Educational Debate

Thesis Statement Should teachers have the authority to remove a disruptive student form their classroom permanently? Teachers work really hard to promote a happy, healthy, and safe learning environment for all of their students. Teachers dedicate themselves, with sacrifice and determination to ensure that their students have the tools they need to learn and to promote the grown of learning for each individual. Most students in each classroom work hard and dedicate themselves throughout the school year to learn.This includes studying day, and night, attending school regularly, obtaining good grades, and behaving according to the best of their ability. If there is a student who is disruptive, it would not only effect the disruptive student, but it puts a hold on the learning lesson for every student. That is very unfortunate because some students really want to learn. Having a disruptive student makes is difficult for a teacher to teach and it only takes one or two disruptive students to completely corrupt an entire lesson plan.Teachers do not have enough time as it is to cram all this information in by the end of one school year to have to waste their time dealing with disruptive students. Teachers should have the authority to remove disruptive students from their classroom permanently. Educational Debate Persuasive Paper When working in a classroom, a teacher works hard try his or her best to promote a safe, happy, and healthy environment to the best of his or her ability.Not only do they work had at trying to come up with certain methods to assure all of the student's ability to learn, bust also tries to incorporate the lesson plans, because they are also work hard to create. A lot of time and thought is put in from the teacher to provide this for their students. In a classroom, every student has a different personality, and are also at different learning academic levels, so it is up to the teacher to have that one on one with the students to pick up, and lear n what their strengths and weaknesses are.From doing this, it allows the instructor to creating lesson plans to try and provide the proper tools needed for the student. This does not only take time from school for the teacher, but it also takes a lot of time from home because there might not be enough time in the day for the teacher to complete the lesson plan so they may have to take the work home. The classroom is a place for quiet learning, and respect for others right to learn. If you have a student who is being disrespectful who has gotten away with being disrespectful, it would be very hard to change it all around.You, as a teacher has to let them know whom it is that is actually in charge. There are strategies that you may want to take to try and assist you in this situation. Try calling home. When you call home and ask to speak to their parents, and even calling home perhaps while standing in front of the misbehaved student, may help to get them to change their attitude for that day, and give them the opportunity to accept how they have been behaving. It may also help out by being an example or the other students, so they can behave accordingly as well.Since students are disruptive, (on account to behavior issues mostly), and still you know that some of those students may even have potential aside to their behavioral issues, you may try to even reason with them. Sometimes, trying to have an open mind about what is really causing the student to misbehave may help the situation. Most of the time disruptive students bring so much of themselves to the classroom, because it may be an attention call for inner help.Try to listen to them and see what it is that makes them â€Å"them†, what it is that makes them think, and finding out their interest. By learning and understanding what it is that gives them motivation, could allow you to shape their learning experience, and support how they think, so they too can grow with the classroom. For a student to behave disruptive in a classroom, not only is it extremely time consuming for the teacher, and not only does it make learning difficult for the other students, but it can also be dangerous if it gets too out of control.If you as a teacher had already tried making the phone calls home, tried having that one on one with the student, and tried leveling with the students to the best of your ability using all of the resources that you know, ask yourself, could removing this student from my classroom permanently, help me to provide that environment that I have envisioned for my students? For most teachers, teaching does not just comes as â€Å"a career†, but more as a passion.It is not fair for a teacher to continue to put in his and her all, and have to constantly deal with day to day disruptions when the teacher’s main goal is to initially teach. This does not just go for being a teacher, but it also goes for any job. At any job, who would want to look forward to returning to a daily, out of control negative environment that removes most of your focus allowing you to do your very best? Not only does it affect the misbehaved student, and the classroom but it puts a toll on the teacher as well, the next step would be to have the student removed from the classroom.It is unfortunate because you’ve tried your best in trying to help out the situation within the classroom, you must figure out what other options are left for you to take now. It seems like the only other option would be removing the disruptive student from your class because you have tried your best at everything else, and nothing seems to work. You may have the authority to remove that student from your classroom for the period, the day, or even a few days. If that does not seem to work, you may even have the authority (with a few steps) to have the child removed to another classroom or even another school.I know it would not be something that you might be looking forward to doing, bu t you also have to consider the welfare of the other students, as well. Mike Ford states that even if students who promote disruptive behavior do get led into suspension, it is detrimental for teachers, staff, culture and of course student learning overall. (Ford, Mike the impact of disruptive learning in Wisconsin public schools, Vol. 26. No. 5, April 2013) Basically, it really is not as easy as it sounds.There is a process of course, but eventually if it takes removing a student from the classroom to assist you as a teacher to provide a better learning environment for those students who actually want to learn, then it should be suggested and ok to do so. Every teacher should know their Disciplinary Code in order for them to become able to assign a range of disciplinary actions, and steps needed to take for every and or any situation if needed. By knowing the code as an instructor, and by using, it can help to teach students how to behave accordingly what is expected of them or els e they may have to face consequences.If the student continues to be chronically disruptive, then you as their teacher then have the right by the SAVE Law (Safe Schools against Violence in Education) to take the next few steps in order to bring your classroom back into order, if removing the student from the class is what it takes. In your classroom, you not only work had to organize and arrange your classroom for the order to go, and flow the way you want to, and how you may imagine it to be, and a lot of the times when students are disruptive, a phone call home may just not be the key to fixing the problem.There are students who work very hard and do everything they need to do to learn and better their future. They actually want to learn. Those are the students who do their homework, follow direction, get good grades, study, come to class on time, and overall behave. Why is it that just because other students may feel the need to interrupt a classroom lesson be fair in any way to t he other students who actually want to learn? The students who actually want to learn, have to have their education put on hold every time there is a disruption within the classroom. Then students who actually want to learn end up getting their learning time wasted.You as a teacher, barely get enough time as it is to teach all this information within one entire school year. Do you see why teachers should have the authority to remove a student from their classroom permanently if they need to? There is just only so much a teacher can handle and do all at once. Sometimes if a teacher allows such disruptions to occur within the classroom, it causes other students to follow and then there would not be any respect within the classroom. Respect should be one of the main thing to be enforced from the begging of the school year.Everyone should learn to respect theirselves and each other. Following directions is one of the number one keys to respect. In order to become a teacher there is a lo t of sacrifice and dedication. As a teacher, you take all the steps there is to providing all you can, to the best of your ability. Removing a child out of your classroom permanently may be the last step you have to take, but you most likely took all the other steps you had to, in order to get your there. Even so, by doing so, you were probably able to regain your class respect, and have things in order again.There are other students who not only need this education, but actually want it, since teaching has always been your passion to do provide that education for them these may be ways to provide that for your learning students. Everyone who have dreamed of becoming a teacher, may not have envisioned having to permanently remove students from their classroom. Nothing ever goes quite as planned, it may even help the disruptive student to either learn his or her lesson, or it may help by providing the attention that they have been looking for after all.Maybe the disruptive student wo uld be sent off into a different classroom, where he or she may pick up more information with other methods from other teachers. Maybe they will learn better strategies from alternative schools. Even though they have been disruptive, it does not mean they would not receive the education that there are also entitled to, but by them no being able to disrupt your classroom anymore, their absence will definitely help you to provide that education to the classmates who were willing to learn. Educational Debate Should teachers have the authority to remove a disruptive student form their classroom permanently? Teachers work really hard to promote a happy, healthy, and safe learning environment for all of their students. Teachers dedicate themselves, with sacrifice and determination to ensure that their students have the tools they need to learn and to promote the grown of learning for each individual. Most students in each classroom work hard and dedicate themselves throughout the school year to learn. This includes studying day, and night, attending school regularly, obtaining good grades, and behaving according to the best of their ability.If there is a student who is disruptive, it would not only effect the disruptive student, but it puts a hold on the learning lesson for every student. That is very unfortunate because some students really want to learn. Having a disruptive student makes is difficult for a teacher to teach and it only takes one or two disruptive students to completely cor rupt an entire lesson plan. Teachers do not have enough time as it is to cram all this information in by the end of one school year to have to waste their time dealing with disruptive students.Teachers should have the authority to remove disruptive students from their classroom permanently. Educational Debate Persuasive Paper When working in a classroom, a teacher works hard try his or her best to promote a safe, happy, and healthy environment to the best of his or her ability. Not only do they work had at trying to come up with certain methods to assure all of the student's ability to learn, bust also tries to incorporate the lesson plans, because they are also work hard to create.A lot of time and thought is put in from the teacher to provide this for their students. In a classroom, every student has a different personality, and are also at different learning academic levels, so it is up to the teacher to have that one on one with the students to pick up, and learn what their stre ngths and weaknesses are. From doing this, it allows the instructor to creating lesson plans to try and provide the proper tools needed for the student.This does not only take time from school for the teacher, but it also takes a lot of time from home because there might not be enough time in the day for the teacher to complete the lesson plan so they may have to take the work home. The classroom is a place for quiet learning, and respect for others right to learn. If you have a student who is being disrespectful who has gotten away with being disrespectful, it would be very hard to change it all around. You, as a teacher has to let them know whom it is that is actually in charge. There are strategies that you may want to take to try and assist you in this situation.Try calling home. When you call home and ask to speak to their parents, and even calling home perhaps while standing in front of the misbehaved student, may help to get them to change their attitude for that day, and giv e them the opportunity to accept how they have been behaving. It may also help out by being an example or the other students, so they can behave accordingly as well. Since students are disruptive, (on account to behavior issues mostly), and still you know that some of those students may even have potential aside to their behavioral issues, you may try to even reason with them.Sometimes, trying to have an open mind about what is really causing the student to misbehave may help the situation. Most of the time disruptive students bring so much of themselves to the classroom, because it may be an attention call for inner help. Try to listen to them and see what it is that makes them â€Å"them†, what it is that makes them think, and finding out their interest. By learning and understanding what it is that gives them motivation, could allow you to shape their learning experience, and support how they think, so they too can grow with the classroom.For a student to behave disruptive in a classroom, not only is it extremely time consuming for the teacher, and not only does it make learning difficult for the other students, but it can also be dangerous if it gets too out of control. If you as a teacher had already tried making the phone calls home, tried having that one on one with the student, and tried leveling with the students to the best of your ability using all of the resources that you know, ask yourself, could removing this student from my classroom permanently, help me to provide that environment that I have envisioned for my students?For most teachers, teaching does not just comes as â€Å"a career†, but more as a passion. It is not fair for a teacher to continue to put in his and her all, and have to constantly deal with day to day disruptions when the teacher’s main goal is to initially teach. This does not just go for being a teacher, but it also goes for any job. At any job, who would want to look forward to returning to a daily, out of control negative environment that removes most of your focus allowing you to do your very best?Not only does it affect the misbehaved student, and the classroom but it puts a toll on the teacher as well, the next step would be to have the student removed from the classroom. It is unfortunate because you’ve tried your best in trying to help out the situation within the classroom, you must figure out what other options are left for you to take now. It seems like the only other option would be removing the disruptive student from your class because you have tried your best at everything else, and nothing seems to work. You may have the authority to remove that student from your classroom for the period, the day, or even a few days.If that does not seem to work, you may even have the authority (with a few steps) to have the child removed to another classroom or even another school. I know it would not be something that you might be looking forward to doing, but you also have to consider the welfare of the other students, as well. Mike Ford states that even if students who promote disruptive behavior do get led into suspension, it is detrimental for teachers, staff, culture and of course student learning overall. (Ford, Mike the impact of disruptive learning in Wisconsin public schools, Vol. 26. No. 5, April 2013) Basically, it really is not as easy as it sounds.There is a process of course, but eventually if it takes removing a student from the classroom to assist you as a teacher to provide a better learning environment for those students who actually want to learn, then it should be suggested and ok to do so. Every teacher should know their Disciplinary Code in order for them to become able to assign a range of disciplinary actions, and steps needed to take for every and or any situation if needed. By knowing the code as an instructor, and by using, it can help to teach students how to behave accordingly what is expected of them or else they may have to face consequences.If the student continues to be chronically disruptive, then you as their teacher then have the right by the SAVE Law (Safe Schools against Violence in Education) to take the next few steps in order to bring your classroom back into order, if removing the student from the class is what it takes. In your classroom, you not only work had to organize and arrange your classroom for the order to go, and flow the way you want to, and how you may imagine it to be, and a lot of the times when students are disruptive, a phone call home may just not be the key to fixing the problem.There are students who work very hard and do everything they need to do to learn and better their future. They actually want to learn. Those are the students who do their homework, follow direction, get good grades, study, come to class on time, and overall behave. Why is it that just because other students may feel the need to interrupt a classroom lesson be fair in any way to the other student s who actually want to learn? The students who actually want to learn, have to have their education put on hold every time there is a disruption within the classroom. Then students who actually want to learn end up getting their learning time wasted.You as a teacher, barely get enough time as it is to teach all this information within one entire school year. Do you see why teachers should have the authority to remove a student from their classroom permanently if they need to? There is just only so much a teacher can handle and do all at once. Sometimes if a teacher allows such disruptions to occur within the classroom, it causes other students to follow and then there would not be any respect within the classroom. Respect should be one of the main thing to be enforced from the begging of the school year.Everyone should learn to respect theirselves and each other. Following directions is one of the number one keys to respect. In order to become a teacher there is a lot of sacrifice a nd dedication. As a teacher, you take all the steps there is to providing all you can, to the best of your ability. Removing a child out of your classroom permanently may be the last step you have to take, but you most likely took all the other steps you had to, in order to get your there. Even so, by doing so, you were probably able to regain your class respect, and have things in order again.There are other students who not only need this education, but actually want it, since teaching has always been your passion to do provide that education for them these may be ways to provide that for your learning students. Everyone who have dreamed of becoming a teacher, may not have envisioned having to permanently remove students from their classroom. Nothing ever goes quite as planned, it may even help the disruptive student to either learn his or her lesson, or it may help by providing the attention that they have been looking for after all.Maybe the disruptive student would be sent off into a different classroom, where he or she may pick up more information with other methods from other teachers. Maybe they will learn better strategies from alternative schools. Even though they have been disruptive, it does not mean they would not receive the education that there are also entitled to, but by them no being able to disrupt your classroom anymore, their absence will definitely help you to provide that education to the classmates who were willing to learn.

Present complex internal business information Essay

P2: present complex internal business information using three different methods appropriate to the users needs. Four methods of business communication Written communication: Written communication involves any type of interaction that makes use of the written word. It is one of the two main types of communication, along with oral/spoken communication. Written communication is very common in business situations and they use this type of communication a lot. Written communication includes reports, orders, memos, instructions, rules, policies, agreements, and minutes. Visual Communication: Visual communication is direct face-to-face communication between two or more individuals. Speeches, presentations, discussions, meetings are all forms of oral communication. Face-to-face communication is very easy and useful and you could build a rapport and get people to gain trust in you. Verbal Communication: Verbal communication has more to do with listening than speaking because you are always dealing with an audience. It is one way to communicate with someone face-to-face. Telephone conversations are very useful for this type of communication. People who use verbal communication can share their feelings, thoughts, and emotions by way of them communicating. Staff and students in CCA use this communication every day. Non-Verbal Communication: Non- verbal communication is any kind of communication not involving words. When the term is used, most people think of facial expressions and gestures, but while these are important essentials of nonverbal communication, they are not the only ones. Nonverbal communication can include vocal sounds that are not words such as grunts, sighs, and whimpers. Even when actual words are being used, there are nonverbal sounds such as voice tone, pacing of speech and so forth. When you use non-verbal communication you can use your hands to move them around or your body to get the message across without saying a word. CCA exam results: When students are in year 11 they start to take their GCSE exams in the summer. This will give them opportunities for what they want to use at college or sixth form. However, CCA need to provide students with their results they using a document to present their exam results. After students have taken their exams the exam board will sent a document of all the grades they have achieved in their exams. This document will be given to the students so they know what grade they have got. CCA will provide a certificate to the students who have passed their exam. This certificate will be proof that they have passed it and it can be shown when they apply for sixth forms, colleges or even at a job interview. The document includes the name of the exam they have taken, the board they have taken it in for example EDEXEL or AQA, the exam number, the time of the time, the date of the exam and the duration of the exam. This exam result document will also include all the students’ personal information, for example date of birth and full name. The document is not very attractive; it is just a simple piece of paper that has all the information about the exam. It is very easy and simple to read. There is nothing fancy in the document. However, the certificate CCA make for all students when they pass the example is very attractive and it is made out of very hard paper which shows affection as CCA will put a lot of work just to make one certificate perfect. For CCA to make the exam result documents they had to use couple of methods to make it work. They used web based to make a suitable and presentable design to put on the certificate. Students feel very nervous when they are getting their exam results. They do not mostly care about what it looks like; they just rush to know what grades they got as it can change their life. This is why CCA do not spend much time making these documents as students will not pay attention to anything apart from their grade. The improvement CCA could make would be to make the document more interesting and colourful. This would make the document more interesting and attractive. I think using a document is the right type of method to use as all they are getting is there exam result it does not need to be presented or any other sort. So I personally thing document is the perfect method. For my report above, I have chosen to use a document. The reason for this is because it is a much easier way to present my report out. I think using a report is one of the best methods. This is because it takes less time to use it and it looks very smart and professional without adding any colour objects or font. It is also easier for my teacher to read it. The font is also very clear which means my teacher will not have any problem reading it.

Advertising and Sex

Sex and indecency are very mature areas and should not be used loosely. In todays society almost anything goes. This should not hold true for certain areas; like sex. I intend to use many examples of sex in advertising and various studies to show how this strategy is not only over used, but is improperly used and viewable to all consumers, including young children. The advertising industry has taken a low blow at society and needs to focus their attentions on preserving human decency and uphold a higher standard of moral concern. What are we really dealing with here?As time grows older, the acceptance of more and more ideals is growing by the second. Not only ten years ago were standards different. I remember when girls couldnt wear shorts that came higher than four finger widths above their knees to school. Today this standard is not only unheard of, but laughed at. Foul language on television is more accepted. Video games are more graphic than ever before and advertisements are using the idea of sex or sexuality to sell products to all ages (including video games: they now have nudity in video games). Do we really want our children growing and learning room these explicit images?How can companies sleep at night knowing they are using corrupt techniques to sell products to our children? We are talking about corporate social responsibility (CARS). CARS is defied that a corporation should be held accountable for any of its actions that affect people, their communities, and their environment (McGraw-Hill, 1999, peg. 3). Companies have two choices in this world today. They can either be for CARS or against it. This paper will use both sides of the coin to view the argument about sexuality in advertising. Is the burger really that good?The advertisement industry is a no-holds-barred industry where just about anything goes. Companies need to focus their attention on their CARS more than getting the edge in ads. We might ask ourselves, who exactly is watching these ads? Who are they intended for? What are they selling? Sometimes an advertisement can actually be confusing as to what is being sold. I do not agree with a sexual display for irrelevant products. The reason I take an anti- sexuality view on the subject started from a Carols Jar. Commercial. In this particular commercial, Paris Hilton was displayed eating a Caracals. Ambusher. While eating she was dressed in black bathing suit crawling over a Bentley. Some might find it attractive and enticing while others find this a little explicit for them. This commercial is basically soft-core porn. The way she moves, the way she puts her finger in her mouthits very suggestive and very titillating (http://money. CNN. Com/2005). Said Melissa Caldwell, research director for the Parents Television Council (APT). Carols Jar. Responded by saying that the group needs to get a life. This isnt Janet Concessionaires no nipple in this.Its a beautiful model in a swimsuit washing a car (http:// none. CNN. Com/2005). The APT is very concerned about this matter considering this commercial airs in the hours of popular television shows such as The O. C. And sporting programs. Milton Friedman (1970) would agree with Carols Jar. Friedman believes in the interest of the business and the business only. In his article with the title that speaks his opinion, The Social Responsibility of Business is to Increase Profits, Friedman states that only people have responsibilities business as a whole cannot be said to have responsibilities (Freidman, 1970, Peg. ). From Friedmans point of view if this immemorial, which more than likely improved profits, did not air because of some social value or norm then the company lost money. More specifically they would be spending someone elses money; the stockholders. The corporate executive made a decision to improve revenue for the company, which in turn makes more money for stockholders. He is not about to hold back from higher profits because of some social backlash. In the world of advertising sometimes bad press is good press. !Hold! A Mexican restaurant showed a lascar-clad woman posed with her hands on her hips over the headline 0 Tickle my Taco (Rotifer, 2003). In this case the owner probably thought this would be a good slogan to have. What he doesnt realize that the use of irrelevant sexual innuendos is actually more distracting attracting. He actually thought this was the best campaign he had ever had because of the numerous complaints he got. Another backfire experience involves a trucker business that had passed out calendars for his business with half naked women on each month.This was thought to be a perfect ad scheme until most of the people with the calendars actually forgot the name of his company. Advertising creators are so myopic as to believe hat publicity from offending people is always beneficial. They do not see it as being a distraction from saying positive things about the restaurant or store (Rotifer). Joe cool? Advertising is not created and used just to provide a smug example of public morality; advertising is honest because it has to be. What I mean by honesty is the product information is not all ways how it is displayed.Lets address the issues of what we care about, the way we raise our children, our ideas of right and wrong conduct, these in my view are all together. Lets take a look at liquor and tobacco advertising. The image of the Marlboro Man is one example. This type of advertisement depicts a buff, handsome, cool man smoking a cigarette. What message is this conveying to our young people? That it is cool to smoke. We all know it has been proven that smoking cigarettes can cause cancer. This type of advertisement causes the consumer to subliminally change their opinion of various items.This is why most advertising is geared towards the younger more susceptible crowd. Firebombed and who? The Caracals. Case is not alone in sexual content. Sex is everywhere we look in todays society. In The Prevalence of Sexual Imagery in Ads Targeted to Young Adults, Firebombed Fitch made an advertising attempt at combining a magazine with a catalog. They call it the analog. In this analog they TA regret young adults by using sexual imagery throughout their products. They increased their revenues from $50 million to over SSL . 5 billion in 2001.From these numbers one could say that sex does sell. In a survey taken in 2001 results found that 44% of young adults (age-24) said they are more likely to buy the clothes if the ad contains sexual imagery (Richter, 2003). Others may not agree that sex sells. Most people (61 %) report that sexual imagery in ads makes them less likely to buy the products (Richter). This quote was taken from the same article, but was used as a generalization about all people young and old. Other than being aimed at a much too young audience, there are more issues that are raised with sexuality in ads.Who wants to look like a celebrity? Lets talk about images. For example, most advertisements for clothing (I. E. Bathing suits etc), show shapely thin women and men. This has led our country to think that fat is demeaning and not socially accepted. This type of advertising has caused everyone to want to look like the people in the ads. Diets of all sorts have been developed to try to meet these expectations. But when their goals are not reached it causes depression, low self-esteem that in turn causes a poor image is developed.In my opinion these advertisements have a negative outreach. Who is to say only thin people look great? Advertisements do. These ads also have created anorexic teenagers, which has lead to serious health problems and even death. Advertisements often do not explicitly urge the consumer to buy a given product; rather they promise hat the products will enhance a persons life. If a stunningly attractive person claims to use a beauty product, that product may be assumed to be an element of the beauty formula.Ads arguing that consumers will be more attractive, accepted or appealing to other offer relevant to teens and young adults, for whom dating and group memberships are important (Richter). I Whats it goanna be? From one of my readings I have gathered two hypotheses about advertising that find relevant to our study. Hypothesis 1: A higher proportion of ads with sexual imagery appear in ads targeted to young adults compared to those targeted to mature adults. Hypothesis 2: Overall, ads contain a higher proportion of sexually dressed women than men (Richter).These two combined show that most advertising is targeted towards young males and that females are the primary source of sexual content in media and advertising. This could possibly lead to a bad outcome. Studies have shown that males viewing these sexual ads of women are far more accepting of sexual aggression towards females, including rape. These studies agree with the theories of Moses Papa (1997). Papa believes hat there are four criteria to our thought of social responsibility and that there is a trade-off between three of these four.These areas are; local knowledge, level of responsibility, shared consensus and relationship to financial performance. We find that most of the time local knowledge and relationship to financial performance are the one being traded off. Local knowledge would mean that the company designing the ad would know the background of the product being displayed and the target audience. Most of the time they do not take the product and audience into consideration, as we have seen. These companies are more focused on the relationship to financial performance: making a profit.Reaching perfect social responsibility seems very unattainable. These four criterion were setup as a guideline to reach such a goal. No program will meet all of these standards. They are purposely couched as ideals to be pursued, rather than as minimalist goals to be obtained easily (Papa). Whos doing it right? The idea of Corporate Social Responsibility is an optimistic outlook for todays society. A perfect example would be the Cummins Engine Company. Year after year this company insisted on donating to charitable foundations. And year after year they were threatened by bankruptcy.Any business or economics professor will tell you that their choices were not the smartest in the world. Their short term benefits suffered greatly because of these choices. Their long term, however have not suffered. They now produce over $5 billion in revenues each year. The iron law of responsibility states that in the long run, those who do not use power in ways that society considers responsible will tend to lose it (McGraw-Hill, peg. 4). Cummins Engines saw their long run capabilities and stuck with them. They prove the stewardship Renville that profits and social responsibility can coexist.

Doea a dividend policy matter Essay Example | Topics and Well Written Essays - 2000 words

Doea a dividend policy matter - Essay Example But the practitioners are of the opinion that dividend policies do play an important role in this regard. They provide examples in this regard that there are numerous companies whose share prices have jumped to a new high after their announcement to pay regular dividends. The process of paying dividend by companies is considered very important because it sends a powerful message to outsiders of the company about the future prospects of the organization. If an organization is able to pay out consistent dividends over time to its shareholders, it can be concluded by the general public that the fundamentals of the organization are very strong. It should be noted in this regard that focusing solely on the dividend policy of an organization is not sufficient. The company must also have the money that is required to pay dividends to its shareholders. Any company’s sources of funds must equal its uses of such funds. If an organization pays dividends to its shareholders and this is considered as use of funds, there must be something that has to change in the uses and sources statement. In this regard it could be said that given the investment policy of the firm, the dividend policy decisions of any firm is dependent on the choice of its financing strategy. An organization has to take a decision in this regard whether it wants to rely heavily on external funds to finance its projects and then paying back those funds to the providers of finance in the form of higher dividends. The other way is to retain a part of its earnings to finance its growth. Ploughing back of profits is an important tool by which an organization ca n effectively finance its projects without relying too much on outside sources of funds (Miller, 1977, pp. 261-265). It can be said at this point that generous dividend policies may not be considered as the best for an organization. The organization’s

What strategies can policy makers employ to promote successful policy Essay - 1

What strategies can policy makers employ to promote successful policy implementation - Essay Example The researchers of this generation have identified that the research implementation process is not as simple as it is thought to be and there are a lot of complications that need to be considered. This generation has identified that there are several factors that are involved in the implementation of policy and these factors somehow influence the policy implementation therefore it is important to identify and consider these factors as well (Hill, 1997) On the other hand, the second generation is a bit realistic and it is considered as the classical generations to be too pessimistic. The scholars in the second generations are Berman, O’Toole and O’Toole and Montjoy, Hjern and Porter, and Tasmanian and Sabatier. This generation has kept its focus on the top-bottom approach and bottom-top approach. This generation has debated whether the top-bottom approach or bottom-top approach should be implemented for successful results. This generation has demonstrated that the implementation is a political process and to a great extent ignored other factor which has been later criticized by the third generation (Pitts, 2006). The last but not the least generation is the third generation or the analytical generation. This last generation is called the analytical generation as the researchers in this generation have more focused on the methods being used rather than the results that have been achieved. This generation has been criticized both the previous generations for ignoring the social factors. This generation called for better methods and more social factors within the implementation process. It could be said that this generation was not concerned regarding the failure or success of the process but were more interested in learning and understanding how the process works. This generation was more focused on improving the methods and procedures that could used to implement the policy successfully. Implementation,

International trade ( Economic ) Essay Example | Topics and Well Written Essays - 500 words

International trade ( Economic ) - Essay Example In the perception of many in the developing world, the IMF has played major roles in helping countries overcome financial problems such as those that occurred in Mexico, Brazil, Argentina and Mexico, and Turkey. The problem with Turkey sticks out like a sore thumb: the country has had it eighteenth program with the IMF but its problem persists. In 1997, the IMF thrust itself into prominence when it intervened in the Asian Financial Crisis as countries such as Malaysia, Singapore, the Philippines – and more particularly, South Korea, Thailand, and Indonesia -- saw the value of their currencies plummet to unprecedented lows. The timely assistance provided by the world financial body helped these countries tide over the crisis but the process was fraught with painful adjustments and even triggered harsh criticism of IMF policy measures in these countries as to their appropriateness, given the peculiar domestic macroeconomic conditions. South Korea obtained a $55 billion credit from the IMF with certain attached conditions. South Korea was to open its economy and banking system to foreign investors and eliminate trade-related subsidies and import licensing, thereby making it vulnerable to foreign competition . The IMF also required the country to maintain a low inflation rate of 5 per cent. This was inconsistent with th e fact that the fall in the value of the Korean won and subsequent rise in import prices would create pressures on domestic prices. The unpleasant consequence of this was that the high interest rates made all the more difficult for South Korean companies to service their debts, thus the IMF was criticized for exacerbating the crisis these companies were facing instead of abating them. By applying cut-and-dried solutions to problems in countries with unique problems, the IMF opened itself to criticism of lack of

Ancient Part Essay Example | Topics and Well Written Essays - 1250 words

Ancient Part - Essay Example The western Roman empires started to collapse during this period of time and early modern age had its point of initiation from the end of this era. The phase between 5th and15th centuries is segmented into three phases; early, high and late middle age. After the collapse of the Roman Empire the provinces were under the control of barbarian invaders. Carolingian and East Francian Empires existed in Germany in the early middle ages. These dynasties were taken as the starting point of modern Germany. The institute, administration and regime in the Carolingian empire were in the court of its ruler Charlemagne. The political changes of the empire were made in the capital of Aachen in the province that had an extensive impact in the economy of German in the later ages. Historians often suspect the depth of emperor’s authority and rule. Monarchy was the system of rule when the central power and authority was in the hands of the emperor. This rule was known as Bannan; it was the right of law and charge that the emperor had over his territory (Caviness 49). The various rules of law were introduced by the king and he had complete judicial control over his provinces. The army or the defence of the province was also led by the ruler. It was the responsibility of the king to look after the underprivileged people and protect the church. People in the province were bound to be loyal to the king. The main objectives of the ruler were to systematize the sovereignty, church and cordiality around him. At the end of every norm the efficacy of the king was directly proportional to the effectiveness, support and trustworthiness of his subjects. There was an inbuilt body known as the Royal household who made sure that proper supervision was held in the localities. The count of the palace looked into the activities of the royal household. The priestly affairs of the kingdom were under the supervision of the chaplains, they had great power and importance over the people of the p rovince. Coinage had a strong association with the Roman Empire, after the collapse of Roman administration Charlemagne took control over the coinage system with its own regulations (Bruce 67). The Carolingians exercised control over the silver coinage of the dominion by domineering its concerto and standards. The name of the king, but not its minter appeared on the silver coins. The existence of silver coins showed that the economy was rich with resources. The king concealed the mints in northern Germany on the Baltic Sea and thus kept a secret reserve of wealth hidden from rest of the world. The brief analysis of the state of affairs long back in Germany reveals that before industrial revolution the common people had no freedom over their own decisions (Duby 87). The representative of the God was the chaplains, and the representative of the chaplains was the king. The common folk had no authority over their own political, economic and social activities. The sovereignty of the peop le was completely under the control of the king. Catering to the above factors Germany before 1800 was a heavily rural nation. There were only a few urban trade centres across the domestic borders of Germany. A business treaty of trading cities with their gilts existed in the trading centres of Germany. The farmers lived in the villages

Health Financial Management Essay Example | Topics and Well Written Essays - 1500 words

Health Financial Management - Essay Example The goal that becomes the end in the health financial matters involves the creation of an operational knowledge network. Various opportunities arises that help in the application of a real life situations in matters relating to healthcare. It is also important to note a complete usage of spreadsheet. This knowledge system helps in the compilation of data in the most efficient way (McLean, 2003). Introduction Financial management of the health sector provides an easy approach that streamlines the labor health care intensively. The system of management helps to ensure an increase in the efficiency level, accuracy and reduced labor cost in the entire life of an enterprise. The implementation level provides the best solution if the optimal way is applied in the course of the operation of the business (Latimer, 2012). The National Case mix Scenario The National case under study is an Australian based program that ensures development of the Refined Diagnosis and the related groups. The cla ssification of this form of diagnosis includes the statistical body and the diagnosis centre. The statistical body is involved in the dealing and classification of disease related problems and other bodies. These include the coding standards, classification and intervention body and the modification segment (France, 2001). The model applied at the funding level created an alarming effect with senior members of the health department. This case was felt in the New South Wales with great magnitude. The magnitude emanated from the opposition in the funding process. The hospital association in Australia accepted the idea of funding. Believe in the ideology of better performance evolved from the existence of favorable arrangements at the time. Later, a committee for case mix evolved. It performed the work of determination of clinical changes as per the US regulations. This gave rise to the creation of Australian National and Australian Refined. The entire national case system gets fund fr om the Australian health department. The seventh edition of Australian modification happens to take place at the end of June 2013. Another event will also unfold on first of July 2013. This event will feature under the seventh edition partnership program. The seventh edition will ensure that planning and implementation takes place in the entire phase of the heath management (Willis, Reynolds & Helen, 2008). National Health and Hospitals Reform Commission (NHHRC) Report The birth of COAG is a signaling factor to the NHHRC. The COAG had a meeting that raised important agendas to focus on the NHHRC (Appleby & Aroney, 2012). Some of the recommendations included the requirement on the address of peculiar issues of regulation as a rule in the commonwealth. The Council of Australian Government (COAG) body had an agreement to increase the funding requirements of the state aimed to increase health issues. The funding initiative had a focus on capacity improvement as a main goal. It is impera tively important to appreciate work performed by the COAG (Crase, 2008). The body comprises of on dignitaries including the prime minister and other state dignitaries. The body schedules to have a meeting on April 13 2012 at Canberra. The main agendas at any meeting must revolve at some of the most important issues like the major reforms, delivery of Medicaid and the funding level aimed at the sustainability of the

MKT Unit 3 Individual Project Research Paper Example | Topics and Well Written Essays - 1750 words

MKT Unit 3 Individual Project - Research Paper Example Part 2 deals with Application to Product/Service, this part mainly focus on Strategic Marketing Plan of Pentax PocketJet 3. Introduction: This Project will be mainly about the Strategic Marketing Plan of Pentax PocketJet 3 using the integrated marketing communications method. According to the American Association of  Advertising Agencies, integrated marketing communications identifies  the  value  of a  comprehensive  plan  that assesses the  planned  roles  of a variety of   public relations,  communication  disciplines  advertising,   sales promotion  and   personal selling, and joins them to  give   consistency, clarity,  and highest communication  impact. PART 1: General Research: Communication channel: A  communication channel refers to a physical  transmission medium  for example a wire or to a  logical connection  more than a  multiplexed  medium for instance a radio channel. A channel is used to  suggest  an  infor mation  sign, such as a digital  bit stream, from one or several  senders  to one or several  receivers. â€Å"Communication channels have evolved with more emphasis on multiplexing of multiple channels at higher data rates over the same link or channel† (Hura & Singhal 215). The Advertising Pros and Cons: There are a lot of contrasting estimations about advertising. Those in favor state that advertising educates customers regarding new products and services that can assist them develop their lives. It also enhances sales so that organizations can produce things at lesser costs and create things cheaper. And it helps the financial system and provides jobs to several people. With no advertising some free TV and radio channels would not be able to exist. Gaming and other procedures are promoted by ads. Ticket costs will be high without advertisements. In contrast, critics say that customers pay for advertising during higher product costs. They say that small organizat ions sometimes must close as they cannot fight with larger ones. Through advertising, persons sometimes buy goods that they cannot require and often may not afford. This guides to a high personal debt. It also guides to a casual society products are thrown away and more waste and pollution is produced. Children are so often the main aim of advertisers. They sometimes do not recognize which products are good and buy wrong things. Fast food and snack firms show ads, which guide to diabetes and obesity. Direct Marketing Pros & Cons Direct marketing contains direct trade. So it is cost helpful for customers, because there is no cost hike due to retailers or wholesalers. Marketing managers may state certainly of the correct answer to their goods. The profit or loss may be extra correctly judged. In contrast, it can be seen as attack of privacy, as consumer questions where we increased their private details. And negative figure of direct mail and not needed phone calls. â€Å"Relatively expressed due to high costs of making direct contact rather than the broad approach of advertising† (Somers, Cain, and Jeffery 335). Sales Promotions Pros & Cons: By running a sales promotion, a business owner can increase the sales and also improve the bottom line. Sales promotions have the prospective to develop relationships with customers and also the suppliers. One of the advantages of using sales promotions is that it influences customer behavior. The thought of the sale may well influence the consumer to do a purchase when they were not planning to do so. The notion of missing out on the

Energy use in developing countries ((In indea )) Research Paper

Energy use in developing countries ((In indea )) - Research Paper Example The countries that are under industrial revolution are three to four times less in energy consumption than the developing states. Energy supply is based on coal, whereby, the developing countries tend to rely on coal in conjunction with renewable energies rather than nuclear energy as gas and oil (Verma, 2008, P.124). Strategy documents for the reduction of poverty are hitherto under the control of the energy cooperation. Furthermore, there is framework strategy of cooperation that is; aspect in horizontal war where the basis is of two factors, reform of energy, and technology transfer. Moreover, there is demand-side and the supply-side cooperation. Diversification of energy is essential in that it enhances the use of different types of energy other than relying on the primary source such as gas, oil, and fossils. Long-term objectives are in place to guarantee the access of core energy servicing to individuals for a longer period of term (Anderson, 2008, P.87). Development plans of India should have horizontal energy integration in order to manage the long-term strategy. Furthermore, the institutional support should offer technical networking and assistance. The energy systems have several polluting factors that are alarming. They can cause harm to an individual, and if not put into consideration, its impact is massive. Some of the factors include; A-Bo, this contains elements like abatement, activism, and Addams that are harmful. In addition, there is air pollution which has hence put into propel the air pollution control act. Other factors might be br-co, co-ea, and the ec-fi factors. This is converter by a catalyst, the diesel dilution and lastly the electromagnetic fields, which usually cause harm to human era (International energy agency, 2009, P.2009). It is pertinent that the renewable energy and wastes forms about one fourth of energy use in India. Coherently

The Lottery by Shirley Jackson Essay Example for Free

The Lottery by Shirley Jackson Essay The Lottery written by Shirley Jackson tells such a story: There is an ancient traditional annual event held in a small town in America. Anyone who wins the â€Å"lottery† will be stoned to death for harvest. Tessie is the new unluckier this time, who has to suffer this cruel and inhumane punishment. Seen deeply, females’ inferior position is showed elaborately in this novel. First, the appellation to females shows that they are in subordination to males. â€Å"Mrs. Hutchinson came hurriedly along the path to the square† (Jackson, 2), â€Å"she said to Mrs.   Delacroix† (Jackson, 2), â€Å"Mrs. Dunbar said regretfully† (Jackson, 3). Here â€Å"Mrs. Delacroix†, â€Å"Mrs. Hutchinson† and â€Å"Mrs. Dunbar† all suggest that one female cannot be an individual being after her marriage, since she has to be a part of her husband by calling her â€Å"Mrs†. When Tessie comes lately, the villager’s addresses that â€Å"Here comes your Missus, Hutchinson† (Jackson, 2) instead of calling her own name also shows that she has become a subordinate object for her husband. Just like Lakoff says in his book Language and Womans Place, â€Å"It is with Mrs, Miss, and Mr.  Since a significant part of the opinion one normally forms about a womans character and social station depends on her marital status as is not the case with men† (Lakoff, 73). This phenomenon is common all over the world. Why don’t males change their appellations like female do? Actually, the marriage cannot change anything but the couple’s new relationship and family lifestyle. So does a female have to compromise to become her husband’s stooge? Perhaps only when she makes accomplishment can she be introduced as an independent individual. Those who are satisfied with their status quo are likely to accept the new subsidiary address. Thus, females’ subordinated appellations gradually become accustomed. Second, the role of being a housewife unconsciously influences a female’s equal right to fulfill her own accomplishment. In the novel, â€Å"Mrs. Hutchinson came hurriedly along the path to the square, her sweater thrown over her shoulders†¦ â€Å"Clean forgot what day it was,† she said to Mrs. Delacroix†¦She dried her hands on her apron†¦Wouldnt have me leave mdishes in the sink, now, would you, Joe? † (Jackson, 3) Tessie’s words and the act of â€Å"drying her hands on her apron† suggest the female’s low social position at that time. Obviously, if she does not â€Å"win the lottery†, her next work is to rush home and serve meals for the family, since the traditional allocation of family roles has subsided into an established social norm: once a woman is married, she will give up her career and play the role of a housewife, heart and soul. So how can a female have more time to do something more prominent fulfillment since she has been limited into such situation? It’s no wonder that females do not share the equal position to do something more meaningful to some extent. Just like Journalist Ruth Franklin subtitled her 2010 piece in The New Republic: â€Å"On Shirley Jackson and the challenge of being both a mother and a writer† (p. 1). She says, â€Å"In the 1950s, just as much as now, women can only write when the baby naps, or while the children are at school, or after the dishes are done and the lunches are packed and the house is, at last, quiet. This sort of logistics has always worked with efficiency, once the woman understands that no matter how smoothly the thoughts are flowing, they will have to stop when the school bus comes. It works as a resignation to frustration† (FRANKLIN, 2010). It’s easy to perceive that Shirley Jackson’s writing career is somewhat influenced demonstrably because of her female identity. Being both as a mother and a wife, she has to regard her career—writing as the secondary mission to the family. The embarrassing situation she faced is linked with any females at that time. Thus, the role of being a housewife unconsciously influences a female’s equal right to fulfill her own accomplishment. Third, females don’t have the power to make decisions. As it is showed in the novel, males govern all the affairs, â€Å"The lottery was conducted by Mr. Summers; The postmaster, Mr. Graves carried a three- legged stool; Mr. Martin†¦ came forward to hold the box steady on the stool† (Jackson, 1). Three most powerful men dominate the whole village politically and financially. â€Å"There were the lists to make up of heads of families, heads of households in each family† (Jackson 2), which suggests the male’s dominant position in a family. Moreover, â€Å"Dunbar’s wife substituted him to draw the lottery because he had broken his leg, but Mr.  Summers asked whether she had a grown boy to do it† (Jackson, 2) also shows that the unusuality of a female to do such an essencial and decisive thing. In the end, Tessie’s death is another evidence to show that female is not only inferior, but a victim in that lamentable social circumstance. Having no rights to make decisions, females doom to be decided instead of deciding. Thus, the female’s inferior position has formed. In a world, females’ inferior position is shown elaborately in The Lottery. Their appellations, their family division of the labor and their no power to make decisions all display the inferior position of females.

Should Models Have a Minimum Weight Limit Essay Example for Free

Should Models Have a Minimum Weight Limit Essay When we have a job that we love, we want to keep it no matter what. That’s understandable, but we have to be careful how far we actually go in order to keep it. There are things much more important than any job in the world like our health. Even for those who’s jobs, looks are everything. We all want to look our best at all time, especially if we are in the modeling business. There have been many issues with models and their ways of losing weight. These models have eating disorders that can truly harm them. The way that they do their weight lost can have terrifying consequences. These consequences many times cause them their lives or threats just as delicate. Due to all these horrible deaths and serious threats to models health some argue that a minimum weight should be mandatory. They want the models to not be one pound under the healthy weight limit that they require. The problem is that not everyone agrees. Anonymous people argue that models look great while advertising just the way they are as an now. Some argue that if models have a minimum weight limit and it’s passed as a requirement many ordinary people are going to want to go into the modeling business. The other argument is that the models will have to wear always closed clothing, since they will look horrible in a bathing suit. Another point made by the once against minimum weight is that not all models have the same height. They argue that how will they have the same minimum weight if they have different hight. There arguments are said that models are made to be thin and thats the way they should stay. I have to say to the once that are against it that no one argues that they don’t look great while advertising something on television or magazines now, but as good as they look a couple pounds more won’t make a difference. These models are great models that don’t do great at their jobs because of their weight; they do great at their job for the way they model. These models are great at their job for the way they walk, the way their makeup looks, and wearing all the beautiful clothing that they advertise. When they say that ordinary people are going to want to become models they make it sound like it’s a bad thing. In reality that is a good thing, the more models the more business. The more models that we have the more clothing and products that companies get to advertise. Also due to that models are meant to be skinny we don’t have many models left, and the models that are modeling as an now many are in serious danger for having eating disorders. If models are a couple pound heavier that doesn’t mean that they can’t wear bathing suits. I don’t believe that they would look horrible I actually think that it would help the company sell more bathing suits if they are seen on models who don’t look like walking sticks. The truth is that not everyone wears a bathing suit because we don’t feel confident since we don’t look like the models who advertise them. Although if we see the product on people who aren’t as thin we will gain that confidence and the company will sell many more products. It’s very true that not all models have the same height, but that shouldn’t be a problem. The minimum weight limit can be based on height and any other circumstances. It is very important that all models have the same requirements and very understandable that this statement has been given by these anonymous people. I understand the point that they are trying to make, but of course if a model is going to be told how much they have to weight there will be taking the hight, body fat, and muscle weight all into consideration before deciding their minimum weight. To all models the requirement will be the same and their minimum weight will be determine as an individual. Models are made for modeling thats why they are called models. They are not exactly made to be thin. There is a huge difference between thin and unhealthy. People who think that models are made to be thin are’t thinking that because of people who think that way is usually why models fall into eating disorders. Models should be able to model staying in figure, but with a healthy weight that won’t harm them. All these points made by anonymous people are regardless pointless thats probably why they stay anonymous. If they truly believed in the points they are making they wouldn’t stay anonymous Many models take it too far, risking their lives. Many models do many unhealthy things to fit into a size zero and that just bring bad health problems. Nineteen year old Cover Girl model Bethaney Wallace dies of anorexia and bulimia (Andrew Levy). She started with these eating disorders since she was sixteen. These eating disorders weakened her heart until one night she died in her sleep at age nineteen. Three years she suffered trying to be thiner that she already was. This was a young girl who couldn’t see how beautiful she was and became anorexic and bulimic making every meal a crises for her. Bethaney was 5feet 3inches and weighted only 94 pounds (Andrew Levy). In 2006 another famous models dies as consequences of her eating disorder (Tom Phillips). Ana Carolina Reston was a Brazilian model who was warned she was fat at 112 ponds, ever since then this beautiful model stopped eating until she starved to death. Ana was 5ft 6inch and died weighting 84 pounds (Tom Phillips). Isabelle Caro was another beautiful model who dies due to anorexia, she was told by Parisian modeling scout that in order for her to â€Å"find a job she needed to lose 10 pound† (Barbie Latza Nadeau) and she did, she quickly lost 20 pounds she ended up weighting 55 pounds. Isabelle was 5ft 4inch tall with a weight of 55 pounds, she ended having to go to the hospital due to her rapid weight lost, Isabelle was in the hospital in comma for months (Barbie Latza Nadeau). It’s a shame to lose such beautiful models just because they consider themselves fat when in reality they are to skinny I truly believe that all these deaths have a solution, because besides from the models I have mention previously there are many more models who die due to their eating disorders. The solution is for the minimum weight limit to become a requirement. The minimum weight limit will make all modules feel comfortable by the way they look because they would look exactly how they were told but in a much healthier way. Having to weight at least the minimum weight should be come a requirement because, by reinforcing a minimum weight limit and making it one of the prerequisites for being or become a module all the modules who love their job will do their best to meet all the requirements. If models are conscious that if they weight less than they are supposed to they will keep themselves at that weight in order to keep their job. This will help models all around the world to become healthier and it will also help prevent all these deaths because of their eating disorders.

Treating Cystic Fibrosis with Gene Therapy

Treating Cystic Fibrosis with Gene Therapy In this dissertation we shall consider the field of gene therapy in specific relation to cystic fibrosis.   We examine the different delivery vector mechanisms that have already been explored and concentrate primarily on the adeno-associated vectors. We examine the current state of research and consider the advantages and drawbacks of the various methods considered. We conclude with a discussion and analysis of our findings and   make anumber of assumptions relating to the future direction of the researchin the field.   The rate of progress in the field of gene therapy has been enormous. We must remind ourselves that the first clinical gene transfer experiment took place in 1989 when a patient with malignant melanoma received genetically modified auto logous T cells. (Rosenberg SA et al1990) Gene therapy encompasses two major areas. The in vivo field, where genes are incorporated into the target cells of the living body and the ex-vivo field where the target cells themselves are genetically modified outside the body and then re-implanted. Medical science has been using the basic techniques of gene transfer for a long time. The technique has been exploited when viral genes are introduced to human cells when a viral vaccine is administered. The key technologies that allowed the transition from vaccination to gene therapy were the evolution of methods that allowed the genes to be isolated and replicated (cloned) and manipulated (engineered) prior to transfer into human cells (Freeman SM et al 1996) The key principle in this process is the efficient transfer of the manipulated therapeutic genes into the nuclei of target cells usually be means of various vectors. This dissertation will be considering the utilisation of these vectors in some detail. In broad terms, the new or modified genetic material is able to produce new proteins which can restore deficient or abnormal functions of genetically diseased tissues, to generate tissues that have entirely new properties or to create transplantable tissues for the controlled release of therapeutic proteins. (Russell SJ  1997) In terms of viral vectors, prior to 1996 science was dependent on the use of modified retroviral vectors (eg.MMLV) to effect gene transfer into the chromosomes of a target cell and the adenovirus vectors when such integration was not needed. Neither vector was particularly successful as the intact nuclear membrane (in then on-dividing state) was a major barrier for chromosomal gene integration. (Sikorski R et al 1998). A breakthrough came with the realisation that lentiviruses (e.g. HIV) have the same ability to transfer genetic coding into the cellular genome but could do this in the non-dividing or dormant phase cells. (Amado R G et al 1999) In vitro, lentiviruses have been shown to change the target cell’s expression of proteins for up to six months. importantly, they can be used for terminally differentiated cells such as respiratory epithelium. The only cells that the lentivirus cannot penetrate the nucleus are those in the quiescent (G0) state as this blocks the reverse transcription stages of protein synthesis. (Amado R G et al1999) Cystic fibrosis Cystic fibrosis is the most commonly lethal inherited recessive inthe caucasian population. It affects about 1 per 2,500 livebirths. Thetreatment of cystic fibrosis has improved enormously in the last fiftyyears with the life expectancy increasing from an average 10 years to30-40 years now. The prime cause of death in affected individuals is the repeatedcycle of infection, inflammation and fibrosis of the respiratory tractwhich eventually culminates in respiratory failure and death. The disease itself is caused   by mutations in the single gene forthe cystic fibrosis transmembrane conductance regulator (CFTR) whichproduces a protein found in sweat and pancreatic ducts, gut,seminiferous tubules, lungs and many other tissues. The mutationsresult in an abnormal protein which, when expressed in the lungs,produces thick viscous and dehydrated secretions. This does not allow for the efficient expulsion of bacterial pathogensfrom the lungs and a number of highly resistant forms of bacteria arecommonly found in cystic fibrosis (viz pseudomonas aeruginosa)(Porteous DJ et al 1997). An individual must receive a defective copy of the cystic fibrosisgene from each parent in order to develop the clinical picture ofcystic fibrosis. Following normal genetic principles, if two carriersconceive a child, there is a 25% chance that it will have cysticfibrosis, a 50% chance that it will be a carrier and a 25% chance thatit will have two normal cystic fibrosis genes. Viral and non viral vectors Viruses have an ability to enter a host cell and combine their owngenetic material with that of the host cell. This is the basicrationale behind the science of gene transfer therapy.   As we shalldiscuss in some detail in this dissertation, there are a number ofpotential viral vectors that have been explored, evaluated andexploited in the search for an efficient and safe form of therapy.Viruses are not the only vector that can be utilised . Simply placingDNA in the nasal mucosa will produce some incorporation into theepithelial cells (Knowles MR et al 1998). This â€Å"absorption† can bedemonstrably enhanced further by the combination of the DNA withvarious plasmid or lipid complexes(Zabner et al 1997) The advantages of lipid or plasmid assisted transfer mechanisms arethat they do not appear to generate the immunological responses thatare seen with the viral vectors. They can also be used to facilitatethe transport of much larger pieces of DNA which would otherwise belimited by the packaging consideration incumbent on the viral vectors.(Felgner P 1997). The use of retroviral vectors is far from straightforward. The heavilypublicised case in April 2000 brought some of the problems to theattention of the media. A retroviral manipulation of   a case of X-SCID(X linked severe combined immunodeficiency) was treated by gene therapywith an apparent degree of success (BBC 2002). This particular diseaseprocess is caused by a mutation on the gene which codes for the C chainof the cytokine receptors which is situated on the X chromosome andvital for the functional development of T Killer lymphocytes which aretherefore completely absent in the condition A multinational team used a retroviral vector to insert a functionalcopy of the gene into bone marrow stem cells which were thenre-transfused back into the patient. (Cavazzana-Calvo M et al 2000).This particular case resulted in a return to normal levels of T cellsin a comparatively short period of time. This was hailed in both thepopular media and the peer reviewed journals as a major success and itcan indeed be considered a landmark as it pioneered the successful useof an ex-vivo procedure that avoided direct in vivo transfer of thevector. The reason for specifically highlighting this particular case isthat following the initial optimism of the clinical team, two of thefirst ten patients with this condition who were treated in the same waysubsequently developed a leukaemia-like illness. Genetic analysis ofthe malignant cells suggested that the retroviral vector used in thetransfer had also activated an oncogene LIM-only2 (LMO2) which is knownto be associated with some forms of leukaemia. The clinicians reviewingthe situation felt that, although it was not the only cause of themalignancy it was one of the events that triggered it. Similar concernshave been raised in respect of other clinical trials. (Lehrman S 1999) The prime reason for presenting these events is to demonstrate thefact that there is both a theoretical and practical risk of insertionalmutagenesis. Reduction of the risk requires greater specificity of thetargeting of the genetic deficit   perhaps by directing the expressionof the therapeutic genes to various specific tissues utilising bothtransductional and transcriptional targeting. Relph K et al 2004), In terms of specific considerations of the arguments in favour of theuse of retroviral   vectors, one can cite the fact that they have ahighly efficient mechanism of gene transfer together with lowimmunogenicity. It is a well researched and well studied system and isknown to selectively infect actively dividing cells. The conversearguments reflect their disadvantages including their ability todisturb or activate oncogenes, the fact that they are difficulty tospecifically target and it is difficult to obtain high titres in theclinical situation (after Olsen, J. C. 1998). In broad terms, the principles behind the use of retroviral vectorsare that they must be modified in order not to be able to transmit anyovertly pathological coding. This involves the deletion of viral helpergenes such as gag, pol and env   to render the replication processinvalid. This is done by utilisation of a producer or packaging cellline. (Nichols, E. K 1998). An example of a commonly utilised and extensively researched vector isthe MoMuLV. It is an engineered vector which can store 8 kb of RNAwithout compromising packaging efficiency. It is a hybrid cell lineeasily grown in mouse fibroblast cells There is a subdivision of the retroviral vectors known as thelentivirus, which is the only retroviral vector capable of integratinginto the chromosomes of non-dividing cells. This has been effectivelydemonstrated in vitro (Naldini L et al 1996).    The biggest problem with the lentivirus vectors is that theyappeared to only produce very low titres. Some recent researchsuggested that a modification to a amphotropic envelope protien wascapable of allowing higher titre levels. (Rolls M et al 1999) At about the same time that the scientific press was learning aboutthe problems with retroviral transfer (see above) other investigatorswere working with adeno-associated viruses (AAVs). A similar processwas invoked using adeno-associated viruses to correct a genetic defectinvolving coagulation factor IX. The adeno-associated viruses were usedas they were considered to be amongst the safest candidates for genetransfer. They do not naturally cause disease processes in humans andhave only rarely been found to incorporate in a random fashion into thehuman genome. Although it is noted that adenoviruses do cause oncogeneactivation in rodents although it has not been found in humans(Blacklow NR 1988).   The trial had a very positive outcome. (Kay MA et al 2000), but thetrial author (in later research work) published a study which suggestedthat, in study mice, the vector used in the trials actually integrateditself into gene containing regions of DNA more frequently that it didinto non-coding regions (Kay MA et al 2003). The findings were reportedas the fact that new genetic material was randomly distributed amongstall of the chromosomes particularly at sites of gene activity. On thisbasis, there appears to be at least a theoretical basis for thepossibility of similar cellular defects such as occurred in the X-SCIDpatients. Adenoviruses are comparatively simple structures. They arecategorised as double stranded DNA viruses. They have icosahedralcapsids with twelve vertices and seven surface proteins. The virionitself is spherical and non-enveloped and in the region of 70-90 nm insize. Their natural history is that they are spread easily in the naturalstate by the faeco-oral route and also by respiratory inhalation whichclearly has great implications for the treatment of cystic fibrosis. A theoretical analysis would immediately suggest that the adenovirus should be a suitable candidate for gene therapy as they can codefor specific proteins and they do not produce infection pathogenicviral offspring.    The early trials into this particular area were reviewed by Griesenbach(Griesenbach U et al 2002) who pointed out that the cystic fibrosisgene was first cloned in 1989 and in the subsequent   years, 18different trials were carried out, all with rather low degrees ofsuccess. They collectively trialed three different vectors, namelyadenoviruses, adeno-associated viruses 2 and cationic liposomes, andalmost universally found that each vector had a very low rate ofclinically significant gene transfer and none was sufficient to achieveclinical benefit    Plasmid Complexes At its most basic level, a plasmid is a small accessory collection ofDNA which is found in the cytoplasm outside of the nucleus. They arecapable of independent replication and can be manipulated with rathermore ease than nuclear DNA. Early investigations into the field of gene transfer explored thepossibility of plasmid vectors   and demonstrated the feasibility of themethod to effect CFTR gene transfer in vitro (Alton EW 1993). Otherteams had demonstrated the fact that, in clinical use theplasmid-liposome is both nontoxic and non-immunogenic (Hyde,SC et al1993).   This appeared to raise the possibility that many of theimmunological problems encountered by teams working with viral mediatedgene transfer mechanisms might be circumvented. In vivo work (Yoshimura,K et al. 1992) had demonstrated that genescould be transferred into the cytoplasm by this method and Stribling, R(et al 1992) demonstrated that, once there, they would then replicatenormally. Alton experimented with a CFTR-plasmid preparation in miceand demonstrated that it was capable of correcting the chloride levelsin cystic fibrosis mice back to normal levels (Alton EW 1993) Although the initial results were encouraging, clinical trials weredisappointing as the plasmid complex could not easily penetrate thethick mucous residues in the diseased lungs of patients with cysticfibrosis. (Erickson,R 1993) The plasmids typically have a positively charged head-group which isable to bind to the DNA strand and a hydrophobic tail group whichfacilitates the transfer of the complex across the cellular membranes.Initial studies suggest that   between 100-1000 times more DNA isrequired to effect successful gene transfer when this method iscompared to viral vectors. (Santis,G et al 1994). One alternative adaptation has been reported by Stern M (et al 2003)who points out that one of the solution of delivery is to ensure thatthe respiratory epithelium is exposed to the DNA over a long period.Their solution was to encapsulate the CFTR-plasmid in a slow releasebiocompatible polymer. Clinical trials are underway but not yetreported. The adeno-associated vectors appear to have (at least on atheoretical basis) a number of advantages over the vectors that we havealready discussed. They are based on a virus vector that is alreadynon-pathogenic (Berns, KI et al 1995) and has a mechanism that allowsit to be a long-term persistent entity in human cells (Blacklow, NR etal 1989). The adeno-associated vectors are particularly useful indealing with disease process that involve single gene mutations. This,therefore   makes it particularly suitable for single gene disorderssuch as cystic fibrosis and alpha 1 antitrypsin deficiency. (Flotte, TRet al 1998). In addition, some workers have also developed vectors which are capableof   producing either inducible or constitutive expression of thecytokine, interlukin-10   (IL-10) which is an importantanti-inflammatory protein which, on a theoretical basis, could beuseful not only in cystic fibrosis   but in other disease process whichhave chronic inflammation as their prime manifestation (viz Type Idiabetes mellitus or inflammatory bowel disease) (Egan, M et al 1992).These manifestations have been studied and have now reached the stageof early clinical trials (Wagner J et al 2002). With specific reference to the implications of cystic fibrosis, wecan point to trials which have resulted in the expression of cysticfibrosis transmembrane conductance regulator (CFTR) from rAAV(recombinant adeno-associated vectors) in cell cultures (Flotte, TR etal 1993), in animal models (primates) (Afione, SA et al 1996), andagain in early phase I clinical trials (Wagner, J et al 1998) The rAAV-IL-10 model has been studied in bronchial cell culturesfrom cystic fibrosis patients, to determine the functional consequencesof CFTR complementation. This has not yet been demonstrated in vivowith humans but in both mice (Song, S et al 1998), and monkeys (Conrad,CK et al 1996) The overall results of these (and other) studies have shown that   itis possible to achieve long term gene transfer and functionalexpression of the replaced gene (some studies for as long as 18 months)without any overt pathological findings. The histological findings are something of a surprise however, as,at least in both primate and mouse studies, the vector-introduced DNAin this form does not appear to be assimilated into the geneticmaterial of the chromosome, but persists in log strings or concatemersthat are episomal, which is in complete contrast to what happens whenthe naturally occurring agent infects the cell. There is some evidenceto suggest that host cell intrinsic factors such as DNA-dependentprotein kinase play some role in this process (Song, S 2001). The significance of this finding could be that the exclusion of thefunctional, newly introduced DNA from the rest of the nuclear gene poolmay be less likely to produce effects that could be either potentiallydisruptive to the host cell and less likely to activate oncogenes.Phase I trials have demonstrated significant rises of CFTR levels inboth sinus and lung tissue with no evidence of vector-related toxicity.(Wagner, JA et al 1999)   The adeno-associated vectors are constructed from proviraladeno-associated vectors plasmids, which have the Rep and Cap proteinsdeleted and substituting the appropriate gene (CFTR or equivalent)between the rAAV2 inverted terminal repeats together with other signalsequences such as promoter and polyadenylation sequences (Flotte, TR etal 1994) The packaging processes allows for about 5 kb of rAAV genomes to becarried   in the vectors which are prepared using a cotransfectiontechnique utilising human embryonic kidney cells (HEK-293) where thevector plasmid is cotransfected into the cells with helper agents(plasmid pDG) being used to encode the rAAV2-rep and -cap genestogether with the adenovirus helper functions (Grimm, D et al 1998).These are incubated for between 48 and 72 hrs. The cells are then lysedand the resultant agents are then separated by ultracentrifugationagainst a density gradient and affinity chromatography (Zolotukhin, Set al 1999).   The vectors are thereby amenable to being separated by both theirphysical characteristics and also their biological characteristics(infectious units). They are carefully screened to ensure the absenceof any possible contamination from non-modified (replication competentAAVs) prior to clinical usage. (Muzyczka N 1994) The comparatively small â€Å"payload† of the adeno-associated vectorsis proving to be a significant problem. The vector itself is small whencompared to the comparatively large size of the CFTR gene. (Flotte TRet al 1993) It does not leave any room to manoeuvre to manipulate thevector-specific sequences in the way that we have described with theretroviral and adenoviral groups. (Flotte TR et al 2001). A number of authors have characterised the problem with theobservation that the rAAV is typically about 20 nm across which allowspackaging of about 4.7 kb (kilobases) of transferable modified gene(exogenous DNA). (Dong JY et al 1996), If   it is combined with otherenhancers such as the promoter, the polyadenylation signal, thisclearly reduces the capacity for the DNA component. (Duan D et al2000). The Yan paper (Yan Z et al 2000) has outlined a novelexploitation of the unique ability of the rAAV genomes to link togetherin strings which appears to have the ability to bypass this particularlimitation.( Flotte TR 2000). The mechanism itself is the capacity of two distinct rAAV genomes thathappen to simultaneously infect the same target cell to undergo anintermolecular recombination insider the transduced nucleus of thetarget cell. This was a chance finding which arose from work involvingrAAV-derived episomes (Kearns WG et al 1996) in primate airways. It wasfound that some of these episomes were configured as circular head totail concatemers (Duan D et al 1999). This could have been either froma â€Å"rolling circle† replication from a single vector or alternatively,from an intermolecular recombination of material from multiple cellularpenetrations which combined within the palindromic inverted terminalrepeat sequences that are an intrinsic part of the AAV genomestructure. The authors were of the opinion that it was likely to be thelatter eventuality (Duan D et al 1998) It was a logical progression to try to exploit this phenomenon andthereby bypass the limitations imposed by the relatively smallpackaging capacity of rAAV. The adeno-associated vectors capsid onlyhas a capacity of about 5 kb. If we consider that the 145 nucleotidestretch of the AAV-ITR (inverted terminal repeat) sequence has to be inplace at both ends of the single-strand DNA for the vector DNA to beboth replicated and packaged, this only leaves in the region of 4.7 kbof genetically active material in each rAAV particle. As we have cited earlier in relation to the Dong paper (Dong JY et al1996) the CFTR gene accounts for about 4.5 kb which leaves very littlespace for other enhancing material. Because of this, the actual CFTRvector that has been used in the clinical trials to date uses only theminimal promoter activity of the AAVs-ITR itself to actually activateand drive the CFTR expression (Flotte TR et al. 1993). To look at this potentially important development in a little moredetail we can consider Duan’s original paper (et al 2000) and theauthors describe what they call a â€Å"superenhancer†. They describe acombination of a potent simian virus (SV40) and CMV immediate earlyenhancer elements as being packaged in one rAAV vector and a luciferasegene assisted by a small minima;l promoter in another rAAV vector. Invitro experiments suggested that either the SV40 or the intrinsicpromoter activity of the AAV-ITR was sufficient for this purpose. Theintermolecular recombination described above, was found to occur inboth vitro and in vivo experiments and was found to be sufficient tohave a greater than additive effect. Initial results from these varying methods are encouraging insofaras they are producing results of transgene expression which are 100-600times greater than with the unenhanced vector alone. (Yan, Z et al2000) Although not directly referable to our considerations of cysticfibrosis, we should note that Yan’s group and other workers have doneexperimental work which has culminated in the long term expression offunctional levels of erythropoetin with this two vector method in micein vivo. (Naffakh N et al 1995), This basic principle has been further enhanced by Sun (Sun L et al2000) with an ingenious manipulation of the system. They triedinserting the promoter and the first half of the coding sequence in onerAAV vector, immediately followed by a splice donor and then theupstream half of an intron. In the other rAAV vector was the downstreamhalf of the intron, the splice acceptor, the second half of the geneand the polyadenylation signal. To quote the author verbatim: This strategy is efficient enough to mediate high-level expressionand the intermolecular junctions are apparently stable enough tomediate expression for several months in vivo. Although this is clearly an ingenious augmentation of the sameprinciple , we should note that there are both advantages anddisadvantages to both pathways. The strategy that adopts the superenhancer takes its strengths fromthe fact that the recombination mechanisms optimise theposition-independent and orientation-independent functions of theenhancers.   Consideration of the options would suggest that there arefour potential recombination outcomes from the process described.Either of the two vectors could be on the 5’ end of the heterodimericmolecule and clearly either molecule could be in either orientation. With the superenhancer option, all four of these possibleintermolecular recombination outcomes should be functional fortransgene expression whereas if compared to the split intron strategy,by using the same reasoning, it is clear that only one out of the fourcould work. On the other side of the argument, the superenhancer option has thedisadvantage that the actual coding sequence of the gene to betransferred must still fall within the packaging capacity of the vectoritself whereas the split intron allows for a greater functionalexpansion of the packaging capacity. (after Flotte TR et al 2000)   In either event it can be seen that these ingenious modificationseffectively eliminate the main size limitation of the rAAV deliverysystem. Although initial pre-clinical work is encouraging it appearsthat there is still some potential for a degree of immune responseparticularly if the host organism has not experienced the newlyproduced protein before. A number of studies have been done on animal (vertebrate andprimate) with only minimal success. Different administration methodshave been studied including direct administration into the lung (WagnerJ et al 1999), IM injection (Song, S et al 2001 B) and hepatic portalvein infusion (Song, S et al 2001 A)       Human clinical trials have taken place with these vectors (Flotte T etal 1996)(Wagner J et al 1998) (Virella-Lowell, I et al 2000). Thestudies were done on adult male and female patients (18-47 yrs) whowere pseudomonas free and had recently been hospitalised for IVantibiotic infusions The disappointing results were probably a reflection of the factthat the CFTR defect is also interconnected in some way with   aproinflammatory phenotype which appears to be triggered by the abnormalprotein via an unfolded protein response. The authors were able to showevidence that the rAAV-CFTR mechanism was able to   correct the proteinproduction defect, they found it clinically difficult to transduce asufficient number of cells in the airway to reverse the inflammatoryresponse. It is proposed to run further experimental work which combines the  CFTR expression with an anti inflammatory   gene such as the IL-10.There is some in vitro work to suggest that this may be a possibleworkable approach (Teramoto, S et al 1998). Other work on ways ofenhancing the phenotypic expression of the modified genotype hassuggested that the use of various promoters and the rAAV-CMV/beta-actinhybrid promoter (CB-AAT) was found to be tone of the most efficient, atleast when it was compared to the other tested options such as the CMV,E1, U1a and U1b promoter constructs (Teramoto, S et al 1998) Overall, the initial results appear to be encouraging. A singleinjection of an rAAV-CB-AAT vector in animal studies has resulted inhigh level, stable transgene expression which has persisted over thelife span of the experimental animals and that there was no detectableinflammatory response in the animals who had received this form oftreatment (Flotte TR 2002) Flotte (et al 2002) reports that four human clinical trials at bothPhase I and Phase II level are currently underway examining the effectsof the rAAV-CFTR vector. They had an entry cohort of seven patientswith the vector being applied to the nasal lining, the maxillary sinusand the bronchus. The authors report no adverse effects being found andthat they have observed transgene expression at doses of 6 x 108 drp inthe sinus or 1 x 1013 drp in the lung. There are no reported interimfindings from the Phase II trials as yet.    There is clearly a potential for clinical benefit on the basis of theresults found to date if one can extrapolate from in vitro and animalexperiments. The authors comment that, in contrast to the adenovirusvectors there is a marked lack of inflammatory toxicity with the rAAVvectors. Despite these positive comments, we should not, however, overlook thepotential limitations of this particular delivery system. These havebeen identified by various authors as:    The inhibitory effect of preexisting airway inflammation on rAAV transduction in the lungs (Virella-Lowell, I et al 2000) A relative paucity of receptors on the apical surface of airway epithelial cells (Summerford, C et al 1998), The relatively weak nature of the minimal promoters used in the first-generation rAAV-CFTR vectors(Flotte, TR et al 1993), The potential for adverse long-term effects from rAAV vector DNA persistence. (Wu, P et al 2000) The Flotte group are currently investigating this problem by examiningthe hypothesis that the barriers in the airways of the cystic fibrosissufferer are primarily   due to the neutrophil-derived -defensins (HNP1and HNP2) and are actually reversible by the mechanism of AAT proteindelivery (Virella-Lowell, I 2000) Wu and his co-workers have been looking at ways of manipulating thegenetic make up of the rAAV2 capsid and thereby trying to enhance thetargeting ability so that the vector specifically targets the serpinenzyme complex receptor on IB3–1 cells – which is virtually specificfor the Cystic fibrosis bronchial cells Zabner, J (et al 2000), have considered alternative rAAV serotypesin the hope of finding one that will bind more specifically to thebronchial cells Other peripheral adjuncts have also been explored includingpromoters to enhance the effects of complementation and superenhancerswhich have been shown to improve the ability of the rAAV toconcatermerise with the help of smaller amounts of promoter agents  (Duan, D et al 2000). Perhaps it is appropriate to conclude this section on considerationof adeno-associated vectors with a critical analysis of a very recentmulticentre, double-blind, placebo-controlled trial (Moss RB et al2004) This was a well constructed, fully statistically significant anddouble blinded trial which considered   both the safety and thetolerability of repeated doses of adeno-associated serotype 2 vectorrepeatedly given by aerosol inhalation. The vector contained â€Å"cysticfibrosis transmembrane conductance regulator (CFTR) complementary DNA(cDNA) [tgAAVCF], an adeno-associated virus (AAV) vector encoding thecomplete human CFTR cDNA.† The entry cohort was comparatively small with 42 patients, of whom20 received the active agent. A number of indices of airway functionwere measured. Of particular interest to our considerations in thisdissertation was the fact that   vector shedding was found in alltreated subjects up to 90 days after inoculation. And that all subjectswho received the active agent exhibited at least a fourfold increase inthe serum AAV2 neutralising antibody levels. Of the 20 treated patients, six subsequently underwent bronchoscopy.Of those six, gene transfer but not gene expression was demonstrated inall of them. On this basis, it would appear that the actual transfermechanism is effective, but there are other factors present whichappear to interfere with the subsequent expression of the gene in termsof protein production. The study did not comment on the possiblereasons for this. The authors were able to conclude that the delivery system workedwell with no evidence of adverse effects and that treated patientsdemonstrated an â€Å"encouraging trend in improvement in pulmonary functionin patients with CF and mild lung disease.† Lipid 67 We have discussed the various shortcomings of the virus-associatedvectors and this has prompted researchers to explore and consider otheroptimising options for facilitating gene transfer. Zabner (J et al1997) considered the use of cationic lipids in this process and foundone   GL-67:DOPE (colloquially known as lipid 67) which appeared to beparticularly helpful in the process. Cationic lipids appear to show a degree of promise as possible vectorsfor CFTR cDNA transfer into respiratory epithelial cells