to voice their thoughts and opinions regarding its proposed Fiscal Year 2014 budget. During the public hearing, Mayor Carlisle Davis said that the budget had been available to the public the week before but that "not a single person" obtained a copy.
Tuesday's Kershaw County Council meeting kicked off with a public hearing in which Billy Smith, the Santee Wateree Transit Authority Board Representative for the area, took the opportunity to remind council of how important funding is to keep transportation in parts of the county intact. Smith that said "$18,000-plus" may be cut for the 2013-14 fiscal year and that if there is no money, there may be no routes.
Joan A. Inabinet recently received the Robert N. Pryor Volunteer Service Award from Confederation of Local Historical Societies (CLHS) at its Landmark Convention in Spartanburg. Presenting her with the award were CLSH President J.R. Fenell and Ex-Officio Mike Scoggins.
A light agenda for Tuesday's Kershaw County Council meeting will feature a public hearing on budget appropriations for the county's 2014 fiscal year. Council held the second reading of the budget at its May 31 meeting, but did not have third and final reading set for Tuesday evening.
Marketing Director Roshanda Pratt likes to describe the Kershaw County Farmers Market (KCFM) has having "a little something for everybody." That idea will grow even more beginning Saturday as the market begins accepting SNAP (formerly known as Food Stamps) in an effort to expand its boundaries for providing the community healthy and locally-grown options to eat.
Tonight, Kershaw County Council will consider approving a resolution regarding the S.C. Department of Natural Resources' (DNR) pending acquisition of approximately 1,829 acres ...
It took a little time, thanks to an extra bout of rain Saturday, but dozens of people showed up for the grand opening of the ...
Thursday, a pick-up truck towing a trailer followed a tractor trailer as it left Camden Military Academy (CMA) for Columbia, filled with a combined load ...
A Camden native and Elgin resident received recognition as an "Angel in Adoption" at an awards ceremony and separate gala in Washington, D.C., held ...
Kershaw County is now among those in South Carolina eligible for assistance from the U.S. Federal Emergency Management Agency (FEMA). S.C. Gov. Nikki ...
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It remains to say something of the conduct of this design. Public events will be stated with fidelity. Historical characters shall be but sparingly combined with feigned actions, but, where they, are, great care shall be taken that they be neither flattered, calumniated, nor overcharged; and, I believe, they may be found to have behaved in much the same manner to others, as I shall represent them to do to the imaginary persons whom I bring on the scene. The long space of years which this narrative embraces, is, I know, a great abatement of its interest. It is a fault which could not be avoided without falsifying chronology at a period familiar to every well-read person, or losing sight of the admonitory lesson which the tale was intended to convey.
I know that there is no small share of hardihood in my attempt: Bigotry, superstitious adherence to existing institutions, exclusive partiality to a sect, and pertinacious resistance to the increase of liberal information, ar
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VIDEO: First Look at THE WALKING DEAD's Midseason Return
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Coming Soon has unveiled the newest trailer for THE WALKING DEAD's midseason premiere - check it out below!
"With his group in tatters, his sanity in question, and his own son questioning his every move," AMC says of the show, "Rick must somehow pull everyone together to face their greatest challenge - the Governor. In order to survive, he must risk everything, including the group's very humanity."
Based on the comic book series written by Robert Kirkman and published by Image Comics, The Walking Dead stars Andrew Lincoln, Laurie Holden, Steven Yeun, Norman Reedus, Chandler Riggs, Lauren Cohan,Scott Wilson, Melissa McBride, Chad Coleman, David Morrissey and Danai Gurira. The second half of season 3 premieres on Sunday, February 10th.