Newsletter No. 410

2 No. 410, 4.1.2013 R ichard Dawkins thinks that Darwin is the greatest mind that ever lived. He also admits that he feels the same sense of reverential hush towards R.A. Fishe r, founder of modern statistics. The marriage of statistical theories and methods and the biological sciences have brought us the modern discipline of biostatistics. However, neither the impact of Fisher nor that of biostatistics is always duly recognized. According to Prof. Benny Zee of the Jockey Club School of Public Health and Primary Care, CUHK, biostatistics encompasses the design of biological experiments, especially in medicine and agriculture, on the collection, summarization, and analysis of data from those studies, and their interpretation and inference of the results. Biostatisticians are men of two trades, one in numbers and the other in the field of application. They use statistical reasonings, models and methods to re-formulate the problems into quantifiable functions and optimize the results for solutions and decisions. It is because of their ability to straddle and expand the boundary of a larger terrain of enquiry that they are often in a better position to act as problem-solvers and play a policy and advisory role. Common applications of biostatistical methods include quality control in industrial engineering, genetics in biology, clinical research methods in medicine, and actuarial and life tables in healthcare. The British statistician, Sir David Cox , has made many important contributions, of which the best known is perhaps the proportional hazards model, which is widely used in the analysis of survival data. An example is survival times in medical research that can be related to information about the patients such as age, diet or exposure to certain substances. Professor Zee had extensive experience in clinical trial methodology for drug development in North America before he came back to Hong Kong in 2001 to help build the discipline of biostatistics at CUHK. He would apply statistical reasonings to the testing and performance of new drugs to determine the optimal conditions under which a new drug was effective or otherwise, with the aim to enhancing the screening efficiency of new drugs. Such work obviously has immense impact on the pharmaceutical industry and the welfare of patients. His most recent innovation is in developing an algorithm for an automatic diagnostic system for cerebral vessel conditions and evaluation of the risk of stroke. This grew out of a collaboration with Dr. Jack Lee , a biostatistician with expertise in finance and bioinformatics, and Dr. Li Qing , an ophthalmologist and a PhD student of his who set out to identify vascular diseases before stroke happens. Up to 80% of all diabetics of over 10 years would develop diabetic retinopathy (DR) which is damage to the retina caused by diabetes mellitus, with a concomitant higher chance of suffering stroke at a later stage. DR screening has become a standard procedure in diabetic care but its effectiveness is hampered by several factors: not enough specialists to administer the screening, human variability in diagnosis, long waiting time for the result, and high cost. To address these issues, the team had to find a methodology to turn the analogue images of the retina into quantifiable and analyzable data. The finding of a pattern out of seemingly chaotic information was what Professor Zee had learned from his teacher at the University of Pittsburgh, Prof. C.R. Rao . According to Professor Zee, the first difficulty encountered in the process was the location of the optic disc (the spot where the light-sensitive ganglion cell axons leave the eye to form the optic nerve to the brain, also known as the physiological blind spot). Although methods of locating it already existed, his team developed a new method that best fit their purpose. A greater hurdle, however, laid in the detection of new vessels in the eye whose growth is a sure sign of havoc to come. As new blood vessels are short, irregular and squiggly, the determination of their existence and state of growth eluded all existent automatized technology. Applying the skills of a biostatistician in pattern recognition and quantification, the team was able to devise an algorithm which reads pixel by pixel the retinal images and analyze such pixels to come up with measurements on exudates, haemorrhages, new vessels and finally achieve the overall evaluation of retinopathy. Standard retinal images can be transmitted through the Internet to a server installed with the algorithm and the result or report is available within a short period of time. The new method is non-invasive and will substantially reduce bias due to human perception as well as cost and time. Initial tests have confirmed its dependability and high accuracy rates. Next, Professor Zee intends to expand the technology and apply it to both diabetes and non-diabetes patients for the early detection of strokes. The eye is the window to the soul, and so is it to sickness. Usually another human eye is required to judge if any hazard is forthcoming—that is the role of the traditional physician. Professor Zee and his team have devised an algorithm that does the job of the expert eye, so that the tool can benefit a wider population of individuals and make bigger impact on health care in general. 靈魂之窗窺探隱患 A Clearer Window to Health Hazards 徐仲鍈教授 Prof. Benny Zee 徐仲 鍈 教授1987年獲美國匹茲堡大學生物統計學博士學位，隨後加入加拿 大國立癌症研究所臨床試驗組任高級生物統計員，並任加拿大女王大學公共 衞生及流行病學系及數學和統計系教授。徐教授現為中大賽馬會公共衞生及 基層醫療學院教授，同時為學院生物統計學學部主任。 Prof. Benny Zee obtained his PhD in Biostatistics from the University of Pittsburgh in 1987. He then joined the National Cancer Institute of Canada Clinical Trials Group as senior biostatistician, and Queen’s University as a faculty member in its Department of Community Health and Epidemiology and the Department of Mathematics and Statistics. He is a professor at the CUHK Jockey Club School of Public Health and Primary Care heading the Division of Biostatistics. （左起）徐仲鍈教授、李作為博士及莫仲棠教授展示全自動化視網膜圖像分析系統 (From left) Prof. Benny Zee, Dr. Jack Lee and Prof. Vincent Mok with the automatic retinal image analysis system 理 查德·道金斯 推崇達爾文是古往今來頭腦最好的人， 而連帶對其理論繼承者、現代統計學奠基者 費雪 ，同 樣敬重有加。統計學的理論和方法，跟生物科學結合之後， 衍生了現代生物統計學。可是，不管費雪的成就還是生物統 計學的影響，能獲大眾認識者寥寥無幾。 據賽馬會公共衞生及基層醫療學院 徐仲 鍈 教授表示，生物統 計學涵蓋生物實驗的設計，尤其是醫學和農業，並包括蒐集、 總結和分析研究數據，以及解讀和推論結果。生物統計學家 精通數字與應用，他們會以統計學的思路、模型和方法，把問 題分拆成可量化的函數，以尋找最佳的答案和計策。生物統 計學家擅於跨越界別，能夠從更寬廣的層面探討問題，是故 更適宜擔當排難解疑，或制定政策和諮詢的角色。 生物統計學方法常應用於幾方面︰檢定工業工程質量、檢測 遺傳基因、臨床醫學研究，以及編制人口生命表。英國統計 學家 戴維·科克斯 爵士最為人熟悉的貢獻是他所創製的比 例風險模型，廣泛應用於分析存活數據，按照病人的年紀、 飲食習慣或接觸某些有害物質的情況，推算其存活時間。 徐教授在2001年加入中大，協助成立生物統計學學部前，在 北美洲專職測試新藥，驗證療效，從而找出一種新藥在甚麼 條件下能發揮最佳藥效，藉此提高篩檢效率。有關工作對製 藥行業和病人有莫大裨益。 他的最新創意成果是開發出一套演算法，供評估腦血管情 況和中風風險的自動診斷系統之用。與徐教授共同研發的， 包括專長於財經和生物資訊的生物統計學家 李作為 博士，以 及徐教授指導的博士研究生、致力透過檢查血管病變防範中 風的眼科醫生 李青 。 患糖尿病達十年以上的人，超過八成會有糖尿病視網膜病 變，即俗稱「糖尿上眼」，到後期中風機會亦相應增加。現 時，糖尿病視網膜病變篩查屬於常規檢查，但成效受幾方面 影響︰專科人手不足，不同醫生判斷有差異，等候結果時間太 長，以及成本高昂。 為此，研究團隊戮力尋找方法，把視網膜的模擬影像轉換成 可量化及可分析的數據。從看似雜亂無章的資料中找出脈 絡，正是徐教授早年在匹茲堡大學 拉奧 教授指導下的訓練。 他遇到的第一個難題，是如何找出視神經盤（俗稱「盲點」， 感光的神經節細胞軸突匯集成視神經，並由該處離開眼球 連接大腦）的準確位置。現成辦法是有的，但團隊也研發了 一套更切合本身需要的方法。至於最大困難，莫過於偵測眼 內增生的血管，它們一旦出現，就是大禍逼近的先兆。增生 的血管都是既短且彎，呈不規則形狀，要發現並查出它們的 生長情況並不容易。團隊施展生物統計學家最擅長的模式 識別和量化工夫，設計了一套運算法，把視網膜圖像分拆為 像素單位，逐點分析，以量度眼底滲液、出血和血管增生情 況，從而得出視網膜病變的整體評估結果。 一般視網膜圖像可以透過互聯網，傳送至內置演算法的伺 服器，不一會即可取得檢查報告。這種嶄新的非入侵檢查方 法，不受體檢人員的主觀影響，既省錢又省時。初步測試證 實可靠，而且準確度高。下一步，徐教授將會應用到糖尿及 非糖尿病人身上，及早防範中風。 眼睛是靈魂之窗，也是健康的晴雨表。一直以來，要判斷是 否有隱患，靠的是醫生的一雙眼。徐教授團隊研發的檢測 法，搖身一變為醫學專家的慧眼，讓廣大市民受惠，對提升 本地整體醫療水平有極大貢獻。 正常視網膜 Normal 糖尿病視網膜病變 Diabetic retinopathy 擷取視網膜影像 Retina image taking 篩查技術 Our screening technology 糖尿病視網膜病變分析報告 DR analysis report 邊註邊讀 Marginalia 「跨學科」這個詞聽得多了，但究竟怎樣才能做到「跨學 科」，卻鮮見實例。今期「洞明集」介紹一門由數字與人體 科學交叉孕育出的學問。 徐仲 鍈 教授告訴我們，生物統計 學的歷史遠較一般人所想的悠久，影響也較一般人所知的 密切，是最博大而影響廣泛的知識合體。 中大的學生和職員可能更為熟悉校園內的另一種「混合」， 就是大學游泳池旁的合作社混合多款草藥和茶葉炮製的 特色小吃。不過最令人回味的除了在熱騰騰的滷汁中浸泡 而成的茶葉蛋外，還有這家社會企業散發的人情味，這你可 在「舌尖上的中大」感受得到。 每個地方都有自己的獨特性格，有的更自有氣派。唐寧街 10號不單是住址，更是英國政府的中樞；美國白宮的橢圓 形辦公室亦復如是。在中大，祖堯堂也有相若地位。這個 音響設備先進的會場，是舉行重要會議、研討會和典禮的 地方，置身其中，可隱隱感受到四壁迴響過來的大學使命。 多年下來，牆上所掛的歷任校監、校董會主席和校長的 肖像隨歲月而增加，但你可知道，1971年剛啟用時，這裏 所掛的，就只得 關祖堯 爵士的肖像嗎？請看「昔與今」。 We often hear the word interdisciplinary but rarely see an example of how it works. The ‘In Plain View’ article in this issue brings you a vivid example of the cross- fertilization of ideas from the science of numbers and the science of the human body. Biostatistics, as Prof. Benny Zee explains, has an older history and a closer impact than most people would think. It is fusion of the most sophisticated and impactful kind. Students and staff are perhaps more familiar with fusion of another kind on campus. Sundry herbs and tea leaves go into the preparation of one of the most popular homemade specialties of the small cooperative store by the poolside. What is so appetizing is not only the tea eggs simmering in the tea-coloured marinade but also the friendliness and warmth exuded from this campus social enterprise, as you will find out in ‘Mouth-watering Morsels’. Places have characters. Some are even dignified. 10 Downing Street is not only a home address but also the nerve centre of the British government. So is the Oval Office to the White House. At CUHK, Cho Yiu Hall plays a similar role. Important meetings, conferences and ceremonies are held in this premium venue with sophisticated acoustics. One could almost feel the University missions resounding off its paneled walls. Over the years, more portraits of Chancellors, Council Chairmen and Vice-Chancellors adorn its walls. But do you know it started out with only one, that of Sir Kwan Cho-yiu , in 1971? Check out ‘Then vs Now’. ———————■■■——————— 目錄 Contents 洞明集 In Plain View 2 讓非形式學習一目了然 3 A Systematic Presentation of Non-formal Education 校園消息 Campus News 4 昔與今 Then vs Now 5 宣布事項 Announcements 6 舌尖上的中大 Mouth-watering Morsels 6 人事動態 Ins and Outs 7 古明達如是說 Thus Spake Shekhar Kumta 8