Acute Myeloid Leukemia: Causes and Treatment Strategies

Acute Myeloid Leukemia: Causes and Treatment Strategies Pathology Acute myeloid leukemia is a disease that primarily afflicts adults. The likelihood of being diagnosed with AML increases with age; the median age of diagnosis is 65 with very few cases reported in those under the age of 40 [4]. Several risk factors have been associated with increased incidence of AML including: Li-Fraumeni disease, Klinefelter’s syndrome, radiation exposure, chemotherapy, and chemicals (benzene, herbicides, etc) (See supplementary figure S.1) [4]. However, the initiation of AML is a multistep process and can be the result many different genetic aberrations [4][5]. Therefore, the aforementioned risk factors do not account for all cases of AML [4]. Acute myelogenous leukemia is the result of oncogene-driven accumulation of immature myeloblasts within the bone marrow [5]. Myeloblasts are progenitor cells, which will ultimately give rise to neutrophils, basophils, eosinophils, and mast cells (collectively known as the granulocytes) [6]. In AML, the genes that govern proper differentiation of myeloblasts into one of the aforementioned cell types are mutated. This prevents differentiation and leads to a buildup of myeloblasts within the marrow [5]. The clinical consequences of myeloblast buildup are marrow failure leading to low white-blood cell count, low red-blood cell count, and insufficient levels of clotting factors [5]. Therefore, clinical symptoms are depressed immune function, anemia, and continued hemorrhaging. The molecular pathogenesis of AML (and all cancers) begins with the acquisition of genetic abnormalities. There are two models that describe how these acquisitions arise. The conventional model of cancer cell initiation proposes that the cell gradually acquires certain mutations to genes involved in mitotic signaling (KRAS or APC) and tumor suppression (P53), thereby allowing the cell to divide uncontrollably [7]. However, Recent work by Stephens et al. [8] showed that multiple mutations can be induced in a â€Å"one off† event by the random shattering and re-ligation of one or more chromosomes [8]. They termed this event â€Å"Chromothripsis† [8]. Chromothripsis results in massive translocations and changes to copy number state, but is distinct from the conventional model of cancer cell initiation by the presence of large-scale inter-chromosomal rearrangements [8]. Thus, the chromothripsis model differs from its conventional counterpart in the time taken for the cell t o reach malignancy and the scale to which the genome is altered. Chromothripsis is observed in a portion of AML cases; Rausch et al. [9] found nearly half of the AML cohort showed chromosomal rearrangements consistent with chromothripsis [9]. This shows that, accumulation of the necessary mutations that drive AML may occur by more than one mechanism. By either mechanism of AML initiation, myeloblasts lose the ability to differentiate. The molecular pathogenesis commonly shows two frequent chromosomal aberrations – a translocation between chromosome 8 and 21, and an inversion of chromosome 16 [5]. These changes affect two genes crucial for myeloid differentiation (CBF1ÃŽ ± and CBF1ÃŽ ²) [5]. The effect of the inversion and translocation results in a gene chimera, which is translated into a protein that interferes with proper CBF1ÃŽ ± and CBF1ÃŽ ² function [5]. However, these specific chromosomal alterations are not observed in every case of AML. DNA-damage inducing agents like radiation or certain chemicals, may cause aberrations to chromosome 5 and 7, which has also been implicated in the initiation of AML [5]. This shows that there are several factors involved in proper myeloid differentiation and that interference to any of them may result in AML. Visual differentiation of healthy myeloblasts from leukemic myeloblasts can be challenging. Myeloblasts should contain 3 5 nucleoli, which are full of uncondensed chromatin [6]. Some leukemic myeloblasts may show more than 3 – 5 nucleoli [5]. Also, they do not normally contain granules, however, leukemic myeloblasts may have granules, which can serve as a potential marker for diagnosis [5]. It is important to stress that these morphological changes may not appear in all cases of AML. Therefore, prognosis is confirmed by the presence of greater than 20% myeloblasts in bone marrow biopsy [5]. Treatment There are different avenues for treating AML. Treatment may include supportive care (in advanced cases), chemotherapy, and stem cell transplantation. However, chemotherapy is the most common and effective method of treatment [3]. When medicinal chemists began isolating antibiotics produced from bacteria in search of potential leads for drug design, Aurelio Di Marco and his research team discovered a new species of bacteria, Streptomyces peucetius, within a soil sample they obtained from an area near Bari, Italy [10][11]. This new strain of bacteria was produced a compound that was efficacious as a chemotherapeutic agent against many tumors; the compound was later named daunorubicin and is now considered a key intervention administered to patients with AML [12]. Daunorubicin and doxorubicin are part of the class of antibiotics collectively known as the anthracyclines. Anthracyclines can cause cytotoxicity by different mechanisms depending on their intracellular concentration. As reviewed by Gerwitz [13], in vitro studies show there are several possible mechanisms for the anti-tumor effects of these agents including: Inhibition of DNA synthesis, free radical generation leading to either DNA damage or lipid peroxidation, inhibition of DNA topoisomerase resulting in helix super-coiling, DNA alkylation, and DNA cross-linking [13]. The induction of apoptosis was also mentioned as a mechanism of cytotoxicity, but it is likely that apoptosis is a byproduct of the aforementioned cellular stresses, rather than a direct consequence of anthracycline exposure [13]. It is important to note that these mechanisms were observed in vitro, and that in vitro conditions allow for exposure at concentrations that may greatly exceed in vivo concentrations [13]. Pharmacodynamics Although, daunorubicin and doxorubicin are thought to cause cytotoxicity by several different processes, their ability to bind to DNA and prevent DNA replication or transcription is considered to be the primary means of anti-tumor activity in vivo [13][14]. This is because replication is inhibited at anthracycline concentrations that can be reached in vivo following a standard dosage [13]. The two anthracyclines appear to intercalate preferentially to regions of DNA with select base-pair composition, specifically, regions with CGATCG sequences [14]. Rabanni, Finn, Ausio [15] suggest that intercalation stabilizes hydrogen bonds between the two strands of DNA [15]. This means that the energy required to separate the strands is higher, and cannot be achieved by DNA helicase [15]. Thus, strand separation is inhibited, preventing DNA replication and tumor cell proliferation. For both compounds, the chromophore portion (DCBA in fig. 1) of the molecule intercalates between complementary guanine-cytosine (GC)  base pairs on each side of the DNA double-helix (fig. 2). The compound is stabilized in this position by hydrogen bonds on either side of the molecule. The â€Å"D† side of the molecule is held in position with aid from a solvent atom (believed to be ionic sodium), which forms hydrogen bonds between oxygen 4 and 5 to  nitrogen 7 of guanine12 (fig. 2) [14]. The â€Å"A† side of either drug is coordinated by hydrogen bonds from oxygen 9 to nitrogens 2 and 3 of guanine 2 (fig. 2) [14]. As previously mentioned, all of these interactions occur between both daunorubicin/doxorubicin and C/G DNA sequences. However, the added hydroxyl group on C14 of doxorubicin creates an extra association. The hydroxyl appears to shift solvent molecules such that indirect interactions between itself and the phosphate backbone of DNA are created (fig. 3) [14 ]. This added interaction might explain the slightly higher in vitro affinity constant between doxorubicin-DNA (Ka = 1.610-5) as compared to daunorubicin-DNA (Ka = 1.210-5) (in vitro Ka determination performed at 37 °C in 10% fetal calf serum) [17]. Doxorubicin is more potent than daunorubicin. In the case of anthracycline induced inhibition of DNA strand separation, the potency and efficacy are directly related. The increased binding affinity of doxorubicin means that it will associate with DNA and prevent DNA separation at a lower concentration (See supplementary fig.S2). Therefore, pharmacological factors aside, it will be more potent and will prevent tumor cell proliferation at lower concentrations. Synthesis Doxorubicin is a semi-synthetic analog of daunorubicin. The daunorubicin producing bacteria, Streptomyces peucetius, was mutated to the doxorubicin producing subspecies Streptomyces peucetius subsp. caesius [18]. This mutated strain was found to carry an oxidizing cytochrome P450 isoform capable of hydroxylating the C14 of daunorubicin [19]. The gene that encodes this P450 is called doxA [19]. Although, this gene is crucial for doxorubicin production, its presence does not guarantee collectable quantities of doxorubicin (See supplemental figure S.2) [20]. Enzymes, such as dnrH and dnrX, may further oxidize or reduce the newly formed doxorubicin into other metabolites that do not have antitumor abilities [18]. Therefore, in order to make doxorubicin production sustainable, the down regulation of such genes is required to increase doxorubicin yield. Pharmacokinetics Despite their similar molecular structure, daunorubicin and doxorubicin have distinct pharmacokinetic properties. This section will begin by contrasting the differences in elimination, metabolism, and distribution. Bioavailability will not be contrasted because both of these agents are administered intravenously. The section will then conclude with a description of tissue distribution, intracellular distribution, and toxicity. Administration As already mentioned, both anthracyclines are administered via intravenous injection [21][22]. They should not be injected subcutaneously or intramuscularly due to the significant risk of tissue death at and near the injection site [23]. The exact dosage schedule for both daunorubicin and doxorubicin is dependent on several different factors including: age, health, pre-exisiting heart conditions, and renal functioning, therefore exact dosages vary among different patient populations. In terms of daunorubicin, dosage ranges between 30 and 45 mg/m2, whereas doxorubicin dosages range between 40 and 75 mg/m2 during the initial course of treatment [24][25]. Elimination Both compounds are eliminated from the plasma via urinary and biliary mechanisms [23]. However, a much greater proportion of a daunorubicin dose is excreted through the kidneys (14-23%) as compared to doxorubicin (5%), while a larger proportion of doxorubicin was reported to be excreted through the bowels (50%) compared to daunorubicin (40%) [23]. Daunorubicin and doxorubicin are considered to be high clearance drugs. They have a similar clearance value of 1-2 L/Kgà ¯Ã¢â‚¬Å¡Ã… ¸h [26]. The elimination of either drug, along with their metabolites, follows a triphasic decline in plasma concentration [23]. After a 60ml/m2 infusion of daunorubicin/doxorubicin, the plasma concentration/time graph shows that both drugs are eliminated with a similar rate (fig.3) [26]. However the Medsafe ® [23] datasheet for daunorubicin/doxorubicin reports that the plasma T1/2 for the first phase averages 45min daunorubicin and 12min doxorubicin, while the second phase is 18.5hrs daunorubicin, 3.3hrs doxorubicin. Metabolism The primary metabolites of daunorubicin and doxorubicin are daunorubicinol and doxorubicinol respectively. Because of their similar structures, the metabolism of either compound occurs in a likewise fashion. The enzyme most implicated in metabolism is NADPH (nicotinamide-adenine-dinucleotide-phosphate) dependent cytochrome P450 reductase [27]. This enzyme reduces the ketone at C13 to an alcohol to produce daunorubicinol and doxorubicinol [28]. These two products are believed to retain their cytotoxicity and are cleared from the plasma at a similar rate [28][29]. Another common metabolite for either compound is generated via reduction of the glycosidic bond by gycosidases. Glycosidic reduction results in removal of the amino-sugar that is bonded to C7 [28]. This reaction eliminates the anti-tumor capabilities of either compound [28]. Following removal of the amino-sugar, the remaining aglycone is demethylated and then undergoes phase II metabolism (sulfonation or glucuronidation) [23]. Phase II metabolism by sulfonation or glucuronidation increases plasma clearance and enhances elimination. Two other metabolites are listed in literature, 7-deoxydoxorubincolone and 7-deoxydoxorubinone, however the enzyme or enzymes that facilitate these reactions were not noted [30]. Two other enzymes metabolize both daunorubicin and doxorubicin under aerobic conditions, xanthine dehydrogenase and xanthine oxidase, and produce reduced semiquinones and oxygen radicals [31]. These radicals could provide added efficacy to the drug therapy. It has been suggested that advanced stage cancer cells exhibit high oxidative stress and that it may be advantageous to exploit this finding to preferentially and specifically attack and destroy them [30]. Under anaerobic conditions, xanthine dehydrogenase metabolizes doxorubicin to 7- deoxydoxorubicin aglycone, which has been found to be efficacious in the reduction of the drug’s toxicity [31]. Volume of Distribution Daunorubicin and doxorubicin localize in the tissues. The Vd for daunorubicin is 39.2 L/Kg, while the Vd for doxorubicin is 24.6 L/Kg [26]. This indicates that both compounds have high tissue distribution [26]. Although the addition of a hydroxyl group at C14 markedly reduces doxorubicin’s ability to distribute into the tissues (relative to daunorubicin), doxorubicin remains within leukemic cells for a longer duration than daunorubicin (fig. 5) [26]. Upon administration, daunorubicin accumulates within leukemic cells more rapidly than does doxorubicin (fig 5). This is likely because of the increased polar surface area brought on by the added hydroxyl group of doxorubicin, which hinders its ability to cross membranes. However, the added hydroxyl group provides increased binding affinity to DNA [17]. Therefore, it will not leave the cell as rapidly because it will remain bound to DNA [26]. Toxicity The clinical use of doxorubicin and daunorubicin may be limited by their similar inherent toxicity. It goes without saying that chemotherapeutics should not be administered to women who are lactating or pregnant due to significant health complications that can be incurred by the infant or fetus, respectively, therefore these drugs should not be considered in these populations [33]. The use of these agents in a long-term manner is cautioned due to their ability to cause cardiotoxicity [29]. Under aerobic conditions, the semiquinone radical that may be produced during metabolism undergoes redox cycling [27]. Accumulation of reaction oxygen species soon occurs and can cause cytotoxicity [27]. This is believed to account for tissue death in cardiac cells, and is one of the major implications of using the anthracycline class of anti-tumors agents [27]. The cardiotoxicity itself includes effects such as functional damage to mitochrondrial DNA, interference of cytochrome c oxidase, and dysf unctional lipid peroxidation [13]. Personalised Cancer Treatment: Known Markers in Treatment Personalised Cancer Treatment: Known Markers in Treatment Personalised cancer treatment – known markers and what they mean for treatment Contents (Jump to) Known markers and what they mean for treatment Overview Drug target markers Diagnostic and prognostic markers Meta description Keywords Copyscape Known markers and what they mean for treatment Overview Personalised, targeted and hormonal treatments all depend on genetic mutations that can be identified in cancer cells to be effective. These mutations are sometimes referred to as â€Å"markers†. The markers can manifest through over-expression, lack of expression or mutated expression of specific proteins. Some markers can be targeted using specific treatments whereas some can act as measurements for disease diagnosis, prognosis and treatment response. Drug target markers The genes listed below have all been associated in cancer, the majority of which can also be treated. (*) – Targetable genes and proteins that can also be measured to determine treatment response, cancer diagnosis and prognosis. Diagnostic and prognostic markers The following markers are all related to diagnosis, prognosis and treatment progress. Meta description Cancer markers can help with the diagnosis and treatment of cancer and can give access to targeted therapies. Keywords Cancer markers, genetic markers, diagnostic markers, drug target markers Copyscape Checked Sep 2014 CIGNPOST: KNOWN MARKERS AND WHAT THEY MEAN FOR TREATMENT © Cignpost Ltd 2014PAGE | 1 [EB1]If these are genes not proteins then they should be in italics Psychology Christianity: Five Views | Eric L. Johnson Psychology Christianity: Five Views | Eric L. Johnson Review of â€Å"Psychology Christianity- Five Views† by Eric L. Johnson. Title: Psychology Christianity Five Views Author: Eric L. Johnson Publisher: InterVarsity Press. (U.S.A.) 2000 Price:  £14.37 ISBN: 978-0-8308-2848-7 Introduction: In this book review, I intend to cover the following outcomes: evaluate psychological theories against biblical teaching, discuss the contribution psychology has to make to Christian counselling, assess the compatibility of psychology (research and psychotherapy) with Christian counselling and critical examination of psychological theories. About the editor Eric L. Johnson is a teacher, editor, author and director. He attended Toronto Baptist Seminary and proceeded on to Calvin College before going on to Michigan State University where he bagged his PhD. He is an academic psychologist and initially lectured for nine years at the Northwestern College in Minnesota teaching Christian worldview, psychology and theology. Johnson wrote â€Å"Foundations for Soul Care: A Christian Psychology Proposal† and contributed several articles for the Baker Encylopedia of Psychology and Counselling. He argued for the necessity of theology in counselling and psychological research. He is with the Journal of Psychology and Theology as an associate editor. Johnson edited a special issue of the Journal of Psychology and Christianity, entitled â€Å"Psychology within the Christian Tradition† in 1998. He made contributions in two books: â€Å"Christianity and Psychology: Four Views† and â€Å"God under Fire: Modern Scholarship Reinvents God† in addition to editing this book that I am reviewing. Johnson is currently the director of the Society for Christian Psychology and the Lawrence and Charlotte Hoover Professor of Pastoral Care at The Southern Baptist Theological Seminary in Louisville, Kentucky. About the Book Psychology and Christianity: Five Views, is divided into seven chapters and has three hundred and nineteen pages. It is a review and expansion of the first edition titled â€Å"Psychology and Christianity: Four Views†. This book essentially lends to give a precise understanding of human nature and this is an issue that has refused to go. In page 104, we see that Adams argues that the Bible is sufficient to understand human nature and there is nothing psychology can offer but there are opposing arguments. Freud cited in Chapman (2007:41) argues that religion is an illusion. However, Crabb cited in Lutzer (1998:72) argues that we can spoil the Egyptians; take the best of both Christianity and Psychology for our use and become more effective as long as they are not in conflict with the Bible because the Bible will always be superior. The Wesleyan Quadrilateral advocates that four factors (Scripture, Tradition, Experience and Reason) must be considered when reaching decisions. In view of all this on-going debates, Johnson tries in this book to advance the argument for a relationship between Psychology and Christianity, and address the issue of helping Christians to understand and grasp the nettle of psychology. In this edition, there is a fifth view which has been added to the first edition of four views. This fifth view is contributed by John H. Coe and Todd W. Hall and it is titled â€Å"A Transformational Psychology view†. The other four view contributors were still involved in this edition but with revised contributions. The authors put forward five different views of how Psychology and Christianity can be integrated. They are David G. Myers who deals with the levels of explanation; an integration view by Stanton L. Jones, biblical counselling view by David A. Powlison and Christian psychology by Robert C. Roberts co-authored by P.J. Watson. Johnson wrote the opening chapter discussing the history of Christian psychology and also the closing chapter which talks about gaining understanding through the five views put forward by the various authors. The authors gave very good account of themselves in their respective views. Every chapter is concise, well laid out and the thought flow pattern is quite consistent and credible. Content of the book Johnson sandwiches the five views in between two chapters that he authored. He started in this first chapter by looking at the history of Christians in Psychology. In this chapter, Johnson looks at a generic background of psychology but with special reference to how psychology is viewed today. He argues (page 10) that science is a gift from God and that the scientific revolution was initiated by mostly Christians. Some Christians have unreservedly incorporated modern psychology while others like (Bobgan Bobgan 1987) have out-rightly rejected it and called it â€Å"psychoheresy†. Johnson explained in this chapter about the neutrality of this book and that it is rather a picture of the views of the majority of Christians. The second chapter was by David Myers and it deal with levels of explanation. This chapter delves into the subject of human characteristics. This view recognises that Christian theology and Psychology are different and should be treated so but that both should combine well. Myers argues (page 49) that both vary especially in the methodology of research and so each should free to explore as they deem fit. He further argues (page 72-74) that scientific data has enabled him along with some other Christian thinkers to shift from their view of seeing homosexuality as a sin, to understanding the biological explanation of prenatal influences to brain differences especially also considering the fact that the Bible did not have much coverage on the subject matter. Stanton Jones wrote the third chapter which is on the integration view. He shares the same view as Myers; that both Christian theology and Psychology have something to contribute to each other and consequently should be integrated; an aspect that is contrary to Myers view that they should be separated. Christianity is God’s word and psychology is God’s work. Jones argues (page 101) that God’s sovereignty prevails over every facet of human life and that Christian psychologists should benefit from that. However, Jones also shares a common view as Myers with regards to the fact that the Bible does not address some issues adequately (page 101). Jones shares a personal testimony of the tension points that he struggled with in-between Christianity and Psychology. (103-104). Jones became more confused as he desired to be faithful to the Bible, yet, he could not argue with the result that he was actually learning a lot about human nature in Psychology and so through excl usion, he found himself blending both Psychology and Christian theology. The fourth chapter deals with Christian psychology and was co-authored by Roberts and Watson. They argue that understanding God which is revelation (general and special) should be the starting point for the development of psychological theories. These authors (page 155-156) argue that Christian sermons (using Jesus’ sermon on the Mount as an example) are aimed at helping people to live well; dealing with character and transformation of persons and that psychology also deals with how to live, and changing a person’s character with the aim of living well. They identify terminology as the only difference between both. They argue (page 157) that sermon conceptualises psychology. John Coe and Todd Hall co-authored this fifth chapter which deals with the transformational view. They set out, not to develop or defend a model but to shed light on their argument, (page 200) that psychology and Christianity are closely related and that psychology is only an expression of faith and love. This view is the view that has just been added in this edition making it five views. They argue (page 200) in favour of the process and methodology of psychology as a process to new ways of transforming people. This approach looks into the psychologist’s transformation (emotional and spiritual). David Powlison authored the sixth chapter which discusses a Biblical counselling view. He started with a very bold statement â€Å"Christian faith is a psychology†. Also that â€Å"Christian ministry is a therapy† These statements summarises his view. Powlison argues (page 245) that the Scriptures talks about thoughts and intentions of the heart. He further argues that God through the scriptures reveals how human beings should achieve their potentials and a clear change process of attaining such too. Powlison assumes a very new approach in his view; the approach is to delve into the meanings of the word â€Å"psychology† in the very context in which it is used. He argues (page 248) that obviously the meaning is relative. In a bid to drive home his argument, he develops sub themes; Psych 1 – 6. Psych 1 looks at how you work,; Psych 2 looks at the detailed knowledge of human functioning; Pych 3 looks at the competing theories of human personality; Psych 4 de als with the practical application to psychotherapy; Psych 5 looks at a system of professional and institutional arrangements and Psych 6 deals with a mass of ethos. Powlison was really keen on ensuring that his readers have a very clear understanding of his view and goes a step further with a case study as he argues (page 262) that looking at cases is the best way to understand psychological views including biblical counselling. Eric Johnson authored the seventh and closing chapter where he made reference to similar books that has multiple views on the same subject. According to him, this book helps to highlight the point that a group of people, and specifically Christians in this instance, have the same belief but varied perspectives even within the same belief. Johnson (page 293) uses Proverbs 12:15 to affirm that a wise man will be humbled, by that awareness of what he does not know. No one has absolute knowledge except God. He argues that because we are finite creatures, we are limited in terms of views but God is the omniscient observer. He further argues that the more views we are open to, the better our understanding will be, and he encourages his readers especially Christians to dialogue, engage, critique and integrate the strengths of these views as it will enhance their understanding and scope in other to develop their own â€Å"postformal synthesis† (page 309). There is something I found very fascinating about this book. I found out that each chapter have contributing responses from the perspective of the other authors highlighting the strengths and weaknesses of the particular view in light of their own view. My thought. I think that the writing style is easy to read and understand. The chapters are logically laid out and concise and the literary genre is prose. The subsequent contributions from diverse perspectives to each chapter are not common and made it all seem like a conference, answering most questions that readers could have raised. I am the pastor of my local church; I encourage members through prayers, teaching, preaching and pastoral care, based on the Scriptures. I have found myself at crossroads in some contemporary issues which are similar to the observations of Myers and Jones, where they have found the Bible silent on some issues and inadequately addressing some other issues. This is one of my reasons of studying Counselling, and a book like this has opened me up to differing views highlighting both strengths and weaknesses of those views. This review has been an eye opener for me. CONCLUSION In conclusion, I consider the book well-structured as Johnson sets the stage with the historical background and after taking the five views, he borders the book at the end, encouraging scholars to critically and constructively engage to progress the work. Finally, I observe that Johnson claims (page 10) that the book is neutral and that the views represent the collective views of a majority of Christians. This is a very good claim but it would have been very good if he had gone a step further to substantiate his claim with data. However, overall, I consider this book to be of immense value to any Christian psychologists irrespective of their chosen model; it will open them up to differing views even within the Christian community of Psychotherapists. . I identify with Stanton Jones who authored the Integrative view and I will recommend this book to anyone who is seeking a clearer understanding of the integrative model of counselling. References: Chapman, C.N. (2007). Freud, Religion, and Anxiety. USA: Lulu.com. Page 41 Lutzer, E.W. (1998) Pastor to Pastor: Tackling the Problems of Ministry. USA: Kregel Publications. Page 72 Peter Emordi Psychology of Christian Counselling COU2001 1

Diversity and Individual Behaviour

Diversity is what the world is made of. Without diversity, the world would be an uninteresting and inhospitable place. Without diversity, there would be no variety of opinions or alternate views. There would be no different views or ways of thinking. Being diverse provides a way for people to express opinions and views to others who may not have pictured a situation the same. Four factors that cause diversity are ethnicity, gender, religion and sexual affinity. These groups have an outcome on the course of daily choices. The author of this paper will look into each of the groups and how the aspects have an impact on individual behavior. Ethnicity has an influence on behavior that cannot easily be ignored. At work the influences of ones ethnicity is dealt with everyday. African-American stereotypes have led to â€Å"being black as similar to having a felony conviction when regarding the chances of finding a job. The results of a study suggested black men must work at least twice as hard as equally qualified white men to rise above the stigma their skin color provides (Pager, 2009).† The humiliation is, for the most part, due to labeling. According to Devine and Elliot (1995), in the 1930’s the adjectives used to describe an African-American were superstitious, lazy, and ignorant, and today the adjectives vary from unintelligent, loud, and criminal to musical, athletic and very religious. Discrimination is often difficult to observe, and yet, despite the antidiscrimination laws discrimination still occurs. The author of this paper is a case manager for individuals with developmental disabilities, and observes the subtle nuance of bigotry almost on a day to day basis. Being articulate and having a name that belies the true ethnicity frequently surprises people when meeting in person. The dumbfounded expression is not easily hidden regardless of one’s efforts to mask it. Statements such as ‘you sounded different over the phone, or you look nothing as I imagined’ are uttered frequently during these meetings. After such meetings, those who are truly prejudiced will request to work with someone else; giving superficial explanations to the request.  For example, ‘we prefer to work with someone with more experience’, or with a man, regardless of the fact the author has more than 20 years of experience in the profession. Being African-American has its hardships. In addition to that adversity, consider the privation of being an African-American woman. The author’s supervisor admitted to being cautious with relaying the information about the requests of those who had recently met the author in person. Why was the supervisor afraid to approach the author? Because, the African-American woman is often portrayed as a defiant, smart-mouthed, sassy, finger-waving and eye-rolling person, it is easy to understand her fear. The African-American woman has to be diligent in the efforts to contradict the assumptions. Just being female impacts a woman’s behavior. Women are portrayed as and believed to be whiners, nags, flakes and shopaholics. Women are thought to be helpless and in need of rescuing; by a man, of course. In the business world certain jobs have traditionally been considered gender specific. A woman who holds a stereotypical masculine position, such as construction ‘foreman’, is capable to use the equipment just as successfully has the men, but often the men see her as delicate; unable to work too hard, resulting in less productivity and more stress in the workplace. Women want the same respect, opportunities and responsibilities as men. However, chauvinistic attitudes often obstruct a woman’s advancement. The author has overheard such comments as: ‘she doesn’t need a promotion, her husband makes more’, presuming a female employee has no right to a full fledged career, or a larger salary comparable to the male employees. Surprisingly, th e comment was made by a female. Sexism is evident in all areas of life. For example, people debate if women should play a sport traditionally played by men. The year 1896 is when women playing football was first documented. The men’s reaction to the football game was mentioned more than the game itself: ‘the crowd of men looking on, excited by the struggle, closed in with a rush.’ It was not until 1970 that a woman was allowed to play on a men’s semipro football team and not until 1999 did  The Women's Professional Football League begin playing professional women’s tackle football games (Women's Professional Football League, n.d). Sexism exists in religion as well. To the Catholic Church, Mary, the mother of God is the most perfect human being. Yet, a woman cannot be ordained as a priest. The woman’s highest role in the Catholic Church is that of a Nun; a servant living under vows of poverty, chastity, and obedience. In other faiths women have more of a role, for instance in the Episcopalian religion; a woman may be a priest. In Judaism rabbis have been known to depict women as envious, unproductive, lazy, greedy, and prone to gossip. In Judaism a Jewish woman’s role in life is traditionally a wife, mother and keeper of the household. The Jewish woman knows her place and the depictions have discouraged many women from pursuing an education, career advancement and sexual affinity (Marcy Hyatt, personal communication, January 7, 2009). Marcy Hyatt, a Jewish woman and a homosexual, also reported her experience of being homosexual and being Jewish as parallel. She has fought prejudice and fought for civil rights, and although she no longer has to fear being visible, she continues to work to maintain her self-worth in the face of ignorance and bigotry. According to the American Psychological Association (2004) while sexual orientation is not a conscious choice that can be voluntarily changed, several homosexual and bisexual people seek to change their sexual orientation through therapy, often coerced by family members or religious groups. In the United States, homosexual and bisexual people often meet widespread violence, discrimination, and prejudice. The discrimination takes many forms from being denied raises, promotions and getting poor performance evaluations to bullying in schools. The fear of being known as a homosexual or bisexual has led to men hiding sexual orientation from loved ones and doctors thereby possibly putting themselves and loved ones at an increased risk for HIV/AIDS. Regardless of the fact that no one can avoid diversity, people fear differences and seek only what is perceived as safe; remaining ignorant to what others have to offer. Fearing people different from us is a natural tendency because of how we were raised. When we treat one another as individuals with feelings, then we will experience true multiculturalism.

Obesity Improving Health Outcomes - 520 Words

While exploring possible health issues and a population to focus on for my project, I was overwhelmed by the number of issues we are faced with everyday. I narrowed the search down to obesity and the population I would like to focus on is the adolescents. Health People 2010 identified overweight and obesity as one of the top ten leading health indicators that needs serious attention. Obesity has reached epidemic levels globally; being a significant threat to our own nation’s health. Adolescent obesity rates have more than tripled, as the adult obesity rate has doubled since 1980’s (Trust for Americas Health, 2011a). It was interesting to learn of particular statistics and trends concerning adolescent obesity in our nation. Geographic†¦show more content†¦It’s not easy growing up in today’s world as an adolescent. The psychological, physical, social, and environmental factors can have significant negative impacts on their health. During the adolescent phase it is a very â€Å"extraordinary plasticity† period (Steinbeck, Baur, Cowell Pietrobelli, 2009, p. 2). These individual’s habits, attitudes, and physical morbidity develop during this phase. This establishes the pathway and blueprint that influence their long term health and wellbeing. When deciding what approach I would take when addressing this epidemic problem, I decided on health promotion and prevention. The two are so closely interrelated that it is hard to separate. However, health promotion and prevention also have over lapping boundaries with health management, marketing, community empowerment, and policy. In order to promote and prevent this epidemic, we need to rely on the policies (that regulate food and exercise in our schools and communities), the marketing (that promote and provide the tools to make our nation aware about this epidemic), and community empowerment (to support our nation about how to permanently change their lifestyles and way of thinking). I chose health promotion and prevention as it draws from the actions of these other elements. In order to be most effective, a system-wide approachShow MoreRelatedThe Healthy People 2020 Objective Nutrition And Weight Status Essay1451 Words   |  6 PagesThe Healthy People 2020 objective Nutritio n and Weight Status has a goal of improving the diet of Americans, thus improving their overall health. â€Å"Diet quality is critically important to the prevention of many types of chronic disease† (Wilson et al, 2015, p. 302.) 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Escapism And Disassociation In The Sun Also Rises - Free Essay Example

Sample details Pages: 6 Words: 1841 Downloads: 8 Date added: 2019/08/16 Category Literature Essay Level High school Tags: The Sun Also Rises Essay Did you like this example? In The Sun Also Rises, written by Ernest Hemingway, we are met with many problems faced by the lost generation after WW1, including the search for fulfillment, love, and the aimlessness of the lost generation. However, readers are also met with another and more problematic conflict. Dissociation and escapism which is presented through the main protagonists Jacob Barnes and Lady Brett Ashley who display similarities with Maladaptive Daydreamers. Don’t waste time! Our writers will create an original "Escapism And Disassociation In The Sun Also Rises" essay for you Create order Just like those who are Maladaptive Daydreamers, Jake and Brett are constantly trying to dissociate and escape from the world around them, because they cant bear to live the life they have post-war or stand to be the people they have become, this results in them further losing their sense of self and becoming more dissatisfied. As shown above Maladaptive daydreaming is an under researched and a unrecognized mental disorder. In a article written by Eli Somer, he describes it as a extensive fantasy activity that replaces human interaction and/or interferes with academic, interpersonal, or vocational functioning (1). The symptoms include highly vivid daydreams that are abnormally long, a strong attachment to such daydreams, inability to carry out everyday tasks, insomnia, and daydreams triggered by real life events or stimuli. Those who maladaptive daydream tend to have some other underlying mental disorders alongside it, for example, within the article it is mentioned that six patients who were identified to be maladaptive daydreamers, four were diagnosed with dissociative disorder, and two were diagnosed with narcissistic personality disorder. However, if they dont have a mental health issue, they have some sort of traumatic experience that has happened to them instead. According to the article Maladaptive Daydreaming: A Qualitative Inquiry, written by Eli Somer, people who maladaptive daydream, often do so to cope with what is going on in their lives or an traumatic experience, but also as a way to express themselves. Through their daydreams they are able to disengage from stress and pain, have fulfilling fantasies, and companionship. In their dreams there is recurring themes such as violence, power, control, and an idealized-self (1). Many people view this disorder as an quirky trait, but its much more than that, some think of it as a addiction, not being able to stop it, others view it as a much deeper issue. The issue of you not wanting to be you. Which therefore leads to them daydreaming a different world in which they are someone they want to be and are able to escape who they are in reality. Just like the maladaptive daydreamers both Jake and Brett had gone through a traumatic experience themselves, which leads to both of them trying to disengage from themselves in order to forget and not feel the pain caused from those experiences. Jakes traumatic experience is being wounded while fighting in WW1, in which it can be assumed he also saw many horrors. Bretts traumatic case would be losing the so called love of her life in WW1, but it can also be assumed since she was a nurse during WW1 that she some horrific injuries and the deaths of other soldiers who could have possibly been under her care. Therefore, in order to forget such incidents, they try to suppress their emotions, and both start to dissociate from the world around them and themselves hoping to escape, especially Jake. Therefore, Jake resorts to alcohol, in which he uses it to suppress his emotions, and just like any Maladaptive Daydreamer, Jake cuts ties with his ego and insecurities. An example of this, I swung at him and he ducked. I saw his face duck sideways in the light. He hit me and I sat down on the pavement. As I started to get on my feet he hit me twice. I tried to get up and felt I did not have any legs. (Hemingway, 195). Leading up to this Jake shows a great deal of anti semitism and hate towards Robert Cohn, however, when he is sober Jake holds it back, and at most is passive aggressive. Whereas in this scene, Jake being intoxicated, gets in a argument with Cohn, starts a fight and throws the first punch, and ultimately ends up getting knocked out and losing the fight. The significance of this scene shows us that by attempting to escape through the use of alcohol and in a attempt to abandon his emotions, he only engages in them, doing the exact opposite of what he intended to do thro ugh the use of alcohol. According to the article, Painful interpersonal experiences encountered during a time when basic assumptions about the world and their self-images were developing, sent these young persons into their much safer imaginary world. (Somer 14). For many Maladaptive Daydreamers, when daydreaming, will often have their daydreams, even though a complete fantasy, reflect the emotions they feel, because through these daydreams just like Jakes alcoholic tendencies, they express what they fail to express in real life. We see the feelings they didnt express, the words they didnt say, the journeys they didnt make, and the beliefs they didnt defend. Jake in his attempts to cut ties with who he is, fails in cutting ties with his emotions, and in his attempt to escape and dissociate he ends up causing more misery and despair for himself. Whereas Brett uses neither alcohol nor Maladaptive Daydreaming to escape, but rather uses relationships instead. By trying to seek that happiness and fulfillment and essentially fill that role of the true love she lost, she only ends up becoming more and more dissatisfied. She uses these relationships thinking theyll fix everything yet they always fail and some poor mans heart is broken for the most part. Brett is especially aware of the role she is playing in her relationships, and she is also aware of the fact that she is hurting others whenever she goes into and out of such relationships, however she continues to act like this. In the end of it all, she leaves, every time she isnt able to get what she wants, or when she isnt able to gain full control of the relationship. She has troubles in her interpersonal relationships just like Maladaptive Daydreamers. For example, Im going back to Mike. I could feel her crying as I held her close. Hes so damned nice and hes so awful. Hes my s ort of thing. (Hemingway 247). After which Pedro Romero and Brett end their relationship, for the first time in the novel we see Brett not only truly upset. But we also see that Brett is capable of emotional depth, and that she is also capable of expressing it, yet she doesnt and in fact tries to avoid doing so in an attempt to dissociate from herself. Furthermore, just like Maladaptive Daydreamers, Brett is running, because shes afraid of emotional depth because it means commitment, but it also means coming to terms with who she is and acknowledging what she feels. As a result, Brett chooses not to express her emotions and ends up trying to hide them in an effort of trying not to ever face them, so she engages in these meaningless relationships with no emotional connections. However, by running and trying to get away by having these disconnected relationships, we can see Brett only further disappoints herself, and even though she breaks someone elses heart, she also ends up breakin g her own in the process. And in all these attempts of running and the constant search of fulfillment she only finds more heartache and sorrow, the very things she didnt want to find. Jake is also very clearly not happy, not only with himself but the life he is living, because of his wound he is not capable of having children nor is he able to be in a relationship with Brett, his true love, which is not only the main source of conflict in the novel, but also one of the main reason for his unhappiness and why he doesnt want to be who he is. Jake is constantly dissociating, shifting focus from himself to immediately something else as though by not thinking about the pain and bitterness, that itll go away. For example, Undressing, I looked at myself in the mirror of the big armoire beside the bed. That was a typically French way to furnish a room. (Hemingway 38). Through this example we can see the shame Jake feels by immediately changing narration and the main focus from himself to something immensely different. Not only is Jake depressed, unhappy, but he is also not proud of himself, because just like Maladaptive Daydreamers, he is not his idealized self. Hes this veteran of World War 1, hes suppose to be the traditional male hero, and what better way to show that by him fighting in a war and coming back alive. However, he isnt or at least he doesnt feel like it, but instead he feels insecure because hes emasculated since he doesnt have the ability to have sex anymore. By having Hemingway present Jake the way he is, he allows for Jake to represent the lost generation, including their feelings of aimlessness and unhappiness. He does this by making Jake display the actions that some of those of the lost generation did. Such as becoming an expatriate, and leaving behind America, his home country, which is a clear and physical example of an attempt to escape, because perhaps by physically leaving jake could leave behind the part of himself he doesnt like, and give himself a fresh start. However, by leaving America, living and working in Paris, and traveling all over Europe, Jake doesnt change, he doesnt get that fresh start, he doesnt gain more power or control over his situation. He doesnt magically get with Brett and everythings happily ever after, and he doesnt stop drinking, and he certainly doesnt reach nirvana, but even in the last lines of the novel, Bretts still there beside him, and nothing much changes for her either. If anything, nothing from the beginning of the book changed towards the end, but maybe thats how things are suppose to be. By constantly trying to escape and dissociate from the world around them and who they are, in an attempt to disengage from their emotions as well, how would Brett and Jake ever know what made them happy, or more importantly how would they ever know how to move on, when they couldnt confront the issue head on or be capable of being who they really are. They werent able to change their situations because they never confront ed the issue that was the source of their pain because such confrontations or conflicts are too difficult to face. So they ran and tried to live being something else, just like how Maladaptive Daydreamers dreamed another life, the life they wanted to live, but thats the problem, they dreamed and nothing more, and tried to be something they werent. They couldnt be happy because they werent themselves, after all thats what they were running from ultimately leading to their dissatisfaction and despair.