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.