Charles Dickens Essay

Great Expectations, written by Charles Dickens, is one of the most popular classics of our time. Dickens novel was, some may say the work of a genius. The tale is of a boy who starts from humble beginnings and whom the story follows through to young adulthood each entering a new experience for the boy. Charles Dickens wrote the novel in 1860-61. He was born into a respected middle class family, in Charlton. He incorporated local features and happenings into his books when he could. His father went into debt and then prison after his finances collapsed. The rest of the family had to go to, so Charles spent time in prison. This is where Charles Dickens got some of his inspiration for his book. He eventually died at the age of fifty-eight from a stroke and was buried in his local churchyard. Chapter eight is an essential part of the book because it conveys a clear image of the characters personality and is a key part for the rest of the story. I will look in Chapter 8, where Pip goes to see Miss Havishams house for the first time, for a number of different techniques and devices which the writer uses to make us feel sympathy for Pip. Charles Dickens starts making the reader feel sorry for Pip when he and Mr Pumblechoke arrive at the gates, and Estella greets them. They completely over look Pip. This shows that Pip is unessential and insignificant. â€Å"This†, said Mrs Pumblechoke, â€Å"is Pip† â€Å"This is Pip, is it? † returned the young lady â€Å"come in† â€Å"Oh she says, â€Å"you wish to see Miss Havisham? † â€Å"If Miss Havisham wishes to se me. † Returned Mr Pumblechoke. As you can see, from this initial conversation, Pip does not have the opportunity to introduce himself. This shows that he is considered to be insignificant, even though it was he who Miss Havisham had sent to see. This makes the reader feel condolence for Pip because it is as if people don’t care about him. After the initial conversation, when Pip was marched inside with Estella, Estella starts to patronise Pip, which makes us feel sorry for him. â€Å"But don’t loiter, boy† Though she called me â€Å"boy† so often, and with a carelessness that was far from complimentary, she was about my own age. She seemed much older than, of course, being a girl, and a beautiful and self-possessed; and she was as scornful of me as if she had been one and twenty, and a queen† This paragraph shows us that Pip is already feeling downhearted about Estella constantly making him feel bad. Even though Estella was about the same age as Pip, she considers herself to be wiser, more mature and generally above Pips level. This is showed in the film by Estella being taller than Pip and looking down on him making her think herself bigger than him. This makes the reader feel sympathetic towards Pip because it is his first visit to Miss Havishams. He is evidently nervous and anxious, and having someone of his own age being scornful towards him, his self-confidence just breaks. The third time in chapter eight that the reader is made to feel sorry for Pip is when Pip was left in the hallway on his own with no light. â€Å"Scornfully walked away, and – what was worse – took the candle with her. This was very uncomfortable and I was half afraid† This makes the reader feel sympathetic for Pip because he is portrayed as being vulnerable. Estella leads Pip into the house and to a door, and was proclaimed by Estella to go in. Pip declines and returns with â€Å"after you miss†. Estella telling him not to be so stupid and scornfully walks off with the light. You would think that now Estella had gone, his situation would have improved but this is not the case. He is about to embark on his first meeting with Miss Havisham, making him hesitant and nervous. His confidence is not helped by standing outside the door in darkness, with no candle. Pip is now viewed as being vulnerable. Soon after Pip swallows his pride and opens the withered and wrecked door handle. â€Å"No glimpse of daylight was to be seen in it. It was a dressing room, as I supposed from the furniture, though much of it was of forms and uses quite unknown of to me† Pip enters through the door and is met by a milky white room. Although well lit by candle. There is antiqued furniture, all of which added to the mood, as if nobody had lived there for quite some time. The clocks had also stopped at twenty minutes to nine. The reader then feels sympathetic towards Pip because of his already nervous state being placed in an eerie, scary atmosphere, which seems unnatural to the poor boy. The reader once again feels sorry for Pip when he is ordered to play cards with Estella, for Miss Havishams viewing. Estella once again starts to be obnoxious towards Pip.

Psychology as a Science Essay

According to Russell & Jarvis(2003: 469) â€Å"the word ‘science’ comes from the Latin word ‘scire’, meaning ‘to know'†; thus it is the knowledge of specific study. Psychology was defined by Atkinson et al. (2000: 3, cited by Mestre. et al. 2002: 811) as the â€Å"scientific study of behaviour and mental processes†. Psychology has been universally recognised as a science since the late 1800’s when James (1890, cited by Gross 1999: 3) stated that ‘Psychology is the Science of Mental Life†. Though many praise the study of psychology for it’s findings and achievements there will always be those who are sceptical of these findings and whether or not they can be seen as ‘solid’. Wilhelm Wundt (1832-1920) is widely seen as the ‘founding father’ of ‘new psychology’, in which we mean psychology as a separate scientific discipline, rather than it had been previously; a part of philosophy. Wundt created ‘structuralism’, this is the study of the mind by breaking all chains of thought down in to such things as images, feelings and sensations, for example, if one were to think of chocolate, one may picture the bar, have a feeling of desire for the bar which may produce the sensation of hunger. By studying the conscious mind using introspection he would record the results of his studies, these would be performed under controlled conditions, by which we mean no outside interferences or influences. However, his methods were heavily criticised as it only studied conscious processes, he was also very select in whom he selected for these tests, children and the mentally disturbed for example, were not considered for his studies as he believed they could not use introspection to a successful degree. Thus, introspection cannot be considered a scientific study as it does not aim to discover the mental processes for all humans; it does not allow for generalisation as not all possible subjects have been tested. There are many arguments for and against psychology as a science, let us focus on the arguments for psychology first. Classical and operant conditioning are still widely used on various different subjects, classical (or ‘Pavlovian’) conditioning is the method of teaching a response when a conditional stimulus is in place, for example the study of Pavlov’s dog – the dog was trained to salivate at the sound of a bell, this study was performed under lab conditions and therefore in a controlled environment in which and influences could be eradicated, this was fully testable and as proposed by Popper(1969, cited by Russell & Jarvis 2003: 469) â€Å"a theory or hypothesis needs to be fully testable to be scientific†. This method of conditioning is used in every day society, for example, though when young, one is never told that during ‘play time’ if a teacher or someone of authority blows a whistle one is meant immediately to stop what he or she is doing, it is a natural reaction to pay attention to the person whom commanded the attention and, in a case of a teacher/student situation, follow their instructions. Operant conditioning also follows the proposal that Popper suggested as it is used every day, when teaching an animal or human, whether they be an adult or a child. For example, operant conditioning is used when teaching a pet a new trick such as sitting down or shaking hands, the pet is initially guided in what it is supposed to do by it’s owner, then treated after the act as been performed, over time the pet will ‘learn’ that if it obeys the command of â€Å"sit† then it will be rewarded, though it is no longer necessary to reward the animal after every completion of the command, instead rewarding it every now and then. This was also found in Skinner’s box, in which the rat learnt to press a lever in order to receive a food pellet, psychologists would therefore argue that both of these methods of conditioning are considered objective studies which provide clear findings. Popper also argued that in order for a hypothesis or theory to be considered scientific it must be falsifiable, in practise this means that for the study to be valid there must also be subjects which prove the study to be false. For example, to say that â€Å"all lions are mammals† would not be falsifiable, as it would be impossible to conduct the amount of study necessary to disprove this theory, however, to say â€Å"all lions have yellow fur†, it would only be necessary to find one lion with brown fur in order to prove this falsifiable, Popper(1959, cited by Hill 2009: 19) argued that â€Å"science advances through refutation rather than support†. Psychology, namely the biological approach, has been helped through the advancements in technology, for example, now it is possible to use medical equipments to see the functions of the brain via electrical pulses, though obviously this does not give us an image of what someone is thinking it does provide us with information as to which different triggers the varying reactions which until recently we have not been able to understand, obviously, this provides us with clear findings. Until the 1950s, Behaviourism dominated psychological experimentation as psychologists such as John Watson believed that only observable behaviour should be investigated if psychology wished to be considered an objective science. Thus, though psychology may not have directly effected the advances in technology the benefit it has seen from these advances are clear, it is now possible for psychologists to view the workings of the brain through the advances in other areas of science, therefore this can only inflate psychology’s status as a separate scientific discipline. Despite the arguments for psychology to be considered a science there are, of course, those that believe it should not. Those who are against the idea of psychology as a science believe there are many issues surrounding areas of psychology and the methods of investigation it carries out, one area of concern is that of sampling; random, stratified, opportunity, self-selecting/volunteer. The first in the above list, random sampling, is very rarely used, or at least it is very rare that it can be considered ‘true’; â€Å"true random sampling only occurs when every member of a target population has an equal chance of being selected† (Hill, 2009: 35), this is rarely the case as in a large target audience, in order for everyone to have an equal chance there would be a severe drain on the available resources so that the list could be compiled; many studies do not have the funding or resources available to them to waste on said list, so a truly random list of subjects is rarely achieved. Stratified sampling provides the same constraints on resources as random sampling; it is very time consuming and costly, this is due to the method that is used in order to perform stratified sampling – dividing the target population in to various subcategories then selecting members of these subcategories in to the proportion necessary to conduct the relevant research. Opportunity and self-selecting methods of sampling both provide problems in terms of bias, though from different perspectives. In terms of opportunity sampling not only does it give unrepresentative samples it is often biased on the part of the researcher, whom may pick people to take part in their study whom they believe will be more ‘helpful’ to his or her hypothesis.

Mini Paper

Advance Practice Nursing Jake Freeman University of SST. Francis Abstract This paper primarily explores the article from the Journal of Nursing called â€Å"Demographic Profiles of Certified Nurse-Midwives, Certified Registered Nurse Anesthetists, and Nurse Practitioners: Reflections on Implications for Uniform Education and Regulation†. It will also include insight from other resources in support to the information provided by the article preceding.The article will be summarized in regards to Advanced Practice Nursing (PAN) work history within the ultra of nursing and whether or not the Pan's should be mandated to further their education to the doctorate level in order to maintain there positions as Pan's. The paper will also provide a brief analysis by the author in regard to the quality of the paper's content. Keywords: advanced practice nursing, DEN, history of, history, clinical nurse specialist In Summary a Brief History of Advance Practice Nursing Nursing practice has e xpanded exponentially especially in the last 10 years.With aggressive legislation from our nursing leaders, respect, reimbursements, and the right to well deserved leadership has come forth. Although for many of us nurses it may seem as though many of these breakthroughs have spontaneously emerged, yet with a little respect to our roots we need to realize this emergence has been transforming nursing society since the sass's. The recent chaos and disorientation in health care has rendered an opportunity for nurses to take what is theirs, and that is leadership in healthcare.Preventative care has always been a forte of nursing and now it's a realization that it is the best approach to health care today, and that is why we are the leaders. Certified Registered Nurse Anesthetists are the pioneers of advance practice nursing as evidenced by the first formal education in 1909 at SST. Vincent Hospital in Portland, OR and have roots dating back to the Civil War while caring for the wounded and administering medicine like ether in the battlefields.Nurse Midwives shortly there after developed formal education in 1932 at the Maternity Center Association in New York and have roots dating back to the times of biblical writings. In 1965 the first formal Nurse Practitioner program was developed at the University of Colorado in collaboration with a physician Dry. Henry Silver and Registered Nurse Loretta Ford. Clinical Specialists devised a program of formal education at Rutgers University in 1954 (Englander et al. , 2006). As you can see advance practice nursing has came a long way and has overcome an insurmountable amount of hurdles.In the Journal of Professional Nursing a study was conducted by Sips, Fullerton, and Schilling (2009) which consisted of a sample survey and was designed to determine 6 categories of gathered information in regards to gender and race, age and years experience, education, employment, practice privileges, and salary. In the article the author aggr essively directs to the possible fact that â€Å"men Leary indicate that they chose nursing because they expected a good salary' (p. 182) and that there was a good possibility that they were inclined to choose nursing to empower themselves rather than their patients.Based on the quality of the study and the amount of professionals that actually participated this finding could be considered loosely based and also offensive to men of the profession. On a more refreshing note it was encouraging to see that Naps have the highest amount of ethnic diversity among the three PAN groups. This will highly contribute to collaboration between Pan's to provide a better understanding of culturally impotent care. Sacra's have longevity in experience, where as Naps are the youngsters of advanced practice, yet will be the largest entity of advanced practice nurses shortly in the future.Currently employment greatly consists of a physician- based practice, although this statistic will most likely cha nge as well in the near future. Unfortunately the study of demographics of the 3 groups of Pan's is loosely associated to the need for Pan's to advance their practice to the doctoral level. There where references to the concern of collegiate faculty and the necessity of doctoral repaper professors to teach doctoral prepared course work. This was in regards to the question whether or not we have enough DEN prepared nurses out there to teach to the masses that might be interested in furthering their credentials.In the time of when the article was written it was reported that there was a drop off of students studying for their PhD. Presently there will be no mandate for a Doctorate in 2015. In this paragraph we will discuss some issues that might have some more relevance to the question of whether or not we need to mandate Naps to DEN status. In the book Advanced Practice Nursing Jansen et al. 2010) makes an empowering statement reminding us of how some or our greatest attributes for e xample: modesty of our clinical skills have actually hindered some of our potential for growth.This example is finely expressed in this statement â€Å"Given the history, philosophy, and values, the concept of power holds ambivalence for many nurses, even Pan's† (p. 80). This statement makes a good realization of maybe how ill adapted we are as nurses coming into a position of such responsibility, which requires the understanding of how to properly utilize power. Instead of concerning ourselves with whether or not he DEN should be mandated maybe nurses need to learn how to harness their currently new development of high stature as autonomous providers.Our undistinguished and unparalleled ethics ironically have provided us with another hurdle that will be easily overcome in the near future as do any hurdles for nursing. Pan's are also in the midst of becoming autonomous in the politics of business and legal aspects of nursing which can be significantly foreign to many new Pan' s Suppers (2015). Not only recently hurdles in politics within nursing have been overcome such as the identity crisis of Can's and attempting to maintain a niche in he nursing profession.While Naps advance into the spotlight due to demand of needed providers that have privileges, Can's struggle to maintain position Cur (1996). In summary it's evident that Pan's still have continued hurdles, yet their achievements come from centuries of hard work from our forefathers that pioneered the practice. In recent times it's evident that the path paved by our forefathers will enable Pan's to evolve into the highest entity of health care. This is a new and exciting perspective of conceptualizing Pan's instead of physicians controlling the direction of health care, but it is now a reality. Mini Paper Advance Practice Nursing Jake Freeman University of SST. Francis Abstract This paper primarily explores the article from the Journal of Nursing called â€Å"Demographic Profiles of Certified Nurse-Midwives, Certified Registered Nurse Anesthetists, and Nurse Practitioners: Reflections on Implications for Uniform Education and Regulation†. It will also include insight from other resources in support to the information provided by the article preceding.The article will be summarized in regards to Advanced Practice Nursing (PAN) work history within the ultra of nursing and whether or not the Pan's should be mandated to further their education to the doctorate level in order to maintain there positions as Pan's. The paper will also provide a brief analysis by the author in regard to the quality of the paper's content. Keywords: advanced practice nursing, DEN, history of, history, clinical nurse specialist In Summary a Brief History of Advance Practice Nursing Nursing practice has e xpanded exponentially especially in the last 10 years.With aggressive legislation from our nursing leaders, respect, reimbursements, and the right to well deserved leadership has come forth. Although for many of us nurses it may seem as though many of these breakthroughs have spontaneously emerged, yet with a little respect to our roots we need to realize this emergence has been transforming nursing society since the sass's. The recent chaos and disorientation in health care has rendered an opportunity for nurses to take what is theirs, and that is leadership in healthcare.Preventative care has always been a forte of nursing and now it's a realization that it is the best approach to health care today, and that is why we are the leaders. Certified Registered Nurse Anesthetists are the pioneers of advance practice nursing as evidenced by the first formal education in 1909 at SST. Vincent Hospital in Portland, OR and have roots dating back to the Civil War while caring for the wounded and administering medicine like ether in the battlefields.Nurse Midwives shortly there after developed formal education in 1932 at the Maternity Center Association in New York and have roots dating back to the times of biblical writings. In 1965 the first formal Nurse Practitioner program was developed at the University of Colorado in collaboration with a physician Dry. Henry Silver and Registered Nurse Loretta Ford. Clinical Specialists devised a program of formal education at Rutgers University in 1954 (Englander et al. , 2006). As you can see advance practice nursing has came a long way and has overcome an insurmountable amount of hurdles.In the Journal of Professional Nursing a study was conducted by Sips, Fullerton, and Schilling (2009) which consisted of a sample survey and was designed to determine 6 categories of gathered information in regards to gender and race, age and years experience, education, employment, practice privileges, and salary. In the article the author aggr essively directs to the possible fact that â€Å"men Leary indicate that they chose nursing because they expected a good salary' (p. 182) and that there was a good possibility that they were inclined to choose nursing to empower themselves rather than their patients.Based on the quality of the study and the amount of professionals that actually participated this finding could be considered loosely based and also offensive to men of the profession. On a more refreshing note it was encouraging to see that Naps have the highest amount of ethnic diversity among the three PAN groups. This will highly contribute to collaboration between Pan's to provide a better understanding of culturally impotent care. Sacra's have longevity in experience, where as Naps are the youngsters of advanced practice, yet will be the largest entity of advanced practice nurses shortly in the future.Currently employment greatly consists of a physician- based practice, although this statistic will most likely cha nge as well in the near future. Unfortunately the study of demographics of the 3 groups of Pan's is loosely associated to the need for Pan's to advance their practice to the doctoral level. There where references to the concern of collegiate faculty and the necessity of doctoral repaper professors to teach doctoral prepared course work. This was in regards to the question whether or not we have enough DEN prepared nurses out there to teach to the masses that might be interested in furthering their credentials.In the time of when the article was written it was reported that there was a drop off of students studying for their PhD. Presently there will be no mandate for a Doctorate in 2015. In this paragraph we will discuss some issues that might have some more relevance to the question of whether or not we need to mandate Naps to DEN status. In the book Advanced Practice Nursing Jansen et al. 2010) makes an empowering statement reminding us of how some or our greatest attributes for e xample: modesty of our clinical skills have actually hindered some of our potential for growth.This example is finely expressed in this statement â€Å"Given the history, philosophy, and values, the concept of power holds ambivalence for many nurses, even Pan's† (p. 80). This statement makes a good realization of maybe how ill adapted we are as nurses coming into a position of such responsibility, which requires the understanding of how to properly utilize power. Instead of concerning ourselves with whether or not he DEN should be mandated maybe nurses need to learn how to harness their currently new development of high stature as autonomous providers.Our undistinguished and unparalleled ethics ironically have provided us with another hurdle that will be easily overcome in the near future as do any hurdles for nursing. Pan's are also in the midst of becoming autonomous in the politics of business and legal aspects of nursing which can be significantly foreign to many new Pan' s Suppers (2015). Not only recently hurdles in politics within nursing have been overcome such as the identity crisis of Can's and attempting to maintain a niche in he nursing profession.While Naps advance into the spotlight due to demand of needed providers that have privileges, Can's struggle to maintain position Cur (1996). In summary it's evident that Pan's still have continued hurdles, yet their achievements come from centuries of hard work from our forefathers that pioneered the practice. In recent times it's evident that the path paved by our forefathers will enable Pan's to evolve into the highest entity of health care. This is a new and exciting perspective of conceptualizing Pan's instead of physicians controlling the direction of health care, but it is now a reality.

Intergenerational Transmission of Education Research Paper

Intergenerational Transmission of Education - Research Paper Example However, others have believed associated demographic phenomena and drawn contradictory conclusions. Mare (1997) in his article, â€Å"Differential Fertility, Intergenerational Educational Mobility, and Racial Inequality† talks about the impacts of differential fertility prototypes among African-American and white women for secular drifts in educational ability within each of these populations and for race differentiations in educational ability. Mare has developed models that combine regeneration of population with intergenerational mobility for the 1925-1995 periods and look into the aggregate outcomes of demographic drifts on socioeconomic interests and inequality with a focus on the trend and allocation of educational achievement. He depicted the extent to which differential productiveness within the black and white populations has given to dissimilarities in the educational achievements of these two groups. Although this paper discusses current issues relating to communal inequality, it is provoked by theoretical issues about communal stratification as well. The study f ocused on the intergenerational transmission of socioeconomic position. He described the population projection model that is applied to replicate trends in educational achievement for blacks and whites. He built discrete-time models of population expansion that include the impacts of age-specific fertility and mortality in addition to communal mobility for blacks and whites. Differential fertility by educational achievement of mother has hindered the expansion of average educational accomplishment over the past 70 years; however, this consequence is small. Although the differential level of fertility of women has decreased but the differential timing of fertility has approximately no impact. Diversifications in fertility, mortality, and intergenerational flexibility have self-effacing effects on racial disparity1. . It is obvious that there should have been differences

The Dynamics of Design High Street and High Design Essay

The Dynamics of Design High Street and High Design - Essay Example The modern theory sticks to the similar assumption that jeans are a comfort statement, yet it also stresses on the fact that it is a necessity. Here, the modern theory takes off on a more interpretative note. While a pair of jeans are a necessity, the tone for luxury has been set by celebrities lending their names to a line of jeans and other designer jeans that 'fit and look better' than the normal brands. For example, while most people would opt for a pair of Lee or Levis', design high street fashion is achieved with Zara and Marks and Spencers', and high design is achieved by a couture label like Armani or that of Victoria Beckham's. On the other hand, within the modern theory comes the second twist. Here, design high street meets high design to a great extent when a celebrity endorses a certain brand. This can be better understood through the following lines: When something has been perceived, then it has been noted and the message is recorded. In the words of psychologist, W. H. Ittelson and F. T. Kilpatrick, perception can't be definite, of 'what is'. Rather what we perceive is created by ourselves, which is mostly based on past experiences (Arnorld,1992). Also people's perceptions of brand are governed by some factors which are personal and public. It is one of important challenges for an advertiser trying to reach the customers, either by any form of mass communication like newspaper, or television ad so that they could notice it. Even sometimes the consumer miss out some messages directed to them. So the main thing is to give them exposure. (Arnold, 1992, p. 241). For example if all the ads are in colors then a black and white will be noticed. So by this the customers attention can be taken. Awareness: Awareness implies that the message has made an impression on the audience or reader, who can then identify the pair of jeans. Although awareness is a low form of impact, but it is objective of a great ad. Relative low level of attention can create minimum awareness for low interest product (Sudijic,1985). . Brand equity: This is a very important concept from 1990s. This refers to the use of respected brand name to add value to the jeans. Branding is a way to help the customer's memory

Business Event Management Assignment Example | Topics and Well Written Essays - 3000 words

Business Event Management - Assignment Example The legal obligations in organizing a career event mainly constitute of getting the permission from the Institute and officially inviting the companies to the event. Usually, a department from within a university, college or a school organizes such events. They need the permission from the school authorities. Second, the venue needs to be booked, which has its legal requirements. Similarly, the sponsors that the management readily seeks need to qualify the legal requirements for sponsoring such an event. The sponsors should not be promoting an illegal product or services. The Operations Team liaised closely with The Legal Department regarding licenses, insurances, and contracts required for the event. This department also worked closely with other departments to ensure they meet all regulations required by the LSBF. Also they provided information regarding minor legal issues encountered and ensured they provide the legal department with and correspondence and legal documentation that is crucial to this event. The operations department is the main body of the whole event. It is about making arrangements, the timing, resources, logistics, ambience, supervision, registration of attendees and on the spot coordination between the team members, so the whole event proceeds as planned and the participants gain as much from it as possible. This section of the business event is about promotion. The marketing is not only to attract the potential employees but also the companies and institutes that will communicate their market knowledge. Also, marketing ventures out into designing flyers, posters, websites and social media pages. Public relations is also a crucial element in marketing. People love to attend seminars and job fairs that have great public speakers sharing their knowledge. This part is the lifeline of the whole event. Funding the event requires

Should the President Be Required To Have Served in the Military GP Essay

Should the President Be Required To Have Served in the Military GP week5 - Essay Example As the leader of the free world, our military servicemen look towards the man or woman sitting in the White House for leadership, guidance, and moral support. Our military has seen a long line of active or war veteran presidents stemming from George Washington who fought in the earliest civil war battles that freed our country from the British empire, all the way to George H.W. Bush who, although only a member of the Air National Guard (â€Å"Should Presidential Candidates and Elected Officials be Required to Serve in the Military?†, n.d.) , proved to be the last great American president who knew that there was a lot more at stake for the United States after the 9/11 attacks than just a vendetta upon those who took American lives in an act that rivaled the bombing of Pearl Harbor back in World War II. It is of the utmost importance that the American president have some sort of military service tucked under his belt, whether as a veteran of an international war effort or simply as a stateside based serviceman because our countrys history is steeped deeply in these â€Å"war efforts†. By actively serving the interests of the American military even during what is perceived to be â€Å"peacetime† America, the next president of this great nation ensures that he has a thorough understanding of the importance of the United States as a peacekeeping nation on the world stage, and also has a thorough grasp of the international foreign relations of the United States. By actively serving in the military, the next U.S. president will have an advantage over his non-active opponents, that of actually having been in the center of the great â€Å"wartime† political debate. He will have a greater knowledge and understanding that being an American is a privilege and should be r epaid by service. He will have come to the conclusion that, as a military veteran, he understands the needs of the international community in terms of U.S.

Is Neonatal Hyperbilirubinemia Associated with Autism Spectrum Research Paper

Is Neonatal Hyperbilirubinemia Associated with Autism Spectrum Disorders - Research Paper Example The two articles have a similar hypothesis. Both articles are trying to investigate whether neonatal jaundice is also known as neonatal/infant hyperbilirubinemia might be related to Autism Related Disorders (ARDs). The first article, Pediatrics, retrieved from the official journal of the American Academy of Pediatrics employs the case-control cohort study while the second article, retrieved from online publications uses retrospective case-control design. Therefore, this paper will examine how each investigation in each article was conducted. It will address the strengths and weaknesses the two approaches. The paper will conclude with suggestions on how I would design an ideal study to investigate the hypothesis. The research objective with regard to both journal articles was to investigate the association between neonatal hyperbilirubinemia/jaundice and autism spectrum disorders. As stated earlier, the investigations carried out in the journal article of paediatrics employed case-control cohort study. A large, population-based case control study, was carried out within an integrated health plan with extensive computerized data resources involving prospectively laboratory collected results and diagnoses (Pediatrics Digest as cited in Lisa et al., 2005). Case and control subjects were identified from the cohort of infants who were born at a northern California Kaiser Permanente (KP) facility between January 1995 and December 1998 and remained KP members for more than two years after birth (n=73 291) (Pediatrics Digest as cited in Lisa et al., 2005). Case subjects (n=393) were defined as children for whom an ASD diagnosis, i.e., Asperger’s syndrome or pervasive development disorder were recorded in KP outpatients clinical databases at any time between January 1995 and December 1998†¦All the children were between the 4 and 7 years old at the time the database was  scanned. 5 control subjects per case subject, were randomly selected from the cohort of children who did not have the diagnosis of ASD recorded in the clinical database.

Strategic Plan Essay Example | Topics and Well Written Essays - 1500 words

Strategic Plan - Essay Example The focal point of this notion declares that it has become highly necessary for school managements to realize and acknowledge the importance of developing a comprehensive strategic design in governing the operations of the institution. Therefore, the purpose of this strategic plan for Paulo Freire Charter School (PFCS) is to critically analyze, examine and assess the extensive categories of strategic planning and implementation with respect to the organization. The report aims to achieve this purpose by specifically addressing particular areas of strategy which are classified under the implementation plan, organizational change management strategies, strategic financial management and risk management plan for Paulo Freire Charter School (PFCS). Implementation Plan Gamage (2006) states that the stage of planning is conducted prior to decision-making as the entire concept fundamentally defines the chronological activities that are to undertaken by an organization for the attainment of its overall objectives. Once conducted in an effective manner, planning can also aid the enhancement of various processes within the school; these processes include resource utilization, agreement on management practices and leadership styles or approaches and granting the management, staff and students with a shared vision and a sense of direction (Gamage 2006). To understand the concept of strategic planning in a systematic manner it is important to realize the basic processes which it is comprised of, these processes include; establishing objectives, setting targets and placing appropriate monitors of performance and allocating organizational resources (Spee and Jarzabkowski 2011). The subsequent sections of the strategic plan for Paulo Freire Charter School (PFCS) aim to follow this pattern of progress with the integration of pertinent educational management concepts and dimensions. Objectives Davies and Ellison (2013) highlight the distinguishing features of an Improvement Obje ctive (IO) which is defined as the focus of what an educational institution aims to attain as a consequence of commencing development projects for the school. This notion presents a contrast from the long-term objectives of a school because it is specific to a particular phase or associated with a specific activity. Accordingly, identifying the association between the objectives and the vision of an educational institution holds immense importance because each concept is a reflection of the other. As a centre of learning, PFCS aims to be the forerunner in a highly competitive industry by promoting the highest standards of knowledge, ethics and innovation. The foundations of the school rest on four principles which are that of Inquiry, Investigation, Reflection and Action (Paulo Freire Charter School 2012). This notion postulates that the organization’s adoption of the inquiry based instructional model is the focal point in the achievement of its long-term objectives. Conseque ntly, the formulation of appropriate objectives and there subsequent achievement by the school is also critical to its financial

The over dependence on computers and the internet Essay

The over dependence on computers and the internet - Essay Example However, in the past decade, they have undergone convenient transformations. They have now become handier and cheaper (Ray, â€Å"Article†). Rates offered by telecommunications companies have also been one of the most modern lowered and have become affordable to the middle and lower income groups in society. Its added features in text messaging, as a calculator, a camera, videophone, planner, radio, music storage, and other similar usages have added to its attraction and its popularity. Many developing nations have even embraced the technology for their businesses – to check market prices for their goods in market placed which may be two or three mountains away (Butler, â€Å"News†). Cell phones have become a convenient way for family members and friends to keep track and to contact each other, wherever they may be and whatever they might be doing. In this regard, it is also important for us to consider how the computers and the internet have become one of the mo st modern conveniences available to many people around the world. Computers have become a learning tool for many people, especially when they are used to access the internet in this currently globalized world. Countries and people which used to be an ocean away are now closer with the internet and all its features like social networking sites, search engines, and knowledge sharing. I believe that we have become too dependent on modern conveniences, both in our businesses and for our personal lives.

The entrepreneurial process that brought about the creation and growth Essay

The entrepreneurial process that brought about the creation and growth of the business venture, mySmoothie, by the innovative entrepreneur, Domeniqu - Essay Example Even though managers and staff may have their own roles, the role of the entrepreneur is most pivotal because the entrepreneur represents the vision and future if the business (McCarthy, 2001). This is to say that, the entrepreneur has vital roles to play in terms of process and behavior and it is only when these roles are played well that growth and expansion can come about. To this effect, the writer is putting mySmoothie on the periscope to critically analyze, using theories and concepts from entrepreneurship to explain how the business venture has operated and the positive outcomes that has resulted particularly from its entrepreneurial process. Entrepreneurial Processes adopted by mySmoothie As far as entrepreneurship processes are concerned, mySmoothie has adhered to three major and important concepts and theories of entrepreneurship. These are recognizing opportunities and generating ideas, decision making and planning, and marketing. Diagrammatically, the write-up shall be pr esented as below: Firstly, Domenique and for that matter mySmoothie has in place entrepreneurial processes that ensure that production and operations of the company meet the needs of consumers. According to the International Institute for Management Development, IMD (2007), mySmoothie was started out of the theory of recognizing opportunities and generating ideas in the sense that, Domenique Forsberg took advantage of the absence of winter in Sweden in 2004 to start a company that rightly matched the prevailing whether at the time. The opportunity was the absence of winter and the idea generated was to start a fruit drink company that would produce chilled drinks to cool the thirst of consumers. This indeed worked perfectly and was a step in the right direction. Indeed, in entrepreneurship, the process of meeting the needs of consumers is paramount in choosing what to deal in. This is because consumers are becoming more and insightful of the need to purchase products that match thei r needs rather than those that match their wants. It is no wonder therefore that after just two year of operation, mySmoothie was reported to have made â‚ ¬1 million in 2006 (IMD, 2007, p.1). Such operations of recognizing opportunities and generating ideas have continued to be one of the most adhered theories for mySmoothie in all its business processes. For instance the company has recognized the prevailing health concerns associated with the use of sugar, preservatives and other additive and come up with the idea of eliminating the use of these compounds from its products (BevNET, 2011). The process of decision making and planning at mySmoothie is also in conformity with entrepreneurial concepts and theory on leadership. Ashley (2010) opines that â€Å"leadership philosophy is a set of beliefs and principles that strongly influence how we perceive ourselves within an organization and those that we lead.† This explanation goes a long way to explain the importance of lead ership in any given organization or establishment, of which mySmoothie is not excluded. According to Ashley (2010), one important component of leadership is decision making. In entrepreneurial theories, there are three major types of entrepreneurs as far as decision making is concerned. These are authoritarian or autocratic leaders, participative or democratic leaders and delegative or free reign leadership (Clark, 2006). According to Clark (2006), â€Å"a good leader (entrepreneur) uses all three styles, depending on what forces are involved between the followers, the leader and the situation.† Relating this assertion to mySmoothie, it will be right to say that the process of decision making and planning is at its best in the organization. This is because at mySmoothie,

Kite Runner Essay Example for Free

Kite Runner Essay Human beings are morally ambiguous people. We are neither purely evil nor purely good, but often a mix. And maybe that’s why many of us are attracted to literature works with morally ambiguous characters such as The Kite Runner by Khaled Hosseini. The Kite Runner was set in Kabul, Afghanistan, proceeds to United States during the Soviet Union invasion, and then the setting goes back to Kabul when the Taliban rises in power. In this novel, Amir, to whom the whole story of the book is centered around, is a morally ambiguous character. Amir is a Pashtun boy; he betrays his friendship with Hassan, a Hazara son of Amir’s father’s servant. Guilt haunts Amir for years even after he had left Kabul and moved to United States. Amir is a morally ambiguous character because he’s a coward, he’s selfish, he betrays his friend and lies, but he also finds courage to face what he had done wrong and finds salvation. The first part of the book The Kite Runner proves how Amir is not a purely good character. Amir often hangs out with the Hazara boy, Hassan and would tell Hassan that they are friends, but he still feels he’s above Hassan because Amir is Pashtun and Hazara people are considered below the Pashtun people. Amir wouldn’t hang out with Hassan when other Pashtun boys are with him, he also mocks the fact that Hassan can’t read, not considering the fact that Hassan doesn’t have the opportunity to get an education. Amir couldn’t stand Hassan’s intelligence: Amir had written a story about how a man’s tears turn into pearls when they fall into this magic cup, and the story ended with man’s wife dead in his arms on a mountain pile of pearls. When Hassan heard the story, he had enjoyed it, but he also raised a few questions that angered Amir, â€Å"Why did the man kill his wife? In fact, why did he ever have to be sad to shed tears? Couldn’t he have just smelled an onion? † (p. 34). Amir was angry because a mere Hazara boy who couldn’t read had taught Amir something he, an educated boy, didn’t figure out. These few examples that show how Amir is mean and arrogant are nothing compared to what he does to Hassan later on. Assef is a Pashtun boy that truly hates Hazaras and believes that Hazaras should all disappear. When Amir catches Assef raping Hassan, instead of stepping in, Amir runs away and pretends nothing had happened. When guilt started eating Amir up and he couldn’t stand facing Hassan because Hassan reminds him of his cowardly action, he pinned a crime of thievery on Hassan in order to have Hassan evicted from his house. The second part of the book shows that Amir isn’t purely evil despite what he has done. For a while, Amir’s life is filled with the guilt of not saving Hassan from the rape and it kept Amir from being completely happy, even though he found the love of his life in America and got married. Then one day, Amir’s father’s friend, Rhahim, called him to give him a chance to redeem himself. â€Å"There’s a way to be good again† (p. 226). Amir did find a way to be good again. Amir went back to Afghan to find Hassan’s son, Sohrab, to take him with Amir because Hassan and his wife had been shot to death on the street by the Taliban. Amir finds Sohrab with Assef and ends up getting into a physical fight with Assef. Amir basically lets Assef beat him up and while being beat up, Amir feels relieved. â€Å"My body was broken – just how badly I wouldn’t find out until later – but I felt healed. Healed at last† (p. 289). Amir felt that he was being healed from the guilt that has been crawling beneath his skin every single day. He had betrayed his one and only friend, Hassan, lied, and destroyed a chance where Hassan might have left to United States with him and would still be alive. Amir felt that he finally got what he deserved and he felt much better, he had found salvation. And he had afterwards taken in Sohrab as his own son. Amir had been a coward; he had made selfish decisions and ruined Hassan’s live, but if he had been purely evil then he would not have felt guilt, nor would he have risked his life to bring back a mere Hazara’s son. But he had been filled with guilt and he had gone to find Sohrab and redeemed himself. And thus, Amir is a perfect example of a morally ambiguous character.

Analysis Of The Problem Of Evil Philosophy Essay

Analysis Of The Problem Of Evil Philosophy Essay In the paper written by Collins entitled, The Problem of Evil Basics, It has been noted that reconciling the concept of existence of a perfectly good God and evil is necessary in solving the problem of evil. Collins presented two valid arguments in clarifying the problem of evil in the theistic perspective. One argument is coming from theodicy. Theodicy argues that God exists and He permits evils in this world. The Defense argument proposes that the existence of evil is not dependent on the notion that God exist. The Defense argument further claims that if there is God and He is good, then evils in the world would not exist. However, since evils exist, then there is no God because the existence of a supreme being presupposes that good would prevail. With this, should we justify evils in relation to the existence of God? Or should we deny the existence of God in order to justify evils? Basically, the analysis of this paper would revolve around the above contentions. Basically, the problem of good and evil is quite a complicated and complex topic. It has no definite answer since it goes beyond the sphere of the material world and human knowledge is limited. This is not to say that the finite capacity of the human knowledge is inadequate in comprehending the said topic. Plausible explanations can still be formulated and accepted in responding to the issues mentioned above. Accordingly, if we would provide a justifiable explanation about the problem of evil, ones personal analysis is necessary but it has to be coupled with the arguments coming from the philosophical claims of the experts. Of course, everybody has his/her own explanation about the existence of evils in this world. Evils are usually viewed as something harmful or destructive to the normal flow of things. It can be caused by man or by nature. The issue of morality would also be tackled in line with the existence of evil. In this sense, it is inevitable that the concept of right and wrong actions when it comes to human actions would have to be explained. On the other hand, natural occurrences such as floods, typhoons, earthquakes, tsunamis and the like are judged based on the harm done to man, other living creatures and the planet in general. In short, harm as a result of a natural phenomenon is equated with evil. In addition, the natural inclination of other primitive creatures such as lions, tigers, sharks and other ferocious animals could also be seen as evil producing actions. This is because the actions of these predators normally bring more harm than good to their prey. If deeply analyzed, the survival of the fittest within the world of the primitive creatures inevitably create destructive condition in the wild. Though they are part of the evolutionary process, as argued by most biologists or other natural scientists , the whole process can be equated to an evil producing condition where subduing other species is a natural phenomenon. Now, how does the concept of God situate in the mentioned assumptions? In the paper entitled, In Connection Building Theodicy Handout, the Greater Good Principle is explained in relation to the problem of evil. This principle suggests that if God is perfectly good then He has all the power to eliminate evils in the world. Consequently, God allows evils but those which are freely chosen by man. This strengthens the proposition that God doesnt exist because evils are ever-present in this world. On another angle of the debate, the Theodicy argument has been criticized by many experts. In the paper of Collins, the flaws of theodicy argument were explicated. It is said that suffering in this world is a result of committing sin. This is why by committing sinful acts, man receives certain kind of punishment in the form of suffering. Thus, suffering is inevitable and should be accepted. However, as argued by Collins, this argument is flawed because it does not explain clearly why God allows evil and the reason why the innocents have to suffer also. The second theodicy argument is the fall theodicy which states that suffering was a result of the fall of man. This line of thinking claims that man has to suffer because of the original sins committed by Adam and Eve. However, this is also flawed because no concrete explanation could be extracted as to why God allows evils to happen. The third argument is the Satan theodicy which declares that suffering is a consequence of the rebellion of Satan from God. This is another invalid argument simply because it would be hard to prove that such situation is real. Also, it does provide any concrete explication as to the reason why God has to allow evils to exist in this world. In a related academic paper, Evolution and the Problem of Evil, the Intelligent Design argument in the creation of the universe as perfect has been debated by the natural scientists and advocates of evolutionary theory. It is argued in this perspective that the Intelligent Design theory conveys that God is cruel since He allows sufferings of lower forms of animals. The anatomy of the ferocious animals such as tigers, lions, and the like is basically designed to cause sufferings to other creatures. Thus, this implies that the God we know who created the universe is either evil or doesnt exist. In an article, Why Does God Allow Evil? written by Eric V. Snow , it was explained the basic reason why God allows evil to exist in this world based on the Christian perspective. The premise of the article is that God created man in his own image and with 100% free will. As Gods creation, man has to choose to be 100% righteous. It was based on the thesis coming from Genesis 1:26 which states that Then God said, Let Us make man in Our image, according to Our likeness; let them have dominion over the fish of the sea, over the birds of the air, and over the cattle, over all the earth and over every creeping thing that creeps on the earth. This is one of the basic arguments of the theist. This proposes a belief that God created man in his own image which has a righteous path. However, the goodness of man should be chosen because of free will. Being righteous is not an easy and immediate process. It has to be intended and calculated by man. Man must also know and will it. Moreover, the ar ticle argued that God created man with free will like himself. Without free will man would be nothing like God. Incidentally, total obedience to Gods laws is the only way to be righteous. Hence, pain and suffering are caused by mans free will as a result of bad motive, ignorance and miscalculated intentions. In connection, the article further explains that suffering would make man trust God. Pain is experienced so that faith in God would be attained. It was also the position of the article that mans knowledge is inadequate enough to understand why God allows evil. Man is not in the position to question the intention of God. Like Job, man has to believe and obey God without question. Since death is inevitable, we would be judged by God based on our actions in the material world. Hence, God allows evils in this world because of His benevolent intention for us whatever it may be. Free will is given to man in order for him to know and obey Gods laws. Pain and suffering are merely temporary tests in attaining the rightful path, as argued by the article (Snow). In another article, The Problem of Evil, by P.J. McHugh (2006), the same argument was put forward about the problem of evil. As stated by McHugh (2006), the common ground of all who believe why God allows evil to prosper in this world is the free-will defence. Man is a self-directing agent with a limited source of freedom that would make him responsible for his every decision. With freedom, man is free to choose between right and wrong as a moral agent. However, with free will it also recognized by McHugh (2006) that evil actions are unavoidable. Good cant be separated by bad actions. This is why man has to be careful in making decision because every decision has an accompanying good and evil consequences. Accordingly, the free-will defence is challenged by the idea that if free will is God-given and that it is the cause of evil actions, then it is logical to assume that God is also responsible for creating a creature that produces harm because of free will. The question still arises, why did God create a being that can do harm to the world? McHugh (2006) presented the Augustinian Theodicy in answering the above question. According to McHugh (2006), Augustine (354-430 A.D.) formulated explanations that influence the thoughts of the Christians for many centuries. One of the fundamental premises of the philosophical view of St. Augustine is that the universe is good because it was created by a good God with a good intention. Every creation has a good purpose in line with Gods good intention. Evil is a result of an on-going process of attaining good that is innate in all the things created. The universe is perfect and out of that perfection is the ultimate purpose of goodness. In short, evil is an intended consequence of taking the path of goodness which is divine. However, those who dont abide with the divine path imposed by God, would be punished as they would be judged at the end of human history. McHugh (2006) claims that the Augustinian theodicy seems to be removing the responsibility from God when it comes to evil act ions of man. The Augustinian theodicy further assumes that evil is the consequence of free will as misused by man. McHugh (2006) also presented criticisms of the said theodicy by St. Augustine. According to him, the universe that God created might have gone wrong. With all the evils in the world that we would observe, this universe might not have went to the things that God wanted it to be. It is either God committed a mistake of creating the universe or He did not really intend to make the universe perfect as assume by some Christians. The second criticism offered by McHugh (2006) is the one proposed by the scientific perspective about the evolution of mankind. As explained by the Augustinian point of view, man was created perfect and good. However, the scientific evidence would prove that man evolved from the lowest form of animals that can be argued as imperfect and hostile creatures. Primitive man has crude knowledge of morality and that hostility seemed to be his natural response to his environment. In the same argument, natural disasters and calamities existed long before man came into this world, as proposed by the evolutionary perspective. These natural phenomena certainly cause evils and sufferings. Consequently, if these phenomena already existed before man, then it is logical to assume that they were not caused by man. If they were not caused by mankind, then God was the one responsible for evil effects of such natural calamities. The third argument against the Augustinian theodicy is the existence of hell as a venue for those who will not abide by the law of God. The concept of hell is a punishment for those who will choose to do wrong. This concept is challenged because it only show how Gods justice works. Sinful acts are punishable according to St. Augustines argument that is why man is compelled to do good which is the main intention of God. If this is true, then majority of the human race might be tormented in hell since humanity now is characterized by immorality and sinful acts. Is this the justice that God wants man to realize? Whatever the answer to this question, it is certain that the concept of hell acquits of Gods purpose of punishing the disobedient. In a related article, The Problem of Evil, written by Vincent Cheung (2004), it discusses the problem and solution in the issue of the existence of evil. Cheung (2004) also recognizes that the basic problem of the Christian point of view about good and evil is that there is a God who is omnipotent and omnibenevolent. In this line of thinking, if God is all-powerful, then He has the ability to eradicate all the evils in the world. If God is a loving supreme being, then He would not allow evil to thrive that causes pain and suffering to mankind. What complicates the Christian perspective is the notion that God and evil are irreconcilable concepts. If God really exists then there is no evil, as argued by Cheung (2004). Accordingly, if evil exists, then there is no God who is ever loving. In case that God really exists and evil also prevails in this world, then the God that really exists is not an ever-loving supreme being. In this line of thought, the God that exists might be a being wh o loves suffering and pain because He allows evils to prevail. In short, it is a choice between God or evil. Cheung (2004) offered insightful analysis in reconciling they contradictions of God and evil. It was argued in his article that the flow of argument of the problem of evil cant be answered by the Christian perspective. The Christian point of view of God is illogical and cant be accepted because it has many flaws. If one has to take the route of the Christian perspective an all-powerful and all-loving God would not exist with the evil prevailing in this life. This is why in the article, Cheung presented a more logical argument that emanated from the fundamental premises of the Christian perspective. In a gist, Cheung (2004) argued that there is God who is all-powerful and all-loving. With Gods power, He is capable of eliminating suffering and pain. His benevolence would result to His intention of eradicating evils. Consequently, evil still exists because God a good purpose for it. With Gods power and goodness, He would eventually end all these sufferings and pains in life. The prevalence of evils doesnt mean that God doesnt exist. It merely implies that it would eventually be eliminated because God is good. Analysis and Conclusion With the surveyed articles presented above, this paper has formulated its own analysis to answer the quite controversial issue of the existence of evil. First and foremost, this paper proposes that there is God. If we would formulate a notion of God, it is always good and logical to assume that He is all-powerful and all-benevolent. It would be difficult and more painful to imagine that there is supreme being who exists for the sole purpose of punishing us. There is God because there is a creation. The cause and effect analysis of St. Thomas Aquinas is quite a convincing argument for this. It would be natural for a creator to produce something with no good intention. For instance, a sculptor would not create a work of art with bad intention on his/her mind creating it. It is innate to him/her to produce a beautiful and as much as possible perfect masterpiece. Of course, the actual product would not be as perfect as it is in his/her mind. However, this doesnt imply that the sculptor is evil. He may be innately good even if there is imperfection in his/her creation. Needless to say that this analogy also applies with the existence of a n all-loving and all-powerful God. There is a supreme creator who made man in his own image. As an all-powerful being, God couldnt interfere with the affairs of man because of free will. Free will has unintended consequences, that we call evils. Inasmuch as God wants to eradicate evils and harms in this world, His authority could have superseded by the power of free will which He gave to man as a sign of love. Through free will, man make choices so as not being controlled by God. If free will doesnt exist, man is like a puppet that is being controlled by a puppet master. Subsequently, since God loves man, He took his control out of mans life. In connection, free will doesnt mean doing evil. It is a powerful instrument of choosing the right path. With it, man should take the right path. Although evils seem to reign in life, they could be viewed as temporary. It is logical to assume life is meaningless if we are just expecting bad things to happen. We might have to annihilate humanity if that would be true. However, it is the position of this paper that every choice that we make has an accompanying equally balanced results that may good or evil. There are no options that have purely good or bad consequences. In other words, there is no situation in this world that would only produce an unpleasant result because that would mean complete annihilation of everything. The result would come from a balance of good and evil actions. Now, when it comes to the nature of things in the lower form of animals, harm really exists. It is the normal flow of things that other creatures to subdue other species. It is part of the grand design. It is a design that can only be sustained if man would not interfere in it. It would be valid to assume that mans interference with nature has caused destruction to the planet. This is because the natural laws are perfect. It has all the necessary functions for the planet to survive. Typhoons, earthquakes, and the like are natural occurrences that are caused by the overproduction and overconsumption of man through the utilization of the environments resources. The natural inclinations of the lower forms of animal are also necessary for the survival of each and their own species and for the emergence of the new species. These phenomena are all beneficial to the existence of the planet. Man seems to be the unnecessary component in sustaining the equilibrium of the planet if free will would not be used properly. It is certainly true that man is capable of moral actions. Mans actions may interfere or not with the natural flow of things in nature. However, as mentioned earlier, there are actions that are good-producing. These actions may contribute to the well being of the planet if man would only realize the power of free will. In contrast, evils caused by man are unintended consequences of the free will given by God. This is why free will is coupled with superior intellect. Man is guided by free will and a superior intellect for him to do good and avoid harm to others. The superior intellect is here to compensate with mans free will. There are no absolute standards of good and evil. It has to depend on the ability of man to evaluate a particular situation. It can be judged based on the motive, actual behavior and the consequences of the action. In short, actions should be based on the use of the ability of man to calculate, rationalize and good intention. Man has to plan his actions with the intention of doing good. In relation to theodicy, it is the position of this paper that there is God but He doesnt want evils to happen. Evils can be speculated as a result of unintended consequences of free will and superior intellect of man. With regards to the Defense argument, it is more valid to claim that evils dont have to be equated with the non-existence of God. The problem of evils doesnt depend on whether there is God or not. It is a necessary result of the free will, miscalculation or ignorance of man. Definitely, there are choices to be made in life. The best choice is coming from many choices with the use of the intellect and free will. Evils would arise because of irrationality, lack of planning, miscalculation or ignorance. Equating evil with the non-existence of God is like blaming God for mans mistakes. In this line of thinking, man is removing himself from accountability that makes God his scapegoat. Finally, it is the position of this paper that part of the theodicy argument is valid more particularly the argument that God exists but he has no intention of bringing harm to this universe. Evils, as emphasized above, are unintended consequences brought about by mans ignorance, miscalculation and bad intention. It is also the point of this paper that it is illogical to accept the Defence argument since the existence of evil cant be equated with the denial of God. Of course, it would be noted that this paper doesnt assume that it provided all the absolute answers nor it has figured all out the problem of evil. The problem of evil is quite complicated issue that it cant be discussed easily in a single paper. The analysis of this paper has been deduced from several articles and from the finite capacity of the writer. Message from client: Can I have a rewrite? None of my sources were used and they need to be in the paper. Please just use the sources I provide in the rewrite and no other sources. Thank you.

Enantioselective Disposition of MDMA and its Metabolites

Enantioselective Disposition of MDMA and its Metabolites INTRODUCTION Amphetamine-type stimulants (ATS) are a group of drugs, mostly synthetic in origin, that are structurally derived from ÃŽ ²-phenethylamine (Figure 1). Amphetamine (AMP, Speed) was initially synthesized in Berlin in 1887 as 1-methyl-2-phenethylamine. It was the first of several chemicals, including methamphetamine (MET, Ice) and 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy), which have similar structures and biological properties, and are referred to collectively as amphetamines (Cody, 2005). Since 1887, amphetamine was thought to be a human invention (Berman et al., 2009), but the compound was found in 1997, along with methamphetamine, nicotine and mescaline, within two species of Texas acacia bushes (Clement, Goff and Forbes, 1998). AMP and MET are most commonly abused drugs. They have asymmetric centre and exists as one of the two possible enantiomers (see Figure 2) (Cody, 2005). In attempt to maintain anorexic activity while limiting undesirable side effects, substitutions have been made to amphetamine and methamphetamine. Others have been made to enhance the stimulatory activity or to avoid legal restrictions on the manufacture and use of the drugs (Cody, 2005). The related groups of amphetamine derivatives are shown in Figures 3 and 4. Figure 5 shows another group of precursor drugs that is metabolized by the body into AMP and MET. Administration and neurotoxicity of amphetamines Amphetamines are generally administered as oral capsules. This route results in a gradual increase in drug concentration, which peaks in around an hour and maintains effective drug levels for 8 – 12 hours. Amphetamines can also be injected into the circulation (Parrott et al., 2004). Amphetamines readily cross the blood-brain barrier to reach the sites (Berman et al., 2009) of action in the brain. The acute administration of amphetamines produce a wide range of dose-dependent behavioral changes, including increased arousal or wakefulness, anorexia, hyperactivity, perseverative movements, and, in particular, a state of pleasurable affect, elation, and euphoria, which can lead to the abuse of the drug (Berman, 2009). This causes amphetamines to be associated with acts of violence. Acute drug abusers will develop tolerance, where the same dose of drug has diminishing physiological and psychological effects. They need to increase their dosage if they wish to generate the same stre ngth of effect. Cross-tolerance will also occur as tolerance to one drug affects another drug with similar neurochemical profile. As a result, drug abusers will seek for another class of drug and become polydrug users (Parrott et al., 2004). Chronic drug abusers usually take in amphetamines through injection or smoking ice amphetamines. These abusers suffer many health problems and a reduced life expectancy. They are more susceptible to HIV (human immunodeficiency virus), AIDS (acquired immunity deficiency syndrome) and SIDS (sudden infant death syndrome) (Parrott at al., 2004). Clinical uses In accordance with the Convention on Psychotropic Substances of 1971, amphetamines are enlisted as narcotic compounds in the List of psychotropic substances under international control. The list is prepared by the International Narcotics Control Board. These compounds are prohibited to be imported and exported in countries like Japan, Nigeria, Pakistan, Thailand and etc (International Narcotics Control Board, 2003). Amphetamines and related compounds are clinically used for narcolepsy (sudden day-time onset sleep) and Attention Deficit Hyperactivity Disorder (ADHD) in young children. It was formerly used as a short-term slimming agent, as an antidepressant and to boost athletic performance (Parrott et al., 2004). 3,4-METHYLENEDIOXYMETHAMPHETAMINE (MDMA, ECSTASY) History of MDMA abuse MDMA, also known as ecstasy, ETC, or Adam, is one of the most commonly abused amphetamine derivatives that was re-synthesised by Alexander Shulgin during his research career at the Dow Chemical Company in 1970s. Soon MDMA was being synthesised in illicit laboratories, and became popular as recreational drug since then. As MDMA does not have any clinical/medical use, it is scheduled as Class I illicit drug by the American Drug Enforcement Agency in 1985 (Parrott et al., 2005). Also, MDMA other ring-substituted phenylethylamines were generically classified under the Misuse of Drugs Act as Class A drugs, in United Kingdom (Wikipedia, 2009). Chemical Properties of MDMA The methylenedioxy analogues of amphetamine (see Figure 3) are series of compounds referred to designer drugs. They include methylenedioxyamphetamine (MDA), methylenedioxyethylamphetamine (MDEA) and MDMA (Hensley and Cody, 1999). The synthesis of N-alkyl-MDA derivatives only produces ( ±) racemic mixtures. As a results, only racemic forms of (capsules, loose powder or tablets) the compounds are sold in the illicit market and abused (Matsushima, Nagai and Kamiyama, 1998; Fallon et al., 1999). MDMA is chiral, possessing two enantiomers, S-(+)-MDMA and R-(-)-MDMA (see Figure 6), with S-(+)-MDMA is more potent than R-(-)-MDMA (Lyon, Glannon and Titeller, 1986; Shulgin 1986). The basic structure of MDMA is ?-phenylisopropylamine group (see Figure 6), with a methylenedioxy group forming a 5-membered ring including C-3 and C-4 of the benzene ring (Cho and Segal, 1994). The empirical formula of MDMA is C11H15NO2 (Shulgin, 1986). MDMA is a phenylisopopylamine derived from safrole, aromatic oil found in sassafras, nutmeg, and other plants. The methyl group on ÃŽ ±-carbon (R2) (see Figure 6) of MDMA confers resistance to oxidative deamination of this compound and, therefore, increased its metabolic half-life (Cho and Segal, 1994). According to Cone and his colleague Huestis (2009), S(+) isomer of MDMA is responsible for its psychostimulant and empathic effects and the R(-) isomer for its hallucinogenic properties. Uptake, absorption, metabolism and elimination of MDMA in human body MDMA is usually formulated in tablets of its racemate (1:1 mixture of its enantiomers) in doses ranging from 50 to 200 mg (Pizarro et al., 2004), which is most commonly sold in batches of 3–5 for ?10 (Wikipedia, 2009). MDMA powder is also found in the market at a higher price, indicating that it has higher purity. MDMA powder is not usually insufflated (snorted) as it causes sneezing, pain and nosebleeds. MDMA cannot be smoked and is very rarely injected intravenously (AMCD, 2008). MDMA is absorbed into the blood streams and distributed in body. Postmortem analysis by Letter et al. (2002) shows that MDMA is distributed in cardiac muscle, both lungs, liver, both kidneys, spleen, the four brain lobes, cerebellum and brainstem, adipose tissue, serum, vitreous humor, urine, hair and bile upon administration. Rapid distribution of MDMA in body is mainly due to its basic property of pKa around 9.9 and low plasma protein binding, MDMA can diffuse across biological matrices that is more acidic than blood (Pichini, 2005). After an oral administration of MDMA, the plasma concentration peaks in within 1.5 to 2 hours (Cone and Huestis, 2009). MDMA is metabolized by multiple pathways (see Figure 7), primarily involving N-demethylation and O-demethylenation. The enzymes involved in the pathway are a group of cytochrome P450 isoenzymes, including CYP1A2, CYP3A4, and CYP2B6. Firstly, MDMA is O-demethylenated to 3,4-dihydroxymethamphetamine (HHMA) followed by O-methylation to 4-hydroxy-3-methoxymethamphetamine (HMMA). The enzymes involved in the metabolic process are CYP2D6 and catechol-methyltransferase respectively. At a lower rate, MDMA is N-demethylated to 3,4-methylenedioxyamphetamine (MDA) (a reaction regulated by CYP2B6), which is further metabolized to the catechol intermediate (3,4-dihydroxyamphetamine) and finally O-methylated to 4-hydroxy-3-methoxyamphetamine (HMA). In the reactions, the ÃŽ ±-carbon responsible for stereochemical properties of MDMA is not affected and all the metabolites are chiral compounds that may be presented as a mixture of their enantiomers. In addition to these major compounds, some other minor metabolites derived from the activity of monoamine oxidase on the amine residue are also formed (Kolbrich et al., 2008; Pizarro et al., 2004). N-demethylation of MDMA yields 3,4-methylenedioxyamphetamine (MDA), an active metabolite exhibiting similar pharmacological properties as the parent drug. A further O-demethylenation of MDA produces 3,4-dihydroxyamphetamine (HHA) which is mainly regulated by CYP2D6. Additional metabolites are formed by O-methylation of HHMA to 4-hydroxy-3-methoxymethamphetamine (HMMA) and of HHA to 4-hydroxy-3-methoxyamphetamine (HMA), deamination, and conjugation (Cone and Huestis, 2009). The metabolic pathway mainly happens in the liver. Some people with reduced CYP2D6 shows lower metabolic rate of MDMA and thus are more susceptible to MDMA toxicity (ODonohoe et al., 1998; Schwab et al., 1999). Physiological and psychological effects of MDMA Berman et al. (2009), Hensley and Cody (1999) and Piper (2008) reported an increased alertness and euphoria, increased heart rate, blood pressure, respiration and body temperature upon administration of MDMA. United Nation Office on Drugs and Crime (2006) conveys that chronic amphetamines abuse causes agitation, tremors, hypertension, memory loss, hallucinations, psychotic episodes, paranoid delusions, and violent behavior. Withdrawal from high doses of amphetamine-type stimulants (ATS) could result in severe depression. MDMA impairs the temperature control by hypothalamus. This causes MDMA users to die of hyperthermia (Piper, 2008) and some die from hyponatraemia, i.e. the dilution of blood due to excessive fluids taken to counteract heat exhaustion (Parrott et al., 2004). Neurotoxicity of MDMA Nichols (1986) and Vollenweider et al. (1998) categorize MDMA as entactogens, a special class of drug that produce changes in mood, social interactions or feelings of interpersonal closeness and changes in perception. MDMA shares some of the pharmacological effects of stimulants and serotonergic hallucinogens (Cami et al. 2000; Gouzoulis-Mayfrank et al. 1999; Liechti Gamma and Vollenweider, 2001; Tancer and Johanson 2003). MDMA acts an agonists on various neurotransmitters action especially serotonin. Boost in serotonin turnover induced by MDMA tends to generate feelings of contentment, elation, liveliness and intense emotional closeness to others. This causes people to enjoy themselves without their normal concerns and inhibitions. MDMA is classified as neurotoxin. Studies have found evidence for dopaminergic nerve destruction in higher brain regions. As shown in Table 2, the higher brain function such as memory, information processing and storage, complex stimulus analysis and decision making of MDMA users are impaired. CHIRAL DRUG ANALYSIS Chirality Chirality is formally defined as the geometric property of a rigid object (like a molecule or drug) of not being superimposable with its mirror image (McConathy and Owen, 2003). Achiral molecules can be superimposed on their mirror images. Molecules that are not superimposable with their mirror images are said to be chiral. Each chiral molecule will have at least one chirality centre or stereogenic centre (Leffingwell, 2003). Chirality centre of an organic molecule is usually a carbon atom, bonded to four different groups of atoms. Chiral molecules with one chirality centre exist in two enantiomeric forms (see Figure 8). The two mirror images are termed enantiomers. Both molecules of an enantiomer pair have the same chemical formulae and can be drawn the same way in 2 dimensions but in chiral environments such as the receptors and enzymes in the body, they will behave differently. Enantiomers are identical in all physical properties except for their optical activity, or direction in which they rotate plane-polarized light (McMurry, 2004). Some optically active molecules rotate polarized light to the left (levorotatory) while others to the right (dextrorotatory) (Baker, Prior and Coutts, 2002). A racemate (often called a racemic mixture) is a mixture of 1:1 amount of both enantiomers of (+) and (-) enantiomers and is optically inactive. The optical inactivity results from the rotation caused by one enantiomer canceling out that produced by its complementary enantiomer (Beesley and Scott, 1998). The absolute configuration at a chirality center is designated as R or S to unambiguously describe the 3-dim ensional structure of the molecule. R is from the Latin rectus and means to the right or clockwise, and S is from the Latin sinister for to the left or counterclockwise (McConathy and Owen, 2003; Baker, Prior and Coutts, 2002). Pharmacological aspect of chiral drugs In pharmacology, chirality is an important factor in drug efficacy. About 56% of the drugs currently in use are chiral compounds, and about 88% of these chiral synthetic drugs are used therapeutically as racemates (Leffingwell, 2003). As previously mentioned, MDMA is a chiral drug that exists in two enantiomeric forms as shown in Figure 6. Chemical modification at the positions R1 to R9 (refer to Figure 9) of MDMA results in unlimited number of pharmacologically active compounds, some of which are more potent stimulants than others. Although there are several possibilities for side chain modification, substitution on the aromatic ring contributes the most to substantial qualitative differences in pharmacological effects. Hence, it is important to discriminate between the enantiomers present in the drugs administrated as both the enantiomers of a chiral drug may differ significantly in their bioavailability, rate of metabolism, metabolites, excretion, potency and selectivity for receptors, transporters and/or enzymes, and toxicity (McConathy and Owen, 2003). The difference in interaction between a chiral drug and its chiral binding site is illustrated in Figure 10. The different domain of a drug molecule has different binding affinity towards the active site of biochemical molecules in the body. As shown in Figure 10, it is obvious that the active enantiomer has a 3-dimensional structure that allows drug domain A to interact with binding site domain a, B to interact with b, and C to interact with c. In contrast, the inactive enantiomer cannot be aligned to bind the same 3 sites simultaneously. Due to the difference in 3-dimensional structure, binding of the active enantiomer exerts a biological effect, while the inactive enantiomer does not possess any (McConathy and Owen, 2003). The hypothetical interaction of drug enantiomers is supported by the studies done by Matsushima, Nagai and Kamiyama (1998) and Kolbrich et al. (2008) shows that stereoselective cellular transport of MDMA allows the drug to accumulate at different extent in biological matrices. According to ODonohoe et al. (1998) and Schwab et al. (1999), stereoselectivity also affects genetic differences in the expression of metabolic enzymes that are responsible to metabolize MDMA in the body. For example, CYP2D6 is expressed as 2 phenotypes; one being extensive and another as poor metabolizers. Thus, it is obvious that the stereospecificity of a chiral drug can alter absorption, elimination and cellular transport of the drug itself. Analytical aspect of chiral drugs Approximately 50% of marketed drugs are chiral, and of these approximately 50% are racemix mixtures of enantiomers rather than single enantiomers (McConathy and Owen, 2003). Differences in pharmacokinetic and pharmacodynamic activities of the enantiomers of drugs administered as racemates are increasingly appreciated (Porter, 1991). Thus, quantification and qualification of drugs of abuse play important roles in the prediction of and protection from the risk to human health (Nakashima, 2006). Two main approaches to chiral drug analysis have been taken. In the indirect approach, the drug enantiomers are derivatized with an optically pure chiral reagent to form a pair of diastereomers, which may then have sufficiently different physical properties for separation to occur on conventional chromatographic columns (UNODC, 2006; Porter, 1991). In the direct approach, the enantiomers form transient rather than covalent diastereomeric complexes with a chiral selector present either in the mobile or the stationary chromatographic phase (Porter, 1991). Each of these analytical approaches has advantages and disadvantages prevail, depending upon factors such as time, purity, chemical processing, and inherent side reactions (Carvalho et al., 2006). Indirect chiral drug analysis In order to successfully resolve the enantiomers, a stable, optically pure chiral derivatizing reagent (CDR) has to be available for the covalent formation of diastereomeric derivatives (Porter, 1991). Diastereoisomers of amphetamine-type stimulants can be prepared using different reagents such as acylchlorides, alkylsulphonates, isothiocyanates, chloroformates. Moshers acid [R(+) or S(-)-methoxy(trifluoromethyl)phenylacetic acid], Moshers acid chloride, and N-trifluoroacetyl-1-prolyl chloride (TPC, also known as TFAP-Cl) are the most popularly used chiral derivatizing agents (UNODC, 2006). The reaction scheme may be illustrated as follows: The purity of the chiral derivatizing agent is vital in the process of separation of the racemic mixture. The resolution of a racemic drug by the R-enantiomer of a CDR contaminated with its S-enantiomer causes an additional pair of diastereoisomers to be formed, each of which is the enantiomer of one of the first pair (Porter, 1991), as shown in Figure 12. As a result, the enantiomers R-R, S-S and S-R, R-S would coelute in conventional chromatographic systems due to their similar physical properties. Racemization during the reaction would bring about analytical error especially when attempting to quantitate small quantities of one enantiomer in the presence of a large excess of its antipode (Porter, 1991). Methods using chiral derivatization are essentially less expensive and do not require specialized equipment or columns. The use of normal, achiral columns allows easy integration of chiral separations into routine analysis schemes (UNODC, 2006). Thus, considerable flexibility in chromatographic conditions is available to achieve the desired resolution and to eliminate interferences from metabolites and endogenous substances. Moreover, a reasonably good selection of chemically and optically pure CDRs is available for derivatizing various functional groups (Porter, 1991). Direct chiral analysis Chiral gas chromatography (GC), High Performance Liquid Chromatography (HPLC) or Capillary Electrophoresis (CE) are popular methods in direct analysis of illicit drugs (UNODC, 2006). Direct analysis does not require a CDR for covalent diastereomeric complexation. Instead, separation of chiral drugs occurs via the interaction between the enantiomers and a chiral selector. The chiral selector is an optically active compound that may be present in the mobile phase for use with conventional HPLC columns or it may be incorporated into the stationary phase to provide specialized chiral stationary phases (Porter, 1991). Calvalho (2006) lists the most successful chiral packing materials i.e. amylose, Pirkle type stationary phase, cyclodextrin, proteins, and cellulose ester and carbamate derivatives used in GC. Sometimes, derivitization may be carried out with a nonchiral reagent, in order for appropriate molecular interactions with the chiral discriminator to occur and/or to impart requisite spectral or fluorescent properties to the molecule (Porter, 1991). HPLC with fluorescence detection method is done by Al-Dirbashi et al. (1999) in attempt for the determination of methamphetamine in human hair. Nakashima (2006) claimed that the use of a chiral stationary phase in GC to separate pairs of enantiomers after suitable derivatization with an achiral reagent is able to achieve a powerful separation. Recently CE has become a highly competitive tool for chiral analysis of many compounds since it allows for the highly efficient separation of enantiomers without derivatization and specialty columns (capillaries) (Porter, 1991; Ramseier, Caslavska and Thormann, 1999). For the separation of amphetamine-type stimulant using CE, chiral additives such as hydroxyl-propyl beta-cyclodextrin are added in the running buffer. This eliminates the need of derivatization in analysis of chiral drugs commonly used (Iio et al., 2005; Ramseier, Caslavska and Thormann, 1999). Separation of chiral drugs using gas chromatography UNODC (2006), Pirnay, Abraham and Huestis (2006) and Rouen, Dolan and Kimber (2001) agree that gas chromatography/mass spectrometry (GC/MS) is the most common instrumental technique for analysis of amphetamines and derivatives. However, GC/MS still has its limitations. Chiral gas chromatography is selected as the separation technique if the materials are volatile and stable at elevated temperatures. In addition, if the solutes can be derivatized to form a sufficiently volatile product without racemizing the enantiomers, or changing their racemic proportion, then GC may be the choice. GC offers much higher efficiencies, much higher peak capacities and significantly higher sensitivities than LC. It follows, that GC can easily contend with multicomponent mixtures, especially mixtures from biological samples. In addition, the columns have short equilibrium times, trace impurities are easily assayed, and the analyses are shorter providing much faster sample throughput (Beesley and Scott, 1998). Prior to analysis by GC, compounds containing functional groups with active hydrogens such as COOH, OH, NH, and SH have to be derivatized. This is because these compounds tend to form intermolecular hydrogen bonds, hence reducing volatility of the compounds in the machine. They are also thermally unstable and can interact with either fused silica or the stationary phase, causing peak broadening (Danielson, Gallgher and Bao, 2000). Most underivatized amphetamine-type stimulants (ATS) have fragment ions of low m/z ratio, low intensity, and only one fragment ion of higher abundance (base peak). Derivatized ATS usually produces fragment ions of higher m/z ratio and higher abundance. Molecular ions with greater molecular mass have greater diagnostic value, due to the reason that they are not affected by interfering background ions such as column bleed or other contaminants (UNODC, 2006). Capillary electrophoresis as a complementary method in the analysis of MDMA According to Meng et al. (2006), capillary electrophoresis (CE) can be used to complement GC and HPLC methods of amphetamines analysis due to their high efficiency, accuracy, very high resolution, and tolerance to biological matrices. Capillary electrophoresis utilizes the electrical nature of charged molecules and enables the separation of molecules based on charged in an applied electrical field (Landers, 1995). MDMA is an organic compound and so its enantiomers are not charged. Hence, for the separation of enantiomers of MDMA, micellar electrokinetic chromatography (MEKC) is utilized (Beesley and Scott, 1998). This is a modified electrophoresis system in which the chiral selector is added to the electrolyte as additives, or be immobilized on the capillary tube surface as a traditional type of stationary phase (Beesley and Scott, 1998). The applied voltage causes the analytes to migrate through the capillary and being separated (Landers, 1995). Figure 13 shows the instrument used for micellar electrokinetic chromatography (MEKC). As seen in the figure, during sample separation, the individual analytes are driven in the appropriate direction by their inherent electrophoretic mobility (neutral species are static, anionic species move towards the anode, and cationic species move towards the cathode) with a magnitude represented by the arrows. Concurrently, the EOF of buffer towards the cathode, with a magnitude greater than the individual electrophoretic mobilitles, results in electrophoretic zone formation as all analytes (neutral, positive, and negative) are swept past the detector (Landers, 1995). The detector produces an electropherogram that is almost the same as the one obtained from the gas chromatography (see Figure 14). The chiral selector used in micellar electrokinetic chromatography is usually beta cyclodextrin. Cyclodextrin is an oligosaccharide with an external hydrophilic surface and a hydrophobic cavity, in which they can include other compounds by hydrophobic interaction (Tagliaro, Turrina and Smith, 1996). This allow for the separation of molecules with different sizes, charges and polarity. The aim of this literature review is to investigate the effectiveness of GC/MS and CE in the analysis of MDMA enantiomers. Not only that, the enantioselective disposition of MDMA in hair and urine is also reviewed. The use of hair and urine as a medium for drug detection is also explored. CASE STUDY Urine analysis Urine is the most widely used biological specimen for the analysis of illicit drugs (Nakashima, 2006; Rouen, Dolan and Kimber, 2001). According to Ramseier, Caslavska and Thormann (1999), urinary screening of drugs of abuse is usually performed with immunoassay, whereas GC/MS is the standard approach employed for confirmation of the presence and absence of a specific drug or metabolite. The goal of urine drug testing may be stated as the reliable demonstration of the presence, or absence, of specified drugs or metabolites in the specimen (Chiang and Hawks, 1986). Despite a number of persistent shortcomings, such as its susceptibility to tampering, urinalysis is a well-researched technology in which most of the problems have been identified and addressed, if not resolved. It offers an intermediate window of detection making test scheduling an important issue in many situations (Rouen, Dolan and Kimber, 2001). The Physiology of Urine Production Blood is drained through the kidney in the rate of 1.5 litres per minute. Ultrafiltration of blood that occurs at the kidney leads to the production of urine continuously. During urine production the kidneys reabsorb essential substances. Excess water and waste products, such as urea, organic substances and inorganic substances, are eliminated from the body. The daily amount and composition of urine varies widely depending upon many factors such as fluid intake, diet, health, drug effects and environmental conditions. The volume of urine produced by a healthy adult ranges from 1-2 litres in a 24 hour period but normal values outside these limits are frequently reported (Rouen, Dolan and Kimber, 2001; Pichini, 2005). Incorporation of Drugs into Urine The possible ways of drug disposition in the human body is shown in Figure 15. When a drug is smoked or injected, absorption is nearly instant and excretion in urine begins almost immediately. According to Pichini (2005), 80% of the drug is metabolized by the liver, leaving 20% of the drug to be excreted unaltered. However, absorption is slower when a drug is orally administered and excretion may be delayed for several hours. Generally, a urine specimen will contain the highest concentration of parent drug and metabolite within 6 hours of administration. As for MDMA, the peak concentration is reached after 2 hours of administration (Cone and Huestis, 2009). As drug elimination usually occurs at an exponential rate, for most illicit drugs a dose will be eliminated almost completely within 48 hours. A number of factors influence the detection times of drugs in urine including the quantity of drug administered, parent drug and its metabolite half-life, cut-off level used, and a number of physiological factors. Fallon et al. (1999) reported that the plasma half-life in humans of (R)-MDMA (5.8  ± 2.2 h) was significantly longer than that of (S)-MDMA (3.6  ± 0.9 h). It is also noted that for many of drugs, frequent, multiple dosing over extended periods of time can cause the drug to accumulate in the body resulting in significantly extended detection times, and leads to the possibility of hair analysis which will be discussed in the later part. The detection times in urine are significantly greater than the detection times in blood because most drugs are rapidly eliminated from blood both by the bodys metabolic system and by excretion into urine (DuPont and Baumgartner, 1995). As the bladder is emptied only a few times during the day, the urine becomes a reservoir of drugs and metabolites (AIC Research and Public Policy, 2003). According to DuPont and Baumgartner (1995), most abused drugs, including their metabolites, fall to low levels in the blood within a few hours of last drug use and so urine samples generally have a short surveillance window (SW) of about l-3 days (see Table 3). AIC Research (2003) also reported that longer detection time of drugs is due to high doses and high urine pH. Despite of its small detection time, urine testing is still a reliable and convenient way of investigating whether a person has abused drugs in the past few days. The comparison between commonly used specimens for drug analysis is shown in Table 3. Case Study One: Stereochemical Analysis Of 3,4-Methylenedioxymethamphetamine And Its Main Metabolites In Human Samples Including The Catechol-Type Metabolite (3,4-Dihydroxymethamphetamine) Objectives This case study aims to determine the enantioselective disposition of MDMA and its major metabolites, 3,4-methylenedioxyamphetamine (MDA), 3,4-dihydroxymethamphetamine (HHMA) and 4-hydroxy-3-methoxymethamphetamine (HMMA) in human urine. The R versus S enantiomer of MDMA and its metabolites in urine samples after administration of known amount of MDMA is also calculated. Other than that, the use of indirect method in determining concentration of MDMA and its metabolites by chemical derivatization is also illustrated. Results and Discussion Urine samples were obtained from seven healthy recreational users of MDMA. They were given a single 100-mg oral dose of (R,S)-MDMA ·HCl (Pizarro et al., 2004). Participants were phenotyped with dextromethorphan for CYP2D6 enzyme activity and all were categorized as extensive metabolizers (Schmid et al., 1985). Urine samples were collected before and after drug administration at 0 to 2, 2 to 6, 6 to 12, 12 to 24, 24 to 48 and 48 to 72 hour time periods, acidified with HCl, and stored at around 20 °C until analysis (Pizarro et al., 2004). The samples and standard solutions were analyzed by GC/MS using achiral column with 5% phenyl 95% dimethylpolysiloxane cross link (15 m Ãâ€" 0.25 mm Ãâ€" 0.25  µm film thickness) before and after a chiral derivatization. MDMA in the urine sample was derivatized using (R)-(-)-ÃŽ ±-methoxy-ÃŽ ±-trifluoromethylphenylacetyl chloride (Figure 16) in ethyl acetate/hexane (50:50) that contained 0.015% triethylamine as described by Pizarro et al. (2003). Derivatization step functions to induce volatility to the sample for GC analysis (Beesley and Scott, 1998). A baseline enantiomeric separation was obtained for all the studied compounds in a single run. Chiral analysis of plasma and urine samples was carried out by combining the extraction procedure developed for the high performance liquid chromatography analysis method for HHMA quantification (Segura et al., 2002) and derivatization steps developed for GC/MS determination of enantiomers of MDMA, MDA, HMMA, and HMA (Pizarro et al., 2003). Extraction and derivatization coupling was not achieved easily because chemical properties of extracted samples make it impossible for the target compounds to be derivatized. The presence of considerable amounts of HCl in t he elution mixture was responsible for the formation of the corresponding amine chlorhydrate salts making amine reaction unfeasible. An attempt using evaporation of extracts to eliminate HCl be