Changes to British Identity and Attitude Since the 1950s

Changes to British Identity and Attitude Since the 1950s How has British identity and attitude changed since the 1950s? Introduction Many people find it difficult to cope with changes in people’s attitudes and identity, particularly since the 1950s. They struggle with the direction in which society appears to be going. The expanding nature of contemporary society means that there are more opportunities for people, this coupled with an expansion in skills and a less authoritarian attitude in the workplace gives people greater individual freedom. However, the continuing changes that have taken place in society over the last fifty years requires that people develop a greater adaptability in regards to their personal identities their attitude towards self and society. They need to be ready to move along with the rate of change and this requires a corresponding change in how they understand themselves. Thus, for Giddens (1991), the self is an ongoing project whereby identity is made and remade to meet the conditions of modern life. This paper will look at how British identity and attitude have changed since the 1950s. There will be a brief look at what life was like in nineteen fifties and how identity was understood. This will then be compared to attitudes and identity today to highlight the changes. 1950s Britain Post-war Britain was quite different to today. In the early 1950s there was still a good deal of war damage which led the Government to introduce massive building programmes to ensure adequate housing for the population. Immediately after the war the welfare state was set up. The funding of this was based on the notion that the (predominantly male) workforce would continue to have full employment, which led the Government to claim that it would be able to look after its citizens from the cradle to the grave. They were overly idealistic in their views and in the last fifty years Britain has witnessed massive changes in both welfare and employment work and welfare. Attitudes have changed towards family structures and this, along with other cultural changes, has had corresponding implications for peoples’ identities. In the years following the Second World War people felt that they were secure in their employment. In industry working class men were conditioned to the view that if they worked hard then they would have a job for life, even though they may not have earned a lot of money (Giddens, 2001). This is no longer the case however, and is one of the many reasons that there are now so many women in the workforce (Abbott and Wallace, 1997). In 1950s Britain society was clearly class ridden and people did not often move from one class to another. The class into which a person was born therefore was very often the one in which they stayed and this had implications for their life chances in other areas. People did not have the choices that they have nowadays few women went out to work and it was the father’s responsibility to go out and earn money to support his family (Walby, 1986). In the years since the nineteen fifties the face of Britain has altered. There have been massive changes in employment patterns and this has, in many cases, led to changing roles in society which has had further implications for people’s sense of identity. Post-War immigration along with rapid social and technological change has brought with it n increasing focus on contemporary racialised and ethnicised identities. This mixing of new identities along with older ones, and the introduction of new cultural forms contributes to the sense of uncertainty that many people feel is a feature of modern life (Hall, 1992). British Identity The concept of identity is extremely important in sociological thinking, furthermore, constructions of identity are also closely linked to culture and people’s identities are reflected in the cultures and sub-cultures to which they belong (Willis, 1967).Smith (1991) claims that in Britain in the 1950s there was a fairly homogenous cultural, aristocratic sense of Britishness, which dated back to the sixteenth century. The British nation state, therefore was, essentially, seen as English with elements taken from Wales and Scotland. Langlands (1999) maintains that: As it is true of all national identities, the meanings and saliency attached to Englishness are fluid and have varied considerably; it has at some times drawn upon Celtic sources; and at other times it has been conflated with Britishness (the myth of our island race for instance) (Langlands, 1999:60). The Arts Council was established in 1947. This was an attempt to bring art to as many people as possible. Ballet, Opera and the theatre were publicity and held up as models of British cultural life. During the 1950s collectivist policies were pursued which resulted in cultural stability. Cultural heritage is of great importance. (the National Heritage site tells us) it is also crucial to the construction of identities and to social behaviour (Turnpenny, 2004). These policies which promoted what were seen as ‘high’ culture were stable until the late nineteen sixties and seventies. The growing number of immigrants was changing the way Britain looked and the way it had to find new understandings of itself By the 1970s things had changed and opinions on the far left held all cultural values as a reflection of the interests of white middle class males (Abbott and Wallace, 1997).. In the nineteen eighties the market principles of Margaret Thatcher’s Government meant that art had to justify its continued existence on the basis of its marketability. In 1986 the cultural policy advisors to the Greater London Council wrote: In an age when we know longer expect to find a single all- encompassing truth, the best strategies for survival often involve creating alternative, exclusive realms, which reject dominant modes (Mulgan and Worpole, 1986:32) When New Labour came to power in the 1990s it took over elements of the left and the right in an attempt to promote a more diverse and inclusive view of culture and cultural heritage (Pearce, 2000). Pearce contends that: Cultural heritage is something that can be inherited, which enables the inheritors to enter into their rightful states and be their true selves (Pearce, 2000:59). This cultural heritage consists of artefacts, practices, objects and cultural spaces which people recognise as part of their cultural heritage. Turnpenny (2004) maintains that this heritage relates to all aspects of a nation’s life. Current cultural policy concentrates on buildings or monument, making heritage very tightly defined and denying wider cultural interpretation (Turnpenny, ibid). Social practices which are a source of group identity have been omitted from Government legislation on cultural heritage yet they traditional, and cultural significance and should therefore be considered as part of our cultural heritage (Jones, 1996). Turnpenny (2004) argues that this is oppressive as it does not take into account community values and the communities’ perceptions of their cultural heritage and it thus contributes to social exclusion. Current cultural policy, in its neglect of the intangible, separates fact from value. In doing so it imposes a form of national identity that does not truly reflect the identity of community groups in Britain. Changes in society affect social structures which in turn affect people’s identities in myriad ways. Because identities are no longer fixed, but as Bradley (1996) has argued are fractured, they are a source of continuing uncertainty. This uncertainty leads to further changes in the social structure. Contemporary people’s identities are unsettled because the changes mentioned above tend to cross ethnic boundaries. For example the changing role of women and their greater inclusion in the labour market has affected not only women’s and men’s identities, it has also led to changes in family structures. Changing Attitudes and the Family Over the last fifty years, Britain has witnessed changes in marriage, household, and family forms that would not have been thought possible prior to the Second World War (Giddens, 2001). The rise in the divorce rate and the number of single parent families, has largely been blamed on the 1960s rise of the feminist movement. There has also been a growth in the rate of women who have children but have not married (Social Trends, 2000). Attitudes have changed considerably in this regard and it is rare to hear of the lonely old spinster. People do not think that women who don’t want to marry are in some way strange. Parsons (1955) argued that (what has been called)the traditional family serves two major purposes that are common to societies, the primary socialisation of children into the norms and values of society, and the stabilisation of adult personalities. For Parsons the institution of the family provided the mutual love and support needed by individuals in order for them to be fit enough to take their places in society (Giddens, 2001). In 1997 when Blair’s Government came to power the above ideology of the family that had existed in Britain for almost a century was breaking down and unemployment was continuing to rise. Death, divorce, and the rise in the number of single parent families meant that the traditional ideal of the male breadwinner and the female carer/homemaker were becoming less common (Giddens, 2001). Single mothers (although not a strong favorite) were no longer seen as shamed women, as they might have been in the nineteen fifties. The concerns of the Welfare State were with the traditional, nuclear family where the man was the breadwinner and the woman cared for the home and children. It was not therefore, set up to deal with single parent households. In this way changing family structures result in an increase in other social problems, particularly poverty (Giddens, 2001). Traditional family structures are no longer the norm in the UK and this has led to a change of attitudes towards those w ho do not live in the traditional nuclear family that Parsons described. However, this leads to other social problems because the state system is not equipped to deal with either the increased burden on the benefits system or in making the employment and childcare systems more equitable. Conclusion British identities and attitudes have changed considerably since the 1950s. This is largely as a result of changing employment patterns, cultural policy, mass immigration, and changes in family structures. Human behaviour is based on guidelines that are shared by a group and in order for that group/society to function effectively the guidelines must apply to all its members. Thus culture is learned and shared and without it members of a society would be unable to communicate effectively and chaos would result (Giddens, 2001). This is why attitudes have had to change in Britain and this has had corresponding effects on how people understand both their Britishness and their identities. Bibliography Abbott, P. and Wallace, C. 1997. An Introduction to Sociology: Feminist Perspectives. London, Routledge. Bradley, H. 1997. Fractured Identities: Changing Patterns of Inequality. Cambridge, Polity Press. Cohen, R. 1996 â€Å"The poverty trap† Community Care; 1 Aug 96, p.26-7 Crowe, G. and Hardey,M.1992. â€Å"Diversity and ambiguity among lone-parent households in modern Britain†. In Marsh, C. and Arber, S. (Eds.) 1992. Families and Households: Divisions and Change. London: Macmillan. Giddens, A. 2001. (4th ed). Sociology. Cambridge, Polity Press. Giddens, A. 1991 Modernity and Self Identity Cambridge, Polity Press Hall, S. and Gleben, B. eds. (1992) Formations of Modernity. Cambridge, Polity Press in association with the Open University Press. Pearce, S. M. 2000 ‘The Making of Cultural Heritage’, In Values and Heritage Conservation, edited by E. Avrami, R. Mason and M. de la Torre. Los Angeles: Getty Conservation Institute (2000) 59–64. Parsons, T. and Bales, R. 1955. Family, Socialisation, and Interaction Process. Glencoe, Illinois: Free Press Smith, A. 1991 National Identity Harmondsworth, Penguin Social Trends 30 2000. General Household Survey in Giddens, A. 2001. (4th ed). Sociology. Cambridge, Polity Press.p.181 Turnpenny, M 2004 â€Å"Cultural Heritage, an ill defined concept? A call for joined-up policy† International Journal of Heritage Studies 10 (3) July 2004 pp. 295-307 Walby, S. 1986. Patriarchy at Work. Cambridge: Polity.

San Francisco Bay Consulting

San Francisco Bay Consulting (SF Bay Consulting), as described in the Harvard Business School case by Baker and Monsler (1995), is a leading business consultancy and litigation support group following the goal of providing â€Å"practical application of economic theory to business problems† (p. 1). In order to manipulate and analyze data, high-end software and computers are used to serve clients’ needs.The company faces serious internal problems regarding the relationship between their consultants and the computer services (CS) staff because of disagreements concerning the transfer pricing system, which is applied to alleviate the procurement and payment of computer resources. The major challenges for this system are the heavy price drops for computer hardware and the broadness of the researchers demands.The management of SF Bay Consulting forbids their employees to purchase their own computer hardware and software which leads to frustration among the consultants, espec ially in the case when the CS department refuses to buy and supply certain hardware and software requested by the consultants. The worst scenario occurred when transfer prices produced charges to clients’ bills that exceeded the current market price for the computer as it has happened with the SUN workstation.Donald Learner, Chief Financial Officer of SF Bay Consulting, now sees himself in charge to find a solution to the current problems that is able to satisfy both, the consultants as well as the CS employees. For this purpose, he has identified three options: a) Stick to the current system, b) make CS a profit center, or c) run CS as an expense center. Due to the fact that the current situation at SF Bay Consulting is going to escalade if it is further made use of, option a) is not recommendable and a different solution has to be found.Otherwise the working environment will be seriously affected in the long run and thus efficiency of the company might decrease to an undesi rable level. Option b), to make CS a profit center, would lead to the situation that consultants themselves are allowed to purchase any hardware or software they like and thus focus on problems, others as they are supposed to do. However, this option would lead to the freedom for researchers to purchase the equipment they would like to work with and might free them of their frustrations.Since IT specialists are running the CS department their core competency is not to focus on earning a profit within a competitive environment. While focusing on equipment procurement would distract researchers, the argument of distraction also holds true for the computer experts, which have to refocus and be in charge not only for maintenance but also running a business in a competitive manner. On the other hand this could lead to a more competitive price management that could cause lower costs for the two internal groups.Notwithstanding, Learner and Alex Whalen (founder, president, & CEO of SF Bay C onsulting) both agree that computer purchasing decisions should stay within CS to secure a certain level of compatibility among hardware and software and to avoid maintenance problems. Lastly, option three, to run CS as an expense center, would eliminate internal billing and lead to group profit generated from client charges greater than the CS overhead costs.Even though, there is a possibility of researchers ignoring the costs they provoke with a great deal of requests for CS, this problem might be minor due to the fact that they are not as frustrated as before and thereby reaching a higher level of overall satisfaction. In order to make all employees more sensitive for working efficiently an elaborated group-profit-related bonus system could be introduced at SF Bay Consulting.However, the impact of the bonus system for CS employees has to secure a balance between profit orientation and reasonable investments into hardware and software. Moreover, if all employees generate one overa ll profit together, there will not be any internal competition but a jointed overall goal. In conclusion, choosing option c), to run CS as an expense center is the right recommendation for SF Bay Consulting in order to solve its internal problems.

Critique of Systematic Research Review SRR Essay

Critique of Systematic Research Review (SRR) Introduction   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚   There are several health conditions that adults suffer from and one of those health issues is lung cancer. Lung cancer in adults is seen as one of the prevalent conditions that needs to be fully addressed so that the rate of deaths that occur as a result of the condition. There is lots of evidence which indicate that the numbers of adults that are suffering from lung cancer have increased. It is to be noted that the adults that suffer from lung cancer require a lot of attention so that they can be able to recover and get better (Wood, Molassiotis, & Payne, 2011). This is based on the reason that lung cancer is a chronic illness that takes a long time before they can recover although if proper care is not given then there are chances that they may end up dead. The rate of death from lung cancer increases as a result of the lack of proper care for the patients.   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚   According to the research conducted on patients with lung cancer indicates that health care providers have a great role that they play in the lives of the patients. The health care providers are required to ensure that they should provide sufficient management of the symptoms. Furthermore, there is need for the health care providers to ensure that they promote quality life for the adults that suffer from lung cancer(Wood, Molassiotis, & Payne, 2011). Through several studies that have been conducted, it has been observed that patients that suffer from lung cancer are the ones that experience symptom distress more than those patients that suffer from different types of cancer. Therefore, symptom management among the patients that suffer from the lung cancer is very important and the health care providers are required to ensure that they provide this type of management. The research conducted on patients that suffer from lung cancer indicate that understanding the needs of the patients is very important in handling and managing this condition as one way of reducing the rate of deaths that result from lung cancer.   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚   From this systematic review of the research that was conducted, it is to be noted that there are several symptoms that can be used to identify an adult that suffers from lung cancer. Some of the major symptoms as observed through the systematic review include cough, whereby the adults often develop new coughs and to a great extent the cough often becomes chronic and does not end even with continued medication(Wood, Molassiotis, & Payne, 2011). The other symptom that has been identified is that the patients suffer from shortness in breath and find a lot of difficulty in breathing. The systematic review have also identified wheezing as well as whistling sound production when breathing as some of the other symptoms which are associated with lung cancer among the adults. Furthermore, it is the finding of the systematic review that lung cancer patients also suffer chest pains which often may range from those that are sharp pains, dull or even s tabbing pains on the chest as an indication of lung cancer(Wood, Molassiotis, & Payne, 2011). Finally, hoarseness of the voice as well as the face swelling, neck, arms or even having lots of headaches have been identified as some of the symptoms through this particular systematic review.   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚   From the various symptoms which have been identified above in this systematic review, it can be noted that there is great importance in the management of the symptoms among the patients that suffer from lung cancer. The systematic review indicates that it is important to understand the way the research on the symptoms of lung cancer have been conducted so that future research can be based on these findings as indicated in the systematic review(Wood, Molassiotis, & Payne, 2011). It is important to note that lung cancer is one of the major conditions that many nations are grappling with especially among the adults. The rate of deaths have driven researchers to find ways through which they can identified the suitable ways of managing and reducing the rate of deaths as a result of lung cancer.   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚   The systematic review provided on the symptoms of lung cancer among adults is quite extensive in its approach and has provided enough detail in addition to allowing for further research to be conducted on the same topic. From the systematic review, it is noted that there have been a lot of strides which have been made towards understanding the various symptoms that relate to lung cancer in adults. The systematic review is quite detailed in its analysis of the symptoms which are related to lung cancer among the adults(Wood, Molassiotis, & Payne, 2011). The review can be said to be sufficient as it touches on various theoretical, methodological as well as conceptual issues which need to be addressed through future research on the topic. The review however limits its information in terms of the theoretical framework that has been used in the identification of the symptoms which are related to the lung cancer condition. This lack of theoretica l framework in the study means that there is need for more research on the topic to be able to identify the various theoretical issues which are part of the research in identifying the symptoms(Wood, Molassiotis, & Payne, 2011). The strength of this particular systematic review is that the presentation of the information and data has been done in such a way that it is easy to follow from the beginning to the end. Each step of the review is clearly identified which makes it easy for a reader to read through the work. Furthermore, the presentation of data and information has also been accompanied with graphics in terms of tables and charts which helps in understanding the information on the symptoms of lung cancer among adults.   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚   The systematic review also requires the use of tools and equipment in terms of data collections that are reliable and can provide valid data and information which can be used in the identification of the various symptoms that are also associated with lung cancer. It is to be noted that the systematic review however, despite not showing the use of theoretical frameworks that can be used to establish the symptoms of lung cancer, it identifies some of the ways through which patients that suffer from lung cancer can be assisted(Wood, Molassiotis, & Payne, 2011). One of the recommendations that has been suggested by the systematic review is that there is great need for the health care providers to ensure that they practice what is known as symptoms management It is also the recommendation of this systematic review that gender issues should be incorporated in to future research to find out if there is any significance of gender in terms of sympt oms of lung cancer in males and females(Wood, Molassiotis, & Payne, 2011). References Wood, M. M., Molassiotis, A., & Payne, S. (2011). What research evidence is there for the use of art therapy in the management of symptoms in adults with cancer? A systematic review.Psycho-Oncology, 20(2), 135-145. Accessed fromhttp://eds.b.ebscohost.com/ehost/pdfviewer/pdfviewer?sid=5932c2d1-f4fe-432a-b9ad-48c737b75200%40sessionmgr111&vid=0&hid=11 Source document

Whole Exome Network Analysis Identifies CXCR5-CXCL13 Signaling as a Key Driver in Breast Cancer - Free Essay Example

Sample details Pages: 8 Words: 2498 Downloads: 2 Date added: 2019/02/06 Category Medicine Essay Level High school Tags: Breast Cancer Essay Did you like this example? I am delighted to submit the concept paper with the title â€Å"Whole Exome Network Analysis Identifies CXCR5-CXCL13 Signaling as a Key Driver in Breast Cancer† for consideration under the NIH Research Fellowship Program, Ruth L. Kirschstein National Research Service Award Individual Predoctoral Fellowship. The primary aim of the Kirschstein-NRSA Individual Predoctoral Fellowship is to provide financial support for mentored research training, leading to a doctoral degree in the biomedical, behavioral, or clinical sciences. Don’t waste time! Our writers will create an original "Whole Exome Network Analysis Identifies CXCR5-CXCL13 Signaling as a Key Driver in Breast Cancer" essay for you Create order However, this fellowship program also strives to enhance the diversity of the scientific workforce in the United States by providing opportunities for academic institutions to identify and recruit students from diverse population groups. This fellowship program encourages diverse population groups to seek graduate degrees in health-related research. The long-term goal of the Kirschstein-NRSA Individual Predoctoral Fellowship program is to enhance the number of scientists from diverse population groups and prepare them for research careers in the biomedical, behavioral, and clinical sciences. I am a fourth-year graduate student at Morehouse School of Medicine (MSM), a historically Black College or University in the Atlanta University Center. The mission of MSM is to increase the health and well-being of individuals and communities with emphasis on people of color. This mission is primarily focused on underserved urban and rural populations in Georgia. MSM also seeks to increase the diversity of the health professional and scientific workforce. This mission shares a similar objective to that described in the mission of the Ruth L. Kirschstein NRSA Individual Predoctoral fellowship. I am obtaining a Ph.D. in Biomedical Science and a Master’s degree in Clinical Research (MSCR). The PhD/MSCR program has provided me with a strong foundation in research design, methods, and analytic techniques. My ability to conceptualize and think through research problems has also been enhanced through my participation in this dual degree program. I have gained experience conducting re search as well as presented my research findings as first author. The PhD/MSCR program has afforded me the opportunity to interact with members of the scientific community at scientific meetings and workshops. Moreover, the dual degree program has provided me with a versatile skill which I can utilize in the next stage of my research career. Overall, I believe the Ruth L. Kirschstein NRSA Individual Predoctoral fellowship will provide me with financial support that will take my graduate career to the next level. My dissertation committee consists of 3 experts in Oncology (James Lillard Jr. PhD, MBA, Shailesh Singh, PhD, and Sanjay Jain, MD), 1 expert in Toxicology (Danita Eatman), and 1 Biostatistician (Fengxia Yan, MD). Bioinformatics support will be provided by the bioinformatics core at Morehouse School of Medicine, The Georgia Institute of Technology, and Emory University. PURPOSE Breast cancer (BrCa) is the second leading cause of cancer related deaths in American women (American Cancer Society, 2018). Approximately, 1 in 8 (12%) women in the United States will develop invasive BrCa during her lifetime (American Cancer Society, 2018). In 2018, approximately 250,000 new cases of invasive BrCa will be diagnosed in women and of these women, approximately 40,500 will die from the disease, about 1 in 36 (3%) (American Cancer Society, 2018). More recently, incidence rates have been stable in Caucasian women, but have increased in African American women. This BrCa health disparity is most notably observed in Triple Negative Breast Cancer (TNBC). TNBC is characterized by a lack of molecular markers; estrogen receptor (ER), progesterone receptor (PR), and the human epidermal growth receptor 2 (HER-2). It accounts for 10-20% of all BrCas and is an aggressive disease with poor prognosis (Pierobon, 2013). TNBC incidence rates are higher in Caucasian women. However, the number of fatalities associated with TNBC is significantly higher in African American women, than compared to other ethnic groups. If no major changes in prevention or treatment occur, the number of lives lost to TNBC will continue to rise. More recently, rapid increases in early stage, BrCa incidence have been reported in pre-menopausal women less than 45 years of age. Additionally, many of these young, early stage breast cancer patients are of ethnic descent. The mechanisms responsible for early stage BrCa in young women of ethnic descent remains unknown. Furthermore, it remains controversial whether early breast cancer has unique tumor biology, which may be highly influenced by race. Despite new developments in early detection and treatments, approximately 5% of women diagnosed with BrCa in the United States will develop metastatic disease at the time of first presentation (EBCTCG, 2005). Additionally, another 30% of women with early-stage, non-metastatic BrCa at diagnosis, will develop distant metastatic disease that is not curable (EBCTCG, 2005). Additional predictive markers and new drug targets are needed to prolong survival and improve the quality of life for BrCa patients. It is essential to understand the mole cules and mechanisms responsible for the aggressive phenotype of breast cancer to develop new, more effective drug targets for the disease. Currently, there are no specific targeted therapies for TNBC due to the lack of ER, PR, and HER-2 markers. Current chemotherapy consists of a combination of drugs including paclitaxel (TAX), doxorubicin (DOX), and cyclophosphamide (CTX)]. TAX is a taxane, which disrupts microtubule function, inhibiting the process of cell division (Singh, 2014). It is more commonly prescribed than docetaxel, another member of the taxane family, due to its tolerable toxicity and is noted as first line therapy in metastatic disease (Erba, 2010). DOX is an anthracyclin, which inhibits DNA and RNA synthesis by intercalating between base pairs of a DNA/RNA strand (El Haibi, 2011). In an effort to combat the acute toxicity associated with DOX, it is often prescribed in combination with TAX (Eralp, 2004). CTX is an alkylating agent, which adds alkyl groups to DNA, which in turn interferes with DNA replication by forming DNA crosslinks (Singh, 2014). It is conditionally prescribed in combination with TAX and DOX, based on disease progression. The ability of CTX to induce the death of certain T regulatory cells contributes to its efficacy. However, this combination therapy produces undesirable side effects. A response rate for a treatment regimen of TAX + DOX + CTX in TNBC patients is a mere 12% for a single agent and can widely vary, 27-65%, for use of multiple agents (Singh, 2014). Patients eventually relapse as a result of chemoresistance and metastasis, ultimately succumbing to this disease. This brings attention to the cells potentially responsible for drug resistance in the tumor microenvironment. The tumor microenvironment is composed of tumor cells as well as various types of stromal cells, such as fibroblasts and endothelial cells. Several types of inflammatory cells including neutrophils, macrophages, and lymphocytes are recruited to breast tumors and play either a positive or negative role in cancer progression. The infiltration of inflammatory cells is regulated by a variety of biologically active molecules in the tumor microenvironment. Chemokines play a significant role in this process (Singh, 2011). Chemokines are 8-10 kilo Dalton (kD) chemotactic cytokines involved in cell trafficking events and normal homeostasis. They are grouped into 4 major subfamilies (C, CC, CXC, and CX3C) based on the pattern of the two NH2-terminal cysteine residues. The extended N-terminus functions to recognize, bind, and activate the receptor. BrCa cells express Chemokine Receptor 5 (CXCR5). Chemokine Ligand 13 (CXCL13) is the sole ligand for CXCR5, which plays a role in cancer progression (Singh, 2009; Singh, 2009; Singh 2011). Our laboratory was the first to show that CXR5-CXCL13 signaling mediates prostate cancer metastasis and progression i.e., growth, migration, and invasion, and survival (El Haibi, 2010-2012). We also demonstrated that CXCR5-CXCL13 signaling induces cancer progression signaling pathways: PI3K, AKT, ERK, and Jun (El Haibi, 2010-2011). However, the mechanisms, by which, CXCL13-CXCR5 signaling promotes breast cancer is unknown. Panse et al revealed CXCR5 and CXCL13 are overexpressed in BrCa tissue (Panse, 2008). This study also showed elevated serum levels of CXCL13 in BrCa patients with metastatic disease, then compared to controls and disease-free patients. Additionally, a recent study provided evidence that co-expression of CXCR5 and CXCL13 showed a significant correlation with lymph node metastasis and independently, CXCL13 had EMT-inducing potential (El Haibi, 2010). Taken together, these findings suggest the CXCR5-CXCL13 signaling axis contr ibutes to the aggressive phenotype of breast cancer (BrCa). The central research questions of this project focus on determining the mechanisms and molecules responsible for differences in tumor biology of young BrCa patients and how these mechanisms and molecules contribute to poor BrCa prognosis. The purpose of this study is to characterize the molecular phenotype of (BrCa) in the context of Chemokine Receptor 5 (CXCR5), Chemokine Ligand 13 (CXCL13), and associated gene expression. This study is novel as uses a bioinformatic approach and gene enrichment analyses to identify the specific molecules and mechanisms responsible for the aggressive phenotype of BrCa, especially in young and early stage BrCa patients. These two unique populations account for a high proportion of BrCa cases and are also associated with unfavorable prognosis. The results from this study have the potential to benefit young and early stage BrCa patients as it will serve as a new predictive factor and therapeutic target for young and early stage BrCa patients. PROJECT DESCRIPTION Breast cancer (BrCa) is the most frequently diagnosed cancer and the second leading cause of cancer-related death among women worldwide (American Cancer Society, 2018). Several targeted and adjuvant therapies exist for estrogen receptor (ER) and human epidermal receptor-2 (HER-2) positive breast cancers. Currently there are no targeted therapies for Triple Negative Breast Cancer (TNBC), which lacks the three main receptors used to characterize breast cancer subtypes; estrogen receptor (ER), progesterone receptor (PR), and human epidermal receptor-2 (HER-2). Despite new developments in early detection and treatments, approximately 5% of women diagnosed with BrCa in the US will develop metastatic disease at the time of first presentation (EBCTCG, 2005). Additionally, another 30% of women with early-stage, non-metastatic BrCa at diagnosis will develop distant metastatic disease that is not curable (EBCTCG, 2005). Additional predictive markers and new drug targets are needed to prolong s urvival and improve the quality of life for BrCa patients. Panse et al revealed levels of CXCR5 and CXCL13 are elevated in serum and overexpressed by tumor tissue in metastatic BrCa patients. The long-term goal of this study is to further characterize the molecular phenotype of BrCa in the context of CXCR5, CXCL13, and associated gene expression. We hypothesize the CXCR5-CXCL13 signaling axis contributes to the aggressive phenotype of BrCa. A bioinformatic approach will be used to aid in characterizing this new drug target for BrCa. Our patient cohort (1,049 female patients of Caucasian, African American, Latin American, and Asian/Pacific Island descent, age 35-82, diagnosed with ductal and lobular carcinoma ) will be obtained from The Cancer Genome Atlas (TCGA). All patients within the cohort have verification of informed consent and IRB approval. Differential Expression Sequencing (DESeq) analysis will be performed to identify genes differentially expressed among primary tumor and matched normal, solid tissue groups. Weighted Gene Network Co-expression (WGCNA) analysis will be performed to identify modules of co-expressed which will be correlated to factors influencing BrCa prognosis, such as age at diagnosis, TNM staging, race, menopausal status, breast cancer subtype, and survival time. Finally, canonical pathway, upstream regulator, and gene interaction analysis will be performed using Ingenuity Pathway Analysis. Our findings suggest CXCR5, CXCL13, and associated genes driving tertiary lymphoid structure formation, is present in BrCa, may serve as a predictive factor, and a new therapeutic target. GOALS AND OBJECTIVES The long-term goal of this study is to further characterize the molecular phenotype of BrCa in the context of CXCR5, CXCL13, and associated gene expression. We hypothesize the CXCR5-CXCL13 signaling axis contributes to the aggressive phenotype of BrCa. The objective of this study is to identify the molecules that contribute to the aggressive phenotype of BrCa in silico. METHODOLOGY Data Collection and Normalization The data used in this study will be obtained from The Cancer Genome Atlas (TCGA). Clinical and RNA-seq data, for a total of 1049 female patients of Caucasian, African American, Latin American, and Asian/Pacific Island descent, age 35-82, diagnosed with ductal and lobular breast cancer carcinomas will be obtained. All patients within the cohort have verification of informed consent and IRB approval. Detecting Low counts, Batch Effect Correction, and Removal of Outliers A minor limitation of RNA-Seq analysis is the presence of missing expression counts, which alters the distribution of the population. Due to this limitation, normalized counts for all 1,049 patients with 26,000 protein coding genes will be log2 transformed (expression value+1) to create a standard normal distribution. Genes possessing greater than 50% zero counts will be removed to prevent a skewed distribution and remaining genes will be filtered by a standard deviation of 1. We predict that between 5,000-8,000 protein coding genes will be analyzed for batch (center) effect. Using ComBat algorithm, batch effect correction will be applied to detect variance from a total of 52 sequencing centers that contributed to the TCGA BRCA dataset. ComBat, an Empirical Bayes method in the Bioconductor SVA package, will be used to remove all outliers. Detection of Differentially Expressed Genes among Primary Tumor and Matched Normal Samples using DESeq Differential Expression Sequencing (DESeq) is a free software package in R that detects genes that are differentially expressed between two groups. In this study, we will detect genes that are differentially expressed between 113 primary tumor and 113 matched normal samples. Normalized counts for approximately 26,000 genes will be used to determine differential expression. Identification of modules associated with different stages of breast cancer primary tumors using WGCNA Between 5,000 and 8,000 genes will be entered into Weighted Gene Co-Expression Analysis (WGCNA) software. WGCNA is a free software package in R that extracts information on single genes from large scale gene expression profiles, across all patient samples, and uses this information to construct gene network modules of co-expressed genes. These co-expressed genes will be built on a manual threshold power of 6. Modules containing co-expressed genes have the potential to be associated with specific clinical traits. Association is based on a scale of 0-1 with an alpha of 0.05. Network calculation will allow for the identification of a module(s) of genes highly co-expressed with Chemokine Receptor 5 (CXCR5) and Chemokine Ligand 13 (CXCL13) and strongly correlated with clinical traits, such as age at diagnosis, TNM staging, race, menopausal status, breast cancer subtype, and survival time. Functional Enrichment analysis of genes within each module using IPA Following WGCNA, a network module(s) will be identified for functional enrichment containing genes co-expressed with CXCR5 and CXCL13. Ingenuity Pathway analysis (IPA) will be used to elucidate the biological roles of genes inside modules of co-expressed genes. Often modules contain co-expressed genes that contain co-regulated genes, with similar biological functions. These modules of co-expressed genes regulate epigenetic features downstream of particular transcription factors. Genes with high connectivity will be pooled together and IPA will be used to perform an analysis that shows the canonical pathway of selected module hubs. Upstream Regulator Analysis using IPA The Upstream Regulator analysis feature in IPA will be used to identify the biological function of significantly associated gene co-expression module(s) to BrCa stage. Co-expressed genes in this module will most likely be regulated by the same or similar upstream regulators, including transcription factors. We will identify the upstream transcriptional regulators in each module with a p-value of overlap