Advantages and Disadvantages of A Single Sex Education

Why would anyone want to go to an all girls' school? This is a question I have often pondered. Can you imagine school without the obnoxious comments from boys, football games, and gossiping about boys? This doesn't sound like a lot of fun, does it? You girls may think about this and decide there are no advantages to an all girls' school, but in reality, all girls' schools have many. Believe it or not, having boys around is not the most important factor in our education. In fact, boys in the classroom are actually a setback. All girls' schools are more advantageous than coeducational schools because there are fewer distractions, you will have a higher self esteem socially and academically, and you will be more successful academically. Let's face it, we are obsessed with boys. We act and dress with only a boy's opinion in mind. Boys not only preoccupy our minds in a social setting, but in the classroom as well. We know that we know the answers to the questions in school, but we often avoid raising our hand in class. Why? We are afraid that the answer might be wrong, and the boys will laugh at us. Even worse, we might be right, and then they will think we are nerds! We also must confess that we tend to space out during lessons and daydream about the star quarterback two seats over. These distractions could be eliminated if boys are removed from the setting. Without them, we could focus on education rather than what they think of us. Self-esteem is another issue that will improve with the absence of the male species in the classroom. In high school, there is an extreme amount of pressure to fit in. Some may not fit in, and some prey on others in order to fit in and increase their own self esteem. Usually it is the boys who will tease us, whether it's because they like us or they want to get a laugh out of their friends. This teasing can crush our confidence and cause us to become very self-conscious. Without boys, we can confidently walk down the hallway without dodging annoying boys who relentlessly torture us. Some may say, â€Å"What about other girls? † Girls can definitely be cruel and catty, but usually this bitterness towards another girl sprouts from a boy, whether she stole your boyfriend or he likes her better. How many times have you found yourself gossiping with your friends about how you are much prettier than the girl your crush likes? Girls would get along better if there were no boys around to fight about. Boys will not get in the way of friendships, which are far more important than relationships, making the high school experience much better for a girl. A single sex atmosphere will also increase our self-esteem academically. Studies prove that women do better in single sex schools and have higher self-esteems (Cooner, Knight, and Wiseman 90). In coed classrooms, boys receive more attention, whether it is criticism or praise, than we do (Cooner, Knight, and Wiseman 91). How often does a teacher stop a class to yell at a typically obnoxious boy? We therefore feel ignored by our teachers. This has a dramatic effect on our confidence in the classroom. In an all girls' school we can receive our teacher's attention more frequently and ask questions without feeling embarrassed. More attention means more praise, which we clearly deserve. The increase in attention from our teachers will help to increase our academic self-esteem. The most important advantage of an all girls' school, however, is academic success. Did you know that coed schools are structured around the development of male students? Writing, reading, and math concepts, such as long division, are introduced to us when a boy's mind is ready to process and understand the information (Cooner, Knight, and Wiseman, 90). The fact that we were developmentally ready to understand this information a few years ago is ignored. I find that completely unfair and I'm sure that you can agree. Girls develop math and verbal skills faster than boys do, so we rarely experience any challenges in the classroom. No wonder we are so bored! Our boredom can negatively affect our achievement. I reiterate the fact that the teachers often ignore female students, even high achieving females. This discourages us from exerting ourselves in their schoolwork. Why bother pulling an all-nighter preparing for a presentation when a boy is going to receive more attention for his presentation anyway? An all girls' school is structured around our development, which poses an academic challenge to us. We will then strive to succeed and in turn receive praise from our teachers. Our increased interest in our schoolwork improves our attitudes as well as our grades, which will help us in the future. Better grades will increase our opportunities to attend good colleges and get good jobs. Our increase in confidence will prepare us for these jobs that we will be able to get with a good education. You still may not be convinced that an all girls' school is better than a coeducational school because you are wondering how it's possible to meet boys if they are not in school. Don't worry girls! There are tons of places to meet boys. There are boys everywhere (except in all girls' schools of course) including the mall and your neighborhood. Let's consider another fact. If an all girls' school exists in your town or nearby, chances are an all boys' school is not far off. If not, where would all of the boys go? Trust me, the boys are looking for us girls as much as we are looking for them. Clearly, this issue is not an obstacle in your social life. Life without boys? It sounds worse than it really is. You can now see that having boys in the classroom is a setback for us girls. Without them around, we can focus on our valuable education. We will have all attention focused on our work and our needs, which is very beneficial to receiving an effective education. We can also focus on forming friendships with other girls in the school without worrying about them stealing our boyfriends. Catty gossip can be eliminated from everyday school life, allowing us to fully concentrate on our education. Our education should be our first priority in life, and an all girls school in turn makes us their first priority, improving the quality of our education.

My Life Goals

Pete Blankenship Mr. Letz English 101 25 September 2012 My Life Goals I’m eighteen years old and my birthday is on February 23, 1994. My name is Thomas Earl Blankenship IV, but I go by Pete. I am from Mobile, Alabama and I live on Dog River. I played soccer, basketball, and ran cross country in high school. Soccer is my favorite sport and the team I was on in high school won the state championship twice, and I got named MVP the past two seasons. I have two little brothers Murray(17) and Jack(14). I also have an older sister Katherine(24). Being the oldest boy in the family is challenging sometimes but its a responsibility that I love to have.I attended a military high school called UMS-Wright, and their code of conduct was very strict. My life love is music and my ultimate dream is to become a music producer in Nashville, Tennessee. My goals on a short term scale for this semester are primarily academic, emotional, spiritual, and personal/professional. By the end of this semes ter I will have accumulated a g. p. a. of a 3. 5 or higher. To do this I will have to give up nights with friends and partying, but I believe it will all be worth it. I want to have a fantastic resume academically. My personality and work ethic are what I think will gain me the career choice that i desire.Another goal I will have achieved by the end of the semester is to find a group of people that I can play music with and practice my recording abilities with. I want to do this because music is the love of my life and without it I think I would be depressed. It’s too soon to tell if life without music effects me emotionally or spiritually because it has only been a few weeks in college, but it has been something that will always cheer me up in bad times and relieves stress when I am feeling overwhelmed. I want to find people to play with to achieve my personal goal of becoming a music producer in Nashville.A goal on a spiritual level is to grow stronger in my faith with Chri st. I have always been a relatively religious person, but I have noticed that when I am not being made by my parents to say my prayers and go to church it is much harder to do so. After coming to the realization that a relationship with Christ is something that I believe I need to be truly happy, I have a set a goal to go to my fraternities bible study every week and to begin going to Campus Crusade. By the end of the year my goals are to finish the year with a minimum 3. 5 G. P. A. to have a house reserved and have selected roommates that I believe will better me as a person, to have achieved at least 80 hours of community service, and to be playing with a band for money. I need to finish with a great G. P. A. because grades are important to me and are a small symbol of your work ethic, so that my resume looks well enough to get the interviews and opportunities that I desire. I want to have 80 service hours to have an outstanding and philanthropic resume. I also want to be a lot mo re frugal with my money and begin playing gigs for money to earn an income and become more responsible.I also want to have accepted and be on the way to an internship in Nashville, Tennessee that I was offered last summer. These final goals I hope to be completed by the time I am 45 years old. I will have a small family in Mobile, Alabama. I will own a recording studio out of Nashville, Tennessee that I can manage from Mobile. I will be able to do this because most music production can be done online and sent through the internet through email. I will also be a millionaire by this point through smart stock investments. I will be known as a man of character and integrity, through honest business transactions and kind actions.I will be a spiritual leader in my family and my community. I will achieve this reputation through a strong group of Christian people to keep me accountable for my actions. My life goals are very important to me now that I am in college. I feel much more obligate d to continue trying my best and staying responsible. Now that there is added pressure to be my best and school is not just school now, it’s training for a career. I will do my best to accomplish my short term goals and continue to gain ground on my ultimate goal of owning a recording studio and achieving happiness through my walk with Christ and providing for my family.

Causes of Unemployment Essay

There are many quotes about unemployment according to Calvin Coolidge unemployment occurs ‘’When large numbers of men are unable to find work unemployment results’’. According to Frank P. Louchheim ,  Ã¢â‚¬â„¢Ã¢â‚¬â„¢An ‘acceptable’ level of unemployment means that the government economist to whom it is acceptable still has a job’’. While George Walker Bush said,  Ã¢â‚¬ËœÃ¢â‚¬â„¢In the long run, the right answer to unemployment is to create more jobs’’. Keeping the above quotations in mind. Unemployment may be defined as. ‘’When there is the shortage of job and people are not able to find work that is when unemployment occurs’’. (94 Words) The presence of many problematic factors can result in unemployment. Firstly illiteracy the lack of education or the state of being unable to read or write is a very big cause of unemployment. Due to illiteracy people do not know how to find and do jobs. Secondly bribery refers to the offering, giving, soliciting, or receiving of any item of value as a means of influencing the actions of an individual holding a public or legal duty. By the help of bribery people with more money are able to get jobs they do not deserve hence not letting the people who deserve get them. Thirdly One more problem of unemployment and under-employment is nepotism and favoritism. It means selection according to relation not according to ability. Here deserving candidates do not get jobs and remain unemployed. Fourthly injustice the violation of the rights of others causes unemployment. Due to injustice the deserving are not able to have jobs. Than poverty the state of having little or no money is also a serious cause of unemployment. Poor persons due to lack of income has low saving and shortage in investment. So, they are unable to established self-employment opportunities. After that corruption the dishonest or fraudulent conduct by those in power yields in unemployment. Funds that can be used to create employment are embezzled and even investors shy away from setting up their business due to corruption levels and thus jobs are not created. Lastly terrorism which is the  terroristic method of governing or of resisting a government raises unemployment. Because of terrorism people avoid going out and getting jobs. When factors like bribery, nepotism and injustice become common in a society they lead to unemployment. (16 Sentences) Lack of many factors can be the cause of unemployment. Firstly the shortage of industry in a country can also lead to the shortage of jobs. The location of most industries is very uneconomical which also leads to industrial unemployment. Secondly lack of health is also a very big cause of unemployment. A healthy mind needs a healthy body, lack of health does not permit the energy needed for doing a job. Thirdly due to lack of technical education people are not able to get jobs. There is no awareness regarding technical education and its importance due to its absence a lot of people are not able to get jobs. Fourthly money is needed to start industries and other job opportunities. The lack of money does not permit the chance of starting any businesses which results in unemployment. After that the lack of knowledge has caused a lot of unawareness about employment. Due to this unawareness people do not know what they wish to do or what job they wish to get. Then the lack of jobs is the main cause of unemployment. Unavailability of opportunities and the shortage of industry leads to the lack of jobs which leads to unemployment. Lastly the lack of opportunities rises when the job is present but people for the job are not or the people present are not skilled enough. Proper training should be given so people can seek our opportunities. Shortage of technical education, knowledge, money and industry causes unemployment. (16 Sentences) Many influencing factors which when not kept under observation lead to unemployment. Firstly due to political instability investor hesitates to invest. It creates less opportunity of employment and results in unemployment. Secondly underdevelopment in countries results in unemployment. These countries are not developing and hence do not have enough job opportunities. Thirdly the government should set a merit eliminate the nepotism and favoritism. Employment opportunities should be provided in accordance to skill and ability. Fourthly the fast growth rate of population should be controlled. Due to population control there will be  more employment opportunities and less unemployment. Then in the past century technology has advanced to a great level. Machines are much quicker and very economical and due to these reasons a lot of machines have replaced man which has resulted in unemployment. After that improper government policies lead to unemployment. The government should be more careful while making these policies. Lastly economic policies are the policies set by the government in economic field. These policies are usually very problematic and seldom useful and can result in unemployment. Therefore these policies and factors must be periodically monitored. (16 Sentences) There are many causes of unemployment some are due to the negligence of the government and some are due to our own negligence. We all must try overcome unemployment. We must do our duty to spread awareness must be spread about these causes so that more and more people can know about them and so that more people can try to overcome them. Unemployment is very harmful for an economy it should be overcome at all costs. (76 Words)

Culture dependent vs culture independent methods Lab Report

Culture dependent vs culture independent methods - Lab Report Example 104). Some of the techniques that can be applied include, but not limited to performing rDNA PCR amplification on clinical specimens regarded sterile, such as blood. It is however advisable that this technique should not be employed with specimens originating from nonsterile sites such as faeces (Litton, 2010 p. 56). Collection of specimens such as conventional assays needs aseptic precautions. Litton (2010, p.57) claims that in order to curb contamination DNA brought by specimen collection vials, ensuring that the environment where work goes on is well organised also helps with this. Contamination linked to personnel working in the laboratory can be avoided by wearing cloves made of gloves or latex plus white coats. As for those contaminations resulting from consumable reagents and plastic wares, prior screening of each and every reagent before use in diagnostic assays (Litton, 2010 p. 56). 3. Find at least one peer-reviewed scientific research article regarding the bacteria that normally reside in the human mouth and provide references. Describe the groups of bacteria these studies identified to be present in the human mouth. Some of the bacteria that reside in the mouth include but not limited to, staphylococcus with the most common ones being S.epidermidis and S.aureus. They are oval in shape and posses a thick cell wall, named gram-positive. They cause infections in human population when presented with optimal conditions (â€Å"New bacterial species found in human  mouth† 2008, p.26). Bacteria from the genus streptococcus forms the largest number of all the organisms found in the mouth. Some of the species here include, but not restricted to, S. mutans, S. mitis, S. salivarius, S. pneumoniae and S. Pyogenes. They are also oval in shape like the staphylococcus. S.mutans is also responsible for cavity formation in teeth by converting sucrose sugar into lactic acid which

Negotiation and communication skills Essay Example | Topics and Well Written Essays - 1250 words

Negotiation and communication skills - Essay Example This discussion presented a strategizing negotiation on the part of Chris as exemplified by his offer to possibly develop Mark’s involvement in the CI project at Jordan Tectonics. There is also an aspect of planning in the discussion as evident in Chris’ remarks to coordinate with both Vincent and Frank Edwards, who are both keen on the project of broadening the computer base of their company with the mentioned CI project. This is an interesting case presented in a concise manner. The temperamental talent definitely speaks of Mark, Jordan Tectonic’s lead software designer. The problem stems from Mark’s diverse characteristics bordering on genius and hard to manage (temperamental). He possesses an attitude problem but also possesses an exemplary talent needed by the company to work on the required tasks. Further, in the point of view of Chris, the Head for Research and Development, the company could not afford to lose Mark – knowing that their competitors are luring him to join their team. Actually, this case presented facts which provide a good discourse for identifying negotiation and communication skills. However, other than that, I honestly believe that this scenario is also a good material for a case in human behaviour in organizations. The firm would have to decide which to prioritize – depending on their mission and vision statements, as well as their code of discipline – talent or attitude. Further, this case made me reflect on Chris’ remark that the company cannot afford to lose Mark. There are ethical issues involved as well as the concept of indispensability. Is there really such thing as being indispensable? Could Jordan utilize other alternatives like recruiting and training other personnel as software designer to be better equipped and who has a better personality in terms of possessing people-relation skills. If not, should the

Vulnerabilities Research Paper Example | Topics and Well Written Essays - 500 words

Vulnerabilities - Research Paper Example Certificate Authority (CA) and is considered to be the most efficient control in terms of email security (Ellison & Schneier, 2000). In case of secure email, one has to make sure about the sender possessing the key is the one who is the authentic sender. Likewise, when signed email is verified, one of the checks includes the source of the email i.e. the sender. However, if encryption is applied to the public key infrastructure, there is a requirement of identifying people possessing the relevant key to decrypt the message (Ellison & Schneier, 2000). This is the point where email certificates starts to operate, as the certificate ID is a digitally signed message from the CA that is transmitted to the user linked with the public key. However, the (PKI) possess many risks that may lead to vulnerabilities and in the end threats. One of the risks incorporates a breach of keys associated with the signer via unauthorized access or by any other means (Ellison & Schneier, 2000). However, efficient Certificate Authorities can mitigate risks by en effective physical security, personnel security and secure network. Pretty Go od Privacy ‘PGP’ counters these issues as well by incorporating ‘Web of Trust’ including self-governing signatures linked with the single certificate (Ellison & Schneier, 2000). Moreover, for addressing internal security, monitoring of employee emails is a regulatory requirement. However, there are many procedures, tasks and functions associated with it. The requirements can be met by utilizing tools from outlook express that are capable of retrieving certain keywords used in the email. For example, the keyword ‘account’ can retrieve all emails including this specific word. (Bhatnagar, 2012). However, these outlook tools only work individually on each workstation and can be solved by incorporating Microsoft Exchange server. As the server will retrieve all emails of all employees containing the specific

Que Onda Urban Youth Culture and Border Identity Essay - 1

Que Onda Urban Youth Culture and Border Identity - Essay Example There are also the issues of changing economic conditions where Mexicans are seen as the main economic contributors yet; they do menial and inferior jobs. There is also lack of upward mobility by the inferior ethnic groups, who immigrate across the border. The history and geopolitics of the groups determine the social capital each group is going to enjoy, and whether the group is going to assimilate easily. For instance, Chicanas/os are adapted to youth experimentation and popular culture in the United States and their parents put â€Å"fewer restrictions to them† than the Mexicanas/os parents do to their youths (45). The other lines of politics are projected along the legal and policy context of their immigration status (14). This way, the Mexicanas/os and Chicanas/os are made to feel inferior based on their ethnic grouping and social hierarchies (46). These politics is also perpetrated by the issue of whiteness as the top hierarchy and the fact that â€Å"without the social capital and social networks and English skills, immigrant youths cannot succeed in the United States education† (14). This also triggers identity politics where Chicanos use English, the language of America, while Mexicans use Spanish but at their own detriment. The teaching of different languages leads to a division in these two ethnic groups, which share the same ethnicity. In this case, the politics are too heavy for them as students from both sides â€Å"harbor ill feeling towards each other† because of border politics as â€Å"bantering over each other’s style, language, class, and gender and citizens status† (119). The political Chicano movement does not bar the youths from identifying themselves with inferior ascriptions, as opposed to the perpetrated positive proscriptions (46). Therefore, the book bounds all these issues among others to show the value of each aspect in the lives of Mexicanas/os and Chicanas/os in a way that can be viewed non-hege monically. It is because of the bonder politics and race wars that saturate our society that Mexicanas and Chicanas experience discriminations from one another and others (45). What factors influence identity development for Latinas/os along the border region? Many factors have been established, by the book, as influencing identity development for Latinos along the border region. For instance, Latino youths use â€Å"aspects of Mexicana/os, Chicana/os and American culture to create their alternative youth cultures† (96). In this case, the identity of Latinas/os is influenced by the Mexicana/o and Chicana/o youth who share many characteristics. There is also the factor of language where English is considered to be the dominant class language. For this case, the Latinos are influenced to identify with American culture by learning English language. Even though the American pop culture has appropriated Latino culture, this does not bar it from identifying itself with top social c lass in the hierarchies (96). There is also the issue of boundary or geographical position of the Latinos. This is closely linked to their immigration status and proximity to the Mexican border. Those who are close to the border experience extreme discrimination and less social property than those who are far away. On the other hand, those who migrated to the United States earlier have

The Role of Innovation in Kodak's Dowfall Research Paper

The Role of Innovation in Kodak's Dowfall - Research Paper Example From digital consumer electronics to household trinkets, everything can be sourced out from one part of the globe no matter how remote it may be. He also emphasized that introduction of different communication devices and platform that has increased the rate of information transfer. However, his comments about sustainability of a business in a globally competitive world is true. While consumers enjoy the benefits such as low prices and more options, local markets can also lose their business. Unemployment rises as downsizing occurs since global companies prefer outsourcing services due to a lower rate. Moreover, workers are not the only affected but big companies as well. Even big name companies like Eastman KODAK was not spared from the ugly head of globalization. Only this year, the Wall Street Journal announced the company’s filing or bankruptcy. It was a shock to the public considering that it has existed for 133 years. Yet, this is a glaring example that competitiveness i s the key to survival in a globalized economy. Hence, this paper will cite the main reasons behind the downfall of KODAK. Innovation is the main element for modern businesses to survive the rigors of globalization. The areas mainly responsible in an organization’s drive towards globalization would be marketing and management. Businesslink has stated in an article the necessity of innovation after creating a product or service. More so, when innovation is applied, it can help increase profitability because the value of products or services have increased. Consumers are always on the lookout for better products that go beyond their expectations. Apple is a market leader due to the ingenuity and creativity of its beloved founder- Steve Jobs. If a company fails to improve itself, it will bite the dust just as Kodak suffered. Management gurus like Peter Drucker is one of the most innovative minds despite his age. He has this uncanny sense of seeing how businesses should market the mselves in an evolving environment. In fact , he said that If an established organization , which in this age necessitates innovation, is not able to innovate, it faces decline and extinction. Drucker (qtd. in Trout, 2006) emphasized that Because the purpose of business is to create a customer, the business enterprise has two--and only two--basic functions: marketing and innovation. Marketing and innovation produce results; all the rest are costs. Marketing is the distinguishing, unique function of the business." Such words of truth should be the golden mean by companies today; moreover, Drucker emphasized the need to differentiate one’s products from the rest in order to survive the competition. Unfortunately, many businesses focus more on finances and operations and wonder later where they have failed. Although marketing does involve costs (along with innovation), it will be a constant source of revenue as long as the consumers are happy with the products. Innovation is oft en left behind because many managers are busy crunching numbers rather than developing ideas. Plus, innovation is often viewed by many business owners as costs, not as an investment. Innovation involves many creative processes that includes technology transformation as well as introduction of new strategies administered by the management (Shukla, 2009). Likewise, innovation, by itself, can be the main competitive feature of a company to rise

Personal Statement about Elctronics engineering Essay

Personal Statement about Elctronics engineering - Essay Example The hope to develop a capacity to assemble electrical components into a device for constructive application such as processing and transmission of information has for example encouraged me to study electronics engineering. I also look forward to undertake a future research into innovation of a cheaper and more efficient radio waves transmission device. Application of ‘active electrical components’ for completing circuits into electrical applications is what interests me the most in the course because it exhibits capacity to power appliances. This interest encouraged me to participate in voluntary work in an electronics company in my locality where I gained knowledge and skills in identification and testing of electronic components, and basic connectivity of appliances. Electronics engineering also directly fits into my career, being an electrical engineer, as it is a recognized academic qualification into the profession. I desire to pursue my course in the UK because of the international recognition of its universities for quality education that will give me an advantage in the international job market. I would also like to assure the faculty that I have made necessary arrangements for finances to facilitate my uninterrupted study. Besides my academic interest in your institution, I am likely to add to the institution’s competitiveness through participation in football and swimming competitions since these are my developed and refined hobbies. Portsmouth 2012, Advice on personal statements, Portsmouth, United Kingdom, viewed 17 June 2012, < http://www.port.ac.uk/departments/studentsupport/international/howtoapply/adviceonpersonalstatements/

In the name of the father Essay Example for Free

In the name of the father Essay Often a film conveys a message about a character through various film techniques. This is true in the film â€Å"In The Name of the Father†. This story is mainly about a young man who is arrested for a crime he did not commit and how a relationship between father and son deepens throughout the tragedy. The main character, Gerry Conlon, is first portrayed to the viewer as an unruly rebel but is later developed into a more docile and compliant character. The director, Jim Sheridon, uses film techniques such as costume design, dialogue and extended metaphors to convey the development of Gerry as a character. 1st paragraph: -1st time we see gerry, scruffy, uncut -costume design baggy jeans, long hair, dirty appearance -gives idea that gerry doesn’t care about his appearance or what people think of him -as film progresses he sharpens up appearance -combed pulled back hair 2nd: -change also shown through dialogue -lawyer asks him if he is scared of the court: -he replies â€Å"i just don’t want to be humiliated again† -this brief piece of dialogue shows that he has now changed and does care what others think of him -helps viewer understand how desperate an innocent man can be in the fight for justice 3rd: -use of extended metaphor -viewer sees lawyer gareth pierce driving through a long tunnel while listening to gerrys story -this could be viewed as an extended metaphor for the long dark road gerry has gone down while fighting the legal system -as the story draws to a conclusion she reaches the end of the tunnel, or the ‘light at the end of the tunnel’ -could refer to the point in the story where gerry and the others are finally set free. Read more:  My Father Goes to Court by Carlos Bulosan

Haemoglobin-related Diseases Management Strategies

Haemoglobin-related Diseases Management Strategies Abstract Haemoglobinopathies or inherited disorders of haemoglobin are the most common monogenic disorders in humans. Red cell transfusion is a well accepted therapy for clinical management of the most severe form of haemoglobinopathies namely, sickle cell disease (SCD) and ÃŽ ²-thalassaemia major. Patients affected by SCD need red blood cell transfusions on a regular basis to reduce morbidity and mortality. The transfusions are administered intermittently to control or prevent a serious complication of SCD, and as a perioperative measure. Or, as a chronic procedure, transfusion strategy is applied to prevent the recurrence, or the first occurrence, of stroke which is a major crisis in SCD, and to manage pulmonary hypertension and other sources of morbidity and mortality. Exchange transfusions are used to reduce the sickle cell haemoglobin (HbS) levels during crisis. Several situations also exist wherein the indication for red cell transfusion is controversial, uncertain, or downright injudic ious. Many side effects of transfusion have been identified and methods to overcome them have been developed. Iron overload (remedy: iron chelation), and alloimmunisation (remedy: phenotypical matching of transfused blood) are two notable examples. Association of haemoglobinopathies and neurologic sequelae after transfusion is also known. At the present time, bone marrow transplant is the only curative procedure available for both SCD and ÃŽ ²-thalassaemia major. Potential therapies involving stem cell transplantation and gene techniques are being vigorously researched. A detailed discussion of the current status of clinical management strategies as applied to inherited haemoglobin-related diseases in particular, sickle cell disease and the thalassaemias, is presented in this paper. 1. Introduction Anaemia is a syndrome characterised by a lack of healthy red blood cells or haemoglobin deficiency in the red blood cells, resulting in inadequate oxygen supply to the tissues. The condition can be temporary, long-term or chronic, and of mild to severe intensity. There are many forms and causes of anaemia. Normal blood consists of three types of blood cells: white blood cells (leucocytes), platelets and red blood cells (erythrocytes). The first generation of erythrocyte precursors in the developing foetus are produced in the yolk sac. They are carried to the developing liver by the blood where they form mature red blood cells that are required to meet the metabolic needs of the foetus. Until the 18th week of gestation, erythrocytes are produced only by liver after which the production shifts to the spleen and the bone marrow. The life of a red blood cell is about 127 days or 4 months (Shemin and Rittenberg, 1946; Kohgo et al., 2008). The main causes of anaemia are blood loss, product ion of too few red blood cells by the bone marrow or a rapid destruction of cells.   Ã‚  Ã‚  Ã‚  Ã‚  Haemoglobin, a protein, present in the red blood cells is involved in the transport of oxygen from the lungs to all the other organs and tissues of the body. Iron is an important constituent of the haemoglobin protein structure which is intimately involved in the transport of oxygen. Anaemia is generally defined as a lower than normal haemoglobin concentration. The normal blood haemoglobin concentration is dependent on age and sex, and, according to the World Health Organisation (WHO) Expert Committee Report, anaemia results when the blood concentration of haemoglobin falls below 130 g/L in men or 120 g/L in non-pregnant women (WHO, 1968). However, the reference range of haemoglobin concentration in blood could vary depending on the ethnicity, age, sex, environmental conditions and food habits of the population analysed. According to Beutler and Warren (2006), more reasonable benchmarks for anaemia are 137 g/L for white men aged between 20 and 60 years and 132 g/L for older men. The value for women of all ages would be 122 g/L. Also, the lower limit of normal of haemoglobin concentrations of African Americans are appreciably lower than that of Caucasians (Beutler and Warren, 2006).   Ã‚  Ã‚  Ã‚  Ã‚  Besides the well recognised iron deficiency anaemia, several inherited anaemias are also known. These are mostly haemoglobinopathies. Adult haemoglobin is a tetrameric haeme-protein. Abnormalities of beta-chain or alpha-chain produce the various medically significant haemoglobinopathies. The variations in amino acid composition induced genetically impart marked differences in the oxygen carrying properties of haemoglobin. Mutations in the haemoglobin genes cause disorders that are qualitative abnormalities in the synthesis of haemoglobin (e.g., sickle cell disease) and some that are quantitative abnormalities that pertain to the rate of haemoglobin synthesis (e.g., the thalassemias) (Weatherall., 1969). In SCD, the missense mutation in the ÃŽ ²-globin gene causes the disorder. The mutation causing sickle cell anemia is a single nucleotide substitution (A to T) in the codon for amino acid 6. The substitution converts a glutamic acid codon (GAG) to a valine codon (G TG). The form of haemoglobin in persons with sickle cell anemia is referred to as HbS. Also, the valine for glutamic acid replacement causes the haemoglobin tetramers to aggregate into arrays upon deoxygenation in the tissues. This aggregation leads to deformation of the red blood cell making it relatively inflexible and restrict its movement in the capillary beds. Repeated cycles of oxygenation and deoxygenation lead to irreversible sickling and clogging of the fine capillaries. Incessant clogging of the capillary beds damages the kidneys, heart and lungs while the constant destruction of the sickled red blood cells triggers chronic anaemia and episodes of hyperbilirubinaemia.   Ã‚  Ã‚  Ã‚  Ã‚  Fanconi anaemia (FA) is an autosomal recessive condition, and the most common type of inherited bone marrow failure syndrome. The clinical features of FA are haematological with aplastic anaemia, myelodysplastic syndrome (MDS), and acute myeloid leukaemia (AML) being increasingly present in homozygotes (Tischkowitz and Hodgson, 2003). Cooleys anaemia is yet another disorder caused by a defect in haemoglobin synthesis.   Ã‚  Ã‚  Ã‚  Ã‚  Autoimmune haemolytic anaemia is a syndrome in which individuals produce antibodies directed against one of their own erythrocyte membrane antigens. The condition results in diminished haemoglobin concentrations on account of shortened red blood cell lifespan (Sokol et al., 1992).   Ã‚  Ã‚  Ã‚  Ã‚  Megaloblastic anaemia is a blood disorder in which anaemia occurs with erythrocytes which are larger in size than normal. The disorder is usually associated with a deficiency of vitamin B12 or folic acid . It can also be caused by alcohol abuse, drugs that impact DNA such as anti-cancer drugs, leukaemia, and certain inherited disorders among others (Dugdale, 2008).   Ã‚  Ã‚  Ã‚  Ã‚  Malaria causes increased deformability of vivax-infected red blood cells (Anstey et al., 2009). Malarial anaemia occurs due to lysis of parasite-infected and non-parasitised erythroblasts as also by the effect of parasite products on erythropoiesis (Ru et al., 2009).   Ã‚  Ã‚  Ã‚  Ã‚  Large amounts of iron are needed for haemoglobin synthesis by erythroblasts in the bone marrow. Transferrin receptor 1 (TfR1) expressed highly in erythroblasts plays an important role in extracellular iron uptake (Kohgo et al., 2008). Inside the erythroblasts, iron transported into the mitochondria gets incorporated into the haeme ring in a multistep pathway. Genetic abnormalities in this pathway cause the phenotype of ringed sideroblastic anemias (Fleming, 2002). The sideroblastic anemias are a heterogeneous group of acquired and inherited bone marrow disorders, characterised by mitochondrial iron overload in developing red blood cells. These conditions are diagnosed by the presence of pathologic iron deposits in erythroblast mitochondria (Bottomley, 2006).   2. Classification of anaemia Anaemia can be generally classified based on the morphology of the red blood cells, the pathogenic spectra or clinical presentation (Chulilla et al., 2009). The morphological classification is based on mean corpuscular volume (MCV) and comprises of microcytic, macrocytic and normocytic anaemia. (a) Microcytic anaemia refers to the presence of RBCs smaller than normal volume, the reduced MCV ( 15 would probably indicate IDA (Chulilla et al., 2009).   Ã‚  Ã‚  Ã‚  Ã‚  In macrocytic anaemia, erythrocytes are larger (MCV > 98 fL) than their normal volume (MCV = 82-98 fL). Vitamin B12 deficiency leads to delayed DNA synthesis in rapidly growing haematopoietic cells, and can result in macrocytic anaemia. Drugs that interfere with nucleic acid metabolism, such as.hydroxyurea increases MCV (> 110 fL) while alcohol induces a moderate macrocytosis (100-110 fL). In the initial stage, most anaemias are normocytic. The causes of normocytic anaemia are nutritional deficiency, renal failure and haemolytic anemia (Tefferi, 2003). The most common normocytic anaemia in adults is ACD (Krantz, 1994). Common childhood normocytic anaemias are, besides iron deficiency anaemia, those due to acute bleeding, sickle cell anaemia, red blood cell membrane disorders and current or recent infections especially in the very young (Bessman et al., 1983). Homozygous sickle cell disease is the most common cause of haemolytic normocytic anemias in children (Weat herall DJ, 1997a).   Ã‚  Ã‚  Ã‚  Ã‚  In practice, the morphological classification is quicker and therefore, more useful as a diagnostic tool. Besides, MCV is also closely linked to mean corpuscular haemoglobin (MCH), which denotes mean haemoglobin per erythrocyte expressed in picograms (Chulilla et al., 2009). Thus, MCV and MCH decrease simultaneously in microcytic, hypochromic anaemia and increase together in macrocytic, hyperchromic anemia.   Ã‚  Ã‚  Ã‚  Ã‚  Pathogenic classification of anaemia is based on the production pattern of RBC: whether anaemia is due to inadequate production or loss of erythrocytes caused by bleeding or haemolysis. This approach is useful in those cases where MCV is normal. Pathogenic classification is also essential for proper recognition of the mechanisms involved in the genesis of anaemia. Based on the pathogenic mechanisms, anaemia is further divided into two types namely, (i) hypo-regenerative in which the bone marrow production of erythrocytes is decreased because of impaired function, decreased number of precursor cells, reduced bone marrow infiltration, or lack of nutrients; and (ii) regenerative: when bone marrow upregulates the production of erythrocytes in response to the low erythrocyte mass (Chulilla et al., 2009). This is typified by increased generation of erythropoietin in response to lowered haemoglobin concentration, and also reflects a loss of erythrocytes, due to bleeding or haemolysis. The reticulocyte count is typically higher.   Ã‚  Ã‚  Ã‚  Ã‚  Sickle cell disease is characterised by sickled red cells.   The first report of SCD was published a century ago noting the presence of peculiar elongated cells in blood by James Herrick, an American physician (1910). Pauling et al. (1949) described it as a molecular disease. The molecular nature of sickle haemoglobin (HbS) in which valine is substituted for glutamic acid at the sixth amino acid position in the beta globin gene reduces the solubility of haemoglobin, causing red cells to sickle (Fig. 1). Sickling of cells occurs at first reversibly, then finally as a state of permanent distortion, when cells containing HbS and inadequate amounts of other haemoglobins including foetal haemoglobin, which retards sickling, become deoxygenated (Bunn, 1997). The abnormal red cells break down, leading to anaemia, and clog blood vessels with aggregates, leading to recurrent episodes of severe pain and multiorgan ischaemic damage (Creary et al., 2007). The high levels of inflammatory cytokines in SCD may promote retention of iron by macrophage/reticuloendothelial cells and/or renal cells. SCD care commonly depends on transfusion that results in iron overload (Walter et al., 2009). 3. Pathogenesis of anaemia Anaemia is a symptom , or a syndrome, and not a disease (Chulilla et al., 2009). Several types of anaemia have been recognised, the pathogenesis of each being unique. Iron deficiency anaemia (IDA) is the most common type of anaemia due to nutritional causes encountered worldwide (Killip et al., 2008). Iron is one of the essential micronutrients required for normal erythropoietic function While the causes of iron deficiency vary significantly depending on chronological age and gender, IDA can reduce work capacity in adults (Haas Brownlie, 2001) and affect motor and mental development in children (Halterman et al., 2001). The metabolism of iron is uniquely controlled by absorption rather than excretion (Siah et al., 2006). Iron absorption typically occurring in the duodenum accounts for only 5 to 10 per cent of the amount ingested in homoeostatis. The value decreases further under conditions of iron overload, and increases up to fivefold under conditions of iron depletion (Killip et al., 2008). Iron is ingested as haem iron (10%) present in meat, and as non-haem ionic form iron (90%) found in plant and dairy products. In the absence of a regulated excretion of iron through the liver or kidneys, the only way iron is lost from the body is through bleeding and sloughing of cells. Thus, men and non-menstruating women lose about 1 mg of iron per day while menstruating women could normally lose up to 1.025 mg of iron per day (Killip et al., 2008). The requirements for erythropoiesis   which are typically 20-30 mg/day   are dependent on the internal turnover of iron (Munoz et al., 2009) For example, the amount of iron required for daily production of 300 billion RBCs (20-30 mg) is provided mostly by recycling iron by macrophages (Andrews, 1999).   Ã‚  Ã‚  Ã‚  Ã‚  Iron deficiency occurs when the metabolic demand for iron exceeds the amount available for absorption through consumption. Deficiency of nutritional intake of iron is important, while abnormal iron absorption due to hereditary or acquired iron-refractory iron deficiency anemia (IRIDA) is another important cause of unexplained iron deficiency. However, IDA is commonly attributed to blood loss e.g., physiological losses in women of reproductive age. It might also represent occult bleeding from the gastrointestinal tract generally indicative of malignancy (Hershko and Skikne, 2009).   Ã‚  Ã‚  Ã‚  Ã‚  Iron absorption and loss play an important role in the pathogenesis and management of IDA. Human iron disorders are necessarily disorders of iron balance or iron distribution. Iron homeostasis involves accurate control of intestinal iron absorption, efficient utilisation of iron for erythropoiesis, proper recycling of iron from senescent erythrocytes, and regulated storage of iron by hepatocytes and macrophages (Andrews, 2008). Iron deficiency is largely acquired, resulting from blood loss (e.g., from intestinal parasitosis), from inadequate dietary iron intake, or both. Infections, for example, with H pylori, can lead to profound iron deficiency anemia without significant bleeding. Genetic defects can cause iron deficiency anaemia. Mutations in the genes encoding DMT1 (SLC11A2) and glutaredoxin 5 (GLRX5) lead to autosomal recessive hypochromic, microcytic anaemia (Mims et al., 2005). Transferrin is a protein that keeps iron nonreactive in the circulation, and del ivers iron to cells possessing specific transferrin receptors such as TFR1 which is found in largest amounts on erythroid precursors. Mutations in the TF gene leading to deficiency of serum transferrin causes disruption in the transfer of iron to erythroid precursors thereby producing an enormous increase in intestinal iron absorption and consequent tissue iron deposition (Beutler et al., 2000). Quigley et al. (2004) found a haem exporter, FLVCR, which appears to be necessary for normal erythroid development. Inactivation of FLVCR gene after birth in mice led to severe macrocytic anaemia, indicating haem export to be important for normal erythropoiesis.   Ã‚  Ã‚  Ã‚  Ã‚  The anaemia of chronic disease (ACD) found in patients with chronic infectious, inflammatory, and neoplastic disorders is the second most frequently encountered anaemia after iron-deficiency anaemia. It is most often a normochromic, normocytic anaemia that is primarily caused by an inadequate production of red cells, with low reticulocyte production (Krantz, 1994). The pathogenesis of ACD is unequivocally linked to increased production of the cytokines including tumour necrosis factor, interleukin-1, and the interferons that mediate the immune or inflammatory response. The various processes leading to the development of ACD such as reduced life span of red cells, diminished erythropoietin effect on anaemia, insufficient erythroid colony formation in response to erythropoietin, and impaired bioavailability of reticuloendothelial iron stores appear to be caused by inflammatory cytokines (Means, 1996;2003). Although iron metabolism is characteristically impaired in A CD, it may not play a key role in the pathogenesis of ACD (Spivak, 2002). Neither is the lack of available iron central to the pathogenesis of the syndrome, according to Spivak (2002), who found reduced iron absorption and decreased erythroblast transferrin-receptor expression to be the result of impaired erythropoietin production and inhibition of its activity by cytokines. However, reduced erythropoietin activity, mostly from reduced production, plays a pivotal role in the pathogenesis of ACD observed in systemic autoimmune diseases (Bertero and Caligaris-Cappio, 1997). Indeed, iron metabolism as well as nitric oxide (NO), which contributes to the regulation of iron cellular metabolism are involved in the pathogenesis of ACD in systemic autoimmune disorders. Inflammatory mediators, particularly the cytokines, are important factors involved in the pathogenesis of the anaemia of chronic disease, as seen in rheumatoid arthritis anaemia (Baer et al., 1990), the cytokines causing impai rment of erythroid progenitor growth and haemoglobin production in developing erythrocytes.     Ã‚  Ã‚  Ã‚  Ã‚  Anaemia is also commonly found in cases of congestive heart failure (CHF), again caused by excessive cytokine production leading to reduced erythropoietin secretion, interference with erythropoietin activity in the bone marrow and reduced iron supply to the bone marrow (Silverberg et al., 2004). However, in the presence of chronic kidney insufficiency, abnormal erythropoietin production in the kidney plays a role in the pathogenesis of anaemia in CHF.   Ã‚  Ã‚  Ã‚  Ã‚  The myelodysplastic syndromes (MDS) are common haematological malignancies affecting mostly the elderly as age-related telomere shortening enhances genomic instability (Rosenfeld and List, 2000). Radiation, smoking and exposure to toxic compounds e.g., pesticides, organic chemicals and heavy metals, are factors promoting the onset of MDS via damage caused to progenitor cells, and, thereby, inducing immune suppression of progenitor cell growth and maturation. TNF- and other pro-apoptotic cytokines could play a central role in the impaired haematopoiesis of MDS (Rosenfeld and List, 2000). Premature intramedullary cell death brought about by excessive apoptosis is another important pathogenetic mechanism in MDS (Aul et al., 1998).     Ã‚  Ã‚  Ã‚  Ã‚  SCD arising from a point mutation in the ÃŽ ²-globin gene and leading to the expression of haemoglobin S (HbS) is the most common monogenetic disorder worldwide. Chronic intravascular haemolysis and anaemia are some important characteristics of SCD. Intravascular haemolysis causes endothelial dysfunction marked by reduced nitric oxide (NO) bioavailability and NO resistance, leading to acute vasoconstriction and, subsequently, pulmonary hypertension (Gladwin and Kato, 2005).    However, a feature that differentiates SCD from other chronic haemolytic syndromes is the persistent and intense inflammatory condition present in SCD. The primary pathogenetic event in SCD is the intracellular polymerisation or gelation of deoxygenated HbS leading to rigidity in erythrocytes (Wun, 2001). The deformation of erythrocytes containing HbS is dependent on the concentration of haemoglobin in the deoxy conformation (Rodgers et al., 1985). It has been demonstrated that sickle mono cytes are activated which, in turn, activate endothelial cells and cause vascular inflammation. The vaso-occlusive processes in SCD involve inflammatory and adhesion molecules such as the cell adhesion molecules (CAM family), which play a role in the firm adhesion of reticulocytes and leukocytes to endothelial cells, and the selectins, which play a role in leukocyte and platelet rolling on the vascular wall (Connes et al., 2008). Thus, inflammation, leucocyte adhesion to vascular endothelium, and subsequent endothelial injury are other crucial factors contributing to the pathogenesis of SCD (Jison et al., 2004). 4. Current therapies for clinical management of sickle cell disease including a critical appraisal of transfusion Between 1973 and 2003, the average life expectancy of a patient with SCD increased dramatically from a mere 14 years to 50 years thanks to the development of comprehensive care models and painstaking research efforts in both basic sciences especially molecular and genetic studies, and clinical aspects of SCD (Claster and Vichinsky, 2003). The clinical manifestations of SCD are highly variable. Both the phenotypic expression and intensity of the syndrome are vastly different among patients and also vary longitudinally within the same patient (Ballas, 1998). New pathophysiological insights available have enabled treatments to be developed for the recognised haematologic and nonhaematologic abnormalities in SCD (Claster and Vichinsky, 2003). The main goals of SCD treatment are symptom alleviation, crises avoidance and effective management of disease complications. The strategy adopted is primarily palliative in nature, and consists of supportive, symptomatic and preventative approaches to therapy. Symptomatic management includes pain mitigation, management of vasoocclusive crisis, improving chronic haemolytic anaemia, treatment of organ failure associated with the disease, and detection and treatment of pulmonary hypertension (Distenfeld and Woermann, 2009). The preventative strategies include use of prophylactic antibiotics (e.g., penicillin) in children, prophylactic blood transfusion for prevention of stroke in patients especially young children who are at a very high risk of stroke, and treatment with hydroxyurea of patients experiencing frequent acute painful episodes (Ballas, 2002). Currently, curative therapy for sickle cell anaemia is only available through bone marrow and stem cell transplantation. Hematopoietic cell transplantation using stem cells from a matched sibling donor has yielded excellent results in paediatric patients (Krishnamurti, 2007). Curative gene therapy is still at the exploratory stage (Ballas, 2002). 4.1 Current and potential therapies The potential treatment strategies basically target cellular dehydration, sickle haemoglobin concentrations, endothelial dysfunction, and abnormal coagulation regulation (Claster and Vichinsky, 2003). HbS concentrations are essentially tackled through transfusions while approaches to reduce HbS polymerisation which is the main mechanism for the development of vaso-occlusion include (a) increasing foetal haemoglobin (HbF) concentration using hydroxyurea (Fig. 2), butyrate, or erythropoietin, and (b) preventing sickle cell dehydration using Clotrimazole (Fig. 3) or Mg2+pidolate. Hydroxyurea therapy increases the production of HbF in patients with sickle cell anaemia, and, thereby, inhibits the polymerisation of HbS and alleviates both the haemolytic and vaso-occlusive manifestations of the disease (Goldberg et al., 1990). Recombinant erythropoietin also increases the number of reticulocytes with HbF. Additionally, it has been observed that administration of intravenous recombinant eryt hropoietin with iron supplementation alternating with hydroxyurea enhances HbF levels more than hydroxyurea alone (Rodgers et al., 1993). As SCD is essentially characterized by an abnormal state of endothelial cell activation   that is, a state of inflammation, a pharmacologic approach to inhibit endothelial cell activation has proved clinically beneficial (Hebbel and Vercellotti, 1997). Thus, administration of sulfasalazine which is a powerful inhibitor of activation of nuclear factor (NF)-B, the transcription factor promoting expression of genes for a number of pro-adhesive and procoagulant molecules on endothelium to humans has been found to provide transcriptional regulation of SCD at the endothelium level (Solovey et al., 2001). 4.2 Red blood cell transfusion A key therapy that is applied regularly in the clinical management of patients with SCD is packed red blood cell transfusion. RBC transfusion improves the oxygen-carrying capacity which is achieved by enhancing the haemoglobin levels, causes dilution of HbS concentration thereby, reducing blood viscosity and boosting oxygen saturation. Furthermore, RBC transfusion is helpful in suppressing endogenous production of sickle RBCs by augmenting tissue oxygenation ( Josephson et al., 2007). There are two major types of RBC transfusion therapy: intermittent and chronic which are further classified as prophylactic or therapeutic. Intermittent transfusions are generally therapeutic in nature and administered to control acute manifestations of SCD whereas chronic transfusions are performed as general preventative measures to check complications of SCD. RBC transfusion given as a single dose is termed as simple transfusion. Exchange transfusion involves administration of a larger volume of RBCs replacing the patients RBCs that are simultaneously removed. Details of the various types of RBC transfusion and the major clinical indications for the same in SCD patients are listed in Table 1. 4.3 Indications for intermittent transfusions Indications for intermittent transfusions include acute manifestations of SCD, as indicated in Table 1, that require redressal through therapeutic transfusions. However, under certain circumstances intermittent transfusions could be prophylactic such as for instance, when SCD patients are transfused before specific surgeries viz., those related to pregnancy complications or renal failure (Table 1). Acute Chest Syndrome (ACS) describes a manifestation of SCD in which, due to sickling, infectious and noninfectious pulmonary events are complicated, resulting in a more severe clinical course. The diagnosis is the presence of a new infiltrate on chest radiography that is accompanied by acute respiratory symptoms. ACS accounts for nearly 25% of all deaths from SCD (Vichinsky, 2002). Repeated episodes of ACS are associated with an increased risk of chronic lung disease and pulmonary hypertension (Castro, 1996). The severe pulmonary events occurring in SCD may be precipitated by any trigger of hypoxia (Vichinsky, 2002). Transfusions are very efficacious and provide immediate benefit by reversing hypoxia in ACS. Transfusion of leucocyte-poor packed red cells matched for Rh, C, E, and Kell antigens can curtail antibody formation to below 1% (Vichinsky, 2002). Simple transfusions suffice for less severe cases; however, exchange transfusion is recommended to minimise the risk of increased viscosity. Also, chronic transfusion appears promising for prevention of recurrence in selected patients (Styles and Vichinsky, 1994). In a multicentre ACS trial, prophylactic transfusion was found to almost completely eliminate the risk of pulmonary complications (Vichinsky, 2002).   Ã‚  Ã‚  Ã‚  Ã‚  Acute Symptomatic Anaemia arises in SCD as a result of blood loss, increased RBC destruction, suppression of erythropoiesis etc. and is effectively treated with intermittent transfusion of RBCs to relieve symptoms of cardiac and respiratory distress (Josephson et al., 2007).   Ã‚  Ã‚  Ã‚  Ã‚  Aplastic Anaemia is commonly caused in SCD on account of infection of haematopoietic precursors in the bone marrow by Parvovirus B19 leading to a steep fall in RBCs. According to Josephson et al. (2007), therapeutic intermittent transfusion of RBCs is again the recommended first-line of treatment to improve total haemoglobin count and prevent cardiac decompensation. However, in those patients who are prone to fluid overload on account of cardiac or renal dysfunction an alternative transfusion strategy is to remove the whole blood and replace it with packed cells while avoiding the addition of excess volume (Josephson et al., 2007).   Ã‚  Ã‚  Ã‚  Ã‚  Acute Stroke is a high risk especially in paediatric SCD cases because of elevated cerebral flow. Enormous decline in stroke rate have occurred in children receiving intermittent simple transfusion (Adams et al., 1998). However, the identification of the stroke type would be necessary in all SCD patients in order to determine the appropriate treatment approach since the occurrence of infarctive strokes is higher in children as opposed to a higher incidence of haemorrhagic strokes in adults (Adams, 2003). 4.4 Indications for Chronic Transfusions Prophylactic chronic RBC transfusion every 3 to 4 weeks to maintain HbS levels lower than 30% is crucial for preventing first as well as recurrent strokes in children (Johnson et al., 2007). The transfusions could either be chronic simple transfusion or prophylactic chronic RBC exchange transfusion. Prophylactic chronic transfusions are recommended for patients with chronic renal failure so as to avoid severe symptomatic anaemia and for those patients with SCD undergoing pregnancy with complications. However, prophylactic transfusion is not indicated for SCD patients with normal pregnancy (Tuck et al., 1987). 4.5 Controversial and indeterminate indications for transfusion Several situations also exist wherein the indication for red cell transfusion is controversial, uncertain, or downright injudicious in SCD management. Some examples are indicated in Table 1.   Ã‚  Ã‚  Ã‚  Ã‚  According to Hankins et al. (2005), chronic transfusion therapy is helpful in reducing the incidence of strokes in children but not the severity of strokes. In the case of acute priapism, improvement in patients has been observed after exchange or simple transfusion (Rifikind   et al., 1979). Yet, due to the ASPEN syndrome, transfusion therapy currently is only a second-line therapy in the management of priapism ( Miller et al., 1995).   Ã‚  Ã‚  Ã‚  Ã‚  RBC transfusion is a vital component in the management of symptoms and complications of SCD. It has drastically reduced the morbidity and mortality of SCD. Yet, immune-related effects such as FNHTRs (Febrile Non-Haemolytic Transfusion Reaction i.e., fever resulting from a blood transfusion) and alloimmunisation to HLAs (Human Leucocyte Antigens),   and nonimmune-related effects e.g., iron overload and transfusion-transmitted infections are serious adverse effects of the transfusion therapy that need to be attended to in SCD patients receiving transfusion (Johnson et al., 2007). Chronic transfusions could result in an inexorable accumulation of tissue iron that could become fatal if not treated (Cohen, 1987). Excess iron damages the liver, endocrine organs, and heart and may be fatal by adolescence (E Haemoglobin-related Diseases Management Strategies Haemoglobin-related Diseases Management Strategies Abstract Haemoglobinopathies or inherited disorders of haemoglobin are the most common monogenic disorders in humans. Red cell transfusion is a well accepted therapy for clinical management of the most severe form of haemoglobinopathies namely, sickle cell disease (SCD) and ÃŽ ²-thalassaemia major. Patients affected by SCD need red blood cell transfusions on a regular basis to reduce morbidity and mortality. The transfusions are administered intermittently to control or prevent a serious complication of SCD, and as a perioperative measure. Or, as a chronic procedure, transfusion strategy is applied to prevent the recurrence, or the first occurrence, of stroke which is a major crisis in SCD, and to manage pulmonary hypertension and other sources of morbidity and mortality. Exchange transfusions are used to reduce the sickle cell haemoglobin (HbS) levels during crisis. Several situations also exist wherein the indication for red cell transfusion is controversial, uncertain, or downright injudic ious. Many side effects of transfusion have been identified and methods to overcome them have been developed. Iron overload (remedy: iron chelation), and alloimmunisation (remedy: phenotypical matching of transfused blood) are two notable examples. Association of haemoglobinopathies and neurologic sequelae after transfusion is also known. At the present time, bone marrow transplant is the only curative procedure available for both SCD and ÃŽ ²-thalassaemia major. Potential therapies involving stem cell transplantation and gene techniques are being vigorously researched. A detailed discussion of the current status of clinical management strategies as applied to inherited haemoglobin-related diseases in particular, sickle cell disease and the thalassaemias, is presented in this paper. 1. Introduction Anaemia is a syndrome characterised by a lack of healthy red blood cells or haemoglobin deficiency in the red blood cells, resulting in inadequate oxygen supply to the tissues. The condition can be temporary, long-term or chronic, and of mild to severe intensity. There are many forms and causes of anaemia. Normal blood consists of three types of blood cells: white blood cells (leucocytes), platelets and red blood cells (erythrocytes). The first generation of erythrocyte precursors in the developing foetus are produced in the yolk sac. They are carried to the developing liver by the blood where they form mature red blood cells that are required to meet the metabolic needs of the foetus. Until the 18th week of gestation, erythrocytes are produced only by liver after which the production shifts to the spleen and the bone marrow. The life of a red blood cell is about 127 days or 4 months (Shemin and Rittenberg, 1946; Kohgo et al., 2008). The main causes of anaemia are blood loss, product ion of too few red blood cells by the bone marrow or a rapid destruction of cells.   Ã‚  Ã‚  Ã‚  Ã‚  Haemoglobin, a protein, present in the red blood cells is involved in the transport of oxygen from the lungs to all the other organs and tissues of the body. Iron is an important constituent of the haemoglobin protein structure which is intimately involved in the transport of oxygen. Anaemia is generally defined as a lower than normal haemoglobin concentration. The normal blood haemoglobin concentration is dependent on age and sex, and, according to the World Health Organisation (WHO) Expert Committee Report, anaemia results when the blood concentration of haemoglobin falls below 130 g/L in men or 120 g/L in non-pregnant women (WHO, 1968). However, the reference range of haemoglobin concentration in blood could vary depending on the ethnicity, age, sex, environmental conditions and food habits of the population analysed. According to Beutler and Warren (2006), more reasonable benchmarks for anaemia are 137 g/L for white men aged between 20 and 60 years and 132 g/L for older men. The value for women of all ages would be 122 g/L. Also, the lower limit of normal of haemoglobin concentrations of African Americans are appreciably lower than that of Caucasians (Beutler and Warren, 2006).   Ã‚  Ã‚  Ã‚  Ã‚  Besides the well recognised iron deficiency anaemia, several inherited anaemias are also known. These are mostly haemoglobinopathies. Adult haemoglobin is a tetrameric haeme-protein. Abnormalities of beta-chain or alpha-chain produce the various medically significant haemoglobinopathies. The variations in amino acid composition induced genetically impart marked differences in the oxygen carrying properties of haemoglobin. Mutations in the haemoglobin genes cause disorders that are qualitative abnormalities in the synthesis of haemoglobin (e.g., sickle cell disease) and some that are quantitative abnormalities that pertain to the rate of haemoglobin synthesis (e.g., the thalassemias) (Weatherall., 1969). In SCD, the missense mutation in the ÃŽ ²-globin gene causes the disorder. The mutation causing sickle cell anemia is a single nucleotide substitution (A to T) in the codon for amino acid 6. The substitution converts a glutamic acid codon (GAG) to a valine codon (G TG). The form of haemoglobin in persons with sickle cell anemia is referred to as HbS. Also, the valine for glutamic acid replacement causes the haemoglobin tetramers to aggregate into arrays upon deoxygenation in the tissues. This aggregation leads to deformation of the red blood cell making it relatively inflexible and restrict its movement in the capillary beds. Repeated cycles of oxygenation and deoxygenation lead to irreversible sickling and clogging of the fine capillaries. Incessant clogging of the capillary beds damages the kidneys, heart and lungs while the constant destruction of the sickled red blood cells triggers chronic anaemia and episodes of hyperbilirubinaemia.   Ã‚  Ã‚  Ã‚  Ã‚  Fanconi anaemia (FA) is an autosomal recessive condition, and the most common type of inherited bone marrow failure syndrome. The clinical features of FA are haematological with aplastic anaemia, myelodysplastic syndrome (MDS), and acute myeloid leukaemia (AML) being increasingly present in homozygotes (Tischkowitz and Hodgson, 2003). Cooleys anaemia is yet another disorder caused by a defect in haemoglobin synthesis.   Ã‚  Ã‚  Ã‚  Ã‚  Autoimmune haemolytic anaemia is a syndrome in which individuals produce antibodies directed against one of their own erythrocyte membrane antigens. The condition results in diminished haemoglobin concentrations on account of shortened red blood cell lifespan (Sokol et al., 1992).   Ã‚  Ã‚  Ã‚  Ã‚  Megaloblastic anaemia is a blood disorder in which anaemia occurs with erythrocytes which are larger in size than normal. The disorder is usually associated with a deficiency of vitamin B12 or folic acid . It can also be caused by alcohol abuse, drugs that impact DNA such as anti-cancer drugs, leukaemia, and certain inherited disorders among others (Dugdale, 2008).   Ã‚  Ã‚  Ã‚  Ã‚  Malaria causes increased deformability of vivax-infected red blood cells (Anstey et al., 2009). Malarial anaemia occurs due to lysis of parasite-infected and non-parasitised erythroblasts as also by the effect of parasite products on erythropoiesis (Ru et al., 2009).   Ã‚  Ã‚  Ã‚  Ã‚  Large amounts of iron are needed for haemoglobin synthesis by erythroblasts in the bone marrow. Transferrin receptor 1 (TfR1) expressed highly in erythroblasts plays an important role in extracellular iron uptake (Kohgo et al., 2008). Inside the erythroblasts, iron transported into the mitochondria gets incorporated into the haeme ring in a multistep pathway. Genetic abnormalities in this pathway cause the phenotype of ringed sideroblastic anemias (Fleming, 2002). The sideroblastic anemias are a heterogeneous group of acquired and inherited bone marrow disorders, characterised by mitochondrial iron overload in developing red blood cells. These conditions are diagnosed by the presence of pathologic iron deposits in erythroblast mitochondria (Bottomley, 2006).   2. Classification of anaemia Anaemia can be generally classified based on the morphology of the red blood cells, the pathogenic spectra or clinical presentation (Chulilla et al., 2009). The morphological classification is based on mean corpuscular volume (MCV) and comprises of microcytic, macrocytic and normocytic anaemia. (a) Microcytic anaemia refers to the presence of RBCs smaller than normal volume, the reduced MCV ( 15 would probably indicate IDA (Chulilla et al., 2009).   Ã‚  Ã‚  Ã‚  Ã‚  In macrocytic anaemia, erythrocytes are larger (MCV > 98 fL) than their normal volume (MCV = 82-98 fL). Vitamin B12 deficiency leads to delayed DNA synthesis in rapidly growing haematopoietic cells, and can result in macrocytic anaemia. Drugs that interfere with nucleic acid metabolism, such as.hydroxyurea increases MCV (> 110 fL) while alcohol induces a moderate macrocytosis (100-110 fL). In the initial stage, most anaemias are normocytic. The causes of normocytic anaemia are nutritional deficiency, renal failure and haemolytic anemia (Tefferi, 2003). The most common normocytic anaemia in adults is ACD (Krantz, 1994). Common childhood normocytic anaemias are, besides iron deficiency anaemia, those due to acute bleeding, sickle cell anaemia, red blood cell membrane disorders and current or recent infections especially in the very young (Bessman et al., 1983). Homozygous sickle cell disease is the most common cause of haemolytic normocytic anemias in children (Weat herall DJ, 1997a).   Ã‚  Ã‚  Ã‚  Ã‚  In practice, the morphological classification is quicker and therefore, more useful as a diagnostic tool. Besides, MCV is also closely linked to mean corpuscular haemoglobin (MCH), which denotes mean haemoglobin per erythrocyte expressed in picograms (Chulilla et al., 2009). Thus, MCV and MCH decrease simultaneously in microcytic, hypochromic anaemia and increase together in macrocytic, hyperchromic anemia.   Ã‚  Ã‚  Ã‚  Ã‚  Pathogenic classification of anaemia is based on the production pattern of RBC: whether anaemia is due to inadequate production or loss of erythrocytes caused by bleeding or haemolysis. This approach is useful in those cases where MCV is normal. Pathogenic classification is also essential for proper recognition of the mechanisms involved in the genesis of anaemia. Based on the pathogenic mechanisms, anaemia is further divided into two types namely, (i) hypo-regenerative in which the bone marrow production of erythrocytes is decreased because of impaired function, decreased number of precursor cells, reduced bone marrow infiltration, or lack of nutrients; and (ii) regenerative: when bone marrow upregulates the production of erythrocytes in response to the low erythrocyte mass (Chulilla et al., 2009). This is typified by increased generation of erythropoietin in response to lowered haemoglobin concentration, and also reflects a loss of erythrocytes, due to bleeding or haemolysis. The reticulocyte count is typically higher.   Ã‚  Ã‚  Ã‚  Ã‚  Sickle cell disease is characterised by sickled red cells.   The first report of SCD was published a century ago noting the presence of peculiar elongated cells in blood by James Herrick, an American physician (1910). Pauling et al. (1949) described it as a molecular disease. The molecular nature of sickle haemoglobin (HbS) in which valine is substituted for glutamic acid at the sixth amino acid position in the beta globin gene reduces the solubility of haemoglobin, causing red cells to sickle (Fig. 1). Sickling of cells occurs at first reversibly, then finally as a state of permanent distortion, when cells containing HbS and inadequate amounts of other haemoglobins including foetal haemoglobin, which retards sickling, become deoxygenated (Bunn, 1997). The abnormal red cells break down, leading to anaemia, and clog blood vessels with aggregates, leading to recurrent episodes of severe pain and multiorgan ischaemic damage (Creary et al., 2007). The high levels of inflammatory cytokines in SCD may promote retention of iron by macrophage/reticuloendothelial cells and/or renal cells. SCD care commonly depends on transfusion that results in iron overload (Walter et al., 2009). 3. Pathogenesis of anaemia Anaemia is a symptom , or a syndrome, and not a disease (Chulilla et al., 2009). Several types of anaemia have been recognised, the pathogenesis of each being unique. Iron deficiency anaemia (IDA) is the most common type of anaemia due to nutritional causes encountered worldwide (Killip et al., 2008). Iron is one of the essential micronutrients required for normal erythropoietic function While the causes of iron deficiency vary significantly depending on chronological age and gender, IDA can reduce work capacity in adults (Haas Brownlie, 2001) and affect motor and mental development in children (Halterman et al., 2001). The metabolism of iron is uniquely controlled by absorption rather than excretion (Siah et al., 2006). Iron absorption typically occurring in the duodenum accounts for only 5 to 10 per cent of the amount ingested in homoeostatis. The value decreases further under conditions of iron overload, and increases up to fivefold under conditions of iron depletion (Killip et al., 2008). Iron is ingested as haem iron (10%) present in meat, and as non-haem ionic form iron (90%) found in plant and dairy products. In the absence of a regulated excretion of iron through the liver or kidneys, the only way iron is lost from the body is through bleeding and sloughing of cells. Thus, men and non-menstruating women lose about 1 mg of iron per day while menstruating women could normally lose up to 1.025 mg of iron per day (Killip et al., 2008). The requirements for erythropoiesis   which are typically 20-30 mg/day   are dependent on the internal turnover of iron (Munoz et al., 2009) For example, the amount of iron required for daily production of 300 billion RBCs (20-30 mg) is provided mostly by recycling iron by macrophages (Andrews, 1999).   Ã‚  Ã‚  Ã‚  Ã‚  Iron deficiency occurs when the metabolic demand for iron exceeds the amount available for absorption through consumption. Deficiency of nutritional intake of iron is important, while abnormal iron absorption due to hereditary or acquired iron-refractory iron deficiency anemia (IRIDA) is another important cause of unexplained iron deficiency. However, IDA is commonly attributed to blood loss e.g., physiological losses in women of reproductive age. It might also represent occult bleeding from the gastrointestinal tract generally indicative of malignancy (Hershko and Skikne, 2009).   Ã‚  Ã‚  Ã‚  Ã‚  Iron absorption and loss play an important role in the pathogenesis and management of IDA. Human iron disorders are necessarily disorders of iron balance or iron distribution. Iron homeostasis involves accurate control of intestinal iron absorption, efficient utilisation of iron for erythropoiesis, proper recycling of iron from senescent erythrocytes, and regulated storage of iron by hepatocytes and macrophages (Andrews, 2008). Iron deficiency is largely acquired, resulting from blood loss (e.g., from intestinal parasitosis), from inadequate dietary iron intake, or both. Infections, for example, with H pylori, can lead to profound iron deficiency anemia without significant bleeding. Genetic defects can cause iron deficiency anaemia. Mutations in the genes encoding DMT1 (SLC11A2) and glutaredoxin 5 (GLRX5) lead to autosomal recessive hypochromic, microcytic anaemia (Mims et al., 2005). Transferrin is a protein that keeps iron nonreactive in the circulation, and del ivers iron to cells possessing specific transferrin receptors such as TFR1 which is found in largest amounts on erythroid precursors. Mutations in the TF gene leading to deficiency of serum transferrin causes disruption in the transfer of iron to erythroid precursors thereby producing an enormous increase in intestinal iron absorption and consequent tissue iron deposition (Beutler et al., 2000). Quigley et al. (2004) found a haem exporter, FLVCR, which appears to be necessary for normal erythroid development. Inactivation of FLVCR gene after birth in mice led to severe macrocytic anaemia, indicating haem export to be important for normal erythropoiesis.   Ã‚  Ã‚  Ã‚  Ã‚  The anaemia of chronic disease (ACD) found in patients with chronic infectious, inflammatory, and neoplastic disorders is the second most frequently encountered anaemia after iron-deficiency anaemia. It is most often a normochromic, normocytic anaemia that is primarily caused by an inadequate production of red cells, with low reticulocyte production (Krantz, 1994). The pathogenesis of ACD is unequivocally linked to increased production of the cytokines including tumour necrosis factor, interleukin-1, and the interferons that mediate the immune or inflammatory response. The various processes leading to the development of ACD such as reduced life span of red cells, diminished erythropoietin effect on anaemia, insufficient erythroid colony formation in response to erythropoietin, and impaired bioavailability of reticuloendothelial iron stores appear to be caused by inflammatory cytokines (Means, 1996;2003). Although iron metabolism is characteristically impaired in A CD, it may not play a key role in the pathogenesis of ACD (Spivak, 2002). Neither is the lack of available iron central to the pathogenesis of the syndrome, according to Spivak (2002), who found reduced iron absorption and decreased erythroblast transferrin-receptor expression to be the result of impaired erythropoietin production and inhibition of its activity by cytokines. However, reduced erythropoietin activity, mostly from reduced production, plays a pivotal role in the pathogenesis of ACD observed in systemic autoimmune diseases (Bertero and Caligaris-Cappio, 1997). Indeed, iron metabolism as well as nitric oxide (NO), which contributes to the regulation of iron cellular metabolism are involved in the pathogenesis of ACD in systemic autoimmune disorders. Inflammatory mediators, particularly the cytokines, are important factors involved in the pathogenesis of the anaemia of chronic disease, as seen in rheumatoid arthritis anaemia (Baer et al., 1990), the cytokines causing impai rment of erythroid progenitor growth and haemoglobin production in developing erythrocytes.     Ã‚  Ã‚  Ã‚  Ã‚  Anaemia is also commonly found in cases of congestive heart failure (CHF), again caused by excessive cytokine production leading to reduced erythropoietin secretion, interference with erythropoietin activity in the bone marrow and reduced iron supply to the bone marrow (Silverberg et al., 2004). However, in the presence of chronic kidney insufficiency, abnormal erythropoietin production in the kidney plays a role in the pathogenesis of anaemia in CHF.   Ã‚  Ã‚  Ã‚  Ã‚  The myelodysplastic syndromes (MDS) are common haematological malignancies affecting mostly the elderly as age-related telomere shortening enhances genomic instability (Rosenfeld and List, 2000). Radiation, smoking and exposure to toxic compounds e.g., pesticides, organic chemicals and heavy metals, are factors promoting the onset of MDS via damage caused to progenitor cells, and, thereby, inducing immune suppression of progenitor cell growth and maturation. TNF- and other pro-apoptotic cytokines could play a central role in the impaired haematopoiesis of MDS (Rosenfeld and List, 2000). Premature intramedullary cell death brought about by excessive apoptosis is another important pathogenetic mechanism in MDS (Aul et al., 1998).     Ã‚  Ã‚  Ã‚  Ã‚  SCD arising from a point mutation in the ÃŽ ²-globin gene and leading to the expression of haemoglobin S (HbS) is the most common monogenetic disorder worldwide. Chronic intravascular haemolysis and anaemia are some important characteristics of SCD. Intravascular haemolysis causes endothelial dysfunction marked by reduced nitric oxide (NO) bioavailability and NO resistance, leading to acute vasoconstriction and, subsequently, pulmonary hypertension (Gladwin and Kato, 2005).    However, a feature that differentiates SCD from other chronic haemolytic syndromes is the persistent and intense inflammatory condition present in SCD. The primary pathogenetic event in SCD is the intracellular polymerisation or gelation of deoxygenated HbS leading to rigidity in erythrocytes (Wun, 2001). The deformation of erythrocytes containing HbS is dependent on the concentration of haemoglobin in the deoxy conformation (Rodgers et al., 1985). It has been demonstrated that sickle mono cytes are activated which, in turn, activate endothelial cells and cause vascular inflammation. The vaso-occlusive processes in SCD involve inflammatory and adhesion molecules such as the cell adhesion molecules (CAM family), which play a role in the firm adhesion of reticulocytes and leukocytes to endothelial cells, and the selectins, which play a role in leukocyte and platelet rolling on the vascular wall (Connes et al., 2008). Thus, inflammation, leucocyte adhesion to vascular endothelium, and subsequent endothelial injury are other crucial factors contributing to the pathogenesis of SCD (Jison et al., 2004). 4. Current therapies for clinical management of sickle cell disease including a critical appraisal of transfusion Between 1973 and 2003, the average life expectancy of a patient with SCD increased dramatically from a mere 14 years to 50 years thanks to the development of comprehensive care models and painstaking research efforts in both basic sciences especially molecular and genetic studies, and clinical aspects of SCD (Claster and Vichinsky, 2003). The clinical manifestations of SCD are highly variable. Both the phenotypic expression and intensity of the syndrome are vastly different among patients and also vary longitudinally within the same patient (Ballas, 1998). New pathophysiological insights available have enabled treatments to be developed for the recognised haematologic and nonhaematologic abnormalities in SCD (Claster and Vichinsky, 2003). The main goals of SCD treatment are symptom alleviation, crises avoidance and effective management of disease complications. The strategy adopted is primarily palliative in nature, and consists of supportive, symptomatic and preventative approaches to therapy. Symptomatic management includes pain mitigation, management of vasoocclusive crisis, improving chronic haemolytic anaemia, treatment of organ failure associated with the disease, and detection and treatment of pulmonary hypertension (Distenfeld and Woermann, 2009). The preventative strategies include use of prophylactic antibiotics (e.g., penicillin) in children, prophylactic blood transfusion for prevention of stroke in patients especially young children who are at a very high risk of stroke, and treatment with hydroxyurea of patients experiencing frequent acute painful episodes (Ballas, 2002). Currently, curative therapy for sickle cell anaemia is only available through bone marrow and stem cell transplantation. Hematopoietic cell transplantation using stem cells from a matched sibling donor has yielded excellent results in paediatric patients (Krishnamurti, 2007). Curative gene therapy is still at the exploratory stage (Ballas, 2002). 4.1 Current and potential therapies The potential treatment strategies basically target cellular dehydration, sickle haemoglobin concentrations, endothelial dysfunction, and abnormal coagulation regulation (Claster and Vichinsky, 2003). HbS concentrations are essentially tackled through transfusions while approaches to reduce HbS polymerisation which is the main mechanism for the development of vaso-occlusion include (a) increasing foetal haemoglobin (HbF) concentration using hydroxyurea (Fig. 2), butyrate, or erythropoietin, and (b) preventing sickle cell dehydration using Clotrimazole (Fig. 3) or Mg2+pidolate. Hydroxyurea therapy increases the production of HbF in patients with sickle cell anaemia, and, thereby, inhibits the polymerisation of HbS and alleviates both the haemolytic and vaso-occlusive manifestations of the disease (Goldberg et al., 1990). Recombinant erythropoietin also increases the number of reticulocytes with HbF. Additionally, it has been observed that administration of intravenous recombinant eryt hropoietin with iron supplementation alternating with hydroxyurea enhances HbF levels more than hydroxyurea alone (Rodgers et al., 1993). As SCD is essentially characterized by an abnormal state of endothelial cell activation   that is, a state of inflammation, a pharmacologic approach to inhibit endothelial cell activation has proved clinically beneficial (Hebbel and Vercellotti, 1997). Thus, administration of sulfasalazine which is a powerful inhibitor of activation of nuclear factor (NF)-B, the transcription factor promoting expression of genes for a number of pro-adhesive and procoagulant molecules on endothelium to humans has been found to provide transcriptional regulation of SCD at the endothelium level (Solovey et al., 2001). 4.2 Red blood cell transfusion A key therapy that is applied regularly in the clinical management of patients with SCD is packed red blood cell transfusion. RBC transfusion improves the oxygen-carrying capacity which is achieved by enhancing the haemoglobin levels, causes dilution of HbS concentration thereby, reducing blood viscosity and boosting oxygen saturation. Furthermore, RBC transfusion is helpful in suppressing endogenous production of sickle RBCs by augmenting tissue oxygenation ( Josephson et al., 2007). There are two major types of RBC transfusion therapy: intermittent and chronic which are further classified as prophylactic or therapeutic. Intermittent transfusions are generally therapeutic in nature and administered to control acute manifestations of SCD whereas chronic transfusions are performed as general preventative measures to check complications of SCD. RBC transfusion given as a single dose is termed as simple transfusion. Exchange transfusion involves administration of a larger volume of RBCs replacing the patients RBCs that are simultaneously removed. Details of the various types of RBC transfusion and the major clinical indications for the same in SCD patients are listed in Table 1. 4.3 Indications for intermittent transfusions Indications for intermittent transfusions include acute manifestations of SCD, as indicated in Table 1, that require redressal through therapeutic transfusions. However, under certain circumstances intermittent transfusions could be prophylactic such as for instance, when SCD patients are transfused before specific surgeries viz., those related to pregnancy complications or renal failure (Table 1). Acute Chest Syndrome (ACS) describes a manifestation of SCD in which, due to sickling, infectious and noninfectious pulmonary events are complicated, resulting in a more severe clinical course. The diagnosis is the presence of a new infiltrate on chest radiography that is accompanied by acute respiratory symptoms. ACS accounts for nearly 25% of all deaths from SCD (Vichinsky, 2002). Repeated episodes of ACS are associated with an increased risk of chronic lung disease and pulmonary hypertension (Castro, 1996). The severe pulmonary events occurring in SCD may be precipitated by any trigger of hypoxia (Vichinsky, 2002). Transfusions are very efficacious and provide immediate benefit by reversing hypoxia in ACS. Transfusion of leucocyte-poor packed red cells matched for Rh, C, E, and Kell antigens can curtail antibody formation to below 1% (Vichinsky, 2002). Simple transfusions suffice for less severe cases; however, exchange transfusion is recommended to minimise the risk of increased viscosity. Also, chronic transfusion appears promising for prevention of recurrence in selected patients (Styles and Vichinsky, 1994). In a multicentre ACS trial, prophylactic transfusion was found to almost completely eliminate the risk of pulmonary complications (Vichinsky, 2002).   Ã‚  Ã‚  Ã‚  Ã‚  Acute Symptomatic Anaemia arises in SCD as a result of blood loss, increased RBC destruction, suppression of erythropoiesis etc. and is effectively treated with intermittent transfusion of RBCs to relieve symptoms of cardiac and respiratory distress (Josephson et al., 2007).   Ã‚  Ã‚  Ã‚  Ã‚  Aplastic Anaemia is commonly caused in SCD on account of infection of haematopoietic precursors in the bone marrow by Parvovirus B19 leading to a steep fall in RBCs. According to Josephson et al. (2007), therapeutic intermittent transfusion of RBCs is again the recommended first-line of treatment to improve total haemoglobin count and prevent cardiac decompensation. However, in those patients who are prone to fluid overload on account of cardiac or renal dysfunction an alternative transfusion strategy is to remove the whole blood and replace it with packed cells while avoiding the addition of excess volume (Josephson et al., 2007).   Ã‚  Ã‚  Ã‚  Ã‚  Acute Stroke is a high risk especially in paediatric SCD cases because of elevated cerebral flow. Enormous decline in stroke rate have occurred in children receiving intermittent simple transfusion (Adams et al., 1998). However, the identification of the stroke type would be necessary in all SCD patients in order to determine the appropriate treatment approach since the occurrence of infarctive strokes is higher in children as opposed to a higher incidence of haemorrhagic strokes in adults (Adams, 2003). 4.4 Indications for Chronic Transfusions Prophylactic chronic RBC transfusion every 3 to 4 weeks to maintain HbS levels lower than 30% is crucial for preventing first as well as recurrent strokes in children (Johnson et al., 2007). The transfusions could either be chronic simple transfusion or prophylactic chronic RBC exchange transfusion. Prophylactic chronic transfusions are recommended for patients with chronic renal failure so as to avoid severe symptomatic anaemia and for those patients with SCD undergoing pregnancy with complications. However, prophylactic transfusion is not indicated for SCD patients with normal pregnancy (Tuck et al., 1987). 4.5 Controversial and indeterminate indications for transfusion Several situations also exist wherein the indication for red cell transfusion is controversial, uncertain, or downright injudicious in SCD management. Some examples are indicated in Table 1.   Ã‚  Ã‚  Ã‚  Ã‚  According to Hankins et al. (2005), chronic transfusion therapy is helpful in reducing the incidence of strokes in children but not the severity of strokes. In the case of acute priapism, improvement in patients has been observed after exchange or simple transfusion (Rifikind   et al., 1979). Yet, due to the ASPEN syndrome, transfusion therapy currently is only a second-line therapy in the management of priapism ( Miller et al., 1995).   Ã‚  Ã‚  Ã‚  Ã‚  RBC transfusion is a vital component in the management of symptoms and complications of SCD. It has drastically reduced the morbidity and mortality of SCD. Yet, immune-related effects such as FNHTRs (Febrile Non-Haemolytic Transfusion Reaction i.e., fever resulting from a blood transfusion) and alloimmunisation to HLAs (Human Leucocyte Antigens),   and nonimmune-related effects e.g., iron overload and transfusion-transmitted infections are serious adverse effects of the transfusion therapy that need to be attended to in SCD patients receiving transfusion (Johnson et al., 2007). Chronic transfusions could result in an inexorable accumulation of tissue iron that could become fatal if not treated (Cohen, 1987). Excess iron damages the liver, endocrine organs, and heart and may be fatal by adolescence (E

The Purpose Of A Business Plan Business Essay

The Purpose Of A Business Plan Business Essay In most cases, a business plan is created to explain and illustrate the vision you have for your business, and to persuade others to help you achieve that vision. To accomplish this, your plan will need to demonstrate on paper that you have a firm visualization of what your business is going to be. It needs to convince others that your business concept can be successful and that you possess the expertise-alone or collectively-to assure that it will be both successful and profitable. Why is it important It is important to use a business plan when starting and running the business as it indentifies the business aims and objectives, also it is important to have one as it will allow the business to go back and see if the business is progressing in the developing business and if the business is on the track to achieve the aim. RANGE OF POSSIBLE IDEAS I had many potential ideas of the businesses that I would like to set up in Lisburn. My most favourite ideas which I was considering to start up are: Restaurant In the current time in Lisburn there are several restaurants and there is no which serves multinational menus which include European, Asian and American foods. I believe that this business could be successful as many of peoples would like to try other nationalities foods. To run this business successfully I will have to create a very warm and welcome premise to which lots of peoples will be able to like it and. Also the service and food will need to be high quality so the customers will love to come back. Advantages Original menu as no restaurants serves the food I would If the business will gain loyal customers the business will survive Disadvantages Risk of not getting into the taste of locals Competition with well established restaurants Unknown local suppliers product quality Inexperienced staff Sandwich bar In modern days more peoples are buying ready to do foods such as chips, crisps, sweets which are bad for health. My idea is to let adults and children to have a healthy break time eating fresh ingredients and healthy sandwiches. To survive I will need to provide my business with the equipment such as Toaster, Micro wave, Panini maker, Serving Unit Hot/Cold, Grills, Till and much more. Advantages Disadvantages Competition with well established businesses Inexperienced staff Unknown local suppliers product quality Coffee shop Many people are in the hurry in these days, where most of them dont have time to consume their breakfast at home. The coffee shop idea will allow to those peoples who have to travel long time to their jobs, to buy tea or coffee and the snack and consume on the way, this could save enormous amount of time if they could decide to do their lunch and coffee themselves. I will have to spend about  ¼ of my budget on the equipment where I will need to buy equipment such as coffee machine, cups (glass and plastics), plates and more. Advantages Disadvantages Competition with well established businesses Inexperienced staff Unknown local suppliers product quality Ice Ring Lisburn does not have many attractions in the city, so it could be a good idea to get everyone enjoy their afternoons on the ice cold ring. It could be a very good place to have fun with the family and friends away from their troubles. The business could survive as the only other attractions could be the swimming pool and cinema which are located in the city centre. Advantages Disadvantages Expensive to run and insure Lots of health and safety issues will need to be complete. After concluding my potential businesses ideas I had rejected some of the ideas as there was the possibility that they wont survive the first year of trading. This is the list in order of the businesses I want to operate. The first one is the business I am currently going for, the last one is the least possible for me to go for. Coffee shop Sandwich bar Restaurant Ice Ring After knowing what business I am going to open I had thought about the name for it. The name that the most attracts my attention is CS. It is short and easy to remember which is excellent name. LEGAL STATUS There are several legal statuses available for my chosen business: Solo trader This is when the business is owned and run by one individual; however this is mainly the local business and will normally not expand on an international level. Main advantages of a solo trader à ¢Ã¢â€š ¬Ã‚ ¢ 100% of control over the business it means that the entire business is controlled by one person only which is mainly owner. à ¢Ã¢â€š ¬Ã‚ ¢ Quicker at decision making it allows to easy and fast make decision as there is only one person whom make the decisions and dont have anyone to make the decisions. à ¢Ã¢â€š ¬Ã‚ ¢ Can keep 100% of profit if the business is well operating it even can make high wage and dont have to share profit with anyone. à ¢Ã¢â€š ¬Ã‚ ¢ Local business, therefore loyal customers from that area loyal customers may result in a consistent flow of money into the business. Main disadvantages of a sole trader à ¢Ã¢â€š ¬Ã‚ ¢ Unlimited liability this may meant that the owner may lose his personal possessions because of the business depth and cannot pay it back. à ¢Ã¢â€š ¬Ã‚ ¢ Heavy stressful workload because it is a solo trader business it means that the one person has to do all of the activities which includes paperwork and more, which could cause stress, about not completing it and of the lack of time. à ¢Ã¢â€š ¬Ã‚ ¢ Finance problems because the business small and is financed by one person and maybe by a bank loan. The solo trader may face finance difficulties if the business will get into the debt. Partnership a partnership is when between two and twenty peoples own a business, as there is large number of co-workers each is investing money in to the business and share the profit or loses of the business. Main advantages of a Partnership à ¢Ã¢â€š ¬Ã‚ ¢ More peoples investing money because there is many partners the large capital and large funds are raised quickly, this means that the business can easily and faster earn stable finance source than a solo trader. à ¢Ã¢â€š ¬Ã‚ ¢ More ideas because there is more than one person who owns the business, each has different ideas how to improve the business. à ¢Ã¢â€š ¬Ã‚ ¢ Shared workload as the business has more than one owners the workload can be easy shared between partners which decrease the possibility of stress. Main disadvantages of a Partnership à ¢Ã¢â€š ¬Ã‚ ¢ Disagreements as each of the partners have different ideas to improve the business the disagreements can appear as other person doesnt like the idea which is currently discussed. à ¢Ã¢â€š ¬Ã‚ ¢ Breakdown in communication this can be cause when one of the partners will decide to go ahead with their own ideas, in which case may cause other departments become confused and may lose the communication between each other. à ¢Ã¢â€š ¬Ã‚ ¢ Unlimited liability if the business will be in the debt there is possibility the owners will lose their personal processions to pay back the debt. Over considering different legal status available, I decided that the most appropriate status for my business is solo trader. Despise of all the disadvantages. I had chosen this legal status for the reason that I can test my self if I can run business on my own. Also I had choose it for the reason the I wont rely on any one with decision making and I will operate the business as I want. I did not choose the partner ship as we may have disagreements which may have effects on business which may lead to close down; this is the risk that I dont want to take, as I may loose lots of my money. RESEARCH COMPREHENSIVE ANALYSIS The primary research that I had carried out was a questionnaire which I had held in the city centre of Lisburn. I choose this destination as this is where I am hoping to set my business. From the questionnaire I will receive the overview and the opinions of my future target market. Primary research The first question I had asked in the questionnaire was What age group would you be in? Form this question I had found the majority of my target market would come from 18-20 age group. The second popular age group was 21-30age group and 31-40 age group as both has the same percentage. The second question I had asked in the questionnaire was How often to you visit coffee shop? The result was very interesting as 40% of people who had fill in this questinoaire had said that they are visiting coffee shops every day. The 28% said that they are visitgin coffee shop weekly. I also asked if they would be interested if I would provide any refreshments suchas sandwitches and fresh salad. For the pie chart I noticed that 72% of people thinks that this is a good idea. As I know thatthey would like to have a sandwitches and salad I had asked them how much they would like to be charged for them. I had allowed them to choose the costs starting form  £1.50 up to  £4+. More than 56% said that they prefeer the price to be  £2.50 as for this price the best igridients can be purchased. As there are many students living in the Lisburn I had asked peoples in their opinion would the discount for students encourage them to go to coffee shop. The 56% of votes said that they would be encouraged to visit the coffee shop. Secondary research The UK branded coffee chain market continues to expand rapidly, exceeding 3,000 outlets for the first time and an estimated  £1.3 billion in turnover as UK consumers taste for coffee bars continues unabated. According to Allegria Strategies, the market is forecast to nearly double over the next decade to reach up to 6,000 outlets and turnover in excess of  £2.5 billion within 7-10 years. Growing at more than 15 per cent for the past eight years, UK coffee bar culture has extended well beyond UKs major urban centres and is penetrating smaller towns and the provincial areas due to phenomenal consumer demand and rapid opening programmes by coffee bar chains Starbucks, Costa Coffee, Caffà ¨ Nero, Pret A Manger and others. Results from more than 6,300 telephone and face-to-face interviews with UK consumers (the largest sample ever conducted in the UK) reveal that consumers are visiting branded coffee chains more frequently than ever before: Coffee shops are now mainstream and form an important part of UK lifestyles with more than 11 million adults visiting coffee shops at least once per week and more than 20 million persons visiting the venues at least once per month AIMS/OBJECTIVES OF A BUSINESS An aim is a long term intention that business wants to achieve. All businesses have different aims and sometimes some businesses have more than one. To achieve the aims an objectives are set. Objectives are the goal outcomes or targets. Many businesses are using SMART method to set their objectives achievable. Smart stands for; Specific they must set out clearly what a business sis aiming to do. Measurable they must be capable of being met Achievable everyone involved in reaching the objective must agree with the objective and understand what is meant by it. Realistic the objectives must be achievable from the source that are available form and for the state of the market conditions Time specific the objective should state over what time of period the objective has to be achieved. Many businesses create a mission statement, which states the purpose of the business and it values. It is meant to stake both the aims of the business and the provide a vision of the business for the stakeholders. The aim for my business is; Achieve the loyal customers by offering an efficient and reliable service at a low cost. The objectives for my business are; Survive when I first start out Get loyal customers and staff To break even within the first year Become market leader within next five years PROMOTION STRATEGIES Marketing mix refers to the primary elements that must be attended to in order to properly market a product or service. Also known as The 4 Ps of Marketing, the marketing mix is a very useful, if a bit general, guideline for understanding the fundamentals of what makes a good marketing campaign Elements of the marketing mix are often referred to as the four Ps: Product A tangible object or an intangible service that is mass produced or manufactured on a large scale with a specific volume of units. Price The price is the amount a customer pays for the product. It is determined by a number of factors including market share, competition, material costs, product identity and the customers perceived value of the product. Place Place represents the location where a product can be purchased. It is often referred to as the distribution channel. Promotion represents all of the communications that a marketer may use in the marketplace. Promotion has four distinct elements advertising, public relations, word of mouth and point of sale This is the marketing mix for my business considering 4ps; Product The product which I am going to provide is a wide range of coffees, teas, snacks, sandwiches and fresh salads and fizzy drinks. Price Because of the recession not many peoples will allow them selves for the take away coffee. There fore I will need to sell my product in the lowest price as possible. All the hot drinks will be sold between  £2  £4, all the soft drinks  £1 and the snacks, sandwiches and salads between  £1,50- £3. Place The premise which I choose for my coffee shop is located in the centre of the city centre. The premise which I found is for the rental purpose and costs  £1,000 per month. This property has 2 floors with reasonable good sizes. The ground floor will be used as a main area of the shop where customers will be served and use the Wi-Fi, where as the first floor will be the office area. Promotion To promote my business I am going to us local news papers to advertise my coffee shop. To support my promoting method I am going to use leaflets which will be delivered by the local postman. The leaflet details will include the prices, available coffees types, and location and contact details. LIKELY COMPETITORS I discovered my likely competitors by doing research on yell.co.uk and from local knowledge. There are four well established businesses which I will compete with for survival. This are; Esquires coffee shop The house of Vic-Ryn Street cafe Coffee Inc Each of those businesses are well established and have regular customers. Because all of them are mainly located in the city centre the competition will be heavy on me as the premise which I will use form my business is also in the city centre. SWOT ANALYSIS SWOT analysis can be defined strategic planning method used to evaluate the Strengths, Weaknesses, Opportunities, and Threats involved in a business venture. It involves specifying the objective of the business venture or project and identifying the internal and external factors that are favourable and unfavourable to achieving that objective. SWOT represents; Strengths: attributes of the person or company those are helpful to achieving the objective(s) Weaknesses: attributes of the person or company those are harmful to achieving the objective(s). Opportunities: external conditions those are helpful to achieving the objective(s). Threats: external conditions which could do damage to the objective(s). Strengths and Weaknesses can be controlled within the business. It is up to the manager to deal with these at the right time and in the appropriate way. Opportunities and Threats are out of control of the manager. Theyre therefore external. This is my swot analyse for my business CAFE LATTE. Strengths Sit in facility Wi-Fi facilities Offering different types of foods and snacks Located in the city centre Weaknesses Not well known Competition with established businesses Opportunities Expand locally Buy more specious premises allowing being more welcome Threats Esquires coffee shop The house of Vic-Ryn Street cafe Coffee Inc SECTION B PHYSICAL RESOURCES Physical resources are defined as resources that are available to business organisations in the form of buildings and other machineries which are needed for the day to day running of the organisation. To smoothly operate my business I need meet physical requirements which will allow me to survive and operate my business. the equipments which I need for my business are listed bellow. The equipment list Item Quantity Unit Price Total Price Timing Buy/Lease Counter 1  £10,000  £10,000 Start Up Buy Seating (chairs and tables) 15  £8,000  £8,000 Start Up Buy Water boiler 1  £464.13  £464.13 Start Up Buy Coffee machine 2  £500  £1,000 Start Up Lease Coffee (12 kg) 4  £60  £240 Start Up Buy Cookery 60  £329.50  £329.50 Start Up Buy Knives, forks and spoons 40  £50  £50 Start Up Buy Refrigerated display units 1  £2,010.  £2,010 Start Up Buy Cleaning fluids 6  £600  £600 Start Up Buy HUMAN RESOURCES Human resources are known as people employed by a business. This means that human resources are the number of people working for the business. The number of human resources is related to the business, for example a small business such as a window cleaning service has small human resources which may include two or five employees. The big international businesses on the other wise, such as Tesco, or Sainsbury are more likely to have thousands or even more workers. Because my business is small and is just starting up I wont need too many human resources. To be able to successfully operate the business I am going to employ 2 full time and 1 part time employees. Each employee will be required to have good communication skills and be able to work in the busy atmosphere. Because I want to encourage my staff to perform on their best abilities I am going to award them by adding additional  £1.00 to theirs minimal wage. There are several policies that I will need to take into consideration if I want my business to operate legally and satisfy my customers and staff. Health and safety issue is the most important regulation which I need to consider. I will be required to make sure that I will create a safe environment for my workers and the customers. If the accident will happen because of not making any health and safety requirements I can be sued which could cost me money and time, including it could reflect my business reputation. Equal Pay Act, 1970 Sex Discrimination Act, 1995 is another important law which I have to make sure I will consider within my business. When I will going to advertise my vacancy I cannot specify what sex I am looking for as this is how the law is broken. I have to make sure that I will give a fair chance for both sexes to try to apply for the job. The National Minimum Wages Act, 1998 this law simply clarified that people cannot be underpaid under the minimum national wage. There are three branches of this legislation; Between 16 and 17 years  £3.57 an hour Between 18 and 21 years  £4.83 an hour 22 and over  £5.80 an hour Data Protection Act, 1984 I need to consider this act in order to keep my staff and my business details save. Because I will need to store the private and financial details I will need to make sure that no on unauthorised will have access to these details. Disability Discrimination Act, 1995 I need to make sure that I wont discriminate any employee because of theirs disability. I am not going to consider the disability in picking appropriate employee for my business. The only fair way is by picking the qualifications and experience. RESOURCES AND QUALITY CONSTRAINTS LEGAL AND ECONOMIC Pestle analysis is one of framework that categorizes environmental influences as political, economic, social and technological forces. Sometimes two additional factors, environmental and legal, will be added to make a PESTEL analysis, but these themes can easily be subsumed in the others. Political influences These refer to government policy such as the degree of intervention in the economy. Economic influences These include interest rates, taxation changes, economic growth, inflation and exchange rates. Social influences Changes in social trends can impact on the demand for a firms products and the availability and willingness of individuals to work. Technological influences new technologies create new products and new processes. Legal influences environmental factors include the weather and climate change. Changes in temperature can impact on many industries including farming, tourism and insurance. Environmental influences these are related to the legal environment in which firms operate. For my business there are several constraints relevant to me are legal, economic, technical, and environmental. Legal constraints The legal constraints that will affect my business are regulations for a contract for example how long is the credit on it. Anther legal constraint would be DPA (Data Protection Act) in the UK gives the right to individual to know which companies hold their personal details and they are allowed to ensure that the information is accurate. This data should be also being protected within the business to ensure no one unauthorised will access the personal details. Economic constraints due to the current economy it will be harder for me to get a bank loan. Also because of the recession not every one will be able to afford the take away or sit in coffee. Technical constraints I will need to make sure that all the Environmental constraints as I will provide a take away service I will provide with recycle cops which will be easily recycle and good for environment. Also I will provide customers with business plastic take away cups with the lids which will allow them to use it to refill. SECTION C SOURCES OF FINANCE There are different sources of finance I can use to finance my business. Those sources are; Money from family or friends because I am a sole trader I may be able to borrow money from family or friends without paying interest, which would be very beneficial for me. Bank loan another way to finance my business I may use a bank loan. Loans from a bank or a building society can be expensive as they will include the interest. An agreed amount is borrowed and repaid over a fixed period of time with interest. To start up my business I am going to use the  £10,000 that I was left by my grandparents. Although my physical resources of total of  £22.694. I decided that I am going to take a bank loan. The loan which I will take will cover both my start up cost and running costs. I am hoping to get a loan that will be for 4-5 years which also will cover the unexpected expenses. The loan which I choose is Platinum Loans. I got a loan for  £30,000 and will be repaid by 5 years. The monthly amount to repay is going to be  £601.63 and the 7.8 APR which I total I will need to repay  £36,098. FORECASTS: CASH FLOW AND BREAKEVEN SUSTAINING IDEA After analysing project figures and the information that I had gathered I can say that the business will make profit within the first year. If I would considering expanding my business locally in the future I will need to consider all the major expenses to pay. Into these expenses I am considering a bank loans which will be repaid within 5 years and capital purchase. After two or more years of trading the external factors will need to be considered, as they may change the impact on the business. Those external factors that would change are due to Political, Legal, Social and Economic influences Political influences Legal influences Social influences Economic influences SECTION D BREAK EVEN ANALYSIS Most of the businesses frequently want to know the amount of the business need to produce or to reach break even. If the business has collect the information about fixed costs and variable cost and what process it is going to charge, it will allows to calculate how many units will be required to sell to cover all of its costs. The stage of sales or outputs where total costs are exactly the same as the total revenue is called a breakeven point. There are several uses of the break even and the most common one which are used by almost most of the businesses are based on: Calculate in advanced the level of sale needed for break even See chow changes on the in cost affect the break-even point and profit See how effect in output affects profit. To calculate a break even point I am going to use following formula; BE= SP-VC/FC. (BE- Break Even, SP Selling Price, VC Variable Cost, FC Fix Costs). I also used this formula to draw up business break even point graph what will show exactly how much units needs to be sold to break even. Selling price Is the price that a unit is sold for. Sales Tax is not included the selling price and a sales tax paid is not included as a cost. The selling price of my products is 2,50 per unit Variable cost Variable costs are costs directly related to production units. Typical variable costs include direct labour and direct materials. Coffee, Cups, Lead and Sugar the total of those materials is 0.40 per unit. Fix costs Cost that do not change when production or sales levels do change, such as, rent, property tax, insurance, or interest expense. The total fix cost is  £55,934 Break even calculation BE= 2.50-0.40/55,934 BE = 26,636 This is the graph which shows the break even unit point. As you can see to break even I need to sell 26,636 units of coffee in a year. To get more specific figures that 2,220 coffees a month, which I think is achievable.  £ 0 RATIO ANALYSIS EXCLUSIVE SUMMARY The business that I had decided to set up is CS which will be located in - in Lisburn. The opening hours will be 8 am to 5 pm form Monday to Friday and 10 am to 3pm in Saturday and Sunday. Products The products that my coffee shop is going to sell is a wide range of coffee, teas, snacks, sandwiches and fresh salads and fizzy drinks. All the foods will be home made which will Employees I am going to employ two full times and one part time employee. Each of the employees will be paid  £1 over their minimal wage, which will allow me to motivate them. Finance Because  £10,000 which I got from my grandparents will be not enough to start the business I will take the loan. The amount I am taking is  £30,000 which will be repaid over 5 year time. Competition Esquires coffee shop The house of Vic-Ryn Street cafe Coffee Inc