The PIUMA study

Relation Between Serum Uric Acid and Risk of

Cardiovascular Disease in Essential Hypertension

The PIUMA Study

Paolo Verdecchia,Giuseppe Schillaci,GianPaolo Reboldi,Fausto Santeusanio,

Carlo Porcellati,Paolo Brunetti

Abstract—The question of serum uric acid as an independent risk factor in subjects with essential hypertension remains controversial.For up to12years(mean,4.0)we followed1720subjects with essential hypertension.At entry,all subjects were untreated and all were carefully screened for absence of cardiovascular disease,renal disease,cancer,and other important disease.Outcome measures included total cardiovascular events,fatal cardiovascular events,and all-cause mortality.During6841person-years of follow-up there were184cardiovascular events(42fatal)and80deaths from all causes.In the4quartiles of serum uric acid(division points:0.268,0.309,and0.369mmol/L[4.5,5.2,and6.2 mg/dL]in men;0.190,0.232,and0.274mmol/L[3.2,3.9,and4.6mg/dL]in women),the rate(per100person-years) of cardiovascular events was2.51,1.48,2.66,and4.27,that of fatal cardiovascular events was0.41,0.33,0.38,and1.23, and that of all-cause deaths was1.01,0.55,0.93,and2.01,respectively.The relation between uric acid and event rate was J-shaped in both genders.After adjustment for age,gender,diabetes,total cholesterol/HDL cholesterol ratio,serum creatinine,left ventricular hypertrophy,ambulatory blood pressure,and use of diuretics during follow-up,uric acid levels in the highest quartile were associated with increased risk for cardiovascular events(relative risk,1.73;95%CI,

1.01to3.00),fatal cardiovascular events(relative risk,1.96;95%CI,1.02to3.79),and all-cause mortality(relative risk,

1.63;95%CI,1.02to

2.57)in relation to the second quartile.In untreated subjects with essential hypertension,raised

uric acid is a powerful risk marker for subsequent cardiovascular disease and all-cause mortality.(Hypertension.

2000;36:1072-1078.)

Key Words:uric acidⅢblood pressureⅢcardiovascular diseaseⅢhypertension,essential

Ⅲblood pressure monitoringⅢhypertrophy,left ventricular

S everal cohort studies conducted over the past5decades showed a link between serum uric acid(SUA)and subsequent cardiovascular(CV)disease.1–15However,in some of these studies such association did not remain significant after adjustment for concomitant risk factors for CV disease2,4,5,12,15or it was detected only in women.6,8,10 Thus,the role of SUA as an independent risk marker remains controversial.16An increase in SUA might be simply a marker of obesity,hyperinsulinemia and glucose intoler-ance,17,18hypertension,5hyperlipidemia19and renal disease.20,21

The assessment of the independent prognostic value of SUA is clinically relevant in the specific setting of essential hypertension,in which hyperuricemia is frequent22and car-diovascular risk stratification is of utmost importance.In a recent cohort study in subjects with hypertension,14the association between SUA and future CV events remained significant after adjustment for concomitant diuretic therapy,previous CV events,and other risk factors including office blood pressure(BP).In contrast,pretreatment SUA was not an independent predictor of CV events in the setting of the European Working Party on High Blood Pressure in the Elderly trial.23

Because of the discrepancy between these findings,we analyzed the Progetto Ipertensione Umbria Monitoraggio Ambulatoriale(PIUMA)database to clarify the independent prognostic value of SUA in a large cohort of initially untreated and apparently healthy subjects with essential hypertension.

Methods

PIUMA Study

The design of the PIUMA study has been reported previously.24,25 Office BP had to be?140mm Hg systolic and/or?90mm Hg diastolic on?3visits,and all of the subjects fulfilled the following inclusion criteria:no previous antihypertensive treatment or treat-

Received March13,2000;first decision April12,2000;revision accepted June6,2000.

From Ospedale Raffaello Silvestrini,Unita`Operativa di Malattie Cardiovascolari,Perugia(P.V.,C.P.);Ospedale Beato G.Villa,Citta`della Pieve (G.S.);and Dipartimento di Medicina Interna,Universita`di Perugia(G.R.,F.S.,P.B.),Italy.

Correspondence to Dr Paolo Verdecchia,Ospedale“R.Silvestrini,”Dipartimento di Discipline Cardiovascolari,S.Andrea delle Fratte,06156Perugia PG,Italy.E-mail verdec@tin.it

?2000American Heart Association,Inc.

Hypertension is available at https://www.sodocs.net/doc/c612020567.html,

ment withdrawn from?4weeks;no clinical or laboratory evidence of heart failure,coronary artery disease,significant valvular defects, secondary causes of hypertension,or other concomitant important disease;?1valid BP measurement per hour over the24hours. Procedures

The present analysis involved1720subjects enrolled from June1986 to December1996,for whom SUA levels were available.An additional group of429PIUMA subjects,who were excluded from the study because SUA levels were not available for technical or administrative reasons,did not differ by age,gender distribution, body mass index,prevalence of diabetes and left ventricular(LV) hypertrophy,office and ambulatory BP,total cholesterol(TC),HDL cholesterol(HDL-C)and LDL cholesterol(LDL-C),triglycerides, and creatinine(all P?NS)from the study population.BP was measured by a physician with a calibrated mercury sphygmomanom-eter in the outpatient clinic,with the subject sitting and relaxed for ?10minutes.The average of3measurements was used for analysis. Ambulatory BP was recorded with an oscillometric device

(SpaceLabs5200,90202,and90207,SpaceLabs),and measurements were automatically taken every15minutes throughout the24hours. Data editing was done as previously described.24Standard12-lead ECG was recorded in all subjects at25mm/s and1mV/cm calibration.LV hypertrophy was diagnosed by using a score recently developed in our laboratory26and prognostically validated.27 Follow-Up

Subjects were followed by their family doctors in cooperation with the colleagues of the outpatient clinic of the referring hospital and treated with the aim of reducing office BP?140/90mm Hg,with standard lifestyle and pharmacological measures used.There were frequent contacts with family doctors and telephone interviews with patients to ascertain the vital status and the occurrence of major cardiovascular complications.All interviews were conducted with-out knowledge of the patient’s data.

End Point Evaluation

Hospital record forms and other source documents of patients who had an end point event were reviewed in conference by the authors of this study.CV events included myocardial infarction,unstable angina with concomitant ischemic ECG changes,stroke,transient cerebral ischemia,symptomatic aortoiliac occlusive disease verified at angiography,congestive heart failure requiring hospitalization, renal failure requiring dialysis,and death from all causes.The international standard criteria used to diagnose outcome events in the PIUMA study have been described elsewhere.24,25,27

Data Analysis

Statistical analyses were performed with SAS/STAT(SAS Institute) release6.12.Parametric data are reported as mean?SD.Standard descriptive and comparative statistical analyses were undertaken.In 2-tailed tests,probability values?0.05were considered statistically significant.For the subjects who had multiple events,survival analysis was based on the first event.Survival curves were estimated by means of the Kaplan-Meier product-limit method28and compared by the Mantel(log-rank)test.29The effect of prognostic factors on survival was evaluated by means of the Cox model.30We tested the following variables:age(years),gender(women,men),diabetes(no, yes),serum cholesterol(mmol/L),serum creatinine(mmol/L),smok-ing habits(current smokers,previous smokers,never-smokers),body mass index(kg/m2),LV hypertrophy at ECG26,27(no,yes),and diuretic therapy during the follow-up(yes,no).Diabetes mellitus was defined by a fasting blood glucose level?140mg/dL,a random nonfasting blood glucose level?200mg/dL,or the use of an oral hypoglycemic agent or insulin.Diastolic BP and pulse pressure(PP) were tested as average24-hour values because their predictive value is superior to that of office BP.31Because the rate of CV events and all-cause mortality did not increase linearly with SUA(Figure1),it was not tested as a continuous variable in the Cox model.30 Consequently,subjects were grouped according to the gender-specific quartile of SUA distribution(division points:0.268,0.309, and0.369mmol/L[4.5,5.2,and6.2mg/dL])in men;0.190,0.232, and0.274mmol/L[3.2,3.9and4.6mg/dL]in women).

Results

Patient Characteristics

Table1presents demographic and clinical characteristics for the study population.Several baseline characteristics differed among the4quartiles of distribution of SUA.Subjects in the highest quartile showed a cluster of demographic,biochemical, and BP features potentially associated with increased CV risk. The prevalence of subjects with concomitant diabetes showed a J-shaped distribution,with higher values in the first than in the second quartile(P?0.01),and another rise in the third and fourth quartile.SUA showed a direct association with serum creatinine (r?0.31,P?0.001),TC/HDL-C(r?0.23;P?0.001),and body mass index(r?0.28;P?0.001)and a weaker although signifi-cant direct association with glucose(r?0.07;P?0.01)and average24-hour systolic(r?0.11;P?0.01)and diastolic (r?0.11;P?0.01)BP.There was also an inverse association between SUA and HDL-C(r??0.22;P?0.001). Antihypertensive Therapy

At the follow-up contact,38.8%of the subjects were receiv-ing lifestyle measures alone,11.4%?-blockers alone or combined with other agents,22.3%ACE inhibitors or cal-cium antagonists alone or combined,and27.5%other drug combinations.Such distribution did not differ among the4 quartiles of SUA(P?NS).However,the proportion of subjects treated with diuretics,alone or combined with other agents,during follow-up,was13.0%,14.2%,16.4%,and 19.4%,respectively,in the4quartiles of pretreatment SUA (P?0.008).

Prognostic Value of SUA

The subjects who developed a first CV event during follow-up were184(10.7%).In the429subjects excluded from the study because SUA determination was not available, there were46CV events(10.7%;P?NS versus the study group).There were48subjects with stroke,36with myocar-dial infarction,10with sudden cardiac death,5with cardiac death from other causes,20with transient cerebral ischemia, 21with unstable angina,5with aortocoronary bypass

sur-Figure1.Unadjusted rate of total CV events,fatal CV events, and all-cause deaths in the4quartiles of the distribution of serum uric acid.Division points for quartiles:0.268,0.309,and 0.369mmol/L[4.5,5.2,and6.2mg/dL]in men;0.190,0.232, and0.274mmol/L[3.2,3.9,and4.6mg/dL]in women.

Verdecchia et al Uric Acid and Cardiovascular Risk1073

gery,15with heart failure requiring hospitalization,19with new-onset aortoiliac occlusive disease,and5with renal failure requiring dialysis.Fifteen of the42fatal CV events were preceded by a nonfatal event,and the others occurred as first clinical manifestation.In detail,there were8cases of fatal stroke,5cases of fatal myocardial infarction,13cases of sudden cardiac death,and16cases of non–sudden cardiac death.Overall,there were80deaths from any cause.

As shown in Table2,the subjects who had a CV event were older that the subjects who did not.Moreover,diabetes and LV hypertrophy were more common among the subjects with future CV events,who also showed a higher BP(both office and ambulatory)and higher levels of TC,TC/HDL-C, triglycerides,glucose,creatinine,and SUA.In the4quartiles of SUA distribution,the rate(per100person-years)of future CV events was2.51,1.48,2.66,and4.27;that of fatal CV events was0.41,0.33,0.38,and1.23;and that of all-cause deaths was 1.01,0.55,0.93,and 2.01,respectively(all P?0.01;log-rank test).The rate of total CV events,fatal CV events,and all-cause deaths showed a J-shaped distribution in both genders(Figure1),with the bottom level in the second quartile of SUA distribution(268to309mmol/L[4.5to5.2 mg/dL]in men;190to232mmol/L[3.2to3.9mg/dL]in women).

Results of multivariate survival analysis are reported in Table3.After adjustment for age,gender,diabetes,TC/HDL-C,LV hypertrophy,and24-hour PP,SUA levels in the highest quartile were associated with increased risk for total CV events(relative risk,1.73;95%CI,1.01to3.00)in comparison with the second quartile.Furthermore,SUA levels in the highest quartile also predicted an increased risk of fatal CV events(relative risk,1.96;95%CI,1.02to3.79) and all-cause deaths(relative risk,1.63;95%CI,1.02to2.57) in relation to the second quartile.Serum creatinine,24-hour diastolic BP,and diuretic treatment during follow-up did not enter the final model.The age-adjusted and TC/HDL-C–adjusted4-year risk of CV disease,standardized to different levels of significant explanatory variables in either gender,is reported in Figure2.

Discussion

In our large cohort of subjects with essential hypertension, pretreatment SUA showed an association with subsequent CV events and death from all causes.In the highest quartile of SUA(?0.369mmol/L[6.2mg/dL]in men;?0.274mmol/L[4.6mg/dL]in women),such association was clinically consistent and independent of many potential confounders including age,gender,body mass index,diabe-tes,TC/HDL-C,serum creatinine,LV hypertrophy,ambula-tory BP,and diuretic treatment during follow-up.At entry into the study,when SUA was determined,all subjects were untreated,important concomitant disease were excluded,and,

TABLE1.Demographic and Clinical Characteristics in Total Population and by Quartile of Distribution of Serum Uric Acid

Variable All Subjects

(n?1720)

Serum Uric Acid(Quartiles)

1

(n?454)

2

(n?431)

3

(n?433)

4

(n?402)

Age,y51(12)50(12)50(12)52(12)54(13)*??

Women,%46.548.044.843.649.8

Known duration of hypertension,y 4.3(6) 3.8(5.1) 3.9(5.8) 4.5(5.7) 5.1(6.6)*

Weight,kg75(14)72(13)75(14)77(13)78(14)?

Body mass index,kg/m226.9(3.9)25.6(4)26.6(4)27.2(4)28.2(4)*??

Diabetes,%8.29.7? 5.6 5.512.2*?§

Cigarette smoking,%2326212620

TC,mmol/L 5.52(1.1) 5.33(1.01) 5.54(1.03) 5.55(1.08) 5.69(1.14)*

HDL-C,mmol/L 1.25(0.31) 1.28(0.29) 1.28(0.29) 1.23(0.31) 1.21(0.34)?

LDL-C,mmol/L 3.57(0.96) 3.52(0.92) 3.59(0.95) 3.57(0.98) 3.59(1.00)

TC/HDL-C 4.64(1.33) 4.42(1.34) 4.52(1.18) 4.73(1.33) 4.96(1.45)*?

Triglycerides,mmol/L 1.67(1.11) 1.35(0.81) 1.52(0.78) 1.75(1.05) 2.12(1.54)*?§

Creatinine,mmol/L87.5(30)81.7(19)84.7(16)87.6(17)97.0(51)*?§

Uric acid,mmol/L0.282(0.085)0.198(0.046)0.257(0.041)0.304(0.045)0.380(0.073)*?§

LV hypertrophy,%18.014.217.719.720.9*

Office BP,mm Hg

Systolic157(19)157(18)156(18)158(19)159(21)??

Diastolic98(10)97(9)97(9)98(10)97(11)

Average24-h BP,mm Hg

Systolic138(15)137(15)136(14)138(16)140(16)??

Diastolic87(10)86(10)86(10)87(11)86(11)

Data expressed as mean(SD).

*P?0.01vs1;?P?0.01vs2;?P?0.05vs3;§P?0.01vs3;?P?0.05vs1.

1074Hypertension December2000

in addition to traditional risk markers,ambulatory BP was available in all subjects.Consequently,the PIUMA database offered the unique opportunity to test the independent prog-nostic value of pretreatment SUA in a large,apparently healthy hypertensive population without the disturbing influ-ence of several powerful confounding factors including di-uretic therapy,race,and overt concomitant disease. Comparison With Previous Studies

Our results are in agreement with the findings of a study by Alderman et al,14who found an association between SUA and subsequent CV events in a large multiracial population of subjects with essential hypertension.In that study,CV dis-ease risk was better predicted by in-treatment than by pretreatment SUA,and such association persisted after ad-justment for diuretic therapy,serum creatinine,and race in addition to traditional risk factors.However,the prognostic value of SUA was not significant in whites as well as in subjects without a history of CV disease.In the European Working Party on High Blood Pressure in the Elderly trial,a significant univariate association between pretreatment SUA and cardiac mortality disappeared after adjustment for age, gender,and previous CV disease.23In the Systolic Hyperten-sion in the Elderly Program32SUA was a univariate predictor of coronary events,and its predictive value bordered statis-tical significance in the multivariate analysis(relative risk, 1.09;95%CI,1.00to1.19).32

Conflicting epidemiological data on the independent prog-nostic role of SUA might be accounted for by the complex interrelations between SUA and a variety of risk markers for CV disease,including male gender,BP,and previous CV events.18–21The Systolic Hypertension in the Elderly Pro-gram32and the Chicago Studies6included several individuals with previous CV events.Furthermore,the effect of diuretics on glucose and lipids,33in addition to that on SUA,34might lead to subtle interactions of potential prognostic value that could be difficult to control in a multivariate survival analysis.

An example of the difficulties that may arise when the conclusions of general population studies are applied to particular clinical conditions comes from a recent analysis of the Framingham Heart Study,15which did not detect any association between SUA and CV events after adjustment for age,office BP,total cholesterol,smoking,diabetes,and diuretic therapy.In that study,only one third of men and30% of women were hypertensive,5%of men and10%of women were taking diuretics at the time of SUA determination,and renal function was not included among the potential con-

TABLE2.Clinical Characteristics of Subjects With and Without Cardiovascular End Points

Characteristic No Cardiovascular

End Points

(n?1536)

Cardiovascular

End Points

(n?184)P

Age,y50(12)61(11)0.0001

Women,%47.439.10.034

Known duration of hypertension,y 4.2(6) 5.2(7)0.002

Weight,kg75.5(14)74.1(12)0.21

Body mass index,kg/m226.9(3.9)26.8(4)0.87

Diabetes,% 5.828.30.0001

Cigarette smoking,%23270.24

TC,mmol/L 5.50(1.1) 5.67(1.1)0.060

HDL-C,mmol/L 1.27(0.31) 1.15(0.30)0.0001

LDL-C,mmol/L 3.55(0.96) 3.72(0.95)0.050

TC/HDL-C 4.58(1.28) 5.25(1.60)0.0001

Triglycerides,mmol/L 1.65(1.12) 1.63(1.01)0.038

Creatinine,mmol/L86.3(27)97.7(45)0.0001

Glucose,mmol/L 5.57(1.2) 6.45(2.1)0.0001

Uric acid,mmol/L0.279(0.083)0.309(0.093)0.0001

LV hypertrophy,%16.036.30.0001

Office BP,mm Hg

Systolic156(18)165(21)0.0001

Diastolic98(10)96(12)0.007

Pulse58(17)70(20)0.0001

Average24-h BP,mm Hg

Systolic136(14)148(18)0.0001

Diastolic86(10)88(11)0.020

Pulse50(9)60(14)0.0001

Data expressed as mean(SD).

Verdecchia et al Uric Acid and Cardiovascular Risk1075

founders.15Therefore,the conclusions of that study that SUA should not be used as a predictor of CV risk15might be more relevant to the general population than to the clinical context of untreated subjects with essential hypertension free of overt renal failure or CV disease.Conversely,the results of the present study can be applied to such a context,but possibly not to the general population.

In our study,the relation of SUA to CV events and all-cause mortality was J-shaped(figures),with a nadir in the second quartile.A similar J-shaped relation is also apparent from inspection of studies by Alderman et al14in subjects with hypertension,Lehto et al7in subjects with type2 diabetes,and Bengtsson et al9in a general population.In the Framingham Heart Study,15the relation of SUA to coronary heart disease,CV mortality and all-cause mortality appeared to be J-shaped in men but not in women.In our study, prevalence of diabetes mellitus was J-shaped across the4 quartiles of SUA,possibly reflecting clusters of diabetic patients with low and high levels of SUA,and this might be one reason for the nonlinear increase of CV risk with SUA. The prognostic value of SUA in the general population is supported by results of the National Health and Nutrition Examination Survey I Epidemiologic Follow-up Study.35 Subjects with history of myocardial infarction,stroke,or gout at entry were excluded from the study.SUA was a potent predictor of CV mortality over a16-year follow-up period after adjustment for age,race,body mass index,smoking, alcohol consumption,cholesterol levels,diuretic use,and history of hypertension or diabetes.35

Increased SUA in Hypertension

The mechanisms underlying the increase in SUA and its potential prognostic implications in patients with essential

TABLE3.Multivariate Survival Analysis

Variable Comparison Relative Risk(95%CI)P Cardiovascular morbidity

Age(5y) 1.23(1.12–1.34)0.00001 Sex(men vs women) 1.71(1.17–2.50)0.0055 Diabetes(yes vs no) 1.91(1.21–2.99)0.0050 LV hypertrophy(yes vs no) 1.74(1.18–2.57)0.0052 24-h PP(10mm Hg) 1.37(1.17–1.62)0.0002 TC/HDL-C(1U) 1.24(1.10–1.40)0.0006 SUA Quartile1vs2 1.14(0.62–2.06)0.66

Quartile3vs2 1.46(0.84–2.52)0.17

Quartile4vs2 1.73(1.01–3.00)0.0492 Cardiovascular mortality

Age(5y) 1.81(1.49–2.21)0.00001 Sex(men vs women) 1.94(0.96–3.93)0.060 Diabetes(yes vs no) 1.92(0.96–3.85)0.066 24-h PP(10mm Hg) 1.41(1.11–1.79)0.0046 SUA Quartile1vs2 2.03(0.61–6.81)0.86

Quartile3vs2 1.03(0.30–3.62)0.85

Quartile4vs2 1.96(1.02–3.79)0.042 All-cause mortality

Age(5y) 1.68(1.48–1.91)0.00001 Sex(men vs women) 2.66(1.64–4.34)0.0001 Diabetes(yes vs no) 1.67(1.02–2.72)0.0401 24-h PP(10mm Hg) 1.28(1.08–1.50)0.0034 SUA Quartile1vs2 1.73(0.77–3.89)0.18

Quartile3vs2 1.43(0.64–3.20)0.38

Quartile4vs2 1.63(1.02–2.57)

0.037

Figure2.With multivariate Cox regression,age-and cholester-ol-adjusted4-year risk of CV disease was standardized to differ-ent levels of signi?cant explanatory variables in either gender. See Table1for abbreviations.

1076Hypertension December2000

hypertension are still not completely known.Uric acid,a final product of purine metabolism,is bound for5%to plasma proteins,36is freely filtered at the glomerulus as a function of renal blood flow,is99%reabsorbed in the proximal tubule, secreted by the distal tubule,and subjected to considerable postsecretory reabsorption.37Fractional secretion of uric acid is about?7%to10%.37A direct association exists between SUA and renal vascular resistance in subjects with essential hypertension.20In the present study,SUA showed an associ-ation with serum creatinine(r?0.31,P?0.001).Increased SUA levels in asymptomatic and uncomplicated subjects with essential hypertension may reflect early renal vascular alter-ations,with reduction in cortical blood flow and depressed tubular secretion of urate caused by its reduced delivery to the tubular secretory sites.Longitudinal studies are needed to clarify the potential value of SUA to reflect and predict the vicious cycle leading to progressive renal damage and ele-vated blood pressure.Increased activity of the sympathetic nervous system has also been associated with reduced renal excretion of uric acid,38but the basic mechanisms are unknown.Hyperinsulinemia may cause a reduction in urinary excretion of uric acid and sodium through a reduced tubular secretion,increased reabsorption,or both.39Because hyper-insulinemia may increase sympathetic nervous system activ-ity,40elevated SUA levels may reflect both these mecha-nisms.Also,the direct association between SUA and proximal tubular sodium reabsorption41could be mediated by insulin.

In the present study,the highest quartile of SUA was characterized by a cluster of powerful predictors of increased CV disease risk(Table1).Nevertheless,the association between SUA and CV events,CV mortality and all-cause mortality persisted after adjustment for the influence of the above factors.Thus,our results indicate that SUA should not be necessarily viewed as a causative factor for CV disease but most likely as a valuable biological marker that reflects and integrates different risk factors and their possible interactions. It is worth noting that under the present experimental condi-tions,SUA was more accurate than other markers for predic-tion of CV disease risk and all-cause mortality. Limitations of the Study

A strength of the present study was the statistical adjustment for ambulatory BP,which is more accurate than office BP for CV risk stratification,24,42thereby allowing a more conserva-tive estimate of the prognostic value of SUA and other covariates.The main limitation of this study is the absence of information regarding the prognostic value of SUA deter-mined during treatment,previously reported by Alderman et al.14Furthermore,caution is needed when applying the results of this study to nonwhite populations or different clinical settings.

Implications

The present study demonstrates a strong independent associ-ation between SUA and CV risk in initially untreated and asymptomatic adult subjects with essential hypertension,but it is unable to answer the question of whether SUA exerts direct toxic effects.As extensively reviewed by Puig and Ruilope,22both uric acid and superoxide radicals are pro-duced for the effect of xanthine oxidase in the late phase of purine metabolism.Superoxide radicals,which may cause tissue and vascular damage,43are increased in subjects with essential hypertension.44It would be important to clarify whether such increase is due,at least in part,to enhanced xanthine oxidase activity and whether inhibition of this enzyme by allopurinol may reduce CV risk.

Acknowledgments

This study was supported in part by grants from the Associazione Umbria Cuore e Ipertensione,Perugia.The authors thank Mariano Cecchetti and Paolo De Luca for nursing assistance.

References

1.Gertler MM,Garn SM,Levine SA.Serum uric acid in relation to age and

physique in health and coronary heart disease.Ann Intern Med.1951;34: 1421–1431.

2.Reunanen A,Takkunen H,Knekt P,Aromaa A.Hyperuricemia as a risk

factor for cardiovascular mortality.Acta Med Scand Suppl.1982;668: 49–59.

3.Yano K,Reed DM,McGee DL.Ten-year incidence of coronary heart

disease in the Honolulu Heart Program:relationship to biologic and lifestyle characteristics.Am J Epidemiol.1984;119:653–666.

4.Brand FN,McGee DL,Kannel WB,Stokes JD,Castelli WP.Hyper-

uricemia as a risk factor of coronary heart disease:the Framingham Study.Am J Epidemiol.1985;121:11–18.

5.Klein R,Klein BE,Cornoni JC,Maready J,Cassel JC,Tyroler HA.

Serum uric acid:its relationship to coronary heart disease risk factors and cardiovascular disease,Evans County,Georgia.Arch Intern Med.1973;

132:401–410.

6.Levine W,Dyer AR,Shekelle RB,Schoenberger JA,Stamler J.Serum

uric acid and11.5-year mortality of middle-aged women:findings of the Chicago Heart Association Detection Project in Industry.J Clin Epi-demiol.1989;42:257–267.

7.Lehto S,Niskanen L,Ronnemaa T,Laakso M.Serum uric acid is a strong

predictor of stroke in patients with non–insulin-dependent diabetes mellitus.Stroke.1998;29:635–639.

8.Freedman DS,Williamson DF,Gunter EW,Byers T.Relation of serum

uric acid to mortality and ischemic heart disease:the NHANES I Epide-miologic Follow-up Study.Am J Epidemiol.1995;141:637–644.

9.Bengtsson C,Lapidus L,Stendahl C,Waldenstrom J.Hyperuricaemia

and risk of cardiovascular disease and overall death:a12-year follow-up of participants in the population study of women in Gothenburg,Sweden.

Acta Med Scand.1988;224:549–555.

10.Persky VW,Dyer AR,Idris-Soven E,Stamler J,Shekelle RB,Schoen-

berger JA,Berkson DM,Lindberg HA.Uric acid:a risk factor for coronary heart disease?Circulation.1979;59:969–977.

11.Ward HJ.Uric acid as an independent risk factor in the treatment of

hypertension[published erratum appears in Lancet1998;352:912].

Lancet.1998;352:670–671.

12.Wannamethee SG,Shaper AG,Whincup PH.Serum urate and the risk of

major coronary heart disease events.Heart.1997;78:147–153.

13.Fessel WJ.High uric acid as an indicator of cardiovascular disease:

independence from obesity.Am J Med.1980;68:401–404.

14.Alderman MH,Cohen H,Madhavan S,Kivlighn S.Serum uric acid and

cardiovascular events in successfully treated hypertensive patients.

Hypertension.1999;34:144–150.

15.Culleton BF,Larson MG,Kannel WB,Levy D.Serum uric acid and risk

for cardiovascular disease and death:the Framingham Heart Study.Ann Intern Med.1999;131:7–13.

16.Vaccarino V,Krumholz HM.Risk factors for cardiovascular disease:one

down,many more to evaluate.Ann Intern Med.1999;131:62–63.

17.Lee J,Sparrow D,Vokonas PS,Landsberg L,Weiss ST.Uric acid and

coronary heart disease risk:evidence for a role of uric acid in the obesity-insulin resistance syndrome:the Normative Aging Study.Am J Epidemiol.1995;142:288–294.

18.Modan M,Halkin H,Karasik A,Lusky A.Elevated serum uric acid:a

facet of hyperinsulinaemia.Diabetologia.1987;30:713–718.

19.Puig JG,Michan AD,Jime`nez ML,Pe`rez de Ayala C,Matetos FA,

Capitan CF,de Miguel E,Gijon JB.Female gout:clinical spectrum and uric acid metabolism.Arch Intern Med.1991;151:726–732.

Verdecchia et al Uric Acid and Cardiovascular Risk1077

20.Messerli FH,Frohlich ED,Dreslinski GR,Suarez DH,Aristimuno GG.

Serum uric acid in essential hypertension:an indicator of renal vascular involvement.Ann Intern Med.1980;93:817–821.

21.Frohlich ED.Uric acid:a risk factor for coronary heart disease.JAMA.

1993;270:378–379.

22.Puig JG,Ruilope LM.Uric acid as a cardiovascular risk factor in arterial

hypertension.J Hypertens.1999;17:869–872.

23.Staessen J.The determinants and prognostic significance of serum uric

acid in elderly patients of the European Working Party on High Blood Pressure in the Elderly trial.Am J Med.1991;90:50S–54S.

24.Verdecchia P,Porcellati C,Schillaci G,Borgioni C,Ciucci A,Battistelli

M,Guerrieri M,Gatteschi C,Zampi I,Santucci A,Santucci C,Reboldi G.

Ambulatory blood pressure:an independent predictor of prognosis in essential hypertension.Hypertension.1994;24:793–801.

25.Verdecchia P,Schillaci G,Borgioni C,Ciucci A,Gattobigio R,Zampi I,

Reboldi G,Porcellati C.Prognostic significance of serial changes in left ventricular mass in essential hypertension.Circulation.1998;97:48–54.

26.Schillaci G,Verdecchia P,Borgioni C,Ciucci A,Guerrieri M,Zampi I,

Battistelli M,Bartoccini C,Porcellati C.Improved electrocardiographic diagnosis of left ventricular hypertrophy.Am J Cardiol.1994;74: 714–719.

27.Verdecchia P,Schillaci G,Borgioni C,Ciucci A,Gattobigio R,Zampi I,

Porcellati C.Prognostic validation of a new electrocardiographic method for diagnosis of left ventricular hypertrophy in essential hypertension.

J Am Coll Cardiol.1998;31:383–390.

28.Kaplan ER,Meier P.Nonparametric estimation from incomplete obser-

vations.J Am Stat Assoc.1958;53:457–481.

29.Mantel N.Evaluation of survival data and two new rank order statistics

arising in its consideration.Cancer Chemother Rep.1966;50:163–170.

30.Cox DR.Regression models and life-tables.J R Stat Soc(B).1972;34:

187–220.

31.Verdecchia P,Schillaci G,Borgioni C,Ciucci A,Pede S,Porcellati C.

Ambulatory pulse pressure:a potent predictor of total cardiovascular risk in hypertension.Hypertension.1998;32:983–988.

32.Frost PH,Davis BR,Burlando AJ,Curb JD,Guthrie GP Jr,Isaacsohn JL,

Wassertheil-Smoller S,Wilson AC,Stamler J.Coronary heart disease risk

factors in men and women aged60years and older:findings in the Systolic Hypertension in the Elderly Program.Circulation.1996;94: 26–34.

33.Lewis PJ,Kohner EM,Petrie A,Dollery CT.Deterioration of glucose

tolerance in hypertensive patients on prolonged diuretic treatment.

Lancet.1976;1:564–566.

https://www.sodocs.net/doc/c612020567.html,ngford HG,Blaufox MD,Borhani NO,Curb JD,Molteni A,Schneider

KA,Pressel S.Is thiazide-produced uric acid elevation harmful?analysis of data from the Hypertension Detection and Follow-up Program.Arch Intern Med.1987;147:645–649.

35.Fang J,Alderman MH.Serum uric acid and cardiovascular mortality:the

NHANES I Epidemiological Follow-up Study,1971–1992.JAMA.2000;

283:2404–2410.

36.Klindberg JR,Kippen I.The binding of urate to plasma proteins

determined by means of equilibrium dialysis.J Lab Clin Med.1970;75: 503–510.

37.Holmes WEN,Kelley NW,Wynguarden JB.The kidney and uric acid

excretion in man.Kidney Int.1972;2:115–118.

38.Ferris TF,Gorden P.Effect of angiotensin and norepinephrine upon urate

clearance in man.Am J Med.1968;44:359–365.

39.Quinones Galvan A,Natali A,Baldi S,Frascerra S,Sanna G,Ciociaro D,

Ferrannini E.Effect of insulin on uric acid excretion in humans.Am J Physiol.1995;268:E1–E5.

40.Reaven GM,Lithell H,Landsberg L.Hypertension and associated met-

abolic abnormalities:the role of insulin resistance and sympathoadrenal system.N Engl J Med.1996;334:374–381.

41.Cappuccio FP,Strazzullo P,Farinaro E,Trevisan M.Uric acid metabo-

lism and tubular sodium handling:results from a population-based study.

JAMA.1993;270:354–359.

42.Perloff D,Sokolow M,Cowan R.The prognostic value of ambulatory

blood pressure.JAMA.1983;249:2792–2798.

43.McCord JM.Oxygen-derived free radicals in postischemic tissue injury.

N Engl J Med.1985;312:159–163.

https://www.sodocs.net/doc/c612020567.html,cy F,O’Connor DT,Schmid-Schoenbein GW.Elevation in plasma

hydrogen peroxide in hypertensive and normotensive subjects at genetic risk for hypertension.J Hypertens.1998;16:292–303.

1078Hypertension December2000

and Paolo Brunetti

Paolo Verdecchia, Giuseppe Schillaci, GianPaolo Reboldi, Fausto Santeusanio, Carlo Porcellati

Hypertension: The PIUMA Study

Relation Between Serum Uric Acid and Risk of Cardiovascular Disease in Essential

Print ISSN: 0194-911X. Online ISSN: 1524-4563

Copyright ? 2000 American Heart Association, Inc. All rights reserved.

is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231

Hypertension doi: 10.1161/01.HYP.36.6.1072

2000;36:1072-1078Hypertension.

https://www.sodocs.net/doc/c612020567.html,/content/36/6/1072World Wide Web at:

The online version of this article, along with updated information and services, is located on the

https://www.sodocs.net/doc/c612020567.html,//subscriptions/is online at: Hypertension Information about subscribing to Subscriptions:

https://www.sodocs.net/doc/c612020567.html,/reprints Information about reprints can be found online at: Reprints:

document. Permissions and Rights Question and Answer this process is available in the click Request Permissions in the middle column of the Web page under Services. Further information about Office. Once the online version of the published article for which permission is being requested is located, can be obtained via RightsLink, a service of the Copyright Clearance Center, not the Editorial Hypertension in Requests for permissions to reproduce figures, tables, or portions of articles originally published Permissions:

(完整版)雅思口语part1试题库

个人信息类 Studies 1.What subject(s) are you studying? 2.Why did you choose to study that subject? 3.Do you like your subject? (Why?/Why not?) 4.Is it very interesting? 5.(Possibly) Are you looking forward to working? 6.Do you prefer to study in the mornings or in the afternoon? Teachers 1.Do you have a favorite teacher? 2.Do you want to be a teacher in the future? 3.What kinds of teachers do you like? 4.Do you think teachers should be angry at students or not? 5.Do you like strict teachers? 6.What's the different between young and old teachers? 7.Is it important for teachers to interact with students frequently? 8.What’s the most important part in your study, teachers or classmates? Hometown 1.What’s (the name of) your hometown (again)? 2.Is that a big city or a small place? 3.Please describe your hometown a little. 4.How long have you been living there? 5.Do you like your hometown? 6.(Possibly) Do you like living there? * 7.What do you like (most) about your hometown? 8.Is there anything you dislike about it? 9.Do you think you will continue living there for a long time? Accommodation 1.What kind of housing/accommodation do you live in? 2.Do you live in a house or a flat? 3.Who do you live with? 4.How long have you lived there? 5.Do you plan to live there for a long time? 6.(If you answer you haven't lived there long) What's the difference between where you are living now and where you have lived in the past? 7.Can you describe the place where you live? 8.Which room does your family spend most of the time in? 9.What do you usually do in your house/flat/room? 10.Are the transport facilities to your home very good? 11.Do you prefer living in a house or a flat? 12.Please describe the room you live in. 13.What part of your hometown do you like the most?

雅思口语Part1参考答案大全

Advertisement广告 1. Do you like advertisements on TV? Oh no, TV is a purgatory. The TV advertisements today appear to be not only boring but also disturbing. They interrupt in the midst of our enjoyment of a game or a film. Most of the advertisement materials are irritating and of course of low taste. The presentation is mostly awkward and obscene. 绝不，电视简直就是炼狱。现在电视上的广告变得不仅仅是无聊了，而且还特别烦人。这些广告往往在我们欣赏比赛或电影时候的中间跳进来。大多数广告特别让人愤怒，当然品味还很低。这些广告的描述又傻又低俗。 2. What kind of advertisement do you like the most? Word of mouth is hands down the BEST advertising. It's one of the most credible forms of advertising because every time people make a recommendation, they have nothing to gain but the appreciation of those who are listening. 口碑绝对是最好的广告。这是最可信的广告方式之一，因为每当人们对一个产品做出评价时，他们除了能得到听者的感谢外，得不到任何其他好处。 3. Why do you think there are so many advertisements now? Whether you do like them or not, whenever and wherever it's possible that you can meet them. For biz sellers, ad could be very helpful to promote their products. For acceptors, ads might show some latest information. To buy or not to buy, to be fond of or not, all depend on your decisions. 无论你是否喜欢广告，你都有可能随时随地遇到它们。对于那些销售人员来说，这也许对推销商品有帮助。对于接收者来说，广告或许能展示给他们最新的信息。买或者不买，喜欢或不喜欢，就取决于个人决策了。

2020转正定级申请书范文

2020转正定级申请书范文 导读：本文是关于2020转正定级申请书范文，希望能帮助到您！ 转正定级申请书范文篇一 明光市教育局：我叫郑建，男， 1982 年 10 月 4 日生于安徽省明光市，20xx 年 7 月毕业于滁州学院政史教育专业(专科学历)，后经进修于 20xx 年 7 月毕业于福建师范大学思想政治教育专业(本科学历)。20xx 年 11 月参加明光市教师招聘考试，通过笔试、面试、体检，20xx 年2 月被分配到明光市旧县中学参加教育工作。自 20xx 年 2 月参加工作以来，认真贯彻落实党的教育方针，坚持“爱岗敬业、教书育人”的原则，服从上级及学校工作安排，认真完成教育教学任务，同时不断学习新的教育教学理论，不断提高自己的思想觉悟和教育教学水平。 一、思想政治方面：自觉加强理论学习，努力提高政治思想素质，积极参与师德师风活动和创先争优活动，并用心实践;认真学习新的教育理论，及时更新教育理念;积极参加校本教研和校本培训;积极参与上级和学校组织的各项活动，在真抓实干中提升自我。 二、教育教学方面：定期给自己充电，自觉学习新的教育教学理念，及时更新教学方法，全面推行素质教育，努力提升教学质量;积极参加学习培训、课堂教学模式活动及上级组织的各项活动;虚心向同行请教，博采众长，为成为一名新形势下的好教师不断开拓进取。 三、工作成绩与不足：在上级领导、学校领导和同事的关心支持下，我在思想、工作、学习各方面都取得了很大进步，同时得到校领导和同事、学生、家长的充分肯定，使稚嫩的我逐渐成熟，实现了从学生到教师的快

速转变。工作三年来，每年都担任三个班级的思想品德课的教学任务(其中两个毕业班)，所带毕业班的中考平均分连续两年位列明光市中上等，20xx 中考中所任教的三 (2)班中考平均分位列明光市第 14 名。在工作的同时积极进行教科研，20xx 年我撰写的《关于网络环境下青少年德育工作的几点新认识》获明光市三等奖。同时，我在工作中也存在一些不足之处，在今后的教育教学工作中，我将不断学习，总结得失，积极进取，在努力工作的同时更要用心工作，用更大的热情投入到今后教育教学工作中，在实践中不断激发潜能和提升自我，实现自己的价值，为教育事业贡献力量。特申请转正定级，请领导审核批准。 申请人：郑建 20xx 年 11 月 8 日 转正定级申请书范文篇二 ***县人力资源和社会保障局：我叫***，男，汉族，大学文化程度，出生于***年*月， ***年*月毕业于*********。20xx 年 1 月，到***工作。参加工作对于年轻人，是人生的一个转折点，也是一个新的起点。在***工作一年来，在领导的关心和同事们的帮助下，我逐步完成着从学校到政府机关、从学生到国家工作人员这种环境和角色的双重转变和适应，自己的思想、工作、学习等各方面都取得了一定的成绩，个人综合素质也得到了一定的提高，现将自己的思想、工作、学习情况作以下汇报。 一、自觉加强理论学习，努力提高思想道德素质一年来，自己主动加强政治学习，按时参加单位每周三的学习例会，系统学习了党的xx大、xx届五中全会精神、中央经济工作会议精神以及省市县最新会议指示、安排，认真做好每次的笔记，并将其运用到指导自己工作的实际当中。作为一名思想要求进步的青年，我还利用业余时间认真学习党章等党的知识，

雅思口语part1试题库

What subject(s) are you studying Why did you choose to study that subject Do you like your subject (Why/Why not) Is it very interesting (Possibly) Are you looking forward to working Do you prefer to study in the mornings or in the afternoon Do you have a favorite teacher Do you want to be a teacher in the future What kinds of teachers do you like Do you think teachers should be angry at students or not Do you like strict teachers What's the different between young and old teachers Is it important for teachers to interact with students frequently What ' s the most important part in your study, teachers or classmates What ' s (the name of) your hometown (again) Is that a big city or a small place Please describe your hometown a little. How long have you been living there Do you like your hometown (Possibly) Do you like living there * What do you like (most) about your hometown Is there anything you dislike about it Do you think you will continue living there for a long time What kind of housing/accommodation do you live in Do you live in a house or a flat Who do you live with How long have you lived there Do you plan to live there for a long time (If you answer you haven't lived there long) What's the difference between where you are living now and where you have lived in the past Can you describe the place where you live Which room does your family spend most of the time in What do you usually do in your house/flat/room Are the transport facilities to your home very good Do you prefer living in a house or a flat Please describe the room you live in. What part of your hometown do you like the most 个人信息类 Studies 2. 3. 4. 5. 6. Teachers 1. 2. 3. 4. 5. 6. 7. 8. Hometown 1. 2. 3. 4. 5. 6. 7. 8. 9. Accommodation 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13.

如何做case study

ecom Case Study规范 一、详细过程 【描述要求】 1．请使用自然语言描述完整的事例过程； 2．请说明每个问题点的具体时间； 3．请说明每次处理问题花费的时间的多少； 4．请说明分析查找问题的具体方法； 5．若进行了紧急处理，请详细描述其具体方法； 二、重点分析 1．问题点1： 描述：【关于问题点1的具体描述】 原因：【造成该问题的具体原因】 处理：【处理该问题的具体方法】 总结：【从对该问题的原因分析及处理中值得总结的经验教训】2．问题点2： 描述：【关于问题点2的具体描述】 原因：【造成该问题的具体原因】 处理：【处理该问题的具体方法】 总结：【从对该问题的原因分析及处理中值得总结的经验教训】3．问题点3： 描述：【关于问题点2的具体描述】 原因：【造成该问题的具体原因】 处理：【处理该问题的具体方法】 总结：【从对该问题的原因分析及处理中值得总结的经验教训】4．问题点4： 描述：。。。 原因：。。。

处理：。。。 总结：。。。 三、改进措施 1．总体原则： 【填写项目将来的改进措施的总体原则】2．实施计划：

【Case Study规定】 1．某产品线的在线服务升级，若遇到意外情况，导致升级完全失败或部分失败，或对预期的升级进度产生严重影响的情况，需进行Case Study； 2．某产品线的新功能上线后，根据各方面反馈，若发现与升级的预期效果严重不符，需进行Case Study； 3．其他技术总监/部门经理/项目经理认为需要进行Case Study的情况； 【Case Study会议流程】 1．开场白：由项目经理简单介绍Case Study的原因； 2．背景介绍：若多数与会人员对进行Case Study的项目不了解，则请项目负责人首先对项目本身做一下简单的介绍；目的是使与会人员对项目的背景环境有一个大致的了解；3．详细描述：由项目负责人描述该Case发生的完整过程；目的是使与会人员了解Case事例的起因、过程、进展、结果及各个着眼点的相互关系； 4．重点分析：由项目负责人分析需要进行Study的各个Case的原因、结果、处理方法，并进行总结；该部分应作为Case Study的会议重点； 5．讨论交流：由项目经理组织与会人员对需要进行Study的各个Case原因、结果、处理方法及其总结进行讨论与交流，由项目负责人进行书面记录； 6．改进计划：由项目经理或项目负责人描述改进计划； 7．结束语：由项目经理或部门经理/技术总监做总结陈词。 【Case Study附加说明】 1．关于文档提交时间： Case Study的文档，应在其所描述的具体事例发生后的3天之内提交； 2．关于文档审核流程： Case Study文档，应有项目负责人负责根据本文文档规范撰写，完成后提交项目经理或部门经理审阅；需要修改的，由项目经理或部门经理提出修改意见，由项目负责人根据意见进行修改，并再次提交审阅，直至最终定稿；定稿后由项目经理或部门经理提交技术总监审阅。 3．关于会议举行时间与与会人员； Case Study会议，应在其所描述的具体事例发生后的一周之内进行；与会人员应是相应项目组内的所有成员，及测试组的测试经理及相关人员，必要时由部门经理或技术总监发起组织其他项目组的成员参与； 4．关于改进计划 本Case Study中列出的改进计划为初步计划，若Case Study中与会人员的讨论结果涉及到改进计划的修订，则由项目经理或部门经理负责进行评估，并根据最终方案监督执行。

雅思口语Part1话题汇总(话题归类版)

Part1: https://www.sodocs.net/doc/c612020567.html, ●What is your full name? ●How should i address you? ●Have you got any English name? ●Are there any special meanings about your name? ●Who gave you this name? 2.Studies or work ●Which school are you studying now? what is your major? ●Who choose the major for you before you entering your university? ●What are the advantages and disadvantages of your university? ●Which subject you like most and which subject do you dislike most? Why? ●Do you like the school you are studying at? 3.Home ●Do you live in a house or a flat? ●Please describe the place where you live. ●How have you decorated your home (or, your room)? ●Is there anything (hanging) on the walls of your home (or your room)? (e.g., decorations) ●What can you see when you look out the window of your room (or, the windows of your home)? 4.Hometown ●Where is your hometown? (Or, what part of China do you come from?) ●Do you think you'll always live there? ●Where do you live at the moment? ●Do you like your hometown? (Why?/Why not?) ●What sorts of buildings are there in your hometown? 5.Books & Reading ●Do you like reading (books)? (Why?/Why not?) C ●What (kinds of ) books do you like to read? C ●(Similar to above) What (kinds of ) books do read (for enjoyment)? ●Are you reading any books at the moment? N ●Did you read much when you were a child? 6.Newspapers & Magazines ●What kind of newspaper do you have in China? ●What is your favorite magazine? ●When did you begin to read newspaper? ●What’s the difference between Chinese newspapers? ●Which one do you prefer to read, newspaper or magazine?

个案研究法(Case Study)

个案研究法（Case Study） 陈姿伶 中兴大学农业推广教育研究所 早在1870年，美国哈佛大学法学院即创用此一个案研究法来训练学生思考法律的原理原则。依叶重新（2001）的考证，此法最初多用于医学方面，应用于研究病人的案例；尔后，陆续地于心理学、社会学及工商管理学等领域相继被沿用，至今于教育界的运用也相当广泛，大都采此法于教学与相关的学习研究上，或者应用于教育心理与儿童心理等领域，特别对于超常儿童、特殊才能儿童、学习落后或低度缺陷儿童等类型学习者的心理研究。 而在这当中几位举足轻重的关键学者，如实验心理学家菲吉纳于1860年创立新物法，针对个别对象，进行有系统的感官研究，建立著名的Fecher’s Law。之后，弗洛伊德及皮亚杰等，于其所涉及的相关研究中皆不难发现「个案研究法」被运用的例证。以弗洛伊德为例，可被视为是运用个案研究法于精神病学的先驱，就其处理精神神经症的病人方面言之，则是致力于发现所谓的「一致的经验模式」。在其细心的探求下，使得病人能够回忆自己在儿童及年轻时代所发生的，但却已遗忘良久的，有关创伤性的或与性有关的意外事件，根据弗洛伊德的假设：这些意外事件或可用来解释病人的神经性行为，以所曾研究之Sergei Petrov 的—位狼人（the Wolf Man）的生活史来说，其最后并以「来自婴幼期神经症的生活史」（From the History of an Infantile Neurosis）为标题，将研究结果撰写成书并于1918年出版问世，此书则是弗洛伊德应用个案研究的典型例举之一，且其所归结获致之个案的结果，事实上与其假设一致吻合，这亦使得心理的个案分析因此一时蔚为时尚，且被认定视为一项有效的处理事情的方法。 总言之，个案的运用与分析，在法律和医学知识的传授上，早就成为最基本的教学工具之一。法律的名词称个案为「案例」或「判例」，医学的名词则称其为「病例」。至于个案分析在社会学上的发展沿革，则可依年代顺序归纳如下：（1）1908年，哈佛大学创设企业管理研究所，由经济学家Edwin F, Gay担任首任院长，他认为企管教学，应仿效哈佛法学院的教学方法，Gay称作「问题方法」（problem method），自此哈佛大学设置个案发展单位。 （2）在1920年代早期，Wallace B. Donam出任哈佛企管研究所主任。他到职后，敦促所属教授，从企业活动中直接搜集资料，拟订新的教材，鼓励教授搜 集有关市场交易，工商财务及其他方面的个案，并从事工商业的实验工作。 他亦吸收不受传统研究方法所约束的学者来一起从事研究。 （3）Elton Mayo，其中一位参与者。领导了「霍桑实验」（Hawthorn Studies）。在社会学方面，「实地研究」这个观念，从研究人类行为的个案已收到了效果。（4）第二次世界大战中后期，哈佛教授搜集了许多其他的个案，设立了一个委员会，用以促进个案研究之教学。该委员会于1937年致力介绍「个案报告」

基础隐蔽工程签证单

塔号G2 施工单位虢都变-交口变110kV输电 线路工程项目部 日期2013年12月10日 基础型式现浇台阶式基础 检查项目： √基础埋深符合图纸要求√基坑各部几何尺寸符合图纸要求 √插入角钢/地螺规格符合图纸要求√钢筋规格、数量及绑扎符合图纸要求√各部模板几何尺寸符合图纸要求√砂、石、水泥、水及钢筋经检验合格√砼配合比、塌落度符合规范要求√砼搅拌、振捣、浇筑符合规范要求√砼试块近制作符合规范要求√基础根开、对角线符合图纸要求√基础拆模后表面质量达到优良/合格级标准要求 以上检查项目经自检合格申请隐蔽 承包商（章） 施工负责人： 年月日监理部审查意见： 项目监理部（章） 总（副）监理师：年月日 监理工程师：年月日

塔号G3 施工单位虢都变-交口变110kV输电 线路工程项目部 日期2013年12月04日 基础型式现浇台阶式基础 检查项目： √基础埋深符合图纸要求√基坑各部几何尺寸符合图纸要求 √插入角钢/地螺规格符合图纸要求√钢筋规格、数量及绑扎符合图纸要求√各部模板几何尺寸符合图纸要求√砂、石、水泥、水及钢筋经检验合格√砼配合比、塌落度符合规范要求√砼搅拌、振捣、浇筑符合规范要求√砼试块近制作符合规范要求√基础根开、对角线符合图纸要求√基础拆模后表面质量达到优良/合格级标准要求 以上检查项目经自检合格申请隐蔽 承包商（章） 施工负责人： 年月日监理部审查意见： 项目监理部（章） 总（副）监理师：年月日 监理工程师：年月日

塔号G4 施工单位虢都变-交口变110kV输电 线路工程项目部 日期2013年11月30日 基础型式现浇台阶式基础 检查项目： √基础埋深符合图纸要求√基坑各部几何尺寸符合图纸要求 √插入角钢/地螺规格符合图纸要求√钢筋规格、数量及绑扎符合图纸要求√各部模板几何尺寸符合图纸要求√砂、石、水泥、水及钢筋经检验合格√砼配合比、塌落度符合规范要求√砼搅拌、振捣、浇筑符合规范要求√砼试块近制作符合规范要求√基础根开、对角线符合图纸要求√基础拆模后表面质量达到优良/合格级标准要求 以上检查项目经自检合格申请隐蔽 承包商（章） 施工负责人： 年月日监理部审查意见： 项目监理部（章） 总（副）监理师：年月日 监理工程师：年月日

跨文化交际案例case study 6

Chapter 5 Verbal and Non-verbal Communication Case 1 Two strangers have been chatting. A: So you’re been here for a year? B: Yes. One more year to go, then I’ll go back to china. A: What will you do back home? B: It’s hard to know. There’s a lot change at the moment. A: Yeah.Everything’s changing, everythere. Sometimes it’s difficult to keep up. B: That’s true. Maybe I’ll… (A’s mobile phone rings.) A: Excuse me, I’d better answer this. It’s probably work. B: Sure. Take your time. 分析：有时在与人交谈中，难免要有什么原因要离开一会儿，或是去接一个电话，或要去洗手间。礼貌再此被提出来。出于礼貌起见，要记住做一些恰当解释再离开。不管理由是什么，即便是要接一个手机电话，在打开电话回话前，向对方说声对不起。 如果只离开几分钟，没有必要找一个理由。你说了对不起，就表明你确实是有事要离开一会儿。 Case 2 One cold winter day in a Chinese city, Wang Lin on his way to the library met an American pro fessor who knew very little about China. After greeting him, Wang said: “It’s rather cold. You’d better put on more clothes.” But the professor didn’t appear happy on hearing this. 分析：美国人以及大部分西方国家的人们不喜欢被告知要怎么做怎么做，他们比较喜欢独立，然而中国人则习惯关心别人，这个案例中王林的建议表达的就是一种对他人的关心，可是美国教授却不习惯这样的表达。 Case 3 Li Ping is calling his colleague and friend Tony. Tony lives in the student dormitory. Someone else answers the phone. Student: Hi, Student Dormitory. Li: Hello. I’d like to speak to Tony please. Student: Okay, just a moment. I’ll see if he’s in. Li: Thanks. Student: He’s on his way. Won’t be long. Li: Thanks for your help. Tony: Hello? Tony is here. Li: Hello, it’s Li Ping. Tony: Hi. Is everything okay? Li: Yes, fine. I wanted to call you to see if you’d like to come over for dinner tonight. I’m cooking a Chinese meal. Tony: That’s fine. By the way, how is your major essay coming along? Have you finished all the reading? Li: Almost. I have to finish the reading by next Sunday. Then I can start writing the

雅思口语Part1问题和答案(各个话题)

Confirmation Questions Good morning/afternoon. How are you? Morning/afternoon. Fine, thank！ How do you do? How do you do? Hi, good to meet you. Good to meet you too. Hi, how are you doing? Not too bad. And you? 1.Can I see your ID card please? Sure, here you are. 2.Could you tell me your full name please? My full name is ……. But you can call me…. 3. And what shall I call you? Mo st people call me …... Hometown Questions 4. Whereabouts is your hometown? Xian is located in Shanxi province, which is in central China. 5. Let's talk about your hometown or village. What kind of place is it? My hometown is a small place, just outside of Beijing. It takes about an hour to reach/get to there. The people there are mostly farmers, but a lot of the young people work in Beijing. It's a quiet place and I like it. 6. Could you tell me something about your hometown? a. Well, it's quite big and it's the capital of Shanxi province. The population's about 6 million and it's famous for its historic sites, especially for the Terracotta Warriors. Xi' an used to be the capital of China, and it's the beginning of the famous Silk Road. b. Okay. Well, my hometown is Beijing and I live just outside of it near the 4th ring road. As you probably know, Beijing's the political and cultural center of China, and it's quite a historical place as well. It's huge-about 12 or 13 million people live in it now-and it seems to be getting bigger every year. 7. What kind of landscape surrounds your hometown? a. Harbin's right near the Song Hua Jiang River and it's kind of in a flat area, with mountains in the distance. b. Indio's a coastal city near the sea, so the main landscapes are the beaches and bays. There are also some nice hills nearby. 8. What are the main tourist attractions in your hometown? There's the Great Wall and the Forbidden City. These are the two that are most well known. They are also symbols of China. They attract most visitors, but there are quite a lot of other famous sites as well. 9. What are the people like in your hometown? They're usually very friendly, but a bit conservative. People still hold onto a lot of old customs and traditions, which is what I mean by conservative. But I think people there are very hospitable and kind. If you ask someone for directions, they'll always try to help you out, or find someone else who can. 10. What places in your hometown do you like best and tell me why? I like the Temple of Heaven best because it's very beautiful. It has a lot of space and there are lots of really nice and old trees there. In the early morning, it's very peaceful.

Case Study 案例分析

Praising Japanese in Public Workplaces （在工作场所当众表扬日本人） 琼斯先生（美国经理）当众表扬苏琦木拓（日本员工）工作做得很棒，本以为苏琦木拓会高兴的接受，却不料….. Case description: American: Mr. Sugimoto, I have noticed that you are doing an excellent job on the assembly line. I hope that the other workers notice how it should be done. Japanese: (He is uneasy). Praise is not necessary. I am only doing my job. (He hopes other Japanese workers do not hear.) American: You are the finest, most excellent, dedicated worker we have ever had at the Jones Corporation. Japanese: (He blushed and nods his head several times, and keeps working.) American: Well, are you going to say “thank you,” Mr. S ugimoto, or just remain silent? Japanese: Excuse me, Mr. Jones … May I take leave for five minutes? American: Sure. (He is annoyed and watched Sugimoto exit). I can’t believe how rude some Japanese workers are. They seem to be disturbed by praise and don’t answer you … just silent. Questions for discussion: 1.Why was the conversation between Mr. Jones and Mr. Sugimoto not so pleasant? 2.Why did they have such different reactions towards praising in public workplaces? 3.If you were Mr. Sugimoto, would you accept praise from Mr. Jones in public workplaces? 4.If you were Mr. Jones, how would you deal with the situation more appropriately?

转正定级表自我鉴定(自我鉴定)

转正定级表自我鉴定 范文一 时光如梭，我参加工作已将近一年。在领导的教导和培养，同事的关心和帮助下，我通过虚心学习和努力工作，在思想及工作方面取得一定成绩，个人综合素质也得到提高，完成了从学生向职业人的转变。 思想上，关心时事政治，自觉树立高尚的世界观、人生观、树立社会主义荣辱观，用先进思想武装自己，同时深入学习了宇通“崇德、协调、鼎新”的企业文化，铭记宇通人的行为准则，时刻约束自身行为，严于利己，主动奉献，弘扬宇通精神，激发正能量。另外，对于公司组织的活动，能够积极参加与配合，平常乐于助人，人际关系融洽，爱护公共财产，关心集体荣誉。 工作上，严格遵守并执行公司的规章制度，积极主动完成上级交代的任务。在老员工师带徒的“传、帮、带‘下，很快熟悉了工作情况，提早进入角色，少走了弯路。按要求参加了公司内部客车知识的系统培训，努力夯实专业基础，扩大了知识面，力求理论联系实际，在车身内饰设计的岗位上，更好的完成自己的本职工作，提高实际工作能力。通过积累，熟悉了sap系统操作、cad绘图技巧，能够独立完成医疗车内饰部分总成的设计和日常订单技术资料的处理，并且能服务车间，跟踪生产。 经过一年的锤炼，我认为我能胜任自己的工作，已达到转正定级要求，现申请转正定级，望批准。 范文二

距离研究生毕业，我参加工作已满一年。这一年来，在各级领导的教导和培养下，在同事们的关心和帮助下，自己的思想、工作、学习等各方面都取得了一定的成绩，个人综合素质也得到了一定的提高： ●一、思想上，我自觉加强理论学习，努力提高政治思想素质，通过以上努力， 我感到自己的政治素质有了长足进步。 ●二、在业务上，努力完善自身知识结构的和健全知识体系，让自己尽早、尽快 的熟悉工作情况，少走弯路。 ●三、在日常生活中，我认真服从领导安排，遵守各项规章制度和各项要求，养 成良好的工作作风，争取在以后的工作生活中以更加努力的优秀成绩来回报。 在今后的工作和学习中，自己要更进一步严格要求自己，加强思想政治、业务知识方面的学习，认真总结经验教训，克服不足。

雅思口语范文part1 2 3

口语经典part1问题+答案 本答案只可用做熟悉如何答题，可以根据答案进行修改，切记不可原文背诵！ 口语Part1范文：INTRODUCTION 1. Hello. Could you show me your identification card please? Hello. Sure, here you are. 2. Could you tell me your full name please? My full name is XXX. Friends usually call my English name, XXX. 3. What shall I call you? my name is michael. its a very regal sounding name. king of kings, and he who is like god. i like it, and i would never change my name, it has history. riches, intelligence, glory, and belong to michaels over the ages..." 4. How are you? I am fine, thank you, and you? 5. How old are you? I am 22 years old. In other words, I was born in 1980. March 8, 1980, to be exact. 6. Does your name have any special meaning? ( 5 - 6 ) Yes, my name does have some special meaning. My family name means …peace?, and my first name has the meaning of …strong one?. My English name was given by one of my high school teachers, and it does not have any special meaning really. 6. Does your name have any special meaning? ( 7 - 8 ) I presume you are referring to my Chinese name. Yes, the English equivalent of my family name would be something like …peace?, and in the case of my first name it would be …strong one?. My English name was randomly chosen by one of my high school teachers, and it re ally doesn?t have any special meaning. 7. Is your name important to you? ( 5 - 6 ) No. I don?t think it can do anything for me. I believe a person has to work out his own life. I am planning to do this as wel l as I can. 7. Is your name important to you? ( 7 - 8 ) Not really. I belong to the new generation who do not attach too much significance to our names. Names were important to the older generation as they are of the opinion that it will determine your destiny to some extent. However, I personally believe that I myself will determine my destiny no matter what my name is. I will do this by acquiring good qualifications and by working hard. ? 口语Part1范文：HOMETOWN 8. Where do you come from? 8. How long have you lived in your hometown? ( 5 - 6 ) I come from Guangzhou. My parents have been living here for the past thirty years or so. I grew up here and attended a well-known high school called Zhixin High School. We live in a nice area with many shops, restaurants, and other businesses. 8. Where do you come from? 8. How long have you lived in your hometown? ( 7 - 8 ) I come from Guangzhou. My parents have been living here for the past thirty years or so. I grew up here and attended a well-known high school called Zhixin High School, a major middle school in the province. We live in a respectable area with many shops, restaurants, and a variety of other businesses. The people in our building are generally friendly and quiet, which makes it a pleasure to live there. 9. Where do you live? ( 5 - 6 ) Well, that is not so easy to answer. Please allow me to explain. During the week I live in a dormitory at the university, but over weekends I live with my parents in a village about one hour by car from Guangzhou. So I really do not know which of the two to call my home at the moment. 9. Where do you live? ( 7 - 8 ) I live with my parents here in Guangzhou at the moment. To be more exact, we live in an apartment building in one of the northern