Patient Teaching

Patient Teaching: Importance of Repositioning Sean Crayton University of Toledo College of Nursing Patient Teaching: Importance of Repositioning Assessment of Patients Learning Needs M. C. is an elderly male who was admitted and treated for a fall and hip fracture. He had surgery, is bed ridden but is soon to be released. He and his family need proper teaching on the importance of reposition as to avoid obtaining pressure ulcers during his limitations to extensive bed rest and staying off of his feet or performing any unnecessary movements that could cause irritation or reinjuring the recently repaired hip.As requested we are including the family who will be his primary care takers at home and it is necessary that they all learn how to take care of M. C. properly due to his inability to adequately reposition himself successfully in the early stages of his release. Priority Nursing Diagnosis Knowledge deficit. Patient will need proper positioning teaching. The teaching will pertain to the deliberate placement of the patient or body part in order to promote proper physiological and psychological well-being. r/t.Lack proper knowledge related to how position/reposition M. C. to avoid development of pressure ulcers. AEB. M. C. was admitted with a hip fracture and received surgery. He is soon to be release to go home but is ordered to long term bed rest. Desired Patient Outcome(s) At the conclusion of the patient teaching and proper diagnosis care we hope to ensure that M. C. and his family adequately know how to position/reposition the body to reduce the risk of pressure ulcers, at more importantly the critical, but all areas of the body.Time Frame. Being realistic we are giving M. C. and his family the duration of his projected discharge week in order to properly and thoroughly learn the information and techniques required to successfully position/reposition a patient at risk for pressure ulcers. Interventions Managing patients at risk for pressure ulcers relies on a multitude of different interventions implemented by nurses in a hospital or responsible care takers and family members in the home setting.These interventions include but are not limited to: using support surfaces, optimizing nutritional status, moisturizing critical areas and of course, what we are focused on in this particular patient teaching instance, repositioning the patient (Reddy, Gill & Rochon 2006). Regular turning of patients is routinely used ostensibly to decrease the risk of pressure ulcers, and is considered a standard of care (Peterson, Schwab, Van Oostrom, Gravenstein & Caruso 2010). Pressure from lying or sitting on a particular part of the body results in oxygen deprivation to the affected area.This normally results in pain and discomfort which stimulates the individual to move. Failure to reposition will result in ongoing deprivation; poor wound healing and further tissue damage. Patients who cannot reposition themselves require assistance (Moore 2010). To bet ter ensure that this will be handled for M. C. we will be including his family in the teaching. Teaching strategies. In order to teach and relay this process and the importance of patient repositioning to M. C. and his family I will be focusing on the utilization of pictures and demonstration.Teaching will take place throughout the duration of M. C. ’s projected discharge week. During this teaching there will be a chance for them to return the demonstration to me so that they can practice and show they understand before it is necessary for them to do it in the real setting all the while allowing adequate breaks and time for them to process the information and ask questions if any do arise (remember to stay open to conversation with my patient and his family). Rationale. The most important thing that I feel to remember is that all patients or people in general do not learn in the same fashion.You have your different visual (learn best when presented with graphs and other illus trations, maps, written material), auditory (learn best when they can listen to a lecture or a fast paced exchange of information) and kinesthetic (learn best when they can just do it and are hands on) learners. Before trying to teach your patient or possible care takers how to perform or ensure proper intervention application you should first figure out the best way to teach them. I chose to provide pictures, demonstrate and allow a return demonstration or practice session with M.C. and his family because from inference and their replies to my questions pertaining to their learning strategies they all learn best visual and when performing and practicing themselves. I will be including M. C. ’s family because they are who he preferred and indicated to take care of him while he is rendered unable at home. Neither M. C. nor his family have experience dealing with caring for a person at risk for pressure ulcers so it is important that I cover all bases and be specific with infor mation.Knowing that not everyone learns at the same speed or has the same mental capacity is my reason for breaking it up and allowing for conversation and questioning so that everyone is able to comprehend and understand the information and techniques that are being provided during this teaching session. I don’t expect them to learn and understand all this in one day and it is important to break up the session so during the week of M. C. ’s discharge I will be spacing the learning sessions out. Evaluation of LearningDuring the return demonstration and their responses to my questions I evaluated their understanding to rate their processing of the information and techniques. M. C. and his family understood all the information and seemed thoroughly prepared to perform the necessary tasks related to patient repositioning and reducing risk of pressure ulcers at the end of the teaching course. It is important that when documenting I provide the patient teaching including th e information covered and the resources I used to demonstrate and infuse the importance of repositioning to M.C. and his family. Reference Moore, Zena. (2010). Systematic review of Repositioning for the Treatment of Pressure Ulcers. EWMA Journal, 10(1), 5-12. Peterson, M. , Schwab, W. , Van Oostrom, J. , Gravenstein, N. , Caruso, L. (2010). Effects of turning on skin-bed interface pressures in healthy adults. Journal of Advanced Nursing, 66(7), 1556-1564. Reddy, M. , Gill, S. S. , & Rochon, P. A. (2006). Preventing Pressure Ulcers: A Systematic Review. JAMA, 296(8), 974-984.

The road to Mecca Essay

The play ‘The road to Mecca’ by Athol Fugard is a feminist play that expresses the struggle for freedom, identity and meaning through personal fulfilment. In the statement â€Å"There’s nothing sacred in a marriage that abuses the woman† (p23), Elsa expresses her feelings towards women’s rights, because these rights are supported by the law: â€Å"She has got a few rights, Miss Helen, and I just want to make sure she knows what they are.†(p23). Helen finds it interesting that Elsa has a liberal way of thinking and can express her feelings so freely. Elsa believes in the equal rights to all races and that no one should be treated unworthy: she believes Katrina must get rid of that â€Å"drunken bully† (p23), because she can â€Å"Find somebody who will value her as a human being.† (p23) Elsa represents women that believe in human rights and freedom of speech. When Elsa and Miss Helen are discussing ‘Getruida’, Elsa states that Helen should â€Å"Tell her to demand her rights to get up there and put her case† (p24). Helen does not agree with Elsa’s point of view; that women should stand up for their rights and tells her â€Å"you’re terrible† to which Elsa replies: â€Å"And you’re an old hypocrite, Miss Helen† (p24). Elsa believes each person has the freedom to make their voice heard; regardless of gender, age, religion or race: â€Å"Has anybody bothered to ask the colored people what they think about it all?† (p25) Miss Helen is part of the conservative White Afrikaners of Nieu Bethesda that still have fixed ideas about religion and Christianity. Miss Helen does not express her views and rights as a woman verbally but visually creates her own â€Å"Mecca† of beauty and freedom. She decorates the inside of her house with dozens of candles and mirrors; Helen’s room is a â€Å"little miracle of light and colour† (p33). The inside of ‘The owl House’, represents the link between creativity and light, the candles being Miss Helen’s freedom of expression. The outside, the ‘camel yard’, is a myriad of cement wise men, camels, owls, mermaids and other figures, mostly facing east (representing that the figures are looking towards the city of Mecca in Saudi Arabia).  Miss Helen’s ‘Mecca† is a metaphor for the relationship between freedom and imagination. Miss Helen sees her art as being her right of personal expression of her own i dentity and inner feelings: â€Å"It is the best of me, Elsa† (p34) Miss Helen was a woman devoted to her church, but after the death of her husband she did not mourn as many expected, instead she lit her house with candles and sculpted bright, lifeless figures and allowed her to escape â€Å"the darkness that nearly smothered† her life. Miss Helen now has the right to make her own choices; she does not to become another churchgoing widow, but instead set herself free by doing what she loves and creating a wonderland of art because she â€Å"dared to be different†. Miss Helen alienated herself from the Afrikaner community of Nieu Bethesda because they judged her vision and rejected her art. The community expected Miss Helen to stay inside behind closed curtains, but Miss Helen did the opposite and let as much light into her life as she possibly could. Elsa said: â€Å"Light is a miracle, Miss Barlow, which even the most ordinary human being can make happen.†(p32). Through Helen’s art she survives in an isolated community and freely expresses herself. When Miss Helen met Elsa, she showed her the inside of her house and when Elsa saw Helen’s home, lit by candle light, she knew she had found a true friend: â€Å"I so desperately wanted you to like what you saw.† (p34) followed by â€Å"If you only knew what you did for my life that day†. When Elsa saw Miss Helen’s ‘Mecca’ for the first time she was overwhelmed: â€Å"I just stood there and gasped† (p33). Miss Helen was pleased: â€Å"How much courage, how much faith in it you gave me.† (p35). Elsa admired Helen’s courage to fulfil her dream despite the religious views of the community. Miss Helen finds happiness and piece in her own ‘Mecca’ and does not concern her with the vision of the community on what is considered to be â€Å"right† but rather believes her â€Å"Mecca has got a logic of its own,† (p36). Elsa and Miss Helen are both women in a crisis point in their life and rebels against social conventions in their own special way. Miss Helen is a strong  woman that is not dependent on men unlike Elsa who had an affair with a David, a married man, and always believed he will leave his wife for her, where she ended up â€Å"being a victim of the situation†(p30) Elsa hides her secret until the end of the play. The local priest of Nieu Bethesda, Marius Byleveld, wants Miss Helen to move to â€Å"Sunshine home for the aged† (p40) in Graaff-Reinet, because he fears for her safety after she had an accident where she burnt herself when a candle fell over. Miss Helen wrote a letter of distress to Elsa, who then drove all the way from Cape Town to assist Miss Helen. Marius Byleveld came to see Miss Helen to express his concern that the community labelling Miss Helen as ‘mad’. He came to tell her that a room is available in an old age home and he ensured that she was moved to the top of the list â€Å"as a personal favour† (p56): he also expresses that there is a â€Å"decision to be made, one way or the other†. Marius is a â€Å"persuasive talker† (p42) and puts a lot of pressure on Miss Helen by asking her many questions such as why she doesn’t go to church anymore (p66) and accuses her of idolatry (p67). He is trying to make decisions on her behalf saying it is his â€Å"duty as a Christian† (p67). Marius does not respect Miss Helen’s art or her opinion, when speaking to her, seemingly passive Miss Helen, has to stop him and say: â€Å"Can I please talk now†. Marius is not only interested in Helen’s spiritual well-being but also fears for Miss Helen’s health and safety, because her appearance displays â€Å"personal neglect† (p15) and he feels she will be better off in an Old Age Home. His concern also has deeper meanings because he is concerned about her self-imposed exile from church and that she does not act what is socially expected of her. He evokes Miss Helen when he calls her statues â€Å"ornaments† and â€Å"cement monstrosities†. Marius Byleveld does not understand why Miss Helen is so persistent to stay in her own house where her ‘hobby’ seemed to have taken over her life and backyard: â€Å"You call that †¦ nightmare out there an expression of freedom?† (p67). He believes her â€Å"life has become as grotesque as those creations out there† Miss Helen was pulled in two directions by the two people closest to her; Elsa encourages Helen to be strong and independent and to stand up for her rights as an independent woman, while Marius motivates her to give in and move to a home where people can help take care of her needs; where she can become an active member of the church and community. Elsa challenges Miss Helen to stand up for herself and not give into Marius’s request; â€Å"You haven’t got enough faith in your life and your work to defend them against him† Helen explains herself to Marius: when her husband, Stephanus, died she â€Å"lost faith† and used as many candles as she could find, because the â€Å"candles did all the crying†. She created her own â€Å"Mecca† as personal goal to set herself free. The candles that were lit after the funeral inspired Miss Helen to express her inner feelings: â€Å"I had all the candles I wanted† (p46). Elsa says it beautifully: Miss Helen is â€Å"the first truly free spirit I have ever known†. Elsa believes that all people have rights, as that is what she teaches her children in her class. Elsa empowers Miss Helen to choose freedom and not move to the retirement Home: â€Å"When he comes around tonight, hand this back to him †¦ unsigned †¦ and say no.† (p42) because Elsa believes â€Å"You’ve got to prove to the village that you are quite capable of looking after yourself.† (p44). Elsa vehemently urges Helen to resist Marius Byleve ld’s â€Å"help,† and that she should refuse his offer: â€Å"You’re still living your life, not drooling it away†(p43). Miss Helen has both the right and freedom to choose where she wants to live. With the help of Elsa, Miss Helen takes a stand for her personal rights to remain in her own little â€Å"mecca† rather than going to the retirement Home. Elsa is proud of Miss Helen who is now â€Å"A free woman.†(p66) and states: â€Å"You affirmed your right as a woman† (p75)

Family Assessment and Nursing Process Essay

According to Stanhope & Lancaster (2001), a family nursing assessment is considered to be the cornerstone for family nursing interventions and is used in a systematic fashion for the identification of the family’s developmental stages and risk factors. There are many tools available that provide guidelines for how to best get to know a family and to determine their strengths and weaknesses. One such tool is the Friedman Family Assessment tool which provides a guideline for nurses to interview a family. Theory is also a necessary tool when assessing a family because it is theory that most powerfully explains clinical situations and provides guidelines when working with families (Friedman, Bowden, and Jones, 2003). The theory that will be applied to family assessment in this paper is the structural-functional theory. The structural-functional theory recognizes the interaction between family members within their internal and external environment (Friedman et al., 2003). Once a co mprehensive family assessment is complete and health issues are identified, the nursing process is implemented in order to render care that is imperative for assisting each family member to achieve an optimum level of wellness (Gilliss & Davis, 1993). In compliance with HIPPA regulations of strict confidentiality, the fictitious name of Listo will be used to identify the family that is assessed in this report. The Friedman Family assessment model will be followed as a guideline to discuss the family’s identifying data, the structure-function of the family members, and how the family handles stress, coping and adaptation. Lastly, key assessment data will be used in the nursing process in order to assess, diagnose, plan, intervene, and evaluate a family member’s diagnosis. The Listo family is an extended family that is composed of a marital dyad, their two adult sons, the maternal grandmother and the son’s girlfriend who is in her second trimester of pregnancy. The husband and wife have been married for 30 years and their sons are ages 23 and 26years old. The husband identifies his ethnicity as Italian. His primary language is English and he  was born and raised in California. His parents migrated to the United States from Italy in the early 1940’s. Because they migrated at such a young age, his patents have acculturated to the American way of life, but still feel strongly about their cultural heritage (McCallion, Janicki, & Grant-Griffin, 1997). The wife identifies her ethnicity as Caucasian. She was also born and raised in California. Both husband and wife grew-up in the Catholic faith and attended church primarily on holidays. In their mid-thirties, they accepted Christ as their personal savior and became born again Christians; first the husband and then a few months later the wife. The husband owns a painting business for residential properties and the wife sales residential real estate and works for a local real estate company. They are considered a lower-middle class family. The major distinguishing characteristics of the lower-middle class family are respectability, achievement, hard work and honesty (Friedman et al., 2003). Neither husband nor wife has a college degree. Both are hard-working and are proud that they have provided financially for their sons who have both received a college education. Previously, the 25 year old son and his girlfriend were living together and were a dual income household. They both moved in with his parents when the girlfriend had to quit her job because of complication she suffered during the first few months of her pregnancy. They plan to marry once they are financially stable. The son is currently working as a physical fitness coach for a college football team and contributes financially to the family. In June of this year, the 22 year old son graduated with a Bachelor’s degree and moved back home. He is currently looking for employment and hopes to move out within the year. The grandmother is 76 years old and has lived with the family for the past year due to the progression of her COPD. FAMILY STRUCTURE According to Friedman, Bowden and Jones (2003), the concept of analyzing the structure of a family refers to how the family is organized, how the components are arranged and how they relate to each other. The four main structures of the family are roles, values, communication processes and power and decision-making. The role theory is the structure that is the focus of the Listo family. Family roles play a critical part in the organization of the family and because of this the family nurse must understand role relationships in order to be able to promote healthy role behaviors and identify role problems (Friedman et al., 2003). According to the role theory, a family member will play many roles in a family. There are both formal and informal roles within the family structure. Formal family roles include the more obvious roles such as mother-wife, father-husband, and father-son. The less obvious roles are that of encourager, harmonizer, initiator, scapegoat, compromiser, etc. Informal roles are more likely to be based on personality than age or sex (Kievit, 1968). Within the Listo family, the husband-wife dyadic relationship is complimentary exhibited by a contrasting relationship (Friedman et al., 2003). As the formal role of wife, Mrs. Listo is the leading dominant personality and makes most of the decisions in the family including decisions about the children and the household finances. She is also the main source of income for the family. As the formal role of husband, Mr. Listo is more of a follower, a position he appears to be content with. According to Friedman, Borden, and Jones (2003), there is a strong element of dependency between the husband and wife in a complimentary relationship. This is true for the Listo family; they have a close bond and seem to be comfortable with their husband-wife give and take relationship. Assessment of the Listo family revealed numerous informal family roles. The grandmother takes on the informal role of recognition seeker. As explained by Friedman, Bowden, Jones (2003), the recognition seeker goes to great lengths to draw attention to self. When questioning the grandmother about other members of the family, she continued to turn every conversation back to a subject that involved her as the center figure. The two Listo boys have the informal role of caretaker. During the interview the grandmother continued to ask the boys to get her purse, find her glasses, and bring her some tea. When the boys were out of the room, the grandmother complained about how lazy the boys are and that they don’t understand her condition and what she’s going through with her COPD. The husband has the informal role of  follower. He goes along with the wishes of the family and if there is a dispute over how or what to do, he just listens and only participates in the conversation if he is directly asked a question. The wife has the informal role of Initiator-Contributor. She motivates the children with ideas and ways to accomplish goals and solve problems. According to Kantor and Lehr (1975), the Initiator-Contributor causes movement in the family and is characterized by the initiation of action. The girlfriend has the informal role as the encourager. She gives compliments freely and often. She appears to be genuinely interested in listening to others and she rarely draws attention to herself. â€Å"The greater the perceived clarity of role expectation the higher the quality of role enactment† (Friedman et al., 2003, p. 324). When evaluating the quality of each role, it was determined that the family members clearly understand their roles and are content with the expectation that is attached to each role. The exception was the 23 year old son, who exhibited role conflict with his duties as caregiver for the grandmother. After having the freedom of college life, it has been difficult for the 23 year old to be living back at home and having specific expectations put upon him. According to Friedman, Bowden, and Jones (2003), the youngest son is experiencing intersender role conflict, which happens when there are conflicting expectations regarding the enactment of a role. FAMILY HEALTH FUNCTION According to the Structure-Function theory, a function is an outcome or consequence of the structure. Function is described as being what the family does. Friedman, Bowden, and Jones (2003) describe 5 specific functions: affective, socialization, reproductive, economic and health care. The focus of the Listo family assessment is the function of health care. The Friedman Assessment Model was used as a guide. According to Friedman, Bowden, and Jones (2003), health practices and health care services are extremely varied from family to family. Families are diverse in the way they conceptualize health and illness and when to seek health care. The Listo family prides themselves on how healthy they have been. Until recently, the family had what they described as â€Å"catastrophic† medical insurance. The mother and father are both independent contractors and do not have insurance through their place of employment. Their insurance policy carried a $1,500 deductible. This high deductible deterred the family from visiting the doctor for regular check-ups. The Listo family falls under the umbrella of â€Å"underinsured† which has prevented them from receiving comprehensive health care. With the wife’s real estate doing so well over the past couple of years, the Listos now have an insurance plan that covers standard check-ups and dental care as well. The 25 year old son receives health coverage from his employer and the girlfriend has private insurance. With so many years without health care access, the Listo family has not participated in health management. According to Friedman, Bowden, and Jones (2003), the family needs to be in direct partnership with health care providers. Clients also need to be the ultimate decision makers and managers of the health issues that affect their lives. Health education is needed so that the Listo family can feel empowered to direct their own health care (Friedman, et al., 2003). The 2 sons exercise regularly and eat a well-balanced diet that includes fruits, vegetables and grains and are in good health. The girlfriend takes charge of her health and the health of unborn child by keeping all of her scheduled appointment, asking important questions, and following the guidelines agreed upon between her and her physician. The husband is overweight and has hypertension and hyperlipidemia. The hypertension and hyperlipidemia are controlled with medication. The husband is not consistent with getting his check-ups and having his blood The wife is slightly overweight which she attributes to a bad diet and lack of exercise. Generally, the Listo family is in good health. In the case where the family is healthy, health promotion is the goal of family nursing (Friedman, et al., 2003 p. 436). One goal for the Listo family is health promotion. The one member of the Listo household that is chronically ill is the Grandmother. She admits that her COPD was caused by 40 years of smoking 1-2 packs of â€Å"Camel† no filter cigarettes a day. Each year in the United States,  hundreds of thousands die prematurely due to living unhealthy lifestyles (Friedman, et al., 2003). As the caretakers for the grandmother, the Listo family is at risk for role strain. The grandmother’s condition is progressive and as time goes on she will become more dependent on the family members for care. Orem’s self-care model is applicable to this family. According to Orem’s self-care theory, nursing care is required when an adult is no longer able to care for themselves. It also states that nursing care may need to be directed toward the caretakers (Friedman et al., 2003). FAMILY STRESS, COPING, AND ADAPTATION The Listo family is resilient and they have recovered, adjusted, and adapted to stressful situations in their family. This is why The Resiliency Model of Family Stress, Adjustment, and Adaptions Model best describes the way the Listo family deals with stressors. According to this theoretical framework, there are four basic assumptions about the family: First, it’s a natural part of life to encounter hardship and changes. Second, families develop strength and capabilities that cause them to grow and develop as a family unit. Third, the strengths and capabilities gained during a stressful event provide protection for the family and allow the family to adapt to the new situation. Fourth, families benefit from the contribution they make to the network of relationships and community during times of family stress (McCubbin & McCubbin, 1991). The stressors that have caused the Listo family to gain strength and capabilities and to grow as a family are many. Some current stressors are caring for a chronically ill family member, unmarried son’s girlfriend is pregnant, son and girlfriend moving in with the family, financial insecurity due to self-employment, and youngest son is unemployed. SOCIAL AND SPIRITUAL COPING STRATEGIES. According to Friedman, Bowden and Jones (2003), there are two types of coping strategies; internal and external. Internal family coping strategies are when the family becomes reliant on their own resources such as pulling together and creating more structure and organization in the home, whereas with external coping strategies the family relies on community, extended family, neighbors and friends. Most often, the Listo family uses an internal family coping  strategy. They have restructured their lives so that each member can contribute to the care of the grandmother since she moved into the family home. They have also pulled together and reorganized their home to accommodate the son’s girlfriend. When business is slow for the parents, the eldest son contributes financially to assist with finances. The husband and wife also use external family coping through spiritual strategies such as having faith in God and prayer (Friedman et al., 2003). The Christian faith is where the husband and wife draw comfort and peace in times of stress. Their faith in God is strong. They believe that the Lord will guide them during a crisis and will not allow them fall. â€Å"Numerous studies have shown the clear linkage between spiritual well-being and an individual’s or a family’s enhanced ability to cope with stress and illness† (Friedman et al., 2003, p. 486). The Listo parents believe that their enhanced ability to cope with stress and illness comes from their personal relationship with Christ. DYSFUNCTIONAL COPING STRATEGIES. According to Friedman, Bowden, and Jones (2003), Dysfunctional families most often unconsciously choose to use coping strategies that have been passed down through the generations. These defensive coping strategies usually do not relieve stress nor eliminate the stressor. The Listo family’s dysfunctional coping strategy is authoritarianism. This happens when the family members submit to a dominant, ruling figure. The husband and sons are very submission to the authority of the wife-mother. They sons are adults in their twenties, but they constantly call their mother prior to making any relevant decisions in life. The husband also defers to his wife for any family decision. The dominant figure, Mrs. Listo, is also dependent on her subordinates because it satisfies her need for power and control (Friedman et al., 2003). The family adores their mother and the husband also speaks very kindly of her. She is domineering, but very loving and often lavishes the family with gifts. INTERVIEW NOTES BASED ON THE FRIEDMAN FAMILY ASSESSMENT MODEL IDENTIFYING DATA 1. Family Name: Confidential (Listo is the fictitious family name) 2. Address and Phone: Confidential 3. Family Composition: see Family Genogram (Figure 1) 4. Type of Family Form: Extended Family Father – Painter, Mother – Real Estate Agent, two unmarried adult sons Grandmother, Son’s girlfriend 5. Cultural (Ethnic) Background: Caucasian American and Italian (English Speaking) 6. Religious Identification: (Born-again Christian) 7. Social Class Status: Lower-middle class, family works hard to pay the bills. Income sources: Painting business – father, Real estate business – mother, Sports Trainer – son, grandmother – social security Father and mother have high school education Two sons – first generation to receive a college degree 8. Social class mobility: stationary at this time. Limited income and live paycheck to paycheck. The parents are supporting the grandmother, 2 sons, and son’s girlfriend. DEVELOPMENTAL STAGE AND HISTORY OF FAMILY 9. Family’s developmental stage_: Stage VI: Families launching young adults_ 10. Extent Family is Fulfilling Developmental Tasks: parents were empty nesters until 1 month ago when the eldest son moved back home with his girlfriend who is 5 months pregnant, the youngest son just graduated college and moved back home, and the grandmother moved in less than a year ago. The parents are adjusting to having children back in the home. 11. Nuclear Family History: both father and mother come from traditional nuclear families. 12. History of Family of Origin of Both Parents: Both husband and wife come from nuclear families in which the father was the provider and the mother was a homemaker. ENVIRONMENTAL DATA 13. Characteristics of Home: home is a little crowded with all the members currently living there. The youngest son shares a room with his grandmother. The home has 3 bedrooms and 2 baths with a medium size kitchen with attached family room. The home is clean and well organized. 14. Characteristics of Neighborhood and Larger Community: The neighborhood has similar single family homes that were all built around the same year. The lawns are well maintained and the streets are clean. The neighbors participate in a neighborhood watch group to keep the area safe. Children can be seen riding the bikes and skateboards on the block. The city is in the Foothills, not far from Los Angeles and the home is in walking distance to the market and other shopping. 15. Family’s Geographical Mobility: The family lived in a more affluent area when the boys were growing up. At that time, the husband had steady work as he was partnered with a contractor who built estate homes. Approximately 10 years ago the partnership broke up and the husband found it difficult to market himself. The house went into foreclosure and the family borrowed  money from family to help them purchase the home they’re in now. The family is stationary in their current geographical setting. 16. Family’s Association and Transaction with Community: The mother and father are involved in the local church. They attend regularly and volunteer to help with special events. They know some of their neighbors, but they don’t get together with them socially. The younger son volunteers at the YMCA working with youth. There are 4 vehicles in the family, so the family is not dependent on public transporation. FAMILY STRUCTURE 17. Communication Patterns: According to Mrs. Listo, a majority of the conversation between the father and the sons revolve around sports and is void of any discussion of an intimate matter. The father tends to be quiet until the subject of baseball comes up and then he sits up straight and gets enthusiastic about the conversation. Mrs. Listo often interrupted the conversation of other family members to make an announcement about subjects she feels are relevant. The grandmother doesn’t seem to have an audience when she’s trying to communicate to family members. She continues to converse even when it’s obvious no one is really listening to her. Mr. Listo appeared to get annoyed with the grandmothers complaints, but he didn’t verbally communicate his feelings. There were some obvious gender differences in communication. 18. Power Structure: The mother is dominant and the father is passive. This marital relationship would be considered complementary. When asking each member of the family who the dominant figure was, each stated that it was the mother. The mother also said that she was the dominant figure in the house. No one in the family seems to be discontent with where the power lies. 19. Role Structure: The formal roles are father-husband, mother-wife, son-brother, grandmother, and girlfriend. Informal roles: follower- father, initiator/contributor – mother, family caretaker – mother /sons, encourager – girlfriend, grandmother- recognition seeker 20. Family Values: Respect, honesty, hard-working, college education, Christianity, giving to help others (volunteering), helpful commitment and trust. FAMILY FUNCTIONS 21. Affective Function: The husband wife relationship is close and the mother and eldest son seem close. The relationship between the youngest son and mother seems to be strained due to the 23 year old wanting his independence. See Family Attachment diagram 22. Socialization Function: The father and mother have been married for 30 years and have raised their 2 sons. The mother stayed home with her sons until they were both in elementary school. The mother is a homemaker/real estate agent. Attending church was mandatory when the children were growing up. Once they reached the age of 18, the parents didn’t require that their sons attend church. The boys are now adults, but are currently living at home. They show respect for both parents and authority and appear to be well-adjusted. The father and mother are excited about the upcoming birth of their first grandchild. Health Care Function: The father has controlled hypertension and hyperlipidemia. The wife is slightly overweight, but has no medical condition. She admits to eating too much sugar and fried foods. The two sons are healthy. The pregnant girlfriend had difficulty in her first trimester, but she is doing well now. The grandmother is in poor health. She has COPD that is progressing to the point where she is on constant oxygen. The family has not been consistent with regular check-up until recently when they upgraded their medical insurance coverage. FAMILY STRESS, COPING, AND ADAPTATION 24. Family Stressors, Strengths, and Perceptions: stressors: financial struggles, sons that don’t practice the Christian faith, eldest son is  unmarried and expecting his first child, youngest son doesn’t have employment and will be moving out of the home as soon as he does, grandmother has COPD. Strengths: Mother and Father have a strong faith, the children are respectful, the eldest son helps financially, they have paid down their debt and are building credit, the family is managing their health 25. Family Coping Strategies: There number one source of peace and comfort comes from their relationship with God and their faith – external source of coping. The family members help each other out financially and emotionally- Internal source of coping. 26. Family Adaptation: The family is resilient. They take one day at a time and face the challenges as they come. They readjust their lives when stressors come along and they seek God’s plan to help them learn and grow through the stress of circumstances. Overall, the family adapts to the stressors that come their way and become closer as a unit as a result. NURSING DIAGNOSIS RELATED TO MANIFESTED BY KEY ASSESSMENT DATA & RATIONALE FOR RANKING (1) Ineffective self Health management (father) Lack of health care access. For the past 25 years, the family has had inadequate insurance and does not qualify for state assistance. They have avoided doctor visits as much as possible due a high deductible and out of pocket expense Uncontrolled hypertension & hyperlipidemia, obesity, sedentary life-style, poor diet, inconsistent medication adherence, infrequent check-ups This is ranked first because the father’s lack of maintenance could lead to Cardiovascular disease and Myocardial Infarction. Although the grandmother’s disease (COPD) is incurable and progressive, it is the father who has the capability to change the outcome of his condition with health maintenance. If the father’s condition deteriorates, he will not be able to run his business and the family will suffer financial strain. (2) Risk for caregiver role strain Caring for the grandmother who has a progressive disease (COPD) Physical exhaustion, frustration, emotional fatigue, isolation The mother works full time and runs the household. She is exhausted by the end of the day, but still needs to make time to care for her mother. There are multiple doctor appointments every week than she or her son the grandmother to. Most days the mother has nothing left over for herself and is too tired to socialize or go out. The youngest son is frustrated that he is expected to help care for the grandmother. He is looking for work so he can move out and get away from the situation (3) Dysfunctional Family Communication Wife and husband, Husband and sons, Grandmother and family Husband does not voice his opinion to his wife. Husband and sons only communicate about impersonal information. No one listens to the grandmother and the grandmother only discusses negative issues and complaints. The husband is submissive to the wife. He doesn’t voice his opinion or challenge decisions that he disagrees with. He avoids any kind of confrontation. The Father and the son’s keep the conversation on the surface. They don’t talk about feelings or ideas. The grandmother has gotten into the habit of complaining and possibly doesn’t know how to show care or concern for others. She is overwhelmed by her condition. (4) Ineffective family coping The youngest son’s frustration over his caregiver role The youngest son’s outbursts and his threats to move out as soon as possible. The youngest son is 23 years and has just moved home after having the freedom of living in a dorm at a university. Because he is the one member of the family that is not currently employed, he has the responsibility of caring for the grandmother during the day and taking her to all of her doctor appointments. His way of coping is closing himself in his room and threatening to leave the house forever. (5) Risk for complicated grieving Potential loss of significant person (grandmother) Inability of the family members to discuss the course of the grandmothers COPD. The youngest son verbalizes anger over caring for his grandmother. The family does not discuss the end result of grandmother’s COPD. When there is a decline in the grandmother’s functioning or an exacerbation of her condition, the family refers to it as just a temporary set-back. The youngest son refuses to be social with the grandmother because he resents  that he is needed to care for her. It is likely that he will have some guilt feeling and more difficulty with grieving after her death. FAMILY NURSING PROCESS The word â€Å"process† refers to a deliberate and conscious act of moving from one point to another toward goal fulfillment (Friedman et al., 2003, p. 174). The nursing process moves systematically from assessment, diagnosis, planning, implementation, and evaluation and is said to be interrelated and continuously cyclical of thought and action (Friedman et al., 2003). After a trusting relationship was established, the first step in the Listo family assessment was gathering information in a systematic fashion using the Friedman Family Assessment Model. The information was then classified, and analyzed to interpret their meaning. The following document outlines the nursing process as it relates to the Listo family. MAIN DIAGNOSIS PLANNING (GOALS) INTERVENTION (IMPLEMENTATION) RATIONALE FOR INTERVENTION EVALUATION Ineffective self Health Management (father) Short-term goal: The father will discuss his fear and inhibition to implementing a health regimen prior to the end of the nurses’ visit with the family. (1) Assess the client’s feelings, values, and his reasons for not adhering to the prescribed plan of care (2) Assess the father’s family patterns, economic issues, and cultural patterns that may be influencing compliance with a given medical regimen. (Ackley, J. G., Ladwig, G. B., 2011). Change theory is applicable to the Listo family: According to this theory, the nurse works with families to facilitate change. These changes can include structure as well as health behaviors. (Friedman et al., 2003). (1) Evidence Based Practice: assessment of an individual’s preferences for participation in health care decision making encourages involvement in decision making at the preferred level. (Ackley, B.J., & Ladwig, G.B., 2011) (2) Evidence Based Practice: Adherence to a treatment regimen is significantly influences by the family’s culture, spiritual beliefs and family norms (Ackley, B.J., & Ladwig, G.B., 2011) Short-term goal achieved: the father discussed his reluctance to manage his health. He admits that his own family was proud of how healthy they were without involving health care professionals. Another reason he explained for his lack of involvement in his own care is his fear that a regular check-up would reveal something serious. He verbalized his understanding that it is better to discover an illness early for prevention. He expressed a desire to be more involved in his own care. Long-term goal: The father will visit his health care provider within the next 30 days in  order to decide on a therapeutic regimen that is congruent with health goals and lifestyle. (1) Help the client to choose a healthy lifestyle that will address his condition and to encourage appropriate diagnostic screening tests (2) Review how to contact health providers that are listed under his insurance plan and how to address issues and concerns regarding self-management. King’s Theory of Goal Attainment is applicable to the father in this family. In King’s model, the nurses’ goal is to help the client maintain their health so they can adequately function in their role. (Friedman, et al., 2003). (1) Healthy lifestyle measures, such as exercising routinely, maintaining a healthy weight, eliminating smoking and limiting alcohol intake can help to reduce the risk of chronic illnesses. (Ackley, B.J., & Ladwig, G.B., 2011) (2) Evidence Based Practice: people with chronic illnesses need to know how to obtain interventions that are needed to address issues and concerns regarding self-management. (Ackley, B.J., & Ladwig, G.B., 2011) Recommend: Revisit the family in 30 days to follow up on the fathers visit to his health-care provider. Evaluate the father adherence to his therapeutic regimen and his lifestyle goals. Conclusion The Friedman Family Assessment Model served as a guide to complete a comprehensive assessment of the Listo family. Nursing theories, including  the structure-function theory, helped to analyze the data collected. A systematic approach through use of the nursing process was implemented in order to devise a nursing care plan for the identified needs of the Listo family. This exercise required the author to spend a substantial amount of time getting to know a family and learning the intricate details of how to interview and observe a family for the purposes of health-care analysis. References Friedman, M., Bowden, V., and Jones, E. (2003). _Family nursing: research, theory, and practice_. Upper Saddle River, NJ: Prentice Hall. Gilliss, C. L., Rose, D. B., Hallburg, J. C., & Martinson, I. M. (1989). Does a family intervention make a difference? An interactive review and meta-analysis. In S. L. Feetham, S. B. Meister, J. M. Bell, & C. L. Gilliss (Eds.), _The nursing of families: Theory, research, education_ _and practice_ (pp. 259-265). Newbury Park, CA: Sage.. Kievit, M. B. (1968). Family roles. In Rutgers School of Nursing, _Parent-child_ _relationships – Role of the nurse._ Newark, NJ: Rutgers University. Kantor, D., & Lehr, W. (1975_). Inside the family; Toward a theory of family process_, San Francisco: Jossey-Bass. McCallion, P., Janicki, M., & Grant-Griffin, L. (1997). Exploring the impact of culture and acculturation on older families’ caregiving for persons with developmental disabilities. Family Relations, 46(4), 347-357 McCubbin, M. A., & McCubbin, H. I. (1991). Family stress theory and assessment: The resiliency model of family stress, adjustment, and adaption. In H. I. McCubbin & A. Thompson (Eds.), _Family assessment inventories for research and practice_ (p. 3). Madison, WI: University of Wisconsin-Madison. Nye, F. I., & Gecas, V. (1976). The role concept: Review and delineation. In F. I. Nye (Ed.), _Role structure and analysis of the family_ (Vol. 24). Beverly Hills, CA: Sage. Stanhope, M., & Lancaster, J. (2001). Community health nursing (5th ed.). St. Louise: Mosby.

Burger Kings famous advertising slogan Essay Example | Topics and Well Written Essays - 500 words

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GNSS VS Total Station) Base for Deformation Monitoring of Bridge - Essay Example To investigate the relationship between the surveying instruments GNSS and Total station and the difference in the effect of the deformation monitoring measurement of the dynamic Bridge. Additionally the aim is also to identify which instrument is more accurate and as it relate to deformation monitoring of the bridge Do a comparison of resultant data from both the GNSS and Total station as compared to GPS data and check for accuracy. To this end the dissertation will be divided into two parts. The first is a review of the importance of monitoring bridges for deformation, the problems that can occur with bridges over time, as well as the different categories of bridge contraction. This will set the background for the second part: comparing the use of GPS through GNSS and the use of total station monitoring for bridge deformation. While I was unable to meet with neither surveyors nor GPS operators, I will use other resources, such as online information, to compare these two instruments and present the results in an easy to understand

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THE CURRENT POLITICAL AND ECONOMIC RELATIONSHIP BETWEEN EUROPE AND CHINA - Essay Example During the Cold War Era, China was the largest and most powerful ally of the Soviet Union and the EU was the largest and most powerful ally of the US during the Cold War Era. What makes these alliances all the more important and interesting is the fact that the US and the USSR were divided in terms of political ideologies. The US represented capitalism and the USSR represented Socialism. With the collapse of the USSR in the late 1980s, China did not take over the role of successor to the USSR in leading the charge against capitalism, but demonstrated a desire to buy into capitalism to a certain extent. That China would remain committed to its Socialist system and embrace change with the aid of capitalist powers such as the EU is an enigma. The EU’s role in the strategic partnership is also interesting. The EU represents and promotes international standards for human rights protection and is at odds with the standard of human rights protection in China. Moreover, the EU imposed an armed embargo on China in the 1980s, just after signing a trade agreement with China. Yet the EU has been able to form a strategic partnership with China that appears to have strengthened over the years. Therefore studying the political and economic features of the relationship between China and the EU provides interesting insights into the politics and economics of bilateralism and multilateralism. The current political and economic relationship between China and the EU is contained in a strategic partnership which was announced in 2003. The strategic partnership arose out of Communications by the European Council in 1998 and 2001both of which addressed the shortcomings in a purely economic relationship in the trade agreement between the two in 1985. Although some scholars have criticized the strategic partnership between the EU and China on the grounds that it is unclear, the relationship has survived for more than a decade. Both the EU and China have expressed satisfaction wi th the political and economic gains enabled by the strategic partnership. This research report collects reports in the literature that shed light on the strategic partnership and demonstrates that, despite its problems, it has provided both the EU and China with economic and political benefits. These political and economic benefits appear to offset any differences between the two: the EU’s dissatisfaction with China’s human rights standards and China’s dissatisfaction with the EU’s attempt to interfere with the internal affairs of China. Annotated Bibliography Algieri, F. (2002). â€Å"EU Economic Relations with China: An Institutionalist Perspective.† In Edmonds, R. L. (Ed.) China and Europe Since 1978: A European Perspective. The China Quarterly Special Issues, New Series, No. 2. Cambridge, UK: Cambridge University Press. Algieri’s (2002) chapter which appears in a book on China and Europe’s relationship since 1978 provides detailed insight into the various agreements between the two and communications by the European Council on the changes that took place. Algieri’s (2002) account only goes as far as the 2001 Communication by the European Council, but does provide important background information for further research into this developing relationship. Algieri (2002) makes sense of

ESL II Essay Example | Topics and Well Written Essays - 2500 words

ESL II - Essay Example On the other hand, some students would be happy to wait and listen to their teachers of the lesson delivered and then develop strong concepts in learning English. Some students are keen to learn the basics or grammar as the foundation of learning English while others would be try to put the words in place by listening to the language conversation. It is, therefore, important for the teachers to switch to right approaches by understanding the needs of the classroom. Traditional methods The traditional methods of teaching English as a foreign language talk about the approaches of teaching English in a way that has been followed over the years. Various educationalists and eminent personalities could be spotted who have learnt English in the traditional approach. The traditional methods have been described below. Grammar Translation The grammar translation approach is one of the oldest approaches that were carried out in earlier days for teaching Latin in the countries of Europe. This is an intellectual way of learning language which was later applied by the teachers in the lessons of English as a foreign language. The method concentrates more on the reading and writing of English language. The speaking and the listening skills are not really tested in this approach. The teacher provides the students with the grammatical exercises and the students are asked to solve the problems. The students are first questioned orally and followed by answering the exercises in writing which is the major part of grammar translation. The only communication in this method is between the student and the teacher where the teacher plays the authoritarian role. Example of grammar translation method includes explaining the grammatical rules and concepts with the help of presentation, written exercises to the students. Direct Method The direct method of teaching developed languages in the nineteenth century when the educationalists observed the child language learning trends and applied t he direct method of learning English as a foreign language for the learners. In this method, the translation of the foreign language is not required. The students are required to read aloud the specialized texts of grammar and vocabulary in English language. The emphasis is put on guided conversation of the students where the teachers play an important role in helping the students to understand the usage of various words in English. Examples of the direct method of learning English as a foreign language includes conduct of exercises using fill-in-the-blanks, dictation and demonstration to the students by the teachers. The students also required to undertake comprehension exercises directly in English in order to understand the foreign language through the direct method. Audio lingual The audio-lingual method of teaching English as a foreign language developed from the time of Second World War when the army personnel were trained to speak in different languages such as German, French , Japanese, etc. This method has been later applied for teaching English

Risk management Essay Example | Topics and Well Written Essays - 3250 words

Risk management - Essay Example An assessment for each risk in terms of impact of the risk and probability of occurrence was made that prompted the formulation of strategies address the risks, to take advantage of the opportunities, or to control the identified threats. BAT’s main strategies basically facing the risk head on and go on with combatting the illicit trade and the increasing excise taxes or shock the may come from government initiate to raise taxes. For finance risks, hedging was the better strategy than not hedging. For the market risks which include inability to obtain required price increase, geopolitical tensions and major climate chance separate strategies at the corporate level were done and should give priority to those with high-level risks which include competition from illicit trade, excise shocks from tax rate increase or structure changes, and management of cost base. This paper aims to identify major risk factor faced by British American Tobacco plc (BAT) using appropriate models/classification. A discussion of possible opportunities or threats would follow the identification. This would be followed by a structure assessment, using a risk map or risk matrix of the impact of the particular risks and the likely occurrence of these risks. The third part would be to formulate strategies for taking advantage of the opportunities, or strategies for controlling the identified threats. The last part of the paper before the conclusion would be to respond to a statement hypothetically made by an executive of saying something about the uselessness of corporate governance. The respond would focus on the relevance of the corporate governance regulation. Illicit trade is defined as proliferation of illegal competition in the form of counterfeit products (Ortiz &. Tajes, 2009; Dandeker, 1992), genuine but smuggled products and even those of locally manufactured products on which applicable taxes are evaded (British American Tobacco, 2011). The

Case study #1 Essay Example | Topics and Well Written Essays - 1000 words

Case study #1 - Essay Example Thus, for the better understanding of the competencies and shortcomings of Forest International, aimed at suggesting rational strategies to overcome the identified issue, a SWOTT analysis has been assessed in the below mentioned section. Strengths. Forest International has annual revenue of $11 billion along with employee strength of 45,000, which makes it quite competent to invest in safety measures. Although employee turnover is negligible, it does not embark on the employee loyalty but rather on the economic construction of the region where workers are somewhat forced to work in hazardous conditions. Opportunities. In the course of improvement of safety records of the company, it can seek for the assistance of standards developed by Federal OSHA, to ensure the safety of paper mills industry. Correspondingly, the company must abide with the 1910.145 standard under the OSHO Code, which emphasizes the prevention of accidents during the duty work of the employees (US Department of Labor, â€Å"Pulp, Paper, and Paperboard Mills†). Threats. The major threat that Forest International have been facing is the downfall of its market share as compared to that of its competitors. Due to its lack of sustainability concerns and frequent workplace accidents, the company also faces threats in terms of lowering stakeholders’ loyalty. Trend. In accordance to the past records, it was observed that the accidents occurred in Forest International was the consequence of the management’s negligence. Jack Taylor, crew leader had once reported an accident caused due to the loosened up jack in the machinery and suggested the management on ways of improving safety lines. However, it was ignored by the management. Thus, emphasizing this particular issue in the report, few of the measures for improvement of safety lines in the company is being suggested gauged with rational

Knowledge management structures in NATO versus the United Nations Essay

Knowledge management structures in NATO versus the United Nations - Essay Example n and knowledge far better then it was previously possible, knowledge management in organizations has also the added dimension of interaction, knowledge sharing, communication and analysis. A lot of organizational knowledge is contained in the heads of personnel within the organizations. Because humans have a finite life – span and ambitions about better opportunities, all organizations have structures which not only create new knowledge but also transfer existing knowledge to those in need of it. The nature of the knowledge which is important to an organization is dependant on the task or mission which the organization is expected to perform and different organizations may have different requirements associated with the speed, reliability, volume of information or knowledge which has to be communicated for organizational use. The knowledge management structures which are put into place within organizations are shaped by the organizational requirements for knowledge management , which are different for various organizations. In this essay, an attempt has been made to compare the knowledge management structures within NATO with those which exist in the United Nations. NATO, which is a military alliance, has a requirement to manage large amounts of information which can quickly become obsolete and convert this information into knowledge for reliable and secure communications for the use of designated personnel. The pace at the United Nations is more leisurely. Hence, the knowledge management structures at these two organizations are slightly different. The term knowledge management refers to the management of intellectual capital which has bee described as: â€Å"Intellectual capital is intellectual material – knowledge, information, intellectual property, experience – that can be put to use to create wealth. It is the collective brainpower†. The term knowledge is subjective to the organizational and social context in which it is being thought of. Knowledge

Strategic Staffing in Global Communications Incorporation Assignment

Strategic Staffing in Global Communications Incorporation - Assignment Example Many of those procedures are now bound to the theories and texts. There is a little process which is in practice right now. Here we go with questionnaires, surveys, employees’ diaries and 360 degree feedback from employers, peers and subordinates (Dessler, 2000)1. Person job fit is analyzed through various techniques in real world out of which human resource information system is most significant. We have a powerful Human Resource Information System installed in our server. It is helpful in defining the scenario which updates and excommunicates about what are the current practices going on and where is discrepancy lying in the air. Another reasonable approach which is currently in practice refers to employees questionnaires in order to conduct a credible Job Analysis. This is what we know about our employees and it’s all about the ways we use to identify the required skills in the employees. We are more likely to post the positions on the basis of prior experience of certain skills required. We focus on interpersonal and innovative skills of personnel. While posting the jobs to the concerned source, we often use only signaling by only mentioning degree requirements, prior experience and age limits. The further identifications are taken from face to face interactions and job recruitment tests. We get the applications online under career tab of our web page. It is directly reached to HR department who is liable to evaluate person to job and person to organization match by analyzing the curriculum vitae and revealing in application forms. After that the list of recommended candidates are added in minutes and they are called through phone as well as through surface mail. 20. Write a brief objective statement explaining why do you feel yourself as a better fit for this job, how your skills may be helpful in value maximization of the organization supporting your career plans, mission and vision? Â  

From the Original Sin to Buddha Nature Essay Example for Free

From the Original Sin to Buddha Nature Essay When Adam and Eve disobeyed God in the Garden of Eden, they were sent to earth to work on themselves, with the promise that they would ultimately find deliverance, along with their children, provided that they obey God on earth. The very fact that they were disobedient to God is referred to as the ‘original sin’ of man (Harent). Although theologists have ascribed various meanings to ‘original sin’ through the ages, it is the original sin that is believed to have brought mankind from the Garden of Eden down to earth – a place where toil and suffering are realities of daily living. Believers in the original sin are made to agree that they are imperfect beings, unlike God, which is why they were sent down to earth by the almighty God (Harent). But, the Christ taught his followers to become perfect like God in order to save themselves from all suffering, especially in the hereafter. This teaching of the Christ is consonant with the concept of ‘Buddha nature’ in Buddhism. Both the Christ and the Buddha taught that every individual is capable of becoming perfect, like the Buddha or the Christ, if not God Himself (King). In order to become perfect, human beings have to rid themselves of all baseness, including negative emotions and thoughts, that is, the roots of all evil. Without a negative thought or emotion, evil deeds are not possible. Thus, clearing of the mind to make way for ultimate peace is the way of the Buddha. Buddhism is concerned with individuals ridding themselves of suffering here and now (King). To become Christ-like – here and now – is the aim of the Buddhist, although Buddhism does not refer to Jesus Christ by his name as the Christians do. The Bible teaches its followers that human beings were made in the image of God, and that, in fact, the Lord of the universe breathed His Spirit into man. The Christ is the Spirit of God. Hence, every human being has the Christ within. When human beings indulge in evil deeds, it is Satan that is urging them to do so. It was Satan that urged man to disobey God in the Garden of Eden. The concept of original sin carries with itself the belief that Satan would continue to urge human beings – the children of Adam and Eve – to disobey God. But, the prophets of God taught humanity to remember God and worship Him in all sincerity so as to save themselves from Hellfire or eternal suffering. Buddhists do not believe in the idea of eternal suffering. They believe in â€Å"samsara† instead, which is a cycle of birth and rebirth, so long as human beings have not attained the perfection of the Buddha (King 1). Christians do not believe in this cycle of birth and rebirth. It is only special people such as Jesus Christ, Elias and some of the best believers that may be reincarnated. For ordinary mortals, Christianity does not promise a second birth, except in paradise or hell, both of which are believed to be eternal, unlike temporary lives on earth. Buddhists believe that the Buddha nature cannot exist outside of the human mind, although the Buddha is like the Spirit of God – all-encompassing (King). To be a Buddha, an ordinary mortal is advised to work on his mind. According to a master of Zen Buddhism: To realize our Buddha-nature, two general conditions must be met. First, we must be sentient beings. Looking around, I think that we all qualify! The Buddha calls this the direct cause. It is analogous to milk from which cream can be derived. Next, it is important to know what a sentient being is. A sentient being is, roughly speaking, spirit. Dont be confused and just assume that a sentient being is an animal or a plant, or even the five aggregates. It isnt. Your thoughts, for example, are sentient beings— but not a common fence post. The second condition you must fulfill in order to realize Buddha-nature is the indirect cause. The indirect cause refers to the six paramitas according to the Maahaparinirvaana Sutra†¦ The first paramita is charity. By mastering it, we surpass the robber of the visual world and thereby become spiritually wealthy†¦ The second paramita is discipline. By mastering it, we surpass the robber of the auditory world and acquire good spiritual practices and concentration†¦ The third paramita is patience. By mastering it, we surpass the robber of the olfactory world and acquire inner peace, both for self and for others†¦ The fourth paramita is strength. By mastering it, we surpass the robber of the world of taste and acquire devotion†¦ The fifth paramita is meditation. By mastering it, we surpass the robber of tactile sensations†¦ The sixth paramita is wisdom. By mastering it, we surpass the robber of consciousness†¦ (â€Å"Buddha-Nature†). The fact that the Buddhist master writes about realizing the Buddha nature – just as the Christ taught about becoming perfect and holy like God – underlines the concept of the original sin. Because human beings are capable of turning the wrong way, people like the Buddha and the Christ are sent as guides, according to Biblical beliefs about the presence of such people. The Bible teaches its believers that Adam and his children are all capable of sinning or indulging in evil deeds. God desires for them to perform good deeds instead, with the use of His Spirit within. To realize the Buddha nature is to attain knowledge of the Christ within each human being. Because human beings perform evil deeds in order to feel like masters over their environment – and Adam disobeyed God because God’s Spirit was capable of using freewill – the Christ taught his followers to shun all evil in order to experience their own power in God. Satan had the power to tempt the Christ as well, but the latter did not give in. If evil is all about attaining mastery over things, perfect peace, according to the Buddha and the Christ, is to live in the purity of God – although Buddhists do not refer to God as the Christians do. To realize the Buddha nature, one must not only be aware of the Christ within, as a Christian would understand it; but also to comprehend the concept of the original sin. A realized human being, according to Buddhist understanding, is aware that negative thoughts and emotions may arrive through the senses. Coming across a criminal, for example, may fill an innocent human being with negative thoughts and emotions. These thoughts and emotions may give rise to further problems; the innocent human being may decide to kill the criminal. In order to be safe from all suffering and worries, the Buddha taught his followers to contain their thoughts, and trust in the absolute peace available to every soul. This peace is only attainable through control of the mind (King). Buddhists are also taught to empty their minds because thoughts may lead individuals to continue on the path of the original sin (King). According to the Christ, on the other hand, the mind must be infiltrated by thoughts of God. To live in God – a Christian concept – is also to discover ultimate peace here and now. Because of the original sin, however, it is important to worship God – according to Christian belief. Buddhists are clear about the fact that the mind may lead the individual to err. Of course, Adam had thought to err before he actually sinned. As its name implies, the concept of Buddha nature is to be like the Buddha, an individual referred to as the holy one or the perfect one. Once again, according to Buddhists, clearing of the mind is essential to being like the Buddha. In reality, however, it is not always possible to keep the mind clear of all thoughts. This is the reason why the Christ’s teachings are essential to discuss with reference to the Buddha nature. Living in God is to remember Him as much as possible. Some of the names of God are Love and Peace. The aim of the Buddhist is also to realize these attributes in order to be saved from the suffering of the original sin. Neither the Buddha nor the Christ taught that it is possible to save oneself from the perpetual possibility to err in this lifetime. Thus, believers in the Buddha and the Christ are required to make a constant effort to save themselves from eternal damnation. Buddhists must be practicing meditation to stay close to their essential nature, that is, the Buddha nature or the Christ within. Christians, on the other hand, must be worshipping God as the principle form of meditation to stay close to God. According to the Bible, the consequences of the original sin would follow all human beings during their stay on earth. In the hereafter, Satan would be in hellfire with those that refused to shun all evil. Those that remembered and worshipped God as He wanted them to would be saved. Of course, when Buddhists speak of compassion and charity, they are also remembering God’s attributes, albeit in a different way altogether. Followers of the Buddha and the Bible also believe in the perpetual negativity of the original sin, that, in fact, negative thoughts and emotions are always available to humanity on earth. The principle difference between the two beliefs systems is that the God mentioned in the Bible does not allow all human beings to be reincarnated. Buddhists belief in a perpetual cycle of life and death so long as an individual has not attained permanent liberation. According to the Biblical belief system, however, the present life is the only chance for most human beings to catch up with masters such as the Christ. Adam and Eve were sent to earth with the potential to err. At the same time, each of them carried the Spirit of God or the Christ within. By meditating on this reality, the Buddha nature can be realized. Then again, according to the Bible, even the prophets of God had to continue worshipping God to keep themselves from evil thoughts that lead to evil deeds. In reality, therefore, all human beings are perfect like the Buddha and the Christ; at the same time, nobody is saved from the possibility to err. Works Cited â€Å"Buddha-Nature. † Dark Zen. 26 Oct 2008. http://www. darkzen. com/teachings/buddha_nature. htm. Harent, Stephane. Original Sin. The Catholic Encyclopedia. Vol. 11. New York: Robert Appleton Company, 1911. 26 Oct. 2008 http://www. newadvent. org/cathen/11312a. htm. King, Sallie B. Buddha Nature. New York: SUNY Press, 1991.

Challenges Faced By General Motors

Challenges Faced By General Motors The United States (U.S) Multi National Enterprise (MNE) General Motors (GM) is one of the worlds largest automakers, tracing its roots back to 1908. With its global headquarters in Detroit, GM employs 235,000 people in every major region of the world and does business in some 140 countries. GM and its strategic partners produce cars and trucks in 34 countries, and sell and service these vehicles through the following brands: Buick, Cadillac, Chevrolet, GMC, Golden, Oldsmobile, Pontiac, Saturn, Opel Vauxhall and Saab. In 2006 it sold over 9 million cars and trucks globally in 5 continents with a global market share of 13.5 %. GM has been involved in a range of global ventures aimed at extending their penetration in the carmakers market and has also increased its share of the market as well as sales. GM uses exports, acquisitions, joint ventures and strategic alliances to enter foreign markets based on business considerations. GM has also expanded its capabilities in manufacturing through technological competences. This was achieved by forming subsidiaries, strategic alliances and joint ventures with other automobile companies in different parts of the world. According to (GM Press Release, 2006), the company has been involved in a range of global ventures throughout its history, each of which has aimed at extending its market penetration. Partnering enables GM to rapidly expand its technical fields and brings that knowledge in-house transferring it to multiple levels within the business, even extending it sometimes to corporate issues. Through the various stages of internationalisation, GM was able to enl arge its distribution and provide access to essential materials. Additionally, the company developed and improved its operations, facilities and processes all of which have provided access to new technologies and a rich database of knowledge and new capabilities. The American automobile industry is the biggest in the world in terms of number of cars manufactured and sold. The U.S. automobile market is saturated with the global car manufacturing companies however; the majority of the market share is occupied by domestic and Japanese companies. The outcome of this is a drop in the level of consumption as there are too many entrants competing in the same industry. Because of this decrease in consumption, the automobile industry leaders have been offering attractive incentives and lower prices leading to a loss in profitability. The world-class automakers are gradually expanding into foreign markets, as new emerging markets in China, South East Asia and South America are showing signs of sustainable economic growth. GM overseas operations were a method of diversifying themselves against the risks and uncertainties in their domestic market life cycle, by setting up new operations abroad multinationals can diminish adverse economic downturns. Most MNEs also follow a pattern that has often been laid out in front of them by competitors or similar sized companies that have adopted or mimicked behaviour that has been tested and proven to be success, if the right measures are taken when adopting it. For instance, it has been argued that organizations tend to imitate actions that have been taken by large numbers of organizations, because such practices are legitimized or their success is taken for granted (Fligstein; Haunschild; Haveman; Kraatz; Lewitt). This can also have an adverse affect on an MNE when entering a new market, leaving them less cautious and with a diminished aspiration towards growth, knowing that the chances of that market already being saturated and that the first come first served knowledge is already guaranteed not to be in their possession. This often happens when the specific market they enter does not suit their domain of expertise and experience, resulting in them investing much faster and with a lesser de gree of uncertainty that they would have usually applied. GMs move to internationalise was mainly to reduce costs, attract a larger market and the creation of strategic alliances. The company strategically allied with Fiat in 2000 by acquiring 20 percent of Fiats equity to establish a joint procurement venture. With a split of 50 percent of the capital each, giving them a concentrated purchasing power of about $32 billion per annum, this alliance has the capacity to strengthen their bargaining power as well as reducing the supplier management cost. GM also moved production overseas, as the number of internal competitors grew too high in most of the emerging country home markets. GM needed to find a new incentive to manage a new market while remaining at low cost. GM is a good example of an MNE which underwent internationalization whilst maintaining its position as one of the leading carmakers. It has also followed the theories laid out about internationalisation such as the typical way a company proceeds to penetrate and enter a foreign market. Firstly it will look at the options available and analyse what will be best suited for them considering the high degree of uncertainty and risk associated with entering an unknown market. One such option is licensing but it has to be assessed in a precautious way, due to the fact that they might be risking firm specific advantages by engaging in premature licensing agreements, this is also the least preferred of all three options due to the fact that there is a risk of knowledge dissipation. The only instance when licensing will be considered as a viable option is if the revenue generated from the licensee exceeds the cost of policing it. But also, if they do choose go for an early licensing agreement it may be because their firms specific advantage is hard to duplicate or they have a tight control over the licensee, meaning that they would find it very hard and potentially dangerous to resell any kind of sensitive material to any potential competitor or a third party of any kind. The second option is the possibility that the MNE might only be willing to export at first if the demand of the local market is not high enough for them to want to engage in foreign direct investment and set up an overseas subsidiary, or they may also consider this as a possibly a bit longer down the line depending on the potential growth generated from initial sale patterns and the profitability a larger scale operation would yield. The exporting option also depends on the trade agreements, tariff barriers, taxes, transportation costs and quotas between the two countries involved which sub sequentially determine if the operation will be profitable or maybe another option should be considered. There are two strong examples of how this has been reproduced by GM. The first is the case of General Motors do Brasil, which is GMs third largest operation outside of the U.S after being recently overtaken by China. In the beginning, the activities were in the assembly of vehicles imported from the United States. After five years, GMB officially opened its first plant in 1930 in Sà £o Paulo. Here we can see that exporting lead to the full scale creation of a production facility which was so successful a second one was opened 28 years later, thus resulting in Brasil being the main exporter of GM automobiles in the whole of South America. Breaking out of their domestic market and becoming an exporter themselves in a very short space of time and for such a large operation really does provide evidence that internationalisation does not spread from one point outwards with only one epicentre at its core but rather creates and distributes smaller nodes that in time expand themselves and r epeat the process so on, just as how it is described in the network approach. Once the firm has passed the cultural barriers and had its first experience of foreign operations, it is generally willing to conquer one market after another (Carlson, 1966). The second example is when the Cadillac brand was introduced to China in 2004, starting with imports from the U.S, which then lead to the Chevrolet making its first appearance on the Chinese market one year later. They were then able to move production operations to their Shanghai GM plant which opened as a joint venture with SAIC in 1997, initially created for the Buick brand that is especially strong in China. In this case exporting was clearly used as a testing method for foreign products penetrating the Chinese domestic market, market-specific knowledge and general knowledge are important for firms internationalization (Johanson and Vahlne, 1977). Dunnings Eclectic theory which sets out to explain that foreign direct investment as a theory can be unified as long as the firms applying it consider the ownership, location and internalisation of the process that will produce substantial benefits if applied accordingly. This is also the case if the extent, the form and pattern of international production is founded on the juxtaposition of the ownership to specific advantages that a firms posses when contemplating foreign production. This is reflected in GMs move to manufacture most of its China-market vehicles locally, through its Shanghai GM joint venture, GM also plans to create a research facility in Shanghai for $250m to develop hybrid cars and alternative energy vehicles. Therefore GM follows a path suggested by Dunning to gain advantage in terms of competitiveness and cost by ownership in foreign market and aim to expand. The Network Approach emphasises the industry as a system of networks, each firm within network has relationships with customers, suppliers etc†¦ These relations are important competitive advantages which the Network model also suggests the firm needs to take into account and evaluate not only its own position in the market in relation to its customers, but also the environment of that market in relation to others such as competitors, new entrants etc†¦ GM and Fiat formed a strategic alliance, with GM owning a 20% share in Fiat and Fiat SpA receiving 5.1% of GMs shares in exchange. Production and ownership have both been improved when a recent alliance took place under the form of two joint ventures (owned 50% by Fiat and 50% by GM). The first will conduct purchasing activities, while the second will produce engines and gear equipment which is mainly aimed at cutting expenses. Hence GM has followed the network model to some degree as their joint venture come in terms of rela tions with Fiat. By collaborating they have reduced the cost and the innovation has resulted in new production techniques. Which gave both of them some degree of competitiveness as they have gained purchasing power as well as reduced cost in terms of purchasing from the suppliers.

Mechanisms drug resistance to cancer chemotherapy

Mechanisms drug resistance to cancer chemotherapy Introduction Cancer is one of the major causes of death in the developed world and statistics show that one in three people will be diagnosed with cancer during their lifetime [1]. Cancers are malignant tumours and can be distinguished from normal cells by four characteristics; uncontrolled proliferation, dedifferentiation and loss of function, invasiveness, and ability to metastasise [2]. These characteristics are caused by altered gene expression, as a result of genetic mutations that inactivate tumour suppressor genes and / or activate oncogenes. Most cancer chemotherapeutic drugs affect only one characteristic aspect, which is uncontrolled proliferation [3]. In many cases the antiproloferation action is caused by damage to DNA, which initiates apoptosis and cell death [4]. As their main target is cell division, they affect all rapidly dividing cells, including normal cells. This produces general toxic effects, such as myelosuppression, alopecia, damage to gastrointestinal epithelium, sterility and severe nausea and vomiting. Besides the toxic effects of chemotherapy, another major problem is chemoresistance [5]. Resistance to chemotherapy is when the cancer cells do not respond to the drugs. It can be inherented, as a genetic mutation, or it can be acquired, as a cellular response to drug exposure. Mechanisms of resistance include: increased efflux or decreased influx of cytotoxic drugs; insufficient activation of the drug; increased inactivation of the drug; increased concentration of target enzyme; rapid repair of DNA lesions; or mutations in various genes. When patients develop resistance, multiple drugs with different pathways of entry and different cellular targets are used. However, cancer cells can become multidrug resistant, a phenomenon due to cells expressing mechanisms that cause simultaneous resistance to many different, structurally and functionally, unrelated drugs [6]. Multidrug resistance, generally, results from over expression of ATP-dependent efflux pumps [5]. These pumps have broad drug specificity and belong to a family of ATP-binding cassette (ABC) transporters, of which P-glycoprotein (PGP) is one of the most important members. Increased drug efflux, via these transporters, lowers intracellular drug concentration, allowing cancer cells to escape the toxic effects of the drugs. PGP inhibitors are being developed to overcome multidrug resistance and two that have reached clinical trials are varapamil, a calcium channel blocker, and cyclosporin A, an immunosuppressant [7]. The remainder of this review will focus on the different chemotherapeutic agents currently being used for the treatment of cancer and their mechanism of action. Also the main mechanism of resistance to these drugs will be explored, particularly focusing on the role of P-glycoprotein and how it can be modulated to reverse drug resistance. Drugs used in cancer chemotherapy Drugs used in the treatment of cancer are summarised in table 2. They are grouped into: cytotoxic drugs, which preferentially but not exclusively target rapidly dividing cancer cells; hormone therapy, which is a more specific form of treatment used for tumours derived from hormone sensitive tissues; and miscellaneous agents, which include a number of recently developed drugs such as monoclonal antibodies. Cytotoxic drugs Cytotoxic drugs can be further divided into the following; alkylating agents, which act by forming covalent bonds with DNA and impeding replication; antimetabolites, which block one or more of the metabolic pathways involved in DNA synthesis; cytotoxic antibiotics, which are of microbial origin and prevent cell division by directly acting on DNA; and plant derivertives, which affect microtubule function and hence the formation of the mitotic spindle. Alkylating agents Alkylating agents form carbonium ions, which are highly reactive and interact instantaneously with nucleophilic sites such as N7 of guanine in DNA [8]. They are bifunctional, which means they have two alkylating groups, and can cause intra- or inter-chain cross-linking between DNA strands. This prevents strand separation for DNA synthesis or transcription. They can also cause base mispairing between strands, which interferes with the progression of the replication fork [3]. These actions block DNA synthesis, causing a block at G2 phase and subsequently apoptotic cell death. Alkylating agents currently being used in chemotherapy primarily belong to the following families: nitrogen mustards (Cyclophosphamide, Chlorambucil, Melphalan, Ifosfamide, Busulfan); nitrosoureas (Carmustine, Lomustine, Fotemustine); aziridines (Thiotepa); Dacarbazine and platinum compounds (Cisplatin, Carboplatin, Oxaliplatin) [9]. Nitrogen mustards, nitrosoureas and aziridines are believed to kill tumour cells by inducing DNA inter-strand cross-links, while platinum compounds induce intra- and inter-strand cross-links, as well as DNA-protein cross-links under certain circumstances [8]. Resistance to these drugs can develop as a result of cancer cells rapidly repairing drug induced lesions [10], which will be discussed in detail later. Antimetabolites Antimetabolites interfere with the metabolic pathways involved in DNA synthesis. An example of an antimetabolite is Methotrexate, which is a folate antagonist [11]. Folates are essential for the synthesis of purine nucleotides and thymidylate, which in turn are essential for DNA synthesis and cell division. Folates are actively taken up into cells by the reduced folate carrier (RFC), where they are converted to polyglutamates. Polyglutamate folates are then reduced to tetrahydrofolate (FH4) by the enzyme dihydrofolate reductase (DHFR). Methotrexate exerts its action by being taken up into cells by the follate carrier, and like folate being converted to the polyglutamate form. It has a higher affinity for DHFR than the endogenous folate and thus inhibits the enzyme, depleting intracellular FH4, and therefore hindering DNA synthesis. Another example of an antimetabolite is Fluorouracil, which is a pyrimidine analogue [12]. It interferes with DTMP synthesis by forming a ternary complex with thymidylate synthetase (TS); the enzyme that produces DTMP. DTMP is required for the synthesis of DNA and purines, so the irreversible inhibition of the enzyme by fluorouracil results in is inhibition of DNA but not RNA or protein synthesis. Fludarabine is a purine analogue, which is another group of antimetabolites [13]. It is metabolised to its triphosphate form, which inhibits DNA polymerase. As well as the general side effects associated with chemotherapy, patients may develop resistance to antimetabolites; due to a decreased amount of drug uptake [14] or altered concentration of target enzymes [15], which will be discussed later. Cytotoxic antibiotics Cytotoxic antibiotics, such as the anthracyclines (Doxorubicin, Idarubicin, Daunorubicin, Epirubicin, Aclarubicin, Mitoxantrone) bind to DNA and inhibit both DNA and RNA synthesis [16]. Their main cytotoxic action is mediated through an inhibitory effect on topoisomerase II, the activity of which is markedly increased in proliferating cells. During DNA replication, reversible swivelling needs to take place around the replication fork in order to prevent the daughter DNA molecule becoming inextricably entangled during mitotic segregation [17]. The swivel is produced by topoisomerase II, which nicks both DNA strands and subsequently reseals the breaks. Doxorubicin intercalates in the DNA, and its effect is in essence, to stabilise the DNA-topoisomerase II complex after the strands have been nicked, thus halting the process at this point [18]. Dactinomycin is also a cytotoxic antibiotic, which intercalates in the minor groove of DNA, interfering with the movement of RNA polymerase along the gene and thus preventing transcription [19]. Bleomycins are a group of metal-chelating glycopeptide antibiotics that degrade preformed DNA, causing chain fragmentation and release of free bases [20]. This action is thought to involve chelation of ferrous iron and interaction with oxygen, resulting in the oxidation of iron and generation of superoxide and/or hydroxyl radicals. They are most effective in the G2 phase of the cell cycle and mitosis, but are also active against non-dividing cells, that is cells in the G0 phase. This class of drugs cause resistance by altered activity of topoisomerase II, aswell as reduced uptake of the drugs [21]. Plant derivatives One sub group of plant derivatives is the vinca alkaloids, which includes Vincristine, Vinblastine, Vindesine and Vinorelbine [22]. They bind to tubulin and inhibit its polymerisation into microtubules. This prevents spindle formation in dividing cells, which causes arrest at metaphase. They also inhibit other cellular activities that involve microtubules, such as leucocyte phagocytosis, chemotaxis and axonal transport in neurons. They are relatively non-toxic in comparison to the previously mentioned cytotoxic drugs. Another group of plant derivatives is the taxanes, which include Paclitaxel and Docetaxel [23]. They act on microtubules by stabilising them, in effect freezing them in the polymerised state, which achieves a similar effect to that of the vinca alkaloids. Campothecins is another group of plant derivatives and include Irinotecan and Topotecan [24]. They bind to and inhibit topoisomerase I; high levels of which occur throughout the cell cycle. Hormone therapy Tumours derived from hormone sensitive tissues may be hormone dependent [25]. This is due to the presence of steroid receptors in the malignant cells. Their growth can be inhibited by agents with apposing actions, hormone antagonists or drugs that inhibit the endogenous hormone synthesis. The most important group of drugs used to treat cancer are the steroids, namely the glucocorticoids (Prednisolone and Dexamethasone), oestrogens (Diethylstilbestrol and Ethinyloestradiol) and gonadotrophin-releasing hormone analogues (Octreotide and Lanreotide), as well as agents that antagonise hormone action (Tamoxifen, Toremifene and Fulvestrant). Such drugs rarely act as a cure but do mitigate the symptoms of the cancer and thus play an important part in the clinical management of sex-hormone-dependant tumours. Miscellaneous agents Crisantaspase Crisantaspase is a preparation of the enzyme asparaginase and therefore, like asparaginase, can break down asparagine to aspartic acid and ammonia [26]. It is active against tumour cells, such as those of acute lymphoblastic leukaemia, which have lost the capacity to synthesise asparagine and therefore require an exogenous source. As most normal body cells are able to synthesise asparagine, the drug has a fairly selective action and very little suppressive effect on the bone marrow, the mucosa of the gastrointestinal tract or hair follicles. Monoclonal Antibodies Antibodies are immunoglobulins that react with defined target proteins expressed on cancer cells. This activates the hosts immune response, which kills cancer cells by complement-mediated lysis or by killer cells. Monoclonal antibodies can also attach to and activate growth factor receptors on cancer cells, thus inhibiting the survival pathway and promoting apoptosis. Rituximab is a monoclonal antibody that is licensed (in combination with other chemotherapeutic agents) for treatment of certain types of lymphomas [27]. It lysis B lymphocytes by binding to the calcium- channel forming CD20 protein and activating completment. It also sensitises resistant cells to other chemotherapeutic drugs. Trastuzumab (Herceptin) is a humanised murine monoclonal antibody that binds to a protein termed HER2 (the human epithelial growth factor receptor 2); a receptor with integral tyrosine kinase activity [28]. It induces the host immune response as well as inducing the cell cycle inhibitors p21 and p27. Imatinib Mesylate Imatinib is an inhibitor of signalling pathway kinases [29]. It inhibits the platelet-derived growth factor (PDGF); a receptor tyrosine kinase, and the Bcr/Abl kinase; a cytoplasmic kinase. These are considered to be unique factors in the pathogenesis of chronic myeloid leukaemias. Imatinib is licensed for the treatment of this tumour when it has proved to be resistant to other therapeutic strategies, as well as for the treatment of some gastrointestinal tumours that are not susceptible to surgery. Resistance to Anticancer Drugs As mentioned previously patients can develop resistance to many chemotherapeutic agents. This can be caused by a number of mechanisms, which are summarised in figure 1. A decrease in the amount of drug taken up by the cell Resistance can develop as a result of decreased drug uptake. This can be due to the loss of transporter function, for example RFC [30]. Decreased influx of Methotrexate in tumour cells has been widely associated with decreased RFC gene expression. Down-regulation of the transporter protein is due to alterations in the transcription and translation factors. Transcriptional factors, such as the Sp1 family, CREB (cyclic AMP-response element binding protein) and p53, regulate RFC gene expression [31]. Therefore loss of function of these transcription factors cause silencing of the RFC gene, which results in reduced protein level. Also post-translational modifications of transcription factors alter phosphorylation patterns, which abolishes Sp1 and CREB function thereby resulting in loss of RFC gene expression and subsequently resistance [32]. Mutations in the human RFC gene can also decrease drug influx. Jensen et al (1998) have reported a mutation that causes marked changes in the kinetic properties of RFC mediated transport of folates [14]. The structurally altered RFC was functionally characterized by a 9- and 31-fold increased affinity for transport of reduced folate cofactors and folic acid, respectively. This allowed the accumulation of intracellular folates, which sustained cell growth and DNA replication, allowing cancer cells to escape the cytotoxic effects of antifolate drugs. Altered concentration of target enzyme Increased expression of target enzyme is a common mechanism of acquired resistance. For example Methotrexate resistance can develop as a result of DHFR gene amplification and subsequent enzyme overexpression [15]. Gene amplification is thought to occur as a consequent of antifolate inhibitors binding to DHFR, which causes a conformational change that alters the translational autoregulatary negative feedback mechanism, wherein DHFR protein specifically interacts with its own mRNA and negatively controls translational efficiency. The drug concentration will be limited to the dose administered, which will not be able to block the additional enzyme that is synthesised, resulting in cancer cells overcoming the inhibitory effect of the drug. Insufficient activation of the drug Some drugs require metabolic activation to manifest their antitumour activity for example Cytarabine has to undergo catalytic conversion, by the action of deoxycytidine kinase, to an active form [33]. So under expression or mutation of this drug-metabolising enzyme can reduce drug efficacy and cause resistance. Another example of resistance due to insufficient activation of the drug is Mercaptopurine, which is a prodrug [34]. Mercaptopurine is activated by hypoxanthine guanine phosphoribosyl transferase (HGPRT) and mutations that reduce the activity of this enzyme will allow the cancer cells to escape the toxic effects of the drug. Increase in inactivation Resistant to Mercatopurine can also develop as a result of increased inactivation of the drug [35]. The mechanism behind this is thiopurine s-methyltransferase (TPMT), which inactivates Mercaptopurine and thereby prevents the formation of the active drug. Mutations in the TPMT gene will alter its activity and may cause resistance. Rapid repair of drug-induced lesions Patients can develop resistance as a result of cancer cells recognizing DNA lesions and rapidly initiating repair pathways [9]. This is the main cause of resistance to alkylating agents as their mechanism of action is DNA damage There are several repair pathways and include the Direct Repair (DR) pathway, Base Excision Repair (BER) pathway, Nucleotide Excision Repair (NER) pathway, Homologous Recombination (HR) pathway and Non-Homologous End Joining (NHEJ) pathway. The DR pathway is mainly mediated by the DNA repair protein: O6-alkylguanine DNA alkyltransferase (AGT) [36]. AGT transfers the alkyl adducts from the nucleotides to the cysteine residue within its active site, independently from other proteins and without causing DNA strand breaks. The BER pathway recognizes and accurately removes bases that have been damaged by alkylation [37]. A damaged base is removed by a damage-specific DNA glycosylase, leading to the formation of a potentially cytotoxic apurinic or apirimidinic site intermediate. This is then processed by an AP endonuclease (APE1), which generates a strand break that is further processed by Poly ADP-Ribose Polymerase (PARP), DNA polymerase b (Polb) and ligase III to restore the damage. The NER pathway deals with the repair of bulky DNA lesions formed by DNA-alkylating agents such as Cisplatin, which distort the DNA double helix and block DNA replication and transcription [38]. Two major mechanisms of DNA repair have been recognized in this pathway: the transcription-coupled repair, which specifically targets at and removes lesions that block the progression of RNA polymerase II, and the global genome repair, which deals with lesions in the rest of the genome. Generally, nucleotide repair is a complex multi-step process that sequentially deploys a group of proteins to reorganize the lesion, remove the damage, and support new DNA synthesis. The HR and NHEJ pathways are involved in the repair of DNA double strand breaks, commonly considered to be the most lethal of all DNA lesions. Double strand breaks are induced by chemotherapeutic agents such Bleomycin, and Etoposide. In the HR pathway, ATM (ataxia talagiectasia mutated kinase) and its related ATR proteins sense the severe DNA lesions, and are mobilized to phosphorylate a wide range of substrate proteins [39]. Also a number of regulatory proteins, including BRCA1, BRCA2 and p53, are recruited to coordinate the DNA repair. The NHEJ pathway involves the alignment of the broken ends followed by recruitment and activation of the DNA-dependent protein kinase catalytic subunit (DNA-PKcs) and DNA ligase IV to complete the ligation step [40]. Mutations Mutations in various genes can give rise to resistant target molecules, for example the p53 gene [41]. The p53 protein is an important regulator of the cell cycle and is sensitive to any DNA damage caused during replication. Following DNA damage it will normally induce G1 arrest and/or apoptosis to prevent the production of defective cells. Mutations in this gene will cause the loss of p53 function, which will allow cells with damaged DNA to continue replicating, resulting in resistance to DNA damaging drugs. Other genes, such as h-ras and bcl-2/bax, involved in the apoptotic pathway, have also been implicated in resistance [42]. Resistance due to mutations in genes will affect a wide range of anticancer drugs as all cells contain the same genetic material. It also potentially increases the proportion of surviving mutant cells, which leads to greater tumour heterogeneity. Increased expression of efflux pumps Resistance to natural hydrophobic drugs, such as vinca alkaloids and taxanes, as well as the cytotoxic antibiotics, such as anthracyclines and Dactinomycin, occurs due to the over expression of ATP-dependent efflux pumps in cancer cells [5]. These pumps belong to a family of ATP-binding cassette (ABC) transporters, which are divided into eight distinct subfamilies, shown in table 1. Of these subfamilies PGP, also known as MDR1, has a broad drug specificity, which explains the cross-resistance to several chemically unrelated compounds. It is a multidrug efflux pump that has 12 transmembrane regions, which bind hydrophobic drug substrates that are either neutral or positively charged [6]. It also has two ATP-binding sites, as hydrolysis of two ATP molecules are needed for the transport one drug molecule [43]. Binding of substrate to the transmembrane regions stimulates the ATPase activity of PGP, causing a conformational change that releases substrate to the extracellular space. Hydrol ysis at the second ATP site is required to re-set the transporter so that it can bind substrate again, completing one catalytic cycle. Increased expression of the PGP transporter in cancer cells increases the amount of catalytic cycles that occur, which increases the amount of drug effluxed [5]. This lowers the intracellular drug concentration below a cell-killing threshold, which results in resistance. Not all multidrug-resistant cancer cells express PGP. Resistance in these cells was discovered to be linked with the expression of the multidrug-resistance-associated protein 1 (MRP1) [44]. MRP1 is similar to PGP in structure (table 1) but, unlike PGP, it recognizes neutral and negatively charged hydrophobic natural products, and transports glutathione and other conjugates of these drugs, or, in some cases, such as for Vincristine, co-transports unconjugated glutathione. Some anticancer drugs, such as Mitoxantrone, are poor substrates for PGP and MRP1. Mitoxantrone resistance is due to a more distant member of the ABC transporter family, MXR (Mitoxantrone-resistance gene) [45]. This transporter is thought to be a homodimer of two half-transporters, each containing an ATP-binding domain at the amino-terminal end of the molecule and six transmembrane segments (table 1). Resistance can also develop as a result of increased expression of ABC transporters in the apical membrane of the gastrointestinal tract [46]. ABC transporters play a key physiological role, where they extrude toxins thus forming a protective mechanism and a first line of defense. Increased expression of these transporters decreases drug uptake and therefore decrease drug bioavailability. Examples of chemotherapeutic agents that develop resistance by this mechanism include antimetabolites, such as Methotrexate and Fluorouracil, and alkylating agents, such as Cisplatin. Also water-soluble drugs that piggyback on transporters and carriers or enter by means of endocytosis can fail to accumulate as they will not be able to enter the body. Additionally, PGP actively secretes intravenously administered drugs into the gastrointestinal tract [47]. Resistance due to increased levels of PGP transporters in the gastrointestinal tract is illustrated by MDR1a/MDR1b-knockout mice, which have shown to have increased tissue concentrations of PGP substrates. Studies have also shown increased tissue absorption of PGP substrates, following oral administration, when co-administered with a PGP inhibitor. Reversal of drug resistance in cancer Ways to overcome multidrug resistance due to the over expression of ABC transporters are being researched. Some of the main approaches include developing PGP inhibitors, antibodies against the PGP transporter, antisense oligonucleotides and liposome-encapsulated drugs. Drugs that can reverse multidrug resistance, such as PGP inhibitors, could be useful interventions to improve bioavailability, by increasing oral uptake of anticancer drugs and decreasing drug excretion, thereby reducing dosing requirements [7]. Two inhibitors that are used in the laboratory and in clinical trials that attempted to reverse drug resistance are the calcium channel blocker, verapamil and, the immunosuppressant, cyclosporin A. Another method that can be used to inhibit PGP is by competitive inhibition [48]. PGP binds many different hydrophobic compounds so any drug that interacts with the substrate-binding region is likely to be a competitive inhibitor of other drugs. Thus, two drugs that are transported by PGP will compete for this transport, resulting in increased oral absorption of both, decreased excretion, and redistribution. This kind of drug interaction can be used to inhibit the multidrug transporter, when the inhibitor drug has little or no other pharmacologic e ffect. Monoclonal antibodies (MAbs) against PGP have been used to kill multidrug resistant cells [49]. MAbs are of therapeutic use as they can activate the immune response, which results in complement mediated lysis or antibody dependent cellular cytotoxicity of the cells. An example of a MAb is MRK-16, which has shown selective toxicity towards tumours that are over expressing PGP. Molecules, which are normally involved in signal transduction on T and B cells can also be targeted for antibody therapy [50]. Such molecules include CD19, which is a membrane receptor involved in signal transduction and potentiates the response of B cells to antigens. MAbs directed against CD19 can induce cell-cycle arrest due to negative growth signals that cross-link immunoglobulin M and CD19. Antisense drugs work by down regulating gene expression [51]. This occurs by sequence-specific blinding of either DNA or RNA, which inhibits transcription or translation, respectively. Different antisense-oligodeoxynucleotides have been reported to chemosensitize resistant tumour cells to anticancer drugs through down regulation of PGP expression and thus increasing the intracellular accumulation of anticancer drugs in the cancer cells. The efficiency of a synthetic oligodeoxynucleotide (ODN) in regulating gene expression in living cells depends on its thermodynamic stability, resistance toward nucleases and cellular uptake [52]. A number of studies indicate that a synthetic ODN coupled with a DNA intercalator such as acridine, naphthyl imide, psoralen or pyrene might act to increase stability. Novel drug delivery systems such as liposome-encapsulated drugs have also been developed to overcome multidrug resistance [53]. Liposome formulations contain a small fraction of polyethylene glycol (PEG)-derivatised phospholipid, which has been shown to dramatically alter the pharmacokinetic properties of certain anticancer drugs. These pharmacokinetic alterations include long elimination half-life and small volume of distribution. Another formulation developed to bypass PGP transporters is anionic liposomes, which are internalised by certain cells and are able to provide drug release in intracellular compartments. Conclusion Cancer is prevalent in the western world and much research is dedicated to produce effective chemotherapy. Current chemotherapy includes alkylating agents, antimetabolites, cytotoxic antibiotics, plant derivertives, hormone therapy and monoclonal antibodies. However the efficacy of these chemptherapeutic agents is limited to patients developing multidrug resistance. This is mainly due to the over expression of ABC transporters, particularly the PGP transporter, as they have broad drug specificity so can bind many structurally unrelated drugs [5]. Techniques to reverse multidrug resistance are being developed and include co-administration of PGP inhibitors, which prevent the binding of anticancer drugs the transporter [7], the use of antibodies, which kill cells over expressing the PGP transporter [49], antisense oligonucleotides that down regulate PGP expression [51] and liposome-encapsulated drugs, which alter the pharmacokinetic properties of anticancer drugs [53]. A better understanding of the mechanism by which ABC transporters efflux chemotherapy and further analysis, in clinical trials, of known mechanisms of multidrug resistance would increase the development of agents that reverse multidrug resistance. 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