The American War in Vietnam - 1012 Words

Dominos. One falls then they all fall. People spend hours to set them up, just to watch them all fall in the blink of an eye. This is similar to the theory of what the U.S. believed would happen if one country, Vietnam, was to fall to communism. This is what caused the war between North Vietnam the communist lead government and the anti-communist South (Encyclopedia Britannica1). How does a war relate to a game enjoyed by millions of people all over the world? Just like in a game of dominos, you set them up and watch them fall, the Vietnam War was the same. Vietnam and the countries surrounding it had worked very hard for independence, that they no longer cared how their government was run. But, the U.S. believed that if Vietnam became†¦show more content†¦The Peace accords took place in 1954, and are what ended the French rule, and temporarily divided the country, down the 17th parallel line, to separate the Viet Minh forces from what was left of the French forces. The peac e accords stated that Vietnam would reunite in 1956 after the elections for the new government were held. But, the elections did not happen because the U.S. and South Vietnam did not allow the elections to take place because they were made nervous when they realized that the Viet Minh leaders seemed popular and determined to win (Vietnam War1). And one final important event that changed the course of the Vietnam war occurred on March 29th 1973, when the last of the U.S. troops left, but North Vietnam and South Vietnam did not stop the war, and continued to fight, but the U.S. did not return as explained on CNN Library5. One of the atrocities that took place in this war had a lot to do with the Geurrilla force. The Guerrilla force began their terrorism and assassination of the South officials and functionaries in 1957. The guerrilla force fought through many different forms such as ambush attacks, terrorism, sabotage, night time attacks, harassing the government, police, and security forces with booby traps, mines, raids, kidnappings, and murders as found on Encyclopedia Britannica1. The impact on the civilians in this war was big. The citizans of Vietnam had to put up with this war for over 20 years. There were over 3Show MoreRelatedThe American Of The Vietnam War Essay1872 Words   |  8 PagesMany contemporary American artists address an extensive variety of themes significant to their adopted country while some focus on issues relevant to their country of origin like the subject of war . War has been considered as a major theme, and it’s reality is a great inspiration in writing and has created endless creativity for artists. In particular, the Vietnamese-American artist Dinh Q. Là ª often chooses the subject of the Vietnam war to express his thoughts, concerns, and the message of peaceRead MoreAmerican War And The Vietnam War Essay1714 Words   |  7 PagesSecond World War and the Vietnam War, national unity in the United States and American patriotism began to disintegrate and morph as the nation progressed from the 1940s through the 1970s. During WWII, the United States military fought a foe that the American public, and the world alike, saw as an enemy to the human race, which caused Americans to unify in their efforts to fight in the battle. In contrast, US military actions in Vietnam were not fully backed by the American public or American allies,Read MoreThe American Of The Vietnam War1208 Words   |  5 PagesWhen Penn first sat down with me to tell me his story, he asked if anyone in my family had ever served in a war. I responded by telling him my father was a marine before I was born. â€Å"No, your father is a marine. Once you’re a marine, you’re always a marine,† Penn corrected. Gentle in his demeanor and free with his sense of humor, Penn went on to tell me his story as a veteran of the Vietnam War. Penn graduated from the University of St. Thomas with a degree in business in 1967. He initially tookRead MoreThe American War : The Vietnam War1379 Words   |  6 PagesConsider the Vietnam War, The Cold War, or even the Spanish-American War: it’s safe to assume that the mere mention of these wars evoke some feeling of recognition, whether it resurfaces a rather passionate opinion or an unwelcome flashback to U.S history class. The Philippine-American War illicites a much tamer response, unless, of course, you’re asking a Filipino or a history buff. In fact, the Philippine-American War is often times referred to as ‘The Forgotten War’ for that very reason. DespiteRead MoreVietnam War and American Culture1684 Words   |  7 Pages Vietnam Wars Impact on American Culture Donna Whittle DeVry University Introduction to Humanities I. Introduction and Thesis Statement In the 1960’s America went through many cultural changes. Martin Luther King Jr., a civil rights activist, delivered his famous, â€Å"I have a dream† speech. African Americans were fighting for peace, freedom and equality. The United States was involved in the Vietnam War, committed to anti-communism. African Americans were deployedRead MoreThe Vietnam War On American Society932 Words   |  4 Pagesaccentuating the growing success and power that Vietnam held. America was calm at first as they held the belief that Vietnam would serve as a barrier to communism. Unfortunately, when communism kept spreading, America panicked. American troops were sent into Vietnam and the citizens of America were lied to about the reason for the presence of the troops in Vietnam. The years 1964 to 1975 were characterized by the negative effects of the Vietnam war on American society and how they heightened social, politicalRead MoreThe American Civil War And The Vietnam War1561 Words   |  7 Pagesnever, never believe any war will be smooth and easy, or that anyone who embarks on the strange voyage can measure the tides and hurricanes he will encounter. The statesman who yields to war fever must realize that once the signal is given, he is no longer the master of policy but the slave of unforeseeable and uncontrollable events.† - Sir Winston Churchill. Throughout history, men have fought battles to protect and serve for their country. Some men become injured at war and others don t get toRead MoreAmerican History: The Vietnam War1670 Words   |  7 Pagesof the American Independent Party. The candidates did not know it at the time, but they would become part of the Presidential Election that would help shape American Politics to what they are today. The election of Richard Nixon in 1968 marked a turning point in the American political ideology, ultimately sparking a conservative revolution that would last the better part of the next 24 years. 1968 was one of the most chaotic and violent years in American history. The Vietnam War was beingRead MoreAmerican Involvement in the Vietnam War1078 Words   |  5 Pagesinternational affairs. In this particular case communism in Vietnam was the flame that leered American bugs in, not knowing that they would be brutally burned by communism in the end. From 1953 to 1961, all the initial decisions involving Vietnam were made by President Dwight D. Eisenhower, who once served as the Supreme Commander of the Allied forces in Europe as well as the first Supreme Commander of NATO. Thus, Eisenhower was very knowledgeable about war issues and was prepared to tackle pending conflictsRead MoreAmerican Culture : The Vietnam War2157 Words   |  9 Pages1102 February 22, 2015 The Vietnam War On February 28th 1991 after the speedy 100-hour ground war against Iraqi troops, George W Bush proclaimed proudly: â€Å"By God, we’ve kicked the Vietnam Syndrome once and for all† The fall of Saigon had not marked the end of the Vietnam as Bush accurately conceded to the people, the repercussions of the war can still be seen today in American culture, it has sustained through the Vietnam veterans, as the basis for the support of anti-war precedencies, and morphed

Jane Austen s Pride And Prejudice Essay - 2236 Words

Alexander Pope, a great poet of the 18th century, once said, â€Å"Nothing so true as what you once let fall, most women have no characters at all matter too soft a lasting mark to bear, and best distinguish d by black, brown, or fair. In the 1800s, women were expected to look beautiful, act in a refined manner, and follow the expectations of her elders. They were not to speak their minds and pursue their own interests. This concept of conformity is highlighted in Jane Austen’s Pride and Prejudice in which the majority of women lack individuality in their pursuit of marriage causing marriages to be based purely around self interest, money, or titles. In Jane Austen’s Pride and Prejudice, Elizabeth and Darcy’s relationship is juxtaposed with numerous other loveless relationships to highlight the importance of a woman’s free thought and uniqueness in her search for a successful relationship. To begin, in looking at the relationship of Elizabeth and Darcy, one can see that Elizabeth is young women who fails to fall to the pressures placed on her by society through her feminist ideals. Elizabeth distinguishes herself from society in her ability to make decisions for herself, rather than the persuasions of her community. â€Å"She finds life more amusing than others do because she is superior in discernment and abilities. (Tave 21). Elizabeth’s intelligence allows her to choose a man to marry for the reason of love, rather than money or social status. Unlike many other women, ElizabethShow MoreRelatedJane Austen s Pride And Prejudice1294 Words   |  6 PagesJane Austen s exceptional novel Pride and Prejudice has been depicted as a classic that is as much a social study on class, marriage and gender as it is a romantic tale. It is an amusing representation of the social atmosphere of the late eighteenth and mid nineteenth century England, and it is primarily requir ed with courtship rituals of the English high class. The novel is more than a romantic tale, however through Austen s subtle, and ironic style, it addresses gender, class, and marriageRead MoreJane Austen s Pride And Prejudice1231 Words   |  5 Pagesfinancial stability. In the novel Pride and Prejudice, Jane Austen states that the desire for better social connections interferes with the workings of love through the relationship between Darcy and Elizabeth to criticize the social class structure of the 19th century. Anxieties about social connections or the desire for better social connections, interfere with the workings of love. Darcy and Elizabeth s realization of a mutual and tender love seems to imply that Jane Austen views love as something independentRead MoreJane Austen s Pride And Prejudice992 Words   |  4 Pages It is unfortunate that many people tend to dismiss Jane Austen’s novel, Pride and Prejudice, as simply a romantic love story, even labeling it a â€Å"chick flick.† Upon a shallow reading, it may appear to be such, but a closer look at the novel reveals so much more embedded in the story. In addition to describing the entertaining relationship between Elizabeth and Mr. Darcy, the novel serves to forward Austen s personal values and ideas. Furthermore, there is one issue of her era that she particularlyRead MoreJane Austen s Pride And Prejudice1138 Words   |  5 PagesPride and Prejudice is a novel about the superficiality of marriage during the late 19th and early 20th century, which largely influenced the decisions made by individuals, based on connections and social rankings. The novel takes its characters through various changes influenced by their decision to or rather not to marry certain individuals. It begins not by a man desiring to marry for love, but by a mother who desires nothing more than to marry her daughters well. As the novel develops, Jane AustenRead MoreJane Austen s Pride And Prejudice1211 Words   |  5 PagesJane Austen’s Pride and Prejudice was greatly influenced by the time period in which it was written, This novel follows the story of Elizabeth Bennet and her sisters as they are faced with marriage proposals. The marriage and roles of women in this time period are shown throughout this story. During the time Austen was writing this novel, a woman’s role for her family changed. Daughters started to become a way for their family to achieve more money. Because their family depended on this finan cialRead MoreJane Austen s Pride And Prejudice1678 Words   |  7 PagesAfter reading Jane Austen’s most popular piece of work, the effects of the high societal expectations can be acknowledged through viewing the lives of the Bennet family and friends and noting such effects. Through the examination of the characters in Pride and Prejudice it is easily deciphered between marriages based upon true love and marriage based upon the expectations of society. Society’s main goal for woman in the Victorian era was marriage. As seen many in Pride and Prejudice, marriage wasRead MoreJane Austen s Pride And Prejudice1675 Words   |  7 PagesIn Jane Austen’s Pride and Prejudice, she has specific criteria that her characters follow when choosing their mates. In today’s society, most couples still follow these criteria and more when choosing their ideal mate. What are these important criteria that Austen’s characters consider when choosing a mate? For Austen, the important criteria that she has for choosing a mate are that couples are personally compatible, they are in love with each other, and they must have a good moral character. Read MoreJane Austen s Pride And Prejudice1434 Words   |  6 PagesJane Austen’s Pride and Prejudice was considered a radical novel back in 1813 when she wrote and published the piece. It is a social commentary on the treatment and societal standards of women, as well marriage expectations at the turn of the 19th century. Austen criticizes the patriarchal society, materialism, double standards of men and women by centering the book around Elizabeth Bennett, a young woman of decent means who does not understand the reason for the pressure to find a suitable husbandRead MoreJane Austen s Pride And Prejudice1468 Words   |  6 Pagesestablished over time. In Jane Austen s novel, Pride and Prejudice Elizabeth Bennet is the main character who is a lady in the Regency Era. Elizabeth lives in Longbourn with her parents, Mr and Mrs Bennet and her four sisters. In the beginning of the novel, Elizabeth s prejudice mindset and strong opinion blinds her from realizations happening arou nd her. Soon, Elizabeth s prejudice disappears allowing her to open up and fall in love. Throughout Jane Austen s novel, Pride and Prejudice, Elizabeth growsRead MoreJane Austen s Pride And Prejudice1649 Words   |  7 PagesIn her novel, Pride and Prejudice, Jane Austen is pre-occupied with the theme of marriage. Marriage is a central issue of a woman’s life but it was even more crucial for the women of her society where women were largely dependent on the men in their lives. As a result, women pursued socio-economic stability through marriage. However, it is clear through the novel that Austen did not agree with this part of her society. In Pride and Prejudice, she gives preference to a marriage which is based on love

Accounting Theory and Contemporary Issues Assignment

Question: What is sustainability accounting and describethecost benefit. Answer: Definition of Sustainability Accounting Corporate sustainability is way of business that makes endurable shareholders worth by grasping prospects and overseeing dangers getting from monetary, natural and social advancement. Corporate sustainability pioneers accomplish long haul shareholders esteem by equipping their techniques and administration to strike-less the market's prospective for sustainability items and administrations whereas in the meantime effectively diminishing and evading sustainability expenses and dangers. Background: Sustainability reporting, or sustainability reporting, is wilful within Australia and includes organizations and associations exhibiting their corporate obligation by assessing and reporting on their financial, social and ecological execution and effects. It can be conveyed by means of the organization's yearly report, a separate sustainability report, an expansive business report or an ecological or social effect report. Sustainability and business might formerly have been a farfetched counterpart, yet this is no more the case. The time is currently, time to remain up and begin! However John Jackson is not convinced in this reporting. Purpose of the report The report would propose John, if the sustainability bookkeeping is fundamental or not and the way it believes captivating the representatives getting it done. It is there to learning-Should it be presented inside the bookkeeping practice? Should the bookkeeping practice think about implementing sustainability in its personal exercise? The rationale of sustainability bookkeeping is to assess the ecological, social and administration execution of organizations by a record of their administration of different manifestations of non-budgetary investment by Jonathan connected with sustainability natural, human and social and corporate administration issues, which they depend on for managed, long haul esteem making. At last, Jackson has to be informed that the objective of sustainability bookkeeping and revelation is to illuminate improvement of a coordinated business technique for corporate administration and survey sustainability dangers and opportunities intrinsic to venture choices. Sustainability accounting and exposure is expected like a supplement to budgetary bookkeeping, such that monetary data and sustainability data is capable of being assessed alongside and give a comprehensive perspective of a business's execution and worth formation, mutually money related and non-monetary, and over all types of funds (Kotlikoff and Burns, 2004). Scope Sustainability reporting is about coordinating material money related and non-monetary data in the direction of empowering financial specialists and different stakeholders to see the way an association is truly executing (Merton and Bodie, 1992). An sustainability report looks past the conventional time allotment and extent of the existing monetary report by tending to the more extensive and also more term results of choices for John and activity and by building apparent the connection in the middle of money related and non-budgetary worth. It is imperative that an sustainability report exhibits the connection among an association's procedure, administration and plan of action. Research methods Instead of just depending on generally accepted accounting principles like the main estimation system, Bedford required the improvement of new instruments to give administration and choices creators with helpful data: (a) An extension of the extent of clients as of shareholders, lenders, supervisors and the overall population, to gatherings of stakeholders; (b) An extension of the extent of clients as of assessing financial advancement, to accommodating intercompany synchronization, fulfilling particular client data requirements and creating open trust in business exercises; (c) An extension of the kind of data from exchange-based money related valuations, to information meaning to uncover both inside exercises and the ecological setting of the inner exercises; (d) An extension of estimation systems as of number juggling and the accounting framework to the aggregate administration science territory; (e) An extension of the nature of revelation from phenomenal as far as precedent necessities to enhanced significance for particular choices; (f) A development of exposure gadgets from ordinary finances. Cost-benefit on using sustainability accounting Cost-benefit is an indispensable ingredient of the SASB (SUSTAINABILITY ACCOUNTING STANDARDS BOARD) principles. While lawful models have exposed, the SEC have got to deposit a transformed focal point on cost-benefit study like a major litmus check for extended revelation needs. Cost benefit is considered amid the benchmarks advancement procedure while recognizing bookkeeping measurements for material sustainability problems. In creating this kind of measurements, SASB will evade to the base data that is yet choice valuable (i.e., it introduces a virtual perspective of execution by which companions can be looked at), instead of a comprehensive bookkeeping that might be vital for open approach-or government target-laying. SASB is apprehensive of separating execution in the middle of guarantors and commercial enterprises, not with giving a logically exact and complete bookkeeping, for administrative purposes. The SASB will carry out a cost-benefit examination of the principles utilizing the essential components of a decent administrative financial investigation laid out in the SEC's existing supervision on Economic Analysis in SEC law-makings: 1. An announcement of the requirement for the anticipated activity; 2. The meaning of a benchmark in opposition to which to gauge the feasible monetary results of the anticipated regulation; 3. The ID of optional administrative methodologies; and 4. An assessment of the benefits and costsmutually quantitative and subjective of the anticipated activity and the principle choices recognized by the investigation. As a major aspect of this examination, thought will be certain to the way that organizations are as of now needed, by law, to reveal material sustainability data and that they as of now uncover a lot of sustainability data in different structures, together with SEC filings, yearly reports in addition to sustainability reports. Furthermore, to the degree that divulgence of SASB data speaks to an additional cost, it is a cost of lawful consistence. In that connection, the SASB principles reflect to an additional cost compelling path for organizations to correspond with financial specialists on material sustainability data. On the cost-region, SASB for Jonathan will think about a cluster of contemplations together with: costs to organizations for get-together, reporting, and evaluating data, and its incorporation in Form 10-K and other SEC documentations; and the costs of related inner controls and preparing. On the benefit region, SASB will think about the cost investment funds to organizations of further modernized industry- particular revelation and more successful correspondence with financial specialists on material issues, and in addition execution upgrades on ESG concerns that interpret into functioning and budgetary execution and expanded allure to the wealth markets. Benefits to speculators will likewise be viewed as, together with promptly accessible, choice valuable data that empowers distributed organization correlation of sustainability execution, a comprehensive examination of monetary and sustainability execution, and an appraisal of sustainability dangers and prospects in expanded portfolios. Arguments against use of sustainability accounting Assured conspicuous sustainability issues, for example, environmental transform, water exercise, human resources, and political commitment, produce extraordinary enthusiasm from people in general, government organizations, or speculators who require comprehending the total impact of business on a particular issue so as to focus extremist activities, government programs, venture technique, or portfolio designation. By its industry centre, SASB deliberately evaluates the materiality of these problems, seeing how these concerns particularly and interestingly affect, or are affected by, trade in every one of the 10 parts and 88 commercial enterprises for which it creates norms. Then again, SASB won't, as an issue of rule, deliberately incorporate certain sustainability issues in the revelation standard for all commercial enterprises. Rather, SASB will efficiently survey the materiality of these issues, seeing the way they particularly and remarkably affect, or are affected by, business in each of the 10 parts and 88 commercial ventures for which it creates principles. At last, SASB will guarantee that any systemic sustainability issue included in the standard meets the meaning of materiality in Section 2. This methodology adjusts the expansive financial specialist and societal enthusiasm for exposure on systemic sustainability issues with the production of sustainability norms restricted to issues that are material in their particular industry. SASB takes after a thorough methodology to evaluate the particular effect of systemic sustainability issues for each of the 88 businesses, including: 1. defining the sorts of effect of systemic sustainability issues on organizations' monetary or budgetary execution (e.g., for environmental change, the probability of valuing of green house gases. 2. emissions or costs connected with adjustment) Based on the kind of effect, characterizing attributes of commercial ventures influenced by the issue (e.g., expansive immediate emitters for green house gases outflows or operations effortlessly upset by climate occasion for adjustment) To guarantee inside consistency, cross-cutting sustainability issues will be treated with a steady (however not so much uniform) approach. While the SASB won't be compelled to use a typical execution pointer to the detriment of a more suitable industry-particular marker, reliable treatment of comparative issues and comparable bookkeeping measurements will be supported wherever conceivable. Assumptions Generally as truth and decency are inseparably connected to unwavering quality, sustainability bookkeeping data must display the subjective qualities of straightforwardness and likeness in a pertinent sustainability connection to empower stakeholder, such as John to survey the ecological and social effect of the association (Lamberton, 2005). The theory behind the execution of the GRI Guidelines is that the created pointers, incorporated in reports regarding the Principles, ought to offer a solid prospect of getting away from the issues of story and uniqueness that have influenced the reporting of ecological and social effects. Despite the fact that much significant data stays unquantifiable, institutionalized reporting encourages efficient between firm and between fleeting correlations (Graham Woods, 2006). Discussion Consenting to applicable bookkeeping standards must be clearly checked up in the monetary articulations, while the sustainability affirming individual has yet the GRI Principles and subjective attributes to report upon. These days there are a current that exact that this standards: We materiality, sustainability connection, and culmination and subjective attributes: offset, convenience, exactness, clarity, similarity and dependability are ambiguously characterized and give extensive motivating forces to managerial circumspection. (Voicu D., 2009) Audit's motivation and instruments are required just for the individual whom confirms a circumstance which may change believability in the accumulation and translation of proof. A late set of investigations (Kolk, 2004) of check articulations included in sustainability reports have demonstrated that the audit task had shifted generally in substance and extension, running from affirmation on information combining, information era at the neighbourhood level, culmination of the issues secured, inside consistence with arrangements, consistency with the information in the budgetary report, to the sufficiency of organizations' data on ecological administration frameworks. Of the audit proclamations 40% contained subjective wordings, which were not completely focused around the work performed. Along these lines, the very actuality that a partners report has been audited does not infer that its information and all its substance have been checked completely and are completely dependable. Should the accounting practice consider adopting sustainability in its own practice The regular objective of the two entwined calculated truths is forcing a train that goes past legitimate consistence (Buhmann, 2006). Straightforwardness and responsibility are commonly fortifying. Straightforwardness for the business upgrades responsibility of John by encouraging observing, and responsibility improves straightforwardness by giving a motivating force to operators to guarantee that the explanation behind their activities are appropriately scattered and comprehended (Dragomir, 2008). The procedure of revealing particular parts of unsustainability, with a nitty gritty presentation of its causes and thought of option ways could demonstrate a huge and cathartic experience (Lamberton, 2005: 7). Experimental confirmation supporting these declarations has demonstrated the presence of a positive relationship between ecological execution and the level of optional revelations in natural and social reports (Greuning, 2006). As such, unrivalled ecological entertainers are all the more imminent in really optional exposure channels, as anticipated by financial matters based intentional revelation speculations (Clarkson et al., 2007). There are various explanations behind not reporting by John Jackson; among them, the questions about the favourable circumstances it may bring, the officially great notoriety of the organization, the cost-benefit contemplations, or the trouble to accumulate predictable information are the absolute most unmistakable (Kolk, 2004). Notwithstanding, when Jonathan does decided to write about sustainability, the most noticeably awful situation generally includes key exposure. Numerous creators like John Jackson have communicated worry that reporting methods have ended up inclined to 'managerial catch' in that corporate administration has taken control of the whole methodology of reporting (Hess, 2005), in this manner bringing about data dispersed just when regarded fitting to gather reputational benefits, instead of looking for genuine straightforwardness and responsibility to stakeholders (O'dwyer Owen, 2005). Sustainability accounting and ways it links in with the work undertaken by the firm at present Sustainability Accounting is a device utilized by the firms to turn out to be further sustainable. The generally recognized broadly utilized dimensions are the Corporate Sustainability Reporting and the triple bottom line accounting. These identify the responsibility of financial information and demonstrate how conventional accountingis comprehensive by getting better lucidity and accountability by coverage on the Triple-P's. It is recommended for John that the procurement of free confirmation led by gatherings or people outside to the association who are evidently 1. capable in both the topic and affirmation rehearses; 2. Utilizes gatherings or people to direct the certification who are not unduly restricted by their association with the association or its stakeholders to achieve and distribute an autonomous and fair-minded conclusion on the report; 3. Assesses the degree to which the report preparer has connected the GRI Reporting Framework (counting the Reporting Principles) over the span of arriving at its decisions; and 4. Results in a notion or set of conclusions that is openly accessible in composed structure, and an announcement from the affirmation supplier on their relationship to the report preparer (Ballou et al., 2006). Sustainability can enhance the budgetary main concern It is not a cost trouble Climate change has created impressive level headed discussion from those pushing activity to those denying an issue exists yet from a business point of view a realistic methodology is more helpful. As opposed to seeing practical business hones as a trouble, it is considerably more profitable to see them as a business opportunity and 'danger reducer'. From a monetary perspective, sustainability can lower potential hazard as well as extensively enhance the money related primary concern. Receive sustainability reporting Sustainability reporting is about joining money related data (as in "conventional" yearly reports) and non-budgetary data (e.g. sustainability execution measurements) so that speculators and different stakeholders can survey the hidden wellbeing of the association. A sustainability report looks past the customary time span and extent of monetary reports by tending to the more extensive and more term outcomes of business choices and by making clear the connection in the middle of money related and non-budgetary quality. The structure intends to give clients a superior understanding of an association's key quality drivers, its plan of action, its dangers and opportunities and in addition the soundness of its assets and connections to drive methodology over the short, medium and long haul. An sustainability report exhibits the connections between an association's procedure, administration and plan of action. To Apply the Sustainability accounting with other accounting practices the business can make the accompanying moves to guarantee they have the essential skill to offer a sustainability administration and In order to Offer a Sustainability Service: Construct organizations The business ought to create coordinated effort with neighbourhood natural sustainability specialists keeping in mind the end goal to increase nearby get to dependable information. Addition encounter This starts in the business's own particular business. Professionals ought to audit the ecological sustainability they could call their own business and afterward utilize that profitable experience to have adjusted, significant discussions, based on certified experience, with their customers. Look for data Practitioners ought to acclimate themselves with data sources that they could prescribe to others or utilization to increase their own particular learning. Formalize responsibility Where suitable, professionals ought to formalize their dedication to offering natural sustainability exhortation through advertising and mindfulness bringing up in bulletins, their documentation, and site. Eventually, offering a sustainability administration can help the firm both increase the value of the administrations they offer and help their customers/executives enhance the way they maintain their organizations. Applying the same standards to the practice itself can help bookkeepers enhance the way they maintain their own particular organizations too. Ways to engage employees in the program and to provide them with examples of best accounting practices Bookkeepers working in this business can help their head honchos at every turn, on the expenses/advantages of behavioral changes went for lessening waste, to interest in new supplies and interchange wellsprings of vitality, to creating an extensive ecological administration framework (EAF). Nonetheless, the business may fail to offer the ability to do this without outside help. They will probably look for the assistance of somebody they believe their bookkeeper, conceivably producing new income open doors for the business. In any case first the firm needs to realize that they can expect aid of this nature from their bookkeepers. Given that the business is quick to understand the monetary profits of embracing more sustainable practices, a beginning stage for the business may be to offer to help their customers execute the arrangement do-check-act system for the control and ceaseless change of methods and items. This warning administration could incorporate enhancing business opportunities and making efficiencies, distinguishing the dangers to money stream that social, monetary, and ecological change will present, and guaranteeing that customers or head honchos exploit the expense decreases, minimize any expense builds, and boost the potential income by receiving business systems that recognize and location those sustainability issues that are most applicable to their specific business circumstances. References 1. Ballou, B., Heitger, D. L., Landes, C. E., Adams, M. (2006) The Future of Corporate Sustainability Reporting Journal of Accountancy, 202(6), pp. 65-74. 2. Buhmann, K. (2006) Corporate social responsibility: what role for law? Some aspects of law and CSR Corporate Governance, 2(6), pp. 188-202. 3. Clarkson, P. M., Li, Y., Richardson, G. D., Vasvari, F. P. (2007) Revisiting the relation between environmental performance and environmental disclosure: An empirical analysis Accounting, Organizations and Society, doi:10.1016/j.aos.2007.05.003. 4. Dragomir, V. (2008) Eco-management and the paradigm of self-regulation Environmental Engineering and Management Journal, 7(4) 5. Graham, D., Woods, N. (2006) Making Corporate Self-Regulation Effective in Developing Countries. World Development, 34(5), pp. 868-883. 6. Greuning, H. v. (2006) International Financial Reporting Standards. A Practical Guide (4th edition ed.) International Bank for Reconstruction and Development/World Bank 7. Hess, D. W. (2005) Social Reporting and New Governance Regulation: The Prospects of Achieving Corporate Accountability through Transparency Available at SSRN: 8. Igalens, J. (2006) Institutional Acceptance of Corporate Social Responsibility, In Allouche, J. (Ed.), Corporate Social Responsibility Volume 1: Concepts, Accountability and Reporting (pp. 317332), Palgrave Macmillan, New York 9. Kolk, A. (2004) A decade of sustainability reporting: developments and significance International Journal of Environment and Sustainable Development, 3(1), pp. 51-64. 10. Kotlikoff, L.J. and S. Burns (2004). The Coming Generational Storm. Cambridge: MITPress, 11. Merton, R.C., Bodie, Z. (1992) On the Management of Financial Guarantees. Financial Management 21, 87-109. 12. O'Dwyer, B., Owen, D. L. (2005) Assurance statement practice in environmental, social and sustainability reporting: a critical evaluation The British Accounting Review, 37, pp. 205-229. Voicu D., (2009) A Conceptual Framework for Sustainability Reporting: A Case Study of the Global Reporting Initiative, The International Journal of Environmental, Cultural, Economic and Social Sustainability pp.149-164.

Business Performance of Leadership

Question: Discuss about the Business Performance of Leadership. Answer: Introduction Choi and Kim (2014) opined that leadership is the capability of the management of a company to make vital decisions, inspire as well as motivate others to perform their work in the workplace. Effective leaders can set as well as achieve challenging goals, take decisions at difficult situations, calculate the risks as well as persist in the face of failure. The characteristics of a good leader are to manage the workplace, have communication skills as well as self-confidence. However, the IT leaders are different from other leaders. Loveridge (2014) argued that the IT leadership is the group of the senior executives those are responsible for implementing an IT infrastructure as well as applications that can drive the IT business strategies. The report is based on the leadership in the IT business of Australia and its importance for the business. The selected organization for this report is Melbourne IT. It reflects on the impact of the leadership on the success of the IT business. Leadership style is also discussed in this report for the IT leader. As the business is based on Information Technology, therefore the leader face IT challenges in their business, and respective solutions are also given. Impact of leadership on the success of the IT business Australian IT businesses are facing innovation shortfalls and failure in the development of the leadership programs. The selected IT business for the report is Melbourne IT and as the leader of the business, different leadership functions are conducted. Melbourne IT is an Australian Internet company with its primary business is the registration of the domain name. This IT business also provides the web as well as email hosting services as well as online marketing services to the Australian population (Melbourneit.com.au 2015). When it comes to achieving business success, most of the leaders of the organization think of a strategy which most of the business comes up with. The following are some of the quality traits that should be there within a good leader who leads an IT business organization: Character: The leader requires to be trusted as well as known to live their life with honesty (Katsos and Fort 2016). As in the current era, technology becomes the most vital needs of the population; therefore, the leaders should do the delivery of the IT services from respect for the good character as well as trustworthiness of the person who leads the business. Communicate: In order to reach new benchmarks of achievement, it is required an art of clear communication (Anvari et al. 2014). With good communication skills, the leaders are also required good listening skills that help to drive results and hear to the employees. As a leader of the organization, it is the responsibility to respond to the employees concern and questions. Direction: The leader can work to achieve the goals and objectives of the organization. As a leader of an IT business organization, the leader can create impressive change within the organization as the use of technology changes day-by-day (Harney 2016). The leader can act according to the needs and requirements of their customers and provides with better IT service delivery. Optimistic: The leaders are the source of the positive energy. They are helpful as well as concern for others welfare (Almog-Bareket 2012). In order to avoid personal criticism, they start to gain the consensus of the employees to work effectively as team members. Honesty: The leader should be ethical, believable; honesty as well as reliability forms the foundation of the business success (Marco and John 2013). In order to avoid conflicts, the leader shares information openly to the employees. Leadership Style in an IT leader Transformational Leadership Style An IT leader encompasses of two various types of leadership styles such as transformational as well as transactional. The transformational leadership inspires the followers by raising consciousness about the specified values and motivates the followers in order to address the high level of personal needs (Minavand 2013). As this particular report is based on an IT business organization, Melbourne IT, therefore this style of leadership plays an important role as the leader works with the subordinates in order to identify the required changes and create an organizational vision in order to guide changes through inspiration. As a transformational leadership style, the leader is focused on increasing the effectiveness of the organization. This style of leadership stresses that the leader understands as well as adapts to the followers motives as well as requirements (Brandt and Uusi-Kakkuri 2016). An IT leader has the responsibility to achieve good role models who can empower the staff me mbers in order to achieve higher standards. In the last few years, many transformational changes are taken place in technology. As for example, the development of computing technology by Apple, Intel was the transformational events that are taken place. Steve Jobs, the co-founder of Apple transformed their business processes through the software applications as well as high-speed microprocessors. At Apple, Steve Jobs is seen as a leader who has an idealistic vision to provide computers as a tool to change the world (Davenport 2014). Jobs were passionate about the company as well as enthusiastic about the announcements of products. Figure 1: Transformational Leadership Style (Source: Minavand 2013, pp-47) Transactional Leadership Style Apart from this leadership style, another type of style is transactional leadership that focuses on the exchange, which occurs between the leaders as well as followers. The leader can have a concern with maintaining the normal flow of the business operations (Minelle 2014). Disciplinary powers, as well as an array of incentives, are used to motivate the employees to work. This style of leadership conforms to the existing structure of the IT business as well as measures success as per the organizational system of rewards as well as penalties (Antonakis and House 2014). Performance review is required to judge the performance of the employee. Steve Jobs also acts a transactional leader who directs their efforts through tasks as well as structures. Steve influenced the employees for a strong desire to work, shared their passion with the staffs as well as provided with the organizational vision (Moors 2012). The leadership style of Steve Jobs is desired to create great products that would give enjoy to the clients by using it rather than the products that bring profit to Apple. Figure 2: Characteristics of Transactional Leadership Style (Source: Minelle 2014, pp-47) Both this style of leadership is required to guide the Melbourne IT to success. The transactional leader provides with an ability to address small operational details that on the other hand, the transformational leader is crucial to the strategic development of the business. Apart from this, the transactional approach features both positive as well as negative enforcement while the transformational leadership features both motivation as well as inspiration (Salovaara and Bathurst 2016). Transactional leadership appeals to the self-interest of the individuals, and transformational leadership focuses on the group progress. Challenges that IT leader is facing There are various challenges that the IT leaders are facing in Melbourne IT business organization: Rate and pace of change: According to Moore's law, the doubling of the speed of the computer processing takes place every 18 months. It is one of the manifestations of the technological trend that all the changes occur at exponential rates (Sethuraman and Suresh 2014). Due to the exponential rate of change in the technology, the IT leader is also making changes according to the business requirements. This rapid change in the business affects the leadership quality. Complexity in the integration of the system: Sometimes, change in the system becomes complex. Therefore, the leader is not able to cope up with the complex situation, and it affects their responsibility as a leader (Brandt and Uusi-Kakkuri 2016). Due to rapid change in the technology, the IT department of the company requires changing their IT infrastructure in order to meet the requirements of their clients. Ongoing pressure to cut the cost: Due to rapid change in the technology, the implementation of the new system requires more cost and budget. Therefore, it becomes a vital task for the leader to implement the new system within the estimated budget. The threat to cyber security: Cyber attack is the most vital concern for the IT leader as there is a high risk of threat of hacking of the information from the database system (Ali Shurbagi 2014). The main function of the IT leader is to give high-security measures to the client's information so that any third party person cannot access it. Solutions to the IT challenges for the leader In order to exploit the technology as well as information is fast becoming a prerequisite for the leadership programs. The IT leaders must help the company to value their business as possible from the technology (Sethuraman and Suresh 2014). The following are the solutions that the leader should follow to have a great role in technology decisions and cope up with IT challenges as: Information Technology Leadership Development Program: It is one of the best solutions for the IT leader to change their character according to the change in technology (Antonakis and House 2014). This program takes the IT leader in the IT application management, operations, technical services as well as IT planning for Melbourne IT. The development program gives a full-time position to the leader with benefits as well as design in order to create a sustainable career path with Melbourne IT. The building of strategic IT leadership skills: A strong IT leaders can create a clear vision for the future, a design of the competitive strategy for the business; create an agile as well as flexible culture for Melbourne IT. Consultation with the IT business analyst to develop a new existing system for the business: Due to change in the technology, the business leader can develop and implement a new legacy system for their organization with the help of the IT business analyst (Salovaara and Bathurst 2016). With consulting their ideas with the analyst, they can implement such a system that should be beneficial for the organization in the future. Take the ownership of information: The vital part of managing the information technology is to manage the data quality as well as accessibility (Marco and John 2013). The IT business leader is responsible for the usability of the data gathered as well as stored in the technology and service. The IT providers should have required integration capabilities, but the leader does managing the information. Improve the technology vendor management capabilities: Technology vendors can double contract value when they are circumventing to the IT. The IT business leaders can also look in order to corporate IT for guidance as well as support with the vendor negotiations (Antonakis and House 2014). One of the techniques to nudge in this direction is to measure the effectiveness of the vendor management as well as negotiations. Conclusion It is concluded that the IT leader must be self-achiever, and they are motivated to become a proactive leader. Rapid change in the technology produces a chaos situation of the leader, and they must be ready to cope up with the technological change. In this report, two types of leaders are used such as a transactional style of leaders such as they used to motivate through the system of rewards as well as penalties. The managers use this style and it is focused on the basic management process to control, organize as well as do short-term planning. The leader can act as indicated by the necessities and prerequisites of their clients and offers with better IT administration delivery. As a transformational leadership style, the leader is engaged to build the adequacy of the Association. This style of initiative anxieties that the leader comprehends and additionally adjusts to the followers thought processes and necessities. The transformational leadership inspires the followers by raising consciousness about the predefined values and inspires the supporters to address the high state of individual needs. Therefore, these two types of leadership style are to be in an IT business leader. References Ali Shurbagi, A., 2014. The Relationship between Transformational Leadership Style Job Satisfaction and the Effect of Organizational Commitment.IBR, 7(11). Almog-Bareket, G., 2012. Visionary leadership in business schools: an institutional framework.Journal of management development,31(4), pp.431-440. Antonakis, J. and House, R., 2014. Instrumental leadership: Measurement and extension of transformationaltransactional leadership theory.The Leadership Quarterly, 25(4), pp.746-771. Anvari, R., Irum, S., Shah, I., Mahmoodzadeh, N. and Ashfaq, M., 2014. Determinants of Information Technology Leadership Program.Review of European Studies, 6(2). Brandt, T. and Uusi-Kakkuri, P., 2016. Transformational Leadership and Communication Style of Finnish CEOs.Communication Research Reports, 33(2), pp.119-127. Choi, S.I. and Kim, D.I., 2014. A Study on The Effect Business Performance of Leadership on Global Corporate.Journal of Digital Convergence,12(10), pp.191-199. Davenport, B., 2014. From A to Google: How Technology Is Impacting Information and Leadership.Journal of Leadership Studies, 8(2), pp.41-45. Harney, B., 2016. Book review: Developing leadership: Questions business schools dont ask.Management Learning. Katsos, J. and Fort, T., 2016. Leadership in the promotion of peace: Interviews with the 2015 Business for Peace honorees.Business Horizons. Loveridge, R., 2014. Leadership in the Innovative Organization.Nang Yan Business Journal, 1(1). Marco, R. and John, F., 2013. The role of need for achievement in self-leadership: Differential associations with hope for success and fear of failure.African Journal of Business Management, 5(20), pp.8368-8375. Melbourneit.com.au, 2015.Melbourne IT. [online] Melbourneit.com.au. Available at: https://www.melbourneit.com.au/about-us/ [Accessed 5 Jul. 2016]. Minavand, H., 2013. The impact of project managers leadership style on employees job satisfaction, performance and turnover.IOSR Journal of Business and Management, 11(6), pp.43-49. Minelle, F., 2014. Business Leadership for IT Projects.PROJECT MANAGER (IL), (17), pp.47-47. Moors, G., 2012. The effect of response style bias on the measurement of transformational, transactional, and laissez-faire leadership.European Journal of Work and Organizational Psychology, 21(2), pp.271-298. Salovaara, P. and Bathurst, R., 2016. Power-with leadership practices: An unfinished business.Leadership. Sethuraman, K. and Suresh, J., 2014. Effective Leadership Styles.IBR, 7(9).

Euthanasia In The United States Essay Research free essay sample

Euthanasia In The United States Essay, Research Paper Euthanasia in the United States Every twelvemonth two million people die in North America. Chronic unwellness, such as malignant neoplastic disease or bosom disease, histories for two of every three deceases. It is estimated that about 70 per centum of these people die after a determination is made to waive vital intervention ( Choice in Dying ) . In America and all around the universe, the on-going argument is whether patients should hold the chance to implement this critical option of mercy killing. Although controversial, it is imperative that United States citizens are non denied this right to a humane decease. Groups in resistance to euthanasia state that patients who yearn to do this determination are neither in a healthy psychological province of head nor have the God-willing right to make so. These groups feel if mercy killings were to go a publically accepted option to the terminally ill that doctors, household, and even patients may mistreat it. We will write a custom essay sample on Euthanasia In The United States Essay Research or any similar topic specifically for you Do Not WasteYour Time HIRE WRITER Only 13.90 / page They besides strongly back up modern end-of-life intervention, known as alleviative attention, as a more logical and moral option. Possibly the strongest belief that mercy killing is incorrect comes from those who follow the words of the Bible and believe that every facet of life belongs to God. The Old Testament records an incident affecting King Saul of Israel, who became earnestly wounded on the battleground. Fearing the progressing enemy, Saul took his ain blade and tried to fall against it. He cried to a soldier, ? Come and set me out of my wretchedness for I am in awful hurting but life lingers on. ? The soldier acted in conformity with the wants of the male monarch and killed him. The soldier so brought some of Saul? s armour to David and said, ? I killed him, for I knew he couldn? t live. ? David ordered the soldier put to decease ( Eareckson, 111 ) . Those who believe in the Bible clearly see here that, whether a sovereign or a common individual, clemency violent death is perceived as sinful in the Lord? s eyes. To see a more recent illustration of the Catholic Church? s dissension of mercy killing we merely have to look back a few old ages. In 1994, for case, the Dutch telecasting station IKON? s cinematography of the decease of a adult male with Lou Gehrig? s disease in a docudrama, ? Death on Request, ? brought a denouncement from the Vatican ( Branegan, 30 ) . Equally of import to those back uping the anti-euthanasia cause is the idea of any doctor, household member or patient who would mistreat this right if given the opportunity. Naturally, much trust is bestowed in these cardinal participants of our lives if anything were to go on to us. The inquiry in this sense is how do we know that they will do determinations in the best involvement of the patient if they are unable to talk for themselves? Would the fiscal and emotional load on the household of a terminally sick patient do them to do an irrational determination to straight impact the life of the patient? If the emotional emphasis doesn? t get to some people, the fiscal load may decidedly hit some households hard these yearss with the high costs of modern medical intervention. And who couldn? T usage 1000s of dollars in life insurance? The enticement is decidedly at that place. A rough illustration of this can be seen in the experience of a fifty-year-old adult female with malignant neoplastic disease of the castanetss, liver, lungs, and chest. Her physician was a Polish-born oncologist, Dr. Ben Zylicz. Dr. Zylicz explained to the adult female that he could decrease her hurting with drugs, and offered her a infirmary room. Aware of Holland? s policy leting physicians to stop the lives of the terminally ill by such agencies, the adult female stated, ? I am Catholic. My spiritual beliefs would neer let me to accept euthanasia. ? Zylicz assured the adult female that he would take attention of her, and she agreed to take the room. After 24 hours of morphia intervention she was able to see her household ( Eads, 93 ) . Subsequently, a nurse called Zylicz at place with some straitening intelligence. After Zylicz had left the infirmary, another physician entered the patient? s infirmary room and asked her hubby and sister to go forth. He so ordered an addition in her morphia dose, but refused to corroborate the order in authorship. Within proceedingss the adult female was dead. Zylicz demanded an account from his co-worker. The other physician? s answer was, ? It could hold taken another hebdomad before she died. I needed the bed? ( Eads, 93 ) . For grounds like these, if a individual were to go handicapped without antecedently finishing a life will in a clear province of head, they should non be put to decease. Anyone that would genuinely wish to decease in that province would hold taken the enterprise to do his or her purposes clear before the disabling event took topographic point. As in all instances, the duty of the patient? s life should be up to a medical staff in concurrency with the patient and household. Undoubtedly, mercy killing can be ghastly and downright immoral if non managed with utmost duty, but groups in support of mercy killing still back up terminally sick patient? s option to decease with self-respect and regard. Euthanasia can be administered with positive effects every bit long as certain situational factors are ever considered. These factors include: the type of aid, the type of helper, the type of unwellness being dealt with, and the age of the patient. Furthermore, mercy killing or assisted self-destruction should merely be a last ditch attempt after optimum alleviative attention has been administered. Euthanasia, which means? good decease? in Greek, became a universe fame motion launched by a famed 1973 instance of a physician who helped her female parent dice and so was acquitted of condemnable charges ( Branegan, 31 ) . Since so it has been praised and protested all around the universe, the United States is a particular instance though. In the land of life, autonomy, and the chase of felicity, I ab initio assumed that this should non truly be an issue. Regardless of race, faith, colour, or credo, everyone in this state should hold the right to do their ain determinations sing their quality of life and where it is heading. A instance in point of where mercy killing may be accepted comes in the undermentioned narrative: On her eighty-fifth birthday, Virginia Eddy celebrated with her household at a party with all the fixingss. Then, her boy wrote, # 8220 ; She relished her last piece of cocoa, and so stopped eating and drinking. # 8221 ; Her boy arranged for her to be placed on a self-administered morphia trickle to alleviate the hurting of desiccation. She died six yearss subsequently. # 8220 ; This decease was non a sad decease ; it was a happy decease, † Eddy wrote. â€Å"She had done merely what she wanted to make, merely the manner she wanted to make it? ( Euthanasia.com ) . Harmonizing to Eddy, his female parent had chosen the clip and mode of her decease and this had been a positive experience for the full household. # 8220 ; Although we will lose her greatly, her ability to accomplish her decease at the right clip and in her right manner transformed for us what could hold been a desolate and devastating loss into a clip for joy? ( Euthanasia.com ) . Obviously, this adult male genuinely cared for his female parent and her well being, merely as any boy would. Another presentation of where mercy killing worked out in the best involvement of the patient and household can be found a narrative of merely holding the option of mercy killing available to them. When Annemie Douwes Dekker? s hubby Hink was foremost told he had multiple induration in 1978, his household physician agreed to discourse the possibility of mercy killing when the clip of all time came to earnestly see it. ? That was a great aid to us, ? Annemie recalled ( Choice in deceasing ) . Five old ages subsequently Hink, now 50 old ages old, had been in a nursing place for a twelvemonth and was deteriorating quickly, losing his abilities to pass on and command bodily maps. His widow, now sixty-two, says, ? he had a strong bosom ; he could hold gone on life for years. ? When Hink originally requested to be put to decease he was denied, but after multiple months and multiple petitions he came place from the nursing place to be with his household and was administered toxicant by a physician. ? I? m convinced we did the right thing, ? said Annimie, ? He died a good decease? ( Choice in deceasing ) . Personally, I prefer to believe that human factors change society, non that society changes the human factor. The pick of mercy killing is a particular thing, and is a determination that belongs to persons and their effects. Courts and legislative assembly truly have no portion in doing this an illegal or legal issue ( The right to take to decease, 15 ) . Although it is widely believed that mercy killing is incorrect under any conditions due to religion, many people are non spiritually strong plenty to manage a terminal unwellness such as malignant neoplastic disease or multiple induration in its concluding phases. I am personally comfy with the place of my faith, but that does non blind me to the retching worlds and soul-searching involved in mercy killing determinations. If a terminally sick patient in great hurting makes an informed pick to decease and inquire for the aid of a loved one or a long-time personal doctor, that should non be publically viewed as a job. It shouldn? T be incorrect to make it for person? s female parent if it were her deceasing wish. When doing a determination that entails the expiration of a life, it should be left up to the patient or the patient? s life will to show what minimum quality of life would be acceptable to that person. The position this paper has taken is non to state that mercy killing or assisted self-destruction should be level out legal, but instead that it should be accepted by the populace in regard of those who suffer more than they can manage and wish to set it to an terminal. In order to pull off these instances efficaciously there should be restrictions to the types of instances that receive this signifier of intervention. Much like the guidelines put together by the Royal Dutch Medical Association in 1984, the patient? s status should be one of? intolerable agony that can non be relieved, and the patient must freely bespeak to decease. When a patient does inquire, the physician should non continue without confer withing another independent doctor. Then each instance must be reported as an? unnatural decease? to local functionaries? ( Eads, 95 ) . In add-on to these guidelines I propose the patient should besides hold to supply cogent evidence beyond a sensible uncertainty that he or she would hold made this determination in a stable psychological province. I besides feel the patient and immediate household should see a psychologist on at least two separate occasions before the mercy killing takes topographic point to guarantee that the purposes are within acceptable bounds. Finally, physicians who violate these guidelines before supplying their services should hold to confront anything up to first-degree slaying charges. When I foremost chose to look into this subject I was merely concerned that Americans should be given the right to decease if it is their wish to make so. After all of my research and analyzing of resources I have been enlightened that this truly isn? t merely about rights. This issue is truly about the strength of people? s spiritual will to populate. I have seen narratives of people paralyzed from the cervix down, had both of their legs amputated, but have still been satisfied with their quality of life. On the other manus, there are people that could hold been in a comatose province for less than a twenty-four hours and wake up somewhat encephalon damaged but non hold the will to try a recovery. Neither mentality on mercy killing should needfully hold a publically moral significance inferior to the other to anyone on the outside universe, but merely to the patient. Most significantly, irrespective of the concluding determination, the patient should hold the option to do that critical determination and their overall mentality on the quality of life will do the difference between a pick for life or decease. Without this option, the members our ain households may endure someday more than anyone would of all time desire to see them hold to. Branegan, Jay. ? I want to pull the line myself. ? Time. 17 March 1997: 30-31. Choice in deceasing. Partnership for Caring Inc. 12 May 1997. Eads, Brian. ? A licence to kill. ? Reader? s Digest. Sep. 1997: 93-97. Euthanasia.com. 19 January 2000. Not Dead Yet. Ed. Stephen Drake. 12 May 1997. ? The right to take to die. ? The Economist. 21 June 1997: 15-16. Rosenblatt, Stanley M. Murder of Mercy: mercy killing on test. New York: Prometheus Books, 1992. Tada, Joni Eareckson. When is it right to decease? Michigan: Zondervan Publishing House, 1992. Plants Consulted ? Death by Doctor. ? By Mike Wallace. 60 Minutes. CBS. 22 November 1998. MacDonald, William L. ? Situational factors and attitudes toward voluntary euthanasia. ? Social Science A ; Medicine. Jan. 1998: 73-81. ? Mercy or Homicide? ? By John Donovan and Forrest Sawyer. ABC Nightline. ABC. 23 November 1998 Rollin, Betty. ? Last Rights. ? Ms.. Aug./Sep. 1999: 31. Will, George F. ? Life and Death at Princeton. ? Newsweek. 13 September 1999: 80-82.

Free Essays on What Is Humes Problem Of Induction

What is Hume’s problem of induction? How successful is his sceptical solution to the problem? David Hume was born in 1711 and studied at Edinburgh University, his influences were great natural scientists like Isaac Newton and Rene Descartes. Hume first wrote â€Å" a treatise of Human nature â€Å" which as Hume put it â€Å"fell stillborn from the press† it was â€Å"An enquiry concerning human understanding† (from here this will be referred to as â€Å"the enquiry†) in which Hume put forward, in the form we are concerned with, the problem of induction and his own response to that problem. Although as we shall see his own response may be far from adequate. This essay is concerned with explaining Hume’s problem of induction as put forward in the enquiry, and explaining his sceptical solution to this problem. The essay is also concerned with assessing how successful his solution is. Arguably Hume’s most famous contribution to philosophy was the problem of induction. The problem of induction arises from Hume’s belief that propositions fall into one of two categories, relations of ideas and matters of fact. It is in the latter of these two categories, matters of fact that the problem of induction occurs. It was Hume’s view that matters of fact are statements about the world, justification for their validity comes from experience. This is fine for the present or past but it is the future that throws up the problem of induction. How can we justify expectations of the future? Or to put it another way how can we justify the belief that we know what will occur in unobserved events. If we use the same method as for the present and the past i.e. experience then we are assuming that nature will stay the same. But as Hume points out it is conceivable that nature will change in some way, therefore in Hume’s philosophy it is possible that nature will change, therefore you cannot justify beliefs about the future using past experien... Free Essays on What Is Hume's Problem Of Induction Free Essays on What Is Hume's Problem Of Induction What is Hume’s problem of induction? How successful is his sceptical solution to the problem? David Hume was born in 1711 and studied at Edinburgh University, his influences were great natural scientists like Isaac Newton and Rene Descartes. Hume first wrote â€Å" a treatise of Human nature â€Å" which as Hume put it â€Å"fell stillborn from the press† it was â€Å"An enquiry concerning human understanding† (from here this will be referred to as â€Å"the enquiry†) in which Hume put forward, in the form we are concerned with, the problem of induction and his own response to that problem. Although as we shall see his own response may be far from adequate. This essay is concerned with explaining Hume’s problem of induction as put forward in the enquiry, and explaining his sceptical solution to this problem. The essay is also concerned with assessing how successful his solution is. Arguably Hume’s most famous contribution to philosophy was the problem of induction. The problem of induction arises from Hume’s belief that propositions fall into one of two categories, relations of ideas and matters of fact. It is in the latter of these two categories, matters of fact that the problem of induction occurs. It was Hume’s view that matters of fact are statements about the world, justification for their validity comes from experience. This is fine for the present or past but it is the future that throws up the problem of induction. How can we justify expectations of the future? Or to put it another way how can we justify the belief that we know what will occur in unobserved events. If we use the same method as for the present and the past i.e. experience then we are assuming that nature will stay the same. But as Hume points out it is conceivable that nature will change in some way, therefore in Hume’s philosophy it is possible that nature will change, therefore you cannot justify beliefs about the future using past experien...

Naturalism Research Paper Example | Topics and Well Written Essays - 1000 words

Naturalism - Research Paper Example In trying to understand nature and seek explanations of natural processes, naturalists use science as their main resource. Some people believe that science and religion are very different and irreconcilable as science is based on rationality as opposed to faith which is irrationality. Other people believe that naturalism is the home of reconciliation between science and religion with yet some irreconcilable discrepancies showing conflict between naturalism and science. Evolution is the scientific explanation of the origin of life in nature that was proposed by Charles Darwin and it remains one of the most contentious and hotly debated issues in religious naturalism. This paper will explore naturalism in religion with a bias in evolution as put across by science and scientific theory of evolution and natural selection. First, the paper will have a brief description of naturalism and then have a look at evolution and the controversies surrounding the evolutionary theory. Naturalists ca n be described as pragmats who have their basis of reality in empirical logic and do not consider testimony as a source of truth of reality (Anderson 111). All the conscious differentiations of reality are based on the way that human beings identify the various qualities of world experience and how they think and reason about them. The natural world is the centre of the most significant experience and understanding of nature and thus it is the most valuable thing in the assessment of an individual’s well being. The idea of a supreme being is considered to have no grounds and everything is approached from a rational point of view and the harmony of reason and our understanding of the universe as informed by science (Griffin 56). Naturalism is presumably not a religion as such as it stands but it plays a vital role just like a religion does which is that of giving adherent to a world view. It provides explanations of why thing happen the way they happen, it tells us what fundam entally the world is and what is important in the world and the essence of human life and general life in the world. This is to a great extent what other religions do except for a few differences which might arise from worship and rituals which are not necessarily part of naturalism. There have been concerns whether theology is compatible with naturalism which has often elicited different responses and controversies. Theology and naturalism are compatible but not all forms of naturalism are compatible with theology as it is both the science about God and also the science about the human experience of God’s manifestation in individual life, the society or nature (Francis, Robbins & Astley 95). With science being the underpinnings of naturalism as it provides the explanations for the fundamental structure of the universe, one may think that the theory of evolution is one of the major pillars in naturalism. The theory of evolution which was put forward by Charles Darwin stipulat es that all life in the universe is related and share a common ancestry. It further says that life originated from non life with more complex organisms forming out of more simple organisms and that human beings have an animal descent (Smith 3). The theory puts it that more complex organism evolve from simple organisms over a long period of time and that there are mutations that occur on the genetic makeup of organisms that may favour their survival in a process called natural selection (Smith 4). This

Industry Report OR Design of a Performance Essay - 1

Industry Report OR Design of a Performance - Essay Example The improvement is not restricted to any individual employee; a performance management process locates the performance of whole team and ensures versatile improvement. Performance management can reveal the current position and skills of employees and areas where employees need to be developed. The research paper will describe and analyze the performance management system and good business practices of one healthcare organization in UAE, named RAK Hospital. In hospital industry the performance of employees are vital for company’s success. It can ensure good customer satisfaction and create a good image of company. This paper will describe the good business practices of RAK Hospital which is one the reasons for its success. Further, it will recommend the possible solutions which can improve the performance management system in RAK Hospital. ... Office of Personnel Management, n.d.) Performance management is defined as a continuing procedure of communication that is commenced by an employee and his immediate boss. Through performance management an employee can recognize the essential task that the company expects from him and how the task of the employee can contribute to the mission and objectives of the company. Performance management can ensure to improve the performance of employees in case any employee is performing below the desired level of efficiency or replicating similar mistakes (Bacal, 1999). To mange the performance efficiently it requires an understanding of the framework in which the performance management procedure occurs. The performance management procedure must be initiated along with keeping in mind the strategic goals and core values of the company. It is important for any company to select the right employee into the system (Cardy & Et. Al., 2011). The performance management process includes planning, m onitoring, developing, rating and rewarding. Source: (U.S. Office of Personnel Management, n.d.). These five components can make a successful performance management. RAK Hospital RAK is one of the superior hospitals of the Middle East nation UAE. The hospital was established by the joint venture between government of ‘Ras Al Khaimah’ and ‘ETA Star Healthcare’ in Dubai city. ETA Star Healthcare has a medical library in Dubai city and it is active in the business of medicinal, diagnostic and imaging tools. The RAK hospital is sponsored by Arabian Healthcare. The design of the hospital is developed by Eller Becket which is one of the top engineering, interior design and manufacture companies of the US. This hospital provides variety of premium rooms with a capacity of 65 beds,

Production and Cost Relationships Essay Example | Topics and Well Written Essays - 1500 words

Production and Cost Relationships - Essay Example Profit is measured as the difference between the revenue generated deducted with the costs incurred. Thus, in order to maximize profits, the company could either ensure that it is generating the highest revenue possible by increasing price and quantity demanded or minimize the costs that it incurs (Pindyck and Rubinfeld 2005). This paper will focus on the latter. The following chapters will look at the relationship of average cost, marginal cost, and marginal product in the aim of helping a business organization attain its goal of profit maximization. In the course of its operation, a business organization incurs various costs in order to ensure that products are designed, manufactured, and distributed to customers (Cepeda 2005). In order to understand average total cost, it is best to have a comprehension of what comprises the total cost that a business organization faces. In general, the company is faced with two different costs which make up its total cost namely fixed cost and variable cost (Brue and McConnell 2005). Fixed cost, as the name implies is fixed and does not vary with the level of production. An example of fixed cost is the payment for rent of production plant or retailing store. On the other hand, variable costs are those costs which changes when the quantity of production is changed (Cepeda 2005). Examples of these are the cost of materials and labor which are needed in the production of one unit of a product. The sum of the total fixed cost and the total variable cost is the total cost. Dividing the total cost with the number of quantity produced by the business organization will yield the average total cost (Brue and McConnell 2005). Table 1. Numerical Example for Average Total Cost Quantity Total Fixed Cost Total Variable Cost Total Cost Average Total Cost 50 $600 $1250 $1850 $37 100 $600 $2500 $3100 $31 150 $600 $3750 $4350 $29 200 $600 $5000 $5600 $28 250 $600 $6250 $6850 $27.4 300 $600 $7500 $8100 $27 In order to illustrate fixed cost, it is best to come up with a numerical example. Suppose that a company manufactures figurines and incurs fixed cost as follows in a month: $200 for building rent; $300 for administrative expense; and $100 for utilities. On the hand, it incurs the following variable cost per unit: $10 direct material and $15 direct labor. The company's production capacity is 300 units per month. Table 1 shows the company's variable cost and fixed cost at each level of quantity produced. On the other hand, Figure 1 shows the short run average total cost curve. It should be noted that as the quantity produced is increased, ATC declines because of economies of scale, managerial specialization, and use of more efficient labor. Figure 1. ATC Curve in the Short-run However, in the long run, ATC curve will begin to inflect because of the diseconomies of scale as production expands further (Pindyck and Rubinfeld 2005). Thus, the long run ATC curve will tend to slope downward at first and begin to

Analysis of SAMe as an Antidepressant

Analysis of SAMe as an Antidepressant S-Adenosyl-Methionine (SAMe) And Improved Methylation Offer A Serious Alternative To Orthodox Medications Can S-Adenosyl-Methionine (SAMe) and improved methylation offer a serious alternative to orthodox medications in the treatment of depression? Abstract In this dissertation we consider the issues surrounding the use of SAMe as an antidepressant. There are many different aspects to this consideration. We start by a consideration of exactly what depression is on a clinical basis and examine the psychological and physiological changes that characterise the condition. We then consider and examine the evolution of the current forms of antidepressant medication. We explore the fields of neurochemistry and pathophysiology of depressive states with particular emphasis on the chemistry of the methylation reaction and its relevance to the SAMe compound. Consideration is then given to SAMe specifically as a medication and the evidence that there is to support its apparent beneficial effect in depression. This is then expanded with a review of the chemistry of SAMe and its interactions with other biologically active entities. We conclude the exploration with a critical review of the published literature that is relevant to the role of SAMe as an antidepressant agent. Introduction In order to investigate the full extent of the question at the heart of this dissertation we must examine a number of background issues in some detail first. Depression is a complex clinical state. It has been said that there are as many theories about the aetiology and treatments for depression as there are clinicians thinking about the problem. (LeDoux, J. 1996). A brief examination of the literature on the subject tells us that this comment, although clearly intended to be flippant, may not actually be so very far from the truth. Perhaps it is because of the plethora of hypotheses, ideas and theories on the issue that there are also a considerable number of forms of treatment that are commonly employed. It has to be admitted that some are rational and some appear to be completely irrational. In this dissertation we shall examine some of the more rational forms of psychopharmacology in order to understand the place of SAMe in the therapeutic pharmacopoeia. Depression is a commonly occurring illness. It will significantly affect between 10-25% of women and approximately half that number of men during their lifetimes. Approximately 5 million people in the UK will experience significant depression in any given year. (Breggin 1994) If you suffer from an acute or chronic illness you are even more likely to suffer from depressive states with frequencies ranging from 30-50% depending upon the nature and severity of the illness. (Robertson et al 1997) What is depression ? There are many definitions of clinical depression and indeed many different rating scales which purport to try to quantify it. It is important to distinguish between clinical depression and simply feeling down or miserable. Depressive illness typically occurs in episodes although in some cases it can actually last for many months or even years. (Skolnick, P. 1999). One severe depressive episode is a major independent risk factor for getting further episodes. In other words, having had depression once you are statistically considerably more likely to have another attack. (Post RM. 1992). For our purposes we shall consider a practical overview of the nine classic symptoms that characterise classical depression 1. Depressed mood for most of the day 2. Disturbed appetite or change in weight 3. Disturbed sleep 4. Psychomotor retardation or agitation 5. Loss of interest in previously pleasurable activities; inability to enjoy usual hobbies or activities 6. Fatigue or loss of energy 7. Feelings of worthlessness; excessive and/or inappropriate guilt 8. Difficulty in concentrating or thinking clearly 9. Morbid or suicidal thoughts or actions. (After Zuess 2003) The Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) states that in order to merit a diagnosis of clinical depression you need to demonstrate at least five of these symptoms and that they represent a change in your life. Mood alterations are commonplace in depressive states. The depressed patient will classically feel despair or sadness. Pleasure becomes an alien emotion as they tend to progressively loose interest in activities that they would have previously enjoyed. Mood swings can also occur although they are more commonly found in bipolar states (manic depression). Subjective feelings of tension or irritability are often described as well as just sadness. (Duman et al 1997) In addition to mood changes, depression can also produce changes in the emotional state as well. Feelings of worthlessness and guilt are perhaps the commonest emotions in the clinical spectrum. This is closely followed by both ineptitude and lack of confidence in ones own abilities or capabilities. It is common for depressed people to take action that avoids them having to take responsibility because of an overwhelming fear of failure. (Altar CA 1999) Somatic manifestations of depression are perhaps easier to quantify as they have a qualitative characteristic about them as opposed to the purely subjective. Changes in appetite are commonly found. Generally it is an anorexic change with a decrease in appetite and a loss of interest in food generally. Less frequently, the converse is observed with a voracious increase in appetite (comfort eating) which is normally associated with weight gain. This weight gain can be quite substantial in extreme cases. Sleep disturbances are commonplace. Insomnia and early waking are perhaps the commonest of this type of symptom. This can occur despite severe subjective symptoms of somatic tiredness and fatigue. Some people will find that fatigue is a prominent symptom and may find that this is translated into excessive sleeping and motor retardation generally. Fatigue is actually more difficult to quantify, but it is commonly experienced by the depressed patient. It can either be an overwhelming tiredness (lack of energy) or perhaps lack of stamina (tiring too easily). Associated with this is often a reduction in libido and, if severe, impotence can also occur. It is not unusual to find sexual avoidance behaviours developing in these circumstances. (Janicak et al 1989) Concentration is commonly impaired. Generally speaking the greater the degree of depression, the greater is the degree of concentration impairment. Thinking and reasoning processes slow down and the attention span is often markedly reduced. Students find they can have an inability to study and if severe, patients report an inability to even sit and watch television. (Bazin et al 1994) Somatic symptoms can occur without the psychological elements of the depression being apparent or obvious. This is a common clinical dilemma. Patients may enter a phase of denial or minimisation where they will not accept that they are actually depressed. They can try to rationalise their physical symptomatology into other disease processes. This can be mistaken for hypochondriasis. (De Vanna et al 1992) If depression is severe (or occasionally part of a symptom complex of another underlying pathology), then psychosis can be found. Delusional states are not uncommon in severe depression. Hallucinations can occur, but they are comparatively unusual. Patients can state that they hear voices telling them that they are worthless or perhaps instructing them to kill themselves. Although this is consistent with a depressive diagnosis, one should note that other illnesses such as schizophrenia must clearly be considered and excluded before a confident diagnosis of depression can be made. The actual basis or specific triggering factors for depression are not yet clearly defined but we do know that a number of different biological factors are relevant. Environmental factors, together with both genetic and neurobiological elements are all capable of influencing the overall clinical picture. (Kendler KS, 1998). Depression is broadly divided into endogenous and reactive types. In general terms endogenous depression is thought to be influenced the genetic and neurobiological factors whereas reactive depression may well have environmental factors as being relevant. This has considerable implications in our considerations of the possible actions of SAMe. (Gold et al 1988) Pharmacology of depression This is a vast subject and is generally considered to be a sub-speciality in its own right. It has long been recognised that certain substances appear to be able to exert a mood elevating effect. The advent of modern psychopharmacology allowed us to develop an understanding into just how some of these substances work. The drugs and medicines that are in common use today are the result of a process of evolution that, arguably, began with the uses of herbs at the beginning of recorded history and progressed to the chemically and biologically sophisticated compounds that are in use today. (Peinell and Smith 2003) In order to put the SAMe compounds into their appropriate place in the continuum we need to look at some of the evolutionary developments in the field. Most of the currently used antidepressants work by interfering in some way with the actions of the various neurotransmitters in the brain. Many work by slowing down the biological processes of degradation or destruction of these neurotransmitters. In purely simplistic terms, this results in a greater concentration of the neurotransmitter at the critical synaptic interfaces within the brain. (Levine et al 1998) The first real breakthrough with what could be considered to be a major therapeutic agent for depressive states came with the discovery of the MAOI (Monoamine Oxidse Inhibitors), group of drugs. Three were commonly used in clinical practice isocarboxazid, phemelzine and tranlcypromine. For a while they were used extensively but it became obvious that they had serious drawbacks including some potentially fatal side effects. (Saarelainen et al 2003), Headaches dizziness and tremor were not unusual accompaniments of the drug. They also had the ability to interact with other medications and certain types of food (tyrosine containing foods such as cheese could cause hypertensive crises). Despite these drawbacks, many patients were willing to take them because they indisputably worked. (Skolnick 1999) In time, the MAOis were superseded by the Tricyclic group of drugs. There were four in common use, namely amitriptyline, desipramine, imipramine and nortriptyline. These were generally speaking, marginally more effective than the MAOIs but they were without the worst of the side effects. Despite that, they were still able to cause dry mouth and blurred vision in some people. Constipation and drowsiness were not unusual and they were not commonly used if a person also had hypertension. The pharmaceutical industry then produced a number of different categories of medication in fairly quick succession. SSRIs (Selective Serotonin Reuptake Inhibitors), SNRIs (Serotonin and norepinephrine reuptake inhibitors) and NDRIs (Norepinephrine and dopamine reuptake inhibitors) all emerged into the market place. (Smith et al 2004) It is probably fair to say that they all had their niches in the therapeutic spectrum but the SSRIs were seen to corner the biggest share of the clinical market with citalopram, escitalopram, fluoxetine, paroxetine and sertraline as examples of the group. Fluoxetine was probably the most widely used and its trade name, Prozac was accepted almost as a household word. The side effect profile of this particular group was certainly less significant than their predecessors, but nausea and headaches were not uncommon. (Stewart et al 2000), The SNRIs fell into disuse largely because of their reputation in raising cholesterol levels and the NDRIs were found to cause unacceptable agitation in certain groups. There was then an emergence of a group of drugs which not only blocked the mechanisms that removed the trophic neurotransmitters from the synapse they also had an effect which effectively enhanced their action by blocking the action of the inhibitory neurotransmitters at the same time. There are several types of medication in this category, but perhaps the best known is maprotilene. Like most of the other types of effective medication, it is not without side effects. Drowsiness, nausea, dizziness and a dry mouth are common accompanying symptoms of a therapeutic dose of this medication. (Harmer et al 2003) Neurochemistry and pathophysiology of depression So far we have take a brief and admittedly comparatively simplistic tour of the nature and pharmacology of depression. We shall now look at the neurochemistry and pathophysiology of certain relevant aspects of the subject in more detail. In general terms, stress and antidepressants appear to have reciprocal actions on neuronal growth and to some extent, on their activity (see on). This appears to be through the mediation of various neurotrophins and the action of synaptic plasticity mainly in the region of the hippocampus and some other brain structures (Reid et al 2001). Various stresses appear to disturb and disrupt the activity, both of individual neurones and also larger functional groups, or networks of neurones whereas antidepressants appear to antagonise this disruptive ability. (Henke 1990) There is a large body of opinion which agrees with the hypothesis that regulation of synaptic activity is a major key to the pathophysiology of depression and related disorders. (Drevets et al 1997) The discovery of the MAOI group of drugs (above) led researchers to speculate that the monoamine group of neurotransmitters were central to the aetiology of depression. As more research is done it is becoming apparent that this may not actually be the case. It is now considered more likely that the fundamental problems lie further along the metabolic cascade from the monoamine oxidase activity. It is also considered likely that the pathology may well not be just a chemical imbalance, but may well involve other functions of neural tissue such as various cellular changes in physiology, genetic factors and the ability of neuronal network to change their characteristics. (Czyrak et al 1992) Observational studies have suggested that early life experiences, the impact of stress and the presence or absence of social support or interactions all have an influence on the development of a depressive state. (Gould et al 1998).Consideration of the monoamine chemistry clearly does not account for all of these factors although it is clearly acknowledged that it does play an important contributory role. Some recent work relating to the chronic use of different classes of antidepressants (Duman et al 1997), has appeared to show that they all are able to increase the production of the neuroprotective groups of proteins which, amongst other actions, play a central role in the plasticity of neurones. Current thinking is that this may well be a common function of a number of different pathways that the different antidepressants exploit. It is known that increases in monoamine levels in the synaptic region result (by a number of different mechanisms) and are associated with the induction of enzyme systems that control gene expression within the neurone. This can be inferred from the finding of increases in the levels of messenger RNA which codes for the cAMP response element binding protein (CREB). These levels slowly increase with chronicity of administration of antidepressants and this mechanism may well account therefore for the commonly observed slow and progressive onset of action of most of the antidepressant drugs. It is proposed that CREB triggers the production of BDNF (Brain Derived Neurotrophic Factor). This is significant since other work has shown that stress antagonises the levels of BDNF which is opposed by the actions of the antidepressant drugs. (Smith et al 1995). Further credence is given to this theory with the discovery that placing BDNF directly into the brain of experimental animals appeared to relieve many of the behaviour patterns that are associated with depression (Siuciak et al 1997) Some authors have suggested that depression may represent a particularly subtle form of neural degenerative disorder as it has been shown that the hippocampus becomes progressively atrophic in chronic depressive states. This is particularly significant as BDNF is thought to reverse such findings. (Shah et al 1998). There is associated supporting evidence in the form of a study by Vaidya (et al 1999) which shows that ECT treatment (which was always assumed to be detrimental to the neural structure and physiology) is associated with both increased levels of BDNF and trophic changes in the hippocampal neurones. A paper by Czyrak (et al 1992) looked at the antidepressant activity of SAMe in mice and rats in a way that clearly is not possible in humans. It is not always possible to directly extrapolate findings from animals to humans, but there are some pieces of evidence in this work which strongly implicate SAMe in the pathogenesis of depression. The paper itself is extremely long and complex but the relevant parts to our considerations here are the fact that normal geographical exploratory behaviour in rodents tends to diminish if a depressive state is induced. To some extent, exploratory behaviour is therefore considered a marker for the depressive state. It was found that SAMe tended to increase exploratory activity in mice. This, and other more sophisticated testing of the pharmacological interactions of SAMe showed that it tended to have the same psychopharmacological profile as many of the mainstream antidepressants. Many of the neurotransmitters and for that matter some neuroactive hormones have been variously implicated in the aetiology of depression (eg thyroid hormones and noradrenaline). (Nemeroff, 1998). Modern research has most consistently found that alterations in the levels of serotonin (5-HT) (Melzter H, 1989), system and the chemicals of the Limbic Hypothalamic-Pituitary-Adrenal (LHPA) axis. (Kathol et al 1989), as the most consistently implicated mechanisms that appear to be associated with the control of the mood stabilising and regulating mechanisms. It is in fact very likely that both these mechanisms are in some way interlinked as part of the regulatory mechanism of mood. We have already referred to the role of stress in the aetiology of depression. We know that the adrenal glucocorticoid hormones subtly interact with the 5-HT system and these are produced in direct response to stress. (Lopez et al 1999) (I). We also know that the glucocorticoids have a number of direct effects on the Limbic Hypothalamic-Pituitary-Adrenal (LHPA) axis. It may be that this is the mechanism by which stress antagonises the changes brought about by SAMe. (Lopez et al 1999) (II) We do not need to consider the effects of the corticoids on the LHPA axis in detail as it is only of peripheral relevance to our considerations here. The important consideration in this regard is that the LHPA axis is intimately connected to the hippocampus. It is this structure that is the intermediate step and connection between the bodys hormonal response to stress and the response of the higher functions of the brain. (Dallman et al 1987). The immediate relevance of all this to the actions of SAMe are that hyperactivity of both the hippocampus and the LHPA axis are both well documented in cases of clinical depression. This has been shown to also be associated with high levels of corticosteroid production (Kalin et al 1987), but one study has shown that in suicide cases who have had profound depression the hippocampus has fewer corticosteroid receptor sites than one might normally expect (Lopez et al 1998). One further piece of clinical evidence in the role of the corticosteroids in depression is that patients with Cushings disease have a high incidence of depression. This incidence returns to normal when their hormonal over-activity is treated and returned back to physiological levels. (Murphy 1991) SAMe as a medication SAMe was discovered in Italy in 1952 during research into the chemistry of neurotransmitters. It was not, however, introduced in a useable form for patient benefit until 1974 (as SAMe sulphate-paratoluene-sulphonate). It is for this reason that the majority of the early papers and work on the subject are almost exclusively Italian in origin. (De Vanna et al 1992) SAMe has been used clinically in a number of conditions including cholestasis, osteoarthritis and depression. (Carney et al 1987) Although there is a wealth of literature on the first two elements it is not relevant to our considerations here. We shall therefore restrict this discussion to the spectrum of its use in the field of depression. A number of studies have shown that SAMe has useful activity in depressive illness. Studies that have compared it to placebo have found that it can consistently produce about a 6 point increase on the Hamilton rating scale after about three weeks of optimum treatment. This finding is approximately in line with the results that are found with most of the other clinically effective antidepressant medications. (Cooper et al 1999) (De Vanna et al 1992) Some studies have found that using SAMe in a large dose has produced an unusually rapid onset of beneficial effects (Kagan 1990) One could argue that, because it is a naturally occurring substance, it would not be likely to have a high side-effect profile. Although these two statements do not always follow, it is generally true. A study by Bressa (1994) on the issue showed that it did have a particularly low side-effect profile, particularly when compared to the other antidepressants (Tricyclics). To demonstrate this point further, we can point to the study by Caruso (et al 1987) where there were a greater number of patient withdrawals due to the side effects of the placebo than withdrew because of the SAMe drug. For the record, that particular trial was in its use as an antiarthritic rather than an antidepressant, but the point is made. The two major unwanted clinical effects are nausea and hypomania. The nausea is not a local effect on the gut lining but appears to be a centrally mediated effect and is possibly caused by the same phenomenon of over-stimulation of the neuronal networks which causes the other major clinical manifestation of hypomania. For this reason it is generally not used in cases of bipolar disorder. (De Vanna et al 1992) It is probably not strictly accurate to refer to SAMe as a drug as it is normally found in the cellular matrix. It has been found to be effective in patients who have been unable to tolerate other forms of antidepressants or, for that matter, have had minimal response to them. (Reynolds et al, 1984) Young (1993) produced a particularly interesting review of dietary treatments for depression. A lot of his article is not relevant to our considerations here, but he makes a number of interesting and relevant observations. Low serotonin levels are known to be associated with depression even though low levels on their own do not appear to cause the condition. It appears that it needs to be in combination with a low level of folic acid. We know that low levels of folic acid are also often found in combination with depressive illness and that low levels of folate are often associated with low levels of SAMe. The evidence points to the fact that the low levels of serotonin are more likely to be a result of the low SAMe levels in neural tissue and that this is more likely to be nearer to the root of the main anomaly that causes depression. Pregnancy is known to be associated with low levels of folate and post natal depression is a well recognised clinical entity. Salmaggi (et al 1993) considered the effects of SAMe in the postnatal period. This was a well considered and constructed study. It was a double blind placebo controlled trial over a 30 day period and had an entry cohort of 80 women. The degree of depression was assessed before, during and after the trial on the Hamilton Scale. The results showed a statistically significant improvement in the SAMe group when compared to the placebo group. The authors comment that there were no significant side effects of the medication encountered. Because we know that any beneficial effect that SAMe is likely to have on a patient tends to be seen more quickly than with the other antidepressants, and also, by virtue of what we suspect about its probable mode of action in the hippocampus and elsewhere in the brain, it seems a logical step for someone to look into the effects of giving SAMe alongside a conventional antidepressants to see if there is either any synergistic effect or possibly a speeding up of the clinical onset of the secondary medication. The study by Berlanga (et al 1992) did exactly that. Unfortunately the trial was not particularly rigorous in its design as although it was double blind, it was not placebo controlled, which would appear to have been the method of choice in this type of investigation. Its other problem as that it only had an entry cohort of 40 patients. Despite these limitations it was indeed shown that depressed patients who took SAMe in conjunction with other antidepressant medication found that the depressive symptoms resolved faster with the SAMe added to their normal treatment regime. There are one or two other less important papers which we shall only mention in passing. Kagan (et al 1990) ran a small trial on 15 inpatients (with very severe depression) and found SAMe to be a safe, effective antidepressant with few side effects and a rapid onset of action. This particular trial is notable as it was the first to report the side effect of mania in a patient who didnt have a previous history. Another is the trial by Rosenbaum (et al 1990). This particular trial is notable for the demonstration of the fact that about 20% of other treatment resistant patients experienced benefit with SAMe. Faya (et al 1990) (II) considered the fact that SAMe is thought to exert its effect through its action in increasing dopamine levels in the synaptic cleft. It is known that dopamine inhibits the production of both Thyroid stimulating hormone (TSH) and Prolactin from the pituitary gland. Faya considered measuring the levels of both TSH and Prolactin during treatment with SAMe. His findings constituted something of a surprise insofar as in the men in the trial group had their levels of TSH and Prolactin reduced which is consistent with the hypothesis that SAMe increases the dopamine levels in the brain. Much to everybodys surprise, this effect was not seen in the female group. The authors do not offer any explanation of this fact. For the record, there is another trial (Thomas et al 1987), which obviously considered the same phenomenon and their trial did not show any sex linked difference in the suppression of the Prolactin levels With regards to efficacy, a trial by Carney (et al 1986) suggests that the beneficial action of SAMe is restricted to endogenous depression and it does not appear to have any action above placebo on reactive depression. As far as we can ascertain, this is the only trial published that has made this suggestion, although from a first principles basis, one can see the biochemical rationale for believing that it might well be the case. On a purely empirical grounds, some authors have recommended (on the basis of scant hard evidence), that SAMes action can be maximised by the addition of B12, B6 and folic acid. It is known that SAMe is required to convert these agents into their active form as a coenzyme. (Morrison et al, 1996). The same author also recommends the simultaneous adminstration of Trimethylglycine (TMG) which is necessary for the intracellular conversion of methionine into SAMe by the provision of the necessary methyl- groups. Comment has to be made that again, this appears to be a completely empirical (and logical) suggestion, but we cannot find any hard evidence to substantiate its clinical use. Chemistry SAMe is a basic component of cellular biochemistry. It occurs in every living cell and is second in importance only to ATP in both the number variety and significance of the reactions in which it serves as a cofactor. (Stramentinoli 1987). It is central in the chemistry of the transmethylation reactions. In essence its cellular function is to transfer the active methyl group form carrier molecules to a multitude of other molecules. In general terms, this methylation makes inert molecules biologically active. In addition to the transmethylation reactions it also plays a central role in transsulfuration and aminopropylation reactions It is involved in the synthesis of proteins including the nucleic acids, fatty acids, lipids and phospholipids, porphyrins and polysaccharides. In terms of our considerations here, perhaps the most significant reaction type that SAMe is involved in is the generation of the neurotransmitter amines. In this regard it is considered to be the most biologically significant provider of methyl groups within the cell. (Baldessarini 1987). Significantly it is also involved in the pathways to produce a number of other neurologically active compounds such as adrenaline, the neuronutrients acetyl l-carnitine and phosphatidyl choline (Mathews et al 1990) It is also to be found in the metabolic pathways of both serotonin and dopamine. Oral administration has been shown to increase the metabolites of these compounds in the CSF (implying increased turnover). It is thought to exert its antidepressive effect partly through the mechanism of increasing the levels of both dopamine and serotonin as neurotransmitters, but it also appears to have some form of trophic action on some of the neurones in the brain cortex. (Baldessarini 1987) It has been demonstrated that the tissue levels of SAMe tend to diminish with age and blood levels are also found to be low in some cases of clinical depression (Baldessarini 1987) A methyl group (CH3) is a group of three hydrogen atoms bound to one carbon atom. It does not exist in a stable isolated form and is transported between molecules by intermediaries such as SAMe. Methylation is the process by which this group is transferred from the methyl donor molecule to the recipient molecule. In general terms this process is central to the control of many of the intracellular pathways. Giving a methyl group to an enzyme is often the key to activating it, and thereby beginning a synthesis or degradation process elsewhere in the cell. Equally removing the methyl group will render the enzyme inactive and stop that particular pathway. Similar mechanisms are involved in the expression of genes and therefore the production of proteins within the cell. Some specific methylation reactions include the methylation of phenols which detoxify them and thereby aid in their excretion. (Stramentinoli 1987) In the context of this dissertation, methylation is also central to the metabolic chemistry of serotonin (and therefore also melatonin). The activity of both these compounds is effectively regulated by the presence of a methyl group. SAMe is synthesised from methionine, a naturally occurring amino acid. As the name implies (METH-ionine), it contains a methyl group. By utilising the energy supplied by ATP and in the presence of magnesium, it is converted into SAMe. The process is catalysed by the intervention of the enzyme MAT (methionine adenosyl Analysis of SAMe as an Antidepressant Analysis of SAMe as an Antidepressant S-Adenosyl-Methionine (SAMe) And Improved Methylation Offer A Serious Alternative To Orthodox Medications Can S-Adenosyl-Methionine (SAMe) and improved methylation offer a serious alternative to orthodox medications in the treatment of depression? Abstract In this dissertation we consider the issues surrounding the use of SAMe as an antidepressant. There are many different aspects to this consideration. We start by a consideration of exactly what depression is on a clinical basis and examine the psychological and physiological changes that characterise the condition. We then consider and examine the evolution of the current forms of antidepressant medication. We explore the fields of neurochemistry and pathophysiology of depressive states with particular emphasis on the chemistry of the methylation reaction and its relevance to the SAMe compound. Consideration is then given to SAMe specifically as a medication and the evidence that there is to support its apparent beneficial effect in depression. This is then expanded with a review of the chemistry of SAMe and its interactions with other biologically active entities. We conclude the exploration with a critical review of the published literature that is relevant to the role of SAMe as an antidepressant agent. Introduction In order to investigate the full extent of the question at the heart of this dissertation we must examine a number of background issues in some detail first. Depression is a complex clinical state. It has been said that there are as many theories about the aetiology and treatments for depression as there are clinicians thinking about the problem. (LeDoux, J. 1996). A brief examination of the literature on the subject tells us that this comment, although clearly intended to be flippant, may not actually be so very far from the truth. Perhaps it is because of the plethora of hypotheses, ideas and theories on the issue that there are also a considerable number of forms of treatment that are commonly employed. It has to be admitted that some are rational and some appear to be completely irrational. In this dissertation we shall examine some of the more rational forms of psychopharmacology in order to understand the place of SAMe in the therapeutic pharmacopoeia. Depression is a commonly occurring illness. It will significantly affect between 10-25% of women and approximately half that number of men during their lifetimes. Approximately 5 million people in the UK will experience significant depression in any given year. (Breggin 1994) If you suffer from an acute or chronic illness you are even more likely to suffer from depressive states with frequencies ranging from 30-50% depending upon the nature and severity of the illness. (Robertson et al 1997) What is depression ? There are many definitions of clinical depression and indeed many different rating scales which purport to try to quantify it. It is important to distinguish between clinical depression and simply feeling down or miserable. Depressive illness typically occurs in episodes although in some cases it can actually last for many months or even years. (Skolnick, P. 1999). One severe depressive episode is a major independent risk factor for getting further episodes. In other words, having had depression once you are statistically considerably more likely to have another attack. (Post RM. 1992). For our purposes we shall consider a practical overview of the nine classic symptoms that characterise classical depression 1. Depressed mood for most of the day 2. Disturbed appetite or change in weight 3. Disturbed sleep 4. Psychomotor retardation or agitation 5. Loss of interest in previously pleasurable activities; inability to enjoy usual hobbies or activities 6. Fatigue or loss of energy 7. Feelings of worthlessness; excessive and/or inappropriate guilt 8. Difficulty in concentrating or thinking clearly 9. Morbid or suicidal thoughts or actions. (After Zuess 2003) The Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) states that in order to merit a diagnosis of clinical depression you need to demonstrate at least five of these symptoms and that they represent a change in your life. Mood alterations are commonplace in depressive states. The depressed patient will classically feel despair or sadness. Pleasure becomes an alien emotion as they tend to progressively loose interest in activities that they would have previously enjoyed. Mood swings can also occur although they are more commonly found in bipolar states (manic depression). Subjective feelings of tension or irritability are often described as well as just sadness. (Duman et al 1997) In addition to mood changes, depression can also produce changes in the emotional state as well. Feelings of worthlessness and guilt are perhaps the commonest emotions in the clinical spectrum. This is closely followed by both ineptitude and lack of confidence in ones own abilities or capabilities. It is common for depressed people to take action that avoids them having to take responsibility because of an overwhelming fear of failure. (Altar CA 1999) Somatic manifestations of depression are perhaps easier to quantify as they have a qualitative characteristic about them as opposed to the purely subjective. Changes in appetite are commonly found. Generally it is an anorexic change with a decrease in appetite and a loss of interest in food generally. Less frequently, the converse is observed with a voracious increase in appetite (comfort eating) which is normally associated with weight gain. This weight gain can be quite substantial in extreme cases. Sleep disturbances are commonplace. Insomnia and early waking are perhaps the commonest of this type of symptom. This can occur despite severe subjective symptoms of somatic tiredness and fatigue. Some people will find that fatigue is a prominent symptom and may find that this is translated into excessive sleeping and motor retardation generally. Fatigue is actually more difficult to quantify, but it is commonly experienced by the depressed patient. It can either be an overwhelming tiredness (lack of energy) or perhaps lack of stamina (tiring too easily). Associated with this is often a reduction in libido and, if severe, impotence can also occur. It is not unusual to find sexual avoidance behaviours developing in these circumstances. (Janicak et al 1989) Concentration is commonly impaired. Generally speaking the greater the degree of depression, the greater is the degree of concentration impairment. Thinking and reasoning processes slow down and the attention span is often markedly reduced. Students find they can have an inability to study and if severe, patients report an inability to even sit and watch television. (Bazin et al 1994) Somatic symptoms can occur without the psychological elements of the depression being apparent or obvious. This is a common clinical dilemma. Patients may enter a phase of denial or minimisation where they will not accept that they are actually depressed. They can try to rationalise their physical symptomatology into other disease processes. This can be mistaken for hypochondriasis. (De Vanna et al 1992) If depression is severe (or occasionally part of a symptom complex of another underlying pathology), then psychosis can be found. Delusional states are not uncommon in severe depression. Hallucinations can occur, but they are comparatively unusual. Patients can state that they hear voices telling them that they are worthless or perhaps instructing them to kill themselves. Although this is consistent with a depressive diagnosis, one should note that other illnesses such as schizophrenia must clearly be considered and excluded before a confident diagnosis of depression can be made. The actual basis or specific triggering factors for depression are not yet clearly defined but we do know that a number of different biological factors are relevant. Environmental factors, together with both genetic and neurobiological elements are all capable of influencing the overall clinical picture. (Kendler KS, 1998). Depression is broadly divided into endogenous and reactive types. In general terms endogenous depression is thought to be influenced the genetic and neurobiological factors whereas reactive depression may well have environmental factors as being relevant. This has considerable implications in our considerations of the possible actions of SAMe. (Gold et al 1988) Pharmacology of depression This is a vast subject and is generally considered to be a sub-speciality in its own right. It has long been recognised that certain substances appear to be able to exert a mood elevating effect. The advent of modern psychopharmacology allowed us to develop an understanding into just how some of these substances work. The drugs and medicines that are in common use today are the result of a process of evolution that, arguably, began with the uses of herbs at the beginning of recorded history and progressed to the chemically and biologically sophisticated compounds that are in use today. (Peinell and Smith 2003) In order to put the SAMe compounds into their appropriate place in the continuum we need to look at some of the evolutionary developments in the field. Most of the currently used antidepressants work by interfering in some way with the actions of the various neurotransmitters in the brain. Many work by slowing down the biological processes of degradation or destruction of these neurotransmitters. In purely simplistic terms, this results in a greater concentration of the neurotransmitter at the critical synaptic interfaces within the brain. (Levine et al 1998) The first real breakthrough with what could be considered to be a major therapeutic agent for depressive states came with the discovery of the MAOI (Monoamine Oxidse Inhibitors), group of drugs. Three were commonly used in clinical practice isocarboxazid, phemelzine and tranlcypromine. For a while they were used extensively but it became obvious that they had serious drawbacks including some potentially fatal side effects. (Saarelainen et al 2003), Headaches dizziness and tremor were not unusual accompaniments of the drug. They also had the ability to interact with other medications and certain types of food (tyrosine containing foods such as cheese could cause hypertensive crises). Despite these drawbacks, many patients were willing to take them because they indisputably worked. (Skolnick 1999) In time, the MAOis were superseded by the Tricyclic group of drugs. There were four in common use, namely amitriptyline, desipramine, imipramine and nortriptyline. These were generally speaking, marginally more effective than the MAOIs but they were without the worst of the side effects. Despite that, they were still able to cause dry mouth and blurred vision in some people. Constipation and drowsiness were not unusual and they were not commonly used if a person also had hypertension. The pharmaceutical industry then produced a number of different categories of medication in fairly quick succession. SSRIs (Selective Serotonin Reuptake Inhibitors), SNRIs (Serotonin and norepinephrine reuptake inhibitors) and NDRIs (Norepinephrine and dopamine reuptake inhibitors) all emerged into the market place. (Smith et al 2004) It is probably fair to say that they all had their niches in the therapeutic spectrum but the SSRIs were seen to corner the biggest share of the clinical market with citalopram, escitalopram, fluoxetine, paroxetine and sertraline as examples of the group. Fluoxetine was probably the most widely used and its trade name, Prozac was accepted almost as a household word. The side effect profile of this particular group was certainly less significant than their predecessors, but nausea and headaches were not uncommon. (Stewart et al 2000), The SNRIs fell into disuse largely because of their reputation in raising cholesterol levels and the NDRIs were found to cause unacceptable agitation in certain groups. There was then an emergence of a group of drugs which not only blocked the mechanisms that removed the trophic neurotransmitters from the synapse they also had an effect which effectively enhanced their action by blocking the action of the inhibitory neurotransmitters at the same time. There are several types of medication in this category, but perhaps the best known is maprotilene. Like most of the other types of effective medication, it is not without side effects. Drowsiness, nausea, dizziness and a dry mouth are common accompanying symptoms of a therapeutic dose of this medication. (Harmer et al 2003) Neurochemistry and pathophysiology of depression So far we have take a brief and admittedly comparatively simplistic tour of the nature and pharmacology of depression. We shall now look at the neurochemistry and pathophysiology of certain relevant aspects of the subject in more detail. In general terms, stress and antidepressants appear to have reciprocal actions on neuronal growth and to some extent, on their activity (see on). This appears to be through the mediation of various neurotrophins and the action of synaptic plasticity mainly in the region of the hippocampus and some other brain structures (Reid et al 2001). Various stresses appear to disturb and disrupt the activity, both of individual neurones and also larger functional groups, or networks of neurones whereas antidepressants appear to antagonise this disruptive ability. (Henke 1990) There is a large body of opinion which agrees with the hypothesis that regulation of synaptic activity is a major key to the pathophysiology of depression and related disorders. (Drevets et al 1997) The discovery of the MAOI group of drugs (above) led researchers to speculate that the monoamine group of neurotransmitters were central to the aetiology of depression. As more research is done it is becoming apparent that this may not actually be the case. It is now considered more likely that the fundamental problems lie further along the metabolic cascade from the monoamine oxidase activity. It is also considered likely that the pathology may well not be just a chemical imbalance, but may well involve other functions of neural tissue such as various cellular changes in physiology, genetic factors and the ability of neuronal network to change their characteristics. (Czyrak et al 1992) Observational studies have suggested that early life experiences, the impact of stress and the presence or absence of social support or interactions all have an influence on the development of a depressive state. (Gould et al 1998).Consideration of the monoamine chemistry clearly does not account for all of these factors although it is clearly acknowledged that it does play an important contributory role. Some recent work relating to the chronic use of different classes of antidepressants (Duman et al 1997), has appeared to show that they all are able to increase the production of the neuroprotective groups of proteins which, amongst other actions, play a central role in the plasticity of neurones. Current thinking is that this may well be a common function of a number of different pathways that the different antidepressants exploit. It is known that increases in monoamine levels in the synaptic region result (by a number of different mechanisms) and are associated with the induction of enzyme systems that control gene expression within the neurone. This can be inferred from the finding of increases in the levels of messenger RNA which codes for the cAMP response element binding protein (CREB). These levels slowly increase with chronicity of administration of antidepressants and this mechanism may well account therefore for the commonly observed slow and progressive onset of action of most of the antidepressant drugs. It is proposed that CREB triggers the production of BDNF (Brain Derived Neurotrophic Factor). This is significant since other work has shown that stress antagonises the levels of BDNF which is opposed by the actions of the antidepressant drugs. (Smith et al 1995). Further credence is given to this theory with the discovery that placing BDNF directly into the brain of experimental animals appeared to relieve many of the behaviour patterns that are associated with depression (Siuciak et al 1997) Some authors have suggested that depression may represent a particularly subtle form of neural degenerative disorder as it has been shown that the hippocampus becomes progressively atrophic in chronic depressive states. This is particularly significant as BDNF is thought to reverse such findings. (Shah et al 1998). There is associated supporting evidence in the form of a study by Vaidya (et al 1999) which shows that ECT treatment (which was always assumed to be detrimental to the neural structure and physiology) is associated with both increased levels of BDNF and trophic changes in the hippocampal neurones. A paper by Czyrak (et al 1992) looked at the antidepressant activity of SAMe in mice and rats in a way that clearly is not possible in humans. It is not always possible to directly extrapolate findings from animals to humans, but there are some pieces of evidence in this work which strongly implicate SAMe in the pathogenesis of depression. The paper itself is extremely long and complex but the relevant parts to our considerations here are the fact that normal geographical exploratory behaviour in rodents tends to diminish if a depressive state is induced. To some extent, exploratory behaviour is therefore considered a marker for the depressive state. It was found that SAMe tended to increase exploratory activity in mice. This, and other more sophisticated testing of the pharmacological interactions of SAMe showed that it tended to have the same psychopharmacological profile as many of the mainstream antidepressants. Many of the neurotransmitters and for that matter some neuroactive hormones have been variously implicated in the aetiology of depression (eg thyroid hormones and noradrenaline). (Nemeroff, 1998). Modern research has most consistently found that alterations in the levels of serotonin (5-HT) (Melzter H, 1989), system and the chemicals of the Limbic Hypothalamic-Pituitary-Adrenal (LHPA) axis. (Kathol et al 1989), as the most consistently implicated mechanisms that appear to be associated with the control of the mood stabilising and regulating mechanisms. It is in fact very likely that both these mechanisms are in some way interlinked as part of the regulatory mechanism of mood. We have already referred to the role of stress in the aetiology of depression. We know that the adrenal glucocorticoid hormones subtly interact with the 5-HT system and these are produced in direct response to stress. (Lopez et al 1999) (I). We also know that the glucocorticoids have a number of direct effects on the Limbic Hypothalamic-Pituitary-Adrenal (LHPA) axis. It may be that this is the mechanism by which stress antagonises the changes brought about by SAMe. (Lopez et al 1999) (II) We do not need to consider the effects of the corticoids on the LHPA axis in detail as it is only of peripheral relevance to our considerations here. The important consideration in this regard is that the LHPA axis is intimately connected to the hippocampus. It is this structure that is the intermediate step and connection between the bodys hormonal response to stress and the response of the higher functions of the brain. (Dallman et al 1987). The immediate relevance of all this to the actions of SAMe are that hyperactivity of both the hippocampus and the LHPA axis are both well documented in cases of clinical depression. This has been shown to also be associated with high levels of corticosteroid production (Kalin et al 1987), but one study has shown that in suicide cases who have had profound depression the hippocampus has fewer corticosteroid receptor sites than one might normally expect (Lopez et al 1998). One further piece of clinical evidence in the role of the corticosteroids in depression is that patients with Cushings disease have a high incidence of depression. This incidence returns to normal when their hormonal over-activity is treated and returned back to physiological levels. (Murphy 1991) SAMe as a medication SAMe was discovered in Italy in 1952 during research into the chemistry of neurotransmitters. It was not, however, introduced in a useable form for patient benefit until 1974 (as SAMe sulphate-paratoluene-sulphonate). It is for this reason that the majority of the early papers and work on the subject are almost exclusively Italian in origin. (De Vanna et al 1992) SAMe has been used clinically in a number of conditions including cholestasis, osteoarthritis and depression. (Carney et al 1987) Although there is a wealth of literature on the first two elements it is not relevant to our considerations here. We shall therefore restrict this discussion to the spectrum of its use in the field of depression. A number of studies have shown that SAMe has useful activity in depressive illness. Studies that have compared it to placebo have found that it can consistently produce about a 6 point increase on the Hamilton rating scale after about three weeks of optimum treatment. This finding is approximately in line with the results that are found with most of the other clinically effective antidepressant medications. (Cooper et al 1999) (De Vanna et al 1992) Some studies have found that using SAMe in a large dose has produced an unusually rapid onset of beneficial effects (Kagan 1990) One could argue that, because it is a naturally occurring substance, it would not be likely to have a high side-effect profile. Although these two statements do not always follow, it is generally true. A study by Bressa (1994) on the issue showed that it did have a particularly low side-effect profile, particularly when compared to the other antidepressants (Tricyclics). To demonstrate this point further, we can point to the study by Caruso (et al 1987) where there were a greater number of patient withdrawals due to the side effects of the placebo than withdrew because of the SAMe drug. For the record, that particular trial was in its use as an antiarthritic rather than an antidepressant, but the point is made. The two major unwanted clinical effects are nausea and hypomania. The nausea is not a local effect on the gut lining but appears to be a centrally mediated effect and is possibly caused by the same phenomenon of over-stimulation of the neuronal networks which causes the other major clinical manifestation of hypomania. For this reason it is generally not used in cases of bipolar disorder. (De Vanna et al 1992) It is probably not strictly accurate to refer to SAMe as a drug as it is normally found in the cellular matrix. It has been found to be effective in patients who have been unable to tolerate other forms of antidepressants or, for that matter, have had minimal response to them. (Reynolds et al, 1984) Young (1993) produced a particularly interesting review of dietary treatments for depression. A lot of his article is not relevant to our considerations here, but he makes a number of interesting and relevant observations. Low serotonin levels are known to be associated with depression even though low levels on their own do not appear to cause the condition. It appears that it needs to be in combination with a low level of folic acid. We know that low levels of folic acid are also often found in combination with depressive illness and that low levels of folate are often associated with low levels of SAMe. The evidence points to the fact that the low levels of serotonin are more likely to be a result of the low SAMe levels in neural tissue and that this is more likely to be nearer to the root of the main anomaly that causes depression. Pregnancy is known to be associated with low levels of folate and post natal depression is a well recognised clinical entity. Salmaggi (et al 1993) considered the effects of SAMe in the postnatal period. This was a well considered and constructed study. It was a double blind placebo controlled trial over a 30 day period and had an entry cohort of 80 women. The degree of depression was assessed before, during and after the trial on the Hamilton Scale. The results showed a statistically significant improvement in the SAMe group when compared to the placebo group. The authors comment that there were no significant side effects of the medication encountered. Because we know that any beneficial effect that SAMe is likely to have on a patient tends to be seen more quickly than with the other antidepressants, and also, by virtue of what we suspect about its probable mode of action in the hippocampus and elsewhere in the brain, it seems a logical step for someone to look into the effects of giving SAMe alongside a conventional antidepressants to see if there is either any synergistic effect or possibly a speeding up of the clinical onset of the secondary medication. The study by Berlanga (et al 1992) did exactly that. Unfortunately the trial was not particularly rigorous in its design as although it was double blind, it was not placebo controlled, which would appear to have been the method of choice in this type of investigation. Its other problem as that it only had an entry cohort of 40 patients. Despite these limitations it was indeed shown that depressed patients who took SAMe in conjunction with other antidepressant medication found that the depressive symptoms resolved faster with the SAMe added to their normal treatment regime. There are one or two other less important papers which we shall only mention in passing. Kagan (et al 1990) ran a small trial on 15 inpatients (with very severe depression) and found SAMe to be a safe, effective antidepressant with few side effects and a rapid onset of action. This particular trial is notable as it was the first to report the side effect of mania in a patient who didnt have a previous history. Another is the trial by Rosenbaum (et al 1990). This particular trial is notable for the demonstration of the fact that about 20% of other treatment resistant patients experienced benefit with SAMe. Faya (et al 1990) (II) considered the fact that SAMe is thought to exert its effect through its action in increasing dopamine levels in the synaptic cleft. It is known that dopamine inhibits the production of both Thyroid stimulating hormone (TSH) and Prolactin from the pituitary gland. Faya considered measuring the levels of both TSH and Prolactin during treatment with SAMe. His findings constituted something of a surprise insofar as in the men in the trial group had their levels of TSH and Prolactin reduced which is consistent with the hypothesis that SAMe increases the dopamine levels in the brain. Much to everybodys surprise, this effect was not seen in the female group. The authors do not offer any explanation of this fact. For the record, there is another trial (Thomas et al 1987), which obviously considered the same phenomenon and their trial did not show any sex linked difference in the suppression of the Prolactin levels With regards to efficacy, a trial by Carney (et al 1986) suggests that the beneficial action of SAMe is restricted to endogenous depression and it does not appear to have any action above placebo on reactive depression. As far as we can ascertain, this is the only trial published that has made this suggestion, although from a first principles basis, one can see the biochemical rationale for believing that it might well be the case. On a purely empirical grounds, some authors have recommended (on the basis of scant hard evidence), that SAMes action can be maximised by the addition of B12, B6 and folic acid. It is known that SAMe is required to convert these agents into their active form as a coenzyme. (Morrison et al, 1996). The same author also recommends the simultaneous adminstration of Trimethylglycine (TMG) which is necessary for the intracellular conversion of methionine into SAMe by the provision of the necessary methyl- groups. Comment has to be made that again, this appears to be a completely empirical (and logical) suggestion, but we cannot find any hard evidence to substantiate its clinical use. Chemistry SAMe is a basic component of cellular biochemistry. It occurs in every living cell and is second in importance only to ATP in both the number variety and significance of the reactions in which it serves as a cofactor. (Stramentinoli 1987). It is central in the chemistry of the transmethylation reactions. In essence its cellular function is to transfer the active methyl group form carrier molecules to a multitude of other molecules. In general terms, this methylation makes inert molecules biologically active. In addition to the transmethylation reactions it also plays a central role in transsulfuration and aminopropylation reactions It is involved in the synthesis of proteins including the nucleic acids, fatty acids, lipids and phospholipids, porphyrins and polysaccharides. In terms of our considerations here, perhaps the most significant reaction type that SAMe is involved in is the generation of the neurotransmitter amines. In this regard it is considered to be the most biologically significant provider of methyl groups within the cell. (Baldessarini 1987). Significantly it is also involved in the pathways to produce a number of other neurologically active compounds such as adrenaline, the neuronutrients acetyl l-carnitine and phosphatidyl choline (Mathews et al 1990) It is also to be found in the metabolic pathways of both serotonin and dopamine. Oral administration has been shown to increase the metabolites of these compounds in the CSF (implying increased turnover). It is thought to exert its antidepressive effect partly through the mechanism of increasing the levels of both dopamine and serotonin as neurotransmitters, but it also appears to have some form of trophic action on some of the neurones in the brain cortex. (Baldessarini 1987) It has been demonstrated that the tissue levels of SAMe tend to diminish with age and blood levels are also found to be low in some cases of clinical depression (Baldessarini 1987) A methyl group (CH3) is a group of three hydrogen atoms bound to one carbon atom. It does not exist in a stable isolated form and is transported between molecules by intermediaries such as SAMe. Methylation is the process by which this group is transferred from the methyl donor molecule to the recipient molecule. In general terms this process is central to the control of many of the intracellular pathways. Giving a methyl group to an enzyme is often the key to activating it, and thereby beginning a synthesis or degradation process elsewhere in the cell. Equally removing the methyl group will render the enzyme inactive and stop that particular pathway. Similar mechanisms are involved in the expression of genes and therefore the production of proteins within the cell. Some specific methylation reactions include the methylation of phenols which detoxify them and thereby aid in their excretion. (Stramentinoli 1987) In the context of this dissertation, methylation is also central to the metabolic chemistry of serotonin (and therefore also melatonin). The activity of both these compounds is effectively regulated by the presence of a methyl group. SAMe is synthesised from methionine, a naturally occurring amino acid. As the name implies (METH-ionine), it contains a methyl group. By utilising the energy supplied by ATP and in the presence of magnesium, it is converted into SAMe. The process is catalysed by the intervention of the enzyme MAT (methionine adenosyl