Plot and Precis of the Lumber Room Essay

The text under analysis â€Å"The Lumber-room† written by Hector Munro is the problem psychological story which revolves around a little orphan Nicholas and his tyrannical and dull-witted aunt, who because of the cruel methods of education couldn’t not only find approach to children, but also understand their soul. The conflict between the aunt and the nephew as if the conflict between prose and poetry. But softness, purity and tenderness of soul of the boy could resist to staleness, misunderstanding and callousness of his aunt. The story is narrated in the 3rd person. This allows the reader to access the situation and the characters in an objective manner, because the characters are having both positive and negative viewpoints. The third person point of view is impersonal which fits the impersonal atmosphere of the household. In this text the author colorfully describes interesting childhood of the little boy whose name is Nicholas. The story begins with the exposition when the author describes one morning, when at breakfast Nicolas make a joke as a result of which he is punished. So his cousins are to be taken to Jagborough sands that afternoon and he stays at home. Nicholas’s aunt goes to work in the garden and commands him to stay out of the gooseberry garden. The Aunt is absolutely sure that the boy is determined to get into the gooseberry garden because she has told him he is not to. But despite her punishment Nicolas decides to gain his objective, and from this very moment the complication takes place. Nicholas takes the key from a shelf in the library and sneaks into the lumber room, where he is never allowed to go. He has lots of fun in the lumber room. The lumber-room is described as a storehouse of unimagined treasure. He sees lots of beautiful and strange objects, such as old ornaments, tapestries, and a teapot shaped like a duck. He finds a large square book full of colored pictures of birds. And such birds! They allow Nicholas to learn in a fun and exciting way. The conflict in the story gradually grows and flows into the climax of the text. While he is looking at a picture of a duck, the voice of his aunt came from the gooseberry garden. Nicholas finds that she has fallen into a tank of water, and refuses to help her out on the grounds that she is an alien-impostor. You may be the Evil One tempting me to be disobedient. Justice must be done. The Aunt tasted the fruit of her own punishment on the children and feels what it is like to be condemned. The denouncement reveals the author’s social comment about the differences between the world of the child and adult. Though the Aunt is furious, Nicholas is happy because he is thinking of a tapestry depicting hounds and a stag. And for all life he remembered those amazing things from the lumber-room. The plot of the story seems to me not complicated, even in spite of the fact that many events are crossed with each other. It is ordered chronologically, each episode is given with more and more emphasis. The story is full of colorful descriptions and deep feelings which the reader experiences while reading the text. To sum up, the author’s style is remarkable for its powerful sweep, brilliant illustrations and deep psychological analysis. The story reveals the author’s great knowledge of man’s inner world. He penetrates into the subtlest windings of the child heart. Character The major character of this psychological story, represented as the protagonist is an extraordinary boy Nicholas, who being an orphan is forced to live with his cousins and imperious aunt in the family which in appearance is noble and well-to-do, but as a matter of fact, the family, which frankly speaking lives much to be desired. So from the very beginning a little boy, established the reputation of an incorrigible naughty, frolicsome and absolutely disobedient child, appears in our sight. And the role of his opponent plays the antagonist, a flat character without tendency to develop, in this case, a very proud and oppressive woman, who being Nicholas’s aunt and the guardian at the same time, prevails over the boy, hankering only for one thing, namely for a total control. And suddenly we see Nicholas, the pool boy, being at the mercy of his aunt in another light. Without her tations we can say that Nicholas is a round, multidimensional character, containing a number of qualities and traits, appearing through an indirect method of characterization, so skillfully used by the Author. Into position of a lively prankster, playing practical jokes, which are nothing more, than innocent childish escapades in an attempt to have just an air of independence and fun, comes a resourceful boy with quick imagination, struggling against the great dullness and outrageous injustice. And even in very tense and hopeless situations Nicholas, having a sense of adventure and inexhaustible desire for breaking loose from wearisome reality, shows his genuine originality, proving in my opinion one of the most fantastic and fabulous ability for taking cover in our own imagination in cases, when you really free out of a place and there’s nothing to be done. We remember, that we’re obviously impressed by this clever boy, manages to evade a watchful eye of his aunt, who being a woman of impatience, great indignation and going beset only from the thought of disobedience, punishes him. To be more precise, Nicholas having no fear about resisting such a dictatorial woman, never having a nay with children and constantly being of fine with dissatisfaction, breaks her just another ridiculous prohibition and proving a little bit of sophistication finds himself in a forbidden, but so alluring room, serving for stoning milliard of ancient things, which are most likely meant for an investigative child’s mind than for everlasting vegetation in trour right for life. And exactly this truly gorgeous place bares candidly the boy’s immeasurable soul.

Cultural Boundaries Essay

Youth culture has been studied from several ideological perspectives on assumptions that they are ‘not isolated and untouched by the surrounding culture’ (Keyes, 2000). This notion has lead researchers to assume that youth culture is not part of ‘growing up’, but a phenomenon that occurs as a precipitation of the social, political, cultural and ideological factors. There is not one monolithic youth culture that defines all young people. Popular youth culture embraces a diversity of sub-cultures or â€Å"tribes† such as skaters, druggies, snobs, band geeks, Satanists, Jesus freaks, techno-goths, computer dweebs, blacks, Latinos and white trash. Groups distinguish themselves by dress, style, music, body modification practices, race, ethnicity, and language. (Hines, 1999) Thus a researcher, who intends to study the ethnic, racial, political, cultural, sociological or linguistic aspect of a subculture, often ends up in analysing one of the factors and tend to romanticise or over-politicise these aspects. Thornton’s study on club cultures and Nava’s treatise on youth and consumerism are good examples in this genre. The debates on how best to conceptualise both the structural and cultural transitions of young people remains a central issue in the sociology of youth. In these debates cultural approaches have been criticised for neglecting the role of social divisions and status inequalities in lifestyle ‘choices’ (Bennett 2002). The cultural night lives of young people have provided fertile ground for social researchers. There have been explorations of the character and division of dance scenes (Thornton 1995), the relationship between femininities, women’s clubbing experiences and feminism (Pini 1997a, 1997b), clubbing experiences (Malbon 1999) and the relationship between drug use and clubbing (Henderson 1993; Merchant & Macdonald 1994; Forsyth 1997). What has not been studied so well is how people become clubbers, what practices this entails, what kind of young people invest in this lifestyle, what resources are required to do so, whether this process is gendered as well as if and how this experience has impacted on their sense of identity. Earlier studies portrayed Rave culture as being a social arena where social divisions were put aside and anyone and everyone mixed together (Henderson 1993; Merchant & Macdonald 1994). Yet, more recent studies suggest that distinctions do operate between ‘mainstream’ and ‘hip’ club scenes (Thornton 1995), that ‘nightlife provision exploits existing cleavages in the youth population, and segregates young adults into particular spaces and places’ (Hollands 2002, p. 153). Given this it seems important to unpack further the nature of boundaries: the divisions between ‘us and them’: the boundary work that we do and how boundaries are constituted in social interaction. Thornton asserts ‘club cultures are taste cultures’, but as she also points out, practices of distinction do not just involve taste and cultural hierarchies are numerous (1995, p. 3). What other practices of distinction are involved in identification and differentiation processes, both within and between club scenes? It seems unlikely that these processes and practices are wholly elective. Young people’s experiences of clubbing, their lifestyle ‘choices’, need to be contextualised and conceptualised in such a way that recognise that some young people are more able than others to engage in particular styles of life, and consumer and cultural activities, such as clubbing. Boundaries are about both the individual and the collective, notions not new to youth research. Willis (1978) suggested that ‘becoming’ a hippie or a bike boy involved not only cultural knowledge, but also a process of developing group sensibilities, and these sensibilities could be used to identify and differientiate one group from another. The notion of ‘becoming’ is a way of exploring both individual and group processes (Becker 1991): how young people learn to use ‘recreational’ drugs, learn particular practices, affiliate with a culture, lifestyle or social group and invest in additional forms of identification, as well as encounter cultural barriers that constrain participation and processes of ‘becoming’. Symbolic interactionist theories would suggest that notions of what and who you are, as well as what and who you are not, only become meaningful and significant through interaction with others. When social anthropological and symbolic interactionist conceptualisations of boundaries are brought together they can help us understand how people come to form into collective groups, groups that construct shared meanings through interaction. Symbolic boundaries, group life or how ‘people do things together’ (Becker 1986), are interactional resources that groups draw upon to create their own boundaries. These notions offer a fruitful way to explore the relationship between the individual and the group, and the divisions between ‘us and them’ found in the empirical studies exploring the cultural night-lives of young people. Moreover, it may be that identifying as and ‘becoming a clubber’ may only acquire meaning in relation to and in contrast to those who do not identify as or become ‘clubbers’.

Econ paper Essay Example | Topics and Well Written Essays - 500 words

Econ paper - Essay Example The key reason behind rising student debt is that in the peaceful era, prior to the Great Recession, millions of youthful Americans secured loans to go through university, just to graduate in an economy that did not really need workers any longer. The graduates are thus finding it more difficult to repay their loans than they probably had anticipated (Lankford, 67). Forgiving the student debt would result in an immediate effect on the economy. Responsible individuals who devoted themselves to pursing a university education would have more extra dollars every month to use and this would fuel the economy presently. The extra dollars being pumped into the economy would result to a multiplying outcome, unlike most of the provisions of the latest incentive package. Consequently, there will be an increase in tax revenue, the credit markets will be active and there will be creation of jobs. Consumers spending accounts for more than two thirds of the whole US economy and in the current months, there has been a decrease in consumer spending at an alarming and extraordinary rate. Thus, it is reasonable to argue that the quickest manner of reviving the ailing economy is to act drastically to get consumers to spend (Lankford, 68). This proposal would rapidly regenerate the housing market, travel and tourism industry, the automobile industry, durable goods and other numerous sectors of the economy. This is because the individuals who maintain those sectors will have a lot of extra dollars to spend per month. The motivating factor in the economy today is fear. Unless the individuals in the middle class feel comfortable enough that they will have their health insurance, jobs and additional money to use not just the following month, but the month following that, the economy cannot and will not indeed grow fast enough to avoid the bleeding (Lankford, 69). According to analysts, the student debt loan has a broad economic impact. In a report that was published

The Implementation of Social Learning Theory by Anytowns Department of Essay

The Implementation of Social Learning Theory by Anytowns Department of Job and Family Services - Essay Example The forceful separation of a child from its parents will lead to the emotional turmoil of all the family members involved in the issue, no matter how legally and theoretically justified an organization is in doing so. However, the cases have to be studied closely because there are many instances where the parents can pose real threat to the physical existence and mental health of children. In such cases, there cannot be any other option than separating children from their homes. The key factors that should determine it has to be clear evidence, proper understanding of the situation and ensuring the well-being of the child who is taken to the care of the state or foster care services. It is possible that the department has misinterpreted/misappropriated the finding of Social Learning Theory, which states, â€Å"aggressive children have parents who use similar tactics when dealing with others. For example, the children of wife batterers are more likely to use aggressive tactics themselves than children in the general population, especially if the victims (their mothers) suffer psychological distress from the abuse†. The quantitative nature of the study makes it impossible to judge isolated cases where children who feel more secure with their parents who happened to be abusive on rare occasions, than to be brought up in an institutional ambience. Moreover, there could be instances of some parents losing their control over themselves under the influence of intense emotional turmoil due to extraneous affairs.

Why Extrinsic Essay Example | Topics and Well Written Essays - 250 words

Why Extrinsic - Essay Example The failure of organization to provide perceived equity for employees results in a lot of resentment (especially when there is secrecy and people overestimate each other’s pay) and resulting inefficiencies. The failure of extrinsic rewards is even more obvious in executive positions as incentive systems had very weak or negative correlations to corporate profits as at higher incomes, prospect of more money fails to be a motivator. Locke’s (1960) research suggests a reason for such results – incentives actually discourage risk-taking and people perform easier tasks to complete as much work as possible. Employees look at short-term benefits (monetary rewards) rather than long-term organizational interests. Another research proved that in the long-term, even the removal of a financial incentive system that has been long in place could not drive down productivity. Merit pay has also failed as a motivator of performance as few managers feel that higher pay would make them work harder. Therefore, intrinsic rewards such as training and goal-setting is a much stronger motivator of performance. To treat workers with respect and appreciation is what motivates them to stay at an organization and higher pay has failed to reduce employee turnover in the

EXPRESSION ON B CELLS IN HEALTHY INDIVIDUALS AND IN CHRONIC Literature review

EXPRESSION ON B CELLS IN HEALTHY INDIVIDUALS AND IN CHRONIC LYMPHOCYTIC LEUKIMIA - Literature review Example Components of the immune system such as the white blood cells protect the body through the creation of specific antigens. However, in some cases, the immune system itself can be a source of problems, such as in autoimmune diseases, where the immune system recognizes cells of the host body as invaders and attacks these. The cells that form an important part of the immune system can also function incorrectly. Chronic lymphocytic leukemia (CLL) is one example of a disorder where the cells of the immune system are functioning incorrectly. This is a cancer where the B cells of the immune system are highly activated, show increased levels of proliferation and decreased rates of apoptosis. This results in the accumulation of affected cells, which prevents the immune system functioning normally. This review considers the role that Toll-like receptors (TLRs) have on immune system functioning, with a specific focus on CD180 (also known as RP105) and its role on CLL. Toll-like Receptors The imm une system plays a crucial role in protecting the body against pathogens and allows the body to effectively defend itself. One class of molecules that have been shown to have an important role in the effectiveness of the immune system is Toll-like receptors (TLRs). ... Image from Akira et al. (2001) However, while the TLR pathway has been shown to be crucial for the defense and protection of the body, it also can have a significant role in immune system diseases and allergies. This can be due to high levels of signaling or deficiencies of molecules that are involved in the signaling pathway . Thus, TLRs play a significant role in the immune system and related diseases. Understanding their functions both collectively and individual is important to understand the occurrence and progression of many different diseases, as well as looking for treatment for these. Studies have revealed that one potentially important TLR in many immune system diseases is CD180, also known as RP105. This molecule is expressed on the outer membrane of B cells that is known to be a leucine-rich repeat (LLR). LLRs are known to be important in the way in which pathogens within the immune system are recognized. A homolog of the protein has been found on mouse B cells, and has b een associated with a decreased rate of cell death. Experimental evidence shows that cells that were negative for CD180 were susceptible to apoptosis induced by corticosteroids, while those that expressed CD108 were not . In mice, almost all mature B cells expressed CD180; however, this is not true in humans. For example, in individuals suffering from systemic lupus erythematosus (SLE) almost 16% of patients tested were not expressing CD180 in a significant quantity. Individuals who did not have SLE had a significantly lower average level of CD180 expression than those who were affected with SLE . In humans, CD180 is involved in the recognition of B cells and signaling of lipopolysaccharides. However, little more is known about its function . In mice, almost all

Is it worth investing in a pension (UK context) Dissertation

Is it worth investing in a pension (UK context) - Dissertation Example (Nader, 1991). As such, the overall importance of investing into pensions is critical from the point of view of maintaining a certain level of life style. It also ensures that the individuals have the sufficient funds apart from the State related benefits to maintain a very decent life style. (Lluberas, 2007). This is also evident from the fact that the overall pension funding gap is increasing rapidly every year and individuals require up to ?10,000 every year to fill that pension gap and the overall gap will be over ?300 billion per year.1 Trends also suggest that as the population ages, the overall ratio of people working to support the State Pension will decrease from 3.32 in 2001 to 2.44 in 2060. This decline in the overall number suggests that more and more people will be on the State Pension and as such the overall benefits may continue to decline due to the increasing pressure on the government to pay off State Pension to such large number of people every year. (Bonoli & Shin kawa, 2005) It is however, important to note that the different studies have suggested that the pension funds in which individuals invest for their pensions may not be performing well. Though most of the pension funds in UK achieved positive returns in 2010 however, considering the long term nature of such investments, it may be relatively arbitrary to conclude that the pension funds can provide sufficient and desired returns to ensure that the investors (individuals) will have sufficient pensions to live a comfortable retirement life. (Blake,2000) The choice of this topic has been mostly based on the assumptions that as the number of people grow and rely more on the State Pension, their overall standards of living may decline sharply when they are in the retirement age. Such sharp decline in the standards of living therefore requires that the people must consider investing into the Pensions from the days when they are earning higher amounts every year. (Cohen, 1981). A gradual cont ribution of the certain sum of money every year can help individuals to become more self sufficient in their retirement age. However, given the fact that the overall performance of the pension funds has not been up to the mark in recent times, a natural question arises as to whether it is rational to invest into pension funds? Could they provide the desired returns to the individuals when they are in retirement so that they can live a more comfortable life? Considering the above situation, the logical question also arises as to whether it is good to invest into pension funds? Can pension funds provide the desired level of returns over the period of time to ensure that they meet the objectives of the pension holders? The basic aim of this paper therefore is to explore and analyze the question of whether it is good to invest in pensions with special reference to UK market. This research project will also attempt to explore the question of whether the tax saving benefits can help the p ension industry, are there any factors which provide the incentive to save for the pensions considering the factors such as job mobility, with the stretching of the pension age by the government, what effect this could have on the overall planning for the retirement life of the

Tower of london Essay Example | Topics and Well Written Essays - 1000 words

Tower of london - Essay Example It has also served as a historic landmark in England because it was the venue of the execution of three of the past queens of the land. The Tower Bridge is a symbol of technological and economic superiority of the English civilization, besides being a historical landmark. The Tower Bridge stands strong today, and it is expected to continue being a symbolic structure in London. This paper reviews the technological and economic significance of the Tower Bridge of London. The technology used to develop the Tower Bridge of London surpasses many in the 19th Century. The Tower Bridge was constructed to ease traffic across the Thames because London was crowding owing to population increase. Unlike other constructions, the authorities in London took more than eight years to design the structure. Their goal was not only to develop a bridge that would solve the issues of traffic in crossing the Thames, but a structure that would stand the test of time. They wanted to develop a bridge that would be used for centuries. Horace Jones and John Wolfe Barry were the contracted architects for the bridge, and they completed the design in 1894. The framework of the Tower Bridge of London was made of 11,000 tons of steel. The bridge is 265 meters long, and it was designed in a Victorian gothic architecture. One of the most intriguing aspects of the Tower Bridge of London is the movable bridge. The bridge splits into two and is raised mechanically to accommodate the pa ssage of large boats heading to the harbor. The bridge was contracted very close to the harbor, and this brought the challenge of building it too high to accommodate the boats, but the designers came up with the moveable bridge technology. The technology remains viable to date because larger vessels have been developed and they cruise through the moveable bridge very safely. The movable bridge was initially powered by steam power. The steam was used to create sufficient pressure to pump

The Reform Movement Essay Example for Free

The Reform Movement Essay 1: Temperance: moderation of self, restraint in action, statement and self-control or PROHIBITION. Americans were worried about the effects of alcohol. 1st. This movement first urged people to stop drinking hard liquor and limit drinking beer and wine to small amounts. Later the movement wanted to ban the sale of alcohol-banning became a major goal, it was banned in the 18th Amendment, which was later repealed by the 21st Amendment. 2: Women’s Rights: women couldn’t vote in many states and had little control over own property; could not get a higher education; didn’t get equal pay for equal work; weren’t allowed to enter traditional male professions. Declaration of Independence: signed by 100 people began to shape the future of women’s rights movements. Fight turned into a political movement many women were arrested and jailed in 1860 states gave women rights of ownership, but many reforms (right to vote) weren’t achieved. Lucretia mott and Elizabeth Cady Stanton organized Seneca Falls Convention wrote Declaration of Sentiments for Convention. Susan B. Anthony had organized skills that further helped the movement. Led campaign for equal pay for equal work, allowing women to enter traditional professions, and for changing laws regarding women’s property. Organized petitions for new laws that were passed. 3: Public Education: families did not expect formal schooling because they needed children to work to help support the families. Common-School Movement: which wanted all children educated in a common place, regardless of class or background. It set the standard for education reform and brought children out of factories. Horace Mann: leading voice of education reform in mid 1800’s. He explained the idea of the Common School. 4: Abolitionism: Slavery in America. a movement was formed (ABOLITION) to completely end slavery in U.S. Did this through news papers, articles and pamphlets, speeches. PROPAGANDA use written word and pictures to get sympathy. Eventual end of slavery: North outlawed, South refused because they needed help with the economy. William Lloyd Garrison: published abolitionists newspaper, The Liberator. Frederick Douglass: former slave who became one of the most important African American leaders of the 1800’s. Sojourner Truth: African American who became famous from her dramatic and fiery speeches. Harriet Beecher Stowe: wrote Uncle Tom’s Cabin. the most powerful anti-slavery novel ever written. 5: Prisons: terrible prison conditions. 2 and 3. state hospitals for mentally ill were created. Reform schools were established for children in prison. Houses of correction were established, which tried to change prisoners’ behavior through education. 4. Dorothea Dix: middle-class reformer who helped change the prison system by reporting on terrible prison conditions.

Meritocracy As An Ideology Sociology Essay

Meritocracy As An Ideology Sociology Essay Meritocracy can also refer to an idealised society where discrimination on the basis of race, nationality, gender, age, and other irrelevant characteristics is completely absent. Merit is the encompassing value, the basic and morally correct criterion for any and all social classifications, particularly in respect to socioeconomic standing and in public space. A notion, emphasising societal consensus on the means and processes of selection for particular roles through a system of sifting, sorting, and rewarding talent and ability, motivated by competition for qualifications that in turn structure access to wealth, prestige, and personal satisfaction. It is conceived as a repudiation of systems like aristocracy where individuals inherit their social status. A meritocracy resembles aristocracy in the classical sense of the term meaning rule by the best. What has happened over the centuries, however, is that aristocracy has become associated with hereditary privilege and a rigid class s ystem. Instead of this, a meritocracy promotes worthy individuals regardless of which social strata they happen to be born in and each individual has good fortune in proportion to the individuals deservingness (Rawls, 1999, Nozick 1974, Miller 1999). IQ tests primarily tap analytical, logic-based reasoning; and surely that kind of cognitive ability is related to performance in many job settings. But other kinds of cognitive ability are also related to performance and thus also represent merit. For instance: imagination, practical sense, and the ability to interpret others perspectives. By the same token, the effort component of Youngs formulation suggests that a number of personality factors may figure into a reasonable conception of merit. For example, being conscientious may enhance job performance. Of course, some individual traits and social skills may be rewarded because they reflect conformity to arbitrary group norms. It is not clear why the term merit should be identified so closely with mental ability as distinct from many other conditions and traits that improve the chances of social and economic success (Hauser et als, 2000, p. 203). David Miller (1996, 300) eluding on Walzer (1983) has indicated that a meritocracy is not only more stable but also more socially just if there are a number of socially recognised forms of merit: economic contribution would be one kind of merit, education and scholarship another, artistic achievement a third, public service yet another, and so forth. However these other conditions and traits do not contribute to a fair opportunity. In Rawls view, the correlation between ones social origins and ones outcome in life is zero in a meritocracy and as long as some form of the family exists in society fair opportunity cannot be achieved as (Rawls 1971, 64). The social context within which individuals grow up influences the achievements of equally competent persons. Success in the labour market is transmitted from parents to children, and the advantages of the children of successful parents go considerably beyond the benefits of the best education, wealth and genetic cognitive ability. Many of the criteria associated with individual talent and effort do not measure the individual in isolation but rather parallel the phenomena associated with aristocracy; what is called individual talent is actually a function of that individuals social position or opportunities gained by virtue of family and ancestry. Among these, for example, one might list ambition or drive, perseverance, responsibility, personal attractiveness, and physical or artistic skills or talents, along with access to social support and to favourable social and economic networks and resources. Access to education is partly defined by inheritance as much research has demonstrated (Bowles and Gintis, 2002; Bourdieu and Passeron 1990; Aschaffenburg and Maas 1997; Sacks, 2003; Ballantine 2001). Compiling evidence from other studies Herrnstein concludes that 80% of the differences in IQ among individuals is explained by inherited factors and 15% is explained by environmental factors (Herrnstein 1971, 171). Children from the upper class get upper class education, middle class children get middle class education, working class people get working class education, and poor people get poor education. Privileged young people can perceive reachable goals and develop lofty aspirations because they tend to benefit from high expectations and support networks from the fa mily and social milieu, as well as extensive economic and educational resources. Those who have the resources, via their parental background, will move through higher education, get well paid jobs, and postpone family plans until they are well into their thirties, building their financial and cultural capital significantly prior to family formation. Inheritance may provide access to powerful forms of social capital (who you know) and cultural capital (what you know). Bourdieu Passeron (1990) indicate that students who lack the required knowledge and skills with which to successfully navigate the parameters of middle class culture inevitably fail at school. It therefore seems that unequal educational opportunity is the driver of individual achievement. Research shows that as class rises so does the level of education. As a consequence, the expansion of higher education will broaden the gulf between rich and poor (Blanden et al. 2005). So achievement capacities are ascribed to social class. Thus, IQ tests measure intelligence as a reflection of inherent intellectual capacity combined with environmental influences. Thus parents can predispose their children to succeed or fail in life as they are a part of the environment that affect the abilities that children attain. Thus the first and foremost among non-merit factors is the effect of social class at birth on future life. Therefore truly equalizing childrens environments in an effort to create a system with equal opportunities for all would mean having to eliminate the family. Meritocracy thus could lead to a hereditary caste system that, far from promoting social mobility, actually makes social advancement nearly impossible for the lower orders. This could be the case if wealth and social position are or primarily distributed by unchangeable genetic characteristics of individuals. This argument can be reworked into the form of a Hernsteins syllogism: 1. If differences in mental abilities are inherited, and 2. If success requires those abilities, and 3. If earnings and prestige depend on success, 4. Then social standing (which reflects earnings and prestige) will be based to some extent on inherited differences among people. (Herrnstein 1971, 197-8) This implies that absolute equality of opportunity is an ideal that cannot be achieved. (Loury 1977, p. 176). For John Rawls, the question of distributive justice is rather different. He is not content to say that any person begins at some point in the process of acquisition and then is merely constrained by a set of rules and procedures to ensure fairness. Rather, the socioeconomic position of the agent is also considered. Rawls bases his query on how the agent is presented with the distribution of talents and social position. His conclusion is that these distributions are accidental and arbitrary. It is an accident that someone is born with whatever natural traits he may possess. The question is raised whether a meritocracy based on natural abilities is thus unfair. Some might contend, for example, that even if we do not deserve our natural abilities it is not unfair if we reap the rewards of those abilities because the system of reward is independent of the system of deserts. However, Rawls makes the case that social position is also random and arbitrary. The fact that natural abilities may or may not be rewarded in that society is an accident. To be rewarded based merely on an accident is not deserved. Thus, a meritocracy that is based on reward from undeserved social position is similarly unfair. Therefore, both natural abilities and social position may not be the basis of distributive justice because they are unfair. The naturally advantaged are not to gain merely because they are more gifted. The individual cannot help how she begins life. Why make her pay for her positive talents and advantages? The rectification of these disparities in Rawls is his difference principle that makes all inequalities subject to the stipulation that the least advantaged will benefit from them.

Fair Value Practice: Suitability in Accounting

Fair Value Practice: Suitability in Accounting Introduction The issue of the use of fair value as a model for financial standards and reporting has been subjected to significant debate and argument since the IASB[1] Framework was first introduced in 1989. As can be seen from a number of accounting industry responses, such as that of Peter Willams (2005), the use of fair value is becoming increasing contentious and could pose difficulties for the ISAB. Some fear that if this issue is not addressed to the satisfaction of all parties, it could affect the power and influence of the ISAB. The intention within this paper is to discuss the theoretical concept of â€Å"fair value† and to assess its suitability of use for accounting reporting purposes. The paper will also look at the practical application of the â€Å"fair value† measurement as determined by the IASB within their current international reporting and accounting standards. The Concept of Fair Value The concept of â€Å"fair value† is to enable recognition of the reliable economic future value of certain assets and expenses, the latter of which is intended to ensure the correct level of increase or decrease of balance sheet assets or liabilities. The result of this method is to create a defined link between income and expense to reflect the movement in the value of assets and liabilities. For those who promote the concept of fair value, or what is sometimes known as fair â€Å"market† value, it is the sale price achieved for an asset offered on the market at the time of the statement, based upon the reasonable opinion of a professional evaluator (A.M. King 2006, 45). Fair value at present has no specific and identifiable measurement definition within current international accounting standards. It is currently determined through an amalgamation of a number of different and diverse accounting measurements used by corporations in accounting and financial reporting, although these models all have their disadvantages. For example, in the case of the historical cost measurement basis, fair value is deemed to be at the measured at the date of purchase, as this reflects market value at that time. Although this model is seen as one of the least volatile methods of value measurements, it is perceived to have shortcomings. The main issues are that cost dates are earlier than sale date leading to a potential for profit overstatement, and that it is not the ideal model on which to based future business decisions. In fact some commentators see that the current moves on fair value, although they may signify a move away from the less volatile performance of the previously used historical cost method, produce a measurement that is more in line with the real volatility of life and business activity generally (Mary Barth 2006, p.324). An alternative measurement, which uses a price index system such as the RPI[2], and is still based on transactions, is current purchasing power. The fair value determination here is set to reflect the capital of the business in relation to the general price trends. The difficulty with this model is that it assumes all prices move in line with the index, which is clearly not the case and thus can create an artificial monetary unit. The replacement cost and net realisable value model (NBV) use a fair value system based upon market entry and exit costs respectively. The former has the advantage of being able to calculate current values on a realistic basis, and can therefore identify gains in operating and other business areas, thus preserving the capability of the business. However, its subjectivity is aggravated by the speed of technological development and the fact that this leads to the possibility of no similar asset being available to compare values. The NBV model is clearer as it is based upon the probable selling price of the asset. It also does away with the estimation of depreciation as that selling price already reflects this. However, NBV does not take into account that the majority of assets are not disposed of, but utilised within the business. The problem with this calculation of fair value can threaten the concept of the business being a going concern. The ISAB intend to move towards a definitive fair value model, which supporters see as a positive action, the cost of which will not â€Å"be significantly higher than the cost of trying to implement the mixed measurement system† (Langendijk et.al. 2003, p.292). Mary Barth (2006), a member of the IASB, agrees with this statement, adding that a more definitive â€Å"fair value† model will assist in the elimination of some of the perceived volatility presently in existence. However, the opponents are equally vocal in their objections. A.M. King (2006, p.45) poses the question whether â€Å"all assets on a balance sheet [should] be shown at Fair Value?,† continuing to comment that the ability to achieve a particular model does not necessarily mean that it should be implemented. De Vries (quoted in Langendijk et.al. 2003, p.174) also questions whether it is a move in the right direction for financial reporting, and others fear that it will lead to less, rather than more reliance upon financial statements by investors and other stakeholders (Peter Williams, 2005). In the author’s opinion it appears that, whilst professional preparers of financial statements understand the concept of the â€Å"fair value† model being sought, those who utilize the statements as a basis for making investment and other business decisions, including stakeholders of all sizes, find difficulty equating the results with other factual information. In addition, the term fair value will only be valid at the date of preparation of the statement and, as a result, itself becomes historic from that moment. Thus, there is an argument for maintaining its use with the commonly used historical cost model. Use of Fair Value in accounting and reporting standards The term â€Å"fair value† is liberally spread throughout the international accounting and reporting standards. It is referred to in four of the IFRS[3]’s and at least fourteen of the international accounting standards, as shown in the summaries of the IAS (2006). The context of fair value within IFRS relates to treatment of the initial adoption of the standards, business combinations, insurance contracts and non-current assets and discontinued operations. In terms of the initial adoption, IFRS grants exemption of some non-current assets from the fair value model. The intention of the inclusion of fair value here is to ensure that the movement in the market value of an asset or liability, in other words the increase or decrease in value, is reflected within the financial statements at the prevailing date of those statements, identifying if this is different from actual cost. With the movements being recognised within the profit and loss, the anticipated result is to enable, a more accurate reflection of the capital (or share) value of the business at the given date (Antill and Kenneth 2005). In addition, IFRS demand that these fair value measurements be performed at each subsequent financial and accounting statement date, thus endeavouring to provide for the organisation’s Balance Sheet to reflect the impact of market conditions at all times. The inclusion of fair value within the international accounting standards is concentrated mainly within the areas of assets and liabilities, and in relation to specific business sectors, such as banks and similar financial organisations (IAS 30), Investment property (IAS 40) and agriculture (IAS 41). Two of the IAS’s do relate specifically to non balance sheet items. IAS 18 deals with fair value within the context of revenue. In this respect, it deals refers to the treatment of deferred income, where the fair value is achieved by the discounting of future receipts. The intention here is to take into account the change in revenue value by deferring the time of receipt, for example, how a rise in RPI[4] might influence the income in real terms. In IAS 21, which deals with foreign exchange transactions, the presenter of the financial statement is required to determine a fair value in the foreign currency in question before converting at the exchange rate applicable at the determination date. When dealing with the treatment of assets, impairment of assets and liabilities, as in IAS 16, 17 and 19, the fair value model intends the financial statements to include a valuation that accurately reflects the realisable worth in the marketplace of that asset or liability at the date of the valuation, notwithstanding whether the intention is to retain or dispose of that asset. In this respect fair value differs from historical cost accounting, which records the value of such items as at the date of purchase and, in many cases applies a depreciation content to the items, irrespective of their worth to a prospective purchaser. The historical cost result is twofold. Firstly, the financial statement recognition of any gain or loss against the real market value of an item may be delayed by several years and secondly, the statements will therefore not portray an accurate and fair view of the real value of the business at the date of the statements. The fair value model aim is to accurately align the varying fortunes of the business and its capital worth with the market forces of the date, allocating gains and losses within the period of time that they actually occur, rather than, as is the case with the historical cost model, creating an unrealistic movement in value within the space of one accounting period. A simple example of this in action is where, in the historical system, depreciation is attached to an asset at a predetermined annual rate, annually reducing the asset value. In reality, the sale of that asset would often achieve greater value than the statements showed, leading to a sudden annual increase in profits and growth in capital. Fair value proponents’ state that, by reassessing the market value on an annual basis, the real annual growth achieved by a business entity is more accurately defined, and that this provides investors with statements from which they can make more realistic judgments and use of as comparisons against other organisations, which is of benefit in their investment decision making process. Conclusion The core intention in the adoption of a fair value model as the most appropriate method of measurement for financial and accounting statement is to create a balance sheet and capital value of an organisation that accurately reflects the real market position of that organisation at the date of the statement. One difficulty and concern with this is the inherent problem in the evaluation and establishment of the fair value in respect of all of the items included within the statements. Langendijk et. al. 2003, p.52). At the time of this paper, the IASB has entered into further discussions with the various parties involved with, and affected by the fair value model. This is an attempt to arrive at a clearer definition of the model itself, and to seek a position on fair value, which is more acceptable for the future. References Antill, Nick and Lee, Kenneth (2005). Company Valuation Under IFRS: Interpreting and Forecasting Accounts Using International Financial Reporting Standards. Harriman House Publishing. UK Barth, Mary (2006). Fair Values and Financial Statement Volatility. International Accounting Standards Board, UK. ISAB Framework (2001). Framework for the preparation and presentation of Financial Statements. International King, A.M (2006). Fair Value for Financial Reporting: Meeting the New FASB Requirements. John Wiley Sons Inc., New Jersey, US. Langendijk, Henk., Swagerman, Dirk and Verhoog, Willem (eds) (2003). Is Fair Value Fair?: Financial Reporting from an International Perspective. John Wiley and Sons Ltd. UK Staff Team (2004). Fair Value Accounting and Financial Stability. European Central Bank. Occasional Paper Series, No. 13, April 2004. Retrieved 19 January 2007 from http://www.ecb.int/pub/pdf/scpops/ecbocp13.pdf Summary of International Accounting Standards (2006). International Accounting Standard Boards. Retrieved 20 January 2007 from http://www.iasb.org/Home.htm Williams, Peter (2005). Accounting – The next wave of convergence. Financial Director, 1 Feb 2005. 1 Footnotes [1] International Accounting Standards Board [2] Retail Price Index [3] International Financial Reporting Standards [4] Retail Price Index

Genii’s In the Making Essay -- Science Technology Mechanics Essays

Genii’s In the Making â€Å"†¦molecular machines of nanotechnology will increase, by orders of magnitude, our individual and collective capacity to transform desires into material reality† (Crandall, viii). What is the goal of technology? Most answers include some form of ways of increasing speed, or decreasing size all for the ultimate goal of convenience. Ok, so what is convenience? Convenience is the skill level at which something can be achieved, in other words, how desires can be met. So the true goal of technology is to assist in meeting desires. The quicker and smaller technology is, the easier it is to obtain those desires. Nanotechnology is the newest wave of technology that will potentially make a huge breakthrough in technology’s goal. Though not a science secure as of yet in our world, it is waiting for the time to make its momentous break though into the modern world, bringing with it a global effect on the human way of life. Nanotechnology is defined as â€Å" a technology executed on the scale of less than 100 nanometers, the goal of which is to control individual atoms and molecules, especially to create computer chips and other microscopic devices† (Webster’s Dictionary, 1999). In the early 1970’s an MIT student by the name of K. Eric Drexler came up with the idea of manufacturing things, both biological and non-biological, from the molecular level up. Drexler noticed the amazing talents of natural biology and wondered if humans could mimic biology on a mechanical level, â€Å" what if you were able to design them [molecular machines] and get them to do, locally, the kinds of thing you see them doing in nature, but yet have those parts [molecular machines] fit together in a new way to make a†¦pattern... ...M., Lewis, J. (1995). Prospects in Nanotechnology: Toward Molecular Manufacturing. New York, NY: John Wiley & Sons, Inc. 4)Random House Webster’s College Dictionary (1999). New York, NY: Random House, Inc. 5)Hengerer, R., Illsley, M. Nanotechnology and Business: The Power of Being Small. 03/07/05 www.accenture.com. 6)Ghandchi. S. Is Nanotechnology Real?. (03/07/05) www.iranscope.com. 7)Ricadela, A. Q&A: Former Intel Exec and Direction Les Valdasz. (03/16/05)www.informationweek.com/shared.printableAriThe cleSrc.jhtml?artivclID=60401273. 8)Stodder, D (April, 2004). The Mobil Mandate. (03/16/05) www.intelligententerprise.com/article=18700554. 9)Ricadela.A.( 10/18/2004). What the Future Holds. (3/16/2005) www.informationweek.com 10)Ricadela, A. (02/01/2005). HP Reports A Nanotech Breakthrough. (3/16/05) www.informationweek.com.

Dissociative Identity Disorder Essay -- Biology Essays Research Papers

Dissociative Identity Disorder (DID), formerly known as Multiple Personality Disorder (MPD) is considered by the American Psychiatric Association to be one of 4 main kinds of dissociative disorders (DSM-IV): "The essential feature of dissociative disorders is a disturbance or alteration in the normally integrative functions of identity, memory, or consciousness" (8). If identity is the main function affected, the person is said to have DID. Most non-DID people have one identity comprised of many parts that work harmoniously together. They have only one I-function which consists of a conglomeration of thoughts and feelings formed from connections between many different brain areas. People with MPD, however, have a decentralized, internal network of 2 or more I- functions or "alters," each with its own physiology, behavior, and cognitions. Dissociation often enables victims to maintain a relatively healthy level of functioning because traumatic memories are disconnected from other information in their minds. A multiple presents her view of DID: "We do not SUFFER FROM MPD. We SURVIVE because of MPD" (6). Living with this disorder is often an extremely lonely, confusing experience. Luckily, there has been much success in treating this disorder thanks to the extensive research conducted into DID etiology. The etiology may be explained by the diathesis-stress model. There appears to be a biological component given the fact that most people with DID have a family history of the disorder. It has also been found that people who are easily hypnotized are more susceptible to DID (5). The stress is known to come from severe physical, emotional, and/or sexual abuse at a developmentally sensitive stage in childhood (3). When a per... ...ted. Another possibility is that everyone possesses different centers of connections and somehow after repeated dissociation episodes, some people's links become severed. Findings from DID research may be helpful for DID and non-DID sufferers alike. Research into this area has shed a lot of light into what kinds of cognitions lead to healthy functioning, among the most important of which are the need for a sense of control and self-love and respect. The research also highlights the interconnectedness of the mind and body: the fact that the psychological has a very real affect on the physiological and vice versa. Internet Sources: http://www.sidran.org/casa.html http://www.sidran.org/didbr.html http://rossinst.com/case2.htm http://www.rossinst.com/2yr_study.htm http://www.trauma-pages.com/vanderk4.htm http://www.trauma-pages.com/vanderk2.htm

Cystic Fibrosis

————————————————- Introduction Cystic fibrosis  (also called  CF  or  mucoviscidosis) is an  autosomal  recessive  genetic disorder  that affects most critically the  lungs, and also the  pancreas,  liver, and  intestine. It is characterized by abnormal transport of  chloride  and  sodium  across an  epithelium, leading to thick, viscous secretions. The name  refers to the characteristic  scarring  (fibrosis) and  cyst  formation within the  pancreas that was first recognized in the 1930s.Difficulty in breathing  is the most serious symptom and results from frequent  lung infections  which are treated with  antibiotics, therapies and several other medications. Other  symptoms, including  sinus infections,  poor growth, and  infertility affect other parts of the body. A breathing treatment for cystic fibrosis, usi ng a mask nebulizer and a ThAIRapy Vest A breathing treatment for cystic fibrosis, using a mask nebulizer and a ThAIRapy Vest CF is caused by a  mutation  in the  gene  for the  protein  cystic fibrosis trans-membrane conductance regulator  (CFTR).This protein is required to regulate the components of sweat,  digestive  juices, and  mucus. CFTR regulates the movement of  chloride  and  sodium ions across epithelial membranes, such as the alveolar epithelia located in the  lungs. Although most people without CF have two working copies of the CFTR gene, only one is needed to prevent cystic fibrosis due to the disorder's recessive nature. CF develops when neither gene works normally (as a result of mutation) and therefore has  autosomal recessive  inheritance.CF is most common among  Caucasians; one in 25 people of European descent  carries one  allele  for CF. The  World Health Organization  states that â€Å"In the European Union, 1 in 200 0–3000 new-borns is found to be affected by CF†. Individuals with cystic fibrosis can be diagnosed before birth by  genetic testing or by a  sweat test  in early childhood. Ultimately,  lung transplantation  is often necessary as CF worsens. ————————————————- Signs and symptomsThe hallmark symptoms of cystic fibrosis are salty tasting skin,  poor growth and poor weight gain despite a normal food intake,  accumulation of thick, sticky mucus, frequent chest infections, and coughing or shortness of breath. Signs and symptoms often appear in infancy and childhood, such as  bowel movement obstruction  in new-born babies. As the children grow, they must exercise to release the mucus present in the alveoli. Ciliated  epithelial cells present  in the patient have a mutated protein that leads to abnormally viscous mucus production.The poor growth in children typically presents as an inability to gain weight or height at the same rate as their peers and is occasionally not diagnosed until investigation is initiated for poor growth. The causes of growth failure are multifactorial and include chronic lung infection, poor absorption of nutrients through the gastrointestinal tract, and increased metabolic demand due to chronic illness. In rare cases, cystic fibrosis can manifest itself as a coagulation disorder. A double recessive allele is needed for cystic fibrosis to be apparent.Young children are especially sensitive to vitamin  malabsorptive disorders because only a very small amount of vitamin K crosses the placenta, leaving the child with very low reserves. Because factors II, VII, IX, and X (clotting factors) are vitamin K–dependent, low levels of vitamin K can result in coagulation problems. Consequently, when a child presents with unexplained bruising, a coagulation evaluation may be warranted to determine whet her there is an underlying disease. Lungs and sinuses Lung disease results from clogging of the airways due to mucus build-up, decreased  mucociliary clearance, and resulting  inflammation.Inflammation and infection cause injury and structural changes to the lungs, leading to a variety of symptoms. In the early stages, regular incessant coughing along with copious  phlegm  production, and decreased ability to exercise are common. Many of these symptoms occur when  bacteria that normally inhabit the thick mucus grow out of control and cause pneumonia. In later stages, changes in the architecture of the lung, such as pathology in the major airways (bronchiectasis), further exacerbate difficulties in breathing.Other symptoms include coughing up blood (hemoptysis), high  blood pressure  in the lung (pulmonary hypertension),  heart failure, difficulties getting enough  oxygen to the body (hypoxia), and respiratory failure requiring support with breathing masks, such asà ‚  bi-level positive airway pressure  machines or  ventilators. Staphylococcus aureus, Haemophilus influenzae, and  Pseudomonas aeruginosa  are the three most common organisms causing lung infections in CF patients. In addition to typical bacterial infections, people with CF more commonly develop other types of lung disease.Among these is  allergic bronchopulmonary aspergillosis, in which the body's response to the common  fungus  Aspergillus fumigatus  causes worsening of breathing problems. Another is infection with Mycobacterium avium  complex (MAC), a group of bacteria related to  tuberculosis, which can cause a lot of lung damage and does not respond to common antibiotics. Mucus in the  paranasal sinuses  is equally thick and may also cause blockage of the sinus passages, leading to infection. This may cause facial pain, fever, nasal drainage, and  headaches.Individuals with CF may develop overgrowth of the nasal tissue (nasal polyps) due to inflammati on from chronic sinus infections. Recurrent sinonasal polyps can occur in as many as 10% to 25% of CF patients. These polyps can block the nasal passages and increase breathing difficulties. Cardiorespiratory complications are the most common cause of death (~80%) in patients at most CF centers in the United States. Gastrointestinal Prior to prenatal and  newborn screening, cystic fibrosis was often diagnosed when a newborn infant failed to pass feces (meconium).Meconium may completely block the  intestines  and cause serious illness. This condition, called  meconium ileus, occurs in 5–10%  of newborns with CF. In addition, protrusion of internal  rectal  membranes (rectal prolapse) is more common, occurring in as many as 10% of children with CF, and it is caused by increased fecal volume, malnutrition, and  pressure due to coughing. The thick mucus seen in the lungs has a counterpart in thickened secretions from the  pancreas, an organ responsible for provi ding digestive  that help break down food.These secretions block the  exocrine  movement of the digestive enzymes into the  duodenum and result in irreversible damage to the pancreas, often with painful inflammation (pancreatitis). The  pancreatic ducts  are totally plugged in more advanced cases, usually seen in older children or adolescents. This causes atrophy of the exocrine glands and progressive fibrosis. The lack of digestive enzymes leads to difficulty absorbing nutrients with their subsequent excretion in the feces, a disorder known as malabsorption. Malabsorption leads to  malnutrition  and poor growth and evelopment because of calorie loss. Resultant hypoproteinemia  may be severe enough to cause generalized edema. Individuals with CF also have difficulties absorbing the fat-soluble vitamins  A,  D,  E, and  K. In addition to the pancreas problems, people with cystic fibrosis experience more  heartburn, intestinal blockage by  intussusception , and constipation. Older individuals with CF may develop  distal intestinal obstruction syndrome  when thickened feces cause intestinal blockage. Exocrine pancreatic insufficiency occurs in the majority (85% to 90%) of patients with CF.It is mainly associated with â€Å"severe† CFTR mutations, where both alleles are completely nonfunctional (e. g. ?F508/? F508). It occurs in 10% to 15% of patients with one â€Å"severe† and one â€Å"mild† CFTR mutation where there still is a little CFTR activity, or where there are two â€Å"mild† CFTR mutations. In these milder cases, there is still sufficient pancreatic exocrine function so that enzyme supplementation is not required. There are usually no other GI complications in pancreas-sufficient phenotypes, and in general, such individuals usually have excellent growth and development.Despite this, idiopathic  chronic pancreatitis  can occur in a subset of pancreas-sufficient individuals with CF, and is a ssociated with recurrent abdominal pain and life-threatening complications. Thickened secretions also may cause liver problems in patients with CF. Bile  secreted by the liver to aid in digestion may block the  bile ducts, leading to liver damage. Over time, this can lead to scarring and nodularity (cirrhosis). The liver fails to rid the blood of toxins and does not make important  proteins, such as those responsible for  blood clotting. Liver disease is the third most common cause of death associated with cystic fibrosis.Endocrine Clubbing in the fingers of a person with cystic fibrosis Clubbing in the fingers of a person with cystic fibrosis The  pancreas  contains the  islets of Langerhans, which are responsible for making insulin, a hormone that helps regulate blood  glucose. Damage of the pancreas can lead to loss of the islet  cells, leading to a type of diabetes that is unique to those with the disease. This cystic fibrosis-related diabetes  (CFRD) shares characteristics that can be found in  type 1and  type 2  diabetics, and is one of the principal non-pulmonary complications of CF.Vitamin D is involved in  calcium  and  phosphate  regulation. Poor uptake of vitamin D from the diet because of malabsorption can lead to the bone disease  osteoporosis  in which weakened bones are more susceptible to  fractures. In addition, people with CF often develop clubbing  of their fingers and toes due to the effects of chronic illness and  low oxygen  in their tissues. Infertility Infertility  affects both men and women. At least 97% of men with cystic fibrosis are infertile, but not sterile and can have children with assisted reproductive techniques.The main cause of infertility in men with cystic fibrosis is congenital absence of the vas deferens  (which normally connects the  testes  to the  ejaculatory ducts  of the  penis), but potentially also by other mechanisms such as causing  azoospermia,  te ratospermia  and  oligoasthenospermia. Many men found to have congenital absence of the vas deferens during evaluation for infertility have a mild, previously undiagnosed form of CF. Some women have fertility difficulties due to thickened cervical mucus or malnutrition. In severe cases, malnutrition disrupts  ovulation  and causes  amenorrhea. ———————————————— Cause CF is caused by a  mutation  in the  gene  cystic fibrosis trans-membrane conductance regulator  (CFTR). The most common mutation,  ? F508, is a deletion (? signifying deletion) of three nucleotides  that results in a loss of the amino acid  phenylalanine  (F) at the 508th position on the protein. This mutation accounts for two-thirds (66–70%) of CF cases worldwide and 90% of cases in the  United States; however, there are over 1500 other mutations that can produce CF.Althou gh most people have two working copies (alleles) of the CFTR gene, only one is needed to prevent cystic fibrosis. CF develops when neither allele can produce a functional CFTR protein. Thus, CF is considered an  autosomal recessive disease. The  CFTR gene, found at the q31. 2  locus  of  chromosome 7, is 230,000  base pairs  long, and creates a protein that is 1,480  amino acids  long. More specifically the location is between base pair 117,120,016 to 117,308,718 on the long arm of chromosome 7, region 3, band 1 and sub-band 2, represented as 7q31. . Structurally, CFTR is a type of gene known as an  ABC gene. The product of this gene (the CFTR) is a chloride ion channel important in creating sweat,  digestive  juices and  mucus. This protein possesses two  ATP-hydrolyzing  domains, which allows the protein to use  energy  in the form of  ATP. It also contains two domains comprising 6  alpha helices  apiece, which allow the protein to cross the cell membrane. A regulatory  binding site  on the protein allows activation by  phosphorylation, mainly by  cAMP-dependent protein kinase.The  carboxyl terminal  of the protein is anchored to the  cytoskeleton  by a  PDZ  domain interaction. In addition, there is increasing evidence that  genetic modifiers  besides CFTR modulate the frequency and severity of the disease. One example is  mannan-binding lectin, which is involved in  innate immunity  by facilitating  phagocytosis  of microorganisms. Polymorphisms in one or both mannan-binding lectin alleles that result in lower circulating levels of the protein are associated with a threefold higher risk of end-stage lung disease, as well as an increased burden of chronic bacterial infections. ———————————————— Pathophysiology Molecular structure of the CFTR protein Molecular structure of the CFTR protein There are several mutations in the  CFTR  gene, and different mutations cause different defects in the CFTR protein, sometimes causing a milder or more severe disease. These protein defects are also targets for drugs which can sometimes restore their function. ?F508-CFTR, which occurs in >90% of patients in the U. S. , creates a protein that does not  fold  normally and is degraded by the cell.Other mutations result in proteins that are too short (truncated) because  production  is ended prematurely. Other mutations produce proteins that do not use energy normally, do not allow  chloride iodide  and  thiocyanate  to cross the membrane appropriately,  or are degraded at a faster rate than normal. Mutations may also lead to fewer copies of the CFTR protein being produced. The protein created by this gene is anchored to the  outer membrane of  cells  in the  sweat glands, lungs, pancreas, and all other remaining exocrine glands in the body.Th e protein spans this membrane and acts as a  channel  connecting the inner part of the cell (cytoplasm) to the  surrounding fluid. This channel is primarily responsible for controlling the movement of halogens from inside to outside of the cell; however, in the sweat ducts it facilitates the movement of chloride from the sweat into the cytoplasm. When the CFTR protein does not work, chloride and thiocyanate  are trapped inside the cells in the airway and outside in the skin. Then  hypothiocyanite, OSCN, cannot be produced by immune defense system.Because chloride is  negatively charged, this creates a difference in the electrical potential inside and outside the cell causing  cations  to cross into the cell. Sodium is the most common cation in the extracellular space and the combination of sodium and chloride creates the  salt, which is lost in high amounts in the sweat of individuals with CF. This lost salt forms the basis for the sweat test. Most of the damage in CF is due to blockage of the narrow passages of affected organs with thickened secretions.These blockages lead to remodeling and infection in the lung, damage by accumulated digestive enzymes in the pancreas, blockage of the intestines by thick faeces, etc. There are several theories on how the defects in the protein and cellular function cause the clinical effects. One theory is that the lack of halogen and pseudohalogen (mainly, chloride, iodide and thiocyanate) exiting through the CFTR protein leads to the accumulation of more viscous, nutrient-rich mucus in the lungs that allows bacteria to hide from the body's  immune system.Another theory is that the CFTR protein failure leads to a paradoxical increase in sodium and chloride uptake, which, by leading to increased water reabsorption, creates dehydrated and thick mucus. Yet another theory is that abnormal chloride movement  out  of the cell leads to dehydration of mucus, pancreatic secretions, biliary secretions, etc. Chr onic infections The lungs of individuals with cystic fibrosis are colonized and infected by bacteria from an early age. These bacteria, which often spread among individuals with CF, thrive in the altered mucus, which collects in the small airways of the lungs.This mucus leads to the formation of bacterial microenvironments known as biofilms that are difficult for immune cells and antibiotics to penetrate. Viscous secretions and persistent respiratory infections repeatedly damage the lung by gradually remodeling the airways, which makes infection even more difficult to eradicate. Over time, both the types of bacteria and their individual characteristics change in individuals with CF. In the initial stage, common bacteria such as  Staphylococcus aureus  and  Hemophilus influenzae  colonize and infect the lungs.Eventually,  Pseudomonas aeruginosa  (and sometimes  Burkholderia cepacia) dominates. By 18 years of age, 80% of patients with classic cystic fibrosis harbor  Ps eudomonas aeruginosa, and another 3. 5% harbor Burkholderia cepacia. Once within the lungs, these bacteria adapt to the environment and develop  resistance  to commonly used antibiotics. Pseudomonas  can develop special characteristics that allow the formation of large colonies, known as â€Å"mucoid†Ã‚  Pseudomonas, which are rarely seen in people that do not have CF. One way infection spreads is by passing between different individuals with CF.In the past, people with CF often participated in summer â€Å"CF Camps† and other recreational gatherings. Hospitals grouped patients with CF into common areas and routine equipment (such as  nebulizers)  was not sterilized between individual patients. This led to transmission of more dangerous strains of bacteria among groups of patients. As a result, individuals with CF are routinely isolated from one another in the healthcare setting and healthcare providers are encouraged to wear gowns and gloves when examining p atients with CF to limit the spread of virulent bacterial strains.CF patients may also have their airways chronically colonized by filamentous fungi (such as  Aspergillus fumigatus,  Scedosporium apiospermum,  Aspergillus terreus) and/or yeasts (such as  Candida albicans); other filamentous fungi less commonly isolated include Aspergillus flavus  and  Aspergillus nidulans  (occur transiently in CF respiratory secretions), and  Exophiala dermatitidis  and Scedosporium prolificans  (chronic airway-colonizers); some filamentous fungi like  Penicillium emersonii  and  Acrophialophora fusisporaare encountered in patients almost exclusively in the context of CF.Defective mucociliary clearance characterizing CF is associated with local immunological disorders. In addition, the prolonged therapy with antibiotics and the use of corticosteroid treatments may also facilitate fungal growth. Although the clinical relevance of the fungal airway colonization is still a ma tter of debate, filamentous fungi may contribute to the local inflammatory response, and therefore to the progressive deterioration of the lung function, as often happens with allergic broncho-pulmonary aspergillosis (ABPA) – the ost common fungal disease in the context of CF, involving a Th2-driven immune response to Aspergillus. ————————————————- Diagnosis and monitoring CFTR gene on chromosome 7 CFTR gene on chromosome 7 Cystic fibrosis may be diagnosed by many different methods including  newborn screening,  sweat testing, and genetic testing. As of 2006 in the United States, 10 percent of cases are diagnosed shortly after birth as part of newborn screening programs.The newborn screen initially measures for raised blood concentration of immunoreactive trypsinogen. Infants with an abnormal newborn screen need a sweat test to confirm the CF diagnosis. In many cases, a parent makes the diagnosis because the infant tastes salty. Trypsinogen  levels can be increased in individuals who have a single mutated copy of the  CFTR  gene (carriers) or, in rare instances, in individuals with two normal copies of the  CFTR  gene. Due to these  false positives, CF screening in newborns can be controversial.Most states and countries do not screen for CF routinely at birth. Therefore, most individuals are diagnosed after symptoms (e. g. sinopulmonary disease and GI manifestations) prompt an evaluation for cystic fibrosis. The most commonly used form of testing is the sweat test. Sweat-testing involves application of a medication that stimulates sweating (pilocarpine). To deliver the medication through the skin, iontophoresis  is used to, whereby one  electrode  is placed onto the applied medication and an electric current  is passed to a separate electrode on the skin.The resultant sweat is then collected on filter paper or in a capi llary tube and analyzed for abnormal amounts of  sodium  and  chloride. People with CF have increased amounts of sodium and chloride in their sweat. In contrast, people with CF have less thiocyanate and  hypothiocyanite  in their saliva and mucus. CF can also be diagnosed by identification of mutations in the CFTR gene. People with CF may be listed in a  disease registry  that allows researchers and doctors to track health results and identify candidates for  clinical trials. PrenatalCouples who are pregnant or planning a pregnancy can have themselves tested for the CFTR gene mutations to determine the risk that their child will be born with cystic fibrosis. Testing is typically performed first on one or both parents and, if the risk of CF is high, testing on the  fetus  is performed. The  American College of Obstetricians and Gynecologists  (ACOG) recommends testing for couples who have a personal or close family history of CF, and they recommend that carrie r testing be offered to all Caucasian couples and be made available to couples of other ethnic backgrounds.Because development of CF in the fetus requires each parent to pass on a mutated copy of the CFTR gene and because CF testing is expensive, testing is often performed initially on one parent. If testing shows that parent is a CFTR gene mutation carrier, the other parent is tested to calculate the risk that their children will have CF. CF can result from more than a thousand different mutations, and as of 2006 it is not possible to test for each one. Testing analyzes the blood for the most common mutations such as ? F508—most commercially available tests look for 32 or fewer different mutations.If a family has a known uncommon mutation, specific screening for that mutation can be performed. Because not all known mutations are found on current tests, a negative screen does not guarantee that a child will not have CF. During pregnancy, testing can be performed on the  pla centa  (chorionic villus sampling) or the fluid around the fetus (amniocentesis). However,  chorionic villus sampling  has a risk of fetal death of 1 in 100 and amniocentesis of 1 in 200;  a recent study has indicated this may be much lower, approximately 1 in 1,600.Economically, for carrier couples of cystic fibrosis, when comparing pre-implantation genetic diagnosis (PGD) with natural conception (NC) followed by prenatal testing and abortion of affected pregnancies, PGD provides net economic benefits up to a maternal age of approximately 40 years, after which NC, prenatal testing and abortion has higher economic benefit. ————————————————- Management While there are no cures for cystic fibrosis there are several treatment methods. The management of cystic fibrosis has improved significantly over the past 70 years.While infants born with cystic fibrosis 70 years ag o would have been unlikely to live beyond their first year, infants today are likely to live well into adulthood. Recent advances in the treatment of cystic fibrosis have meant that an individual with cystic fibrosis can live a fuller life less encumbered by their condition. The cornerstones of management are proactive treatment of  airway infection, and encouragement of good nutrition and an active lifestyle. Management of cystic fibrosis continues throughout a patient's life, and is aimed at maximizing organ function, and therefore quality of life.At best, current treatments delay the decline in organ function. Because of the wide variation in disease symptoms treatment typically occurs at specialist multidisciplinary centers, and is tailored to the individual. Targets for therapy are the  lungs,  gastrointestinal tract  (including pancreatic enzyme supplements), the  reproductive organs  (including (ART) and psychological support. The most consistent aspect of therapy in cystic fibrosis is limiting and treating the lung damage caused by thick mucus and infection. Intravenous,  inhaled, and oral antibiotics are used to treat chronic and acute infections.Mechanical devices and inhalation medications are used to alter and clear the thickened mucus. These therapies, while effective, can be extremely time-consuming for the patient. One of the most important battles that CF patients face is finding the time to comply with prescribed treatments while balancing a normal life. In addition, therapies such as  transplantation  and  gene therapy  aim to cure some of the effects of cystic fibrosis. Gene therapy aims to introduce normal CFTR to airway. Theoretically this process should be simple as the airway is easily accessible and there is only a single gene defect to correct.There are two CFTR gene introduction mechanisms involved, the first use of a viral vector (adenovirus, adeno-associated virus or retro virus) and secondly the use of  lipo some. However there are some problems associated with these methods involving efficiency (liposomes insufficient protein) and delivery (virus provokes an immune response). Antibiotics Many CF patients are on one or more  antibiotics  at all times, even when healthy, to  prophylactically  suppress infection. Antibiotics are absolutely necessary whenever pneumonia is suspected or there has been a noticeable decline in lung function, and are usually chosen based on the results of a putum analysis and the patient's past response. This prolonged therapy often necessitates hospitalization and insertion of a more permanent  IV  such as a  peripherally inserted central catheter  (PICC line) or  Port-a-Cath. Inhaled therapy with antibiotics such as tobramycin,  colistin, and  aztreonam  is often given for months at a time to improve lung function by impeding the growth of colonized bacteria. Oral antibiotics such as ciprofloxacin or  azithromycin  are given to hel p prevent infection or to control ongoing infection. The  aminoglycoside  antibiotics (e. g. obramycin) with long-term use can cause  several side effects such as hearing loss, damaging the  balance system  present in the  inner ear  and producing many chronic kidney problems  . To prevent these  side-effects, the amount of antibiotics in the blood are routinely measured and adjusted accordingly. Other treatments for lung disease Several mechanical techniques are used to dislodge sputum and encourage its expectoration. In the hospital setting, chest physiotherapy (CPT) is utilized; a respiratory therapist percusses an individual's chest with his or her hands several times a day, to loosen up secretions.Devices that recreate this percussive therapy include the  ThAIRapy Vest  and the  intrapulmonary percussive ventilator  (IPV). Newer methods such as  Biphasic Cuirass Ventilation, and associated clearance mode available in such devices, integrate a cough a ssistance phase, as well as a vibration phase for dislodging secretions. These are portable and adapted for home use. Aerosolized medications that help loosen secretions include  dornase alfa  and  hypertonic  saline. Dornase is a  recombinant  human deoxyribonuclease, which breaks down DNA in the  sputum, thus decreasing its  viscosity.Denufosol  is an investigational drug that opens an alternative chloride channel, helping to liquefy mucus. As lung disease worsens, mechanical breathing support may become necessary. Individuals with CF may need to wear special masks at night that help push air into their lungs. These machines, known as  bi-level positive airway pressure  (BiPAP) ventilators, help prevent low blood oxygen levels during sleep. BiPAP may also be used during physical therapy to improve sputum clearance. During severe illness, a  tube  may be placed in the throat (a procedure known as a  tracheostomy) to enable breathing supported by a  ven tilator.For children living with CF, preliminary studies show pediatric massage therapy may improve patients and their families’ quality of life, though more rigorous studies must be done. Transplantation Lung transplantation  often becomes necessary for individuals with cystic fibrosis as lung function ceases and  exercise tolerance  declines. Although single lung transplantation is possible in other diseases, individuals with CF must have both lungs replaced because the remaining lung might contain bacteria that could infect the transplanted lung.A pancreatic or liver transplant may be performed at the same time in order to alleviate liver disease and/or diabetes. Lung transplantation is considered when lung function declines to the point where assistance from mechanical devices is required or patient survival is threatened. Other aspects Intracytoplasmic sperm injection can be used to provide fertility for men with cystic. .fibrosis Intracytoplasmic sperm injection c an be used to provide fertility for men with cystic. .fibrosis New-borns with intestinal obstruction typically require surgery, whereas adults with  distal intestinal obstruction syndrome typically do not.Treatment of pancreatic insufficiency by replacement of missing digestive enzymes allows the duodenum to properly absorb nutrients and vitamins that would otherwise be lost in the faeces. So far, no large-scale research involving the incidence of  atherosclerosis  and  coronary heart disease  in adults with cystic fibrosis has been conducted. This is likely due to the fact that the vast majority of people with cystic fibrosis do not live long enough to develop clinically significant atherosclerosis or coronary heart disease.Diabetes  is the most common non-pulmonary complication of CF. It mixes features of  type 1and  type 2  diabetes, and is recognized as a distinct entity,  cystic fibrosis-related diabetes (CFRD). While oral  anti-diabetic drugs  are somet imes used, the only recommended treatment is the use of  insulin  injections or an  insulin pump,  and unlike in type 1 and 2 diabetes, dietary restrictions are not recommended. Development of  osteoporosis  can be prevented by increased intake of vitamin D and  calcium, and can be treated by  bisphosphonates, although  adverse effects  can be an issue.Poor growth may be avoided by insertion of a  feeding tube  for increasing  calories  through supplemental feeds or by administration of injected  growth hormone. Sinus infections are treated by prolonged courses of antibiotics. The development of nasal polyps or other chronic changes within the nasal passages may severely limit airflow through the nose, and over time reduce the patient's sense of smell. Sinus surgery is often used to alleviate nasal obstruction and to limit further infections. Nasal steroids such as  fluticasone  are used to decrease nasal inflammation.Female infertility may be overc ome by  assisted reproduction  technology (ART) with the help of embryo transfer  techniques. Male infertility caused by absence of the  vas deferens  may be overcome with  testicular sperm extraction  (TEST), collecting sperm cells directly from the testicles. If the collected sample contains too few sperm cells to likely have a spontaneous  fertilization,  intracytoplasmic sperm injection  can be performed. Third party reproduction  is also a possibility for women with CF. ————————————————- PrognosisThe prognosis for cystic fibrosis has improved due to earlier diagnosis through screening, better treatment and access to health care. In 1959, the median age of survival of children with cystic fibrosis in the United States was six months. In 2008, survival averaged 37. 4 years. In Canada, median survival increased from 24 years in 1982 to 47. 7 in 2007 . Of those with cystic fibrosis who are more than 18 years old as of 2009; 92% had graduated from  high school, 67% had at least some college education, 15% were disabled and 9% were unemployed, 56% were single and 39% were married or living with a partner.In Russia  the overall median age of patients is 25, which is caused by the absence or high cost of medication and the fact that lung transplantation is not performed. Quality of life Chronic illnesses can be very difficult to manage. Cystic fibrosis (CF) is a chronic illness that affects the â€Å"digestive and respiratory tracts resulting in generalized malnutrition and chronic respiratory infections†. The thick secretions clog the airways in the lungs, which often cause inflammation and severe lung infections. Therefore, mucus makes it challenging to breathe.If it is compromised, it affects the quality of life of someone with CF, and their ability to complete such tasks as everyday chores. It is important for CF pati ents to understand the detrimental relationship that chronic illnesses place on the quality of life. Havermans and colleagues (2006) have shown that young outpatients with CF that have participated in the CFQ-R (Cystic Fibrosis Questionnaire-Revised) â€Å"rated some QOL domains higher than did their parents†. Consequently, outpatients with CF have a more positive outlook for themselves.Furthermore, there are many ways to improve the QOL in CF patients. Exercise is promoted to increase lung function. The fact of integrating an exercise regimen into the CF patient’s daily routine can significantly improve the quality of life. There is no definitive cure for Cystic Fibrosis. However, there are diverse medications used such as, mucolytics, bronchodilators, steroids and antibiotics that have the purpose of loosening mucus, expanding airways, decreasing inflammation and fighting lung infections. ————————— Ã¢â‚¬â€Ã¢â‚¬â€Ã¢â‚¬â€Ã¢â‚¬â€Ã¢â‚¬â€Ã¢â‚¬â€-Epidemiology Mutation| Frequency worldwide| ?F508| 66%–70%| G542X| 2. 4%| G551D| 1. 6%| N1303K| 1. 3%| W1282X| 1. 2%| All others| 27. 5%| Cystic fibrosis is the most common life-limiting autosomal recessive disease among people of  Caucasian heritage. In the United States, approximately 30,000 individuals have CF; most are diagnosed by six months of age. In  Canada, there are approximately 3,500 people with CF. Approximately 1 in 25 people of European descent, and one in 30 of Caucasian Americans, is a carrier of a cystic fibrosis mutation.Although CF is less common in these groups, approximately 1 in 46  Hispanics, 1 in 65  Africans  and 1 in 90 Asians  carry at least one abnormal CFTR gene. Ireland has the world's highest incidence of cystic fibrosis, at 1:1353. Although technically a  rare disease, cystic fibrosis is ranked as one of the most widespread life-shortening genetic diseases. It is most common among nations in the Western world. An exception is  Finland, where only one in 80 people carry a CF mutation. In the United States, 1 in 4,000 children are born with CF. In 1997, about 1 in 3,300 Caucasian children in the United States was born with cystic fibrosis.In contrast, only 1 in 15,000 African American children suffered from cystic fibrosis, and in Asian Americans the rate was even lower at 1 in 32,000. Cystic fibrosis is diagnosed in males and females equally. For reasons that remain unclear, data has shown that males tend to have a longer  life expectancy  than females,  however recent studies suggest this gender gap may no longer exist perhaps due to improvements in health care facilities,  while a recent study from Ireland identified a link between the female hormone, estrogen and worse outcomes in CF.The distribution of CF alleles varies among populations. The frequency of ? F508 carriers has been estimated at 1:200 in northern Sweden, 1:143 in Lithuanians, and 1 :38 in Denmark. No ? F508 carriers were found among 171  Finns  and 151  Saami people. ?F508 does occur in Finland, but it is a minority allele there. Cystic fibrosis is known to occur in only 20 families (pedigrees) in Finland. Hypotheses about prevalence The  ? F508  mutation is estimated to be up to 52,000 years old. Numerous hypotheses have been advanced as to why such a lethal mutation has persisted and spread in the human population.Other common autosomal recessive diseases such as  sickle-cell anemia have been found to protect carriers from other diseases, a concept known as  heterozygote advantage. Resistances to the following have all been proposed as possible sources of heterozygote advantage: * Cholera: With the finding and discovery that  cholera toxin  requires normal host CFTR proteins to function properly, it was hypothesized that carriers of mutant CFTR genes benefited from resistance to cholera and other causes of diarrhea. Further studies have not confirmed this hypothesis. Typhoid: Normal CFTR proteins are also required essentially for the entry of  Salmonella typhi  into cells,  suggesting that carriers of the mutant CFTR genes might be resistant to  typhoid fever. No  in vivo  study has yet confirmed this. In both cases, the low level of cystic fibrosis outside of Europe, in places where both cholera and typhoid fever are  endemic, is not immediately explicable. * Diarrhea: It has also been hypothesized that the prevalence of CF in Europe might be connected with the development of cattle domestication. In this hypothesis, carriers of a ingle mutant CFTR chromosome had some protection from diarrhea caused by lactose intolerance, prior to the appearance of the mutations that created lactose tolerance. * Tuberculosis: Another explanation is that carriers of the gene could have some resistance to TB. ——————————————à ¢â‚¬â€Ã¢â‚¬â€- History It is supposed that CF appeared about 3,000 BC because of migration of peoples, gene mutations, and new conditions in nourishment. Although the entire clinical spectrum of CF was not recognized until the 1930s, certain aspects of CF were identified much earlier.Indeed, literature  from Germany and Switzerland in the 18th century warned  Wehe dem Kind, das beim Ku? auf die Stirn salzig schmekt, er ist verhext und muss bald sterbeor â€Å"Woe to the child who tastes salty from a kiss on the brow, for he is cursed and soon must die,† recognizing the association between the salt loss in CF and illness. Dorothy Hansine Andersen Dorothy Hansine Andersen In the 19th century,  Carl von Rokitansky  described a case of fetal death with  meconium peritonitis, a complication of meconium ileus associated with cystic fibrosis.Meconium ileus was first described in 1905 by  Karl Landsteiner. In 1936,  Guido Fanconi  published a paper describing a conn ecting link between  celiac disease, cystic fibrosis of the pancreas, and bronchiectasis. In 1938  Dorothy Hansine Andersen  published an article, â€Å"Cystic Fibrosis of the Pancreas and Its Relation to Celiac Disease: a Clinical and Pathological Study,† in the  American Journal of Diseases of Children. She was the first to describe the characteristic cystic fibrosis of the pancreas and to correlate it with the lung and intestinal disease prominent in CF.She also first hypothesized that CF was a recessive disease and first used pancreatic enzyme replacement to treat affected children. In 1952 Paul di Sant' Agnese discovered abnormalities in  sweat  electrolytes; a  sweat test  was developed and improved over the next decade. The first linkage between CF and another marker (Paroxonase) was found in 1985, indicating that only one locus exists for CF  Hans Eiberg. In 1988 the first mutation for CF,  ? F508  was discovered by  Francis Collins,  Lap-Che e Tsui  and  John R. Riordan  on the seventh chromosome.Subsequent research has found over 1,000 different mutations that cause CF. Because mutations in the CFTR gene are typically small,  classical genetics  techniques had been unable to accurately pinpoint the mutated gene. Using protein markers,  gene-linkage  studies were able to map the mutation to chromosome 7. Chromosome-walking and  -jumping  techniques were then used to identify and  sequence  the gene. In 1989 Lap-Chee Tsui led a team of researchers at the Hospital for Sick Children  in  Toronto  that discovered the gene responsible for CF.Cystic fibrosis represents the first genetic disorder elucidated strictly by the process of  reverse genetics. ————————————————- Research Gene therapy Gene therapy  has been explored as a potential cure for cystic fibrosis. Ideally, gene therapy places a normal copy of the  CFTR gene into affected cells. Transferring the normal CFTR gene into the affected epithelium cells would result in the production of functional CFTR in all target cells, without adverse reactions or an inflammation response.Studies have shown that to prevent the lung manifestations of cystic fibrosis, only 5–10% the normal amount of CFTR  gene expression  is needed. Multiple approaches have been tested for gene transfer, such as liposomes and viral vectors in animal models and clinical trials. However, both methods were found to be relatively inefficient treatment options. The main reason is that very few cells take up the vector and express the gene, so the treatment has little effect. Additionally, problems have been noted in cDNA recombination, such that the gene introduced by the treatment is rendered unusable.With the help of the  Cystic Fibrosis Trust, which has a league of highly professional gene therapists, both somatic and Adeno -associated viral vector have made advances. The  Adenoviridae, or more commonly known as the cold virus, is genetically altered, allowing the CFTR gene to enter lung cells. Small molecules A number of  small molecules  that aim at compensating various mutations of the CFTR gene are under development. One approach is to develop drugs that get the ribosome to overcome the  stop codon  and synthesize a full-length CFTR protein.About 10% of CF results from a premature stop codon in the DNA, leading to early termination of protein synthesis and truncated proteins. These drugs target nonsense mutations  such as G542X, which consists of the amino acid  glycine  in position 542 being replaced by a stop codon. Aminoglycoside antibiotics interfere with DNA synthesis and error-correction. In some cases, they can cause the cell to overcome the stop codon, insert a random amino acid, and express a full-length protein.The aminoglycoside  gentamicin  has been used to treat lun g cells from CF patients in the laboratory to induce the cells to grow full-length proteins. Another drug targeting nonsense mutations is  ataluren, which is undergoing Phase III clinical trials as of October 2011. BIBLIOGRAPHY 1. BIOLOGY TEXTBOOK FOR CLASS – XII (NCERT) 2. TRUEMAN’S BIOLOGY FOR CLASS – XII 3. SCIENCE REPORTER (September, 2007) 4. THE NEWYORK TIMES (December 22, 2009) 5. www. google. co. in/cysticfibrosis 6. en. wikipedia. org/wiki/Cystic_fibrosis 7. www. ncbi. nlm. nih. gov 8. www. cff. org/ 9. www. cysticfibrosis. com/ 10. www. cftrust. org. uk/