Evidence-based practice Essay

Evidence-based practice (EBP) is a system of incorporating research findings into nursing practice so as to improve the therapeutic outcomes. (Polit, F. D & Beck, T. C, 2010). â€Å"The evidence based practice places particular emphasis on the use of evidence, in particular research findings, in clinical decision making†. (Parahoo, K, 2006). During past clinical exposures, the issues regarding post natal depression were found as a less explored one because of the complex involvement of both mental health nursing and maternal and child health nursing. â€Å"Postpartum psychosis is a manifestation of a life time vulnerability to affective disorders with child birth as the precipitating factor† (Spinelli, M. G, 2009).The focused clinical question discussed here, which is an important element in an evidence based practice is as follows; How effective is the education of nurses about postpartum depression in helping to identify and reduce postpartum depression among new moth ers in a maternal ward or community?. According to the PICOT strategy for formulating EBP questions, here, the population is ‘new mothers’, the intervention is education of nurses about postpartum depression and outcome is ‘identify and reduce postpartum depression’. The clinical settings chosen for this focused clinical question is maternal ward in a hospital as well as community settings. It is based on the general assumption that initial care will be given in a Hospital maternal ward followed by contact care given in community settings. Having a baby is a joyous moment, but for some women it also brings worries as well as stress. Many recent study reports highlight alarming rates of occurrence of post natal depression. About 10% of new mothers suffer from the most severe form of post natal depression.(Science Daily, 2010). It is evident that, being the closest aid of a post natal delivered woman, maternal and child health nurse can do a lot in identifying and reducing post natal depression. Here, an attempt is made to explore and analyse the educational aspect of nurses in alleviating the said problem. The online databases chosen for this assignment is CINAHL (Cumulative Index to Nursing and Allied Health Literature) . A systematic search stra tegy has been carried out using key words such as postnatal depression, postnatal emotional disturbance, puerperal depression, perinatal depression, psychosis, nursing care, nurse knowledge, nursing care, and education. More than 700 results were yielded initially when postnatal depression used as the key words. The  results were narrowed by choosing the publication dates between January 2000 and December 2010. Results were further sorted by re arranging them in a date descending order and a suitable article titled ‘Detection, treatment and referral of perinatal depression and anxiety by obstetrical providers’(Goodman ,J,H, Tyer-Viola, L, 2010) obtained. Key words were combined by using Boolean operator ‘AND’. The combination of key words postnatal depression and nursing interventions generated 4 results, and among them, two results with titles, ‘Improving the postnatal outcomes of new mothers’ (Morse C, Durkin S, Buist A, and Milgrom J, 2004) and Comparison of effects of nursing care to problem solving training on levels of depressive symptoms in post partum women’ (Tezel, A and Gozum, S, 2006) were found relevant for the focused clinical question.

Nurse-patient ratio

Nurse-patient ratio laws are state mandates requiring hospitals to keep to a maximum sealing limit of the ratio of nurses to patients. At the moment, states that have yet to apply any nurse-patient ratio limits typically charge each of their nurses the care of at least 6 nurses and even as high as 8 to 10 (Churchouse, 2002). Barnes-Jewish hospital for example has a ratio of 1 nurse to 10 patients (St. Louis, 2004). California's Assembly Bill 394 is one of the forerunning legislations that mandated the regulation of nurse-patient ratios across hospitals. This bill had been largely contested by hospital lobbyists who are now bartering with state officials on the most flexible regulations that could be imposed. While nursing associations and nursing labor unions all over the country are proposing the ideal 1:2 ratio, hospital management firmly claim this to be impossible. In some other states such as Illinois, staging progression procedures have been introduced as a viable means to improve nurse-patient ratios over a period of 5-10 years (Bartolomeo, 2001). Since after the Second World War, the problem of increasing nurse-patient ratios have begun to accrue. By the mid-80s the pressing need for more nurses became even more drastic when the academe saw a decline in the local demand for the profession. This eventually led hospitals to searching for nurses abroad which continued to persist to the present day. However, outsourcing the nurse supply was also coupled by hospital management cutbacks on staffing which still resulted to poor nurse-patient ratios. Hospitals also allegedly implemented management regulations preventing nursing staff from discussing and objecting to nurse-patient hospital policies. However by the late 90s, nursing unions have begun to seek help from media institutions, local communities, and contract negotiators to help them bargain less congested working conditions with hospital management. This led the nursing unions to asking help from their respective state governments. Finally in January of 2002, California’s AB 394 mandated the issue of staffing ratios in hospitals throughout the state, but this victory of the nursing unions was short-lived as hospital management immediately bargained with legislators for staffing ratios that were most advantageous for them. While nursing organizations persisted with a 1:2 to a 1:4 ratio, hospital lobbyists led by the California Healthcare Association, a consortium of 500 hospitals insisted that the acceptable nurse-patient ratio could be no less than 1:6. Currently, one of the country’s largest Health Management Organizations, Kaiser Permanente broke away from the bulk of institutions opposed to lower nurse-patient ratios and advocated a 1:4 ratio that it currently implements in its facilities. Kaiser discussed further ways of lowering the ratio with nursing unions and agreed to have the approved recommendations of such discussions implemented on all Kaiser owned establishments (Bartolomeo, 2001). Current working conditions lead nurses into compromising situations wherein their work suffers because of the immense number of tasks that they have to do all at once. While some hospitals implement â€Å"fair† policies that allow nurses enough room to breathe in their work, a lot more hospitals and health care organizations are run by profit oriented groups whose main concern includes minimizing costs. What’s worse is that since health care in various parts of the country has been transformed into a corporate affair between gigantic businesses who buy health care plans from HMOs who sell them, competition has become a matter of who can provide the better corporate deal over who can provide better hospital service. Since the patients don’t have much choice with respect to which health care deals their employer will take, this rules out quality by competition from ushering hospitals to make nurse-patient ratio improvements on their own. Thus, a state mandated regulation is the only way to force these hospitals to provide an appropriate working environment for their nurses. There are several controversial aspects to the legislation of nurse-patient ratio regulation. One popular controversy is the actual capability of today’s supply of nurses to fill in the vacancies that would be created by such legislation. The Illinois Hospital Association contends that current nursing programs of the state are not viable to handle the demand for the number of nurses required to maintain the ratios mandated by laws like California’s AB394. Another criticism is insensitivity of a rigid nurse-patient ratio to patient’s individual medical differences. Critics also point out differences between hospitals, resources and even nursing units which could be blurred out in the implementation of a state mandate indiscriminately throughout all hospitals. I believe that hospital policies at the moment are more profit-oriented than health oriented. It is this slippery slope that leads to understaffing and overly high nurse-patient ratios. However, I also think that an inflexible legislation on nurse-patient ratios would do little to solve the problem. Nurses from different units are very different and there needs to be more extensive needs analysis studies conducted before a proper legislative action could be taken. Therefore while I am in favor of state legislation in order to curb inherent profit-oriented biases of hospital management, I am not in favor of haphazardly implementing one at the moment without considering factors forwarded by institutions like the Illinois Hospital Association. Like I said, I believe that while the California legislation is a victory for the labor rights of nurses in the state, it does not ensure an increase in nursing quality. I would consider the act positive with respect to labor rights but neutral with respect to patient care. Extensive scrutiny should be placed on the issues that arose after the legislation such as the differences among hospitals, resources, and nursing units. References: Churchouse, C. (2002). Senate Community Affairs References Committee Inquiry Into Nursing. Retrieved: July 19, 2007 from: http://72.14.235.104/search?q=cache:uQtMh4POYlUJ:www.aph.gov.au/senate/committee/clac_ctte/completed_inquiries/2002-04/nursing/submissions/sub04.doc+current+nurse-patient+ratio;hl=tl;ct=clnk;cd=3;gl=ph Bartolomeo, C. (2001). â€Å"Mandated staffing ratios: Health care professionals see the benefits and pitfalls.† Journal of the American Federation of Teachers. Vol. 30 Issue 2. P.114-118. Barnes-Jewish Hospital seeks to lower nurse-patient ratio. Retrieved July 19, 2007 from St. Louis Business Journal Website: http://www.bizjournals.com/stlouis/stories/2004/11/29/daily50.html ;

Analysis of Forgetfullness, by Billy Collins Essay

This poem is really easy to identify with. The first 4 stanzas are clearly relating the reader to the poem. Everyone at some point has to learn these general, seemingly useless facts. â€Å"A state flower† â€Å"The capital of Paraguay† so arbitrary, but so true in that this brings back memories of 3rd or 5th grade for almost all of us, it is bound to strike a chord with the reader. This is also coupled with a slightly nostalgic loss of these facts in the first stanza, as slowly the individual sections of a book (that you as the reader once clearly enjoyed) are systematically removed from your memory by time. Then the tone shifts from musing about facts we don’t remember, to our inability to remember them. It begins to get darker. This is useful contrast from the imagery that the reader experiences during the first few stanzas, remembering childhood, and innocence. Juxtaposed is the now darker â€Å"mythological river† described as vague that, dauntingly, is leading to oblivion. The hopeless tone thus has that much more impact as we make our way to our own â€Å"oblivion† or death, where we will join the dead: â€Å"those who have even forgotten how to swim and how to ride a bicycle.† Then Collins provides a justification for our wanting to remember, wanting to enrich our every moment, as soon memories will be pointless. Really, in the end this is providing a more inherent worth to memories than they ever had before, because of the fleeting nature of life that Collins describes. Not in a fun, youthful â€Å"carpe diem† way, Collins is showing how short we have to live. Only from this presentation can the reader then make the leap that we ought to cherish these good memories, and make good memories, such as the â€Å"moon (out of the) love poem† in the closing lines of the work.

Examine the ways in which business contributes to economic, political, Essay

Examine the ways in which business contributes to economic, political, and social stability and instability - Essay Example Under this section, the global financial recession of 2008 will serve as a classic example of the potential of businesses to contribute to economic instability. Under the second section, a critical analysis of the contribution of businesses to political stability and instability will be discussed. The third section will consider the contribution of businesses to ether social stability or instability. Contribution of Businesses to Economic Stability or Instability Many economists have focused on describing the factors that affect the stability of the economy in different parts of the globe. The adoption of capitalism as an ideology in the business world brings out a clear picture of the dynamics that defined the business world. Capitalism is a system that favoured the rich countries that had the capital to invest, and served as a disadvantage to the lower class in any society that had to work as labourers with minimal wages. The bigger picture of the capitalism indicates that the esta blishment of free markets only serves to promote the interests of the rich. The rich countries have enjoyed the benefits of capitalism. On one side, capitalism has caused the economic stability of the wealthiest developed countries. This is evident from the analysis of the roots of capitalism in Europe and the trends that followed with capitalists occupying different territories. As Chang highlights in his critic of the capitalist system, it is evident that the opening up of markets promoted by capitalism has little benefit to the poor countries and has been the cause of the surging economic crises in these countries in the recent years (Chang & Lane2010, p. 34). Moreover, the capitalist system has only served to build several distinct capital systems that exhibit a level of competition. This competition only results in adversity that compromises the economies of some countries, while promoting the interests of the capitalist hegemony. After the recession experienced in the United S tates during the 1930s, it became evident that there was need for control of the business world. This led to the formation of different organizations that have been at the forefront of controlling the global markets and monetary systems. Evidently, these organizations have exerted a form of regulation of the international markets determining the ensuing business trends. Moreover, regional regulatory bodies that control the business trends in each region. Chang argues that the elimination of opaque financial products may foster a level of certainty concerning the future stability of the economy (Chang & Lane2010, p. 64). Evidently, it has proved impossible to ensure that each country and region maintain the openness and freeness of markets. Many countries have focused on the production of the opaque business products that have affected the stability of some economies. The 2008 financial recession reveals evidence that businesses have the potential of causing instability. The failure of banks was the primary cause of the recession. Prior to the recession, a few of the great banks controlled the financial system and had the security that they were not subject to failure. Moreover, many of the Americans had

Case study on the design of a contemporary Civil Engineering project Essay - 1

Case study on the design of a contemporary Civil Engineering project - Essay Example The bridge is a natural expression of structural engineering and architecture but a city center footbridge is equally about people and the environment; in short a piece of public architecture. The bridge gives the pedestrians unique views of London, free from traffic and high above the Thames. In September 1996, a competition was organized by a London-based newspaper the Financial Times and London Borough of Southwark to design a new Footbridge across the River Thames. The idea behind the competition was to get the best design in every aspect therefore the teams participating in the design were structured to have an engineer, an architect and an artist. More than 200 teams participated and the competition was won by Arup (engineer), Foster (architect) and Sir Anthony Caro (Sculptor). The height restrictions and the view behind the bridge required an innovative design which was provided in the form of a design which included some unusual practices; the suspension design had supporting cables below the deck level. This innovative design was given the name ‘blade of light’ by its designers. The structure of the Millennium Bridge is innovative and complex but it has been designed to achieve an apparent simple form. The design of the Millennium Bridge is based on the following considerations: An evolved support system in which the majority of the bridge stiffness is created by shallow cable profile derived tension. This allows a light bridge deck structure. A modular design in which several structural members and components can be repeated in the structure, thus reducing the fabrication costs. This can also simplify the maintenance after the construction and allows easy execution of the construction phase. The distribution of the forces on the foundations should be such that they do not disturb the existing structures on the north bank and also the foundations of the existing bridges. The aesthetics of the bridge at night were also a big concern and a l ight pipe system illumination was proposed to create a ‘blade of light’ across the river at night. The river traffic analysis is also important while designing a bridge at such a location. A major issue was the provision of planning advice for gaining the necessary approvals to construct a new river crossing in the heart of London. Moreover ways of generating the finances for the bridge were also to be considered while designing the bridge. Superstructure Design The bridge design is a shallow suspension bridge in which the view behind the bridge is facilitated by keeping the suspension cables below the bridge deck. The bridge is supported on two river piers through two groups of four 120mm diameter locked coil cables which span from one bank to the other. The three spans of the bridge have different lengths. The middle span which lies between the two piers is 144m long. The north span is 81m long while the south span is 108m in length. Fabricated steel box sections whic h are known as the transverse arms span between the two

Financial structure and macroeconomic stability Research Paper

Financial structure and macroeconomic stability - Research Paper Example However the ability of the policy makers and financial regulators to implement different rules depends upon the control they have upon reducing inflation and output volatility. The transmission of interest rate fluctuations to output levels and prices depends upon a country’s policies regarding banking and management of financial markets. For most policy makers, in majority of the nations, controlling the interest rates in the short run is considered to be most important. Policy development and interest rate changes are however effective only when they lead to an increase the level finance available to firms and individuals who are willing to invest in projects or shift consumption. In many nations it is observed that the banking system is guarded from the impact caused by monetary policies through barriers which are created by the government (Iakova & Wagner, 2001). Monetary policy which gets transmitted to the real economy and thereby impacts the lending policies of the bank requires to be altered as they hinder growth. When the government sheds the assets of the bank, they indirectly create scope for the central banks to bring about stability in output and inflation rates. Therefore establishing a control over the assets possessed by the bank is a suitable way by which it is possible to manage the macro-economic environment. The deposit insurance system is also identified as a crucial factor in the financial regulatory system which affects the economy. The absence or the presence of a deposit regulatory system affects the readiness of bank managers to undertake risks. Subsequently the access available to firms to raise finance through equity and bonds may also get affected. Financial regulators are frequently seen to use bank loans as a tool to implement monetary policies. Therefore if firms are more dependent upon banks, then the efficient implementation of

Western Civilization.The modern era Essay Example | Topics and Well Written Essays - 1250 words

Western Civilization.The modern era - Essay Example Western civilization is a term used to refer to cultures of European origin. This term sprang up as a way of depicting the difference between the Graeco-Roman culture and its offspring, is in distinction to the older neighboring civilizations of the Middle East. This sustained to provide as a replica of civilization in the "west" for a long time.In Ideas, Peter Watson concludes that the mix, in contemporary culture, of Enlightenment-stytle scientific rationalism and 19th-century Romantic idealism creat what he calls "the modern incoherence": Watson argues that Enlightenment science and Romantic art, Enlightenment empiricism and Romantic fundamentalism, propose inherently irreconcilable views of human experience and of the world. (Peter, Watson 2006)"There are three major themes whose development and interplay have shaped the distinctive characteristics that set Western civilization apart from the other great historic cultures. They are the growth of a tradition of rational scientific inquiry, the persistence of a tension between Judaeo-Christian religious ideals and social realities, the emergence of constitutional forms of government." (Brian Tierney, Donald Kagan and Pearce Williams L p.xi).The theory of Western culture is normally connected to the classical explanation of the Western world. In this definition, "Western culture is the set of literary, scientific, political, artistic and philosophical principles which set it apart from other civilizations. Much of this set of traditions and knowledge is collected in the Western canon."( Jones, Prudence and Pennick, Nigel, 1995). Henry, Boren, C remarks that Western civilization is "still the most dynamic element in the modern world." He further remarks that Western civilization is successor to previous civilizations that urbanized out of the Mediterranean region. In its most wide definition, Western civilization is that accumulation of political, economic, social, and intellectual traditions that has developed for 5,000 years since the appearance of the first civilizations in the ancient Near East. Today, Western civilization is primarily regarded as centering on the Atlantic community or Western Europe and those societies in the Western Hemisphere and Australasia that are offshoots of European tradition and culture (p xiv). The Modern Era Religion in the meantime has waned considerably in Western Europe, where many are agnostic or atheist. Nearly half of the populations of the United Kingdom (44-54%), Germany (41-49%), France (43-54%) and the Netherlands (39-44%) are non-theist. Religious belief in the United States is very strong that is about 75-85% of the population are religious (Zuckerman, P 2005). As Europe discovered the wider world, old concepts adapted. The Islamic world which had formerly been considered "the Orient" ("the East") more specifically became the "Near East" as the interests of the European powers for the first time interferred with Qing China and Meiji Japan in the 19th century. (Davidson, Roderic H 1960) Thus, the Sino-Japanese War in 1894-1895 occurred in the "Far East", while the troubles surrounding the decline of the Ottoman Empire simultaneously occurred in the "Near East" (Hogarth, D G1902). The uncovering and innovation of new classes of energy bring about key change. The tackling of fire contributed to cooking, ceramics, and smelting. The toggle from oxen to horses and into watermills assisted in creating the 12th-century Renaissance. The acceptance of Arab-Latin rigging on Mediterranean ships helped them to get the most of the wind and discover the more unsafe and mysterious Atlantic. Right from the beginning of 18th century, electrical gadgets began to come out, though electricity demanded other forms of energy to produce it. The growth of steam control brought about the Industrial Revolution. The discovery of the electron created 20th-century technology, culminating in the internet (Peter, Watson 2006)

Emotional intelligence is an overlooked aspect of transformational Essay

Emotional intelligence is an overlooked aspect of transformational leadership - Essay Example Several researches have discovered links among emotional intelligence and end result variables of interest to managers. It is very common to recognize community, management and leadership pressure that are parallel in the human history; though, the principle of scientific techniques to the development of knowledge regarding leadership is mainly a twentieth century fact (Cherniss, 2000). The idea that an individuals personal or physical activities or actions might elucidate or estimate leadership capability continued to have prevalence well into the twentieth century. Comprising misconstrued the character of traits in management and before missing the statistical tools to put together self-governing parallel coefficients, trait theory was mainly directed aside in the mid-twentieth century in supporting the behavioral and possibility approaches. A spotlight on what behaviors influential in fact occupied in subjugated leadership study and accounted for important progresses in the accept ance of social control and leadership in the course of the middle to late 1900s (Prati et al, 2003b). Directed by hypothesis, the consideration of transformational leadership has been, comparable to approximately all management examine, paying attention on leader-follower relations. Concentration to transformational leadership has conquered the scientific techniques to the understanding of leadership for just about two decades. As the significance in charismatic and transformational leadership approaches has built-up and developed, a variety of calls have been heard for new holistic techniques to the deliberation of leadership capability and the leadership procedure. One option is to look at leadership not immediately as relations, although moderately as a meaning of a proficiency set possessed and positioned by the individual leader (Cherniss, 2000). While the reality and significance

Prison-Building in the UK Essay Example | Topics and Well Written Essays - 2000 words

Prison-Building in the UK - Essay Example How a job is going to be attained is an issue that relates mainly to procurement. There are three different main routes of procurement which one could follow. The first option is perhaps the most obvious, PFI (private finance initiative) procurement, is classic and actually quite attractive. For the purposes of this project, PFI will not be used. However it is helpful to know what it is exactly. Private finance initiatives are usually used when the public sector arranges to buy services, with very empirically-based outcomes from the private sector. This is ongoing for a long time, which includes the maintenance and/or construction of the appropriate designs so that management by the private sector is maximized by the private finance being at a high risk. Next, which is not as innately apparent, is prime contracting. In this instance, a sole contractor is in the place of being the point man for a client in the public realm to produce deliverable goods-such as a completed construction project with budgetary constraints. The next and final procurement option is design and build, wherein one contractor, also indebted to a client in the public realm, has a single outcome specified. Unlike the prime contracting model, there is no pre-agreed cost data. Basically, the fact that these prisons are not being built with private finance initiative procurement is problematic. First, the fact that the money being spent would be taken from private funding would ensure that the public was not being swindled. Secondly, if something went wrong with the project, the money being spent would not be public monies. In fact, the fact that the monies that will be spent are public monies is highly problematic. How then does the prison industry make sure that it is being faithful to its intended purpose (housing prisoners). Someone, if this is public funds being used, must be kept accountable in terms of how the public's money or tax dollars are being spent. Private finance initiative pro curement monies would be safer to use because if the money is not utilized properly, the private sector could more easily sue for damages. However, since the money is the public's money, the public does not necessarily have a representative in place to represent their interests, needs, and wants with regard to how the project is coming along. In this way, there is much more potential for abuse when it comes to the public's money being spent on the prison programme. SECTION II. III. Question II In the opinion of Ramus, et. al. (2006), "After a client has selected an appropriate procurement strategy for his building project, the next stage will be a review of how best to obtain the resources that will be necessary for him to have the work carried out. In most instances, client organizations will have limited skills and resources" (pp. 68). There are four different types of contracts which could be utilized in this situation: a contract based on bills of

Comparison between Utilitarianism and Idealism Essay Example for Free

Comparison between Utilitarianism and Idealism Essay The two theories that will be compared and contrasted in this essay are Platos Idealism and Mill Benthams Utilitarianism. I chose these two theories because, to me, they are the ones that seem to be the most realistic and interesting. The way to get from the level of the is to the level of the ought of the Philosophers in these theories are the two bests. In this essay, it will be shown that the two theories are not so different in their relation between the level of the is and the level of the ought; it will be shown that Idealism would be a better theory for a society with highly intellectual people, and that a combination of these theory would be the best way for our society to evolve from the level of the is to the level of the ought. Platos way to go from the is to the ought is socratic questioning. He says that we should question ourselves on whether the moral views we have are ideal or not. He also says that the way of looking at things we have is wrong because all men are not the same, and so they do not have the same opinion of things. Part of his theory says that to get to true virtue (ideal moral views) we have to trim down all the false moral views we have and get to the basic, timeless, and unchanging patterns of the Good. With those ideal moral views we would be able to mirror the Good. Examples of false ideal moral views for Plato are seeking for selfish pleasures such as food, sex, and power. For Utilitarians, the way to get from the level of the is to the level of the ought is to reward or sanction a person for his or her actions. In Utilitarism people should choose actions that are the most utile for them but also for society. In other words they should choose the most pleasant and less painful actions and consequences for the greatest number of people. The degree of utility (degree of pleasure) is determined by what is called felicific calculus. This pleasure calculator is composed of different criterions that caracterise the pleasure provided by a certain action. They are intensity, duration, certainty, proximity, fecundity, and purity. These caracteristics of pleasure are calculated for ones self and for the population that his or her action concerns. If an action is said to have a fairly good utility to one but a very big disutility to society, it is said to be an immoral action. In that sense selfish pleasures are immoral. In these two theories, the socratic questioning and the felicific calculus almost play the same role in the way that the result (chosen action) should be the same if one is calculating the utility or one is referring to socratic questioning to take a decision. The socratic questioning of Idealism brings the person at the door of the right moral views by trimming all the layers of appearances and opinions over a concept. Even if one is not seeking those ideal moral views the felicific calculus should take one to the same ideal moral views if it is well performed. In that sense these two theories are the same because they give the same final result. But one of the theories seems harder to realize because everyone has to go through a long process that not every individual wants to perform or is able to perform. This theory is Idealism. On the other hand, in Utilitarianism a scale can be made out to lead people in the right way (and that scale is in fact present in our society). These theories are different in the sense that Utilirianism is easier for a society to perform well. To give rewards and punishments, society needs an authority outside the person who acts; this is why there are governements, theocracies and social opinions to guide people. Utilirianism is the most realistic because people do not have to think about what is right or wrong, they only have to follow the guides (rewards/sanctions). The society we live in is clearly Utilitarian. The many rewards (salary, respect, etc. ) and sanctions (prison, school failure, etc. ) reveal it. Everything works in function of rewards and sanctions. It implies that we only have to follow the rules given and no sanctions should be given to us. If our society was Idealist, it would imply that we would have to think and do the socratic questioning at each dilemma we have. This is impossible because not everybody is intelligent enough to do so, and most of the people would not be willing to go through that process. There is a danger in having a Utilirianism society. We just have to think of the United-States with the war they made to Irak. I believe that the population of that country trusted the felicific calculus scale (which was written by the governement) too much, because most of the population (of the USA, of course ) believed that war in Irak was a good thing. In that case the scale of that population was wrong because it did not care enough about what Irakians really wanted. If that dilemma had been well calculated, I am sure that they would let Irakians rebuild their country all alone and stop occupying the country. An Idealist society would take the time and think about that situation. They would have come to the conclusion that this war was not fair and they would have wanted to wait for real proofs of the presence of massive destruction arms before bombarding Irak. Another problem that Utilitarianism has raised is the sexual inequality. I believe that the situation we are in is caused by an error in the scale of the felicific calculus. The authority in place decided very long ago that women were inferior, and then nobody really thinked about it (or had the courage to change things) until the first feminists movements. With an Idealistic society that problem would never had occurred because Idealists always ask themselves if what they do is right. They would have understood long ago that this situation is completelly wrong. The best way to go from the level of the is to the level of the ought in our society would be to combine these two theories. First, Idealism should be used by a group of intellectuals to create a scale that would be used in felicific calculus. Then, felicific calculus should be used by the population. The scale from the felicific calculus should be adjusted as time goes on so that it evolves well with the new technological, economical and historical facts. But this is only an utopic idea because nobody would be able to create and maintain a fair felicific calculus scale since nobody can totally get to the basic principles of morality.

The drug metabolism

The drug metabolism Introduction: If an exogenous microorganism enters the human body, this invokes the immune system to produce antibodies to come into contact with the foreign potentially pathogenic species and lead to its destruction. Although when drug molecules enter the human body this does not result in the synthesis of antibodies, due to their relatively small molecular weight. This is why the endogenous metabolism of drugs is vital in ensuring no or the minimum toxicity from a very broad spectrum of xenobiotics i.e. molecules/compounds which are found in a given organism, but are not synthesized naturally by it and or normally found within it. We can define drug metabolism as the enzymatically catalysed conversion of exogenous drug molecules into generally less active metabolites, which have a faster rate of clearance from the body. (While this is true for the majority of metabolites it is important to acknowledge that some metabolites actually are of higher toxicity than their precursors.) This occurs throu ghout nearly every organ (excluding ectodermal tissue) in the human body, but specifically the gastro-intestinal tract, lungs, kidneys and most importantly (and abundantly) the liver. While drug metabolism is essential in preventing a specific toxicity being produced from the accumulation of a drug(s), there are drawbacks that need to be addressed; a given drug may be a xenobiotic, but it is taken (or administered) in order to produce some degree of a therapeutic effect for its specifically targeted disease/pathology. Thus drug metabolism can inhibit the therapeutic benefit of a given molecule that ideally needs to be retained in a particular tissue of the body for a set period of time, to bring about a therapeutic effect. This is mainly due to the fact that a large number of drug molecules do mimic the structure of endogenous molecules close enough for the corresponding specific enzymes to target them as well as nonspecific enzymes which only identify certain molecular groups as opposed to the entire pharmacophore of a given drug. This unexpected drug metabolism could result in an undesired decrease in the bioavailability of a drug which would lead to increased d oses or dosage frequencies; this would cause a decrease in patient compliance which in the current medicinal environment is vital. Absorption and clearance: In the case of drug absorption into the desired tissues of the body generally a lipophilic character is required. This is because regardless of the site of drug uptake, it must pass through the cell membranes of targeted cells. These cell membranes are lipophilic in nature as they consist of a phospholipid bilayer. The inside of this bilayer is made up of hydrocarbon tails which are straight chain hydrocarbons which interact with each other via Van der Waal interactions and London forces. Thus drug molecules are designed to have sufficient lipophilic character that they can form these interactions with the lipid bilayers and pass into cells. Unfortunately this means that they are of limited hydrophilicity and either do not go into dissolution in an aqueous environment at all or do so at a very slow rate. As previously mentioned as this is unacceptable due to the accumulation of a given drug that would occur and produce toxicity, the drug must undergo a series of transformations that serve to increase the hydrophilic nature of the drug molecules. This predominately occurs in liver cells (hepatocytes) in processes known as phase I and phase II metabolism. Phase I and Phase II: Phase I metabolism is constituted of oxidative, reductive and hydrolytic reactions. These serve to produce primary metabolites that are susceptible to other reactions, which consist of the following conjugations; glucuronic acid, sulphate, amino acid, glutathione, water, acetyl, fatty acid and methyl. These occur via the corresponding conjugating agents and are known as phase II reactions. They aim to produce secondary metabolites that are far more hydrophilic nature than their precursor drug counterparts. This is with the addition of e.g. amine, carboxylic acid, hydroxyl groups as well as others, simply to increase the number of very electronegative atoms (with lone pairs of electrons) in a given species. Thus these metabolites can from a greater number of hydrogen bonds with the aqueous medium of the nephronal filtrate of the kidneys and be excreted at a faster rate via the passing of urine. The main constituent of phase I transformations are oxidative reactions, as they activate the selected species in generally one of two ways; hydroxylation and epoxidation. We can define oxidation as the gain of oxygen in a molecule or more precisely the loss of at least one electron from a species reacting with molecular oxygen. This is true for the two general mechanisms mentioned above as adding either a hydroxyl group or an epoxide ring to a molecule increases the number of oxygen atoms that the molecule contains. Firstly this increases the ability of the newly formed metabolite to act as a nucleophile due to the lone pair of electrons available for covalent bond formation (from the oxygen atom added to the molecule). Secondly it increases the chances of attack by an electrophilic species, because of the high electron density of the lone pair of electrons on the oxygen atom. Oxidation Properties and mechanisms of the Cytochrome P450 isoenzyme superfamily: The majority of these oxidative metabolic reactions are carried out by a superfamily of enzymes known as cytochrome P450, this can be displayed as: RH + O2 +NAD(P)H + H+ ? ROH + H2O + NAD(P)+ [1] The P450 enzymes catalyse the biodegradation of other exogenous species that are not drugs such as; organic solvents, ethanol (or consumed alcohol), anaesthetics, pesticides and carcinogens [1]; While endogenous molecules such as organic acids, steroids and prostaglandins are also biodegraded [1]. These enzymes are intracellular hemoproteins that function as external monooxygenases (mixed function oxidases) enzymes that serve to incorporate a single atom of molecular oxygen into a lipophilic xenobiotic substrate (i.e. a drug molecule), with the concomitant reduction of the other atom to water [1]. While internal monooxygenases take two reductive equivalents from the substrate in order to reduce one atom of molecular oxygen to water, this is normally done with an external reductant for external monooxygenases [1]. In eukaryotic cells the P450 enzymes consist of around half a thousand amino acid that compose their quaternary structure, these hemoproteins are membrane bound and have a heme prosthetic group at their centres. It is thought that the reason the enzymes can be bound to the cell membranes is the N-terminus of the enzymes tertiary structure has numerous hydrophobic amino acids (i.e. ones which contain aromatic/cyclic groups and have few very electronegative atoms such as oxygen and sulphur) that can interact with the lipid bilayer of the cells. Most hemoproteins in mammalian cells have nitrogen atom from the histidine residues imidazole group to form a ligand with the iron-heme prosthetic group. While for P450 enzymes this ligand is formed between the prosthetic group and the thiol group of a cysteine residue which is located near the C-terminus of the protein. This ligand activates the porphyrin ring (four conjugated pyrrole rings) to nucleophilic substitution by an oxygen atom. This is because the thiol group has an electron inductive effect due to its high electronegativity and so makes the carbon atom it is directly bonded to very electropositive and thus of greater electrophilicity/susceptibility of nucleophilic attack by the lone pair of electrons from the oxygen atom, so allowing oxidation to take place. The general process of the catalytic oxidative cycle of the cytochrome P450 enzyme superfamily: The substrate binds to a specific P450 enzyme and is followed by the first electron of the coenzyme NADPH via the electron transport chain. This is then followed by the binding of an oxygen atom that accepts the second electron from the coenzyme to produce a ferric peroxy anion [1]. The anion forms a ferric hydroperoxy complex via protonation, which in turn is heterolytically cleaved to form a Fe(V)=O species [1]. The newly formed highly electrophilic iron-oxo intermediate then attacks the substrate to form a hydroxylated metabolite. This product disassociates to allow another substrate to bind and the oxidation cycle to continue [1]. Schematic organisation of different cytochrome P450 systems. Upper row, left: bacterial system, right: mitochondrial system. Lower row, left: microsomal system, right: self-sufficient CYP102 (P450-BM3).[1] Aromatic hydroxylation: This leads on to the first major constituent of oxidative reactions; aromatic hydroxylation. This is simply the addition of at least one hydroxyl group to a given substrate although depending on the chemical environment that the product is formed in (e.g. pH) the hydrogen atom may be lost from the hydroxyl group. Aromatic compounds are first metabolized to the corresponding arene oxides; this is by electrophilic addition of the aromatic ring (of the previously mentioned iron-oxo intermediate) to produce either a carbocation species. This carbocation would be formed via the movement of an electron to the Fe(IV) species, giving a Fe(III) species bound to a the mentioned carbocation; or by formation of a radical which serves as a tetrahedral intermediate. The produced arene oxides then take on further transformations, which involve removal of the epoxide group that was added and introduction of a hydroxyl group and potentially another nucleophilic substitute. The simplest transformation is simply intramolecular rearrangement to for a para-arenol. Also hydration can take place in the presence of water and using the enzyme epoxide hydrolase. This causes opening of the epoxide ring and formation of a trans-3,4 arenediol. These primary metabolites can also undergo attack by large macromolecules which serve as nucleophiles. This is because the oxygen in the epoxide ring serves to make both the meta and para carbon positions electropositive and electrophilic in nature. Although any nucleophilic substitution that does go on to occur is at the para position, due to greater resonance stability of the formed secondary metabolite. Another example of aromatic hydroxylation would be the metabolism of isoliquiritigenin. It is a chalcone found in licorice roots and other plants [3] which has shown potent antitumor, phytoestrogenic activity and antioxidant properties. [3] Schematics for its metabolism can be shown below. [3] The metabolism of aromatic compounds that get hydroxylated can be slowed by using para-substituted aromatic compounds with either chlorine or a fluorine atom in the para position. While electron withdrawing groups deactivate the ring towards electrophilic substitution and activate it towards nucleophilic substitution; electron donating groups activate the ring towards electrophilic substitution and deactivate it towards nucleophilic substitution. While most ring deactivators go in the meta position, halogens direct ortho-para, i.e. the same as ring activators. This is because the halogens, especially fluorine and chlorine are very electronegative and thus have an electron inductive effect and decrease the electron density of the ring. This inductivity is far greater than the resonance stability that the halogen can give the ring thus deactivating it. Thus the addition of these halogen atoms decreases the nucleophilic nature of the ring and decreases the rate of metabolism. This can b e shown with the metabolism of the drug Diclofenac (shown below [4]) which is an anti-inflammatory drug as it is has a half-life of around one hour. While its derivative fenclofenac which has a para-substituted chlorine atom has a half-life twenty times longer. Alkene epoxidation: Epoxidation of alkenes occurs readily, because they are more volatile than the ? bonds of aromatic compounds, this simply involves the addition of an epoxide ring to a molecule in order for it to then undergo further transformations. For example the drug Coumarin has been used clinically at high dosages in humans in the treatment of high-protein lymphedemas (Jamal and Casley-Smith, 1989) and as an antineoplastic agent in the treatment of renal cell carcinoma (Marshall et al., 1994) and malignant melanoma (Marshall et al., 1989). [5] It and its 3/7-hydroxy isomers undergo epoxidation and then either glutathione conjugation or non-enzymatic intramolecular rearrangement [5] to secondary metabolites. This is shown schematically below. [5] It is also vitally important that environmental carcinogens are broken down via drug metabolism, in particular by the P450 enzymes. For example acrylonitrile (AN2) is widely used in the production of acrylic and modacrylic fibres, plastics, rubbers, resins, and as a chemical intermediate in the synthesis of many other industrial products (IARC,1999). Early epidemiological studies have suggested that AN may increase the incidence of lung, colon, and stomach cancers among exposed workers (Thiess and Fleig, 1978; Blair et al., 1998).[6] As a result P450 epoxidation is vital for preventing carcinogenic action of AN. While the metabolic basis of the acute toxicity of AN has not been fully elucidated, it is generally attributed to its metabolism to CEO (cyanoethylene oxide) and cyanide, and glutathione depletion. The primary target of acute toxicity of AN is the central nervous system due, at least partially, to the liberation of cyanide (Ahmed and Patel, 1981; Benz et al., 1997). [6] The below diagram illustrates how AN is metabolised by the P450 enzymes, specifically the CYP2E1 isoform.[6] Alcohol and aldehyde metabolism: Alcohols and aldehydes can be metabolized by cytochrome P450 enzymes to aldehydes and carboxylic acids respectively, but the majority of these transformations are catalysed by alcohol dehydrogenase and aldehyde dehydrogenase. These enzymes are predominantly in the liver and require the coenzyme NAD+ or NADP+. General equations for these reactions are shown below. [Alcohol Dehydrogenase]Ez + RCH2OH + NAD + RCHO + NADH + H+ [Aldehyde Dehydrogenase]Ez + RCHO + NAD+ + H2O RCOOH + NADH + H+ Reduction: Cytochrome P450 enzymes are used along with reductases to metabolise drugs that have a carbon atom that is able to be reduced such as a carbonyl or an unsaturated carbon, a nitro group or a compound with an azo group. In addition upon reaction usually a specific stereoisomer is formed. The structure of the rest of the compounds often attribute to which stereoisomer is formed. Some stereoisomers can prove to be toxic. Carbonyl compounds: Carbonyl compounds are reduced by cytochrome P450 into alcohols and are NADP or NADPH dependent. The enzymes involved in the reduction of carbonyls are classified based upon their gene sequence, 3-D structure and cofactor dependence into superfamilies of; medium-chain dehydrogenases/reductases, aldo-keto reductases, short-chain dehydrogenases/reductases which include carbonyl reductases. The majority of these enzymes are present in the cytosol however there are some that are found in the microsomes and mitochondria. Short-chain dehydrogenases/reductases (SDRs) and aldo-keto reductases (AKR) are the most common enzymes used in drug metabolism. These enzymes also exhibit high specificity for the drugs that they reduce. Saturated ketones reduced to alcohols whilst in an unsaturated ketone both the ketone group and the double bonds are both reduced. Steroidal drugs undergo oxidoreduction of the hydroxy/keto group at C17[7]. This makes the compound more water soluble and hence easier to be excreted. Some metabolising enzymes behave differently and undergo different types of reactions when in different cells. An example is carbonyl reductases within tumour cells and normal cells. These have become a target of new drugs such as oracin in the treatment of breast cancer [9]. The enzymes within the cancer cells metabolise oracin and doxorubin more effectively than in normal cells hence reducing the efficacy of the cytostatic effect of the drugs. Some carbonyl compounds however do not undergo reduction via the cytochrome P450 pathway but are rather reduced by other pathways including the aldo-keto reductases (AKR). An example is a drug containing a 1,3-diketone derivative S-1360 which upon reduction produces a key metabolite HP1 which constitutes a major clearance pathway[9]. Nitrogen compounds: The reduction of nitrogen containing compounds are reduced to amines in order to aid excretion as amines are more water soluble than their nitro groups. Azo compounds on the other hand may be metabolised within the body to produce the active drug as opposed to the precursor which may be formulated to get pass the first pass effect or the hydrophilic barrier in order to enter their target cells. The azo group provides 2 compounds with amine groups which can be further metabolised like any other amine. Both of these functional groups are both reduced by cytochrome P450 enzymes and are NADPH dependent. Hydrolysis: This is part of the Phase I metabolism pathway. The metabolites produced are all susceptible to Phase II conjugation and thus being excreted after the conjugation. The functional groups of the drugs that are metabolised by hydrolysis include esters and amides, which produce carboxylic acids, alcohols and amines. Esters are hydrolysed quicker than amides in vivo. Unlike oxidation and reduction the reactions are typically not carried out by the cytochrome P450 system. The most significant enzymes involved in the hydrolysis of the esters and amides are carboxylesterases and arylesterases, cholinesterases and serine endopeptidases. The active site of the enzymes involved may be stereospecific as to which enantiomer of the drug is metabolised and in addition which enantiomer of the drug is generated. Some of these products are toxic and dangerous to the body. Amino acid reactions Several phase I reactions produce a carboxylic acid metabolite. Xenobiotic carboxylic acids can be metabolised before elimination by amino acid conjugation. Glycine; the most common conjugating amino acid forms ionic conjugates that are water soluble with aromatic, arylaliphatic and heterocyclic carboxylic acids. In these reactions, first the xenobiotic carboxylic acid is activated by ATP to form the AMP ester by the enzyme acyl synthetase. Then the AMP ester is converted to a Coenzyme-A thioester. Next, an amide or peptide bond is formed between the thioester and the amino group of glycine. The latter reaction is mediated by the enzyme acyl transferase. These reactions are shown in figure 1. The amino acid conjugate produced is ionic and therefore water soluble, hence it is easily eliminated in the urine and bile. (1) Glutathione conjugation Glutathione is a protective compound in the body that removes potentially toxic electrophilic compounds and xenobiotics. Drugs are metabolised by phase I reactions to form strong elecrophiles that can react with glutathione to form conjugates that are not toxic. This phase II reaction differs from others since electrophiles are subject to conjugations rather than nucleophiles. The nucleophilic thiol group on the glutathione compound (figure 2) attacks elecrophiles (electrophilic carbons with leaving groups). Compounds that can be conjugated to give thioether conjugates of glutathione: Epoxides Haloalkanes Nitroalkanes Alkenes Aromatic halo- and nitro- compounds Glutathione-S-transferases (GST) are enzymes which catalyse the reactions above. There are thirteen different human GST subunits which have been identified and they belong to five different classes. They are located in the cytosol of the liver, kidney and gut. The enzyme GST is thought to increase the ionisation of the thiol group of glutathione, leading to an increase in its nucleophilicity towards electrophiles. (1)(2) Once formed, GSH conjugates may be excreted directly or more often they are further metabolised to N-acetylcysteine conjugates which can then be excreted via phase III metabolism. Phase III Metabolism further modification and excretion Before being excreted in the urine, most xenobiotics are made less toxic and more water soluble as polarity increases by metabolising enzymes in phase II reactions. In phase III metabolism water soluble compounds are excreted in the urine. However, some drug compounds are not metabolised and therefore are not excreted. These non-metabolised compounds are readily reabsorbed from the urine through the renal tubular membranes and into the plasma to be recirculated. (3) Some xenobiotic conjugates from phase II reactions are further metabolised during phase III metabolism reactions. Glutathione-S conjugates may be metabolised further by hydrolysis of the glutathione conjugate (GSR) at the y-glutamyl bond of the glutamate residues by y -glutamyl transferase (y -GT) followed by hydrolysis of glycine residues resulting in a cysteine conjugate containing a free amino group of the cysteine residue. This then undergoes N-acetylation to form mercapturic acid. The final products; mercapturic acids are S-derivatives of N-acetylcysteine synthesised from glutathione (figure 4). (1)(2) First-pass Metabolism The metabolism of many drugs is dependent on the route of administation therefore orally administered drugs are subject to first pass metabolism and consequently their bioavailablity is reduced. This occurs as a result of the orally administered drugs entering the systemic circulation via the hepatic portal vein, so the drug is exposed to the intestinal wall and the liver, which is thought to be the main site of first-pass metabolism of orally administered drugs. Other possible sites are the gastrointestinal tract, blood, vascular endothelium and lungs. First-pass Metabolism in the Liver During first-pass metabolism, the cytochrome P450 enzymes family represent the most significant of the hepatic enzymes. It has been estimated that the endoplasmic reticulum of the liver contains approximately 25 000 nmol of cytochrome P450. Although there are several human P450 subfamilies and multiple individual isozymes within subfamilies, only five P450 enzymes are shown to be significant for the process of first-pass metabolism: CYP1A2 CYP2C9 CYP2C19 CYP2D6 CYP3A4 Cytochrome P450 drug substrates are commonly highly extracted during first-pass metabolism. Examples of these drugs are; morphine, verapamil, propranolol, midazolam, lidocaine. Drugs that are highly extracted such as lidocaine have a low bioavailability when taken orally therefore they are not administered orally. CYP3A4 is the most commonly active isozyme against P450 drug substrates. This is possibly due to the enzymes abundance and broad substrate specificity. Highly extracted substrates for conjugative, reductive or non-P450 oxidative enzymes are less common. These include labetalol, morphine, terbutaline, isoproterenol and pentoxifylline. The gut is also an important organ involved in pre-systemic metabolism. Metabolism here for drugs with high first-pass metabolism leads to a reduced bioavailability. Some metabolizing enzymes such as CYP3A4 is found at a higher level in enterocytes than in the liver. Recent findings state that gut wall metabolism is the major cause of low bioavailability of certain drugs. Intestinal First-pass Metabolism Various drug metabolizing enzymes found in the liver are also found within the epithelium of the gastrointestinal tract. These include cytochromes P450, glucuronosyl transferases, sulfotransferases, N-acetyl transferase, glutathione S-transferases, esterases, epoxide hydrolase and alcohol dehydrogenase. The small intestine contains high amounts of three cytochrome P450 enzymes; CYP3A, CYP2D6 and CYP2C. Unlike the liver which has a relatively uniform distribution of P450enzymes, the distribution of P450 enzymes is not uniform along the small intestine and villi. Proximal mucosal P450 content is normally higher than distal mucosa P450 content. Therefore it has been established that protein level and catalytic activity of drug-metabolizing enzymes in the small intestine are generally lower than those in the liver. This has been demonstrated by comparison of cytochrome P450 enzymes in the liver and the small intestine. The extent of first-pass metabolism can result from interindividual variability: Genetic variation Induction or inhibition of metabolic enzymes Food increases liver blood flow. This can increase the bioavailablity of some drugs by increasing the amount of drug presented to the liver to an amount that is above the threshold for complete hepatic extraction Drugs that increase liver blood flow (similar effects to food) and drugs that reduce liver blood flow Non- linear first pass kinetics, i.e. dose Liver disease increases the bioavailability of some drugs with extensive first-pass metabolism (4) To avoid first pass metabolism a drug can be administered sublingual and buccal routes. These routes lead to drugs being absorbed by the oral mucosa. During sublingual administration the drug is put under the tongue where it dissolves in salivary secretions. An example of a sublingual drug is nitroglycerine. During buccal administration the drug is positioned between the teeth and the mucous membrane of the cheek. Both of these routes avoid destruction by the GI fluids and first pass effect of the liver. Drugs may also be administered via other routes to avoid first-pass metabolism, for example; rectal, inhalation, transdermal, intravenous. (5) Prodrugs Many drugs require metabolic activation in order to exert their pharmacological action; these are described as pro-drugs. There are two types; type I and type II which has subtypes A and B dependent on the site of activation. Type I prodrugs are converted intracellularly at the target cells (A) or at tissues that usually metabolise compounds (B). An example of a type IA prodrug is Zidovudine and type IB prodrug is captopril. Metabolic activation of type I prodrugs is usually linked to phase I metabolic enzymes. Type II prodrugs are converted extracellularly in GI fluids (A) or in the systemic circulation (B). An example of a type IIA prodrug is sulfasalazine and type IIB prodrug is fosphenytoin. Type II prodrugs are very popular as they are involved in overcoming bioavailability problems, which are commonly experienced with many drugs, by improving permeability and reducing the first pass effect. (6) Type I Prodrugs are used to target a drug to its specific site of action; an example of this is the drug used in Parkinsons disease levodopa; the inactive form of the drug which is metabolised in the neurone by the enzyme dopa decarboxylase to the active form; dopamine. Dopamine does not cross the blood-brain barrier so it is given as the levodopa precursor which is lipophilic so it can cross the barrier and then metabolized in vivo to dopamine. (7) Another example of the use of prodrugs is the pharmacological activation of a type II prodrug Azathioprine to mercaptopurine which is a chemotherapeutic agent used in the treatment of leukaemia. When mercaptopurine is administered, its clinical usefulness is restricted because of its rapid biotransformation by xanthine oxidase to an inactive metabolite 6-thiouric acid. Therefore larger doses have to be given as it has a low bioavailability, this leads to toxicity. By administering mercaptopurine as its cysteine conjugate, the limitations can be overcome. This ionic form of the pro-drug conjugate is selectively taken up by the renal organic anion transport system. The kidney B-lyase enzyme system then cleaves the prodrug conjugate to give the active mercaptopurine in the kidney (figure 5). (8)(9) To conclude, prodrugs can be metabolised in different ways to form the active drug. They can be used to target specific sites, improve absorption and improve oral delivery of poorly water-soluble drugs. They can also be used to avoid first pass metabolism in drugs with high first pass extraction and reduce toxicity. (6) Factors affecting metabolism There are several factors that can affect drug metabolism. Age, sex, inducers and inhibitors are some of which can effect drug metabolism which are mentioned below. How does age affect drug metabolism: There are many physiological changes that occur with ageing. The changes have the potential to affect both drug disposition and metabolism. Drug metabolism is mainly functioned by the liver, its size, blood perfusion and synthetic capacity for proteins which all determine the rate of hepatic drug elimination[5]. Paediatric population Phase one and phase two metabolic pathways may not be active at birth due to maturational changes. The paediatric population and elderly population have differences in their capacity to metabolise a drug which can therefore produce a lower or higher plasma concentration of active substances compared with adults depending on the enzyme system used. There are examples of metabolites produced by therapeutic agents in children that are not usually seen in adults. The metabolites produced maybe the reason for some of the efficacy and or toxicity visible with drug administration in children. An example is: caffeine production in a neonate receiving Theophylline. Other therapeutic agents which show changes in metabolite production in children are; Valproic acid, paracetamol, Chloramphenicol, Cimetidine Salicylamide. In most cases the differences that occur between children and adults are in the ratios of the metabolites relative to the parent drug rather than in new metabolites individual to the paediatric population with some exceptions. The paediatric population shows the same set of enzymes as the adult population. (1) In general age related changes in drug metabolism have been shown to occur due to a consequence of diminished enzyme activities within the elderly human liver due to the size of the liver decreasing and hepatic blood flow decreasing. With age the liver blood flow is generally reduced by about 20-30% and there is a decrease in liver size by about (17-36%). Currently there is no clear pattern; however there are two general trends that influence the rate of metabolism. One trend is that drugs that are undergoing hepatic microsomal oxidation are more likely to be metabolised slowly in the elderly and those which are conjugated are not likely to be influence by the age factor. Secondly, drugs that have high hepatic clearance, extraction ratios example-Chlormethiazole, and Labetalol and undergo extensive first pass metabolism whilst oral absorption may show a large increase in bioavailability in the elderly. Elderly population In general in the elderly population hepatic blood flow decreases up to 40% and there can be a considerable reduction in the amount of drug reaching the liver per unit. Studies have shown that the effect of ageing on liver enzymes with particular drug

Personalization In Social Care Services In Uk Social Work Essay

Personalization In Social Care Services In Uk Social Work Essay This essay seeks to discuss the concept of personalization in the health and social care services in the united kingdom whereby highlighting various theories that define the aspect of risk assessment as well as determine the risk concept as it exists in personalization and the available risk assessment models and finalize the discussion by highlighting the national and local reports relevant to personalization in the united kingdom (Keohane, N., 2009). Risk refers to the potential danger that one is exposed to given the situation is operating in or the activities that he is performing. Risk can lead to loss of life or property depending on where the risk happened and what was involved. The issue of risk can also have the influence on the final result of a given process. Any human activity in one way or the other poses some kind of risk and if not well handled it can amount to maximum destruction. Risk in some other situations can be motivated by constant exposure to activities that are dangerous to ones life. This first part of the essay aims at discussing the process of risk assessment, the conceptual frameworks, theoretical models and practice tools which inform the processes of risk assessment with regard to personalization and the associated risks The process of doing risk assessment is aimed at determining various risks in personalization in the health and social care services. Assessment on risk has to be accompanied by intervention since the process of doing risk assessment is to determine the risk and the course of action required. Risk assessment in the health and social care sector need to be a continuous process in order to guide the decision making process for the services providers. Assessment is also important in helping the service providers to come up with strategies that should be applied when dealing with risks (English Community Care Association, 2010). Use of risk assessment in the health and social care services, needs proper planning based on the previous reports in order to establish what is already known about the social services from the past experience and research information (DWP, 2006). Personalization is the process of availing public sources for the users. Its informed as a philosophy and a policy on reform on the various ways public services should be presented to those who require them. It requires very deep thoughts about the services that need to be rendered to the public. One has to think first about the user before thinking about the service, this is so because it assists in determining the kind of service the person requires and then present the same to him to meet his/her needs. Personalization normally takes different forms depending on the service that need to be offered to the public. But in most cases its done in such a manner that it provides many choices to the users through different service providers. This approach has been developed in the service care whereby various budgets are being prepared and funded alongside the universal services that need to be accessed by everybody (Gregg, P., 2008). This policy has become the fastest rationale in reforming various sectors such as the health sector which is one of the most important sectors that deal directly with the people in terms of providing them with healthcare services. The approach of providing the services to the public is something that has received support from many governments, agencies and individuals as indicated in the report on personalization of 2010 during the general election. Personalization process is a public engagement by an individual whereby the social care providers are associated and involved. Since personalization is an agenda that which one needs to take part in, it has some risks to the care providers which include; lack of privacy to personal life and information. The carers in most cases are exposed to the risk of having their personal lives known to the public. They also risk by having to sacrifice much of their time and other commitments for the public activities as well as incurring personal costs in order to provide for the need (DWP, 2008). One of the risks associated with personalization, is the demand to ascertain the advancement the public services providers have attained. The phase of implementation has been a real challenge because of the difficultness to identify what exactly should be done in personalization. Based on the previous discussion, personalization is all about social care and it has been developed in such way that it takes into consideration four main factors namely; the ability to choose and manage the services, social capital as well as prevention and ensuring access to those services that are of the national importance with a strong concern about making users self direct on public services (ESRC/ACEVO, 2009). In some cases, personalization has been established in such away in that its now a broad agenda of ensuring that services are tailored to the users by employing the state-led users approaches. This part of the discussion will take a look at various reforms that have been incorporated to ensure that services are driven to the individuals. We will give consideration to adult social care, health, employment services and housing. Personalization has a long history in adult social care that was initiated by the independent movements in the 1970s that has led to total society care reforms in the 1990s. It campaigned for the need to have people who are physically able to get direct payment, which later show the inclusion of the elderly, disabled children, mental cases as well as those people who have problems in learning. In response to this, the social enterprise in control together with the local authorities developed a budget for direct payments to individuals through an integration of various sources for more creative use (DWP, 2008). The evaluation on this initiative that was done in 2005 revealed that many people appreciated the plan as it empowered them to have a say on their lives Another agenda for personalization has been to provide good housing. Its intended at addressing peoples housing needs in a number of ways to make sure that accommodation is among the care agendas. Decent accommodation is one way of providing social care. Being one of the governments think family initiative housing of families at risk was oriented and became one of the elements that were considered when preparing the budget. Local authorities also provided funds to support people in acquiring decent accommodation for those people who are vulnerable to risk (DWP, 2008). Personal health budgets are currently piloted to various services within the health sector which included mental health, maternity care and drug abuse care. The cost of managing the services individually is not an easy thing for many people and therefore the legislation has been put in place to give direct payments to the health sector. There has also been the tailoring of health support to individuals with chronic diseases like diabetes and HIV/AIDS through the involvement of experts who provide personal care to these patients (Duffy, 2008) Therefore, personalization being an important process that is intended to deliver services to the users, there is need to involve different parties such as the multi-agencies, individuals, different groups and institutions to assess the whole process to establish the associated risks. During personalization more focus is put on adults in most cases and it is believed that emphasis is not put in to recognize children as special people who are at risk and need special attention. The internal control for children has embarked on a journey to establish the need to have personal budgets and a wide range of activities for the children, young persons and their respective families through the taking control programme of 2010. In the year 2007, the department of education by then, announced various pilots that should be applied to provide individual budgets for the children who are disabled and their families through the act of aiming high programme. In Yorkshire and Humber, the work of provi ding children with care has been supported by improving the experiences of the children at that point when they are becoming adults. The special schools were also included through the person centered planning. Those children who may have additional needs such as physical or learning problems were found to be at risk of neglect or abuse and through the (BHLP) model, the budgets were piloted to aid their needs. This model has so far seen children being introduced into a culture of, I can do starting from the bottom up (HM Government, 2007). In the area of providing employment, the jobcentre plus initiative launched in 2002, has since then incorporated personal advisers for those that are seeking jobs. However, through the assessment report, it was found that the caseload was so big and can not be handled to deliver personalized support for individuals and therefore more career training was essential for the advisers to make them more effective according to McNeil report of 2009, on career progression and development. This led to provision of block contracts in order to cover the jobseekers who have different needs (HM Government, 2007). The Gregg report of 2008 came up with the idea of personalized conditionality for the people that are not working by combining the whole idea of personalization with the concept of conditionality to those behaviors that are insensitive to change. The flexible new deal was established by the department of work and pensions in 2008, to help in creating a more personalized service provision for the people that are out of work. The public sector came into agreement to assist in placing people to work through a public funding that will be provide depending on the number of people who have been placed to work(ESRC/ACEVO, 2009). In education sector, personalized learning was put into the agenda in 2004 by David Miliband by then the minister for school standards. He described it as an high expectation of every child, given practical form by high -quality teaching based on a sound knowledge and understanding of each childs needs that is according to the report produced by Miliband in 2004. The Childrens Plan published by the Department for Children, Schools and Families (DCSF) in 2007, stated that there is need to make learning the norm for every year to ensure that every child is given proper education and no one should be left behind. The government announced a 1.2 billion sterling pound for three years plan to support personalization for educational needs (English Community Care Association, 2010). Risk assessment is a technique that is used in social work to assist in setting the ground for making informed decisions since it provides all material facts about the users of the services and different people who are ignored within the community and who require immediate attention. Frequent assessment framework on risk is provided for use in order to give all the participants the opportunity to regularly conduct risk assessments in order to determine the various needs for the users that need to be supplied. This will enable individuals directly deal with evolving needs with regard to health and social care (Hurst, G., 2009). Given the need to reveal the likely risks, a given systematic procedure with specific frameworks, models and practices have to be employed to ensure that the process of assessing the risk is a success. This essay has sort to go through various tools and practices that need to be considered when looking the risks that are likely to occur and they include the following; Time is of essence during then process since its required to enable the assessors to go through all possible areas that may be a course of any eventuality. Its important that all the involved parties are given humble time to accomplish their assessments to come up with a good report. Time is required to collect all historical facts and the same time to compare all information to help generate concrete conclusions. What the assessor should not do at all, is just to collect materials and put them down on record because this avoid the views of the users and other social carers. All concerned people need to be honest to each other at each step as this will create moment consultation and discussions doing the assessment (Hurst, 2009). Those parties that are deemed vulnerable should always be given a hearing to avoid any conflict. Every party should feel honored and respected during the exercise. What must not be done in this case is to avoid recoding any information especially the disagreed areas because this might be the situations that are prone to risk. Its important for the assessors to understand what exactly the service user desire to know. In this case what should be avoided is to assume things especially the way one is supposed to address the other colleagues (ESRC/ACEVO, 2009). Every material needs to be made available to the users. Its supposed to be easy to be retrieved and acceptable by the professionals. At the same time they also need to consider the importance of sharing materials and facts at any given time. Its absolutely very necessary to keep consultations a life for both the assessors and the users. What needs to be avoided here is being selfish in consultations with the advocates especially when they believe that the time of assessment is likely to be a little bit longer and want to rush to avoid criticism and concerns about the assessment report (GSCC, 2008). This part will critically analyze awareness of individual, group and institutional decision-making processes and the implications for multi-disciplinary systems and processes. Individuals, different groups, and decision making processes need to apply risk assessment reports to make their decisions with regard to the needs that are there. Once a need has been identified, it is important for various service providers such as commissioners, users and service providers to work together as a team in order to come up with a strategy that can be used to meet the needs of the users. The process of containing risk is called management of risk and its aimed at reducing any associated dangers that may result from that risk. In most cases the risk that has been there for the services providers is the one associated with lack of information and financial resources to determine and manage their affairs (Duffy and Fulton, 2009). Various agencies and other third party services providers need to come up with various ways to manage new and emerging risks at work especially when dealing with the local authorities in order to be in a position to minimize the danger of failing to meet the users needs. There is need for collaboration between the local authorities and other agencies to avoid the risk of meeting the market demands. Its appropriate in some cases to have contingency funding in place to fund for activities incase there could be a likelihood of the market failure. On the other hand, commissioning organizations need to elaborate the extent to which they can handle the legal liabilities especially if there are legal disputes that may arise in the process of delivering services. Commissioning of personalization is the process of redefining new approaches to be applied in providing services to the users (GSCC, 2008). The approach was developed as a result of the need to reach many people and avail a number of services for the customer choices. The approaches are expected to be convenient and faster in services delivery apart from being cost effective. In the processing of commissioning, however, so many challenges have come into being as result of personalized approach to service delivery. Commissioning of services does not mean that only people whose job title is written commissioning will be doing the job but the service users also need to be involved in the process of providing services to the number of the services providers who can be used at any given time to assist in service delivery (DWP, 2008). Good commissioning is important in attaining the vision described out in Putting People First. It needs a transformation within the commissioning agenda in regard to the investments commissioners have, the different markets they wish to work to shape and the kind of relationships they wish to need to build in order to meet peoples needs (Gregg, 2008). Commissioning in the transformed social care is somehow different but no much important task. As councils differ to increasing proportions for their investments meant to make individuals to come up with their own service decisions, commissioners have to find ways to use to work in partnership with service providers to make sure a wide range of selections are made available and that the right kind of support for budget bearers and self-financiers. This will definitely mean that there is a need to come up with more innovative services that better relate to persons selection decisions (Duffy, 2008). In actual sense personalization is the mechanism developed to tailor services to the users in a more convenient way. The process ensures that all essential services are channeled to the right people at the right time. The activities surrounding the delivery services include a number of key players who take part in the exercise. These services are delivered to meet the needs of individuals. The key players of service delivery are; the social care workforce, third party organizations, the private sector organizations, user-led organizations, commissioning and the policy regulation (DWP, 2008). Social care workforce as an agency is used when there is total need for change at levels on the various strategies that are used to offer the services to the people and their duties include the following; to provide personalized social care and supportive services incase of any need. They are key players used by the government in performing its central role of service delivery to the users. These people are supposed to add value to the lives of people through their distinct contributions especially for those services that relate to bettering life and empowering the people to be independent for all those who use these services including; families, carers and communities. The social workforce is intended in supporting independence, choice as well as control over difficulties that different individuals face such as disabilities, age and mental health related problems (HM Government, 2007). Advocacy workers groups are established to fight for the needs of people and protecting their rights. They support the people in making sure that services for consumption are always available for the users and at the same time ensure that they are safe and life promoting services (Gregg, 2008). Personalization for advocacy workers means working together with people who are the users of the services to ensure that services provided are genuine. They also assist in monitoring the systems that are used to deliver the services. They are also meant to enhance the advocacy levels to make sure that care for people is well funded and does not fall below the required budgets that are used to support services to the public (Hurst, 2009). They also advocate for changes to the types of services that people require and the budgets being spent for the purpose of accountability in the sector of social care. They also assist to negotiate for people to get more support than the usual conventional one. This is aimed at providing more personalized services that support individuals to enhance their capabilities in terms of contribution to the community, improve their lives as well as the community life (ESRC/ACEVO, 2009). Home care service providers in most cases in many occasions assist to offer services that confine with personal needs thus creating the need to have more support from people who use them. These are called the home care service providers and their main agenda is to make sure that services are put closer to the users. These are organizations that are started and within the community to perform various duties in relation to services provided. There duties include developing systems and trainings to assist the staff enhance their knowledge as well as creativeness and innovation in person centered approaches (DWP, 2006). They think on how to add on the expansion of assistance offered to individual workforce so as to increase more specialized services to the diverse markets. Its also important for the home care services providers to find the best to provide their services whether directly through the councils or personal budget bearer. This part seeks to evaluate the local authorities reports on personalization The 2009 report by the Association of Adult Social Services (ADASS) and the Local Government Association (LGA) which carried out a survey on the process of putting peoples needs first when delivering services indicated that a number of recommendations were put forward to assist in delivering well transformed needs which conform with the needs of the users. In the report, the following recommendations were arrived in order to transform service delivery to the people; the transformation of the social care proved very necessary since it was discovered that there was conflict of interest among different service providers since among them, there were those interested in the same services. This has proved difficulty in promoting transparency and accountability within the sector thus requiring total transformation for efficient management of the public services (Hurst, G., 2009) There is need to streamline the process of transferring funds to those who are eligible so that to have personal. There is need for all partners to come up with systems that are cost effective as an intervention to reduce the high demand for services and lastly ensure that people who receive and use these services are well informed of the available options within the community to meet their needs (GSCC, 2008). The report on personalization produced by the centre for Public Service Partnerships (CPSP) indicates that personalization is an important factor in providing services to the public. This reform since then has raised many important questions that need urgent debate on the way forward about personalization using personal budgets. Personalization of public services is meant to last even if it means using individual budgets to empower the users purchase the services. Personalization policy must be supported and maintained. The report went further to state the need to improve on personalization in order to extend service delivery to the public. Many of the public services like social care, handling of long-term diseases among the citizens, child care, developmental training, higher education and support for those people who are not working either because they are retired or aged require a model of personalization will assist in channeling public finances down to the people in order to allow them make their own informed choices on what to purchase and from where (Duffy, 2010). However, this strategy is accompanied with challenges that need to be taken care of. Firstly, it will require that the relationship between the individuals and the state be streamlined in order to determine what services should be channeled and by which provider. This is likely to abolish monopoly in the public sector services enjoyed by third party businesses and other secto rs previously enjoyed the government protection. The whole process of personalization will mean fair competition and dealing within the public services production sector. However, this requires proper regulation to control the quality of services and the costs of obtaining those services (HM Government, 2007). Learning outcomes The services suppliers have to change their way of operation to fit in the competition that involve many suppliers in the pubic service delivery sector. There is need for service providers to develop models that are more personalized thus meeting the specific requirements of the users. The demand for public services will shift from the commissioners to the providers thus creating more demand for services which in some cases will not be easy to manage without enough cash flows. This will require more funding to facilitate (GSCC, 2008). The regulations used should be citizen based to allow for proportionate handling of risk. This is to protect the user from exposed to higher risk than the service provider. No single service provider will enter the sector to reap from the public but must put the interest of the users first. The main function of commissioners in this case is to recognize the needs and various aspirations in relation with the users and other professional bodies that deliver services. They also expected to assess the needs where there is no uniformity in service delivery and allocation of financial resources to the users. They will also be expected to monitor the quality of services and their standards against the legislative requirements. This regulation is very necessary since it protects the users from accessing substandard services (Duffy and Fulton, 2009). Under this strategy, the citizens must be supported to make their own well informed choices from a variety of sources. This model raises a fundamental question on the kind of relationship that is there between the professional adviser and the users that will motivate the discharge of very important information concerning various services as well as information about power and authority between them. A lot of counseling is required for the users to follow the professional advice and access to advocacy (DWP, 2006). However, personalization means that the service users are able to make informed choices. This is necessary to avoid conflicts between the users and the service providers. Personalized services are expenditures incurred on the public budget and must therefore be well managed to benefit the final users. While spending the public budget, there is need to take into considerations various factors such as purists and pragmatists, dogmatic and idealistic so as to provide well balan ced services for all users regardless of whom they are. Personalization in the social care context, require proper knowledge about the divergent needs the users have, their rights and the possible risks that may face the process. Risk assessment and care provision services are supposed to offer more meaningful and legal direction which the various participants will require in order to provide satisfactorily services to the public (DWP, 2006). The personalization process must be designed in such away in order to offer quality services that are more responsive and cost effective so to enable the carers avoid any kind of unnecessary challenges in the execution of social care services to the community. There is need also to start smaller units that offer community care within the society so as to assist in protecting the abused within a given public setting (Gregg, 2008). People who have learning problems need to be provided with special care homes within the community where they can be supported and provided for. The social care workers are expected to practice professionalism while carrying out social duties in order to add value to the services provided.

Antigone Essay :: essays research papers fc

All true Greek tragedies were written using the same basic set of characteristics. One such characteristic was that all the characters were of nobility. This was to ensure that their fall from grace would be greater to those watching the play in action. Another characteristic of all Greek tragedies is that they were written in poetic form, as this was the style of writing at the time. There were also always almost constant references to the gods and to matters of fate. And it was the ever-present chorus who made a great deal of these references. One of the most important characteristics of the Greek tragedy was that the hero of the play always had a fatal flaw which proved not only to be their downfall but the cause of destruction of all those around them. Sophocles play â€Å"Antigone† is a wonderful example of the Greek tragedy because it encompasses all these characteristics.   Ã‚  Ã‚  Ã‚  Ã‚  The major characters in the play are all nobility in some form or another. Antigone is the daughter of Oedipus and Iocaste the former king and queen which makes her a princess (Scene 2, Lines 1-2) (Scene 4, Lines 36-44). She is also the sister of Ismene (Prologue, Lines 1&7) which makes her a princess as well. The ruling king of Thebes at the time is King Creon (Prologue, Line 6). He has a wife Eurydice who is queen (Exodus, Line 25-26) and a son Haimon who is the prince (Exodus, Lines 64-68). The reason that the characters were all forms of nobility is to make their fall from grace and or powers seem even greater and harder for them to bear. This was designed to be uplifting to the common peoples of ancient Greece.   Ã‚  Ã‚  Ã‚  Ã‚  Like other play that were written at this point in time Sophocles wrote his play â€Å"Antigone† in poetic form. This can be seen in various places throughout the play (Parados, Line 1-7). And although some of its poetic form is lost in the translation of the play from ancient Greek to Modern English, it is still evident primarily when the chorus is explaining the passage of time (Scene 4, Lines 33-36). Or describing a battle to the audience (Parados, Lines 34-38).   Ã‚  Ã‚  Ã‚  Ã‚  Antigone is also full of references to the gods and to fate (Exodus, Lines 3-6) and how it has affected specific character’s lives. The chorus made a large amount of these references themselves, when talking about the gods (Ode 2, Lines 13-18) and to fate (Ode 2, Lines 25-28).

Henry ford :: essays research papers

THE LIFE OF HENRY FORD Henry ford was born July 30, 1863. He was the first child out of six born to William and Mary Ford. He grew up on a big farm in Dearborn, Michigan. He went to school in a one room building and did many chores every day after he got home. He did not like farm chores. He did like to work on mechanical things. When he was 16, he left home to move to Detroit. He got a job there working on machinery. Three years later he went back home and began to work on repairing steam engines. In 1888, he married Clara and ran a sawmill to make money. In 1891, Henry Ford began working for Edison Illuminating Company in Detroit. He was promoted to Chief Engineer in 1893. He began to experiment on internal combustion engines on his own time at home. In 1896, he built his own vehicle that moved on its own called the Quadricycle. He was not the first to make a machine that ran on gasoline by itself. In 1903, the Ford Motor Company was created. He became the Vice President and the Chief Engineer of the corporation. There were other people who helped run the business and give money to it. The company only made a few cars a day. In 1908, he made the Model T. It was reliable and did not cost a lot. It was easy to drive and handle on rough roads. It was a huge success. By 1918, almost half of all the cars in America were Model T’s. In 1910, in Highland, Michigan, Mr. Ford built another plant to make a lot more of these cars. In 1913, he created the first true

The Return: Midnight Chapter 11

When M. le Princess Jessalyn D'Aubigne had drunk her fil of Damon's blood – and she was thirsty for such a fragile thing – it was Damon's turn. He forced himself to remain patient when Jessalyn flinched and frowned at the sight of his ironwood knife. But Damon teased her and joked with her and played chasing games up and down the enormous bed, and when he final y caught her, she scarcely felt the knife's sting at her throat. Damon, though, had his mouth on the dark red blood that wel ed out immediately. Everything he'd done, from pouring Black Magic for Bonnie to pouring out the star bal ‘s liquid at the four corners of the Gate to making his way through the defenses of this tiny gem of a castle had been for this. For this moment, when his human palate could savor the nectar that was vampire blood. And it was†¦heavenly! This was only the second time in his life that he'd tasted it as a human. Katerina – Katherine, as he thought of her in English – had been the first, of course. And how she could have crept off after that and gone, wearing just her short muslin shift, to the wide-eyed, inexperienced little boy who was his brother, he would never understand. His disquiet was spreading to Jessalyn. That mustn't happen. She had to stay calm and tranquil as he took as much as he could of her blood. It wouldn't hurt her at al , and it meant al the difference to him. Forcing his consciousness away from the sheer elemental pleasure of what he was doing, he began, very careful y, very delicately, to infiltrate her mind. It wasn't difficult to get to the nub of it. Whoever had wrenched this delicate, fragile-boned girl from the human world and had endowed her with a vampire's nature hadn't done her any favors. It wasn't that she had any moral objections to vampirism. She'd taken to the life easily, enjoying it. She would have made a good huntress in the wild. But in this castle? With these servants? It was like having a hundred snooty waiters and two hundred condescending sommeliers staring her down as soon as she opened her mouth to give an order. This room, for instance. She had wanted some color in it – just a splash of violet here, a little mauve there – natural y, she realized, a vampire princess's bedchamber had to be mostly black. But when she'd timidly mentioned the subject of colors to one of the parlor maids, the girl had sniffed and looked down her nostrils at Jessalyn as if she'd asked for an elephant to be instal ed just beside her bed. The princess had not had the courage to bring up the matter with the housekeeper, but within a week three baskets ful of black-and-off-black throw pil ows had arrived. There was her â€Å"color.†And in the future would her highness be so good as to consult her housekeeper before querying the staff as to her household whims? She actually said that about my â€Å"whims,† Jessalyn thought as she arched her neck back and ran sharp fingernails through Damon's thick soft hair. And – oh, it's no good. I'm no good. I'm a vampire princess, and I can look the part, but I can't play it. You're every bit a princess, your highness, Damon soothed. You just need someone to enforce your orders. Someone who has no doubts about your superiority. Are your servants slaves? No, they're all free. Well, that makes it a little trickier, but you can always yell louder at them. Damon felt swol en with vampire blood. Two more days of this and he would be, if not his old self, then at least almost his old self: a ful vampire, free to walk about the city as he liked. And with the Power and status of a vampire prince. It was almost enough to balance out the horrors he'd gone through in the last couple of days. At least, he could tel himself that and try to believe it. â€Å"Listen,†he said abruptly, letting go of Jessalyn's slight body, the better to look her in the eye. â€Å"Your glorious highness, let me do one favor for you before I die of love or you have me kil ed for impudence. Let me bring you ‘color' – and then let me stand beside you if any of your menials grumble about it.† Jessalyn wasn't used to this kind of sudden decision, but couldn't help but be carried along with Damon's fiery excitement. She arched her head back again. When he final y left the bijoux palace, Damon went out the front door. He had with him a little of the money left over from pawning the gems, but this was more than enough for the purpose he had in mind. He was quite certain that the next time he went out, it would be from the flying portico. He stopped at a dozen shops and spent until his last coin was gone. He'd meant to sneak in a visit to Bonnie as wel while doing his errands, but the market was in the opposite direction from the inn where he'd left her, and in the end there just wasn't time. He didn't worry much as he walked back to the bijoux castle. Bonnie, soft and fragile as she seemed, had a wiry core that he was sure would keep her inside the room for three days. She could take it. Damon knew she could. He banged on the little castle's gate until a surly guard opened it. â€Å"What do you want?†the guard spat. Bonnie was bored out of her mind. It had only been a day since Damon had left her – a day she could only count by the number of meals brought to her, since the enormous red sun stood forever on the horizon and the blood-red light never varied unless it was raining. Bonnie wished it was raining. She wished it was snowing, or that there would be a fire or a hurricane or a smal tsunami. She had given one of the star bal s a try, and found it a ridiculous soap opera that she couldn't understand in the least. She wished, now, that she had never tried to stop Damon from coming here. She wished that he had pried her off before they had both fal en into the hole. She wished that she had grabbed Meredith's hand and just let go of Damon. And this was only the first day. Damon smiled at the surly guard. â€Å"What do I want? Only what I already have. An open gate.†He didn't go inside, however. He asked what M. le Princess was doing and heard that she was at a luncheon. On a donor. Perfect. Soon there came a deferential knock at the gate, which Damon demanded be opened wider. The guards clearly didn't like him; they had properly put together the disappearance of what turned out to be their captain of guard and the intrusion of this strange human. But there was something menacing about him even in this menacing world. They obeyed him. Soon after that there came another quiet knock and then another, and another and so on until twelve men and women with arms ful of damp and fragrant brown paper had quietly fol owed Damon up the stairs and into M. le Princess's black bedchamber. Jessalyn, meanwhile, had had a long and stuffy post-luncheon meeting, entertaining some of her financial advisors, who both seemed very old to her, although they had been changed in their twenties. Their muscles were soft with lack of use, she found herself thinking. And, natural y, they were dressed in ful -sleeved, wide-legged black except for a fril at their throats, white inside by gaslight, scarlet outside by the eternal blood-red sun. The princess had just seen them bow out of her presence when she inquired, rather irritably, where the human Damon was. Several servants with malice behind their smiles explained that he had gone with a dozen†¦humans†¦up to her bedchamber. Jessalyn almost flew to the stairs and climbed very quickly with the gliding motion that she knew was expected of proper female vampires. She reached the Gothic doors, and heard the hushed sounds of indignant spite as her ladies-in-waiting al whispered together. But before the princess could even ask what was going on, she was engulfed in a great warm wave of scent. Not the luscious and life-sustaining scent of blood, but something lighter, sweeter, and at the moment, while her bloodlust was sated, even headier and more dizzying. She pushed open the double doors. She took a step into her bedchamber and then stopped in astonishment. The cathedral-like black room was ful of flowers. There were banks of lilies, vases ful of roses, tulips in every color and shade, and riots of daffodils and narcissus, while fragrant honeysuckle and freesia lay in bowers. The flower peddlers had converted the gloomy, conventional black room into this fanciful extravaganza. The wiser and more farsighted of M. le Princess's retainers were actively helping them by bringing in large, ornate urns. Damon, upon seeing Jessalyn enter the room, immediately went to kneel at her feet. â€Å"You were gone when I woke!†the princess said crossly, and Damon smiled, very faintly. â€Å"Forgive me, your highness. But since I am dying anyway, I thought that I should be up and securing these flowers for you. Are the colors and scents satisfactory?† â€Å"The scents?†Jessalyn's whole body seemed to melt. â€Å"It's†¦ like†¦an orchestra for my nose! And the colors are like nothing I've ever seen!†She burst into laughter, her green eyes lightening, her straight red hair a waterfal around her shoulders. Then she began to stalk Damon back into the gloom in one corner. Damon had to control himself or he would have laughed; it was so much like a kitten stalking an autumn leaf. But once they got into the corner, tangled in the black hangings and nowhere near a window, Jessalyn assumed a deadly serious expression. â€Å"I'm going to have a dress made, just the color of those deep, dark purple carnations,†she whispered. â€Å"Not black.† â€Å"Your highness wil look wonderful in it,†Damon whispered in her ear. â€Å"So striking, so daring – â€Å" â€Å"I may even wear my corsets on the inside of my dress.†She looked up at him through heavy lashes. â€Å"Or – would that be too much?† â€Å"Nothing is too much for you, my princess,†Damon whispered back. He stopped a moment to think seriously. â€Å"The corsets – would they match the dress or be black?† Jessalyn considered. â€Å"Same color?†she ventured. Damon nodded, pleased. He himself wouldn't be caught dead in any color other than black, but he was wil ing to put up with – even encourage – Jessalyn's oddities. They might get him made a vampire faster. â€Å"I want your blood,†the princess whispered, as if to prove him right. â€Å"Here? Now?†Damon whispered back. â€Å"In front of al your servants?† Jessalyn surprised him then. She, who had been so timid before, stepped out of the curtains and clapped her hands for silence. It fel immediately. â€Å"Everyone out!†she said peremptorily. â€Å"You have made me a beautiful garden in my room, and I am grateful. The steward† – she nodded toward a young man who was dressed in black, but who had wisely placed a dark red rose in his buttonhole – â€Å"wil see to it that you're al given food – and drink – before you go!†At this there was a murmur of praise that made the princess blush. â€Å"I'l ring the bel pul when I need you† – to the steward. In fact, it wasn't until two days later that she reached up and, a little reluctantly, rang the bel pul . And that was merely to give the order that a uniform be made for Damon as quickly as possible. The uniform of captain of her guard. By the second day, Bonnie had to turn to the star bal s as her only source of entertainment. After going through her twenty-eight orbs she found that twenty-five of them were soap operas from beginning to end, and two were ful of experiences so frightening and hideous that she labeled them in her own mind as Never Ever. The last one was cal ed Five Hundred Stories for Young Ones, and Bonnie quickly found that these immersion stories could be useful, for they specified the names of things a person would find around the house and the city. The sphere's connecting thread was a series about a family of werewolves named the Dz-Aht-Bhi'iens. Bonnie promptly christened them the Dustbins. The series consisted of episodes showing how the family lived each day: how they bought a new slave at the market to replace one who had died, and where they went to hunt human prey, and how Mers Dustbin played in an important bashik tournament at school. Today the last story was almost providential. It showed little Marit Dustbin walking to a Sweetmeat Shop and getting a sugarplum. The candy cost exactly five soli. Bonnie got to experience eating part of it with Marit, and it was good. After reading the story, Bonnie very careful y peeked through the edge of the window blind and saw a sign on a shop below that she'd often watched. Then she held the star bal to her temple. Yes! Exactly the same kind of sign. And she knew not only what she wanted, but how much it should cost. She was dying to get out of her tiny room and try what she had just learned. But before her eyes, the lights in the sweetshop went dark. It must be closing time. Bonnie threw the star bal across the room. She turned the gas lamp down to just the faintest glow, and then flung herself on her rush-fil ed bed, pul ed the covers up†¦and discovered that she couldn't sleep. Groping in ruby twilight, she found the star bal with her fingers and put it to her temple again. Interspersed with clusters of stories about the Dustbin family's daily adventures were fairy tales. Most of them were so gruesome that Bonnie couldn't experience them al the way through, and when it was time to sleep, she lay shivering on her pal et. But this time the story seemed different. After the title, The Gatehouse of the Seven Kitsune Treasures, she heard a little rhyme: Amid a plain of snow and ice There lies kitsune paradise. And close beside, forbidden pleasure: Six gates more of kitsune treasure. The very word kitsune was frightening. But, Bonnie thought, the story might prove relevant somehow. I can do this, she thought and put the star bal to her temple. The story didn't start with anything gruesome. It was about a young girl and boy kitsune who went on a quest to find the most sacred and secret of the â€Å"seven kitsune treasures,†the kitsune paradise. A treasure, Bonnie learned, could be something as smal as a single gem or as large as an entire world. This one, going by the story, was in the middle range, because a â€Å"paradise†was a kind of garden, with exotic flowers blooming everywhere, and little streams bubbling down smal waterfal s into clear, deep pools. It was al wonderful, Bonnie thought, experiencing the story as if she were watching a movie al around her, but a movie that included the sensations of touch, taste, and smel . The paradise was a bit like Warm Springs, where they sometimes had picnics back at home. In the story, the boy and girl kitsune had to go to â€Å"the top of the world†where there was some kind of fracture in the crust of the highest Dark Dimension – the one Bonnie was in right now. They managed somehow to travel down, and even farther down, and passed through various tests of courage and wit before they got into the next lowest dimension, the Nether World. The Nether World was completely different from the Dark Dimension. It was a world of ice and slippery snow, of glaciers and rifts, al bathed in a blue twilight from three moons that shone from above. The kitsune children almost starved in the Nether World because there was so little for a fox to hunt. They made do with the tiny animals of the cold: mice and smal white voles, and the occasional insect (Oh, yuck, Bonnie thought). They survived until, through the fog and mist, they saw a towering black wal . They fol owed the wal until final y they came to a Gatehouse with tal spires hidden in the clouds. Written above the door in an old language they could hardly read were the words: The Seven Gates. They entered a room in which there were eight doorways or exits. One was the door through which they had just entered. And as they watched, each door brightened so they could see that the other seven doors led to seven different worlds, one of which was the kitsune paradise. Yet another gate led to a field of magical flowers, and another showed butterflies flittering around a splashing fountain. Another dropped to a dark cavern fil ed with bottles of the mystical wine Clarion Loess Black Magic. One gate led to a deep mine, with jewels the size of a fist. And then there was a gate which showed the prize of al flowers: the Royal Radhika. It changed its shape from moment to moment, from a rose to a cluster of carnations to an orchid. Through the last door they could see only a gigantic tree, but the final treasure was rumored to be an immense star bal . Now the boy and girl forgot al about the kitsune paradise. Each of them wanted something from another of the gates, but they couldn't agree on what. The rule was that any party or group who reached the gates could enter one and then return. But while the girl wanted a sprig of the Royal Radhika, to show that they'd completed their quest, the boy wanted some Black Magic wine, to sustain them on the way back. No matter how they argued they couldn't reach an agreement. So final y they decided to cheat. They would simultaneously open a door and jump through, snatch what they wanted, and then jump back out and be out of the Gatehouse before they could be caught. Just as they were about to do so, a voice warned them against it, saying, â€Å"One gate alone may you twain enter, and then return from whence you came.† But the boy and the girl chose to ignore the voice. Immediately, the boy entered the door that led to the bottles of Black Magic wine and at the same instant the girl stepped into the Royal Radhika door. But when each turned around there was no longer any sign of a door or gate behind them. The boy had plenty to drink but he was left forever in the dark and cold and his tears froze upon his cheeks. The girl had the beautiful flower to look at but nothing to eat or drink and so under the glowing yel ow sun she wasted away. Bonnie shivered, the delicious shiver of a reader who had gotten what she expected. The fairy tale, with its moral of â€Å"don't be greedy†was like the stories she'd heard from the Red and the Blue Fairy Books when she was a child sitting on her grandmother's lap. She missed Elena and Meredith, badly. She had a story to tel , but no one to tel it to.