Existing Good or Service Business Proposal

Existing Good or Service Business Proposal T. J. ‘s Corporation Business Plan Tresa Milton ECO 561 March 25, 2013 Dr. Guthlac Kirk Anyalezu T. J’s Corporation Business Plan T. J. ’s Corporation Business Plan In today society the improvement of innovation, which are things that individual typically use being moved into an alternate period. These are the things which, individual’s utilize each day papers, magazines, and now books has been valuable to the innovation world as Kindle, Nook, eBook, or on CD's. T. J. s Corporation will deliver an innovation which, will take a book, which the partnership can utilize and check it into an eBook alongside a precise engineered voice for people to tune in. In any case, T. J. ’s Corporation will show how the income will increment, decide the benefit boosting amount, and peripheral income to amplify benefit. Likewise T. J. ’s Corporation will investigate blend of estimating and non-evaluating. T. J. ’ s Corporation will be searching for an area to deal with the proposition and have the strengthening employee’s to help with transference of books to the computerized design. T. J. s is as of now working out of a little structure and with the new proposition needs something greater. Working in a little structure places the representatives in the circumstance where the individual in question is working with little hurry to work. With the new area it will permit T. J. ’s Corporation to chip away at the new plan and have the consumer’s item out quicker. Suppositions and Market Structure Although other enterprise have books out in eBook, the books are just open in the product gave by that organization. T. J. ’s Corporation stock buyers will have the alternative of perusing the book very or read alongside the computerized sound track.Since, T. J. ’s claims a patent on their innovation their organization is viewed as imposing business model, since T. J. à ¢â‚¬â„¢s is allowed the main business that is selling this sort of product (McConnell, Brue, ; Flynn, 2013). Additionally there is a presumption that any representative which will be working in a month is about $300 dependent on deals. T. J. ’s Corporation needs to create another digitizer for their laborers to have so more books can be downloaded speedier. Development of Revenues TJ’s Corporation requires an improved promoting technique for their digitized books this methodology will permit deals to increment. On the off chance that T.J. ’s changes the costs of their books their income will likewise increment. T. J. ’s Corporation is utilizing a little site and on the sight the costs are: $10 for books with bombed copyright (old books), and $15 for books containing a copyright (new books). T. J. ’s Corporation sold 1,000 old books and 2,000 new books in the initial a half year. T. J. ’s did some examination, found the new books could be bro ught for $5 charge and CD are $20 (R. L. Copple, 2013). With this data the organization can rise their new books cost to $18 to include a $3 benefit and lower their more seasoned books to $7.The change in cost could really help support the deals of the books in light of the fact that the more established books are at a lower cost which could build incomes and the expansion in cost on the more up to date books will expand the benefit. Also, if Bury somehow happened to advertise his books to secondary school and understudies there could be an expansion of income. Cover would need to add course readings to the books being digitized yet in the event that understudies have the alternative of tuning in to somebody read the books the data may be simpler for them to understand.The evaluating on the books would need to be expanded in light of the genuine cost of the course book and a higher copyright charge. The expansion of the books would assist with expanding income and carry more traffic to his site for different books. Benefit boosting Will Bury would need to see his fixed costs (those costs that don't change the yield) and the variable (costs that do change dependent fair and square of yield). Cover's variable expenses are the five dollars for the copyrighted books that will assist with growing his inventory and the expenses related with his website.This can be as number of exchanges or buys and the charges related from them. Likewise, Bury should recruit an aide and the $40,000 that he makes good on will incorporate assessments and advantages, the acquisition of $14,000 in PC gear to propel his innovation, and $6,000 in publicizing. This would be $60,000 every year or about $7,000 per month of fixed expenses. Peripheral expenses and negligible income If there is an expansion in yield there will consistently be a raise in benefit as long as minor income is more prominent than minimal cost.There will consistently be a requirement for books to be digitized so there will consistently be one more unit of good to be delivered and sold. There will consistently be new books being composed and this implies there will be a steady requirement for books to be digitized. There will be numerous decisions for clients particularly when new books are discharged. Valuing and non estimating There are numerous kinds of evaluating that Bury could utilize and needs to investigate all to perceive what might accommodate his business. Cover could offer single or multi unit valuing, amount limits, and any specials or limits that he believes he could offer during holidays.Bury could offer special limits as an approach to build income and acquire more clients. If Bury somehow managed to see when book fairs or deals happen he could set up a table with data and PCs for clients to buy or take a gander at his database. With non valuing the technique is to make the value to a lesser degree a factor with client buy and have item effect a more noteworthy factor (McConnell, Brue, and Flynn, 2009). Showcasing research, new item advancement, and promotion could be considered non valuing rivalry in light of the fact that Bury is attempting to discover approaches to expand his deals. Obstructions to entrySince, Bury's business is viewed as a restraining infrastructure and is the just one with the innovation then there ought to be no hindrances. An obstruction happens when there are different organizations that exist in the commercial center and have built up licenses that will make it hard for the item being duplicated (McConnell, Brue, ; Flynn, 2009). Since, Bury has a patent that implies that he will out expertise his rivals and with his new innovation he will command his industry. With these boundaries there could be an issue toward the start yet once the organization is build up Bury wont have any issues. Item DifferentiationWill Bury's item is totally different based on what is out in the market since it is an advanced and voice combined is more helpf ul than eBooks or books and CD's. With his item he offers clients a progressively advantageous approach to tune in and read books in a single spot. What's more, for those energetic perusers the presentation of eBooks will take into consideration numerous books to be housed in one area. Limited costs Mr. Cover should discover approaches to limit his expenses so he can expand his incomes. Right now Mr. Cover won't have the option to employ a full time colleague however once he has a built up income then he can recruit a full time assistant.Another approach to set aside cash is have his youngsters or spouse help with digitizing the book. Also, if Bury was happy to prepare and work with secondary school and undergrads he can have different individuals to work low maintenance and can have the books digitized quicker. This implies he can build his list of books quick and he will have the option to offer more books for his clients. End At present, Mr. Cover has numerous alternatives access ible to him that he can actualize to have a fruitful business. The primary thing that he needs to consider is the value, cost, and the assembling level for making the advanced books. Mr.Bury has worked superbly of distinguishing the expenses related with copyrighted material and the value that he would need to sell his books. One thing that he would need to consider is the way that he could change the cost of the old and new books to build his income and he can hope to check whether could bring down the value that he pays for the sovereignty of the book. Right now the market is little and with Mr. Cover being an imposing business model with his protected innovation, he can truly grow his market. The one thing the Mr. Cover needs to watch is the economy and needs to recollect that he needs to keep steady over the opposition. References Copple, R. 2012). How do digital books cost. Recovered from http://graspingforthewind. com McConnell, C. R. , Brue, L. S. , ; Flynn, S. M. (2009). Fin ancial aspects: Principles, Problems, and Policies (eighteenth ed. ). New York, NY: McGraw-Hill Company. New Good or administration business proposal This task centers around presentation of another item in the existent line of business and clarifies the strategy for advancement of products for creating more income. The ideas of flexibility of requests, advertise structures notwithstanding benefit maxi augmenting methods are likewise talked about which are useful for the great and furthermore to counter the hindrances

Micromax Info Essay Example for Free

Micromax Info Essay Regd. Office: 21/14, Naraina Industrial Area, New Delhi-110028. Implicit rules FOR DIRECTORS, SENIOR MANAGEMENT, OFFICERS AND EMPLOYEES OF MICROMAX INFORMATICS LTD. MICROMAX INFORMATICS LIMITED is focused on directing its business as per the material laws, rules and guidelines and with best expectations of business morals. This code is proposed to give direction and help in perceiving and managing moral issues, give components to report exploitative lead, and to help encourage a culture of trustworthiness and responsibility. Every Director, ranking director, official and worker is relied upon to follow the letter and soul of this code. The Directors, senior administration, officials and representatives of the Company must not just agree to appropriate laws, rules and guidelines yet ought to likewise advance fair and moral lead of the business. They should submit to the approaches and techniques that oversee the lead of the Companys business. Their obligations incorporate assisting with making and keep up a culture of high moral guidelines and pledge to consistence, and to keep up a workplace that urges the partners to raise worries to the consideration of the administration. A present, by and large, substance of this Code are practically speaking, being as of now followed by the Directors and the Senior Management, be that as it may, in consistence with the new Clause 49 of the posting understanding, the Code as set out beneath, is to produce results from the date, when affirmed by the Board in its gathering 1. Relevance: The Code is relevant to all the individuals from the Board of Directors, Senior Management, Officers and workers of the Company. Senior Management will incorporate all administrators holding the places of Director (Non-Board Member/s), Sr. Supervisor, Managers, Asst. Administrators and all leader of the divisions barring Board of Directors. Such faculty will hereinafter be treated as individuals from its center supervisory group. 2. Ingenuity: The Directors, senior administration, officials and representatives are to practice due perseverance in taking care of their particular obligations and commitments to the greatest advantage of the Company. 3. Irreconcilable circumstances: The Directors, senior administration, officials and workers ought to be scrupulousâ in maintaining a strategic distance from irreconcilable situations with the Company. On the off chance that there is probably going to be an irreconcilable situation, he/she should make total honesty all things considered and conditions thereof to the Board of chiefs or any Committee/official designated for this reason by the Board and an earlier composed endorsement ought to be gotten. A contention circumstance can emerge: a. At the point when a worker, official, ranking director or Director makes a move or has interests that may make it hard to play out their work equitably and adequately, b. The receipt of inappropriate individual advantages by an individual from their family because of ones situation in the Company, c. Any outside business action that diminishes a people capacity to give proper time and thoughtfulness regarding their obligations with the Company, d. The receipt of non-ostensible blessings or over the top diversion from any individual/organization with which the Company has present or forthcoming professional interactions, e. Any noteworthy possession enthusiasm for any provider, client, improvement accomplice or contender of the Company, f. Any counseling or work relationship with any provider, client, business partner or contender of the Company. 4. Straightforwardness: The Directors and the Senior Management are to guarantee that their activity/s in the lead of business are straightforward, aside from where the secrecy of the business requires something else. Such straightforwardness will be brought through fitting approaches, methods, and keeping up supporting and appropriate records. 5. Reasonable DEALING: Every executive, individual from center supervisory crew, official, and representative should manage clients, providers, contenders, and workers of gathering organizations. They ought not exploit anybody through control, camouflage, maltreatment of private, exclusive or competitive advantage data, deception of material realities, or some other out of line managing rehearses. 6. Legit AND ETHICAL CONDUCT: The Directors, senior administration, officials and representatives will act as per the best expectations of individual and expert respectability, genuineness and moral lead on Companys premises andâ offsite as well as at organization supported business, get-togethers just as any spots. They will act and lead liberated from misrepresentation and trickery. Their lead will comply with the best-acknowledged proficient gauges of direct. 7. CORPORATE OPPORTUNITIES: Executives, senior administration, officials and representatives owe an obligation to the Company to propel its authentic advantages whenever the chance to do so emerges. Executives, senior administration, officials, and representatives are explicitly precluded from: a. Thinking about for themselves literally, openings that are found using Companys property, data, or position, b. Contending straightforwardly with the matter of the Company or with any business that the Company is thinking about. Utilizing Companys property, data, or position for individual increase. On the off chance that the Company has at last chosen not to seek after an open door that identifies with the Companys business action, he/she may seek after such movement simply in the wake of revealing the equivalent to the Board of executives or the assigned individual/panel. 8. BUSINESS INTEGRITY: The Directors and the Senior Management are to guarantee that the Company does its business according to acknowledged acts of business honesty, moral principles, reasonable play and lead, truly, truly and as a reasonable contender. 9. WORK PLACE: The Directors and the Senior Management are to guarantee that there is sex amicable work place, equivalent open doors are given to people, and there exists great business rehearses. 1 0. Nature OF PRODUCTS/SERVICES: The Directors and the Senior Management are to try that the items/administrations of the Company fulfill the acknowledged guidelines of value including that of ISO 9001 and some other norm/s, and furthermore the details of the lawful specialists/laws so consumer loyalty is guaranteed. Besides costs are kept sensible. 11. Insurance AND PROPER USE OF COMPANYS ASSETS: The Directors and the Senior Management are to guarantee to secure Companys resources and property and the equivalent ought to be utilized uniquely for genuine businessâ purposes. 12. Classification: The Directors, Senior Management, Officers and Employees will keep up the classification of secret data of the Company or that of any client, provider or business partner of the Company to which Company has an obligation to look after privacy, aside from when revelation is approved or lawfully commanded. The Confidential data incorporates all non-open data (counting private, exclusive, and other) that may be useful to contenders or destructive to the Company or its partners. The utilization of classified data for his/her own bit of leeway or benefit is likewise denied. 13. Consistence WITH LAWS, RULES, AND REGULATIONS: T he Directors, senior administration, officials and representatives will conform to every single material law, rules, and guidelines. Exchanges, legitimately or in a roundabout way, including protections of the Company ought not be attempted without pre-freedom from the Companys consistence official/Company Secretary. Any Director, individual from center supervisory crew, official or representative who is new or dubious about the lawful standards including Company business led by him/her ought to counsel the legitimate branch of the Company before making any move that may imperil the Company or that person. 14. RELATIONSHIP WITH CUSTOMERS AND SUPPLIERS: The Directors and the Senior Management are to try that their dealings with the clients are given due significance, esteem is made and relationship of trust is manufactured. In managing providers it ought to be the undertaking that provisions depend on need, quality, administration, cost, and fitting terms and conditions. 15. Investors: The Directors and the Senior Management are to guarantee that the privileges of investors are met according to law and great corporate practices, and all endeavors are made to offer best types of assistance to them. 16. Network ACTIVITIES: The Directors and the Senior Management are to try that the Company be a confided in corporate resident and, as a vital piece of the Society, satisfies its obligations and obligations to the social orders and networks wherein itâ operates. 17. CODE OF ETHICS FOR CHIEF FINANCE OFFICER: Genuineness, trustworthiness and sound judgment of the senior money related officials is central for the achievement and notoriety of Action Construction Equipment Limited. The expert and moral direct of the senior money related officials is fundamental to the correct working of the Company. The senior money officials just as Directors of the Company will be limited by the accompanying code of morals: 1. Act with genuineness and honesty, including the moral treatment of real or obvious irreconcilable situations between close to home, money related and proficient connections, 2. Make full, reasonable, exact, auspicious, and justifiable divulgence in reports and records that the Company documents with, or submits or makes intermittently, to the investors, government specialists, and to people in general, 3. Conform to administrative laws, rules, warnings and guidelines material to the Companys business, 4. Unveil to the Board or any advisory group/official assigned by the Board for this reason, any material exchange or relationship that sensibly could be required to offer ascent to any infringement of the code including genuine or clear clashes with the interests of the organization, 5. Advance brief announcing of infringement of the Code of Ethics to the Board of Dir

Single-Tasking for Productivity and Stress Management

Single-Tasking for Productivity and Stress Management Stress Management Management Techniques Time Management Print Single-Tasking for Productivity and Stress Management By Elizabeth Scott, MS twitter Elizabeth Scott, MS, is a wellness coach specializing in stress management and quality of life, and the author of 8 Keys to Stress Management. Learn about our editorial policy Elizabeth Scott, MS Medically reviewed by Medically reviewed by Steven Gans, MD on August 05, 2016 Steven Gans, MD is board-certified in psychiatry and is an active supervisor, teacher, and mentor at Massachusetts General Hospital. Learn about our Medical Review Board Steven Gans, MD Updated on July 23, 2019 Multi-tasking isnt as efficient as it looks. John Lamb/Getty Images More in Stress Management Management Techniques Time Management Physical Techniques Relaxation Effects on Health Situational Stress Job Stress Household Stress Relationship Stress  I used to be a big fan of multi-tasking when it became a popular strategy for productivity.  The idea of doubling productivity by doing multiple things at once is quite appealing for busy people, and these days most of us are busy people.  However, several studies show  that in most cases, multi-tasking can negatively affect productivity and efficiency.  Heres how. Multi-Tasking and Your Brain Focusing on more than one task at a time, repeatedly switching back and forth between two or more tasks, or focusing on many things in a short period of time can all be considered multitasking and they can all leave you less focused and efficient than you may think.  This is because it takes time for your mind to adjust to a shift in focus; each time you switch your focus, you are creating another need for your mind to re-focus, and this can drain you of time and energy.  It can also mean that when you multitask between more than one activity that requires thought of focus, it takes longer than it would have taken if  you had  focused on each task individually. When Multi-Tasking  Works When you group a task that requires focus and concentration with one that is mainly physical and something that can be done on auto-pilot,  multi-tasking  works well.  This is because you can put most of your focus on one activity and let the other one get done secondarily; you dont need to keep shifting a high level of focus from one activity to the other.  Here are some examples of paired activities that are more amenable to multi-tasking: Listening to music or audiobooks while exercisingHaving a casual conversation  while doing housework When It Doesnt Work Multi-tasking can be a focus-killer and energy drain when you are attempting two tasks that require conscious thought.  Here are some examples of activities that are best done separately: Listening to music or audiobooks while writingHaving a casual conversation while doing homework (unless you are talking about the homework itself) Alternatives to Multi-Tasking If you find yourself multi-tasking much of the time, consider taking a break from it.  You dont need to give up multi-tasking entirely, but here are some alternatives to try.  See how you feel when you incorporate these when possible. Single-Tasking When you feel tempted to cram too many activities into the same space, give yourself permission to choose the most important thing for the moment and focus solely on it, if possible.  (You may need to create a plan for when you can address the other activities that need doing before you can clear them from your mind, but this is part of the process.  For more on this, see chunking below.)  If there are simply too many things to do, you may need to pare down some of your responsibilities.  (Dont worry, well get to that in a minute, too.) Focusing on one task at a time, as mentioned, really can save you time, so it pays to get into the habit of focusing on one thing at a time as much as possible or as much as it makes sense to do so.   Utilize Chunking When you have many tasks to do throughout the day, chunking is a useful time management strategy that saves you from multi-tasking.  The concept behind chunking is to set  aside chunks of time to focus on one specific task while minimizing interruptions, and  grouping similar tasks together (like checking all email at once rather than throughout the day) to focus on then all at once during a specific chunk of time.  This eliminates the extra time it takes to quickly shuttle from one activity to another and ultimately saves time as long stretches of the day are spent with greater focus and efficiency. Pare  Down Your Schedule If you find yourself chronically multi-tasking out of necessity because theres simply too much to do,  single-tasking can help (because you actually reduce the overall amount of time it takes to get things done) but you may benefit from cutting out some of the commitments in your schedule that are not absolutely necessary.  Do you have any habits that drain your schedule but do not serve you or commitments that you could drop without any lasting, strongly negative consequences?  Looking at your priorities and at your schedule, as it is now, considers if you can reduce the sheer number of things you need to do in a day, and you might feel less stressed and pressed for time.

Sexuality And Gender Social Constructs Essay - 1366 Words

Sexuality and Gender are social constructs. They are more like fluid concepts. Both are on spectrums. Why could they be considered controversial topics, more specifically the spectrum? Well, the idea of sexuality being more than just heterosexuality has been challenged by conservative types and others alike for years. They may even deem anything other than heterosexuality as something abnormal and immoral. For some, it can be quite difficult to understand that sexuality is on a spectrum. Especially with identities like bisexuality and pansexuality, it can be difficult for some people to wrap their minds around that idea. In recent years, the idea of gender being more than just male and female has been getting more and more attention. It is no longer sex that defines people, but gender identity, expression, and presentation. They are not fully understood and sometimes not accepted by people; unfortunately some of that ignorance, and much to my surprise, come from people within the LGB TQ+ community. A lack of understanding about the spectrums of sexuality and gender leads to a lot of confusion, hate, and ignorance. The acronym LGBT has expanded over time to include other identities, becoming LGBTQ+. Whereas heterosexuality means that a person is attracted to the opposite sex, homosexuality mean that one is attracted to the same sex. Bisexuality means that one is attracted to both men and women; however the attraction is not always fifty-fifty; in fact, one can like one genderShow MoreRelatedGender Sexuality As A Social Construct1601 Words   |  7 PagesAlike gender, sexuality is also a social construct, especially when looking at the period before the 18th century, when one’s sexual orientation did not matter, hence there being no need for justification, just as pointed by Foucault: â€Å"Sexual practices had little need of secrecy; words were said without undue reticence, and things were done without too much concealment; one had a tolerant familiarity with the illicit.† (3). And the 19th century came and brought with it a big change, and not onlyRead MoreGender And Gender Essay774 Words   |  4 PagesThe social constructionist viewpoint on gender and sexuality seems to be the one of the most plausible ways to study and examine the topics. Although biology no doubt has an impact on attraction, and quite possibly gender, society influences the choices of everyone, and whether a person realizes it or not, society shapes their identity. The structure of society and its norms influence everything a person does, including their gender and sexuality. Gender is already considered to be a social constructRead MoreSexuality As A Social Construct1486 Words   |  6 PagesHannah St. Lifer Sexuality as a Social Construct Heternormativity is the idea that there exist two distinctive classifications of the genders, males and females, with customary roles in society. The idea asserts that heterosexuality is the only normal sexual orientation of people and that all sexual and marital relations must abide by this norm. Society has adopted this belief and constructed it into a standard of life. It is normal for people to automatically presume that most other people are heterosexualRead MoreHuman Nature : Gender System Is Established On A Basis Of Our Own Standards875 Words   |  4 PagesIn the U.S. the gender system is established on a basis of our own standards. â€Å"The paradox of human nature is that it is always a manifestation of cultural meanings, social relationships, and power politics; not biology, but culture, becomes destiny† (Lorber 117). We do not picture males and females based on their genitalia, but rather the way that people express their gender identity. No matter someoneâ€℠¢s personal identification, the greater society will â€Å"do gender† and categorize them anyway. TheRead MoreGender And Gender Identity1648 Words   |  7 PagesIn light of performativity, political transformation via hegemonic cultural practices continues to advocate for gender parody. Overall, the recent exploration of alterity ethics complements performativity politics by exploiting the subversive potential of gender identity as well as female identity. For the oppressed individuals, power should be subverted via political strategy guided by the consequences and punishment with the objective of maximizing the good in the society. In other words, performativityRead MoreMargaret Atwood s The Handmaid s Tale931 Words   |  4 Pagesculture and society. With the recent exploration of sexuality a new concept of sexual and gender identity has emerged and is being analyzed in various fields of study. The ideology behind what defines gender and how society explains sex beyond biology has changed at a rapid pace. In response various attempts to create specific and catch all definit ions of growing gender and sexual minorities has been on going. This has resulted in the concept of gender becoming a multi- layered shifting hypothesis toRead MoreAnalysis Of Allen Ginsberg s Howl And 1661 Words   |  7 PagesAllen Ginsberg was one of the greatest admired Beat Generation poets, who particularly used free flowing, aggressive and occasionally a discourteous style of language to show that the rule and social structure over heterosexuality can be filled with opposition, so he decided to release queerness. Ginsberg strongly disputed capitalism and conformity that notably consisted of sexual repression, so he incorporated in the development of counterculture and challenged the heteronormative, procreation-drivenRead MoreModern Culture : The Japanese Manga A Sub Culture Based Around Graphic Novels1606 Words   |  7 PagesIn Japanese modern culture, patriarchal constructs rule everyday ideology of what it is to be feminine, how the female body should look, and appro priate female sexual behaviour. Representations (and expectations) of the female form and sexuality are well depicted in the Japanese manga: graphic novel artwork that is read ubiquitously throughout Japan. Exploration of this art-form and the culture that grows around it provides a unique insight into current cultural attitudes in Japan. Shojo manga -Read MoreGender, Gender And Sexuality Essay1748 Words   |  7 Pagesin the class lectures that Women and Gender Studies challenge the idea of whose knowledge is privileged or valued. The article â€Å"Doing Gender, Doing Class† serves as a great example to ask that question in regards to the expression of gender and sexuality, and how those two are heavily influenced by the social class construct. Trautner argues that â€Å"gender in organizations interacts with other major features of stratification - such as class and race - to construct unique organizational cultures thatRead MoreThe Child Is A Child Essay1433 Words   |à ‚  6 Pagestoys. This is not the first time, Marcus has done this, the action of playing with his sisters toys and his shy demeanor, has made his family question Marcus sexuality labeling him possibly gay before he’s had the chance to make this conclusion for himself. Therefore, because Marcus choice in toys and non-rambunctious demeanor, his sexuality was chosen for him because it was outside of the model of what it means to be a male child. Though, this is hypothetical scenario, it is a common one. Within

Essay On Eulogy - 1482 Words

On Monday, October 30 2017, I went to Pruis Hall and heard Alex Sheen, the founder of the nonprofit â€Å"Because I Said I Would.† His dad, a pharmacist in Cleveland, was diagnosed with stage four lung cancer. To combat the disease, he went through chemo radiation which seemed to be working, and he was able to go out with his family for Chinese food. However, the cancer later spread to his liver, pancreas and brain, and resulted in death. Alex decided to give a eulogy at the funeral, in which he decided he would start fulfilling more promises. Here, he first said the phrase â€Å"Because I said I would,† which later led to his going viral on social media with millions of likes and his starting of a blog. Through class discussions and presentations,†¦show more content†¦Although he and followers of his blog did not have to fulfill these promise cards, it shows the importance of being a man of your word and keeping your promises. Although not everyone can afford so much time or money to fulfill a promise, Alex said people should â€Å"do what you can with what you have.† Alex said at the conclusion of his speech that â€Å"everyone is born with the ability to make and keep a promise.† This goes into our yearlong class discussion of â€Å"Is a leader born or made?† Alex, who believes everyone can make and keep their promises, would believe that leaders are made. Prior to writing his blog and eventually starting his nonprofit, Alex had no public works experience, public speaking experience, or leadership experience. As he said, he was â€Å"just some guy who worked at a software company making a six figure income with five figure stock options.† He did not need the money, and thought about stopping, as running a nonprofit in addition to working forty hours a week was a big time commitment and expensive. That was until one day he went into work and saw a letter on his desk by an unnamed follower of his saying that she appreciated and was inspired by his blog and work and said that he inspired her to make a promise of her own. For th e past few years, she had been constantly made fun of for her appearance and for being overweight, so she started cutting herself and was considering suicide.Show MoreRelatedMy Eulogy Essay903 Words   |  4 PagesMy brother is not just someone I share blood with but someone I can rely on and look up to. Patrick, my seventeen-year-old brother, has been by my side since I was a little baby. The earliest memories I have are of Patrick and I running around in our backyard laughing and playing. As he grew older, I began to look up to him. He was everything I aspired to be: intelligent, passionate, and athletic. Patrick always seemed to know what he wanted in life, and I admired how he chased down his goals. ThereRead MoreEulogy Letter Essay2017 Words   |  9 Pages â€Å"Il y a des fleurs partout pour qui veut bien les voir, Henry Matisse,† or as google translate told me, â€Å"There are flowers everywhere for those who want to see them.† That had been the first line of the first letter. I remember every detail of the letter, as if I had found it in my faded yellow mailbox just this morning. How could I not? This letter had changed my life forever. I was having a particularly wearying morning that day, as people with both diabetes and kidney failure often do. IRead MoreMy Eulogy Essay2027 Words   |  9 PagesI can still remember the moment it all shifted. The moment I realized I wasn’t enough. I was six years old sitting in the dusty, dark blue chair at church. I hadn’t gone to Sunday school that morning (I was too shy). My family was taking up the full row of chairs. I was sitting in-between my mother and father, as I always did. As I was watching the pastor do his impassioned speeches, and share stories from family vacations. He always does this, I thought. My mind was wandering. Salty tears startedRead More Baby Eulogy Essay557 Words   |  3 PagesDear Baby, A thousand questions flooded my mind that difficult Friday morning. As I ran my fingers through your hair and kissed you good bye, I wondered: Why? Why? Why? How can this happen? How could we be asked to endure such pain again? How could such a beautiful baby be taken from us? and? Why didn?t we have more time? It took a while for me to stop thinking about us or should I say me and start thinking about you, but once I did it is the last question that I pondered longestRead MoreWedding Eulogy Essay1028 Words   |  5 Pages I met my boyfriend at his father’s funeral. On May 24, 2017, I was at school when my mom got a phone call from my brother in law. He told her that one of his relatives died. Mariam the wife of the one who died. They were planning to do a funeral at their house at 6:00 pm. We got ready to go their house and were wearing all black. My mother, father, brother, sister, brother in law, grandma, and I all got in a car and drove to Mariam’s house. When we got there we knocked the door. Mohammed who sRead MoreTristian Eulogy Essay1090 Words   |  5 PagesSorry, it has been a while since I last wrote. I am working 12 hours overnight shifts on the weekends, and it is killing me. Although I have been sick I do not think it was a virus; I believe it was from work. Working or staying up all night does not agree with my body and bouncing to day shifts to evening shifts makes it worse. My grandson got his first hair cut yesterday, and I will try and send you a picture. He is 14 mont hs old now, and he is never still, so the beautician had a hard time. EvenRead MoreMy Eulogy Essay1130 Words   |  5 PagesMy symbol that represents everything I want to be; is my grandmother Lena Knox. Who is the beginning of the Knox bloodline, and she is also a very strong willed determined individual. The three key points that I will touch on that makes her my symbol, are her adventurous courageous and powerful states of mind. When I was 8 years old we took our first family vacation that I can remember. Our family left Hot Springs, Arkansas headed back to Oakland, California. We drove through Texas, NewRead MoreEulogy Story Essay1903 Words   |  8 Pagesâ€Å"6, 5, 4, 3, 2, 1†¦Ã¢â‚¬  Dr Richard Tumun cries as he calls out to his second born baby, Faith Tumun. She had just closed her eyes, teeth clenched, and was on her way to the land of the sleeping. That day, my body was on the brink of giving up, it refused all the medication given to it. I kept on emptying my bowel by throwing up everything that I consumed, medicine included. I was not able to keep anything down for long. It went in and came out with the same speed that it went in with. It’s an ongoingRead MoreFather Eulogy Essay894 Words   |  4 PagesIn All Circumstances Do not be anxious about anything, but in every situation, by prayer and petition, with thanksgiving, present your requests to God. 7 And the peace of God, which transcends all understanding, will guard your hearts and your minds in Christ Jesus. Philippians 4:6-7(NIV) Dad died on the 2nd of September 2010, he was 70 years old. Dad’s life was extraordinary; he had Rheumatic fever at 8 years old; Rheumatic fever can cause permanent damage to the heart, damaged to heart valvesRead MoreMy Eulogy Essay1065 Words   |  5 Pages I remember how I went from excited to fearful in a matter of seconds. It was December. I was in the 4th grade, happy as I could be, innocent, but have had struggles in life as most kids with divorced parents have. We’ll start at school. That is where it all began. In class, we were making Christmas angel ornaments for our family. I was the only one, in my class of thirty that had divorced parents and decided to make one for each of my parents. I still remember that angel. That angel

Winesburg Free Essays

The word grotesque is an oxymoron in itself. It means beautiful ugly. How a person can have both of these adjectives is the theme of Winesburg, Ohio written by Sherwood Anderson. We will write a custom essay sample on Winesburg or any similar topic only for you Order Now His characters become grotesque by holding onto one truth that make them distorted but unknowingly make them beautiful simultaneously. Anderson uses the motif of isolation on Seth Richmond, the Stranger and Tandy to develop their grotesqueness by making the characters’ isolation be the reason why they hold onto one truth causing their grotesqueness. On the other hand, the author ses biblical allusion to help clarify the truth Jesse Bentley lives by that causes his grotesqueness. Anderson uses the motif of isolation in order to enhance the grotesqueness of Seth Richmond, as the character’s self-imposed isolation causes his grotesqueness. Seth Richmond grows up with his mother, Virginia Richmond who does not know how to discipline him and a deceased father. Seth only stares at his mother apathetically when she scolds him that causes his mother to withdraw from her displeasure. Seth also only shows indifference in things other boys engage in and finds him different rom others, since he does not feel the same emotions people would usually feel. Hence, he holds onto the truth that he does not belong in the town and â€Å"he [wishes] that he himself [be] stirred by something† (133). Seth’s self-imposed isolation is what causes his grotesqueness. He thinks Just because he doesn’t have the same interest as the others and is not â€Å"stirred by something† makes him an outcast and unlike. When in fact, the people of Winesburg admire him because he comes off as a passionate and mature man. Nevertheless, Seth does not acknowledge the people’s houghts because he lives by his truth that he does not fit in Winesburg because he is indifferent about things the people our engaged in. For this reason, he is distorted and grotesque for believing one truth and not accepting the others’ truths. Later, Seth fancies a girl named Helen but with him imposing that he does not belong in the town and wants to leave, he soon drives away Helen and begins to think that the reason of her departure is because of his truth that he is an outcast. When in reality, Helen departs to avoid further sentiment because Seth tells her that it was their last ime they’ll see each other. Nonetheless, He continues to say, â€Å"when it comes to loving someone, it wont never be [him]. It’ll be†¦ someone who talks a lot – someone like that George Willard† (142). Seth continues to hold onto his truth and imposes that he needs be isolated further more from the town and needs to leave Winesburg. This eventually drives Helen away, but Seth believes it is because of his social skills. Hence, he becomes Jealous of George Willard and wants to be like him because he thinks that if he were George, Helen would not have left him. However, George Willard is not that social either, Seth assumes he is a social butterfly because he is a reporter but as a matter of fact he only listens well. Seth is grotesque because he believes in a truth that is not absolute. He believes that Helen left him because he is not as social as George Willard, when it is not the case. He is grotesque tor believing a truth about George Willard that is not true. The author also uses the motif of isolation to develop the grotesqueness of the Stranger and Tandy, as the characters’ isolation causes them to hold onto one truth aking them grotesque. Tandy Hard lives only with her father, Tom Hard because her mother is dead. Tom Hard spends most of his time being an atheist, wrecking the ideas and belief that God exists causing his daughter to be neglected. Not having anyone to nurture her and guide her, she becomes lost and continues to live without an identity, as implied by the author when he does not mention her real name until she the stranger names her Tandy. The stranger comes to Winesburg, Ohio in order to cure his alcohol addiction and addiction to an image of a lover. He claims that his over is named Tandy who has â€Å"the quality of being strong to be loved,† and the only reason he is not with her is because â€Å"she did not come in [his] time† (145). As a result of the stranger being lone and isolated for not having a lover, he holds onto the truth that his lover is named Tandy and she was not born in his time for the stranger does not find her yet. His reasoning makes him distorted because he continues to believe the truth that there is a Tandy that was not born at his time and not acknowledge the truth that there might not be any Tandy at all. In addition, his isolation also makes im grotesque because it makes him live by the truth that his lover is someone like Tandy and does not acknowledge the truth that there are other women out there that can be his potential lovers without necessarily having the same quality as Tandy. Nonetheless, the stranger imposes on the daughter that she should be Tandy and she should be strong and brave in order to beloved. Consequently, the daughter not having an identity starts to incline on the idea of Tandy. When her father calls her, she retaliates and says, â€Å"[she] want[s] to be called Tandy – Tandy Hard† (146). After he daughter’s statement demanding she wants to be called Tandy, it is implied that she will continue to live as Tandy. For that reason, the daughter is grotesque for not accepting that she can have her own truth to live by and not Just the truth of the stranger. However, the only reason she holds onto the stranger’s truth is because she does not acquire her own identity from the isolation and lack of nurture she gets from her father. Therefore, her isolation because of the lack of guidance from her father causes her to live by another person’s truth distorting her and making her rotesque. Anderson uses biblical allusion to help clear up the truth Jesse Bentley lives by creating his grotesqueness. Jesse Bentley inherits a colossal amount of land from his dead father and brothers. Before inheriting the land Jesse Bentley studied to be a minister, so returning home he is filled with religious thoughts. Hence, he begins to think that his farm is an empire of God and thinks that his lands need to be protected from â€Å"the hands of the Philistines† (73). As a man who studied to be a minister, it is understandable to return with the words of God. However, Jesse Bentley ssociating his life to the Bible and calling his neighbors Philistines is Just absurd and twisted. He lives by the truth that his life is parallel with Jesse’s life from the Bible, and even goes to the extent of calling his neighbors Philistines implying that they are enemies. For this reason, Jesse Bentley is grotesque because he lives by the truth that his neighbors are Philistines like in the Bible, causing his distortion and grotesqueness because his truth is not really true. As I said before, Jesse Bentley commences to equate his life to the Jesse of the Old Testament. The Jesse from the Old Testament is known as Christ’s key ancestor. As a result, Bentley prays to God that his wife conceives a son that can be named David in order for the lineage to start. However, his wife conceives a girl, Louise that gives birth to a son named David. Jesse Bentley then starts to get obsessive about contacting God through his grandson David. He thinks that through David they â€Å"will see the beauty and glory of God† (100), so he brings a sheep to sacrifice and uses David as a host in the forest. Jesse Bentley holds onto the truth that he can be a significant person like the Jesse from the Old Testament through his grandson. He strongly believes that his life is parallel to the life of the Bible’s Jesse when it is not the case. In addition, the fact that he still tries to equate his life into the bible when there’s a generation gap and the story that he is reenacting is Abraham and Isaac and not Jesse and David shows that he is so desperate to communicate with God and feel significant that it makes him distorted and grotesque. Furthermore, because Jesse Bentley is blinded by his want to be significant and the truth that he can communicate with God, he does not accept the ruth that God may not exist making him grotesque. In conclusion, the characters’ isolation leads them to live by one truth that enhances their grotesqueness. Additionally, the author uses biblical allusion to explain and clarify the truths the characters’ hold onto that makes them grotesque. In some way, the characters’ or in general people’s grotesqueness can be seen as beautiful. People’s faith in a certain truth can be considered beautiful and no matter how distorted it makes them seem, it’s the fact that people stand on their ground and fght for what they believe in, makes them admirable. How to cite Winesburg, Papers

Common Surgical Complications Surgery

Question: Describe about the Management principles of common surgical complications in Surgery? Answer: Introduction There is several meaning of the term management. Management as a noun termed as a group of managers in an organization (Georgiev, 2012). Management as a process refers to a group of actives such as the function of the entire organization. The functions of the organization are Planning, Organization, Directing, and controlling (Bhatia, 2011). On the other hand, the term management as a discipline can be explained as to any subject related to the organization. Management is termed as an individual or a group of individuals that accepts the all the responsibilities of the organization to run the management (Georgiev, 2012). All the management depending upon the nature of the business has some common organizational goals and objectives. There are different people who join the organization coming from different cultural backgrounds (Bhatia, 2011). Assessment of the Significance of the Managers in achieving the organizational success of Primark Primark is one of the most popular clothing retail brand within United Kingdom. The main features of the Primarks product are to deliver the high fashionable product in low price. The organizational goal of Primark is to build the brand largely and attain more than 67% consumers in United State. Apart from that, the management of Primark take care about their employees through applying the 630 degree performance measurement activities. Moreover, the company provides rewards according to performance to their potential employees. There are some common organizational goals and objectives in every management (Georgiev, 2012). Depending upon the nature of the business, the managers set the goals and objectives of the organization. The basic plans and procedures of the organization followed by every manager are similar to each other. All the managers of an organization depending upon the nature of the business follow the same plans and procedures, which includes Planning, Organizing, Direc ting, Motivating, and Controlling (Dinsmore and Cabanis-Brewin, 2011). These are the major organizational steps, which every manager needs to follow in the entire management. Process Features of Management Continuous Procedure All the managers needs to perform a continuous and never ending procedure of the management Art and Science The entire concept of the management is getting the jobs of the organization done by all the employees Result Orientation The entire concept of the management is to get the job done by the employees to achieve the common organizational goals and objectives Activities The concept the entire management both a group and non group activity Principles and Rules All the employees of the organization follows some basic rules and regulations of the organization Intangible All the services of the entire management is intangible in nature Dynamic All the activities of the entire management are dynamic in nature Pervasive All the plans and actives are purposive in nature Situation All the actives of the entire management depends upon the situation of the organization Professional in Approach All the jobs of organization are professional in nature and needs to follow a professional innature Table 1: Features o Management of Primark (Source: ) Comparison and contrast of organic organizations and mechanistic organizations Specialization: According to Kotler and Armstrong (2012), organic organizations are mainly followed the joint specialization. The employees within the workplace of Organic organizations work together. Most of the employees that are working in Organic organizations are doing their task with higher coordination. On the other hand, in Mechanistic Organizations employees are working separately and they done their task with their specializations. Communication: In the Organic organizations, employees have authority to control the task delegately. On the other hand, the communication in the mechanistic organizations is vertical. Decision making is highly possible in mechanistic organizational structure. Apart from that, in Organic organizations, an employee follows the verbal communications. On the contrary, in Mechanistic Structure based organization firmly follows the written communication. Operational Process: The trend of the Organic Structure within the organization is unpredictable. Whereas, the operating procedure of Mechanistic Organizations is extensive and with high standard rules. The job of the manager is to translate all the efforts of each in a common direction so that the common organizational goals achieved. There are different ways of motivations, which followed by the managers depending upon the requirements of the organization (McMenamin, 2011). Planning: Planning is the primary step of each management that every manager follows to set all the goals and objectives of the organization. Planning bridges the gap between where we are standing and where we want to go (Georgiev, 2012). The concept of planning is futuristic. Without the concept of planning, no managers can implement the plans of procedures of the organization (Haimes, 2012). Planning is an overall basic function of the management, which involves the concept of the formulation of detailed, planned which helps to achieve the optimum balance of needs and demands with the accessible resources of the organization (Minikin, 2012). The steps of the planning process discussed below. On the other hand, the organization based on Mechanistic structure uses the basic and formal planning procedure. All the effective planning and effective implementation of planning play a greater part in the high performance of the organization (Heizer and Render, 2011). The concept of planning is termed as the primary function of the management as it sets the goals and activities of the entire organization (Minikin, 2012). All the managers depending upon the nature of the business sets the overall goals and objectives of the organization, which will result in the optimum utilization of resources. Description of the process that helps Primark to promulgate corporate strategy Bargaining Power of the customers: In United Kingdom, the organization in retail clothing sector faces higher competition. Brimson (2011) cited that customer in the clothing sector in UK has wide range of choice. Majority of consumer demands for the alternative options. Therefore, Mark Spencer, HM, Zara, etc are provided several fashionable products with higher quality. Bargaining power of the customer is high in UK. Bargaining power of suppliers: In the clothing retail sector, there are not any single big suppliers. Therefore, bargaining power of the suppliers is comparatively low rather than other sector. Threats from competitive Rivalry: In the clothing sector, there are several low price retailers with the similar product range. However, the price of the Primarks products is low. Therefore, the company faces less challenges from their competitors. Organizing is the second step of the entire managerial functions. It is a very important and crucial step of the entire managerial function. It is one of the most important steps that the entire managers follows in order allocate jobs for the employees (Kubtov, 2012). To increase the efficiency level and to maintain the concept of the optimum utilization of resources, the theory of the correct job for the accurate employees must applied. . The job of the manager is to translate all the efforts of each in a common direction so that the common organizational goals achieved. There are different ways of motivations, which followed by the managers depending upon the requirements of the organization (McMenamin, 2011). Threats from New Entrants: In the clothing retail sector, there are low threats from the new entrants. The set up cost for starting a new business in clothing sector at UK is high. Therefore, it makes hard to startup a new business in clothing sector. Primark faces low challenges from the new entrants. Threats from Substitute: Primark faces high challenges from the substitute products in clothing sector. There are several substitute product providers such as Zara, Manchester United, Top Shop, etc that provided various types of products and fulfill the requirements of consumers. However, Primark charges reasonable prices rather than their competitors. Apart from that, Primark provided several types of discount offers to their customers in different season as well as different festivals (Bohlander and Snell, 2013). Therefore, recent technological development such as internet allows Primark for providing facilitation to their customers. Understanding of Organizational culture and justification to create an innovative culture Organizational Culture is considered as that environment where the behavior of individuals and values are shared for the betterment of the overall Primark in the competitive or complex environment. On the other hand, it can also be discussed that organizational culture can bring positive change in the attitude and belief of the workers working in a particular firm (Green, 2012).. Apart from that, one firm could be segmented easily from other firms based on organizational culture as each firm follows different internal procedures and policies. For the purpose of incorporating innovative culture within the Primark, the management has to engage qualified and experienced workforces on the board. The workers can help to build a positive change in the behavior and performance of other workers. The workers should be provided equal opportunities and chances of taking initiative should be given as it can help the organization to receive best and workable ideas. As a result, it could be useful in terms of productivity and minimization of wastage (Huhtala et al. 2013). Apart from that, the management of the company would develop innovative culture by collaborating with other groups or making alliance. It will help in the gaining new ideas and perspective that can deliver benefit to the workers and business. On the other hand, the performance of the employees needs to be measured. It will help in knowing the best and worst performing employees. Therefore, the employees that are showing low progress can be provided training that will help in the development of their skills and behavior (Carlstrm and Ekman, 2012). Furthermore, the recognition should be given to the workers that would help in gaining the input from the workers regarding developing cultural innovation. The workers can then be able to make the working environment a feasible place to work. Moreover, they will be sharing their experiences and knowledge in performing the tasks. Apart from that, in order to create innovative culture, the management should control on the employees productivity (Stensaker and Vab, 2013). Conclusion This particular assignment deals with the entire managerial performance of the organization. The basic four steps of the management discussed in a diversified manner in this particular assignment. The basic four managerial functions such as planning, organizing, motivating and controlling elaborated in this assignment. To become successful managers these are the basic requirements of the organization that every manager needs to organize and follow in the management. If all the employees of the organization try to follow their way of working and communication there will be confusion in the entire organization. Depending upon the nature of the business, all the managers translate all the efforts of each in a common direction to achieve the common organizational goals and objectives. All the managers try to follow the same organizational procedure to achieve the common organization goals and objectives. Reference List Bhatia, R. (2011). Management principles of common surgical complications.Surgery (Oxford), 29(2), pp.67-69. Bohlander, G. and Snell, S. (2013).Principles of human resource management. Australia: South-Western/Cengage Learning. Brimson, J. (2011). Management process principles.J. Corp. Acct. Fin., 22(4), pp.83-96. Carlstrm, E. D., and Ekman, I. (2012). Organisational culture and change: implementing person-centred care.Journal of Health Organization and Management,26(2), 175-191. Dinsmore, P. and Cabanis-Brewin, J. (2011).The AMA handbook of project management. New York: American Management Association. Georgiev, V. (2012). Functions, Principles and Problems of the Security System.J Def Manag, 03(01). Goundrey-Smith, S. (2012).Principles of electronic prescribing. London: Springer. Green, T. J. (2012). TQM and organisational culture: How do they link?.Total Quality Management and Business Excellence,23(2), 141-157. Haimes, Y. (2012). Systems-Based Guiding Principles for Risk Modeling, Planning, Assessment, Management, and Communication.Risk Analysis, 32(9), pp.1451-1467. Heizer, J. and Render, B. (2011).Principles of operations management. Boston: Pearson Education. Huhtala, M., Feldt, T., Hyvnen, K., and Mauno, S. (2013). Ethical organisational culture as a context for managers personal work goals.Journal of business ethics,114(2), 265-282. Kotler, P. and Armstrong, G. (2012).Principles of marketing. Boston: Pearson Prentice Hall. Kubtov, J. (2012). INNOVATIVE MANAGERIAL PRINCIPLES FOR CURRENT KNOWLEDGE ECONOMY.ecoman, 17(1). Levitt, D. (2014). Ethical decision-making in a caring environment: The four principles and LEADS.Healthcare Management Forum, 27(2), pp.105-107. Masteralexis, L., Barr, C. and Hums, M. (2012).Principles and practice of sport management. Sudbury, MA: Jones Bartlett Learning. McMenamin, E. (2011). Pain Management Principles.Current Problems in Cancer, 35(6), pp.317-324. Minikin, B. (2012). Sports management, principles and applications.European Sport Management Quarterly, 12(3), pp.309-312. Ogilvie, J. and Ogilvie, J. (2013).CLEP principles of management. Piscataway, N.J.: Research Education Association. Rejda, G. (2011).Principles of risk management and insurance. Boston: Prentice Hall. Stensaker, B., and Vab, A. (2013). Re inventing shared governance: Implications for organisational culture and institutional leadership.Higher Education Quarterly,67(3), 256-274. Strydom, J. and Smith, M. (2011).Principles of business management. Cape Town: Oxford University Press. ZOTOS, A. (2011). PRESERVATION TIME AT 6 2C AND 8 2C OF TROUT (SALMO GAIRDNERII) FILLETS SMOKED BY STEAMING WITH LIQUID SMOKE.Journal of Food Processing and Preservation, 35(4), pp.533-541.

Nuclear Power Essays (1313 words) - Nuclear Technology,

Nuclear Power We use many sources of energy. One of our major sources is oil. Oil has been around for a long time. It is used in lamps, and it is refined into gas. Plastic products are also made from oil. From the 1900s and up oil has been used mostly in cars and boats. Oil is the most used natural resource we use (ChemCom 155). It is used the most because it is easy to find. The next most used source is nuclear energy. Nuclear power plants started to emerge in the 1950s. Russia had the first power plant (Keeler 39). Nuclear power plants are safe and very clean. Nuclear power is also very efficient. For every one million people in a city a nuclear power plant only needs 3 kilograms of uranium (Keeler 39). The third power source is natural gas. Natural gas is used in many household products. The main product in the house is the furnace. Practically all home furnaces run on natural gas. The second thing in the house that could be run by natural gas is the stove and oven. Many homes have gas burners and gas stoves , but there are some homes that use electricity for the stove and oven. The next product is water heaters. Water heaters burn natural gas to heat water. The main reason we use oil so much is because it is used in many things we use. Oil is used in cars, and it is refined into gasoline. The most important reason we use oil so much is because it is cheap. We used coal because it was easy to get. Coal also burned for a long time. Since coal was easy to get it was sold for a very cheap price. We use nuclear power because it is clean and it produces large amounts of energy. Natural gas is the same it burns clean when it produces energy. The effects of the energy we use now are terrible. When oil is burned it produces many harmful chemicals ( ChemCom 155). These chemicals include , carbon dioxide and carbon monoxide. Both of these chemicals pollute and are harmful to people. Oil is a non-renewable rsource, Oil will start to get harder and harder to find. The oil will be expensive to find and expensive to buy. Present day sources of oil will be gone in a little over 60 years (Discovery channel, Beyond 2000). Coal is already practically gone, They dont use it because it costs too much to mine and doesnt produce enough energy to make up for the price paid to mine. Natural gas is clean and efficient. Right now there is a lot of natural gas, but it still is not renewable. That isnt enough to produce the energy made by oil or nuclear energy. Examples of energy alternatives , such as wind mills have been around for centuries. In the 1600s and 1700s wind mills were used to pump water and crush grain. At the end of the 1800s , 6 ? million farms has windmills ( keeler, 69). Now todays windmills dont pump water or crush grain, they spin turbines. Ever since the oil embargo in the 70s people have been looking for energy alternatives. Wind power is very efficient and clean. It doesnt pollute at all (Keeler , 69 ). Since technology keeps getting better, wind power gets better also. Now the most modern wind mill can generate 2500 kilowatts of energy at speeds of 45 miles an hour ( Keeler ,69). If wind get too high the wind mill shuts down automatically. Solar energy is another non polluting energy alernative. Solar energy is collected by the sun from photovallic panels ( Keeler ,69). There are many test sites for solar panels. But they are located on the desert. The electric car is the most popular energy altenative. They have started appearing in california and some other states. Electric cars have gbeen around since 1908 Studabaker automobiles produced the first electric car ( New York Times p. 5bt ), but the car died out because gas powered cars could go faster and farther that the electric car. Now electric cars can go over

Teaching for understanding †Education Essay

Teaching for understanding – Education Essay Free Online Research Papers Teaching for understanding Education Essay Understanding is one of the most cherished goals of education. Teaching for understanding can bring knowledge to life by requiring students to manipulate knowledge in various ways. For instance, understanding a historical event means going beyond the facts to explain them, explore the remote causes, discuss the incident as different people might see it from their own perspectives, ans skeptically critique what various sources say. History of Teaching for Understanding: A number of years ago, several colleagues at Harvard Graduate School of Education, developed the Teaching for Understanding framework, which centers on the idea of performances of understanding (Blythe Associates, 1998; Gardner, 1999; Perkins Blythe, 1994) and investigated the development of learning processes in children, adults, and organizations since 1967. Today, named, Project Zero is building on this research to help create communities of reflective, independent learners; to enhance deep understanding within disciplines; and to promote critical and creative thinking. Project Zeros mission is to understand and enhance learning, thinking, and creativity in the arts, as well as humanistic and scientific disciplines, at the individual and institutional levels. The research programs are based on a detailed understanding of human cognitive development and of the process of learning in the arts and other disciplines. They place the learner at the center of the educational process, respecting the different ways in which an individual learns at various stages of life, as well as differences among individuals in the ways they perceive the world and express their ideas. Teaching for Understanding or, now a days named PZ (Project Zero) has passed through several stages: l. Conceptual Groundwork (1967-1971): During its early years, PZ consisted of a loose collection of 10-15 research assistants and senior scholars. Included in this group were: psychologist Paul Kolers, philosopher Israel Scheffler, literary analyst Barbara Leondar, and Howard Gardner and David Perkins, as founding (and sometimes uncompensated) research assistants. The group met regularly to discuss philosophical, psychological, and conceptual issues in the arts and art education. From the first, the Project took a cognitive view of the arts, viewing artistic activity as involving mental processes fully as powerful and subtle as those used in the sciences or public policy. In that sense, the Project reflected the Cognitive Revolution of the timecountering both the behaviorist past of psychology and the overly romantic view of the arts as matters of mystery, emotion, or entertainment. The Bible for this period was Goodmans influential Languages of Art (1968). During this early period position papers were written, and mode st experiments were undertaken. The results of this first phase of work are captured in a final report for the U.S. Office of Education, prepared by Goodman, Perkins, and Gardner, called Basic Abilities Required for Understanding and Creation in the Arts (1972). During the first years of PZ, Goodman also served as impresario for a dozen memorable lecture-performances at GSE. The purpose of these lecture-performances was to introduce GSE students, and the Harvard community more broadly, to the cognitive processes that characterize artistic planning, performance, and production. In later years, Goodman continued to serve as producer for a series of artistic activities and events at Harvard: these included newly commissioned multimedia performances of John Updikes Rabbit Run (1970), multimedia presentations inspired by Katharine Sturgis drawing series Hockey Seen, and Picassos drawings after Velasquez. Goodman was also catalytic in the formation of the Harvard Summer School Dance Program and the Harvard Business School Program in Arts Management. 2. Empirical Research in Cognitive and Developmental Psychology (1971/2-1983): In 1971, Goodman announced his intention to retire from PZ. He told Gardner and Perkins that they could direct the projectquipping, in characteristic fashion, that means you can raise the money from now on. At first, Perkins took on the directorship and he was joined in 1972 by Gardner. During the following decade, Gardner, Perkins, and a small group of researchers that included Laurie Meringoff (Brown), Ellen Winner, and Dennie Wolf focussed their attention principally on empirical work in the area of cognitive psychology, with a continuing emphasis on artistic issues. An informal division of labor took place, with Gardner and colleagues focussing primarily on developmental issues and populations, while Perkins and colleagues worked primarily with adult artists (and other adult populations). Results of this work can be found in many books and articles, and a number of collections, including Perkins and Leondar The Arts and Cognition (1977) and Gardner and Perkins Art Mind and Educat ion (1989). During this period, much of PZ research was focussed on the arts. Yet across the organization, there was an increased desire to examine issues that went beyond the arts, to look at issues like problem solving, critical thinking, and brain organization. Even in these cases, however, researchers typically were informed by the artistic focus of PZ. 3. The Turn to Education (1983-1993): In 1983, the influential report A Nation at Risk was issued by the U.S. Department of Education. This report catalyzed a lengthy re-examination of American public education as well as newly energized research and development efforts on educational issues at the University Level. PZ had always been housed at the Graduate School of Education and various members had been involved in educational questions and research over the years. Nonetheless, by 1990 PZ had a very different feeling than it had in 1970 (philosophical and conceptual) or in 1980 (primarily psychological research funded by governmental grants). The staff was larger (an average of 50 persons, rather than 20); more of the staff had backgrounds in education rather than in psychology or other scholarly disciplines; and more of the research and development was of a distinctly applied nature. Funding came increasingly from private foundations. At this time, PZ became involved with schools that were based on multiple intellige nces; smart schools that encouraged creative and critical thinking; and collaborations like ATLAS, that included the Coalition of Essential Schools, the School Development Program, and the Education Development Center. In 1992, PZ celebrated its twenty-fifth anniversary at a gala at the Fogg Art Museum. A few hundred individuals attended. Among the speakers were founder Goodman, long term friend Jerome Bruner, and Harvard Deans of Education Theodore Sizer, Patricia Graham, and Jerome Murphy. At the time it was evident that PZ had gone through a number of changes. Compared to the early years, it was much larger; more empirically oriented; extended well beyond the arts; and had a strong applied division, which worked in the schools, museums, and other educational institutions. 4. The Maturing of PZ (1993-2003): PZ has always been self-supporting. In the 1960s and 1970s support came chiefly from the federal government (NSF, NIH). Since the early 1980s support has come increasingly from private foundations. Thanks in significant part to core support from the Atlantic Philanthropic Services Co., Inc. (now The Atlantic Philanthropies), PZ had the opportunity in the last decade to consolidate and mature. We built up a strong central core administration. The former Development Group (led by Gardner) and Cognitive Skills Group (led by Perkins) gave way to a loosely knit but cohesive organization with many internal and external ties and arrangements. PZ became much more prominent on the national and international scene. Details on this most recent period constitute the remaining parts of this report. During the 1990s, Project Zero went through various attempts at reorganization. Each of these phases advanced PZ, and, in retrospect, each seemed a necessary stage of growth. In 2000, Steve Seidel was chosen to be the new Director. Later that year, Cynthia Quense joined Steve as the Administrative Director; Gardner and Perkins were given the honorary title of Senior Director, and continue to function as key advisors and members of the Steering Committee. Research Papers on Teaching for understanding - Education EssayThree Concepts of PsychodynamicStandardized TestingInfluences of Socio-Economic Status of Married MalesResearch Process Part OneThe Project Managment Office SystemRelationship between Media Coverage and Social andIncorporating Risk and Uncertainty Factor in CapitalAnalysis of Ebay Expanding into AsiaComparison: Letter from Birmingham and CritoEffects of Television Violence on Children

The Disquieting Effects of Global Warming Research Paper

The Disquieting Effects of Global Warming - Research Paper Example Studies conducted by the Intergovernmental Panel on Climate Change (IPCC) (2007) conclude that the mean global temperature near the earth’s surface experienced an increase of 0.74 + 0.18 degrees Celsius during a period of 100 years from 1905 to 2005. The IPCC has also projected that the global temperature will experience a further increase of 1.1 to 6.4 degrees Celsius through the twenty-first century. (2007) Owing to the rather obscure nature of changes taking place in the atmosphere, this phenomenon remains surrounded by controversy. A portion of the masses refuses to accept the magnitude of global warming and proclaim that the phenomenon is caused by completely natural sources like solar variations and volcanic eruptions. But some very alarming facts stated later will assure everyone of the damaging implications global warming has had on our planet. The IPCC blames the human race for a major part of global warming, â€Å" most of the observed increase in globally averaged temperatures since the mid-twentieth century is very likely due to the observed increase in anthropogenic (man-made) greenhouse gas concentrations† Greenhouse gases are the gases present in the atmosphere even under normal conditions. These gases, which include (in order of their abundance) water vapour, carbon-di-oxide, methane, nitrous oxide, ozone and CFC’s, are essential to bring about the Greenhouse effect. These gases capture the infrared radiations from the sun’s emission and retain it, thus warming the earth’s atmosphere. If it wasn’t for the greenhouse effect, the earth’s temperature would have been close to –19 degrees Celsius.

Effective culture of the new employees Term Paper

Effective culture of the new employees - Term Paper Example The world of work has rapidly been changing; changes appear to be happening more drastically. As part of an industrial organization, the human resource management (HRM) has to deal with a numerous effects in the changing world of work. This means that an organization does suffer implications like globalization, work force diversity, technological changes, changing skills requirement, employment involvement, continuous improvement initiatives and labour shortages (Bradley, 1998). New employee orientation covers the activities involved in introducing a new employee to the organizations up to one’s work unit. It expands on the information received during the recruitment and selection stages and helps to reduce the initial anxiety one feels when beginning a new job. The orientation program should familiarize the new member with the organizations objectives, history, philosophy, procedures and rules. It should communicate relevant policies such as work hours, pay procedures, overtime requirements and company benefits. Functions of a culture includes: Creating distinction between one organization and others, conveying a sense of identity for organizations members and facilitating the generation of commitment to something longer than other individual’s interest. It also enhances the stability of social system. More so employees do look up to the top management’s behaviour as a bench mark for defining appropriate behaviour. As such, culture communicates ethical expectations in an organization. The code of ethics are effectively designed and disseminated to avoid ambiguities in an organization. The code of ethics therefore, should state the organization’s primary values and ethical rules that employees are expected to follow. Dissemination is through; providing ethical training, setting up seminars, workshops and ethical training programs

Aetiology of Gestational Diabetes Mellitus

Aetiology of Gestational Diabetes Mellitus Abstract Gestational Diabetes is a condition present in the later stages of pregnancy where the mother has insulin resistance leading to glucose intolerance. The aetiology of Gestational Diabetes Mellitus is largely unknown but several theories include autoimmune destruction of the beta cells, monogenic mutations and insulin resistance. In pregnancy it is normal for there to be some levels of insulin resistance and it is thought that the products of the placenta contribute to the state of insulin resistance as GDM usually subsides after pregnancy. GDM in pregnancy can lead to an increased risk of cardiovascular disease in the offspring such as hypertension and atherosclerosis. This is due to the increased levels of oxidative stress and inflammatory mediators present during pregnancy. The placenta is very important as it is able to control and buffer the amount of glucose that is delivered to the fetus but if this level is too high then it is out of the placentas control and the fetus may have increased rate of growth due to this extra glucose. The current focus of research in this area seems to be into finding ways to diagnosis GDM earlier in the pregnancy and to try and reduce the amounts of oxidative stress. Gestational diabetes: consequences for fetal programming of vascular disease in adulthood Introduction Gestational Diabetes Mellitus (GDM) occurs when there is a glucose intolerance that is first detected during pregnancy. It is a form of hyperglycaemia (Buchanan and Xiang 2005). The aetiology of the condition is unknown but there have been many suggestions as to the cause of it, including autoimmune destruction of the ß pancreatic cells and the possibility of a genetic predisposition to the condition. Hormones that are produced in pregnancy help contribute to the insulin resistant state which characterises diabetes. In recent years, there has been an increase in the cases of Obesity and this is a risk factor for both Diabetes Mellitus and Cardiovascular Disease. The intrauterine environment can affect fetal programming and development. This essay will look into how the placenta and its products can affect the insulin resistant state and how this resistance effects programming as well as the role of oxidative stress and inflammation in making the offspring more susceptible to cardi ovascular disease. Gestational Diabetes Mellitus (GDM) GDM is a state of insulin resistance which disturbs the intrauterine environment and can lead to accelerated fetal growth (Radaelli et al 2003).It effects approximately 7% of pregnant women with approximately 200,000 cases seen each year (Schillan-Koliopoulos and Guadagno 2006). The term GDM is applicable when the onset is during the second and third terms of the pregnancy, but it does not exclude the possibility that the insulin resistance was undiagnosed before the pregnancy. If this is the case and is found to occur in the earlier stages of pregnancy then the mother should be treated the same as mothers who are known to have diabetes before pregnancy (Metzger, Coustan 1998). There is a degree of insulin resistance in normal pregnancy which begins towards the middle of the pregnancy but during the later part of the second and the final trimester these can increase to levels of insulin resistance that are associated with type 2 diabetes (Yogev et al 2008 Chapter 10). Insulin resista nce is when the tissues do not produce a response to insulin due to problems with the secretion of insulin or where the tissues are desensitised to insulin and therefore lack the ability to produce a response (Catalano et al 2003). In a normal pregnancy, the mother changes her metabolism to allow a constant supply of nutrients to reach the fetus to support its rapid growth. Among these nutrients is glucose, which is the main energy source used by the fetus. During the later stages of pregnancy the mother becomes hypoglycaemic and although there is increased gluconeogenesis, the hypoglycaemia still occurs because there is a high rate of transport of glucose to the fetus (Herrera 2000 cited in Herrera and Ortega 2008). GDM can have effects that impact the development of the fetus such as hypoglycaemia and macrosomia, which is an increase in body weight and has the possibility of leading to problems when giving birth, such as shoulder dystocia (Schillan-Koliopoulos and Guadagno 2006). During the second trimester of pregnancy there is peripheral insulin resistance but there is also the possibility that hepatic insulin sensitivity is altered in pregnancy, although few studies confirm this. By the end of the pregnancy the levels of insulin that are circulating are thought to be double those at the start (Redman 2001). Insulin Resistance Insulin resistance in GDM can occur in two forms. The first is where it develops in late pregnancy and it has been postulated that there is a post-receptor mechanism that may influence the insulin signalling pathway which leads to a reduced glucose uptake. The second form is where there is already a degree of resistance before the pregnancy but the changes that occur in normal pregnancy aggravate this (Metznger et al 2007). The insulin resistance that develops in pregnancy is much needed to allow the flow of nutrients, from the mother, directly to the fetus to allow for growth (Radaelli 2003). Increased insulin resistance leads to an increase in insulin secretion by the ß pancreatic cells (Buchanan and Xiang 2005). The insulin resistance is thought to be caused by increased adiposity and as the insulin resistance usually stops after pregnancy this suggests that there is a possibility that the products of the placenta are a potential cause of the resistance. During the course of th e pregnancy the actual changes in glucose levels are very small. It would be assumed that the glucose levels would rise due to the increased insulin resistance but the pancreatic ß cells increase their secretion of insulin to maintain homeostatic glucose levels (Yogev et al 2008 Chapter 10). GDM occurs because there is an increased demand for insulin which under normal circumstances can be met unless there are problems with the secretion of insulin leading to the development of hyperglycaemia. The majority of mothers who develop GDM have been discovered to have a degree of insulin resistance before they became pregnant. Therefore, with the insulin resistance that occurs in normal pregnancy it can be said that GDM occurs with a greater insulin resistance than normally present in gestation (Yogev et al 2008 Chapter 10). Insulin resistance causes a decreased uptake of glucose into skeletal muscle, adipose tissue and liver as well as a decreased production of hepatic glucose. (Catala no et al 2003). One suggestion for insulin resistance looks into the possible role of the mitochondria. Studies using Magnetic Resonance Spectroscopy (MRS) have shown that in normal offspring of parents with type 2 diabetes, there is an increased amount of intramyocellular lipid. This has been shown to cause a reduced function in mitochondria which suggests that mitochondrial dysfunction may play a part in insulin resistance (Petersen et al 2004 cited in Morino et al 2005). It has been suggested that this increase in intramyocellular lipid activates a serine kinase cascade which causes an increase in the Insulin Substrate Receptor 1 (IRS-1), which inhibits insulin receptor phosphorylation on tyrosine sites. This can cause a decrease in the effects and utilisation of glucose. One study showed that in the insulin resistant offspring the mitochondrial density was reduced by just over a third to that of a normal offspring. This suggests that offspring who are insulin resistant may inher it a condition that causes a reduction in rate oxidative phosphorylation in mitochondria (Griffin et al 2009 cited in Morino et al 2005). Detection of GDM Diagnosis of GDM helps to identify pregnancies that are at risk of fetal morbidity as well as obesity and glucose intolerance in the offspring (Buchanan and Xiang 2005). GDM is hard to diagnose as it is asymptomatic. Normal diabetes could be diagnosed by glycosuria but in pregnancy the renal threshold to glucose is lowered so that glycosuria doesnt give a true representation of hyperglycaemia (Redman 2001). There are several risk factors of GDM which can be classified into three groups and help in the screening process. Low risk factors include women who are younger than 25, normal weight at conception, no known family members with diabetes and no history of glucose intolerance. High risk factors include obesity of the mother, diabetes in close relatives, a history of glucose intolerance, current glycosuria and previous pregnancies with GDM (Metzger and Coustan 1998 Chapter 25). Causes of Diabetes There are several theories as to why diabetes occurs and this has been thought to be similar to the underlying mechanisms that cause gestational diabetes. Diabetes is a result of pancreatic beta-cell dysfunction which can present in three main ways: autoimmune, a genetic cause and on top of already present insulin resistance (Buchanan and Xiang 2005). Autoimmune diabetes accounts for approximately 5-10% of all diabetic cases (American Diabetes Association 2010). There are circulating antibodies to the ß cells of the Islet of Langerhans. In GDM, there are a small number of women who have with these antibodies present in their circulation. It is thought that these cases present with GDM due to problems with insulin secretion caused by destruction of the Islets by the autoantibodies (Buchanan and Xiang 2005). This form is similar to type 1 diabetes. The Islet Cell Autoantibodies (ICA) have been shown to have four major molecular targets: Insulin, Glutamic acid decarboxylase (GAD 65), Insulinoma-associated antigen-2 (IA-2) and Zinc Transporter 8 (ZnT8) (Tree 2010). Monogenic diabetes has 2 general forms, one where there are mutations in autosomes and the other where there are mutations in the DNA of mitochondria. The first form is commonly referred to as Maturity Onset Diabetes of the Young (MODY). In both cases onset tends to be at a young age and the patient doesnt present with insulin resistance or obesity (Buchanan and Xiang 2005). Mutations that cause MODY have been found in some women with GDM and commonly occur in genes coding for glucokinase, hepatocyte nuclear factor and insulin promoter factor, MODY is associated with beta cell dysfunction (Weng et al 2002). Chronic insulin resistance with beta-cell dysfunction seems to be the most common cause of GDM. As mentioned before there is an increase in insulin resistance in normal pregnancy but if this develops with background insulin resistance then there is an even greater insulin resistance which can lead to GDM. An established suggestion is that women who are unable to increase their secretion of insulin to cope with the insulin resistance developed in late pregnancy are more susceptible to developing GDM (Buchanan and Xiang 2005). However there could be various environmental processes that are involved in the underlying pathophysiology of GDM. The products of the placenta may also have a role in increasing or decreasing insulin resistance and these will be discussed later. Placental Function The placenta is an organ that has many roles during the development of the fetus. One of these functions is that it acts as a barrier to separate the maternal and fetal surfaces such that the syncytiotrophoblast surface exposes the placenta to the maternal circulation and the endothelium is exposed to the fetal circulation. This position between the two circulations means that the placenta is influenced by molecules from both circulatory systems, including cytokines, hormones and growth factors. The placenta produces molecules which can separately affect the maternal and fetal circulation and it expresses a large number of cytokines including leptin, resistin and tumour necrosis factor. However it has been discovered that these molecules are also produced by adipocytes. All molecules that are going from the mother to the fetus have to cross the placenta. Here they are either modified, for example lipids or like glucose, they are metabolised for placental purposes (Desoye et al 2008). The placenta plays an important role in fetal growth and the regulation of pregnancy (Giachini 2008). The placenta acts to sustain normal homeostatic levels and to carry out the functions of the vital organs. It also provides an immunological defence to the fetus and allows the exchange of molecules vital to its development (Jansson and Taylor 2007). Placental Development Approximately 4-5 days after conception, the process of cleavage causes rapid cell divisions and one of the groups of cells to form are called trophoblast cells. Further developmental processes form the blastocyte which is surrounded by an outer layer of the trophoblast cells. As the pregnancy progresses, the trophoblast cells develop into the placenta while the inner parts of the blastocyte form the embryo and umbilical cord (Huppertz 2008). The blastocyte implants itself onto the epithelium of the uterus where it differentiates into a syncitiotrophoblast which is able to implant itself in the epithelium leading to it being embedded into the decidual part of the uterus (Huppertz 2008). After the attachment of the blastocyte, the trophoblast layer divides very quickly and changes into 2 layers; the inner cytotrophoblastic layer and the outer syncytiotrophoblastic mass (Gude et al 2004).The whole implantation process takes 12 days to complete and after this the fetus is fully embedded into the endometrial layer (Huppertz 2008). The chorionic plate is the surface of the placenta that faces the fetus and this is where the umbilical cord inserts. The basal plate is the surface that faces the mother which contains many types of cells including immune cells such as macrophages and killer cells to carry out the placentas immunological function. The maternal basal plate and the fetal chorionic plate converge to form the smooth chorion which is composed of three layers (Huppertz 2008). When the trophopblast invades the endothelium there is a remodelling of the uterine spinal arteries which is necessary to ensure that the fetus and the placenta receive an adequate blood and nutrient supply and is able to remove any waste materials. This direct supply of blood and nutrients to the placenta can define it as being haemochorial villous organ (Gude et al 2004). After the rapid divisions of the trophoblast and development into 2 layers there are two pathways that can occur, th e villous and extravillious pathways. The extravillious pathway results in the trophoblast being able to invade into the decidua and cause the remodelling of the uterine arteries to increase blood supply to the placento-fetal unit. The villious pathway has a transportation function as well as having endocrine and protective functions (Gude et al 2004). Normal Placentation Placentation involves the structure and function of the placenta. The process of placentation is helped by the composition and arrangement of the extracellular matrix (ECM) of the endometrium. Studies on rats induced with diabetes provided results that showed that diabetes has an effect on the distribution of the ECM molecules. This study by Giachini et al illustrates that Types I and III collagen as well as other molecules, such as proteoglycan molecules decorin and biglycan were distributed throughout normal and diabetic placentas. It was shown that diabetes affects the expression of fibronectin and an increase in deposition of fibronectin may cause changes to the ECM structure which could affect the transfer of molecules from the mother to the fetus. One way in which changes in the ECM can be overcome is to test blood glucose levels frequently during the pregnancy and if kept in normal ranges this can dramatically decrease the prevalence of diseases and disorders present in the fe tus (Giachini et al 2008). As the pregnancy progresses the size of the placenta increases which also means an increase in the amount of products that the placenta produces therefore increasing in the insulin resistance (Schillan-Koliopoulos and Guadagno 2006). This is because the net effect of the products of the placenta is to increase insulin resistance. The increase in size of the placenta means that it needs an increased blood supply. Failure of the mother to increase its blood supply to the placenta can lead to placental insuffiency which if exacerbated can be attributed to be a cause of intrauterine growth restriction (IUGR). This growth restriction is more related to poor maternal nutrition rather than to a cause of GDM. GDM have been associated with an increased fetal and placental weight (Jansson and Taylor 2007). One of the reasons why GDM and increased insulin resistance affects the fetus is that while glucose can cross the placenta, insulin is unable to. This means that the fetal pancreas has to compensate by producing more insulin to prevent high blood glucose levels. The fetal pancreas is capable of doing this and the liver responds to the higher levels of insulin by increasing its production of glucose (Schillan-Koliopoulos and Guadagno 2006). Offspring who have an increase in birth weight have been shown to be at risk of developing cardiovascular disease and diabetes later in life. The main risk factor for this is poor transfer of nutrients via the placenta (Jansson and Taylor 2007). How dramatic these changes are depends on how good the control of blood glucose levels have been during the development of the placenta, if any treatment has been received and if there were any periods of away from normal glucose levels (Desoye 2006). How does diabetes affect Placentation? Diabetic insults at the beginning of the pregnancy can have long last effects of the placenta. One of the roles of the placenta is that it is able to buffer excess maternal glucose which can help to keep the fetal glucose levels within range However if the insult lasts longer than the placenta is able to compensate for then excessive fetal growth may occur (Desoye Mouzon 2007). In diabetes there is endothelial dysfunction which can lead to vascular disease. The endothelial cells help to control the vascular tone of the smooth muscle lining the vasculature. They do this by producing substances that help to vasodilate the smooth muscle including Nitric Oxide, Prostacyclin and Endothelium-Derived Hyperpolarising Factor (EDHF). There have been several studies to suggest different mechanisms of how diabetes affects the endothelium including impaired release of these vasodilating molecules, faults with signal transduction and increased release of constricting mediators of the endothelium. The dysfunction of the endothelium in diabetes is thought to be caused by activation of protein kinase C (PKC) as well as increased oxidative stress, non-enzymatic glycation and an increased activation of the polyol pathway (De Vries et al 2000).The main reason why these effects occur is thought to be due the activation of the protein kinase C pathway and the increased oxidative stress. This can cause early damage to the development of vascular vessels (Roberts and Raspollini 2008). These mechanisms will be discussed later. The effect of hormones produced in pregnancy Pregnancy causes changes in the circulating hormones and cytokines which can all have different effects on insulin resistance and this may help explain the mechanism underlying the resistance that is found in pregnancy and in GDM. Cytokines produced in pregnancy, such as TNF-a, Adiponectin and Leptin have been found to cause an increase in the insulin resistance (Gao et al 2008). In early pregnancy, the levels of oestrogen and progesterone rise but no net effect is seen as the two have antagonistic effects. Oestrogen increases the binding of insulin to its receptor whereas progesterone reduces the ability of insulin to bind (Ryan and Enns 1988). Cortisol levels in pregnancy increase so that by the end of the pregnancy the levels are three times that of what they were at the beginning (Gibson and Tulchinski 1980 cited in Yogev et al Chapter 10). Studies have shown that with increased amounts of cortisol there was a decrease in insulin sensitivity causing insulin resistance (Rizza et a l 1982 cited in Yogev et al 2008 chapter 10). During pregnancy the levels of prolactin increase up to ten times the normal amount (Yogev et al 2008 chapter 10). Studies have shown that in a culture of pancreatic beta cells, prolactin can cause an increase in levels of secreted insulin (Sorenson et al 1993 cited in Yogev et al 2008 Chapter 10). However, high levels of prolactin are not seen to be a pathological cause of GDM (Yogev et al 2008 chapter 10). Human placental lactogen (HPL) is a hormone, and its levels rise during the second trimester of pregnancy. This causes a decrease in the phosphorylation of insulin receptor substrate (IRS1) which can lead to significant insulin resistance (Ryan and Enns 2008 cited Yogev et al 2008 ch 10). Leptin is associated with obesity and concentrations of leptin have been shown to be related to the concentration of insulin in the plasma. In pregnancy the leptin levels increase dramatically. During pregnancy the mother uses her fat stores to supp ort fetal growth and it is thought that the leptin levels increase with the mobilisation of these fat stores. Leptin levels relate to the body mass of the individual (Sattar et al 1998). Placental Leptin is the same in structure and charge to the one produced by adipose tissue (Ashworth et al 2000). One study showed that high leptin concentrations in the umbilical cord increased the likelihood of developing fetal macrosomia (Wiznitzer et al 2000). It is also thought that leptin effects insulin sensitivity by effecting glucose metabolism in both skeletal muscle and in hepatocytes. Rats that received an external source of leptin were found to have an increase in gluconeogenesis which accounted for the majority of hepatic glucose production (Rossetti et al 1997). In GDM there is a greater secretion of TNF-alpha in response to glucose. TNF-alpha functions to regulate metabolism of glucose and lipids as well as being involved in insulin resistance. Many studies suggest that TNF-alpha is involved in the progression to GDM. They found that an increase in glucose cause the placenta and adipose tissue to increase production of TNF-alpha in some cases up to 4 times more than non-diabetic pregnant(Coughlan et al 2001). One study showed that the increases in the levels of TNF-alpha during pregnancy increased consistently with increases in body weight (Catalano et al cited in Yogev et al 2008). Adiponectin is a protein derived from adipose tissue and its function is to regulate insulin resistance and maintains levels of glucose. During pregnancy it has been found that its levels drop and could therefore lead to the increase insulin resistance found in GDM (Gao, Yang, Zao 2008). Adiponectin has also been found to decrease the secretion of TNF-alpha which as stated above can lead to insulin resistance (Hotamisligil 1999 cited in Yogev et al Chapter 10 2008). Adiponectin may cause increased insulin sensitivity as its concentration decreases throughout the gestational period ( Desoye and Mouzon 2007). Resistin is a protein that is produced by adipose tissue and is thought to be involved in insulin resistance in diabetes and is associated with obesity (Steppan and Lazar 2002) In pregnancy, resistin is secreted by the placenta and this secretion reaches its peak by the last trimester (Yura et al cited in Megia et al 2008). Studies show that TNF-alpha is an important factor in insulin resistance during pregnancy and with inputs from leptin and cortisol there is altered glucose metabolism whereas inputs from oestrogen, progesterone and prolactin had little significant effects (Kirwan and Mouzon 2002). There are many hormones produced during pregnancy, mainly by the placenta and adipose tissue that have varying affects but with the overall impact being insulin resistance. Inflammation in Diabetes There are genes in the placenta which regulate reorganisation of the endothelium and inflammatory responses and in GDM these were found to be altered. The increase in leptin receptors suggests that in the placenta this can cause proinflammatory responses (Radaelli 2003). One of the current theories is that the abnormal metabolic environment in GDM can lead to increased production of cytokines and inflammatory mediators. Molecules such as TNF-alpha, Resistin and Leptin increase during pregnancy and these increases in these inflammatory mediators produce metabolic changes by increasing insulin resistance (Desoye and Mouzon 2007). Leptin and TNF-alpha activate phospholipase A2 which are a family of eicosanoid precursors that go on to produce essential fatty acids such as w3 polyunsaturated fatty acids (Desoye Mouzon 2007). There has been a recent investigation which found that with increased adiposity at birth there has been an increase in w3 fatty acids in the placenta (Verastehpour et al 2005 cited Desoye and Mouzon 2007). As stated before, the placenta produces cytokines but it is also a site of action of the cytokines. It is the location of the receptors for these cytokines will influence if the cytokines act on the mother, the placenta or the fetus. With cytokines there is very little transfer across the placenta from mother to fetus and the origin of the cytokines in the fetus can be from either the placenta or from the fetus itself (Desoye and Mouzon 2007). Fetal Programming Many studies have highlighted the fact that events that occur while the fetus is developing can alter its developmental pathway and have adverse outcomes in later life. Fetal programming describes how the environment can affect certain developmental events of which the effects are permanent and can affect processes such as metabolism and the organisms physiology. Women with GDM have an increased risk of the fetus developing macrosomia (Catalano 2008 Chapter 11). The main factor that effects the growth of the fetus is the maternal environment and there is a strong association with the weight and height of the mother and the growth of the fetus such that mothers who are heavier and taller will produce heavy babies. (Love and Kinch 1965 cited in Catalano 2008 Chapter 11). The placenta and fetal programming The placenta is very important to the developmental processes of the fetus as it is able to change the quantity of signals and nutrients that the fetus receives. Deviation from normal would alter the fetal programming, thus making it more susceptible to disease in later life. Pregnancies that are complicated by GDM have excessive oxidative and nitrate stress which has been found to change the activity of certain proteins. Oxidative and nitrate stress alter the placentas function and may cause changes in the fetal programming. Nutrient transfer depends largely on the normal development of the vasculature to allow blood flow and this can be affected by GDM which can cause a decrease in the flow of substrates and is a mechanism in which fetal programming can be affected (Myatt 2006). Fetal programming involves a large amount of development plasticity and interruptions to this development may cause abnormalities in the development of certain cells which may progress to structural differe nces in organ development (Gluckman and Hanson 2004 cited in Jansson and Powell 2008 ref 16). Effects to the fetus exposed to GDM If a fetus is exposed to a diabetic environment during pregnancy then there can be certain long term effects. These effects can be classified into three groups; Anthropometric, Metabolic or Vascular and Neurological or Psychological. Anthropometric changes are concerned with the rates of growth for both height and weight and in a diabetic environment these can be excessive leading to macrosomia and obesity in later life. Metabolic and vascular changes that occur are abnormal glucose tolerance which can eventually lead to diabetes mellitus. Finally the neurological and psychological changes that can occur are usually minor but development of psychological and intellect can sometimes be deficient (Dabelea and Pettitt 2008). Potential problems that may arise with the fetus from an exposure to maternal diabetes include abnormal organ mass, altered angiogenesis and increased levels of fetal insulin (Fetita 2006). It has also been found that if there is an increase in weight during pregnan cy then there is usually a higher birth weight of the fetus (Humphreys 1954 cited in Catalano 2008 Chapter 11). The developing fetus cannot synthesise glucose and is dependent on the mother to produce it where it is transported to the fetus via facilitated diffusion through the placenta (Aerts et al 1996 cited in Mello, Parretti and Hod 2008). The result of decreased insulin sensitivity is that there is more glucose available to the developing fetus which can lead to a greater birth weight (Mello, Parretti and Hod 2008). Using animal models, it has been shown that exposure to high levels of glucose in utero can lead a diminished number of nephrons in the offspring (Amri et al 1999 cited in Fetita 2006 ref 68). This is important as nephrogenesis only occurs in the fetus and stops after birth (Gomez, Norwood 1999). It has been shown that a reduction in the numbers of nephron may affect the rate of progression of renal disease in adults due to an inability to secrete sodium. This may l ater develop into salt-sensitive hypertension (Brenner et al 1988). The mechanisms of reduced organ mass, high levels of fetal insulin and defects in angiogenesis may help explain how the fetus programs abnormal glucose tolerance in adulthood as a result of exposure to GDM (Fetita 2006). Transmission of diabetes from mother to offspring Exposure to gestational diabetes mellitus increases the risk of the fetus developing abnormal glucose tolerance which may develop into type 2 diabetes. (Fetita et al 2006). The association between greater incidences of the offspring having diabetes with a mother with GDM is greater than what would be predicted that could be passed on by maternal genetics (McLean et al 2006). One study showed that the phenotype for GDM/T2D was more common in daughters of mothers who were diabetic rather than daughters of fathers who were diabetic suggesting that the transmission is from mothers with GDM to their daughters. However there were limitations of the McLean study. Patients may not be aware of their fathers diabetes status due to men having lower inclinations to report symptoms and share illnesses with the family. One study showed that the mass of the pancreatic beta cells is relatively fixed by the end of fetal growth and this can be influenced by an intrauterine environment of hyperglycaema (McLean et al 2006). Congenital defects are more common in babies born to diabetic mothers (Farrel et al 2002 cited in Fetita et al 2006). There are many factors that can influence the prevalence of these malformations including the duration, severity and age of onset of GDM (Kousseff 1999). If the onset of GDM is at the beginning of development then development of some organs may be affected. However as said before, the majority of GDM develops during the second trimester. This can then lead to embryopathy which includes defects such as failure of neural tube closure and malformations in the Renal, Cardiac and Gastrointestinal systems which present in childhood (Fetita 2006). In diabetes the hexosamine pathway is activated and inhibits the pentose shunt pathway which decreases the production of antioxidants and therefore leads to an increase in oxidative stress. This oxidative stress has been found to disrupt gene expression and may contribute to congenital defects. One example is that oxidative stress inhibits a gene called pax-3 which is needed for neural tube closure and in diabetes there is an increased risk of neural tube defects (Horal et al 20 Aetiology of Gestational Diabetes Mellitus Aetiology of Gestational Diabetes Mellitus Abstract Gestational Diabetes is a condition present in the later stages of pregnancy where the mother has insulin resistance leading to glucose intolerance. The aetiology of Gestational Diabetes Mellitus is largely unknown but several theories include autoimmune destruction of the beta cells, monogenic mutations and insulin resistance. In pregnancy it is normal for there to be some levels of insulin resistance and it is thought that the products of the placenta contribute to the state of insulin resistance as GDM usually subsides after pregnancy. GDM in pregnancy can lead to an increased risk of cardiovascular disease in the offspring such as hypertension and atherosclerosis. This is due to the increased levels of oxidative stress and inflammatory mediators present during pregnancy. The placenta is very important as it is able to control and buffer the amount of glucose that is delivered to the fetus but if this level is too high then it is out of the placentas control and the fetus may have increased rate of growth due to this extra glucose. The current focus of research in this area seems to be into finding ways to diagnosis GDM earlier in the pregnancy and to try and reduce the amounts of oxidative stress. Gestational diabetes: consequences for fetal programming of vascular disease in adulthood Introduction Gestational Diabetes Mellitus (GDM) occurs when there is a glucose intolerance that is first detected during pregnancy. It is a form of hyperglycaemia (Buchanan and Xiang 2005). The aetiology of the condition is unknown but there have been many suggestions as to the cause of it, including autoimmune destruction of the ß pancreatic cells and the possibility of a genetic predisposition to the condition. Hormones that are produced in pregnancy help contribute to the insulin resistant state which characterises diabetes. In recent years, there has been an increase in the cases of Obesity and this is a risk factor for both Diabetes Mellitus and Cardiovascular Disease. The intrauterine environment can affect fetal programming and development. This essay will look into how the placenta and its products can affect the insulin resistant state and how this resistance effects programming as well as the role of oxidative stress and inflammation in making the offspring more susceptible to cardi ovascular disease. Gestational Diabetes Mellitus (GDM) GDM is a state of insulin resistance which disturbs the intrauterine environment and can lead to accelerated fetal growth (Radaelli et al 2003).It effects approximately 7% of pregnant women with approximately 200,000 cases seen each year (Schillan-Koliopoulos and Guadagno 2006). The term GDM is applicable when the onset is during the second and third terms of the pregnancy, but it does not exclude the possibility that the insulin resistance was undiagnosed before the pregnancy. If this is the case and is found to occur in the earlier stages of pregnancy then the mother should be treated the same as mothers who are known to have diabetes before pregnancy (Metzger, Coustan 1998). There is a degree of insulin resistance in normal pregnancy which begins towards the middle of the pregnancy but during the later part of the second and the final trimester these can increase to levels of insulin resistance that are associated with type 2 diabetes (Yogev et al 2008 Chapter 10). Insulin resista nce is when the tissues do not produce a response to insulin due to problems with the secretion of insulin or where the tissues are desensitised to insulin and therefore lack the ability to produce a response (Catalano et al 2003). In a normal pregnancy, the mother changes her metabolism to allow a constant supply of nutrients to reach the fetus to support its rapid growth. Among these nutrients is glucose, which is the main energy source used by the fetus. During the later stages of pregnancy the mother becomes hypoglycaemic and although there is increased gluconeogenesis, the hypoglycaemia still occurs because there is a high rate of transport of glucose to the fetus (Herrera 2000 cited in Herrera and Ortega 2008). GDM can have effects that impact the development of the fetus such as hypoglycaemia and macrosomia, which is an increase in body weight and has the possibility of leading to problems when giving birth, such as shoulder dystocia (Schillan-Koliopoulos and Guadagno 2006). During the second trimester of pregnancy there is peripheral insulin resistance but there is also the possibility that hepatic insulin sensitivity is altered in pregnancy, although few studies confirm this. By the end of the pregnancy the levels of insulin that are circulating are thought to be double those at the start (Redman 2001). Insulin Resistance Insulin resistance in GDM can occur in two forms. The first is where it develops in late pregnancy and it has been postulated that there is a post-receptor mechanism that may influence the insulin signalling pathway which leads to a reduced glucose uptake. The second form is where there is already a degree of resistance before the pregnancy but the changes that occur in normal pregnancy aggravate this (Metznger et al 2007). The insulin resistance that develops in pregnancy is much needed to allow the flow of nutrients, from the mother, directly to the fetus to allow for growth (Radaelli 2003). Increased insulin resistance leads to an increase in insulin secretion by the ß pancreatic cells (Buchanan and Xiang 2005). The insulin resistance is thought to be caused by increased adiposity and as the insulin resistance usually stops after pregnancy this suggests that there is a possibility that the products of the placenta are a potential cause of the resistance. During the course of th e pregnancy the actual changes in glucose levels are very small. It would be assumed that the glucose levels would rise due to the increased insulin resistance but the pancreatic ß cells increase their secretion of insulin to maintain homeostatic glucose levels (Yogev et al 2008 Chapter 10). GDM occurs because there is an increased demand for insulin which under normal circumstances can be met unless there are problems with the secretion of insulin leading to the development of hyperglycaemia. The majority of mothers who develop GDM have been discovered to have a degree of insulin resistance before they became pregnant. Therefore, with the insulin resistance that occurs in normal pregnancy it can be said that GDM occurs with a greater insulin resistance than normally present in gestation (Yogev et al 2008 Chapter 10). Insulin resistance causes a decreased uptake of glucose into skeletal muscle, adipose tissue and liver as well as a decreased production of hepatic glucose. (Catala no et al 2003). One suggestion for insulin resistance looks into the possible role of the mitochondria. Studies using Magnetic Resonance Spectroscopy (MRS) have shown that in normal offspring of parents with type 2 diabetes, there is an increased amount of intramyocellular lipid. This has been shown to cause a reduced function in mitochondria which suggests that mitochondrial dysfunction may play a part in insulin resistance (Petersen et al 2004 cited in Morino et al 2005). It has been suggested that this increase in intramyocellular lipid activates a serine kinase cascade which causes an increase in the Insulin Substrate Receptor 1 (IRS-1), which inhibits insulin receptor phosphorylation on tyrosine sites. This can cause a decrease in the effects and utilisation of glucose. One study showed that in the insulin resistant offspring the mitochondrial density was reduced by just over a third to that of a normal offspring. This suggests that offspring who are insulin resistant may inher it a condition that causes a reduction in rate oxidative phosphorylation in mitochondria (Griffin et al 2009 cited in Morino et al 2005). Detection of GDM Diagnosis of GDM helps to identify pregnancies that are at risk of fetal morbidity as well as obesity and glucose intolerance in the offspring (Buchanan and Xiang 2005). GDM is hard to diagnose as it is asymptomatic. Normal diabetes could be diagnosed by glycosuria but in pregnancy the renal threshold to glucose is lowered so that glycosuria doesnt give a true representation of hyperglycaemia (Redman 2001). There are several risk factors of GDM which can be classified into three groups and help in the screening process. Low risk factors include women who are younger than 25, normal weight at conception, no known family members with diabetes and no history of glucose intolerance. High risk factors include obesity of the mother, diabetes in close relatives, a history of glucose intolerance, current glycosuria and previous pregnancies with GDM (Metzger and Coustan 1998 Chapter 25). Causes of Diabetes There are several theories as to why diabetes occurs and this has been thought to be similar to the underlying mechanisms that cause gestational diabetes. Diabetes is a result of pancreatic beta-cell dysfunction which can present in three main ways: autoimmune, a genetic cause and on top of already present insulin resistance (Buchanan and Xiang 2005). Autoimmune diabetes accounts for approximately 5-10% of all diabetic cases (American Diabetes Association 2010). There are circulating antibodies to the ß cells of the Islet of Langerhans. In GDM, there are a small number of women who have with these antibodies present in their circulation. It is thought that these cases present with GDM due to problems with insulin secretion caused by destruction of the Islets by the autoantibodies (Buchanan and Xiang 2005). This form is similar to type 1 diabetes. The Islet Cell Autoantibodies (ICA) have been shown to have four major molecular targets: Insulin, Glutamic acid decarboxylase (GAD 65), Insulinoma-associated antigen-2 (IA-2) and Zinc Transporter 8 (ZnT8) (Tree 2010). Monogenic diabetes has 2 general forms, one where there are mutations in autosomes and the other where there are mutations in the DNA of mitochondria. The first form is commonly referred to as Maturity Onset Diabetes of the Young (MODY). In both cases onset tends to be at a young age and the patient doesnt present with insulin resistance or obesity (Buchanan and Xiang 2005). Mutations that cause MODY have been found in some women with GDM and commonly occur in genes coding for glucokinase, hepatocyte nuclear factor and insulin promoter factor, MODY is associated with beta cell dysfunction (Weng et al 2002). Chronic insulin resistance with beta-cell dysfunction seems to be the most common cause of GDM. As mentioned before there is an increase in insulin resistance in normal pregnancy but if this develops with background insulin resistance then there is an even greater insulin resistance which can lead to GDM. An established suggestion is that women who are unable to increase their secretion of insulin to cope with the insulin resistance developed in late pregnancy are more susceptible to developing GDM (Buchanan and Xiang 2005). However there could be various environmental processes that are involved in the underlying pathophysiology of GDM. The products of the placenta may also have a role in increasing or decreasing insulin resistance and these will be discussed later. Placental Function The placenta is an organ that has many roles during the development of the fetus. One of these functions is that it acts as a barrier to separate the maternal and fetal surfaces such that the syncytiotrophoblast surface exposes the placenta to the maternal circulation and the endothelium is exposed to the fetal circulation. This position between the two circulations means that the placenta is influenced by molecules from both circulatory systems, including cytokines, hormones and growth factors. The placenta produces molecules which can separately affect the maternal and fetal circulation and it expresses a large number of cytokines including leptin, resistin and tumour necrosis factor. However it has been discovered that these molecules are also produced by adipocytes. All molecules that are going from the mother to the fetus have to cross the placenta. Here they are either modified, for example lipids or like glucose, they are metabolised for placental purposes (Desoye et al 2008). The placenta plays an important role in fetal growth and the regulation of pregnancy (Giachini 2008). The placenta acts to sustain normal homeostatic levels and to carry out the functions of the vital organs. It also provides an immunological defence to the fetus and allows the exchange of molecules vital to its development (Jansson and Taylor 2007). Placental Development Approximately 4-5 days after conception, the process of cleavage causes rapid cell divisions and one of the groups of cells to form are called trophoblast cells. Further developmental processes form the blastocyte which is surrounded by an outer layer of the trophoblast cells. As the pregnancy progresses, the trophoblast cells develop into the placenta while the inner parts of the blastocyte form the embryo and umbilical cord (Huppertz 2008). The blastocyte implants itself onto the epithelium of the uterus where it differentiates into a syncitiotrophoblast which is able to implant itself in the epithelium leading to it being embedded into the decidual part of the uterus (Huppertz 2008). After the attachment of the blastocyte, the trophoblast layer divides very quickly and changes into 2 layers; the inner cytotrophoblastic layer and the outer syncytiotrophoblastic mass (Gude et al 2004).The whole implantation process takes 12 days to complete and after this the fetus is fully embedded into the endometrial layer (Huppertz 2008). The chorionic plate is the surface of the placenta that faces the fetus and this is where the umbilical cord inserts. The basal plate is the surface that faces the mother which contains many types of cells including immune cells such as macrophages and killer cells to carry out the placentas immunological function. The maternal basal plate and the fetal chorionic plate converge to form the smooth chorion which is composed of three layers (Huppertz 2008). When the trophopblast invades the endothelium there is a remodelling of the uterine spinal arteries which is necessary to ensure that the fetus and the placenta receive an adequate blood and nutrient supply and is able to remove any waste materials. This direct supply of blood and nutrients to the placenta can define it as being haemochorial villous organ (Gude et al 2004). After the rapid divisions of the trophoblast and development into 2 layers there are two pathways that can occur, th e villous and extravillious pathways. The extravillious pathway results in the trophoblast being able to invade into the decidua and cause the remodelling of the uterine arteries to increase blood supply to the placento-fetal unit. The villious pathway has a transportation function as well as having endocrine and protective functions (Gude et al 2004). Normal Placentation Placentation involves the structure and function of the placenta. The process of placentation is helped by the composition and arrangement of the extracellular matrix (ECM) of the endometrium. Studies on rats induced with diabetes provided results that showed that diabetes has an effect on the distribution of the ECM molecules. This study by Giachini et al illustrates that Types I and III collagen as well as other molecules, such as proteoglycan molecules decorin and biglycan were distributed throughout normal and diabetic placentas. It was shown that diabetes affects the expression of fibronectin and an increase in deposition of fibronectin may cause changes to the ECM structure which could affect the transfer of molecules from the mother to the fetus. One way in which changes in the ECM can be overcome is to test blood glucose levels frequently during the pregnancy and if kept in normal ranges this can dramatically decrease the prevalence of diseases and disorders present in the fe tus (Giachini et al 2008). As the pregnancy progresses the size of the placenta increases which also means an increase in the amount of products that the placenta produces therefore increasing in the insulin resistance (Schillan-Koliopoulos and Guadagno 2006). This is because the net effect of the products of the placenta is to increase insulin resistance. The increase in size of the placenta means that it needs an increased blood supply. Failure of the mother to increase its blood supply to the placenta can lead to placental insuffiency which if exacerbated can be attributed to be a cause of intrauterine growth restriction (IUGR). This growth restriction is more related to poor maternal nutrition rather than to a cause of GDM. GDM have been associated with an increased fetal and placental weight (Jansson and Taylor 2007). One of the reasons why GDM and increased insulin resistance affects the fetus is that while glucose can cross the placenta, insulin is unable to. This means that the fetal pancreas has to compensate by producing more insulin to prevent high blood glucose levels. The fetal pancreas is capable of doing this and the liver responds to the higher levels of insulin by increasing its production of glucose (Schillan-Koliopoulos and Guadagno 2006). Offspring who have an increase in birth weight have been shown to be at risk of developing cardiovascular disease and diabetes later in life. The main risk factor for this is poor transfer of nutrients via the placenta (Jansson and Taylor 2007). How dramatic these changes are depends on how good the control of blood glucose levels have been during the development of the placenta, if any treatment has been received and if there were any periods of away from normal glucose levels (Desoye 2006). How does diabetes affect Placentation? Diabetic insults at the beginning of the pregnancy can have long last effects of the placenta. One of the roles of the placenta is that it is able to buffer excess maternal glucose which can help to keep the fetal glucose levels within range However if the insult lasts longer than the placenta is able to compensate for then excessive fetal growth may occur (Desoye Mouzon 2007). In diabetes there is endothelial dysfunction which can lead to vascular disease. The endothelial cells help to control the vascular tone of the smooth muscle lining the vasculature. They do this by producing substances that help to vasodilate the smooth muscle including Nitric Oxide, Prostacyclin and Endothelium-Derived Hyperpolarising Factor (EDHF). There have been several studies to suggest different mechanisms of how diabetes affects the endothelium including impaired release of these vasodilating molecules, faults with signal transduction and increased release of constricting mediators of the endothelium. The dysfunction of the endothelium in diabetes is thought to be caused by activation of protein kinase C (PKC) as well as increased oxidative stress, non-enzymatic glycation and an increased activation of the polyol pathway (De Vries et al 2000).The main reason why these effects occur is thought to be due the activation of the protein kinase C pathway and the increased oxidative stress. This can cause early damage to the development of vascular vessels (Roberts and Raspollini 2008). These mechanisms will be discussed later. The effect of hormones produced in pregnancy Pregnancy causes changes in the circulating hormones and cytokines which can all have different effects on insulin resistance and this may help explain the mechanism underlying the resistance that is found in pregnancy and in GDM. Cytokines produced in pregnancy, such as TNF-a, Adiponectin and Leptin have been found to cause an increase in the insulin resistance (Gao et al 2008). In early pregnancy, the levels of oestrogen and progesterone rise but no net effect is seen as the two have antagonistic effects. Oestrogen increases the binding of insulin to its receptor whereas progesterone reduces the ability of insulin to bind (Ryan and Enns 1988). Cortisol levels in pregnancy increase so that by the end of the pregnancy the levels are three times that of what they were at the beginning (Gibson and Tulchinski 1980 cited in Yogev et al Chapter 10). Studies have shown that with increased amounts of cortisol there was a decrease in insulin sensitivity causing insulin resistance (Rizza et a l 1982 cited in Yogev et al 2008 chapter 10). During pregnancy the levels of prolactin increase up to ten times the normal amount (Yogev et al 2008 chapter 10). Studies have shown that in a culture of pancreatic beta cells, prolactin can cause an increase in levels of secreted insulin (Sorenson et al 1993 cited in Yogev et al 2008 Chapter 10). However, high levels of prolactin are not seen to be a pathological cause of GDM (Yogev et al 2008 chapter 10). Human placental lactogen (HPL) is a hormone, and its levels rise during the second trimester of pregnancy. This causes a decrease in the phosphorylation of insulin receptor substrate (IRS1) which can lead to significant insulin resistance (Ryan and Enns 2008 cited Yogev et al 2008 ch 10). Leptin is associated with obesity and concentrations of leptin have been shown to be related to the concentration of insulin in the plasma. In pregnancy the leptin levels increase dramatically. During pregnancy the mother uses her fat stores to supp ort fetal growth and it is thought that the leptin levels increase with the mobilisation of these fat stores. Leptin levels relate to the body mass of the individual (Sattar et al 1998). Placental Leptin is the same in structure and charge to the one produced by adipose tissue (Ashworth et al 2000). One study showed that high leptin concentrations in the umbilical cord increased the likelihood of developing fetal macrosomia (Wiznitzer et al 2000). It is also thought that leptin effects insulin sensitivity by effecting glucose metabolism in both skeletal muscle and in hepatocytes. Rats that received an external source of leptin were found to have an increase in gluconeogenesis which accounted for the majority of hepatic glucose production (Rossetti et al 1997). In GDM there is a greater secretion of TNF-alpha in response to glucose. TNF-alpha functions to regulate metabolism of glucose and lipids as well as being involved in insulin resistance. Many studies suggest that TNF-alpha is involved in the progression to GDM. They found that an increase in glucose cause the placenta and adipose tissue to increase production of TNF-alpha in some cases up to 4 times more than non-diabetic pregnant(Coughlan et al 2001). One study showed that the increases in the levels of TNF-alpha during pregnancy increased consistently with increases in body weight (Catalano et al cited in Yogev et al 2008). Adiponectin is a protein derived from adipose tissue and its function is to regulate insulin resistance and maintains levels of glucose. During pregnancy it has been found that its levels drop and could therefore lead to the increase insulin resistance found in GDM (Gao, Yang, Zao 2008). Adiponectin has also been found to decrease the secretion of TNF-alpha which as stated above can lead to insulin resistance (Hotamisligil 1999 cited in Yogev et al Chapter 10 2008). Adiponectin may cause increased insulin sensitivity as its concentration decreases throughout the gestational period ( Desoye and Mouzon 2007). Resistin is a protein that is produced by adipose tissue and is thought to be involved in insulin resistance in diabetes and is associated with obesity (Steppan and Lazar 2002) In pregnancy, resistin is secreted by the placenta and this secretion reaches its peak by the last trimester (Yura et al cited in Megia et al 2008). Studies show that TNF-alpha is an important factor in insulin resistance during pregnancy and with inputs from leptin and cortisol there is altered glucose metabolism whereas inputs from oestrogen, progesterone and prolactin had little significant effects (Kirwan and Mouzon 2002). There are many hormones produced during pregnancy, mainly by the placenta and adipose tissue that have varying affects but with the overall impact being insulin resistance. Inflammation in Diabetes There are genes in the placenta which regulate reorganisation of the endothelium and inflammatory responses and in GDM these were found to be altered. The increase in leptin receptors suggests that in the placenta this can cause proinflammatory responses (Radaelli 2003). One of the current theories is that the abnormal metabolic environment in GDM can lead to increased production of cytokines and inflammatory mediators. Molecules such as TNF-alpha, Resistin and Leptin increase during pregnancy and these increases in these inflammatory mediators produce metabolic changes by increasing insulin resistance (Desoye and Mouzon 2007). Leptin and TNF-alpha activate phospholipase A2 which are a family of eicosanoid precursors that go on to produce essential fatty acids such as w3 polyunsaturated fatty acids (Desoye Mouzon 2007). There has been a recent investigation which found that with increased adiposity at birth there has been an increase in w3 fatty acids in the placenta (Verastehpour et al 2005 cited Desoye and Mouzon 2007). As stated before, the placenta produces cytokines but it is also a site of action of the cytokines. It is the location of the receptors for these cytokines will influence if the cytokines act on the mother, the placenta or the fetus. With cytokines there is very little transfer across the placenta from mother to fetus and the origin of the cytokines in the fetus can be from either the placenta or from the fetus itself (Desoye and Mouzon 2007). Fetal Programming Many studies have highlighted the fact that events that occur while the fetus is developing can alter its developmental pathway and have adverse outcomes in later life. Fetal programming describes how the environment can affect certain developmental events of which the effects are permanent and can affect processes such as metabolism and the organisms physiology. Women with GDM have an increased risk of the fetus developing macrosomia (Catalano 2008 Chapter 11). The main factor that effects the growth of the fetus is the maternal environment and there is a strong association with the weight and height of the mother and the growth of the fetus such that mothers who are heavier and taller will produce heavy babies. (Love and Kinch 1965 cited in Catalano 2008 Chapter 11). The placenta and fetal programming The placenta is very important to the developmental processes of the fetus as it is able to change the quantity of signals and nutrients that the fetus receives. Deviation from normal would alter the fetal programming, thus making it more susceptible to disease in later life. Pregnancies that are complicated by GDM have excessive oxidative and nitrate stress which has been found to change the activity of certain proteins. Oxidative and nitrate stress alter the placentas function and may cause changes in the fetal programming. Nutrient transfer depends largely on the normal development of the vasculature to allow blood flow and this can be affected by GDM which can cause a decrease in the flow of substrates and is a mechanism in which fetal programming can be affected (Myatt 2006). Fetal programming involves a large amount of development plasticity and interruptions to this development may cause abnormalities in the development of certain cells which may progress to structural differe nces in organ development (Gluckman and Hanson 2004 cited in Jansson and Powell 2008 ref 16). Effects to the fetus exposed to GDM If a fetus is exposed to a diabetic environment during pregnancy then there can be certain long term effects. These effects can be classified into three groups; Anthropometric, Metabolic or Vascular and Neurological or Psychological. Anthropometric changes are concerned with the rates of growth for both height and weight and in a diabetic environment these can be excessive leading to macrosomia and obesity in later life. Metabolic and vascular changes that occur are abnormal glucose tolerance which can eventually lead to diabetes mellitus. Finally the neurological and psychological changes that can occur are usually minor but development of psychological and intellect can sometimes be deficient (Dabelea and Pettitt 2008). Potential problems that may arise with the fetus from an exposure to maternal diabetes include abnormal organ mass, altered angiogenesis and increased levels of fetal insulin (Fetita 2006). It has also been found that if there is an increase in weight during pregnan cy then there is usually a higher birth weight of the fetus (Humphreys 1954 cited in Catalano 2008 Chapter 11). The developing fetus cannot synthesise glucose and is dependent on the mother to produce it where it is transported to the fetus via facilitated diffusion through the placenta (Aerts et al 1996 cited in Mello, Parretti and Hod 2008). The result of decreased insulin sensitivity is that there is more glucose available to the developing fetus which can lead to a greater birth weight (Mello, Parretti and Hod 2008). Using animal models, it has been shown that exposure to high levels of glucose in utero can lead a diminished number of nephrons in the offspring (Amri et al 1999 cited in Fetita 2006 ref 68). This is important as nephrogenesis only occurs in the fetus and stops after birth (Gomez, Norwood 1999). It has been shown that a reduction in the numbers of nephron may affect the rate of progression of renal disease in adults due to an inability to secrete sodium. This may l ater develop into salt-sensitive hypertension (Brenner et al 1988). The mechanisms of reduced organ mass, high levels of fetal insulin and defects in angiogenesis may help explain how the fetus programs abnormal glucose tolerance in adulthood as a result of exposure to GDM (Fetita 2006). Transmission of diabetes from mother to offspring Exposure to gestational diabetes mellitus increases the risk of the fetus developing abnormal glucose tolerance which may develop into type 2 diabetes. (Fetita et al 2006). The association between greater incidences of the offspring having diabetes with a mother with GDM is greater than what would be predicted that could be passed on by maternal genetics (McLean et al 2006). One study showed that the phenotype for GDM/T2D was more common in daughters of mothers who were diabetic rather than daughters of fathers who were diabetic suggesting that the transmission is from mothers with GDM to their daughters. However there were limitations of the McLean study. Patients may not be aware of their fathers diabetes status due to men having lower inclinations to report symptoms and share illnesses with the family. One study showed that the mass of the pancreatic beta cells is relatively fixed by the end of fetal growth and this can be influenced by an intrauterine environment of hyperglycaema (McLean et al 2006). Congenital defects are more common in babies born to diabetic mothers (Farrel et al 2002 cited in Fetita et al 2006). There are many factors that can influence the prevalence of these malformations including the duration, severity and age of onset of GDM (Kousseff 1999). If the onset of GDM is at the beginning of development then development of some organs may be affected. However as said before, the majority of GDM develops during the second trimester. This can then lead to embryopathy which includes defects such as failure of neural tube closure and malformations in the Renal, Cardiac and Gastrointestinal systems which present in childhood (Fetita 2006). In diabetes the hexosamine pathway is activated and inhibits the pentose shunt pathway which decreases the production of antioxidants and therefore leads to an increase in oxidative stress. This oxidative stress has been found to disrupt gene expression and may contribute to congenital defects. One example is that oxidative stress inhibits a gene called pax-3 which is needed for neural tube closure and in diabetes there is an increased risk of neural tube defects (Horal et al 20