The Impact of Disruption to Sleep Patterns in the Intensive Care Unit Essay

The Impact of Disruption to Sleep Patterns in the Intensive Care Unit - Essay Example One undeniable truth is that absence of rest influences the wellbeing and progress of the recuperating for patients in the ICU. An investigation on the effects of rest interruptions in the ICU demonstrated that the idea of rest designs in a nursing situation has some critical relationship with the death rates (Friese, 2007, p. 1210). Nursing foundations that advance great rest propensities for patients in the ICU have additionally indicated huge decreases in the degrees of mortality. Then again, nursing foundations that don't have any structures for advancing great rest propensities were likewise connected with high death rates. The discoveries of this examination were steady with different discoveries that indicated a positive relationship between the conditions of strength of patients in the ICU with the quantity of long stretches of rest that the patients figured out how to get (Friese, 2007, p. 1212). For example, these discoveries indicated that a large portion of the patients w ho figured out how to get continuous rest had the option to react quicker and preferable to treatment over the individuals who were every so often hindered by the medical caretakers or different components. Conversation Various examinations have built up a relationship between the pace of patients’ readmission to the nursing homes and the interruptions to the rest designs (Patel, Chipman, Carlin and Shade, 2008, p. 309; Patel, Chipman, Carlin and Shade, 2008, p. 310). A portion of the surmisings drawn from this investigation are that the rest examples of the patients in the ICU advanced the regular safeguards of the body, therefore, permitting the patients to grow long-terms wellbeing dependability. These affiliations are likewise steady with different investigations that have set up the presence of positive impacts between long haul wellbeing adjusts of people to the nature of rest that they get (Eliassen and Hopstock, 2011, p. 140). Assessments of some nursing specialists r ecommend that the advancement of natural conditions that help quality dozing designs is more feasible than mediations that include the utilization of rest inducers. Patients who are at times exposed to rest inducers regularly slip by into wooziness after a brief time and may require more grounded inducers with the goal for them to obtain a similar measure of rest (Patel, Chipman, Carlin and Shade, 2008, p. 310). A portion of the investigations have set up an association between the disability of the body’s capacity to battle contaminations (Eliassen and Hopstock, 2011; Friese, 2007). Quality rest fortifies the insusceptible framework and gives the empowering condition to the working of the guarded component of the body. Helpless resting designs are normally connected with delayed mending and negative reactions to the treatment forms. Patients who neglect to get adequate rest are additionally liable to experience the ill effects of mind flights and shaky mental states. This is on the grounds that the condition of a patient’s mental parity is influenced by the sort of weight and strain that happen during the time of alertness. All together for a patient in the ICU to build up the essential protections, it is important to build up a steady resting plan with adequate time that would take into consideration the arrival of the strain and weight that work at the psychological level. The job of medical attendants in alleviating the unfriendly

The Execution of the Rosenbergs Essay Example for Free

The Execution of the Rosenbergs Essay During the Cold War, Americans lived in a general public where the pressure between the Soviet Union was at its top ever. It was the point at which the scorn against socialism and the possibility of patriotism were developing exponentially. In the mean time, Julius and Ethel Rosenberg were captured for the allegations of helping the Soviets make the nuclear bomb, which was the United States’ just preferred position over the Soviets. Their capture in the long run prompted the first since forever execution of surveillance in Quite a while history. Notwithstanding, the defense of their execution is as yet being bantered right up 'til the present time. Did the Rosenbergs merit such a cruel sentence or was it a misinterpretation driven by the dread of socialism? The political and social parts of society unquestionably guided the dread of socialism to dominate the honesty of the Rosenbergs, making them the most dubious government agents in American history. During World War II, numerous nations including the Soviet Union were suspicious about the presence of the nuclear bomb. Be that as it may, after the bombings of Hiroshima and Nagasaki, the quality of the nuclear bomb turned out to be notable. Obviously as long as the United States had this weapon, no nation would challenge them. This weapon was one of only a handful not many favorable circumstances the United States had against the Soviet Union going into the Cold War. Maybe the nuclear bombs were the United States’ shield and defensive layer against the Soviet Union’s assaults. In the interim, the intensity of socialism was consistently ascending in Eastern Europe and alongside that, the American’s dread of socialism was developing in equal. â€Å"Communists were trashed; devils had no spirits; no adoration in their hearts† (Garber/Walkowitz 25). The circumstance required the â€Å"blueprint† of the nuclear bomb to be securely taken care of from the socialists. The U. S. overnment expected that the Soviet covert agents may get their hands on the mystery data. In any case, it was inevitable that the Soviet Union would â€Å"somehow† build up its own nuclear bomb†¦ Eventually on August 29th 1949, news was accounted for that the Soviets have effectively tried a nuclear bomb in Kazakhstan. Americans were stunned, angry, and startled. â€Å"When news came that the Soviets tried a bomb, years before it was normal, there were without a doubt numerous demagogic calls, in the media and on the stump, to discover and seriously rebuff, even execute, the criminals, the traitors† (Cohen 49). The American individuals didn't stop to think once that the Soviet Union could have made the nuclear bomb with their own capacity and innovation. A great many people recently expected that it was accomplished through a work of spies that sold the mystery data for cash. In this manner, the administration didn't sit around time to discover the individual who was liable for passing data about the nuclear bomb. The developing trepidation of socialism in the long run arrived at its pinnacle and the legislature was begun taking activities to forestall any demonstrations of secret activities. Following quite a while of examination by the FBI, Julius Rosenberg was called for addressing. He has recently been in socialist gatherings and there were admissions from the Soviet government operatives that he was liable for sending dispatches and data from Los Alamos, where the Manhattan venture was run. His better half, Ethel Rosenberg, was not denounced from the outset on the grounds that there was no evidence of her movement in any unlawful demonstrations. She was uniquely as an all day specialist as a secretary and a mother of two children. In any case, she was later called for addressing when her sibling, David Greenglass, was likewise captured for secret activities. As the examination went on, the media was beginning to warm up and cause national to notice the Rosenbergs. The Rosenbergs were to be recollected the greatest outrage producers in U. S. history. As the dread of the Soviet Union became after their advancement of the nuclear bomb, the U. S. government was not going to release the examination easily. After various admissions from Soviet covert agents that Julius Rosenberg was mindful, he was sent to prison. A couple of months after the fact, the FBI additionally captured Ethel Rosenberg with the possibility that she may have assisted her better half. The Rosenbergs were in the long run both captured and sent to court under Judge Kaufman. Nonetheless, there were insufficient proof going into court that the Rosenbergs were truly liable. â€Å"No records connecting the Rosenbergs with surveillance were delivered, regardless of an exhaustive hunt of their home by FBI specialists, who put in proof just an assortment can for the Spanish Refugee Appeal, authorized by the City of New York, found in their home† (Rosenberg 15). Consequently, the preliminary took an extremely extensive stretch of time. The main confirmations conflicting with the Rosenbergs were that David Greenglass and other Soviet government operatives have admitted to the Rosenbergs’ inclusion in surveillance. In any case, regardless of whether there were any demonstrations of surveillance by the Rosenbergs, it was later uncovered that none of the data that was passed by Julius Rosenberg was even valuable in the improvement of the nuclear bomb. On the off chance that any data that was passed off was not valuable, why rebuff or even murder that individual? The preliminary was only an endless loop between a few American regular folks and a political domineering jerk that was blinded by war. On the off chance that there was a lot more supporting confirmations for the Rosenbergs’ proof, for what reason did the United States government continued containing the Rosenbergs? It was all in light of the fact that the U. S. government would not like to appear to be frail according to the Soviet Union. Neither one of the countries needed to show any shortcoming and lose the battle like in a bout where neither one of the fighters needs to give their indications of weariness and injury. The two nations attempted to look more grounded and more extravagant than the other. â€Å"In turning down Ethels enthusiastic interests, Eisenhower said over and over that we were unable to show up weak† (Cohen 50). The Cold War was changing a great deal of people’s sees. Indeed, even President Eisenhower’s mindset shows the amount he has become upset and the estimation of people on account of the force of the war. In the long run on April fourth 1951, the Rosenbergs were condemned to execution by Judge Kaufman. The last expressions of Judge Kaufman were cold and unsympathetic. â€Å"Your wrongdoing is more terrible than murder, for you put under the control of the Russians the A-bomb a very long time before our best researchers anticipated Russia would consummate the bomb has just caused, as I would like to think, the Communist animosity in Korea, with the resultant setbacks surpassing 50,000 and who knows yet what that millions progressively guiltless individuals may follow through on the cost of your treachery. Surely, by your disloyalty, you without a doubt have adjusted the course of history to the drawback of our country† (Wexley 67). In a significant case this way, it is basic for the adjudicator to consider all the proof that is raised for the situation, however rather, Judge Kaufman overlooked the confirmations that bolstered the Rosenbergs. The appointed authority was under an excess of control of President Eisenhower and the American government. Additionally, many accept that censuring the Rosenbergs for the reason and passings of the Korean War was route over the top. A wrongdoing in that kind of scale can't be demonstrated in court, which makes this preliminary a â€Å"scandal† in excess of a genuine â€Å"crime†. But then the Judge expressed the â€Å"unproven crime† in the last sentence and thought about it in the Rosenbergs’ execution. Judge Kaufman reprimanded them for the Korean War, and President Eisenhower considered them answerable for the butcher in any conceivable future atomic war with the Soviet Union. These outrageous allegations were rarely verified and, while there is no law requiring, they ought to have been† (Root 292). There was just no verification that the Rosenbergs were liable for every one of these catastrophes. In spite of the fact that they were Americans with socialist perspectives, they were just a little level of the socialist populace in the United States during that timespan. Likewise, the United States being associated with the Korean War was exclusively the government’s choice. Saying that a future atomic war is altogether their flaw is a lot of an exaggeration to make on two blameless regular folks who were simply condemned to death. Thinking back a long time from now, the media was likewise one-sided and announced bogus data about the Rosenbergs that had critical effect on the decision of capital punishment. â€Å"It is basic that the verifiable realities be known to all. Unfortunately, the data in the press and different broad communications isn't reality, however rather is a twisted, shortened, nearsighted abnormality of our case. Plainly the essential use being presented of our defense is to pressure political dissenter, and to make sure about conformity† (Rosenberg 132). That was a statement taken from a genuine letter composed by Ethel Rosenberg to her significant other just before their execution. Telling from the tone of the letter, the Rosenbergs were given up from the manner in which the media was detailing bogus data and making the preliminary much harder for them. The media has consistently been a key factor on political and social issues. In light of the developing trepidation of socialism, the media would not like to advance socialism and secret activities in any capacity to people in general. Therefore, the Rosenbergs were by and by casualties of the one-sided society and its bogus announcing media. The media was not by any means the only effect on the social inclination against the Rosenbergs. Numerous books were distributed to call up the American’s outrage against the Rosenbergs around then. For instance, there was the book, â€Å"Betrayers: the Rosenberg Case †a reappraisal of an American crisis† and â€Å"The Rosenberg Case: Fact and Fiction†, which was distributed on that time of the execution. One of the statements from the book was â€Å"Yes. The Rosenbergs’ case is finished, yet the abhorrent that they did is endless† ( Fineberg 148). On the off chance that the shrewd that the

The Escape – Creative Writing

I was unable to relax. I could feel an enormous load on me yet when I looked there was nothing there. It was getting heavier and heavier. I attempted to shout yet every time that I attempted I felt a shooting torment in my chest. All that I could do was pause and supplicate. I imagined that it was impossible that I would be found and I propped up over what had occurred and couldn't see how a real existence so flawless could turn out badly as effectively as it had. It wasn't right. I looked down and discharged an ear parting scream†¦ The earlier month I had quite recently been an ordinary young person, going to class and going out to shop at the end of the week. At that point everything changed. I returned home from school to locate that a huge wagon was stopped before our home and a man was completing our things. I saw my TV, sound system and Game solid shape being done of the front entryway by two huge men. From the start I felt that we were being looted however then I saw my mum and father show up at the front entryway. My mum was in surges of tears and my father was remained with another man and marking papers. It never happened to me what was going on. I stumbled into the nursery and tossed my arms around my mum. In spite of the fact that I didn't have the foggiest idea what was happening I began to cry. I believed that I should attempt to be bold as my mum was so vexed however it was the main time that I had seen her cry. I realized that something must be genuinely off-base. I discharged her tenderly from my arms and delicately asked her what was going on and who the men were. She said that my father would clarify everything when he had marked the papers. It was around five minutes, yet appeared to be a lifetime, before my father could come and clarify what we would do straightaway. As my father began to talk I got stunned. How could this occur? We hadn't done anything incorrectly yet we were the ones that were being rebuffed. I was unable to take in what was being disclosed to me. It was out of line to such an extent that in light of the fact that my father had made the best decision we would need to move out of our home and leave our life that my folks had developed for me. What had happened was that my father had been associated with a theft at work, the men had been caught yet my father had been approached to give proof in court so as to get them put in jail. My father had done this enthusiastically however what he had not understood was that the men who he had assisted with sending to jail were a piece of an enormous pack who were exceptionally savage. The other pack individuals were presently out for retribution, with my father. He had been getting quiet calls; abhorrent instant messages and he had even been sent passing dangers through the post. Be that as it may, what had happened the earlier day was a lot for anybody to adapt to. Somebody had blasted into his office to attempt to assault him. It could have all turned out badly for my father in the event that it hadn't been for a gathering being called at last and him leaving his office to go along with it. I felt dreadful, it had been the earlier day that I had been groaning on the grounds that I wasn't permitted to go out with my companions. I could now comprehend that they had done it for my wellbeing and similar men that had needed to slaughter my father could have executed me. I hadn't thought anytime in my life that I would need to be cautious where I go and who I go with for an incredible danger. Everything appeared to be so unbelievable. I had sat in front of the TV projects and blood and gore movies about things like this event however I never pondered what it must resemble for individuals to be placed in this circumstance. I felt baffled in myself since I recollected when I was at a sleepover and I had kidded that this kind of thing could never occur and that on the off chance that it did the individual who was on the run probably accomplished something incorrectly. In any event, when I had this disclosed to me I didn't hope to hear what they let me know straightaway. We were being placed in the ‘Witness Protection Program'. I didn't completely comprehend what this implied. I felt that all it implied was that we needed to move away from our home so as to escape from the individuals that were pursuing us. As my folks kept on talking I understood that it implied that we would get another character and that we were not permitted to mention to anybody what we would do. That was the hardest thing that I needed to adapt to. I said bye to my companions when I left school that day yet it never entered my head that it was the exact opposite thing that I would state them. I had consistently been mainstream at school and I was unable to comprehend why something like this would transpire. For what reason wouldn't it be able to happen to Laura and her family? Nobody enjoyed her and she didn't have any companions so there wouldn't be any individual who might miss her. I realized that it was a loathsome thing to think however I was unable to support myself. What might my companions think in the event that I didn't utter a word before I left? I begged my mum to let me telephone them, I even said that one would be sufficient and that they could give the message to the others. This wasn't going to happen regardless of the amount I argued. They clarified that it was for my wellbeing. On the off chance that I had told my closest companion and she said something to my different companions, somebody could catch what she was stating and this issue could begin once more. I understood what they were stating however it appeared to be so undeserved. After we had the discussion I concluded that I would have one final look inside the house. I was truly shocked. The house despite everything had the backdrop and the rugs yet the remainder of the house was so uncovered. I climbed the steps to where my room was. It was abnormal realizing that it was the last time that I would be in my room once more. It despite everything resembled my live with the rugs and the banner yet everything else was exposed. I felt a tear tumble down my face. I was attempting to be solid however there was nothing that I could do, I just couldn't prevent the tears from consistently falling. I gradually strolled down the steps and unobtrusively sat in the vehicle. The enormous wagon began to drive off down the road and I knew then that it was the finish of what I knew as my life. As my folks got into the vehicle a police officer came to sit in the back. Everything felt so unusual and I was unable to take the risk of looking behind me since I didn't have the foggiest idea how I would respond. At the point when we turned the corner onto the fundamental street my telephone began to bleep to reveal to me that I had a message so I ventured into my pack to get it out. It was no sooner that I had the portable in my grasp that the police officer grabbed it off me. She was thoughtful with me yet she said that i should didn't peruse what it said on the grounds that it might disturb me to realize that I couldn't react to whatever was said. As we maneuvered onto the motorway it struck me that I didn't have the foggiest idea where we were going. I had been so enveloped with my considerations that we could have been traveling to another country and I wouldn't have known. I asked my father however he said that he would reveal to me when we had shown up. It appeared to me as though I was being kept in obscurity about everything that was going on. Did my folks not understand what amount of this was influencing me? My entire world was being flipped around and they wouldn't reveal to me anything about what was occurring. It wasn't as if I wouldn't comprehend; I was a young person so is there any good reason why they wouldn't confide in me. I didn't have any way that I could contact anybody so I was unable to place us in any peril from these individuals who were pursuing us. We eased back down and I saw a sign that was in welsh and when I saw it I knew where my folks were taking me. We had been on vacation here the earlier year and my folks had communicated the amount they cherished it her. I was extremely irate at this point. They were wrecking as long as I can remember and they were making me remain in this spot. They realized the amount I loathed it in view of how much there was to do. There were handle all around, no shops and nobody who was close to my age. I was unable to perceive how I was going to adapt in a spot this way. My life would rotate around school in light of the fact that there was nothing else to do. On the off chance that we needed to move for what reason would we be able to move to an enormous town like London or Birmingham? This would have been my most exceedingly awful bad dream, nothing to do except for stroll up slopes and go to class. I had never acknowledged how incredible my life was previously. It causes me to see how obvious the platitude ‘you never acknowledge what you have until its gone' is. The measure of times my folks had said this I hadn't generally gotten it, I recently expected that on the off chance that you lost something you would have the option to become acclimated to your existence without it. I could never become acclimated to this. We crashed into the town and there was no one about despite the fact that it was a Friday night. There were consistently individuals about when you needed to go out. I hadn't seen one individual here. We pulled up before this little cabin. They couldn't genuinely imagine this was large enough for three individuals however when I looked round it was by all accounts perhaps the greatest cabin in the zone. I reluctantly strolled through the front way to find that it appeared to be greater within than it looked all things considered. I realized that there was nothing that I could do now to adjust their perspective so I returned outside and removed one of the bags from the boot of the vehicle. As I pivoted I saw that there was a kid and a young lady strolling towards me. They appeared to be well disposed and they looked about my age. I made proper acquaintance and presented myself. It appeared to be peculiar when I needed to present myself by an alternate name. They didn't appear to see the uncomfortable tone in my voice since the two of them acquainted themselves with me. They said that the two of them lived not far off and that they went to the school that I would be going to. I disclosed to them that I needed to take my things inside yet I would ideally observe them later. They said bye and strolled off. Things looked obviously superior to I had initially believed that it could be. I gradually became accustomed to living in a peaceful town and before the second's over week I had heaps of new companions and I had explained to then why I had moved here-The made up form clearly. Everybody appeared to be decent but since it was so confined there was just six individuals in my group. It was peculiar regardless and I would return home miracle b

Low density lipoprotein (ldl) cholesterol - Free Essay Example

Elevated cholesterol, particularly low density lipoprotein (LDL) cholesterol, is a well defined risk factor for the development of atherosclerosis (NCEP, 2002). Atherosclerotic lesions are thought to form in response to endothelial damage caused by excess LDL (Steinberg, 2005). Most cases of cardiovascular disease (CVD), the leading cause of mortality and disability in the developed countries, are ascribed to pathology of atherosclerosis. Strategies to lower plasma LDL cholesterol levels are therefore crucial in the prevention and treatment of CVD (OKeefe et al., 2009). Conversely to plasma LDL levels, elevated high density lipoproteins (HDL) are protective against the development of CVD. Low density lipoproteins are responsible for the transport of cholesterol and fatty acids from the liver to the various tissues of the body. In contrast HDL is responsible for the majority of reverse cholesterol transport (RCT), in which cholesterol from the peripheral cells are returned to the liver for excretion in the bile (Joy and Hegele, 2008). It is this major role that HDL plays in RCT that is attributed with HDLs anti-atherogenic effects. Therefore strategies which elevate HDL levels are also beneficial in the prevention and treatment of CVD. Plasma cholesterol can be synthesized by the body (hepatic or extra-hepatic sources) or absorbed from the intestines (dietary or biliary sources). Statins, which are a family of HMG-C OA reductase inhibitors, reduce cholesterol synthesis and are very effective and can achieve plasma cholesterol lowering of up to 55% and have been shown to reduce CVD risk by one-third (Stein, 2002). Statin therapy has also been shown to increase plasma HDL levels from 2-16%, it is not know if this increase is clinically significant to the efficacy of statin therapy as it is difficult to separate this small and variable increase from the benefit of the significant LDL lowering (Hou and Goldberg, 2009). Regardless of the statins efficacy of return LDL cholesterol levels to their desired range, a significant proportion of statin users continue to have adverse events (Alsheikh-Ali et al., 2007). Therapies which reduce intestinal cholesterol or bile acid absorption are also available. Plant sterol/stanols, dietary fibre, bile acid sequestrants have been shown to be effective, with LDL cholesterol reductions of 10-15%, 8.5-13% and 5-30% respectively (Hou and Goldberg, 2009). The drug Ez etimibe, which binds to Niemann-Pick C1 Like 1 (NPC1L1) protein a crucial mediator of cholesterol absorption (Chang and Chang, 2008), has also been demonstrated to lower LDL cholesterol levels by 16-19% (Pandor et al., 2009). The wide ranges of cholesterol lowering seen in each treatment are likely the product of genetic factors which vary the rates of cholesterol synthesis and absorption, as well as modulate the effectiveness of each intervention. Because of this genetic heterogeneity of cholesterol synthesis and absorption, being able to effectively measure these parameters and how they respond to different dietary, pharmaceutical or lifestyle interventions is paramount to understanding interventions effect on cholesterol metabolism. Methods to assess cholesterol absorption Direct Method A direct method of measuring cholesterol absorption refers to measuring cholesterol flux from the intestines to the lymph. It is a direct method because it does not use a faecal or plasma level of cholesterol to infer absorption (Gibson, 1984). The first direct method of measuring cholesterol absorption required a duodenal cannula for infusion and cannulisation of the mesenteric or thoracic lymph ducts to sample lymph (Pouteau et al., 2003a). This method has been successfully used to access cholesterol absorption in rats, dogs and rabbits. The use of radioactively labelled cholesterol in the duodenal infusion allows for the distinction between exogenous and billiary cholesterol and can be used to calculate the percent absorption of exogenous cholesterol. An alternative direct method for use in humans was introduced by Grundy and Mok (1977). The intestinal perfusion method (sometimes refered to as Method VII) requires intubation with a three-lumen tube. Liquid formula and ÃÆ'Ã… ¸-s itosterol (though to be a non-absorbable cholesterol degradation marker at the time) is infused into the duodenum at the Ampulla of Vater though the first tube, and intestinal content is aspirated from the 2nd and 3rd tube, 10 and 100 cm distal to the first, respectively. Analysis of the aspirate from allows for the calculation of net hourly cholesterol absorption across the 100 cm long segment of intestine. Discriminating between exogenous and endogenous sources of cholesterol can be done by infusing radioactive cholesterol. The use of ÃÆ'Ã… ¸-sitosterol as a non-absorbable marker in this method may not have been the most appropriate choice given what is known about plant sterols and inhibition of cholesterol absorption at even very low levels (Calpe-Berdiel et al., 2009; Ostlund et al., 2002a; Ostlund et al., 2002b). Plant sterols complete with cholesterol for absorption into gut enterocytes, but are then exported back into the intestines by ABCG5 and ABCG8 transporters. This inh ibition was seen by Grundy and Mok, who noticed that even small increases in ÃÆ'Ã… ¸-sitosterol concentration caused noticeable reductions in measured cholesterol absorption (Grundy and Mok, 1977). The use of an inhibitor of cholesterol absorption in a method to access cholesterol absorption obviously leads to underestimation of actual cholesterol absorption capacity, and this must be taken into account when comparing absorption values among different methods. Another downside to the direct measurements techniques is their invasiveness, however they are the only methods which yield direct measures of total, exogenous and endogenous cholesterol absorption across a section of the intestine (Gibson, 1984). Cholesterol balance methods Cholesterol balance methods use the differences between dietary cholesterol and faecal cholesterol, excluding cholesterol of endogenous origins, to estimate cholesterol absorption (Matthan and Lichtenstein, 2004). Radioactive labelled cholesterol is used to distinguish endogenous from exogenous cholesterol and faecal and plasma levels of cholesterol are measured. There are 4 main balance methods, following the nomenclatures from Grundy and Arhens (1969), they are Method I, II, III and V. Method I consists of a single dose of [14C] or [3H] radio-isotope labelled cholesterol administered intravenously (Grundy and Ahrens, 1969; Quintao et al., 1971). This radio-isotope labels endogenous cholesterol and its subsequent steroid products. Using the formula: daily exogenous absorbed cholesterol (mg/day) = daily cholesterol intake (mg/day) à ¢Ã¢â€š ¬Ã¢â‚¬Å" daily unabsorbed dietary cholesterol (mg/day), and daily unabsorbed cholesterol (mg/day) = faecal neutral steroids per day (mg/day) endogenous faecal neutral steroids per day (mg/day). Endogenous faecal neutral steroids are calculated by dividing the total radioactivity (dpm/day) in the total faecal neutral steroids by the specific activity (dpm/mg) of the plasma cholesterol 1-2 days prior (depending on gastrointestinal transit time). Method II requires continuous oral labelling with radioactive cholesterol (Grundy and Ahrens, 1969; Quintao et al., 1971). The radio-labelled cholesterol is generally incorporated into a liquid diet to insure a precise daily intake of radiosterol for many weeks. Cholesterol absorption is calculated using the formula Z = X + Y, and Z * SA(Z)= X *SA(X) + Y * SA(Y), where Z = total faecal neutral steroids (mg/day), SA(Z) = specific activity of total faecal neutral steroid (dpm/mg), X = faecal neutral steroids of endogenous origin (mg/day), SA(X) = specific activity of plasma cholesterol (dpm/mg), Y= daily unabsorbed dietary cholesterol (mg/day), and SA(Y) = specific activity of diet ary cholesterol (dpm/mg). The equations are solved for Y, and absorption measurements can be done at any time after 4 days of continuous radioisotope feeding, a isotopic steady state is not required. It has been shown that Method II provides more consistent data on cholesterol absorption than, and is therefore recommended over, Method I (Gibson, 1984; Matthan and Lichtenstein, 2004). Method III was introduced by Wilson and Lindsey (1965) and requires an isotopic steady state. Continuous feeding with radioisotope labelled cholesterol for greater than 100 days is required to reach an isotopic steady state. When an isotopic steady state is reached daily cholesterol turnover is calculated, and daily absorbed dietary cholesterol is calculated by the formula: Dietary cholesterol absorption (mg/day) = daily cholesterol turnover (mg/day) * (specific activity of plasma cholesterol/specific activity of dietary cholesterol). Failure to reach an isotopic steady state will yield an underestim ate of actual dietary cholesterol absorption (Gibson, 1984). The long period required to reach an isotopic steady state and difficulty determining when this state has been reached make Method III a difficult and unreliable method. Method III was shown to give lower values of cholesterol absorption than both Method I and II in direct comparison (Quintao et al., 1971). Method V (Grundy et al., 1971) is a combination of methods I and II. Subjects are continuously fed isotopically labelled cholesterol as in Method I and then given a single bolus of different isotopically labelled cholesterol as in Method II. The equations for Method II are used, with only the modification of the X *SA(X) term which is replaced by [(R)(SA(X oral)) / (SA(X intravenous))], where R= daily faecal neutral steroid excretion of intravenous cholesterol (mg/day), SA(X oral) = plasma specific activity of oral isotope taken 1 day before R (dpm/mg), SA(X intravenous) = plasma specific activity of intravenous isot ope taken 1 day before R. Method V was designed for situation when rates of cholesterol synthesis are unusually high (due to surgical or pharmacological interference with enterohepatic circulation), which can lead to endogenous cholesterol being secreted into the intestines prior to isotopic equilibration(Gibson, 1984). In this circumstance (very high synthesis) Method I would underestimate and Method II would overestimate cholesterol absorption. Methods I, II and V all require a marker for gastrointestinal transit time, and for cholesterol degradation in the gut. Chromic oxide is often used as a marker of gastrointestinal transit time. ÃÆ'Ã… ¸-sitosterol has been used as a control for cholesterol degradation, however it must again be mentioned that if ÃÆ'Ã… ¸-sitosterol is used as a marker then the cholesterol absorption values obtained are likely lower than the actual values. However, in these methods if the degradation of cholesterol in the gut is not accounted for, the calc ulated cholesterol absorption will be higher than the actual values (Quintao et al., 1971). Isotope ratio methods Isotope ratio methods measure only the percentage cholesterol absorption (Pouteau et al., 2003a), unlike balance methods, and require accurate record of dietary cholesterol intake to estimate the mass of exogenous cholesterol absorbed from the percentage (Matthan and Lichtenstein, 2004). Method IV (also called faecal isotope ratio method), first introduced by Borgstrom (1969) calculates cholesterol absorption as the percentage of a single oral dose of radio-labelled cholesterol not recovered in the faeces. A single 1 ÃŽÂ ¼Ci radio-labelled dose of both cholesterol and ÃÆ'Ã… ¸-sitosterol is administered orally and feces are collected for seven to eight days. The ratio of labelled cholesterol to labelled ÃÆ'Ã… ¸-sitosterol in a sample of the pooled faeces samples is compared to the ratio that was given orally and cholesterol absorption is calculated using the formula: Cholesterol Absorption (%) = 1 à ¢Ã¢â€š ¬Ã¢â‚¬Å"((Faecal Cholesterol (dpm) /Faecal ÃÆ'Ã… ¸-sitosterol (dpm) ) * (Oral Cholesterol (dpm)/Oral ÃÆ'Ã… ¸-sitosterol (dpm))) *100. This method has been modified to allow a single faecal sampling, Sodhi et al. (1974) administered a faecal flow marker, such as chromic oxide or carmine red, with the original test dose, and calculated the faecal isotopic ratio at the peak level of the marker in the faeces rather than a sample of the pooled faeces. This single faecal sampling modification of Method IV has been compared to the original Method IV and Method I in baboons and it yielded consistently higher absorption levels, suggesting that this modification may weaken the accuracy (Mott et al., 1980). Method IV, despite the long period of faecal collection required, uses a far smaller dose of radioactivity than the balance methods, and is relatively straightforward and simplistic in execution (Gibson, 1984). It does still require ÃÆ'Ã… ¸-sitosterol as a marker of cholesterol degradation in the gut, so it shares the drawbacks previously discussed. Th e plasma isotope ratio method (IRM or Method VI), was first introduced by Zilversmit (1972) in rats and then subsequently carried out in humans (Samuel et al., 1978). The IRM involves simultaneous oral and intravenous administration of C14 and H3 radio-labelled cholesterol and requires only a single blood sample 3-4 days afterwards. The methods principles are based on the measurement of drug absorption used in pharmacology. If the absorption of cholesterol was 100% than the specific activity curve of both radio labelled cholesterols would be the same, if absorption was zero, none of the orally administered cholesterol, and therefore zero radioactivity from the oral radioisotope would appear in the plasma. Since cholesterol absorption falls between zero and 100%, the ratio of the two plasma radioactivities, after normalization for dose, are used to calculate absorption using the formula: Cholesterol Absorption (%) = 100 * (% oral dose in plasma/ % IV dose in plasma), where % oral dos e and % IV dose in plasma are the percentage of IV and oral tracer in the plasma sample, respectively (Samuel et al., 1982). The ratio is calculated 3-4 days after radioisotope administration because the specific activity time curves of both radioisotopes must be parallel. This does not occur in human until 3-4 days due to a delay in the appearance of the oral radioisotope in the blood related to the mechanisms of cholesterol absorption (Gibson, 1984). The IRM advantages over previous methods include: 1)only a single blood sample is required, 2) a low dose of radioisotope is used, 3)it does not require faecal collection 4) it does not required markers, such as ÃÆ'Ã… ¸-sitosterol, to correct for faecal losses. The IRM lends its self to repeated use because of its short duration and low level of labelling, this allows for investigation of variations in cholesterol absorption under different experimental parameters in the same individual in a comparatively short time period. The IRM m ethod has been validated in human numerous times against method IV under different conditions yielding similar results(Samuel et al., 1978; Samuel et al., 1982). A third isotope ratio method, Method VIII was introduced by Crouse and Grundy (1978), it shares similarities to Method IV, average cholesterol absorption is calculated using the ratio administered cholesterol to ÃÆ'Ã… ¸-sitosterol measured in the faeces, but differs in the method of isotope administration. C14 Cholesterol and H3 ÃÆ'Ã… ¸-sitosterol are administered orally three times daily for 10 days, and faeces can be collected from day 4-10 (Gibson, 1984; Matthan and Lichtenstein, 2004). Following day 3 of isotope administration the ratio of isotopes in the faeces becomes essentially constant and cholesterol absorption is calculated by the formula: Absorption (%)= 100* ((Faecal cholesterol (dpm)/Faecal sitosterol (dpm))/1-dietary cholesterol (dpm)/ dietary sitosterol (dpm)) This method requires only the ratio o f radioactivity in a single faecal sample to be measured; faecal mass need not be calculated (Crouse and Grundy, 1978). Since ÃÆ'Ã… ¸-sitosterol is also administered with the labelled cholesterol it may underestimate actual cholesterol absorption. Plasma cholesterol specific radioactivity following the consumption of a test meal has also been investigated a measure of cholesterol absorption. Lin et al. (2005) measured cholesterol absorption in 11 individuals with Smith-Lemli-Opitz syndrome (SLOS), a cholesterol synthesis disorder, and compared plasma cholesterol apecific activity with cholesterol absorption measured by Method IV. They sampled blood 24, and 48 hours following radioisotope enriched tests meals, and calculated the specific radioactivity of the cholesterol in the plasma (dpm/mg cholesterol). These values correlated significantly with cholesterol absorption calculated by Method IV (r=0.594, p=0.009, and r=0.474, p=0.047 for 24 and 48 hours respectively). While this m ethod cannot calculate cholesterol mass or percent absorption, it could allow for investigation of relative changes in cholesterol absorption within an individual across different conditions. It requires only a single blood sample, no stool collection, and no use of a cholesterol degradation marker, such as ÃŽÂ ²-sitosterol. This method is very similar, to the single isotope tracer method that will be discussed in the stable isotope methods section (Wang et al., 2004). This relationship between plasma radioactivity at 24 hours and cholesterol absorption requires further validation, especially in healthy individuals. The use of radio-isotopes has been invaluable to the investigation of cholesterol absorption, however the advent of stable isotope laboratory techniques, especially developments in isotope ratio mass spectrometry has allowed radio-isotopes such as C14 and H3 tracers to be replaced with safer 13C, 2H and 18O stable isotope labelled tracers (Pouteau et al., 2003a). T his has reduced the difficulty related to containment, handling, disposal and overall safety associated with radioisotopes and allowed for investigation of cholesterol absorption in certain populations (children, pregnant and lactating mothers) which had previously been impossible do to the ethical considerations around radioisotope administration. Stable isotope methods for cholesterol absorption Cholesterol labelled with stable isotopes has been shown to have identical kinetics as radio-labelled cholesterol. This has led to the development of stable isotope techniques to investigate cholesterol absorption. Lutjohann et al. (1993) introduced a stable isotope version of Crouse and Grundy s (1978) Method VIII discussed above. Deuterated cholesterol and sitostanol were used in place of C14 cholesterol and H3 ÃÆ'Ã… ¸-sitosterol, and quantified using gas-liquid chromatography -selected ion monitoring. Cholesterol absorption was calculated as in Method VIII. The stable isotope method was twice compared to Method VIII, in six monkeys, yielding similar results. The stable isotope method produced and absorption range of 49-73% (mean of 60%), with coefficient of variation ranging from 3.9%-15.1% (mean 7.1%). The radioisotope produced a range of 51-69% (mean 61%) with coefficient of variation ranging from 1.9-13.6% (mean 5.1%) (Lutjohann et al., 1993). This stable isotope Method VIII was determined to be as effective as the radio-isotope Method VIII, without the risk of radioactive exposure to subjects and research staff. This method uses sitostanol, rather than ÃŽÂ ²-sitosterol, as a marker for faecal losses of cholesterol. This, however, does not remedy the problem other methods suffer from when using ÃŽÂ ²-sitosterol, as sitostanol is also an inhibitor of cholesterol absorption (Gylling et al., 1997; Miettinen et al., 1995). The plasma isotope ratio method (Method VI) (Samuel et al., 1982; Zilversmit, 1972) was also adapted to stable isotopes. Bosner et al. (1993) used 2H labelled oral and 13C labelled IV cholesterol to calculate the plasma stable isotope ratio and cholesterol absorption percentage. This method uses gas-chromatography à ¢Ã¢â€š ¬Ã¢â‚¬Å" mass spectrometry with select ion monitoring (GC/MS-SIM) or GS/MS- chemical ionization mode (CI) to determine isotopic enrichment. Bosner et al. (1999) further modified the Method VI to a single isot ope dual tracer method, using oral [2H]5 and IV [2H]6 cholesterol. Isotope detection in the plasma cholesterol is done by GC/MS- selected mass monitoring. Jones et al. (2000) were the first to use isotope ratio mass spectrometry to determine isotopic enrichment using the plasma isotope ratio method. Oral 13C and IV 3H cholesterol were administered to 15 hypercholesterolemic men, followed by blood sampling 2-3 days post administration. Free cholesterol from red blood cells was purified by thin layer chromatography and subsequently combusted to yield carbon dioxide and water. The CO2 was then measured for 13C enrichment against the international standard Pee Dee Belemetite (PDB) on an isotope ratio mass spectrometer (IRMS). The water was reduced to hydrogen gas via zinc reduction and 3H enrichment was measured against Standard Mean Ocean Water (SMOW) international standard by IRMS. The ratio of plasma enrichment of 13C to 3H cholesterol on day 3 after tracer administration was used to calculate cholesterol absorption. Recently, continuous flow gas chromatograph pyrolysis IRMS (GC/P/IRMS) systems and 18O or 3H cholesterol with gas chromatograph combustion IRMS (GC/C/IRMS) systems and 13C cholesterol have been used in calculating cholesterol absorption using IRM (Method VI)(Gremaud et al., 2001; Pouteau et al., 2003b). The use of IRMS vs GC/MS-SIM has vastly increased the precision of this method. The two single stable isotope methods for accessing cholesterol absorption were introduced by Ostlund et al. (1999) and Wang et al. (Wang et al., 2004). Ostlund et al. (1999) administered deuterated cholesterol to volunteers and measured the average oral cholesterol tracer in plasma ((mmol deuterated cholesterol/mol natural cholesterol) in blood samples taken 4 and 5 days post tracer administration using GC/MS. Wang et al. (2004) administered 13C cholesterol orally followed by blood sampling at 24, 48, 72 and 96 hours. 13C enrichment in plasma free cholesterol was mea sured using GC/C/IRMS. Average 13C enrichment from 24-96 hours and area under the curve (24-96 hours) of 13C enrichment were compared the cholesterol absorption percentage measured using the plasma dual stable isotope ratio method (Bosner et al., 1993) in 2 studies. The average and area under the curve of 13C enrichment in plasma free cholesterol correlated with cholesterol absorption percentage measured by stable isotope method VI (r values ranging from r=0.81, p=0.0001 to r=0.88, p=0.0001)(Wang et al., 2004). Both of these single isotope methods are used to compare treatment effects, such as pharmaceutical or dietary interventions and their effects relative to control, on cholesterol absorption. Absorption surrogate method The use of serum plant sterol levels to predict cholesterol absorption was first developed by Tilvis and Miettinen (1986). They showed that serum levels of ÃÆ'Ã… ¸-sitosterol and campesterol, when normalized for total serum cholesterol, correlated positively with cholesterol absorption as measured by Method VIII of Crouse and Grundy (1978). This measurement involves lipid extraction from a single blood sample followed by GC or HPLC to quantify serum plant sterol and cholesterol levels. The use of campesterol or ÃÆ'Ã… ¸-sitosterol to cholesterol ratio has since been used numerous times as a measure of cholesterol absorption (Gylling et al., 2007; Hallikainen et al., 2006; Matthan et al., 2009; Nissinen et al., 2008; Simonen et al., 2008). Nissinen et al. (2008) showed that ÃÆ'Ã… ¸-sitosterol to cholesterol ratio correlated better with cholesterol absorption than campesterol to cholesterol ratio, as measured by method VIII, across three diets varying in both cholesterol and fat le vels in 29 healthy male volunteers. It is important that when using serum plant sterol as surrogates for cholesterol absorption it is imperative that factors which are known to change serum plant sterol levels, such as the dietary intake of plant sterols (Chan et al., 2006), should be controlled for so as not to perceive a change in cholesterol absorption which may not exist (Vanstone and Jones, 2004). Serum plant sterol levels can be variable within and across different population (Chan et al., 2006), they can also be severely elevated in certain individuals due to genetic disorders (Berge et al., 2000; Lee et al., 2001). It is important that individuals with these genetic disorders are not included in studies using this method of estimating cholesterol absorption as serum plant sterol levels do not reflect cholesterol absorption in these individuals. Recently it has also been shown that serum plant sterol concentrations do not reflect cholesterol absorption in individuals with Smi th-Lemli-Opitz syndrome (Merkens et al., 2009), therefore the use of serum plant sterols as surrogates for cholesterol absorption should be verified prior to its use in a particular populations. The use of plant sterol surrogates does benefit from relative speed and simplicity compared to other previous discussed methods (Matthan and Lichtenstein, 2004; Pouteau et al., 2003a), it is the only estimate of cholesterol absorption which can be done in large scale studies. Methods to access cholesterol synthesis The primary pharmaceutical intervention used to lower elevated cholesterol levels are statins, which are inhibitors of HMG-CoA reductase, a key enzyme in cholesterol synthesis (Stein, 2002). Cholesterol synthesis contributes more to circulating cholesterol levels than cholesterol absorption (Dietschy, 1984; Pouteau et al., 2003a), and maintains cholesterol levels during fasting, therefore accurate assessment of cholesterol synthesis is essential to the field of cholesterol research. Balance Method Cholesterol synthesis can be estimated when intake of dietary cholesterol and excretion of total cholesterol is known during a metabolic steady state (Grundy and Ahrens, 1969). The criteria of this metabolic steady state are: constant plasma cholesterol and faecal cholesterol excretion levels during a period of constant weight. In this steady state, cholesterol synthesis is the difference between cholesterol excretion (faecal neutral sterols and bile acids) and intake. Dietary cholesterol intake must be accurately measured, and faeces must be collected, for a given period of time. Faecal flow must also me monitored to assure collection of faeces from the appropriate time period. Faecal neutral sterols and bile acids are measured in the faeces, typically by GC-MS, and cholesterol synthesis for a given period of time is calculated (Jones et al., 1998; Kempen et al., 1988). Although this method is the gold standard for calculating cholesterol synthesis, it is vulnerable to errors in t he estimation of both cholesterol intake and excretion which can potentially cause significant error. The balance method does determine the actual mass of cholesterol synthesized during a given period, it requires a metabolic steady state, accurate measurement of cholesterol intake and total faecal collection for the period of interest. Therefore this method is not suited for larger trials. Fractional conversion of squalene Daily cholesterol synthesis rate can be estimated by the fraction of infused radiolabelled melavonic acid converted to cholesterol (Liu et al., 1975; McNamara et al., 1977). [14C] mevalonic acid and [3H] cholesterol are administered intravenously, this infusion of labelled mevalonic acid rapidly labels the plasma squalene pool, reaching a maximum enrichment at ~100 minutes. Cholesterol synthesis is estimated by measuring squalene synthesis. Squalene synthesis is calculated by the percentage of melavonate dose converted to cholesterol, divided by the area under the curve of pasma squalene specific activity. This method assumes that plasma squalene synthesis is equivalent to cholesterol synthesis. The cholesterol synthesis rate estimated using this method has been shown to agree with cholesterol synthesis calculated by the balance method within 8% (Liu et al., 1975). The benefits of this method is it requires only 1 hour of a participants time, and can be repeated every 3 weeks (McNa mara et al., 1977), it does however require the administration of intavenous radioisotopes. Cholesterol synthesis precursors The concentrations of plasma precursors along the synthesis pathway of cholesterol have been used to as an indirect qualitative measure of cholesterol synthesis. Squalene (Miettinen, 1982), mevalonic acid (Parker et al., 1982), lanosterol, desmosterol and lathosterol have all been used a surrogates for cholesterol synthesis (Matthan et al., 2000; Miettinen et al., 1990). These precursors have has been shown to fluctuate with diurnal cholesterol synthesis patterns as well as in conditions in which cholesterol synthesis is elevated or reduced (Miettinen, 1982). These precursors correlate more closely with measured cholesterol synthesis when they are normalized for plasma cholesterol level, then as the absolute amount of precursor, and are normally expressed in mmol/mol cholesterol (Miettinen et al., 1990; Nissinen et al., 2008). When using cholesterol precursors as surrogates for cholesterol synthesis, dietary intakes of each precursor should be controlled for, this is particularly i mportant for squalene, which is abundant in olive oil and is at least partially absorbed into the blood (Ostlund et al., 2002b). The most consistent surrogate for cholesterol synthesis has been lathosterol (Kempen et al., 1988; Nissinen et al., 2008). Since cholesterol synthesis surrogates require only one blood sample they are ideal for estimating cholesterol synthesis in very large studies or epidemiological trials. Mass Isotopomer Distribution Analysis (MIDA) Mass isotopomer distribution analysis (MIDA) is a technique that can be used to measure the synthesis of biological polymers in vivo (Hellerstein and Neese, 1999). The technique uses the relative abundance (pattern or distribution) of polymer species which differ only in mass (mass isotopomers) produced during the administration of stable isotope labelled precursors. The distribution of the polymer species produced is compared to the theoretical distributions predicted by binomial and polynomial expansion. Using these theoretical distributions, parameters such a fractional synthesis rate can be calculated using combinatorial probability model. Since cholesterol is synthesized from subunits of acetyl-Coa, fractional synthesis of cholesterol can be calculated during the infusion of 13C labelled acetate (Neese et al., 1993). This method is very invasive, requiring a 24-hr intravenous infusion and serial blood sampling from a indwelling catheter (Di Buono et al., 2000). The cholesterol in the blood samples is measured by GC-MS to determine the distribution pattern of isotopomers from which the rate of synthesis is obtained. The data analysis relies on more complex mathematical modelling than other methods for estimating cholesterol synthesis. Deuterium Incorporation This method is based on the tritiated water uptake method by Dietchy and Spady (1984) used originally in animals. Deuterium incorporation method uses water as a tracer to determine the synthesis of free cholesterol (FC). The fractional synthesis rate (in pools/day) of free cholesterol is calculated from the rate of incorporation of deuterated water into de novo synthesized plasma or erythrocyte cholesterol. Orally administered deuterated water equilibrates with the bodys water and NADPH. Body water and NADPH account are the precursors for 22 of the 46 hydrogen in synthesized cholesterol (Jones, 1990). Deuterium enrichment of the precursor pool, plasma water, and in erythrocyte or plasma cholesterol are measured by IRMS. Fractional synthesis rate of free cholesterol (FSR-FC) is calculated using the following formula: FSR-FC (pools/day) = ( ÃŽÂ ´ cholesterol à ¢Ã¢â€š ¬Ã‚ °/ ÃŽÂ ´ plasma water à ¢Ã¢â€š ¬Ã‚ ° * 0.478) ÃŽÂ ´ refers to the change in deuterium enrichment over 24 hours and 0.478 is the ratio of cholesterol from body water and NADPH to total hydrogen in a cholesterol molecule, or the ratio of hydrogen which could be enriched by oral D2O administration (Jones et al., 1993). From the FSR-FC the ASR -FC (g/day) can be calculated by multiplying the FSR-FC by the M1 pool size (determined by Goodmans equation) and 0.33 the proportion of FC in total cholesterol. The ASR-FC is approximately the daily production of newly synthesized cholesterol. The three main assumptions required for deuterium incorporation are: 1)That the fraction of hydrogen derived from plasma water (22/46, or 0.478) is constant in denovo synthesized cholesterol. 2) That denovo synthesized free cholesterol rapidly exchanges between the site of synthesis and the major free cholesterol (plasma compartment) pool. Within this pool cholesterol migrates rapidly between cellular membranes and lipoproteins as well as between different classes of lipoproteins. 3) Deuterium uptake i nto the free cholesterol of the major (plasma) pool of cholesterol reflects synthesis in this pool and that synthesis of cholesterol in the major pool provides a reasonable measurement of total cholesterol synthesis as most sterol synthesis occurs in the intestines and liver which contribute to the plasma cholesterol pool. It must be acknowledged that the major (plasma) pool of cholesterol is at equilibrium with two other slow turnover pools outside the plasma, and that the slow inter-pool cholesterol exchange would cause insignificant entry of labelled free cholesterol into the central pool within a 24 hour time period (Dietschy and Spady, 1984; Jones, 1990). Although it has been shown that these assumptions are not perfect, the cholesterol synthesis estimates yielded by deuterium incorporation have been sensitive enough to show differences in cholesterol synthesis due to genetic factors, and dietary and pharmaceutical interventions. It has also been shown to correlate well with ch olesterol synthesis measured by the balance method (Jones et al., 1998), MIDA(Di Buono et al., 2000) and cholesterol synthesis surrogate levels (Matthan et al., 2000). Conclusion The methods used to quantify cholesterol absorption and synthesis reviewed in this article have yielded invaluable information, as well as provided effective means of measuring the experimental effects of various interventions, on cholesterol homeostasis. The methods have evolved substantially over the years, from radio-isotopes to stable isotopes, and from highly invasive to less invasive procedures. However, advancement in the quantification of cholesterol homeostasis must still be continued, with a goal of finding more accurate methods to measure cholesterol synthesis and absorption, perhaps simultaneously, something which until now is still unavailable. The advantages and drawbacks, as well as the type of information yielded by each method for measuring cholesterol absorption and synthesis must be weighed carefully when selecting an appropriate method. The cost and available technical expertise and facilities will limit which methods are available to each investigator. However, it is imperative that the assumptions and limitations of each method are checked to insure that its use is valid for each particular experimental question it is used to answer.

How Amazon Uses E-Business and E-Commerce for B2B and B2C - Free Essay Example

Sample details Pages: 1 Words: 348 Downloads: 2 Date added: 2017/09/14 Category Advertising Essay Did you like this example? How Amazon uses E-Business and E-Commerce for B2B and B2C Amazon leads America web services into expose business of today’s technology world. e-business and e-commerce focuses businesses ran on the Internet, while utilizing Internet technologies to improve the productivity or profitability of a business. To best understand the world of Amazon, it must describe the form of electronic business which utilizes a computer to market its products. Purchasing and selling goods using e-business services assist other traditional business aspects. It provides the use of electronic chat that aids the consumers in receiving a form of technical and customer support. â€Å"Online retailer Amazon stated that consumers have accepted the Internet as a sales channel and that selling online can be profitable† (Thomas). Additionally, an e-business saves incredible amounts of time while providing opportunities unavailable through traditional support. Don’t waste time! Our writers will create an original "How Amazon Uses E-Business and E-Commerce for B2B and B2C" essay for you Create order By using virtual computer systems, as technical support operators can tenuously access a customers computer and assist them in correcting a problem. The B2B and B2BC can be benefited by using the website in order to reveal globally and it makes it more fitting for the customer and business. Amazon uses B2B by providing the opportunity to purchase and sell all types of products via the internet. It allows for relationships to be established in order to complete sales and business transactions. Additionally, providing email address and having personalized memberships are methods for dispensing sale ads and providing discount coupons is a use of the internet by Amazon. Rather than producing time-intensive and costly physical copies for each consumer, a central server or email list can serve as an efficient method for distributing necessary information to the general public. Amazon uses B2C as a way to illustrate an online retailer that offers thousands of products for customers. Each customer purchase is relatively small, but the companies must manage that transaction as if that customer were its most important one. https://www. computerweekly. com/Articles/2002/01/31/184899/amazon-proves-b2c-can-turn-in-a-profit. htm Thomas, D. , Amazon Proves B2C Can Turn in a Profit, retrieved on August 13, 2010, https://www. computerweekly. com

The Purpose of Sati in Jane Eyre Essay - 2082 Words

The general image of Sati and the reasoning that surrounded it filled the Western imagination with repulsion as well as admiration. In the nineteenth century, Westerners publishing diaries of their travels always included their experiences when viewing Sati. Although these travelers, usually men, watched with horror, they also admired the courage and the dignity of the women involved (Hawley 3). What was known in England of Sati was from the accounts of the colonial officials and travelers who witnessed it (Courtright 28). It would not surprise one to assume that Charlotte Bronte, in her drive for knowledge and her stand on womens freedom, would have taken an interest in such an act; and indeed she incorporates it in Jane Eyre. In 1829,†¦show more content†¦Nothing has excited the attention of the Europeans than the burning of wives upon the funeral piles of their husbands (Perera 91). Another important aspect of the act of Sati was that it became an element in the vindicati on of British Imperialism . . . and was also used as a moral justification to the Britishers to impose their rule on India (Perera 92). With an attempt to distinguish between the old and the new, Charlotte Bronte creates the character of Bertha Mason as the exhibition of female repression and desire frequently found in the East. Bertha Rochester is the emblem of Eastern society, one which the British see as static and barbaric, and Jane Eyre is representative of the Western Civilization. In Reaches of Empire, Suvendrini Perera argues that if the barely human prisoner caged in the Thornfield attic is the truest expression of womens anger and aspiration . . . [it is overlooked] that she is also the racial Other incarnate - a bestial, violent creature with an inordinate sexual appetite, caught in the colonized West Indies and confined for her own good by a master who has appropriated both her body and her wealth (82). If the reader only sees Bertha as the surrogate of Jane, one neglects to take note of the enriching importance of the texts suppression of Bertha. Charlotte Bronte presents Bertha as a sexually vigorous wo man. This can be seen when Rochester indirectly describesShow MoreRelated The Bildungsroman Genre Essay4241 Words   |  17 Pagesby the English author Charles Dickens, and Emma (1926), by another English author, Jane Austen, can be analysed under this perspective. Througout Dickens’ novel, Pip, the main character, goes through many changes in his personality to eventually coming to terms with his own actions. Austen’s novel deals with a female character, Emma, a rich young woman who learns how to balance power and propriety. The purpose of this paper is to analyze these two novels as pertaining to the bildungsroman genre

Services Market People Technology Strategy -Myassignmenthelp.Com

Question: Discuss About The Services Market People Technology Strategy? Answer: Introduction The assessment is designed to implement the knowledge and skills to evaluate the internal and external environmental factors of a company and the determination of new offering in the market based on the result of environmental scanning. The company that has been selected for the analysis is Adidas. The report shows the analysis of strength, weakness, opportunity, and threats of the company. The recommendations to the company are stated in the report which includes the description of the target market, new product or service of the company and marketing mix strategies of the company. Background of company Adidas is a multinational corporation with the head office in Herzogenaurach, Germany. The company is one of the worlds largest sports goods and accessories manufacturer. Adi Dassler listed the Gebruder Dassler Schuhfabrik in the year 1924 with the objective to offer athletes with the best possible equipment. The company is offering the best product with the affordable product range. In the year 2006, the company acquired Reebok and since then the company started providing the product for the premium segment customers with the brand name Adidas. Reebok changed its segment and started offering products to the middle-income group people (Adidas, 2017). Analysis of marketing environment Marketing environment refers to as the combination of the internal and the external factors that create an impact on the companys ability of decision making and establishing a relationship with the customers (Keller and Kotler, 2016). SWOT analysis SWOT analysis refers to as the study for the organization to determine the internal strengths and weaknesses along with the external opportunities and threats (Forte, et.al, 2017). Adidas managers make use of the SWOT analysis to reduce the weakness, to exploit the opportunities and avoid the potential threats (Bull, et.al, 2016). The company can grab the opportunities to expand the business and also to enhance the growth and revenue. Strengths: - It shows the characteristics of the organization that provide the advantage over others. Weakness: - It shows the characteristics related to the organization at a disadvantage relative to others. Opportunities: - It includes the elements that the business could exploit to its advantage. Threats: - It includes the elements that could cause the trouble for the organization. Strengths Diversified: - Company has a diversified position in the market as the company offers a wide range of footwear and accessories under its brand name. Distribution network: - Company has an effective network of distribution for its products. Adidas sells its products through online stores, with their own retail stores, supermarket stores, and the other departmental stores. Strong financial position: - Adidas has a strong financial position in the market with more than 2400 store across the world having worth of $4.3 billion. This reflects that company can invest the amount in the innovation of new product (Bhasin, 2017). Strong market reputation: - Adidas has a strong market reputation across the national and international markets where the company has its business operations. Weaknesses Outsourced manufacturing: - The company outsources approximately 93% production from the 3rd party manufacturers (mainly from Asia) to gain the easy availability and low labor cost. Outsourcing might create the impact on the new product or services of the company (Hasseb, 2015). Premium price range: - The product offered by the company is available for limited customers due to the high price range of products. The prices of the products are high due to the innovative technology and production methods which makes the products affordable for the limited customers. Opportunities Changing lifestyle: - The saturation of the developed economies reflects the rise in the lifestyle of the peoples with the change in tastes and preferences of the consumers. Nowadays, most of the people prefer to wear branded stuff which leads to a rise in the demand for the products and services offered by the company. Tie-ups: - Company can form the tie-ups with the emerging sports teams/clubs/players internationally that help the company in boosting the Adidas's brand presence in the competitive market. Expansion in product line: - Company has an opportunity in expanding its products line and for that, the company needs to introduce the new products or services in the market (Mba Skool, 2017). Threats Competition: - Adidas is one of the well-known leading brands in the market and has many competitors in the market which include Nike, Puma, Converse and many others. These competitors bring changes in their strategies which is a threat for the Adidas. One of the strong competitors of Adidas is Nike who provides the similar products to the customers. Government Regulations: - Changes in the government regulations act as a threat to the company because they outsource products from other countries. Approximately 35% and 93% of products manufacturing takes place in China and Asia respectively. These manufactured products are outsourced by Adidas for which they have to pay a huge amount of tariffs, duties and import regulations. Apart from it, for the expansion of the product line, Adidas relies on its manufacturing units that are situated in China and Asia. Recommendation Considering the business environment of the company below given are some of the recommendations to the Adidas. Segmentation Market segmentation is the process that divides the broader customers into sub-groups of customers based on different types of shared characteristics (Boone, and Kurtz, 2013). Market segmentation of Adidas is discussed below: - Demographic segmentation It refers to dividing the market based on gender, age group, and income. Adidas offers its products mainly to men, women, and kids considering their age and life cycle of segmentation and gender segmentation (Needle, 2010). The company offers the variety of men and women clothing, shoes, body-care, and eyewear. Psychographic segmentation This segment divides the group on the basis of social class, lifestyle or the personality characteristics (Harrison, and Kjellberg, 2010). Adidas emphasis on the people belongs to the high social class and tends to have the similar buying traits. People having a high standard of living are mostly targeted by the company. A high standard person likes to purchase the product provided by the brand like Adidas (Bhasin, 2017). Target Market Target market refers to as the group of customers at which the company is aiming to provide products and services. To identify the particular group to whom the company should target there is need of the segmentation. It is recommended to the company to target demographic segment as primary target market as the company offers athletic footwear and apparel for the sports person being it male or female. The strongest customer market for Adidas is a youth with the age group of 20-29 years (IAC, 2018). It is recommended to the company to add the age group of 14-19 years as this age group reflects the next generation of athletes. The company already target the people who like to wear the sports shoes. It is recommended to the company to extend the product target market which is possible with the expansion of the product line in the market. With the introduction of a new product, the company will be able to target new segment. New product/ new services description The company is well-known for its sports shoes for the athletics who likes feel conformable after wearing it. Considering, the external analysis the company has an opportunity to expand its product line in the market. It is recommended to the company to introduce formal shoes for the people who like to wear brand like Adidas. With the introduction of the product in the market, the target market range of the company will increase and the Adidas will be able to add businessman and are professionals in their target market. The demand for the formal shoes is increasing in the competitive world. The businessmen are involved in the corporate society are restricted to wear the formal shoes at the office working hours. These people have to wear shoes for approximately 8 hours due to this the demand for comfortable shoes is increasing in the market. Marketing mix relevant strategies The marketing mix is defined as the set of marketing tools that the firm uses to pursue its marketing objectives in the target. In other words, marketing mix defines as a set of tactics or actions that are used by the company to promote its brand or product in the market. The marketing mix consists of product, price, place, promotion, and people (Lovelock, 2011). The marketing mix strategies of Adidas considering the new product are discussed below: - Product: - Company is leading sportswear but with the proper investment the company can bring new products, Formal shoes in the market. With the help of the research and development team, the company can understand the needs of the customers. The company can bring the innovation in the formal shoes (Wright, and Watkins, 2010). The product strategy of the Adidas should cover the entire product line including different types and styles of formal shoes. Price: - Products of the company are available at premium prices and due to this the company targets the people belongs to the high-income group. The company should implement the high-low pricing strategy in which the company can keep the high or low price than the competitor for the same product (Bolton, Shankar, and Montoya, 2010). At the initial step, it is recommended to the company to keep the low price for the product as it is beginning and to grab the attention of the customers it is a must. Later on, after setting the customer market and loyal customers the company can increase the price of the product (Mba Skool, 2017). Place: - Company can provide the product across the world with the use of the effective distribution channel which includes franchises, online retailers, mass merchandise, and on their outlets. The company should offer its product through multi-brand e-commerce websites (Baker, 2014). If the company will be able to make the product (Formal Shoes) available at a maximum number of stores than a maximum number of people will get aware of the product. Promotion: - Promotion of the new product in the market is essential for the company because effective promotion strategy will help the company in generating awareness. Adidas should make use of the endorsed strategy in which they can get the product promoted by the celebrity. The company can also make use of the print media, commercial campaigns on online platforms, TV, billboards (Shank, and Lyberger, 2014). At the stores of the company, the personal selling can be conducted by the employees of the company in which the staff members generate the awareness about the product in the market. People: - Company needs the staff for their existing business operations and for the new business operations. The introduction of the new product needs more people within the organization. The company hires the people depending on the skills and knowledge that they have related to the industry. Moreover, the company provides the training to new employees if they have lack of knowledge about the industry. Adidas need employees who can help the company in research and development, manufacturing and promotion of the product (Keller, Parameswaran, and Jacob, 2011). The company provides the numerous benefits to the employees that include provident fund, health and travel reimbursement and many others. Conclusion It is concluded from the report that the SWOT analysis is an essential tool for the company to evaluate the internal and the external factors that can impact the decision making and the working of the company. SWOT analysis helps the company in identifying the new product and services after scanning the result of the environmental analysis. Furthermore, the report includes the recommendations related to the target market of the company and the new products. The company should introduce a new product in the market and consider the new product the relevant marketing mix strategies are also discussed in the report related to the new product launched in the market. The successful implementation of the strategies will help the company to achieve the maximum growth and profitability. References Adidas, 2017, Products, viewed on 26th January 2018, https://www.adidas.co.in/help-topics-products.html Baker, M.J., 2014.Marketing strategy and management. Palgrave Macmillan. Bhasin, H., 2017, Adidas SWOT analysis SWOT analysis of Adidas, viewed on 26th January 2018, https://www.marketing91.com/adidas-swot-analysis/ Bhasin, H., 2017, Marketing strategy of Adidas, viewed on 26th January 2018, https://www.marketing91.com/marketing-strategy-of-adidas/ Bolton, R.N., Shankar, V. and Montoya, D.Y., 2010. 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