critical review of “Why I Am Not a Professor or The Decline and Fall of the British University”

Critical Review怎么写Writing a Critical ReviewThe advice in this brochure is a general guide only. We strongly recommend that you also follow your assignment instructions and seek clarification from your lecturer/tutor if needed.Purpose of a Critical ReviewThe critical review is a writing task that asks you to summarize and evaluate a text. The critical review can be of a book, a chapter, or a journal article. Writing the critical review usually requires you to read the selected text in detail and to also read other related texts so that you can present a fair and reasonable evaluation of the selected text.What is meant by critical?At university, to be critical does not mean to criticize in a negative manner. Rather it requires you to question the information and opinions in a text and present your evaluation or judgment of the text. To do this well, you should attempt to understand the topic from different perspectives (i.e. read related texts) and in relation to the theories, approaches and frameworks in your course. What is meant by evaluation or judgment?Here you decide the strengths and weaknesses of a text. This is usually based on specific criteria. Evaluating requires an understanding of not just the content of the text, but also an understanding of a text’s purpose, the intended audience and why it is structured the way it is.What is meant by analysis?Analyzing requires separating the content and concepts of a text into their main components and then understanding how these interrelate, connect and possibly influence each other.Structure of a Critical ReviewCritical reviews, both short (one page) and long (four pages), usually have a similar structure. Check your assignment instructions for formatting and structural specifications. Headings are usually optional for longer reviews and can be helpful for the reader.IntroductionThe length of an introduction is usually one paragraph for a journal article review and two or three paragraphs for a longer book review. Include a few opening sentences that announce the author(s) and the title, and briefly explain the topic of the text. Present the aim of the text and summarize the main finding or key argument. Conclude the introduction with a brief statement of your evaluation of the text. This can be a positive or negative evaluation or, as is usually the case, a mixed response.SummaryPresent a summary of the key points along with a limited number of examples. You can also briefly explain the author’s purpose/intentions throughout the text and you may briefly describe how the text is organized. The summary should only make up about a third of the critical review. CritiqueThe critique should be a balanced discussion and evaluation of the strengths, weakness and notable features of the text. Remember to base your discussion on specific criteria. Good reviews also include other sources to support your evaluation (remember to reference).You can choose how to sequence your critique. Here are some examples to get you started: •Most important to least impor tant conclusions you make about the text.•If your critique is more positive than negative, then present the negative points first and thepositive last.•If your critique is more negative than positive, then present the positive points first and the negative last.•If there are both strengths and weakness for each criterion you use, you need to decide overall what your judgment is. For example, you may want to comment on a key idea in the text and have both positive and negative comments. You could begin by stating what is good about the idea and then concede and explain how it is limited in some way. While this example shows a mixed evaluation, overall you are probably being more negative than positive.•In long reviews, you can address each criteria you c hoose in a paragraph, including both negative and positive points. For very short critical reviews (one page or less) where your comments will be briefer, include a paragraph of positive aspects and another of negative.•You can also include recommendatio ns for how the text can be improved in terms of ideas, research approach; theories or frameworks used can also be included in the critique section. ConclusionThis is usually a very short paragraph.•Restate your overall opinion of the text.•Briefly prese nt recommendations.•If necessary some further qualification or explanation of your judgment can be included. This can help your critique sound fair and reasonable.ReferencesIf you have used other sources in you review you should also include a list of references at the end of the review.Summarizing and paraphrasing for the critical reviewSummarizing and paraphrasing are essential skills for academic writing and in particular, the critical review. To summarize means to reduce a text to its main points and its most important ideas. The length of your summary for a critical review should only be about one quarter to one third of the whole critical review. The best way to summarize is to:1.Scan the text. Look for information that can be deduced from the introduction, conclusion and the title and headings. What do these tell you about the main points of the article?2.Locate the topic sentences and highlight the main points as you read.3.Reread the text and make separate notes of the main points. Examples and evidence do not need to be included at this stage. Usually they are used selectively in your critique.Paraphrasing means putting it into your own words. Paraphrasing offers an alternative to using direct quotations in your summary (and the critique) and can be an efficient way to integrate your summary notes.The best way to paraphrase is to:1.Review your summary notes2.Rewrite them in your own words and in complete sentencese reporting verbs and phrases (eg; The author describes…, Smith argues that …).4.If you include unique or specialist phrases from the text, use quotation marks.。

IntroductionIn Man’s Search for Meaning, Viktor E. Frankl tells the very per sonal story of his experience as a prisoner in a concentration camp during the Holocaust. He presents this story in the form of an ess ay in which he shares his arguments and analysis as a doctor and psychologist as well as a former prisoner. This paper will review Fra nkl’s story as well as his main arguments, and will evaluate the qu ality of Frankl’s writing and focus on any areas of weakness within the story.SummaryThis section contains a summary of Man's Search. Frankl begins his book by stating that his purpose in writing the book is not to present facts and details of the Holocaust, but to provide a persona l account of the everyday life of a prisoner living in a concentration camp. He states, “This tale is not concerned with the great horror s, which have already been described often enough (though less oft en believed), but…it will try to answer this question: How was ever yday life in a concentration camp reflected in the mind of the aver age prisoner?”(21). Frankl then goes on to describe the three stag es of a prisoner’s psychological reactions to being held captive in a concentration camp.The first phase, which occurs just after the prisoner is admitted to the camp, is shock. The second phase, occurring once the priso ner has fallen into a routine within the camp, is one of apathy, or “the blunting of the emotions and the feeling that one could not anymore”(42). The third phase, which occurs after the prisoner ha s been liberated from the camp, is a period of “depersonalization”, in which “everything appears unreal, unlikely, as in a dream”(11 0). In this phase, released prisoners also feel a sense of “bitterness and disillusionment”when returning to their former lives (113). Fr ankl describes each of these phases using psychological theory and provides personal experiences to exemplify each of the stages.Author’s ArgumentsAs described above, Frankl’s main purpose for writing this book is to pr esent and analyze the average prisoner’s psychological reactions to the every day life of a concentration camp. His three main arguments are his presentat ion and analysis of each of the psychological stages that the average concent ration camp prisoner experiences: shock, apathy and depersonalization. He b ases his analyses of each of these stages on the actions of the prisoners and his own personal thoughts and reactions as he experienced life in a concent ration camp.For example, Frankl argues that the second phase of apathy forces “the prisoner’s life down to a primitive level”(47) in which “all efforts and all e motions were centered on one task: preserving one’s own life and that of t he other fellow”(47). He bases this theory on events he witnessed while livi ng in the camp himself, and states, “It was natural that the desire for food was the major primitive instinct around which mental life centered. Let us ob serve the majority of prisoners when they happened to work near each other and were, for once, not closely watched. They would immediately start discu ssing food”(48). Frankl continuously uses examples from his experiences in t he concentration camp to illustrate and strengthen his psychological argumen ts throughout the text.EvaluationThis section contains an evaluation of Frankl’s book. Firstly, the author i s a survivor of the Holocaust and was a prisoner of a concentration camp hi mself, which gives him the personal insight to be able to comment on the ps ychological conditions of an average prisoner. However, this also creates a bi as and because of his personal experience, he is unable to be entirely objecti ve in writing his analysis. Frankl acknowledges this bias in the beginning of his book, by stating, “Only the man inside knows. His judgments may not b e objective, his evaluations may be out of proportion. This is inevitable. An attempt must be made to avoid any personal bias, and that is the real difficu lty of a book of this kind”(24-25). Although he is aware of this bias, it crea tes a partiality that will sway the readers throughout his story and it serves a s a minor weakness in his writing style.A second weakness in Frankl’s writing is in the assumptions he sometim es makes to prove his point. He makes overarching generalizations several ti mes in his book, making statements that, although may have been true for hi mself and those around him, might not have been true for every prisoner in every concentration camp during the Holocaust. For example, in one instance, he says, “The prisoner of Auschwitz , in the first phase of shock, did not fear death”(37). It is very bold to say that no prisoner of Auschwitz, one of t he most well-known and deadly concentration camps of the Holocaust, did n ot fear death, as death was all around them and was a very real threat in th eir daily lives. Although he might have not feared death during his phase of shock, it is impossible for him to guarantee that no prisoner was at all fearf ul of death in this first psychological phase, and for him to make overarching assumptions like this is a weakness to the overall quality of his book.Finally, Frankl sometimes becomes too technical and verbose in his writin g style, which makes it very hard for the average reader to understand. One example of this is as follows. Frankl states, “I remember an incident when t here was an occasion for psychotherapeutic work on the inmates of a whole hut, due to an intensification of their receptiveness because of a certain exter nal situation”(102). This sentence, which is overly wordy and complicated, m akes it difficult for the average reader to understand exactly what he is sayin g. A reader can easily get frustrated when trying to decipher the author’s m eaning due to overly complicated language, and this is a third weakness of F rankl’s writing.ConclusionThis critical review has evaluated the book Man’s Search for Meaning by Viktor E. Frankl. The psychological theories that Frankl presents are very inte resting and he does a good job of illustrating these theories with his own pe rsonal experiences. However, his writing is weakened by the presence of bias, the overarching assumptions he occasionally makes, and his sometimes overl y technical and verbose language.。

Critical reviewThe meaning of critical reviewBeing critical:•involves or requires making judgments as to the truth, merit, relevance, effectiveness, breadth, contribution of something to a particular field, as well as its informational structure.Review:•the process of going over a subject again in study or recitation in order to fix it in the memory or summarize the facts.• a general survey, esp. in words; report or account.•to survey mentally; examine: to review the situation.•to present a survey of in speech or writing.There are a couple of underlying assumptions which you should be aware of when attempting to critically review any academic work in the area of your research:•The literature is often written in expository, not literary style, and deals with information which is arranged accordingly.•To be able to make useful comments about any topic in your field, there should at least be an underlying knowledge base which provides a context and an understanding of the breadth of the subject matter (who is important, what is their contribution, what did he/she find etc.).•The first step is to acquire that knowledge base by wide reading according to the main descriptors or concepts that you have used to find the readings in the first place.Skills to cultivate for research and critical reviewYou need to ask the reading questions. For example...For textbooks:•What is the topic or subject area of this book?•What is the main purpose of this person's writing?•Why has this person written this book? (aims)•What is the information structure of this writing? How is the information arranged? •What is the order of presentation? Was it according to time or topic or importance? •What are the writer’s main points and sub-points?•Who are the most important researchers mentioned?•What conclusions are reached?•Was the text easy to read? Why/why not?•Was the information arranged for easy retrieval?•Did the writer fulfill his/her aims?•How new is the content? Are there other books on this subject matter?•Did the writer miss any important researchers in this field? Does it seem to be up-to-date?•Which points are of most interest to your areas of interest?•Did it stimulate your interest? Is it relevant to your situation?For articles (journal, collection of readings and dissertations)•What were the aims of this study? Why has the researcher done this study?•What were the researcher's hypotheses? Were they clearly expressed?•What were the results of the study? What conclusions were reached?•Did this study advance the knowledge base of the discipline, confirm other research in the same area, or simply repeat what is already known by way of confirmation? •Does it suggest to you areas for further research? Did it stimulate your interest? Is it relevant to your situation?Language for reading and writing criticallyTo be critical in the context of reading and writing involves being able to:•make judgements about what you read. These judgements may be positive or negative.Examples:•Several authors have categorised the effects of X in very useful ways.•Many papers ignore factors such as X when considering the applications of Y.•define a phenomenon clearly by drawing on the key aspects of definitions provided by other authors. Examples:•X is a difficult concept to define, because . . .•The key concepts/aspects that are covered in existing definitions are A, B and C.•establish the relative significance or importance of different aspects of what you read.Examples:•The most urgent of these questions/challenges is X, because . . .•The most important category identified appears to be X, since . . .•The most frequently mentioned advantages are A, B, and C.•distinguish between contexts, and make judgments about the validity or relevance of certain ideas/information/solutions within those contexts. Example:•This solution has been shown to be extremely effective in small to medium enterprises, but it is debatable whether it would be appropriate in large enterprises.•show the relationship (similarities, differences) between different ideas, information, theories. Example:•While X theory focuses on the role of relationships in building trust, Y theory deals primarily with the way in which the technology itself may enhance or diminish trust.•show the implications of different ideas/theories/solutions. Example:•From the perspective of X (theory), then, solutions would have to address ways of building relationships in an online environment, while from the perspective of Y(theory) solutions would involve developing effective user interfaces.•show an awareness of possible counter-claims on any issue. Example:•The predominant view on X is that it can best be solved by means of Y. However, it could be argued that Y would only work in the case of there being certainconstraints on competition between different organizations.•identify any gaps in the literature. Example:•One factor upon which appears to be overlooked is the influence of organizational structure on X practices.•identify trends and patterns in existing work. Examples:•Problems relating to X are increasingly being related to the use of . . .•While the value of X is being emphasized in the context of Y, there is also a trend towards considering X in the context of Z rather than Y.•sum up key issues, implications, or problems that emerge from each section that you cover. Examples:•It would seem, then, that X leads to Y, while A usually leads to F and G. This means that, in taking a two-pronged approach, the disadvantages of introducing X can, to some extent, be mitigated by using A at the same time.•To sum up, then, the crucial points to be taken into account are X and Y.Adapted from the following sources:Royce, T 2009, The meaning of critical review, ELSSA Centre, UTS.Royce, T 2009, Skills to cultivate for research and critical review, ELSSA Centre, UTS. Royce, T 2009, Reading and writing critically, ELSSA Centre, UTS.。

一些英文审稿意见的模板最近在审一篇英文稿，第一次做这个工作，还有点不知如何表达。

幸亏遇上我的处女审稿，我想不会枪毙它的，给他一个major revision后接收吧。

呵呵网上找来一些零碎的资料参考参考。

+++++++++++++++++++++++++++++++1、目标和结果不清晰。

It is noted that your manuscript needs careful editing by someone with expertise in technical English editing paying particular attention to English grammar， spelling，and sentence structure so that the goals and results of the study are clear to the reader。

2、未解释研究方法或解释不充分。

In general, there is a lack of explanation of replicates and statistical methods used in the study。

Furthermore, an explanation of why the authors did these various experiments should be provided。

3、对于研究设计的rationale：Also， there are few explanations of the rationale for the study design。

4、夸张地陈述结论/夸大成果/不严谨：The conclusions are overstated。

For example, the study did not showif the side effects from initial copper burst can be avoid with the polymer formulation.5、对hypothesis的清晰界定：A hypothesis needs to be presented。

Anatomical entity recognition with a hierarchical framework augmented by external resources PLOS ONEThank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit, but is not suitable for publication as it currently stands. Therefore, my decision is "Major Revision."We invite you to submit a revised version of the manuscript that addresses all of the concerns raised by the two reviewers. It is critical that you specifically address the following issues: 1) Provide more details on your methodology and data sources (possibly with examples), so that the reviewers can better evaluate the summary results provided in the tables; 2) Describe precisely what will be publicly available; 3) Thoroughly edit your revised manuscript before submission. Please note that PLoS ONE does not provide copy editing.We encourage you to submit your revision within forty-five days of the date of this decision.When your files are ready, please submit your revision by logging on to / and following the Submissions Needing Revision link. Do not submit a revised manuscript as a new submission. Before uploading, you should proofread your manuscript very closely for mistakes and grammatical errors. Should your manuscript be accepted for publication, you may not have another chance to make corrections as we do not offer pre-publication proofs.If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter.In addition, when submitting your revision please include the following items:∙ A rebuttal letter that responds to each point brought up by the academic editor and reviewer(s). This letter should be uploaded asa 'Response to Reviewers' file.∙ A clean revised manuscript as your 'Manuscript' file.∙ A marked-up copy of the changes made from the previous article file as a 'Revised Manuscript with Track Changes' file. This can be done using 'track changes' in programs such as MS Word and/orhighlighting any changes in the new document.For more information on how to upload your revised submission, see our video:/everyone/2011/05/10/how-to-submit-your-revised-manuscript/If you choose not to submit a revision, please notify us.Yours sincerely,Ramin Homayouni, Ph.D.Academic EditorPLOS ONEJournal requirements:When submitting your revision, we need you to address these additional requirements:1. We note that you have stated that you will provide repository information for your data at acceptance. Should your manuscript be accepted for publication, we will hold your manuscript until you get in touch with us with the accession numbers or DOIs necessary to access your data. If you wish to make changes to your data availability statement, please describe these changes in your cover letter and we will make them on your behalf.Reviewers' comments:Reviewer's Responses to QuestionsComments to the Author1. Is the manuscript technically sound, and do the data support the conclusions?The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.Reviewer #1: PartlyReviewer #2: Yes2. Has the statistical analysis been performed appropriately and rigorously?Reviewer #1: NoReviewer #2: Yes3. Does the manuscript adhere to the PLOS Data Policy?Authors must follow the PLOS Data policy, which requires authors to make all data underlying the findings described in their manuscript fully available without restriction. Please refer to the author’s Data Availability Statement in the manuscript. All data and related metadata must be deposited in an appropriate public repository, unless already provided as part of the submitted article or supporting information. If there are restrictions on the ability of authors to publicly share data—e.g. privacy or use of data from a third party— these reasons must be specified.Reviewer #1: YesReviewer #2: No4. Is the manuscript presented in an intelligible fashion and written in standard English?PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.Reviewer #1: NoReviewer #2: Yes5. Review Comments to the AuthorPlease use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)Reviewer #1: This paper presents an interesting hierarchical framework to recognize anatomical entities, which is important in healthcare domain. Authors also bring the importance and the challenges of this task. To the best of my knowledge, I summarize my comments and suggestions as follows:1) Features for the sequence labeling problems under CRF are comprehensive and acceptable. Authors include baseline natural language features, semantic features from external knowledge about Wikipedia and WordNet, co-reference, and dictionary matching.2) Authors conducted relatively comprehensive experiments to show the contribution of each individual features and combination of features to the overall precision and recall.3) Problem introduction and annotation are good too.However, some major points need to be fixed:1) The writing of this paper is really poor. All table references are not correct, grammar errors can be seen almost every paragraph. It is very very difficult to read. It took me hundreds of hours to understand what authors try to deliver. Let me just show examples based on the abstract:a) The first sentence is not a complete sentence. "To develop....in medical records."b) "They infer relevant anatomical...in the record but also by other diverse..." ==> "They infer relevant anatomical entities based on both explicit anatomical expressions in the record and other diverse... "c) "The hierarchical framework was demonstrated..." ==> "The hierarchical framework was demonstrated...in F1 comparing to ???"many others in the paper!!!!!2) For the annotation, authors used A3 to check (A1, A2), then obtain the coefficient. Why not A3->(A1, A2), A1->(A2, A3), and A2->(A1, A3), then obtain the average coefficient? What if there is a annotation conflict, meaning that all 3 annotators do not agree? In addition, authors claim that their golden standard is not perfect, then why you still use them to do evaluations?3) From the experimental results, CF seems to be the smallest contribution to the precision in table 5 and table 8, then why adding CF gets a lot increase in table 6 and 9? I don't believe this result. Can you give some explanations.In addition, some suggestions,It would be great if the paper gives some formal definition of each concept and shows some real or toy examples in figure. They can help readers to catch the point.Reviewer #2: The manuscript by Yan Xu et al. describes the construction of an anatomical entity recognition framework based on a machine learning algorithm. This framework can recognize not only explicit expressions of anatomical entities, but also implicit expressions such as diseases, clinical treatments, and clinical tests. The authors insisted that the recognition of the implicit expressions was important because the implicit expressions are abundant in clinical records and it is from these implicit expressions that medical experts can infer the anatomical entities described in the documents.The framework consists of three layers of entity recognizers, all of which are based on conditional random field (CRF) models. The first layer is the multi-class CRF recognizer developed for the 2009 and 2010 I2B2 challenge; this layer recognizes entities of three semantic classes: diseases, clinical treatments, and clinical tests. The other two recognizer layers are developed in this study. One (the second layer) is for explicit anatomical expression and the other (the third layer) is for implicit expression.For use in the training and testing of the CRF models, the authors carefully made an annotated corpus of 300 clinical records (i.e., the discharge summaries in this study). The resulting annotations include 16690 explicit anatomical entity tokens and 5564 implicit anatomical entity tokens.The authors used the following features for the construction of the CRF models and considered the relative impact on the recognition performance using precision, recall, and F-score: baseline features (a standard set of useful features for general named entity recognition tasks), ontological features DF1 and DF2 (based on some of the representative anatomical ontologies: UMLS, MeSH, RadLex, and BodyParts3D), coreference features, and world knowledge features WF1, WF2, WF3, and HF, which is based on the dictionary constructed from the terms in Wikipedia and WordNet,whose definition sentences contain explicit anatomical entities, for the purpose of extracting implicit anatomical entities; HF is referred to as a hierarchical feature.This study is original and addresses an important task in processing medical documents in general. Their analytical approach seems to be sound in the sense of ordinal research on natural language processing. Therefore, this manuscript seems to warrant publication in PLOS ONE.The main criticism I have is the lack of consideration of concrete instances of anatomical dictionaries, clinical record corpuses, annotations, and experiment results. The authors only provided several numerical tables of the precision, recall, and F-score. All the main conclusions were drawn from observation of these numerical tables. Although I know that this style is common in NLP research papers, I believe that without an investigation of concrete instances, readers cannot evaluate the relative impact of the many factors that will affect the final performance.With only a little thought, one can list up many factors that affect the final results: data sources selection for the construction of the anatomical dictionaries, relative contribution of the (four) data sources on the performance, whether there exists some particular anatomical term in the four dictionaries that has a significant effect on the performance, the total size of anatomical dictionaries, semantic type of terms included in the anatomical dictionaries, type of clinical records, total number of clinical records and sentences which are annotated by the experts, target semantic types, the choices of machine learning algorithms, and the selection of the features for the CRF models, as well as many other factors. However, observation of the series of numerical tables yields only limited information about the impact of the factors and what entities can/cannot be recognized under the proposed framework.Therefore, at very least, the authors should provide a part of the list of 16690 ―explicit anatomical entity tokens‖ and 5564 ―implicit anatomical entity tokens‖ with their numbers of occurrences in the corpus, because these define the problem that this manuscript is addressing.In addition, the authors should discuss what terms in the anatomical dictionary match the annotated tokens and/or the results of the Begin/Inside/Outside (BIO) calling by the CRF model. Then some explanation of the relative impact of the framework components should be provided based on the concrete instances of matching results.A second criticism concerns the reproducibility of this study. Although the authors wrote at the end of the abstract section, ―The resources constructed for this research will be made publicly available.‖ since the resources needed for the reproduction of this study are not provided at this time, I could not evaluate whether the results can be reproduced using the resources that the authors say will be eventually provided. I know that the authors have made a great contribution to the NLP research field, not only by introducing novel concepts, but also by providing many useful resources, including software and annotated corpuses, and so I believe that the resources that will be available to the public will be quite useful for NLP researchers, but I believe that it is quite important to meet the reproducibility criteria stated in the publication criteria of PLOS ONE(―described in sufficient detail for another researcher to reproduce the experiments described‖), and in order to meet these criteria, I expect that the authors will need to write additional paragraphs describing in sufficient detail how to reproduce the result tables. I believe that the results have been largely affected by the content of the dictionaries and annotated corpuses constructed by the authors, and therefore, without these resources, it will be quite difficult for other researchers to reproduce exactly the results described in the tables.Minor pointsPage 8, lines 7–10I do not understand the meaning of the numbers described in Table 4.What is the denominator of ―Coverage of explicit named entity‖? Total number of annotated tokens in the corpus? Or number of unique tokens annotated? In typical cases, rather simple anatomical terms such as ―brain‖, ―liver‖, and ―blood‖ frequently appear in the corpus, and of course these are matched readily to the anatomical dictionaries.Page 12, lines 7–13.The table numbering in the main text is not consistent with the actual table numbers. (Table 4, ..., Table 9 in the main text should be Table 5, …, Table 10.)Page 14, lines 3–5Near the top of the DISCUSSION section, the author wrote: ―While the features based on the dictionary of anatomical entity expressions greatly improved the performance on explicit anatomical entities, they do not enhance the performance on explicit anatomical entities.‖ But the second occurrence of the word ―explicit‖ should be ―implicit‖.6. If you would like your identity to be revealed to the authors, please include your name here (optional).Your name and review will not be published with the manuscript. Reviewer #1: (No Response)Reviewer #2: (No Response)[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files to be viewed.]。

C r i t i c a l-r e v i e w-o f-W h y-I-a m-n o t-a-p r o f e s s o r-o r-t h e-D e c l i n e-a n d-F a l l-o f-B r i t i s h-U n i v e r s i t yCourse: Advanced English WritingInstructor: Professor Guo FenrongName:吴梓涵Student Number: 2014013585Review of “Why I Am Not a Proffessor or The decline and Fall of the British University”IntroductionUniversity education has been expanded widely. And more and more students get a opportunity to complete higher education. Without many benefits, there comes up with many problems such as a lower entrance standard, poor teaching quality and less quality degree.These kinds of problem have arouse worries among some experts. Dr. Mark Tarver, a professor of computer science in UK, in his article "Why I Am Not a Proffessor or The Decline and Fall of the British University", expresses his opinions over British university education. He cites his own story to points out the decline and fall of British university education under egalitarianism driven by government. From his writing, Dr. Mark Tarver doesn't mentioned the merits but present us some existed problems over university education which really have the universality among universities all over the world.SummaryDr. Mark Tarver states his own story of quoting job as a tenured lecturer and says his story is “also the story of decline and fall of British university and corruptionof the academic ideal”. Dr. Mark Tarver points out “universities are extraordinary”because of their poor “foundation blocks” medievalism left. And Dr. Mark Tarver takes his experience as a lecturer in the period of “expansion of university system” , which is in order to argue that the decline and fall begin under the egalitarianism driven by government. He believes that the expansion is noble but it brings enviousness among lecturers, and government simply choose to “water down the education system to a lower standard” rather than making efforts to “improve the educational qualities”. According to Dr. Mark Tarver, a few years later, problems of this system appear. In case of not failing students, there are two ways: “scaling” the marks and ignoring plagiarism, which result students' lower “level of attainment”. Dr. Mark Tarver illustrates two criterions of assessment: “Teaching Quality Assessment”and “Research”, which are useless and don't really work for improving educational qualities. And toward egalitarianism, he expresses his worries such as staff crisis, lower teaching quality and debt and degree inflation. He concludes that new university education systems have many hidden problems.Arguments and evaluationIn his article, Dr. Mark Tarver doesn't state the merits of university education under egalitarianism. But coins always have two sides. Dr. Mark Tarver only illustrates the problems, and readers are very likely to deny the university education. Actually university education system does have merits in many aspects. For instance, it provides valuable opportunities for those low-born students to make a better futurefor themselves. It is no doubt that egalitarianism does help in some ways. Moreover, widening access to university generally improves citizens' educational level.However, those negative points that Dr. Mark Tarver puts forward are more thought-provoking. First, government choose to " widen access to university", then they choose an easier but careless way: Simply “watering down the educational system to a lower standard” attracts more student to university. However, we know that university education is superior which provides strong backup for the needs of elites. But elites are just a small part in our society. The lower standard hurts teaching quality which is crucial to foster elites.Under the new system, Dr. Mark Tarver talks about the criterion of assessment. The ostensible aims are sounding noble but the results are not what are expected. What lectures do are mostly about completing teaching tasks, winning bonus and getting promotion. No one focus on real academy and true scholars and proffessors are less than before. These existed phenomenons are normal but no one talks about them straightly. Dr. Mark Tarver writes them down to awaken readers to current situation of university education.Conclusion:As a university professor, Dr. Mark Tarver analyses weak spots of British university education based on his own experience, although he doesn't list good parts. But his opinions are truly stunning and giving public a warning "the decline and fall of British university". So government and university should be altered and reconsider the existing system as soon as possible, and then take measures.。

英文论文审稿意见汇总1、目标和结果不清晰。

It is noted that your manuscript needs careful editing by someone with expertise in technical English editing paying particular attention to English grammar, spelling, and sentence structure so that the goals and results of the study are clear to the reader.2、未解释研究方法或解释不充分。

◆ In general, there is a lack of explanation of replicates and statistical methods used in the study.◆ Furthermore, an explanation of why the authors did these various experimentsshould be provided.3、对于研究设计的rationale:Also, there are few explanations of the rationale for the study design.4、夸张地陈述结论/夸大成果/不严谨：The conclusions are overstated. For example, the study did not showif the side effects from initial copper burst can be avoid with the polymer formulation.5、对hypothesis的清晰界定：A hypothesis needs to be presented。

Dr. XU JianheThe State Key Laboratory of Bioreactor EngineeringEast China University of Science and Technology, Shanghai 200237, ChinaTel: +86-21-64252498; Fax: +86-21-64252250Elsevier 投稿各种状态总结1. Submitted to Journal当上传结束后，显示的状态是Submitted to Journal，这个状态是自然形成的无需处理。

2. With editor如果在投稿的时候没有要求选择编辑，就先到主编那，主编会分派给别的编辑。

这当中就会有另两个状态：3. Editor assigned4. Editor Declined Invitation如果编辑接手处理了就会邀请审稿人了。

5. Reviewer(s) invited如果审稿人接受那就会是以下状态：6. Under review这应该是一个漫长的等待。

当然前面各步骤也可能很慢的，要看编辑的处理情况。

如果被邀请审稿人不想审，就会decline，编辑会重新邀请别的审稿人。

7. required review completed 审稿结束，等编辑处理。

8. Decision in Process到了这一步就快要有结果了，编辑开始考虑是给修改还是直接拒，当然也有可能直接接受的，但可能性很小，呵呵。

9. Minor revision/Major revision这个时候可以稍微庆祝一下了，问题不大了，因为有修改就有可能。

具体怎么改就不多说了，谦虚谨慎是不可少的。

10. Revision Submitted to Journal又开始了一个循环。

11. Accepted如果不要再审，只是小修改，编辑看后会马上显示这个状态，但如果要再审也会有上面的部分状态。

一步会比较快，但也有慢的。

Effective Oral Treatment of Unconjugated Hyperbilirubinemia in Gunn Rats Anja M.Hafkamp,1Rick Havinga,1Maarten Sinaasappel,2and Henkjan J.Verkade1We sought to develop an oral treatment for unconjugated hyperbilirubinemia.In the Gunn rat model of unconjugated hyperbilirubinemia,dietary supplementation with the lipase inhibitor orlistat(Orl)or with calcium phosphate(CaP)decreases plasma unconjugated bilirubin(UCB)levels.We determined whether Orl,CaP,or their combination is superior to phototherapy,the conventional treatment,and whether the effects of Orl and CaP are influenced by dietary fat content.Gunn rats were treated with Orl(200mg/kg chow),CaP (20g/kg chow),Orl؉CaP,or continuous phototherapy(19␮W/cm2/nm)during a low-fat (LF)diet(13energy%)or high-fat(HF)diet(35energy%).Plasma UCB and fecal fat excretion were measured before,during,and/or at the end of treatment.Orl treatment for2 weeks(HF diet)reduced plasma UCB concentrations similar to phototherapy(؊34%and ؊28%,respectively);the combination of both was more effective than either treatment alone (؊48%;P<.001).After3weeks of a HF diet,plasma UCB was46%lower compared with the LF diet(P<.001).Plasma UCB concentrations were negatively correlated with fecal fatexcretion(r؍؊0.96;P<.001).Irrespective of dietary fat content,3weeks of combined treatment(Orl؉CaP)decreased plasma UCB by approximately50%(P<.01)and was more effective than phototherapy(P<.05)at the intensity provided.In conclusion,plasma UCB concentrations in Gunn rats are negatively related to fecal fat excretion and dietary fat content.Orlistat is equally effective as phototherapy for the treatment of unconjugated hyperbilirubinemia in Gunn rats,and combined oral treatment with Orl؉CaP is more effective than phototherapy.The present results support the feasibility of an efficient oral treatment of unconjugated hyperbilirubinemia.(H EPATOLOGY2005;41:526-534.)C rigler-Najjar disease is characterized by a perma-nent unconjugated hyperbilirubinemia due toabsent(type I)or decreased(type II)activity of the hepatic enzyme bilirubin-UDP-glucuronosyltrans-ferase.1Severe unconjugated hyperbilirubinemia can lead to bilirubin encephalopathy,kernicterus,and death.2,3 Phenobarbital treatment can usually control unconju-gated hyperbilirubinemia in Crigler-Najjar type II pa-tients via residual enzyme induction.4,5Phenobarbital is not effective in Crigler-Najjar disease type I,how-ever,so these patients have to undergo daily photo-therapy,which has considerable disadvantages. Phototherapy becomes less effective with age,probably due to skin alterations,6,7a decrease in the surface area to body mass ratio,8and a diminishing compliance to the intensive phototherapy regimen,which may take up to12hours per day.6To prevent irreversible brain damage due to kernicterus,many patients with Crigler-Najjar disease type I undergo liver transplantation in their second decade.9,10We sought to develop an alternative treatment for unconjugated hyperbilirubinemia based on oral ad-ministration and with equal or higher efficacy than phototherapy.The oral treatment strategy used in the present study is based on reducing the reabsorption of UCB11,12through intestinal capture.Reabsorption of UCB can contribute substantially to the pathogenesisAbbreviations:Orl,orlistat;CaP,calcium phosphate;UCB,unconjugated bili-rubin;LF,low-fat;HF,high-fat;HPLC,high-performance liquid chromatogra-phy.From the1Division of Pediatric Gastroenterology,Department of Pediatrics, Center for Liver,Digestive,and Metabolic Diseases,University Medical Center Groningen,Groningen,The Netherlands;and2Department of Pediatrics,Erasmus Medical Center,Sophia Children’s Hospital,University Medical Center,Rotter-dam,The Netherlands.Received October11,2004;accepted December7,2004.Grant support was received from the Najjar Fonds.H.J.V.is a Fellow of the Royal Netherlands Academy of Arts and Sciences.Address reprint requests to:Anja M.Hafkamp,M.D.,Department of Pediatrics, Center for Liver,Digestive,and Metabolic Diseases,CMC-IV,Room Y2117,Uni-versity Medical Center Groningen,Hanzeplein1,P.O.Box30.001,9700RB Groningen,The Netherlands.E-mail: a.m.hafkamp@med.rug.nl;fax:(31) 50-3611746.Copyright©2005by the American Association for the Study of Liver Diseases. Published online in Wiley InterScience().DOI10.1002/hep.20589Conflict of interest:Nothing to report.526of unconjugated hyperbilirubinemia(e.g.,in neonatal jaundice).Even under conditions of diminished glucu-ronidation,bilirubin can enter the intestinal lumen via biliary secretion of low amounts of UCB.13In addition, UCB can diffuse from the blood,across the intestinal mucosa,into the intestinal lumen.14,15Particularly when plasma UCB levels are high,as in Crigler-Najjar disease,large amounts of UCB can enter the intestinal lumen via extrabiliary(transintestinal)excretion.14,15 In humans,under certain conditions up to25%of the total amount of bilirubin that enters the intestine might be reabsorbed as UCB.16Amorphous calcium phosphate(CaP)was shown to bind to UCB in vitro,17 and intestinal capture of UCB by CaP decreased plasma UCB concentrations in Gunn rats,18a well-established animal model for Crigler-Najjar disease type I.19,20In Crigler-Najjar patients,however,the ef-fects of CaP treatment were less pronounced.7Other capturing agents like agar,21activated charcoal,22and cholestyramine23are no longer used for the treatment of unconjugated hyperbilirubinemia because of incon-sistent clinical results and side effects.24-26More re-cently,zinc salts were shown to decrease plasma bilirubin levels in patients with Gilbert syndrome,but serum zinc levels increased simultaneously.27Other pharmacological interventions for treatment of neona-tal jaundice and Crigler-Najjar disease include metal-loporphyrins,which inhibit heme degradation,and modified bilirubin oxidase;however,concerns about safety and efficacy have limited their widespread use.28,29Recently,we demonstrated that dietary supplemen-tation with the lipase inhibitor orlistat(Orl)decreased plasma UCB concentrations in Gunn rats,parallel to an increase in fecal fat excretion.30The decrease in plasma UCB concentration was strongly related to the amount of fat excreted via the feces,supporting the concept of intestinal capture of UCB.This observation raised the question of whether dietary fat content in-fluences plasma UCB concentration.It was also un-known whether Orl treatment or combined treatment with Orl and CaP is similarly or more effective in re-ducing plasma UCB levels than the conventional treat-ment,phototherapy.In the present study,we addressed these issues byfirst comparing the efficacy of Orl with that of phototherapy in Gunn rats.Second, we studied the influence of dietary fat content on plasma UCB concentration in control Gunn rats and in Gunn rats treated with Orl,CaP,or with both.Finally, combined treatment with Orl and CaP was compared with continuous phototherapy in Gunn rats.Materials and MethodsMaterialsAnimals.Homozygous male Gunn rats(RHA/jj) weighing210to270g were obtained from the breeding colony of the Academic Medical Center(Amsterdam, The Netherlands).All animals were housed in an environ-mentally controlled facility with a12/12-hour light/dark cycle,were fed ad libitum,and had free access to water. Animals were housed individually or,in the case of pho-totherapy treatment,per experimental group.Experimen-tal protocols were approved by the Ethics Committee for Animal Experiments(Faculty of Medical Sciences,Uni-versity of Groningen,The Netherlands). Phototherapy Lamps.Two phototherapy devices were developed according to the prototype designed by Ostrow.31Each device consisted of two blue photother-apy lamps(Philips,TL20W/03T)suspended in a reflec-tive canopy20cm above the bottom of the cage. Phototherapy(19␮W/cm2/nm from380-480nm,as measured by an Elvos LM-1010Lux meter at a distance of 20cm)was administered continuously to Gunn rats that were shaved every7to10days on their backs andflanks. The light intensity at the level of each rat’s back was therefore higher than19␮W/cm2/nm. Chemicals.Xanthobilirubin-methyl ester was a gen-erous gift from Dr.J.Fevery(Leuven,Belgium).Hepta-decanoic acid(C17:0)was purchased from Sigma Chemical Co.(St.Louis,MO).Orl(Xenical)was ob-tained from Roche Nederland BV(Woerden,The Neth-erlands).Orl is a selective inhibitor of gastrointestinal lipases that dose-dependently inhibits hydrolysis of di-etary triglycerides.Diets.Diets were custom synthesized by Hope Farms BV(Woerden,The Netherlands).The HF control diet (code4141.07)was a semisynthetic,purified diet con-taining35energy%fat and16.2wt%long-chain fatty acids(fatty acid composition[in mol%]:C8-C12:0,1.7; C14:0,1.3;C16:0,11.9;C16:1,1.2;C18:0,1.1;C18:1, 21.6;C18:2,53.3;C18:3,8.0).The LF control diet(code 4063.02)was a semisynthetic,purified diet containing13 energy%fat and5.2wt%long-chain fatty acids(fatty acid composition[in mol%]:C8-C12:0,6.9;C14:0,0.7; C16:0,30.0;C18:0,3.7;C18:1,29.9;C18:2,28.8).Sup-plemented diets were identical to control diets except for supplementation with Orl(200mg/kg chow)and/or CaP (20g/kg chow).The codes of these diets were:HFϩOrl, 4141.13;HFϩCaP,4141.15;HFϩOrlϩCaP, 4141.16;and LFϩCaP,4063.04.For LF diet studies, Orl(200mg/kg chow)was mixed into diets4063.02and 4063.04.Similar to previous studies,Gunn rats in all experiments were fed the control diets for a run-in periodHEPATOLOGY,Vol.41,No.3,2005HAFKAMP ET AL.527of at least4weeks.30All diets were semisynthetic and purified for comparability.The composition of the LF control diet was comparable with standard rat chow (RMH-B;Hope Farms BV,Woerden,The Netherlands). The HF control diet was chosen to contain approximately 35energy%fat,thus resembling human dietary fat intake in an industrialized country.Study DesignEffects of Orl and/or Phototherapy on Plasma UCB Concentrations.Three groups of Gunn rats(nϭ4-5per group)on a HF diet were randomly assigned to the Orl-supplemented diet,continuous phototherapy,or to the combination of Orl-supplemented diet and continuous phototherapy for2weeks.Before starting treatment and after1and2weeks of treatment,blood samples were obtained by tail bleeding under isoflurane anesthesia for determination of plasma UCB concentrations.After2 weeks of treatment,the enterohepatic circulation was in-terrupted through surgical cannulation of the common bile duct,32after which bile was collected for20minutes under light-protected conditions.Bileflow was deter-mined gravimetrically,assuming a density of1g/mL.Af-ter bile collection,a large blood sample was obtained via vena cava inferior puncture.Effects of Orl and/or CaP on Plasma UCB Concen-trations and Fecal Fat Excretion During LF or HF Diet.After a run-in period of7weeks on a LF diet,four groups of Gunn rats(nϭ4-5per group)were fed a LF diet for3weeks,followed by a HF diet for3weeks.Both diets were either not supplemented(controls),or supple-mented with Orl,CaP,or both.Blood samples were ob-tained every1.5weeks via tail bleeding under isoflurane anesthesia.Feces were collected per animal after2.5and 5.5weeks during72hours to determine fecal fat and calcium excretion.Plasma UCB,fecal fat,and fecal calcium concentrations were determined using high-performance liquid chromatography(HPLC),gas chro-matography,andflame spectrometry,respectively(see Analytical Methods).Effects of Phototherapy Compared With Combined Oral Treatment With Orl and CaP.We compared the efficacy of continuous phototherapy with the efficacy of combined oral treatment with Orl and CaP.Three groups of Gunn rats(nϭ5per group)were fed a LF diet for3 weeks,followed by a HF diet for3weeks.One group was continuously treated with phototherapy during these6 weeks.The diets of another group were supplemented with Orl and CaP.Blood samples were obtained every1.5 weeks via tail bleeding under isoflurane anesthesia.Analytical MethodsPlasma.For UCB measurements,blood samples were protected from light and processed immediately.Plasma was submitted to alkaline methanolysis and chloroform extraction.Theoretically,it is not necessary to use alkaline methanolysis for the determination of plasma UCB con-centrations in Gunn rats.Nevertheless,this standard method was chosen because it is a validated HPLC method for clinical samples of patients with an undeter-mined type of hyperbilirubinemia and because it has been used in previous studies.14,30After evaporation under ni-trogen,the residue was redissolved in chloroform and analyzed using reversed-phase HPLC,as previously de-scribed,33,34using a Li-Chrosorb51605-␮m column (VDS Optilab,Montabaur,Germany),a detection wave-length of430nm,and xanthobilirubin-methyl ester as the internal standard.Plasma hemoglobin and hematocrit were determined on a Sysmex XE-2100hematology analyzer(Goffin Meyvis,Etten-Leur,The Netherlands). Aspartate aminotransferase activity,alanine aminotrans-ferase activity,triglycerides and cholesterol were deter-mined with routine clinical chemical procedures on a Mega analyzer(Merck,Darmstadt,Germany).Bile.All analytical procedures were performed in dim light.UCB was extracted from bile according to the method described above for UCB in plasma.Bile salt concentration was determined by the3␣-hydroxysterol dehydrogenase method.35Cholesterol and phospholipids were measured after lipid extraction36according to the methods of Gamble et al.37and Bo¨tcher et al.,38respec-tively.Feces.Feces were freeze dried for at least2days and mechanically homogenized.For determination of fatty acids,aliquots of freeze-dried feces were extracted,hydro-lyzed,and methylated according to the method of Lepage and Roy,39with the modification that methanol/hexane was used for methylation and extraction.Resulting fatty acid methyl esters were determined using gas chromatog-raphy(HP Ultra-1-column;Hewlett-Packard,Palo Alto, CA),and fatty acid contents were calculated in molar amounts,using C17:0as an internal standard.Determi-nation of calcium concentration was performed in dupli-cate in plastic tubes as follows.Two aliquots of approximately10mg freeze-dried feces were taken from homogenized feces and weighed.One milliliter of69% HNO3was added and the mixture was heated at95°C for 5minutes,after which5mL of0.1%lanthanum chloride (LaCl3)was added.After mixing,the samples were cen-trifuged for10minutes at1500g.The supernatant was diluted20times with0.1%LaCl3andfiltered.Calcium concentration was determined viaflame spectrometry528HAFKAMP ET AL.HEPATOLOGY,March2005(Atomic Absorption Spectrometer 3300,PerkinElmer BV,The Netherlands).Statistical AnalysesAnalyses were performed using SPSS version 11.0for Windows (SPSS Inc.,Chicago,IL).All results are ex-pressed as the mean ϮSD.Based on a normal distribu-tion of plasma bilirubin levels in large groups of Gunn rats in previous studies,30parametric tests were used for statis-tical analysis.The Student t test was used to test between two treatment groups.For comparison of more than two treatment groups,ANOVA with post hoc Bonferroni cor-rection was performed.Repeated-measures ANOVA was used for analysis of within-group differences.Linear re-gression analysis was performed to compare treatment efficacies when LF and HF diets were used consecutively,and to analyze the relationship between fecal fat excretion and plasma UCB concentration.The level of significance was set at a P value of less than .05(two-tailed).ResultsEffects of Orl and/or Phototherapy on Plasma UCB Concentrations.Figure 1shows the effects of Orl,con-tinuous phototherapy,and combined treatment on plasma UCB levels in Gunn rats fed a HF diet.Orl treat-ment decreased plasma UCB concentrations by 34%after 2weeks of treatment (P Ͻ.01),similar to continuous phototherapy (Ϫ28%;P Ͻ.01).Combined treatment with Orl and phototherapy induced a more profound decrease in plasma UCB concentrations than either Orl or phototherapy alone (Ϫ48%;P Ͻ.001).Compared with pretreatment values,1week of treatment decreasedplasma UCB concentrations by 16%(Orl,P ϭ.06),15%(phototherapy,P Ͻ.01),and 43%(Orl ϩphototherapy,P Ͻ.01),indicating that combined treatment decreased plasma UCB concentrations more rapidly.The three groups did not significantly differ in growth rates during the experiment,which is consistent with our previous experience that Orl treatment does not affect the net amount of energy uptake or growth rate in Gunn rats.30Table 1shows that relevant hematological and liver func-tion parameters did not differ among the three treatment groups.Also,bile flow rates and biliary secretion rates of bile salts,cholesterol,and phospholipids were similar after 2weeks of treatment with Orl,phototherapy,or their combination (Table 2).The biliary excretion rate of UCB was higher in the two groups that received phototherapy compared with the Orl-treated group (phototherapy,ϩ280%,P Ͻ.01;phototherapy ϩOrl,ϩ180%,P Ͻ.01).Effect of Dietary Fat Content on Plasma UCB Concentrations and Fecal Fat Excretion.Figure 2shows that dietary fat content has a profound effect on plasma UCB concentration in Gunn rats.Changing from a LF to a HF diet decreased plasma UCB concentrations by 46%after 3weeks (P Ͻ.01).Fecal fat excretion in-creased from 0.07Ϯ0.03mmol/24hours on a LF diet to 0.74Ϯ0.12mmol/24hours on a HF diet.Consistent with our previous observation that an increased fecal fat excretion is associated with an increased fecal UCB excre-tion,30plasma UCB concentrations were negatively cor-related with fecal fat excretion (r ϭϪ0.96;P Ͻ.001).Effects of Orl and/or CaP on Plasma UCB Concen-trations,Fecal Fat Excretion,and Fecal Calcium Ex-cretion During a LF or HF Diet.Figure 3shows the efficacies of Orl and/or CaP treatment during a LF and a HF diet.During a LF diet,treatment with either Orl or CaP decreased plasma UCB concentrations compared with controls by 30%(P Ͻ.05)and 40%(P Ͻ.001),Table 1.Plasma Parameters After 2Weeks of TreatmentOrlPhototherapyOrl ؉PhototherapyHemoglobin (mmol/L)8.6Ϯ0.38.4Ϯ0.38.6Ϯ0.4Hematocrit (V/V)0.41Ϯ0.010.40Ϯ0.010.41Ϯ0.02Aspartateaminotransferase (U/L)21.0Ϯ4.723.6Ϯ2.824.4Ϯ9.4Alanineaminotransferase (U/L)63.0Ϯ12.257.6Ϯ12.148.2Ϯ11.7Cholesterol (mmol/L) 1.9Ϯ0.2 2.1Ϯ0.1 1.9Ϯ0.2Triglycerides(mmol/L)2.2Ϯ0.81.9Ϯ0.61.7Ϯ0.3NOTE.Gunn rats were fed a HF diet for 4weeks followed by treatment for 2weeks with dietary Orl supplementation,continuous phototherapy,or Orl ϩcontinuous phototherapy.Blood samples were taken after 2weeks of treatment.Data represent the mean ϮSD (n ϭ4–5animals pergroup).Fig.1.Effects of Orl,continuous phototherapy,and combined treat-ment (Orl ϩPT)on plasma UCB concentrations in Gunn rats.Animals (n ϭ4-5per group)were fed a HF diet for 4weeks followed by treatment for 2weeks with dietary Orl supplementation,phototherapy,or Orl ϩphototherapy.Blood samples were taken before treatment (white bars )and after 1(striped bars )and 2(black bars )weeks of treatment.Plasma UCB values at T 0(␮mol/L):Orl,159Ϯ16;phototherapy,135Ϯ7;Orl ϩphototherapy,145Ϯ14.Data represent the mean ϮSD.*P Ͻ.01;**P Ͻ.001;†P ϭ.06compared with before treatment;#P Ͻ.01.UCB,unconjugated bilirubin;PT,phototherapy.HEPATOLOGY,Vol.41,No.3,2005HAFKAMP ET AL.529respectively.During a HF diet,plasma UCB concentra-tions in Orl-treated animals were28%lower compared with untreated controls(PϽ.01),whereas CaP treatment did not significantly decrease plasma UCB levels(Ϫ21%, P value not significant).Combined treatment with Orl and CaP decreased plasma UCB concentrations by54% on a LF diet(PϽ.01)and by44%on a HF diet(PϽ.01).During both a LF and a HF diet,combined enteral treatment was more effective in reducing plasma UCB concentrations than CaP alone(PϽ.05).When com-pared with Orl,combined treatment was only more effec-tive during a LF diet(PϽ.05).Figure4shows the relationship between fecal fat excre-tion and plasma UCB concentration of individual Gunn rats from the different groups(controls,Orl,CaP,and OrlϩCaP)after3weeks of LF or HF diet.The two pa-rameters were negatively correlated(rϭϪ0.87;PϽ.001).When the relationship between fecal fat excretion and plasma UCB concentration was analyzed separately for controls and CaP-treated Gunn rats(Fig.5),it ap-peared that the amount of fat in the diet influenced the efficacy of CaP to decrease plasma UCB concentrations. The higher efficacy of CaP on a LF diet(UCBϪ40%) compared with a HF diet(UCBϪ21%)corresponded with a relatively larger increase in fecal fat excretion on a LF diet(ϩ199%)versus a HF diet(ϩ95%)upon CaP supplementation.Figure6shows that a positive correlation existed be-tween fecal calcium excretion and fecal fat excretion on a LF diet with or without calcium and/or Orl supplemen-tation(rϭ0.96;PϽ.001),as well as on a HF diet with or without supplementation(rϭ0.93;PϽ.001).Orl treatment alone increased fecal calcium excretion (mmol/24h)on a LF diet(LF:1.09Ϯ0.19;LFϩOrl: 1.54Ϯ0.28;PϽ.05)but not on a HF diet(HF:2.34Ϯ0.38;HFϩOrl:2.03Ϯ0.09;P value not significant) (data not shown).Effects of Phototherapy Compared With Combined Oral Treatment With Orl and CaP.We compared the efficacy of combined oral treatment with Orl and CaP with the efficacy of continuous phototherapy.Figure7 shows that phototherapy alone decreased plasma UCB concentrations by45%on a LF diet(PϽ.001)and by 29%on a HF diet(PϽ.001)compared with controls. On a LF diet(Ϫ54%;PϽ.05),as well as a HFdiet Fig.3.Effects of Orl,CaP,and their combination(OrlϩCaP)on plasma UCB concentrations in Gunn rats during(A)a LF diet and(B)a HF diet.Gunn rats(nϭ4-5per group)were fed a LF diet for3weeks followed by a HF diet for3weeks.Diets were either not supplemented (controls)or were supplemented with Orl,CaP,or both.Data after3and 6weeks of treatment are shown and represent the meanϮSD.(A) Plasma UCB values(␮mol/L):controls,248Ϯ31;Orl,173Ϯ26;CaP, 150Ϯ31;OrlϩCaP,114Ϯ14.(B)Plasma UCB values(␮mol/L): controls,135Ϯ10;Orl,97Ϯ6;CaP,106Ϯ8,OrlϩCaP,76Ϯ7. *PϽ.05;**PϽ.01;***PϽ.001compared with controls;#PϽ.05. UCB,unconjugated bilirubin;Orl,orlistat;CaP,calcium phosphate;NS, not significant.Table2.Bile Flow and Biliary Excretion Rate of UCB and Biliary Lipids After2Weeks of TreatmentOrl Phototherapy Orl؉Phototherapy Bileflow(␮L/min/100g BW) 3.19Ϯ0.49 3.39Ϯ1.08 3.73Ϯ0.83 Bilirubin(nmol/min/100g BW)0.09Ϯ0.010.34Ϯ0.12*0.25Ϯ0.08* Bile salts(nmol/min/100g BW)153.9Ϯ49.2159.5Ϯ105.6162.4Ϯ57.0 Cholesterol(nmol/min/100g BW)0.77Ϯ0.310.74Ϯ0.23 1.02Ϯ0.29 Phospholipids(nmol/min/100g BW)18.6Ϯ6.918.6Ϯ7.526.9Ϯ8.9NOTE.Gunn rats were fed a HF diet for4weeks followed by treatment for2weeks with dietary Orl supplementation,continuous phototherapy,or Orlϩcontinuous phototherapy.After2weeks,bile was collected during a20-minute period.Data represent the meanϮSD(nϭ4–5animals per group).Abbreviation:BW,body weight.*PϽ.01,compared withOrl.Fig.2.(A)Effect of dietary fat content on plasma UCB concentrationsin Gunn rats and(B)relationship between fecal fat excretion and plasmaUCB concentrations.Gunn rats(nϭ5)were fed a LF diet for3weeksfollowed by a HF diet for3weeks.Data after3and6weeks of diet areshown and represent the meanϮSD.*PϽ.01.Plasma UCB values(␮mol/L):LF diet,248Ϯ31;HF diet,135Ϯ10.Fecal fat excretion(72h)was determined after2.5and5.5weeks.Diamonds(ࡗ)representindividual animals(rϭϪ0.96;PϽ.001).UCB,unconjugated bilirubin.530HAFKAMP ET AL.HEPATOLOGY,March2005(Ϫ44%;P Ͻ.01),combined oral treatment with Orl and CaP was more effective in reducing plasma UCB concen-trations than continuous phototherapy.DiscussionWe sought to develop an efficient treatment for uncon-jugated hyperbilirubinemia based on oral administration and with equal or higher efficacy than phototherapy.Pre-viously,we reported that treatment with the lipase inhib-itor Orl decreased plasma UCB concentrations in Gunn rats,a well-established model for unconjugated hyperbil-irubinemia.In the current study,we show that Orl treat-ment is equally effective as continuous phototherapy inGunn rats,and that combined oral treatment with Orl and CaP is more effective than continuous phototherapy at the intensity of phototherapy provided.The dose of phototherapy used (19␮W/cm 2/nm)was comparable with doses used for (single)phototherapy in hyperbiliru-binemic human neonates.In the clinical setting,intensive (double-sided)phototherapy is occasionally used with doses above 30␮W/cm 2/nm.40Understandably,our re-sults can only refer to the use of phototherapy at the specific dose provided.As previously demonstrated,31phototherapy increased the amount of UCB secreted into bile.The observation that phototherapy enhanced the efficacy of Orl supports the proposed concept that Orl treatment reduces the reabsorption of UCB.Rather than by intestinal capture of UCB by unab-sorbed fat,Orl might theoretically exert its hypobiliru-binemic effect via other mechanisms,such asbyFig.4.Relationship between fecal fat excretion and plasma UCB concentrations in Gunn rats.Gunn rats (n ϭ4-5per group)were fed a LF diet for 3weeks followed by a HF diet for 3weeks.Diets were either not supplemented (controls)or were supplemented with Orl,CaP,or both.Feces were collected per animal after 2.5and 5.5weeks during a 72-hour period to determine fecal fat excretion.Diamonds (ࡗ)represent individual animals (r ϭϪ0.87;P Ͻ.001).UCB,unconjugatedbilirubin.Fig.5.Relationship between fecal fat excretion and plasma UCB concentrations in Gunn rats,analyzed separately for controls and CaP-treated animals during LF and HF diets (see Fig.4).UCB,unconjugated bilirubin;LF,low-fat;CaP,calcium phosphate;HF,high-fat.Fig.6.Relationship between fecal fat excretion and fecal calcium excretion in Gunn rats.Gunn rats (n ϭ4-5per group)were fed (A)a LF diet for 3weeks followed by (B)a HF diet for 3weeks.Diets either were not supplemented (controls)or were supplemented with CaP or CaP ϩOrl.Feces were collected per animal after 2.5and 5.5weeks during a 72-hour period to determine fecal fat excretion and fecal calcium excretion.Each symbol represents an individual animal.(A)LF diet:r ϭ0.96,P Ͻ.001.(B)HF diet:r ϭ0.93,P Ͻ.001.HEPATOLOGY,Vol.41,No.3,2005HAFKAMP ET AL.531influencing intestinal transit time,bile salt metabolism,or intestinal microflora.The effects of Orl on gastric empty-ing and intestinal transit time are equivocal.Guerciolini 41reported no significant effects of Orl on intestinal transit time or gastric emptying,whereas others have reported accelerated gastric emptying,particularly after consump-tion of a fatty meal.42,43In a previous study in Gunn rats,30we showed that the decrease in plasma UCB levels preceded the increase in fecal bilirubin excretion during Orl treatment.This observation does not support a sig-nificant role for an increased intestinal transit time to explain our present results.Orl treatment increases fecal fat excretion and might therefore increase fecal bile salt excretion.However,bile flow rates and biliary secretion rates of bile salts were similar after treatment with Orl,phototherapy,or their combination (present study)and were not different between controls and Orl-treated Gunn rats.30Similar biliary excretion rates of bile salts between controls and Orl-treated Gunn rats are not com-patible with major differences in the intestinal concentra-tion of bile salts.Vitek et al.44recently showed that the intestinal microflora can substantially affect the metabo-lism of bilirubin.Effects of Orl on the composition of the intestinal microflora or on intestinal bilirubin metaboliz-ing activity are not known.Previously,we found similar fecal UCB excretion rates in Orl-treated and control Gunn rats under steady-state conditions.30Fecal fat excretion was again negatively associated with plasma UCB concentration in Gunn rats,similar to our previous report.30The present data indicate that plasma UCB levels are almost twice as high in Gunn rats fed a LF diet compared with a HF diet.Gollan et al.45showed that a fat-free diet increased plasma bilirubin concentrations threefold in Gunn rats.They reported that dietary sup-plementation with a variety of fats largely reversed the increased hyperbilirubinemia,regardless of their fatty acid chain length or degree of saturation.The present results allow to put these observations into perspective.Plasma UCB concentration is strongly determined by the amount of fecal fat excretion,which in turn is determined strongly by dietary fat content.Therefore,it seems justi-fiable to conclude that,under conditions of absent biliru-bin conjugation,dietary fat content negatively determines plasma UCB concentration by affecting excretion of fecal fat and probably UCB.The present data do not confirm whether UCB actually associates with unabsorbed fat (e.g.,partially hydrolyzed triacylglycerol,fatty acids,phospholipids).In vitro experiments will be needed to characterize the exact mechanism.Orl treatment effectively reduced plasma UCB con-centrations during both a HF and LF diet.CaP treatment,however,was only significantly effective during a LF diet.Previously,van der Veere et al.showed that plasma UCB concentrations decreased by approximately 40%in Gunn rats on a LF diet,18similar to our current LF diet results.CaP treatment in Crigler-Najjar type I patients,however,decreased plasma UCB levels only by 18%.7In type II patients,CaP treatment was not effective,possibly be-cause these patients did not receive phototherapy,which enhances the biliary excretion of UCB.We hypothesize that dietary fat content could partly explain the lower efficacy of CaP treatment in Crigler-Najjar patients com-pared with Gunn rats.The human Western-type diet is a HF diet containing 35to 40energy%fat,compared with the LF diet (13energy%fat)of the Gunn rat in the study by van der Veere and colleagues.We used the identical LF diet in our studies.Furthermore,we have observed in Gunn rats that combined treatment with CaP and con-tinuous phototherapy for 3weeks decreases plasma UCB concentrations more effectively on a LF diet (Ϫ70%)than a HF diet (Ϫ39%)(Hafkamp and Verkade,unpub-lished data).An explanation for the low efficacy of CaP treatment during a HF diet (compared with a LF diet)could be that UCB capture (by fat)has reached a certain maximum,and therefore CaP cannot act properly as cap-turing agent.In our study,fecal fat excretion was positively associ-ated with fecal calcium excretion.Dietary supplementa-tion with CaP has been shown to increase fecal fat excretion in rats and humans,probably through the for-mation of calcium soaps.46,47We cannot exclude that part of the effect of Orl and of CaP is based on the formation of calcium–fatty acid soaps and subsequent capture of UCB by these soaps.The low efficacy of CaP treatment during a HF diet,however,suggests that other mecha-nisms must beinvolved.Fig.7.Efficacy of combined oral treatment with Orl and CaP com-pared with continuous phototherapy in Gunn rats.Gunn rats (n ϭ5per group)were fed (A)a LF diet for 3weeks followed by (B)a HF diet for 3weeks.Animals were either not treated (controls)or were treated with continuous phototherapy or Orl ϩCaP.Data after 3and 6weeks of treatment are shown and represent the mean ϮSD.(A)Plasma UCB values (␮mol/L):controls,248Ϯ31;phototherapy,137Ϯ14;Orl ϩCaP,114Ϯ14.(B)Plasma UCB values (␮mol/L):controls,135Ϯ10;phototherapy,96Ϯ9;Orl ϩCaP,76Ϯ7.*P Ͻ.001compared with controls;#P Ͻ.05;##P Ͻ.01.UCB,unconjugated bilirubin;PT,photo-therapy;Orl,orlistat;CaP,calcium phosphate.532HAFKAMP ET AL.HEPATOLOGY,March 2005。

Dr. Plopper’s Guide to Critical Reading of Primary Literature Overall tips: 总技巧1. Just because a scientific study has been published, this does not mean it is perfect. And the imperfections are not so minute that a non-expert cannot find them. Any student of science can, and indeed should, read science critically. This means you can read a paper by a Nobel laureate and find fault with it. It is in fact expected that, as a practicing scientist, you can criticize any science. The level of your critical analysis will differ with your experience level, but you should be able to criticize science even as a relatively inexperienced undergraduate.1、科学研究不能仅因为已发表，就认为它是完美的。

它们的不足也不是微小到只有专业人员才能发现。

任何从事科研的学生都能，而且确实应该能够，批判性地阅读科学文献。

这意味着你读一篇诺贝尔奖获得者的文章都能在其中发现不足。

它实际上期望作为科学工作者的你能对任何学科进行分析评论。

你分析评论的水平会因你的经验水平而有差异，但你应该至少能够象一名相对无经验的本科生来分析科学文献。