Telecommunication Act of 1996 essays

Media transmission Act of 1996 papers In February of 1996, the U.S. Congress sanctioned the Telecommunications Act of 1996. The Act was one of the most significant changes in the guideline of any industry in ongoing history. The Act supplanted every single current law, FCC guidelines, and the assent degree and ensuing court decisions under which AT The essential objective of the Act was to advance rivalry for neighborhood telephone utilities, significant distance telephone utilities, and satellite TV administrations. Between trade transporters (IXC, (for example, AT I accept that the Act had the most effect on Local telephone utility. Nearby telephone utility had been a regul... <!

Frank Lloyd Wright Essay Example for Free

Straight to the point Lloyd Wright Essay Forthcoming Lloyd Wright was an engineer, inside fashioner, author, and teacher. He structured in excess of 1,000 tasks and more than 500 of them were finished. He advanced natural design in his time which is very famous at this point. (Baruffii, 2008) He additionally planned official, places of worship, schools, high rises, and galleries. He wrote in excess of twenty books and numerous articles. He was a well known instructor in both Europe and the United States (Toronto Star, 1987). This paper will examine Frank Lloyd Wright’s history and contrast it with the reasons why he is as yet well known today and will stay famous later on. Straightforward Lloyd Wright was conceived in Richland Center Wisconsin into a cultivating family who battled to get by. His folks isolated when he was 14. Plain at that point got liable for his mom and sister as he never observed his dad again. There is no record of him moving on from secondary school yet he was acknowledged as an uncommon understudy at University of Wisconsin in 1886. He wedded in 1889 and constructed his own home around then. Straight to the point Wright at that point went to work for another designer however lost his employment when that modeler found that he was structuring for some all alone. He at that point set up his very own business out of his home. He revamped and included to the house a few times. He moved his office downtown and afterward moved it a few different occasions (Huxtadey, 2009). Straight to the point Lloyd Wright left his better half with six youngsters to invest energy in Europe while composing his first book, with the spouse of a companion. He at that point got back home and assembled Taliesin on 200 sections of land acquired by his mom. His then spouse and her two youngsters were killed in this home. The home turned into his winter home and is currently the Frank Lloyd Wright School of Architecture. This house is situated in Scottsdale Arizona and couldn't be more â€Å"green† than if it had been worked as a major aspect of that development today. Wright at that point met and moved into to Taliesin again with a divorced person however he was as yet hitched to his first spouse. He, simultaneously started to the structure of the Imperial Hotel in Tokyo. He lived in Tokyo during the development of the structure. Keeping his inventive style, he planned the Imperial Hotel utilizing both Japanese and Western design. He needed to show that Japan was turning into a cutting edge country and that they had connections toward the West. The Imperial Hotel was destroyed in 1968 however a portion of the passageway was held in a gallery. It is read right up 'til today for configuration tones for now and tomorrows structures. During the downturn, similar to every other person work was hard to track down. Wright started addressing and composing right now and had at long last gotten a separation from his first spouse and wedded a second. He completed a few books at this point and was adding to engineering magazine. Presently, he opened his school at Talesman. The educational cost was $1,100 and he in no time had a holding up list. In 1934 Wright structured and manufactured Fallingwater which has gotten one of the most acclaimed bits of design on the planet. The house was worked for Edgar Kaufmann in Bear Run Pennsylvania. It was based on a cascade. During this time Wright was additionally starting to structure his unobtrusive lodging. The first was his Usonian house in Madison Wisconsin. He accepted that everybody ought to have a planner and not a cutout house. (wright. htm) Wrights Fallingwater house is one of those plans that address our theory. It is a plan of his day, a structure of today and is accepted to be a structure for tomorrow. There are things about keeps an eye on human instinct that we will in general overlook. We are a piece of nature. At the point when Wright structured this home he loved the incredible sound of the cascade and the quality and magnificence of the woodland around it. There were emotional stone edges and excellent hues in the rock all around. He needed the plan to stream as a feature of nature and it did and does and will. It takes ones creative mind to a spot a large number of need to go yet discover trouble in getting to. A huge number of individuals see this home each year and are in amazement of its magnificence and structure (Steffenson, 2009). Wright at that point came back to Arizona where he engaged in numerous activities in the Phoenix and Scottsdale zone. He planned the Opera House at the University of Arizona which was initially intended to be worked in the Mid-East however was worked here. He had a brief period in his history when he out of nowhere prefers what must be called retro-science fiction innovation. Around then, he structured what was to be the Southwest Christian Seminary. Many state the structure was straight out of Flash Gordon. The structure was rarely constructed. Benjamin Adelmans House was structured and worked in Scottsdale in 1951. The Norman Lykes house was the last house in the zone as it was planned not long before Wright passed on in 1959. It was a 2,800 sq. ft. home that was roundabout in plan and was really worked in 1967. He had a lot of impact in engineering in the zone as he was this zones most acclaimed snow fowl. He came here each winter and reliably had another thought for the desert. That was a delightful aspect regarding Wright is that he could see excellence all over and had the option to utilize the scene as a feature of the structure. Is that not what we are searching for now and presumably tomorrow? To wrap things up there is the Guggenheim Museum. It turns 50 this year (Lubow, 2009). Wright had longing to raise human culture through its engineering. He felt that how we lived was the manner by which we learned. The magnificence of where we lived ought to be mainted and nature ought to be a piece of all structure. The Guggenheim Museum is a piece of the fantasy and the vision that Wright had for an incredible duration. This would be the last structure he planned. It opened in New York City October 21, 1959 (Lubow, 2009). Straight to the point Lloyd Wright kicked the bucket a half year before it opened. He had numerous issues in getting it going. There were spending issues, construction law issues, and even issues with the craftsmen that would inevitably show in the structure. He went through basically 16 years of his life structuring and regulating this structure. There are a portion of those issues that the specialists were worried about. It is hard to balance compositions in the gallery in light of the inclining of dividers in addition to other things. Be that as it may, it is one of the most excellent structures on the planet and it is said that it is prophetic in its method of addressing the requirements of today and the universe of craftsmanship (Lubow, 2009). Wright appeared to see today’s world and how we would imagine workmanship when he structured the structure. This author would think about whether the following 100 years they will feel the equivalent. One of the numerous things that Wright accepted shows in his plan of the spaces at the Guggenheim. He felt that however we as a whole pine for being separated from everyone else in some cases, we are possibly genuinely very much evolved people when we are for the most part socially created. The Guggenheim is worked to oblige that. It is colossal and appears to be greater than life however as one strolls through, it feels as though one is separated from everyone else with the workmanship and simultaneously a piece of people around them. Just the structure can cause one to feel thusly. Once more, is this not a plan for what's to come? There are such a large number of excellent spaces worked by Frank Lloyd Wright. We can just start to recognize what he was genuinely thinking. In his history he discusses his convictions about human instinct and the spaces they live in. His Prairie houses were worked for the normal property holder but they resemble no house that any of us can possess however a significant number of us might want to. The Prairie houses were low even structures with open inside spaces. You see their impact in homes everywhere throughout the United States. Taking everything into account, clearly the impact of Frank Lloyd Wright has not left. His unique plans are the absolute most excellent structures on the planet and he is refreshing as the most well known engineer of his time. He keeps on being well known today as we attempt to advance toward plans that are progressively common and all the more piece of the nature around us. In the entirety of the plans that have been created to take in the effects of the scene around them we discover Wright components. These are the things that help the way that Frank Lloyd Wright was a visionary of his time, our time and what's to come. Assets Baruffi, K. , (2008). 10 extraordinary spots to observe Frank Lloyd Wright’s vision. USA Today. Accessible at http://www. ebscohost. com http://draftsman. design. sk/straight to the point lloyd-wright-designer/blunt lloyd-wright-modeler. php Huxtadey, A. , (2009). The hand and eye of virtuoso. Money Street Journal. 25(24) pg. 7. Lubow, A. , (2009). The triumph of Frank Lloyd Wright. Smithsonian; 40 (3) pg 52-61. Prairie Styles, Frank Lloyd Wright (1997). http://www. prairiestyles. com/wright. htm Steffensen, I. , (2009). Blunt Lloyd Wright and the endowment of virtuoso. The Journal of American Culture, 32:3. pg. 257-268. Toronto Star. (1987). Candid Lloyd Wright: his impact lives on in home goods; AP news highlights. Pg 6.

Serum Blood Levels and Medication

Serum Blood Levels and Medication Bipolar Disorder Treatment Print Serum Blood Levels and Medication By Marcia Purse Marcia Purse is a mental health writer and bipolar disorder advocate who brings strong research skills and personal experiences to her writing. Learn about our editorial policy Marcia Purse Medically reviewed by Medically reviewed by Steven Gans, MD on August 05, 2016 Steven Gans, MD is board-certified in psychiatry and is an active supervisor, teacher, and mentor at Massachusetts General Hospital. Learn about our Medical Review Board Steven Gans, MD Updated on June 17, 2019 ERproductions Ltd / Getty Images More in Bipolar Disorder Treatment Medications Symptoms Diagnosis Serum blood level describes the amount of a given medication present in your blood at the time of testing. Many medications used to treat bipolar disorder have what is known as a small therapeutic window meaning the difference between a therapeutic level and toxic level can be small in some individuals. The only way to test these levels for a certain medication is to test a persons serum blood levels. By doing so, that window can be assessed and the proper dosage for a certain medication can be given. What Is Serum Blood Level? Blood serum is the liquid part of the blood that contains no clotting factors or blood cells. When doctors check for serum blood levels, they are usually checking for lithium levels in the bloodstream to be sure that the right dosage is being administered. If other medications are being taken, blood serum levels could be monitored regularly to ensure that lithium is not interfering with the medication. Specifically, the therapeutic range for lithium has been established at 0.6 - 1.2 mmol/L. Within this range, most people will respond to the drug without symptoms of toxicity. Some patients may be more or less sensitive to lithium and thus need to be tracked to alleviate side effects and avoid toxicity of medication. Medications That Require Testing In addition to lithium, some medications used to treat bipolar disorder require serum blood level testing. Other medications that require serum blood level testing include Tegretol (carbamazepine) and Depakote/Depakene (sodium valproate, valproic acid). Testing serum blood levels are usually done before medication is prescribed and follow-up can be as soon as one week up to every 6 months or more, depending on your physicians treatment strategy and how the medication is affecting your bipolar disorder. The test is usually performed by a professional phlebotomist in a lab or clinic setting. The blood is then separated into serum using a centrifuge. This separates the serum to be tested. Serum Blood Levels and Your Kidneys Long-term lithium treatment can result in chronic kidney disease. For this reason, serum blood levels may be monitored to check kidney function while the medication is being given for bipolar disorder. Other medications used for bipolar disorder may also cause kidney issues depending on how long and how frequently the drugs are used. A total serum protein test may be conducted to check organ function. Specifically, globulin and albumin levels will be checked. High globulin or low albumin levels are causes for concern. Other Important Serum Blood Tests Your doctor may test your serum blood levels for sodium, magnesium, cholesterol and other important levels that may indicate changes in your blood profile. Serum blood levels showing increased levels of these markers may spell an increased risk for chronic medical conditions or psychotic episodes. Talk to your doctor if you feel serum blood level testing may help you assess your health.

Brutal Treatment of Women Suffragists at Occoquan

An email has been circulating that tells of the brutal treatment in 1917 at Occoquan, Virginia, prison, of women who had picketed the White House as part of the campaign to win the vote for women. The point of the email: it took a lot of sacrifice to win the vote for women, and so women today should honor their sacrifice by taking our right to vote seriously, and actually getting to the polls. The author of the article in the email, though the emails usually omit the credit, is Connie Schultz of The Plain Dealer, Cleveland. Alice Paul led the more radical wing of those who were working for womens suffrage in 1917. Paul had taken part in more militant suffrage activity in England, including hunger strikes that were met with imprisonment and brutal force-feeding methods. She believed that by bringing such militant tactics to America, the publics sympathy would be turned towards those who protested for woman suffrage, and the vote for women would be won, finally, after seven decades of activism. And so, Alice Paul, Lucy Burns, and others separated in America from the National American Woman Suffrage Association (NAWSA), headed by Carrie Chapman Catt, and formed the Congressional Union for Woman Suffrage (CU) which in 1917 transformed itself into the National Womans Party (NWP). While many of the activists in the NAWSA turned during World War I either to pacifism or to support Americas war effort, the National Womans Party continued to focus on winning the vote for women. During wartime, they planned and carried out a campaign to picket the White House in Washington, DC. The reaction was, as in Britain, strong and swift: the arrest of the picketers and their imprisonment. Some were transferred to an abandoned workhouse located at Occoquan, Virginia. There, the women staged hunger strikes, and, as in Britain, were force-fed brutally and otherwise treated violently. Ive referred to this part of woman suffrage history in other articles, notably when describing the history of the suffragist split over strategy in the last decade of activism before the vote was finally won. Feminist Sonia Pressman Fuentes documents this history in her article on Alice Paul. She includes this re-telling of the story of Occoquan Workhouses Night of Terror, November 15, 1917: Under orders from W. H. Whittaker, superintendent of the Occoquan Workhouse, as many as forty guards with clubs went on a rampage, brutalizing thirty-three jailed suffragists. They beat Lucy Burns, chained her hands to the cell bars above her head, and left her there for the night. They hurled Dora Lewis into a dark cell, smashed her head against an iron bed, and knocked her out cold. Her cellmate Alice Cosu, who believed Mrs. Lewis to be dead, suffered a heart attack. According to affidavits, other women were grabbed, dragged, beaten, choked, slammed, pinched, twisted, and kicked.(source: Barbara Leaming, Katherine Hepburn (New York: Crown Publishers, 1995), 182.) Related Resources An image of Emmeline Pankhurst, who led the militant British woman suffragists, including hunger strike tactics, which inspired Alice Paul  and the National Womans PartyA firsthand account of this is in Doris Stevens Jailed for Freedom (New York: Liveright Publishing, 1920. (Gutenberg text)The movie Iron Jawed Angels focuses on this period of the woman suffrage movement.Sewall-Belmont House, home of the National Womans Party, is now a museum that includes many archives of these events.The Library of Congress presents some photos of women suffrage prisoners: Suffrage Prisoners

Choosing 5th Grade Essay Samples with Green, Yellow and Red

Choosing 5th Grade Essay Samples with Green, Yellow and Red What You Should Do to Find Out About 5th Grade Essay Samples with Green, Yellow and Red Before You're Left Behind Numerous pages, printed on only a single side, should be taken out of the book and used for activities. One of the main features of LLATL is literaturein the sort of both short excerpts and total novelsused as a springboard into other regions of language arts. The great thing about this writers-workshop anchor chart, which might be utilized with any elementary grade, is that if you get to number 10, you're prepared to go back to number one. CBD is growing widely recognized and the amount of men and women using CBD supplements because of their wellness and well-being benefits is becoming significantly greater. Choosing Good 5th Grade Essay Samples with Green, Yellow and Red The yellow block is the initial body paragraph. Be certain to highlight the advantages of the food that you bring! This makes it si mple to differentiate. If you've visited the school, reference your visit to demonstrate that you've made an attempt to learn more in regards to the school. Starting now, taking notes are going to be a mainstay of your youngster's education. You've got an idea to increase your school. When you have test taking strategies that help your students to be successful, please don't hesitate to share them below. It's also a rather efficient approach to cover the wide swath of language arts skills. You are unable to listen to music that doesn't harken back to your very own social experience. When students are learning how to write, there are numerous facets of the procedure that may present difficulty. Teaching writing though, isn't always simply. Following this, you're ready to begin the very first YELLOW. You already understand what color you prefer or what your favourite color is. At first, the green color has been connected with spring and nature renewal. Meaning of green color in various cultures. The Benefits of 5th Grade Essay Samples with Green, Yellow and Red Dyari goes across the yard and receives the infant's bottle. Imagine that you live either 100 years previously or 100 years later on. For the exact same reason, race tracks don't have a good deal of green automobiles. Write about your day in the life span of that individual. Discuss why those paragraphs appear to g et the job done. The introduction is colored red because it ought to find the reader's interest. Essay plans instantly provide an essay structure, they stop you from forgetting to incorporate any essential points, and they block you from losing your way as you write. An essay plan doesn't have to be a huge thing. The Basics of 5th Grade Essay Samples with Green, Yellow and Red Finding a hold of previous exams and using them to practise is a remarkable idea. And that's what we're likely to do within this self assessment example. If students do very well on the pre-assessment, it's important to stress there are many different words that they'll still learn, and they will have the chance to become experts on the words they already know. Their normal test scores and subscores determine the maximum score in the red selection. Almost anyone can find the proper type of entertainment for themselves. Today internet has brought a world in one room. Through the assistance of the Wor ld Wide Web and websites, the web has come to be very helpful in a variety of ways for the typical man. Since it has become popular, it's being used for many purposes. The ideal thing to do is to purchase from companies who include each one of these information on their site and on the labels of their goods. Currently a day's almost anything can be bought by means of the world wide web. You can easily locate them on the market if you're one of those who would like to be sure that there is not any THC in their system. The fourth alternative is the sole option that adheres to the properties mentioned previously.

Fundamental Causes, Inequity and Public Health Free Essays

Social injustice particularly that of [public] health, has been a constant pariah to the common society. Various ‘theories’ were posited as to the root cause of public health inequity; Phelan and Link (2005) directly associated the ‘fundamental’ causes of public health inequity with the ‘socioeconomic statuses (SES)’, the ‘social conditions’, the ‘gradients’ that existed therein. The fundamental cause lies on the material/ resources imbalance as the authors Phelan and Link (2005), Farmer (1999), and Lynch et al (2000) demonstrated. We will write a custom essay sample on Fundamental Causes, Inequity and Public Health or any similar topic only for you Order Now The fundamental causes of morbidity and mortality consist of: (1) influences to multiple disease outcomes, (2) operation through multiple risk factors, (3) intervening mechanism reproduce the association, and (4) finally, the most important feature of ‘fundamental causes’, it involves accession to resources that can be used to avoid risks or minimize the consequences of the disease involved. Health accession is shaped by extent of socio-economic resources (Phelan and Link, 2005). Here it is noted that the cognitive ability or intelligence cannot explain the relation between resource and health. SES, is, admittedly a ‘constant’ and persistent state of the general society (Phelan and Link, 2005). Not even the introduction of knowledge or the epidemiology of the disease was able to completely eradicate the health maladies present; instead, it seems to encourage health inequity. The US, a supra-economic world engine, has a systematic health care delivery system yet a relatively large proportion of their population—American Indians, Blacks and Hispanic and Asian immigrants—do not enjoy the benefits of the health care system as much as their rich counter parts. Localization of public health inequity is fed by the health biased terms like ‘Third World’, ‘Blacks’, ‘the poor’, and other terms that denote social stigma and racism . The aggravation of health inequity is destined to worsen with the current trend on ‘commodifying’ medicine and health and their ‘money-making’ participation in the market industry. Health inequity, as a result of multi-faceted elements of the society, is, as much as a disease as the feared bacillus ‘tubercle’, the causal agent of tuberculosis; Farmer (1999) illustrated the consumption of the disease agent ‘consuming the lives of the lower strata that existed in the late twentieth century. Farmer illustrates the case of societal ‘infection’ with different experiences of three stereotype tubercle patients—Jean Dubussoin (Haitian rural peasant), Corina Valdivia (Latin American with a multi-resistant drug strain of bacillus tubercle) and Calvin Loach (Afro-American and injection drug user). It was ‘social factors’ that determined the fate of these three-infected persons. Their struggle against their disease demonstrates the common obstacles they faced during health accession. Jean’s very low income and the long distance from the hospital dilapidated her chance at having a good accession to medical services offered. Corina’s case was exactly the same except that it demonstrated that of improper treatment of her disease and medical wariness. Calvin’s case was psychosocial wherein there was suggested wariness between him and the medical practitioner due to ‘[racial] wariness’ and late detection. Health inequity of tubercle bacillary patients does not stem from medical mismanagement, from physician-directed errors, as the three ‘stereotypes demonstrate, but more on the conglomeration of factors like race, income, economic policies, ease of health accession and fear of being apprehended or ignored by the medical staffs (Farmer, 1999). According to Lynch et al (2000), health inequity may also be associated with neomaterial interpretation —differential accumulation of exposures and experiences that have their sources in the material world—and differences in individual income. Health inequity, then, in general, is highly dependent on the resources of the individual. This is in opposition of the psychosocial theory which precludes that inequity is, more or less, a result of hierarchy stress or the combination of maladaptive behaviours as a reaction to the SES. The association between the standard of living and health cannot be easily dismantled, yet, on the face of such social health injustice, what actions are available for the State to remedy this particular problem? Lynch et al’s (2000) on solubilizing the problem was vague and inconclusive: .. trategic investments in neo-material conditions via more equitable distribution of public and private resources that are likely to have the most impact on reducing health inequalities and improving public health in both rich and poor countries in the 21st century†¦ (p. 1203) Farmer’s (1999) ultimate solution is pragmatic solidarity. The term was rather vague and inconclusive with no proper defin itum; Pragmatic solidarity was loosely defined as something that would mean ‘increased funding for control and treatment [of diseases]’, ‘making therapy available in a systematic way’ and preventing ‘emergence [of diseases]. Farmer’s primary intent is to target the health anathema at the specific level. On the other hand, Link and Phelan’s approach was different. Link and Phelan (2005) posited a barrage of solutions which capitalizes on policy consideration as macro-level approach to the problem— creating intervention that benefit state members irregardless of their own resources and actions, monitoring the dissemination of health enhancing information and interventions and creating policies that would distribute resources to the poor. A good solution to the problem would be targeting health inequity using combinatorial methods on the macro and micro-level approach. Interventions created at the larger scale such as policy consideration is a good approach and finding out the etiology of various diseases obviously have positive outcomes for ‘curing’. Such interventions are necessary to preserve not only the health of the general public but also to maintain a relatively pure, socially just and a healthy environment. How to cite Fundamental Causes, Inequity and Public Health, Papers

Lombards history Essay Example

Lombards history Essay ONeill: (Very angry, in Tyrone accent) I think so. And this is my country. (Quietly, in his usual accent) I have married a very talented, a very spirited, a very beautiful young woman. This sudden change of accent is a method of gaining presence and making a point for ONeill, the use of his Irish accent shows he is in command and he is still in charge of his country. ONeills outburst of anger is also whilst defending and justifying his marriage to Mabel this really shows how loyal he is to her deep down and that he respects Mabels betrayal of her own country.ONeills description of Mabel (talented, spirited) is very accurate and is how Friel portrays her throughout the play. Mabel is a unique character as she manages to stay neutral to both opposing factions, as a character she represents peace and harmony because of this. Archbishop Lombard is described by the narrator, By profession he is a church diplomat and his manner is careful and exact. These careful choice of words tell the audience that Lombard is quite a sly character with a good sense of language and means to talk his way out or in to a situation well.He is not likely to be very religious but exploits his profession in order to gain himself an advantage. Lombard decides to write ONeills history, and, true to his character, refers to history as a story (p. 8), avoiding ONeills questions when asked if he will be telling the truth. Lombard: Im not sure that truth is a primary ingredient is that a shocking thing to say? (p. We will write a custom essay sample on Lombards history specifically for you for only $16.38 $13.9/page Order now We will write a custom essay sample on Lombards history specifically for you FOR ONLY $16.38 $13.9/page Hire Writer We will write a custom essay sample on Lombards history specifically for you FOR ONLY $16.38 $13.9/page Hire Writer 8-9) It is clear from this conversation that both ONeill and Lombard have completely different stances on writing history.ONeill believes it should be an accurate document of events whereas Lombard believes it should be twisted in order to become an entertaining tale based on events. This presents ONeill with another pair of identities Hero vs. the real ONeill. How he will be portrayed through Lombards history will certainly not be the real, womanising, careless ONeill, but a brave leader and hero of Ireland.These ideas Friel has implemented challenges the audience to think about what they would themselves prefer as history the truth or a fairytale created to entertain in order to be passed down to others. Lombards rhetorical question ( is that a shocking thing to say? ) shows he knows that it is slightly devious, but its the truth never the less. The second act contrasts entirely with the first. Only eight months have passed in the play, but the Battle of Kinsale has been lost and ONeill is now living in poverty, He is using a wooden box as a table the narrator describes. ONeill: Have you any food? (p. 43) The mood is now desperate and sinister, ONeill is no longer the charismatic and talkative character he was eight months ago, but now an ageing man with growing regret, his rich and happy life no longer apart of him but now placed with a criminal identity.Wanted by both the Irish and English, both of ONeills identities have abandoned him. The end of Act 1 Scene 1 announces the death of both Mabel and her baby the cross-breed that Mabels sister Mary had warned her about. Friels use of herbs have also pre-empted the inevitable fate of Mabel and the baby. ONeill: (Almost in a whisper) Yes, I think Ill take some of that whiskey now, Hugh. Just a thimbleful, if you please. And no water. Oh, dear God (Quick black. ) (p. 54) The stage directions that show ONeill almost unable to speak after hearing the shocking news shows how unexpected it is for him.The quick black tells the audience it is the end of the scene and also adds further dramatic effect to the abrupt news the way this is delivered most probably leaves the audience is a state of shock also. Scene 2 is set in Rome, many years later (p. 54), ONeill and the others have been forced to flee, where they are no longer welcome in both Ireland or England. The narrator tells us he has a volatile and bitter temper, carries a walking stick and has begun to lose sight in his eyes. This image paints the picture of an elderly, dishevelled man burdened with the regret of many terrible mistakes.Throughout most of this final scene ONeill is scarcely sober, this indicates he must be very unhappy with his life and how it has ended up for him to drink so much. ONeill: (He bumps into a stool and knocks it over. As he straightens it) Forgive me. (p. 54) As ONeill drunkenly bumps into a stool and then apologises to it for knocking it over, you feel instantly embarrassed and sympathetic for ONeill. He is now a shadow of his former self, no longer his bubbly, talkative and distracted character.It appears to the audience that ONeill has lost sense of any identity he once had, which isnt hard to believe considering he has been banished from not one but both of his homes, and now resides in a foreign country that has been alien to him most of his life. ONeill: You said Mabel will have her place. That place is central to me. (p. 63) As the play draws to an end we see a scene shared by Lombard, Harry and ONeill, ONeill desperately trying to convince Lombard to tell the truth in his history, about his failure and corruption, and most interestingly to include Mabel.This shows how deeply he cared for her and enforces the idea of the bond they had over their dual identities. This must have comforted ONeill and made him feel at home, to lose that was really the turning point in his personality, almost as if when Mabel died she took his identity with her, as she was the last thing holding it together and making sense from it all. Act 2 Scene 2 reaches a close as ONeill finally accepts defeat and realises Lombard will write the history how he wants it, Lombard continuously asks What changes do you want me to make? But despite the details ONeill wants included, Lombard will still tell it in a way that is entertaining. Lombard begins to read the history as ONeill starts to cry and mourn for Mabel, (ONeill is now crying. Bring the lights down slowly. ) (p. 71). The slow fade of lights signifies the end of the play. Friel presented identity by portraying a man who had everything, and slowly stripped him of every last meaningful thing he had in order to convey the message of what makes us who we are.ONeill lost both of his countries, and his wife and baby, the loss of Mabel being pivotal she was the one person he could relate to and feel close to, and the baby symbolised a new beginning where the English and Irish could live in harmony together. Through Lombards history we will not learn about ONeills duality, his close friend Harry or wife Mabel that helped shape his character, but a Hero who fought a tough battle for Ireland, fled with the Flight of the Earls, and shall be king for the span of his life (p. 71), thus telling us that identity exists in many forms.

Analysis and Review of the Decisions made in the Simulation of the Lenity Hospital for Advanced Care (LHAC)

Analysis and Review of the Decisions made in the Simulation of the Lenity Hospital for Advanced Care (LHAC) Introduction Organizations in the society exist in an environment that requires comparison with other similar organizations for improvement purposes. Depending on the objectives of an organization, performance benchmarking has proved to be an effective way of ensuring that they maintain a competitive advantage in the industry.Advertising We will write a custom research paper sample on Analysis and Review of the Decisions made in the Simulation of the Lenity Hospital for Advanced Care (LHAC) specifically for you for only $16.05 $11/page Learn More The health sector is not an exception. Through simulation, performance benchmarking is done to ensure that health organizations maintain quality service, the safety of the patients, staff and other people in the sector while fulfilling the standards of the regulators. The health sector is faced with various issues that require to be addressed. The online simulation process in the health sector is crucial in the trai ning of personnel, making their decision making process easier and ensuring the safety of the patients while making use of innovations in this case. This paper addresses the decisions made in the online simulation of Lenity Hospital for Advanced Care. Summary of the Simulation The simulation carried out on Lenity Hospital for Advanced Care was to address the increases in the nosocomial infections. These infections are a threat to the hospital due to its role in ensuring the safety of the patients and other personnel and people involved in the process (Jarvis, 2008). The increases proved to be unsustainable from a liability perspective since the personnel and other resources were concentrating more on them yet they originated from the hospital practices. The costs involved in their treatment and management proved to be inefficient. The infections also proved unsustainable from a quality perspective since LHAC was questioned on its quality maintenance and assurance in the process. Thi s was done through performance benchmarking to identify the root causes of the problem, the establishment of airway recommendations and identification of process improvement strategies. The simulation identified the root causes as the equipment practices that were rather inefficient in the hospital and offered recommendations based on effective sanitation and the incorporation of the functional strategy to the business strategy. Analysis of the Decisions Made in the Simulation This section addresses the decisions made from the simulation classified as the root cause, the airway recommendations established, the benchmarking partnership and the process improvement strategies.Advertising Looking for research paper on health medicine? Let's see if we can help you! Get your first paper with 15% OFF Learn More Identification of the root cause The Lenity Hospital for Advanced Care (LHAC) has experienced increases in the rates of nosocomial infections. Nosocomial in fections as Jarvis (2008) assert comes as a result of transmission of an infectious disease which could be contagious or caused by a pathogenic organism. The types of these nosocomial infections range from surgical related infections, central nervous system infections, skin infections, blood stream infections, gastrointestinal infections, urinary tract infections, and respiratory infections which all are facilitated by the conditions and practices at the hospital facilities (Health Grades Inc, 2010). The process of addressing nosocomial infections is critical due to the diagnosis that is sensitive and the fact that some of them turn out to be drug resistant. The identification of the root cause of the infections was the most prudent way of addressing the issue to avoid recurrences and reduce costs in management. The simulation on Lenity Hospital for Advanced Care (LHAC) identified the root cause of the nosocomial infections increase as the equipment practices in the hospital that we re inefficient. This cause was motivated by the exposures to diseases and environmental pollutants in the hospital (Health Grades Inc, 2010). The inefficient use of facilities was related to lack of homogeneity in the use of equipment in the various departments, sharing of the equipments among departments, poor sanitation of the equipment, the fact that the equipment was not enough while personal responsibility and proper use of the equipment was limited. The infections thus spread even as the number of patients in the departments increased. The infections were further encouraged by lack of coordination of equipment use. For example, two or more different departments could be using the same equipment in their diagnosis of conditions, which could lead to the easier transmission between patients due to exposure to contaminants. The hospital also lacked tracking systems to monitor the use and care of equipment (Thornton, De Rosa Craven, 2002). In addressing the root cause of the probl em of nosocomial infections, personally, I could include more monitoring systems and checks of the environmental pollutants and training process of personnel to be able to identify whether their lack of experience with the equipment caused them to be unable to use them or whether it was out of negligence and ignorance and provide the necessary recommendations accordingly. Establishment of Airway The identification of the root cause of the nosocomial infections being inefficient handling of equipment at Lenity Hospital, there was a need to offer recommendations that would seek to ensure proper management of the equipment and an environment of safety and caution.Advertising We will write a custom research paper sample on Analysis and Review of the Decisions made in the Simulation of the Lenity Hospital for Advanced Care (LHAC) specifically for you for only $16.05 $11/page Learn More The recommendations offered were on the basis of the risks they posed through contamination to patients, staff and visitors at the hospital. They were also based on the regulations requirements for health safety in the health sector as a way of improving the health care and quality health (Moller Sonntag, 1998). The recommendations offered include the effective training of personnel on the use of the equipment and increasing their awareness of the nosocomial infections (Lack, 1996). This recommendation is necessary since the equipment in the health care facilities do require knowledge in the use and maintenance. The skills on the use of the equipment would make the personnel aware of their contributions in nosocomial infections and provide ways of minimizing them. Another recommendation was the use of a tracking system. This system would serve to ensure the sanitation of the equipment. The sanitation would be necessary to ensure safety through avoidance of sharing of equipment that poses a high risk of infection (Cohen, 2006). Additionally, the system would require accountability of inventory. It is also recommendable that Lenity hospital ensures the availability of equipment and distribution through out the departments and also ensures reliability where the equipment would be available when needed to avoid the use of other equipment that would increase the risk of infection. Further, the equipment that is very risky would require being disposable to avoid contamination through reuse due to the sensitivity of the equipment (Moller Sonntag, 1998). For example the equipment dealing with the injections blood and so on. The outcome of the recommendation was impressive. Lenity management set up a tracking system for the sanitation of the equipment. They additionally, instituted inventory controls with the employment of inventory clerks. The clerks have the mandate of ensuring that the inventory bought meets the safety requirements and minimizes the risk of infections as much as possible. They also have the responsibility of ensuring that the equipment is supplied in the hospital in due time and track the stock levels to ensure that the equipment is bought in time. The hospital management also sought on reducing infection through the use of disposable equipment and the maintenance of a sterilizing department to oversee the safety after the cleaning of equipment before reuse.Advertising Looking for research paper on health medicine? Let's see if we can help you! Get your first paper with 15% OFF Learn More In doing of the simulation for another time, I could have followed the steps and measures I took in this current one since it was conclusive and the recommendations proved feasible and would not only ensure safety and reduce nosocomial infections, but would also improve the reputation of LHAC and reduce the costs of operation (Zulch Rinn, 1999). Benchmarking Partner The benchmarking partner chosen for this simulation was the information services department of the Lenity Hospital for Advanced Care. This was based on the reason that this was part of the LHAC and so would provide internal information regarding the safety. Additionally, the department would offer statistics to base the simulation on and provide the resources of the best practice in the sector (Cohen, 2006). The department proved reliable in providing the information needed on the safety levels, use of the equipment, data on nosocomial infections as well as the comparisons with the industry since LHAC covers a great sha re of market in the health sector. In doing the simulation again, I would incorporate the safety department to assess the levels of safety and comparisons with the safety expectations of the health sector. Process Improvement Strategies The functional strategy was chosen to be incorporated in the overall business strategy since the strategy is feasible and applicable in the reference area of ensuring the management of equipment. This strategy emphasizes resource productivity and uses specialized work force (Thornton et al., 2002). This is recommendable to ensure that the use of equipments at Lenity Hospital is by specialized people to avoid misuse and increase the sensitivity to safety. It was observed that there is need to incorporate the functional strategy to the overall business strategy (Jarillo, 1993). This would be by emphasizing the need for safety and proper management of equipment in every department and the endeavor to reduce the nosocomial infections from a departmental basis. Summary and Conclusion The simulation carried out on Lenity Hospital for Advanced Care revealed the root cause of the increasing nosocomial infections as the inefficient equipment practices. This scenario is common not to LHAC only, but in major health care facilities. The inefficient equipment practices are attributable to the strategies of safety and management, lack of awareness in the use of the equipment or lack of personal responsibility. The simulation recognized the need to address the nosocomial infections as a way of reducing the costs involved in the treatment and management, the improvement of the reputation of LHAC and the fulfillment of the industry safety and legal requirements. The recommendations provided were the establishment of a tracking system, effective training of personnel and the increase in sanitation practices. The benchmark partner used for the simulation was the information services department of Lenity Hospital while the functional strategy was emphasized with the need to ensure that the overall business strategy acts as the guide in this. The simulation was effectively done without the need for major changes in the approach although the benchmark partner would further incorporate the safety department of Lenity Hospital. Reference List Cohen, S. (2006). Virtual Decisions. New Jersey: Lawrence Erlbaum Associates Publications. Health Grades Inc. (2010). Nosocomial Infections. Web. Jarillo, C. (1993). Strategic Networks: Creating Borderless Organizations. Oxford: Butterworth-Heinemann. Jarvis, W. (2008). Bennett Brachmans Hospital Infections. London: A C Black Publishers Limited. Lack, R. (1996). Essentials of Health and Safety Management. New York: CRC Press. Moller, J., Sonntag, H. (1998). Systematic analysis and controlling of health care organizations lead to numerical health care improvements. Health Manpower Management, 24(5), 178-182. Thornton, D., De Rosa, F., Craven, D. (2002). Nosocomial pneumonia: emerging con cepts in diagnosis, management, and prophylaxis. Current Opinion in Critical Care, 8(5), 421-429. Zulch, G., Rinn, A. (1999). Simulation based performance analysis and benchmarking. International Journal of Business Performance Management, 1(2), 200-218.

Nietzsches The Use And Abuse Of History

Nietzsches The Use And Abuse Of History Between 1873 and 1876 Nietzsche published four â€Å"Untimely Meditations.†Ã‚   The second of these is the essay often referred to as â€Å"The Use and Abuse of History for Life.† (1874)   A more accurate translation of the title, though, is â€Å"On the Uses and Disadvantages of History for Life.† The Meaning of History and Life The two key terms in the title, â€Å"history† and â€Å"life† are used in a very broad way.   By â€Å"history,† Nietzsche mainly means historical knowledge of previous cultures (e.g. Greece, Rome, the Renaissance), which includes knowledge of past philosophy, literature, art, music, and so on.   But he also has in mind scholarship in general, including a commitment to strict principles of scholarly or scientific methods, and also a general historical self-awareness which continually places one’s own time and culture in relation to others that have come before. The term â€Å"life† is not clearly defined anywhere in the essay.   In one place Nietzsche describes it as â€Å"a dark driving insatiably self-desiring power,† but that doesn’t tell us much.   What he seems to have in mind most of the time, when he speaks of â€Å"life,† is something like a deep, rich, creative engagement with the world one is living in.   Here, as in all his writings, the creation of an impressive culture is of prime importance to Nietzsche.   What Nietzsche Is Opposing In the early 19th century, Hegel (1770-1831) had constructed a philosophy of history which saw the history of civilization as both the expansion of human freedom and the development of greater self-consciousness regarding the nature and meaning of history.   Hegel’s own philosophy represents the highest stage yet achieved in humanity’s self-understanding.   After Hegel, it was generally accepted that a knowledge of the past is a good thing.   In fact, the nineteenth century prided itself on being more historically informed than any previous age.   Nietzsche, however, as he loves to do, calls this widespread belief into question.   He identifies 3 approaches to history: the monumental, the antiquarian, and the critical.   Each can be used in a good way, but each has its dangers. Monumental History Monumental history focuses on examples of human greatness, individuals who â€Å"magnify the concept of man†¦.giving it a more beautiful content.†Ã‚   Nietzsche doesn’t name names, but he presumably means people like Moses, Jesus, Pericles, Socrates, Caesar, Leonardo, Goethe, Beethoven, and Napoleon.   One thing that all great individuals have in common is a cavalier willingness to risk their life and material well-being.     Such individuals can inspire us to reach for greatness ourselves.   They are an antidote to world-weariness.   But monumental history carries certain dangers.   When we view these past figures as inspirational, we may distort history by overlooking the unique circumstances that gave rise to them.   It is quite likely that no such figure could arise again since those circumstances will never occur again.   Another danger lies in the way some people treat the great achievements of the past (e.g. Greek tragedy, Renaissance painting) as canonical.   They are viewed as providing a paradigm that contemporary art should not challenge or deviate from.   When used in this way, monumental history can block the path to new and original cultural achievements. Antiquarian History Antiquarian history refers to the scholarly immersion in some past period or past culture.   This is the approach to history especially typical of academics.   It can be valuable when it helps to enhance our sense of cultural identity.   E.g. When contemporary poets acquire a deep understanding of the poetic tradition to which they belong, this enriches their own work.   They experience â€Å"the contentment of a tree with its roots.† But this approach also has potential drawbacks.   Too much immersion in the past easily leads to an undiscriminating fascination with and reverence for anything that is old, regardless of whether it is genuinely admirable or interesting.   Antiquarian history easily degenerates into mere scholarliness, where the purpose of doing history has long been forgotten.   And the reverence for the past it encourages can inhibit originality.   The cultural products of the past are seen as so wonderful that we can simply rest content with them and not try to create anything new. Critical History Critical history is almost the opposite of antiquarian history.   Instead of revering the past, one rejects it as part of the process of creating something new.   E.g. Original artistic movements are often very critical of the styles they replace (the way Romantic poets rejected the artificial diction of 18th-century poets).   The danger here, though, is that we will be unfair to the past.   In particular, we will fail to see how those very elements in past cultures that we despise were necessary; that they were among the elements that gave birth to us.   The Problems Caused by Too Much Historical Knowledge In Nietzsche’s view, his culture (and he would probably say ours too) has become bloated with too much knowledge.   And this explosion of knowledge is not serving â€Å"life†Ã¢â‚¬â€œthat is, it is not leading to a richer, more vibrant, contemporary culture.   On the contrary. Scholars obsess over methodology and sophisticated analysis.   In doing so, they lose sight of the real purpose of their work.   Always, what matters most isn’t whether their methodology is sound, but whether what they are doing serves to enrich contemporary life and culture. Very often, instead of trying to be creative and original, educated people simply immerse themselves in relatively dry scholarly activity.   The result is that instead of having a living culture, we have merely a knowledge of culture.   Instead of really experiencing things, we take up a detached, scholarly attitude to them.   One might think here, for instance, of the difference between being transported by a painting or a musical composition, and noticing how it reflects certain influences from previous artists or composers. Halfway through the essay, Nietzsche identifies five specific disadvantages of having too much historical knowledge.   The rest of the essay is mainly an elaboration on these points.   The five drawbacks are: It creates too much of a contrast between what’s going on people’s minds and the way they live.   E.g. philosophers who immerse themselves in Stoicism no longer live like Stoics; they just live like everyone else.   The philosophy is purely theoretical. Not something to be lived.It makes us think we are more just than previous ages.   We tend to look back on previous periods as inferior to us in various ways, especially, perhaps, in the area of morality.   Modern historians pride themselves on their objectivity.   But the best kind of history isn’t the kind that is scrupulously objective in a dry scholarly sense.   The best historians work like artists to bring a previous age to life.It disrupts the instincts and hinders mature development.   In supporting this idea, Nietzsche especially complains at the way modern scholars cram themselves too quickly with too much knowledge.   The result is that they lose profundity.   Extreme specialization, a nother feature of modern scholarship, leads them away from wisdom, which requires a broader view of things. It makes us think of ourselves as inferior imitators of our predecessorsIt leads to irony and to cynicism. In explaining points 4 and 5, Nietzsche embarks on a sustained critique of Hegelianism.   The essay concludes with him expressing a hope in â€Å"youth†, by which he seems to mean those who have not yet been deformed by too much education. In the Background – Richard Wagner Nietzsche does not mention in this essay his friend at the time, the composer Richard Wagner.   But in drawing the contrast between those who merely know about culture and those who are creatively engaged with culture, he almost certainly had Wagner in mind as an exemplar of the latter type.   Nietzsche was working as a professor at the time at the University of Basle in Switzerland.  Ã‚   Basle represented historical scholarship.   Whenever he could, he would take the train to Lucerne to visit Wagner, who at the time was composing his four-opera Ring Cycle.   Wagner’s house at Tribschen represented life.   For Wagner, the creative genius who was also a man of action, fully engaged in the world, and working hard to regenerate German culture through his operas, exemplified how one could use the past (Greek tragedy, Nordic legends, Romantic classical music) in a healthy way to create something new.

Impact of the world bank and UNCTAD on developing countries Essay

Impact of the world bank and UNCTAD on developing countries - Essay Example This research will begin with the statement that UNCTAD (United Nations Conference on Trade and Development) is a trade development agreement and the world’s apex financial institutions like World Bank have highly conjectured on the welfare dynamics of the developing nations. In the exorbitant milieu of a complex business process and developing globalization, economic inequality can be said to be one of the primal parameters in the measurement of the growth and the developmental judgment of several economies of the world. Capitalism, colonialism, an influx of capital spread and concentration of wealth has generated prosperity among several territories of the world and has given rise to the developed and rich nations. In the trading pattern also the developed countries have been seizing a mammoth amount of wealth with the dominance over the less developed and developing nations and have brought the mechanism of the trading pattern in their own hands with the dictating behavior of the wealth in their own hand and the drawing of the valuable resources for production and economic development in their own territorial entity. The less developed and the developing nations of the world have been highly lacking in resources and lacking in wealth accumulation with the dominance of the developed and rich nations in their favor. The lack of resources, as well as the lack in the wealth accumulation of these countries, have made these countries plunge into the realms of a vicious circle of poverty and have lead to the utter misfortune of these countries. Thus there has been the requirement of various international financial institutions to try and develop the economic deterioration of these countries and impart these countries towards the trajectory of sustainable growth. UNCTAD’s motive was directed towards a stylized development mission. At that juncture, the world has been changed drastically and the critical division of the East-West was making the very lit tle significant change after the collapse of the Berlin Wall. The axis of the North-South was a reality of the world with the North being depicted as the developed nations and the south being that of the developing as well as the developing nations. The trajectory of the development on the angle of North-South division was becoming the prime concern regarding the division of the developing as well as the developed nations. At this critical juncture, there was a high emergence of a developmental strategy which would be throwing the developing nations towards a domain where they will be receiving a high sigh of relief. The creation of UNCTAD was basically conjectured on the agenda of promoting development and advancement to the un-developed as well as the under-developed and newly independent countries as well as the newly industrialized countries (NICs). The main purpose of its establishment was focused on the economic integration of these economies into the world economy through the method of a balanced approach. It was the time when UNCTAD was developed, the world was at the summit of the East-West conflict and the south has been emerging as an economic clustering of poor countries vis-a-vis the northern countries which are the rich countries.

The Impact of European Influence on the Sioux and Iroquois Nations Essay

The Impact of European Influence on the Sioux and Iroquois Nations - Essay Example They had an intricate democratic system of government within the confederacy. The Iroquois were divided into 3 different clans: the bear, the wolf and the turtle. These clans were not segregated from one another; rather, they were a support network to others within the same clan providing lodging and food for one another while on hunting trips. This support system allowed the trade patterns of the Iroquois to encompass hundreds of miles. The Iroquois society was closely tied to the natural environment. Villages were primarily located near waterways as the canoe was a primary mode of transportation. The women were responsible for planting and harvesting of their staple vegetables: corn, beans and squash. The men hunted deer and bear and fished, providing meat for the family. The land of the Iroquois was rich in a variety of natural resources which were traded within the Nation as well as to the Plains Indians to the west and the tribes to the south. Some of the more important trade it ems included quartzite, copper, jasper and flint. The Northern Plains was home to the Sioux Nation (Oceti Sakowin). Their land was vast, mostly consisting of open plains. Family was central to the Sioux. Mutual respect between the sexes was evident in their daily lives. Unlike the Iroquois to the east, the Sioux tribe was nomadic, following buffalo herds which were their primary source of meat.

Septic Shock Case Study: Causes and Effects

Septic Shock Case Study: Causes and Effects Introduction Septic Shock is a serious circulatory disorder often characterised by a whole- body inflammatory state and the systemic response to infection (Titheradge, 1998), with the most common cause being the contamination of blood with bacteria. Septic shock is defined as sepsis with hypotension which develops in almost half of all septic patients as a complication with a mortality rate of 40-60% (Titheradge, 1998). Septic shock often results in a progressive failure of the circulation to provide blood and oxygen to vital organs of the body resulting in impaired tissue perfusion and oxygen extraction (Thiemermann, 1997). The key symptoms include a severe fall in blood pressure (hypotension) with hypo-reactivity to vasoconstrictor agents (vasoplegia) which may lead to the dysfunction or failure of major organs including lungs, liver, kidneys and brain (multiple organ dysfunction, MODS) and ultimately death (Goligorski et al., 1997). Presently it is widely assumed that septic shock rarely shows similar symptoms in affected individuals and therefore it is difficult to detect and then consequently treat it (Groeneveld and Thijs, 1986). It is, however, also agreed that most of the therapeutic interventions invariably focus on the primary aim of fighting the refractory hypotension by the use of aggressive fluid infusions, glucocorticoids, large doses of vasoconstrictors (Baumgartner and Calandra, 1999) and occasionally renal replacement therapy (Wheeler Bernard, 1999). Yet these interventions do not offer consistent success (Parratt, 1997). In recent times, our understanding of the pathophysiology of septic shock has developed significantly through experimental and clinical trials, though the discovery of a suitable treatment with therapeutic efficacy is proving elusive (Baumgartner and Calandra, 1999). This is probably because of the heterogeneity of the clinical situations and the differences in host response to i dentical pathogens. Moreover evidence suggests that different pathogens which cause septic shock respond differently to the conventional treatments. Still, no effort has been made to treat patients according to the nature of the infecting organism (Gao, Anonymous, 1992). During the early 1990s nitric oxide (NO) emerged as a potentially substantial step towards the treatment of septic shock. This finding directed scientists to carry out numerous clinical trials and animal experiments with the objective of finding out more about the interrelation of NO and Sepsis (Cobb, 1999; Kilbourn, 1999). Later, the discovery of nitric oxide synthase (NOS) made this enzyme the primary target of therapeutic agents (Rosselet et al., 1998). However, recently a substantial amount of literature has been published with evidence contradicting the discoveries of earlier studies. Today more than a decade has elapsed without any resolution to the matter and even in this 21st century Septic Shock is invading the developing countries rapidly (Cobb, 1999; Kilbourn, 1999). This problem of a lack of significant advances in this field can be highlighted by the fact that 17 years have passed since the final publication of the Consensus Conference on sepsis and sepsis related syndromes (Rangel-Frausto, 2005). This paper conclusively defined sepsis and its symptoms with the hope of finding a suitable treatment in order to eradicate the disease (Rangel-Frausto, 2005). Today, however, the situation has not changed significantly with up to 750,000 new sepsis cases every year and 215,000 annual deaths in the United States (Trzeciak et al., 2008, Mitchell M. Levy, 2007). Additionally, in the population that survives such attacks, there is considerable morbidity with many scoring low in health related quality of life assessments (Kaarlola et al., 2003, Perl et al., 1995). Hence the 5 million lives campaign instigated by the US Institute of Healthcare Improvements, aims to minimize the prevalence of nosocomial sepsis (sepsis originating in a hospital) (Gao et al., 2008). This campaign aimed specifically at increasing safety and transforming the quality of hospital care (McCannon et al., 2007). Moreover, the Surviving Sepsis Campaign aims to improve the quality of life of septic patients using the best evidence available currently (Dellinger et al., 2004). Though the world mortality rates have declined in recent times, sepsis is gradually becoming more prevalent in the elderly in the developing countries (Gao et al., 2008).This is mainly due to the extended longevity of patients with chronic illnesses, the increased occurrence of immunosuppression, and the more frequent use of invasive procedures (Bone, 1991; Parrillo, 1993). Sepsis, severe sepsis, septic shock and multiple organ failure still dominate the mass cases of non coronary intensive care units (ICUs). This essay will attempt to explore the fundamental mechanisms leading to tissue and organ damage in septic shock through the investigation of a case study. Following this, the discovery and general biology of nitric oxide (NO) shall be discussed, and the experimental evidence implicating NO as an effector in sepsis, will be examined in detail. The results obtained from various pharmacologic interventions directed at NO in animal studies will also be considered. This report will also give an account of conventional and innovative treatments for the management of septic shock. Finally, data from the few available relevant clinical trials will be reviewed and possible future avenues of interest will be discussed. Systemic Inflammatory response syndrome and Septic Shock (Clinical Manifestation) Sepsis, severe sepsis and septic shock were inaccurately defined until a recently reviewed consensus conference in 1992 (Bone et al., 1992, Dellinger et al., 2004). In this meeting the term systemic inflammatory response syndrome (SIRS) was invented insinuating a clinical response arising from a nonspecific tissue damaging event (insult) (Rangel-Frausto, 2005). Sepsis as mentioned earlier is the result of substantial release of inflammatory mediators in response to an infection. However, often the same mediators are released in the absence of a documented infected in several medical conditions such as cardiopulmonary bypass (Wan S. et al., 1997), pancreatitis and trauma (Shanley TP. et al., 2006). Due to this, the early definitions of sepsis or septic shock were found to be misleading hence a North American consensus conference proposed a new terminology. In this conference sepsis was defined as a condition in which critically ill patients meet criteria for SIRS, in the context of infection. SIRS was defined as two or more of the following: 1) heart rate >90/min; 2) temperature >38Â °C or 12,000 or 20/min or a PCO2 3.5 L min-1 M-23; 2) hyperglycaemia (plasma glucose >120 mg/dL) in the absence of diabetes; 3) significant oedema or positive fluid balance (20 mL/kg over 20 h); 4) inflammatory variables: plasma C-reactive protein >2 SD above t he normal value or plasma procalcitonin >2 SD above the normal value and 5) mixed venous oxygen saturation (SVO2) >70% . (Dellinger RP et al., 2004). SIRS is generally not considered as a disease and its recognition does not provide any clinical conclusion. However, since it has proven to be a very useful for the identification of sepsis and its sequelae namely severe sepsis and septic shock it is regarded as a very important tool (Shanley TP. et al., 2006). Case Study: A 3-year-old boy was admitted to the intensive care unit because of fever, hypotension, and lethargy. A purpuric rash was noted on his arms and legs. Arterial blood gas analysis demonstrated hypoxemia and metabolic acidosis. The arterial lactate level was 10 mmol/L. He was intubated, resuscitated with crystalloid solution, started on broad-spectrum antibiotic therapy, and given dopamine to maintain a MAP above 55 mmHg. His chest radiograph revealed bilateral interstitial-alveolar infiltrates with a left sided predominance. Gram stain of the cerebrospinal fluid showed gram-negative cocci. The dopamine infusion was increased to 18Â µg kg-1min-1 for persistent hypotension and oliguria. Pulmonary and radial arterial catheter data yielded the following blood pressure, 85/30 mm Hg; MAP, 48 mm Hg; heart rate, 140 beats per minute; CVP, 10 mm Hg; pulmonary artery pressure, 22/14 mm Hg; PCWP, 12 mm Hg; cardiac index, 2.5L min-1m-2; and SVRI, 1226 dyne-sec-cm-5m-2. The boy was treated with ad ditional saline and an epinephrine infusion, which increased the MAP, cardiac index, and urine output. Arterial lactate levels decreased over the next 12 hours. Subsequent cultures of blood and cerebrospinal fluid grew Neisseria meningitidis. In this case the patient with acute organ failure and hypotension was diagnosed with septic shock. The young boy with meningococcal septic shock had a borderline-low cardiac index. Due to this a decrease in the cardiac index in this patient by the administration of an NOS inhibitor might not be desirable. This is suggestive of the fact that NO or its synthesising means cannot always be targeted in order to battle septic shock. I will attempt to go into further details with regards to this statement as we go along the essay. Nitric Oxide discovery: Joseph Priestly first identified gaseous NO in 1772. NO also named Nitrogen Monoxide is a very simple and tiny molecule consisting of one nitrogen and one oxygen molecule. Unknown of its fundamental physiological roles in the mammals, until the 1980s NO was widely considered as a mere toxic atmospheric pollutant (Konstantin J. Ovodov et al., 2000). In the 1980s researchers were examining how blood vessels expand (dilate) hence regulate the mean arterial blood pressure. Dilation of blood vessels, also termed vasodilation is a very important physiological response which partly regulates the blood pressure. By increasing the diameter of blood vessels, vasodilation causes the blood to travel more freely due to lower resistance (RF Furchgott, 1980). Since the blood vessel lumen widens during vasodilation, the blood imposes less outward pressure on the vessel wall hence reducing the blood pressure. In opposition, vasoconstriction reduces the diameter of the lumen increasing the BP. These physiological responses occur all the time in the human body regulating the BP and therefore are one of the most fundamental mechanisms of the human body. Dr Robert Furchgott and his group, later in 1980s investigated the role of acetylcholine in the smooth muscle relaxation and found that relaxation only occurred if a special class of cells called endothelial cells were present (RF Furchgott, 1980). These cells line the interior surface of blood vessels, forming an interface between circulating blood in the lumen and the rest of the vessel wall. Behind the endothelial cells are the smooth muscle cells which either relax or contract thus regulating the vascular tone (RF Furchgott, 1991). The same research group also discovered that smooth muscle were only able to vasodilate the blood vessels in the presence of endothelial cells. This indicated that there was some kind of factor that was being released by the endothelial cells which was involved in the dilation of the blood vessel. This factor was named Endothelium Derived Relaxing Factor (EDRF) and subsequently specified as NO (S Moncada et al., 1997). In 1977, Ferid Murad independantly investigated the mechanism of action of nitroglycerin and found that it worked by inducing the release of NO which in turn was able to cause relaxation of smooth muscle cells (F Murad et al., 1977). Louis Ignarro in 1986 finally resolved the whole perplex of EDRF and NO by declaring that EDRF was in fact NO. It was stated that both molecules showed identical properties when he compared gas Nitric Oxide and EDRF (Ignarro, L. J. Et al. 1987). In 1998, Nobel Prize in Physiology and Medicine was awarded to Drs. Robert Furchgott, Louis Ignarro, and Ferid Murad for their discoveries that vascular endothelial cells make nitric oxide (NO) and that such endothelium-derived NO stimulates cyclic guanosine monophosphate (cGMP) synthesis in the underlying vascular smooth muscle, causing relaxation (Kilbourn, 1999). Since the discovery of NO, vast number of its physiological roles in normal conditions have been reported including in the immune system, nervous system, reproductive system and other cellular functions. It has also been found to play important roles in variety of species ranging from mammals, to insects and plants. Role of Nitric Oxide in Biology Since it was first discovered to play a role in the dilation of blood vessels many new roles for Nitric Oxide (NO) have been discovered. In human body, NO is metabolised by its diffusion into red blood cells where it oxidizes the ferrous iron of oxyhemoglobin yielding methemoglobin and nitrate ions (NO3-) (J.M. Hevel et al., 1994 and Konstantin J. Ovodov and Ronald G. Pearl, 2000). This meachanism limits local NO build up and is particularly important in keeping NO concentration in naomolar range, at least in nonhydrophobic compartments (i.e. outside cell membranes) (Beckman Koppenol, 1996). Nitric oxide has been found to be produced by effectively every cell type in vivo and plays an important role in both controlling the normal function of cells as well as in regulating larger scale processes such as the reproductive, immune and nervous systems. A few of these biological functions for NO are described in more detail below. The Immune System Nitric oxide plays many important roles in the immune system although it is expressed in many cell types following endotoxin or pro-inflammatory cytokine treatment (C. Nathan et al., 1991 and R.G. Knowles et al., 1994). NO, in immune system, is produced in high amounts from specific cells called macrophages. Proceedingly to an infection, chemicals known as cytokines are release in vivo which activate the cells of the immune system such as macrophages, and help guide them to the site of infection (S. Moncada et al., 1991 and C. Nathan et al., 1991). NO produced by the macrophages is toxic to the bacteria and play an important role in their destruction (Fig 1). The production of nitric oxide in this way also helps protect against other types of infection including parasites and viruses (S. Moncada et al., 1991). However, too much nitric oxide production can not only lead to septic shock but has also been implicated in conditions where the immune system is too active autoimmune diseases like arthritis (Jang D and Murrell G A, 1998). The Nervous System Nitric oxide has been shown to be involved in both the peripheral and central nervous system. The three nitric oxide producing isotypes of enzyme (iNOS, eNOS, nNOS) (see section) in humans, one isotype (neuronal NOS (nNOS)) is found almost exclusively in the nervous system (Forstermann et al., 1995). nNOS is thought to be involved in promoting the transfer of interneuronal nerve signals. This is thought to take place by the stimulation of exocytosis (release) of endogenous chemicals called neurotransmitters of one neurone (Moncada et al., 1991; Forstermann and Kleinert, 1995). These NT then diffuse across the synaptic cleft (gap between neuronal terminals) and stimulate the neighbouring nerve cell terminal to transmit the signal (Otto Loewi, 1961). NO has shown to play a substantial role in diseases of the nervous system like Alzheimers and Parkinsons. In both diseases, the inhibition of NO has shown to slow down the progression of the disease in mice (Weill Cornell Team, 2005 and Jo hns Hopkins et al., 2004). Reproductive Biology Nitric oxide is one of the most important molecule in the course of reproduction and is involved in many aspects of it. As well as dilating the blood vessels and thereby helping to regulate maternal blood pressure, NO is also involved in implanting the early embryo in the uterus (Rogers, 1995). During pregnancy, nitric oxide is also suggested promote angiogenesis (a process in which new blood vessels are formed) (RayChaudhury et al., 1996). It is also known to play a role in the survival of trophoblasts (form placenta) (Enders et al., 1978). Furthermore deficiency of NO has been found in patients with preeclampsia (a medical condition in pregnancy) suggesting its partial role in growth of embryo (Yallampalli et al., 1994; Liao et al., 1996). In addition, drugs (Viagra) used to treat erectile dysfunction also affect nitric oxide signalling. Cellular function A notable number of cellular activities can be controlled by nitric oxide including cell division, cell movement and cell survival. The majority of cells in human body have the ability to undergo programmed cellular death. This is a self-destructive mechanism usually called apoptosis which often occurs when a cell is damaged and beyond repair, infected with a virus, or undergoing stressful conditions such as starvation (Kerr et al., 1972). Cells in these conditions go through apoptosis so that they dont hinder the proper functioning of the rest of the tissue. During apoptosis, the structures of the cell break down in an organised manner, forming a packaged cell that is smaller in size so that it can be easily removed by the cells of the immune system (Kerr et al., 1972). Nitric oxide was first shown to inhibit apoptosis hence promoting cell survival in human B lymphocytes (Mannick, J. B. Et al., 1994). Subsequently similar finding were reported in an ample number of other cells. However, high doses of nitric oxide also have deleterious effects. They can be toxic to many cell types and can lead to septic shock and multiple organ dysfunction syndrome (MODS) in which case NO causes cell death instead of promoting cell survival (Beal Cerra, 1994). Nitric Oxide and Inflammation (Pathophysiology of septic shock) This section will deal with mechanism by which wall fragments of Gram-negative or Gram-positive bacteria and other inflammatory agents induce nitric oxide synthase (iNOS) in cells and tissues. Exogenous toxins which enter the circulation stimulate the synthesis and release of a number of endogenous cytokines. During a gram-negative infection which can lead to septic shock, lipopolysaccharide (LPS) and endotoxins present on bacterial wall and many other inflammatory agents bind to a co-receptor (CD14) on the surface of specific immune cells like macrophages, resulting in their activation (J.C. Lee et al., 1996). LPS also bind to LPS-binding proteins which are produced by the liver. These proteins facilitate LPS binding to the CD14 co-receptor of the macrophages. The CD14 co-receptor is activated through the binding of LPS to a toll-like molecule (TLR4), (Re F, Strominger J. Et al., 2001) which is responsible for initiating the transmembrane signaling. TLR2 molecules act in the same way as TLR4, (Leppper PM et al., 2002) though; these are activated by gram-positive bacteria, mycobacteria and yeast. Gram-positive bacteria such as Staphylococcus aureus have further additional wall fragments such as peptidoglycan (PepG) and lipoteichoic acid (LTA). Both PepG and LTA have been shown to synergise to produce the characteristic features of septic shock, MODS and ultimately death in rodent models (S.J. De Kimpe et al., 1995 and G.M. Millar et al., 1997). These effects were not observed with either LTA or peptidoglycan alone, although high doses of LTA can cause circulatory failure but not MODS (S.J. De Kimpe et al., 1995). Gram-positive bacteria may also release other enterotoxins and exotoxins, for example toxic shock syndrome toxin 1, which are involved in the pathogenesis of sepsis (reviewed in (R.C. Bone et al., 1994)). The additional fragments released by Gram-positive bacteria bind to unknown receptors however, like LPS binding, cause the release of proinflammatory cytokines TNF-a, IL-1ß, and IFN-? (Thiemermann, 1997, Titheradge, 1999). These cytokines as well as IL-6 are often produced in response to immune stimulation of macrophages and monocytes hence also in septic shock patients. IL-1 and TNF each occur in two forms, a and ß. TNF- a and both forms of IL-1 are made by activated monocytes and macrophages, whereas TNF- ß is made by activated T lymphocytes (Review by J. Saklatvala et al., 1996). There are two receptors for both IL-1 and TNF and the two forms of each cytokine interact with the same receptors. IL-1 a and ß interact with the type 1 IL-1 receptor for signal transduction, whereas type II does not appear to transmit any signal and functions as an inhibitor of IL-1 action (J. Saklatvala et al., 1996). The two types of TNF receptor, p55 (type I) and p75 (type II) have different end effects; p75 mediates the proliferative actions of TNF- a while p55 receptor signals the inflammatory response and apoptosis (J. Saklatvala et al., 1996). Complex interactions between these different mediators produce intense pathophysiological modification, which eventually lead to diffuse tissue injury and ultimately sequential system failure (multiple organ dysfunc tion syndrome), which accounts for the majority of deaths among patients with sepsis, severe sepsis and septic shock (Beal Cerra, 1994). IL-1ß and TNF-a have a very short half life compared to IL-6 and therefore IL-6 is a very good indicator of cytokinemia. The initial studies of septic shock, showed a very strong positive correlation between IL-6 levels and fatal outcome (Casey L. Et al., 1993). NO is equally a very short lived molecule with an estimated in vivo half life of only 0.1 seconds hence again it is hard to measure its levels in order to detect the severity of cytokinemia hence the severity of sepsis or septic shock. There are several molecules that contribute to the pro and anti-inflammatory responses in septic shock (Table 4); however I shall only focus on a few due to the limited word allowance. In response to inflammatory agents in septic shock, the released cytokines (TNF-a, IL-1ß, and IFN- ?), bind to their specific receptors activating a protein kinase called tyrosine kinase leading to both the activation of the nuclear factor-kB (NF-?B) (a transcription factor) and the phosphorylation of intracellular protein (Gao et al., 2008). A precise mechanism by which these cytokines act was proposed by J. Saklatvala et al. in 1996 however this has yet to be confirmed. Nitric oxide producing cells contain I-?B which is an inhibitor of NF-?B. For the activation of NF-?B, proteolytic cleavage of I-?B from NF-?B is required which forms NF-?B. This biological change allows the activated NF-?B to translocate to the nucleus, where it binds to the promoter region of the iNOS gene inducing transcription. It has also been reported to induce other inflammatory agents, such as cytokines and leukocyte-endothelial adhesion molecules (Janssen-Heininger et al., 2000). Tyrosine kinase present inside the cell acts as a messenger molecule involved in the proteolytic cleavage of I-?B/NF-?B and hence in the activation of NF-?B and iNOS expression (Hecker M, et al., 1996). In septic shock, the translated products of iNOS mRNA subsequently assemble forming the iNOS protein which in turn causes local NO proliferation (Thiemermann, 1997). Fig 2 shows the signal transduction pathway of iNOS expression in response to inflammatory agents. The physiological role of iNOS is to enhance the formation of NO (due to iNOS activity), which in turn may contribute to either the pathophysiology of septic shock (clinbical symptoms) or the host defence (Reviewed in Gao et al., 2008). Fig 3 shows a simplified schematic of the Anti Inflammatory cascade in the context of septic shock. Excess NO produced by iNOS has been reported to both induce and inhibit NF-?B (Kalra et al., 2000; Umansky et al., 1998). In year 2000, it was proposed that low levels of NO may induce further NO production while high concentrations do the opposite exhibiting a feedback mechanisms that would oppose the over expression of genes regulated by NF-?B (Janssen-Heininger et al., 2000). In addition NO at high concentrations competes with O2 at the active site of NOS, thus providing a feedback mechanism of its own synthesis (Griscavage et al., 1995; Rengasamy Johns, 1993). Biological Synthesis of Nitric Oxide (Nitric Oxide Synthases) NOS structure and substrates for NO production: In mammals, NO is exclusively formed from the enzymatic oxidation of one terminal guanidino nitrogen of the amino acid L-arginine. When expressed in moles, this reaction utilizes 1 mol each of arginine and O2, and 1.5 mol of NADPH, yielding 1 mol of NO, 1 mol of L-citrulline and 1.5 mol of NADP (R.G. Knowles et al., 1994). The reaction sequence involves the generation of an Ng-hydroxy-L-arginine intermediate, followed by the oxidation of Ng-hydroxy-L-arginine in presence of molecular oxygen to form L-citrulline and NO (Dennis J. Stuehr et al., 1991 and R.G. Knowles et al., 1994). The enzymes that accelerate the reaction above are a family of relatively large heme proteins known as NO synthase (NOS) which resemble cytochrome P450 structurally (M. M. Chan et al., 2001 and Francois Feihl, 2001) (The general mechanism of NO production from NOS is illustrated in Fig 4). All members of this family share a similar homodimeric structure, where each monomer consists of a an oxygenase domain and a reductase domain, separated by a short amino acids (30aa) sequence for the attachment of the Ca2+-binding protein calmodulin. In addition to calmodulin attachment, enzymatic activity requires the presence of four cofactors: FAD, flavin mononucleotide (FMN), tetrahydrobiopterin (BH4), and heme (Francois Feihl, 2001). Fig 5 shows the general structure of the NOS enzymes. Nitric Oxide Synthase isoforms and their locus in the Human Body: There are three known isoforms of NOS, each the product of a different gene: neuronal NOS (nNOS or NOS-1), inducible NOS (iNOS or NOS-2), and endothelial NOS (eNOS or NOS-3). nNOS and eNOS were first described in rat cerebellum and bovine aortic endothelial cells, respectively, but their tissue distribution is far wider than suggested by their names. eNOS and nNOS are involved in regulating vascular tone (R.G. Knowles et al.,1992 and S. Moncada et al., 1991) and neurotransmission respectively, whereas iNOS is involved in the immune defence although it is expressed in many cell types following endotoxin or pro inflammatory cytokine treatment (R.G. Knowles et al., 1994). nNOS is typically expressed in skeletal muscle and myenteric plexuses. eNOS is ubiquitous in vascular endothelium, but may also be found in the kidney tubular epithelial cells, placenta (Forstermann et al., 1995), and neurons (Nathan Xie, 1994). In these tissues, the expression of nNOS and eNOS is constitutive, although it may be regulated (Michel Feron, 1997). For instance, the levels of transcript for eNOS in vascular endothelial cells is increased by shear stress (Topper et al., 1996; Uematsu et al., 1995) and exercise (Wang et al., 1997), reduced by inflammatory stimuli such as TNF-a (Nathan Xie, 1994) and variably affected by hypoxia (Le Cras et al., 1998; Toporsian et al., 2000). In the physiological state, the iNOS isoform is only present at a few locations, notably the respiratory epithelium, the gravid uterus (Nathan Xie, 1994), and perhaps the ileal mucosa (Hoffman et al., 1997). iNOS expression has been demonstrated in numerous cell types including macrophages, neutrop hils, vascular endothelial (Hoffmann et al., 1999), smooth muscle cells, endocardium, myocardium, fibroblast, mesangial cells, renal tubular epithelium (Kunz et al., 1994), neurons, hepatocytes, pancreatic islet cells and astrocytes (Nathan Xie, 1994). iNOS can be induced by a number factors including UV light; cyclic AMP-elevating agents; trauma; ozone and bacterial products described earlier (see section). On the other hand, many endogenous agents may oppose cytokine induction of iNOS. These include anti-inflammatory cytokines such as IL-10, chemokines such as monocyte chemoattractant protein-1 and growth factors such as tumor growth factor-ß (Forstermann et al., 1995). In all NOS isoforms, calmodulin binding is an absolutely vital for enzymatic activity. In the cases of eNOS and nNOS, this binding necessitates relatively high concentrations of Ca2+ (see Fig 7), in the range of 0.1-1 mM (Forstermann et al., 1995). In contrast, iNOS is able to bind calmodulin virtually independ ant of Ca2+ (Table 2). Therefore, once iNOS is expressed, NO synthesis may only be limited by the availability of substrates and cofactors (J. Stuehr, 1990). As NO produced from iNOS predominantly depends only on iNOS expression, it lasts much longer than NO formed from the other isoforms of NOS. In addition iNOS produces much higher concentrations of Ca2+ compared to the consecutive forms of NOS (Cobb et al., 1996). The production of NO by eNOS and nNOS, compared to iNOS, can be controlled relatively easily by decreasing or increasing intracellular Ca2+, whereas iNOS can only be controlled through transcription (Cobb et al., 1996). In most cell types iNOS protein levels are either very low or undetectable. However, stimulation of these cells by cytokines or growth factors, can lead to increased transcription of the iNOS gene, with subsequent production of NO. On the other hand, for the prevention of iNOS expression through endotoxins, TGF-ß (Szabo, 1995) and anti inflammatory gl ucocorticoids can be administered which lower the magnitude of vascular hyporeactivity. Glucocorticoids such as Dexamethasone inhibit iNOS activity by blocking arginine transport and inhibiting tetrahydrobiopterin biosynthesis (A.J.B. Brady et al., 1992 and Thiemermann C et al., 1993). Regulation of NO production In the normal as well as in extreme physiological states (e.g. during infection), nitric oxide is considered as one of the most important signalling molecules in vivo. It is however also highly reactive and highly diffusible due to it being a free radical (one unpaired electron) (see fig 8). It is therefore important that there is strict control and regulation of nitric oxide production. The synthesis of NO within cells can be regulated in several ways such as the cellular distribution of NOS, changes in NOS gene expression, enzymatic activation by phosphorylation and the presence of cellular inhibitors NOS activity. Intracellular distribution of NOS Nitric oxide is principally regulated through strict control over the location of NO production. The NOS isoforms can be targeted to different regions of the cell, where NO will be produced in close contact with its target proteins. The image below shows the distribution of iNOS (shown in green in image 1) and eNOS (shown in red) in a trophoblast cell. The nucleus is shown in blue. Co-localisation between iNOS and eNOS will show up as a yellow colour (Phil Dash, University of Reading). The image shows that eNOS and iNOS are fairly variably distributed inside the cell, with hardly any yellow colour suggesting very little overlap in their cellular distribution (Phil Dash, University of Reading).Although both iNOS and eNOS produce NO it is likely that their different cellular distribution will lead to NO interacting with different targets and therefore having different effects (Phil Dash, University of Reading). It is very likely that the distribution of NOS isoforms is an important mechanism for regulating when and where NO is produced. Therefore the current research on NOS mainly focuses on how endogenous signals trigger NOS transport and redistribution (Rahul S. Koti et al., 2005). Activation of NOS activity NOS enzyme synthesis is principally regulated by changes in intracellular calcium levels. The constitutive isoforms of NOS, (eNOS and nNOS) have shown to proliferate following increases in Ca2+, and therefore calmodulin levels, in the cell (Rameau et al., 2003). Additionally both nNOS and

Balanced Scorecard: Management Control System Essay

â€Å"Balanced scorecard† means different things to different people. At one extreme, measurement-based balanced scorecards are simple dashboards of performance measures grouped into categories that are of interest primarily to an organization’s managers and executives. Typical categories include financial measures, and customer, process, and organization capacity measures. Measurement-based scorecards almost always report on operational performance measures, and offer little strategic insight into the way an organization creates value for its customers and other stakeholders. At the other extreme, a strategic performance scorecard system is an organization-wide integrated strategic planning, management and measurement system. Strategy-based scorecards align the work people do with corporate vision and strategy, and communicate strategic intent throughout the organization. In other words, these systems incorporate the culture of the organization into the management system. In strategy-based scorecards, performance measures are only one of several important components, and the measures are used to better inform decision making at all levels in the rganization. In strategy-based balanced scorecard systems, performance measures are the result of thinking about business strategy first, to measure progress toward goals. In strategy-based systems, the first question to answer is the strategic question: â€Å"Are we doing the right things? † The operations, process, and tactical questions come later: â€Å"Are we doing things right†. Over the past decade balanced scorecards have evolved from systems that simply measure performance to holistic strategic planning and management systems that help manage and track strategy execution. Despite this evolution, the majority of balanced scorecards that we have seen over the past 10 years use a â€Å"just give me the measures† philosophy. These measure-centric dashboard scorecards are interesting, but not very robust and not nearly as helpful as they could be. These scorecards remind me of the old Wendy’s commercial: â€Å"Where’s the beef? † Strategy-based scorecard systems, on the other hand, create a â€Å"strategic thinking† mentality in an organization, and can help lift the organization and its workforce to a higher, more performance-oriented way to think and work. Each organization is unique, and there is no â€Å"one scorecard fits all† solution. This article describes how to develop a strategy-based balanced scorecard system for technology companies. We’ll share some lessons learned from developing strategic performance scorecard systems in dozens of businesses and industries over the past 10 years. The Balanced Scorecard as a Technology Company’s Strategic Planning and Management System Technology company management teams are challenged by: †¢ Rapidly shrinking product cycles †¢ Recruiting, retaining and rewarding technology talent Making and communicating critical product development decisions †¢ Tracking the evolution of customer feature demands and use models †¢ Disruptive, enabling technologies that can invalidate products or entire business models In addition, executives rarely communicate the strategic manner in which the business is being directed. The typical result is disagreement and misalignment in how these challenges are perceived and addressed throughout the company. Any technology company strategy needs to embrace these challenges. Strategy is a company’s approach to achieving its vision–it’s the organization’s â€Å"game plan† for success. One thing the technology company’s strategy needs to define is how it will measure product planning and development success. Strategy needs to define how ideas are advanced into opportunities. Passionate technology workers need to know why their ideas and views were embraced, delayed, or discarded. Strategy must describe the timing of such considerations, so that investments in programs underway are protected from an ill-timed innovation capturing the minds of employees. Similarly, programs that are off track need to sound alarms so that corrective action can be taken. Strategy needs to guide when and how to sound those alarms and ensure necessary corrections are taken. Strategy needs to dictate tracking customer feature evolution, and if the company wields the core technology its products need to be successful in the marketplace. Using a balanced scorecard as the strategic planning and management framework allows a company to deal with these and other issues that matter to creating value for customers and stakeholders, such as process efficiency, financial performance, and organizational capacity and readiness. Starting with a strategic view of how the organization creates value for customers, a scorecard system links strategy to what must be done operationally to be successful. Good scorecard systems focus on the critical few performance measures that provide real business intelligence and contribute to the achievement of operational excellence, employee excellence, and business success. But more important, these systems focus on the elements of strategy that can be made actionable – strategic objectives that are the building blocks of strategy. Developing a Technology Company Balanced Scorecard System The logic of building a scorecard system and using the system as the organization’s strategic planning and management framework starts with an understanding of the organization’s customers and stakeholders, and their needs. The management team then develops and validates the strategic components of the management system. The components include mission, vision, core values, strategic perspectives (i. e. , performance dimensions), strategic themes and desired strategic results, strategic objectives, an organization-wide strategy map, performance measures and targets, and strategic initiatives aligned with the objectives. Strategy is the common thread through the scorecard system and forms the basis for communicating the organization’s approach for gaining competitive advantage (for a business), or in the case of a public or non-profit organization, for improving mission effectiveness for stakeholders. The finished strategy-based balanced scorecard system translates customer needs, mission, and values into organization goals, strategy, objectives, performance measures, and new initiatives. In a strategy-based scorecard system, strategy is analyzed through four performance dimensions (perspectives): financial (stewardship for government and non-profits), customer/stakeholder, business processes, and organization capacity. A key strategy development step is the creation of several high-level strategies (i. e. , strategic themes), associated strategic results, and strategic objectives for each theme. Strategic themes are aligned with the organization’s vision and mission, and the theme’s strategic result describes a high-level outcome of successfully implementing the strategic theme. Usually three or four themes define the business strategy of the organization at a high level. Examples of strategic themes include Customer-Focused Operational Excellence, Market Driven Technological Excellence, Strategic Partnering, and Growth Through Innovation. Many other themes are possible, and the selection of vision and aligned strategic themes and results make for unique performance scorecard systems for different organizations. Another key development step is the creation of strategic objectives — the â€Å"DNA† of strategy. Objectives are expressed as continuous improvement actions that can be documented, measured, and made actionable through initiatives and projects. Once developed, objectives are linked to form a â€Å"strategy map. † A strategy map shows graphically how the organization creates value for customers, stakeholders, and employees. The strategy map is constructed by linking strategic objectives using cause and effect relationships. A strategy map is one of the most effective communication tools an organization can use to build transparency, alignment, and a focus on results.