高医大肾脏内科PPT课件

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1、顧進裕顧進裕高醫大腎臟內科高醫大腎臟內科,啟川大樓啟川大樓14ES07-3121101 EXT.735312guhjykmu.edu.tw Introduction Research Logic Causation Hypothesis DiscussionRen Descartes(March 31,1596 February 11,1650)1.1.除了除了清楚明白清楚明白的觀念外，的觀念外，絕不接受其他任何東西絕不接受其他任何東西 2.2.必須將每個問題分成若必須將每個問題分成若干個干個簡單的部分簡單的部分來處理來處理3.3.思想必須思想必須從簡單到複雜從簡單到複雜4.4.我們應該時常進

2、行徹底我們應該時常進行徹底的檢查，確保的檢查，確保沒有遺漏沒有遺漏任任何東西何東西 讀書時，不要急著辯駁，也不讀書時，不要急著辯駁，也不要盲目信從，或僅僅想找一個要盲目信從，或僅僅想找一個茶餘飯後的話題，而是茶餘飯後的話題，而是要去思要去思考和判斷考和判斷。有些書淺嚐即可，有些書不妨有些書淺嚐即可，有些書不妨狼吞虎嚥，有些書卻需要細細狼吞虎嚥，有些書卻需要細細嚼、慢慢嚥，換句話說，有些嚼、慢慢嚥，換句話說，有些書只需要選讀，有些書只需要書只需要選讀，有些書只需要瀏覽，瀏覽，有些書卻需要從頭到尾，有些書卻需要從頭到尾，仔細地體悟與省思仔細地體悟與省思。Francis BaconThe diffi

3、culty lies,not in the new ideas,but in escaping the old ones.-John Maynard Keynes,English economist遺傳努力工作(genius is 99%perspiration)知識(Francis Bacon)忘記學校所教的(H.P.);遊戲蘋果;在沙灘撿石頭;站在巨人肩上洗澡犯錯(Penicillin)看星星(PCR)做夢(aromatic)修行(朱銘),頓悟Quantum leap If at first the idea is not absurd,then there is no hope for

4、it.Imagination is more important than knowledge.Education is what remains after one has forgotten everything he learned in school.The important thing is not to stop questioning.Curiosity has its own reason for existing.Anyone who has never made a mistake has never tried anything new.Sir Arthur Conan

5、 Doyle,1859-1930Inspector Gregory:“Is there any other point to which you would wish to draw my attention?”Holmes:“To the curious incident of the dog in the night-time.”“.”“That was the curious incident,”remarked Sherlock Holmes.-The adventure of Silver BlazeGoogleGoogle scholarPubmedWikimediaLibrary

6、 of KMU1.If you are having difficulty understanding a problem,try drawing a picture.2.If you cant find a solution,try assuming that you have a solution and seeing what you can derive from that(working backward).3.If the problem is abstract,try examining a concrete example.4.Try solving a more genera

7、l problem first(the inventors paradox:the more ambitious plan may have more chances of success).-How to Solve(1)清晰及合符邏輯(Logical and Clear)(2)內部一致(Internal Consistency)(3)提供可驗證的假說(Testable Hypotheses Can be Deduced)(4)可被推翻和否定的(Can be Disconfirmed or Falsified)(5)通則性(Generalizability)(6)簡約的(Parsimonio

8、us):Occams razor(1)需要抽象的思維及合理的邏輯邏輯推論。(2)合乎科學理論的標準。(3)難有具體的指引及系統的步驟可供跟隨。(4)必須對相關的文獻文獻作一回顧，先了解前人對相關構念及題目的研究。(5)最好是把這些研究用不同的準則來分類，也試看一下有那些問題是尚未為它們所回答的。(6)到一定程度時嘗試用簡單的構念和它們之間的關構念和它們之間的關係係來回答那些有趣的問題。(1)真正的科學研究必由理論出發，而以驗證及改良理論為終(2)如果尚未建構清楚的理論模型及假說理論模型及假說，不應以碰運氣的方式從實證的資料中看那些變項呈相關，然後撰寫報告，我們稱這樣的做法為在資料中採礦(dat

9、a mining)，是不應該的，因為這與科學研究的本意相違背(3)如果我們在理論時，從資料中發現意外的現象，那就作為日後進一步驗證新的假說的基礎 Introduction Research Logic Causation Hypothesis Discussion類類A:1.Hypothesis-driven2.Discovery-driven3.MethodB:1.基礎研究基礎研究:分子分子、細胞細胞、動物動物2.臨床研究臨床研究:診斷或篩檢診斷或篩檢、治療治療、預後預後、病病因或副作用因或副作用C:1.1.相關相關:Observational2.2.因果因果:Experimental 重要

10、性重要性:貢獻性貢獻性 原創性原創性常見性常見性花錢性花錢性致病性與致命性致病性與致命性相關性相關性影響性影響性知識性與理論性知識性與理論性 實用性實用性 可行性可行性 Goal:Long-term goal to solve the problem Objectives(specific aims):Short-term objectives to solve the specific problems or answer the questions(hypotheses).It should be logical(inevitable from the background)Explora

11、tion,description,hypothesis testing,case studyWould you tell me,please,which way I ought to go from here?said Alice.That depends a good deal on where you want to get to,said the Cat.I dont much care where-said Alice.Then it doesnt matter which way you go,said the Cat.-so long as I get SOMEWHERE,Alic

12、e added as an explanation.Oh,youre sure to do that,said the Cat,if you only walk long enough.題目與摘要題目與摘要:敘述敘述問題與答案問題與答案 前言前言:為什麼為什麼(Why)問這個問題問這個問題 材料與方法材料與方法:如何如何(How)解決這個問題解決這個問題 結果與圖表結果與圖表:發現什麼發現什麼(What)去解決這個問題去解決這個問題 討論討論:提出並解釋提出並解釋對於這個問題的對於這個問題的答案答案 參考文獻參考文獻:我站在巨人的肩上我站在巨人的肩上,所以所以(對於這個問題對於這個問題)能看得

13、更遠能看得更遠 -牛頓牛頓 The most important statement in“Introduction”A super-topic sentence(in present tense)Sometimes stated as objectives(specific aims)Logical(inevitable)from the background(every question must have a background)If question has been stated completely in the unknown in“Background”:To answer

14、this question,If question has been stated only partially in the unknown:Therefore(Hence),we tested the hypothesis that we asked(the question)whether we(attempted to)determine were studied to address X questions:First,If question is to be stated as an objective:To determine whether(which),we Introduc

15、tion Research Logic Causation Hypothesis Discussion探究方法定義概念範例歸納法組合各明確且特定的單項概念，求出其關聯性而歸結出一個總括性的概念現象觀察綜合歸納導出理論觀察人口流動現象：(1)經濟繁榮的城市人口移出率不高。(2)經濟衰退的鄉村人口移出率很高。綜合歸納出：貧窮可能是造成人口移出的主要因素。導出人口推拉理論：鄉村多貧窮，形成人口移入的推力；城市因就業機會多，經濟發達，形成人口移入的拉力。演繹法由較總括性的概念推演出一個明確、特定且有關聯的單項概念引用理論演繹推論現象驗證 引用地震發生理論：(1)地震是地殼受外力擠壓而產生的震動。(2)

16、板塊碰撞帶因地殼受碰撞而擠壓，容易發生地震。演繹邏輯：臺灣位於板塊碰撞帶，地震頻繁，應可發現火山和斷層等地震所產生的地形特徵。實察驗證：進行野外實察以驗證假說。表1歸納法與演繹法比較 Given preconditions,postconditions and the rule R1:(therefore).Deduction:determining.It is using the rule and its preconditions to make a conclusion(R1 ).Induction:determining R1.It is learning R1 after numer

17、ous examples of and.Abduction(溯因溯因):Inference to the best explanation.One chooses hypothesis which would,if true,best explain the evidence(R1 ).1.Generalization:My cat likes tuna,his cat likes tuna,etc.All or most cats like tuna2.Statistical syllogism:Most cats like tuna.Sloth is a catSloth likes tu

18、na3.Simple induction:All of the cats Ive known like tunaThis new cat will like tuna4.Analogy:Jim and Bill have similar characteristics.Jim is loved by his classmatesBill is liked by his classmates1.已知所有的藥物都有副作用,若某甲宣稱他的新藥沒有副作用此話為真,則邏輯上如何?2.某奶粉公司添加抗體,宣稱能預防病菌?3.某酵素能在試管中化痰,請問該酵素口服後是否可能有效?4.某科學家訓練一隻跳蚤在聽到

19、大聲後便會跳高,當他把該跳蚤的雙腿剪斷後,跳蚤在聽到大聲後卻不會跳高,因此證明了跳蚤是用雙腿聽聲音?科學論文是由論證科學論文是由論證(argument)所構所構成的成的 論證論證=前提前提(premise)+推論推論(inference)+結論結論(conclusion)有效的有效的(valid)論證論證:前提蘊含結論前提蘊含結論,若你接受前提若你接受前提,則你必須接受結論則你必須接受結論 真確的真確的(sound)論證論證:“前提是真前提是真”的有效論證的有效論證 已知已知:若若 P 則則 Q 演繹法演繹法(deduction,數學上的必然數學上的必然):若若 P 則則 Q;若若 Q 則則

20、P 歸納法歸納法(induction,統計上的可能統計上的可能):簡單枚舉法、排除歸納法與統計歸納法簡單枚舉法、排除歸納法與統計歸納法 假設法假設法(abduction,科學上的創新科學上的創新):若若Q 則則 P;若若 P 則則 Q 已知已知:若若p53基因突變基因突變(P)則有癌症則有癌症(Q)演繹法演繹法(deduction,數學上的必然數學上的必然):一定一定對對 某甲的某甲的p53基因有突變基因有突變,因此有癌症因此有癌症 某乙沒有癌症某乙沒有癌症,因此他的因此他的p53基因沒有突變基因沒有突變 歸納法歸納法(induction,統計上的可能統計上的可能):可能可能對對我所遇見的每一

21、個癌我所遇見的每一個癌症病人其症病人其p53基因都有基因都有突變突變,因此我歸納因此我歸納:若若p53基因突變則有癌症基因突變則有癌症 假設法假設法(abduction,科學上的創新科學上的創新):可能可能對對 某丙有癌症某丙有癌症,因此他因此他的的p53基因可能有突變基因可能有突變;若若p53基因沒有突變基因沒有突變,則則某丙不會有癌症某丙不會有癌症 Introduction Research Logic Causation Hypothesis Discussion1.The organism must be found in all animals with the dis.(but n

22、ot in healthy animals).2.The organism must be isolated from a dis.animal and grown in pure culture.3.The cultured organism should cause dis.when introduced into healthy animals.4.The organism must be reisolated from the experimentally infected animal.1.1.一致性一致性:所有的研究結果都一致所有的研究結果都一致2.2.強度強度3.3.特異性特異性

23、:沒有其他的原因或解釋能造成這沒有其他的原因或解釋能造成這樣的結果樣的結果 4.4.劑量劑量-效應性效應性:因素愈強因素愈強,效果愈大效果愈大5.5.時間性時間性:原因一定要出現在結果之前原因一定要出現在結果之前6.6.生物學的可能性生物學的可能性:生理病理學上的可能性生理病理學上的可能性7.7.凝聚性凝聚性:與現有的理論不矛盾與現有的理論不矛盾8.8.實驗性實驗性:可用實驗來改變原因而改變結果可用實驗來改變原因而改變結果 Introduction Research Logic Causation Hypothesis Discussion變項變項:被研究對象的某一屬性因時地人物不同而在質或量

24、上的變化操作型定義操作型定義:根據可觀察測量或可操作的特徵來界定某一名詞或概念 假設假設:變項之間的假設性關係 假說假說:經過證實的假設 定律定律:經過重複驗證的假說 理論理論:有組織、有架構、具有邏輯關係的假說或定律The more precisely the position is determined,the less precisely the momentum is known in this instant,and vice versa.-Heisenberg,uncertainty paper,1927 Karl Raimund Popper1902-1994真不能被證明，只有偽

25、可以被證明真不能被證明，只有偽可以被證明 (真理真理是到現在為止尚未被否証的假說是到現在為止尚未被否証的假說)科學的假說事實論點皆須客觀地驗證，而非不證自明。不能完全依賴傳統、主觀信念、或常識來檢驗科學知識。科學思維是要抱持懷疑、批判的態度。沒有不證自明(self-evidence)的事知識是來自人們的經驗所有知識是暫時性的強調科學知識應基於經驗方面可觀察的假設之上。科學家目前採用的証據、方法和理論，來提出其暫時性的知識，它有可能隨時被修正。A suggested explanation for a phenomenon or of a reasoned proposal suggesting

26、 a possible between multiple phenomena.The scientific method requires that one can test a scientific hypothesis.Hypotheses are based on previous observations or on extensions of scientific theories.1.If a particular independent variable changes,then a certain dependent variable also changes.This for

27、mulation,also known as an If and Then statement.2.Investigators may have more difficulty in verifying causal relationships than other correlations,because quite commonly intervening variables also become involved.有時候以有時候以問題問題的方式提出的方式提出,每一個假設都每一個假設都要有背景要有背景 目的目的:解釋舊事實解釋舊事實、預測新事實、挑戰舊、預測新事實、挑戰舊理論、建構新理論

28、、尋找真理理論、建構新理論、尋找真理能回答能回答的的能被否證能被否證(falsifiable)的的要素要素:研究的族群、變數研究的族群、變數(自變數與應變數自變數與應變數)之之間的間的關係關係(因果相關或純相關因果相關或純相關)To explain old facts To predict new facts To challenge an old theory To build a new theory To search for truth(research=to search again)Falsifiable(measurable&testable):虛無假設虛無假設(否証否証,若若P

29、0.05 P0.05 則否証失敗則否証失敗)、對立假設、對立假設 Answerable(methods to answer)Species/population studied,relationship(causal or correlational)between in-dependent&dependent variables1.Gather data(something that is unknown,unexplained,or new)2.Hypothesize an explanation for those observations.3.Deduce a consequence

30、of that explanation.(A prediction)3.Design an experiment to see if the predicted consequence is observed.4.Wait for corroboration.If there is corroboration,go to step 3.If not,the hypothesis is falsified.Go to step 2.1.Testibility2.Simplicity(as in the application of Occams Razor,discouraging the po

31、stulation of excessive numbers of entities)3.Scope-the apparent application of the hypothesis to multiple cases of phenomena 4.Fruitfulness-the prospect that a hypothesis may explain further phenomena in the future 5.Conservatism-the degree of fit with existing recognised knowledge-systems A proposi

32、tion about the solution to a problem,the relationship of variables:1.An expected relationship between variables2.Based on either theory or evidence3.Testable4.Brief with clarity5.Stated in declarative form6.Be operational by eliminating ambiguity in the variables or proposed relationships Testibilit

33、y(compare falsifiability as discussed above)Simplicity(as in the application of Occams Razor,discouraging the postulation of excessive numbers of entities)Scope-the apparent application of the hypothesis to multiple cases of phenomena Fruitfulness-the prospect that a hypothesis may explain further p

34、henomena in the future Conservatism-the degree of fit with existing recognised knowledge-systems 1.Contingency,defeasibility,or falsifiability:Counterexamples to the hypothesis are logically possible 2.Feasibility of observing a reproducible series of such counterexamples if they do exist.In short,a

35、 hypothesis is testable if there is some real hope of deciding whether it is true or false of real experience.Upon this property of its constituent hypotheses rests the ability to decide whether a theory can be confirmed or falsified by the data of actual experience1.Subject group:Who are you intere

36、sted in studying?2.Treatment or exposure:What is being done to your subject group?3.Outcome measure:How is the treatment or exposure assessed?(defined precisely and unambiguously)4.Control group:Who are you comparing to.It is important for the control group to be as similar as possible to those who

37、receive a treatment or exposure.Not every research hypotheses will have all four components.For example,a cross-over design involves applying both a new treatment and a standard treatment using the same patients.For this study,the hypothesis would not involve a separate control group.Correlational s

38、tudies look at relationships within a single group,such as a study of the factors that cause medication errors.This type of study would not have a treatment/exposure.The structure mentioned here,however,is still useful for developing most research hypotheses.用反駁法來證明 建立虛無假設（null hypothesis），以及替代假設(al

39、ternative hypothesis)虛無假設自變數與應變數之間沒有關聯 替代性假設自變數與應變數之間有關聯 以推翻虛無假設來支持實驗的假設 Introduction Research Logic Causation Hypothesis Discussion 一般而言，假說型實驗較受喜歡。假說型實驗之決定點在於新穎性及可行性。但這兩者常是相互矛盾，所以通常會用混合型。敘述型實驗，不管有些科學家喜不喜歡，是很重要，常是重要科學發現之基礎。敘述型實驗常是用來產生假說，所以在描述敘述型實驗，應再說明可能產生之假說及如何進一步深入探討。或在敘述型實驗中加入重要性及比較性。The basic st

40、udy of E.coli system lead to the development of recombinant DNA.Human Genome Project Knockout mice experiments lead to important scientific developments.Structural study or structure-function study are mostly non-hypothesis based.Assay of MAPK,JNK,ERK pathways,systematic analysis.Complex things is r

41、educed to the nature of sums of simpler or more fundamental things,e.g.objects,phenomena,explanations,theories,meanings:Chemistry is based on physics,biology and geology are based on chemistry,psychology is based on biology,sociology is based on psychology,and political science,anthropology,and even economics are based on sociology.The component parts of a system will act differently when isolated from its environment or other parts of the system,and argues against Descartess reductionist view.It views systems in a holistic manner,rather than through purely reductionist techniques