Sample on Audit Risk In Respect To The Company Of Mathra Tool

Question: Depict about the Assessment of Audit Risk in regard to the organization of Mathra Tool Inc.? Answer: Presentation Reviewing is the system of checking of the considerable number of records book and exchanges whether it is expressed in Financial Statement appropriately or not (Gramling, Rittenberg and Johnstone, 2010). It is the system of making a decision about budget reports appeared (Balance Sheet and Profit Loss Account) with all the records of record and budgetary exchange whether it is right or bogus. Examiner chance alludes to the hazard that is distinguished by an evaluator with respect to budget report. An off-base assessment with respect to the budget summary is communicated by the Auditor. Review chance comprises of three hazard, for example, Inherent hazard, control hazard and discovery chance (Cosserat and Rodda, 2009). Natural hazard emerges because of mistake contingent upon such factors regardless of from the wastefulness of controls. Innate hazard will more where the business includes judgment and estimation with high degree or includes complex exchange. Control chance emerges because of wastefulness in the operational exercises from the side of business element. Location hazard alludes to the hazard which is raised by the blunder or extortion in material misquote in regard to fiscal report (Leung, 2011). The fundamental estimation of control chance is the methodology of evaluating the value of an associations bookkeeping and in-house control framework by forestalling or distinguishing and improving the material misquotes (Moeller and Brink, 2009). Mathra Tools Incorporation is an apparatus instruments delivering organization. It is rumored organization in creating high caliber of machine parts and it has developed into a $10 million-a-year business. The proprietor of the MTI is George Mathra. Thomas Smith selected as reviewer in control in this organization has distinguished a few issues in regards to the activity of the business. This examining plan incorporates the appraisal of inside control chance and the judgment for discovery chance. It additionally contains the portrayal in regards to the considerable methods that could be led for the WIP stock. Appraisal of Internal Control Risk Fundamental appraisal of hazard gauges and forestalls the arrangement of bookkeeping and the inside controlling arrangement of an association with respect to material misquotes (Pickett, 2010). The hazard can't be moderated completely on the grounds that there are sure intrinsic constraint in the arrangement of bookkeeping and controlling. The appraisal of control hazard is required when the in-house control frameworks of the association are not valuable and the bookkeeping frameworks of the association are not proficient (Pickett and Pickett, 2011). There are a few methods which can be utilized to record the data with respect to the frameworks of bookkeeping and inside control (Hargie and Tourish, 2009). A specific strategy is chosen for the judgment by the reviewers. The strategies can be utilized by alone or together. The instances of procedures are story depiction, surveys, agenda and flowcharts (Reding, 2009). The layout and length of the documentation rely upon the size and unp redictability of the business and sort of applied framework in regard to bookkeeping and inner control (Pickett, 2011). Trial of control are executed to discover the review proof with respect to the value to assess whether the business planned the frameworks accurately to forestall material misquote and the viability of inward operational exercises over the period (Shim, 2011). There are a few things are remembered for trial of control. These are as per the following: 1. Trial of control includes checking of records related with exchange and different exercises to acquire the review proof that business has worked the inward control accurately or not (Louwers, 2011). For example, it is checked that whether exchange is approved or not.2. It includes enquiry and perceptions with respect to the inner controls which leave no review preliminary, for example, discovering who truly plays out the all capacities as opposed to who should perform.Lastly, it incorporates the re-execution of inward control, for example, compromise of bank proclamation to see whether it was really performed by the business effectively. Business should embrace compelling interior controls in the activity for forestalling and distinguishing the event of mistake and extortion (Beasley, 2009). The misrepresentation can be suspected under after circumstances: In the event that any paper is missing viewing budgetary exchange, for example, checks, vouchers, solicitations, etc.If auxiliary books doesn't coordinate with control account. On the off chance that there is enormous distinction in preliminary equalization and it is extremely hard to coordinate the parity. On the off chance that variety of Gross Profit Ratio and Net Profit Ratio are high.If there is confound between the parities as indicated by the organization and the check of the parity by the parties.If the stock as per the companys record isn't same with the stock genuinely tallied. In the event that the customer doesn't ready to give any good information.If the some bookkeeping figures have found overwriting There are a few stages through which blunders can be recognized. These are as follows:1. Checking the offset of opening with the end equalization of last year.2. Checking all the posting made in record accounts.3. Checking the all out parity of auxiliary books.4. Checking every single convey forward.5. Making affirm whether all record accounts are incorporated or not.6. Checking the complete rundown of indebted person and leasers coordinate with the record accounts or not.7. Looking at the changed things of preliminary offset with the things of past year.8. Checking any distinctions including round figures, for example, $10000 is composed as $1000.9. Checking any removal of summing figures, for example, 91 is composed as 19.10.Identifying any passage is leaved unposted from the genuine books. Obligations need to perform by reviewer are as follows:1. Examination all the whole movement of budgetary operation.2. Affirm all the receipts from the counterfoils or duplicates or money updates, deals report.Confirm the register of pay and wages.1. Check the methods utilized in stock valuation.2. Look at the all registers, notes and challans related with stock, inwards and outwards of products and conveyance, etc.3. Figure various proportions which are required to distinguish the fake exercises and errors.Examine the subtleties the things which are not used.Investigate the region where the issue is suspected.Perform the review procedure by applying sound ability and with care.Do shock visit in the association to look at the records activities.There is discovered a few issues and mistakes in-house control arrangement of MTI however the organization is utilizing modernize framework for the creation of hardware instruments. The gear and machine are worked through computer.The control dangers identifying with business activity of MTI are as follows:1. The organization has no authorized antivirus to secure the modernize framework and there is no framework expert.2. There is no appropriate upkeep of systems administration framework and it is kept up by just a proprietor of PC shop which situated a long way from the workplace. Along these lines, there is no such master to keep up the systems administration framework unsurpassed. Just Mr. Lee is answerable for looking after gear, updating programming and keeping up client security profiles on the network.The staffs of the association don't keep up the framework related with client secret key. Two staffs utilize basic secret key for making section information of bookkeeping transaction.1. The reinforcement is taken each finish of the in tape cartridge. There are seven tape cartridges for taking for taking full arrangement of reinforcements for seven days. However, the cartridges are not kept securely and systematicall y.2. There is no any assurance utilized between office framework and home arrangement of the senior staff. Home framework can be utilized like as office framework fully.3. There is just one bookkeeping staff that is answerable for all bookkeeping exercises. There is no other staff who can manage creditor liabilities and money distributions. Judgment for Detection hazard Location emerges due to applying of wrong methodology in examining by the reviewers to assess and discover the material misquotes in all exercises of money related viewpoint (Taylor and Osborne, 2013). The all out review chance is the blend of control hazard, natural hazard and recognition chance. In the wake of surveying of control hazard and inborn hazard, the location chance is appointed to comprehend and lessen the absolute review chance. It is never conceivable to take out the discovery hazard completely in light of the fact that it is hard to check every single money related exchange totally (Beasley, 2009). Be that as it may, the goal of review is to decrease the identification chance however much as could reasonably be expected. There are a few components of location hazard which are depicted underneath: Utilizing of wrong methodology in review The utilization of wrong methodology can build the discovery chance (Weirich, Churyk and Pearson, 2012). For example, certain proportions are utilized to break down the fiscal summary. Be that as it may, the choice of proportion is significant. In the event that the reviewer pick wrong proportion (has no connection with the target of review) in surveying the error in money related exercises, it can build the recognition chance. Wrong understanding of review results In the wake of reviewing with right strategy, if wrong translation is produced using the outcomes, it can build the review chance. For example, it might be deciphered that the records payable is demonstrated accurately however it is discovered a material error in genuine. Choosing of wrong testing strategy Identification hazard can be diminished by utilizing of explicit testing procedures for identifying the blunders in budgetary exchange (Millichamp and Taylor, 2012). For example, to affirm a specific deal happened, it isn't required to check the receipt whether is scientifically right. During the checking of records payable, it is seen that accounts payables are really paid or not by making test the solicitations. It might be the right review method for attesting the records payable

Public Relations and Social Media

Figure 1: BDI Logo An exposition on the Black Dog Institute’s utilization of web based life for advertising purposes. Significant Assessment: How is internet based life being utilized by not-revenue driven associations for PR purposes? Pick one not-revenue driven association working in Australia and examine †concerning advertising and new media hypothesis †how the association is utilizing internet based life to deal with their key partners and local gatherings on the web. The act of advertising has seen an adjustment as of late, and now incorporates numerous and changed devices; including new media.The term ‘new media’ envelops an assortment of non-conventional techniques including internet based life. This exposition examines the utilization of web based life in an advertising limit, to help with dealing with an organisation’s key partners and local gatherings on the web. The center association is the Black Dog Institute (BDI), a notfor-benefit a ssociation and a â€Å"educational, investigate, clinical and network arranged office offering pro ability in temperament disorders† (Black Dog Institute, 2012).When thinking about how as an association utilizes web-based social networking, it is essential to comprehend who the key partners are and furthermore what establishes online life apparatuses. A portion of the institute’s key partners (also called the particular objective crowd) incorporate wellbeing experts, benefactors/backers and government offices. All in all, with a portion of the key partners characterized, what at that point is internet based life? Web-based social networking, all in all, is online media with which you †the client can participate.Mayfield (2008) states that web based life of every single kind offer most (or the entirety) of the accompanying qualities †interest, receptiveness, discussion, network and connectedness. The Black Dog organization has utilized a few online life device s to get their message out to the more extensive network. The utilization of these new media instruments, explicitly internet based life devices, helps not-revenue driven associations, for example, The Black Dog Institute in dealing with their key partners and local gatherings on the web. Internet based life is quick turning into a successful instrument for advertising purposes and The Black Dog Institute has mplemented an assortment of devices, for example, wikis, long range informal communication, blogging, video, an intelligent site and applications reasonable for iPhone, iPad and iPod. Figure 2: Social Media The Black Dog Institute takes part in wikis, for example, The Mental Health Wiki. The Mental Health Wiki (2012) which professes to be â€Å"a collective, open stage for catching excellent data in the psychological well-being field† is available to anybody anyway the site just permits appropriately qualified individuals to contribute. So how does this wiki help The Bla ck Dog Institute deal with their key stakeholders?Through investment, the establishment can show their aptitude in the territory of psychological wellness along these lines upgrading their notoriety among other wellbeing associations. Wikis are a potential goal for online Page 2 of 7 PRN101 †Major Assignment research and in this way by adding to such, the association can constantly improve connections among themselves and their partners (clinical experts) As a central capacity of advertising is to construct commonly advantageous connections, the commitments provided by the organization on the Mental Health Wiki would be open by other human services professionals.This availability is a key in building such connections, and thus, the foundation approaches different organisation’s examine material. On the other side be that as it may, it is significant for the establishment to think about the lawful repercussions of adding to such a discussion. Flynn (2012) states that inte rnet based life substance can be summoned and used to help (or sink) an association in case of suit, consequently it is significant that the establishment holds fast to laws influencing PR, for example, copyright, protection and the Trade Practices Act.Facebook is a person to person communication website offering network, discussion and connectedness and is another to a great extent open online life device with which The Black Dog Institute has locked in. Their dynamic Facebook site permits local gatherings to communicate and stay associated with the foundation. The site offers news sources, occasions, recordings and the choice for similarly invested individuals to add to the site through ‘posts’ †conversations. Figure 3: BDI FaceBook Page According to Solis (2009) interpersonal interaction isn't just about mingling, it’s about utilizing the system to expand perceivability for ability, notoriety and activity.As you can see with the picture, the Black Dog Ins titute’s Facebook page incorporates an image of their office, yet is this the sort of perceivability we allude to in PR? To build their perceivability (or presentation) the organization uses interpersonal organization I. e. Facebook to advance forthcoming occasions, VIP affiliations, and other online existences, for example, sites/twitter and to give another road to get to their items available to be purchased. By utilizing person to person communication to expand their perceivability, the foundation builds up another road to expand gifts and genuinely necessary funds.Page 3 of 7 PRN101 †Major Assignment Blogging is another web-based social networking device that has been received by The Black Dog Institute, using Twitter †a miniaturized scale blogging webpage. Their Twitter web journals permit perusers to ‘pull’ data that is applicable to them and with the dynamic idea of blogging; the foundation increases a veritable knowledge into the assessments of their open. Regarding advertising, blogging helps the association to keep up a consistent and state-of-the-art association with its publics.The Black Dog Institute grasps that association and keeps on building a system (or network) of similarly invested individuals and stay associated with their crowds. With one of the most significant elements of advertising being to make understanding, blogging destinations, for example, Twitter permits The Black Dog Institute to make this comprehension. A few media instruments don't permit investment from an organisation’s open, anyway through blogging a two-way process is supported in this way making a shared understanding.It is essential to recognize that a discussion including two-way discussion can again put the association in a helpless position †both its’ lawfully and socially dependable position. Accordingly keeping up a moral way to deal with the blogging procedure, with a conscious game-plan, can assist with lessening this powerlessness. Figure 4: YouTube Videos are another online networking apparatus that an association can use to stay associated with their open. Locales like YouTube are getting progressively mainstream with people and associations alike.The Black Dog Institute has a YouTube channel, where supporters can transfer recordings and furthermore remark on recordings transferred by others. The organization joined the YouTube ‘phenomenon’ in September, 2011. At present there are just two recordings accessible on their own channel, anyway when you search the term ‘black hound institute’ a few others have been transferred (as demonstrated in the above picture). This shows an expanding attention to the organization through a frequently engaging and carefree discussion. Recordings offer the establishment the chance to introduce their association in a fair and exact way.Further improvement of their YouTube channel can be accomplished Page 4 of 7 PRN101 †Major A ssignment through remarking on other supporter transfers with respect to the foundation and its exercises from different clients. Different devices used by the organization, which are somewhat out of the extent of this paper, incorporate an iPod/iPad application †â€Å"The Black Dog Pedometer†. This instrument gives the institute’s partners/network access to a pedometer as well as a connect to become familiar with the establishment and furthermore a gift option.In terms of advertising, the pedometer application expands the associations picture as an expert regarding the matter of psychological well-being and disposition issue. The organization additionally has a site grown explicitly for adolescents †www. biteback. organization. au which all in all is definitely not an online networking device; anyway the blog segment of the webpage offers connection and support by endorsers. The Bite Back site permits the BDI advertising group to adopt a proactive strategy t o their subject of ability, offering a connecting with and intuitive discussion for their more youthful network groups.As you can see all through this exposition, web based life helps the Black Dog Institute in its’ advertising plans. Apparatuses recently laid out, for example, wikis, interpersonal interaction, blogging and recordings help the establishment in building and improving associations with their key partners and to expand mindfulness and perceivability of their association. As the energy of web based life proceeds, further open doors may create for the foundation. Trimester 1, 2012 Page 5 of 7 PRN101 †Major Assignment Reference List: Figures Figure 1: Black Dog Institute Logo †www. lackdoginstitute. organization. au (got to 30 April, 2012) Figure 2: Social Media †http://masoncadeagency. com/wpcontent/transfers/2011/07/SMO_Social_Media_Optimization. jpg (got to 3 May, 2012) Figure 3: Black Dog Institute Facebook page †http://www. facebook. com/bl ackdoginst (got to 5 May, 2012) Figure 4: YouTube screen capture †Available: http://www. youtube. com/results? search_query=black+dog+institute+&oq=black+dog +institute+&aq=f&aqi=&aql=&gs_l=youtube. 3†¦ 16614. 20473. 0. 21177. 22. 19. 1. 2. 2. 1. 30 3. 2779. 5j7j6j1. 19. 0†¦ 0. 0. (gotten to 6 May, 2012)Bibliography Texts: Ali, M 2006, Public Relations †Creating an IMAGE, Heinemann, Oxford, GB Chaffey, D and Smith, PR. 2010, eMarketing eXcellence †Planning and streamlining your computerized m

Orange Krush is back!

Orange Krush is back! On Friday night, myself, my sister and my friend Kirby went to the first basketball game included in our Orange Krush student passes. We were ecstatic as the Illini played Southern Universitys Jaguars and won 102-55. I dont think there is a better seat in State Farm Center than the ones located in the Orange Krush student section. With every shot made and rebound gained, our student section shows that our fan support runs deep. This is my third year of being a member of Orange Krush and it is more fun than it has ever been before. This year, my freshman sister is attending as well and found that she loves the Krush experience too. Every time we go to a game, we have a fantastic time because of the amazing support of our student section. Each of the students dancing, chanting, and singing during the Krush experience add to a great time. A sea of orange is sure to show up to each and every game and cheer on the Illini. Being a member of Orange Krush is an essential part of my experience at the University of Illinois. Whether its  a snoozy Sunday afternoon or a snowy Wednesday night, if there is a Illini home game, I will most likely be there. It is a great place to be if you want to get away from studying or homework in general. Plus, if you have friends in Orange Krush, it is a great place to meet up with them as well. My message to every future Illinois student is clear: join Orange Krush. You wont regret it. Myself (left), my sister Sarah (middle), my friend Kirby (right) Jacob Class of 2019 I’m an Advertising student within the College of Media. My hometown is a place called Fairmount, Illinois, which is about 30 minutes from campus. I began my Illinois journey in the Division of General Studies.

Animal Testing Should Be Banned Essay - 1646 Words

Animal Testing Should Be Banned Throughout the decades, animals have been used in medical research to test the safety of cosmetics including makeup, hair products, soaps, perfume and countless of other products. Animals have also been used to test antibiotics and other medicines to eliminate any potential risks that they could cause to humans. The number of animals worldwide that are used in laboratory experiments every year exceeds 115 million animals. Unfortunately, only a small percentage of countries collect and publish data concerning animal use for testing and research, so the exact number of animals used in experiments are unknown. (Author, Year). Whether we should or shouldn’t use animals in medical research has been a heated debate for countless generations. Many American’s value the achievements that animal experimentation has provided but new understandings about the nature of animals have caused people to reconsider the ethics of using animals for human gain (Driscoll and Finley para 1). D espite the numerous benefits of animal experimentation, there are many negative aspects. Animals should not be used in medical testing because they are abused, many drugs/antibiotics that are tested on animals and were deemed safe were not safe for humans and lastly, there are alternate ways that are more cheap and effective in testing the safety of products. Animal experimentation can sometimes be driven by curiosity, the belief that animals do not experience pain orShow MoreRelatedShould Animal Testing Be Banned?844 Words   |  3 PagesShould animal testing be banned? Nowadays, a lot of animals has been tested on a range of experiments over the world. You could be supporting animal teasing cruelty without knowing it. 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The article also talks about the overallRead MoreAnimal Testing Should Not Be Banned1572 Words   |  7 PagesAnimal Testing Every year, over two hundred million innocent animals are injured or killed in scientific experiments across the world. Of those animals, between seventeen and twenty million are used in the United States alone. It is said that an animal dies in a laboratory every three seconds (Animal Testing 101). Those in favor of animal experimentation say they are taking animals’ lives to save humans. It is not necessary to subject animals to torturous conditions or painful experiments in theRead MoreAnimal Testing Should Not Be Banned1581 Words   |  7 PagesAnimal testing is being used by different organizations all over the world to prevent specific diseases, especially cancer. Americans see animal testing having a harmful effect but it is one of the main reasons why society has most cures for some illnesses. 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Animals are often abused, suffer, and even die during laboratory testing for the benefits of people to make sure medications, household products, newest procedures, and cosmetics are safe and effective for human use. Humans have benefited from animal testing for years while these animals suffer consequences with no positive outcomes for themselves. Even if a product or procedure is deemed successful, these animals are frequentlyRead MoreAnimal Testing Should Be Banned Essay1632 Words   |  7 Pages Animal Testing Should Be Banned Throughout the decades, animals have been used in medical research to test the safety of cosmetics including makeup, hair products, soaps, perfume, and countless of other products. Animals have also been used to test antibiotics and other medicines to eliminate any potential risks that they could cause to humans. The number of animals worldwide that are used in laboratory experiments yearly exceeds 115 million animals. Unfortunately, only a small percentage of

The American Dream Is Everyone s Dream - 1934 Words

â€Å"I think the American Dream is everybody’s dream.† When Ralph Lauren, the corporation, chose this quote from their respective patriarch as the basis for an advertisement in October 2017’s issue of Esquire Magazine, they were making a bold, blanket statement. They also made an assumption. While this advertisement uses many traditional American stereotypes, portraying a sense of optimism and nostalgia centered around civic nationalism, it makes a mistake in itsit’s overly broad appeals that render the ad ineffective; the American dream is not everyone’s dream, it’s not even every American’s dream. To make sense of this, one must define both â€Å"The American Dream† and â€Å"eEverybody† within the context of this statement. The American Dream may†¦show more content†¦The Jeep is known as the vehicle that won World War II. The family represents the idea that America is a place where one’s children ca n grow up to maximize their full potential. These items are all tied together by their identity within an American context. Of these classic American stereotypes, the cowboy hat atop Lauren’s head carries with it as much nostalgia as nearly any other possible non-government affiliated symbol (i.e. the American Flag). The cowboy hat represents American concepts such as the west, wide open spaces, and manifest destiny. A secondary interpretation, which actually makes more sense in the context of the ad, being that the form and shape of this hat renders itself much more commercial than functional, is that the hat references the â€Å"Golden-Age of Hollywood,† a time in 1950’s and 1960’s America when Western film was at its height and â€Å"every† young boy in America wanted to be John Wayne. On an even deeper analysis, one may notice that the pose of Lauren in this photograph bears a striking resemblance to a famous portrait of President Ronald Reagan in his cowboy hat and work shirt. 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Internship Experience Free Essays

Health Care Management Internship Experience Labovitz School of Business and Economics University of Minnesota Duluth Description of the Program The purpose of the internship program is to provide juniors and seniors with an opportunity to enhance and apply what they learn in their academic program while working in a health service organization. Students are pursuing a degree in business administration and are majoring in health care management. Those that enroll in the Labovitz School of Business and Economics (LSBE) Health Care Management Internship Program will need to accumulate a minimum of 200 hours of work experience over the course of an academic semester or during the summer. We will write a custom essay sample on Internship Experience or any similar topic only for you Order Now The intent of the program is to provide relevant organizational experience to students who otherwise would not have the opportunity to work before completing a degree. Employers are encouraged to participate in the cooperative education internship program. The basic requirements include a clear agreement regarding program requirements, the type of experience being provided, and a line of communication between the student’s mentor/supervisor and the faculty advisor. Internship Objectives The Health Care Management Internship Program enables students to gain added knowledge and skills through structured work experience. Opportunities are available to the student through an internship that cannot be achieved in the classroom. The primary goal of this endeavor is student learning. The specific objectives are to enable students to learn more about health care management; inform the health care community of student abilities and career preparation; give students the opportunity to develop a sense of responsibility for their continued learning by working independently and collaboratively within the parameters of an internship experience; familiarize students with the experiences related to the process of seeking employment; and strengthen ties between LSBE and the health care community by seeking advice from health care leaders concerning curriculum planning, tudent recruitment, and graduate placement. The internship should be designed to provide the student a hands-on experience in a health service organization. It should provide a first hand look at day-to-day operations of a facility and provide the student an opportunity to observe and assist employees in various departments, if possible. It should provide the student an opportunity to observe and be actively involved in management activities using basic management skills of communication, problem solving, management of relationships, and analysis of information. Roles and Responsibilities of the Parties Employers of student interns are an integral part of the work experience program. It is important that employers understand that the internship is an educational program integrated with practical work experience. This requires the employer to give careful thought to the utilization of students who will be employed. During the internship the student is not a volunteer or an additional staff member but a trainee working to fulfill his/her learning needs in as active a manner as possible with the capability to make positive contributions to the achievement of organizational goals. The following items are basic responsibilities of the employer, mentor, faculty advisor, and student. Employer: 1. Interview students who apply for an internship with your organization to provide them with the added benefit of going through an interview and to help you decide which student best meets your employment needs. 2. Review and discuss student learning objectives during the interview or at the start of the internship, in order to identify means by which they will be accomplished during the employment period. 3. Plan work assignments progressively so that the student will advance from routine activities at the beginning of the internship to more job variety and complexity as needed knowledge and skills are gained. 4. Evaluate student work performance. As a role model and supervisor of students, employers are in a position to provide interns a thorough performance evaluation. The LSBE Internship Office will provide evaluation forms; or you may want to use your organization’s standard appraisal form to assess the intern’s performance and provide feedback. . Provide liability coverage for student intern. The University of Minnesota Duluth Worker’s Compensation and Liability coverage does not extend to student interns. Employers may be concerned about injuries to students on-the-job or problems that could arise due to student inexperience. We recommend that concerns of this nature be addressed to your legal counsel. Your existing worker’s compensation covers paid empl oyees and could possibly be extended to volunteers for a nominal fee if this work arrangement is established. 6. Abide by the University of Minnesota employment policies regarding the treatment of employees, including prevention of sexual harassment in the work place. Detailed descriptions of these policies can be found in the UMD Employer Handbook. 7. Contact Jennifer Schultz, Director of the Health Care Management Program, at 218-726-6695 should problems arise. Mentor/Supervisor: 1. Serve as a model, coach, mentor, and tutor to the student. 2. Assist the student in identification of learning outcomes and activities to achieve them. 3. Assign the student specific and significant duties and projects that contribute to the student’s education but are also beneficial to the operations of the organization. 4. Ensure that opportunity is provided to permit the student to achieve agreed upon learning outcomes within the allotted time. 5. Observe and/or obtain observations of the student’s interactions and work within the organization and provide feedback. 6. Share information and thought processes with the student to provide as much insight as possible into successful approaches to management responsibilities. 7. Provide the student orientation concerning policies, rules and regulations. 8. Provide a concluding evaluation of the student’s performance during the internship upon completion in a manner which will encourage the student to grow in his/her administrative skills. 9. Report misconduct on the part of the student immediately to the faculty advisor and work with the faculty advisor to determine appropriate action to rectify problems or conclude the internship experience at the organization. Faculty advisor: 1. Provide the student and mentor information concerning institutional policies governing internship experiences. . Provide the mentor with written guidelines concerning the content and conduct of the internship and such additional advice and consultation as may be necessary or requested to ensure a satisfactory learning experience for the student. 3. Provide instruction to the mentor concerning learning objectives for a successful internship and procedures to follow to struct ure and supervise a successful internship. 4. Take action to withdraw a student whose conduct violates organizational rules or who proves not to benefit from the learning experiences provided by the organization. 5. Maintain contact with the student and mentor during the internship to ensure that objectives are being met and that problems are dealt with in a timely manner. At least one on-site visit will be performed. 6. Ensure that all internships are initiated with a signed learning agreement approved by the student, mentor and faculty advisor. 7. Review student’s journal, final written report, and performance evaluations. Student: 1. Apply for academic credit through college registration and work with a faculty advisor for placement with a mentor. 2. Learn and abide by organizational standards as applied to personnel, e. . follow facility hours and dress code policies, etc. 3. Take as active a role as possible in the operations of the organization, performing actual duties within the department as permitted by staff to learn first-hand the activities and their contribution to the overall effectiveness of the organization. 4. Prepare a list of learning outcomes expected from the interns hip and obtain approval for it from the mentor and faculty advisor, then identify and pursue specific experiences which will achieve those outcomes, again in consultation with the faculty advisor and mentor. 5. Identify and agree with the mentor upon a special project to be completed to satisfy course requirements while providing a learning experience which assists in meeting the student’s learning outcomes. 6. Meet course requirements for completion of assignments including preparation of two reports and weekly journal entries. 7. Taking into consideration course requirements and the student’s personal work and volunteer experience, prepare a schedule of the amount of time to be spent at the organization, obtain approval of the proposed schedule from the mentor and faculty advisor and ensure that it is implemented. How to cite Internship Experience, Papers

The Controversy of Clinical Versus Actuarial Prediction Essay Example

The Controversy of Clinical Versus Actuarial Prediction Paper In clinical prediction, psychologists use their clinical experience to formulate a prediction based on interview impressions, history ATA and test scores (Melee, Clinical versus Statistical 4). The formula in the title refers to statistical or actuarial prediction. In actuarial prediction, clergies access a chart or table which gives the statistical frequencies of behaviors (Actuarial Prediction). Advocates of the clinical method say that clinical prediction Is dynamic, meaningful and sensitive but actuarial prediction Is mechanical, rigid and artificial (Melee, Clinical versus Statistical 4). On the other hand, advocates of the actuarial method claim that actuarial method Is empirical, precise and objective but alnico prediction Is unscientific, vague and subjective (Melee, Clinical versus Statistical 4). The controversy of clinical versus actuarial judgment is not limited to the field of psychology; it also affects education in terms of predicting school performance, criminal justice system in terms of parole board decisions and business in terms of personnel selection. Although this controversy can be traced back half a century ago, social scientists today are still asking: Which of the two methods works better? Can we view any prediction dichotomously as either clinical or actuarial? And, if actuarial predictions are more accurate, should we abandon clinical predictions all together? On one side of the controversy, some people feel that using mere numbers to determine whether students can enter graduate schools or whether prisoners should be released Is dehumidifying (Melee, Causes and Effects 374). We will write a custom essay sample on The Controversy of Clinical Versus Actuarial Prediction specifically for you for only $16.38 $13.9/page Order now We will write a custom essay sample on The Controversy of Clinical Versus Actuarial Prediction specifically for you FOR ONLY $16.38 $13.9/page Hire Writer We will write a custom essay sample on The Controversy of Clinical Versus Actuarial Prediction specifically for you FOR ONLY $16.38 $13.9/page Hire Writer In her book about social psychology, Thompson describes a young woman who complains that It Is horribly unfair that she has been rejected by the Psychology Department at university of California on the bases of mere numbers, without even n interview (88). When my psychology teacher surveyed our class on this issue, about 20 percent of students believe that it is unethical to make predictions based on mere numbers (Brenner). The crux of this ethical concern lies on the belief that each individual is so unique that rigid statistics or equations cannot make the correct prediction in every single case. Indeed, most psychologists agree that rigid statistics are not sensitive to special cases. Paul Mà ªlà ©es well-known broken-leg example Illustrates how the special powers of the clinician can predict behaviors ore accurately in some special cases: If a sociologist were predicting whether Professor X would go to the movies on a certain night, he might have an equation Involving age, academic specialty, and Introversion score. The equation might yield [a very high probability] that Professor X will go to the movie tonight. But if Professor X Ana Just Darken Nils leg Ana en Is In a nil cast Tanat wont NT In a denature seat, no sensible sociologist would stick with the equation. (Clinical versus Statistical 24-25) Essentially, it is very important for clinicians to detect the characteristics of each unique individual and make predictions accordingly because clinicians deal with individual cases; they make predictions for each unique individual, not for a group of people. Thus, it is the individual case that defines the clinician (Melee, Clinical versus Statistical 25). Because of the insensitivity of statistics to special cases and the importance of predicting individual cases, many psychologists argue that statistics simply cannot apply to individuals (Melee, Causes and Effects 374). They believe that clinicians can make predictions about individuals can transcend the predictions bout people in general (Melee, Causes and Effects 374). For example, Patriots emphasized in his research on personality inventory that: In [nonproductive] tests, the results of every individual examination can be interpreted only in terms of direct, descriptive, statistical data and, therefore, can never attain accuracy when applied to individuals. Statistics is a descriptive study of groups, not of individuals. (633) On the other side of controversy, advocates of the actuarial approach have questioned the logic behind the assumption that statistics do not apply to single individuals or events. Stanchion uses a very good analogy to illustrate the fallacy behind this assumption (179). He asks us whether we want our operation done by an experienced surgeon who has a low failure probability or an inexperienced surgeon who has a high failure probability (179). Of course, any rational man will choose the experienced surgeon. However, if we believe that probabilities do not apply to the single case, we should not mind to have our operation done by the inexperienced surgeon. This question brings us to think about the role of chance in making reductions. Stanchion noted: Reluctance to acknowledge the role of chance when trying to explain outcomes in the world can actually decrease our ability to predict real-world events Acknowledging that our predictions will be less than 100 percent accurate can actually help us to increase our overall predictive accuracy. (175) An experiment done by Fainting and Subsidiaries (58-63) demonstrates Stanchions last point that we must accept error in order to reduce error. In this experiment, the participant sits in front of a red light and a blue light and is asked to predict which eight will be flashed on each trial (60). The experimenter has programmed so that the red light will flash 70 percent of the time and the blue light 30 percent of the time (59). Participants quickly pick up the fact that the red light is flashing more, thus they predict the red light roughly 70 percent of the time and the blue light roughly 30 percent of the time (62). The problem is that they do not understand that if they give up on trying to predict correctly on every trial, they can actually be more accurate. We can demonstrate the logic of this situation through a calculation on 100 trials. In 70 of the 100 trials, the red light will come on and the participant will be correct on about 70 percent of those 70 trials. That means, in 49 of the 70 trials (70 times . 70), the participant will correctly predict that red light will flash. In the same way, we can calculation that approximately in 9 trials (30 times . 30), the participant will correctly predict that the blue light will flash. Therefore, the participant can only predict correctly 58 percent of the time (49 percent from the red light and 9 percent from the (B). However, IT ten participant simply gives up on getting every trial relent Ana just predicts the red light on every trial, he can predict correctly 70 percent of the time (because the red light will come on 70 percent of the time), which is 12 percent better than switching back and forth trying to get right on every trial. This is what Stanchion means by accepting error in order to reduce error. Research on this controversial issue has consistently indicated that actuarial prediction is more accurate than clinical prediction. In Paul Mà ªlà ©es classical book Clinical versus Statistical Prediction, he had reviewed 22 studies comparing clinical and actuarial prediction (83-126). Out of these 22 studies, twenty show that actuarial prediction is more accurate than clinical prediction. These twenty studies cover almost all the clinical prediction domain, including psychotherapy outcome, criminal recidivism, college graduation rates, parole behavior and length of psychiatric hospitalizing. A graduate student at JIBE had also done a study comparing clinical and actuarial prediction (Simmons 3). In this study, Simmons compared the predictions made by a regression equation and by two experienced counselors on the school performance of JIBE freshmen (Simmons 3). The results again indicate the actuarial prediction using the regression equation was more accurate (Simmons 64). In addition, a recent meta-analysis using 136 studies has also confirmed that actuarial prediction is better regardless of the Judgment task, type of Judges, or Judges amount of experience (Grove et al. 9). Researchers found that actuarial prediction substantially outperformed clinical prediction in 45 percent of the studies whereas clinical prediction was more accurate in only 10 percent of the studies (19). Regarding the research consistently showing that actuarial prediction is more accurate , Paul Melee said, There is no controversy in social science which shows such a large body of qualitatively diverse studies coming out so uniformly in the same direction as this one (373-374). Mà ªlà ©es actuarial stance is strongly challenged by Robert R. Holt, who is also a renowned clinical psychologist. Holt criticizes that the twenty studies Melee cited in his book only focus on the final step of the prediction-making process, which is making the prediction (339). Holt rejects the dichotomous classification of studies as clinical or statistical because in field settings, clinicians do not simply make a prediction by evaluating the given data (338). In field settings, before the clinician can make the prediction, he has to carefully identify the criterion he can predict and choose predictive variables he wants to use. (Holt 339-340). For example, if a counselor wants to predict the school performance of first year university dents, he first identifies the criterion he is able to predict; the criterion can be Gaps or average marks of the students, but it can also be the students lecture attendances. He also has to choose which predictive variables he should use; he may use the students entrance grades or their scores on an aptitude test or a combination of both. Then, finally, he can make the prediction using either an equation or his own Judgment. This example shows that even if the clinician uses actuarial approach in the final step of the prediction-making process, he still plays an important role in all the preceding steps. I agree with Holt that Melee has oversimplified the distinction between clinical and statistical prediction. I believe that we should view these two methods as falling on a continuum rather than make an all-or-none distinction. Some predictions that can be completely done on computers are more statistical toner protections, Tort wanly psychoanalysts need to collect Ana analyze data, are more clinical. I also agree with Holt that we should still value clinical judgment although it is not as accurate. Without clinical Judgment, scientists will to be able to form hypotheses and theories, and to analyze research results and data. Like Western and Weinberg said in their article reviewing this controversial issue, try as we might to eliminate subjectivity in science, we can never transcend the fact that the mind of scientists, clinicians or informants is the source of much of what we know (609). Nevertheless, when countless research findings point toward one direction, I think we should recognize that actuarial predictions are more accurate than clinical predictions (at least in the final step of the prediction-making recess). Some people think that using mere numbers to make predictions is dehumidifying. They feel that using an equation to forecast a persons action is treating the individual like a white rat or an inanimate object (Melee Causes and Effects 374). However, I argue that in certain cases, it is unethical to use clinical judgment when actuarial approach has shown to be accurate. For example, when a clinical psychologist makes a prediction about whether a student is going to commit suicide within a year, would it be more ethical to use the actuarial prediction that is here times more accurate than the clinical prediction (Brook et al. 03)? The answer to this question should be as obvious as the question about whether we want our operation done by an experienced or an inexperienced surgeon. By admitting that actuarial Judgment is more accurate, clinicians who engage in activities in the role of experts and imply that they have unique clinical knowledge of individual cases may lose prestige and income; however, the field of psychology, and society, will benefit if we underst and that accepting error is reducing error.

Film Analysis of Field of Dreams essays

Film Analysis of Field of Dreams essays Ray Kinsella is an ordinary man from Eastern Iowa who has an extraordinary event happen to him that will change the life for him and his family forever. The movie "Field of Dreams" was released in 1989 and stared Kevin Costner, James Earl Jones, Amy Madigan, and Burt Lancaster. The film was nominated for three academy awards including "Best Picture". The film begins with a narrative of the life of Ray's father. His father played baseball when he was younger but never made it professionally. Instead, he got married and had a son and worked at a factory his entire life to support his family. Ray played baseball early in his life and was forced to live out the dreams of his father. Ray's father wanted him to go on and play baseball professionally since he never got the chance too. However, Ray saw things differently and rebelled against his father's wishes. He went to college at the University of California- Berkeley. He attended Berkeley he majored in English but really majored in the youth movement of the 1960's "Peace, Love, and Dope" was among his favorite saying of the era. While attending Berkeley, he met the love of his life Annie. They were married and after college moved, to Iowa near her parents bought some land and had a girl (Katie). Ray was now a farmer who loved his family, the 60s, and baseball. He is an ordinary man from a small farming community in Iowa. Life was all too normal for Ray until the day he heard a voice from the cornfield. "If you build it he will come". Ray at first does not know what the voice means by the statement "id you build he will come". He eventually ties the message from the voice to his Dad's baseball hero Shoeless Joe Jackson. Jackson was a Chicago White Sox baseball player that (along with his teammates) was kicked out of baseball for throwing games. Ray believes that if he builds a baseball filed that Shoeless Joe Jackson will come. Despite the financial concerns Ray supported by his wife...

Lockheed U-2 Spy Plane

Lockheed U-2 Spy Plane In the years immediately after World War II the US military relied on a variety of converted bombers and similar aircraft to collect strategic reconnaissance. With the rise of the Cold War, it was recognized that these aircraft were extremely vulnerable to Soviet air defense assets and as a result would be of limited use in determining Warsaw Pact intentions. As a result, it was determined that an aircraft capable of flying at 70,000 feet was needed as existing Soviet fighters and surface-to-air missiles were incapable to reaching that altitude. Proceeding under the codename Aquatone, the US Air Force issued contracts to Bell Aircraft, Fairchild, and Martin Aircraft to design a new reconnaissance aircraft capable of meeting their requirements. Learning of this, Lockheed turned to star engineer Clarence Kelly Johnson and asked his team to create a design of their own. Working in their own unit, known as the Skunk Works, Johnsons team produced a design known as the CL-282. This essentially married the fuselage of an earlier design, the F-104 Starfighter, with a large set of sailplane-like wings. Presenting the CL-282 to the USAF, Johnsons design was rejected. Despite this initial failure, the design soon received a reprieve from President Dwight D. Eisenhowers Technological Capabilities Panel. Overseen by James Killian of the Massachusetts Institute of Technology and including Edwin Land from Polaroid, this committee was tasked with exploring new intelligence weapons to protect the US from attack. While they initially concluded that satellites were the ideal approach for gathering intelligence, the necessary technology was still several years away. As a result, they decided that new spy plane was needed for the near future. Enlisting the aid of Robert Amory from the Central Intelligence Agency, they visited Lockheed to discuss the design of such an aircraft. Upon meeting with Johnson they were told that such design already existed and had been rejected by the USAF. Shown the CL-282, the group was impressed and recommended to CIA head Allen Dulles that the agency should fund the aircraft. After consulting with Eisenhower, the project moved forward and Lockheed was issued a $22.5 million contract for the aircraft. Design of the U-2 As the project moved forward, the design was re-designated U-2 with the U standing for the deliberately vague utility. Powered by the Pratt Whitney J57 turbojet engine, the U-2 was designed to achieve high altitude flight with a long range. As a result, the airframe was created to be extremely light. This, along with its glider-like characteristics, makes the U-2 a difficult aircraft to fly and one with a high stall speed relative to its maximum speed. Due these issues, the U-2 is difficult to land and requires chase car with another U-2 pilot to help talk the aircraft down. In effort to save weight, Johnson originally designed the U-2 to take off from a dolly and land on a skid. This approach was later dropped in favor of landing gear in a bicycle configuration with wheels located behind the cockpit and engine. To maintain balance during takeoff, auxiliary wheels known as pogos are installed under each wing. These drop away as the aircraft leaves the runway. Due to the U-2s operational altitude, pilots wear the equivalent of a spacesuit to maintain proper oxygen and pressure levels. Early U-2s carried a variety of sensors in the nose as well as cameras in a bay aft of the cockpit. U-2: Operation History The U-2 first flew on August 1, 1955 with Lockheed test pilot Tony LeVier at the controls. Testing continued and by spring 1956 the aircraft was ready for service. Reserving authorization for overflights of the Soviet Union, Eisenhower worked to reach an agreement with Nikita Khrushchev regarding aerial inspections. When this failed, he authorized the first U-2 missions that summer. Largely flying from Adana Air Base (renamed Incirlik AB on 28 February 1958) in Turkey, U-2s flown by CIA pilots entered Soviet airspace and collected invaluable intelligence. Though Soviet radar was able to track the overflights, neither their interceptors nor missiles could reach the U-2 at 70,000 ft. The success of the U-2 led the CIA and US military to press the White House for additional missions. Though Khrushchev protested the flights, he was unable to prove that the aircraft were American. Proceeding in complete secrecy, flights continued from Incirlik and forward bases in Pakistan for the next four years. On May 1, 1960, the U-2 was thrust into the public spotlight when one flown by Francis Gary Powers was shot down over Sverdlovsk by a surface-to-air missile. Captured, Powers became the center of the resulting U-2 Incident which embarrassed Eisenhower and effectively ended a summit meeting in Paris. The incident led to an acceleration of spy satellite technology. Remaining a key strategic asset, U-2 overflights of Cuba in 1962 provided the photographic evidence that precipitated the Cuban Missile Crisis. During the crisis, a U-2 flown by Major Rudolf Anderson, Jr. was shot down by Cuban air defenses. As surface-to-air missile technology improved, efforts were made to improve the aircraft and reduce its radar cross-section. This proved unsuccessful and work began on a new aircraft for conducting overflights of the Soviet Union. In the early 1960s, engineers also worked to develop aircraft carrier-capable variants (U-2G) to extend its range and flexibility. During the Vietnam War, U-2s were used for high-altitude reconnaissance missions over North Vietnam and flew from bases in South Vietnam and Thailand. In 1967, the aircraft was dramatically improved with the introduction of the U-2R. Approximately 40% larger than the original, the U-2R featured underwing pods and an improved range. This was joined in 1981 by a tactical reconnaissance version designated TR-1A. The introduction of this model re-started production of the aircraft to meet the USAFs needs. In the early 1990s, the U-2R fleet was upgraded to the U-2S standard which included improved engines. The U-2 has also seen service in a non-military role with NASA as the ER-2 research aircraft. Despite its advanced age, the U-2 remains in service due to its ability to perform direct flights to reconnaissance targets on short notice. Though there were efforts to retire the aircraft in 2006, it avoided this fate due to the lack of an aircraft with similar capabilities. In 2009, the USAF announced that it intended to retain the U-2 through 2014 while working to develop the unmanned RQ-4 Global Hawk as a replacement. Lockheed U-2S General Specifications Length:  63 ft.Wingspan:  103 ft.Height:  16 ft.Wing Area:  1,000 sq. ft.Empty Weight:  14,300 lbs.Loaded Weight:  40,000 lbs.Crew:  1 Lockheed U-2S Performance Specifications Power Plant:  1 Ãâ€" General Electric F118-101 turbofanRange:  6,405 milesMax Speed:  500 mphCeiling:  70,000 ft. Selected Sources FAS: U-2The CIA the U-2 Program: 1954-1974

What Should government do to protesct society from mass shootings Research Paper

What Should government do to protesct society from mass shootings - Research Paper Example The debate rages on. In recent years, the debate has become increasingly vocal, as mass shootings have begun to invade the American landscape. Some argue that such shootings are the very reason why the Constitution guarantees citizens the right to bear arms. Others, however, argue that society has changed in the past 300 years and the time for strict gun control has come. There are valid points to both sides and this paper will highlight some major positions, while arriving at the conclusion that the right to own and maintain a gun must remain a part of the American fabric for now and the foreseeable future. The Argument for Gun Control Individual freedom and liberty is a cornerstone birthright that comes with being an American citizen. There are certain rights that are written into the Constitution in an effort to prevent any future government from taking that liberty away. As time goes on, however, and society develops, the language written into the Constitution can become muddled and filled with doubt and uncertainty. There are some, for example, that claim the right to own a gun is not actually a fundamental right guaranteed under the second amendment. Much of this opinion involves cause and effect, and examining that actual reasoning behind the second amendment. There are multiple reasons a person might own a gun. Some may own a gun to hunt wild game, while others will maintain a functioning weapon for purposes of self-defense. Still others might have a gun due to military or police service, and some might own a gun to commit a crime such as robbing a bank. The modern day argument in support of gun control, then, largely centers on this issue. Since the Constitution does not possibly permit the right of a gun owner to use such a weapon in the commission of a crime, then it certainly does not permit the right of every individual in the country to own a gun. Guns are permitted under the second amendment for purposes of military service. Few would argue that point. Many would argue, however, that the Constitution does not inherently protect the right of gun ownership for other reasons (Stevens para. 4). The center of this debate is on the language in the Second Amendment. While it seems so clear to some, it is far from it to others. While the courts have generally upheld the principle that Americans have the right to gun ownership, there is a growing movement in government circles to have the courts take another look at the language and to issue new rulings. On this side of the issue, the opinion is that gun ownership is a right for some, but not for others. The distinction comes in the language used to write this part of the Constitution. The actual purpose governing the inclusion of the Second Amendment into the Constitution was to allow citizens to protect themselves from a well-regulated militia. In other words, if the government took away the rights of the people, the people had a right to fight back, or to defend themselves. In th is vein, people have argued for gun control on the basis that gun control, and the limiting of gun ownership, is permissible under these guidelines (Faria 133). In recent years, there has been an unfortunate rise in violence on school campuses, particularly colleges and universities. Some have used this as an argument for gun ownership and the permissibility of students to be able carry guns on campus in order to better protect themselves against threats, such as mass shootings. Others, however, have argued that this is the very reason we should have gun control. By taking guns out of the hands of all individual citizens, they claim

Bipolar disorder Term Paper Example | Topics and Well Written Essays - 1000 words

Bipolar disorder - Term Paper Example Bipolar disorder falls among the oldest illnesses, which are known. The recognition of the disorder was during the second century and the discovery was in a Turkey’s city. The findings were not noticed and neither were they substantiated up to the year 1650, when Richard Burton, a scientist wrote his book called The Anatomy of Melancholia. The book majorly laid much emphasis on depression. The findings of the scientist are still used today even by fields related to mental health (Brent and Pan, 2008). In the year 1952, a journal article was written that critically analyzed the disorder’s heredity. The article showed that manic depression is capable of being passe own in families that already have patients with the disorder. In 1960’s, several people with bipolar disorder were placed at a given institution and provided with little financial help since the Congress refused to acknowledge that manic depression is a legitimate illness. However, during the 1970â€℠¢s, laws were enacted and besides, standards were put into place to aid the afflicted individuals. Similarly, in the year 1979, National Association of Mental Health was established (Reich, Clayton and Winokur, 1969). During the 1980’s, research was finally capable of distinguishing between childhood as well as adult bipolar disorder. Presently, a number of studies are still needed to unravel the possible causes as well as the probable means of treating the illness (Baloch & Soares, 2010). Generally, bipolar disorder develops when an individual is approaching his late teens although it also develops when individuals approaches their adulthood. However, there are a number of cases commences before the age of 25 (Kessler et al, 2005). In a number of individuals, first symptoms occur during their childhood, while in others, symptoms may develop very late in their lives. Diagnosis of bipolar disorder is done after individuals report their experiences; however, it may also be done after friends, family members and co-workers detect an abnormality. Secondary signs of the illness may be detected by clinical psychologist, social workers, psychiatrist, nurses, and also through clinical evaluation. However, the diagnosis of the condition is dependent on the presence as well as the duration of specific signs as well as symptoms (Sadock & Sadock, 2007). For an individual having bipolar disorder to be diagnosed correctly, it takes roughly 20 years. In approximately 37% of patients, bipolar disorder is usually diagnosed erroneously since it is always mistaken for unipolar depression. Surveys also prove that about 50% of individuals suffering from the disorder fail to take the medications that are prescribed (Brent & Pan, 2008). In general, the problem is not caused by the patient, though impaired judgment offer powerful incentives for skipping the medication. In order to control the disorder, drugs should be used. However, the drugs have side effects, which include g aining of weight as well as cognitive dulling (Young et al., 1978). In about 90% of marriages, that involves partners with bipolar disorder result into divorce due to the diseases adverse effects. Moreover, researchers have made estimation that about 40 percent of individuals having the disorder abuse drugs. Researchers also state that approximately 15 to 25% of individuals ha

Advanced Glycation End Products (AGE) for Diabetes

Advanced Glycation End Products (AGE) for Diabetes Diabetes mellitus is a syndrome which defined as a group of metabolic diseases characterized by hyperglycemia, that result from insufficient production of insulin, or body cells poorly respond to the insulin that is produced, or both. Insulin is a hormone produced in the pancreas and secreted in the blood to maintain blood glucose in the body through enables body cells to absorb glucose, to turn into energy. If the body cells enable to absorb the glucose, the glucose will accumulates in the blood (hyperglycemia), leading to many and different potential medical complications (Harmel Mathur, 2004). Diabetes have several categories but the majority of cases fall into two categories which are type 1 diabetes mellitus and type 2 diabetes mellitus. These two types are powerful and highly independent risk factors causing coronary artery disease, stroke, peripheral arterial disease and organ damage and dysfunction including eyes and nerves (Harmel Mathur, 2004). Type 1 Diabetes Mellitus: Type 1 diabetes mellitus resulting from pancreas failure to produce insulin hormone. Person at risk of developing type 1 can be identified by doing serologic test markers that showing evidence of autoimmune destruction of beta cells (islet cells) of the pancreas which is responsible for insulin production. Type 1 diabetes is manifested in childhood and early adulthood, but can patient present at any age (Goroll Mulley, 2009). Type 2 diabetes mellitus: Patients with type 2 diabetes mellitus are prone with wide range of series complications. Type 2 is characterized by high blood glucose due to insulin resistance and relative insulin deficiency. There are 20.8 million people in United State with type 2 diabetes mellitus. Type 2 diabetes traditionally is seen in elderly people. However it is diagnosed in obese children. Many studies shows that type 2 diabetes mellitus are associated with high calorie diet, physical inactivity and life style (Feinglos Bethel, 2008). Other Types of Diabetes: There are other types of diabetes but they are less common but patients who are underlying defect or disease process can be identified in a relatively specific manner. These types are Genetic defects of beta-cell function, Diseases of the exocrine pancreas e.g Fibrocalculous pancreatopathy, Endocrinopathies and cystic fibrosis and Uncommon forms of immune-mediated diabetes. Diabetes mellitus complications: Diabetic complications can be grouped into macrovascular and microvascular disease. Macrovascular diseases are result from atherosclerosis which develops in earlier age in patient with diabetes. There are several factors contribute to atherosclerosis such as lipidemia, hypertension, increased platelets adhesion and aggregation, elevated factor V, factor VII and fibrinogen concentration. Macrovascular diseases are seen in both type one and two of diabetes mellitus and they include coronary heart disease, Ischemic stroke and peripheral vascular disease (which can lead to ulcers, gangrene and amputation) (Winter Signorino, 2002). Whereas, Microvascular complications is seen in type one diabetes mellitus. Hyperglycemia damages the basement membrane of capillaries in the retina and glomerulars which leads to retinopathy and neuropathy. Microvascular diseases include neuropathy (nerve damage), nephropathy (kidney disease) and vision disorders (eg retinopathy, glaucoma, cataract and corneal disease). Furthermore there are other complications of diabetes include infections, metabolic difficulties, dental disease, autonomic neuropathy and pregnancy problems (Winter Signorino, 2002). Several clinical research show a strong relationship between hyperglacemia and diabetic microvascular complications in both type 1 and type 2 diabetes. High glucose and insulin resistance play important roles in the pathogenesis of macrovascular complications due to atherosclerosis. Diabetes-specific microvascular disease in the retina, glomerulus and vasa nervorum has same pathophysiological features. Intracellular hyperglycaemia causes abnormalities in blood flow and increased vascular permeability which leads to decreased activity of vasodilators such as nitric oxide, increased activity of vasoconstrictors such as angiotensin II and endothelin-1, and elaboration of permeability factors such as vascular endothelial growth factor (VEGF) (Brownlee, 2001). There are several factors which contribute the formation of inflammation, atherosclerosis and diabetes mellitus complication. These factors are hyperglycemia, accumulation of advanced glycation endproducts, dyslipidemia and oxidative stress which lead to endothelial dysfunction resulting in thrombotic complications and cardiovascular (Altman, 2003). In type 1 diabetes mellitus, high blood glucose is usually as result of low level of insulin secretion whereas in type2 hyperglycemia is caused by resistance of insulin at the cellular level. Low insulin levels or insulin resistance enable the body to convert glucose into glycogen (a starch-as source of energy which stored in the liver). In type 1 diabetes, pancreatic beta cells are attacked by auto-immune which cause infiltration of inflammatory cells and increased expression and secretion of S100-calcium binding protein and high-mobility group protein 1 (HMGP1) through inflammatory cells which consequently lead to islet damage and increased blood glucose level, subsequent accumulation of AGE (Bierhaus Nawroth, 2009). Comparing to T1D, in type 2 diabetes mellitus, different metabolic disturbances stimulates inflammatory cells to secretes RAGE ligands, which cause low-grade inflammation and increased oxidative and carbonly stress, all these play roles in promoting AGE formation and RAGE expression in respective organs (Bierhaus Nawroth, 2009). Insulin resistance and Inflammation: In diabetic patients with hyperglycemia, cause by 1) impaired insulin secretion by the pancreatic ß-cells, 2) muscle insulin resistance, and 3) hepatic insulin resistance all play central roles in the development and progression of glucose intolerance. As I mention before, type 2 diabetes mellitus (T2DM) is characterized by insulin resistance in liver and muscle and impaired insulin secretion. Also include deranged adipocyte metabolism and modified fat topography in the pathogenesis of glucose intolerance in T2DM. Fat cells are resistant to insulins antilipolytic effect, which result in increased plasma free fat acid levels. Long period of increasing plasma fat fee acid stimulates gluconeogenesis, promote hepatic and muscle insulin resistance, and impairs insulin secretion in genetically predisposed patients. These pathways of FFA-induced are known as lipotoxicity. Fat cells Dysfunction makes excessive amounts of insulin resistance-inducing, inflammatory, and atherosclerotic-provoking cytokines and fails to secrete normal level of insulin-sensitizing adipocytokines. Enlarged fat cells are insulin resistant and have minimized capacity to store fat. When storage capacity of adipocyte is exceeded, lipid overflows into muscle, liver, a nd perhaps ß-cells, resulting in muscle, hepatic insulin resistance and impaired insulin secretion. In type 2 diabetics, the ability of insulin to stop lipolysis and to decrease the plasma FFA levels is markedly impaired. It is clearly that chronic elevated levels of plasma free fat acid leads to insulin resistance in muscle and liver, and impair insulin secretion. In addition to FFA in plasma, increase stores of triglycerides in muscle and liver which correlate closely with the presence of insulin resistance in tissues. The triglycerides in liver and muscle are in a state of constant turnover, and the metabolites of intracellular triglyceride lipolysis impair action of insulin in liver and muscle (Bays et al, 2004). This pathway of events has been referred to as lipotoxicity . The accumulation of lipid in dipocytes leads to activate NADPH oxidase which increases the production of reactive oxygen species (ROS). The mechanisms increased production of cytokines including TNF-ÃŽ ±, IL-6 and monocyte chemoattractant protein-1 and reduce the production of adiponectin (Shoelson et al, 2006). Furthermore accumulation of lipid activates the protein response to increased ER stess in fat and liver. All these have accumulated to induce lipotoxicity as an important cause of ß-cell dysfunction (Bays et al, 2004). Receptor for advanced glycation end products (RAGE): RAGE is type I transmembrane receptor of the immunogloblin superfamily. It is a receptor for advanced glycation endproducts (AGE). It is about 45-KD a protein and it is consist of 403 amino acids in human, rate and mouse. Its extracellular region consists of one V-type (variable) immunoglobulin domina, which followed by two C-type (constant) immunoglobulin dominas (Basta, 2004). Its name drive from its ability to bind AGE and also it is known as AGER. It is located within the major histocompatibility complex (MHC) class III region on chromosome 6, which contains numbers of genes involved predominantly in inflammatory and immune responses and several components of complements. Beside AGE, RAGE is able to bind several ligands therefore is called a pattern-recognition receptor. These ligands are high-mobility group protein 1 (HMGP1), S100-calicum binding protein (S100b) which is family of pro-inflammatory cytokines and it can be found in any inflammatory lesion and vascular walls of diabetics patients, amyloid-ß-protein and macrophage-1 glycoprotein (CD11B/CD18). RAGE plays role in diabetes and other metabolic disease. The interaction of RAGE and its ligands cause pro-inflammatory activation. It is involved in several diseases such as innate immune response, mediating immune and inflammatory response, cancer promoting and progressing and microvascular and mi crovascular diseases (Bierhaus Nawroth, 2009). Moreover, RAGE expression is increased in the cells of the vascular walls, at the site where AGEs and S100/calgranulins are accumulated, including endothelium vascular smooth muscle cells, glomerular mesangial cells and mononuclear phagocytes. This destrbution of RAGE and its ligands leads to increased cellular activation, causing further raised expression of the receptor (Basta et al, 2004). Recently the studies have been proved that RAGE and its ligands accumulate in diabetes and contribute to its pathology. Serum levels of S100A8/9 and S100A12 increased in type 2 diabetic patients. Also, evidence was provided by raised serum levels HMGB1 were linked to coronary artery disease in type 2 diabetes. In addition the studies which have been done in streptozotocin-induced diabetic rats proved that diabetes increased amyloid-beta-peptide (1-40) levels in the brain. Furthermore, CML-modification of S100A8 and S100A9 are seen in inflammatory bowel disease and promote RAGE-mediated sustained inflammatory. Moreover, Carboxylated N-glycans on RAGE eases binding of HMGB and mediates ligation of S100A8/A9 to subpopulation of RAGE on colon cancer cells (Bierhaus Nawroth, 2009). Advanced Glycation End products (AGE) and its biochemical mechanism production: There are various pathways involved in stimulation of atherosclerosis in diabetes mellitus. However the most important one is formation and deposition of AGEs through nonenzymetic reaction between extracellular protein and glucose and it accumulates within cells of the vascular walls, in the extracellular space, kidney, nerves and retina (Basta et al, 2004). Possible mechanism of AGEs formation arise from intracellular auto-oxidation of glucose to glyoxal, decompounding of the Amadori product (glucose-derived 1-amino 1-deoxyfructose lysine adducts) to 3-deoxyglucosone and fragmentation of glyceraldehyde-3-phosphate and dihydroxyacetone phosphate to methylglyoxal. These reactive intracellular dicarbonyls (glyoxal, methylglyoxal and 3-deoxyglucosone) which can react with amino groups of intracellular and extracellular proteins to form AGEs (pyrraline, pentosidine, CML, crossline) (Balasubramanyam et al, 2002). Several experimental studies evidenced that advanced glycation end products can alter vascular wall homeostasis in atherogenic through different ways which are: AGEs and mononuclear phagocytes Interaction: The binding of AGEs with mononuclear phagocytes MPs induces the activation of platelet-derived growth factor, insulin-like growth factor-1, and pro-inflammatory cytokines, such as IL-1ß and TNF-ÃŽ ±. Furthermore the interaction of AGEs with its receptor (RAGE) in the mononuclear phagocytes promotes cell migration (chemotaxis) (Basta et al, 2004). AGEs and vascular smooth muscle cells Interaction: Interaction of AGE with smooth muscle cells (SMCs) exhibits the proliferative activity and production of fibronectin. SMC growth are indirectly mediate by cytokines or growth factors which induced by AGEs in the MPs. Transforming growth factor-ß (TGF-ß) act as an intermediate factor in AGE-induced fibronectin formation by SMC(Basta et al, 2004). AGEs with vascular endothelium Interactions: alterations of vascular permeability and of adhesive properties As result its unique position and numerous properties, the vascular endothelium has important role in the regulation of extracellular permeability, the maintenance of blood fluidity, metabolism of hormones and vasoactive mediators and the regulation of vascular growth and tone. The endothelium is exposed to AGEs located on circulating proteins and cells (such as, diabetic RBCs), also those found in the underlying subendothelial matrix. Receptors for AGEs present on the endothelial cell surface, and mediate both the uptake and AGEs transcytosis, and the internal signal transduction. AGE-RAGE interaction leads to alteration of barrier function and an increased permeability of endothelial cells interact with AGEs and increased migrate of macromolecules through the endothelial monolayer. The increase in permeability is associated by alterations of the physical integrity of the endothelium, as shown by the destruction of structures and alterations of cellular morphology (Basta et al, 2004 ). Also, it has been proved that AGEs cause alterations of endothelial anti-hemostatic functions in vitro, through a reduction of thrombomodulin expression and accompanied with induction of tissue factor expression. The promoting of tissue factor and the decreasing in thrombomodulin activity change the dynamic endothelial features with regard to hemostasis from those of an anticoagulant to those of a procoagulant surface (Basta et al, 2004). Intraction of AGEs with endothelial RAGE also causes the depletion of cellular antioxidant defense mechanisms (such as glutathione, vitamin C) and the generation of reactive oxygen species. As a result of the increased cellular oxidative stress, NF-ÃŽ ºB activation occurs, thus inducing the expression of NF-ÃŽ ºB-regulated genes including, in addition to the procoagulant tissue factor, adhesion molecules, such as E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular adhesion molecule-1 (VCAM-1); this past may prime diabetic vasculature towards enhanced interaction with circulating monocytes. Furthermore, the incubation of endothelial cells with EN-RAGE or S100B results in VCAM-1 induction, in a RAGE-dependent manner, as sustained by the inhibitory effect of anti-RAGE IgG or soluble RAGE (Basta et al, 2004). Alterations of endothelium-dependent vasodilatation AGEs linked to the vascular matrix may quench bioavailability of nitric oxide (NO), which is an important regulator of vascular tone inducing smooth muscle cell relaxation. Studies provided that, AGE inhibits NO activity, when it added to NO in vitro. Studies on animal exterminate induced diabetes show that an alteration of endothelium-dependent dilatation occurs in short period, within 2 months, from diabetes induction. A direct reaction between NO radical and other free radicals which are formed during the reactions of AGEs assumable leads to inactivation of NO. In parallel, advanced glyaction end products promote the expression of the potent vasoconstrictor endothelin-1 changing endothelial function towards vasoconstriction (Basta et al, 2004).   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  These four mechanisms promote and alter vascular wall homeostasis. When mononuclear phagocytes migrate to the site of immobilized AGEs in the tissue, their migrations allow them to interact with AGE -modified surface and become activated. This mechanism cause attracting and retaining MPs in tissue where AGEs deposit. Migration and activation of MPs and T cells (inflammatory cells) promote and cause chronic vascular inflammation through alter vessel wall (Basta et al, 2004). Promotion of atherogenesis pathways by AGEs: AGEs are most important factors in endothelial dysfunction in diabetic patients through binding its receptor (RAGE). Advanced Glycation Endproducts stimulate the expression of proinflammatory cells and molecules (Altman, 2003). AGEs can be seriously deleterious to the function of blood vessel walls in various ways. First it causes blood vessel dysfunction through cross bridges among vessel macromolecules. Secondly of damage is that accumulation of AGEs lead circulating blood cells to adhere to the vascular walls which promote atherosclerosis. Third way is through binding different receptors which have been recognized on various cell types such as macrophages, endothelial cells, and smooth muscle cells, renal and neuronal cells (Basta et al, 2004). Hyperglycaemia Mechanisms-caused damage: Hyperglycemia diverse microvascular and macrovascular complications in diabetic patients through several mechanisms such as increased formation and accumlation of advanced glycation end-product (AGE); activation of protein kinase C (PKC) isoforms; and increased generation of reactive oxygen species (Bonke et al,2008) Increased production advanced glycation end-products AGE promote atherogenesis pathway through accumulation of AGEs and AGEs ligation to RAGE on endothelial cells and macrophages induce inflammation through activating pro-inflammatory cytokines including TNF-ÃŽ ±, 1L-6 a L-1ß, induction of reactive oxygen species (ROS) and through increased oxidative stress which lead to degradation of IKBs (IKBs is normally bound to NF-KB to prevent translocation of NF-KB to nucleus). ROS activates NF-KB which results in translocation of NF-KB to nucleus. Activation of NF-KB cause pathological change of gene expression which is highly related to inflammation, immunity and atherosclerosis, increased expression of inflammatory mediators which lead to insulin resistance and increased RAGE expression as well (Basta et al, 2004). Mechanisms by which intracellular production of advanced glycation end-product (AGE) precursors damages vascular cells. Cellular functions are altered by dicarbonyl advanced glycation end products. Alteration of extracellular matrix proteins results in abnormal interactions with other matrix proteins and with integrins. Alteration of plasma proteins by AGE precursors generate ligands that bind to AGE receptors, inducing conversion of gene expression in endothelial cells, mesangial cells and macrophages. Activation of protein kinase C: The protein kinace C (PKC) family compromises at least eleven isoforms, nine are induced by the lipid second messenger diacylglycerol (DAG). Altered DAG-PKC pathway play an important role in diabetic complications. Intracellular hyperglycaemia raises the amount of DAG which activate PKC in cultured vascular cells and in the retina and renal glomeruli of diabetic animals. Hyperglycaemia may also activate PKC isoforms indirectly by AGEs bind receptors and increased activity of the polyol pathway, possibly through increased reactive oxygen species (ROS). AGE stimulated diacylglycerol (DAG) and activate protein kinase C (PKC) in VSMC. PKC is one of important signal transduction elements involved with multiple cell response. In early studies of diabetes, retinal and renal blood flow abnormalities are due to activation of PKC-ß isoforms perhaps through depressing nitric oxide production or increasing endothelin-1 activity. Abnormal activation of protein kinase C has several pathogenic c onsequences: It leads to decreased production of nitric oxide in smooth muscle cells and glomerular mesangial cells that is induced by hyperglycemia (Brownlee, 2001). Activation of PKC causes inhibition of insulin-stimulated expression of mRNA for endothelial nitric oxide synthase (eNOS) in cultured endothelial cells. Hyperglycaemia activates PKC to increased endothelin-1, permeability of endothelia cells and increased expression of the vascular permeability angiogenesis factor (VEGF) in smooth muscle cells (Brownlee, 2001). Increased generation of reactive oxygen species: Increased generation of reactive oxygen species (ROS) is another possible pathways of diabetes complications especially nephropathy complication. Production of Reactive oxygen species can be result from the activation of various enzymes, including NADPH oxidase, nitric oxide (NO) synthase, and myeloperoxidase, with arising evidence that NADPH oxidase is the major cytosolic source of ROS generation in diabetes. NADPH has homologues that are present within the kidney, namely nox-3, seen in fetal kidney, and nox-4, which is predominately expressed in the renal cortex. AGE bind RAGE induces signal transduction and activate NADPH oxidase in endothelial cells. The interaction between AGE-RAGE enhances production of the cytokine vascular endothelial growth factor (VEGF), which is directly induced by NADPH oxidase and is associated with the pathogenesis of albuminuria in diabetes (Bonke et al, 2008). Diabetes mellitus control and treatment: Both type 1 and 2 diabetes mellitus are characterized by elevated blood glucose level due to insufficiency of insulin level. Therefore, diabetes patients need to reduce blood glucose level through healthy diet, drugs such as (hypoglycemic tablets and anti-atherosclerosis drugs), insulin injection and regular physical exercise. Healthy Diet: In general, healthy diet for diabetes patients should include: limit fats (especially saturated fats and trans-fat acid), proteins and cholesterol. Also, patient should consume a lot of fiber and vegetables. Patients with insulin-producing or insulin synthesis treatment should monitor their blood glucose level to avoid hyperglycemia. For example, adults and teenager patients should maintain their blood glucose level between 80-120 mg/dl, and 100-200 mg/dl for children under 12 year old. Type 1 diabetes patients should test their blood glucose level four to more per day. However, in type 2 diabetes, patients recommend to measure blood glucose level 1 to 2 times daily, because glucose level in type 2 diabetes is more stable than in type 1. Such important tests are important during diet plans and treatment. For example, glycosylated hemoglobin test (HbA1 c) is an indicator for carbohydrate level. Micro and macroalbuminuria indicates of the proteinuria and renal function, for instance if the teat showed high level of proteinuria then the patient need to lowering protein intake (Flaws et al, 2002). Exercise: Physical exercise is important to manage diabetes complications. Regular exercise improves the status of both type 1 and 2 diabetes through transporting sugar to muscles, improving blood circulation, and increasing insulin receptors. Exercise has specific effects on diabetes patients include: reducing blood glucose level during and after exercise, increased insulin sensitivity, reduced triglyceride level and increased good cholesterol (HDL) (Flaws et al, 2002). However, diabetes patients may have several risks associated with exercise which include: hypoglycemia if patient under treatment with hyperglycemia agents, hyperglycemia and ketosis in insulin-deficient patients, and exacerbation of cardiovascular disease. Therefore, patients who are over 30 year old should be examined before doing physical exercise. These examinations include: cardiovascular exams such as blood pressure, blood lipid and ECG, and neurological evaluation such as eye exam (Flaws et al, 2002). Anti-inflammatory drugs Various drugs in recent clinical practice have been used as anti-inflammatory agents such as thiazolidinedione (TZD) class of PPARÃŽ ³ agonists and members of statin class of HMG CoA reductase inhibitors. Both of them have importane anti-inflammatory properities and both have action on glucose homeostasis and cholesterol redusing (Shoelson et al, 2006). TZDs are used to induced insulin sensivity and decresed hyperglicemia in patient with type 2 diabetes mellitus. TZDs drugs inculde pioglitazone, rosiglitazone and troglitazone. The role of TZDs is through binding and activiting PPARÃŽ ³ to induce a number of gene expression products in a dipocyte. TZDs action are attributed to fatty acid in the a dipose tissue. TZD decreases circulating free faty acid and keep faty acid out of musle and liver because accumalte of fatty acide in these tissue lead to insulin resistance. In addition, PPARÃŽ ³ is not only present in dipocyte but also in it is expressed in macrophages and other immune cells response, hepatocyte, endothelial cells and vascular smooth mucsle cells (VSMC). TZD play role in reduce the expression of targets gene for cytokines, growth factors, proliferation and migration of cells, and cell cycle progression (Shoelson et al, 2006). Rosigliatozone: Rosigliatozone decreses the inflammatory markers such as serum C-reactive protein, metalloproteinase-9, white blood cell, tumer necrosis factor-ÃŽ ± and serum amyloid-A in type two diabetes mellitus (Altman, 2003). Group of studies done on Diabetes Rodents: The recent research has demonstrated that rosiglitizone, a PPARÃŽ ³ agonist, attenuates diabetes associated atherosclorosis. The reaserch has studied the direct antiathersclosis effects of PPARÃŽ ³ afer long beriod of therapy in an experiment of insulin deficiency. This study show that rosiglitezone has no effect on glucose level in both control or diabetes mice. However, rosiglitizone , PPARÃŽ ³ (acting as insulin sinstiser) significally decresed plasma insulin level in control mice (Calkin et al, 2005). In addition to Calkin study and his collegous, another study shows that rosiglitazone increase the insulin content and iselt cells number and total mass of pancreas in diabetes rats. However, it is unknown if this is adirect effect of rsiglitazone by activation of PPARÃŽ ³ mediated pathway in islets or indirect effect of normalizing the hyperglicemia (Sanchez et al, 2002). Increaesd secration rate of proinsulin relative to insulin is one oa acommon feature in type 2 diabetes mellitus. The normal range of proinsulin in normal subjects is about 2 to 4% of the total amount of insulin and in type 2 diabetes proinsulin rate is about 15%. Curently the studies has been demonstrated that rosiglitazone in type 2 diabetes decrease proinsulin secretion. Proinsulin has been associated with activity of carboxypeptidase E. Fricker and collegous have evidenced that carboxypeptidase are present in secretory pathway and participate in peptide processing. CarboxypeptidaseB has similler feature as carboxypeptidaseE but the precursor sequence of carboxypeptidaseB has been seen in an adult mouse islet cells. Thus suggest that rosiglitazone may has primery effect on increasing the expression of carboxypeptidaseB precursor protein resulting in increse proinsulin to insulin conversion (Sanchez et al, 2002). Further more, rosiglitizone did not affect fasting insluin level in diabetic mice due to streptozotocin which induce insulin insufficency. Also, another group of study has curently demonstrated that short period of treatment with rosiglitizone decreased plaque area in diabetic mice but had no determination if effects seen were linked to insulin sensitization (Calkin et al, 2005). More current sutdies have evedanced that rosiglitezone treatment in diabetes mice reduce gene expression of the NF-KB subunit p65. Further study has shown that rosiglitizone has no direct effect o glucose-induce upregulation of oxidative stress. Same study had investigated RAGE expression acording to preveious finding that first of all, RAGE expression increse oxidative stress and secondly rosiglitezone which used in culture media alter RAGE expression. The study had shown, the expression of RAGE gene wasnt altered by rosiglitizone (Calkin et al, 2005). Some study showed no significant alteretion in gene expression after TZDs treatment. This is because of almost studies were not preformed in human adipose tissue in vivo but they used adipose tissue of rodents and adipocyte cell line. Actually under such study we should consider about some facts that, for example rosiglitazone dose which used in rodents study (10 mg/kg) is higher than human dose about 100-fold. furthermore, TZD may has an action on gene expressed in rodents but it is not necessarily to has same action on human gene. For example carbonic anhydrase 3 protein raised 2-fold after treated the mice with rosiglitazone, however there was no increasing in carbonic anhydrase 3 mRNA in human adipocyte. Although there were similarities in the action of TZD-induced insulin sensitivity, there may be TZD action has different mechanisms on experimental models and human (Kolak et al,2007). Therfore, Im going to discuss about the studies which have been done on human adipose tissue and there findings. Group of studies done in human patient with type 2 diabetes: Overactivity of ubiquitin-proteasome system is associated with the inflammation and atherosclerotic plaques in type 2 diabetes. Study by Marfella and his colegous on human diabetes patients has been shown that the PPAR-ÃŽ ³ agonist rosiglitazone reduce ubiquitin-proteasome activity and thuss prevent plaque progression to unstable phenotype in diabetes individulas (Marfella et al, 2006). Also, same study shows, the production of O2- by monocytes is reduced after rosiglitazone treatment. Thus proteasome reduction is induced by inhibition of oxidative stress and polyubiquitination. As oxidative stress induce insulin resistence through NF-kB activation, rosiglitazone enhance insulin sensivity and plaque stability in diabetes patien through reducing oxidative stress and ubiquitin-proteasome activity. Further possibility that, NF-KB activation is inhibited by rosiglitazone through a PPAR-ÃŽ ³ independent pathway. PPAR-ÃŽ ³ agonist inhibits NF-KB translocation and subsequent DNA binding through inhibits immune response which induce degradation of IKBs (Marfella et al, 2006). Rosiglitazone have significant effects on metabolism of faty acid and lowering circuliting non-esterified fatty acid. Therfore rosiglitazone prevent islet cells through reducing fatty acid exposure (Sanchez et al, 2002) Kolak and his colleagues investigated the gene of expression in human adipose tissue in vivo in type two diabetes mellitus, befor and after tratment with rosigliatozone and metformin. Reosigliatozone modulates expression of gene which involved in free faty acid synthesis and storage, protein strcture, inflammatory cells inculde macrophage and gene associated in glucose transport and insulin sensivity. Whereas metformin has no effect on these gene (Kolak et al, 2007). TZD decrease the expression of RAGE endothelial protien. From preveious finding, TNF-ÃŽ ± increase the expression of RAGE on endothelial cells, so