Lord of the Flies Essay on Fire - 627 Words

Fire is a symbol that cannot be described in one word. Fire represents destruction, death, hostility, unpredictability, and the potential for limitless violence. Fire, however, also has a good side to it. Fire can be health, hospitality, control, food, shelter, light, and strength. With these characteristics in mind, fire has a number of different connotations. Many of these connotations can be found in one book. Fire, in William Golding’s book, Lord of the Flies, is a complex symbol, representing anarchy and the darkness inside of us, civilization and the light in all of us, and hope, the constant motivator for our survival. Fire can represent Anarchy. Fire is naturally found where there is mass panic, destruction, and chaos. Fire can†¦show more content†¦Finally, Fire can represent hope. Fire creates smoke, a very visual symbol for either rescue or panic. In the case of LOTF, the first is true. With the smoke that comes from the fire, the boys have a small chance of signaling a passing ship and finding their way back home. When the Naval officer comes to rescue the boys, he notices them because of the smoke that has now engulfed the island, â€Å"We saw your smoke.† With the hope of the rescue still burning as long as the fire stays lit, the boys have something to survive for. Without the fire, the boys are lost and alone in a hostile world, where it becomes kill or be killed. Fire in the novel Lord of the Flies takes on a new form each time it is presented to us. Sometimes, it takes the form of a violent, evil flame, bent on causing havoc and anarchy wherever it may be. Sometimes, it may take the form of a calm, controlled, civilized flame. Other times, it may be flame that drives a man to feats that he would have never thought he could do. Fire, in William Golding’s book, Lord of the Flies, is a complex symbol, representing anarchy and the darkness inside of us, civilization and the light in all of us, and hope, the constant motivator for ourShow MoreRelatedLord Of The Flies Fire Symbolism Essay813 Words   |  4 PagesDon’t play with fire. Fire is unpredictable, uncontainable, and its results are everlasting. Nonetheless, fireplaces, campfires, and birthday candles, rouse the fascination of children and adults because it is the universal symbol of spirit. Unlike conventional symbols, fire has an intrinsic relationship with the spirit it r epresents. A fire radiates heat and light to create an impression of power and liveliness. The vivacious flames are always dancing in different patterns, but maintain a degreeRead MoreRalph And Simon Essay981 Words   |  4 Pages Ayden Gore Mr. Foley English Literature Honors 9/6/17 Lord of the Flies Essay Lord of the flies is about a group of British boys that are fleeing an ongoing war. Unfortunately, their plane goes down on the way to safety. The boys land on a mysterious island and they have to try and survive until they are rescued. The characters face many problems along the road, from trying to keep a fire going, to trying to stay civil. Near the end, people rebel and slowly evolve into savagesRead MoreThe Lord Of The Flies By William Golding1065 Words   |  5 PagesThe Lord of the Flies Essay The Lord of the Flies written by William Golding and published on September 17, 1954 is a story told about a group of stranded boys and their fight for survival against the wilderness and themselves. In this story many signs of symbolism are used by Golding to point out certain aspects of society that Golding thought strongly of. This story on first read may just seem to be a survival- esque piece of literature but, on a deeper look one can find Golding’s true motiveRead More Importance of Fear in The Lord of the Flies Essay1167 Words   |  5 PagesImportance of Fear in The Lord of the Flies   Ã‚  Ã‚  Ã‚  Ã‚   The boys in the book, The Lord of the Flies, are controlled by their fear of the beast.   This fear is not of the beast itself, but of the unknown. It comes from not knowing whether or not a beast exists.    The children start as one united group.   They are a community in their own.   Slowly, rules started to get broken, individuals began to leave, and the group broke apart.   The one thing that causes this break-up is the beast. TheRead MoreSymbolism in Lord of the Flies by William Golding1153 Words   |  5 PagesGonzalo Barril Merino 3EMC Lord of the Flies Essay Describe the use of symbolism in Lord of the Flies By understanding symbols, you get a better picture of the novel â€Å"Lord of the Flies† and the hidden messages and references to human nature and a criticism of society. The author, William Golding, uses a huge amount of symbolism to reflect society of the outer world with the island. Symbols of fire, the conch and water are described all throughout the novel. Fire represents hope, strength and knowledgeRead MoreLord of The Flies Essay1673 Words   |  7 PagesLord of the Flies was published in 1954 by William Golding. Today Lord of the Flies is a well known literary criticism. Many schools require their students to read Lord of the Flies because of the literary criticisms in the book. In this paper three themes or literary criticisms are talked about: good vs. evil, symbolism of characters, and maturity of characters. Another topic in Goldings Lord of the Flies is the battle of good vs. evil. Everything seems to start out just fine on the island; theRead MoreSymbolism in Lord of the Flies by William Golding1159 Words   |  5 PagesGonzalo Barril Merino 3EMC Lord of the Flies Essay Describe the use of symbolism in Lord of the Flies By understanding symbols, you get a better picture of the novel â€Å"Lord of the Flies† and the hidden messages and references to human nature and a criticism of society. The author, William Golding, uses a huge amount of symbolism to reflect society of the outer world with the island. Symbols of fire, the conch and water are described all throughout the novel. Fire represents hope, strength andRead MoreSimilarities and Differences Between Romeo and Juliet and Lord of the Flies1676 Words   |  7 PagesJack goes from hesitating to kill a pig to being able to viciously kill them †¢ Jack rejects Ralph’s authority and does not respect him †¢ Ralph talks to Piggy and Simon and tells them of their need for adults †¢ One of the â€Å"littuns†, Phil, die in a big fire †¢ Fighting and Arguing gets worse between Ralph and Jack who has form a â€Å"gang† of hunters †¢ Piggy is killed – Stone rolling and knocking him off a cliff †¢ Simon is killed – when he is mistaken for the â€Å"beast† †¢ Ralph was about to be hunted and killedRead MoreComparative Essay: Leadership Lord of the Flies and Animal Farm1120 Words   |  5 Pagesï » ¿Comparative essay: Leadership in Lord of the Flies and Animal Farm Essay question: You are required to write a comparative essay. You should compare one aspect of the texts such as theme, conflict, character or relationship. The texts are ‘Lord of the Flies’ and ‘Animal Farm’. The two books, Lord of the Flies and Animal Farm circle around the themes of power, leadership, law, disorder, good and evil. On a personal level, these themes come up in the way people relate to each other: How theyRead MoreLord Of The Flies Symbolism Analysis733 Words   |  3 Pages Lord of the Flies Lord of the Flies has symbols throughout the story, each character brings a different point of view. Piggy, Ralph, and Jack take a leading role with all the boys, although they vote Ralph in charge both of the other boys take a leadership position. Goulding uses the boys to show the faults of mankind and the roots of all evil. Four symbols Goulding used in the novel were: Piggy’s glasses, the Conch Shell, The Beast, and Simon’s hiding place. Therefore, the symbols show the true

Social Anxiety Disorder Causes, Symptoms And Treatments...

Social Anxiety Disorder: Causes, Symptoms and Treatments The feeling of anxiety is familiar to all of us and we all experienced some anxiety and fear at least once in our life. Whether that was the first day in a new workplace, the first day in college, or before an important meeting, we felt that we were really anxious and nervous. From the evolutionary perspective, the conservation of fear and anxiety among some species is a good indication that those emotions are highly important for survival. Some people, however, experience an excessive and unreasonable amount of anxiety, which may be the result of social anxiety disorder. Social anxiety disorder (SAD) is a psychological disorder during which people experience enormous social phobia and are irrationally afraid of being judged by others in social settings (Lima OsoÃŒ rio, 2013). Although it is considered as a common anxiety disorder, I do believe that with appropriate treatments and therapies, individual approach to each patient and willingness to help them, many people can overcome t he social phobia, can make stronger interpersonal relationships with their friends and relatives, and can integrate into their social community with no or at least less fear of communicating with others. A lot of people may not feel comfortable in certain social settings, but where are the boundaries of just feeling uncomfortable and having social phobia? Descriptions of social phobia may be found as early as since Hippocrates (around 400Show MoreRelatedEssay on Social Anxiety Disorder (SAD)1308 Words   |  6 PagesSocial anxiety disorder (social phobia) can be described as an extreme, persistent fear of being scrutinized or judged by others in social situations. This fear may lead to feelings of embarrassment, humiliation and self-consciousness. 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Because of this I choose to focus much of my emphasis on the difficulties one face, that’s diagnosed with GAD and the hard ship of building and maintain a good client relationship. Generalized anxiety disorder begins at the onset of a worry and or tension that carries on into more severe

Association of Human papillomavirus and Breast Tumours Free Essays

string(215) " apoptosis of abnormal cells, whereas E7 inactivates Rb \(retinoblastoma\) function, which results in abnormal cell proliferation and disturbs the normal cell cycle regulation \(Wang, 2007; WHO, 2006; Mera, 1997\)\." Abstract: Cancer arises due to abnormal changes or mutations, in the genes responsible for regulating the growth of cells. Human papillomavirus (HPV) is considered the aetiological agent for many cancers including cervical cancer. HPV causes disruption and loss of some of the viral genes such as L1 and L2 genes and also increases the expression of the early genes. We will write a custom essay sample on Association of Human papillomavirus and Breast Tumours or any similar topic only for you Order Now Several studies have addressed a relationship with HPV and breast cancer, as different HPVs have been identified. Most of the studies were successful in finding evidence in correlation of HPV 6, 11, 16 and 18 in invasive ductal breast carcinoma by using different techniques including DNA extraction and PCR, however other studies achieved low positivity or negative result. The aim of this study was to find out the association of HPV and Breast cancer. DNA was successfully extracted from archived breast tissue samples using DNA extraction method. This DNA sample could be amplified by using PCR to find HPV genome specifically targeting E1 gene. This is an ongoing work by the supervisors of the project to try and detect HPV genome in breast cancer, if successful a vaccine could be developed against various strains of HPVs worldwide and it could save many lives. Keywords:Human papillomavirus, DNA Extraction, Breast cancer, Vaccine, PCR, 1. Introduction: 1.1. Breast cancer: Breast cancer is a malignant tumour that originates in the breast tissue, mainly from the inner lining of milk ducts or the lobules that supply milk to the ducts, cancers that initiates from ducts are called ductal carcinomas and those originating from lobules are called as lobular carcinomas. Cancer occurs due to abnormal changes or mutations, in the genes responsible for regulating the growth of cells (Sariego, 2010). The change in the genetic information causes a cell to no longer carry out its function properly (Almeida Barry, 2010). The following figures show the two types of cancers Benign and Malignant. (Almeida; Shela, 2010) Figure: 2 malignant tumours Figure 1 and 2: above shows benign vs. malignant cancers. (a) A benign tumour is a mass of cells that remains within the tissue in which it originally developed. (b) The invasion of cancer cells into surrounding tissues is the hallmark of a malignant tumour. Malignant cells may break free from the tumour and travel to other locations in the body through the process of metastasis (Almeida Barry, 2010). 1.2. Epidemiology: Breast cancer is one of the main health problems worldwide (Bao, 2011) and which resulted http://en.wikipedia.org/wiki/Breast_cancer – cite_note-WHO_WCR-2 458,503 deaths in 2008 worldwide out of which 13.7% are of cancer deaths in women and it is about 100 times more common in women than in men (Veto, et al., 2009). The table below shows how females are susceptible to breast cancer at different ages for example there is 1 in 8 risk of developing breast cancer in females in the U.K in lifetime. Table 1: Shows estimated risk of developing breast cancer by age, females, UK, 2008 UK, 2008 Adopted from: www.cancerresearch.uk http://info.cancerresearchuk.org/cancerstats/types/breast/riskfactors/ Date accessed: 20/01/11 The table 2 below shows that more deaths happens in females due to breast cancer than males as it can be seen from the table only 69 males died in 2008 in compare to 12,047 females. Table 2: Shows the number of deaths and mortality rates in the UK in 2008. Adopted from: www.cancerresearch.uk http://info.cancerresearchuk.org/cancerstats/types/breast/mortality/#age Date accessed: 20/01/11 The figure below shows the incidence and mortality rates from female breast cancer in EU countries. As it can be seen from the table Belgium has the highest rates of incidence in female breast cancer. Figure 1 above is a graph of incidence and mortality rates in EU. Adopted from: www.cancerresearch.uk http://info.cancerresearchuk.org/cancerstats/types/breast/incidence/ Date accessed: 20/01/11 1.3 . Breast cancer Pathophysiology: 1.3.1 Aetiology: Some of the suspected aetiological factors which influence the cases of breast cancer are family history, obesity, age, oral contraceptives and alcohol. Family history: A woman who has a family member with breast cancer increases double the risk of getting breast cancer in compare to a woman with no family history (Lancet, 2001). Obesity: obesity increases the risk of postmenopausal breast cancer by up to 30%, since levels of hormones rises with excess body fat such as oestrogen and insulin these are the common features of cancers. Age: older women are at higher risk. Particularly women aged 50-69 are most at risk, predominantly those with a late menopause. Oral contraceptives: increases the risk by approximately a quarter but since people who uses are commonly younger women, therefore the risk is fairly low. Alcohol: drinking alcohol as less as one alcoholic drink each day increases the risk of breast cancer by around 12%. (Cancer Research U.K, 2008) Some other factors include: Lesions to DNA such as genetic mutations. There is link between mutations that can lead to breast cancer and oestrogen exposure, found out by carrying out experiments. Another factor is when a body fails to carry out immune surveillance; it is a theory in which the immune system gets rid of malignant cells throughout one’s life. Other factor is inherited defects in DNA repair genes, such as †BRCA1†, †BRCA2† and †TP53† (Adams, et al., 2011). Figure 2 above shows the percentage of different genes with associated risk. Figure adopted from: Wooster and Webber, (2003) Date accessed: 12/04/11 Moreover according to many authors there is a potential link between the HPV and breast cancer. 1.4. Human papillomavirus and Cancer: HPV genome is normally found in the cytoplasm of infected tissues however, the DNA of HPV types that cause cancer are integrated into the host genome. HPV causes disruption and loss of some of the viral genes for example (L1 and L2 genes) and also increases the expression of the early genes (Wang, 2007; Mera, 1997). Oncoproteins E5 interacts with MHC I and prevents its transport to the cell surface therefore infected cells escapes the immune system consequently allowing the virus to establish persistent infections and thus progressing to cancer. E6 targets p53 for degradation and therefore prevents apoptosis of abnormal cells, whereas E7 inactivates Rb (retinoblastoma) function, which results in abnormal cell proliferation and disturbs the normal cell cycle regulation (Wang, 2007; WHO, 2006; Mera, 1997). You read "Association of Human papillomavirus and Breast Tumours" in category "Essay examples" P53 and Rb are tumour suppressor genes which stop tumours from developing (Mera, 1997). Incorporation of virus into host cell increases and sustains the growth of both virus and the host cell, thus resulting in the alteration of infected host cells into malignant cells (Mera, 1997; Wang, 2007) and ultimately invasive cancer. Figure 3 above shows different genes in HPV. Adopted from: Symptoms of HPV 2010 symptomsofhpv.net/113/hpv-16/ Date accessed: 07/04/11 Table 9 below shows the function of different genes within the HPV virus: Gene/RegionFunction E1/E2Code for proteins which control the function of E6 and E7 genes. E4Function largely unknown but may control virus release from cell. E5Codes for a hydrophobic protein which enhances immortalisation of the cell. E6Codes for proteins which inhibit negative regulators of the cell cycle .E6 products inhibit p53 which is a transcription factor for apoptosis (programmed cell death). E7Codes for products whichbind to the retinoblastoma tumour suppressorproteins thereby permitting the cell to progress through the cell cycle in the absence of normal mitogenic signals. L1/L2Code for structural proteins and formation of complete virus particles. LCRNecessary for normal virus replication and control of gene expression. Adopted from: Eurocytology http://www.eurocytology.eu/static/eurocytology/eng/cervical/LP1ContentMcontA1.html Date accessed: 19/03/11 The HPV (human papillomavirus) is a member of the papillomaviridae family and has a double stranded circular DNA genome (Wang, 2007). These viruses are small in size with 8kbp-long DNA genome and have no envelope (WHO, 2006). HPV genome contains early (E) and the late genes (L) which codes for early proteins (E1-E7), late proteins (L1 and L2) and a non coding long control region (LCR) (WHO, 2006; Mera, 1997; Govan, 2008). 1.4.1. High risk and low risk HPV types: There are more than one hundred different HPV types that have been discovered (WHO, 2006) and these are divided into high risk and low risk types. HPV 16, 18, 31 and 45 are some high risk HPV types associated with most of the cancer, while HPV 6 and 11 are low risk non-oncogenic HPV types (Brown, et al., 2005; Govan, 2008). Table3: the following table shows some high risk, low risk and potentially risk HPVs. ClassificationHPV types High-risk16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 Low-risk82, 6, 11, 40, 42, 43, 44, 54, 61, 70 Potentially high –risk26, 53 Source: Govan (2008) HPV 6 and 11 are linked with up to 90% genital warts (Von Krogh, 2011), nevertheless after the examination of 55 genital wart samples from Slovenia, using polymerase chain reaction (PCR), the authors concluded that HPV 6 and 11 genotypes were detected in 96.4% of genital warts patients (Potocnik, et al., 2007). 1.5. Signs and Symptoms: Changes that could arise due to a breast cancer are: A change in the size or shape of a breast A lump or thickening in an area of the breast Dimpling of the skin A change in the shape of the nipple, particularly if it turns in, sinks into the breast or becomes irregular in shape A blood stained discharge from the nipple (Dixon, 2005; Breast cancer, 2008). Figure 3a: above shows the symptoms of breast cancer Source: Healthbase (2008) http://blog.healthbase.com/2008_09_01_archive.html Accessed date: 11/04/2011 Normal anatomy of the breast: Female breast anatomy The structure of female breast is mainly made up of fat and connective tissue, but also contains milk ducts, lymph nodes, blood vessels and structures known as lobes and lobules (Rosen, 2009). Figure 4 above shows normal anatomy of breast tissue. The above figure adopted from: Mayoclinic (2009) http://www.mayoclinic.com/health/breast-cancer-early-stage/BC00001 Date accessed: 8 April 2011. Lobules and ducts Every breast has 12 to 20 lobules that protrude from the nipple and holds small alveoli; the lobules are connected together by a network of thin ducts (Rosen, 2009). Figure 5 above shows different parts in the female breast The above figure adopted from: Mayoclinic (2009) http://www.mayoclinic.com/health/breast-cancer-early-stage/BC00001 Date accessed: 8 April 2011. Stromata Spaces around the lobules and ducts are filled with fatty tissue, ligaments and connective tissue (stromata). The size of the breast is determined by the amount of fat it contains, the breast tissue is also sensitive to cyclic changes in hormone levels (Rosen, 2009). Figure 6 above shows the position of stromata in female breast. The figure adopted from: Mayoclinic (2009). http://www.mayoclinic.com/health/breast-cancer-early-stage/BC00001 Date accessed: 8 April 2011. Muscles Breasts are muscle free tissues, muscles lie beneath the breasts separating them from the ribs (Rosen, 2009). The above figure adopted from: Mayoclinic (2009) http://www.mayoclinic.com/health/breast-cancer-early-stage/BC00001 Date accessed: 8 April 2011. Arteries and capillaries Blood supply all the essential nutrients and oxygen to the breast tissue through arteries, capillaries and small blood vessels (Rosen, 2009). Figure 8 above shows the position of capillaries and arteries in and around the breast. Figure adopted from: Mayoclinic, (2009) http://www.mayoclinic.com/health/breast-cancer-early-stage/BC00001 Date accessed: 8 April 2011. Lymph nodes and lymph ducts The lymphatic system contains blood vessels, lymph ducts and lymph nodes that helps fight infection, lymph nodes are present behind the breastbone, under the armpit and in other parts of the body engulfs harmful substances that are in the lymphatic system and safely get rid of them (Rosen, 2009; Mayoclinic, 2009). Figure 9 above shows the position of the lymph nodes and lymph ducts. The above figure adopted from: Mayoclinic, 2009 http://www.mayoclinic.com/health/breast-cancer-early-stage/BC00001 Date accessed: 8 April 2011. 1.4. Different types of Breast cancers: There are different types of breast cancer for example ductal and lobular and it depends on the type of tissue that it is derived from. Table 3.1 below shows the list of different types of breast cancer: DCIS – ductal carcinoma in situ LCIS – lobular carcinoma in situ Invasive ductal breast cancer Invasive lobular breast cancer Inflammatory breast cancer Paget’s disease Breast cancer in men The following figures show some of the main types of the cancer that begins in different areas of the breast for example the ducts, the lobules, or in some cases, the tissue in between. These figures also show the different types of breast cancer, including non-invasive, invasive, metastatic and recurrent breast cancers. a. Ductal Carcinoma in situ (DCIS) Range of Ductal Carcinoma in situ (DCIS) Figures: 10 and 11 above show normal breast with non–invasive ductal carcinoma in situ (DCIS) in an enlarged cross–section of the duct. Adopted from: Breast cancer (2008) http://www.breastcancer.org/symptoms/types/dcis/diagnosis.jsp Accessed date: 20/01/2011 Breast profileABCDEFG DuctsLobulesDilated section of duct to hold milkNippleFatPectralis major muscleChest wall/ rib cage EnlargementDuctal cancer cellsNormal lobular cellsBasement membraneLumen ( centre of duct) Table 4: shows the annotation of the above figures (Trentham-Dietz, et al., 2011) b. Lobular Carcinoma in situ (LCIS Figure: 12 above shows normal breast with lobular carcinoma in situ (LCIS) in an enlarged cross–section of the lobule. Adopted from: Breast cancer (2008) http://www.breastcancer.org/symptoms/types/ilc/tests/diagnosing.jsp Accessed date: 20/01/2011 Table 5 shows the annotation of the figure 12. Breast profileABCDEFG DuctsLobulesDilated section of duct to hold milkNippleFatPectralis major muscleChest wall/ rib cage EnlargementNormal Ductal cellsLobular cancer cellsBasement membrane (Trentham-Dietz et al., 2011) a.Invasive Ductal Carcinoma (IDC) Figure 13 above shows normal breast with invasive ductal carcinoma (IDC) in an enlarged cross–section of the duct. Adopted from: Breast cancer (2008) http://www.breastcancer.org/symptoms/types/ilc/tests/diagnosing.jsp Accessed date: 20/01/2011 Breast profileABCDEFG DuctsLobulesDilated section of duct to hold milkNippleFatPectralis major muscleChest wall/ rib cage EnlargementNormal duct cellsductal cancer cells breaking through the basement membrane Basement membrane Table 6 shows the annotation of the figure 13. (Trentham-Dietz, et al., 2011) c. Invasive Lobular Carcinoma (ILC) The above figure 14 shows normal breast with invasive lobular carcinoma (ILC) in an enlarged cross–section of the lobule. Adopted from: Breast cancer (2008) http://www.breastcancer.org/symptoms/types/ilc/tests/diagnosing.jsp Accessed date: 20/01/2011 Table 7 shows the annotation of the figure 14. Breast profileABCDEFG DuctsLobulesDilated section of duct to hold milkNippleFatPectralis major muscleChest wall/ rib cage EnlargementNormal cellsLobular cancer cells breaking through the basement membraneBasement membrane (Trentham-Dietz, et al., 2011) Following are some examples of non-invasive cell growths: d. Non-Invasive Cell Growth Subtypes – Solid Figure: 15 shows A cancer cells B basement membrane Adopted from: Breast cancer (2008) Accessed date: 20/01/2011 e.Non-Invasive Cell Growth Subtypes – Cribriform Figure: 16 above shows (A) cancer cells (B) basement membrane (C) lumen (centre of duct) Adopted from: Breast cancer (2008) Accessed date: 20/01/2011 f. Non-Invasive Cell Growth Subtypes – Papillary Figure: 17 above shows (A) cancer cells (B) basement membrane (C) lumen (centre of duct) Adopted from: Breast cancer (2008) Accessed date: 20/01/2011 g. Non-Invasive Cell Growth Subtypes – Comedo Figure: 18 above shows (A) living cancer cells (B) dying cancer cells (C) cell debris (necrosis) Adopted from: Breast cancer (2008) Accessed date: 20/01/2011 h. Vascular and Lymphatic Invasion Figure: 20 above shows normal breast with cancer cells invading the lymph channels and blood vessels in the breast tissue Adopted from: Breast cancer (2008) Accessed date: 20/01/2011 Table 8 shows the annotation of the above figure Breast profileABCDEF Blood vesselsLymphatic channels EnlargementNormal duct cellscancer cellsBasement membraneLymphatic channelBlood vesselBreast tissue 1.4. Diagnostic tests: Diagnosis of the breast cancer incorporates x-rays and screening tests and following are some of the important diagnostic tests that can be carried out before and after symptoms of breast cancer. Tests: Mammogram: A mammogram is the main screening test for asymptomatic patients who are over the age of 40 as well as for symptomatic adult patients (Bao, 2011).This test has a high sensitivity and specificity (Banks, 2004). If a mammogram does not find out an abnormality in patients with a clinically detected breast mass, additional imaging ultrasound and/or MRI should be carried out for further evaluation (Bao, 2011). Outcome: The results are indicative of malignancy include: an irregular speculated mass, clustered micro-calcifications, and linear branching calcifications (Banks, 2004; breast cancer, 2010). The above figure 21 shows how mammography is carried out. Figure 21 adopted from: Breast cancer (2010) http://www.breastcancer.org/symptoms/testing/types/mammograms/ Accessed date: 02/04/2011 Breast Ultrasound: Ultrasound sends high-frequency sound waves through the breast and changes them into images on a screen. The ultrasound technician places a sound-emitting probe on the breast to carry out the test and there is no radiation involved (Matsuzaki, et al., 2010). Outcome: The results are indicative of malignancy include: a hypo echoic mass, an irregular mass with internal calcifications, and enlarged auxiliary lymph nodes (breast cancer 2010; Moss, 1999). The above figure 22 shows how ultrasound is carried out. adopted from: Breast cancer (2010) http://www.breastcancer.org/symptoms/testing/types/ultrasound.jsp Accessed date: 02/04/2011 Breast MRI: MRI uses magnets and radio to produce detailed cross sectional images of the inside of the body. MRI screens high-risk women (breast cancer, 2010). The Sensitivity is 88% to 91%. Specificity is about 67% (Bluemke, 2004). Outcome: The results are indicative of malignancy include: a heterogeneously enhancing area and significant architectural distortion (Bluemke, 2004). The above figure 23 shows how MRI is carried out. adopted from: Breast cancer (2010) http://www.breastcancer.org/symptoms/testing/types/mri/ Accessed date: 02/04/2011 Biopsy: There are different types of biopsy techniques and among these techniques Fine needle aspiration (FNA) is the least invasive procedure and has high sensitivity and specificity (Dayal, et al., 2011). FNA is good for quick diagnosis of malignancy. Nonetheless, core biopsy is generally favoured, as it effectively differentiates between pre-invasive and invasive disease and is less chance getting inadequate sampling (Dayal, et al., 2011). Outcome: Invasive ductal carcinoma is responsible for almost 80% of all breast cancers, cords of tumour cells among associated glandular formation, which make varying degrees of fibrotic response. Whereas invasive lobular carcinoma, small tumour cells that invade past the basement membrane of the lobules and form an â€Å"Indian file† between collagen bundles, usually appears as well-differentiated tumour cells that display tubule formation (Dayal, et al., 2011). 1.5. Aims and Objectives: The aim of this project was to evaluate the association of Human papillomavirus (HPV) and breast cancer, additionally to collect the studies that support the presence of HPV DNA in patients with breast lesions worldwide. The archived samples diagnosed with breast carcinoma, will be used to extract the DNA by DNA Extraction method which could be further used for amplifying this DNA using PCR to detect HPV genome. This will ascertain the role of this virus in the pathogenesis of breast cancer and will also help the scientist for further investigation of this virus on biology of cancer. The following is the methodology of my project as how I carried out the experiment and extracted the DNA. 2. Methodology: The methodology incorporates materials and method, health and safety, ethical issues and statistical analysis. 2.1. Method and Materials: The following table 9 shows the materials that have been used to extract the DNA. Materials Measurements Universal tubes 20 ml, 5ml Epindorf tube 1.5 ml, 500ul Gilson pipetts 2x 5- 50ul, 2x 0.1 – 2.5 ul,2x 100 – 1000ul, 1x 20 – 200ul Dry heat block ( incubator) Vortex Waterbath ( 37c) Centrifuge and microfuge 70% of alcohol to avoid contamination and spray bottle Ice box 10. Thermometer( to measure the temperature) 11. Spectrophotometer( OD reader) 12. Pipett tips 13. Tissue and Cell LysisSolution 600ul (60ml) 14. Proteinase K4ul ( 200ul) 15. RNase A2ul (400ul) 16. Protein Precipitation Reagent300ul (60ml) 17. Isopropanol1ml (2ml) 18. Ethanol70% 19. TE Buffer35ul (8ml) 2.2. DNA purification method from tissue: The following is the method used to extract the DNA from the archived sample of breast tissue. Lysis of Formalin-Fixed, Paraffin-Embedded (FFPE) Tissue i.Placed 10-50 mg of 10- to 35- µm thick paraffin sections into an appropriate tube. If using a larger amount of tissue, adjust the reagent volumes accordingly. ii.Diluted 4  µl of â€Å"Proteinase K† into 600  µl of â€Å"Tissue and Cell Lysis Solution† for each sample, and mixed. iii.Added 600  µl of â€Å"Tissue and Cell Lysis Solution† containing the â€Å"Proteinase K† to the sample and mixed. iv.Incubated at 65 °C for 30 minutes; followed by a brief (10 seconds) vortex mix. v.Cooled the samples to 37 °C and added 2  µl of â€Å"RNase A† to the sample; mixed thoroughly. vi.Incubated at 37 °C for 30 minutes. vii.Placed the samples on ice for 3-5 minutes and then preceded with total DNA precipitation (below). Precipitation of Total DNA Added 300  µl of â€Å"MPC Protein Precipitation Reagent† to 600  µl of lysed sample and vortex vigorously for 10 seconds. ix.Pellet the debris by centrifugation at 4 °C for 10 minutes at ?10,000 x g in a microcentrifuge. If the resultant pellet was clear, small, of loose, added an additional 25  µl of â€Å"MPC Protein Precipitation Reagent†, mixed, and pellet the debris again. x.Transferred the supernatant to a clean microcentrifuge tube and discarded the pellet. xi.Added 500  µl of â€Å"isopropanol† to the recovered supernatant. Inverted the tube 30-40 times. xii.Pellet the DNA by centrifugation at 4 °C for 10 minutes in a microcentrifuge. Carefully poured off the â€Å"isopropanol† without dislodging the DNA pellet. Rinsed twice with 70% â€Å"ethanol†, being careful to not dislodge the pellet. Centrifuged briefly if the pellet was dislodged. Removed all of the residual ethanol with a pipet. xv.Resuspended the DNA in 35  µl of â€Å"TE Buffer†. Source: Epicentre Biotechnologies 3. Result: DNA is extracted by a DNA histological processing using PCR and DNA extraction techniques. These are techniques used to extract, amplify and copy small segments of DNA. It is fast and inexpensive because significant amounts of a sample of DNA are necessary for molecular and genetic analyses (Mendizabal et al., 2008). 3.1. DNA Extraction: DNA was extracted by using DNA extraction protocol written in the method section. In the DNA extraction different solutions were used for example Proteinase K enzyme is used to digest protein and to remove protein contamination from DNA and to get to the pure DNA (Ebeling, et al., 1974). Also different machines incubators, vortex and centrifuge were used to break down cell walls. Following the DNA extraction PCR is used to amplify the DNA to find HPV genome. 3.2. PCR: Using the PCR to amplify a segment of DNA firstly the sample is heated so that the DNA denatures or divides into two pieces of single-stranded DNA. After that an enzyme called â€Å"Taq polymerase† synthesizes – builds – two new strands of DNA, using the original strands as templates. This process causes the duplication of the original DNA. Each of the molecules now carries one old and one new strand of DNA. After that each of these strands can be utilized to form two new copies, and the process continues in this manner. More than one billion exact copies of the original DNA segment is achieved by repeating the cycle of denaturing and synthesizing new DNA 35 or 40 times. This whole process of PCR is automated and can be done in just a few hours. A thermocycler machine directs this process and is programmed to change the temperature of the reaction every few minutes to cause DNA denaturing and synthesis. Source: Bruce Fouke’s lab Accessed date: 20/01/11. There are many different types of PCR for example conventional PCR assays using consensus primers and highly sensitive Real-Time PCR (Hedau, et al., 2011). Following are the result of the DNA extracted using a machine called nanoviewer. Many concentration of the DNA extracted are within the good range which is 1.8 – 2.0. This indicates that the samples have not been contaminated with protein. The following table 10 shows the result of the DNA extracted: Breast Tissue sample numberConcentration ng/ulResults 33101.5 ng/ulA260/280 = 1.990 847.5 ng/ulA260/280 = 1.939 7733 ng/ulA260/280 = 1.886 5415.9 ng/ulA260/280 = 1.904 76105.5 ng/ulA260/280 = 1.835 2593.0 ng/ulA260/280 = 1.958 1229.5 ng/ulA260/280 = 1.735 1326.0 ng/ulA260/280 = 1.877 7143.0 ng/ulA260/280 = 2.014 4. Health and Safety: The health and safety procedures were followed according to the requirement of the laboratory for this project and a copy of COSSH assessment was given to the laboratory technical staff and to the project supervisor 5.Ethical Issues: Approval of UK’S ethical committee regarding the usage of the breast tissue samples has already been granted to the project supervisor and hence there is no need of further ethical approval for this project. 6. Literature search: To understand the scope of the HPV and breast cancer very well 15 abstracts have been submitted at the beginning to the project supervisor that were conducted by many journals and research papers. 7. Statistical analysis: This project is a laboratory based and therefore does not require any statistical analysis to be carried out. 8. Treatment: Breast cancer is treated with surgery, radiotherapy, chemotherapy and drugs. There are many drugs that are used to either treat or reduce the risk of breast cancer and following are some example of these drugs: 8.1. Drugs: Table11 below shows the list of drugs used for breast cancer treatment Herceptin (chemical name: Trastuzumab ) Tamofen (chemical name: Tamoxifen) Arimidex (chemical name: anastrozole) Aromasin (chemical name: exemestane) Avastin (chemical name: bevacizumab) Carboplatin (brand name: Paraplatin) Cytoxan (chemical name: cyclophosphamide) Daunorubicin (brand names: Cerubidine, DaunoXome) Doxil (chemical name: doxorubicin) Ellence (chemical name: epirubicin) Thiotepa (brand name: Thioplex) Trelstar (chemical name: triptorelin) Tykerb (chemical name: lapatinib) Vincristine (brand names: Oncovin, Vincasar PES, Vincrex) Xeloda (chemical name: capecitabine) Some of the drugs that are used are explained below. Tamoxifen: is a drug that uses SERMs (selective oestrogen receptor modulator) that attaches to the oestrogen receptors in breast cells and blocks the effects of oestrogen (Lacroix, et al., 2010). Uses: to treat men and both pre-menopausal and post-menopausal women, typically is used to: shrink large, hormone-receptor-positive breast cancers before surgery reduce breast cancer risk in undiagnosed women at higher-than-average risk of developing breast cancer However Tamoxifen is very cost effective (Noah-Vanhoucke, et al., 2011) Side effects: irregular menstrual cycles vaginal discharge or bleeding depression endometrial cancer 8.2. Trastuzumab: is a drug that uses HER2 (human epidermal receptor 2) inhibitors that works against HER2-positive breast cancers by blocking the ability of the cancer cells to receive chemical signals that tell the cells to grow. Uses: treat metastatic, HER2-positive breast cancer (Barok, et al., 2011) shrink large, advanced-stage, HER2-positive cancers before surgery Side effects: diarrhea anemia abdominal pain 9. Cancer prevention: 9.1. HPV Vaccines and Cervical Cancer: Cervical cancer and sexual behaviour of population are directly proportional to each other, recent study shows that in the U.K HPV prevalence and possession increased consistently with increasing numbers of lifetime sexual partners, regular partners, and new partners in the last 5 years (Almonte, 2011). The two prophylactic vaccines Cervarix and Gardasil consist of virus-like particles (VLPS), these are recombinant viral capsids made by expressing HPV 16 and 18 L1 proteins in insect cells through the baculovirous (cervarix) or HPV 6, 11, 16 and 18 L1 proteins in yeast cells (Gardasil) (Kahn 2005; Wang 2007; Kirnbauer et al., 1993). The virus-like particles (VLPS) contains no viral DNA and therefore would not in any case cause an infection or cervical cancer in recipients (Wang, 2007). Cervarix: GlaxoSmithKline (GSK) produces cervarix vaccine; it is a bivalent containing HPV 16 and 18 L1 virus-like particle vaccines that works against HPV 16 and 18 infections and cervical cancer (Bayas et al. 2008; Govan 2008). A phase II study illustrated that Cervarix was 91.6% efficacious against occasional infections and 100% effective against persistent infection (Harper et al. 2004). Cervarix is made up of an ASO4 adjuvant which contains aluminium hydroxide and 3-O-deacylated monophosporyl lipid (MPL), ASO4 helps improve the immune system (Bayas et al., 2008). Gardasil: Gardasil is developed by Merck and Co; it is a quadrivalent vaccine containing HPV 6, 11, 16 and 18 virus-like particles (Adams, et al., 2007; FDA, 2006). A phase II efficacy study of Gardasil results demonstrated that the vaccine has 90% efficacy in preventing incident HPV infection and cervaical cancer (Viller, et al., 2005). In June 2006 Gardasil was licensed by the FDA for use in young and adult females between the ages of 9 to 26 for the prevention of cervical cancer, genital warts and precancerous lesions (FDA, 2006), it was also approved in September 2008 for the prevention of vaginal and vulvar cancers caused by HPV 16 and 18 (FDA, 2008). Both of the above vaccines are given in a series of three 0.5ml immunisations over a time period of six months prior to a young person becomes sexually active (Long III, et al., 2007; WHO, 2007). Figure 24 shows how the HPV DNA is detected in cervical cancer. The above figure adopted from: Global Link (2008) Date accessed 07/04/11 9.2. Breast Cancer Vaccine: Vaccine has been developed firstly against cervical cancer and now the scientists are trying to develop a vaccine against breast cancer, however scientists are trying to develop a vaccine which could be useful against all the different strains of HPV such as 16, 18, 33 worldwide (Armstrong, 2010). Prognosis: Table 14 shows the five year survival rates for colorectal and breast cancer. (Howlader, et al., 2011). There is only 23% survival rate for distant spread in breast cancer this shows that there is a need for more research to develop a vaccine against different strains of breast cancers and to treat these cancers affectively and avoid so many deaths. 10. Discussion: Breast cancer is a malignant tumour that starts from cells of the breast. Cancer occurs due to mutations in the genes responsible for controlling the growth of cells thus cells are unable to function properly (Sariego, 2010). Human papillomavirus (HPV) is considered as an aetiological agent for many cancers such as cervical cancer, breast cancer etc. High risk HPV types causes cancer by integrating into the host genome and causes disruption and loss of some of the viral genes such as L1 and L2 genes and also increases the expression of the early genes (Wang, 2007; Mera, 1997). The aim of the research was to find out the association of HPV with breast cancer involving DNA extracted from archived breast tissue samples using DNA extraction method. This DNA sample could be amplified using PCR to find HPV genome specifically targeting E1 gene. This is conjunction with other studies in which samples were amplified using consensus primers CpI CpIIG and targeted the E1 gene in a region conserved for 99% of most common HPV subtypes (Mendizabal, et al., 2008). Given that the tissue samples were not fresh but were paraffin embedded which are not as good as fresh tissue samples because formalin fixation could denature the tissue during sectioning and also the DNA extracted from FFPE (formalin fixed paraffin embedded) tissues are usually at low concentration and disjointed (Shi, et al., 2006). Additionally the experiment was carried out very successfully because most of the results that have been obtained were between the ranges of 1.8 to 2.0, which are regarded as pure DNA sample and therefore contains no protein contamination. A positive and negative control should be carried out while amplifying the DNA because a positive control makes sure the technique is working satisfactorily by using a reacting material relatively similar to the test material and negative control tests the specificity of the reaction and ensures there are no false positives (Mendizabal, et al., 2008). Although good results have been achieved however there were some variations in the purity of DNA extracted from the breast tissue samples and that depends on many different factors such as some tissue samples were darker in colour than normal which suggests the samples were not as fresh therefore it gave a lower result than the normal range of 1.8 to 2.0. Additionally the low results also depended on the way the whole experiment was carried out, there had been some mistakes in adding or mixing different solutions and mistakes were constantly recorded in the lab book therefore the same mistakes were not repeated again. Moreover many different techniques have been learnt from this project including the usage of centrifuge, vortex, incubator and nanoviewer. Carrying out this project has provided a full understanding on how to engage in the practical work which is beneficial in future laboratory projects, this is an ongoing work by the supervisors of the project to try and identify the association between the HPV and the breast cancer, if successful then a broader vaccine could be developed against all different strains of HPVs such as HPV16, 18 worldwide and to cure not only breast cancer but also many different types of cancers such as, cervical cancer, head and neck Squamous cell carcinoma, genital warts etc. This will reduce the amount of vaccination given to each patient and also it will have tremendous effect on the quality of life and will solve many problems and save many lives. Furthermore many studies have been carried out to find out the presence of HPV in breast tissue. Some were successful by getting 86.21% positivity of HPV infection in breast cancer (de Villers et al., 2005) this was in conjunction with other studies that have been successful in obtaining high positive result (Hening, et al., 1999; Gumus, et al., 2006; Kan, et al., 2006, Li, et al., 2002). Additionally according to a largest investigation on breast carcinoma specifically analysing mammoplasty and fibroadenoma specimens as a control group the authors were able to detect HPV DNA in 24.5% of the breast carcinomas but were unable to detect any in benign breast specimens (Damin, et al., 2004). However other authors have either achieved low positivity (Kroupis, et al., 2006; Tsai, et al., 2005) or HPV was totally absent ( Lindel, et al., 2007; Gopalkrishna, et al., 1996). Therefore there are two different views on the association of HPV with breast cancer as it has been indicated by the above studies, which is normal because scientists can have different opinions sometimes. 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Global Business Pharmaceutical Company

Question: Discuss about the Global Business for Pharmaceutical Company. Answer: Introduction: The Alphapharm Company just as any other pharmaceutical firm is involved in the production, development, and marketing of drugs for medical use. The organization is a generic drug provider across the Australian healthcare market with over 13% national share annually. Such a position enables the firm to provide brand and generic medication to the existing and emerging markets. The manufacturing process is subjected to various laws and policies, which governs the patency, analytical tests, product safety and efficacy as well as markets. Currently, new firm relies on and base their source from the local primary apothecaries that were recorded from the tradition of botanical drug distribution. In addition to this is the trending use of synthetic chemicals that enabled researchers to vary the structure and growth of chemical substances in pharmacology. Therefore, it has led to the evaluation of the biological effects of the changed compound structures (Friedli et al. 2016). On the same no te, the innovation costs incurred in discovery and development is high, such that the pharmaceuticals must be thoroughly worked on for approvals. Most nations investigate the products, especially for human use, through boards before release into their markets. Consequently, during implementation, pharmaceutical fraud must be avoided at all costs, to gain consistencies with the potential clients. The need to increase the market coverage for the Alphapharm Companyhas resulted to the establishment of global expansions, which is considering an option between China and South Africa. Pharmaceutical Industry in Australian and the Expansion Strategy Australian pharmaceutical industries are incorporated in bio-medical research, production of medicines; originator and generics, biotechnology and wholesaling and distributional services. Exportation of the pharma products is one of the lead manufacture experts in the country. For instance, in 2012 -2013 financial year total of US$ 3.9 billion sales were made. Also, it creates employment opportunities to citizens approximately 17,000. Operations in the industry are regulated by the Therapeutic Goods Administration (TGA) that has a unit in the health department and responsible for standardization under the" Therapeutic Goods Act." Such legislative control ensures equity that protects the community. However, the supply control of medicinal products in Australia involves pre-market evaluation and approval, development of listing systems, licensing, post-market survey, and drug assessments (Schuhmacher, Gassmann, and Hinder 2016). According to a study of the international businesses, it is true that there is a significant increase in the emerging markets globally that is sufficient. About 52% of those interviewed in this regard stated precisely that they expectations from global sales were to be more than 30% of their total. Despite the fact the public organization to still dominate in the markets, an existing opportunity is from the second-tier are becoming more relevant, such as Southeast Asia. Consequently, the growth and prosperity in nutrition, disease patterns are on the rise and changing into lifestyle diseases and disorders that are becoming standard. Such trends open up more and new opportunities for the existing products. For example, it is estimated that the number of patients with diabetes is expected to increase by 20% in the next five years; also, the cardiovascular and oncological diseases progress in an almost similar trend (Huynh-Ba 2016). Such motions, indicates the general rise in the number of healthcare facilities are likely to be erected for service provision (Huynh-Ba 2016). However, in all of these markets accessibility remains a challenge since a number countries lack adequate infrastructure and public funding to facilitate treatments that bring forward issues of affordability. Consequently, Africa is viewed as a long-term opportunity in foreign business due to poor infrastructure thus investing pharmaceutical companies tends to maintain and look for partnership from the already existing. Despite this, high development rates are expected to rise, and fewer pharma societies are anticipating to employ their sales and marketing forces in such regions for the next five to ten years. To maximize sales, companies that best balance between their competencies globally with useful approaches will emerge the winners for foreign markets (Malhotra 2010). Evaluation of the Pharmaceutical Industry in South Africa The growth of pharmaceutical industries in South Africa is hindered by the existing structural constraints that include inadequate skills and poor infrastructure. However, the healthcare expenditure is slightly above the WHO recommendation where households in medication use 7% of the GDP. In addition, the health system is two-tiered that gives a reflection on the economic disparity amongst private and public sectors. Whereby, 16% of the population can afford the expensive quality care while public health institution is crowded with the remaining percentage. On the contrary, the private sector has the highest expenditure on pharma products where specialists make provisions in 211 major private hospitals and general practitioners, as the state-owned institution are comprised of tertiary facilities (Haakonsson 2009; South Africa 2015). Consequently, private healthcare is availed via medical schemes that are financed by employees and employer contributions, so different contributions off er different coverage levels. Whereas, the central government that gets revenues through taxes to run the facilities funds the public health and in many cases gives subsidies to the services and drugs provided. Further, the South African markets are driven by prices majorly; therefore, generics do have significant sales volumes while the originators stagnate in the markets (Adobor 2011; Djolov 2004) Risks Associated with South African Pharmaceutical Industry Financial Risk South Africa poses various financial risks in the operation of local medical companies due to the shortfalls accrued in capital and skills that involve industrial scientists and pharmacists in the laboratories. For instance, lack of incentives to attract and retain the foreign investors, high tariffs on imported products, unfavorable interest rates from credit facilities, shortages on energy sources, and generally poor infrastructure hinders local production. Operational Risk Various healthcare institutions have been faced off due to lack of working capital or even mere access to it to enable recapitalization. Such situations offer limited global links and technicalities for technology transfers in the intellectual property protection. Also, there is a shortage of professionals and no training facilities for the same that weaken the human resource. Compliance Risk Considering the existence of a weak system of central governance in the region offers no support to domestic investments in the pharma industry. More so, the gaps that exist in the regulatory capacities and enforcement capacity to ascertain quality, safety, and efficacy of the products do not exist thus allows for compliance risks. Strategic Risk Most of the laid approaches for entry in the markets have always failed in South Africa due to complex structures in the population. Also, small markets in the country discourage direct market entry since the sales force is likely to be stronger than output, therefore creates room for losses to be incurred. Evaluation of the Pharmaceutical Industry in China Several situations are associated with the Chinese market that must be considered to ensure success in trade. Consider the existence of poor relations amongst patients and physicians in the healthcare system, whereby a patient has the freedom to attend to a doctor of their choice. Such scenario promotes absurd cases since a patient may present himself or herself to a specialist at a higher level for a little fever that can be dealt with in low hospital level. Thereby, pharma has got the responsibility of managing the idea that the two parties have no open discussions on treatment. On the other hand, patients may doubt the doctor's prescription to especially high-cost drugs and opt not to take them. Particularly, this is of concern to young adults and those with chronic conditions, which can make personal decisions (Wang 2007; KPMG China 2011). As well, there is limited access to physicians in the public sector due to workload from the high number of patients. Thus, provide insufficie nt time to engage and properly interact with the pharmaceutical or medical sales representatives on new treatments and products. Such calls for innovations by the companies to engage increasingly the clients, for instance, utilization of the Chinese memorial events reach the target groups where they can give attention and be more receptive. However, this challenge is not unique to China due to their sales culture and relationship building networks in the markets (Chenly 2016). Meanwhile, the effect of rationing high-cost drugs and self-pay has become a challenge to pharmaceutical companies in China due to the increasing coverage of healthcare by the government without involving the proper funds to facilitate the process in public hospitals. Such a case has made physicians opt into an impossible task of offering treatment with a lesser budget that is within the provisions, thereby, reducing the number of pharmacies that provides costly products in the public sector. In addition, rogue patients may decide on postponing the therapy until the condition worsens to avoid the associated long and expensive queues for consultation. Consequently, these factors discourage markets for therapeutic products where most of the patients as well do not comply with the correct therapy. More so, the undeveloped private sector in health care is also an obstacle for pharmaceutical companies, where the bigger percentage gives preference to the state-owned facilities. Most of the wealthy Chinese citizens seek for the better care and resulting high costs provided by the non-governmental organizations. Despite some of the multiple reasons that could be true, the negative attitudes on private healthcare are in-depth and shared all over the population. In this regard, a vicious circle was difficult to underestimate being the idea that even doctors feel that public institutions offer them a good chance for advancement in their career. Therefore, they would be absorbed by the public rather than attracted by the private hospitals. Regardless of these factors, individual dominance is picking up slowly as it is being encouraged by the government to relieve the burden on itself and an alternative option. In such effect, restrictions on therapists that practice in more than one locality are relaxed; unfavorable regulatory conditions are being removed to foster growth and break cycles in private locations. Possible Risks Associated with Expanding to China Operational Risks China's pharmaceutical distribution market is worth US$ 44 billion though still poses a risk to the global enterprise. The nation has a high rural population that is defined by inadequate logistical expertise and infrastructure development. Therefore, it becomes difficult to satisfy the delivery of drugs to patients safely, in time and at a cheaper expense. As the government takes legal actions to combat these challenges, it becomes risky, since distribution network made of various local distributors takes up the initiative making it hard to monitor the products and track goods to ensure reliability in deliverance (Ecks 2008; Sustainalytics 2014). Although a combination of state guidance, market force, and foreign nations have taken the initiative to upgrade the system. The Chinese distribution channel is three tired, where we have the pharmaceutical companies, wholesalers, hospitals and pharmacies and finally patients. Financial Risks The cost of operating pharmaceutical firms in China is high because of the lack of a comprehensive tracking system between the various distributors, which makes it hard to guarantee product safety that is fundamental to human consumption. However, supply chains are complex that makes vulnerable to the entrance of counterfeited goods, which is a threat to the pharma industry. Therefore, the need to engage multiple distributors possibly tampers the interruption of cold chain and adversely affects the quality of the product thus increasing the cost of operation (Wang 2007). Strategic Risks The strategic planning involved in operating in China is complex because of several factors of diversity within the health sector. The vast size and heterogeneous population that exist in the nation, which the marketers must adjust to, are complicated. Irrespective of the development in the economy, this factor holds just as the case of any other consumer product in the world. Disparities exist in the market force, for instance, the rural clinics cannot be compared to the level 3 hospitals in the main cities such as Beijing, Guangzhou, and Shanghai that have better economies as developed countries (Festel and Geng 2016). Second is the public sector that is composed of complex individuals, country's government assists in the funding, distribution, and organizations of the main healthcare systems. Such motion has led to in-depth coverage that has facilitated supply shortages that require more and better services. Therefore, the stakeholders are seeking more resources, partnerships and improving on their efforts as they narrow the gap needed to implement the changes. Compliance Risks The industry in China is also complex based on the nature of the regulations available in the country. The health sector is flooded based on the need for health services. The loose regulations on drug testing and reliability research conducted in the state have polarized the market making it difficult for genuine drugs to attract high revenue. However, the strict operation in terms of market operation for international organization also limits the capacity of the foreign firms to control a higher level of production, sales, and distribution. The move is meant to protect the local industries but disadvantages the international investors (Chen and Jinag 2015; Yeung 2002). Advantages of Expanding to China Choosing to expand to China is more profitable that to South Africa. One of the benefits is the Chinese healthcare reforms that revealed plans for removal of the overhaul and commitment of vast sums of money to develop the system. Such changes provided for the increase in the basic medical insurance coverage up to 90% of the population by 2011. Others were the revision of the national essential drug list (EDL) to accommodate for more and allow for more prices that are restricted. Currently, there is a second phase of the reforms where universal health systems are to be established to all citizens to access affordable drugs and medication that open doors for pharmacies. Some of the latest improvements include an increase in the number of urban and rural residents covered for in the BMI; this was facilitated for the rise in the annual treatment allowance. In addition, the central government funds have been allocated to upgrade and construct more new county-level hospitals, community he alth institutions, township healthcare centers, and village clinics in remote places. In the public hospitals, mechanisms for separating hospital operations and management together with distinct roles in drug prescription and dispensing have been explored (Wang 2007). Moreover, implementation of the 12th five-year plan that guides the socio-economic and environmental development that helps in understanding the pharmaceutical market is another advantage that favors China over South Africa. Such implications will foster the rise healthcare consumptions and related demand for quality services due to the high incomes. Secondly, upgrade of the rural infrastructure and urbanization is likely to increase demand for pharma products with the shifting demographics. Such advancements are likely to call for consolidations and industrialization that goes in-hand with therapeutic companies. In return, the outdated and excess capacities get eliminated solidifying market structure and technology to create a business, thus the manufacturing and distributing pharmaceuticals shifts to the Eastern side to equalize on the development of central and western China. Concurrently, the existence of the growing and distinctive Chinese pharmaceutical markets has provided great opportunities in the sector. China poses as one of the largest markets for pharma products globally, which are arguably due to the population size and maturity of the markets. Such consideration gives it the room to grow with the joint forces in the government stimulus, enhances health care, solidarity in market operations, improved R D capabilities, economic and demographic development. Much more are the fundamental drives in the expansion of the market, which are the increasing need for healthcare, growth in economy, large and aging populations, and increased average and per capital spending together with the ongoing reforms. In correspondence to having the largest population of the elderly in the world, it stands a better chance for the expansion of therapeutic firms, due to the constant demand for healthcare from the resulting weak immune systems and incidences of illness (Vitry et al. 2016). Currently, the elderly generation makes up to 40% of the OTC drug market. Further, generic drugs are expected to dominate as patents to face significant growth since the world best-selling drugs will slowly lose patent protection, for example, Pfizer's cholesterol lowering Lipitor and Lilly's antipsychotic- Zyprexa. Entry Strategy Companies venturing into the global markets have formulated various marketing strategies depending on the financial capacities and nature of the industry. One of the commonest is the direct penetration of already existing markets that has always been prioritized. The Australian Pharmaceutical Company will employ a direct entry into the market in China since dealing with pharmaceuticals is a sensitive health factor that has been compromised by agents and representatives (Mazumdar 2016). Regarding this effect, expansion of geographical area will be considered a vital initiative compared to the diversification of the portfolio. Implementation of these initiatives requires three key levers that include local operations, research and development, and manufacture of the products and sales excellence through a localized sales force and consistent collaboration with the working government. Such characterization will demand physical availability on the operating ground to gain the market shar e (Walid et al. 2015). Therefore, the move will be capital intensive. However, the same effect would not operate for South Africa and second-tier, as the developed markets focus on improvement of efficacy and costs harmonization. On this effect, there will be layoffs in departments of sales and marketing with a considerable share of funds and resource relocated to emerging market in China. Locally manufacturing pharmaceutical companies have become a useful tool for enhancing market positions in a competitive environment (Malhotra 2010). Conclusion In conclusion, it is clear that China offers a better ground for global business; however, it is not certain that a pharmaceutical company will quickly succeed due to the high risks involved that could come with greater rewards. 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