Essay on Africa vs European Imperialism - 841 Words

DBQ: Imperialism In AfricaAzra Azvar Period 3 2/21/10 Whites vs Blacks In the late 19th and early 20th centuries European imperialism caused its countries to divide up the rest of the world, each country claiming bits as its own. Due to its large amounts of resources, Africa was one of the main areas European nations invaded in the cause if imperialism. In Africa, there were positive and negative effects towards the Africans and the invaders. Some positive effects on Africans were that they were provided with security by their rulers and new technology was introduced to them. Some of the negative effects were that the Africans lost their natural rights such as freedom, the beginning of slavery, and the loss of their land and†¦show more content†¦During the Berlin Conference, the nations of Europe divided up Africa as though no on lived on the continent and the land was free to take. Also, Europeans lived at the expense of the Africans, who received little or no pay for the labor they have to put up with. The Africans were tormented in so man y ways and their deprived souls. Although imperialism was mostly negative fro Africans, they did receive some benefits. One positive effect was that they were provided with security by their rulers (Doc .4). Colonization and the presence of European soldiers reduced warfare within the colony. Another positive effect of imperialism for the Africans was that improved technology gave introduced to the civilized world. Communications improved because Europeans set up telephone and telegraph poles. Also, transportation improved because of railroads and the steam engine. Although, this technology was mostly used by Europeans, the ideas were brought to the African colonies all the same. The Africans did benefit from the imperialism a tinge. European imperialism in Africa had a large impact on the Africans, but it also affected the Europeans who colonized the continent. One positive effect of imperialism on Europeans was that they were able to gain financially from Africas resources (Doc 4). Africa had a large number of resources such as diamonds and rubber which could be sold at a highShow MoreRelatedIn Search of the Unknown: Apocalypse Now1584 Words   |  6 Pagesunder Imperialism. The movie, Apocalypse Now also correlates with the book, but this time the setting does not take place in the 19th century, but in the 20th century when United States was at war with Vietnam. Because of the two pieces sharing differences and similarities, the audiences are able to get a richer understanding of Conrad’s novella. Marlow tells his story that marked his life of his journey through the Congo River, which makes the main scenario be the Congo River in Africa. 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Man in general is quite capable of carrying out every kind of evil, no matter howRead More Patrice Lumumba’s Struggle Against Belgian Imperialism Essay921 Words   |  4 PagesPatrice Lumumba’s Struggle Against Belgian Imperialism It is hard to believe that in 2002 there is still imperialism being practiced in the world, but the fact of the matter is, it is. Imperialism is the policy of extending a nation’s territory or power by establishing dominance over other nations. A modern example of imperialism is the Congo. At the 1885 Berlin Conference, where the European powers carved up most of Africa among themselves, they sanctioned the claim of BelgianRead MoreImperialism, The Middle East, And East Asia990 Words   |  4 Pagesinvoke ideas of West Africa, the Middle East, and West Asia, but all these ideas come from Oriental fantasies from the nineteenth century. Edward Said the author of Orientalism said that â€Å"Orientalism was ultimately a political vision of reality whose structure promoted the difference between the familiar (Europe, West, us) and the strange (the Orient, the East, them).† The nineteenth century was a period of imperialism and tourism that led many western artists to visit West Africa, the Middle EastRead MoreComparative Essay1096 Words   |  5 Pages Literature Comparative analysis: â€Å"Heart of Darkness† â€Å"Apocalypse Now† Student: Mora Vandenbroele Teacher: Azucena Estigarribia Year: 11th â€Å"A† â€Å"Heart of Darkness† vs. â€Å"Apocalypse Now† It is very interesting how humans are so intrigued about the evilness in the world, and the dedication of some men to compare Hell with the Earthly horror. Joseph Conrad, a genius writer, took his time to show this with his masterpiece

The Royal Proclamation Of 1763 - 1336 Words

Introduction Following the end of the Seven Year War, the Royal Proclamation of 1763 was released (Schouls, 2011). This was document that was given by King George II to give details of how the French territories in North Americas would be divided. The royal proclamation was a follow up document of the treaty of Paris, which is what brought the seven year war to an end. The war ended with the cessation of France of its territories in North America which were to be taken over by the British government. This paper looks at the various boundaries that took effect with the implementation of the royal proclamation, along with the rules that were accompanied. Background The seven year took place from the year 1756 to 1763. The participants were†¦show more content†¦These were general Montcalm who led the French and General Wolfe who led the British. The treaty of Paris, signed in 1763 would see the end of the war. The treaty settled many of the issues that had been pending about the division of the colonial lands that were found in most parts of the world. The treaty was signed in various places including France, Spain, Great Britain and Portugal. The main area of concentration, North America, was handed over to the British, after it had defeated France, the previous controllers of the land. Native Americans Native Americans refer to the group of people who are considered to have been the first dwellers of the present day United States (Beaulieu, 2013). When the European settlers first came to the United States, there were several varied groups of indigenous people. However, their number began to dwindle due to things such as wars and foreign diseases. The United States also came up with certain policies that were not very friendly to them, which led them to migrating to other areas. Those who stayed behind found that they had to sign treaties and use other compliance mechanisms in order to survive in the United States government. There was yet another group that remained behind but did not receive recognition from the United States. Currently, there are around 500 tribes of Native Americans in the country (Bird, 1999). This paper discusses the ways and reasons through which the Native Americans have

Ethical Issues In Healthcare

Question: Discuss about the Ethical Issues In Healthcare? Answer: The actions of the physician indicate a lack of work ethics and in an indication of misleading the intended audience of the research report. The physician was involved in deleting data from the research paper that would have changed the outcome of the study. It was observed that on several occasions the physicians had removed valuable data about the research patients from the study. On investigation, it was seen that the cause of removal of the data was the negative effect their data would have on the research paper ("Ethical principles in healthcare", 2015). Thus, it was morally and ethically wrong to support such actions. Thus, the best possible option at hand is to report the activities of the physician to the research board. Before filing a formal complaint against the physician, it is mandatory to collect evidence of misappropriation of research data by the physician. This is possible by gathering the patients, whose data has been deleted by the physician, and letting them testi fy in front of the supervising officer that they were subjects for observation for the research. The legal questions that are involved in the case as mentioned above are an act of misdirecting an individual or a group of individual. It also requires the act of misappropriation of personal data that was collected from the scope of research. It was unethical on the part of the physician to delete the data that has been received for the research (Ho Pinney, 2015). It indicates an action of fraud on the part of the physician to get access to funds to increase the scope of his research. It was unethical on the physicians part to collect data from the individuals when he had no intention of reporting them in his research paper. References Ethical principles in healthcare. (2015).The Pharmaceutical Journal. https://dx.doi.org/10.1211/pj.2015.20068954 Ho, A., Pinney, S. (2015). Redefining ethical leadership in a 21st-century healthcare system.Healthcare Management Forum,29(1), 39-42. https://dx.doi.org/10.1177/0840470415613910 Answer:

Measures of Central tendency free essay sample

Measures of Central tendencyThey are also known as statistical average. They are statistical values which tend to occur at the centre of any well-ordered data. However, whenever they occur they do not indicate the centre of that data. They tell us the point about which items have a tendency to cluster. Such measures are considered as the most representative figure for the entire mass of the data.Measures of central tendency include:MeanModemedianMeanMean is also known as arithmetic average. It may be defined as the value which we get by dividing the total values of the given observations in a series by the total number of the observations.Arithmetic mean = (?x)/n ; where x is the number of values and n is the number of observations. Arithmetic mean represents the values of the most observations in a given population.In grouped data, arithmetic mean is calculated as:Arithmetic mean = Assumed mean + (?fd)/(?f)The ModeThis is the value within a frequency distribution which has the highest frequency. We will write a custom essay sample on Measures of Central tendency or any similar topic specifically for you Do Not WasteYour Time HIRE WRITER Only 13.90 / page On a histogram, it represents the highest bar in a bar chart. It is the most commonly or frequently occurring value in a series. The mode in a distribution is that item around which there is maximum concentration hence it is the size of the item which has the maximum frequency.In data where no single value happens to be the mode, the class with the highest frequency is treated as such – referred to as the modal class.The MedianMedian is a statistical value which is normally located at the centre of a given set of data which has been organized in ascending or descending order of magnitude or size. It divides the series into two halves.Suppose we are asked to calculate the median in the data below:65 55 89 92 56 35 14 56 55 87 45 92We first need to rearrange the data in order of magnitude (smallest first)14 35 55 55 56 56 65 87 89 92 92Our median mark is the middle mark in this case 56

Forests Extinction Essay Research Paper Can you free essay sample

Forests Extinction Essay, Research Paper Can you visualize our Earth without woods? Many of us can? t. Forests cover about one fifth of the universes land surface and play an of import function in our mundane lives ( Dudley 4 ) . Forests provide us with many merchandises and services from assisting keep eroding to supplying occupations for our citizens. Humanity depends on the endurance of a healthy ecosystem and deforestation is doing many societal, economic and ecological jobs. One ecological job is Global heating enchantress is caused when C is released into the air after the combustion of woods. Governments and industries must go more cognizant of these effects of their activities and alteration consequently. They need to collaborate with forest direction and work towards a hereafter that benefits all. Worlds need to be educated about the current issues of the woods in order for us to salvage, preserve or prolong these topographic points that provide us with so much. We will write a custom essay sample on Forests Extinction Essay Research Paper Can you or any similar topic specifically for you Do Not WasteYour Time HIRE WRITER Only 13.90 / page Worlds depend enormously on the universe? s woods, but yet were the 1s destructing them. For worlds, the woods have many aesthetic, recreational, economic, and cultural values. Timber and other merchandises of the woods are of import economically both locally and as exports. They provide employment for those who reap the wood or for those who make merchandises from the life wood. Forests besides provide us with medical drugs, dyes and cloths. There are many people who are dependent on forestland for their supports. One tierce of the universe? s people depend on wood for fuel as a important energy beginning ( Dudley ) . Not merely make the woods provide some people with places, but besides provides a popular puting for ecotourism, which includes hike, bivouacing, bird observation and other out-of-door escapade or nature survey activities. All these activities and merchandises the woods provide us are at great hazard from deforestation. Not merely do woods supply us with all this but besides protect dirt from eroding and reduces the hazards of landslides and avalanches. Trees help prolong freshwater supplies hence are an of import factor in the handiness of one of life? s BASIC demands. Forests affect the clime and are besides a really of import beginning of O. One major factor that the woods carry is that they are the place to over one half of the universe? s entire species ( Dudley ) . Presently we are detecting 20 new species of insects and 15 species of workss each twenty-four hours ( Dudley 13 ) . ? Recent studies by the World Resources Institute have shown that more than 80 % of the works? s natural woods have already been destroyed? ( Hatch ) . Yes world is the cause of deforestation, nevertheless us worlds are besides capable of holding a positive consequence on this crisis. Tropical woods cover about 10 per cent of the universe? s dry land surface, largely located in South America and Asia ( Dudley 6 ) . In the tropical woods of the universe, deforestation is happening for agribusiness and farm animal grazing lands. The chief cause is the unequal distribution of land ( Anderson ) . Temperate woods are found in land countries that are warm plenty and low plenty to back up trees but non so hot to be tropical. They are found in North America, Europe and ice chest parts of Australia ( Dudley 4 ) . The jobs in temperate woods are non so much the lessening in overall forest country, but the significant alteration in the types of woods and their ecological diverseness and stableness. Commercial forestry is the chief cause of deforestation in temperate woods. ? In really wide footings, the entire country of wood in Europe, the USSR and North America is likely to diminish merely somewhat in the medium hereafter, but the proportion of forest bing as plantation is apt to lift aggressively? ( Dudley 66 ) . This nevertheless is traveling to take to an addition in struggle between the recreational and preservation involvements and will besides be given to do forestry a more capital-intensive operation, therefore supplying fewer occupations. Since so many people are dependent on the universe? s woods, deforestation will hold a societal, economical and ecological consequence on the universe. Most of these effects are negative 1s. The loss of forestlands is connected to desertification, which translates into there being fewer trees, therefore diminishing the future forest workers employment. Heavy rainfall and high sunlight rapidly damage the surface soil in tropical rain forest, doing them to regenerate slower and besides supplying deficient farming evidences. When woods are replanted there will besides be a loss in quality. Besides the medical interventions, remedies and vaccinums will neer be discovered if there are no woods to detect them in. There may be a loss of future markets for ecotourism. The value of a wood is frequently higher when it is left standing than it could be deserving when it is harvested ( Dudley ) . Deforestation can do the clime to alter which could cause and increase in inundations and drouths. Global heating is a large factor in the devastation of trees. Forests store big sums of C that are released when trees are cut or burned. It is said that deforestation and the combustion of biomass will be responsible for 15 per centum of the nursery consequence between 1990 and 2025 ( FAO ) . Because of planetary warming scopes of tree species could displacement with regard to altitude and latitude ( Humankind 2 ) . Furthermore, the emphasis of such environmental alteration may do some species more susceptible to the effects if insects, pollution, disease and fire ( FAO ) . Besides, countries of trees may be lost and familial diverseness may diminish. The glade of forestland consequences in addition of eroding and landslides. Landslide is a descent of a mass of Earth and sway down a mountain incline. Landslides may happen when H2O from rain and runing snow sinks through the Earth on top of a incline, seeps through clefts and pore infinites in underlying sandstone, and encounters a bed of slippery stuff, such as shale or clay, inclined toward the vale ( Encarta ) . Loging has straight and indirectly damaged engendering evidences, blocked river channels, raised H2O temperatures and caused H2O degrees in watercourses to fluctuate perilously. Therefore, the remotion of braid can cut down the viability of fist stocks in their water parting and down streams environments. Peoples destroy or degrade woods because, for them, the benefits seem to outweigh the costs. Underliing causes include such issues as poorness, unequal land ownership, adult females? s position, instruction and population. Immediate causes are frequently concerned with a hunt for land and resources, including both commercial lumber and fuel wood ( Dudley ) . The authorities and industry play a immense function in the devastation or stableness of woods. The authorities is the major facet in commanding and keeping the woods. They have a immense say on what can and can? t be done. For illustration on March 14th 1996 the senate voted 54-42 against revoking a subdivision of the 1995 recissions jurisprudence that allows the wood industry to salve burned and downed trees from national woods ( Shuster 1 ) . They can curtail lumbermans by doing Torahs but besides are the nexus between compromising with the conservationists. High unemployment and occupation loss is normally blamed on the limitations set on Foresters. However this is a myth. Most of this unemployment is from world-wide economic alteration. The production of value-added wood merchandises would make more occupations and convey more wealth to these logging communities. The whole end of this would be to cut down the force per unit area on the woods. If commercial forestry is to hold a hereafter, its methods need to go more ecologically sound and sustainable. The technique of salvage logging, taking dead and diseased trees from the wood, is good if the lumbermans wear? Ts take advantage of it and cognize what trees to travel after. Another affectional method lumberman? s usage is known as whole tree harvest home. This uses all of the wood from a tree. The subdivisions and the crowns are converted into wood french friess. Whole tree logging provides more occupations for the people and more merchandises to be sold for the economic system. The authorities must play a greater function in forest direction to protect the environment and employment. The authorities should guarantee that the involvements of all stakeholders and every bit good as the long-run effects associated with forest countries are taken into history during forest planning. Governments should halt supporting the wood industry from unfavorable judgment and stop the pattern of subsidisation. Propaganda arising from authoritiess and corporations requires riddance if the populace is to be able to do the right picks. Probably merely the action of concerned citizens and consumers will oblige authorities and industry to do alterations in the woods. Persons can pass on their uncertainness about the hereafter of the universe? s woods to politicians, corporate executives and non-governmental organisations through personal communicating in the signifier of letters, telephone calls, facsimiles and electronic mails. Deforestation is a serious job, but worlds can do a difference. And single every bit good as a concern can pattern green consumerism. They can do an attempt to buy the most ecologically sensitive merchandises. Recycled paper is ever available, which can cut down the demand for lumber. One of the most of import ways a individual to hold a positive consequence is to cut down his or her ingestion of wood and related merchandises. An addition in the engagement of cut downing, recycling and recycling is necessary. Education is one of the most effectual ways to advance alteration in our environment. Society should educate people of today to alter their ways and learn the younger coevalss to hold regard for nature. The immature people in our society should besides be taught about the biological, societal and economic values of woods. Environmental preservation should be every bit of import as math, natural philosophies, and history in school. Workers should be taught to utilize engineering to heighten forest ecosystems alternatively of destructing them for re-afforestation. If worlds would merely see themselves as a portion of nature, they will esteem it so much more and non merely work it for its resources. Humans bear the duty for deforestation and the planetary ecological crisis. But humankind has the abilities and possible to alter its ways and forestall the devastation of our universe? s woods. If the woods are protected and regenerated they will profit us all in many ways. Trees will assist profit the land from eroding. Endangered species will hold better opportunities for endurance. Human wellness will profit from medicative compounds that are given a opportunity to be disvocered. Local economic systems will profit from ecotourism and consumers worldwide will derive satisfaction from cognizing that their wood merchandises were harvested in a sustainable mode that left four out of five trees standing ( Greenpeace ) . In order for this to happen worlds are traveling to hold to undergo some grade of ideological alteration. Worlds are traveling to hold to live more sustainable lives and go closer with nature. Once the crisis of deforestation has passed, world will bask a finer being, and will look frontward to a bright hereafter.

Communism and its fall essays

Communism and it's fall essays The shocking fall of communism in Eastern and central Europe in the late eighties was remarkable for both its rapidity and its scope. In each of the nations, the communist regimes in power were forces to transfer that power to radically different institutions than they were accustomed to. Democracy had been spreading throughout the world for the preceding two decades, but with a very important difference. In Europe, the shift from communism was taking place in a different context then that of the Soviet Union. The peoples involved were not looking to affect a narrow set of policy reforms, rather what was at stake what the shift from communist ideology to a more western plan for governmental and economic policy development. It seemed that the sole reason that the downfall of communism took so long was the veto power of the Soviet Union. Due to Eastern Europes longtime adherence to communist policies, these nations faced great difficulty in making the transition to a market economy without being forced to unite with another economic system. Mikhail Gorbachev was a different kind of Soviet leader. He recognized that communists in the Soviet Union could not remain politically and economically isolated and that the Soviet system had to be changed if it was to survive. The key pieces to his plan was a series of reforms that included Glasnost - an openness and greater form of expression for the people, Perestroika - a restructuring as to decentralize the soviet economy with market reforms all of which were designed to reform, not abolish socialism, and the renunciation of the Brezhnev Doctrine. Central planning in a modern economy brought many inefficiencies. The socialist system was ineffective in that communism promised a classless society with collective ownership but instead it produced a new class of communist party functionaries. In addition, the soviet state could not longer afford the high defense spending tha...

Health Issue Relate to Hispanic Essay Example | Topics and Well Written Essays - 500 words

Health Issue Relate to Hispanic - Essay Example Asides from this, the population faces more environmental hazards in comparison to other population. There various health promotion activities and community services that are aimed at improving health in this population. This essay discusses the health issues facing the Hispanic poplulation in America. To start with, heart disease refers to the broad spectrum of conditions and illnesses that impact on the heart. The prevalance to heart diseases is higher among the Hispanics owing to factors such as obesity, high cholesterol, tobacco, smoking and hypertension. Research has found that nearly 21 percent of the annual deaths in this population are caused by the heart disease (Vega et al., 2009). This has been made worse by the fact that most of the members of this population do not maintain a healthy diet. Cancer is the second issue that affects the Hispanic population. It has been observed that the most cancers that affect this population include stomach, rectum, breast and uterine or cervix cancer (Smith and Bradshaw, 2006). Lung cancer has been observed to be the leading cause of death among Hispanic men. In general, cancer contributes to 20% of deaths in this population yearly (Vega et al., 2009). It has been found that an active lifstyle and diet that contains antioxidants are cr itical in preventing the chronic illness. Another health issues affecting this population is stroke (Vega et al., 2009). This is widely caused by key factors such as smoking and high cholesterol that have been found to be prevalent among Hispanics. These factors also worsen the health issue in the population. It has been observed that another health risk facing this population is unintended accidents. This includes car accidents and fires. While these accidents impact on children and adults, teenagers have been found to be at the higher risk for these accidents. Based on the findings of a CDC report it is clear that 67

Human and animal interrelationships Essay Example | Topics and Well Written Essays - 1250 words

Human and animal interrelationships - Essay Example Although highly anthropomorphized in their thinking and approaches, the rabbits are true to the idea of wild rabbits. Most animals in the wild make an effort to avoid humanity and their interactions are often that of hunter versus prey, forced domestication, and protection of crops and property (Grandgeorge, and Hausberger 397-399). They, human beings, are seldom beneficial for the animals in the long run. I find this book to be a realistic manifestation of human and animal interactions in that it provides a realistic relationship of avoidance and inadvertent contact. Chapter Summaries/Analysis PART 1: The Journey Chapter 1: The Notice Board The opening introduces us to the rabbits, and the main characters, of the â€Å"Sandleford† Warren. The rabbits are out grazing when they are forced away from a the â€Å"cowslip† growing in the field by the Warren Owsla, which is the ruling class and pseudo military of the warren, who believe that the best foods are reserved for th em. Fiver, Hazel’s brother, is thought to be a bit psychic believes that something bas is going to happen but he does not know what. He directs attention to a sign posted on the property. The rabbits cannot read it, but it clearly states that human construction is coming to this filed; this means that Fiver’s vision may not be entirely unfounded (Adams 11-160). Human beings, although not there in person, have a very important role in the opening of this story; in fact, they are the motivating factor in Five’s fears. The sign represents the human presence and intentions for the area presently being occupied by the rabbit warren. This could be perceived as an example for human shortsightedness and disregard for the consequences of their actions where other species are concerned and the threat they present to other living things homes. The relationship between the animals and man is one of negative cause and effect, without interaction at all. Chapter 2: The Chief Rabbit Fiver's concerns and dreams about the â€Å"bad† things that are coming are getting worse. He wakes Hazel in the night because he believes that they all must leave the warren before it is too late. The next morning Hazel takes his brother to speak to the Chief Rabbit, ruler of the warren, about fiver’s fears. They have to convince BigWig, Owsla guard, that the issue was important enough to disturb the Chief. He relays his vision to the Chief who ultimately dismisses them without really believing them. Hazel defended his brother’s â€Å"gift† but to no avail. BigWig receives an unpleasant admonishment for letting them in the first place (Adams 17-21). The interaction of humans in this chapter is nonexistent. Other than the reference made to Fiver’s vision and the posting in the field. However, no direct or indirect human interaction occurs. This chapter is used to show readers those daily goings-on within the warren. Chapter 3: Hazel’s Decision Hazel decides that he, his brother, and any other warren members that want to will be leaving the Warren. Dandelion and Blackberry explain that life for the bucks, male rabbits, in the warren that were not members of the Owsla life was not very promising. BigWig, also, wants to go. However, Captain Holly, in particular is an Owsla that may mean trouble for them (Adams 22-25). Again the human presence in this chapter is essentially irrelevant. They do not appear in this chapter in any way, shape or form. Chapter 4: The Departure This point in the

Final year project (( part 1 )) Essay Example | Topics and Well Written Essays - 5000 words

Final year project (( part 1 )) - Essay Example There is a lot of information that needs to be managed. Handling all this manually (on paper) would further complex it. Since the league allows the smallest clubs to play, therefore, there are over 140 leagues with 480 divisions. This number varies every year. This indicates the amount of information that is to be managed. This is the age of technology. Every department whether it is related to computer or not is being automated. Automation helps in speeding up processes. It also ensures accuracy. That is why most organizations support automation to a very large extent. There are several departments that take care of the league information. The synchronization of information is not an easy task, especially when the information is on paper. That is why a system that could not only store the information but also maintain is required. The aim of this project is therefore to develop a League Table Management System that should be a stand-alone application that could be accessed through out the organization. The system should provide with the facility of editing team details, match points, allocation of matches, location and time of events, etc. The English football league system, otherwise known as the football pyramid, is a series of interconnected leagues for club football in England. The system consists of a hierarchy of leagues, bound together by the principle of promotion and relegation. Clubs that are successful in their league can rise higher in the pyramid, whilst those that finish at the bottom can find themselves sinking further down. In theory it is possible for a lowly local amateur club to rise to the pinnacle of the English game and become champions of the Premier League. The top five levels contain one division each. Below this, the levels have progressively more parallel leagues, which each cover progressively smaller geographic areas.

Use of HPV Vaccines for Cervical Cancer Prevention

Use of HPV Vaccines for Cervical Cancer Prevention HPV Vaccines: Will They Prevent Cervical cancer Introduction Human papilloma viruses (HPV) belong to the papillomaviridae family, they are double stranded DNA viruses. HPV is the most common sexually transmitted infection (STI) in the world (Urman et al. 2008). HPV is strongly associated with cervical cancer; more than 99% what are the other causes/factors please of cervical cancer cases are positive for HPV DNA and indeed, cervical cancer is the second most common malignancy in the world (Wang et al. 2007). In developed countries the incidence of cervical cancer has been reduced significantly by the introduction of a cervical screening programme. In developing countries where 83% of mortalities due to cervical cancer occur, there are no such programmes (Parkin et al. 2006). Can the introduction of a vaccine against HPV further reduce globally the incidence of cervical cancer? Many diseases caused by viruses are controlled in the developed world by ongoing successful vaccination programmes; Polio, Measles, Mumps and Rubella are a few examples. Smallpox caused by Variola virus was eradicated in 1979 through a successful worldwide vaccination programme. The factors that affect the Polio and MMR vaccine programmes success and those that affected the successful smallpox programme may also be contributory to the success of the HPV vaccination program. Vaccination of HPV is complex and multi factorial. This investigation studies a number of factors including: Vaccine efficacy Vaccine Cost/affordability/practicality of administration Production and Distribution Government backing and financial commitment Other support organisations such as the WHO, UNICEF, Gates Foundation, Social factors Media effects Public awareness Safety, and perceived fears Currently two prophylactic vaccines against HPV types 16 and 18, the most prevalent causes of HPV have been approved by the food and drug administration (FDA). Many developed countries have already introduced vaccination programmes using one of these vaccines. Can the vaccines and programme prevent cervical cancer? In order to effectively understand the implication of such a vaccination programme we must first fully examine the causative agent (HPV) and the consequential potential diseases including the biology, history and prevalence. Human Papillomavirus Approximately 200 types of HPV are identified of which around 40 infect the genital tract (McCance 2004). The majority of HPV types cause no symptoms, some types can cause warts and a minority may lead to cancer. Genital HPVs are transmitted via sexual contact, mainly intercourse, with an infected individual, and the risk of developing an HPV infection generally increases with the number of sexual partners, the sexual history of that partner or the introduction of a new sexual partner. Studies have shown that at least one type of HPV infection occurs soon after sexual debut, with around 30% of women infected with at least one high risk type within two years (Winer et al 2003; Winer et al 2008). HPVs are classified as either high risk or low risk, on the basis of association with cervical cancer. There are 15 types classified as high risk and three as probable high risk. High risk types include 16,18,31,33,35,39,,45,51,52,56,58,59,68,73,probable high risk types include 26,53,66 Low risk types include 6,11,40,42,43,54,61,70,72,81 and CP6108. More than 99% of cervical cancers are associated with HPV, of these 70% are associated with HPV type 16 and 18, with HPV 16 causing 50% and HPV 18 causing more than 15% in Europe (Smith et al..2007). HPV 16 is thus the single, most common high risk HPV. Interestingly HPV types 16 and 18 also cause 80% of anal cancer and 30% of vaginal and why the difference in % oper area research needed here.vulvar cancer and are associated with cancers of the, oropharynx and some rare cancers of the head and neck. (add reference form cervical cancer burden worldwide paper) The majority of HPV infections are asymptomatic, self limiting, and transient, with 70% of new HPV high risk type infections cleared within one year (with the median duration of an infection at 8 months) and 90% within two years (Ho et al 1998). The transient infection usually causes no clinical problems. A small proportion of high risk type infections persist due to host immune evasion, an evasion that results not only from restriction of HPVs to sites that are relatively inaccessible to host defences but also due to several mechanisms of preventing immune response what are these mechanisms please (a sk Dick if this is what he means . This persistence is the most important factor in the development of pre cancerous and cancerous lesions. The time span between infection by HPV and the development of pre cancerous lesions or cervical carcinoma varies from one to ten years (Moscicki et al 2006) and up to 20 years from other sources. HPV show little evidence of dramatic adaptability with phylogenic studies suggesting that the biology of HPVs has remained the same for over 200,000 years (Halpren et al 2000). While HPVs show historically the influence of point mutations, inserts, deletions and duplications, the predominant pattern of mutation within a given type is point mutation, with large scale rearrangements within the most conserved genes of HPVs such as L1 being rare (Myers et al 1996). Intra patient variation within HPV types is uncommon due to their low mutation rate. This low mutation rate is directly linked to the HPV replication strategy that requires host cell machinery, which has stringent proof reading mechanisms that avoid the incorporation of errors, conferring slow mutagenesis. All HPVs exhibit extreme specificity for infection of epithelial cells and do not infect or express their gene products in the underlying dermis. Although the mechanism of infection is not fully understood, the HPV epitheliotrophy resides for the most part in the interaction of specific transcription factors with the viral regulatory region known as the long control region (LCR). Infection with HPV can result in hyperproliferation of the host cell, and with certain high risk HPV types it may lead to transformation and immortalization. This is because high risk HPVs express two or more protein products (E6, E7 and E5) that transiently disrupt the cell cycle and stimulate cell division, knocking out at the same time the cellular mechanisms for growth inhibition. For a productive infection, HPVs require terminally differentiated cells. This HPV biology feature has impeded studies on the full reproduction life cycle because of the lack of highly efficient models of epithelial terminal di fferentiation in vitro. Most of the different stages in the HPV life cycle have been established using genetic engineering and molecular biology strategies. The dsDNA of HPV exists in a non enveloped icosahedral shaped virion 52-55 nm in diameter. The dsDNA genome is circularised and around 8000base pairs in length (Fig1). The genome encodes eight proteins, six early E1, E2, E4, E5, E6, E7, and two late structural proteins L1 and L2 and the previously mentioned noncoding LCR. Fig 1 HPV type 16 Genome structure, gene and functional domain location http://www.dnachip-link.com/Eng/library/HPV.aspusg 15/11/20009 Fig 1 shows the dsDNA genome of HPV type 16, and the location of the early and late genes along with the LCR that contains the origin of replication. An initial infection requires the access of infectious particles to the basal layer of the epithelium. Some HPVs require a break in the stratified epithelium to achieve this. Such breaks are not necessarily obvious and may occur under conditions where the skin is exposed to water or abraded, or subjected to an environment where micro traumas may occur such as possibly in aswiming pool or ect (must put an example)(in fig 2 shows as a cut). Following infection and uncoating it is thought that the virus maintains its genome as an episome in low copy numbers within basal cells of the epithelium. Although the pattern of gene expression in these cells is not well understood, it is generally thought that viral proteins E1 and E2 are expressed to maintain the viral DNA episome (Wilson et al.2002) and possibly to facilitate the segregation of genomes during cell division (You et all.2004). It is not known whether viral transformation proteins E6 and E7 are also expressed in the basal layer, but it does appear that initial infection is followed by a proliferative phase that results in the increase in the number of basal cells harbouring viral episomes. In normal uninfected epithelium, basal cells leave the cell cycle soon after migration into the superbasal cell layers where they undergo a process of terminal differentiation. During infection E6 and E7 are expressed in these cells stopping normal differentiation (Sherman et all.1997). E6 and E7 are believed to work together to achieve this and in lesions caused by high risk HPV types. During a natural infection the ability of E7 to stimulate S-phase progression is limited to a subset of differentiated cells with low levels of p21/p27, or which express high enough levels of E7 to overcome the block in S-phase entry. The viral E6 protein is thought to prevent apoptosis in response to unscheduled S-phase entry brought on by E7. The association of E6 with p53 and the inactivation of p53 mediated growth suppression and apoptosis is well documented, E6 may also associate with other pro-apoptotic proteins including bak (Thomas and Banks,1998) and bax (Li and Dou,2000). E6 is thus considered a predisposing factor in the development of HPV associated cancers, allowing the accumulation of chance errors in host DNA to go unchecked. Furthermore the E6 protein of high risk HPVs can stimulate cell proliferation independently of E7 via a c-terminal PDZ ligand binding domain. E6 PDZ is enough to mediate superbasal cell proliferation and may contribute to the formation of metastatic tumours by disrupting normal cell adhesion (Nguyen et al.2003) Amplification of the viral genome and the ability to package these genomes into infectious particles is essential for the production of infectious virions. For most HPV types this occurs in the mid or upper epithelial layers following an increase in activity of the late promoter. The late promoter gene is located within the E7 open reading frame, and the upregulation of the late promoter is thought to lead to increased expression of proteins involved in viral DNA replication, without directly affecting the expression of E6 or E7 necessary for S-phase entry. The amplification of the viral genome begins in a subset of cells in the proliferative compartment and requires the expression of all viral early gene products, these include E4 and E5 whose role in replication is not yet clearly understood. Binding of E2 to the HPV upstream regulator region is essential for viral DNA replication that is dependent on the differentiated state of epithelial cells. E2 recruits the E1 DNA helicase to the viral origin of replication. Throughout the virus life cycle, the relative levels of viral proteins are controlled by promoter usage and by differential splice site selection, with an increase in E1 and E2 allowing an increase in viral copy numbers in the upper epithelial layers. Current models suggest that a small increase in promoter activation during differentiation may lead to an increase in the level of E1 and E2 and a subsequent increase in genome copy number. The newly replicated genome could then serve as a further template for expression of E1 and E2, facilitating the amplification of viral genome and in turn further expression of E1 and E2 replication proteins. Viral DNA remains latent (not integrated) in basal cells of benign lesions. Replication occurs in the differentiating cells where capsid proteins and viral particles are found. Viral DNA is integrated in cancer cells, which contain no replicating virus. Once viral genome replication is completed, the expression of two virally encoded structural proteins, expressed in the upper layers of infected epithelia may occur. L1 the major capsid protein is expressed after L2 in a sub set of cells that express E4 (fig 2), this allows the assembly of infectious particles in the upper layers of the epithelium (Florin et al.,2002). A successful infection requires the virus to escape from the infected skin cell and survive extracellularly prior to re-infection. HPVs are non-lytic and are as such not released until the infected cells reach the epithelial surface. The intracellular retention of HPV antigen until the cell reaches the uppermost epithelial layers may contribute the compromised immune detection, especially as the virus has molecular mechanisms that limit the presentation of viral epitopes to the immune system in the lower epithelial layers (Ashrafi et al 2002). What are these mechanisms Figure 2 Papillomavirus type 16 Life Cycle and gene expression location within epithelium Taken from, The papillomavirus life cycle by John Doorbar published in the journal of clinical virology 32S (2005) S7-S15 Figure 2 diagrammatic representation of the skin with HPV type 16 gene expression incorporated, colour of arrows are representative of genes expressed within epithelial cells. The frequent detection of high risk HPV DNA in cervical lesions in the absence of any obvious disease, may be explained by the presence of the virus in a latent state, with only very few cells able to support the productive virus life cycle during epithelial cell differentiation. Following immune regression, HPV DNA is thought to remain in the basal epithelial cells waiting to be reactivated once levels of immune surveillance decline there are conflicting opinions (Zhang et al.1999). If regression is not achieved lesions may persist and in some instances progress to cancer. The number of lesion that progress to cancer is very low when compared to the prevalence of high risk HPV infection in the general public. The Progression of productive lesion to high grade lesions may result from the deregulation ( what happen to allow thes proteins to be deregulated intergrattion loss of E2 adn p53 association, be specific add biochemistry here please. in the expression of transforming proteins E6 and E7. The inability of a cell to support the whole virus life cycle is often associated with the development of cancerous lesions. The transformation zone (Fig 3) is particularly susceptible to cervical cancer; it appears that high risk types of HPV such as type 16 cannot complete their life cycle at this site Progression from CIN3 to cancer usually occurs in lesions that contain integrated copies of the viral genome in which E7 expression is elevated. Suggesting that retention of E6 and E7genes and the loss of E2 and E4 genes (that exert negative effect on cell growth) usually accompanies the development of invasive cancer. (reference) Remember for CIN refer to in that section or here but Cin must be corrulated with what causes the cancer and with whats happening with the virus that causes the change in CIN or the causes in CIN to occur. Cervical cancerisa considerable contributor to morbidity and mortality. Being the second most common cancer worldwide and the twelfth most common cancer in women in the UK. Cervical cancer in 2002 was the cause of 274,000 deaths worldwide (the most current data available)REF THIS FIGURE and continues to causes more than 1000 deaths in the UK each year. There are two main types of cervical cancer squamous cell cancer (the most common) and adenocarcinoma, although they are often mixed. They are named after the types of cell that become cancerous through neoplasia. Squamous cells are flat cells covering the cervix; adenomatous cells are found in the passageway from the cervix to the womb. Other rarer cancers of the cervix include small cell cancer. Deaths from cervical cancer in the UK have fallen over the last 20 years mainly because of the NHS cervical screening programme that reduced the mortality rates by 62% between 1987-2006. Screening may detect changes in the cells of the cervix at a pre-cancerous stage. Fig 3 TITTLE Showing location of transformation zone. Cell samples are examined for abnormalities, these abnormality are described in a standard format covering cytology and/or histology. What are these standard format CIN 1 CIN2 CIN3 LISL LGSIL HSIL HGSIL USE FIG 4 and explain whats happening with the proteins expressed and genome intergration where CIN number progression is concerned please. MUST DO From Lowy Schiller, J Clin Invest, 116:1167-73, 2006 Low grade squamous intraepithelial lesion (LSIL or LGSIL) indicates possiblecone biopsy, or laser ablation. High grade squamous intraepithelial lesion (HSIL or HGSIL) indicates moderate or severeCIN 2 or CIN3 (fig 3). While cervical screening has reduced the mortality significantly in the developed world cervical cancer is still a significant burden worldwide. Fig 4 Taken from, The popillomavirus life cycle by John Doorbar published in the journal of clinical virology 32S (2005) S7-S15 Fig. 5. CIN 1 resembles productive infections caused by other HPV types and as such is the most benign form of cervical intraepithelial neoplasia , it is confined to the basal 1/3 of the epithelium, CIN 2 Moderate dysplasia confined to the basal 2/3 of the epithelium,CIN3 Sever dysplasia that spans more than 2/3 of the epithelium, and may involve the full thickness. INCIDENCE An estimated 493,000 new cases and 274,000 deaths in 2002 were caused by cervical cancer. The vast majority, some 83% of these cases, occur in developing countries, where cervical cancer amounts to 15% of female cancers with a risk before age 65 of 1.5%. In developed countries cervical cancer accounts for only 3.6%, with a risk of 0.8% before age 65. REF The highest incidence rates are observed in Sub-Saharan Africa, Melanesia, Latin America and the Caribbean, South-Central Asia, and South East Asia (fig 6) Fig 6 Worldwide Burden of HPV related Cervical Cancer Figures from 2002. Parkin MD et al 2006 The burden of HPV-related cervical cancers The vast majority of cervical cancers are squamous cell carcinoma adenocarcinomas being less common (fig 6). Generally the proportion of adenocarcinoma cases is higher in areas with low incidence of cervical cancer, accounting for up to 25% of cases in western countries (fig 6). This higher incidence of adenocarcinoma may be partially explained by cytological screening, which historically, had little effect in reducing the risk of adenocarcinoma of the cervix, because these cancers, and their precursors, occur within the cervical canal, and were not readily sampled by scraping of the epithelium of the ectocervix. Fig 5 Fig 5 showing the higher % of adenocarcinoma in counties that have screening programmes such as the UK and Denmark What is this showing? Make it clear.do you really need it. MORTALITY RATES Mortality rates are substantially lower than incidence rates. Worldwide 55% (could you double chek that this is the case please misses) of all those that develop the disease die, the figures vary significantly from the developed to the developing world. Low risk regions of the west such as Europe have a death rate of 37% while in developing countries where many cases present at relatively advanced stages, death rates are significantly higher increasing to 70%. Cervical screening programmes in the developed world identify pre-cancerous lesions at a stage where they can be easily treated accounting for the difference in mortality rates. TITTLE IF and figure number staying and refer to in text As cervical cancer affects a relatively high number of young women, it is a significant cause of years of life lost (YLL) in the developing world. Yang et al 2004 found that cervical cancer was responsible for the 2.7 million (age weighted) years of lives lost world wide in 2000, and that it is the single biggest cause of years of life lost from cancer in the developing world. In Latin America, Eastern Europe and the Caribbean, cervical cancer makes a greater contribution to YLL than disease such as Tuberculosis or AIDS. HPV is also associated with many other forms of cancer that could possibly be prevented with use of HPV vaccines; cancers of the penis, anus, vulva, vagina, oropharynx and some rare cancers of the head and neck are included. However cancer of the cervix is by far the most significant, in terms of incidence and mortality (table 1). Cancer of the vulva and vagina have a significantly lower incidence rate compared to cervical cancer, however since 80% of the incidence are caused by HPV types 16 or 18 women vaccinated against these types would also be protected against these forms of cancer. Incidence of squamous cell carcinoma of the anus are twice as common in females as males with HPV types 16 and 18 accounting for 83% of all cases. There is a particularly high incidence of anal cancer among homosexual males, shown by the high incidence rate in populations such as Sanfransisco, where gay incidence are higher than average (fig 7). Globally cancer of the penis is relatively rare accounting for 0.5% of cancers in men (table 1). HPV DNA is detectable in 40-50% of all penile cancers and serological studies have confirmed the role of HPV 16 and 18 (IARC 2005). Cancers of the mouth and oropharynx caused by HPV are very low at 0.06% of all cancers with 0.05% being caused by HPV types 16/18. Due to the small size of most studies and the absence of comparable measurements of prevalence of infection in normal subjects conducted for cancers of the vulva, vagina, penis and anus true prevalence is difficult to quantify. The figures shown in table 1, imply that we are dealing with a virus that discriminates primarily through disease aginst women, in particular young women. Gay men, however are also clearly an at risk group. Currently only young women are vaccinated aginst HPV types 16 and 18, however the JCVI (joint committee on vaccination and immunisation) have noted that the vaccines has not been conclusively trialled on men, and that there is insufficient evidence that the vaccine available would protect against anal, penile or head and neck cancer. However when more data becomes available they will consider vaccinating, high risk groups such as men who have sex with men. Add what this implies for prophylactic use of vaccine with other cancers cause by HPV And what you think about the ue of vaccine on highrisk men and its effectivity against other cancers caused by HPV types 16 and 18. Fig 7 TITTLE add Figure 6 showing that cancer of the anus are more prevalent in women than men with the major noted exception being San Francisco, where the increased incidence can be explained by a large number of homosexual men. Table 3 VACCINATION An effective vaccine should stimulate a suitable range of immune responses, mimic or improve on the protection gained from a wild type infection with little side effects. Critically the vaccine should be inexpensive, easily administered, transported and stored to further reduce cost and maximise convenience, this is especially relevant in the case of HPV vaccine as those that are not protected by the screening programmes of the developed world would benefit the most, ease of administration and storage is paramount in the developing world as stability and healthcare is more sporadic, and people are often more remote. There are many different kinds of vaccines available, and different vaccines have a variety qualities and limitations. Live attenuated vaccines contain a version of the pathogenic microbe that is avirulent, they often elicit an excellent cellular and antibody response with good longevity that can be lifelong with few doses. However there is always the possibility that the vaccine may revert to its virulent form, causing disease. For this reason a live attenuated vaccine is not appropriate for use against oncogenic HPV types. Recombinant vaccines can include one or more proteins that may illicit an immune response. A process has been developed to allow the removal of the genome from an attenuated or avirulent viral vector allowing the insertion of selected genetic material or proteins from another virus. The carrier viruses then ferry that viral DNA into host cells where the genes are expressed. Recombinant vaccines closely mimic a natural infection and therefore illicit a strong immune system. Inactivated vaccines are produced by killing the disease causing microbe by chemical (formaldehyde eg just double check), heat or radioactive means. These vaccines are more stable than live vaccines, and as there is no risk of reversion to virulence. They are also safer than live vaccines. Most inactivated vaccines stimulate a weaker immune response than live vaccines and several doses or boosters may be required to maintain immunity. DNA vaccines dispense with both the whole organism and its parts. They only include the essential part of the microbes genetic material. In particular, DNA vaccines use the genes that code for immunogens. Researchers have found that when the genes for a microbes antigens are introduced into the body, some cells will take up that DNA. The DNA then instructs those cells to make the antigen molecules. The cells secrete the antigens and display them on their surfaces. In other words, the bodys own cells become vaccine-making factories, creating the antigens necessary to stimulate the immune system. A DNA vaccine against a microbe would evoke a strong antibody response to the free antigen secreted by cells, and also stimulate a strong cellular response against the microbial antigens displayed on cell surfaces. The DNA vaccine is unable to cause disease Use of HPV Vaccines for Cervical Cancer Prevention Use of HPV Vaccines for Cervical Cancer Prevention HPV Vaccines: Will They Prevent Cervical cancer Introduction Human papilloma viruses (HPV) belong to the papillomaviridae family, they are double stranded DNA viruses. HPV is the most common sexually transmitted infection (STI) in the world (Urman et al. 2008). HPV is strongly associated with cervical cancer; more than 99% what are the other causes/factors please of cervical cancer cases are positive for HPV DNA and indeed, cervical cancer is the second most common malignancy in the world (Wang et al. 2007). In developed countries the incidence of cervical cancer has been reduced significantly by the introduction of a cervical screening programme. In developing countries where 83% of mortalities due to cervical cancer occur, there are no such programmes (Parkin et al. 2006). Can the introduction of a vaccine against HPV further reduce globally the incidence of cervical cancer? Many diseases caused by viruses are controlled in the developed world by ongoing successful vaccination programmes; Polio, Measles, Mumps and Rubella are a few examples. Smallpox caused by Variola virus was eradicated in 1979 through a successful worldwide vaccination programme. The factors that affect the Polio and MMR vaccine programmes success and those that affected the successful smallpox programme may also be contributory to the success of the HPV vaccination program. Vaccination of HPV is complex and multi factorial. This investigation studies a number of factors including: Vaccine efficacy Vaccine Cost/affordability/practicality of administration Production and Distribution Government backing and financial commitment Other support organisations such as the WHO, UNICEF, Gates Foundation, Social factors Media effects Public awareness Safety, and perceived fears Currently two prophylactic vaccines against HPV types 16 and 18, the most prevalent causes of HPV have been approved by the food and drug administration (FDA). Many developed countries have already introduced vaccination programmes using one of these vaccines. Can the vaccines and programme prevent cervical cancer? In order to effectively understand the implication of such a vaccination programme we must first fully examine the causative agent (HPV) and the consequential potential diseases including the biology, history and prevalence. Human Papillomavirus Approximately 200 types of HPV are identified of which around 40 infect the genital tract (McCance 2004). The majority of HPV types cause no symptoms, some types can cause warts and a minority may lead to cancer. Genital HPVs are transmitted via sexual contact, mainly intercourse, with an infected individual, and the risk of developing an HPV infection generally increases with the number of sexual partners, the sexual history of that partner or the introduction of a new sexual partner. Studies have shown that at least one type of HPV infection occurs soon after sexual debut, with around 30% of women infected with at least one high risk type within two years (Winer et al 2003; Winer et al 2008). HPVs are classified as either high risk or low risk, on the basis of association with cervical cancer. There are 15 types classified as high risk and three as probable high risk. High risk types include 16,18,31,33,35,39,,45,51,52,56,58,59,68,73,probable high risk types include 26,53,66 Low risk types include 6,11,40,42,43,54,61,70,72,81 and CP6108. More than 99% of cervical cancers are associated with HPV, of these 70% are associated with HPV type 16 and 18, with HPV 16 causing 50% and HPV 18 causing more than 15% in Europe (Smith et al..2007). HPV 16 is thus the single, most common high risk HPV. Interestingly HPV types 16 and 18 also cause 80% of anal cancer and 30% of vaginal and why the difference in % oper area research needed here.vulvar cancer and are associated with cancers of the, oropharynx and some rare cancers of the head and neck. (add reference form cervical cancer burden worldwide paper) The majority of HPV infections are asymptomatic, self limiting, and transient, with 70% of new HPV high risk type infections cleared within one year (with the median duration of an infection at 8 months) and 90% within two years (Ho et al 1998). The transient infection usually causes no clinical problems. A small proportion of high risk type infections persist due to host immune evasion, an evasion that results not only from restriction of HPVs to sites that are relatively inaccessible to host defences but also due to several mechanisms of preventing immune response what are these mechanisms please (a sk Dick if this is what he means . This persistence is the most important factor in the development of pre cancerous and cancerous lesions. The time span between infection by HPV and the development of pre cancerous lesions or cervical carcinoma varies from one to ten years (Moscicki et al 2006) and up to 20 years from other sources. HPV show little evidence of dramatic adaptability with phylogenic studies suggesting that the biology of HPVs has remained the same for over 200,000 years (Halpren et al 2000). While HPVs show historically the influence of point mutations, inserts, deletions and duplications, the predominant pattern of mutation within a given type is point mutation, with large scale rearrangements within the most conserved genes of HPVs such as L1 being rare (Myers et al 1996). Intra patient variation within HPV types is uncommon due to their low mutation rate. This low mutation rate is directly linked to the HPV replication strategy that requires host cell machinery, which has stringent proof reading mechanisms that avoid the incorporation of errors, conferring slow mutagenesis. All HPVs exhibit extreme specificity for infection of epithelial cells and do not infect or express their gene products in the underlying dermis. Although the mechanism of infection is not fully understood, the HPV epitheliotrophy resides for the most part in the interaction of specific transcription factors with the viral regulatory region known as the long control region (LCR). Infection with HPV can result in hyperproliferation of the host cell, and with certain high risk HPV types it may lead to transformation and immortalization. This is because high risk HPVs express two or more protein products (E6, E7 and E5) that transiently disrupt the cell cycle and stimulate cell division, knocking out at the same time the cellular mechanisms for growth inhibition. For a productive infection, HPVs require terminally differentiated cells. This HPV biology feature has impeded studies on the full reproduction life cycle because of the lack of highly efficient models of epithelial terminal di fferentiation in vitro. Most of the different stages in the HPV life cycle have been established using genetic engineering and molecular biology strategies. The dsDNA of HPV exists in a non enveloped icosahedral shaped virion 52-55 nm in diameter. The dsDNA genome is circularised and around 8000base pairs in length (Fig1). The genome encodes eight proteins, six early E1, E2, E4, E5, E6, E7, and two late structural proteins L1 and L2 and the previously mentioned noncoding LCR. Fig 1 HPV type 16 Genome structure, gene and functional domain location http://www.dnachip-link.com/Eng/library/HPV.aspusg 15/11/20009 Fig 1 shows the dsDNA genome of HPV type 16, and the location of the early and late genes along with the LCR that contains the origin of replication. An initial infection requires the access of infectious particles to the basal layer of the epithelium. Some HPVs require a break in the stratified epithelium to achieve this. Such breaks are not necessarily obvious and may occur under conditions where the skin is exposed to water or abraded, or subjected to an environment where micro traumas may occur such as possibly in aswiming pool or ect (must put an example)(in fig 2 shows as a cut). Following infection and uncoating it is thought that the virus maintains its genome as an episome in low copy numbers within basal cells of the epithelium. Although the pattern of gene expression in these cells is not well understood, it is generally thought that viral proteins E1 and E2 are expressed to maintain the viral DNA episome (Wilson et al.2002) and possibly to facilitate the segregation of genomes during cell division (You et all.2004). It is not known whether viral transformation proteins E6 and E7 are also expressed in the basal layer, but it does appear that initial infection is followed by a proliferative phase that results in the increase in the number of basal cells harbouring viral episomes. In normal uninfected epithelium, basal cells leave the cell cycle soon after migration into the superbasal cell layers where they undergo a process of terminal differentiation. During infection E6 and E7 are expressed in these cells stopping normal differentiation (Sherman et all.1997). E6 and E7 are believed to work together to achieve this and in lesions caused by high risk HPV types. During a natural infection the ability of E7 to stimulate S-phase progression is limited to a subset of differentiated cells with low levels of p21/p27, or which express high enough levels of E7 to overcome the block in S-phase entry. The viral E6 protein is thought to prevent apoptosis in response to unscheduled S-phase entry brought on by E7. The association of E6 with p53 and the inactivation of p53 mediated growth suppression and apoptosis is well documented, E6 may also associate with other pro-apoptotic proteins including bak (Thomas and Banks,1998) and bax (Li and Dou,2000). E6 is thus considered a predisposing factor in the development of HPV associated cancers, allowing the accumulation of chance errors in host DNA to go unchecked. Furthermore the E6 protein of high risk HPVs can stimulate cell proliferation independently of E7 via a c-terminal PDZ ligand binding domain. E6 PDZ is enough to mediate superbasal cell proliferation and may contribute to the formation of metastatic tumours by disrupting normal cell adhesion (Nguyen et al.2003) Amplification of the viral genome and the ability to package these genomes into infectious particles is essential for the production of infectious virions. For most HPV types this occurs in the mid or upper epithelial layers following an increase in activity of the late promoter. The late promoter gene is located within the E7 open reading frame, and the upregulation of the late promoter is thought to lead to increased expression of proteins involved in viral DNA replication, without directly affecting the expression of E6 or E7 necessary for S-phase entry. The amplification of the viral genome begins in a subset of cells in the proliferative compartment and requires the expression of all viral early gene products, these include E4 and E5 whose role in replication is not yet clearly understood. Binding of E2 to the HPV upstream regulator region is essential for viral DNA replication that is dependent on the differentiated state of epithelial cells. E2 recruits the E1 DNA helicase to the viral origin of replication. Throughout the virus life cycle, the relative levels of viral proteins are controlled by promoter usage and by differential splice site selection, with an increase in E1 and E2 allowing an increase in viral copy numbers in the upper epithelial layers. Current models suggest that a small increase in promoter activation during differentiation may lead to an increase in the level of E1 and E2 and a subsequent increase in genome copy number. The newly replicated genome could then serve as a further template for expression of E1 and E2, facilitating the amplification of viral genome and in turn further expression of E1 and E2 replication proteins. Viral DNA remains latent (not integrated) in basal cells of benign lesions. Replication occurs in the differentiating cells where capsid proteins and viral particles are found. Viral DNA is integrated in cancer cells, which contain no replicating virus. Once viral genome replication is completed, the expression of two virally encoded structural proteins, expressed in the upper layers of infected epithelia may occur. L1 the major capsid protein is expressed after L2 in a sub set of cells that express E4 (fig 2), this allows the assembly of infectious particles in the upper layers of the epithelium (Florin et al.,2002). A successful infection requires the virus to escape from the infected skin cell and survive extracellularly prior to re-infection. HPVs are non-lytic and are as such not released until the infected cells reach the epithelial surface. The intracellular retention of HPV antigen until the cell reaches the uppermost epithelial layers may contribute the compromised immune detection, especially as the virus has molecular mechanisms that limit the presentation of viral epitopes to the immune system in the lower epithelial layers (Ashrafi et al 2002). What are these mechanisms Figure 2 Papillomavirus type 16 Life Cycle and gene expression location within epithelium Taken from, The papillomavirus life cycle by John Doorbar published in the journal of clinical virology 32S (2005) S7-S15 Figure 2 diagrammatic representation of the skin with HPV type 16 gene expression incorporated, colour of arrows are representative of genes expressed within epithelial cells. The frequent detection of high risk HPV DNA in cervical lesions in the absence of any obvious disease, may be explained by the presence of the virus in a latent state, with only very few cells able to support the productive virus life cycle during epithelial cell differentiation. Following immune regression, HPV DNA is thought to remain in the basal epithelial cells waiting to be reactivated once levels of immune surveillance decline there are conflicting opinions (Zhang et al.1999). If regression is not achieved lesions may persist and in some instances progress to cancer. The number of lesion that progress to cancer is very low when compared to the prevalence of high risk HPV infection in the general public. The Progression of productive lesion to high grade lesions may result from the deregulation ( what happen to allow thes proteins to be deregulated intergrattion loss of E2 adn p53 association, be specific add biochemistry here please. in the expression of transforming proteins E6 and E7. The inability of a cell to support the whole virus life cycle is often associated with the development of cancerous lesions. The transformation zone (Fig 3) is particularly susceptible to cervical cancer; it appears that high risk types of HPV such as type 16 cannot complete their life cycle at this site Progression from CIN3 to cancer usually occurs in lesions that contain integrated copies of the viral genome in which E7 expression is elevated. Suggesting that retention of E6 and E7genes and the loss of E2 and E4 genes (that exert negative effect on cell growth) usually accompanies the development of invasive cancer. (reference) Remember for CIN refer to in that section or here but Cin must be corrulated with what causes the cancer and with whats happening with the virus that causes the change in CIN or the causes in CIN to occur. Cervical cancerisa considerable contributor to morbidity and mortality. Being the second most common cancer worldwide and the twelfth most common cancer in women in the UK. Cervical cancer in 2002 was the cause of 274,000 deaths worldwide (the most current data available)REF THIS FIGURE and continues to causes more than 1000 deaths in the UK each year. There are two main types of cervical cancer squamous cell cancer (the most common) and adenocarcinoma, although they are often mixed. They are named after the types of cell that become cancerous through neoplasia. Squamous cells are flat cells covering the cervix; adenomatous cells are found in the passageway from the cervix to the womb. Other rarer cancers of the cervix include small cell cancer. Deaths from cervical cancer in the UK have fallen over the last 20 years mainly because of the NHS cervical screening programme that reduced the mortality rates by 62% between 1987-2006. Screening may detect changes in the cells of the cervix at a pre-cancerous stage. Fig 3 TITTLE Showing location of transformation zone. Cell samples are examined for abnormalities, these abnormality are described in a standard format covering cytology and/or histology. What are these standard format CIN 1 CIN2 CIN3 LISL LGSIL HSIL HGSIL USE FIG 4 and explain whats happening with the proteins expressed and genome intergration where CIN number progression is concerned please. MUST DO From Lowy Schiller, J Clin Invest, 116:1167-73, 2006 Low grade squamous intraepithelial lesion (LSIL or LGSIL) indicates possiblecone biopsy, or laser ablation. High grade squamous intraepithelial lesion (HSIL or HGSIL) indicates moderate or severeCIN 2 or CIN3 (fig 3). While cervical screening has reduced the mortality significantly in the developed world cervical cancer is still a significant burden worldwide. Fig 4 Taken from, The popillomavirus life cycle by John Doorbar published in the journal of clinical virology 32S (2005) S7-S15 Fig. 5. CIN 1 resembles productive infections caused by other HPV types and as such is the most benign form of cervical intraepithelial neoplasia , it is confined to the basal 1/3 of the epithelium, CIN 2 Moderate dysplasia confined to the basal 2/3 of the epithelium,CIN3 Sever dysplasia that spans more than 2/3 of the epithelium, and may involve the full thickness. INCIDENCE An estimated 493,000 new cases and 274,000 deaths in 2002 were caused by cervical cancer. The vast majority, some 83% of these cases, occur in developing countries, where cervical cancer amounts to 15% of female cancers with a risk before age 65 of 1.5%. In developed countries cervical cancer accounts for only 3.6%, with a risk of 0.8% before age 65. REF The highest incidence rates are observed in Sub-Saharan Africa, Melanesia, Latin America and the Caribbean, South-Central Asia, and South East Asia (fig 6) Fig 6 Worldwide Burden of HPV related Cervical Cancer Figures from 2002. Parkin MD et al 2006 The burden of HPV-related cervical cancers The vast majority of cervical cancers are squamous cell carcinoma adenocarcinomas being less common (fig 6). Generally the proportion of adenocarcinoma cases is higher in areas with low incidence of cervical cancer, accounting for up to 25% of cases in western countries (fig 6). This higher incidence of adenocarcinoma may be partially explained by cytological screening, which historically, had little effect in reducing the risk of adenocarcinoma of the cervix, because these cancers, and their precursors, occur within the cervical canal, and were not readily sampled by scraping of the epithelium of the ectocervix. Fig 5 Fig 5 showing the higher % of adenocarcinoma in counties that have screening programmes such as the UK and Denmark What is this showing? Make it clear.do you really need it. MORTALITY RATES Mortality rates are substantially lower than incidence rates. Worldwide 55% (could you double chek that this is the case please misses) of all those that develop the disease die, the figures vary significantly from the developed to the developing world. Low risk regions of the west such as Europe have a death rate of 37% while in developing countries where many cases present at relatively advanced stages, death rates are significantly higher increasing to 70%. Cervical screening programmes in the developed world identify pre-cancerous lesions at a stage where they can be easily treated accounting for the difference in mortality rates. TITTLE IF and figure number staying and refer to in text As cervical cancer affects a relatively high number of young women, it is a significant cause of years of life lost (YLL) in the developing world. Yang et al 2004 found that cervical cancer was responsible for the 2.7 million (age weighted) years of lives lost world wide in 2000, and that it is the single biggest cause of years of life lost from cancer in the developing world. In Latin America, Eastern Europe and the Caribbean, cervical cancer makes a greater contribution to YLL than disease such as Tuberculosis or AIDS. HPV is also associated with many other forms of cancer that could possibly be prevented with use of HPV vaccines; cancers of the penis, anus, vulva, vagina, oropharynx and some rare cancers of the head and neck are included. However cancer of the cervix is by far the most significant, in terms of incidence and mortality (table 1). Cancer of the vulva and vagina have a significantly lower incidence rate compared to cervical cancer, however since 80% of the incidence are caused by HPV types 16 or 18 women vaccinated against these types would also be protected against these forms of cancer. Incidence of squamous cell carcinoma of the anus are twice as common in females as males with HPV types 16 and 18 accounting for 83% of all cases. There is a particularly high incidence of anal cancer among homosexual males, shown by the high incidence rate in populations such as Sanfransisco, where gay incidence are higher than average (fig 7). Globally cancer of the penis is relatively rare accounting for 0.5% of cancers in men (table 1). HPV DNA is detectable in 40-50% of all penile cancers and serological studies have confirmed the role of HPV 16 and 18 (IARC 2005). Cancers of the mouth and oropharynx caused by HPV are very low at 0.06% of all cancers with 0.05% being caused by HPV types 16/18. Due to the small size of most studies and the absence of comparable measurements of prevalence of infection in normal subjects conducted for cancers of the vulva, vagina, penis and anus true prevalence is difficult to quantify. The figures shown in table 1, imply that we are dealing with a virus that discriminates primarily through disease aginst women, in particular young women. Gay men, however are also clearly an at risk group. Currently only young women are vaccinated aginst HPV types 16 and 18, however the JCVI (joint committee on vaccination and immunisation) have noted that the vaccines has not been conclusively trialled on men, and that there is insufficient evidence that the vaccine available would protect against anal, penile or head and neck cancer. However when more data becomes available they will consider vaccinating, high risk groups such as men who have sex with men. Add what this implies for prophylactic use of vaccine with other cancers cause by HPV And what you think about the ue of vaccine on highrisk men and its effectivity against other cancers caused by HPV types 16 and 18. Fig 7 TITTLE add Figure 6 showing that cancer of the anus are more prevalent in women than men with the major noted exception being San Francisco, where the increased incidence can be explained by a large number of homosexual men. Table 3 VACCINATION An effective vaccine should stimulate a suitable range of immune responses, mimic or improve on the protection gained from a wild type infection with little side effects. Critically the vaccine should be inexpensive, easily administered, transported and stored to further reduce cost and maximise convenience, this is especially relevant in the case of HPV vaccine as those that are not protected by the screening programmes of the developed world would benefit the most, ease of administration and storage is paramount in the developing world as stability and healthcare is more sporadic, and people are often more remote. There are many different kinds of vaccines available, and different vaccines have a variety qualities and limitations. Live attenuated vaccines contain a version of the pathogenic microbe that is avirulent, they often elicit an excellent cellular and antibody response with good longevity that can be lifelong with few doses. However there is always the possibility that the vaccine may revert to its virulent form, causing disease. For this reason a live attenuated vaccine is not appropriate for use against oncogenic HPV types. Recombinant vaccines can include one or more proteins that may illicit an immune response. A process has been developed to allow the removal of the genome from an attenuated or avirulent viral vector allowing the insertion of selected genetic material or proteins from another virus. The carrier viruses then ferry that viral DNA into host cells where the genes are expressed. Recombinant vaccines closely mimic a natural infection and therefore illicit a strong immune system. Inactivated vaccines are produced by killing the disease causing microbe by chemical (formaldehyde eg just double check), heat or radioactive means. These vaccines are more stable than live vaccines, and as there is no risk of reversion to virulence. They are also safer than live vaccines. Most inactivated vaccines stimulate a weaker immune response than live vaccines and several doses or boosters may be required to maintain immunity. DNA vaccines dispense with both the whole organism and its parts. They only include the essential part of the microbes genetic material. In particular, DNA vaccines use the genes that code for immunogens. Researchers have found that when the genes for a microbes antigens are introduced into the body, some cells will take up that DNA. The DNA then instructs those cells to make the antigen molecules. The cells secrete the antigens and display them on their surfaces. In other words, the bodys own cells become vaccine-making factories, creating the antigens necessary to stimulate the immune system. A DNA vaccine against a microbe would evoke a strong antibody response to the free antigen secreted by cells, and also stimulate a strong cellular response against the microbial antigens displayed on cell surfaces. The DNA vaccine is unable to cause disease

Essay example --

Throughout life we lose grandparents, parents and grow apart from close friends but sibling relationships can be one of the most enduring relationships an individual will have throughout their lifetime. Although there are many things that can affect sibling relationships such as gender, age gaps and sex composition, this paper will examine the association between the parent-child relationship and the sibling relationships in adolescence. Based on the family systems theory which suggests that families are made up of interconnected subsystems that influence each other (Whitchurch and Constantine, 1993), it is not surprising that researchers use this theory as a way to study the effects that one relationship may have on the other. By examining the research, it is clear that the parent child relationship has an unquestionable effect on siblings’ relationships. The current literature supports this claim by presenting evidence based on the warmth/conflict within sibling relatio nships, parent’s differential treatment of their children, as well as the indirect/direct involvement parents have on their children’s sibling relationships. People believe most siblings have a love/hate relationship but the amount of one emotion over the other may not be directly the siblings own doings. Variables such as the parent-adolescent relationship can shape how siblings interact with one another whether one consciously notices or not. Derkman, Engels, Kuntsche, Van Der Vorst and Scholte (2011) conducted a five year longitudinal study on 428 families that evaluated the perceived parental support towards children, and the warmth/conflict between siblings during adolescence. Using self reports they found that sibling warmth and adolescent parent su... ...ng the problem themselves, and often punishing the behavior. The results demonstrated that mother’s preferential style of involvement was intervention, and fathers more often used coaching. It was found that when mothers and fathers used coaching as their style of involvement during conflicts between siblings it was related to greater levels of sibling warmth afterwards. Although both mothers and fathers used the coaching technique, mothers less often used non-involvement and more often used intervention than fathers. The style of involvement parents choose to use during sibling conflicts influence the way siblings learn to cope and deal with troubling situation, and so the coaching involvement style is reported to be the most effective because it shows the adolescents the parents are involved and care, yet give them room to grow and develop skills of their own.

My Most Embarrassing Situation Essay

Everyone has been embarrassed at one time or another. It is that moment in time when you wish the earth would open up and swallow you. The anxiety and discomfort felt during that time which may only last a few seconds feels like time has stood still. I remember so well when I had my most embarrassing moment. I was in Form 4 and it was during the school recess. The minute the bell rang for recess, I rushed to the toilet because I had been controlling my urges since class started. I didn’t want to miss class because the lesson taught that morning was to include tips for the forthcoming examination. Without realising, I had rushed to the girls’ toilet. The prolonged control and an upset stomach made worse by two glasses of cold milk in the morning made me grunt and groan in what I thought in what I thought was the privacy of the cubicle. I thought I heard giggling outside and wondered why the giggles sounded unusually near. A few minutes later I came out the cubicle and discovered my horror that I had entered the girls’ toilet. To make matters worse, the few girls standing outside didn’t even turn away when I came out. Instead they looked down at me, then only they turned quickly away. Horror of horrors, I had forgotten to zip up! No beetroot could have  matched the colour of my face at this point in time! They news of my predicament spread like wild fire throughout school. I was truly the talk of the town. I felt like I could either walk around feeling perpetually self-conscious and embarrassed or I could turn the situation round, perhaps even to my advantage. I remembered my mother’s words that ‘if you can’t beat them, join them’. So I decided to make fun of myself, to laugh at myself too. It works. Everyone got bored after a while and nobody teased me after that. It was indeed an eye-opening experience for me. I have learnt that when people laugh at you, you should laugh along. You must not take yourself seriously. Learn to look at yourself through other people’s eyes and you will realise that most of the time when they laugh at you, they just want to have some fun. They mean no harm. If you can make people laugh, it’s like bringing sunshine into their lives and as someone said, ‘those who bring sunshine to the lives of others cannot keep it from themselves.’

Performance Measurement for WWP

Performance Measurement for WWP Introduction Performance measurement has been described as a key tool in the achievement of TQM (Total Quality Management) in all types of organizations. The traditional approach to performance measurement has been focused on the examination of financial performance of an organization. This has mainly focused on a performance indicator that is available through changes in either profits or losses.Advertising We will write a custom proposal sample on Performance Measurement for WWP specifically for you for only $16.05 $11/page Learn More However, researchers who work in this area indicate that cost accounting information does not avail a complete bundle of information to support quality journeys. This is because they do not consider a contingent of issues, such as improvements, seen by the customer. Furthermore, they focus on the examination of a stakeholder from the view of an investor or shareholder. This has presented a number of challenges for non-profit organizations with the main aim to serve a specific segment of the society. Furthermore, performance is best measured through an examination of all perspectives of an organization. Regardless of the industry, organizations have the responsibility to come up with strategies that make it easy for customers to not only know about their goods and services, but also have the desire to provide assistance with them (Armstrong, 2007). This feat is not easy to accomplish because of challenges businesses have to face. There is the issue of stiff competition from other businesses in the same industry, economic problems that hinder the customers’ willingness to buy some products, and the presence of several distractions, which have the potential to come in between the customer and the company’s products. These are just some of the challenges that managers have to deal with in their bid to reach out to the intended audience. Need For Performance Measurement Many organizations in th e todays business world recognize that there is the need to capture a complete picture of organizational performance. This has led to the incorporation of a whole cocktail of performance measurement tools in attempts to capture their organizations’ performances. It is within this perspective that the need to institute effective performance measurement mechanisms has attracted a host of organizations and researchers. General understanding is that through the entrenchment of a culture that takes cognizance of organizational objectives, a cocktail of benefits and efforts focused on better organizational performance can be implemented.Advertising Looking for proposal on business economics? Let's see if we can help you! Get your first paper with 15% OFF Learn More According to Kaplan and Norton (1992), the focus of these performance measurement initiatives should revolve around finances, internal processes, learning, growth and, of course, customers. In fa ct, empirical research on performance measurement shows that undertaking this process can help management with implementing the process that supports process improvement and development of a cost-effective product design (Turney, 1991), and avail managers with an integrative framework to manage organizational activities. WWP (Wounded Warrior Project) stands at a vantage position to meet the expectations of the stakeholders by examining the performance of the four major organizational perspectives i.e., learning and growth, customers, internal business processes and finances. The learning and growth perspectives â€Å"will be viewed as an attempt at promoting growth and development by creating an enabling atmosphere that supports change and innovation† (Amstrong, 2007). According to Armstrongs opinion (2007), this strategy should be boned in mind of any Chief Executive Officer of the organization in order to ensure an overall efficiency of the business process. This may be imp lemented through the modernization of the services or goods, especially through the employment of modern technology and replacement of obsolete equipments in order to cultivate and enhance better quality of services to clients’ satisfaction. Focus on infrastructure improvement should be paid cognizance to. The development of staff should also be carried out through creation of a learning organization and where organizational learning takes place at the same time as advocated for by Armstrong (2007). This should be carried out through the provision of avenues that promote learning, training, and development. It should be understood that while technology, products, and services can be replicated, knowledge cannot. In the global competition today, attention to the human capital has grown in bounds. To move forward and drive successful business, staff focus, engagement and involvement should be paid cognizance. Subsequent benefits would include better quality of services to achie ve total customer satisfaction, increase business, obtain lesser complaints, and a train a fully engaged workforce that is fully committed to its responsibilities.Advertising We will write a custom proposal sample on Performance Measurement for WWP specifically for you for only $16.05 $11/page Learn More The internal business perspective, on the other hand, addresses issues related to how business processes are adopted to the needs of the customers and shareholders. This should be implemented through the creation of an internal infrastructure that supports high quality of services in time at a cost effective manner with registered benefits in overall businesses performance. Clients focus should ideally center on better service delivery and should reflect the company’s value attached to the customers (Armstrong, 2007). This should be applied through improvement of service delivery and creation of better efficiency in the delivery of services to the cl ients. Essentially, this should be geared towards timely and efficient services delivery to clients in a cost effective manner that ensures for sustained competitiveness. Ideally, the management should embrace strategies that ensure the delivery of high quality service and integrity, development of products that really match with the needs of the clients, ensure value for money spent and devise mechanisms that make it easier to do business with the clients. Finally, the financial perspective addresses how WWP wishes to be viewed by the stakeholders. The management can implement this though several initiatives. The first one would be the establishment of a price control that would allow for significant improvements in investment in the services that ensure better advantage. WWP will create strategy maps highlighting the areas it want to measure. This will act as the overall architectural framework specifying the critical elements and associated linkages for the overall strategy. This , in essence, acts as a universal message presentation forum for the top executives towards specification and subsequent presentation of the envisaged destination, mapping of the route to be followed and communication mechanisms. Stakeholder Analysis and Recommendation for Participation With the mission to honor and empower wounded soldiers, WWP consists of a number of stakeholders whose interests and views must be given cognizance in performance measurement program. These include the wounded soldiers, donors, families of the wounded soldiers, the government, and social welfare organizations. This is because for WWP to achieve its objectives, it must develop links with other industry players and enlist the support of its stakeholders.Advertising Looking for proposal on business economics? Let's see if we can help you! Get your first paper with 15% OFF Learn More Ideally, the focus on well defined performance dimensions should require that the development of specific measures to be done, that helps to effectively monitor and progress in the articulated dimensions (Armstrong, 2007). As Kanji (1997) has noted, the dynamics of the operational environments dictates that the changing needs of all the stakeholders be captured in the performance measures. Consequently, it is important for WWP to examine performance from an internal as well as external perspectives, listen to customers, suppliers and other stakeholders, and not fall into the trap of building a self-centered performance measurement system. It is therefore necessary that WWP develop an ideal system that leads to the development, which supports learning and innovation. This should be the essential and final aim of a good performance measurement system that captures the interests and expectations of the stakeholders (Kanji, 1997). The complexity of an organizational management entails t he need for managers to view performance in a holistic manner, where several areas are captured simultaneously (Kanji, 1997). This should be structured around the tenets of several factors that provide performance of a multi and interrelated perspective, and is linked to organizations’ values and strategies. Furthermore, WWP’s performance measurement should be based on critical success factors or performance driver, valid, reliable, and easy to use, one that facilitates comparisons to be made and progress to be monitored, that is linked to the rewards system and encourages the appropriate behaviors and finally, one that highlights the improvement areas or recognizes the opportunities and suggests improvement strategies. As it can be deduced form the above presentations, it appears that the approach to performance management needs to be holistic, inclusive, and systematic. Essentially, a good performance system should present the combined effect of measuring different a spects or dimensions that are interacting or interrelating with each other. SWOC analysis of WWP A SWOC analysis is a major way to examine the position of a business and examine areas of weaknesses and challenges it needs to focus on and areas of strengths and opportunities it needs to explore. A SWOT analysis simply means looking at the strengths, weaknesses, opportunities, and challenges to the business in order to achieve its strategic intents (Hill and Westbrook,1997). WWP has several strengths, a couple of weaknesses, several opportunities, and a small number of challenges. For example, WWP has the capacity to attract highly trained personnel from a large pool of wounded soldiers it seeks to serve. Furthermore, WWP has a well-established knowledge base, makes use of technology in its programs, and has extensive contacts with its clients. However, it is encompassed by a number of weaknesses that hinder to strive towards meeting its objectives. These include possible lack of moti vation and low reputation. This because WWP is still in its formative years and as such, has not developed extensive networks and attain reputation of high status. On the other hand, WWP has a number of opportunities, thus it can ensure that it lives up to the expectations of the stakeholders. These include availability of technological innovations to reach larger donor bases and increasing levels of understanding and empathy shown towards wounded soldiers. A number of challenges that reduce its capacity for competence can also be pointed out. WWP relies on donors for support and as such may suffer from the challenge of adequate resources to undertake its programs. Furthermore, it must be subjected to a number of government regulations that may limit its scope in soliciting funds and operations. Performance Measurement Performance management (PM) refers to the assessment of progress at different organizational levels, toward achieving predetermined goals, as well as communication an d action in response to actual progress (Bourne, 2003). Within this perspective, it is fundamental to recognize that PM is not merely a tool for operational management. On the contrary, it is, at its best, an overall, integrative approach, linking operational activities to strategic outcomes. Organizations in the business world employ some type of strategic planning in the development of objectives or initiatives. It has been advanced that the key to achieving success in the organization’s performance is an accurate and insightful linkage of the organizational visions and daily activities within the organization. Empirical evidence would however paint the picture that is not always easy or attainable (Armstrong, 2007). One of the chief bottlenecks has been cited as the use of poor performance measures (Kaplan and Norton, 2007). Several researchers have buttressed this point and pointed out that the lack of appropriate measurement tools as positively correlated to organization ’s failure to attain envisaged goals (Kaplan, 2007). For example, Armstrong (2007) in his study on organization’s use of performance measures has concluded that a majority of organizations fail to link their firms’ strategies with the performance measures. In the opinion of Kaplan (2007), the failure to encapsulate the strategic intents in performance measures has proved to be a major headache to many managers. This is particularly worrying when an effective measurement system provides the managers with an ample tool that can be employed in the assessment of whether activities occurring within a facility, division or department are in support of the attainment of the firms overall objectives as stipulated in the vision and missions of the firm. Brotherton and Hacker (2006) have pointed out that what is missing out in most management strategies may not be the planning aspect but rather the implementation. In their opinions, the implementation should encapsulate a n effective measurement system in order that the actions and plans are appropriately linked and are in tandem with the envisaged corporate objectives. This should ideally present an accurate presentation of where WWP is now and where it intends to be. A salient limitation has conversely been cited as the failure to link other aspects of organizational activities such as internal business organization, employees’ development, learning and organizational growth and customer relations in performance measures and the sole reliant on financial assessments of organizational performance. As Kaplan (2007) has pointed out, â€Å"over 70% of CEO failures came, not as a result of poor strategy, but the inability to execute.† Indeed, the departure from traditional financial measures as the anchorage on which organizational wellbeing is grounded has been pointed out as the reason for the invention of the Balanced Score Cards (Kaplan, 2007). According to Brotherton and Hacker (2006) , putting the organization vision and linking this to the strategy of organizations is the key ingredient to success in performance measurements, and thus, the strategic planning process should ideally encapsulate the strategic intents of the organization. This, to the authors opinion should be the starting point in effective measurement system. Essentially, the vision of the organization needs to be translated into specific, measurable objectives or initiatives. This is because by quantifying the vision through measurable objectives, an organization is able to determine whether it is on the right track. This will enable WWP to assess the rate of progress towards the attainment of the stipulated objectives. Unfortunately, majority of organizations appears not to pay heed to these sentiments (Armstrong, 2007). Armstrong (2007) has pointed out that performance measurements at their broadest forms that should involve the setting up of performance goals and the subsequent measurements o f the organization’s attainment or lack of such goals against a set criteria (Brotherton Hacker, 2006). Towards this, performance metrics are developed for each level and function within the organization, structured around the frameworks in order to facilitate the attainment of the envisaged goals and objectives. Thus, while the specific steps and verbiages may vary among the performance management methodologies and systems, the general bearing is essentially the same among the multitudes of organizations that claim to measure their performances. Kanji (1997) has observed that accounting figures alone do not provide a clear direction or an emphasis on whether the particular elements under scrutiny will result in good or poor financial results. This is because these financial measures may not pay cognizance to the need for improving customer satisfaction, quality, cycle time, or even employees’ motivation. Indicators of the Achievement for the Projected Outcomes As it has been stated above, performance measurement has been described as a key tool for the achievement of TQM (Total Quality Management). The main indicator for the achievement of the projected outcomes of the performance measurement in WWP will be the attainment of TQM constructs. These include leadership, management, and empowerment. In essence, TQM attainment in WWP as a non-profit organization calls for the inclusion of all stakeholders in decision-making. Total quality management (TQM) has been considered an important theme in business and management studies over the years due to its capability of influencing the desired outcomes of individuals and organizations alike (Kaplan, 2007). Various definitions of TQM have been used in numerous studies and no general definition of TQM exists in today’s literature. So far, the concept of TQM has different meanings to different individuals. Dale (1999) states that TQM refers to the overall participation of organizational members to e ffectively make use of their business processes and generate the products and/or services necessary for accommodating the needs and desires of customers. Meanwhile, Yang (2005) defined TQM as â€Å"a philosophy and a set of guiding principles that represent the foundation of a continuous improving foundation.† TQM can also be described as a continual process that aims at providing excellence by developing and maintaining the proper skills and characteristics among organizational members, so they can generate satisfaction among their customers (Lakhe and Mohanty, 1994). Similarly, Yang (2005) believes that TQM is a set of practices that promotes improvement, frequent evaluation of results, as well as long-term planning. Though there have been different definitions for TQM that have been mentioned above, the concept’s general principles and values are still described in each of them (Yang, 2005). TQM’s philosophy of management is centered on customers that encoura ges members of a TQM organization to efficiently facilitate the improvement of their company through the active involvement of employees. Within WWP, the individual concepts of process control, service quality, and quality improvement are all integrated into the TQM approach. Conclusion and Recommendations Many organizations in the business world today are recognizing that there is a need to adopt performance measurement tools that present a complete picture of organizational performance and are mushrooming towards effective tools in their performance measurements. WWP stands to reap a cocktail of benefits through the initiation, development, and implementation of effective performance measurement mechanisms that have the capacity to enhance its performances levels. As it has been stated above, critical organizational perspectives that should emphasize on this program include finances, internal processes, customers, growth and learning. These may be adjustable providing particular o rganizational contexts in terms of the number and perspectives. WWP is best placed to create strategy maps highlighting the areas they want to measure. This will act as the overall architectural framework specifying the critical elements and associated linkages of the overall strategy. This in essence acts as a universal message presentation forum for the top executives towards specification and subsequent presentation of the envisaged destination, mapping of the route to be followed and the communication mechanisms. The philosophy behind this step is developing a measure that goes beyond just financial performance. The advantages are that the manager can adopt a holistic view of the organizational performance, a cohesive and ongoing assessment is also possible, a focused connection of the top level and mid levels strategies is established, and it improves the organizational performance reporting system. The benefits of adopting performance measurement program outweigh its limitatio ns, chief among them the fact that the process of design and implementation is all-inclusive. While being a top down approach, the strategic intents still have to involve the mid level and floor employees. The key to success are therefore reliant on proper planning, implementation, and follow up and the performance measurement tool must have the capacity to present a more holistic approach to the organizational performances that would essentially encapsulate all the key elements of performance. References Armstrong, A. (2007). A hard book of human resources management. Kogan Page Publishers: London. Bourne, O. (2003). The balanced scorecard: translating strategy into action. Cambridge, MA: Harvard Business School Press. Brotherton, L and Hacker, L. (2006). The golden rules for implementing the balanced business scorecard. ,Information Management Computer Security, 45 (3): 12-25. Hill, T. Westbrook, R. (1997). SWOT Analysis: It’s Time for a Product Recall. Long Range Plannin g, 30 (1): 46–52. Kanji, Y. (1997). Total quality management and the performance measurement barrier. The TQM Magazine, 10 (2): 45-63. Kaplan, R. and Norton, D. (1992).The balance scorecard-measure that drive performance. Harvard business Review: Harvard. Lakhe, R.R. and Mohanty, R.P. (1994). Total quality management concepts, evolution and acceptability in developing economies. International Journal of Quality Reliability Management, 11 (9), 9-33. Turney, K. (1991). Essays on performance measurement models, Universitat Pompeu Fabra, Australia. Yang, C.C. (2005). An integrated model of TQM and GE-Six Sigma. International Journal of Six Sigma and Competitive Advantage, 1 (1), 97-105.