Biomedical subjects
Publications and source records attributed to B Kuch.
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Cross-sectional data often fail to show beneficial effects of antihypertensive therapy in patients with hypertension. We, therefore, examined the influence of hypertension control on left ventricular (LV) structure in diabetic persons separated into those having and not having any known cardiovascular disease (CVD) symptoms. The study population consisted of 394 subjects with type II diabetes. According to the presence of CVD, subjects were classified as symptomatic (N=181) or asymptomatic (N=213). In addition, three groups were differentiated: controlled hypertensives (CHs), that is, known hypertension with normal blood pressure (BP), uncontrolled hypertensives (UHs), that is, elevated BP regardless of antihypertensive medication, and normotensives (Ns). Symptomatic subjects showed a significantly higher prevalence of LV hypertrophy (LVH) (34.5 vs 23.4%, P<0.02). In contrast to symptomatic subjects where hypertension control status had no further significant impact on LV geometry, a considerable impact on preservation of normal LV geometry was observed in asymptomatic persons (LVH of 30, 15 and 18% in UH, CH and N, respectively, P<0.001). Control of hypertension in early diabetes seems especially to prevent the development of concentric hypertrophy (24 vs 11% in UH vs CH, P<0.04). In conclusion, in subjects with diabetes and CVD, the prevalence of LV structural abnormalities is very high. Although in this population-based study setting, in the latter group BP control does not seem to positively influence LV mass and function, hypertension control in still asymptomatic diabetic persons is beneficial and has a considerable impact on preservation of normal LV geometry.
For successful fighting against the burden of cardiovascular disease in the community a comprehensive knowledge about the prevalence and the impact of underlying risk factors is important. The present paper summarises some studies undertaken on more than 2000 persons from the MONICA/KORA-studies (parts of S1 and S3) where left ventricular mass (LVM) and other left ventricular parameters were determined by echocardiography. We especially investigated the associations of LVM with blood pressure and obesity. A special focus was on sex-specific factors in the determination of LVM and the influence of different indices of body size when normalising LVM. It could be shown that hypertension and obesity are major determinants of LV hypertrophy. Especially women with both hypertension and obesity on showed a high prevalence of concentric hypertrophy, significantly more than men. We also showed that the prevalence of LV hypertrophy in a representative sample of the general population (25 to 74 years) is 17.5 % for men, and 18.5 % for women. This underscores the need for primary and secondary prevention regarding the development of LV hypertrophy. Finally, our data in a selected group of normal subjects (reference sample) may be used for the development of reference values for left ventricular parameters in the general German population.
The MONICA/KORA surveys are characterized by a careful and broad investigation of multiple cardiovascular phenotypes. Particularly, repeated blinded measurements of blood pressure, comprehensive echocardiographic and electrocardiographic evaluations as well as differentiation between fat and fat-free body mass have led to manifold innovative observations. Specifically, genetic and serological markers of the renin angiotensin system could be associated with high blood pressure and left ventricular hypertrophy. The same applies to the importance of parameters of body composition as obesity and muscular mass. Moreover, the prevalence of heart failure in the general population could be determined for the first time in Germany. Additionally, the prevalence of left ventricular systolic and diastolic dysfunction could be obtained in the region of the survey, exemplarily for the Federal Republic of Germany. Finally, the surveys of the population random sample were used to define normal serum levels of natriuretic peptides. In summary, the evaluation of cardiovascular phenotypes in the MONICA/KORA surveys resulted in a -- in the European region unique -- documentation of cardiovascular functional parameters in the general population. Moreover, multiple epidemiological observations as to pathophysiologically relevant topics of heart and vascular diseases could be studied in extraordinary details.
BACKGROUND AND AIM: Myocardial infarction (MI) is the main single cause of death in adult populations. For the MONICA Augsburg population, MI-morbidity, mortality, and 28-day case fatality and their determinants were assessed by gender, and suggestions for an intensified acute care program were presented. PATIENTS AND METHODS: From 1985 to 1998, 13 499 25- to 74-year-old MI cases (9537 men, 3962 women) were registered; 7873 cases (5300 men, 2573 women) died within 28 days. Cardiac deaths were identified by regional health departments; causes of death were validated by the last treating physician and the coroner (response > 90 %). Hospitalized patients were interviewed about history and circumstances of the acute event; treatment data were abstracted from hospital charts. The prehospital phase, the first and the 2nd to 28thday after hospitalization were analyzed separately. RESULTS: MI-morbidity per 100 000 population declined from 560 to 397 MI cases in men and from 161 to 145 in women; mortality decreased from 317 to 232 in men and from 101 to 96 in women. The decline in men was due to decreasing incident and recurrent MI whereas in women it was only due to a reduction of recurrent MI. One third died before hospitalization, mainly at home. Case fatality (CF) on the first day in hospital increased. In 24 hour survivors, evidence based treatment increased considerably, and was accompanied by decreasing 28-day-CF from 13.0 % to 8.4 % in men, and from 12.5 % to 10.7 % in women. CONCLUSION: Aggressive risk factor management and education of patients with cardiovascular risk factors concerning acute symptoms and the use of the emergency system will consequently improve pre-hospital and 28-day survival of the population.
AIMS: To examine the general influence of the definition of fatal and non-fatal acute myocardial infarction and coronary deaths on the estimation of in-hospital case-fatality, and to show how the definition of acute myocardial infarction influences time-trends of hospital mortality over 11 years. METHODS AND RESULTS: As part of the World Health Organization's MONICA (multinational Monitoring of Trends and Determinants in Cardiovascular Disease) Project in Augsburg all patients aged 25-74 years with a suspected diagnosis of acute myocardial infarction who were hospitalized in the study region's major clinic were registered prospectively between 1985 to 1995 (n=4889). Patient information, including short-term survival status, was obtained from medical records, by interview of surviving patients, and municipal death certificate files which were validated by an extended identification and validation process. In-hospital case fatality was estimated according to different definitions which closely followed the international MONICA criteria. Epidemiological definitions comprised definite and possible acute myocardial infarction, and events with unclassifiable deaths, while the clinical definition was restricted to definite infarction. Overall, case fatality by the epidemiological definitions was 28 to 29.8% (23.5% of those treated in a coronary care unit) compared to 13.5% using the clinical definition. While over the 11 years, the reduction in case fatality according to the epidemiological definitions was modest, highly significant decreases were observed by applying the clinical definition (from 15.8% in 1985-1988 to 10.8% in 1993-1995, P<0.001 adjusted for age and sex). The discrepancy in case fatality between the definitions is explained by the high proportion of patients who die very early (about 70% of all fatal events during the first 24 h) with the consequence of missing data which may preclude a definite diagnosis of acute myocardial infarction. CONCLUSIONS: Applying a broader definition of acute myocardial infarction reveals that in-hospital mortality is higher than believed until now, and it implies that our efforts must be intensified to reduce overall in-hospital coronary heart disease mortality.
Plasma homocysteine has been associated with vascular disease and mortality. Experimental studies and studies on patients with vascular disease have indicated a thrombogenic potential of raised homocysteine levels. Studies on community samples are rare. We investigated the associations between homocysteine levels and selected coagulation factors in population-based random samples of 187 men from Pardubice (Czech Republic) and 147 men from Augsburg (Germany), aged 45 to 64 years. Czech men had higher mean levels of plasma homocysteine (10.3 vs. 8.9 micromol/l, P<.001) and of fibrinogen, von Willebrand factor (vWF), prothrombin fragment 1+2 (F 1+2) and D-Dimer (each P<.05). Plasma homocysteine was positively correlated with fibrinogen (r=.34) and vWF (r=.23, each P<.001) only in Czechs, and with D-Dimer in both Czechs and Germans (r=.26 and.21, respectively). Formal testing for interaction regarding the intercountry differences in the relationship with homocysteine revealed significance only for fibrinogen (P<.01). In multivariate analyses, the association of homocysteine with D-Dimer remained statistically significant after adjustment for indicators of chronic inflammation and fibrinogen. No significant correlation was found with Factor VII (F VII) activity or F 1+2. Homocysteine levels were also unrelated to traditional risk factors. In conclusion, in these cross-sectional studies we found moderate to strong associations between homocysteine and components of the endogenous hemostatic and fibrinolytic systems. The associations were slightly different between Czech and German men. These findings may help to better understand the role of homocysteine in atherothrombotic diseases.
BACKGROUND: Indexation to fat-free mass (FFM) seems to be the best option for adjusting left ventricular (LV) mass. However, measurements of FFM are frequently not available. OBJECTIVES: To define the relation of FFM with commonly available anthropometric measures in order to derive an approximation formula of FFM that can be used for valid indexation of LV mass. SUBJECTS AND METHODS: A total of 1,371 subjects from a community survey were examined by echocardiography to measure LV mass and by bioelectrical impedance analyses (BIA) for the determination of FFM. An approximation of FFM was generated in a healthy subgroup of 213 men and 291 women by non-linear regression techniques. RESULTS: Compared with body height, height2.0, height2.7, (the superscripts following weight and height are raised powers used as a more appropriate method for indexing LV mass) or body surface area, FFM measured by BIA in the healthy subgroups was best predicted by gender-specific equations of the form: FFM = 5.1 x height1.14 x weight0.41 for men and FFM = 5.34 x height1.47 x weight0.33 for women. In the healthy reference group, indexation of LV mass for BIA-determined FFM and approximated FFM (FFMa), respectively, equally eliminated gender differences in LV mass and markedly reduced the influence of body mass index without affecting the associations between blood pressure and LV mass. Validation of FFMa in two independent population-based samples, aged 52 to 67 years, of the same source population confirmed that LV mass indexed by FFMa produced results that were highly consistent with those obtained with indexation by BIA-determined FFM. CONCLUSIONS: We propose a novel approximation of FFM based on exponentials of body height and weight. It performed well in the indexation of LV mass in middle-aged men and women of this study. Evaluation of the equation in other populations should be awaited before its use is recommended in situations where direct determination of FFM is not possible.
Decreased heart rate variability (HRV) is associated with a worse prognosis in a variety of diseases and disorders. We evaluated the determinants of short-period HRV in a random sample of 149 middle-aged men and 137 women from the general population. Spectral analysis was used to compute low-frequency (LF), high-frequency (HF) and total-frequency power. HRV showed a strong inverse association with age and heart rate in both sexes with a more pronounced effect of heart rate on HRV in women. Age and heart rate-adjusted LF was significantly higher in men and HF higher in women. Significant negative correlations of BMI, triglycerides, insulin and positive correlations of HDL cholesterol with LF and total power occurred only in men. In multivariate analyses, heart rate and age persisted as prominent independent predictors of HRV. In addition, BMI was strongly negatively associated with LF in men but not in women. We conclude that the more pronounced vagal influence in cardiac regulation in middle-aged women and the gender-different influence of heart rate and metabolic factors on HRV may help to explain the lower susceptibility of women for cardiac arrhythmias.
BACKGROUND: Fat-free mass (FFM) has been proposed as an optimal normalization of left ventricular (LV) mass to body size. We sought to evaluate the novel FFM-based criteria of LV hypertrophy (LVH). METHODS AND RESULTS: A population sample of 1371 men and women aged 25 to 74 years was examined by echocardiography and bioelectrical impedance analysis. Internal partition values for LVH were generated in a healthy population subgroup on the basis of LV mass divided by FFM and by the traditional indexations to body height, height(2.7), and body surface area. In contrast to the sex-specific criteria required by traditional indexations, the value of LV mass/FFM that divided individuals with and without LVH was identical for men and women (4.1 g/kg). Estimates of LVH prevalence varied significantly by type of indexation used, internally or externally derived cut points, and by population subgroups. Differences were pronounced among hypertensives and the obese. Thus, the application of LV mass/FFM more than halved the risk of LVH in obese versus nonobese women (odds ratio, 2.5; 95% confidence interval, 1.6 to 4.0) compared with criteria based on LV mass/height(2.7) (odds ratio, 5.5; 95% confidence interval, 3.6 to 8.3). Implications among hypertensives were less marked. CONCLUSIONS: Indexation of LV mass to FFM eliminates sex-specific LVH criteria. The proportion of individuals defined as having LVH using the new criteria deviate markedly from traditional indexations. Prospective investigations will be needed to identify the prognostic implications of different indexations, especially in subgroups such as the obese.
OBJECTIVES: The study evaluated the contribution of familial predisposition to the risk of left ventricular hypertrophy (LVH). BACKGROUND: Left ventricular hypertrophy is a multifactorial condition that serves as an important predictor of cardiovascular mortality. At present it is unclear whether familial predisposition contributes to the manifestation of LVH. Thus, we determined whether siblings of subjects with LVH are at increased risk to present with an elevation of LV mass or an abnormal LV geometry. METHODS: Echocardiographic and anthropometric measurements were performed in 2,293 individuals who participated in the echocardiographic substudies of population-based MONICA Augsburg surveys. In addition, a total of 319 siblings of survey participants with echocardiographic evidence of LVH were evaluated. The risk of these siblings to present with LVH or abnormal LV geometry was estimated by comparison with 636 subjects matched for gender and age that were selected from the entire echocardiography study base. RESULTS: Blood pressure, body mass index, age, and gender (i.e., known determinants of LV mass) were comparable in LVH-siblings and the matched comparison group. However, septal and posterior wall thicknesses, relative wall thickness as well as LV mass index were significantly elevated in LVH-siblings (p < 0.001, each) whereas LV dimensions did not differ. Likewise, the prevalence of LVH was raised in LVH-siblings, as was the relative risk of LVH after adjustment for confounders (p < 0.05). More specifically, LVH-siblings displayed increased prevalences of concentric remodeling and concentric LVH (p < 0.05) but not of eccentric LVH. CONCLUSIONS: Familial predisposition appears to contribute to increased LV wall thickness, to the development of LV hypertrophy and abnormal LV geometry.
BACKGROUND: The large differences in cardiovascular disease rates between Eastern and Western Europe have largely developed over the last few decades, and are only partly explained by classical risk factors. This study was set up to identify other potential determinants of these differences. METHODS: This was an ecological study comparing random samples of men aged 45-64 years selected from three cities representing populations with different rates of cardiovascular mortality: Pardubice (Czech Republic), Augsburg (Bavaria, Germany), and Jerusalem (Israel). In total, 191 (response rate 70%), 153 (70%) and 162 (62%) men, respectively, participated. All centres followed the same study protocol. Lifestyle, anthropometry and biochemical risk factors were assessed by identical questionnaires, standardized medical examination, and central analyses of fasting blood samples. RESULTS: The mortality rates in the study populations, as well as the prevalence of coronary heart disease in study samples, were highest in Czech, intermediate in Bavarian and low in Israeli men. This pattern was replicated across the three samples by mean blood pressure (P < 0.001), cigarette smoking (not significant), triglycerides (P < 0.05), fibrinogen or D-dimer levels (P < 0.05). On the other hand, the prevalence of diabetes and obesity were similar; total and high density lipoprotein (HDL)-cholesterol, apolipoprotein B, lipoprotein (Lp(a)) and glucose did not differ between Czech and Bavarian men; and Czechs had particularly low levels of serum insulin and factor VIIc. Israelis had low fasting glucose and total cholesterol, as well as HDL-cholesterol levels and a high Lp(a) (each P < 0.001) compared with the two other samples. Striking differences were found for plasma homocysteine (10.5 in Czechs versus 8.9 mumol/l in Bavarians, P < 0.001) and for alpha-carotene (geometric mean in Czechs 16, Bavarians 21 and Israelis 30 micrograms/l), beta-carotene (60, 110 and 102 micrograms/l), and lycopene (84, 177 and 223 micrograms/l), respectively; all P-values < 0.001). Adjustment for obesity or smoking did not change these estimates. There were no differences in the levels of tocopherol and retinol. CONCLUSIONS: Czech men had high levels of blood pressure, triglycerides, fibrinogen and D-dimer but many other traditional risk factors, as well as indicators of metabolic disorders and vitamins A and E, did not differ between the study samples. The low levels of carotenoids and high concentrations of homocysteine in Czech men seem to reflect their low dietary intakes of fruit and vegetables. The results provide indirect support for the importance of dietary factors in the East-West morbidity and mortality divide.
The purpose of this study was to investigate whether the basal activity of the renin-angiotensin-aldosterone system or the basal levels of the atrial natriuretic peptide (ANP) are related to distinct patterns of left ventricular (LV) geometry in patients with essential hypertension. The left ventricle of patients with arterial hypertension may be exposed to a variety of growth-regulating mechanisms, including pressure overload and humoral activation. The interaction of such growth stimuli may be involved in the modulation of LV geometry. LV geometry was determined echocardiographically in 104 patients with mild to moderate essential hypertension. The same number of age- and sex-matched normotensive subjects served as controls. Plasma renin activity (PRA) and serum concentrations of aldosterone and ANP were measured by radioimmunoassay. Correlation analyses revealed that PRA was significantly associated with septal wall thickness and LV mass index (r = 0.25; p < 0.005 each). In addition, as compared with normal subjects (1.0 +/- 0.7 ng/ml/hr), PRA was significantly increased in patients with concentric LV hypertrophy (LVH) (3.4 +/- 6.6 ng/ml/hr, p < 0.01). Aldosterone displayed a close correlation with septal, posterior, and relative wall thickness (r > 0.27, p < 0.005 each). Compared with normal subjects (74 +/- 27 pg/ml), patients with hypertension and pathologic patterns of LV geometry were characterized by elevations of aldosterone (LV remodeling 203 +/- 93 pg/ml, concentric LVH 123 +/- 67 pg/ml; eccentric LVH 199 +/- 89 pg/ml; p < 0.05 each). ANP was significantly associated with septal wall thickness, left ventricular dimension, and LV mass index (r > 0.22, p < 0.005 each). Furthermore, compared with normal subjects (50 +/- 17 pg/ml), ANP values were significantly increased in patients with hypertension and concentric LVH (80 +/- 44 pg/ml, p < 0.005) and eccentric LVH (88 +/- 24 pg/ml, p < 0.001). Multivariate analysis adjusting for systolic blood pressure, body mass index, and age revealed that renin and ANP were independently associated with LV mass index (p < 0.05 each). Interestingly, adjusted PRA levels were not related to any specific pattern of LV geometry. In contrast, adjusted ANP levels were associated with concentric and eccentric LVH, whereas adjusted aldosterone levels were significantly elevated in subjects with LV remodeling and eccentric LVH (p < 0.005). Thus elevated levels of renin and ANP may be found in patients with hypertension and elevated LV mass index. In addition, ANP and aldosterone are related to specific geometric patterns of the left ventricle. The data may further stimulate the discussion on the mechanisms that account for alterations of LV geometry in hypertension.
OBJECTIVES: We investigated the relationship between body size, body composition and left ventricular mass (LVM) in adults, and assessed the impact of different indexations of LVM on its associations with gender, adiposity and blood pressure. BACKGROUND: The best way to normalize LVM for body size to appropriately distinguish physiologic adaptation from morbid heart morphology was discussed. METHODS: We undertook a community survey of 653 men and 718 women, aged 25 to 74 years. Lean body mass (LBM) was determined by bioelectric impedance analyses and LVM was assessed by two-dimensional guided M-mode echocardiography. RESULTS: After traditional indexations to body height, body height2.7, or body surface area, men had higher LVM than women (p < 0.001). These gender differences disappeared (p > 0.05) when LVM was indexed to LBM. The type of indexation also modified the strength of the association between adiposity and LVM. The estimated impact of body fat on LVM indexed to LBM was less than half that obtained with traditional indexations. In contrast, the magnitude of the associations of blood pressure with LVM was entirely independent of the type of indexation. CONCLUSIONS: This study showed the prominent influence of body composition on adult heart size. Indexation for LBM removed gender differences for LVM and reduced the impact of adiposity, but left the effects of blood pressure unchanged. We suggest that this approach be used for clinical and research applications.
Recent reports indicate that the prognostic implications of left ventricular hypertrophy (LVH) are more profound in women than in men. The prognosis of LVH is also related to the underlying geometric pattern. We therefore assessed the relation of separate and concurrent influences of obesity and hypertension on gender-specific patterns of LV adaptation. Five hundred and twenty participants of a community-based study (aged 52 to 67 years) were examined by M-mode echocardiography. Study subjects were divided into four groups: normals, obese, hypertensives, and subjects presenting with both obesity and hypertension. The groups were compared for various measures of left ventricular mass (LVM) and geometry. Relative to normal subjects, the increments in wall thickness, ventricle diameters, and LVM were all significant and of similar magnitude for obese men and women. Likewise, hypertensive men and women showed similar relative increments of LVM and wall thickness but no changes in end-diastolic internal diameters. Accordingly, obesity was predominantly associated with eccentric hypertrophy (men +/- 14%, women +17%, P<0.05 vs normals) and hypertension with concentric hypertrophy (men +16%, women +30%, P<0.01 vs normals). Women with concurrent obesity and hypertension presented with a further increase of LVM and wall thickness above values in the merely obese or hypertensive (P<0.001) and they displayed LVH more frequently than only obese or hypertensive women (P<0.05). We conclude that the hearts of postmenopausal women respond more susceptibly to the concurrence of hypertension and obesity. In particular the prognostically less favourable concentric LVH is a common finding. Our study may help to explain the higher risk associated with LVH in women.
Overweight and hypertension are considered to be independent contributors to the development of left ventricular hypertrophy (LVH). We investigated a selected subgroup (n = 520, aged 52 to 67 years) of participants from the MONICA Augsburg cohort to assess gender-specificity of left ventricular adaptation in response to increasing weight and blood pressure degrees. M-mode-echocardiographic measurements were made and calculated according to the Penn-convention in 293 women and 227 men. LVH was defined as left ventricular mass indexed to height (LVMIm) > 143 g/m in men and > 102 g/m in women (Framingham criteria). Men and women were comparable with regard to increase in LVMIm from the lowest weight and blood pressure group to the highest groups, respectively. In men the increase in LVMIm was 31% from lean to severely obese subjects (111 vs. 145 g/m, p < 0.003) and 25% from normotensive to treated hypertensive subjects (116 vs. 145 g/m, p < 0.0001); in women respective values were 36% (83 vs. 113 g/m, p < 0.0001) and 27% (88 vs. 112 g/m, p < 0.0001). The combined occurrence of obesity and hypertension had an additional effect on left ventricular mass, which was much more pronounced in women than in men. In particular, the increase in LVMIm from the group of lean normotensives to the group of severely obese treated hypertensives was 85% (72 g/m vs. 133 g/m, p < 0.0001) in women and 49% (96 g/m vs. 144 g/m, p < 0.002) in men (p-value for the gender-interaction term < 0.05). The odds ratio for the LVH-prevalence in hypertensive obese subjects as opposed to normal weight normotensive subjects were 11.9 (p < 0.0001) in women and 4.9 (p < 0.0004) in men. In conclusion, we observed for both genders independently and similarly pronounced effects of hypertension and obesity. The combined occurrence of hypertension and obesity had an additional impact on left ventricular mass and hypertrophy, however, in women the effects were significantly more pronounced than in men. The data underscore the effects of hypertension and obesity in the development of LVH. In addition, gender specific factors seem to modulate the effects of these risk factors on left ventricular mass.
Blood pressure recordings in epidemiological surveys are usually obtained by non-ambulatory, multiple one-occasion, manual sphygmomanometric measurements by trained observers in study participants subjected to standardized examination conditions. High validity and reliability of blood pressure measurements ensure the comparability of study results obtained in different places and at different times, and have a major impact on the detection of correlates and determinants of blood pressure and hypertension. A blood pressure measurement quality assessment was performed within the multi-center collaborative WHO-MONICA Project investigating results of 47 surveys from various geographic regions of the world. In an overall summary assessment, six out of these 47 surveys were found to have had major measurement problems which prohibited their further inclusion in collaborative analyses. Most of the problems were associated with observer-related factors. Therefore, it was contended that automatic blood pressure measurement devices might be able to reduce and abolish most of these "nuisance" factors. In 1995, we had the opportunity to simultaneously study two independent random samples of men and women, aged 45 to 64 years, from the city of Augsburg in Southern Germany. One sample was examined by 16 observers with a random zero sphygmomanometer (MONICA Augsburg), the other sample (J.A.P. Study) was examined by two observers with an invasively validated, automatic oscillometric device (boso Oscillomat). In both surveys, blood pressure was measured three times under similarly standardized conditions. comparing the blood pressure results of the two surveys, the intra-individual measurement variation tended to be slightly higher with the Oscillomat than the random zero, and the population mean blood pressures and hypertension prevalences were found to be significantly lower with the Oscillomat. We conclude that manual measurements of blood pressure by sphygmomanometer should not be indiscriminately replaced externally validated automatic devices. The imponderabilities of automatic devices with varying technical principles have to be assessed in epidemiological settings weighed against recognized disadvantages of sphygmomanometry before any recommendations can be given as to changing the present epidemiological practice.
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