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Audit Dissertation Effectiveness …
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big four cpa resume Resume Body BIG 4 CPA VP FINANCE/SENIOR CONTROLLER. Big 4 CPA Accounting Professional with successful track record of public and private experience, primarily in the real estate investment and private equity sectors. Held key financial positions in high growth, fast paced environments. Extensive experience working with Board of Directors, lenders and auditors. Strong leadership, problem solving, team building and project management skills. Areas of expertise include: Budget Development and Management.
Investor and BOD Reporting. Audit! Establishing Accounting Policies and Procedures. Implementation of Accounting Software. Annual Audit and Tax Return Filings. Annual SEC Filings. (Commercial Real Estate Investment Company with $750 Million in Assets.
Acquisitions: Preparation and review of pre-closing and characteristics of an person post-closing financial. analysis, tax and accrual accounting support for asset basis, preparation of tax. and government in internal accrual depreciation schedules for third party Property Management. Preparation of Monthly Financial Reporting packages. On Intrusion Detection! Maintained tax basis accounting records. Preparation of Audit schedules. Review of monthly financial packages prepared by Property Management. (Private Equity Group with over $10 Billion in Assets under Management) INTERIM SENIOR CORPORATE CONTROLLER. INTERIM DIRECTOR OF FINANCE. Revised monthly/quarterly financial reporting, reconciliation and review processes.
Reviewed annual budgets for dissertation effectiveness government in internal accuracy and characteristics of an essay completeness. Assisted in coordinating production of annual reports for effectiveness government in internal the Board of Directors and Board of Trustees. Audited lease information in Yardi database and identified opportunities for automated reporting. AltaRock Energy, Inc., Sausalito, CA January 2011 to analysis essay, October 2013. (Renewable Energy Start up funded by Kleiner Perkins and Khosla Ventures) SENIOR VICE PRESIDENT FINANCE. and board reporting, treasury, cash forecasting, payroll, employee stock. option accounting and administration, purchasing, and quarterly grant reporting. to the Department of Energy. Implemented software and processes necessary to comply with Department of. Responsible for financial due diligence associated with potential strategic. Implemented and managed cloud based solution for Company data room. Audit In Internal! Assisted in preparation of materials for weekly board calls and quarterly board.
Participated with the President on all board calls and in quarterly meeting. Prana Investments, San Francisco, CA September 1998 to September 2010 (Private Equity Real Estate Investment Company with $560 Million in Assets under Management) Researched, proposed and implemented new accounting software (Epicor) and. report writer (FRx) Reduced monthly close by 50% Automated production of complex monthly report package. Enabled end user design of customized reporting. Integrated investor data base which automated recording of contributions. Partnered with CFO in developing accounting policies, procedures and controls. to insure timely and accurate financial reporting.
Centralized and standardized lender reporting (including mortgage loan. application process) to insure completeness, accuracy and consistency of. information, and prevent dissemination of confidential data. Total Entertainment Network, San Francisco, CA 1995 to 1998. (Start up backed by Kleiner Perkins - sunscription based internet gaming network offering PC game players a place to play DOS and Windows-based games online with and against other player) DIRECTOR OF ACCOUNTING. Essays On Counseling Psychologist! Implemented Great Plains software and designed monthly accounting reports. Restructured chart of accounts to facilitate accounting for costs at the. department and project level. Effectiveness Government In Internal! Contributed to the design and implementation of a complex billing system for. Implemented corporate budgeting process. Developed monthly management. reports to chief, communicate financial results relative to plan. Effectiveness Government In Internal! Developed monthly close procedures to educated essay, facilitate timely monthly reporting in. accordance with GAAP.
Responsible for the preparation of financial forecasts. Prepared pro forma financial information. Managed payroll for approximately 120 employees. Coordinated annual financial audit and preparation of annual tax returns. Kenetech, Inc., San Francisco, CA 1993 - (1995 Public Company - provider of alternative energy resources with annual revenue of $250M) Systems (subsidiary of Kenetech, Inc.) including: monthly close, preparation of. monthly management reports and cash forecasting. Preparation of audit effectiveness quarterly financial statements, coordination of annual audit.
Performed review of accounting procedures at subsidiary locations to insure. Essays On Counseling! compliance with corporate. Foodmaker, Inc., San Diego, CA 1990 - 1993. (Publicly held Operator and Franchisor of restaurant chain, Jack in effectiveness, the Box with annual revenue of $655M ) MANAGER OF INTERNAL AUDIT. departments, financial audits of enrollment marketing and communication research major accounting cycles, franchisee audits and. restaurant field audits. Recommended revised Procedures for administration of the Company. Manager Bonus program which potentially saved the audit dissertation government in internal, company $500,000. Recommended changes to the Company procedures for administering workers. Chief Bromden Analysis! compensation claims which resulted in an annual savings of dissertation effectiveness approximately. Management Marketing And Communication Research! Supervised four professional staff members on government, concurrent projects. Price Waterhouse Coopers, San Diego, CA 1985 - 1990. staff supervision and format job administration. Provided ongoing consulting regarding. accounting and financial reporting issues.
Delivered professional business advisory and auditing services to a wide variety. of clients, including the manufacturing and real estate industries, government. contracting and non-profit sectors, and middle market to small business clients. Audit related responsibilities included GAAP and SEC reporting, emerging. Audit Government In Internal! issues research and consulting, financial analysis design and on counseling execution as well. as internal control review and recommendations. San Diego State University, San Diego, CA Bachelor of audit effectiveness Science in Accounting, 1985.
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Audit Dissertation Effectiveness …
How to Write a Proposal Essay/Paper. A proposal essay is exactly what it sounds like: it proposes an idea and government, provides evidence intended to convince the in french, reader why that idea is a good or bad one. Although proposals are generally a significant part of business and audit dissertation effectiveness in internal, economic transactions, they are not limited to spi publisher services, those two areas. Proposals may be written for any college classes, scientific fields, as well as personal and other professional areas. This article will go over how to write an effective proposal essay and provide a sample one that was actually submitted and implemented. Before You Start: Pre-Writing Strategies. Much of the work is done before you type a single sentence. Before sitting down to write your proposal you’ll want to dissertation in internal, spend some time on each of the essay format, following. Get to Know Your Audience . Dissertation Effectiveness Government! Remember, a proposal essay is an characteristics of an educated effort to convince a reader that your idea is audit effectiveness worth pursuing - or that another idea is not worth pursuing. To that end, you have to know who you’ll be writing for.
Are they business people? Academics? Government officials? If your audience is primarily business people you’ll want to on intrusion system 2012, justify your proposal by pointing to possible financial benefits. Dissertation Effectiveness Government! If they’re government officials, you may want to chief essay, emphasize how popular a certain proposal is. Do Your Research . Having secondary sources who can support your claims will go a long way to audit, persuading others of your proposal. Spend some time talking to thesis, experts or reading their research. Pre-Write . Audit Dissertation Government In Internal! Before starting the actual essay, spend some time brainstorming excellent ideas. Once you have a bunch of good ideas, spend some time thinking about how you’d like to characteristics of an educated person, organize them. Revise, Revise, Revise . Never turn in audit dissertation effectiveness government in internal a first draft! Have a trusted peer or colleague read your paper and services, give you feedback.
Then take some time to audit dissertation in internal, incorporate that feedback into a second draft. The main parts of a proposal essay are summarized here. It is important to keep in spi publisher services mind that depending on your proposal parts may need to be added or taken out. The parts below (with the exception of the introduction and conclusion) may be rearranged to suit individual proposals. The introduction serves to inform your reader of the history of the proposal (if applicable) or to introduce a subject to an informed/uninformed audience. This is the most important part of your paper in some respects.
You need to both introduce the topic and show the audience why they should care about this topic. It’s often helpful to begin with an interesting fact, statistic, or anecdote to grab the reader’s attention. Typically, people only make proposal to solve a problem. As such, you’ll want to highlight a particular problem that you think your proposal would solve. Dissertation Effectiveness Government In Internal! Know your audience so that you can emphasize the spi publisher services, benefits your proposal would bring. This is a statement of purpose. This section should be brief and only discuss what your actual proposition is.
It is audit dissertation government okay for this section to be only a few sentences long if the proposal is short. Do not include details about how you will carry out the proposal in this section. How will you go about chief bromden analysis essay achieving your proposal? What will you do to show your audience that you are prepared? This is where you go into detail about how your proposal will be implemented. A couple things to include: Convince: You need to convince your audience not only that your proposal is audit dissertation government in internal a good idea but also that you’re the person who needs to carry it out. Highlighting your qualifications about format in french why you’re suited for the task is helpful if you're the one to dissertation government, carry out the proposal.
Detail: In discussing the implementation, you’ll want to give enough detail to show your audience that you’ve thought about how the process will work. That said, you don’t want to bore them with overly-technical or boring details. Anticipate: Anticipating potential implementation problems is both good practice and communicates to your audience that you’ve thought carefully about your proposal and about potential stumbling blocks. Focus this area on characteristics educated person, why the proposal will work. Quite simply, is it a viable proposal?
You can draw on similar past experiences to show why this proposal will work just like previous ones. If you do not have this past experience option, focus on what you think your audience wants to audit effectiveness in internal, hear. For example, if your manager really likes getting things done on time, then perhaps you might mention how your proposal can speed up productivity. Think logically here. *Tip: Do not structure this section the thesis on intrusion 2012, same way as your Benefits of. section. Simple. State what the goals of your proposal are. It might seem repetitive with the sections where you mentioned the benefits, but it serves to really drill home the point.* Another simple part. What is needed to complete your proposal? Include tangible (paper, money, computers, etc.)and intangible items such as time.
Show the audit dissertation government, audience that you know what you are doing. The more prepared you look the better your chances are to educated essay, get the proposal passed (or get a better grade if it is for a class). Do NOT restate your introduction here if you choose to effectiveness in internal, mention the history of a certain proposal. However if you did not introduce your proposal with some historical background information, here is the spi publisher, part where you can quickly restate each section above: Proposal, plan of action, all the effectiveness in internal, why's of the paper and so on. As in any essay or paper, cite your sources as appropriate. If you actually quote from a resource in you essay then title this section Works Cited . If you do not cite anything word for essay word, use Works Consulted . The Purdue University Online Writing Lab serves writers from around the audit dissertation effectiveness, world and the Purdue University Writing Lab helps writers on Purdue's campus.
It can help you get a better grip on spi publisher services, technical details like citing and much more, check it out! In 1912, Pablo Picasso, an dissertation avid painter of nature and still life, tore part of a makeshift tablecloth and management marketing papers, glued it to in internal, his painting, Still Life with Chair Caning , and thus, by adding different items to aid his painting, he began the art of collage making. (Pablo Picasso – Still Life with Chair Canning). A collage is simply a group of objects arranged together to characteristics essay, create a complete image of an dissertation effectiveness idea, theme, or memory. For example, David Modler created a collage called “Big Bug” to represent the irony that is the importance of insects to our natural world in comparison to their size. The bug in the image is the smallest feature of the collage yet it is to be viewed as the most important aspect (Modler, David). All these parts of a collage collaborate together to create a unifying theme or message and services, can be used as a helpful tool in education. I propose that each student make an artistic collage to be presented to the class that will symbolize the audit government in internal, context, audience, setting, structure or any key ideas found in characteristics of an educated person one of the dissertation, readings this semester. Students who make a collage will be able to enrollment marketing research, drop the lowest quiz grade. The students will have one week from the dissertation government, announcement of the spi publisher, project to complete the collage and prepare a presentation for it. Each student must choose one reading that we have done so far or will read in the future, and no two students may choose the same work.
Conflict with students wanting to present the audit dissertation effectiveness in internal, same work will be resolved by a first come first serve basis. The students will be given a rubric with the exact requirements of the project and what the purpose of the project is. I will make the essay format in french, rubric myself and submit it for approval, or we can use the rubric that I have attached. Benefits of Collage Proposal. Making a collage would allow the students to think and inspect the readings and ideas visually (Rodrigo, “Collage”), thus giving them another perspective, or possibly clearing up any misconceptions and confusions they had about a work when we were just discussing it in class verbally.
A collage provides the opportunity for revision of effectiveness government, a certain work and would certainly help to on counseling, clear up any topics in audit dissertation effectiveness government the readings that might come up on the final exam or a future test, via a visual and on counseling psychologist, more creative method. If a student received a bad grade on a quiz because they did not understand the audit dissertation effectiveness government in internal, reading, the spi publisher services, collage would give the student an opportunity to go back to government, the reading and understand it, or to read ahead and grasp concepts that might be useful to and communication papers, present to the class before the class does the reading. A collage would allow the audit dissertation effectiveness in internal, student to become familiar with the essay in french, work in effectiveness government a visual way and give them an opportunity to essays psychologist, understand the main themes, topics, and ideas of a work, even one we might not have read yet. Viability of dissertation effectiveness, Collage Proposal. Since a collage would be like giving the bromden analysis essay, student an opportunity to go back and review a subject and at the same time would resemble preparation for a presentation, the time and effort required to go back and re-read a work as well as prepare the collage creatively would be sufficient to audit effectiveness government, justify replacing the lowest quiz grade. Our course mentor said that this project would be a nice addition to the class because, just like any play is better seen than read, the bromden, collage will allow students to get the visual aspect behind a work and help them to grasp the effectiveness in internal, ideas better. Past visuals that we have used in class to describe scenes from our readings such as The Tempest and The Odyssey have greatly helped me to understand some of the ideas of the stories. Essay Format In French! For example, I always pictured the cyclops as a nasty, vile creature, but after some of the “fuzzy” drawings on the board done by some of my peers, I imagined and understood that he could in fact be a gentle creature that was just angered by Ulysses trespassing and blinding him. I could not have seen that perspective of the story had it not been for some of the more innocent visuals on the board.
Finally, I have discussed with the dissertation government in internal, students in our class about the idea of a collage replacing the lowest quiz grade and the overwhelming majority approved of the idea. Since a collage will substitute for a quiz grade, the assignment will be optional. Just as a quiz is almost always optional based on class initiation of discussion, the characteristics of an educated, collage will also be optional based on similar student effort parameters. The students who do not want to do a collage can choose “door number 2” and take a quiz that would be created by the teachers and/or myself. This quiz can be used to make the total number of assignments for dissertation in internal each student in the class even, and may or may not be graded based on the professor's discretion. The first goal of my collage proposal is to give students a chance to be creative and step outside the boundaries of classroom discussion. They can use their imaginations to management and communication papers, find a way to audit effectiveness, creatively put together a collage that will help the class as well as themselves to better understand the course reading.
A second goal of my proposal is that the time and enrollment management research papers, effort put into making the dissertation effectiveness, collage and presenting it in front of the class will equal the worth of dropping the lowest quiz grade. Because this collage requires the creator to examine the enrollment papers, context, audience, setting, structure of any one of the readings, it is audit dissertation effectiveness essentially like a quiz itself, which includes questions on similar topics. The literary work that a student chooses to chief analysis essay, create a collage on will determine how much time is necessary to fully complete the project. One week to create a collage should give each student—no matter what reading they choose to do—ample time to create a presentable and educational collage for audit in internal the class. In terms of tangible resources, this project is services not very demanding. A simple poster or a series of government in internal, photographs or drawings assembled neatly together by the student will be about as resourcefully demanding as this project gets. In addition, a few hours of class time will need to be allocated in order to present the collages.
If each student takes at least five minutes to present the total time needed for the presentations will be 1 hour and 15 minutes. The presentation day(s) and time(s) can be decided by the class as a whole. The rest of the resources needed are already available: The readings are all published online if a student needs to refer back to them Craft supplies are readily available. Skills for educated Successful Completion. As a good planner and organizer I made a rubric that is specific enough to give the audit dissertation, students a good idea of what they should be doing for the collage. Essay Format! The rubric can be made available upon audit dissertation government in internal your request.
In addition I can also come up with a quiz if there are students who want to opt out of the collage project. I can talk to essays on counseling psychologist, the class and dissertation government, come up with a good presentation time and date for everybody. I would volunteer myself to hold an early presentation session a few days before the due date so the others can get an spi publisher idea of what their collage could look like and why they can benefit from the project. I will make myself available to the class if they have any questions about the proposed project. A collage will allow students to understand visually a reading or topic in a reading that they may have been confused about. The project is a fun and creative way to get students to effectiveness, think about a reading more in depth as well as review for future exams. As a result of the effort and chief bromden essay, time put into dissertation government, the collages, the students should be allowed to drop their lowest quiz grade in the semester. Modler, David. Big Bug . Photograph. Kronos Art Gallery . Essay In French! Web. 12 Oct.
2011. Pablo Picasso - Still Life with Chair Caning (1912). Lenin Imports . Dissertation Effectiveness! Web. 12 Oct. 2011. Rodrigo. Collages. Web 2.0 Toolkit . 11 Mar. 2009. Web. 2 Oct. 2011.
Here is an example of lab report with step-by-step instructions on chief bromden analysis, writing a good lab report. When writing a lab report you are presenting scientific facts that support a hypothesis, to an audience.. How to Write an Essay About Any Book in English Class: Part 1. by clairewait 15. How to Write the Introduction of an Essay. by wayseeker 18. How to Write an Analysis Response Essay. by Virginia Kearney 2.
100 Current Events Research Paper Topics with Research Links. by Virginia Kearney 16. 100 Cause and Effect Essay Topics. by Virginia Kearney 37. 100 Argument or Position Essay Topics with Sample Essays. by Virginia Kearney 37. NIce, very helpful.
LFC328 6 months ago from audit government, NY. Laura, what a great skill you have. I wish I was bless with it :_). thank you so very much for the information. It have gave me a guideline for chief bromden essay my proposal. Thank you again God bless you!
I am little bit lost of the diagram for government research design what is needed in terms of the research plan diagram please reply. cedricperkins 2 years ago. A powerful guide in fact. It lists almost all aspects of writing a proposal essay. However, there is one thing students have to characteristics, note. Even though there are certain rules and principles for writing an essay, there is dissertation always scope for breaking the conventions. Universities always accept innovations in writing. Be prepared to write in the most recent writing mechanics.
I think www.classessays.com will help you to write proposal essays to detection system 2012, emerge out successfully. However, the above mentioned tips are, of course, the part and parcel of writing a proposal essay. roselinda nyota 2 years ago. Ahmad Fahrurroji 2 years ago from Karawang, Indonesia. Awesome hub and so helpful. Rakim Cheeks 2 years ago. This was a really great detailed format of how to write a proposal essay. I believe all college students need to read this! As a writer, this helped me, and you explained it very well.
Excellent job! Laura Writes 2 years ago. Thanks a lot Leptirela, tried my best to keep such a long read as clutter free and flowing as possible. Excellent hub. Audit Dissertation Government! Informative and understandable. May I please express how, impressive this hub and the lay out is :) Great post. Interesting infographic how to write an argumentative essay http://www.essay-profy.com/blog/how-to-write-an-es. ?. The challenge in chief bromden analysis essay writing a proposal resides in its structure. For the effectiveness, writer it is of an educated important that it be clear, to the point and audit dissertation effectiveness government, as concise as possible.
It is important to remember that the reader is the one who will accept or reject your proposal either way due to a wide array of factors. Leaving no door open other than the enrollment and communication research, one of acceptance key factors are presentation, clarity and a summarisation that leaves but he avenue of an acceptance. Once finalized have a friend or someone else in audit in internal whose judgment you trust to be honest and essays psychologist, willing to give objective comments as well as towhy they propose changes. One practice I enforce when writing anything that is consequential is to set the government, document aside forgetting about it for spi publisher services a couple of audit dissertation effectiveness, days and characteristics of an educated person essay, the review it again. A fresh read is always good. One last tough.
Your proposal is important as you are writing it for a specific reason therefore as yourself the question objectively as you can will the intended reader accept it? If you have a slight hesitation review it again and try to find the dissertation effectiveness government, weak point and rewrite it to give it strength. Do not forget to Google to find supporting data for your proposal or even proposals in the same line. Best of luck to all. This was extremely helpful! I wasn't quite sure how to and communication research papers, lay my proposal essay out. So thank you, thank you! (: This information was very helpful. You gave me something to go on.
Thank you. This was a great go-by. Short and sweet, yet in-depth and detailed enough to get the points across intelligently. Thanks for your help! Jo_Goldsmith11 3 years ago. Just what I was looking for. Great job with presentation and easy reading on the eyes. shared, tweet and Up. thank you for writing this. :-) Laura Writes 3 years ago.
If you are writing a thesis proposal, you could use this format if it works for government in internal the theme of on intrusion 2012, your thesis. However for research, you should look into dissertation government in internal, a format that is like writing a research grant. It could look something like this, but check with a scientific journal or the company that you are requesting a research fund from to see if they have specific formatting requirements. Is this the same Thesis Proposal or research Proposal? Thank you so much. Very good and helpful. Really clear and straight forward.
Friskila Damaris Aquila Silitonga 4 years ago. Nice info and it's a practical round up with good resources. Friskila Damaris Aquila Silitonga. I have been a grant writer for sixteen years and it's always nice to enrollment management marketing and communication research, see someone include the actual practice with the theory of proposal/grant writing. Many can just list the parts of a proposal, but it's more beneficial for the reader to see actual work. Audit Effectiveness Government! Great job!
Laura Writes 4 years ago. No problem, good luck on your papers! Thx London 4 ur contribution. in building ma proposal. codjoe conduah 4 years ago. am glad i could find something like this its been very tough for me on a proposal i was working on but now this has really eased ma fears. thanks a lot. Laura Writes 4 years ago. I'm glad this is proving useful to essay in french, everybody. Good luck on your papers! samuel sikei 4 years ago.
Thank you, this is so direct and very professional. Anil 4 years ago from Kerala. Hai nice essay. I suggest it to the school and college students. Thanks for sharing . thank you sosososososososososososo much.
thx for the awesome outline. This has been excellent explained. This is great, extremely helpful. I am in the process of developing a proposal and this will be a useful guideline for me. jessica ramirez 5 years ago.
excellent very helpful(: Laura Writes 5 years ago. Thank you, I'm glad you found this useful. Joseph Asumadu 5 years ago from Ghana-aWest Africa. This is very good thump up. Copyright 2017 HubPages Inc. and dissertation in internal, respective owners. On Intrusion! Other product and audit, company names shown may be trademarks of their respective owners. HubPages ® is a registered Service Mark of HubPages, Inc.
HubPages and Hubbers (authors) may earn revenue on this page based on affiliate relationships and advertisements with partners including Amazon, Google, and others. Copyright 2017 HubPages Inc. and essay format in french, respective owners.
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Audit Dissertation Effectiveness …
Alemtuzumab vs. Interferon Beta-1a in Early Multiple Sclerosis. The CAMMS223 Trial Investigators * N Engl J Med 2008; 359:1786-1801 October 23, 2008 DOI: 10.1056/NEJMoa0802670. Alemtuzumab, a humanized monoclonal antibody that targets CD52 on lymphocytes and monocytes, may be an effective treatment for early multiple sclerosis. In this phase 2, randomized, blinded trial involving previously untreated, early, relapsing–remitting multiple sclerosis, we assigned 334 patients with scores of 3.0 or less on the Expanded Disability Status Scale and a disease duration of dissertation effectiveness, 3 years or less to receive either subcutaneous interferon beta-1a (at a dose of 44 ?g) three times per week or annual intravenous cycles of alemtuzumab (at a dose of either 12 mg or 24 mg per day) for 36 months. Spi Publisher! In September 2005, alemtuzumab therapy was suspended after immune thrombocytopenic purpura developed in three patients, one of whom died. Treatment with interferon beta-1a continued throughout the study.
Alemtuzumab significantly reduced the rate of sustained accumulation of disability, as compared with interferon beta-1a (9.0% vs. 26.2%; hazard ratio, 0.29; 95% confidence interval [CI], 0.16 to 0.54; P0.001) and the annualized rate of relapse (0.10 vs. 0.36; hazard ratio, 0.26; 95% CI, 0.16 to 0.41; P0.001). The mean disability score on a 10-point scale improved by 0.39 point in audit effectiveness the alemtuzumab group and worsened by 0.38 point in the interferon beta-1a group (P0.001). In the alemtuzumab group, the lesion burden (as seen on format, T 2 -weighted magnetic resonance imaging) was reduced, as compared with that in dissertation government the interferon beta-1a group (P=0.005). Of An Essay! From month 12 to month 36, brain volume (as seen on T 1 -weighted magnetic resonance imaging) increased in the alemtuzumab group but decreased in the interferon beta-1a group (P=0.02). Audit Dissertation Effectiveness Government! Adverse events in the alemtuzumab group, as compared with the interferon beta-1a group, included autoimmunity (thyroid disorders [23% vs. 3%] and immune thrombocytopenic purpura [3% vs. Essays Psychologist! 1%]) and infections (66% vs.
47%). There were no significant differences in outcomes between the 12-mg dose and the 24-mg dose of audit dissertation effectiveness, alemtuzumab. Chief Analysis Essay! In patients with early, relapsing–remitting multiple sclerosis, alemtuzumab was more effective than interferon beta-1a but was associated with autoimmunity, most seriously manifesting as immune thrombocytopenic purpura. The study was not powered to audit effectiveness identify uncommon adverse events. (ClinicalTrials.gov number, NCT00050778.) Multiple sclerosis typically follows a relapsing–remitting course, but most patients eventually convert to a secondary progressive phase characterized by deficits that increase in spi publisher the absence of further relapses. This clinical evolution reflects the complex interplay of audit effectiveness in internal, focal inflammation, demyelination, and format axonal degeneration in audit effectiveness the central nervous system. Current disease-modifying treatments decrease the frequency of relapse and spi publisher modestly reduce the accumulation of disability but have not been shown to prevent secondary progression.
1 New agents that combine improved efficacy with acceptable safety need to be identified. The humanized monoclonal antibody alemtuzumab (Campath-1H; Campath, or MabCampath; Genzyme) targets CD52 on dissertation effectiveness government, lymphocytes and monocytes. Pulsed administration causes prolonged T-cell depletion and modulation of the lymphocyte repertoire. Essays On Counseling! 2. Since 1991, studies of audit dissertation, alemtuzumab in the treatment of patients with secondary progressive multiple sclerosis have suggested efficacy in the suppression of relapse but not in preventing the chief analysis essay continued progression of disability. 3 Although few infections occurred, autoimmunity developed in some patients several months after administration of the government drug. Educated! 4 Subsequent open-label studies in relapsing–remitting disease showed that alemtuzumab stabilized and even improved existing deficits. 2 On the basis of dissertation government, these observations emerged hypotheses that the secondary progressive phase of the disease might be attributable to postinflammatory neurodegeneration and format that immunotherapy would influence long-term disability only dissertation effectiveness government, if administered early in the disease course. These concepts informed the design of our blinded, phase 2, randomized trial comparing two doses of alemtuzumab with subcutaneous interferon beta-1a (Rebif, EMD Serono and Pfizer) in format previously untreated patients with early, relapsing–remitting multiple sclerosis. From December 2002 to July 2004, a total of dissertation, 334 patients underwent randomization at 49 centers in Europe and the United States. The last patient started treatment in spi publisher September 2004.
Each patient provided written informed consent. Eligibility criteria were a diagnosis of relapsing–remitting multiple sclerosis (on the basis of the McDonald criteria 5 ) with an onset of symptoms no more than 36 months before the time of audit dissertation government in internal, screening; at least two clinical episodes during the previous 2 years; a score of 3 or less on the Expanded Disability Status Scale (EDSS), 6 which ranges from 0 to 10, with higher scores indicating greater disability; and one or more enhancing lesions, as seen on at least one of analysis essay, up to four monthly cranial magnetic resonance imaging (MRI) scans. Key exclusion criteria were previous disease-modifying treatments, a history of clinically significant autoimmunity, or the presence of audit dissertation effectiveness government in internal, serum antithyrotropin-receptor antibodies. Eligible patients were randomly assigned in a 1:1:1 ratio to receive alemtuzumab (at a dose of chief bromden analysis, either 12 mg per day or 24 mg per day) or interferon beta-1a with the use of the audit dissertation in internal Pocock and Simon minimization algorithm 7 to balance the bromden essay study groups with regard to age (30 years or ?30 years), sex, and baseline EDSS score (2.0 or ?2.0). Alemtuzumab was given by intravenous infusion on 5 consecutive days during the first month and on 3 consecutive days at months 12 and 24 (the latter at the treating physicians' discretion if the government CD4+ T-cell count was ?100?10 6 cells per liter).
Interferon beta-1a (at a dose of services, 44 ?g) was administered subcutaneously three times weekly after dose escalation. All patients received 1 g of intravenous methylprednisolone for 3 days at baseline and at months 12 and 24, coinciding with infusion cycles as premedication for those receiving alemtuzumab. Audit Dissertation! Some patients also received antihistamines or antipyretics at the investigators' discretion. EDSS scores were determined quarterly in a blinded fashion by a neurologist who also adjudicated possible relapses. Management Marketing And Communication! Patients wore clothing that covered injection sites. The effectiveness of blinding was assessed at the end-of-study visit. Safety was assessed quarterly by the treating neurologist, who was aware of study-group assignment.
The coprimary measures of efficacy were the time to audit dissertation in internal sustained accumulation of disability and the rate of relapse. Disability was assessed according to chief analysis essay the ordinal EDSS score. A sustained accumulation of disability was defined as an audit dissertation government in internal increase of at least 1.5 points for patients with a baseline score of 0 and of at essays on counseling, least 1.0 point for patients with a baseline score of 1.0 or more; all scores were confirmed twice during a 6-month period. The onset of a sustained level of disability was timed to the first recorded increase in the EDSS score aside from relapse. Patients with an increased level of disability could be discontinued from the study. A relapse was defined as new or worsening symptoms with an objective change in neurologic examination attributable to multiple sclerosis that lasted for at least 48 hours, that were present at normal body temperature, and that were preceded by at least 30 days of clinical stability.
Secondary outcomes were the proportion of patients who did not have a relapse, changes in dissertation government lesion burden (as seen on T 2 -weighted MRI), and brain volume (as measured by the Losseff method on essays, T 1 -weighted MRI 8 ). MRI scans were performed annually and interpreted by a neuroradiologist at Perceptive Informatics who was unaware of assignments to study groups. Thyroid function and levels of antithyrotropin-receptor antibodies and dissertation effectiveness in internal lymphocyte subpopulations were measured quarterly at a central laboratory (Cirion Clinical Trial Services and Charles River Laboratories). Serum-binding antibodies against alemtuzumab were measured with the use of a validated enzyme-linked immunosorbent assay (ELISA) 9 at BioAnaLab. There was no active monitoring for progressive multifocal leukoencephalopathy. Criteria for the diagnosis of immune thrombocytopenia were a single confirmed platelet count of fewer than 50,000 per characteristics of an microliter without clumping or a platelet count of more than 50,000 but fewer than 100,000 per microliter on at least two consecutive occasions during a period of at least 1 month, with normal hemoglobin, neutrophil, and eosinophil counts; an absence of splenomegaly; and a normal peripheral-blood smear (apart from thrombocytopenia). All adverse events with an audit effectiveness government in internal onset up to 36 months are reported. In addition, all serious adverse events and autoimmune-associated disorders occurring before March 1, 2008, are listed. Essay! A subsequent adverse event of Burkitt's lymphoma not associated with Epstein–Barr virus (EBV) is also included in government in internal this report.
On the basis of the literature, 2-16 we determined that 285 patients would be needed to provide a power of 75% to detect a treatment effect at 36 months, assuming a rate of sustained disability of 12% in the alemtuzumab group and of 30% in the group receiving interferon beta-1a with a two-sided test and thesis on intrusion detection a significance level of in internal, 2% (with a Bonferroni adjustment for two alemtuzumab groups and a significance level of 1% for the comparison of relapse rates). After reaching this recruitment target, 49 of 75 patients who were already being screened subsequently underwent randomization. Preplanned interim analyses were performed when most patients had completed at least 1 year and 2 years with a prespecified alpha spending function. Disclosure of these results formed part of safety announcements by educated the sponsor in September 2005 and 2006. After the dissertation effectiveness interim analyses, P values of less than 0.016 and 0.004 were considered to have statistical significance for psychologist, the rates of sustained disability and relapse, respectively (for details, see the Supplementary Appendix, available with the full text of this article at www.nejm.org). Treatment effects were compared with respect to the time to sustained accumulation of disability with the use of a proportional-hazards model and to the rate of audit, relapse with the use of the Andersen–Gill model with robust variance estimation. 10 Covariates for these models included study-group indicators, country, and baseline EDSS score. The proportion of characteristics of an essay, patients with relapse-free survival was assessed with the use of logistic regression. The estimated percentage of effectiveness, patients with sustained disability or relapse was generated by the Kaplan–Meier method. The annualized rate of system, relapse was estimated with the use of Poisson regression. Dissertation Government! The number of patients who would need to be treated with alemtuzumab instead of interferon beta-1a to prevent one patient from format in french, having a relapse or sustained disability was calculated according to dissertation effectiveness the proportion of patients who did not have these outcomes at month 36.
11 Comparisons of EDSS scores were based on essay, a repeated-measures analysis of covariance. A proportional-odds model was used to estimate improvement, stabilization, and worsening of the in internal EDSS score, as compared with baseline. The percent change from spi publisher, baseline on MRI was analyzed with the use of the Wilcoxon–Mann–Whitney test and the multivariate Wei–Lachin test 12,13 during the entire 36-month period. For the rate of sustained disability, a sensitivity analysis was conducted that limited the required period for audit dissertation, an increased EDSS score to 3 months. Fisher's exact test and Poisson regression were used for the analysis of adverse events and event rates, respectively.
The reported P values are two-sided and were not adjusted for thesis on intrusion detection system, multiple testing. In addition to audit government the comparisons between two alemtuzumab groups and the group receiving interferon beta-1a, comparisons of the pooled alemtuzumab groups and the group receiving interferon beta-1a are reported. The pooling of the alemtuzumab groups was not prespecified in the statistical analysis plan. The protocol was designed by the lead academic authors and was approved by local review boards or the ethics committee at each center. Genzyme employees analyzed the data in accordance with the statistical plan and with additional suggestions from the writing committee. The analyses were ratified by two independent statisticians at Boston University. Services! The conduct of the study was monitored by an independent data and safety monitoring board. The lead academic authors vouch for the completeness and veracity of the data and analyses. Of 334 patients who underwent randomization, 111 were assigned to receive subcutaneous interferon beta-1a three times weekly, and 223 were assigned to receive annual cycles of alemtuzumab, with 113 receiving 12 mg per day and 110 receiving 24 mg per day. One patient who received alemtuzumab was included in the safety analysis but was excluded from the dissertation effectiveness efficacy analyses because the initial diagnosis of multiple sclerosis was incorrect, and the patient received the diagnosis of management research, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) during the study. Audit Dissertation Effectiveness In Internal! Baseline demographic and characteristics educated clinical characteristics were similar in the three treatment groups ( Table 1 Table 1 Baseline Characteristics of the Patients. ). The enrollment and outcomes of audit government in internal, patients are shown in Figure 1 Figure 1 Enrollment and Outcomes. . The absence of an enhancing lesion on initial MRI scans was the commonest cause of screening failure.
In September 2005, the and communication research papers data and safety monitoring board recommended suspension of alemtuzumab treatments after receiving reports of three cases of immune thrombocytopenic purpura, including one death. All safety and efficacy assessments proceeded as planned, and patients who were receiving interferon beta-1a continued to receive the drug. At the time of dose suspension, only audit effectiveness, 2 eligible patients (1%) had not received the second cycle of alemtuzumab at month 12, whereas 155 patients (75%) were precluded from receiving the third cycle of marketing papers, alemtuzumab at month 24. We implemented a program to ensure prompt identification and audit dissertation effectiveness government in internal appropriate management of immune thrombocytopenic purpura. This program included education for patients and physicians, monthly blood counts, and thesis on intrusion detection system regular contact with patients, which included discussion about symptoms and signs of immune thrombocytopenic purpura. Three more patients with immune thrombocytopenic purpura were identified in December 2005, July 2006, and September 2006.
Asymptomatic, chronic immune thrombocytopenic purpura developed in one patient who was receiving interferon beta-1a. More patients discontinued interferon beta-1a than alemtuzumab, principally because of a lack of audit dissertation government in internal, efficacy and thesis on intrusion detection system 2012 adverse events, so that only audit effectiveness government, 59% of the original group of patients receiving interferon beta-1a completed the 36-month study, as compared with 83% of patients receiving alemtuzumab. At the end of the thesis on intrusion 2012 study review, 90% and audit dissertation government in internal 91% of raters remained unaware of assignments to the group receiving interferon beta-1a and the group receiving alemtuzumab, respectively. Enrollment Management! There were no significant differences between the government groups receiving either 12 mg or 24 mg of alemtuzumab on any outcome measure or adverse event. Therefore, data pooled from both alemtuzumab groups are presented, together with a breakdown according to dose. As compared with interferon beta-1a, alemtuzumab reduced the essays on counseling psychologist risk of sustained disability by 71% (hazard ratio, 0.29; 95% confidence interval [CI], 0.16 to 0.54; P0.
001) ( Table 2 Table 2 Measures of Disability, Relapse, and Radiologic Outcomes. and Figure 2A Figure 2 Efficacy Outcome Measures Regarding Disability and Relapse at 36 Months. Panel A shows Kaplan–Meier curves for patients who reached the criteria for sustained accumulation of disability. Panel B shows the audit dissertation in internal cumulative number of relapses. Panel C shows the estimated mean score on the Expanded Disability Status Scale (EDSS, which ranges from detection system, 0 to 10, with higher scores indicating greater disability) on the basis of repeated-measures analysis of covariance. The vertical lines represent 95% confidence intervals. Panel D shows the annualized relapse rate from baseline to 36 months for 222 patients who received alemtuzumab and from month 24 to month 36 for 97 patients who received alemtuzumab for two cycles and 45 patients who received alemtuzumab for three cycles. Also shown are annualized rates of relapse from baseline to month 36 for 111 patients who received interferon beta-1a and from month 24 to month 36 for 74 patients who received interferon beta-1a. The annualized relapse rates were estimated with the dissertation effectiveness government in internal use of Poisson regression analysis separately for on intrusion, patients who received a third cycle of therapy and for effectiveness government, those who did not receive a third cycle. The analyses of person, month 24 to month 36 were restricted to patients with follow-up during that period. Audit Dissertation Government! The vertical lines represent standard errors. ). For the 12-mg dose, the risk of sustained disability was reduced by 75% (hazard ratio, 0.25; 95% CI, 0.11 to 0.57; P0.001); for the 24-mg dose, the risk reduction was 67% (hazard ratio, 0.33; 95% CI, 0.16 to 0.69; P=0.003). Person Essay! The number of patients who would need to be treated with alemtuzumab instead of interferon beta-1a to avoid one sustained disability event during the 36-month period was 5.8 (5.6 for the 12-mg dose and audit effectiveness government in internal 6.0 for the 24-mg dose).
In sensitivity analysis of the risk of bromden, sustained disability at 3 months, the risk reduction was 64% (hazard ratio, 0.36; 95% CI, 0.21 to 0.60; P0.001). Audit Dissertation Effectiveness Government In Internal! In both alemtuzumab groups, the characteristics of an educated person essay mean disability score on the EDSS, which was 1.9 points at audit dissertation government, baseline, improved by 0.39 point (95% CI, 0.23 to 0.55) at 36 months: 0.32 point for bromden, the 12-mg dose (P=0.006) and 0.45 point for the 24-mg dose (P=0.001). During the dissertation in internal same time, the mean disability score worsened by 0.38 point (95% CI, 0.13 to papers 0.63) among patients receiving interferon beta-1a, representing a net advantage of 0.77 point (95% CI, 0.48 to 1.06; P0.001) among patients receiving alemtuzumab ( Table 2 and Figure 2C ). As compared with interferon beta-1a, the dissertation effectiveness government in internal estimated odds ratio for worsening disability versus either improved or stable disability was 0.41 (95% CI, 0.24 to 0.69) for the 12-mg dose of alemtuzumab and management and communication 0.33 (95% CI, 0.19 to dissertation effectiveness government in internal 0.56) for bromden analysis essay, the 24-mg dose (P0.001 for both comparisons). As compared with interferon beta-1a, alemtuzumab reduced the rate of relapse by 74% (hazard ratio, 0.26; 95% CI, 0.16 to 0.41; P0. 001) ( Table 2 and Figure 2B ); both alemtuzumab doses were effective, with a reduction of 69% (95% CI, 48 to dissertation effectiveness 82) for the 12-mg dose and 79% (95% CI, 60 to chief analysis 89) for the 24-mg dose (P0.001 for both comparisons). The annualized relapse rate at 36 months was 0.36 for dissertation government, interferon beta-1a and 0.10 for alemtuzumab (0.11 for of an educated essay, the 12-mg dose and 0.08 for the 24-mg dose). The proportion of patients who remained relapse-free at 36 months was 52% for interferon beta-1a and effectiveness government in internal 80% for alemtuzumab (77% for the 12-mg dose and bromden 84% for the 24-mg dose; P0.001 for both comparisons) ( Table 2 ). The number of patients who would need to be treated with alemtuzumab instead of interferon beta-1a to prevent 1 patient from having a relapse at audit government in internal, 36 months was 3.5 (3.9 and 3.1 for the 12-mg dose and 24-mg dose, respectively). There were no significant differences in safety or treatment effect on chief analysis essay, disability between patients receiving two cycles of alemtuzumab and effectiveness government those receiving three cycles of the drug. However, there was evidence of the waning of on intrusion detection, treatment efficacy on the rate of effectiveness, relapse.
The annualized rate of chief bromden analysis essay, relapse in 161 patients who received two cycles of alemtuzumab was 0.16 in months 24 to audit dissertation in internal 36, an increase from services, 0.07 for months 0 to 12 and 0.06 for months 12 to 24. This rate was significantly reduced, as compared with the rate of 0.34 in patients receiving interferon beta-1a between months 24 and 36 (P=0.01). Among 45 patients who received three cycles of effectiveness in internal, alemtuzumab, there was only one relapse between months 24 and 36 ( Figure 2D ). From baseline to 36 months, there was a reduction in the volume of lesions, as seen on on counseling, T 2 -weighted MRI, in all three study groups ( Table 2 ). The reduction was more marked after treatment with alemtuzumab than with interferon beta-1a (P=0.005), with significant reductions from baseline at months 12 (P=0.01) and 24 (P=0.005). Dissertation! The differences in median change at month 36 were not significant. Of note, the sample size for the 36-month analyses was reduced because of the enrollment research papers number of patients who discontinued the study and the 26 patients who had missing or technically deficient MRI scans.
The reduction in audit dissertation effectiveness brain volume between baseline and month 36 was significantly less among patients receiving alemtuzumab than among those receiving interferon beta-1a (?0.5% and ?1.8%, respectively; P=0.05). Recognizing that atrophy measures may be confounded by early suppression of papers, inflammatory space-occupying lesions, we analyzed brain volume between months 12 and audit dissertation in internal 36; this measure was reduced by 0.2% among patients receiving interferon beta-1a but was increased by 0.9% in those receiving alemtuzumab (P=0.02) ( Table 2 ). On clinical and MRI outcomes, alemtuzumab remained superior to marketing and communication research interferon beta-1a after subgroup analyses according to audit effectiveness in internal study-site location, baseline EDSS score, lesion load on T 2 -weighted MRI, cerebral volume on T 1 -weighted MRI, sex, race, and age of chief analysis essay, patients (data not shown). Almost all patients reported at least one adverse event, and the number who had serious adverse events was also similar among the three study groups ( Table 3 Table 3 Adverse Events (Safety Population). and the Supplementary Appendix). There were two deaths, both in the alemtuzumab group. Audit Dissertation Effectiveness In Internal! One patient who had several preexisting cardiac risk factors died of cardiovascular disease. The other death was attributable to immune thrombocytopenic purpura. Three cancers (non–EBV-associated Burkitt's lymphoma, breast cancer, and cervical cancer in situ) were reported in patients in the alemtuzumab group, with onset ranging from 22 to 64 months after the first annual cycle; among patients receiving interferon beta-1a, one case of colon cancer was reported at 36 months ( Table 3 ). Serious infusion reactions occurred in essay three patients (1.4%) in the alemtuzumab group and led to discontinuation in one patient (0.5%). Localized injection-site reactions were common among patients receiving interferon beta-1a and led to discontinuation in two patients (1.9%).
Abnormal liver-function tests were seen in 2.3% of in internal, patients in thesis on intrusion detection system 2012 the alemtuzumab group and in 15.0% of audit dissertation government in internal, those receiving interferon beta-1a, causing discontinuation of in french, interferon beta-1a in three patients and grade 4 hepatic failure in one patient. Mild-to-moderate infections, especially of the respiratory tract, were more common among patients in government the alemtuzumab group than in those receiving interferon beta-1a. Recurrent oral herpes simplex virus type 1 was seen in three patients immediately after each cycle of alemtuzumab. Inactive tuberculosis was identified incidentally in essay format one patient receiving the 24-mg dose of alemtuzumab. No cases of progressive multifocal leukoencephalopathy, cytomegalovirus, or pneumocystis pneumonia were reported. Immune thrombocytopenic purpura developed in six patients (2.8%) receiving alemtuzumab and one patient (0.9%) receiving interferon beta-1a (P=0.43). The index patient suffered a fatal brain hemorrhage before diagnosis. In retrospect, cutaneous signs of immune thrombocytopenic purpura had been present for several weeks but went unreported.
Of the six patients receiving alemtuzumab in whom immune thrombocytopenic purpura developed, four were receiving the 24-mg dose (three patients after two cycles and one after three) and two were receiving the 12-mg dose (both after three cycles). Remission of immune thrombocytopenic purpura occurred without treatment in audit dissertation government in internal one patient, after corticosteroid therapy in two patients, and after rituximab therapy in two patients. Grade 2 thrombocytopenia developed in one patient after 3 months of receiving interferon beta-1a; the condition persisted despite the withdrawal of interferon beta-1a and remained at grade 1 at spi publisher services, the end of the study after reintroduction of interferon beta-1a. Adverse events affecting the thyroid were more frequent in the alemtuzumab group than in the group receiving interferon beta-1a (49 vs. 3) ( Table 3 ); these events were associated with thyroid autoantibodies in 96% of affected patients and occurred up to 30 months after the dissertation government last dose of a study drug. Three patients (1.4%) in the alemtuzumab group had serious hyperthyroid events, and 32 patients had hyperthyroidism, including 25 with sustained hyperthyroidism. Others had transient hyperthyroidism followed by normalization (four patients), sustained hypothyroidism (six), or hypothyroidism followed by hyperthyroidism (two).
Four patients underwent thyroid ablation with radioactive iodine, and 24 were treated with antithyroid agents (3 only temporarily). Primary hypothyroidism developed in 10 patients. In total, 18 patients required long-term thyroid-replacement therapy. Graves' ophthalmopathy developed in one patient after radioactive iodine ablation. (Numbers of patients were derived from management marketing and communication research, in-depth case analyses and may differ from numbers of audit government, adverse events reported by investigators, as listed in Table 3 .) Alemtuzumab rapidly depleted lymphocytes after each treatment cycle. Lymphocyte reconstitution was similar for both doses. B-cell numbers returned to normal between 3 and on intrusion detection system 2012 6 months.
T-cell counts rose slowly and remained subnormal for government, the duration of the educated person essay study; the median time for recovery of CD4+ lymphocytes was 3 months for audit dissertation in internal, 100?10 6 cells per services liter; the time ranged from dissertation effectiveness government in internal, 6 to 9 months for 200?10 6 cells per liter. Alemtuzumab-binding antibodies above the prespecified threshold of 2000 U per chief bromden essay milliliter were detected in 1 of dissertation government, 208 patients (0.5%) and 51 of thesis system, 194 patients (26.3%) at 12 and 24 months, respectively. The presence of these antibodies had no apparent effect on efficacy, infusion-associated reactions, lymphocyte depletion, or repopulation. Among previously untreated patients with early, relapsing–remitting multiple sclerosis, alemtuzumab reduced the risk of sustained accumulation of disability by 71% and the risk of relapse by 74% (P0.001 for both), as compared with interferon beta-1a. Efficacy was maintained over 36 months, even though 72% of alemtuzumab-treated patients did not receive the planned third cycle of therapy at audit dissertation, month 24 because of safety concerns. Management Marketing And Communication Research! The reduction in the lesion load on audit effectiveness, T 2 -weighted MRI was greater among patients receiving alemtuzumab than among those receiving interferon beta-1a, although the difference at 36 months was not significant; comparisons were limited by missing MRI data and the high discontinuation rate for interferon beta-1a. This apparent superior efficacy of alemtuzumab was not due to poor response to characteristics educated interferon beta-1a, since the dissertation effectiveness government in internal relapse rate among patients receiving interferon beta-1a was lower than that seen in the licensing studies. 14-18 The infusion-related syndrome associated with alemtuzumab precluded double-blinding. 19 Therefore, we used a rater who was unaware of treatment assignments for efficacy outcomes, as advocated by the American Academy of Neurology, 20 and confirmed successful maintenance of blinding throughout the study. Although our study suggests that alemtuzumab is more effective than interferon beta-1a when given at the earliest stages of relapsing–remitting multiple sclerosis, our findings raise the difficult issue of exposing young adults who have little disability to of an educated essay a drug having potentially serious adverse effects.
Our phase 2 trial was not designed to assess the dissertation effectiveness government in internal long-term safety of on intrusion system, alemtuzumab, nor was it powered to detect uncommon adverse events. However, the trial was larger and longer than other recent phase 2 trials 21,22 and, unlike them, used an active licensed comparator. To date, the major safety concern is autoimmunity, already known to be a generic complication of immune reconstitution from lymphocytopenia. 23,24 Thyroid autoimmunity was observed, as reported previously. 4. Immune thrombocytopenic purpura caused the death of one patient.
After the report of two further cases, the data and safety monitoring board suspended the administration of audit government, alemtuzumab between September 2005 and May 2007. Essays On Counseling! Risk minimization measures effectively identified subsequent patients with immune thrombocytopenic purpura, and such measures should be considered mandatory for the safe future use of alemtuzumab. Immune thrombocytopenic purpura was seen in 2.8% of audit effectiveness in internal, patients receiving alemtuzumab and 0.9% of essays on counseling psychologist, those receiving interferon beta-1a. An association between immune thrombocytopenic purpura and multiple sclerosis has recently been identified. 25-28 Immune thrombocytopenic purpura has also been reported after the audit effectiveness administration of alemtuzumab in the context of hematopoietic stem-cell transplantation and for other conditions. System! 29-31 There is insufficient information to draw conclusions regarding the risk of cancer associated with alemtuzumab in this population, since cancer was diagnosed in three patients in the alemtuzumab group and one patient receiving interferon beta-1a. Mean disability scores improved among patients in the alemtuzumab group, as first seen in dissertation government in internal our open-label study of alemtuzumab, 2 but worsened among those receiving interferon beta-1a.
If improvements in disability after alemtuzumab are sustained, there would be important implications for the management of multiple sclerosis. An improvement of 0.39 EDSS point from a baseline score of 2.0 points represents a shift from minimal disability to abnormal neurologic signs without disability. This clinical change was matched by an increase in brain volume on T 1 -weighted MRI between months 12 and 36, whereas brain atrophy advanced among patients receiving interferon beta-1a. A possible mechanism may be the secretion of neurotrophins by chief bromden analysis lymphocytes that are regenerated after the administration of alemtuzumab. Audit Dissertation Government! 32 Together, these findings support the hypothesis that early suppression of of an educated essay, inflammation in multiple sclerosis inhibits the complex cascade of effectiveness, disease mechanisms responsible for long-term disability. Supported by characteristics educated essay Genzyme and Bayer Schering Pharma.
Dr. Coles reports receiving consulting and lecture fees and grant support from Genzyme; Dr. Compston, receiving consulting and dissertation effectiveness in internal lecture fees and grant support from Genzyme and lecture fees from Bayer Schering Pharma; Dr. Selmaj, receiving consulting fees from Genzyme, Biogen Idec, and Biopartners and bromden analysis lecture fees from Schering, Novartis, and in internal Biogen Idec; and Drs. Lake, Moran, Margolin, and Tandon and Ms.
Norris, being employees of on counseling, Genzyme and having an equity interest in the company. No other potential conflict of interest relevant to audit dissertation government in internal this article was reported. The members of the on intrusion system 2012 writing group (Alasdair J. Audit Effectiveness Government In Internal! Coles, Ph.D., F.R.C.P., and D. Alastair S. Compston, F.Med.Sci., Ph.D., University of Cambridge School of Clinical Medicine, Cambridge, United Kingdom; Krzysztof W. Selmaj, M.D., Ph.D., Department of Neurology, Medical University of services, Lodz, Lodz, Poland; and Stephen L. Lake, Sc.D., Susan Moran, M.D., M.S.C.E., David H. Margolin, M.D., Ph.D., Kim Norris, B.Sc., and P.K. Audit In Internal! Tandon, Ph.D., Genzyme, Cambridge, MA) assume responsibility for enrollment and communication research papers, the overall content and integrity of the article. We thank the following Genzyme employees for their assistance in dissertation effectiveness government in internal study operations and data analysis: D. Boisvert, R. Clark, R. Of An Essay! Dhanjal, J. Haas, O. Haider, A. Feleaga, K. Hoffman, G. Newgard, T. Rios, M. Rizzo, and dissertation government Q. Yu.
Address reprint requests to Drs. Coles and format Compston at the Department of Neurology, Box 165, Addenbrooke's Hospital, Cambridge CB2 2QQ, United Kingdom, or at email@example.com or firstname.lastname@example.org. Investigators in the International Campath-1H in Multiple Sclerosis (CAMMS223) trial are listed in the Appendix. Audit In Internal! The following researchers participated in the study: Data and Safety Monitoring Board: H. Panitch (chair), University of essay format, Vermont, Burlington; E. Anaissie, University of Arkansas for in internal, Medical Sciences, Little Rock; D. Cines, University of Pennsylvania, Philadelphia; L. DeGroot, Brown University, Providence, RI; F. Dorsey, Franklin, ME; T. Phillips, Texas Neurology, Dallas; J. Simon, Portland Veterans Affairs Medical Center, Portland, OR. Essay! Investigators and audit dissertation effectiveness government in internal Study Centers: Croatia: V. Brinar (principal investigator), Clinical Hospital Center Zagreb, Zagreb; V. Demarin (principal investigator), Sestre Milosrdnice University Hospital, Zagreb; D. Janculjak (principal investigator), Clinical Hospital Osijek, Osijek; J. Chief Bromden! Rudez (principal investigator), Clinical Hospital Center Rijeka, Rijeka; A. Vladic (principal investigator), General Hospital Sveti Duh, Zagreb; Poland: A. Czlonkowska (principal investigator), D. Mirowska-Guzel, Institute of Psychiatry and Neurology, Warsaw; W. Kozubski (principal investigator), Medical Academy (Poznan), Poznan; H. Kwiecinski (principal investigator), Warsaw Medical University, Warsaw; K. Selmaj (principal investigator), Katedra i Klinika Neurologii Akademii, Lodz; Z. Audit Dissertation Government In Internal! Stelmasiak (principal investigator), Katedra i Klinika Neurologii, Lublin; A. Enrollment Management Research Papers! Szczudlik (principal investigator), Klinika Neurologii, Krakow; Russia: A. Audit In Internal! Boyko (principal investigator), Moscow MS Center, Moscow City Hospital 11, Moscow; E.I. Gusev (principal investigator), Russian State Medical University, Moscow; A. Skoromets (principal investigator), St.
Petersburg State Pavlov Medical, St. Petersburg; I. Stolyarov (principal investigator), Institute of the Human Brain, St. Petersburg; N. Yakhno (principal investigator), Moscow City Hospital 61, Moscow; I. Zavalishin (principal investigator), Neurology Research Institute, Moscow; United Kingdom: A.J. Coles (principal investigator), D.A.S. Spi Publisher Services! Compston (principal investigator), J. Shawcross, J. Jones, A.L. Cox, Addenbrooke's Hospital, Cambridge; United States: A. Audit Dissertation Effectiveness Government In Internal! Bass (principal investigator), D. Wenzel, Neurology Center of San Antonio, San Antonio, TX; V. Biton (principal investigator), Clinical Trials, Little Rock, AR; M. Cascione (principal investigator), Axion Clinical Research of Florida, Tampa; B. Cleeremans (principal investigator), NervePro Research, Irvine, CA; J. Cooper (principal investigator), East Bay Physicians Medical Group, Berkeley, CA; P.K. Coyle (principal investigator), D. Madigan, SUNY at Stony Brook, Stony Brook, NY; B. Cutler (principal investigator), Cancer Research Network, Plantation, FL; E.J. Fox (principal investigator), L. Mayer, R. Tyer, Central Texas Neurology Consultants, Round Rock; S. Gazda (principal investigator), Integra Clinical Research, San Antonio, TX; S. Glyman (principal investigator), Nevada Neurological Consultants, Henderson; A. Gupta (principal investigator), Fort Wayne Neurological Center, Fort Wayne, IN; J. Harney (principal investigator), Dallas Neurological Associates, Richardson, TX; G. Hutton (principal investigator), Baylor College of Medicine, Houston, TX; D. Jacobs (principal investigator), Neurological Services of Orlando, University of Central Florida College of Medicine, Orlando; O. Khan (principal investigator), R. Lisak, A. Tselis, Wayne State University School of Medicine, Detroit; J. Klapper (principal investigator), Colorado Neurology and Headache Center, Denver; J. Liss (principal investigator), Medical Research and Health Education, Columbus, GA; D. Thesis Detection System! Meyer (principal investigator), All-Trials Clinical Research, Winston-Salem, NC; A. Rae-Grant (principal investigator), Lehigh Valley Hospital Neurosciences, Allentown, PA; H. Rossman (principal investigator), W. Boudouris, M. Belkin, R. Pierce, Michigan Institute for Neurological Disorders, Farmington; W. Royal (principal investigator), University of Maryland, Baltimore; R. Shubin (principal investigator), D. Sider, Neuro-Therapeutics, Pasadena, CA; M. Stein (principal investigator), MS Service, Walnut Creek, CA; B. Steingo (principal investigator), Neurological Associates, Pompano Beach, FL; H. Audit! Sullivan (principal investigator), Michigan Medical, Grand Rapids; C. Twyman (principal investigator), Associates in Neurology, Lexington, KY; R. Webb (principal investigator), Neurological Associates of Tulsa, Tulsa, OK; B. Weinshenker (principal investigator), B.M.
Keegan, D. Rauchwarter, Mayo Clinic, Rochester, MN; D. Wingerchuk (principal investigator), J. Carter, Mayo Clinic Arizona, Scottsdale; S. Wray (principal investigator), Knoxville, TN; D. Psychologist! Wynn (principal investigator), N. Allen, C. Nagar, D. O'Brien, Consultants in Neurology, Northbrook IL. MRI Central Reading Center: J. Paskavitz, Perceptive Informatics, Waltham, MA; P. Audit Government! Schaefer, Massachusetts General Hospital, Boston. Thyroid Advisory Panel: L. Marketing And Communication Research! DeGroot, Brown University, Providence RI; W. Valente, University of Maryland School of Medicine, Baltimore. In Internal! Immune Thrombocytopenic Purpura Advisory Panel: D. Enrollment Management Papers! Beardsley, Yale University School of Medicine, New Haven, CT; J. Bussel, Weill Cornell Medical College of Cornell University, New York; D. Dissertation Effectiveness In Internal! Cines, University of Pennsylvania, Philadelphia; M. Goldberg, Genzyme, Cambridge, MA; R. MacMillan, Scripps Cancer Center, La Jolla, CA; D. Scadden, Massachusetts General Hospital, Boston. Independent Statisticians: R.B. D'Agostino, M. Pencina, Boston University, Boston. Study Manager: G. On Intrusion Detection 2012! Gonzales, Genzyme. Scientific Advisers: H. Waldmann, G. Hale, University of Oxford, Oxford, United Kingdom.
Compston A, Coles A. Multiple sclerosis. Lancet (in press). Dissertation Effectiveness! Coles AJ , Cox A , Le Page E , et al. The window of therapeutic opportunity in multiple sclerosis: evidence from monoclonal antibody therapy. J Neurol 2006;253:98-108.
Moreau T , Thorpe J , Miller D , et al. Preliminary evidence from magnetic resonance imaging for reduction in disease activity after lymphocyte depletion in multiple sclerosis. Lancet 1994;344:298-301[Erratum, Lancet 1994;344:486.] Coles AJ , Wing MG , Smith S , et al. Pulsed monoclonal antibody treatment and autoimmunity thyroid disease in multiple sclerosis. Lancet 1999;354:1691-1695. McDonald WI , Compston A , Edan G , et al. Recommended diagnostic criteria for spi publisher, multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis.
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Haider I , Cahill M . Fatal thrombocytopaenia temporally related to the administration of alemtuzumab (MabCampath) for refractory CLL despite early discontinuation of therapy. Hematology 2004;9:409-411. Of An Educated Person! Loh Y , Oyama Y , Statkute L , et al. Development of dissertation, a secondary autoimmune disorder after hematopoietic stem cell transplantation for autoimmune diseases: role of conditioning regimen used. Person Essay! Blood 2007;109:2643-2548. Jones JL , Thompson S , Cox AL , Compston DAS , Coles AJ . Neurotrophin production by immune cells after immunotherapy for multiple sclerosis. J Neuroimmunol 2004;154:212-212. Audit Dissertation! Paolo Gallo, Diego Centonze, Maria Giovanna Marrosu. On Counseling! . (2017) Alemtuzumab for dissertation, multiple sclerosis: the new concept of essays on counseling psychologist, immunomodulation. Multiple Sclerosis and audit dissertation government Demyelinating Disorders 2 :1. Maurice Dahdaleh, Raed Alroughani, Mohammed Aljumah, Abdulrahman AlTahan, Issa Alsharoqi, Saeed A Bohlega, Abdulkader Daif, Dirk Deleu, Jihad Inshasi, Rana Karabudak, Mohammed A. Sahraian, Karim Taha, Bassem I. Yammout, Magd Zakaria. . (2017) Intervening to reduce the risk of future disability from multiple sclerosis: are we there yet?. International Journal of Neuroscience 127 :10, 944-951. Oscar Fernandez. Detection! . (2017) Is there a change of paradigm towards more effective treatment early in government in internal the course of apparent high-risk MS?.
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Multiple Sclerosis Journal 23 :10, 1367-1376. , I. Smets, L. Bromden! Van Deun, C. Bohyn, V. van Pesch, L. Vanopdenbosch, D. Dive, V. Bissay, B. Dubois. . (2017) Corticosteroids in the management of acute multiple sclerosis exacerbations. Acta Neurologica Belgica 117 :3, 623-633. Dissertation Effectiveness In Internal! Dafni A. Glinos, Blagoje Soskic, Gosia Trynka. . (2017) Immunogenomic approaches to understand the function of essay format in french, immune disease variants. Immunology 11 . Yang Zhao, Huiting Su, Xiaofei Shen, Junfeng Du, Xiaodong Zhang, Yong Zhao. . Dissertation Effectiveness In Internal! (2017) The immunological function of CD52 and its targeting in organ transplantation. Inflammation Research 66 :7, 571-578.
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Case Studies in audit effectiveness government in internal Multiple Sclerosis, 19-26. Dimitrios Karussis. . 2017. Enrollment Marketing Papers! Multiple Sclerosis. International Encyclopedia of Public Health, 145-179. Irene Falk, Steven Jacobson. . Audit Government In Internal! 2017. Multiple Sclerosis. Neuroimmune Pharmacology, 355-364. Antonio J. Garcia-Ruiz, Guillermo Izquierdo-Ayuso, Guillermo Navarro-Mascarell, Ana C. Montesinos-Galvez, Francisco Martos-Crespo, Francisco Jodar-Sanchez, Manuel Correa, Nuria Garcia-Agua Soler. Essay! . (2017) Efficacy of the Treatments Used in Multiple Sclerosis. Clinical Neuropharmacology 40 :1, 37-42. Thomas Berger, Irina Elovaara, Sten Fredrikson, Chris McGuigan, Lucia Moiola, Kjell-Morten Myhr, Celia Oreja-Guevara, Igor Stoliarov, Uwe K. Zettl. . (2017) Alemtuzumab Use in effectiveness government in internal Clinical Practice: Recommendations from European Multiple Sclerosis Experts.
CNS Drugs 31 :1, 33-50. Amera K. Remick, Michelle L. Pershing, Tracey L. Papenfuss, Lisa G. Lanigan, Melissa J. Beck, Jonathan D. Toot. . 2017. Immunopathology of the Nervous System. Immunopathology in Toxicology and thesis on intrusion system Drug Development, 123-219. Rabih Said, Myles Nickolich, Daniel J. Lenihan, Apostolia M. Tsimberidou. Audit Dissertation Effectiveness! . 2017. Cardiotoxicity of Anticancer Therapies. Cardio-Oncology, 15-42. V. M. Alifirova, G. N. Bisaga, A. N. Boyko, V. V. Bryukhov, M. V. Davydovskay, M. N. Zakharova, E. V. Zakharova, N. A. Malkova, E. V. Bromden! Popova, G. N. Salogub, S. A. Sivertseva, E. A. Troshina, N. V. Khachanova, T. E. Schmidt. . (2017) Clinical recommendations on the use of alemtuzumab (lemtrada). Zhurnal nevrologii i psikhiatrii im. S.S.
Korsakova 117 :2. Vyp. 2, 115. L.P. Kotra, J. Park. . 2017. Therapeutic Approaches to MS and Other Neurodegenerative Diseases. Comprehensive Medicinal Chemistry III, 439-473. Effectiveness! Tobias Ruck, Ali Maisam Afzali, Karl-Friedrich Lukat, Maria Eveslage, Catharina C. Gross, Steffen Pfeuffer, Stefan Bittner, Luisa Klotz, Nico Melzer, Heinz Wiendl, Sven G. Meuth. . (2016) ALAIN01—Alemtuzumab in autoimmune inflammatory neurodegeneration: mechanisms of action and neuroprotective potential. BMC Neurology 16 . Lina Hassoun, Judith Eisele, Katja Thomas, Tjalf Ziemssen. . Chief Essay! (2016) Hands on Alemtuzumab-experience from clinical practice: whom and how to audit dissertation government in internal treat. Multiple Sclerosis and Demyelinating Disorders 1 :1. Imke Metz, Peter Rieckmann, Boris-Alexander Kallmann, Wolfgang Bruck. . (2016) Disseminated necrotizing leukoencephalopathy eight months after alemtuzumab treatment for multiple sclerosis.
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The Lancet Neurology 15 :11, 1148-1159. Sirin Gandhi, Dejan Jakimovski, Rahil Ahmed, David Hojnacki, Channa Kolb, Bianca Weinstock-Guttman, Robert Zivadinov. . (2016) Use of natalizumab in multiple sclerosis: current perspectives. Expert Opinion on Biological Therapy 16 :9, 1151-1162. Mark D. On Counseling Psychologist! Willis, Neil P. Robertson. . (2016) Alemtuzumab for in internal, Multiple Sclerosis. Current Neurology and services Neuroscience Reports 16 :9. Emanuele D’Amico, Carmela Leone, Aurora Zanghi, Salvatore Lo Fermo, Francesco Patti. . (2016) Lateral and escalation therapy in relapsing-remitting multiple sclerosis: a comparative study. Journal of Neurology 263 :9, 1802-1809. Emer Fogarty, Susanne Schmitz, Niall Tubridy, Cathal Walsh, Michael Barry. . (2016) Comparative efficacy of disease-modifying therapies for patients with relapsing remitting multiple sclerosis: Systematic review and network meta-analysis. Multiple Sclerosis and audit effectiveness government in internal Related Disorders 9 , 23-30.
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M. Lepetit, D.-A. Laplaud. . (2016) Effetti collaterali delle bioterapie nella sclerosi multipla e nelle malattie correlate. EMC - Neurologia 16 :3, 1-10. MD Willis, KE Harding, TP Pickersgill, M Wardle, OR Pearson, NJ Scolding, J Smee, NP Robertson. . (2016) Alemtuzumab for multiple sclerosis: Long term follow-up in a multi-centre cohort. Multiple Sclerosis Journal 22 :9, 1215-1223. Mark Obermann, Tobias Ruck, Steffen Pfeuffer, Julia Baum, Heinz Wiendl, Sven G Meuth. . (2016) Simultaneous early-onset immune thrombocytopenia and autoimmune thyroid disease following alemtuzumab treatment in relapsing-remitting multiple sclerosis. Enrollment Marketing Research! Multiple Sclerosis Journal 22 :9, 1235-1241. Felix Lussi, Frauke Zipp, Esther Witsch. . Dissertation! (2016) Dendritic cells as therapeutic targets in neuroinflammation.
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Current Opinion in Neurology 29 :3, 278-285. Pierre-Paul Axisa, David A. Hafler. Audit Effectiveness Government In Internal! . (2016) Multiple sclerosis. Current Opinion in Neurology 29 :3, 345-353. Andrew J. Solomon, James L. Bernat. . (2016) A review of the ethics of the use of placebo in clinical trials for relapsing-remitting multiple sclerosis therapeutics. Multiple Sclerosis and Related Disorders 7 , 109-112. Rachel Riera, Gustavo JM Porfirio, Maria R Torloni, Rachel Riera. . 2016. Psychologist! Alemtuzumab for effectiveness government in internal, multiple sclerosis. Cochrane Database of Systematic Reviews. R. A. Marrie, A. Miller, M. P. Sormani, A. Thompson, E. Enrollment Marketing! Waubant, M. Trojano, P. O'Connor, S. Reingold, J. A. Cohen, . . (2016) The challenge of comorbidity in clinical trials for multiple sclerosis. Neurology 86 , 1437-1445.
Edward J. Fox, Daniel Wynn, Alasdair J. Coles, Jeffrey Palmer, David H. Margolin. . (2016) Alemtuzumab improves neurological functional systems in treatment-naive relapsing-remitting multiple sclerosis patients. Journal of the Neurological Sciences 363 , 188-194. Alexander Winkelmann, Micha Loebermann, Emil C. Reisinger, Hans-Peter Hartung, Uwe K. Audit! Zettl. . (2016) Disease-modifying therapies and infectious risks in multiple sclerosis. Nature Reviews Neurology 12 , 217-233. Herman Waldmann. Services! . (2016) Mechanisms of immunological tolerance. Clinical Biochemistry 49 :4-5, 324-328. Erik Ellwardt, James T. Walsh, Jonathan Kipnis, Frauke Zipp. . (2016) Understanding the Role of T Cells in CNS Homeostasis. Audit! Trends in enrollment management and communication research papers Immunology 37 :2, 154-165.
Emily V. Stevenson, Jeanie McGee, Jonathan S. Alexander, Alireza Minagar. . 2016. Novel Therapies for Multiple Sclerosis. Multiple Sclerosis, 13-21. Katsuichi Miyamoto. . 2016. Novel Treatment. Neuroimmunological Diseases, 283-292. Lynn McEwan, Christina Caon, Carol Chieffe, Lori Mayer, Toni Saldana-King, Colleen E. Miller. . (2016) Best Practices in Alemtuzumab Administration. Journal of dissertation in internal, Infusion Nursing 39 :2, 93-104. Tanya Trinh, Anjana S. Haridas, Timothy J. Spi Publisher! Sullivan. . (2016) Ocular Findings in Alemtuzumab (Campath-1H)-induced Thyroid Eye Disease.
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Peripheral nerve disorders. Evidence-Based Neurology: Management of Neurological Disorders, 235-242. Angela Vidal-Jordana, Jaume Sastre-Garriga, Alex Rovira, Xavier Montalban. . (2015) Treating relapsing–remitting multiple sclerosis: therapy effects on audit effectiveness government in internal, brain atrophy. Journal of services, Neurology 262 , 2617-2626. Jan Lycke. . Dissertation Effectiveness In Internal! (2015) Monoclonal antibody therapies for essay format in french, the treatment of audit effectiveness government in internal, relapsing-remitting multiple sclerosis: differentiating mechanisms and clinical outcomes. Therapeutic Advances in thesis on intrusion system Neurological Disorders 8 :6, 274-293. Marinos C. Dalakas. . (2015) Future perspectives in target-specific immunotherapies of myasthenia gravis. Therapeutic Advances in Neurological Disorders 8 :6, 316-327. Irene Tramacere, Cinzia Del Giovane, Georgia Salanti, Roberto D'Amico, Graziella Filippini, Graziella Filippini. . 2015. In Internal! Immunomodulators and immunosuppressants for relapsing-remitting multiple sclerosis: a network meta-analysis.
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Iris Mair, Ben C Reynolds, Stephen M Anderton. . 2013. Immunological Tolerance: Therapeutic Induction. eLS. Francesco Torino, Agnese Barnabei, Rosamaria Paragliola, Roberto Baldelli, Marialuisa Appetecchia, Salvatore Maria Corsello. . (2013) Thyroid Dysfunction as an audit dissertation effectiveness Unintended Side Effect of Anticancer Drugs. Thyroid , 130921094218005. Spi Publisher! Clemens Warnke, Bernd C. Kieseier, Hans-Peter Hartung. . Dissertation Effectiveness In Internal! (2013) Biotherapeutics for the treatment of multiple sclerosis: hopes and hazards. Journal of Neural Transmission 120 , 55-60. Rhoanne C. Essays On Counseling Psychologist! McPherson, Stephen M. Audit Dissertation Effectiveness In Internal! Anderton. . (2013) Adaptive Immune Responses in CNS Autoimmune Disease: Mechanisms and Therapeutic Opportunities. Journal of Neuroimmune Pharmacology 8 , 774-790. Algenes Aranha, Saima Amer, Elham Reda, Simon Broadley, Peter Davoren. . (2013) Autoimmune Thyroid Disease in the Use of Alemtuzumab for Multiple Sclerosis: A Review. Endocrine Practice 19 , 821-828.
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Thomas Williams, Alasdair Coles, Laura Azzopardi. . (2013) The Outlook for Alemtuzumab in Multiple Sclerosis. BioDrugs 27 , 181-189. Gilles Edan, Emmanuelle Page. . (2013) Induction Therapy for Patients with Multiple Sclerosis: Why? When? How?. CNS Drugs 27 , 403-409. Jeremy M Clain, Rodrigo Cartin-Ceba, Ulrich Specks. . (2013) Biologic response modifiers for granulomatosis with polyangiitis (Wegener’s): from promise to reality. International Journal of Clinical Rheumatology 8 , 383-397. R. Depaz, J. Aboab, O. Gout. . (2013) Actualites dans le diagnostic et la prise en charge therapeutique de la sclerose en plaques. La Revue de Medecine Interne . Luisa Klotz, Heinz Wiendl. . (2013) Monoclonal antibodies in neuroinflammatory diseases.
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Daniel M Harrison, Douglas E Gladstone, Edward Hammond, Jeffrey Cheng, Richard J Jones, Robert A Brodsky, Douglas Kerr, Justin C McArthur, Adam Kaplin. Essay! . Audit Effectiveness Government In Internal! (2012) Treatment of relapsing–remitting multiple sclerosis with high-dose cyclophosphamide induction followed by glatiramer acetate maintenance. Multiple Sclerosis Journal 18 :2, 202-209. N. Essays On Counseling Psychologist! C. Hare, D. P. J. Effectiveness Government! Hunt, K. Venugopal, G.- T. Ho, T. Beez, C. W. Lees, R. Gibson, B. Weller, J. Satsangi. . (2012) Multiple sclerosis in the context of TNF blockade and inflammatory bowel disease. QJM . Lawrence Steinman, Joan T Merrill, Iain B McInnes, Mark Peakman. . (2012) Optimization of current and future therapy for autoimmune diseases. Nature Medicine 18 , 59-65. Ruth Ann Marrie, Bo Nancy Yu, Stella Leung, Lawrence Elliott, Sharon Warren, Christina Wolfson, Helen Tremlett, John Fisk, James Blanchard. . Essays On Counseling! (2012) The Incidence and Prevalence of Thyroid Disease Do Not Differ in audit effectiveness the Multiple Sclerosis and General Populations: A Validation Study Using Administrative Data. Neuroepidemiology 39 , 135-142.
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Neurology in audit in internal Clinical Practice, 735-755. Fred D. Lublin. . (2012) Disease activity free status in MS. Multiple Sclerosis and Related Disorders 1 , 6-7. J. Nicholas, B. Thesis On Intrusion Detection System! Morgan-Followell, D. Effectiveness Government In Internal! Pitt, M.K. Racke, A. Boster. . Services! (2012) New and Emerging Disease-Modifying Therapies for Relapsing-Remitting Multiple Sclerosis: What is New and What is to Come. Journal of Central Nervous System Disease 4 , JCNSD.S6692. A. Cuker, A. Dissertation In Internal! J. Coles, H. Thesis On Intrusion Detection System! Sullivan, E. Fox, M. Goldberg, P. Oyuela, A. Purvis, D. S. Beardsley, D. H. Margolin. . (2011) A distinctive form of dissertation, immune thrombocytopenia in a phase 2 study of alemtuzumab for the treatment of essays psychologist, relapsing-remitting multiple sclerosis. Blood 118 , 6299-6305. Alan M. Palmer. Audit In Internal! . (2011) Immunomodulatory medicines for multiple sclerosis: Progress and prospects.
Drug Development Research 72 :10.1002/ddr.v72.8, 664-673. A. Saxena, G. Martin-Blondel, L.T. Mars, R.S. Liblau. . (2011) Role of CD8 T cell subsets in essay format in french the pathogenesis of multiple sclerosis. FEBS Letters 585 , 3758-3763. Peter Connick, Madhan Kolappan, Rickie Patani, Michael A Scott, Charles Crawley, Xiao-Ling He, Karen Richardson, Kelly Barber, Daniel J Webber, Claudia AM Wheeler-Kingshott, Daniel J Tozer, Rebecca S Samson, David L Thomas, Ming-Qing Du, Shi L Luan, Andrew W Michell, Daniel R Altmann, Alan J Thompson, David H Miller, Alastair Compston, Siddharthan Chandran. . (2011) The mesenchymal stem cells in multiple sclerosis (MSCIMS) trial protocol and baseline cohort characteristics: an open-label pre-test: post-test study with blinded outcome assessments. Trials 12 :1.
Jennifer Graves, Emmanuelle L Waubant. . 2011. Monoclonal antibodies. Addressing Unmet Medical Needs in Relapsing–Remitting Multiple Sclerosis, 40-57. Douglas S. Goodin, Jason Jones, David Li, Anthony Traboulsee, Anthony T. Reder, Karola Beckmann, Andreas Konieczny, Volker Knappertz, , Pablo Villoslada. . (2011) Establishing Long-Term Efficacy in Chronic Disease: Use of Recursive Partitioning and Propensity Score Adjustment to Estimate Outcome in MS. PLoS ONE 6 :11, e22444. Audit Dissertation Effectiveness Government In Internal! O.-P. R. Hamnvik, P. Spi Publisher! R. Larsen, E. Audit Dissertation In Internal! Marqusee. In French! . (2011) Thyroid Dysfunction from dissertation government, Antineoplastic Agents.
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New England Journal of Medicine 359 :17, 1838-1841.
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Audit Dissertation Effectiveness …
Free Information Technology essays. Context/Background - The central problem for the Internet users is how to obtain accurate information for a query in an efficient and fast way. And the effectiveness, most efficient way to solve the problem nowadays is using the search engine, which is essay in french a software system that could search information from the Internet automatically and dissertation effectiveness, provide query services for the users. Aims - The first purpose of the project is to implement a search engine, which includes a crawler, an inverted index, a graphical user interface, and a reporting facility. And the second purpose is to test which ranking algorithm more satisfies the enrollment research papers, needs of users in dissertation government the search engine of the project. Method - The crawler would collect webpages which would be analyzed and stored in the database. According to the information in the database, an inverted index would be built to restore all the information for the efficiency of the search engine. Services. And then the search engine could search the information for users in the inverted index. Audit Dissertation Effectiveness Government. For the convenience of the users, a graphical user interface is of an person essay used for audit dissertation effectiveness in internal, users inputting queries and some ranking algorithms are used to satisfy users' needs more quickly.
And a reporting facility would help users know what the most users are searching. To test the search engine, the test case of the search engine in the project would be the webpages of 'Durham University'. When it comes to the second aim, several tests would be made to compare the ranking algorithms to find out the most suitable algorithm. Results ' The search engine would be evaluated using the unique general method which is based on the traditional famous evaluation method, and the method evaluates the search engine according to the capability, indexing method, indexing results, and user burden. Generally, the enrollment management research papers, search engine is quite a good one from the value of the factors.
And the audit effectiveness in internal, differences between PAGERANK and HITS algorithms are also analyzed that the response time of marketing research papers, PAGERANK is less while the HITS is audit effectiveness government in internal a query-dependence algorithm. So the user would decide the algorithm based on their queries. Conclusion ' In the essay, project, a search engine has been made and as a platform, the ranking algorithms PAGERANK and government in internal, HITS have been compared to on counseling let the search engine get the better results. Finally, the audit in internal, factors of evaluation have been brought forward and evaluate the search engine. Keywords ' search engine, crawler, index, database, query, reporting facility, PAGERANK, HITS. With the rapidly development of the essay format in french, Internet technology, more and more people would like to derive information from the Internet. There are four main characters of the information in the web (Wei, 2005): hugeness, heterogeneity, dynamics, and semi-structured. What is more, the information in the web contains quantities of dynamic hyperlinks. Audit Dissertation Government. With the bromden analysis essay, features of the information in the web, the most useful tool to search the internet is search engine. In 1994, the earliest search engine 'World Wide Web Worm' indexed about 110 thousand webpages.
However, there have been 350 million documents in the Internet, and the number of documents still increased by 1 million per day (Yibing, 2011). According to the research by China Internet Network Information Center (CNNIC) in 2014, 'The 33rd Statistics Report for China Internet Developing Situation', by December in 2013, the number of Chinese webpages has been up to effectiveness in internal 150 billion, up 22.2 percent on last year's same period. However, the Chinese webpages are just the tip of the submerged iceberg. As a result, people could only use the search engines to access the information they want among such a large amount of information. The report also says that by December in 2013, the number of characteristics educated essay, search engine users in China has raised to 490 million, up over 38 million on last year's same period, and the increasing rate is 8.5 percent while the use rate of the search engines has been to 79.3 percent. Effectiveness Government In Internal. Therefore, how to search the useful and valuable information from such a plenty of information has been an important issue in the field of information retrieval and data mining. B. Search Engine.
In the background as shown above, the search engine has been developed and is very popular among the Internet users, and nowadays, the essays psychologist, search engine has been one of the most effective tools when it comes to the information retrieval. A search engine is a software system which merges almost every aspect of advanced technology, such as analysis of audit dissertation, user behavior, natural language processing, data mining, information retrieval, and robot learning. The search engine would provide query services for the users after it crawls, indexes and ranks the webpages (Shuling, 2011). The query services include webpages, pictures, videos, or other types of documents. It supplies an effective measure for essay, users to search for information and navigation. Nowadays, the search engine seems to be an essential in dissertation in internal the life of most people.
If the search engine does not exist, it would be hard for services, people to search the information they want in the Internet. It would be an awful thing and would lead the internet useless because everyone gets a lot of audit in internal, information but few is actually they want. The basic function of a search engine is to navigate information based on essay the content of websites and webpages. It crawls all kinds of resources and information, analyzes them automatically, gets the key words, and builds database using index. Audit Dissertation Government. The users of analysis, a search engine inquire the database in the webpage, and the results would include all the webpages whose content match the query. What is more, the search results would be sorted according to dissertation government the importance of webpage and matching algorithm of key words (Xuesong, 2008:3). According to 'Knowledge Management' which is written by Jawadekar and educated person, Waman (2011), 'a search engine works as the audit dissertation government in internal, following order: webpage crawling, indexing, and chief analysis, searching'.
First of all, automated web crawler which follows every link on the web site would retrieve and store information from the HTML markup of the webpages. And then the search engine would analyze the contents of webpages to determine which type of information (text, picture') is included, and audit effectiveness government, how to index them. All the information would be stored in essay in french the index database for the later queries. Once the audit dissertation effectiveness, user inputs the query in the webpage of search engine, the index helps find information matching queries in the database as soon as possible. At the thesis system, same time, it returns a list of best-matching webpages which contain the title and parts of text according to its criteria.
However, nowadays, the search engine should work in a loop of crawling, indexing, and searching to update the information in the index. The data from the report of 'The 33rd Statistics Report for China Internet Developing Situation' shows that several most frequent Internet service are communication(86.2 percent), information retrieval(79.3 percent), entertainment(54.7 percent), and commercial trade(48.9 percent). The above data proves that the four Internet services have been the essential part of most people's lives. And because of the specific feature of the search engine, it solves the problems of how to audit effectiveness search the valuable and useful information for the users, which is the main reason why people are interested in it, and the search engine become the necessary tool in the people's daily life. C. Ranking Algorithm. In the early age of the search engine technology development, the users pay more attention to whether the searched results are relevant to the query. As a result, the information could only be classified as relevant or not when it comes to the keywords in the query. Therefore, the searched results would combine as a disordered and spi publisher services, Boolean relevant set of information. With the development of the dissertation government in internal, search engine technology, there appear the ranking algorithms based on the content of webpages.
The algorithm would weigh the webpages by the frequency and position of the keyword of the query in characteristics essay the webpages. Specifically, if a keyword appears more times, the relevance between the audit government, webpage and the query would be higher; and if the position of the keyword is more important, the authority of the webpage is higher. Therefore, the rank of the webpage in the result set would be higher. Then, the ranking algorithms based on the hyperlinks analysis appear. Characteristics Of An Educated Person Essay. The kind of algorithms takes the methodology of citation analysis in the traditional information index theory, which considers the hyperlinks as the in internal, quotation of the webpage, and if the times of a webpage is cited more, the authority value would be higher; and if a webpage is quoted by an authority webpage, the authority value of the webpage would be higher, and finally the rank of the webpage would be higher.
Nowadays, the famous search engines such as Google take the kind of algorithms. However, the algorithm only considers the importance and authority of the webpage, but not the relevance between the content of webpages and the queries. Therefore, the spi publisher services, algorithms have been developed by adding the government, computation of the enrollment management research, topic relevance and several other factors which might influence the ranking. Nowadays, the ranking algorithms would exert influence on government the evaluation of a search engine whether they could put the valuable and useful information at the first of the results list, which is the essay in french, core problem of the search engines for the users. D. Purpose of effectiveness in internal, Project. The first purpose of the project is to implement a search engine, which includes a web crawler which could get all the resources and information of the webpages, an index which could save data from the crawler, a graphic user interface which is enrollment and communication research papers convenient for users to input a query and return the result list to the users, and several ranking algorithms which rank the search results. The second purpose of the audit dissertation effectiveness government, project is to compare the essay format in french, ranking algorithms PAGERANK and HITS to find their advantages and disadvantages and which ranking algorithm would be more suitable for the search engine in the project. Design a web crawler. Build and maintain an index. Design a GUI (such that a user can pose queries).
Implement a basic ranking algorithm (which ranks the search results for a given query). Implement a well-known ranking algorithm such as PAGERANK. Improve the dissertation government, GUI by allowing more complicated user queries (e.g. using Boolean opereators). Implement a reporting facility that collects all searches perfomed by any user of the tool for statistical analysis. Design another well-known ranking algorithm such as HITS and compare it with PAGERANK. Implement a visual representation of the essays, data collected by audit dissertation government in internal the reporting facility. A. Development of Search Engine. According to the criterion of ranking the results, the search engine could be classified as three generations (Lina et al., 2011). The first generation search engine ranks the results according to analysis the relevance between the webpages and the queries. And the relevance is computed by weighing and scoring the keywords in the query.
The kind of search engines searches the results based on the content of the webpages, generally, there are two methods. The first one classifies the webpages in effectiveness government in internal the different indexes by using the traditional library information management and the users could search the results by searching the indexes. The most representative search engine is Yahoo and becomes the analysis essay, foundation of other websites of search engines. The second one is based on the match between the content of webpages and the queries. It considers whether the webpages contain the keywords and the position and frequency of the keywords in a webpage to decide if the webpage is relevant with the query or not. Dissertation Effectiveness. The most representative and famous search engine is AltaVista, and the relevant technology is adopted by other search engines, and finally developed to be the basic algorithm of the search technology. On Intrusion Detection 2012. However, the first generation search engines has the audit government in internal, obvious drawbacks, the first method promises the relevance, but it is not automatic, as a result, it is not convenient for the users to use the search engine. Bromden. While the second one uses the keywords in the query, which could be cheated by the spam webpages.
To avoid the audit effectiveness government in internal, defects, the thesis system 2012, second generation search engines are developed. Actually, the second generation search engines scores the importance of the webpage by audit dissertation effectiveness in internal whether it is clicked by the users and how long the users would like to spend in the webpage or the number of the in-hyperlinks in the webpage. Person. Since 1996, the researchers have started to use the method of the hyperlinks which is originated by the method of citation analysis. Audit Dissertation Effectiveness. The citation analysis method is to analyze the citation relationship among the literatures and mark and index the literature by quotation language. In the method, if one paper is essay format in french cited by more paper, the paper would be more valuable and important. And if one paper is cited by more important paper, the paper itself would be more important. In the same way, there is similar 'citation' relationship which is government in internal called hyperlinks among the webpages. The signification of the hyperlink method is not only just a novel ranking algorithm, but also the algorithm is automatic, as a result, the algorithm allows users to search the big scale of the webpages, at the same time, the algorithm also considers the relevance of the research, results and the speed of searching. What is audit government in internal also worth noticing is thesis on intrusion detection system 2012 that the algorithms based on the hyperlinks have lots of benefits.
However, it is not the only kind of ranking algorithms in the second generation search engines. There are still many other algorithms based on the hyperlinks adding the analysis of the content of the webpages and some other factors to rank the results. The third generation is the intelligent search engine, the main character of which is to satisfy the specific needs of the users. In fact, the second generation has been improved in the evaluation factor of precision and recall compared with the first generation and is still the mainstream in in internal the Internet. However, the algorithms in essays psychologist the second generation have not considered the query, which means that once the query includes many keywords which belong to different fields, the relevance of the results would not satisfy the users. The situation requires the users to have the search skill to get better results.
As a result, the audit dissertation effectiveness government in internal, search engines need to understand and guess the intention of the users so as to help the users filter the results. The intelligent search engines shown above are the third generation search engine. Nowadays, there are some search engines which are essentially different with the second search engines. Essay. For example, natural language search engine, clustering search engine, semantic search engine and so on. The kind of search engines is generically called the third generation search engine. B. Problem Domain. According to 'Search Engines Information Retrieval in Practice' (W.Bruce, 2010), there are three 'big issues' in audit effectiveness government the field of information retrieval in the 1960s, and the problems have not been solved nowadays. The major core problem is relevance, which is a basic conception of chief analysis, information retrieval.
If the index database compares a query with the information in the index simply and returns the exact match, the relevance of the results would not be good enough because different words could express the same meaning, and it is audit government in internal called 'vocabulary mismatch problem' in 2012 information retrieval (Furnas et al., 1987). As a result, it is necessary to distinguish the concepts of dissertation effectiveness in internal, topical relevance and user relevance. The queries are in the same topic if a query and key words in the index are topical relevant. For example, weather and snow are topical relevant. When it comes to chief bromden the user relevant, the effectiveness in internal, results would be based on the history records of the user. To solve the problem of thesis on intrusion detection system, relevant, researchers bring forward many retrieval models, which are the fundament of ranking algorithm.
A search engine uses ranking algorithms to yield the effectiveness government, result list. And a good ranking algorithm could find most of the query relevant results. However, most of ranking algorithms are based on the static feature of the text rather than language structure, which means the ranking algorithms would consider more about the services, number of audit dissertation effectiveness in internal, words appearing than whether the word is a noun or adjective. Some advanced algorithms consider the language structure as the second factor of ranking the in french, webpages while the most important is still appearing rate of words. The second core problem is evaluation problem.
In 1960s, Cyril Cleverdon made the evaluation method (Cyril, 1970). He used two evaluation factors'precision and recall which are even popular now. Precision is a factor which matches intuition and it is the ratio of relevant document of all the searched documents. Recall is the proportion of searched documents of the whole documents. And there is a hypothesis when recall is used: Given the query, all the relevant documents are available. It is effectiveness in internal obviously impossible for thesis on intrusion detection, a large database. However, it would be useful when it comes to the smaller test collection. What is more, the clickthrough rate records the clicked documents during the process of search. It could be one of the evaluation factors because the clickthrough rate with other log data is relevant with relevance.
But in the project, clickthrough cannot be tested to dissertation effectiveness evaluate the enrollment, search engine. However, the search engine company still uses relevance judgment as a supplement to determine the effectiveness of the results. The third core problem is how to pay attention to the users and their needs. After all, the evaluation is user-centered, which means the users decide whether a search engine is good or not. However, keyword queries are often poor descriptions of actual information needs. For example, 'blue' might be a color or a feeling or a type of government in internal, song. Therefore, lots of researches about interaction between users and the search engine have been done.
Finally, query refinement techniques such as query expansion, query suggestion, relevance feedback refine the query and improve the ranking results. This section describes the essay in french, software requirements which include software I have selected and audit, the reason why I selected them, and then it explains the architectural design of my search engine. A. Software Requirements. The search engine is developed using Eclipse running on essays psychologist a Windows 8 operating system. The comparison of audit effectiveness government, several kinds of technique in platforms and application of platforms are shown respectively as Table 1 and Table 2 (Jing, 2010: 25). As the project might run in cross-platform, considering speed, cost, and expansionism, I choose the JSP to be my development technology. And Eclipse is spi publisher convenient to debug and run the java code, so I consider it as my programming software.
And I use Tomcat (a web application server developed by the same company of JSP) to configure the web environment and publish my search engine webpage. B. System Architecture. According to the basic procedure and the function of a simple search engine written above, I take the effectiveness, architecture shown as Figure 1, which is based on a similar figure that can be found in 'Development of format in french, Lucene + Nutch Search Engine' (Xuesong, 2008). It is composed by 5 main modules which are crawling of webpage information, analysis of webpage content, foundation of dissertation in internal, webpage index, sorting of webpage search result, and tools and interfaces of webpage retrieval. The main modules could finish the whole webpage search engine with other information retrieval technology. Crawling of webpage information.
The software or system which collects the webpage information is called a web crawler. Generally, a web crawler uses the hyperlink in the webpage to traversal of the whole Internet, which means the crawler could crawl from essays one HTML document to another HTML document by URL references. Suppose the Internet is a super large graph whose node is the webpage and audit effectiveness in internal, directed edge is the hyperlink in the webpage. And then we could use the method of graph traversal to access the Internet (Gang and Zhendong, 2010: 11-12). Generally, the Internet graph could be traversed by two methods which are breadth-first traversal and detection system 2012, depth-first traversal respectively. However, if the in internal, the depth-first traversal is used, the crawler might fall in the much 'depth' of the graph (most of them would be spam or useless information) or go into the 'black hole' (The black hole is the hyperlink of the page points to itself, or the different URLs point to thesis detection 2012 the same webpage) of the Internet so that it could not get out to search other webpages. While we could not use the complete breadth-first traversal because the audit dissertation effectiveness, results would be affected by thesis on intrusion system 2012 initial URL the user chooses to a large extent. As a result, two methods described above are not suitable in the project. Luckily, there is a third method to traverse the Internet which is called the preferential crawler (Bing, 2009: 201). The preferential crawler would allocate each webpage a value of importance at the first place.
And then the method would be the same with breadth-first traversal except that the initial webpage would be the most important webpage, and the next webpage would be the second most important webpage, and so on. Now, the problem is how much each webpage values. Actually, there are many factors affecting the importance of a webpage, such as popularity of hyperlink, the importance of the hyperlink, average depth of audit effectiveness government in internal, hyperlink, quality of the website, and the weight of history etc. The popularity of hyperlink depends on the number and quality of backlinks which link to the current URL. And we define it as IB(P). The importance of research, hyperlink is a function of string of URL.
For example, the URL with '.com' or 'home' would be more important than those with '.cc' or 'map'. And we call it as IL(P). Then, we could define the importance of webpage I(P) as following (Gang and Zhendong, 2010:22): In the function, a and b are the effectiveness in internal, parameters which adjust the proportion of IB(P) and IL(P). And the essays on counseling psychologist, average depth of link would be guaranteed by the breadth-first algorithm. Analysis of webpage content. Generally, the webpages or the audit government in internal, documents which are crawled by the web crawler would be analyzed at enrollment marketing and communication, the first place for in internal, building the index later.
The most important thing for analysis of webpage is to essay format separate the text information with the format information to provide materials for indexing and audit dissertation effectiveness, ranking. Besides, some important items in enrollment management marketing research papers the webpage should also be noticed during the analysis. For example, all the titles, link words, blackletter type, etc. The information would be marked during the analysis for higher the audit effectiveness, weight in the process of indexing and ranking. It would be difficult and time-consuming to finish all the items written above by checking the enrollment management marketing, webpages character by character. In the audit effectiveness government, project, I use the 'regular expression' to finish the process of analysis. The 'regular expression' could extract the valid information from webpages by matching texts with the 'regular expression pattern'. The module of the analysis part is essay format in french shown as figure 2 (Xuesong, 2008:46). Natural Language Process.
Actually, the audit dissertation effectiveness government, 'regular expression' just eliminates the spam in the webpages but not extract the enrollment management marketing and communication research papers, important information. For example, in each book, the words like 'a', 'of' cannot be avoided, however, in most circumstances, these words are not the focus of the search engine users. As a result, these words could be neglected and not listed in the key words. Dissertation Effectiveness. The natural language process should also be used in the query of users. Essays Psychologist. If the user inputs a sentence as a query, the search engine would give worse results compared that break the sentence down to several key words when the natural language process is not used. So, it is very important to let the search engine understand the natural language. The first thing I dealt with is to set a list of stop words like 'of' and dissertation, 'the'. These words are neither the thesis on intrusion detection system 2012, focus of the audit dissertation government, users, nor cannot provide any information. The common of these words is that they appear very frequently so that if consider them as key words, much memory would be wasted and more useless results would appear. The second I have done is to neglect the tense of the verbs and the plural of the nouns.
It could be done by extracting the 'stem' of the educated essay, words so that the tense, the plural or other forms converting would be ignored. For example, the stem word of 'universal', 'universe', 'university', and 'universities' is 'univers'. As a result, conversion of effectiveness government in internal, most words could be found and would not affect the on counseling psychologist, match between the queries and the key words in the index. Foundation of webpage index. The webpages have to be indexed for the later use. And a better designed index could increase searching speed and locate the webpage more preciously so as to decrease the cost. The function of index is to analyze the search information, extract key words from the documents, and build the index table of documents. There are many index models in the field of search engine, such as inverted document index, vector space model, probability model and so on. And it is very important because the structure and government in internal, effectiveness are the keys of bromden analysis, web information index system. As a result, it is required to audit dissertation government be easy to implement, maintain, retrieval information quickly, and need little space.
Nowadays, most search engines use the inverted index to be the index model (Manish, 2011) because the structure is on counseling proper to response the key words retrieval quickly. Its structure considers the key words as index key words and access entrance of linked list. And the inverted index could determine the list of dissertation government in internal, document directly through index keywords. Enrollment Management Marketing Papers. To get the performance of the search engine better, the inverted index is usually stored in the memory. And to reduce the pressure of the memory, the government in internal, document is enrollment represented by a unique document code while all the documents and their codes would be stored in the database. The basic structure of dissertation, inverted index is showed below as figure 3 (Xuesong, 2008: 67). In the figure 3, the key words are the results of 'analysis of webpage content', and the documents in the inverted index are actually the code of documents. Each item in the structure of inverted index is an characteristics of an educated person index item with relevant information generated by the key words.
The advantage of inverted index is dissertation effectiveness that it changes the organization of information to be convenient to retrieval information while other models have to search every document to find out whether the key words are included or not. Sort of analysis, results. There are a lot of webpages (web spams) which include most keywords but only the keywords. Absolutely, they are not the users' needs. To avoid the spams filling in the list of results and let the users find what they want as soon as possible, it is very important to sort the effectiveness, results. During the spi publisher services, sorting process, the audit dissertation government, importance of the webpage itself would take effect.
And PAGERANK and HITS algorithms could calculate the importance of webpages based on the structure of the Web (Gang, 2011: 80). A famous and in french, popular way to sort the audit government in internal, results is the PAGERANK algorithm. The results yielded by the search engine are generally sorted by the importance of the webpage itself which could be measured by the connection among webpages. The PAGERANK method suppose the thesis on intrusion, Internet as a democracy environment, we could measure the importance of webpage by the link structure. For example, when webpage A has a link to webpage B, the weight of webpage B would increase (Xuesong, 2008:235).
There are two hypothesizes in the PAGERANK algorithm (Junlin, 2012: 138). One of them is that if a page is linked many times, the webpage is very important. If a webpage is linked by another important webpage, the webpage is also important. In a word, the importance could be passed among webpages. Audit Dissertation Effectiveness Government. The other hypothesis is that users access webpage randomly, browse the webpage with the format in french, hyperlinks, and never go back to browse the previous webpage. As a result, the next webpage is more important than the audit dissertation government in internal, previous one.
However, there is a serious problem in PAGERANK that the PAGERANK is not query dependent so that each webpage would have the same value of PAGERANK for all queries. What is more, spam pages could link to one webpage to promote the importance of the page. Besides, the third problem in PAGERANK that only uses in-links to a page and never uses out-links. To figure out the problems, we could use the HITS algorithm which defines the authority that many other pages point to the webpage and the hug that the page has outgoing links to many other pages. The basic idea is similar to PAGERANK that dig the useful information by links in the Internet. And HITS algorithm considers authority and hug respectively that it evaluates hug based on the evaluation of authority. Chief Analysis. Finally, a weight would be assigned to audit government in internal the webpage. The authority is relevant with the quality of content information so as to attract many webpages to link while the hug is relevant with the quality of hyperlink page which is provided by the webpage. The higher authority webpages a webpage links, the higher its hug would be (Christopher, 2008). And the input of the HITS algorithm is known query relevant webpages, as a result, HITS algorithm usually supplies the psychologist, webpages which are relevant to the query which is unlike the PAGERANK algorithm.
It means that the number of webpages 'HITS' searched would be more than that of 'PAGERANK'. However, there are some disadvantages in dissertation effectiveness in internal the HITS algorithm. The first of all is that it is a query relevant algorithm which means it could not start calculating until the users input the query. The second problem is that tightly-knit community effect could happen, which means if the query-relevant webpages link to essays other webpages which are not relevant and link to each other, the HITS algorithm would give them a high rank so that users might not get the query relevant information. The third is that the structure is not stable, which means if one webpage is effectiveness government deleted or the few links change, the sorting according to psychologist the HITS algorithm would be great changed (Junlin, 2012: 144). Graphical User Interface. In the section of dissertation effectiveness, graphical user interface (GUI), based on the famous search engine company Google, the home page would be very simple and convenient for users to search the information that he/she wants to. And my home page would be much more simply because the search engine could only bromden essay search the webpage and text. The current home page is shown as figure 4: The users could input the words or the sentence they want to search in the left text box while they could type the number of results per page (n) they want in the right text box. And a brief introduction has been given for the users to use the search engine more easily.
The next webpage would show the previous n results of all the results. And at the same time the page would tell the user how many results in total, the titles of searched webpages, the contents which include the words that the user searches, the dissertation effectiveness government, websites of searched webpages, the time when the webpage is crawled which is on intrusion helpful for the update of the database of the whole search engine, and which page current webpage is. Users could also click the dissertation effectiveness, button to select the first page, the previous page, the next page and the last page. What is thesis detection 2012 more, users could decide which method to rank the effectiveness government, results (HITS or PAGERANK). Services. Suppose a user wants to search the 'robot' information and let the search engine return 3 results per page. They input the word 'robot' in the lefe and '3' in the right, and then press the button 'search'. The next page would be as figure 5: We could find out from the picture above that there are six results in total and it shows the first five webpages that include the word 'robot', which is highlighted in the current page. And at the top of the page, users could choose using the 'PAGERANK' or 'HITS' to rank the pages. At the bottom of the page, users could see other results in the next page by clicking 'Next'.
The pattern of next page is almost the same as the one above. And when users click 'PAGERANK' or 'HITS', the different results and ranking methods would be shown. What is government worth noticing is the essential difference between 'PAGERANK' and and communication research, 'HITS'. In the instruction of the report, three core problems have been brought forward. And a part of the first problem and the third problem could be solved by 'analysis of webpage content' and 'natural language process'.
And the government, main aim of the reporting facility is to provide the information of 'user-relevant' so as to services solve the audit dissertation government in internal, other part of the first problem. The reporting facility is responsible to record every query the user has done. When the new query is input, the search engine would find the similar information of the old queries, and the results would have the characteristic of the user. The other aim of reporting facility is to let the user know what other users are searching. When the user inputs the query, the thesis on intrusion 2012, query would be stored in the database. And at the same time, the old queries could be loaded from the database to compare the new query to find the similar information. Audit Government. The database would store the key words, the times that the key words has been searched, and spi publisher, the last time when the key word is searched. What is more, if any user wants to see what he/she has searched before, the queries could have been visualized in dissertation in internal the graphical user interface. According to the deliveries and typical criterion of search engine, some experiments have been done to evaluate the search engine I have made.
And the on counseling, test case would be the audit effectiveness in internal, webpages of 'Durham University' which means that the webpages the crawler crawls start with 'www.dur.ac.uk'. The criterion and the results of the experiments would be shown. Finally, the solutions to the problems in the part of 'problem domain' and the benefits and deflects of the search engine would be demonstrated. Criterion of Evaluating the Search Engine. In 1973, Lancaster and Fayen listed 6 factors to evaluate the search engines, coverage, recall ratio, precision ratio, response time, user effort, and format output (Lancaster and Fayen, 1973). Although the index has been brought forward over 40 years ago, and the target is the traditional online information retrieval system. Format In French. However, in terms of the essence of information retrieval system, the evaluation factors are still useful even nowadays. Later, after Heting Chu and Marilyn Rosenthal analyze and compare three famous search engines (Alta Vista, Excite, and Lycos), they come up with five aspects to evaluate the audit dissertation effectiveness in internal, search engines, respectively indexing, search power, search effect, output, and users' burden (Chu and Rosenthal, 1996). With the development of the research, the essays psychologist, user experience is paid more and more attention.
Belkin considers the essential issue in the information retrieval system is anomalous state of knowledge (ASK) (Belkin, 1993), which is an important part of the information retrieval model. Bell considers the complexity of the web based on the former research, and focus on the user experience when evaluating the search engine (Bell, 1998). Considering the standard criterion above and the concrete condition of the current mainstream search engines, I think the following criterion is reasonable to evaluate the search engine in general. Capability of the Search Engine. The factor includes the capacity and coverage of the database of the search engine, the content and the depth of indexing, and the novel rate of the database. The first one would affect the 'recall' factor directly according to dissertation government the statistics, which shows that the more webpages the database has, the more results might be searched. Usually, the management and communication papers, index database is composed of URL, name of effectiveness in internal, document, content, titles, sub-titles and so on. Bromden Analysis Essay. The content of the combination would affect the precision of the audit dissertation, search engines directly. In the meanwhile, the organization of the webpages is a multilayered hypertext structure, and the depth of chief, indexing means which layer the search engines index. For example, some search engines only index the home page (the first layer) while some others index deeper layer. The other meaning of the depth is whether the search index all the webpage or just some content.
For example, some search engines only index the name or the title of the HTML document while others index the whole content of the webpages. Generally, the more content a search engine indexes, the better the indexing effect is and the more resources would be occupied. Dissertation Effectiveness. The novel rate includes two aspects, uniqueness and update frequency. Uniqueness of a search engine is the ratio of the unique results which other search engines do not contain in bromden analysis essay all the results the search engine returns. And nowadays, the update frequency is very important because the information in the web varies largely in a second and is unpredictable. As a result, the search engine has to audit promise the ''' of the information and avoid the 'dead hyperlinks'. When it comes to my search engine, the test case is the webpages of 'Durham University', the capacity of the database is limited. Enrollment Management And Communication Research Papers. However, the content and the depth of indexing would be very comprehensive, which means that the database would save all the contents of dissertation government in internal, each webpage.
But, the database would never be updated because it is not an on-line version now. The aim of the test is to evaluate the performance but not the capability. The factor includes construction of indexing expression and the indexing function. In 1998, Rousseau et al. found that one of the difficulties is how to bring forward keywords and use the different command indicators when using the on-line library (Fang and Salvendy, 2000). In fact, the essays on counseling psychologist, search engine has the same problem with the on-line library. And for the most search engines, the queries the users input are the most important factor for the results. However, the queries would be different even if when the different users search the same target. To solve the problem, some search engines (such as AskJeeves) would provide some other relevant keywords to give the dissertation effectiveness, users more choices to spi publisher services get more and better results. And some user-friendly search engine supply the government in internal, toolbar and enrollment management marketing and communication research papers, dropdown menu to help the audit dissertation in internal, users come up with more detailed query so as to get more satisfied results. The number and effects of indexing functions provided by the search engines would affect the indexing results seriously.
And many indexing technologies used in services the traditional on-line indexing system are developed to be the dissertation government in internal, important technologies in the search engine field, such as Boolean index, truncation index, position index, and services, limited index. In the meanwhile, the graphic user interface has been separated as the normal index interface and advanced index interface according to the needs of the users. And almost all the search engines do not differentiate the lowercase and uppercase of the words and consider the list of stop words. In my search engine, I take the simpleness as the most important factor in the graphic user interface. As a result, there is no toolbar and audit, dropdown menu existing. Chief Bromden. However, it has its own stop words list and do not differentiate the audit dissertation effectiveness in internal, lowercase and uppercase of the words. Furthermore, it supports the Boolean query to help users get more satisfied results. This factor is very important to evaluate the search engine I have made because the search engine could be quantized to compare with other search engines. The search engine has to deal with more information, which is the significant different from on-line indexing system. If the indexing algorithms were not improved, it would take lots of time to deal with a simple search. And most of the users would not wait for the search engine when they use it to search the information.
There are no standard test cases to test the average response time of the search engines. And it is not fair to compare my search engine with the famous search engine like Google because the scale of the database is not comparative. As a result, I would give some words randomly and give a simple list of response time of the words. The experiments have been tested when the number of webpages is 998 and the number of the keywords is and communication research papers 185451. The detail information would be listed as table 1. From the table 1, we could see that the process of searching would take too much time for the user.
There are two main reasons slowing down the speed of the search engine. The first one is that the graphic user interface requires the part of content which include the keywords returns. If we just revise it to return just the audit government, title or just one sentence, the time would be reduced to less than 1 second. The second one affecting time is the chief analysis, query in the database. For supporting the fuzzy query, the query 'like' has to be used, however, it takes too much time. If the fuzzy query is not a necessary, the time accessing the database would decrease significantly.
Recall and Precision. These two factors are very important in the past when the information is limited. However, nowadays, the users pay more attention to whether the dissertation effectiveness in internal, hyperlinks of the information they want appear in the first several pages. The following table shows the relationship between the retrieved webpages and relevance (C.J., 2010). The calculation of recall and precision is as follows:
In the function, |.| means the number of '.'. As the essays psychologist, equation shows, the measure of these two factors in effectiveness government in internal the search engine would not be easy, especially for the recall because it is even harder to characteristics of an person essay get the number of 'A'. What is more, in my search engine, we could suggest that in the PAGERANK method, there is no non-relevant retrieved webpage existing because the Boolean match has been used. In a word, the value of these factors would be very high in my search engine but it is useless to compare with other search engines by these two factors. The format and dissertation effectiveness, content of output. The outputs of the results are different among search engines, however, there are almost three parts: title, summary, and URL in all the search engines, what is more, the keywords are highlighted in some search engines. On Counseling Psychologist. What is more, some search engines add introduction, type, webpage size, date, hyperlinks to detail the audit effectiveness in internal, results. Furthermore, the search engine would show that how long it would take and how many results it returns. Of An Educated. If the government in internal, number of the results would be large, the keyword is not useful for searching while the number is management and communication research small demonstrates that the keyword is too special. In the graphic user interface of my search engine, it would return all the basic parts above and the keywords are highlighted. What is more, it would return time and the number of results.
In the part, three more functions are included, post-processing, assistance process, and information filter. The post-processing allows the users to audit government in internal type more keywords to search the information in the former results. During the process of assistance, search engines usually provide the management marketing papers, preview function or cached snapshot function. The information filtering include two aspects, one is that the search engine would filter some unhealthy information for the immaturity while the other aspect is to return different results to different users according to the users' history records. In my search engine, there are no functions such as 'search in the result', preview, and information filtering. Audit Dissertation Government. However, the reporting facility would save the spi publisher, users' queries so as to analyze it later. Comparison between the PAGERANK and HITS. According to the principle of the PAGERANK and HITS algorithm, it seems that they are similar which are based on the hyperlinks and use the eigenvector. However, the differences between the algorithms are obvious according to the principles and experiments. The first one is that HITS algorithm is query-dependent because the authority of the HITS is the weight of the indexing theme. Effectiveness In Internal. However, PAGERANK is on intrusion system a query-independent algorithm because it is audit government independent with the indexing theme.
The PAGERANK algorithm is based on the 'reference analysis', addition with the quality of the Internet. It not only considers the number of the in-linked webpages, but also regards the importance of the in-linked webpages. The second one is on counseling that HITS algorithm gets the initial processing data based on the text search engine, and the importance of the webpages passes from the dissertation effectiveness government, hub page to psychologist the authority page. What is more, in the HITS algorithm, the hub and the authority improve each other. While the PAGERANK algorithm is based on the random surfer model, which means that the importance of the webpages transfers among the authority webpages. The third one is that the audit government in internal, response time of the HITS algorithm is more than that of the PAGERANK algorithm. Although the HITS algorithm analyzes the fewer webpages, however, it has to extract the initial results set from the search engine and expand to the basic results set, which would take lots of of an educated, time. While superficially the PAGERANK algorithm deals with more webpages, but the dissertation in internal, processing runs in advance, as a result, the response time seems less. This section contains evaluations on the work carried out during the course. The first sub-section focuses on evaluating the marketing and communication research papers, solutions selected and the second sub-section assesses the implementation and evaluation of the resulting systems. Evaluation of Solutions.
The final aim of the project is to build a search engine and compare the ranking algorithm PAGERANK and HITS. To realize the aim, the deliverables have been shown in the introduction part. Effectiveness Government In Internal. The following part is to evaluate each part in the deliverables. The first one in the minimum objectives is to design a web crawler. Essay In French. The detail has been introduced and it actually works. Dissertation Effectiveness In Internal. However, there are some problems in marketing and communication papers the crawler part.
The biggest problem is that the effectiveness, crawler crawls the enrollment marketing and communication research papers, webpages so fast that sometimes it would be misunderstood as a malware. For example, when the effectiveness in internal, crawler crawls the test case which is exactly the webpage in the Durham University, the firewall of the chief bromden analysis essay, university is dissertation effectiveness in internal always triggered and stop the crawler continue crawling. The second problem is that the crawler part takes too much time because it has to run on line. Each time the characteristics of an educated person, crawler saves a document, it would save the hyperlinks in the document in a array. However, not all the hyperlinks could be connected, as a result, the code has to get the HTTP code from the Internet, which would take time.
Only when the HTTP code is audit effectiveness in internal 200, the hyperlink could be connected, otherwise, the educated essay, hyperlink could not be access. Another time-consuming part is to remove the duplicated URLs from the array when the scale of array is large. Audit Dissertation Government In Internal. As a result, it is very easy to solve the problem actually. As long as let the crawler wait for 1 or 2 seconds, the firewall would not be triggered, however, the crawler part would take more time because of the second problem. The second in the minimum objectives is to build and maintain an index. Here I choose the inverted index as the index model because it has been widely used in many famous search engines, even the biggest open source search engine Lucene has been using the inverted index. And the benefits of the inverted index are obvious and psychologist, have been introduced in the solution part. The third in the minimum objectives and the second in government in internal the intermediate objectives is to design a graphic user interface.
The principle of the GUI part is essay in french simple and convenient to use, which just include two input boxes which user could input the query and the number of audit effectiveness government in internal, results per page respectively, a very simple instruction guiding users to use the search engine, and several keys for users to choose the ranking algorithm they like. If I have more time, there are lots of things to do. For example, the function of 'search in on intrusion system the results' and cached snapshoot could be added to satisfy the users. The Boolean operators like '+','-' ,'|' could be used in the query to get more accurate information the user wants. More Boolean operators could be added if the more time is given. The last one in the minimum objectives, the third one in the intermediate objectives and the first one in the advanced objectives are to implement ranking algorithms, and the basic ranking algorithm I choose is a simple one, the Boolean model added fuzzy search to return the effectiveness in internal, relevant webpages. The method promises that the essay format, returned results are definitely relevant to the query, which means that the precision of the search engine would be 100 percent. However, some other models have not been tested and cannot be compared each other. The PAGERANK algorithm and HITS algorithm I implement is the most original one, which could compare and analyze the results more easily.
However, the effect of the dissertation in internal, original algorithms might not be good so that it would definitely affect the evaluation of the search engine. The last one in the intermediate objectives and the last one in the advanced objectives are to of an educated person build and visualize a reporting facility which stores the users' query for statistical analysis. The part works but it is not a former work of providing the users their unique results even if they search the dissertation effectiveness government in internal, same word. In the end, although all the given objectives were completed, the improvements could still be done to make the search engine better and to make the test data more convinced. Evaluation of Implementation. According to person the 'Results' part, the search engine has been evaluated. However, there are still some problems need to be solved. First of all, the test case is not good. And because of the dynamics of the Internet, many webpages could not be accessed after it has been crawled.
Furthermore, the disadvantage of the crawler leads to audit dissertation government in internal the limited scale of the test case. As a result, it seems that the capability of the search engine is not good. But it is not true, if more time could be given, the detail in the crawling algorithm would be improved and the scale of the test case would be larger, the and communication papers, speed would rise significantly. The second worth noticing is that the indexing method, the Boolean query could work and the quality of the audit, returned results is high. Of An Educated Person Essay. However, the effectiveness government, toolbar and dropdown menu would be added if I have more time. In the in french, third part, we could see that the response time is a little intolerable, the reasons of which have been analyzed and audit dissertation effectiveness government in internal, the quantities of management marketing and communication research papers, experiments could prove that reading and analyzing the sentence which include the key words from raw file which downloads from the webpages directly take too much time. If just one sentence or just title is effectiveness government in internal returned, the time would be reduced significantly. And it seems that the recall and precision are not good factors to educated evaluate my search engine. However, there are no more famous factors to evaluate the search engine as the problem domain in the 'Related Work' says.
The format and content in my search engine keep the same form with other famous search engines such as Google. The last part of audit government in internal, evaluation in my search engine could not be measured because it is more like a expansion and future work of the project. In a word, the essay in french, experiments could prove that the search engine could work and dissertation effectiveness in internal, be able to compare the PAGERANK and HITS algorithms clearly, which realize the basic purpose of the project. Chief Bromden Analysis. But there are lots of details that could be improved. The purpose of the audit dissertation effectiveness government in internal, project is to build a search engine and compare the PAGERANK and HITS ranking algorithms. Bromden Analysis Essay. The work has been separated to several sub-modules and each part has been done as deliverables, crawler, index, and graphic user interface. During the process of building the search engine, some key techniques have been breakthrough and three key problems have been tried to be solved. The crawler takes the preferential traversal to access the whole Internet. The benefit is that it not only avoids the black hole in the Internet, but also allows the most important webpages to be crawled at first.
And then the documents the effectiveness, crawler has crawled have to be dealt with for the indexing using. The content of the webpages always contains the useless format information and advertisements. As a result, the keywords in the content have to be extracted and the spam in the Internet is also filtered. The aim of the part includes extracting words, eliminating punctuation mark, convert between uppercase and services, lowercase letters, resuming word stem, eliminating conjunction and dissertation effectiveness in internal, high frequency words. What is enrollment management marketing research more, the dictionary of stop words is built to extract the useful key words from the in internal, content and the stems of the essays on counseling, words are used to neglect the tense of the verbs and the plural of the nouns. In the index part, the inverted index is used rather than the normal index which would increase the searching speed significantly. And the ranking algorithms I have implemented include the basic Boolean algorithm, PAGERANK algorithm, and HITS algorithm. The graphic user interface is designed to be simple and convenient to be used by the users.
And the audit dissertation effectiveness government in internal, reporting facility saves all the queries of the users for services, the statistics use and would finally be used in the future. In the problem domain in the part of 'Related Work', three issues have been brought forward. The first one is how to define relevance, in my search engine, the techniques of the dissertation effectiveness, Boolean match, stems of the words, and natural language processing are used to solve the essays on counseling psychologist, problem effectively. The second issue is audit dissertation government how to evaluate the search engine. In the part of 'Results', the whole system of evaluation has been given, although it is not appropriate for evaluating my search engine, however, it is quite a good system for evaluating the common search engine because it covers almost every aspect of the search engine. The last issue is how to satisfy the users. In my search engine, the former work has been done by the reporting facility. However, the problem has not been solved in the project.
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Available at: http://www.dcs.gla.ac.uk/Keith/pdf/Chapter7.pdf (Accessed: 28 April 2014) If this essay isn't quite what you're looking for, why not order your own custom Information Technology essay, dissertation or piece of coursework that answers your exact question? There are UK writers just like me on hand, waiting to help you. Each of us is psychologist qualified to a high level in our area of expertise, and we can write you a fully researched, fully referenced complete original answer to your essay question. Just complete our simple order form and you could have your customised Information Technology work in your email box, in as little as 3 hours.
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