bp 12 study guide
sf-12 生活质量量表 中文版
Brief communicationIs the standard SF-12Health Survey valid and equivalent for a Chinese population?Cindy m1,Eileen Y.Y.Tse1&Barbara Gandek21Family Medicine Unit,the University of Hong Kong,Hong Kong SAR(E-mail:clklam@hku.hk);2IQOLA Project,Health Assessment Lab,Boston,MA USAAccepted in revised form15June2004AbstractIntroduction:Chinese is the world’s largest ethnic group but few health-related quality of life(HRQoL) measures have been tested on them.The aim of this study was to determine if the standard SF-12was valid and equivalent for a Chinese population.Methods:The SF-36data of2410Chinese adults randomly selected from the general population of Hong Kong(HK)were analysed.The Chinese(HK)specific SF-12 items and scoring algorithm were derived from the HK Chinese population data by multiple regressions. The SF-36PCS and MCS scores were used as criteria to assess the content and criterion validity of the SF-12.The standard and Chinese(HK)specific SF-12PCS and MCS scores were compared for equivalence. Results:The standard SF-12explained82%and89%of the variance of the SF-36PCS and MCS scores, respectively,and the effect size differences between the standard SF-36and SF-12scores were less than0.3. Six of the Chinese(HK)specific SF-12items were different from those of the standard SF-12,but the effect size differences between the Chinese(HK)specific and standard SF-12scores were mostly less than0.3. Conclusions:The standard SF-12was valid and equivalent for the Chinese,which would enable more Chinese to be included in clinical trials that measure HRQoL.Key words:Health-related quality of life,SF-12,Chinese,Validity,EquivalenceIntroductionChinese make up nearly a quarter of the world’s population.They should be included in global and cross-cultural clinical trials but this is often not possible in studies that measure health-related quality of life(HRQoL)because of language and cultural barriers.Most HRQoL measures are in English and originate from the Western culture,so they need to be translated and validated before they can be applied to the Chinese.The Chinese (Hong Kong)translation of the MOS36-item Short Form Health Survey(SF-36)and its physical and mental health summary(PCS and MCS) Scales have been shown to be valid and equivalent for the Chinese[1–5],but the length of the SF-36 limits its acceptability in some clinical trials that need to measure a number of outcomes.The standard SF-12Health Survey(SF-12),an abbre-viated form of the SF-36that yields the PCS and MCS scores,is becoming a popular HRQoL measure in clinical trials because it can be com-pleted in a few minutes[6,7].The items and scoring algorithm of the standard SF-12were derived from data of a US general population survey in1990[6–8].The standard SF-12PCS and MCS scores are norm-based on the US general population whose mean is50and standard deviation(SD)is10[6,9].The12items include two from each of the physical functioning, role-physical,role-emotional and mental health scales and one item from each of the bodily pain, general health,vitality and social functioning scales of the SF-36.The items were selected by multiple regressions in order to explain the largest proportion of the total variance in the SF-36PCSQual Life Res(2005)14:539–547ÓSpringer2005and MCS scores.The response to each item is weighted separately by the PCS and MCS regres-sion coefficient and then summated to give the standard SF-12PCS and MCS scores,respectively.A small number and weighting of items may make a HRQoL measure more culture-sensitive [10,11].All previous studies on the validity and equivalence of the standard SF-12were carried out in Caucasian populations[8,12].There was very little data from any Chinese or Asian population whose cultures are quite different from those of the West.The rank orders by item mean of three(PF9, GH3and RE3)SF-36items were found to be different between the HK Chinese and US popu-lations[1].Although the differential item func-tioning(DIF)of a few items did not affect the validity of the SF-36Scales that summated all the items without weighting[1,13],they may have an effect on the validity and equivalence of the much shorter standard SF-12.The aim of this study was to determine if the standard SF-12was valid and equivalent for the Chinese population of Hong Kong,or whether a Chinese(HK)specific SF-12was needed.The standard SF-12is valid if it really measures the SF-36PCS and MCS scores,which are what it pur-ports to measure.The selected items should be representative and adequate in explaining the SF-36PCS and MCS scores(content validity),and the SF-12should give similar PCS and MCS scores as the SF-36(criterion validity).The standard SF-12 is equivalent if no more than three of the12items selected specifically from the Chinese(HK)popu-lation were different from those of the standard SF-12,as that found in other countries(item equivalence)[8];and if there is no important dif-ference between the results of the Chinese(HK) specific and standard scoring algorithms(mea-surement equivalence)[8,14,15].MethodsData of2410Chinese adults randomly selected from the general population of Hong Kong that were collected in the Chinese(Hong Kong)SF-36 norming survey in1998were used for analysis in this study.The detailed sampling and data collec-tion methods have been described in previous pa-pers[16,17].All subjects answered the Chinese (Hong Kong)translation of the SF-36and a structured questionnaire on sociodemographic data.Each subject was also asked to indicate whether he/she had ever been diagnosed by a doctor to have hypertension,diabetes mellitus, heart disease,stroke,chronic pulmonary disease, chronic joint disease,psychological illness or any other chronic disease.A subject was classified as not having any chronic disease if the responses to these chronic disease questions were all negative. Table1shows that the sociodemographic charac-teristics of the subjects were similar to those of the general adult population in Hong Kong[18].The sample was comparable to the US population sample[19]from which the standard SF-12was derived in mean age(42.9vs.43.6years)and sex distribution(47.8%vs.48%males).The Chinese(HK)specific SF-12items were selected by multiple regressions of the Chinese (HK)specific SF-36PCS and MCS scores derived from the HK Chinese adult population[3],based on the criteria of the International Quality of Life Assessment(IQOLA)Project for cross-cultural adaptation of the SF-12[8].The Chinese(HK) specific PCS and MCS regression constants and coefficients for each item response were obtained by regressing the Chinese(HK)specific SF-36PCS and MCS scores on the Chinese(HK)specific item scores.The SAS programme was used for the multiple regressions analyses.The SPSS Pro-gramme for Windows10.0(SPSS Inc.Chicago,IL, USA)was used for all other data analyses.The standard SF-12PCS and MCS scores were calculated by the standard algorithm described in the SF-12Manual[6].The Chinese(HK)specific and standard mean SF-12PCS and MCS scores were determined for all subjects and by self-re-ported chronic disease groups.Content validity was assessed by the proportion of total variance of the SF-36PCS and MCS scores explained by the SF-12PCS and MCS,and P90%was the expected standard[6,8].It was further assessed by Pearson correlations between the SF-12and SF-36PCS and MCS scores and the expected standard was P0.9[6,8].Effect size dif-ference between corresponding SF-12and SF-36 PCS and MCS scores was used to determine if the SF-12gave similar or different results from those of the SF-36(Criterion validity).Effect size dif-ference between the SF-36and SF-12scores was540calculated by dividing their difference by the standard deviation(SD)of the SF-36summary score.Measurement equivalence between the standard and Chinese(HK)specific SF-12wasfirst assessed by Pearson correlations(expected standard P0.9) and then the effect size differences between the standard and Chinese(HK)specific scores.The effect size difference was calculated by dividing the difference between the corresponding SF-12 scores by the SD of the Chinese(HK)specific SF-12score.The standard and Chinese(HK)SF-12 scores were also compared by chronic disease groups in order to determine if they performed differently in different groups.A spectrum of chronic diseases(Heart,chronic pulmonary,psy-chological and chronic joint)that are known to affect HRQoL were used as tracer conditions[20]. There is no consensus on what the minimally important difference(MID)in HRQoL scores should be.Kazis et al.showed that the effect size changes in scores measured by the Arthritis Im-pact Measurement Scale were mostly between0.3 and0.5in the treatment group[21];and Wyrwich showed that the MID of the Chronic Heart Failure Questionnaire scores corresponded to effect size changes of0.34–0.37[22].We therefore adopted Cohen’s moderate effect size of0.3–0.5as the MID in this study[23,24].ResultsThe Chinese(HK)specific SF-12PCS and MCS scalesFirst forward stepwise regressions of the Chinese (HK)specific SF-36PCS and MCS scores on the SF-36items selected two items each from the physical functioning(PF1,PF8)and mental health (MH3,MH4)scales,and one item each from the role-physical(RP3),bodily pain(BP1),social functioning(SF1)and role-emotional(RE3) scales.The second forward stepwise regressions, with the general health item(GH1)and the above items forced into the model,selected the remaining items(RP2,VT4and RE1)that explained the greatest variance of the HK Chinese specific SF-36 PCS and MCS scores.It is an IQOLA criterion that GH1should be included in all versions of SF-12because it is an item common to many HRQoL measures[8].Table2shows the Chinese(HK) specific SF-12items,in comparison with the standard SF-12items.The items that were differ-ent are shown in bold.The numbers in brackets correspond to the question numbers in the SF-36 Health Survey.Table3shows the regression coefficients of the Chinese(HK)specific SF-12items and those of theTable1.Sociodemographic characteristics of study sample compared with the Hong Kong general populationSampleN=2410Hong Kong general adult population a N=5,333,610Mean age(years)42.942.3Age group(years)18–4456.7%58.6%45–6423.7%27.4%65or above15.3%14.0%Refused to answer 4.2%0%Male47.8%48.3%Female52.2%51.7%Marital statusNow married58.0%59.4%Never married33.8%31.9%Widow/widower 5.8% 6.0%Divorced/separated 1.3% 2.7%Refused to answer 1.1%0%Educational levelNo schooling 6.9%8.4%Primary22.3%20.5%Secondary52.2%54.6%Tertiary17.8%16.4%Refused to answer0.9%0%Social class by occupationManagers andadministratorsN.A.10.7%bProfessional 3.1% 5.5%Associate professional14.7%15.0%Skilled worker35.4%33.5%cSemi-skilled worker24.6%15.0%dNon-skilled worker14.4%19.8%eRefused to answer7.7%0%a Data from the Hong Kong2001Population Census.b This occupation category is not applicable to the social classby occupation classification.c Craft workers,plant and machine operators and assemblers.d Service and shop sales workers.e Workers in elementary occupation,agriculture andfishery,and unclassified.541standard SF-12items,derived from the HK gen-eral Chinese population sample.The regression coefficient of the best response choice of each item is not shown because it is the indicator variable. The Chinese(HK)specific PCS and MCS regres-sion coefficients of each item response were used separately to weight each item response for the calculation of the PCS and MCS scores.The weight for the best response choice of each item is zero.Summation of the relevant Chinese(HK) specific regression constant and item response PCS and MCS regression coefficients would give the Chinese(HK)specific SF-12PCS and MCS scores, respectively.Content and criterion validity of the SF-12PCS and MCSThe R2in Table3indicates the proportion of total variance in the SF-36PCS or MCS score that was explained by the corresponding SF-12summary score.The standard SF-12PCS and MCS ex-plained82%and89%of the total variances of the standard SF-36PCS and MCS,respectively.The Chinese(HK)specific SF-12PCS and MCS ex-plained88%and90%of the total variances of the Chinese(HK)specific SF-36PCS and MCS, respectively.Table4shows the correlations between the SF-12and SF-36PCS and MCS scores.The correla-tions between the corresponding SF-36and SF-12 summary scores all reached the expected standard of0.9.The mean and standard deviation(SD)of the Chinese(HK)specific and standard SF12and SF-36PCS and MCS scores of the whole sample and by self-reported chronic disease groups are shown in Table5.The effect size differences(effect size1) between corresponding SF-36and SF-12scores were all less than0.3.Measurement equivalence between the chinese (HK)specific and standard SF-12As shown in Table4,the correlations between the corresponding standard and Chinese(HK)specific SF-12PCS and MCS scores were just short of0.9. The standard and Chinese(HK)specific SF-12 scores are compared in Table5.The mean stan-dard SF-12PCS and MCS for the overall HK Chinese population were50.2and48.4,respec-tively,which were similar to the US general pop-ulation means of50.The Chinese(HK)specific and standard SF-12detected similar significant differences between each chronic disease group and the‘no chronic disease’group.The largest difference between the Chinese(HK)specific and standard SF-12scoring algorithms was the PCS score of people reporting heart diseases,with an effect size of0.36.DiscussionThe standard SF-12did not satisfy the criterion on item equivalence for the Chinese population inTable2.The Chinese(HK)specific SF-12items compared with the standard SF-12itemsSF-36scales Chinese(HK)specific SF-12items Standard SF-12itemsPhysical functioning(PF)PF1(3a)Vigorous activities PF2(3b)Moderate activitiesPF8(3h)Walking several blocks PF4(3d)Climbing severalflights Role-physical(RP)RP2(4b)Accomplished less RP2(4b)Accomplished lessRP3(4c)Limited in kind of work RP3(4c)Limited in kind of workBodily pain(BP)BP1(7)How much bodily painhave you had BP2(8)how much did pain interfered with workGeneral health(GH)GH1(1)Your health is...GH1(1)Your health is...Vitality(VT)VT4(9i)Did you feel tired VT2(9e)Did you have a lot of energySocial functioning(SF)SF1(6)Extent social activitieswas interfered SF2(10)How much time social activities was interferedRole-emotional(RE)RE1(5a)Cut down time on work RE2(5b)Accomplish lessRE3(5c)Didn’t do work as carefully RE3(5c)Didn’t do work as carefully Mental health(MH)MH3(9d)Felt calm&peaceful MH3(9d)Felt calm&peacefulMH4(9f)Felt downhearted&blue MH4(9f)Felt downhearted&blue 542543Table3.Forward stepwise regressions of SF-36PCS and MCS scores on the SF-12item responsesItem_Response scores PCS regression coefficients MCS regression coefficientsChinese(HK)specific Standard Chinese(HK)specific StandardPF1_1)8.042639– 2.795780–PF1_2)3.641426– 1.121187–PF2_1–)6.609693– 3.461042PF2_2–)2.782074– 1.314947PF4_1–)6.269240– 2.586866PF4_2–)2.427698–0.752688PF8_1)16.203705–7.818665–PF8_2)7.963922– 3.164988–RP2_1)4.343623)4.390177)0.705448 1.022170RP3_1)5.044296)5.0474760.256528 1.278842BP1_1)17.012005– 3.635025–BP1_2.2)12.695771– 2.349628–BP1_3.1)9.002881– 1.931547–BP1_4.2)6.377284– 1.507313–BP1_5.4)3.772960–0.652800–BP2_1–)12.257268– 2.208989BP2_2–)10.594807– 2.500285BP2_3–)7.912197– 1.500170BP2_4–)4.970550– 1.033358GH1_1)8.704344)8.042873)0.8411670.184282GH1_2)5.382641)4.663071)1.133139)0.389631GH1_3.4)3.230279)2.706827)0.660725)0.349572GH1_4.4)1.936141)1.671905)0.7950150.330309VT2_1–)1.704222–)7.001461VT2_2–)1.355533–)5.031671VT2_3–)0.262164–)4.012001VT2_4–)0.150904–)2.677302VT2_5–0.150005–)1.396547VT4_1)2.301203–)6.694192–VT4_2)1.673615–)6.555417–VT4_3)1.217702–)4.965228–VT4_4)0.849186–)2.403254–VT4_5)0.495087–)1.041427–SF1_1 2.955278–)14.617923–SF1_2 1.116653–)12.142296–SF1_3 1.433979–)7.841254–SF1_40.861761–)4.676580–SF2_1–0.286656–)8.236227SF2_2–)0.189464–)6.857423SF2_3–0.193895–)5.284785SF2_4–0.482796–)3.301877RE1_1 2.468990–)6.099051–RE2_1– 2.747609–)6.981024RE3_1 1.642657 2.143392)5.120612)5.946570MH3_10.486081 2.865890)8.496928)8.255860MH3_2 1.644377 3.500893)8.257450)6.883770MH3_30.696675 2.694178)6.255882)5.404594MH3_40.864621 2.333822)4.238056)3.439909MH3_50.774435 1.609226)2.544268)1.943186MH4_10.851938 4.534201)12.868018)15.794343MH4_2)0.119061 2.494064)9.187208)12.925241MH4_3 1.319095 2.212045)7.247869)9.157472Hong Kong.Six items of the Chinese(HK)specific SF-12were different from those of the standard SF-12,suggesting some cultural differences in dif-ferential item functioning(DIF)of the SF-36be-tween the Chinese and US populations[13,25]. The number of items that were different between the standard and Chinese(HK)SF-12was larger than those found in nine European countries, probably because there are more differences be-tween the Chinese than European cultures and the US culture[8].No other country has selected PF1, BP1and RE1as the best SF-12items,which may reflect DIF that is unique to the Chinese culture. However,one must be cautious in generalising the results from this study to other Chinese popula-tions because the social system and people’s life style in Hong Kong are very different from those of Mainland China and other Chinese societies. Quality of life assessment is influenced not only by one’s ethnicity;it is also affected by social norms. Chinese populations living in different parts of the world may have developed different social expec-tations and standards of quality of life although they have the same cultural origin.Studies com-paring the population specific SF-12items between Chinese populations in Hong Kong,Mainland China,Taiwan,Singapore and Western countries could provide interesting information on whether DIF is ethnic or population specific.The standard SF-12PCS explained only82%of the total variance of the SF-36PCS score because three items(two from the physical functioning and one from the bodily pain scales)that contributed strongly to the standard SF-12PCS score were not the best items for the HK Chinese population. Despite this deficiency,there were very strong correlations(P0.9)between the standard SF-12 and SF-36PCS and MCS scores,and there were very small differences(effect size<0.3)between corresponding SF-36and standard SF-12scores in different groups of subjects.Thefindings supported the content and criterion validity of the standard SF-12for the Chinese population in Hong Kong. The mean standard SF-12PCS and MCS scores of the HK subjects were only0.2and1.6points different from the US population mean of50, suggesting that the standard SF-12was equivalent for this Chinese population.Pooling of the stan-dard SF-12data between the US and HK Chinese populations may be possible.Table3.(Continued)Item_Response scores PCS regression coefficients MCS regression coefficientsChinese(HK)specific Standard Chinese(HK)specific StandardMH4_40.987409 1.627192)4.368062)5.395771MH4_50.7170320.870407)2.320460)2.871620Constant60.17553455.55153462.74237861.557734R20.87660.82320.90170.8897Table4.Correlations between the SF-36and SF-12PCS and MCS scoresStd36PCS Std12MCS HK36MCS HK12PCSStd36MCS)0.1260.9380.9850.022Std12PCS0.897)0.073)0.0210.847HK36PCS0.9750.0500.0000.936HK12MCS)0.0490.8940.9500.040Notes:Std36PCS=SF-36PCS calculated by the standard(US)scoring algorithm.Std36MCS=SF-36MCS calculated by the standard(US)scoring algorithm.Std12PCS=SF-12PCS calculated by the standard(US)scoring algorithm.Std12MCS=SF-12 MCS calculated by the standard(US)scoring algorithm.HK36PCS=SF-36PCS calculated by the Chinese(HK)specific scoring algorithm.HK36MCS=SF-36MCS calculated by the Chinese(HK)specific scoring algorithm.HK12PCS=SF-12PCS calculated by the Chinese(HK)specific scoring algorithm.HK12MCS=SF-12MCS calculated by the Chinese(HK)specific scoring algorithm. 544As expected,the Chinese(HK)specific SF-12 had better psychometric properties than the stan-dard SF-12,which could imply better sensitivity and responsiveness for the Chinese.However,the Chinese(HK)specific SF-12did not seem to dif-ferentiate between‘chronic disease’and‘no chronic disease’groups better than the standard SF-12.The differences in the SF-12scores ob-tained by the two scoring algorithms were all smaller than the minimally important differenceTable5.Chinese(HK)specific and standard PCS and MCS scores by groupsMean(SD)Std PCS HK PCS Std MCS HK MCSAll subjects(n=2410)SF-3651.4(7.7)50.0(10.0)48.0(9.4)50.0(10.0)SF-1250.2(7.0)50.0(9.4)48.4(8.8)50.0(9.5)Effect size10.1600.040Effect size20.020.17No chronic disease(n=1493)SF-3653.8(5.5)53.5(6.7)48.6(8.7)50.5(9.2)SF-1252.3(4.8)53.2(6.3)49.1(8.1)50.6(8.8)Effect size10.270.040.060.01Effect size20.140.17Any chronic disease(n=917)SF-3647.4(8.9)44.3(11.8)47.0(10.4)49.2(11.1)SF-1246.9(8.5)*44.7(11.0)*47.4(9.8)*49.1(10.5)*Effect size10.060.030.040.01Effect size20.200.16Heart disease(n=94)SF-3641.7(11.0)36.0(14.7)46.9(10.2)49.2(10.9)SF-1241.8(10.6)*37.0(13.4)*46.7(9.4)48.7(10.9)Effect size10.010.070.020.05Effect size20.360.18Psychological diseases(n=94)SF-3645.8(9.6)41.6(12.9)40.2(10.8)41.6(11.8)SF-1245.4(9.0)*42.0(11.7)*41.4(10.1)*42.7(11.4)*Effect size10.040.030.110.09Effect size20.290.11Pulmonary diseases(n=128)SF-3646.6(10.9)43.6(14.2)44.6(10.6)46.0(11.1)SF-1246.3(10.6)*43.9(13.4)*44.4(10.4)*46.3(10.6)*Effect size10.030.020.020.03Effect size20.180.18Joint diseases(n=473)SF-3645.7(9.3)41.8(12.3)47.1(10.3)49.3(11.1)SF-1245.4(9.1)*42.6(11.4)*47.4(9.6)*49.0(10.7)*Effect size10.030.070.030.03Effect size20.250.15Notes:Std PCS=PCS score calculated by the standard(US)scoring algorithm;HK PCS¼PCS calculated by the Chinese(HK) specific scoring algorithm;Std MCS¼MCS calculated by the standard(US)scoring algorithm;HK MCS=MCS calculated by the Chinese(HK)specific scoring algorithm.Effect Size1difference between SF-12and SF-36summary score/SD of SF-36summary score.Effect Size2difference between standard and Chinese(HK)specific SF-12summary score/SD of the Chinese(HK)specific SF-12 summary score.*Difference between‘no chronic disease’and the disease group is significant by the two-sample t-test,with p<0.05.545(MID).Small improvements in cultural specificity and psychometric properties may not necessarily translate to real advantages in practice,and they have to be balanced against a decrease in inter-national comparability.This point has also been highlighted by Skevington et al.[26,27],who found that country specific items did not signifi-cantly improve the performance of the standard WHO Quality of Life(WHOQoL)Assessment Form.A major limitation of this cross-sectional study was that it could not assess the responsiveness of the standard and Chinese(HK)specific SF-12.The information on the sensitivity of the SF-12in discriminating between chronic disease groups was also limited by possible errors in subjects’self-reporting.Further studies are required to deter-mine the responsiveness and sensitivity of the standard SF-12and Chinese(HK)specific SF-12 as outcome measures in clinical trials.It should also be pointed out that subjects in this study answered the full SF-36Health Survey from which the data of the standard and Chinese(HK) specific SF-12were extracted.Further studies should be carried out to determine if people would answer the standard and Chinese(HK)specific SF-12differently if they are presented as two independent stand-alone surveys instead of embedded items of a longer questionnaire. ConclusionsThis was thefirst study to show that the standard SF-12Health Survey was valid and equivalent for a Chinese population.The standard SF-12items and scoring algorithm are recommended for the Chinese so that cross-cultural comparison and pooling of data are possible.The Chinese(HK) specific SF-12showed better psychometric prop-erties than the standard SF-12,thus,the Chinese (HK)specific SF-12may have a place in small local studies that require a more sensitive HRQoL measure instead of international comparability. We hope ourfindings will encourage more studies of the standard SF-12in Chinese popula-tions in other parts of China,Singapore and Western countries to provide more evidence in support of the use of this popular HRQoL mea-sure on the world’s largest ethnic group,so that Chinese can be included in more clinical trials. Further research on the population specific SF-12 items in different Chinese populations could pro-vide interesting information on whether differen-tial item functioning is ethnic or population specific.AcknowledgementsThe general population norming survey of the Chinese(Hong Kong)SF-36was approved by the Ethics Committee of the University of Hong Kong (EC842-96).It was funded by the Health Services Research Grant,the Government of Hong Kong SAR(HSRC#711026).I would like to thank Alex Chan,Willis Ho, Joanna Shing,Ka-Lai Chan,Wai-Hung Yu,June Chan,Chi-Kwan Wong,Wing-Yee Lai,Yick-Lok Chan and Hing-Wai Tsang,for their help in data collection and analysis.Parts of this paper have been submitted to the University of Hong Kong for the award of the Doctor of Medicine degree.Referencesm CLK,Gandek B,Ren XS,Chan MS.Tests of scalingassumptions and construct validity of the Chinese(HK) version of the SF-36Health Survey.J Clin Epidemiol1998;51:1139–1147.m CLK.Reliability and construct validity of 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translation of the SF-36.J Clin Epidemiol1998;51:1189–1202.14.Herdman M,Fox-Rushby J,Badia X.A model ofequivalence in the cultural adaptation of HRQoL instru-ments:The universalist approach.Qual Life Res1998;7: 323–335.15.Bullinger M.Ensuring international equivalence of qualityof life measures:Problems and approaches to solutions.In: Orley J,Kuyken W(eds),Quality of Life Assessment: International Perspectives.Berlin:Springler-Verlag;1994: 33–40.m CLK,Lauder IJ,Lam TP,Gandek B.Populationbased norming of the Chinese(HK)version of the SF-36 Health Survey.H K Pract1999;21:460–470.m CLK,Fong DYT,Lauder IJ,Lam TP.The effect ofhealth-related quality of life(HRQoL)on health service utilisation of a Chinese population.Soc Sci Med2002;55: 1635–1646.18.Census&Statistics Department Hong Kong,Main Tablesof the2001Population Census.Hong Kong:Census& Statistics Department,HKSAR;2002.19.Gandek B,Ware JE.Methods for validating and normingtranslations of health status questionnaires:The IQOLA Project approach.J Clin Epidemiol1998;51:953–959. m CLK,Lauder IJ,Lam TPD.The impact of chronicdiseases on health services and quality of life of a Chinese Pacific Fam Med2003;2:98–106.22.Kazis LE,Anderson JJ,Meenan RF.Effect sizes forinterpreting changes in health status.Med Care1989;27: S178–S189.23.Wyrwich KW,Nienaber NA,Tierney WM,Wolinsky FD.Linking clinical relevance and statistical significance in evaluating intra-individual changes in health-related quality of life.Med Care1999;37:469–478.24.Cohen J.The t-test for measures.In:Cohen J(ed.),Statistical Power Analysis for the Behavioral Sciences.Hillsdale,New Jersey:Lawrence Erlbaum Associates;1988: 19–74.25.Norman GR,Sridhar FG,Walter SD,Guyatt GH.Therelation of distribution-and anchor-based approaches in interpretation of changes in health related quality of life.Med Care2001;39:1039–1047.25.Holman R,Lindeboom R,Vermeulen M,Glas CAW,deHaan RJ.The Amsterdam Linear Disability Score(ALDS) Project,differential item functioning with regard to gender.QOL Newsleter2002;29:13–14.26.Skevington SM.Advancing cross-cultural research onquality of life:Observations drawn from the WHOQoL development.Qual Life Res2002;11:135–144.27.Skevington SM,Bradshaw J,Saxena S.Selecting nationalitems for the WHOQoL:Conceptual and psychometric considerations.Soc Sci Med1999;48:473–487.Address for correspondence:Cindy m,MBBS,MD, FRCGP,FHKAM,Family Medicine Unit,The University of Hong Kong,3rd Floor,Ap Lei Chau Clinic,161Main Street, Ap Lei Chau,Hong Kong SARFax:+852-********;E-mail:clklam@hku.hk547。
《实用医学杂志》编辑部关于论文优先审稿、发表的声明
实用医学杂志2019年第35卷第18期The Journal of Practical Medicine 2019Vol.35No.18［22］LIN Q Q ，REN K ，LIN S H ，et al.MicroRNA ⁃140⁃5p aggra⁃vates hypertension and oxidative stress of atherosclerosis via tar⁃geting Nrf2and Sirt2［J ］.Int J Mol Med ，2019，43（2）：839⁃849.［23］GOU L ，ZHAO L ，SONG W ，et al.Inhibition of miR⁃92a sup⁃presses oxidative stress and improves endothelial function by up⁃regulating heme oxygenase⁃1in db/db mice ［J ］.Antioxid Redox Signal ，2018，28（5）：358⁃370.［24］LIU G ，LI Y ，GAO X G.microRNA⁃181a is upregulated in hu⁃man atherosclerosis plaques and involves in the oxidative stress⁃induced endothelial cell dysfunction through direct targeting Bcl⁃2［J ］.Eur Rev Med Pharmacol Sci ，2016，20（14）：3092⁃3100.［25］LI L ，LI Y ，TANG C.The role of microRNAs in the involvementof vascular smooth muscle cells in the development of atheroscle⁃rosis ［J ］.Cell Biol Int ，2019.doi ：10.1002/cbin.11164.［Epub ahead of print ］［26］ZHANG W ，LIU D ，HAN X ，et al.MicroRNA⁃451inhibits vas⁃cular smooth muscle cell migration and intimal hyperplasia after vascular injury via Ywhaz/p38MAPK pathway ［J ］.Exp CellRes ，2019，379（2）：214⁃224.［27］LIU H ，XIONG W ，LIU F ，et al.MicroRNA⁃133b regulates thegrowth and migration of vascular smooth muscle cells by target⁃ing matrix metallopeptidase 9［J ］.Pathol Res Pract ，2019，215（5）：1083⁃1088.［28］LI H ，ZHAO J ，LIU B ，et al.MicroRNA⁃320targeting neuropi⁃lin 1inhibits proliferation and migration of vascular smooth mus⁃cle cells and neointimal formation ［J ］.Int J Med Sci ，2019，16（1）：106⁃114.［29］艾丽菲热·买买提，杨毅宁，马依彤.MiRNA 在动脉粥样硬化血管新生中的作用［J ］.中国动脉硬化杂志，2015，23（6）：639⁃644.［30］CHEN L Y ，WANG X ，QU X L ，et al.Activation of the STAT3/microRNA⁃21pathway participates in angiotensin II⁃induced an⁃giogenesis ［J ］.J Cell Physiol ，2019，234（11）：19640⁃19654.［31］LIANG H Z ，LI S F ，ZHANG F ，et al.Effect of endothelial mic⁃roparticles induced by hypoxia on migration and angiogenesis of human umbilical vein endothelial cells by delivering microRNA⁃19b ［J ］.Chin Med J （Engl ），2018，131（22）：2726⁃2733.［32］QUN L ，WENDA X ，WEIHONG S ，et al.MiRNA ⁃27b modu⁃lates endothelial cell angiogenesis by directly targeting Naa15inatherogenesis ［J ］.Atherosclerosis ，2016，254：184⁃192.［33］MAIMAITI A ，YANG Y ，MA Y ，et al.MiR⁃106b exhibits an an⁃ti ⁃angiogenic function by inhibiting STAT3expression in endo⁃thelial cells ［J ］.Lipids Health Dis ，2016，15：51.［34］AN T H ，HE Q W ，XIA Y P ，et al.MiR⁃181b antagonizes ath⁃erosclerotic plaque vulnerability through modulating macrophage polarization by directly targeting notch1［J ］.Mol Neurobiol ，2017，54（8）：6329⁃6341.［35］SU Y ，YUAN J ，ZHANG F ，et al.MicroRNA⁃181a⁃5p and mi⁃croRNA ⁃181a ⁃3p cooperatively restrict vascular inflammationand atherosclerosis ［J ］.Cell Death Dis ，2019，10（5）：365.［36］DU X J ，LU J M.MiR⁃135a represses oxidative stress and vascu⁃lar inflammatory events via targeting toll⁃like receptor 4in athero⁃genesis ［J ］.J Cell Biochem ，2018，119（7）：6154⁃6161.［37］ZHANG F ，ZHAO J ，SUN D ，et al.MiR⁃155inhibits transfor⁃mation of macrophages into foam cells via regulating CEH expres⁃sion ［J ］.Biomed Pharmacother ，2018，104：645⁃651.［38］DAI Y ，WU X ，DAI D ，et al.MicroRNA⁃98regulates foam cellformation and lipid accumulation through repression of LOX ⁃1［J ］.Redox Biol ，2018，16：255⁃262.（收稿：2019⁃04⁃16编辑：袁宁）《实用医学杂志》编辑部关于论文优先审稿、发表的声明本刊对符合以下条件的论文给予优先审稿、发表：（1）受国家或部、省级以上基金资助的论文；（2）重点攻关项目的论文；（3）报道的内容属国内外领先水平的论文；（4）有重要指导意义或发表后具有广泛应用价值的论文；（5）针对本刊以往发表论文的学术观点进行延续讨论（即引用了本刊近两年刊出论文）的论文。
antihypertensive drugs抗高血压药精讲
Indapamide Increase in renal Na+ excretion →diuresis Dilate the vascular smooth muscle. Have no effect on the serum lipids.
Section one：introduction
• What is hypertension？ • Hypertension is defined as an arterial pressure greater than or equal to 140/90mmHg for an extended period of time. • BP≥140/90 mmHg • Morbidity:15%-20%
The mechanism for reduction of BP
1.Early：↑Na+ and H2O excretion， ↓extracellular volume and blood volume， ↓cardiac output 2.Long：↓Na+ of vessel wall， ↓Na+-Ca2+ exchange, ↓intracellular Ca2+ ↓sensitivity of VSM to vasoconstrictors (NE) 3.Dilate VSM directly
prevention measures
One is to feel comfortable, to avoid sadness. It will cause hypertension. Second, life regularly. A regular life, the prevention of hypertension is very important. Third, reasonable diet and avoid obesity. Fourth, to actively participate in sports. In addition, according to the characteristics of their hobby. We can Often listen to beautiful music.
antihypertensive drugs抗高血压药
Indapamide Increase in renal Na+ excretion →diuresis Dilate the vascular smooth muscle. Have no effect on the serum lipids.
The mechanism for reduction of BP of thiazide diuretics
பைடு நூலகம்
Thiazide diuretics
Long-term ↓ Na+ in vessel wall ↑ Na+-Ca2+ exchange initial ↓ sodium, water retention
↓ blood volume
↓ Ca+ in smooth musclecell ↓ peripheral resistance
↓ cardiac output
Decrease in BP
Clinical uses and evaluation
Low-dose of thiazide diuretic therapy is safe , effective and cheap for hypertension. Thiazide diuretics are appropriate for most patients with mild or moderate hypertension , particularly elderly patients. Low doses of hydrochlorothiazide(25-50mg/d) exert as much antihypertensive effect as do higher doses.
湖南师大数学培养方案
基础数学专业硕士研究生培养方案一、培养目标本专业主要培养从事数学基础理论及应用研究和教学的高层次人才；要求学生掌基础数学领域的基础知识、具有宽广的知识面，并深入了解某一子学科的专业知识；能熟练地掌握一门外国语；身体健康；毕业后能独立地从事教学、科研及其它实际工作。
二、本专业总体慨况、优势与特色基础数学（Pure Mathematics）是数学学科的基础和核心部分，它不仅是其它数学学科的基础，而且也是自然科学、技术科学和社会科学等必不可少的语言、工具和方法，同时高科技的发展和计算机的广泛应用也为基础数学的研究提供了更广阔的发展前景。
我校具有数学一级学科博士学位授予权，具有数学博士后流动站。
在代数、函数论、微分方程、组合数学、拓扑学等领域具有很好的研究基础。
各方向都建立了一支年龄机构合理、研究水平高、稳定的研究队伍，各方向均取得了许多重要的科研成果。
三、本专业研究方向及简介1. 代数学2. 函数论3. 拓扑学4. 微分方程5. 组合与优化五、专业课程开设具体要求课程编号：010********课程名称：泛函分析英文名称：Functional Analysis任课教师：徐景实适应学科、方向：基础数学、计算数学、概率论与数理统计、应用数学、运筹学与控制论预修课程：数学分析、实变函数主要内容：熟悉距离空间、赋范线性空间、Banach空间、Hilbert空间的基本定理，熟练掌握线性算子和线性泛函的表示、弱收敛性和线性算子的谱等。
了解广义函数的概念和运算。
主要教材及参考文献：1、张恭庆．泛函分析讲义（上、下册）[M]．科学出版社．*****2、夏道衍．实变函数论与泛函分析[M]．高等教育出版社．3.、定光桂．巴那赫空间引论[M]．科学出版社，1999．4、J.B.Conway．A Course in Functional Analysis （2nd Ed.）[M]．GTM. 96 Springer-Verlag，1990．C-algebras and Operator theory[M]．Academic Press，1990．**********5、G.J.Murphy．课程编号：010********课程名称：代数拓扑英文名称：Algebraic Topology任课教师：郭瑞芝适应学科、方向：基础数学、应用数学预修课程：点集拓扑、近世代数主要内容：商空间、基本群、多面体及其单纯同调、奇异同调、范畴与函子、奇异同调群相对奇异同调、正合同调序列、切除定理、多面体的同调群及其应用、CW-复形、上同调群。
MillerLevineBiologyStudyWorkbookAnswersBing…
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下肢康复机器人训练对脑卒中偏瘫患者平衡及步行功能的影响
目前,脑卒中成为了全球范围内的首要致残疾病,且致死率高,我国每年的新发脑卒中患者在250万例及以上,且大部分患者均会遗留一定程度的神经功能缺损,严重影响患者的生存质量。
脑卒中后偏瘫运动功能障碍,特别是步行障碍,是脑卒中致残的一种重要因素[1]。
目前主要通过传统神经促通技术为基础的康复疗法来进行脑卒中后的运动功能恢复[2]。
其能够帮助患者提高日常活动能力,改善其生活质量。
传统的训练方法存在一定局限性:采取一对一的训练模式将会导致康复治疗师的数量严重不足,从而加重康复治疗师的负担;且恢复情况也主要依靠康复治疗师的主观判断,没有客观性的定量评估方法,因此会对患者的精准训练产生影响;治疗师的主观经验也会一定程度限制有效的康复效果评估。
近些年来,下肢康复机器人系统(A3下肢康复机器人训练及评估系统)成为了一种新的临床康复治疗方法,其不仅可以降低康复治疗师的工作负担,同时还可增强康复治疗效果,促进功能恢复[3-4]。
因此,其是目前研究的热点问题,为了进一步探讨对脑卒中偏瘫患者予以下肢康复机器人训练平衡及步行功能的影响,本研究通过将下肢康复机器人训练应用于脑卒中偏瘫患者展开研究,以期为下肢康复机器人训练在脑卒中偏瘫患者中的应用提供一定参考依据,现报道如下。
下肢康复机器人训练对脑卒中偏瘫患者平衡及步行功能的影响罗玲华黄丽钦陈健南昌大学第三附属医院康复医学科,江西南昌330008[摘要]目的探讨下肢康复机器人训练对脑卒中偏瘫患者平衡及步行功能的影响。
方法选取2016年1月~2019年1月在我科住院治疗的50例早期脑卒中偏瘫患者为研究对象,随机将其分为观察组和对照组,每组各25例;其中对照组予以常规基础康复训练,观察组予以下肢康复机器人训练;对比两组治疗前后的平衡及步行功能。
结果两组治疗前BBS、FAC评分比较,差异无统计学意义(P>0.05),两组治疗后的BBS、FAC评分均较治疗前明显改善,且观察组的BBS、FAC评分改善程度明显优于对照组(P<0.05)。
南京大学新的SCI论文奖励政策(试行)---精品管理资料
南京大学新的SCI论文奖励政策（试行）
说明:为提高我校SCI论文质量和师生的科研创新能力，根据校长联
席会议精神,在各院系推荐的基础上,对原有的SCI论文奖励政策进行
了调整，现予公布执行，执行日期自2006年1月1日始。
1、SCI期刊分层方案和奖励标准
注：SCI论文只有article与letter奖励配套经费；其他皆作扩大版对待，每篇只奖励700元现金。
2、超一流期刊目录
超一流期刊
3、一级学科顶级期刊综合版目录
a.NATURE子系列（约26种)
b.影响因子大于20的期刊(根据06年影响因子，去除SCIENCE、NA TURE、NATURE系
列，则为16种）
c。
P NATL ACAD SCI USA（Proceedings of the National Academy of Sciences of the United States of America，06年IF=9.643)
4、一级学科顶级期刊目录
5、二级学科一流期刊目录
数学
物理学
化学
天文学
（2)天体测量与天体力学
地理学
大气科学
地质学
地球物理学
地质资源与地质工程
水科学
材料科学与工程
电子科学与技术
计算机科学与技术
环境科学与工程
生命科学
医学
6、学术榜论文奖及配套经费发放登记表
院系名称: 时间：年月日
总计：现金：元科研经费：元院系领导签字：院系盖章：
领款人签字：科技处领导签字：科技处盖章:
经办人：
注：上报时需附论文首页复印件。
本表请复印使用二OO 年月
40。
基于遗传算法优化的BP神经网络在考研结果预测中的应用
黑铉语言信麵与电睡China Computer & Communication2021年第1期基于遗传算法优化的B P神经网络在考研结果预测中的应用李驰(四川大学锦城学院计算机科学与软件工程系，四川成都611731)摘要：通过遗传算法先对BP神经网络的初始权值和阈值进行优化后，再将BP神经网络用于考研结果的预测模型中。
实验表明，这种优化后的预测模型因为克服了收敛速度慢、易产生局部最小等缺陷，比单纯使用BP神经网络建立的预测 模型准确度更高。
将这个预测模型用于考研报名之前供学生预测参考，方便学生做出合理的决策，具有一定的实际意义。
关键词：考研；预测；BP神经网络；遗传算法中图分类号：TD712 文献标识码：A文章编号：1003-9767 (2021) 01-038-04Application of BP Neural Network Based on Genetic Algorithms Optimization in Prediction of Postgraduate Entrance ExaminationLI Chi(Department of Computer Science and Software Engineering,Jincheng College of Sichuan University,Chengdu Sichuan611731, China) Abstract：F irs tly,the in itia l weight and threshold of BP neural network are optimized by genetic algorithm,and then BP neural netw ork is used in the pre diction model of the results o f the postgraduate entrance exam ination.The experim ent shows that the optim ized prediction model overcomes the shortcomings o f slow convergence speed and easy to produce local m inim um,so it is more accurate than the pre diction model established by BP neural network alone.This pre diction model can be used as a reference for students to make a reasonable decision before applying fo r postgraduate entrance examination.Key words：postgraduate entrance exam ination;prediction;BP neural network;genetic algorithms〇引言随着社会对于高素质知识型人才的需求越来越迫切，我 国报考研究生的人数呈现逐年大幅増加的趋势。
GradingPeriod
1.3 Describing Quantitative Data with Numbers Four Measures of Cent er 5 number summary, IQR, Choosing appropriate measure of center
S-ID.2
Possible Assignments p. 22: 9 – 13, 19 – 24 p.42: 39 – 42, 48, 49
p. 70: 81 – 86, 91, 94
Other Relate d Materials Use of Graphs on the TI-84 Use of Data on TI-84
4.1 Sampling and Surveys Population and sample Sampling techniques Coverage and undercoverage Sampling errors and non-response
4.2 Experiments Observational studies Exp eriment s Experimental vocabulary Randomized Design
4.3 Using studies wisely Inference and causation Data Ethics Bias
Common Core Stan da rd(s ) 7-SP.1 S-ID.5 S-CP .4
A-CED.1 A-SSE.1
美国导管相关血流感染预防与控制技术指南的分析
– 393例CVC导管定植的发生率：锁骨下为5%，颈内 为19%，股静脉为39%
• Raad, et al. Ann Intern Med, 1997
– 266例CVC导管定植的让步比：锁骨下VS 颈内为 0.39(p=0.02);锁骨下VS股静脉为0.28(p=0.002)
3. 手卫生和无菌操作
1.在触摸插管部位前、后，以及插入、重置、触碰、维护 导管及更换敷料前、后时，均应严格执行手卫生程序 ，可以是传统的皂液和水，或者用酒精擦手液。在对 插管部位进行消毒处理后，不应再触摸该部位，除非 采用无菌操作。（ⅠB）
2.在进行插管和维护操作时须无菌操作。（ⅠB） 3.进行周围静脉置管时，若对插管部位进行皮肤消毒后不
教育项目的效果
• 外科ICU • 为ICU护士制定的10页
自学模块材料 • 总体的BSI发生率
– 教育前：10.8/1000 导管 日
– 教育后：3.7/1000导管日
Coopersmith CM, et al. Critical Care Med, 2002
病人/护士比率和人员水平
• 在SICU内，中心 静脉导管相关BSI 爆发与病人数与护 士数比例有关
病学上的研究或理论依据 • 未解决的问题.代表一个尚未解决的争议性措施，因为
没有充分的实证或目前无法判断其实施的效果性
推荐程度总结
• Total 103 recommendations 所有103项推荐
– 21 IA – 37 IB – 3 IC – 31 II – 11项为未解决的问题
1.教育、培训与人员配备
通窍活血汤对颅脑外伤手术患者的治疗效果研究
DOI：10.19368/ki.2096-1782.2024.02.039通窍活血汤对颅脑外伤手术患者的治疗效果研究李心明徐州市贾汪区人民医院神经外科，江苏徐州221011[摘要]目的探究通窍活血汤对颅脑外伤手术患者的治疗效果。
方法选取2022年1月—2023年1月于徐州市贾汪区人民医院进行手术治疗的78例颅脑外伤患者，根据随机数表法分成针刺组与中药组，每组39例。
所有患者均接受手术治疗与术后康复训练（包括常规肢体功能与认知功能训练），在此基础上，针刺组接受针刺治疗，中药组接受通窍活血汤治疗。
比较两组治疗总有效率、神经功能、运动功能、日常生活能力改善情况。
结果中药组的治疗总有效率（92.31%）明显高于针刺组（71.79%），差异有统计学意义（χ2=5.571，P< 0.05）。
经治疗，中药组神经功能评分低于针刺组，肢体运动功能及日常生活能力评分均高于针刺组，差异有统计学意义（P均<0.05）。
结论颅脑外伤手术患者术后采用通窍活血汤治疗，疗效显著，可改善其神经功能、运动功能，加强其日常生活自理能力。
[关键词]颅脑外伤手术；通窍活血汤；针刺疗法；神经功能；运动功能；日常生活自理能力[中图分类号]R840 [文献标识码]A [文章编号]2096-1782（2024）01(b)-0039-04Therapeutic Effect of Tongqiaohuoxue Decoction on Patients with Cranio⁃cerebral Trauma SurgeryLI XinmingDepartment of Neurosurgery, Jiawang District People's Hospital, Xuzhou, Jiangsu Province, 221011 China[Abstract] Objective To explore the therapeutic effect of Tongqiaohuoxue Decoction on patients with craniocerebral trauma surgery. Methods A total of 78 patients with craniocerebral trauma who underwent surgical treatment in Ji‐awang District People's Hospital of Xuzhou City from January 2022 to January 2023 were selected and divided into acupuncture group and TCM group according to random number table method, with 39 cases in each group. All pa‐tients received surgical treatment and postoperative rehabilitation training (including routine limb function and cogni‐tive function training). On this basis, acupuncture group received acupuncture treatment, and TCM group received Tongqiaohuoxue Decoction. The total effective rate and the improvement of nerve function, motor function and daily living ability were compared between the two groups. Results The total effective rate of TCM group (92.31%) was sig‐nificantly higher than that of acupuncture group (71.79%), and the difference was statistically significant (χ2=5.571, P<0.05). After treatment, the scores of nerve function in TCM group were lower than those in acupuncture group, and the scores of limb motor function and daily living ability were higher than those in acupuncture group, and the differ‐ences were statistically significant (all P<0.05). Conclusion Patients with craniocerebral trauma surgery were treated with Tongqiaohuoxue Decoction after operation, which has remarkable curative effect, can improve their nerve func‐tion, motor function, and strengthen their self-care ability in daily life.[Key words] Craniocerebral trauma surgery; Tongqiaohuoxue Decoction; Acupuncture therapy; Nerve function; Motor function; Self-care ability in daily life颅脑外伤常伴有头皮、颅骨及脑损伤，一般病情较为严重，手术治疗的疗效确切，可最大程度挽[作者简介] 李心明（1979-），男，本科，副主任中医师，研究方向为神经外科疾病。
Foreign+Language+Research+Edition+English+Primary
Essays and argumentative articles explaining ideas and concepts related to the unit theme
Text B
Dialogues and conversations for role playing activities
Don't be afraid to make misses Learn from them and use them as opportunities for improvement
Active learning
Participate actively in class, ask questions, and share your ideas and experiences to deep your understanding of the subject matter
The textbook covers a range of topics and themes, including daily life, school life, family, friends, hobbies, and more It aims to provide students with a comprehensive understanding of English language structure and usage through a variety of engaging activities and exercises
Review and preview
Before each lesson, review the previous lesson and preview the content of the next lesson to help establish a solid foundation for learning
P2Y12受体自发激活及Gi和G1213通路在血小板激活和血栓形成中的作用中期报告
P2Y12受体自发激活及Gi和G1213通路在血小板激活和血栓形成中的作用中期报告
P2Y12是一种广泛存在于血小板上的G蛋白偶联受体，它的激活可
以导致血小板的聚集和激活，从而促进血栓的形成。
在缺血性心脏病和
脑血管病的治疗中，P2Y12受体拮抗剂已经成为一种重要的治疗手段。
除了外源性配体的作用，P2Y12受体也可以被自发激活，这种自发
激活可以导致血小板的持续激活和血栓的形成。
目前人们对P2Y12受体
自发激活机制还了解得比较有限，但已经有研究表明，G蛋白介导的通路可能参与了这个过程。
在血小板激活和血栓形成中，P2Y12受体通过Gi和G12/13通路转
导信号，导致血小板的激活和聚集。
Gi通路可以抑制腺苷酸酰化酶(AC)
的活性，从而降低细胞内cAMP水平，促进血小板的激活和聚集。
G12/13通路则可以激活RhoA和ROCK，从而促进血小板的收缩和聚集。
除了P2Y12受体外，其他多种G蛋白偶联受体也能参与血小板的激活和血栓的形成。
未来的研究需要进一步阐明这些受体在血小板功能调
控中的作用，从而为相关疾病的治疗提供新的靶点和策略。
manual for the patterns of adaptive learning scale
manual for the patterns of adaptivelearning scaleAdaptive learning is an important approach in education that aims to personalize and optimize the learning experience for individual students. One tool that is commonly used to measure the effectiveness of adaptive learning is the Patterns of Adaptive Learning Scale (PALS). This manual provides a comprehensive guide on how to use PALS effectively.Introduction to PALSThe Patterns of Adaptive Learning Scale (PALS) is a self-report instrument that assesses students' perceptions of their learning patterns and strategies in adaptive learning environments. It consists of two major sections: Patterns of Adaptive Learning (PAL) and Learning Strategies (LS).Section 1: Patterns of Adaptive Learning (PAL)This section focuses on capturing students' learning patterns in adaptive learning environments. It includes the following subscales:1. Mastery approach: This subscale assesses students' inclination to set challenging goals, persist in the face of difficulties, and actively seek opportunities to expand their knowledge and skills.2. Performance approach: This subscale measures students' motivation to perform well in order to receive recognition or praise from others.3. Performance avoidance: This subscale evaluates students' tendency to avoid tasks or activities that may expose their lack of ability or lead to failure.4. Help-seeking: This subscale examines students' willingness to seek assistance when facing challenges or difficulties.Section 2: Learning Strategies (LS)This section focuses on students' utilization of adaptive learning strategies. It consists of the following subscales:1. Rehearsal: This subscale assesses students' use of rote memorization or repetition to remember information.2. Organization: This subscale measures students' ability to categorize, summarize, and integrate information to facilitate comprehension and learning.3. Elaboration: This subscale evaluates students' capacity to elaborate or expand on information through examples, analogies, or connections to existing knowledge.4. Metacognitive self-regulation: This subscale examines students' awareness and control of their own learning process, including planning, monitoring, and evaluating their learning strategies.Using PALSTo administer PALS, distribute the questionnaire to students and instruct them to respond honestly based on their experiences in adaptive learning environments. Ensure that they understand the instructions and provide a comfortable and confidential setting to encourage candid responses.Once all the responses are collected, calculate the scores for each subscale by summing the relevant items. Higher scores indicate stronger adherence to the respective learning pattern or strategy.Interpreting PALS ResultsWhen interpreting the results, it is important to consider that PALS provides insights into students' perceptions of their learning patterns and strategies, rather than objective measures of their actual behavior. Therefore, the results should be used as a starting point for further analysis and discussions.The Patterns of Adaptive Learning Scale manual also provides guidance on how to interpret the scores, including the recommended benchmarks and comparisons that can be made with other groups or normative data.ConclusionThe Patterns of Adaptive Learning Scale (PALS) is a valuable tool for assessing students' perceptions of their learning patterns and strategies in adaptive learning environments. By understanding students' preferences and approaches to learning, educators can make informed decisions to enhance the effectiveness of adaptive learning interventions. This manual serves as a comprehensive guide to administering and interpreting PALS, enabling educators to gain valuable insights into students' adaptive learning experiences.。
药理学实验教材外国教材
药理学实验教材外国教材以下是一些药理学实验的外国教材推荐：1. "Pharmacology and Experimental Methods in Toxicology" by Dale E. Moffett and Jon C. Cray Jr. 这本教材涵盖了药理学和毒理学的实验方法，包括动物模型的选择、药物给予途径和剂量选择、药物代谢和药理动力学等内容。
2. "Experimental Pharmacology: A Laboratory Guide for the Study of the Pharmacological Actions of Drugs" by Peter G. Furst and Nigel S. Scrutton. 这本实验室指南提供了一系列关于药物作用机制和效应的实验方法，包括离体器官、细胞培养、动物模型等。
3. "Methods in Pharmacology: Molecular and Cellular Biology of Pharmacological Targets" by Paul H. Axelsen and Vincent Cristofalo. 这本教材介绍了分子和细胞生物学在药理学研究中的应用，包括酶动力学研究、药物靶点的鉴定和药物-靶点相互作用等。
4. "Pharmacology: Principles and Practice" by Miles Hacker, William S. Messer Jr., and Kenneth L. Becker. 这本药理学教材涵盖了药物的行为、药物治疗和药物作用机制，同时也包含了一些实验方法的介绍。
这些教材很好地覆盖了药理学实验的相关内容，并提供了详细的实验方法和步骤。
当然，在选择教材时，还应考虑自己的学科需求和教学计划。
药品研发指南(英文)
PRODUCT DEVELOPMENT GUIDE PRE-FORMULATION - TABLETSIntroductionGuidelines for the development of a ANDA product for the US market, Note: some tests or procedures may be unnecessary. The order of performing the various stages may change depending on the product under development. These guidelines may be modified for other geographic zones.Development Stage Scope of Product DevelopmentStage 1L i t e r a t u r e S e a r c hLiterature Research USP BP Pharm. Eur, PDR, Martindale, Merck, Florey, VidalFDA - FOI Summary Basis of ApprovalOn-line computerized searchFDA CDER Electronic Data Base (articles and publication on test methods, Dissolution synthesis procedures, drug impurities, pharmacokinetics and dynamics)Evaluation of Biostudy parameters, Dissolution methods.Patent evaluation Orange Guide + FDA CDER WWW Patent Consultant Stage 2A c t i v e S o u r c i n gSourcing for Active Raw Material International Suppliers US, European, Asian, e.g. (ACIC-Canada) (AllChem-UK) (Lek-Czech), (Esteves; Moehs; Uquifa-Spain); (Biopharma, S.I.M, Midy-Italy) (Chemcaps, Reddy; Tricon-India); (Federa-Brussels) - Review suppliers catalogues & data critically.Potential Suppliers List Request samples and C of A and SpecificationsEvaluate at least two suppliers fully.Stage 3A c t i v e E v a l u a t i o nEvaluate Potential Actives Evaluate at least two to three potential active suppliers • DMF availability• Compliance with USP monograph• Impurity profile and stability• Potential Polymorphic forms• Commitment for physical specifications• Statement of non-patent infringementStage 4A c t i v e P u r c h a s i n gPurchase (Potential) Active Material Evaluate at least two potential active material suppliers for approved supplier statusStage 5A c t i v e T e s t i n gTesting of Active Material sample Chemical testing by the R&D analytical lab as pera. Pharmacopoeia monograph (if present)b. Pharmacopoeia Forum (if available)c. In-house method (based on manufacturer)d. Supplier's test methods and specificationsPRE-FORMULATIONDevelopmentStageScope of Product Development Stage 6I n n o v a t o r's P r o d u c t P u r c h a s i n gDRUG PRODUCT Innovator Samples Purchase at least 3 different lots in smallest and largest pack size for each product strengthStage 7I n n o v a t o r's P r o d u c t T e s t i n gInnovator Testing Evaluate physical parameters:-tablet shape, tablet color, code for punch embossing, pack sizescontainers materials, closure types; cotton and desiccants.Innovator Physical Testing Physical testingWeight; Thickness; Hardness; LOD; Friability; Disintegration: Evaluation of tablet punch; size; score; embossing and shapeEvaluation of Innovator formula ingredients Summary Formula in PDR; International PDRs (Italian, French, Swiss) and Innovators product's insert (obtain latest FOI -FDA) Perform actual analytical testing on innovator's product.Microscopic observation Particle/crystal information onParticle sizeCrystal shape, habit,Differentiation on the presence of specific excipients can be verified from microscopic observation. E.g., Cross-linked cellulose's Starch and Avicel have a specific shapes and morphology and maybe easily detected.Evaluation of Biostudy parameters Review FDA CDER Home page for listing and Biostudy parametersDissolution profile USP monograph and FDA method - (where present)Dissolution; 12 unit Dissolution Profile.Stage 8B u l k A c t i v e T e s t i n gFIRST BATCH FROM APPROVED SUPPLIER Full Physical characterization Physical characterization of bulk batch• Polymorphism• B.E.T.• Particle size distribution (& method development)• Bulk density;• Microscopic observationFULL CHEMICAL CHARACTERIZATION Chemical characterization • Assay• Stressed Analysis• Degradants (Expected)• Impurity profile• Optical rotation• Enantiomeric purity• O.V.I. TestingDEVELOPMENT BATCHESDevelopment Stage Scope of Product Development Stage 9E x c i p i e n t sEvaluation of formu-lation with suitable excipients Excipient compatibility using DSC methods and stability assessmentStage 10C o n t a i n e r C l o s u r e S y s t e mEvaluation of suitable Container-Closure System Choice of container-closure-liner system including:• material composition,• type of thermoplastic resin and resin pigments,• manufacturers and suppliers,• liners and seals used by closure manufacturer,• cotton and desiccants.• manufacturer's DMF numbers for all component parts• Letters of Access for regulatory authorities to view DMF dossiersStage 11M a n u f a c t u r i n g P r o c e s sEVALUATION SUITABLE MANUFACTURING PROCESSESWet GranulationDry Granulation Slugging and Dry Granulation • Wet granulation (aqueous or non aqueous)high shear mixing / low shear mixing• FBD spray procedure), or• Dry mixing, dry granulation and/'or Slugging• Determination of order of mixing• Determination of pre-mixing (in Granulator)• Determination of fluid addition (if relevant)• Determination of granulation time (chopper I & II)• Determination of torque end-point value• Determination of Drying parameters• Determination of LOD limits• Determination of testing temperature for checking LOD limits (State machine used e.g. Mettler™, Computrac™).GRANULATION Physical Properties of Granulate • Flow properties,• Density,• Particle-size distribution • CompressibilityCompression Physical Properties of Compressed Tablets • Weight,• Hardness,• Thickness, • Friability • Disintegration• DissolutionFinal Formula Established Assessment of Final Master Formula and accelerated 1-3 month stability profile.Stage 12B u l k A c t i v e P u r c h a s e dActive material Bulk purchase Ordering of Active material for Process Qualification (PQ) and Pivotal Batch(es).On approval of final formula, order sufficient material for the PQ (2) and Pivotal Lots (sufficient for all strengths and batch sizes). NB: Never mix batch numbers in PQ and Pivotal Lots.FULL LABORATORY EVALUATION Development Scope of Product Development Stage 13A n a l y t i c a l E v a l u a t i o nAnalytical testing of tablets/Caplets • Dissolution - in USP medium (Multipoint profiles) and other relevant media versus Innovator's product• U of C-for low active concentrations. Refer to USP requirements for uniformity of content vs. uniformity of dosage units.• Validation of analytical package i.e. Assay; Dissolution ; Content Uniformity completed prior to Process QualificationPROCESS OPTIMIZATIONDevelopment Scope of Product DevelopmentStage 14P r o c e s s O p t i m i z a t i o nGRANULATIONOPTIMIZATION• Effect of granulation parameters• Granulation time• Speed of choppers (I & II) or mixer blades• Solvent addition rate and overall amount• Ratio of intra-granulate Disintegrant and binders agents• Screen size for milling (e.g. 0.6 or 0.8mm)• Adjusting mill screen size up or down to fine tune hardness• Evaluation of optimized granulate and tablet attributes DRYING• FB Drying temperature versus target LOD and range limits andthe effect on granulate and tablet properties (flow, capping,sticking).BLENDING◊ Blending times◊ Lubricant Split into two parts (pre-blending and final blending)◊ The effect on Content Uniformity, Granule lubrication andDissolution profile.◊ Evaluation of unit dose sampling vs. Content UniformityCOMPRESSION∗ Effect of hardness on tablet properties (aging, dissolution,friability).∗ Evaluation of Hardness Range Limits∗ Evaluation of stability results of optimized mfg. processPROCESS OPTIMIZATION REPORT ∗ Prepare PO Report. This Process Optimization Report forms part of the product Development ReportESTABLISHING AND INVITRO INVIVO CORRELATIONDevelopment Scope of Product DevelopmentStage 15A n a l y t i c a l E v a l u a t i o nIVIV Correlation• Dissolution - in USP medium (Multipoint profiles) and otherrelevant media versus Innovator's product.• Perform IVIV Bioavailability Study (where relevant)Establish a Level A or C correlation without adjusting dissolutionparameters and time scale• Adjust the dissolution parameters or time scale to achieve aLevel A or C correlation (adjust only if necessary)S CA L E UPDevelopment Scope of Product DevelopmentStage 16S CA L E UPScale-up Scale-up lot prepared if larger batch size scale up problemsanticipated.Process Qualification batch and Scale-up batch may beevaluated as a single batch.Scale-up Report The preparation of a Scale-up Report. The Scale-up report formspart of the overall Development ReportPROCESS QUALIFICATIONDevelopmentStageScope of Product DevelopmentStage 17P r o c e s s Q u a l i f i c a t i o nThe process qualification batch is manufactured in order to detect any problems that may arise during the manufacture of production size batches, allowing a solution prior the manufacture of the pivotal demonstration batch. Scale-up to the pivotal batch size or 70% of the pivotal batch may be combined with qualifying the manufacturing process At this stage full manufacturing documentation is prepared alone standard procedures.PRODUCTION FACILITIES Process Qualification batch should be compressed in a production (or production type with same principle and operation) tabletting machineSize of pivotal and marketing batch confirmed (NLT 100 000 net/ packed at target parameters or 10% of proposed market batch).BATCH DOCUMENTATION Preparation of Master Formula and Processing Instructions Discussion of formula, manufacturing process and control parameters with production personnel and QA StaffPROCESS QUALIFICATIONDevelopment Stage Scope of Product Development Stage 17 (Cont)P r o c e s s Q u a l i f i c a t i o nFINAL REVIEW and AUTHORIZATION Review of proposed formula, manufacturing process and control parameters with production personnel and QA Staff with authorization signatures (RD; QA-QC; RA; and Production)PROTOCOL PQ. protocol preparedKEY STEPS Critical manufacturing steps designated and sampling and testingparameters specified.OPERATING CONDITIONS Presence of production and control personnel during PQ manufactureP.Q. REPORT Upon completion prepare Process Qualification Report. This P-Qreport forms part of the overall Development ReportPIVOTAL BATCHDevelopment Scope of Product DevelopmentStage 18P i v o t a l P r o d u c t i o nPRODUCTION FACILITIES Pivotal batch MUST be compressed in a production tabletting machine (or production type with same principle and operation)BATCHDOCUMENTATIONPreparation of FINAL Master Formula and Processing InstructionsREVIEW and AUTHORIZATION Review of FINAL formula, manufacturing process and control parameters with production personnel and QA Staff. Pivotal authorization signatures (RD; QA-QC; RA; and Production) attached.OPERATING CONDITIONS Operation of production and control personnel during Pivotal manufacture, aided by development team.REPORT The preparation of a Pivotal Report. This pivotal report forms partof the overall Development Report. BIOEQUIVALENT STUDYStage Scope of Product DevelopmentStage 19B I O S T U D Y E v a l u a t i o nBIOSTUDY Fasted Perform Fasted / Food Effect Biostudy on Pivotal Lot SamplesBIOSTUDY [Food Effect]Perform Food Effect Biostudy on Pivotal Lot Samples (See food effect guidelines, where appropriate)HIGHEST DOSAGE Biostudy generally performed on highest strength of product One or two studies Fasted AND Food Effect Study may be requiredWAIVER CONDITIONS For multiple strength products Invitro dissolution testing conducted in three different pH media on lower dosage formsSIMILARITY TESTING Perform Similarity Test [F2 Test] on dissolution results.PRE-SUBMISSION AUDITINGDevelopment Stage Scope of Product DevelopmentStage20A N D A P r e-S u b m i s s i o n A u d i t i n g Development Report Audit all raw data supporting Development ReportANDA Regulatory File Audit Plant and Laboratory Documentation as per ANDASOPs Review SOP System and Update levelcGMP Review cGMP of Manufacturing ProcessesBiostudy Report Evaluate and develop a IVIV correlation (Level A where possible.) Validation Protocol Product Process Validation Protocol complete and signedANDA SUBMISSIONDevelopment Stage Scope of Product DevelopmentStage 21A N D A S u b m i s s i o nANDA Submission Submit ANDA structured as Part Two of this Handbook(9 Copies -as per Color system)(1 Field Copy)VALIDATION BATCHESDevelopmentStageScope of Product DevelopmentStage 22P r o c e s s V a l i d a t i o nProtocol Process Validation Protocol for 3 consecutive marketing lots Execute validation Process Validation of 3 consecutive marketing lotsReport Process Validation ReportSimilarity Show intra-batch similarityBio-Validation Similarity Show inter-batch similarity between Biobatch (Pivotal) and the Commercial Validation LotsCOMMERCIAL RE-VALIDATIONDUE TO MAJOR CHANGEScope of Product Development DevelopmentStageStage 23P r o c e s s R e-v a l i d a t i o nFormula Change Revalidate procedure with new formula process or equipment with Process Change a different operating principleEquipment ChangeMinor change Follow SUPAC Rules Level I II or IIIIMPORTANT NOTE ON DEVELOPMENTD evelopers are encouraged to develop IVIVC for IR dosage forms, where applicable to the BCS, (Biopharmaceutical Classification System) in the expectation that the information will be useful in establishing appropriate dissolution specifications and thus permit certain post approval formulation and manufacturing changes to be effected, - without additional bioequivalence studies.T he objective of developing an IVIVC is to establish a predictive mathematical model describing the relationship between invitro dissolution settings and the actual invivo drug-plasma parameters found, (such as AUC, C max, T max).T he invitro dissolution settings are adjusted (via media, pH agitation) until a I : I correlation is achieved (Level A) or a single dissolution point and a plasma parameter is shown to correlate (Level C).When more than one point correlates a multiple Level C is obtained - which may possibly be upgraded to a Level A with additional development work.T his matching of dissolution settings with plasma levels, that are derived from a specific IR formula and its corresponding manufacturing process, is in fact simply an arbitrary set of values that establish the so called 'predictive mathematical model'.A n IVIVC should be evaluated to demonstrate that predictability of the invivo performance of the drug product (i.e. derived from the plasma parameters) from its in vitro dissolution characteristics (e.g. equipment settings / and manufacturing changes) is maintained over the product's dissolution profile。
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Business policyChapter 12Study guide1)What are the 5 overall keys to implementation controla.Fitb.Clear and compelling objectivesc. A single company currencyd.Top management involvemente.Resource allocation2)What is the meaning of single company currencyCompany rewards need to be the same type of reward for every member of the organization.Example, if your bonus is company stock, it should be the same for every employee in thecompany3)Define metricsMetrics are ways a company measures its performance4)Metrics should meet the following 4 criteriaa.Be tied to the overall mission/vision of the organizationb.Be considered both quantitative and qualitative measures of performancec.Can be translated t all levels of employees within the organizationd.Can be ultimately translated to a single corporate currency5)Define quantitative metricsNumerically based measures of success6) Define qualitative metricsMeasures of success that are descriptive and relative rather than point specific7)List the 4 characteristics of effective metricsa.Be both quantitative and qualitativeb.Balanced across functionsc.Appropriate for the function or leveld.Connected to incentives8)Define casual logicAn assessment of why thing work the way they do9)What are the three models used to implementing a strategic plana.Balanced score cardb.Value driver action modelc.7-s framework10)Define balanced scorecardAn implementation method that considers a wide variety of stakeholders in the performance of the company11) The central notion of a balanced scorecard is that financial measures of performance are theresult of a variety of activities that people in the company engage in, not the cause12)List the 3 dimensions of the balanced score carda.Driven by strategyed to address the cause and effect logic across four levels of the organizationed to delineate both lead land lag metrics13)List the four linked perspectives in the balanced scorecard modela.Learning and growth perspectiveb.Internal processes perspectivec.Customer perspectived.Financial perspective14)Define lead metricsRepresent the observable actions of employees that we hope will lead to the results we are ultimately trying to achieve15)Define lag metricsRepresent the results that we would hope and expect to observe for each of the sub dimensions in any one perspective of a balanced scorecard16)List the five components that make up an effective value driven action plana.Identifying key value drivers that will lead to a competitive advantage for the businessb.Outlining the position the company wants to occupy from the perspective of how customers,suppliers , employees, and other stakeholders experience the companyc.Translating desired stakeholder experience to business/market positiond.Creating a list of action to be taken, both short tem and long term, that answer the questionwhat must we do now to ensure successe.Developing metrics that measure progress toward the accomplishment of each value driver17)Define key value driversThose elements of the organization that provide the company with the best opportunity for success in their industry18)List the 3 sources of key value driversa.The list of key success factors developed through industry analysisb.The resource based analysis that pinpoints extraordinary resourcesc.The vision and the mission statements19)What are the two actions identified in stage four of the value driven action plana.Actions that immediately address stakeholder experiences taking advantage of existingresourcesb.Actions to build new resources to address stakeholder experiences and long termaspirations20)Define the 7-S frameworkA method of examining the various aspects of the organization in such a way that somealignment can be achieved. Elements include strategy, structure, systems, style, skills, staff and superordinate goals (shared values)21)List the Hard S’sa.Strategyb.Structurec.Systems22)List the soft S’sa.Styleb.Staffc.Superordinate goalsd.Skills23)Define superordinate goalThese are the overarching goals of the organization24)List the 10 strategic leadership core responsibilitiesa.Establishing mission and goalsb.Build a senior management teamc.Establish structure for communication, coordination and controld.Exert control over directione.Establish a code of ethics for conduct and decision makingf.Evaluate, decide, actg.Rational decision makingh.Establish top management team process that challenges assumptions, surfaces andalternativesi.Establish culture that matches personal leadership stylej.Motivate through incentives and rewards aligned with goals。