Public Service Broadcasting Essay Example | Topics and Well Written Essays - 3000 words

Public Service Broadcasting - Essay Example This essay stresses that globalisation has entailed a larger involvement of private enterprises in global media, both in the western democracies as well as in emerging economies like China. Private involvement necessarily results in a higher concentration in the media industry, thereby the media representing a narrow class interest and not that of portraying the national interest. This paper makes a conclusion that television journalists have taken to the production of analytical documentary making with a great vigor particularly in the modern period of globalization and political uncertainties. As a result, the rigid framework of PSBs that typically catered to national political interests cannot be followed. Greater openness and freedom on content have provided journalists to test uncharted waters. In the process, the researchers for the documentary went back in history to understand the link between the current incidents and the past record of the US military establishments in fueling illusions. Such bold statements, equating the War on Terror with the Cold War, could not perhaps be possible to be voiced on the BBC a decade back, when the television in the UK was more controlled and functioning like a duopoly hence following PSB guidelines was easier. The opening up of television, the multi-channel framework and the entry of cable television has altered the ballgame entirely. There has been a tendency of trivializing content on television to grab eyeballs in the both the government controlled as well as private channels. Yet, these documentaries have attracted much controversy and criticism from within the industry. There are accused of staging events and faking images, often camouflaged as the reality.

Internet Working Essay Example for Free

Internet Working Essay In this paper the functions and the Structure of the Internet is discussed in detail along with the help of figures and diagram in order to make understand that what the internet really is and how it works . The paper discusses in detail the main functions and parts of Internet and how they work according to their functions and features . the Internet has opened the vistas of knowledge for the world so The world has become a global village where the people live their life on the Internet . It has no boundaries or barriers, It is open to all who have access to Internet using computer . The e-commerce and online business has really facilitated the people now days . They can draw money , deposit money , transfer money and shop nay thing on internet in seconds . furthermore people can also share the information with the people living in various countries in research work the internet has really brought a revolution in the world of Information Technology . Introduction: The internet has been a useful source of information for the public and made things possible which were impossible in the past . Such as emailing has accelerated the process of Mailing and it hardly takes seconds to reach in any part of the world as the Client are connected to Server and the Server connects the clients to world wide web . it is like cob web which keeps connected to all users at the same time . The Internets growth has become explosive and it seems impossible to escape the bombardment of www. coms seen constantly on television, heard on radio, and seen in magazines. Because the Internet has become such a large part of our lives, a good understanding is needed to use this new tool most effectively. This whitepaper explains the underlying infrastructure and technologies that make the Internet work. It does not go into great depth, but covers enough of each area to give a basic understanding of the concepts involved. For any unanswered questions, a list of resources is provided at the end of the paper. Any comments, suggestions, questions, etc. are encouraged and may be directed to the author at the email address given above. The Internet Frame Work: As the Internet is a global network of computers each computer connected to the Internet must have a unique address. Internet addresses are in the form nnn. nnn. nnn. nnn where nun must be a number from 0 255. This address is known as an IP address. (IP stands for Internet Protocol; more on this later. ) The picture below illustrates two computers connected to the Internet; your computer with IP address 1. 2. 3. 4 and another computer with IP address 5. 6. 7. 8. The Internet is represented as an abstract object in-between. (As this paper progresses, the Internet portion of Diagram 1 will be explained and redrawn several times as the details of the Internet are exposed. )

The Plight of the Common Man in Herman Melvilles Bartleby, the Scriven

George Edward Woodberry, author of the Heart of Man, published in 1899, emphasized the significance of the role of the individual as an active and equal partner in American democratic rule: The doctrine of the equality of mankind by virtue of their birth as men, with its consequent right to equality of opportunity for self-development as a part of social justice, establishes a common basis of conviction, in respect to man, and a definite end as one main object of the State; and these elements are primary in the democratic scheme. Liberty is the next step, and is the means by which that end is secured. It is so cardinal in democracy to strive for a balance between the individual and the mass, so that the identification of the common man as an American ensures him of the promises proposed by the government. (226-227). During the early 1800's, America struggled with the search for identity and the shift toward Liberal Individualism. The revolutionary words of freedom, equality, and brotherhood gave birth to the doctrine of government by the people, for the people, and of the people. These principles were the substance of democracy; these tenets, though fundamentally sound and idealistically honorable, seemed elementary, but to assume that the ideals of democracy were rudimentary and easily attained was a national betrayal. This betrayal, depicted as the futility of the individual to achieve political and representational inclusion in the government and, more importantly, the realization of his importance, belied the struggle. The shift toward Liberal Individualism created the need for a balance between the individual and the community. The election of 1828, which propelled Andrew Jackson to national prominence, marked... ...ye, Thomas R. and L. Harmon Zeigler. The Irony of Democracy. Belmont: Wadsworth, 1970. Hancock, Ralph C. ?Tocqueville?s practical reason.? Perspectives on Political Science 27 (Fall 1998): 212-19. Hans, James S. ?Emptiness and plenitude in Bartleby the scrivener and The crying of lot 49.? Essays in Literature 22 (Fall 1995): 285-99. Hudson, William E. American Democracy in Peril. Chatham: Chatham House, 1995. Stovall, Floyd. American Idealism. Port Washington: Kennikat, 1943. Strong, Douglas M. Perfectionist Politics: Abolitionism and The Religious Tensions Of American Democracy. Syracuse: Syracuse UP, 1999. Strout, Cushing. Making American Tradition. New Brunswick: Rutgers UP, 1990. Wilentz, Sean. ?Striving for Democracy.? The Wilson Quarterly 23 (Spring 1999): 47-54. Woodberry, George Edward. Heart of Man. London: Macmillan, 1899.

Ethnographic Study: Bikram Yoga

This ethnographic study of the history, rent state and proposed health benefits as understood to be alternative health care of Buckram yoga will consider bibliographic research and will include a first-hand account as well as Informal interviews. Buckram Chuddar was born in Calcutta, India in 1946. He started to learn yoga poses and theory as young as three years old. At the age of five Chuddar began to work with Guru Vishnu Gosh who happened to teach children next door to Shuddery home. It was Gosh who encouraged him to compete In the National India Yoga Championship.Chuddar went on to win the championship three institutive years starting at age eleven, making him the youngest champion. At the age of twenty, however, Shuddery knee was crushed by an eighty pound weight dropped by his weight lifting spotter, Western medicine told him that he would be crippled for the duration of his life. Chuddar was reluctant to accept this reality and decided to better the condition of his knee with yoga under the supervision of Gosh. It is claimed that he was able to walk and was fully recovered from this life- altering Injury in Just six to eight months (Slicked, 2003).This miraculous recovery as Coauthor's Inspiration to dedicate his life to the practice and spread of yoga. Gosh taught Chuddar a more traditional Hath yoga â€Å"picking specific saunas [or postures] for specific ailments,† (Slicked, 2003). From these teachings, Chuddar chose twenty-six poses meant to be completed twice over, punctuated by a savanna, or corpse pose which acts like a rest period, along with two breathing exercises to be completed in the span of ninety minutes. Each pose is designed to work certain areas of the body such as the spine, knees, digestion system and immune system.This sequence is also designed to be performed in a humid room heated to 105 to 108 degrees Fahrenheit; this Is meant to mimic Indians climate, facilitate a deeper range of motion for the yogi and help prevent injur y (Slicked, 2003). Chuddar made a name for himself in Japan prior to bringing his brand of yoga to the United States but the first American Buckram yoga studio was established in California In 1973 after trading yoga treatment for a green card into the country with President Richard Nixon (Gala, 2009).While ;yoga In America was Initially popularized amongst the elites and has been associated with movie stars and intellectuals since 1 OFF blood pressure and lengthened one's life span that practice became fashionable amongst the general public,† (Gala, 2009). Since then, yoga in general has moved from being more or less a past time to being part of a fitness, health and wellness program amongst many types of people.Those practicing western medicine often see yoga as a benefit in the sense that it is a cardiovascular activity, it is considered relaxing by most and will burn calories that might not have been burned otherwise in patients ho might be overweight and reliant on medica tions. Whether or not yoga can live up to its vast health claims in Western medicine standards has yet to be determined. Even still, Buckram yoga's popularity through celebrity status or otherwise has made it a billion dollar industry with Chuddar himself collecting 2. 6 million dollars in 2003 from teacher training alone (Gala, 2009).Shuddery extensive unabashed wealth and endorsement of competitiveness in what is typically considered to be a spiritual pursuit has brought about a certain amount of controversy but has not dampened he interest in the yoga itself. People everywhere continue to believe in its abilities to heal, ward off ailments and keep the body trim and healthy. When I walk into my Buckram yoga studio in Phoenix I am immediately greeted by a cheerful woman dressed in yoga clothes passing out class schedules to those who just finished a class from behind a desk.I sign my name and remove my shoes at the door. The main room includes a large refrigerator should you want to purchase a water bottle, racks of mats and towels that can be borrowed and large, luxurious ouches where people sit to await the next class. The locker room around the corner is equipped with an open shelving unit to place your personal belongings, a shower, a restroom and separate sink unit with a large mirror, towels, decorative soaps, etc. All around, this facility is very well maintained and seems to go out of its way to provide comforts and niceties to its patrons.The locker room provides a place for friends to talk to one another but most stifle conversation in the main room. In the locker room I ask my fellow Buckram followers why they chose to incorporate Buckram yoga into their lives. A woman who appeared to be in mid-thirties explained: â€Å"l read that this yoga is the best out there because the heat helps you push out all your toxins, you know, because you sweat so much. I also read that you burn Just a ton of calories which is good because I don't have all the time in the world to spend at the gym. Another, who appeared to be in her twenties and in good physical shape, told her story: â€Å"I was always really active and played mostly soccer but I tore my CAL a couple years ago and I can't do all the things I used o. A friend of mine, kind of a granola girl, brought me here and I have been coming ever since! I always feel like I had a really good workout but I don't feel like I'm stressing any part of my body too much. † In asking a woman who let me know that she was sixty-five why she considered Buckram yoga to be a benefit to her she said: â€Å"My doctor suggested I try to be more physically active but I'm not the girl I used to be†¦ ‘m not able to do much really and I'm unwilling to subject myself to water aerobics. He [the doctor] is concerned about my blood pressure and my stiffening mints. When he told me about Buckram yoga I about died right there imagining doing something like this in that kind of heat! But I gave it a go, of course I have to bring in a stool to help me balance and I don't do every pose, but I think it's helping. I feel a different take on Buckram yoga from the physical payoffs: â€Å"I'm a new mom and my maternity leave ended a few weeks ago. Vive been practicing yoga for years but I like Buckram the best right now.There's no top 40 music playing in the background, everyone who is here wants to be here for Just this- not to be seen wearing a cute roust outfit and it's Just all about you for an hour and a half. You stare at yourself in the mirror and you hear the instructor but really you Just hear your own breathing. I feel more centered when I leave here. † When I enter the classroom I am immediately overwhelmed by the humidity. Being from Phoenix, Arizona I am no stranger to heat but in this classroom the air is thick and Just bordering on difficult to breathe for me.The lights are low and there are already students lying on their back in savanna position. No one sp eaks in the room as it assumed to be a peaceful place f meditation. Class begins when the instructor turns the lights on and introduces herself. The instructor makes a point of asking if there is anyone in the room new to Buckram yoga, congratulates them for coming and reminds them to stay in the room, lie on their mats if need be and to have fun. We go through all twenty-six poses, including the breathing exercises, with her dispensing instruction as we ease into each new movement.She also reminds us all to focus on our gaze in the mirror and that our bodies our stronger than our minds are at times so getting through class will quire determination on our parts. For safety reasons students are allowed to drink water as they please but it is discouraged to drink outside of the designated times and while the class in the midst of a pose. However, once the class is finished you can observe the majority of people gulping water hurriedly before getting into the final savanna which conclu des the sequence and allows time for personal meditation.While I lay in silence I find myself agreeing with the major points my interviewees offered: Buckram yoga is a tough but gentle workout for people of all levels and remotes a sense of personal well-being and calm that very few workouts I have tried do. This, however, was Buckram Shuddery aim all along. He believes that if you practice this yoga to the best of your abilities you will â€Å"live a better, healthier and more peaceful life,† (Chuddar, 2010).For Chuddar, physical health and mental peace must coincide for one cannot exist without the other. Martin Marty discusses the importance of recognizing that spirituality and physical health are indeed intertwined in his essay Religion and Healing: The Four Expectations. This essay souses more so on faith in the religious sense but for many yoga offers a very spiritual connection to a force that has the power to heal, bring calm and bring like- minded people together to form a sense of community.Marty reminds us that â€Å"in a typical half year of American publishing†¦ Hundreds of†¦ New Age titles on health and well-being appeared†¦ Imaging, breathing, meditation, herbalist, and hypnosis are but a few of the many technique for being in tune with the infinite,† (Marty, 2005). It can be safely assumed that yoga could be added to that list in which ways people reach out spiritually. Harold Koenig writes in Afterward: A Physician's Reflections that we need be focused on healing the â€Å"whole human person,† (Koenig, 2005).

Betrayal in Shakespeare Essay

Breaking the bond of trust in a relationship, and deceiving another person is considered betrayal. In Shakespeare’s Julius Caesar, betrayal can be seen as the base of the whole story, and throughout the play between other characters. Due to the anger of Cassius, the whole of the play deals with the betrayal of Caesar by Cassius, and there are examples of this before and after his death. The first betrayal of Caesar can be looked at in the very beginning of the play, when Flavius and Marcillus sends the commoners away, and then proceed to take scarves off of the statues celebrating Caesar. They make the comment, â€Å"These growing feathers pluck’d from Caesar’s wing will make him fly an ordinary pitch,† (Act 1, Scene 1). In other words, the two conspirators feel that by sending away Caesar’s followers will give Caesar a reality check of sorts, and to bring his ego down a peg. The next example of betrayal can be seen by Cassius working to get Brutus to his side, away from believing in Caesar. He does this by first sending him a fake letter, and then proceeds to tell him about why he is so upset, and that he feels betrayed by Caesar. He tells Brutus about a time before when they were swimming across the Tiber river and Caesar was almost drowning, calling out, â€Å"Help me, Cassius, or I will sink! † (Act 1, Scene 2). He describes how he saved Caesar’s life, then tells Brutus, â€Å"and this man is now become a god, and Cassius is a wretched creature and must bend his body,† (Act 1, Scene 2). This would be describing Cassius bowing down to Caesar as a king, even though he had saved his life. Most of the betrayal in this story is fairly upfront, until Act 3, after Caesar is killed. His friend Mark Anthony acts as though he is betraying Caesar, in order to take his later revenge. When he first arrives at the murder scene, he shakes hands with all of the conspirators that have killed Caesar, even though their hands are covered with blood. He then comments, â€Å"Shall it not grieve thee dearer than thy death to see thy Anthony making his piece, shaking the bloody fingers of thy foes, most noble! In the presence of thy corpse? † (Act 3, Scene 1). He is actually speaking to the spirit of Caesar. Anthony plays this part of fake betrayal to Caesar, continuing by agreeing to Brutus that he will not say anything bad about him after Brutus gets done speaking at the funeral of Caesar. Yet, the true betrayal happens when Anthony begins to discount everything Brutus has just said to the citizens, and he turns the citizens against Brutus and the other conspirators. The citizens become enraged as they feel that their leader, Caesar has been betrayed by the killers. The last example of betrayal can be seen as family betrays family. In Act 5, there is a conversation between Lepidus, Octavius, and Mark Anthony. The first family betrayal is when Lepidus consents to have his brother killed along with the other conspirators. Octavius asks Lepidus, â€Å"your brother too must die; consent you Lepidus? † to which Lepidus answers, â€Å"I do consent,† (Act 5, Scene 1). The next family betrayal is when Mark Anthony then agrees that his sister’s son, Publius will be killed too. Anthony replies without hesitation, â€Å"He shall not live; look with a spot I damn him,† (Act 5, Scene 1). There are other examples of betrayal in Julius Caesar, but betrayal is a concept that the whole story is based on, interweaving between almost all the characters of the story. From the major storyline of the betrayal of Caesar, to the minor betrayals between characters which cause Caesar’s death, or betrayal that is because of it, this is ultimately the theme of the story itself.

Cozumel essays

Cozumel essays Cozumel: Ah-Cuzamil-Peten The place known as modern day Cozumel was settled over 2,000 years ago by people of the Maya Civilization. They discovered the tiny island off the Yucatan Peninsula and named it Ah-Cuzamil-Peten., meaning land of the swallows, after the native birds that live there. The island was an important trade and religious center for the Maya. Merchants used to buy the salt and honey produced on the island. The Maya considered salt and honey more valuable than gold. Historians believe that El Caracol ruin was built as an ancient lighthouse to guide the travelers safely to shore. Cozumel was also the home of the Ixchel (lady rainbow), the Moon Goddess of fertility, pregnancy and childbirth. Ixchel was one of the most important gods in the Maya religious pantheon. Every woman in Mesoamerica was required, at least once in her life, to make a pilgrimage and place an offering on Ixchels altar. Today, Ixchels ruins and ceremonial center can be seen at San Gervasio ruins. . During the early 1500s, shortly after the New World was discovered, Spain began intensely exploring. In 1518, Juan de Grijalva, the nephew to the Cuban Governor, was investigating the Yucatan Peninsula. He left Havana with 300 men and four ships. Eighteen days into his trip, he discovered Cozumel when his ship was blown off course. He mentioned the island to Hernan Cortes who arrived in 1519 in search of gold. In 1519, when Herrnan Cortes, arrived at Cozumel with 11 hips and 750 men, he found two shipwrecked Spaniards. Geronimo de Aguilar and Gonzales Guerrera had been living on the island with the Maya for over 15 years, first as slaves but then finally as citizens of the community. Legend has it that de Aguilar was so happy to be rescued that he jumped from shore and started swimming towards the Cortes ship when it was still 20 miles away. Guerrera chose to remain on the isla...

Africa and the Empire of Ghana essays

Africa and the Empire of Ghana essays The empire of Ghana was an important black trading state in West Africa. Arab camel caravans brought salt and copper from mines in the Sahara and dried fruits from North Africa to Ghana's markets. There, the products were traded for gold, ivory, and slaves from regions south of Ghana. Ghanaian jewelry and leather goods were sold and traded for textiles, clothing, and fine tools from Arabia and Europe. Kumbi Saleh, the capital, and Audagost were probably the largest cities in West Africa. The king of Ghana was paid in gold for the taxes he charged on imports and exports. He also claimed all gold nuggets found in his kingdom. With this wealth, the king maintained an efficient government and an army that kept the trade routes to Ghana safe. Skilled ironworkers produced weapons that contributed to Ghana's strength (World Book 2003). Blacks in America are descendants of a great people. The ancestors of most American blacks came from an area of Africa known as Western Sudan. This area included the empire of Ghana. Their ancestors lived in nations with economies that depended on farming, trade, and gold mining. These skills that Africans possessed were brought with them on the slave ships to the Americas. The rising European demand for sugar helped create fierce competition for slaves and new sugar colonies. "From the 1500s to the mid-1800s, the Europeans shipped about 12 million black slaves from Africa to the Western Hemisphere. Nearly 2 million of these slaves died on the way. About 65 percent of the slaves were brought to Brazil, Cuba, Jamaica, Saint Domingue (now Haiti), and other sugar colonies. Brazil alone received about 38 percent. North America got about 6 percent" (World Book 2003). The importation of millions of slaves to work for free is the biggest contribution of Africa to the growth of America. Hi ghly skilled and hard-working Africans are the backbone of America's wealth. Often, the Greeks are given credit for many innov...

Truckers Your Job Hunt Cheat Sheet

Truckers Your Job Hunt Cheat Sheet Truckers: If you’re looking for your next great gig, why not start with the cream of the crop? Everytruckjob.com did their homework, and recently compiled a list of the top 10 trucking companies in the country- a great place for you to start or continue your job hunt! American FreightwaysA logistics leader with unparalleled shipping and transportation solutions in the industry.SCHNEIDER NationalA shipping capacity titan with a proven on time service delivery record.C.H. RobinsonA true industry veteran with a great reputation and commitment to high quality standards.Con-way TransportationGreat trucking services with deep coverage throughout the U.S., Mexico, and Canada.SAIA LTL FreightA true leader in safety and efficiency, with an impressive array of services for its customers.Fox TransportationGreat, efficient service has put them at the top of the trucking company heap.RyderKnown for superior supply chain management and commercial transportation solutions.MayflowerA consiste nt and reliable player in the freight and transportation industry.J.B Hunt Transport ServicesA top-flight company that understands the value of having qualified employees who can deliver measurable results.WERNERA customized supply chain champion, with a focus on safety and its customers.Consider this your job hunt cheat sheet- any trucker would be well served to work for any of these companies. When you’re looking for your next great trucker job, keep them in mind, do your research and see if any of them have open driver positions, and include them in your job-hunt plan. Best of luck!Top 10 Trucking Companies in The USARead More at www.everytruckjob.com

Lieutenant Nun Essay Example | Topics and Well Written Essays - 500 words

Lieutenant Nun - Essay Example Her change of look was so profound that neither her father, nor her mother and uncle could recognize her. After turning into a man, Catalina did a lot of jobs, and other activities that no woman could be expected to do in her time. The second turning point in Catalina’s life came when she had signed up for selection in army and was hired as her own brother’s soldier. Like her mother, father and uncle, her brother also did not realize it was his sister serving him as a soldier. Particularly, Catalina regretted having killed her own brother as a result of her commitment to her friend who had asked her to kill his second. She personally viewed the funeral of her brother and seeked refuge in the church for months after that. As a soldier, she happened to learn fighting skills which she would later use in the bloody battle. The third turning point in the life of Catalina came when she was declared not only a woman, but essentially a virgin woman as a result of the medical ex amination she goes through to clarify the doubts of the bishop when she made the confession of being a woman to the bishop. The bishop promised to assist her. Therefore, she was sent to the nunnery, and the church, meanwhile, studied her history to know if she had ever considered becoming a nun in the future. Two years after that, when it was found out that she had never taken vows, Catalina was granted the status of a Spanish celebrity.

Children with Autism Extend New Words Research Paper

Children with Autism Extend New Words - Research Paper Example The research in the article was ostensibly to give the difference between the autism children and the normal children with reference to commonalities of objects extraction supporting of the category inference using the context of social-communicative (McGregor, Karla, & Allison, 2011). The different approaches given by the two groups considered in this study has a strong influence in education, for instance in the research findings, the children with autism were found to be notorious of extending nouns in relation to multiple exemplars and this was indicative that they are able to surpass the local perceptual biases (McGregor, Karla, & Allison, 2011). This is an exact opposite of their normal counterparts who suggested narrow extension. It is the deductive that children with autism can have a better grasp of knowledge and inference making that the normal children.The research in the article was ostensibly to give the difference between the autism children and the normal children with reference to commonalities of objects extraction supporting of the category inference using the context of social-communicative (McGregor, Karla, & Allison, 2011). The different approaches given by the two groups considered in this study has a strong influence in education, for instance in the research findings, the children with autism were found to be notorious of extending nouns in relation to multiple exemplars and this was indicative that they are able to surpass the local perceptual biase.

Legal Aspects of Nursing - Homework 5 Case Study

Legal Aspects of Nursing - Homework 5 - Case Study Example On trial, other nurses stated that they frequently made paper records during breaks or at end of shift, often when they could hardly remember the dosages administered to patients. In addition, nurses would electronically sign for narcotics and prepare IV drip bags in advance of when needed and discard the same when no longer required or when physicians changed orders. In addition, nurses deviated from physicians order for an IM injection by thus electing to provide medication by an IV route. In addition, the hospital lacked a clear policy on when nurses such as preceptor and mentee, both had a responsibility for patient care. The suspended nurse also admitted that she recorded the data long after administration and in some cases in the following day (Guido, 2009). Legal aspects in nursing provide the framework for establishing the acceptable care to the client and outline the responsibilities of the nurses. The law in nursing also outlines the boundaries in independent actions of nur sing and provides for the standards of nursing practice. Nursing law ensures that nurses obtain the informed consent of the patients before any treatment and provide information to the clients on any condition that requires diagnosis and also the benefits and risks of the alternative modes of treatment (Guido, 2009). In the above case, the facility has sufficient evidence to suspend the nurse from employment. The nurse is liable since she testified that she recorded their paper documents at the end of the shifts or even the following day. According to legal framework, the nurse must carry out the physician orders unless she reasonably believes that there is an error. The nurse must seek a clarification from the physician or immediate supervisor; otherwise she is liable for any harm experienced by the patient. If nurses are requested to float to another unit, the nurse must have the capacity and experience to carry out the duties since one is held liable for the same standards of car e as those other nurses working regularly in that unit. In addition, the nurse is liable for not reporting unsafe nursing practice such as theft of narcotics in the facility (Guido, 2009). Surprisingly, the facility had allowed nurses to sign for narcotics electronically and prepare IV drips in advance and discard the same IV bags when not needed by the physicians. The evidence of other nurses is critical in determining the outcome of this case since other nurses did not follow the legal procedure in medical documentation. The nurses clarified that they had deviated from physician’s order for an IM injection, thus choosing to provide medication by IV route. Finally, the organisation lacked a standard procedure and policy framework for paper records when a preceptor and a mentee were involved. The testimony other nurses would impact on the outcome of the case. For instance, the testimony proves the negligence of the hospital facility in safeguarding the safety of patients sinc e not policies that outline the working relationship of a preceptor and mentee and who should record the narcotics usage. The institutions should first preview the paper record documentation of all nurses and review the authority of each personnel in the organisation. The institution should also review the nurse-patient relationship before the court of law (Guido, 2009). If I

History of Environmental Education and Environmental Policies Essay

History of Environmental Education and Environmental Policies - Essay Example Today, an Environmental Education includes not only the technical impact that technology has presented, but also the responsibility that industry and individuals have in their approach to maintaining a sustainable geography that is productive as well as healthy. Modern attitudes towards an Environmental Education have been the result of an evolution in thinking towards the environment that has spanned the last two and a half centuries. Environmental Education traces its roots back to 1762 and the publication of Emile, a novel on educational philosophy that argued that education should focus on the environment (McRea). Wilbur Jackman's 1891 publication of Nature Study for the Common School initiated the Nature Study Movement that was pioneered by the American Nature Study Society headed by the naturalist Liberty Hyde Bailey (McRea). A greater environmental awareness was fostered in the United States by the Romantic Nature Movement and the Progressive Education Movement led by John Dewey (Haskin). In essence, "Environmental education did not spring forth fully formed from any one discipline, but rather as a product of a co-evolutionary process within science, public awareness of environmental issues, and educational ideas" (Haskin). The Dust Bowl of the 1930s was accompanied by an even greater awareness of our environment and the need for conservation and sustainability. The movement towards toda... Movement was spearheaded by Aldo Leopold, a Wisconsin educator that advocated an "an approach to science that merged environmental thinking, science and life practice" (Haskin). This thinking led to the first college degree in conservation at the University of Wisconsin-Stevens Point in 1946 and the coining of the phrase 'environmental education' by Thomas Pritchard, Deputy Directory of the Nature Conservancy, at a meeting of the International Union for the Conservation of Nature in Paris in 1948 (McRea). The next decade would see a greater public awareness of nature and the natural surroundings and a call for increased sensitivity and responsibility in our actions that affect our world's environment. These attitudes were brought into greater focus by the 1962 publication of Rachel Carson's Silent Spring, a critical review of the devastating effects that man and technology can have on the environment (Haskin). The modern environmental movement had been born and the first Earth Day in 1970 can be considered the birth of the modern national policies on Environmental Education, as well as environmental law and policy. Since the 1970s, environmental education has been addressed in the US and around the world based on a few basic principles. 1977 marked the world's first intergovernmental conference on environmental education held at Tbilisi, in the former Soviet republic of Georgia (Archie and McRea). The conference set forth five broad objectives for environmental education that the EPA agreed to and continues to support. These five principles are (1) Awareness and sensitivity to the environment and environmental challenges; (2) Knowledge and understanding of the environment and environmental challenges; (3) Attitudes of concern for the environment and motivation to

Hoegh & Jensen's main points Essay Example | Topics and Well Written Essays - 500 words

Hoegh & Jensen's main points - Essay Example The researcher states that Hoegh and Jensen created workshops and activities to determine the usability problems faced by the users of the software along with the problems that the software developers themselves thought to be crucial which users could encounter. Then these users were divided and assigned to different projects that were set up. First, the users’ reactions and the instances, when they got stuck using the software, were recorded which was followed by the listing of problems that the developers identified. It was planned to find out if there were mutual problems that the developers and users identified or there were differences in the identification and realization of diverse usability problems. Then the authors or rather arbitrators were appointed to carry out the procedures and analysis in order to determine what the software developers themselves think about the problems that exist in their software. To identify the authentic usability problems, the developers were asked to list down the problems they thought could be hindering for the users. It was a basic plan to listen and account for both the sides, that is, the developers and the users, and then to merge the usability problems, issues and experiences further on to identify the true usability problems that both parties agreed upon to make the identification process easier for the developers. A certain type of diversity was kept to observe different results from the three different projects.

How can Economic Value Added (EVA) statements be used to improve Essay - 2

How can Economic Value Added (EVA) statements be used to improve financial statement reporting, results, and success What are some problems found with EVA - Essay Example Making financial decisions only based on accounting data is a traditional way that can be misleading for the financial managers to make bad decisions. EVA measures are useful for the business to make decisions that can help the business to grow and help in making future ones. EVA creates the ‘value’ in the business decisions and financial management. The EVA calculations and statements are drawn by evaluating the value that has been added to the company. It shows how much the business has grown in terms of the worth it has. There are many factors that the EVA statements take into consideration to make sure that all the relevant data is considered when measuring the value of the business. It calculates how much the growth of the business is and how much has been invested for that growth. It takes out the net benefit that the business has gained and in regard of that cost that has been put in for that benefit (Grant, 2003). The EVA statements allow the business to take decisions about those projects that have to be accepted by the business. EVA statements would accept those projects that give the business a chance to experience growth and that add to the value the business. However, the financial managers will not accept those projects that seem to bring less benefit to the business and its value, no matter how much financial gain that project may bring. Although it may seem that the EVA statements neglect the financial figures, the concept is simple which suggests that decisions should be taken on account of the business’s financial health, and not taking those decisions that may financially hurt the business. EVA statements are greatly used to improve the business’s financial statement reporting, results and the future success. It allows the business to take decisions that are beneficial for the business financial position. Moreover, it allows the financial managers to evaluate the financial results in relation to

Hoegh & Jensen's main points Essay Example | Topics and Well Written Essays - 500 words

Hoegh & Jensen's main points - Essay Example The researcher states that Hoegh and Jensen created workshops and activities to determine the usability problems faced by the users of the software along with the problems that the software developers themselves thought to be crucial which users could encounter. Then these users were divided and assigned to different projects that were set up. First, the users’ reactions and the instances, when they got stuck using the software, were recorded which was followed by the listing of problems that the developers identified. It was planned to find out if there were mutual problems that the developers and users identified or there were differences in the identification and realization of diverse usability problems. Then the authors or rather arbitrators were appointed to carry out the procedures and analysis in order to determine what the software developers themselves think about the problems that exist in their software. To identify the authentic usability problems, the developers were asked to list down the problems they thought could be hindering for the users. It was a basic plan to listen and account for both the sides, that is, the developers and the users, and then to merge the usability problems, issues and experiences further on to identify the true usability problems that both parties agreed upon to make the identification process easier for the developers. A certain type of diversity was kept to observe different results from the three different projects.

Race in our everyday lives Assignment Example | Topics and Well Written Essays - 750 words

Race in our everyday lives - Assignment Example This conflict involved two people: an African and Irish man. The African ethnic background belongs to the Indo-Mediterranean race. This is one of the southern branches of the big European race. This race is common in southern Europe, North Africa, Arabia, Iraq, southern Iran and North India (Haddon, 22-50). It has local versions. In the zones of contact with Caucasians in North Africa and Arabia two transition anthropological types were formed. On the northern border of the area there is the Balkan- Caucasian race, on the southwest - the Ethiopian and the Negro, the south -east - the Dravidian (Haddon, 22-50). The special mixed racial type combines the features of Negroid, Mongoloid and Caucasoid races. The other man originates from the atlanto -Baltic race of the big European race. This race is an important element of the anthropological composition of Norwegians, Swedes, Scots, Irish, Danish, Russian, Belarusian, Baltic peoples, partly found in the populations of the northern regions of France, Germany and Finland (Haddon, 22-50). A small proportion of this race can be found in the European lands. There are two main Irish values: the first - family and the other is education. In this they are similar to Africans; Africans attitude to life is expressed in the moral values of family, procreation, kinship (Pepin, 245-255). Africans believe that an individual is still not a person but a project person; he becomes only person in the family, when there he has his firstborn. Desire for procreation, augmentation of vital energy is one of the most important incentives for life (Pepin, 245-255). Such an attitude towards children led a number of peoples in the formation of the moral norm th at defines the value of the childs birth in marriage and before marriage and outside marriage. Traditional value of life and the consequent attitude towards children comes into conflict with Christian values and moral standards. A child born

Timberland’s Corporate Essay Example for Free

Timberland’s Corporate Essay How would you characterize Timberland’s exercise of its corporate power in society? Is Timberland using its influence responsibility? If so, how? †¢ I would characterize Timberland’s exercise of its corporate power in society as â€Å"Corporate Social Responsibility†. Timberland is being socially responsible towards society and is acting in a way that enhances society. Timberland is practicing the â€Å"iron law of responsibility† which says that in the long run, those who do not use power in ways that society considers responsible will tend to lose it. The company is using its influence responsibly through charitable giving; cash and in-kind donations, and giving footwear to  schoolchildren in Afghanistan, and sustainability issues. Has Timberland balanced its economic and social responsibilities through its various programs, such as the annual Serv-a-Palooza event and sustainability goals? Are the company’s programs examples of enlightened self-interest? †¢ Serv-a-Palooza was an event that celebrated Timberland’s centennial anniversary where over 500 volunteers worked on various projects to support local New Hampshire communities and areas in Missouri afected by tornados. Timberland’s sustainability goals include reducing carbon emissions and using renewable energy sources. The two programs balanced Timberland’s economic and social  responsibilities. By having a philosophy to further the interests of others and the communities that surround them. Timberland  ultimately serves their own self-interest. What are the arguments for and  against Timberland’s social  responsibility initiatives? †¢ Arguments for Timberland’s social responsibility initiatives include balancing corporate power with responsibility, improving stakeholder relations, and enhancing business reputation. Arguments against Timberland’s social responsibility initiatives include requiring skills businesses may lack and placing responsibility on the business rather than individuals. Although Timberland possesses power and influence, responsibility comes with power and they need to properly manage that power. As previously mentioned, Timberland is using its power responsibly by way of charitable giving and reducing their carbon footprint. By focusing on social issues Timberland has created strong stakeholder relationships and built a loyal customer base. Although one can raise arguments against Timberland’s social responsibility issues, they have done a great job of developing the most important intangible asset- their reputation. If you were an executive of VF Corporation, would you  support continuation of these initiatives? Why or why  not? †¢ As an executive of VF Corporation I would continue to support the initiatives of Timberland to continue to establish trust amongst stakeholders. The current initiatives have been beneficial and have not had a significant cost to stakeholders. It is important that VF Corporation continue this philosophy and still allow stakeholders to profit from the company with little to no cost. The social enterprise created by Timberland has been extremely successful in improving human and environmental well-being. Not only does Timberland care about their local New Hampshire community, but they search all over the world to find ways to give back to society. If VF Corporation continues to support the social initiatives as they did in their first Serv-a-Palooza Timberland will surely be recognized as one of the country’s â€Å"Best Corporate Citiens.†

Colonial Middle Class American Life Essay -- American History essays r

Middle Class Americans American middle class life was greatly influenced throughout 1870-1917. There were many profound changes, however the American industrialization and urbanization were the most rapid and unquestionably the most important. The industrialist brought forth household names that are still around today such as Swift, Armour, Westinghouse, Pillsbury, Pullman, Rocketfeller, Carnegie, and Duke. Due to the rapid movement of industrialization, so began a movement of urbanization. Between 1860 and 1910, urban population increased sevenfold and by the 1920’s more than half of all Americans lived in cities. Along with the cities came more use of electricity, electric lights, telephones, and eventually appliances. Appliances virtually revolutionized the lives of the middle and upper class Americans, as did Henry Ford’s mass production of the Model T. Throughout these forty-seven years many middle class Americans were influenced by the ads from companies, for example Sears Roebuck & Com pany. Not only were there adds for clothing and women’s and men’s’ apparel but for automobiles, phones, and housing. There were many values, hopes, and fears Americans contemplated with as well as the advertising business’ trying to lure Americans into purchasing products by listing consequences of using (or not using) their products.   Ã‚  Ã‚  Ã‚  Ã‚  Throughout the ads that I reviewed there were many of â€Å"so called† expected consequences of using or not using the products advertised. For example, there is an ad for A ScrapBook for â€Å"Homely Women† Only that is dedicated for women who want to have unwanted facial or bodily features removed or hidden. This two-part book gives advice for ugly scars, mouths, fingertips, crooked teeth, unwanted freckles, pimples, moles, etc. The expected consequences of this product are to take a below average looking woman and turn her into an attractive woman. The slogan even read, â€Å"We dedicate this collection of toilet secrets, not to the pretty women (they already have enough advantages, without being told to double their beauty) but to the plainer sisterhood, to those that look in the glass and are not satisfied with what they see.† After reviewing this advertisement, it is obviously directed to women with low self-esteem. Thus, the consequence s being that if a woman were to use the book of remedies it will enhance her beauty and self esteem. As... ... power of credit, but there were those that struggled with payments each month. Also with all the new industries coming into effect it was putting the â€Å"little man† out of business. In turn, this brought fear for the working Americans that were trying to stay financially stable. The biggest fear that Americans had was coming forth of World War I, especially families. Women feared losing their husbands to the draft and visa versa for men. Without their husbands women would have to be the sole providers of the household and men would fear for the sake of their families health and financial income. Middle class Americans coped very well with the changing values, promising hopes, and potential fears they encountered during the turn of the century.  Ã‚  Ã‚  Ã‚  Ã‚   In conclusion to the research I have done on middle class American life, not much has changed. The advertisements are still around today, and some even have the same slogan. Credit is as large as ever, and still is increasing the purchasing power for middle class Amercians. The values of people range dramatically from each individual to another and the fears of financial stability and war still haunt every American one-century later.

Bridging the Gap Essay -- Education

Bridging the Gaps John W. Gardner said, â€Å"Much education today is monumentally ineffective. All too often we are giving young people cut flowers when we should be teaching them to grow their own plants.† Education today is very ineffective. It is in an in between phase of the ways of old and a time of complete reform. The main issue is that people often lose sight of why the education system should even be reformed. It shouldn’t be reformed because â€Å"that’s what everyone else is doing.† It needs to be reformed to bridge the gap for the students who have a different learning style. It should be reformed to expand knowledge for students. Education reform can have good and bad effects. Because the education system is very complex, educators are being faced with changes and they must decide what is best for students. Educators have been faced with so many changes over time. From a one room schoolhouse to three story buildings. Schools have gone from strictly religious to it being illegal for teachers to bring it up. Not even twenty years ago, many students such as farmers’ kids would drop out of school after eighth grade to work on the farm. School was enforced and college was not as highly encouraged. Now, most people go to college. Education has had many reforms. Some have happened over time and some just quickly took place, but all of them have had a huge effect on students. Through all of the changes of education, one has slowly started to take place all over the world. The education system was created with a three month break in the summer. Slowly, the idea of year round school has been planted in education. Students fear it, but should they? The idea of year round school is not what everyone thinks it is. Most year round sch... ...earning." Project Based Learning. Web. Mar. 2012. . Quillen, Ian. "Educational Technology Rides Stimulus Funding Wave." Education Week. 09 Feb 2011: 15. SIRS Issues Researcher. Web. 25 Mar 2012. Sadowski, Michael. "Time and Learning." Harvard Education Letter. March/April 1998: 4-6. SIRS Issues Researcher. Web. 25 Mar 2012. Solomon, Gwen. "Project-Based Learning: A Primer." TechLearning (2003). Web. Mar. 2012. . Sovern, Jeff. "Laptops in Class: How Distracting Are They?." Christian Science Monitor. 06 Jun 2011: n.p. SIRS Issues Researcher. Web. 25 Mar 2012. Thomas, Ph.D, John W. "A Review of Research on Project-Based Learning." The Journal of Learning Sciences (2000): 367-42. Web. Mar. 2012. .

Academic Achievement of Homeschooled Children Essay

These days many American children are schooled at home, with the number growing more and more per year; however, t the same time home schooling has received less attention than other recent changes in the educational system. It could be argued that home schooling may have a much larger impact on educational system, both in the short and long run. This research will basically provide the home school population, its growth and its characteristics. Also, with the beginning of a discussion of the data sources used in the analysis, this research examines characteristics of home schooled children and their families such as those characteristics most relevant for gauging trends in home schooling. Lastly, there will be talked about implications of home schooling for regular schools and a brief conclusion. Therefore, based on all these researches, I am going to research whether or not home-based education cause higher academic achievement than the institutional schooling in U. S. A. Proposal Methods The researchers will use quantitative research regarding the influence of the educational background of parents on the performance of their home schooled children. The performance of the home schooled children will be quantified in comparison with the public school children with also varying educational backgrounds. Survey method—using will be used in order to obtain the more generalized results of the study. Participants will be contacted first through phone to have permission or consent of being part of the study. This part will also inform the family, especially the parents about the research study that will be conducted. According to Timothy Johnson of University of Illinois at Chicago, having an informed consent of the participants is part of the ethics of conducting researches. (Johnson) If the participants agree on being part of the study, mailed questionnaires will be distributed. The group that I propose to study is 75 homeschooled eleventh (11th) and twelfth (12th) graders. The chosen sample size is a significant number in order to study the influence of the educational background of parents on their homeschooled children since 75 is not much of a high number, making it too pricey or having too much effort given on the study, or not too low of a number. Studies were also made regarding the influence of parents on their homeschooled children, but these studies were more focused on the primary education (Grades 1-4, as indicated in the Literature Review), and not on the high school level. This study will further explore if the influence of parent’ educational background will change if the students are at a higher level of schooling. This study will also be limited on eleventh and twelfth graders. The sample size 75 students will be divided into three groups. Group 1 will consist of children that have been schooled at home by parents that have less than a high school education. Group 2 will consist of children that have been homeschooled by parents that have a high school education. Group 3 will consist of 25 children that have been homeschooled by parents. Additionally, 75 public school children also in eleventh (11th) and twelfth (12th) grade will serve as the control group. Group 4 will consist of children that have been schooled in the public school system and whose parents have less than a high school education. Group 5 will consist of 25 children have been schooled in public school and have parents that have a high school education and Group 6 will consist of 25 children that have been schooled in public school whose parents have a college education. These particular groups were chosen to research two key areas addressed in the research proposal. First the area of whether homeschooled children outperform those that are educated by public school. Second this method will attempt to address if the parents education significantly impacts academic achievement in both groups. Eleventh (11th) and Twelfth (12th) grade students were chosen for this research because they are at the end of their respective high school education and one can better assess their overall education. Obtaining the data necessary to conduct the research will consist identifying the test subjects in home school by contacting a home school association within the target state(s) for a mailing list of parents. A small questionnaire will be sent out to ascertain the educational background of parents with return postage and a request that they mail the questionnaire back. This feedback will be divided into the three groups identified to study. At this point, 25 families will be randomly chosen from each group and contacted by the researcher via telephone. If a family elects not to be part of the study group, another family will be randomly chosen from that category. The researchers will continue to distribute questionnaires on families that fit the criteria, until a response is made. Once a telephone interview with the parents is conducted and they have agreed to participate, a paper assessment will be mailed to the family. A return envelope with postage paid will be sent with the assessment. This assessment will be an ACT/SAT style test addressing the four main academic components: Math, Reading, Science, and English. The child or children will have 24 hours to complete the assessment and return it to either the post office or mailbox so that the return envelope can be stamped for that day. This method will put urgency into the test being completed and sent back and may reduce some forms of cheating. While a computerized test was considered, it may not be possible for all children schooled at home to have computer access so a paper assessment was the most versatile method of data collection. The same process will be conducted for the public school children. Eligible families will be identified by contacting the target state(s) Department of Education. Again, a paper questionnaire will be sent asking for data on the parents’ education and a request to return it. These parents will also be contacted for permission. Once consent is given, the assessment will be sent to the family with the same procedure outlined above. In Groups 1, 2, and 3 we can assess the general academic achievement of children schooled at home. We can also measure, to a degree, how much the parents own education impacts the academic achievements of the child or children. The same is true of Groups 4, 5, and 6. In the case of the latter group, parents’ education may not be relevant however it is necessary for the continuity of the study. In order to obtain accurate results, these assessments should be conducted sometime within the school year after the first quarter of either the eleventh (11th) or (12th) grade. Students should be assessed after being accustomed to their routine learning guidelines in their respective schooling. Respondents will also be assured that they will be guaranteed that their responses will be confidential, as also stated in the Code of Standards of Council of American Survey Research Organizations. (Council of American Survey Research Organizations, 2009) In a working paper written for the U. S. Census Bureau, Kurt Bauman pointed out several characteristics that may determine home school trends (Bauman, 2001). However, the purpose of this study is purely to identify academic achievement within both the home school student group and public school student group. SURVEY QUESTIONS: The survey questions will be divided into three parts: basic information, performance section. These questions will be the same for Groups 1, 2, and 3, and Groups 4, 5, and 6. The first part, as the name says, contains all the basic information about the student and the parents. This part will include the educational background of the parents, the reasons for home schooling, what they know about the regulations regarding home schooling of their state, etc. The questionnaire for those that are homeschooled, in order, will provide this series of questions: name, name of parents, age, grade, educational background of parents, number of years being homeschooled, reason/s of being homeschooled, and organizations that are involved in regarding homeschooling. The questions, on the other hand, of those that are in public schools will be the same of the homeschooled questionnaire, except for the last three questions. The next part on the other hand, will include the academic test that will determine the performance of the student. The students will answer questions on subject matters like Math, Science, Reading and English, in order to at least have a grasp about their overall academic knowledge. ETHICS ON RESEARCH The researchers acknowledge the fact that the study can be a critical matter especially for parents since discrimination, especially on educational backgrounds, might be possible. However, it is also an essential for the researchers to keep in mind the ethics of conducting a research as stated by Thomas Watson. First is that the researchers will give privacy to the respondents, meaning they can willingly say or not say information that they aren’t comfortable with. Second, the researchers will ensure voluntary participation—that is, the researchers will respect if they want to be part of the research or not. Lastly, the researchers will maintain confidentiality and non-attribution. The respondents will remain to be anonymous. (Watson, 1996) References Bauman, Kurt J. , Home Schooling in the United States: Trends and Characteristics, (2001). Retrieved April 13, 2010 from the U. S. Census Bureau website: http://www. census. gov/population/www/documentation/twps0053/twps0053. html Literature Review Academic Achievement of Homeschooled Children Does home-based education cause higher academic achievement than the institutional schooling in California? Early studies as well as the more recent studies illustrate that this is indeed possible, as they examine the academic performances of homeschooled students in different locations and with various independent variables. For instance, Belfield and Levin (2005) showed that homeschooled students have better SAT verbal scores than the non-homeschooled students. Although homeschooled students have higher SAT math scores as well, the gap seems to be greater in the verbal scores (Belfield & Levin, 2005). After controlling for 21 independent variables, Belfield and Levin showed that the advantage of homeschooled students over private school students was reduced, but the great gap still exists when the comparison is between homeschooled students and public schools students. Moreover, the scores of the homeschooled students and private school students in SAT are at par with each other, with no group outperforming the other (Belfield & Levin, 2005). According to Basham et al. (2007), whether having at least one or no parent as a certified teacher do not significantly matter on the achievement levels of the homeschooled children, although parents who acquired university degree have homeschooled children who outperform significantly those parents who did not earned a degree. However, Bansham illustrate that regardless of these parental backgrounds, homeschooled children all scored between the range of 80 to 90 percent, as opposed to the average score of 63 percent for public school students, who have parents with university degree and average score of 28 percent of public school students who have parents with no degree. Moreover, around 25 percent of homeschooled students have academic performances better than students above their age-level studying either in public or private schools (Bauman, 2002). This can be seen in grade 1 to 4 homeschooled students. All of them perform better compared to the performance of the non-homeschooled students of at least one-grade level higher (McDowell & Ray, 2000). When it comes to 8th grade, the homeschooled students have academic performances better than non-homeschooled students at least four grade levels higher. All these evidences illustrate that being homeschooled leads to better academic performances despite the children’s background, which would have played negative roles when the children were not homeschooled (McDowell & Ray, 2000). Homeschooling reduce or eliminate altogether the negative effects low family income, low parental educational attainment, large family size, race or ethnicity or even gender would have played if the students were not educated in the home setting (Bansham et al. , 2007, Ray, 2000; Ray & Eagleson, 2008). Not having computers or other materials required by formal schools or not having access to public libraries seems not to matter as much for homeschooled students as compared to homeschooled students as well (Bansham et al. , 2007). All these factors do not affect how the children perform academically either. The academic achievements of homeschooled children cannot be generalized. Researchers doubt generalizations because it is difficult to compare homeschooled children and those who are not. However, despite all the doubts of the generalizabilty of the better academic performance of homeschooled children, more and more studies are producing evidence that homeschooled children achieve better performance against their non-homeschooled peers on various types of tests (Basham et al, 2007). The present study will determine if in California, the same findings would emerge. the scores of the homeschooled students and certain Californian private school students in SAT will be examined to test this. Factors such as socio-economic background, gender and ethnicity will also be tested to determine whether each of them will have a significant relationship with the academic achievement of homeschooled students in California. Homeschooling laws depend on the state where the family is residing—whether be it the requirements of the parents, the testing procedure, etc. In a state like Washington, parents are required to have 45 quarter units of college level credit, complete parent qualifying course, an average of an hour a week meeting with a certified teacher, and a qualification to provide home-based teaching instruction by the superintended of the local school district. (Russell, 2008) The case is otherwise different in Michigan since no law requires for parents or teachers to have certain qualifications in order to teach. ( Home School Legal Defense Association, 2009) According to Home School Legal Defense Association, there are already 40 states that adopted the home school regulations. It is also stated in their website that â€Å"Forty-one states do not require home school parents to meet any specific teacher qualifications. The eight states which require only a high school diploma or a GED are: GA, NC, NM, OH, PA, SC, TN, and WV. DC also requires either a high school diploma or GED. (In TN, there is no qualification requirement for grades K-8 if home school is associated with a church-related school). The remaining state has the following qualification requirements: ND requires only a high school diploma or GED, provided that the parent is monitored by a certified teacher for two years. † There are three states who qualify home school teachers to be â€Å"competent† such as CA, KS, and NY. Having less than GED are considered to be competent in those three states. (Home School Legal Defense Association) References Bansham, P. , Merrifield, J. , Hepburn, C. R. (2007). â€Å"Home Schooling: From the Extreme to the Mainstream. Studies in Education Policy. † The Fraser Institute. Retrieved from http://www. netzwerk-bildungsfreiheit. de/pdf/From_the_extreme_to_the_mainstream. pdf Bauman, K. J. (2002). Home schooling in the United States: Trends and Characteristics. Education Policy Analysis Archives, 10(26). Retrieved from http://epaa. asu. edu/epaa/v10n26. html. Belfield, Clive R. and Henry M. Levin (2005). Privatizing Education Choice: Consequences for Parents, Schools and Public Policy. Boulder, C. O. : Paradigm Publishers. McDowell, Susan A. and Brian D. Ray (2000). â€Å"The Home Education Movement in Context, Practice, and Theory. † Peabody Journal of Education, 75(11), 1-7 Ray, B. D. (2000). Home schooling: The ameliorator of negative influences on learning? Peabody Journal of Education, 75(1 & 2), 71-106. Ray, B. D. , & Eagleson, B. K. (2008, August 14). State regulation of homeschooling and homeschoolers’ SAT scores. Journal of Academic Leadership, 6(3). Retrieved from http://www. academicleadership. org/emprical_research/State_Regulation_of_Homeschooling_and_Homeschoolers_SAT_Scores. shtml Bibliography Home School Legal Defense Association. (2009). Home Schooling in the United States: A Legal Analysis. Retrieved April 30, 2010, from Home School Legal Defense Association: http://www. hslda. org/laws/analysis/Michigan. pdf Council of American Survey Research Organizations. (2009). CASRO Code of Standards and Ethics for Survey Research. Retrieved April 29, 2010, from Council of American Survey Research Organizations: http://www. casro. org/codeofstandards. cfm Home School Legal Defense Association. (n. d. ). Summary of Home School Laws in the Fifty States. Retrieved April 29, 2010, from Home School Legal Defense Association: http://www. hslda. org/laws/Summary_of_Laws. pdf Johnson, T. (n. d. ). Ethical Issues in the Conduct of Survey Research. Retrieved April 29, 2010, from College of Urban Planning and Public Affairs: http://www. srl. uic. edu/seminars/ethicsint. htm Russell, L. (2008, June 12). Washington Homeschool Law. Retrieved April 29, 2010, from Suite 101: http://homeschool-regulations. suite101. com/article. cfm/washington_homeschool_law Watson, T. (1996). Survey and Interview Ethics for Data Gatherers and Respondents. Retrieved April 30, 2010, from Independent Job Analysis: http://www. ijoa. org/imta96/paper64. html

Hsbc Scandal

The HSBC scandal shook Europe as a whole! Britain’s largest institutional bank was accused of a â€Å"drugs and gun-running† scandal. The bank failed to monitor a staggering ? 38trillion of money moving across borders from places that could have posed a risk, including the Cayman Islands, Switzerland, Iran, and Mexico. One of the highest noted disregards by the bank was their financial dealings with Al Rajhi, the Saudi Arabian bank that was linked with funding the 9/11 terrorist scheme.Another report showed that the bank accepted ? 9. 6billion in cash over two years from subsidiaries without checking where the money came from, showing blunt disregard for the obviousness of the transactions. Mexican and US authorities warning HSBC that there was a volume limit (? 4. 5billion) in money sent to the US from its Mexican subsidiary that would exemplify â€Å"illegal drug proceeds†. A HSBC officer admitted that the accounts in the Cayman Islands were abused by â€Å"or ganized crime†, ? 1. 3billion total.The bank became the subject of a US senate investigation, and they dropped a 335 page report that accused the bank of ignoring all of the warning and safeguards that should have stopped the laundering of money from Mexico, Iran and Syria. In December they agreed on a settlement to pay a penalty of ? 1. 2 billion that would further scorch their already diminished reputation. With the settlement of the fee, comes the bank admitting to violating US laws meant to prohibit money laundering including the Bank Secrecy Act and the Trading with the Enemy Act.When presented with the 335 page senate report, the head of HSBC’s compliance division, David Bagley, quit in front of the Senate committee. Being at his post since 2002, one can understand why he resigned when pressed with these concerns. He felt guilty being with the bank for so long and did not want to take responsibility for the actions and accusations of the bank. The affair is also a n embarrassment for David Cameron, because his trade envoy Stephen Green chaired HSBC during the period covered by the allegations.Lord (Barron) Green is probably the person most to blame for these disregards for policy on money laundering and regulations. He was the chief executive and the executive chairman of HSBC. Being a trade minister, it was his duty to ensure that the issues brought to the senate’s attention would be regulated for legality concerns. In failing to successfully do so, the fault of the accusations falls on his lap. The regulators of money laundering actively, domestically, and internationally are the countries of the FATF. Forming in 1989, the FATF has 3 primary functions with regard to money laundering.These 3 functions are monitoring member’s implementation of anit-money laundering measures, review and report trends and techniques of laundering, and promote standards globally. Combined with a unified effort within these countries, the US being o ne of the main ones, money laundering activities will be noted quickly before large scale transactions may go through unnoticed and through the means of illegal activities. The US promotes the most laws against these sorts of offensives. HSBC needs to come to a complete â€Å"retake†.All historical transactions, accounts, and services need to be reviewed and mended to meet the golden standard of banking that they have held themselves to ever since becoming the primary bank of Europe. With the removal and replacement of key executive level positions, they may bring in new, fresh minds and with that comes a new approach to the regulating of the activities of the bank. In short, re-staffing the bank with new executives over the previous ones shows the public that the bank takes serious note to what has happened and a serious effort to mend and fix it. Shipman, T. & Davies, R. (2012, July 7). Hsbc let drug gangs launder millions: First barclays, now britain. Retrieved from http:/ /www. dailymail. co. uk/news/article-2174785/HSBC-scandal-Britains-biggest-bank-let-drug-gangs-launder-millions–faces-640million-fine. html (n. d. ). Retrieved from http://www. guardian. co. uk/business/2012/dec/10/standard-chartered-settle-iran-sanctions Yost, P. , & Pylas, P. (2012, December 11). Hsbc to pay $1. 9 billion to settle money-laundering scandal. Retrieved from http://www. salon. com/2012/12/11/hsbc_to_pay_1_9bn_to_settle_money_laundering_scandal/

Business Cross Cultures Essay

The above article is about a western suburb of Sydney, called Greenacre. The article, aptly named â€Å"What happened to the suburb I used to know† is a reflection and analysis of the past and current status of the suburb and how, over time it has changed from what was described as a â€Å"home† to â€Å"a minefield, or a battlefield, or a refuge of drug dealers, criminals, drive-by shooters and terror† (Roberts, 2013). This report will discuss and explore a number of theoretical principles and topics of cross-cultural management in the everyday life of Australian’s living in this suburb, through such theories and topics as Oberg’s six-month cycle of culture shock, Cultural dimensions- Ethnocentrism/stereotyping/parochialism, Hofstede’s value dimensions theory, as well as Harris’s and Moran’s cultural profiles. Oberg’s six-month cycle of culture shock Oberg’s theory identifies 4 major stages of cultural shock and explains the â€Å"typical† transition process for a foreigner adjusting to a new county/culture. Below is a list of the stages and a brief description for each- 1. Honeymoon- minor problems will be over looked, with the excitement and anticipation of learning new things. This phase can last from a few days, up to a month. 2. Crisis/hostility- the new environment begins to seem less idealistic and can therefore lead to focusing upon the negative aspects of the host country. This period is characterised by frustration, and confusion and typically lasts up to two/three months. 3. Adjustment/humour- a respect, understanding and a further adjustment to the local culture occurs, and with this a change in attitude toward the new environment- occurs around the four/five month mark. 4. Mastery/honour- acceptance of the new culture, a sense of eagerness to help other integrate and even absorbs the habits of the new society which in turn makes him feel secure and develops a sense of dual cultural identity (biculturalism)- occurs in the 6-12 month time frame. The article focuses on the perspective of the writer and his experiences, however it does explore some of the above stages. In particular, it is apparent in Roberts recount of his memories of his parents, in the way that they stereotyped the foreigners to be â€Å"wogs, unless they were Asian†¦ which were dirty† (Roberts, 2013). This stereotype has evidently been infused in the culture and attitude towards the â€Å"foreigners† and due to this it appears that the people seem to be stuck in the crisis/hostility stage of Oberg’s culture shock. Roberts recounts that they were just told this hostility was â€Å"multiculturalism (and this) was the justification of all things hard to accept† (Roberts, 2013). Furthermore, they were told that this was just â€Å"†¦part and parcel of the greater good, of the New Australia, of the emergence of alternative cultures – it’s just a settling-in process† (Roberts, 2013)- potentially moving toward the adjustment period. However, this was over 50 years ago and it appears not a lot has changed with this â€Å"drive-by shooting† culture, which seemingly still has a firm grasp on the suburb, with â€Å"local residents living in permanent fear of reprisals† (Roberts, 2013). Cultural dimensions/effects Culture is made up of a number of dimensions and each has its effect on the culture as a whole. Below is a list of dimensions that collectively make up a culture- – Religion – Languages – Education – Economic system – Norms – Values – Social stratification The prominent religion in Greenacre is Islam, with 38.9% of the surveyed population identifying that as their religion. Furthermore, 73.6% of the population was born overseas and 42.2% of the population speaks Arabic as their first language (statistics gathered from Census 2011). These statistics are indicative of the overall population within Greenacre and as a result of this, the impending culture that was formed because of it- â€Å"little Lebanon, with all the worst features from a failed country to a new one† (Roberts, 2013). Religion is such a fundamental part of these peoples lives, and ultimately underlies both their moral and ethical norms and in turn has a dramatic affect on how their overall culture is formed. In Greenacre, 36.1% of people were attending an educational institution. Of these, 27.6% were in primary school, 23.6% in secondary school and 18.8% in a tertiary or technical institution. Evidently, from these statistics there isn’t a huge amount of the population continuing onto further education after high school. This may be a contributing factor to the increased crime rates, as this age group turn to alternative methods of income and ways of applying themselves (not necessarily in a positive manner). It is evident through the above statistics and the article, that the overseas culture has imbedded itself within the suburb and as a result, so too has ethnocentrism. Ethnocentrism is an attitude whereby doing things ‘their way’ is the only way, no matter the situation. Unfortunately, this subculture that has subsequently developed within Greenacre, has become somewhat of a dominant part of the overall culture and has more than likely prevented the progression/transition through Oberg’s cycle of cultural shock. Although it is very apparent that ethnocentrism is rife within Greenacre, so too is parochialism. Parochialism is where people from the host nation (in this case Australia), expect people from another country to fall into the same patterns and behaviours as them- which isn’t plausible, at least not fully. Because of this, it proves difficult for a subculture/society, such as that in Greenacre, to become apart of the greater culture of Australia and can be unfairly stereotyped. Stereotyping, particularly in a social context, is unfortunately inevitable. Hofstede’s value dimensions theory/ Harris and Moran’s cultural profiles Furthermore, Hofstede’s value dimensions theory discusses- in this case, a high-level of- uncertainty avoidance and the extent in which the feel threatened by ambiguous situations. Although this isn’t highly prevalent in Australia, it is however relevant to this situation, as there are signs of high levels of violence and misconduct (in the eyes of the law). This demographic of people also has a high level of collectivism, as they have heavy focus on family/ religion (nepotism) and also high external locus of control. They also tend to have more of a masculine skew to their culture, with â€Å"assertiveness, materialism and a lack of concern for other† (Christopher and Dersky, 2012). Recommendations Due to the situation exponentially becoming worse, it is recommended that the local and state governments provide a number of induction/education seminars on Australian culture, to aid in the transition into Australian life. Another recommendation would be to provide information days (in the local area and at high schools) for universities/TAFEs to encourage high school students to further their education- resulting in them applying themselves in a positive fashion, rather than turning to violence due to lack of mental stimulation, which will then lead to gainful employment. This would not only assist immigrants in the gradual transition into the local culture, but also would facilitate their acceptance within the greater community and encourage the youth further their education and community involvement. By proactively aiding in this transition and encouraging the youth to further educate themselves, it may reduce the amount of conflict between cultures and also hasten the â€Å"cycle of culture shock†, described by Oberg- ultimately resulting in a happier community. And not resulting like it did for Peter Roberts, having to move â€Å"to a safe haven on the north side- looking back not in anger, but disbelief† (Roberts, 2013). Conclusion This article depicts how cultures can often not mix well together and furthermore how if it isn’t managed efficiently and effectively it can lead to devastating consequences. Although this is an extreme case, with shootings, rapes and general discriminative behaviour, it shows that if the transition isn’t properly managed how far it can go wrong. Through the explanation, analysis and use of theoretical principles and relevant cross cultural management topics, it is clear that people can make a relatively smooth transition into a new culture and society, if it is managed efficiently and effectively. This would occur not only in the situation that has been exemplified in the article, but also in a within a business context- where it is markedly more important.

What causes regime change Research Paper Example | Topics and Well Written Essays - 2000 words

What causes regime change - Research Paper Example South Korea and Taiwan are some of the East Asian countries that have faced many challenges towards their democratization. In fact, South Korea and Taiwan share a lot as far as their democratization and regime changes are concerned. The aim of this document is to conduct a comparative study of the democratization of South Korean and Taiwanese political regimes. South Korea and Taiwan are some of the East Asia countries that have come a long way in so far as establishing democratic systems are concerned. The two countries certainly share a lot in common as far as their democratic histories are concerned. For one, the two countries were once ruled by autocratic regimes that curtailed the development of democracy. Nevertheless, the two countries fought very hard by establishing democratic institutions that have made them some of the best examples of democracies in the world. Secondly, both countries achieved their democracies after successful industrialization. Both countries shared a lot in common with regards to the roles they played in post-war foreign relations. Kihl (2005) notes that both Taiwan and South Korea were once anticommunist military outposts. Additionally, both Taiwan and South Korea were once dominated by the Japanese colonialists in the pre-war era. Therefore, in the global perspective, the two countries represent the latest examples of Western European-type modernization because the social changes that resulted from industrialization finally promoted the establishment of democratic systems and institutions in them. Although Taiwan and South Korea share a lot in common with regards to the democratization process, the two countries also differ in some areas. One area where the two countries differ is in the state of political stability. In this regard, history shows that South Korea has experienced many political changes compared to Taiwan. Some of the changes

Reflection Assignment Example | Topics and Well Written Essays - 250 words - 3

Reflection - Assignment Example Also, this will enable me to implement the decisions I have taken with boldness. I would like to be a humble leader because I will be able to respect the ideas of other people in my place of work. In addition, I would like to be a just leader because this will enable me to consider the welfare of others and treat them fairly and without favor. Morality will guide me in discerning what is acceptable in the society and help me to do what the society considers as upright. Being compassionate will help me to treat others with dignity. Finally, as a leader I would like to be wise so that I can be able to make decisions that worthwhile (Chapter 3). A leader can acquire morality by learning from the environment they are brought up in such as schools, family, friends, states and religion. They can learn by emulating others or by experiencing the challenges they face in life (Chapter 3). In conclusion, a leader should possess certain traits that will guide them to relate well with others and remain moral in the society. Good qualities are acquired through personal experience or by learning from

What is Profession Essay Example | Topics and Well Written Essays - 500 words

What is Profession - Essay Example An individual in this profession would need to have strong interpersonal skills in order to relate to others’ problems. The individual would also need training in psychology to be able to identify disorders and productive/functional ways of treating these disorders. In this way, the individual would need specific training in psychology and counseling. 4. According to our study of what qualifies as a profession (meets the central and common features, is one of the more important needs on the Hierarch of Needs, and requires specific technical resources or training) would we consider this occupation a profession? Why or Why not? This occupation would qualify as a profession. The occupation clearly meets the requirements for both central and common features. The profession meets at least two categories on the hierarchy of needs. Finally, this profession requires specific training. The central feature that applies to this occupation is extensive training. In this way basketball players must have practiced for countless hours. The common feature of this profession is the need to be drafted into the National Basketball Association. 4. According to our study of what qualifies as a profession (meets the central and common features, is one of the more important needs on the Hierarch of Needs, and requires specific technical resources or training) would we consider this occupation a profession? Why or Why not? In terms of central features paramedics are required to complete a paramedic training program at the college level. There is also a significant intellectual component through the various tasks required. The common features are that the individual must be certified as an EMT-B; this involves a state certification test. In the hierarchy of needs this profession would fit purpose of life needs as it this occupation directly contributes to helping others. Additionally, there is a significant biological

Literature Review (Topic may be decided by writer) Research Paper

Literature Review (Topic may be decided by writer) - Research Paper Example This literature review aims to explore the factors that encourage people to recycle. In order to achieve this, I will discuss the findings of a series of waste management reports including Barr et al (2001) who measured a series of reported waste management behaviours, including recycling, re-use and waste minimisation. They concluded that recycling emerged as the most popular sustainable waste management activity, due to the ease of access to recycling facilities. Ebreo and Vining (2000) also claimed that people’s behaviour can be linked to their attitudes, values and perspectives towards the environment, in which people with more positive views towards the environment would recycle more frequently. ... Figure 1 illustrates the TPB and highlights how a combination of subjective norms, attitudes towards recycling behaviour and perceived behavioural control affect social behaviour and the likelihood an individual is to engage in sustainable waste management practices. Tonglet et al (2004) have claimed that the TPB is an effective model in assessing the driving forces behind individual’s waste management behaviours. Figure 1 - The Theory Of Planned Behaviour (TPB) Attitude towards the behaviour Subjective norm Intention Behaviour Perceived behavioural control Adapted from Ajzen (1991) However, research by Barr et al (2001) has concluded that the structure of waste management behaviour is complex and they became dissatisfied with the TPB in explaining waste management behaviour. They suggest that other important factors have been neglected. It is therefore important for research to draw upon several environmental framework models that explain the interaction of different key vari ables and factors. One such framework designed by Barr et al (2005) complements the TPB and is depicted in Figure 2. It seeks to appreciate how different forms of reported environmental action can be predicted. Figure 2 – Environmental Behaviour Model Situational Variables Environmental Values Behavioural Intention Environmental Behaviour Psychological Variables Adapted from Barr et al (2001) The role of three key factors have emerged that have been shown to influence people’s level of commitment to environmental action. These are: The situational circumstances in which individuals are placed The socio-environmental values individuals hold Attitudes towards specific

1) answer these 3 questions using slides uploaded. 2) summarize slides Essay

1) answer these 3 questions using slides uploaded. 2) summarize slides - Essay Example Task-focused approach is directive and consultative as the same time. This is common in universities where the senate makes decisions and communicates them formally through instructions, emails, and memos due to its bureaucratic nature.Managers at low levels may consult to gain commitment of staff. Banks on the other hand, mostly engage in charismatic transformation through directed business process re-engineering. This is because its success is based on how it functions and often needs to restructure processes. Multinational enterprises operate in a dynamic environment hence need to adapt to changes frequently. In this case, it may engage in facilitated as well as directed change styles and its scale of change may vary from fine tuning to corporate transformation. It is therefore likely to engage in turnarounds hence use directive style with some coercion. A good example is the Toyota lean manufaturing technique referred as the Just-in-Time manufacturing and involves eliminating was te in the production process.This type of change may not be applicable to universities which mostly deal with people and not manufacturing processes. There are many factors that can cause organisations to fail in their change initiatives. One key factor is inefficient communication. The way management communicates change determines whether it will be succesful or not as communication is meant to gain engagement and commitment to a cause. The leader needs to explain why change is vital, how they will benefit from it and what will not change so as to minimise anxieties and resistance. Communication also allows the leader to give a vision or direction of where the company is going and what is expected of everyone. In this way, staffs will be commited to the change implementation otherwise they will resist. However, it is not only communication that matters but

By close reference to the Lumber Room Essay Example for Free

By close reference to the Lumber Room Essay By Close Reference to The Lumber Room and The Destructors examine the behaviour of Nicholas and Trevor and stay how far you feel that actions are understandable and justified The two boys, Trevor and Nicholas have a very different behaviour but they have the same reason to perform their actions on their enemies. This reason is revenge. Although, the action they take to gain revenge are very different. Trevor carries out his revenge on society by destroying Mr Thomass or Old Miserys house whereas Nicholas takes his vengeance on his sio-distant aunt by spoiling her image as an adult. Trevor plans to destroy the house when Mr Thomas will be away all tomorrow and Bank Holiday, and after he becomes the leader of the Wormsley Common Gang. This gives him more confidence and power to plan the tactics, and more respect from the gang. Trevor does this by going to see the interior design and structure of the house. As Trevor said to Blackie; He showed it to me, proves this. He is determined to demolish the house with the help and support of the gang. As Blackie said to the gang; Its proposed that to-morrow and Monday we destroy Old Miserys house, shows this. He orders them to perform different jobs using different tools such as nails, chisels, saws, and hammers to carry out the operation. As Trevor orders Blackie; When youve finished in here crack the plaster in the passage up with you sledge-hammer, illustrates an idea of this. To completely tear down the house they attach a piece of rope from the house to a lorry and wait for the lorry driver to start the vehicle. However, Nicholas prepares to ruin his sio-called aunts image as an adult. When Nicholas is not given a special meal he puts the frog in his milk to prove to the adults that they can be wrong at certain times and that they dont listen to him. This causes his aunt to make him stay at home after annoying them. Nicholas goes into the lumber room to trick her into thinking that he has entered the gooseberry garden when he is not suppose to. As the aunt remarked to herself; Only because I have told him he is not to, proves this. She tries to catch him into doing something wrong by entering the garden but slips into the rain-water tank. Nicholas then hears her calling him and reaches the front of the garden. He informs her that he is not allowed to enter the garden and accuses her of being the Evil One as she lied to him. As Nicholas shouts to his aunt; Now I know that you are the Evil One and not aunt, illustrates this. Nicholas finally punishes his aunt by not rescuing her out of the tank. His behaviour is excessive and unnatural as a young child. Trevors action is understandable because the house was constructed and designed by Christopher Wren and not by his father, it contained panellings and stairs, its survived in the Blitz, and its state was still looking beautiful. Trevor also did this as his family had dropped down their position in society. This was that his father had lost his high position job as an architect and had to apply for a low position job as a clerk. As Trevor said to the gang; Wren built that house, father says, proves this. All of these factors make Trevor jealous as he does not have these things now, and so this causes him to destroy the house to take his revenge on society. Although, Nicholass action is understandable because he tries to prove to the adults that they can be wrong at certain occasions and that they dont listen to him when he mentions something important. As Nicholas repeated to them; You said there couldnt possibly be a frog in my bread-and-milk; there was a frog in my bread-and-milk, proves this. This causes him to stay at home as a punishment from his aunt. All of these aspects cause Nicholas to take his revenge on his soi-distant aunt by spoiling her image as an adult. Trevors action is not justified because he is taking his revenge on the wrong sector of society. This is futile as it does not affect the people who made Trevors family descend down in society but Mr Thomas, an innocent and old person who lived in the beautiful house all alone, and did not cause any of this to them. I also feel that Trevor does not have the right to destroy the house because it is not his property but Mr Thomass. Nevertheless, Nicholass action is justified because he was debarred to go to Jagborough sands with the other children by his soi-distant aunt, and so had to stay at home as a form of punishment from her. Therefore, my opinion on this is beneficial because Nicholas feels that his aunt should not have punished him in trying to prove the characteristics of the adults. I also approve of his action because I feel that adults should admit their mistakes, listen to what children say, and not disregard their views.

Immune Privilege of Tissue Engineered Articular Cartilage

Immune Privilege of Tissue Engineered Articular Cartilage The immune privilege of tissue engineered articular cartilage derived from mouse adult mesenchymal stem cells and the potential of tissue engineered cartilage as a gene delivery method Chapter 1 Stem cell biology 1.1 Categorization of stem cells Stem cells are generally defined as cells possessing the following 3 characteristics: (1) self-renewal, (2) the ability to produce all cell types made in that tissue, and (3) the ability to do so for a significant portion of the life of the host (Alberts et al., 1989; Reya et al., 2001), while progenitor cells are capable only of multi-lineage differentiation without self-renewal (Weissman, 2000). Stem cells can be classified by their ability to differentiate. The most primitive, totipotent stem cells have the ability to divide and produce all the differentiated cells in an organism, including both the embryonic and extraembryonic tissues of an organism. Totipotent stem cells include the fertilized egg and the cells produced by the initial divisions of it. In mammals, these cell divisions result in an implant in the uterus called the blastocyst. The blastocyst contains an outer sphere of trophoblast cells. Trophoblast cells are capable of implanting into the uterus and helping the form of placenta which provides nutrients to the embryo. Within the blastocyst are 10 to 20 pluripotent cells called the inner cell mass. In mammalian uterus, these inner mass cells will participate in the production of all tissues and organs of the developing embryo, then fetus, then born organism. Such pluripotent cells can produce any differentiated cells in the body, but are usually unable to for m the trophoblast cells. The best-known pluripotent stem cell is the embryonic stem (ES) cell, which are obtained from the inner cell mass of the blastocyst and exist for only a brief stage of embryonic development. The last major class of stem cells, multipotent stem cells, gives rise to a limited number of cell types which are responsible for organ growth and renewal such as neural stem cells, skin stem cells and haematopoietic stem cells (HSCs) (Cheshier et al., 2009). 1.2 Selected milestones of stem cell research In 1981, Martin isolated a pluripotent stem cell line from early mouse embryos (Martin, 1981). Wilmut in 1996 first cloned a mammal, a lamb named Dolly by transferring nuclear from the adult mammary gland cell to an enucleated unfertilized egg (Wilmut et al., 1997). In 1998, Thomson obtained the first human embryonic stem cell line from human blastocysts (Thomson et al., 1998). In 2001, President Bush banned scientists from using federal funds to study stem cells from sources other than those that had already been grown because of the ethical concerns. To avoid ethical dispute over the use of human embryonic cells for research purposes, many efforts have been taken on obtaining pluripotent stem cells from differentiated donor cells. In 2006, Yamanaka find a way to obtain pluripotent cells by reprogramming the nucleus of adult mice skin cells (Takahashi and Yamanaka, 2006). Such cells are now known as induced pluripotent stem (iPS) cells. 1.3 A brief introduction of several types of multipotent stem cell The best known multipotent stem cells are haematopoietic stem cells (HSCs), that give rise to all the blood cell types including myeloid (monocytes and macrophages, neutrophils, basophils, eosinophils, erythrocytes, megakaryocytes/platelets, dendritic cells), and lymphoid lineages (T-cells, B-cells, NK-cells). HSCs are vital elements in bone-marrow transplantation, which has already been used extensively in therapeutic settings (Reya et al., 2001). In the long-term culture systems, human and rodent Central Neural System (CNS) cells maintain the capacity to produce the three main mature cell classes of the CNS: neurons, astrocytes, and oligodendrocytes, which suggest stem cells and/or progenitors exist and can survive in the culture medium (Weiss et al., 1996; Carpenter et al., 1999). In 2000, Human CNS stem cells (hCNS-SCs) have been successfully isolated by FACs (Uchida et al., 2000). Cancer stem cell hypothesis was proposed by Reya 2001 (Reya et al., 2001). This hypothesis consists of 2 components. The first component postulates that normal tissue stem cells are the target for transforming mutations and successive mutations result in the formation of a tumor. The second component is that within every cancer a specific subset of cancer stem cells continuously gives rise to all the other cancer cells and only these cells within a tumor possess the ability to self-renew, continuously proliferate. Conflicting to the first component of the hypothesis, evidences indicate cancer stem cells can also arise from mutated progenitor cells rather than stem cells (Cheshier et al., 2009). In addition, mature cells such as Lymphocytes can lead to mouse T cell leukemia independently from HSCs (Yuan et al., 2006). For the latter component of cancer stem cell hypothesis, it is likely that the cancer stem cell hypothesis is applicable to some tumors but not to others. In hematopoiet ic and some solid malignancies, only 1 in 100 to 1 in 10 000 primary tumor cells are capable of reproducing the tumor in vivo, such as human breast cancer, human neuroepithelial tumors, head and neck squamous cell carcinomas, and colon cancer. But in melanoma, nearly 1 in 4 cells possessed the ability of proliferation and developing into cancer (Cheshier et al., 2009). Cancer stem cells and CNS stem cells were reviewed by Cheshier et al. (Cheshier et al., 2009). 1.4 Mesenchymal stem cells (MSCs) and their differentiation potential Bone marrow is composed of two main systems of cell, hematopoietic cells and the supporting stromal cells (Bianco et al., 2001). MSCs reside within the marrow, maintain a level of self-renewal, and give rise to progenitor cells that can differentiate into various lineages of tissue, including chondrocytes, osteoblasts, adipocytes, fibroblasts, marrow stroma, and other tissues of mesenchymal origin. The traditional opinion about the multipotent differentiation potential of MSCs was challenged by further studies. Interestingly, MSCs reside in a diverse host of tissues throughout the adult organism and possess the ability to ‘regenerate cell types specific for local tissues e.g. adipose, periosteum, synovial membrane, muscle, dermis, pericytes, blood, bone marrow, and most recently trabecular bone, reviewed by Tuan et al. (Tuan et al., 2003). Furthermore, in 2002, Jiang et al. reported a rare cell within human bone marrow mesenchymal stem cell cultures that can be expanded extensi vely without obvious senescence. This cell population can differentiate, not only into mesenchymal cells, but also cells with visceral mesoderm, neuroectoderm and endoderm characteristics in vitro. Most somatic cell types could be derived after this population of cells was injected into an early blastocyst (Jiang et al., 2002). These studies suggest mesenchymal stem cells maintained pluripotent properties. Chapter 2 Features of Articular Cartilage 2.1 Introduction Joint cartilage formed highly sophisticated structure during the evolutionary development. There have been considerable research interests related to the cartilage cells, chondrocytes. In the last decades these studies made cartilage the first and very successful tissue engineering treatment (Brittberg et al. 1994). 2.2 Categorization of cartilage tissues Cartilage tissue is categorised in three major types by different biochemical compositions and structures of their extracellular matrix (ECM). Elastic cartilage has a small concentration of proteoglycans (PGs), and a relatively high proportion of elastin fibres. It exists in the epiglottis, small laryngeal, the external ear, auditory tube, and the small bronchi, where it is generally required to resist bending forces. Fibrocartilage also possesses a small concentration of PGs, but far less elastins. The meniscus in the knee joint is made of fibrocartilage. Hyaline is the most widespread cartilage in the human body. It is resistant to compressive or tensile forces due to its special type II collagen fibril mesh filled with a high concentration of PGs. Hyaline cartilage can be found in the nose, trachea, bronchi, and synovial joints. In the latter case, it is termed as articular cartilage (Schulz and Bader, 2007). 2.3 Compositions of articular cartilage Chondrocytes contribute to only 1%- 5% of the tissue volume; the remaining 95%-99% being extracellular matrix (ECM). Chondrocytes sense and synthesize all necessary ECM components (Mollenhauer, 2008; Schulz and Bader, 2007). The ECM of articular cartilage consists of about 60-85% water and dissolved electrolytes. The solid framework is composed of collagens (10-20%), PGs (3-10%), noncollagenous proteins and glycoproteins. In articular cartilage, 95% of collagen in the ECM is type II collagen fibrils. The rest other types are collagen type IX and XI and a small fraction of types III, VI, XII and XIV. Normal articular cartilage does not present type I collagen, which is concerned with fibrous tissue. Unlike Type I and Type III collagens which form thick fibres and thin  ¬Ã‚ bres respectively, Type II collagen present in hyaline and elastic cartilages does not form  ¬Ã‚ bres. It forms very thin  ¬Ã‚ brils which are disposed as a loose mesh that strongly interacts with the groun d substance. Type II collagen provides tensile stiffness and strength to articular cartilage and constrains the swelling capacity generated by highly negatively charged glycosaminoglycans (GAGs) of the proteoglycans (PGs). The majority (50-85%) of the PG content in articular cartilage were presented by large molecule aggrecan. It consists of a protein backbone, the core protein, to which unbranched GAGs side chains of chondroitin sulphate (CS) and keratan sulfate (KS) are covalently attached (Figure 1.1). The composition of articular cartilage was extensively reviewed by Schulz and Bader (Schulz and Bader, 2007). Figure 1. Illustration of the extracellular matrix (ECM) organization of articular cartilage (Left) and the schematic sketches (Right) of the most relevant polysaccharides of proteoglycans (PGs) in articular cartilage. The PGs consist of a strand of hyaluronic acid (HA), to which a core protein is non-covalently attached. On the core protein, glycosaminoglycans (GAGs) such as keratan sulphate (KS) and chondroitin sulfate (CS) are covalently bound in a bottle brush fashion (Modified from Schulz and Bader, 2007 and Mow and Wang, 1999). 2.4 Low capacity of self-repair in articular cartilage The aneural and avascular nature of articular cartilage, coupled with its low cellularity, contribute to both the limited rate and incomplete nature of the repair process following damage (Heywood et al., 2004). The low mitotic potential of chondrocytes in vivo also contributes to its poor ability to undergo self-repair (Kuroda et al., 2007). Some researchers believe that cartilage lesions less than 3mm in diameter self-repair with normal hyaline-like cartilage (Revell and Athanasiou, 2009; Schulz and Bader, 2007). In animal studies, full thickness cartilage defects, extending into the subchondral bone, have been reported to heal with the formation of fibrous tissue, which contains relatively low amount of type II collagen and aggrecan, but a relatively high concentration of type I collagen which is not present in normal adult articular cartilage and accordingly exhibits impaired mechanical properties (Hjertquist et al., 1971). 2.5 Metabolism of articular cartilage Joint cartilage is supplied with nutrients and oxygen by the synovial fluid diffusion facilitated by compressive cyclic loading during joint movements which acts as a pumping function (Mollenhauer, 2008). Within synovial joints, oxygen supply to articular chondrocytes is very limited, from 7.5% at the superficial zone down to 1% oxygen tension at the deep zone. It is supposed to be even further decreased under pathological conditions, such as osteoarthritis (OA) or rheumatoid arthritis (RA). The metabolism of chondrocytes is largely glycolytic. Oxygen-dependent energy generated by oxidative phosphorylation is just a minor contributor to the overall energy in chondrocytes. Nevertheless, changes in O2 tension have profound effects on cell metabolism, phenotype, gene expression, and morphology, as well as response to, and production of, cytokines (Pfander and Gelse, 2007; Gibson et al., 2008). The most important component of this hypoxic response is mediated by transcription factor hypo xia-inducible factor-1 (HIF-1), which is present in most hypoxia inducible genes (Pfander and Gelse, 2007; Gibson et al., 2008). Moreover, the matrix turnover in articular cartilage is extremely slow. Proteoglycan turnover is up to 25 years. Collagen half-life is estimated to range from several decades up to 400 years (Mollenhauer, 2008). Chapter 3 Osteoarthritis (OA) 3.1 Prevalence Osteoarthritis (OA) is the most common form of arthritis. More than 40 million US American citizens (approximately 15% of the overall population of the USA) suffer from arthritis (Schulz and Bader, 2007). OA can occur in any joint but is most common in certain joints of the hand, knee, foot and hip. OA is the most common reason for total hip- and knee-joint replacement (Wieland et al., 2005). Among US adults 30 years of age or older, symptomatic disease in the knee occurs in approximately 6% and symptomatic hip osteoarthritis in roughly 3% (Felson and Zhang, 1998). 3.2 The symptoms and diagnosis The symptoms of OA include pain, stiffness and loss of function. OA can be monitored by radiography, magnetic resonance imaging (MRI), and arthroscopy, but radiographs are still considered the gold standard (Wieland et al., 2005). 3.3 The pathology of OA The pathologic characteristics of OA are the slowly developing degenerative breakdown of cartilage; the pathological changes in the bone, including osteophyte formation and thickening of the subchondral plate; the changes in the synovium such as inflammatory infiltrates; ligaments, which are often lax; and bridging muscle, which becomes weak. Many people with pathologic and radiographic evidence of osteoarthritis have no symptoms (Martel-Pelletier, 1999; Felson et al., 2000). A protease family of matrix metalloproteases (MMP) is responsible for the initial occurrence of cartilage matrix digestion. Of this family, collagenases, the stromelysins and the gelatinases are identified as being elevated in OA. Another group of MMP is localized at the cell membrane surface and is thus named membrane type MMP (MT-MMP) (Martel-Pelletier, 1999). Proinflamatory cytokines such as interleukin (IL)-1ÃŽ ², Tumor necrosis factor (TNF)-ÃŽ ±, IL-6, leukemic inhibitor factor (LIF) and IL-17 are first produced by the synovial membrane and then diffuse into the cartilage through the synovial fluid, where they activate the chondrocytes to produce proinflammatory cytokines. These proinflamatory cytokines are considered responsible for the catabolic pathological process (Martel-Pelletier, 1999). In OA cartilage, an increased level of an inducible form of nitric oxide synthase (iNOS) leads to a large amount of nitric oxide (NO) production (Pelletier et al., 2001). NO can inhibit the synthesis of cartilage matrix macromolecules such as aggrecans and can enhance MMP activity (Taskiran et al., 1994; Murrell et al., 1995). It is well stablished that proinflammatory cytokines such as IL-1ÃŽ ² act as the key mediators of cartilage breakdown and stimulate the release of inflammatory products (NO) and prostaglandin (PG)E2, via induction of iNOS and cyclo-oxygenase (COX)-2 enzymes (Chowdhury et al., 2008). 3.4 Risk factors Osteoarthritis is considered to be a systemic disease although severe joint injury may be sufficient to cause osteoarthritis. There are several systemic risk factors related to OA. (1) Age: Osteoarthritis increases with ages, the incidence and prevalence of disease increased 2- to 10-fold from 30 to 65 years of age and increased further thereafter in a community-based survey (Oliveria et al., 1995). (2) Hormonal status and bone density: women taking estrogen have a decreased prevalence of radiographic osteoarthritis (Nevitt et al., 1996). Before 50 years of age, the prevalence of osteoarthritis in most joints is higher in men than in women. After about age 50 years, women are more often affected with hand, foot, and knee osteoarthritis than men. In most studies, hip osteoarthritis is more frequent in men (van Saase et al., 1989). Evidence suggests an inverse relationship between osteoarthritis and osteoporosis (Felson et al., 2000). (3) Nutritional factors: evidence indicates that co ntinuous exposure to oxidants contributes to the development of many common age-related diseases, including osteoarthritis. McAlindon et al. reported a threefold reduction in risk for progressive radiographic osteoarthritis was observed in persons in the middle and highest tertile of vitamin C intake compared with those whose intake was in the lowest tertile (McAlindon et al., 1996a). Vitamin D intake was observed associated with the progression of OA although not associated with risk for new-onset radiographic osteoarthritis (McAlindon et al., 1996b; Lane et al., 1999). (4) Genetics: genetic factors account for at least 50% of cases of osteoarthritis in the hands and hips and a smaller percentage in the knees (Spector et al., 1996). Candidate genes for common forms of osteoarthritis include the vitamin D receptor gene, insulin-like growth factor I genes, cartilage oligomeric protein genes, and the HLA region (Felson et al., 2000). Local mechanical factors include the body weight and the pathological alterations of the mechanical environment of the joint. Persons who are overweight have a high prevalence of knee osteoarthritis (Felson et al., 1997). OA is also considered to be related to alterations in joint mechanical environments such as knee laxity, the displacement or rotation of the tibia with respect to the femur; proprioception, the conscious and unconscious perception of joint position and movement; knee alignment , knee position in reference to the hip and ankle (Felson et al., 2000). In addition, joint dysplasias, fractures of articular surfaces, and tears of menisci and ligaments that increase joint instability precede the development of osteoarthritis in a high percentage of affected joints. Risk factors for posttraumatic osteoarthritis include high body mass, high level of activity, residual joint instability or malalignment, and persistent articular surface incongruity (Buckwalter et al., 1997; Honkonen 1995). 3.5 Treatments The medicine treatment of OA was dominated by COX2 inhibitors (Flower 2003). The other medicines include glucosamine, chondroitin (McAlindon et al., 2000), and hyaluronic acid (Lo et al., 2003). In addition, both aerobic walking and muscle strengthening exercise reduce pain and disability from osteoarthritis (Roddy et al., 2005). Articular cartilage lesions, both of traumatic or pathological origin, do not heal spontaneously and often undergo progressive degeneration towards osteoarthritis (OA). The most frequently used treatments include the artificial joint replacement, mosaicplasty, marrow stimulation, and autologous condrocyte implantation (ACI) (Steinwachs et al., 2008). Total joint replacement is most commonly performed in people over 60 years of age. (NHS 2006; Brittberg et al., 1994) Mosaicplasty is an autologous osteochondral transplantation method through which cylindrical periosteum grafts are taken from periphery of the patellofemoral area which bears less weight, and transplanted to defective areas. This transplantation can be done with various diameters of grafts (Haklar et al., 2008; NHS, 2006). Marrow stimulation methods include arthroscopic surgery to smooth the surface of the damaged cartilage area; microfracture, drilling, abrasion. All marrow stimulation methods base on the penetration of the subchondral bone plate at the bottom of the cartilage defect. The outflowing bone marrow blood contains the mesenchymal stem cells which are stabilised by the clot formation in the defect. These pluripotent stem cells which are able to differentiate into fibrochondrocytes, result in fibrocartilage repair with varying amounts of type I, II and III collagen (Steinwachs et al., 2008). The ACI tissue engineering treatment will be discussed in the next chapter. Chapter 4 Tissue engineering and autologous chondrocyte implantation (ACI) 4.1 Overview of tissue engineering technologies Tissue engineering is defined as ‘‘the application of the principles and methods of engineering and the life sciences toward the fundamental understanding of structure-function relationships in normal and pathological mammalian tissues and the development of biological substitutes to restore, maintain, or improve tissue function† (Langer and Vacanti, 1993). Three factors are considered as the principles of tissue engineering, including the utilization of biocompatible and mechanically suitable scaffolds, an appropriate cell source, and bioactive molecules to promote the differentiation and maturation of the cell type of interest (Song et al., 2004). Potential applications of tissue engineering are involved in the following fields: skin, cartilage, bone, cardiovascular diseases, organs (e.g. liver, pancreas, bladder, trachea and breast), central nervous system (e.g. spinal cord), and miscellaneous (e.g. soft tissue, ligaments). Although research is being carried out in all these fields, only few products have already entered the market. The most successful products up to now are: tissue engineered skin which is mainly used for wound cover, autologous chondrocyte implantation (ACI), and artificial bone graft (Hà ¼sing et al., 2003). 4.2 Autologous chondrocyte implantation (ACI) In 1984, a study in rabbits reported successful treatment of focal patellar defects with the use of ACI. One year after transplantation, newly formed cartilage-like tissue typically covered about 70 percent of the defect (Grande et al. 1989). In 1987, Brittberg firstly performed ACI in 23 people with deep cartilage defects in the knee. ACI is described as the following procedure: cartilage cells are taken from a minor load-bearing area on the upper medial femoral condyle of the damaged knee via an arthroscopic procedure, cultivated for four to six weeks in a laboratory and then, in open surgery, introduced back into the damaged area as a liquid or mesh-like transplant; at last, a periosteal flap sutured in place to secure the transplant (Figure 2; Brittberg et al., 1994). Genzyme Biosurgery with its product Carticel ® was the first company which introduced ACI into market and is the market leader in USA. Carticel ® is a classic ACI procedure using the periosteal cover (Hà ¼sing et al., 2008). Today the periosteum is often replaced by an artificial resorbable cover such as collagen I/III and hyaluronan membrane, such as ChondroGide or Restore (De Puy, Warzaw, Indiana) (Gooding et al., 2006; Jones and Peterson, 2006). Another new method uses chondrocytes cultured on a tri-dimensional (3D), biodegradable scaffold. This kind of scaffold, cut to the required size, is fixed into the lesion by anchoring stitches or its sticky nature. The 3D cell seeded scaffold eliminates the using of cover, thus simplifies the surgery procedure, saves the surgery time, and opens up the possibility of an arthroscopic surgery instead of the open surgery which causes more tissue damage. HYALOGRAFT from Italy is one of the European market leaders. It is a cartilage substit ute made of autologous chondrocytes delivered on a biocompatible 3D matrix, entirely composed of a derivative of hyaluronic acid (Marcacci et al. 2005). 4.3 Clinical results of ACI Brittberg studied the long-term durability of ACI-treated patients, 61 patients were followed for at least five years up to 11 years post-surgery (mean 7.4 years). After two years, 50 out of 61 patients were graded good-excellent. At the five to 11 years follow-up, 51 of the 61 were graded good-excellent (Brittberg et al., 2003). Since 1997 the year FDA approved ACI, this method has been widely performed in more than 20,000 patients all over the world. It has been reported to be effective in relieving clinical symptoms, such as pain and function (Wakitani et al., 2008). In a randomised controlled study, Knutsen et al. studied 80 patients who needed local cartilage repair with lesions on the femoral condyles of 2-10 cm2. There were no signi ¬Ã‚ cant differences in clinical results at 5 years follow-up (Knutsen et al., 2007). In another randomised controlled study that compared mosaicplasty with ACI, there was no significant difference in the number of patients who had an excellent or good clinical outcome at 1 year (69% [29/42] and 88% [51/58], respectively). In the subgroup of patients who had repairs to lesions of the medial femoral condyle, significantly more patients who had ACI had an excellent or good outcome (88% [21/24]) compared with those who had mosaicplasty (72% [21/29]) (p Clinical results of ACI were reviewed by Gikas 2009 (Gikas et al., 2009). Generally speaking, the outcomes of ACI treatment have been encouraging. However, most randomised controlled studies showed no significant difference between ACI and traditional treatments. 4.4 Limitations of ACI Microfracture is a very simple and low-cost procedure whereas ACI costs about $10 000 per patient. If ACI is not found to be more effective for improving articular cartilage repair than microfracture, the procedure will not be continued (Wakitani et al., 2008). There are several possible reasons to be blamed for the limitations of the traditional ACI procedure. The cell source in ACI is the cartilage tissue derived via an arthroscopic procedure from the low load-bearing area on the upper medial femoral condyle of the damaged knee. However, Wiseman et al. found the chondrocytes isolated from the low loaded area of the knee joint respond to mechanical stimulations in a distinct manner with the chondrocytes from the high loaded area, which suggests the traditional cell source of ACI may not provide enough mechanical response and may further lead to the insufficient mechanical properties of the repaired tissue (Wiseman et al. 2003). As cultured in monolayer, chondrocytes undergo a process of dedifferentiation and adopt a more  ¬Ã‚ broblast-like morphology, which is accompanied by an increase in proliferation and an altered phenotype. Type II collagen, the major protein produced by chondrocytes in articular cartilage, are down-regulated in the culture, while collagen types I and III are increased (Glowacki et al., 1983; Stocks et al., 2002; Benya et al., 1978). The agregating proteoglycan aggrecan of articular cartilage, is down-regulated during dedifferentiation and replaced by proteoglycans not speci ¬Ã‚ c to cartilage, such as versican (Glowacki et al., 1983; Stocks et al., 2002). Therefore, monolayer cultured chondrocytes do not express the origninal phenotype, and their ability to regenerate damaged cartilage tissue is impaired. Upon implantation, dedifferentiated cells may form a  ¬Ã‚ brous tissue expressing collagen type I that does not have appropriate mechanical properties, which may lead to deg radation and failure of the repair tissue (Brodkin et al., 2004). Chondrocytes grown in conditions that support their round shape, such as plating in high-density monolayer (Watt, 1988) and seeding in 3D structure (Benya and Shaffer, 1982) can maintain their differentiated phenotype much longer compared to cells spread in monolayer cultures. Although ACI can still be considered to be one of commonly form of repair of cartilage defects, it does have a number of scientific limitations. Some of those can be resolved using more comprehensive tissue engineered strategies which incorporates cells, scaffold materials and potentially biochemical, biomechanical and/or physical stimulation in a controlled bioreactor environment. 4.5 Tissue engineering strategies for ACI Chondrocytes derived from the low load bearing area of the knee joint respond in a distinct manner with the chondrocytes from the high loaded area. Chondrocytes cultured in monolayer have a dedifferentiation phenomenon as described above. In addition, the limitation of the transplant volume is always a major problem in autograft to be overcome (Kitaoka et al., 2001; Vinatier et. al, 2009). Accordingly, potential cell sources are widely studied for the future improvement of ACI approach, which will be discussed in Chapter 4. Seeding in 3D structures (Benya and Shaffer, 1982) can maintain chondrocytes differentiated phenotype. Ideally, cell scaffolds for tissue engineering should meet several design criteria: (1) The surface should permit cell adhension and growth, (2) neither the polymer nor its degradation products should provoke inflammation or toxicity when implanted in vivo, (3) the material should be reproducibly processable into three dimensional structures, (4) the porosity should be at least 90% in order to provide a high surface area for cell-polymer interactions, sufficient space of extracellular matrix regeneration, and minimal diffusional constraints during in vitro culture, (5) the scaffold should resorb once it has served its purpose of providing a template for the regenerating tissue, since foreign materials carry a permanent risk of inflammation, and (6) the scaffold degradation rate should be adjustable to match the rate of tissue regeneration by the cell type of interest (Freed et al., 1994). Synthetic materials such as poly (glycolic acid) (PGA), poly (lactic acid) (PLA), and poly (lactic-co-glycolic acid) (PLGA) have been investigated for use as cartilage tissue engineering scaffolds (Cima et al., 1991; Vacanti et al., 1991). Both, in vitro and in vivo studies have demonstrated these scaffold maintained the chondrocyte phenotype and the production of cartilage extracellular matrix (ECM) (Barnewitz et al., 2006; Kaps et al., 2006). Moreover, PLGA is used as a scaffold material for matrix-based autologous chondrocyte transplantation clinically (Ossendorf et al., 2007). Natural materials have also been investigated in the application of tissue engineering scaffolds in ACI. Collagen-based biomaterials are widely used in todays clinical practice (for example, haemostasis and cosmetic surgery). Collagen is also be commonly used as main components in tissue engineered skin products. Several commercial ACI products have used collagenous membraneas as the replacement for the periosteum to close the defect, such as ChondroGide or Restore (De Puy, Warzaw, Indiana) (Cicuttini et al., 1996; Jones and Peterson, 2006). The combination of type I collagen with GAG in scaffolds had a positive effect on chondrocyte phenotype (van Susante et al., 2001). Hyaluronic acid is a non-sulphated GAG that makes up a large proportion of cartilage extracellular matrix (Schulz and Bader, 2007). Matrices composed of hyaluronan have been frequently used as carriers for chondrocytes. Facchini et al. con ¬Ã‚ rms the hyaluronan derivative scaffold Hyaff  ®11 as a suitable scaff old both for chondrocytes and mesenchymal stem cells for the treatment of articular cartilage defects in their study (Facchini et al., 2006). Sugar-based natural polymers such as chitosan, alginate and agarose can be formulated as hydrogels and in some cases sponges or pads. Although these materials are extensively used in in vitro research, their role in in vivo cartilage reconstruction is still limited (Stoop, 2008). Growth factors are proved to be able to promote the formation of new cartilage tissue in both explants and engineered constructs. Insulin-like growth factor-I (IGF-I), transforming growth factor-ÃŽ ²1 (TGF-ÃŽ ²1) increases, basic fibroblast growth factor (bFGF) can stimulate cell proliferation and/or biosynthesis in chondrocytes which were Immune Privilege of Tissue Engineered Articular Cartilage Immune Privilege of Tissue Engineered Articular Cartilage The immune privilege of tissue engineered articular cartilage derived from mouse adult mesenchymal stem cells and the potential of tissue engineered cartilage as a gene delivery method Chapter 1 Stem cell biology 1.1 Categorization of stem cells Stem cells are generally defined as cells possessing the following 3 characteristics: (1) self-renewal, (2) the ability to produce all cell types made in that tissue, and (3) the ability to do so for a significant portion of the life of the host (Alberts et al., 1989; Reya et al., 2001), while progenitor cells are capable only of multi-lineage differentiation without self-renewal (Weissman, 2000). Stem cells can be classified by their ability to differentiate. The most primitive, totipotent stem cells have the ability to divide and produce all the differentiated cells in an organism, including both the embryonic and extraembryonic tissues of an organism. Totipotent stem cells include the fertilized egg and the cells produced by the initial divisions of it. In mammals, these cell divisions result in an implant in the uterus called the blastocyst. The blastocyst contains an outer sphere of trophoblast cells. Trophoblast cells are capable of implanting into the uterus and helping the form of placenta which provides nutrients to the embryo. Within the blastocyst are 10 to 20 pluripotent cells called the inner cell mass. In mammalian uterus, these inner mass cells will participate in the production of all tissues and organs of the developing embryo, then fetus, then born organism. Such pluripotent cells can produce any differentiated cells in the body, but are usually unable to for m the trophoblast cells. The best-known pluripotent stem cell is the embryonic stem (ES) cell, which are obtained from the inner cell mass of the blastocyst and exist for only a brief stage of embryonic development. The last major class of stem cells, multipotent stem cells, gives rise to a limited number of cell types which are responsible for organ growth and renewal such as neural stem cells, skin stem cells and haematopoietic stem cells (HSCs) (Cheshier et al., 2009). 1.2 Selected milestones of stem cell research In 1981, Martin isolated a pluripotent stem cell line from early mouse embryos (Martin, 1981). Wilmut in 1996 first cloned a mammal, a lamb named Dolly by transferring nuclear from the adult mammary gland cell to an enucleated unfertilized egg (Wilmut et al., 1997). In 1998, Thomson obtained the first human embryonic stem cell line from human blastocysts (Thomson et al., 1998). In 2001, President Bush banned scientists from using federal funds to study stem cells from sources other than those that had already been grown because of the ethical concerns. To avoid ethical dispute over the use of human embryonic cells for research purposes, many efforts have been taken on obtaining pluripotent stem cells from differentiated donor cells. In 2006, Yamanaka find a way to obtain pluripotent cells by reprogramming the nucleus of adult mice skin cells (Takahashi and Yamanaka, 2006). Such cells are now known as induced pluripotent stem (iPS) cells. 1.3 A brief introduction of several types of multipotent stem cell The best known multipotent stem cells are haematopoietic stem cells (HSCs), that give rise to all the blood cell types including myeloid (monocytes and macrophages, neutrophils, basophils, eosinophils, erythrocytes, megakaryocytes/platelets, dendritic cells), and lymphoid lineages (T-cells, B-cells, NK-cells). HSCs are vital elements in bone-marrow transplantation, which has already been used extensively in therapeutic settings (Reya et al., 2001). In the long-term culture systems, human and rodent Central Neural System (CNS) cells maintain the capacity to produce the three main mature cell classes of the CNS: neurons, astrocytes, and oligodendrocytes, which suggest stem cells and/or progenitors exist and can survive in the culture medium (Weiss et al., 1996; Carpenter et al., 1999). In 2000, Human CNS stem cells (hCNS-SCs) have been successfully isolated by FACs (Uchida et al., 2000). Cancer stem cell hypothesis was proposed by Reya 2001 (Reya et al., 2001). This hypothesis consists of 2 components. The first component postulates that normal tissue stem cells are the target for transforming mutations and successive mutations result in the formation of a tumor. The second component is that within every cancer a specific subset of cancer stem cells continuously gives rise to all the other cancer cells and only these cells within a tumor possess the ability to self-renew, continuously proliferate. Conflicting to the first component of the hypothesis, evidences indicate cancer stem cells can also arise from mutated progenitor cells rather than stem cells (Cheshier et al., 2009). In addition, mature cells such as Lymphocytes can lead to mouse T cell leukemia independently from HSCs (Yuan et al., 2006). For the latter component of cancer stem cell hypothesis, it is likely that the cancer stem cell hypothesis is applicable to some tumors but not to others. In hematopoiet ic and some solid malignancies, only 1 in 100 to 1 in 10 000 primary tumor cells are capable of reproducing the tumor in vivo, such as human breast cancer, human neuroepithelial tumors, head and neck squamous cell carcinomas, and colon cancer. But in melanoma, nearly 1 in 4 cells possessed the ability of proliferation and developing into cancer (Cheshier et al., 2009). Cancer stem cells and CNS stem cells were reviewed by Cheshier et al. (Cheshier et al., 2009). 1.4 Mesenchymal stem cells (MSCs) and their differentiation potential Bone marrow is composed of two main systems of cell, hematopoietic cells and the supporting stromal cells (Bianco et al., 2001). MSCs reside within the marrow, maintain a level of self-renewal, and give rise to progenitor cells that can differentiate into various lineages of tissue, including chondrocytes, osteoblasts, adipocytes, fibroblasts, marrow stroma, and other tissues of mesenchymal origin. The traditional opinion about the multipotent differentiation potential of MSCs was challenged by further studies. Interestingly, MSCs reside in a diverse host of tissues throughout the adult organism and possess the ability to ‘regenerate cell types specific for local tissues e.g. adipose, periosteum, synovial membrane, muscle, dermis, pericytes, blood, bone marrow, and most recently trabecular bone, reviewed by Tuan et al. (Tuan et al., 2003). Furthermore, in 2002, Jiang et al. reported a rare cell within human bone marrow mesenchymal stem cell cultures that can be expanded extensi vely without obvious senescence. This cell population can differentiate, not only into mesenchymal cells, but also cells with visceral mesoderm, neuroectoderm and endoderm characteristics in vitro. Most somatic cell types could be derived after this population of cells was injected into an early blastocyst (Jiang et al., 2002). These studies suggest mesenchymal stem cells maintained pluripotent properties. Chapter 2 Features of Articular Cartilage 2.1 Introduction Joint cartilage formed highly sophisticated structure during the evolutionary development. There have been considerable research interests related to the cartilage cells, chondrocytes. In the last decades these studies made cartilage the first and very successful tissue engineering treatment (Brittberg et al. 1994). 2.2 Categorization of cartilage tissues Cartilage tissue is categorised in three major types by different biochemical compositions and structures of their extracellular matrix (ECM). Elastic cartilage has a small concentration of proteoglycans (PGs), and a relatively high proportion of elastin fibres. It exists in the epiglottis, small laryngeal, the external ear, auditory tube, and the small bronchi, where it is generally required to resist bending forces. Fibrocartilage also possesses a small concentration of PGs, but far less elastins. The meniscus in the knee joint is made of fibrocartilage. Hyaline is the most widespread cartilage in the human body. It is resistant to compressive or tensile forces due to its special type II collagen fibril mesh filled with a high concentration of PGs. Hyaline cartilage can be found in the nose, trachea, bronchi, and synovial joints. In the latter case, it is termed as articular cartilage (Schulz and Bader, 2007). 2.3 Compositions of articular cartilage Chondrocytes contribute to only 1%- 5% of the tissue volume; the remaining 95%-99% being extracellular matrix (ECM). Chondrocytes sense and synthesize all necessary ECM components (Mollenhauer, 2008; Schulz and Bader, 2007). The ECM of articular cartilage consists of about 60-85% water and dissolved electrolytes. The solid framework is composed of collagens (10-20%), PGs (3-10%), noncollagenous proteins and glycoproteins. In articular cartilage, 95% of collagen in the ECM is type II collagen fibrils. The rest other types are collagen type IX and XI and a small fraction of types III, VI, XII and XIV. Normal articular cartilage does not present type I collagen, which is concerned with fibrous tissue. Unlike Type I and Type III collagens which form thick fibres and thin  ¬Ã‚ bres respectively, Type II collagen present in hyaline and elastic cartilages does not form  ¬Ã‚ bres. It forms very thin  ¬Ã‚ brils which are disposed as a loose mesh that strongly interacts with the groun d substance. Type II collagen provides tensile stiffness and strength to articular cartilage and constrains the swelling capacity generated by highly negatively charged glycosaminoglycans (GAGs) of the proteoglycans (PGs). The majority (50-85%) of the PG content in articular cartilage were presented by large molecule aggrecan. It consists of a protein backbone, the core protein, to which unbranched GAGs side chains of chondroitin sulphate (CS) and keratan sulfate (KS) are covalently attached (Figure 1.1). The composition of articular cartilage was extensively reviewed by Schulz and Bader (Schulz and Bader, 2007). Figure 1. Illustration of the extracellular matrix (ECM) organization of articular cartilage (Left) and the schematic sketches (Right) of the most relevant polysaccharides of proteoglycans (PGs) in articular cartilage. The PGs consist of a strand of hyaluronic acid (HA), to which a core protein is non-covalently attached. On the core protein, glycosaminoglycans (GAGs) such as keratan sulphate (KS) and chondroitin sulfate (CS) are covalently bound in a bottle brush fashion (Modified from Schulz and Bader, 2007 and Mow and Wang, 1999). 2.4 Low capacity of self-repair in articular cartilage The aneural and avascular nature of articular cartilage, coupled with its low cellularity, contribute to both the limited rate and incomplete nature of the repair process following damage (Heywood et al., 2004). The low mitotic potential of chondrocytes in vivo also contributes to its poor ability to undergo self-repair (Kuroda et al., 2007). Some researchers believe that cartilage lesions less than 3mm in diameter self-repair with normal hyaline-like cartilage (Revell and Athanasiou, 2009; Schulz and Bader, 2007). In animal studies, full thickness cartilage defects, extending into the subchondral bone, have been reported to heal with the formation of fibrous tissue, which contains relatively low amount of type II collagen and aggrecan, but a relatively high concentration of type I collagen which is not present in normal adult articular cartilage and accordingly exhibits impaired mechanical properties (Hjertquist et al., 1971). 2.5 Metabolism of articular cartilage Joint cartilage is supplied with nutrients and oxygen by the synovial fluid diffusion facilitated by compressive cyclic loading during joint movements which acts as a pumping function (Mollenhauer, 2008). Within synovial joints, oxygen supply to articular chondrocytes is very limited, from 7.5% at the superficial zone down to 1% oxygen tension at the deep zone. It is supposed to be even further decreased under pathological conditions, such as osteoarthritis (OA) or rheumatoid arthritis (RA). The metabolism of chondrocytes is largely glycolytic. Oxygen-dependent energy generated by oxidative phosphorylation is just a minor contributor to the overall energy in chondrocytes. Nevertheless, changes in O2 tension have profound effects on cell metabolism, phenotype, gene expression, and morphology, as well as response to, and production of, cytokines (Pfander and Gelse, 2007; Gibson et al., 2008). The most important component of this hypoxic response is mediated by transcription factor hypo xia-inducible factor-1 (HIF-1), which is present in most hypoxia inducible genes (Pfander and Gelse, 2007; Gibson et al., 2008). Moreover, the matrix turnover in articular cartilage is extremely slow. Proteoglycan turnover is up to 25 years. Collagen half-life is estimated to range from several decades up to 400 years (Mollenhauer, 2008). Chapter 3 Osteoarthritis (OA) 3.1 Prevalence Osteoarthritis (OA) is the most common form of arthritis. More than 40 million US American citizens (approximately 15% of the overall population of the USA) suffer from arthritis (Schulz and Bader, 2007). OA can occur in any joint but is most common in certain joints of the hand, knee, foot and hip. OA is the most common reason for total hip- and knee-joint replacement (Wieland et al., 2005). Among US adults 30 years of age or older, symptomatic disease in the knee occurs in approximately 6% and symptomatic hip osteoarthritis in roughly 3% (Felson and Zhang, 1998). 3.2 The symptoms and diagnosis The symptoms of OA include pain, stiffness and loss of function. OA can be monitored by radiography, magnetic resonance imaging (MRI), and arthroscopy, but radiographs are still considered the gold standard (Wieland et al., 2005). 3.3 The pathology of OA The pathologic characteristics of OA are the slowly developing degenerative breakdown of cartilage; the pathological changes in the bone, including osteophyte formation and thickening of the subchondral plate; the changes in the synovium such as inflammatory infiltrates; ligaments, which are often lax; and bridging muscle, which becomes weak. Many people with pathologic and radiographic evidence of osteoarthritis have no symptoms (Martel-Pelletier, 1999; Felson et al., 2000). A protease family of matrix metalloproteases (MMP) is responsible for the initial occurrence of cartilage matrix digestion. Of this family, collagenases, the stromelysins and the gelatinases are identified as being elevated in OA. Another group of MMP is localized at the cell membrane surface and is thus named membrane type MMP (MT-MMP) (Martel-Pelletier, 1999). Proinflamatory cytokines such as interleukin (IL)-1ÃŽ ², Tumor necrosis factor (TNF)-ÃŽ ±, IL-6, leukemic inhibitor factor (LIF) and IL-17 are first produced by the synovial membrane and then diffuse into the cartilage through the synovial fluid, where they activate the chondrocytes to produce proinflammatory cytokines. These proinflamatory cytokines are considered responsible for the catabolic pathological process (Martel-Pelletier, 1999). In OA cartilage, an increased level of an inducible form of nitric oxide synthase (iNOS) leads to a large amount of nitric oxide (NO) production (Pelletier et al., 2001). NO can inhibit the synthesis of cartilage matrix macromolecules such as aggrecans and can enhance MMP activity (Taskiran et al., 1994; Murrell et al., 1995). It is well stablished that proinflammatory cytokines such as IL-1ÃŽ ² act as the key mediators of cartilage breakdown and stimulate the release of inflammatory products (NO) and prostaglandin (PG)E2, via induction of iNOS and cyclo-oxygenase (COX)-2 enzymes (Chowdhury et al., 2008). 3.4 Risk factors Osteoarthritis is considered to be a systemic disease although severe joint injury may be sufficient to cause osteoarthritis. There are several systemic risk factors related to OA. (1) Age: Osteoarthritis increases with ages, the incidence and prevalence of disease increased 2- to 10-fold from 30 to 65 years of age and increased further thereafter in a community-based survey (Oliveria et al., 1995). (2) Hormonal status and bone density: women taking estrogen have a decreased prevalence of radiographic osteoarthritis (Nevitt et al., 1996). Before 50 years of age, the prevalence of osteoarthritis in most joints is higher in men than in women. After about age 50 years, women are more often affected with hand, foot, and knee osteoarthritis than men. In most studies, hip osteoarthritis is more frequent in men (van Saase et al., 1989). Evidence suggests an inverse relationship between osteoarthritis and osteoporosis (Felson et al., 2000). (3) Nutritional factors: evidence indicates that co ntinuous exposure to oxidants contributes to the development of many common age-related diseases, including osteoarthritis. McAlindon et al. reported a threefold reduction in risk for progressive radiographic osteoarthritis was observed in persons in the middle and highest tertile of vitamin C intake compared with those whose intake was in the lowest tertile (McAlindon et al., 1996a). Vitamin D intake was observed associated with the progression of OA although not associated with risk for new-onset radiographic osteoarthritis (McAlindon et al., 1996b; Lane et al., 1999). (4) Genetics: genetic factors account for at least 50% of cases of osteoarthritis in the hands and hips and a smaller percentage in the knees (Spector et al., 1996). Candidate genes for common forms of osteoarthritis include the vitamin D receptor gene, insulin-like growth factor I genes, cartilage oligomeric protein genes, and the HLA region (Felson et al., 2000). Local mechanical factors include the body weight and the pathological alterations of the mechanical environment of the joint. Persons who are overweight have a high prevalence of knee osteoarthritis (Felson et al., 1997). OA is also considered to be related to alterations in joint mechanical environments such as knee laxity, the displacement or rotation of the tibia with respect to the femur; proprioception, the conscious and unconscious perception of joint position and movement; knee alignment , knee position in reference to the hip and ankle (Felson et al., 2000). In addition, joint dysplasias, fractures of articular surfaces, and tears of menisci and ligaments that increase joint instability precede the development of osteoarthritis in a high percentage of affected joints. Risk factors for posttraumatic osteoarthritis include high body mass, high level of activity, residual joint instability or malalignment, and persistent articular surface incongruity (Buckwalter et al., 1997; Honkonen 1995). 3.5 Treatments The medicine treatment of OA was dominated by COX2 inhibitors (Flower 2003). The other medicines include glucosamine, chondroitin (McAlindon et al., 2000), and hyaluronic acid (Lo et al., 2003). In addition, both aerobic walking and muscle strengthening exercise reduce pain and disability from osteoarthritis (Roddy et al., 2005). Articular cartilage lesions, both of traumatic or pathological origin, do not heal spontaneously and often undergo progressive degeneration towards osteoarthritis (OA). The most frequently used treatments include the artificial joint replacement, mosaicplasty, marrow stimulation, and autologous condrocyte implantation (ACI) (Steinwachs et al., 2008). Total joint replacement is most commonly performed in people over 60 years of age. (NHS 2006; Brittberg et al., 1994) Mosaicplasty is an autologous osteochondral transplantation method through which cylindrical periosteum grafts are taken from periphery of the patellofemoral area which bears less weight, and transplanted to defective areas. This transplantation can be done with various diameters of grafts (Haklar et al., 2008; NHS, 2006). Marrow stimulation methods include arthroscopic surgery to smooth the surface of the damaged cartilage area; microfracture, drilling, abrasion. All marrow stimulation methods base on the penetration of the subchondral bone plate at the bottom of the cartilage defect. The outflowing bone marrow blood contains the mesenchymal stem cells which are stabilised by the clot formation in the defect. These pluripotent stem cells which are able to differentiate into fibrochondrocytes, result in fibrocartilage repair with varying amounts of type I, II and III collagen (Steinwachs et al., 2008). The ACI tissue engineering treatment will be discussed in the next chapter. Chapter 4 Tissue engineering and autologous chondrocyte implantation (ACI) 4.1 Overview of tissue engineering technologies Tissue engineering is defined as ‘‘the application of the principles and methods of engineering and the life sciences toward the fundamental understanding of structure-function relationships in normal and pathological mammalian tissues and the development of biological substitutes to restore, maintain, or improve tissue function† (Langer and Vacanti, 1993). Three factors are considered as the principles of tissue engineering, including the utilization of biocompatible and mechanically suitable scaffolds, an appropriate cell source, and bioactive molecules to promote the differentiation and maturation of the cell type of interest (Song et al., 2004). Potential applications of tissue engineering are involved in the following fields: skin, cartilage, bone, cardiovascular diseases, organs (e.g. liver, pancreas, bladder, trachea and breast), central nervous system (e.g. spinal cord), and miscellaneous (e.g. soft tissue, ligaments). Although research is being carried out in all these fields, only few products have already entered the market. The most successful products up to now are: tissue engineered skin which is mainly used for wound cover, autologous chondrocyte implantation (ACI), and artificial bone graft (Hà ¼sing et al., 2003). 4.2 Autologous chondrocyte implantation (ACI) In 1984, a study in rabbits reported successful treatment of focal patellar defects with the use of ACI. One year after transplantation, newly formed cartilage-like tissue typically covered about 70 percent of the defect (Grande et al. 1989). In 1987, Brittberg firstly performed ACI in 23 people with deep cartilage defects in the knee. ACI is described as the following procedure: cartilage cells are taken from a minor load-bearing area on the upper medial femoral condyle of the damaged knee via an arthroscopic procedure, cultivated for four to six weeks in a laboratory and then, in open surgery, introduced back into the damaged area as a liquid or mesh-like transplant; at last, a periosteal flap sutured in place to secure the transplant (Figure 2; Brittberg et al., 1994). Genzyme Biosurgery with its product Carticel ® was the first company which introduced ACI into market and is the market leader in USA. Carticel ® is a classic ACI procedure using the periosteal cover (Hà ¼sing et al., 2008). Today the periosteum is often replaced by an artificial resorbable cover such as collagen I/III and hyaluronan membrane, such as ChondroGide or Restore (De Puy, Warzaw, Indiana) (Gooding et al., 2006; Jones and Peterson, 2006). Another new method uses chondrocytes cultured on a tri-dimensional (3D), biodegradable scaffold. This kind of scaffold, cut to the required size, is fixed into the lesion by anchoring stitches or its sticky nature. The 3D cell seeded scaffold eliminates the using of cover, thus simplifies the surgery procedure, saves the surgery time, and opens up the possibility of an arthroscopic surgery instead of the open surgery which causes more tissue damage. HYALOGRAFT from Italy is one of the European market leaders. It is a cartilage substit ute made of autologous chondrocytes delivered on a biocompatible 3D matrix, entirely composed of a derivative of hyaluronic acid (Marcacci et al. 2005). 4.3 Clinical results of ACI Brittberg studied the long-term durability of ACI-treated patients, 61 patients were followed for at least five years up to 11 years post-surgery (mean 7.4 years). After two years, 50 out of 61 patients were graded good-excellent. At the five to 11 years follow-up, 51 of the 61 were graded good-excellent (Brittberg et al., 2003). Since 1997 the year FDA approved ACI, this method has been widely performed in more than 20,000 patients all over the world. It has been reported to be effective in relieving clinical symptoms, such as pain and function (Wakitani et al., 2008). In a randomised controlled study, Knutsen et al. studied 80 patients who needed local cartilage repair with lesions on the femoral condyles of 2-10 cm2. There were no signi ¬Ã‚ cant differences in clinical results at 5 years follow-up (Knutsen et al., 2007). In another randomised controlled study that compared mosaicplasty with ACI, there was no significant difference in the number of patients who had an excellent or good clinical outcome at 1 year (69% [29/42] and 88% [51/58], respectively). In the subgroup of patients who had repairs to lesions of the medial femoral condyle, significantly more patients who had ACI had an excellent or good outcome (88% [21/24]) compared with those who had mosaicplasty (72% [21/29]) (p Clinical results of ACI were reviewed by Gikas 2009 (Gikas et al., 2009). Generally speaking, the outcomes of ACI treatment have been encouraging. However, most randomised controlled studies showed no significant difference between ACI and traditional treatments. 4.4 Limitations of ACI Microfracture is a very simple and low-cost procedure whereas ACI costs about $10 000 per patient. If ACI is not found to be more effective for improving articular cartilage repair than microfracture, the procedure will not be continued (Wakitani et al., 2008). There are several possible reasons to be blamed for the limitations of the traditional ACI procedure. The cell source in ACI is the cartilage tissue derived via an arthroscopic procedure from the low load-bearing area on the upper medial femoral condyle of the damaged knee. However, Wiseman et al. found the chondrocytes isolated from the low loaded area of the knee joint respond to mechanical stimulations in a distinct manner with the chondrocytes from the high loaded area, which suggests the traditional cell source of ACI may not provide enough mechanical response and may further lead to the insufficient mechanical properties of the repaired tissue (Wiseman et al. 2003). As cultured in monolayer, chondrocytes undergo a process of dedifferentiation and adopt a more  ¬Ã‚ broblast-like morphology, which is accompanied by an increase in proliferation and an altered phenotype. Type II collagen, the major protein produced by chondrocytes in articular cartilage, are down-regulated in the culture, while collagen types I and III are increased (Glowacki et al., 1983; Stocks et al., 2002; Benya et al., 1978). The agregating proteoglycan aggrecan of articular cartilage, is down-regulated during dedifferentiation and replaced by proteoglycans not speci ¬Ã‚ c to cartilage, such as versican (Glowacki et al., 1983; Stocks et al., 2002). Therefore, monolayer cultured chondrocytes do not express the origninal phenotype, and their ability to regenerate damaged cartilage tissue is impaired. Upon implantation, dedifferentiated cells may form a  ¬Ã‚ brous tissue expressing collagen type I that does not have appropriate mechanical properties, which may lead to deg radation and failure of the repair tissue (Brodkin et al., 2004). Chondrocytes grown in conditions that support their round shape, such as plating in high-density monolayer (Watt, 1988) and seeding in 3D structure (Benya and Shaffer, 1982) can maintain their differentiated phenotype much longer compared to cells spread in monolayer cultures. Although ACI can still be considered to be one of commonly form of repair of cartilage defects, it does have a number of scientific limitations. Some of those can be resolved using more comprehensive tissue engineered strategies which incorporates cells, scaffold materials and potentially biochemical, biomechanical and/or physical stimulation in a controlled bioreactor environment. 4.5 Tissue engineering strategies for ACI Chondrocytes derived from the low load bearing area of the knee joint respond in a distinct manner with the chondrocytes from the high loaded area. Chondrocytes cultured in monolayer have a dedifferentiation phenomenon as described above. In addition, the limitation of the transplant volume is always a major problem in autograft to be overcome (Kitaoka et al., 2001; Vinatier et. al, 2009). Accordingly, potential cell sources are widely studied for the future improvement of ACI approach, which will be discussed in Chapter 4. Seeding in 3D structures (Benya and Shaffer, 1982) can maintain chondrocytes differentiated phenotype. Ideally, cell scaffolds for tissue engineering should meet several design criteria: (1) The surface should permit cell adhension and growth, (2) neither the polymer nor its degradation products should provoke inflammation or toxicity when implanted in vivo, (3) the material should be reproducibly processable into three dimensional structures, (4) the porosity should be at least 90% in order to provide a high surface area for cell-polymer interactions, sufficient space of extracellular matrix regeneration, and minimal diffusional constraints during in vitro culture, (5) the scaffold should resorb once it has served its purpose of providing a template for the regenerating tissue, since foreign materials carry a permanent risk of inflammation, and (6) the scaffold degradation rate should be adjustable to match the rate of tissue regeneration by the cell type of interest (Freed et al., 1994). Synthetic materials such as poly (glycolic acid) (PGA), poly (lactic acid) (PLA), and poly (lactic-co-glycolic acid) (PLGA) have been investigated for use as cartilage tissue engineering scaffolds (Cima et al., 1991; Vacanti et al., 1991). Both, in vitro and in vivo studies have demonstrated these scaffold maintained the chondrocyte phenotype and the production of cartilage extracellular matrix (ECM) (Barnewitz et al., 2006; Kaps et al., 2006). Moreover, PLGA is used as a scaffold material for matrix-based autologous chondrocyte transplantation clinically (Ossendorf et al., 2007). Natural materials have also been investigated in the application of tissue engineering scaffolds in ACI. Collagen-based biomaterials are widely used in todays clinical practice (for example, haemostasis and cosmetic surgery). Collagen is also be commonly used as main components in tissue engineered skin products. Several commercial ACI products have used collagenous membraneas as the replacement for the periosteum to close the defect, such as ChondroGide or Restore (De Puy, Warzaw, Indiana) (Cicuttini et al., 1996; Jones and Peterson, 2006). The combination of type I collagen with GAG in scaffolds had a positive effect on chondrocyte phenotype (van Susante et al., 2001). Hyaluronic acid is a non-sulphated GAG that makes up a large proportion of cartilage extracellular matrix (Schulz and Bader, 2007). Matrices composed of hyaluronan have been frequently used as carriers for chondrocytes. Facchini et al. con ¬Ã‚ rms the hyaluronan derivative scaffold Hyaff  ®11 as a suitable scaff old both for chondrocytes and mesenchymal stem cells for the treatment of articular cartilage defects in their study (Facchini et al., 2006). Sugar-based natural polymers such as chitosan, alginate and agarose can be formulated as hydrogels and in some cases sponges or pads. Although these materials are extensively used in in vitro research, their role in in vivo cartilage reconstruction is still limited (Stoop, 2008). Growth factors are proved to be able to promote the formation of new cartilage tissue in both explants and engineered constructs. Insulin-like growth factor-I (IGF-I), transforming growth factor-ÃŽ ²1 (TGF-ÃŽ ²1) increases, basic fibroblast growth factor (bFGF) can stimulate cell proliferation and/or biosynthesis in chondrocytes which were