Middle Age Religion

During the Middle Ages, the Catholic Church was the sole church in Europe, where it has its own laws and its own treasury. The church was considered as an important law-making body, recognized not only by the people, but also by its leaders. The heads of the Catholic Church played big roles in the government, as they used their influence to get their way on things. Bishops were rich people at that time, and has come from a line of noble families. They have a tight hold on the people, especially since they are the ones who are â€Å"closer† to God.The lives of the people living in the Middle Ages were greatly dominated by the church. The church’s influence is limitless, from peasants, to noble lords and even the Kings – they all succumb to the will of the Church. Many of the medieval people dedicated their lives in the service of the Catholic Church and the religion they are in. They offer a life of service to the people of the Church, in hope that their actions w ould be acknowledged by God, the creator. This had been the usual threat being issued by the people of the church in order to get what they wanted from the people (Carr).During the early years of the Christian religion, its growth was being suppressed by the Roman Empire. This is because the Christians have refused to worship the Roman gods or acknowledge the power of the Roman Emperor. Christians have been persecuted all throughout the empire. These persecutions ended during the reign of Emperor Constantine, who made Christianity the official religion of the Roman Empire. Constantine the Great then proclaimed himself as the emperor of the Christian people, thus spreading the religion throughout the Empire (Middle-Ages.org.uk).The beginning of the 5th century saw the crumble of the Roman Empire. This is caused by invading Germanic tribes conquering the city of Rome. This has led to the period referred to as the Dark Ages. The fall of Rome however, signals the rise of the Christian C hurch. The Dark Ages became a stepping stone for the Catholic Religion to flourish. From the Dark Ages up to the Early Middle Ages, the only accepted Christian religion was the Catholic religion. Catholic means universal, or as a whole. Any sect that was established was viewed to be as acts of heresy and the people are heretical (Middle-Ages.org.uk).The power of the Catholic Church in the middle ages was so great, that it owned lands, imposed its own taxes, and created its own laws. It is a very powerful institution that even Kings succumbed to its influence. The Church also accepted gifts and special offerings made by those who wanted to make sure that they have a place in heaven. The influence of the church extended to various lands. They were alongside the kings and rulers of Europe when it comes to power. Those who oppose the Church will instantly receive excommunication – they would go straight to hell when they die (Oakley).One of the major events in the Catholic Religi on in the middle ages occurred in the latter part of the middle ages. This is when the Eastern and Western Christian Churches split because of issues which arise from the crusades. This is called as the Great Schism, separating the two halves of Christian Churches. Another split occurred in the Western Christendom when two Popes have been elected and established at two different places. This is caused by disagreement in the elections. This continued to a few decades, up until the issue was healed at the Council of Constance, and the Catholic Religion finally became known as the Roman Catholic Religion.Works Cited:Carr, Karen. â€Å"Medieval Religion†.   1998. November 4 2007. .Middle-Ages.org.uk. â€Å"Middle Ages Religion†.   2002. November 4 2007. .Oakley, Thomas P. â€Å"Religion and the Middle Ages†.   2007. November 5 2007. .

Assessing what appears to be the use of LAMP in Eduardo Gamarra’s CVA

In January 2003, Eduardo Gamarra and his research team set out to lend their professional and academic expertise in mitigating the probable causes of Bolivian conflicts through the Conflict Vulnerability Assessment or CVA of Bolivia (Gamarra, 2003, p. 1). Assessing the possible causes of conflicts in Bolivia will stop the ongoing threats to countrywide instability.The Bolivian instability may have started and peeked during the 2002 elections where parties started to clamor for position by entering into party coalitions; due to this, the majority vote that should have been echoed as the Bolivian democracy has been counterproductive to insure the satisfaction of party coalition based interests (Gamarra, 2003, p. 4). Through the CVA, Gamarra deems that it is possible to predict possible events that could turn into violent confrontations by taking into account the premises set by the present Bolivian political landscape.In relation to the main objectives of this research paper, Eduardo G amarra’s preemptive and predictive research to address future Bolivian conflicts will be assessed through the methodology that Gamarra employed in his research. As of this point, Gamarra’s CVA appears to employ predictive methodologies in its attempts to prevent the occurrence of violent confrontations in Bolivia. Furthermore, CVA appears to follow conventions of predictive research such as those prescribed in LAMP. As the center of this research paper, Lockwood Analytical Method of Prediction (LAMP) is one of the widely used predictive research methodologies (LAMP, 2010, p.n. pag. ). This methodology offers a new methodological approach from the conventional quantity based projections in predictive researches (LAMP, 2010, p. n. pag. ). LAMP can be assumed as the methodology used by Gamarra in CVA since CVA is also highly predictive in terms of its generalizations. This research paper will assess whether Gamarra’s CVA as a predictive work follows the guidelines set by LAMP. By qualifying the CVA parts and foci with the twelve steps prescribed in LAMP, this paper seeks to fulfill its objective and deems that a definitive conclusion is possible to arrive at. Gamarra as a follower of LAMP as seen in his CVATo conclusively qualify whether Gamarra used the LAMP method in writing the CVA would require the tedious work of identifying whether the part of the LAMP are present in the CVA. This task is impeded by the fact that the final format of the CVA does not have the same labels as the LAMP; at least not as blatant. However, the idea that Gamarra used the LAMP in his CVA can be seen through the parts that his CVA put so much attention on (which follows LAMP prescriptions). These parts appears to have been presented in the CVA; these parts entails almost fifty percent accordance to the prescribe methodology in LAMP.In the whole CVA, the issue that holds the most bearing is the mitigation and prevention of conflicts in Bolivia. Gamarra and his tea m was more than solid in reiterating that the CVA will focus on Bolivia as a conflict prone country. This is the reason why Gamarra and his team spent a lot of time in trying to predict the possibilities of the occurrence of conflicts. Through the extensive research facts presented in the paper, it can even be said that the whole CVA seeks to answer one primary question, â€Å"What are the probable reasons that would cause conflicts to arise in Bolivia?† The CVA tried to find the answer for this question by grouping the conflicts in Bolivia in five major classifications, institutional, economic, land, coca/cocaine, and citizen and public security (Gamarra, 2003, p. 4). In the CVA, Gamarra and his team identified two major actors that can very much affect the outcome of the conflict resolution and mitigation in Bolivia- government and opposition. The MNR or Nationalist Revolutionary Movement represents the government; while the MAS or Movimiento al Socialismo leads the opposit ion. CVA attributed that these parties are the main actors in the Bolivian politics and conflicts.Misunderstandings and apathy between these two parties can easily translate the strong political divide to violent confrontations (Gamarra, 2003, p. 4). However, the CVA did not dismiss the possibility that the 2002 elections can also improve the conflict situation through these parties (Gamarra, 2003, p. 4). The government and the opposition perceive the issues of conflict in terms of their participations on the issues. The government side pride themselves in terms of the international economic and security support it has (Gamarra, 2003, p. 6).On the other hand, the opposition takes pride in the intermediation they are able to contribute to the conflict resolution process (Gamarra, 2003, p. 6). In the CVA Gamarra and his team provided contextualizing facts that would put the MAS led opposition and MNR led government in their places in the conflict situation. This attempt can be seen wi th the graphical representation that Gamarra and his team presented to show the divided opinions of the national actors regarding the appropriate type of government in Bolivia (Gamarra, 2003, p. 14).Gamarra further contextualized the conflicts in terms of the partisan opinion in considering the plausibility of military uprising (coup d’etat) in installing new types of government that parties see as more fitting to Bolivia (Gamarra, 2003, p. 12). Even if Gamarra and his team are loyal to LAMP in these parts of CVA, there are other parts of CVA that show that the CVA was not exclusively written through LAMP. The Contradictions, Shortcomings and Disloyalties of CVA to LAMP As said earlier, the CVA appears to be written through the LAMP; this can hold for the almost fifty percent of the CVA.However, in terms of the data gathering and presentation part of the CVA Gamarra and his team took a different path apart from LAMP. This claim can be supported with the different formulation of the conflict scenarios in the CVA when compared to the LAMP. In LAMP, the permutations of the alternative futures (z) follow a strict formula XY=Z that is determined by the number of actors (x) and the numbers of major scenarios (y) (LAMP, 2010, p. n. pag. ). The formula basis of LAMP insures uniformity in terms of the numbers of scenarios that would be required in predicting through certain national actors.In the CVA there are five major scenarios provided (counter narcotics, political institutions, citizen and public security, economic arena and land ownership). Raising the two identified actors by the five major scenarios will require thirty-two scenarios. On the other hand, the CVA was only able to provide 16 scenarios under the five major scenarios. Another shortcoming of the CVA was its failure to conduct proper pair wise comparison among the scenarios; this resulted to different scenarios provided under the five major scenarios.The scenarios of citizen and public security have four scenarios as compared to the three scenarios of all of the remaining major scenarios (counter- narcotics, political institutions, economic arena and land ownership. Due to the absence of a pair wise comparing mechanism, the CVA also lacks the qualifications of probabilities that are determined through â€Å"votes† from comparing pair wise. These characteristics of the CVA deviated by twenty- five percent from the total twelve steps prescribed in LAMP.On the other hand, CVA delivered the remaining twenty-five percent of LAMP in accordance to the prescriptions of LAMP. Gamarra and his team provided the needed information to establish consequential analysis, which the step 9 of LAMP prescribed. The steps 10, 11 and 12 are also included in the CVA through the imaginative conclusion presented in the CVA. The high dependency rate of the Gamarra and his team’s conclusion with the numbers presented by the graphical representations follow the predictive nature of LAMP . Conclusion and RecommendationsTaking into account all of the investigations presented in this research paper it can be concluded that the Conflict Vulnerability Assessment of Bolivia is a hybrid research in terms of the methodologies it employed. The seventy five percent of the CVA was written in accordance with LAMP, but the twenty five percent of CVA does not coincide with the quantitative requirements of LAMP. The difference between LAMP and the methodology employed in CVA does not imply that the CVA is a failed predictive research. CVA’s use of different methods only show the flexibility that Gamarra and his team sought to establish in the CVA.Given this conclusion, this paper would recommend improvements for the two major aspects of the CVA- structure and methodology. It is recommendable that the CVA would use a paper structure or format that is more accessible in answering specific aspects of predictive research. The current arrangement of the CVA tends to make the is sue of Bolivian conflict too broad to discuss and even solve. The discussions without the recommended segmentation appear not only to be reiterating but also to be too general since the reference focal points overlap each other (as seen in the presentation of the scenarios).On the other hand, the methodology employed with the CVA appears to be improvable in terms of making the quantitative aspect of the methodology isolated and only catered as additional empirical references. A qualitative research method is probably more fitting to the undeniable culture sensitive and politics laden conflicts in Bolivia. Eduardo Gamarra and his team could have broken away from the conventions of quantitative predictive research by providing more vivid narrative accounts of the current and predicted conflict situations instead of standing on the methodological position of LAMP.The quantitative elaborateness in LAMP makes the quantitative shortcomings in CVA either half-truths or irrelevant; both pro babilities could have avoided if the CVA was treated as a qualitative research. Bibliography Gamarra, E. A. (2003). Conflict Vulnerability Assessment Bolivia. Retrieved August 5, 2010, from www. digitalcommons. flu. edu: http://digitalcommons. fiu. edu/cgi/viewcontent. cgi? article=1002&context=laccwps LAMP. (2010). The Application of LAMP. Retrieved August 5, 2010, from www. lamp-method. org: http://www. lamp-method. org/2. html

Healthcare Management

The speedy shifts in the healthcare system, the opportunities to advance or develop my career, and a wide-ranging business edification which is helpful in facing the â€Å"real-world healthcare industry† are only some of the major reasons why I extremely want to earn a masters degree on Healthcare Management (World Wide Learn, 2008).Explaining further, the fast-changing system in healthcare industry makes me feel obliged to educate myself on â€Å"health care organizations, finance, infrastructure, strategic management, quality management, database management, etc† and learn more about trends, develops, tendencies, etc (World Wide Learn, 2008).In addition to that, the development of my career also lies in the accomplishment of this Master Degree since it entails market-relevant courses that will enhance the managerial skills that I possess into productive leadership and executive powers (World Wide Learn, 2008).Also, a Masters Degree in Healthcare Management will help m e achieve familiarity, comprehension, expertise needed to recognize, scrutinize, as well as, work out multi-faceted dilemmas in relation to management (World Wide Learn, 2008).Meanwhile, the qualities that would make me a successful candidate for this distance learning program include the following:First of all, I am self-motivated and driven to attain my personal goals and objectives. I do not really need to be reminded of doing something and so I am confident that I can make it in the world of distance learning.Second, I am not a â€Å"tardy type of person†. In fact, I am disciplined enough to accomplish my to-do-list on time. This is why even if distance learning entails studying at your own pace, I am very sure that I won’t be behind in the tasks assigned to students like me.Last but not least, I am a reader. I understand that distance learning entails reading a lot since there would be less face-to-face classes, if not none at all, and so lessons will be mailed/em ailed, thus, excessive reading is really required in this endeavor.ReferenceWorld Wide Learn. (2008). Health Care Management. Retrieved January 15, 2008 fromhttp://www.worldwidelearn.com/online-master/health-care-management-2.htm

The effects of cell phones in the busness workplace Research Paper

The effects of cell phones in the busness workplace - Research Paper Example It is based on observation and anecdotal evidence, with some recourse to published material as cited. Chapter 1: The Effects of Cell Phones in the Business Workplace Early adopters of the cellular phone, as it was originally and briefly known, pioneered a new era of business communication, even if at some considerable expense. Not unusually for breakthrough technology, the cost of a Motorola DynaTac in 1983 was $3,995.00, which, in today’s terms and taking inflation into account, would be in the region of $8,500. (1) The cost of acquisition, however, was overall perceived to be outweighed by the benefits of the new technology and the status conferred on those who used it. The race to produce more affordable, smaller and more versatile handsets for a market that could only grow is till showing little sign of slowing. Gartner Says Worldwide Mobile Phone Sales Grew 17 Per Cent in First Quarter 2010. (2) Figures released in 2002 by the International Telecommunication Union (3) rev eal that, in terms of units per person, Taiwan topped the list at 106.45 per 100, with Burma at the bottom. Weighted average was 59.3 per 100, with the United States at 48.81. The cost of initial models confined sales almost exclusively to the business sector, and indeed the benefits were immediate and enormous. On another level, the magical new device lent an aura of power to its owner; if you were in a position to purchase one of these vastly expensive, exotic devices, you clearly needed to communicate with other powerful, decision-making corporate warriors. Either that, or you were a very savvy criminal (3), which, to some sideline observers not yet equipped to enter the game, was also an exotic and enviable career. So we can safely say that the cell phone changed business for the better as soon as it became clear that to not have one was a disadvantage. Let us call this ‘Effect One’, the addition of a vital tool to the company toolbox, sometimes one you had to earn by distinction until the price enabled the purchase of a handset for personal use. It needed little to no effort to sell this new, potent symbol of progress and dynamism. It also introduced a set of changes in etiquette and behavior, both in and beyond the workplace, which can be referred to as ‘Effect Two’. Effect Two, like most changes to social norms, started with a minority who took on the role of being at the forefront of change, leading the charge, brushing past the fuddy-duddies on the way to wherever it was they were going. And, for a while at least, the alpha males in the workplace were the ones who got the cell phones, and who changed them as soon as the next model with better features came along. The rest waited their turn and resigned themselves to being followers. Here, like a well-cut suit, an expensive wristwatch and hand finished shoes, was an accessory that set the owner apart, allowed them to adopt a different attitude. Indeed, the new power prop had a far more immediate effect than good tailoring or discrete and tasteful jewelry, as its appeal to many lay in its ability to be the opposite of discrete and sophisticated. Chapter 2: Now, whereas in conventional ordered, civilized workplaces it would once have been considered rude or inappropriate to ignore, interrupt loudly or suddenly terminate a conversation with a colleague, the

Covenant of the Old Testament Research Paper Example | Topics and Well Written Essays - 1500 words

Covenant of the Old Testament - Research Paper Example Meaning of Covenant Covenant is considered as an agreement taking place between two people as a method to relate with the God. The term ‘covenant’ has been derived from Hebrew roots which refers the action ‘to cut’. With concern to the meaning of covenant as specified in the Holy Bible’s Old Testament, it has often been categorised as the most significant term defining the relationship between God and His people. In a Biblical sense, a covenant means much more than a contract or a mere concurrence taking place between two parties. The term ‘covenant’, in the Old Testament, offers an additional insight to the meaning of God’s expectation from humans. The act of covenant, in particular tends to demonstrate the tradition, where two people with agreement attempted to pass through the cut bodies of assassinated animals as a method to get closer to the divine soul. However, other acts of covenant were learnt to have possibly taken place in terms of circumcision and also by sprinkling animal blood on the people engaged in the agreement. Such a ceremony escorted the making of the agreement in the Old Testament. ... However, it has been noted that He approves of entering into an agreement with the man who tends to be weak, sinful as well as flawed in order to direct them in the path of wisdom and peace (Schulten, â€Å"Legal Models For The Old Testament Covenants: An Issue of Contract or Real Property Law†). While entering into relationship with man, God was found to possess unilateral freedom. Therefore, He began, defined as well as confirmed each of the agreement not depending upon the human merits but completely according to His own elegance as well as clemency. Consequentially, the role of human beings has been to act as a recipient rather than acting as a contributor. People did not bargain, barter or dared to contradict with God. However, it was found that man beheld his power to decide upon whether to keep with the promises made to the God or to reject them; to obey Him or to transgress. Hence, stating precisely, God was completely accountable to look after covenantal security. The role of man was thus restricted to believe and obey (Weinfeld, â€Å"The Covenant of Grant in the Old Testament and in the Ancient Near East†). There are nearly six covenants in the Old Testament. The Covenant with Adam It is worth mentioning that the first covenant enacted in the Garden of Eden was in agreement with Adam and Eve where the Holy Spirit explicitly directed them stating, â€Å"You must not eat from the tree of the knowledge of good and evil, for when you eat it, you will surely die†. According to the description given in the Old Testament, Eve was the first sinner as she had contradicted the order of the Holy Spirit. Consequentially, when Adam followed the same path making a sin,

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Economy - Essay Example Rising interest rates will devastate the government and would become much expensive for the local government to borrow cash, and home loans will be out of reach for citizens except for the very wealthy, by next year. Consequently, US may be wiped out financially, thus, bring the economic activities to a standstill (National Bureau of Economic Research 45-6). The Federal Reserve has strived to keep US interest rates debt at a low level, and they have succeeded. Until recently, investors and nations around the world continue to participate in this system regardless of the fact that the federal system is not honest. However, there are indications that too many foreign direct investors are lastly outsourcing their investments to other countries. For instance, China and Russia have been dumping US regime debt. Other direct investors are Renowned investors like Jim Rodgers say he will dump 30years of US government bonds. When investors put such comments forward, there is a high probability that by 2013, US will have few direct foreign investors. The decline of the dollar will lead to reduced consumption and will shift consumer expenditure from imported goods to domestic goods and services while supplementing demand in domestic products with increased exports. Unfortunately, the lower dollar value is expected to last longer than anticipated. The Congressional Budget Office predicts that the budget deficit will approximate to 5.2% of the GDP in the coming years. It is more likely that foreign lenders like China will not continue lending money to US. Due to the reduced demand and decline of the dollar, the trade deficit will decline. The loss of reverse status will be disastrous for the dollar value. Foreigners will rash to get out of the dollar, either through outright currency conversion or through bidding up the US goods value as they rash to unload the dollar holdings. Though it is hard to tell

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Culture competent care in nursing - Essay Example This can eliminate communication problems created by differences in language. It is not necessary to master the whole language, but basic dialectical jargons can be essential in understanding and meeting the needs of Aboriginal people. Besides learning the language, nurses should take a keen interest in the health-related cultural practices of Aboriginal people. For instance, Aborigines have some beliefs regarding the treatment of men by women (Leever, 2011). The men prefer to be managed by fellow men and not women. Another important aspect of Aboriginal culture is respect, and nurses should understand this in order to minimize the difficulties faced when taking care of Aboriginal people. Dignity, respect, and humility should be part of nurses’ ethos when dealing with Aborigines (Bearskin, 2011). Finally, it is ideal for nurses to understand the religious dynamics of Aboriginal culture that influence their view of medicine. Some Aborigines use religious beliefs to shape their health perspectives, and nurses will have an easier time managing them if they comprehend the relationship between Aboriginal health and religion. Cameron, B., Plazas, M., Salas, A., & Hungler, K. (2014). Understanding inequalities in access to health care services for aboriginal people a call for nursing Action. Advances in Nursing Science, 37(3),

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Sensory Perceptions - Essay Example Senses play an intricate role in an individual’s thinking. It is, therefore, vital to understand some of the weaknesses they exhibit, and how these weaknesses affect an individual’s thinking. The need to process sensory information is crucial in the growth and development of individuals (Marie, 2010). This paper will examine why individuals need not entirely believe in the accuracy of sensory information, and how this might affect the decisions they make daily. There are reasons why sensory information cannot be relied on entirely by individuals. How people interpret sensory information, is dependent on their judgement. People often choose to look at things in their surrounding objectively, even though, they try not to believe they do this. These psychological biases and cognitive factors make everybody choose what to believe. What one might perceive in one way, another may choose to look at it differently (Barth & Giampieri-Deutsch, 2012). This creates a rift in the perception by individuals about their present situations. Another reason why it is hard to place trust in sensory information provided by the senses includes past experiences. How people interpret the immediate situation may be based on past experiences that led one not to trust their instincts (Barth & Giampieri-Deutsch, 2012). This affects the decisions they might make regarding the given situation. Moreover, the environmental effects affect the interpretation of data. Communication, for example, may be distorted before reaching the intended party. This may be because of noise. These environmental factors affect our perceptions, hence; would not be right to believe entirely in sensory information (Barth & Giampieri-Deutsch, 2012). Repeatability is one factor that may contribute to an individual’s accuracy of sensory data. Senses being exposed to certain conditions on a regular basis may offer an individual accuracy during the interpretation of

Impact of Nursing Theory comment Essay Example | Topics and Well Written Essays - 250 words

Impact of Nursing Theory comment - Essay Example The most critical elements of transformational theory are the individualized theory and motivation (Rogolosi & Rigolosi, 2005). The most significant element in the workplace is the care and concern afforded to the nurses by their nurse leaders (Rogolosi & Rigolosi, 2005). In this case, individualized consideration entails offering support and encouragement, which promotes interpersonal relations between the nurses and their leaders. This, as articulated, promotes openness between the leader and the nurses and offers an avenue through which they can share ideas and direct recognition. This creates a high sense of autonomy and satisfaction among the nurse workers. This, in turn, has effects on the delivery of care to the patients and the attainment of set goals by the organization (Rogolosi & Rigolosi, 2005). The example outlined on how transformational model can best be used in an administrative setup portrays the two most significant aspects of the theory. This example demonstrates a nurse leader who inspires the rest of the nurses and offering support and encouragement, which promotes interpersonal relations between the nurses and their leaders. By developing a focus group, the manager takes huge steps in creating interpersonal relationships and openness within the

Philadelphia Fight Organization Assignment Example | Topics and Well Written Essays - 1000 words

Philadelphia Fight Organization - Assignment Example Besides just being concerned with the development of research and treatments, the organization provides a home to prevention, education and providing more information services concerning the disease. It has AIDS library and carry out a number of projects which are related to the disease as well as activism in combating the disease (Philadelphia Fight Organization, 2012). The organization is not big enough and it has its operations centered at Philadelphia where it provides the free services to the affected. The organization being a charitable and non profit organization, its hands are tied and can not get involved to activities which can make it get income. This has made the organization to depend entirely on the services of the volunteers which to a certain extent has some challenges. The reliance of the organization to volunteers has made it not to have clear human resource policies making it have challenges when it comes to human resource developments. The staffs do not undergo th orough recruitment since there is lack of money to pay the well qualified personnel. This has been the big challenge that the organization has been experiencing since its inception. The major legal concern of the organization is how to get justice done for the HIV/AIDS victims as many of them are suffering as a result of actions which were beyond them. Some of the victims of HIV they are working with were subjected to that status as result of rape by gangs which were beyond the patient’s control. The organization finds it challenging to get justice for these victims owing to the nature of events which is very difficult to follow. Similarly, the organization lacks the professionalism in dealing with legal challenges affecting the organization as many of the staffs are from medical field and don’t know more about law. This has rendered a legal challenge which the organization has to deal with in attempts to promote justice (Philadelphia Fight Organization, 2012). The org anization can competently deal with these legal concerns through setting a separate entity of staffs which deals with legal matters. This will help in dealing with the legal concerns which will see justice done to the patients who felt victims as a result of actions which were beyond their control. For this exercise to be effective, the organization needs to get experts through recruitment of staffs that can diligently deal with these issues and solve them. It also requires the organization to have money which will be used in recruiting staffs who will be addressing legal issues which are concern to the organization. Addressing legal concern which affects the employees needs experts hence this can only be dealt with through recruiting those suitable for it. The organizations need to take a number of actions into consideration in order to expand into other markets in the international arena. The organization needs to embark on the qualified staffs within its department’s in or der to get good and efficient services. This can begin from recruiting and training of staffs responsible for the human resource in order to equip them with the task they will be carrying out. Training of the staffs will also increase the competency among the human resource personnel which will intern be reflected to other departments resulting to quality of services being rendered by the organization. When the staffs are equipped more so

Comparing the scientific method and the engineering method of problem Essay

Comparing the scientific method and the engineering method of problem solving - Essay Example Conversely, engineering is based on the tenets of coming up with new inventions that have not been in existence before. However, it is worthwhile noting that both scientific and engineering approaches may be integrated to solve a problem. Nevertheless, the need to create better understanding necessitates a comparison of scientific and engineering approaches in relation to problem solving. Due to objective differences, science and engineering follow different processes in coming up with solutions. A scientific approach begins with a question seeking answers to a particular phenomenon. This is then followed by a background research on the various studies related to the phenomenon at hand. The background research may touch on directly related studies considered to be standard or accurate. As such, a scientist is able to identify loop holes, if any, in the current studies giving guidance on the particular problem at hand. However, more importantly is that a background research enables formulation of an appropriate hypothesis. The hypothesis purports to offer a better explanation compared to already existing ones in relation to given problems. As such, before advancing further, the proposed hypothesis must first be tested against the existing ones. This implies that a new proposition must explain a phenomenon that has not been explained by the already existing ones. A valid proposed hypothesis is then subjected to a number of tests to prove its workability and validate its predictions. If the proposed hypothesis shows the predicted results, it is accepted and adopted as the new best hypothesis giving a solution to the particular problem in play. However, if a hypothesis arrives at already known phenomena it only increases credibility of already existing hypothesis rather than replacing them. Conversely, if a hypothesis fails to meet the predicted threshold, it is rejected. However, a hypothesis normally undergoes a couple of experiments to eliminate room for error.

Relationship between Science and Religion Essay Example for Free

Relationship between Science and Religion Essay The article â€Å"Relationship between Science and Religion† outlined the different relationships that the said two domains have had over the years. Historically, religion and science were viewed as strictly separate fields that could not be unified. This view is more popularly known as the conflict thesis . On the other hand, Stephen Jay Gould (1999, quoted in Wikipedia 2007) stated that the two fields could â€Å"co-exist peacefully† if they do not intervene with each other’s business. The article also enumerated different kinds of interactions between the two as presented by Polkinghorne (1998, quoted in Wikipedia 2007). Aside from the constant opposing views regarding the natural world or reality, Polkinghorne illustrated that religion and science may reach a common ground or may even be united with regard to a particular occurrence. After this, the article then went on discussing the early efforts of some religious groups to complement their doctrines with scientific facts. But of course, there were groups, particularly Islam that resisted the proliferation of science in what they believe as sectarian-dominated world. Inevitably, with the advancement of science and fast modernization of societies, there were new groups formed embodying beliefs apart from the fundamentalist view of religion. These groups range from the liberal Enlightenment advocates to non-fundamentalist sects such as Protestant Christian. There were even organizations formed that are not religiously affiliated but perform functions congruent to what religion usually does. Though there were new groups organized, some religion, which date back to ancient times claim that their dogma is capable in adjusting with scientific advancement and this has been actually used by them to explain their own theories toward the strengthening of their own beliefs. The last parts of the article list the varied point of views of scientists toward religion. Some view that religion and science are distinct from each other while others believe that the two could be unified. Others simply believe that the two fields share the same objectives in trying to provide explanation of the happenings in the environment they live in. And also, since religious beliefs are part of cosmos, they can be scientifically tested. Lastly, the article presented studies and findings on relevant issues being tackled. Since the article is not argumentative in nature, it is difficult to determine fallacious statements. The article did not clearly propose or suggest anything nor did it draw any conclusion. It was presented in a seemingly objective manner. I used the words â€Å"seemingly objective† because if one read the paper, it would be observed that the relationship between religion and science were clearly outlined without favoring any of the items. However, as one analyzed the pattern on how the article was written, the biases would be realized. The article enumerated four kinds of interaction between religion and science. However, as the article progresses, only the CONFLICT and INDEPENDENCE kinds of interaction were substantiated. The paper presented early efforts and manifestations of well-established, if not ancient, religious denominations to reconcile the two fields but it failed to elaborate on this matter. The article could have cited instances, findings or any on-going research wherein the two subject matters were integrated. Instead, the article highlighted some points in history when scientific advancements were sanctioned by religious authorities. Moreover, as if strengthening the idea that religion and science are irreconcilable, the article pointed out the formation of non-religious organizations. Though the article presented the â€Å"non-fundamentalist relationship views†, it fell short in showing that the sectarian side is attempting to make a world where they are both accommodated. For example, aside from mentioning the non-sectarian groups, it could have also stated some religious institutions that support scientific and technological development. The second bias that allude to the favoring of the separation of the two domains are the surveys showing that a higher percentage of scientists do not believe in any religious systems. How about presenting data on spiritual leaders who also uphold basic principles of science? Lastly, towards the end of the article, it showed findings on the â€Å"correlation between religiosity and intelligence†. Though this study didn’t categorically stated that those who observe holy practices and those who are strict believers of religious doctrines have low serotonin levels, it seems to create the stigma. If this line of thinking were continuously propagated, many would be discouraged to associate themselves with any religious beliefs. All the biases lean towards the implication that efforts to settle the differences between religion and science should be abandoned. This is what makes the article problematic. At first, the writing tried to present the relationship between the two in an objective way. But it failed because biases were evident. If the author had really wanted his output to be presented objectively, he should have shown the two sides of the coin. For example, he asserted the aggressive progression of science but mentioned only historic accounts on the side of religion. Also, he cited a list of studies disputing the validity of religious co-existence with science, but he again failed to mention the side of religion. Is religion also trying to draw a clear line against science or is it accepting the recent wonders of the latter? Since the author failed to be impartial in writing the article, he should have instead taken a clear-cut position on the issue so readers would be guided in the direction he’s driving at. Bibliography Greene, Perry (1997) Logical Fallacies [Internet], Available from: http://www. engl. niu. edu/wac/fallacies. html [Accessed 24 March 2007]. Johnson, George (1998) Science and Religion: Bridging the Great Divide. The New York Times Archives, [Internet], June 30, 1998 Available from: http://www. nytimes. com/library/national/science/063098sci-essay. html [Accessed 24 March 2007]. Raymo, Chet (1998) Skeptics and True Believers: The Exhilarating Connection Between Science and Religion. New York, Walker and Company. Relationship Between Religion and Science (2007) [Internet]. Available from: http://en. wikipedia. org/wiki/Relationship_between_religion_and_science#_note-3 [Accessed 24 March 2007]. Shelp, Earl Edward ed. (1985) Theology Bioethics Exploring the Foundations Frontiers II Series. Holland, D. Reidel Publishing Company.

Features of Karate

Features of Karate Karate-do Introduction Karate is a martial art that was originally created in Japan. The main idea of karate is battling and defending by using defensive and counteroffensive body movements including punches and kicks. The psychological and ethical characteristics of karate aim to advance and improve the student in general. The term karate is a mixture of two Chinese characters: kara (empty) and te (hand), thus karate means empty hand. The suffix -do is added to the word karate to indicate that karate as an overall way of life. An individual who practices karate is sometimes referred to as a karateka. The conventional karate-do is a difficult sport and it takes time and dedication to become a master in this martial art. Three components of karate   Ã‚   The five main karate styles are: Shotokan, Shito-ryu, Goju-ryu, Wado-ryu, and Kyokushin. Karate training is separated into three sections: Kihon, Kata, and Kumite. Kihon means basic techniques. These techniques are mostly attacking moves, blocking moves, stances, and other movements. The trainer demonstrates a certain move, which is then imitated by the student. It is vital to practice and repeat the basic fundamental movements because as a result, the student develops the right techniques. Kata means form. It is a sequence of certain movements displayed in a pattern that the student has to memorize. It represents a battle or a fight against an enemy or enemies. In karate training, every kata begins with a block and this proves that defense is the most significant aspect of karate. In karate, there are numerous katas as they help at shaping the body and mind. The katas are performed slowly with full strength and help at developing control of the entire body, mind, breathing, rhythm, and breathing. In order to perform the katas in the right way, they have to be repeated thoroughly and carefully with full relaxation and focus. Kumite means partner work. In karate, there should not be any opponents or enemies, only partners. Traditional kumite help advance karate students both mentally and physically with the help of their partners. Karate ranks In karate, different colored belts indicate the ranking and the skill level of a karate practitioner. Once a karate student has obtained a karate belt of a certain/rank, people can see your ranking and that you have dedicated your time getting to that level. Simply because somebody has a white belt tied to him/her, it doesnt mean that he/she is not experienced in karate, it means that the person is ready to thrive to gain the skill. There are nine belt colors in karate: white, orange, blue, red, black, yellow, green, purple, and brown. Not all karate schools/clubs use all of these colors and the arrangement of the belts/ranks differ from school to school. The role of an instructor is very important in karate and they have different behaviors. Some teachers easily hand out new belts without thinking and others are careful when choosing the student who deserves a higher rank. Karate belt colors vary from school to school. Some schools include the colors red and purple in their system, while others only have 7 colors. Some schools also use stripped belts with different colors. The order of the belt colors may vary, but most of the time, the white belt is for the beginner and the black belt is the highest ranked belt color. Three of the most common orders of belt colors are: 1. White, yellow, orange, green, blue, purple, red, brown, black. 2. White, red, yellow, orange, green, blue, purple, brown, black. 3. White, yellow, green, orange, red, blue, purple, brown, black. To get to the next phase/belt, the student is required to dedicate his time into improving every day and trying his/her best. Generally, it takes anywhere from 8 to 18 months of training and practice to move to the next phase in karate. The more you practice, the faster you will get a new belt. Each of nine colors of belts in karate have meaning behind them. White Belt: The white belt is the symbol of purity. This makes sense because those who are just starting out in karate are innocent and do not know how much work and discipline is required in order to become a master in karate. This level introduces the basics and the first ideas about karate. This is the beginning of a path to mastery. Yellow Belt: Once a student gets a yellow belt, it means that he/she is past the introductory level of karate and has basic understanding of the art and has the ability to do basic karate. The yellow belt represents energy. The student now has more control over their bodys energy. Orange Belt: The symbol of an orange belt is stability. Practicing karate includes basic punches, kicks, blocks, and postures. The basic skills gained from the first three belts will be necessary to progress in karate because all of the techniques learned in higher belts will be learned upon the basic skills. Purple belt: Once a student gets a purple belt, it means that he/she has advanced from beginner to intermediate level. At this stage, students should be able to understand all basic strikes and blocks. They should also be comfortable with controlling and moving their body in order to do a certain strike/block. Blue belt: A student who has a blue belt must learn to adapt to given situations. Karate belt colors vary from school to school. Some schools include the colors red and purple in their system, while others only have 7 colors. Some schools also use stripped belts with different colors. The order of the belt colors may vary, but most of the time, the white belt is for the beginner and the black belt is the highest ranked belt color. Three of the most common orders of belt colors are: 1. White, yellow, orange, green, blue, purple, red, brown, black 2. White, red, yellow, orange, green, blue, purple, brown, black 3. White, yellow, green, orange, red, blue, purple, brown, black To get to the next phase/belt, the student is required to dedicate his time into improving every day and trying his/her best. Generally, it takes anywhere from 8 to 18 months of training and practice to move to the next phase in karate. The more you practice, the faster you will get a new belt. Each of nine colors of belts in karate have meaning behind them. White Belt The white belt is the symb ol of purity. This makes sense because those who are just starting out in karate are innocent and do not know how much work and discipline is required in order to become a master in karate. This level introduces the basics and the first ideas about karate. This is the beginning of a path to mastery. Yellow Belt Once a student gets a yellow belt, it means that he/she is past the introductory level of karate and has basic understanding of the art and has the ability to do basic karate. The yellow belt represents energy. The student now has more control over their bodys energy. Orange Belt The symbol of an orange belt is stability. Practicing karate includes basic punches, kicks, blocks, and postures. The basic skills gained from the first three belts will be necessary to progress in karate because all of the techniques learned in higher belts will be learned upon the basic skills. Purple belt Once a student gets a purple belt, it means that he/she has advanced from beginner to interme diat

Causes, Symptoms and Treatments of Anaemia

Causes, Symptoms and Treatments of Anaemia 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‚  Ã‚  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‚  Ã‚  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 (GTG). 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‚  Ã‚  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‚  Ã‚  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‚  Ã‚  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‚  Ã‚  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‚  Ã‚  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.   Ã‚  Ã‚  Ã‚  Ã‚  (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‚  Ã‚  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 hematopoietic cells, and can result in macrocytic anemia. 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 anaemia of chronic disease (ACD) (Krantz, 1994). Common childhood normocytic anaemias are, besides iron deficiency anaemia, those due to acute bleeding, sickle cell anemia, 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 h aemolytic normocytic anemias in children (Weatherall DJ, 1997a).   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  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 anemia and increase together in macrocytic, hyperchromic anemia.   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  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 erythrocyt es, due to bleeding or haemolysis. The reticulocyte count is typically higher.   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  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 (Hb S) in which valine is substituted for glutamic acid at the sixth amino acid position in the beta globin gene reduces the solubility of Hb, 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‚  Ã‚  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 (GI) tract generally indicative of malignancy (Hershko and Skikne, 2009).   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  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 delivers 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‚  Ã‚  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 characterist ically impaired in ACD, 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 cyt okines causing impairment of erythroid progenitor growth and haemoglobin production in developing erythrocytes.     Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  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‚  Ã‚  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‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Sickle cell disease (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 monocytes 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 diseaseincludingacritical 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). 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). Red blood cell transfusion : a critical appraisal 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.   Ã‚  Ã‚  Ã‚  Ã‚  SCD (Source: Josephson et al., 2007) 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).   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  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. ACD 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 recomm ended 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‚  Ã‚  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‚  Ã‚  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‚  Ã‚  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). 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). Controversial and indeterminate indications for intermittent or chronic transfusion 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 currently is only a second-line therapy in the management of priapism ( Miller et al., 1995).   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  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 and alloimmunisation to HLAs,   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 (Engle, 1964). 5. Critical review of thalassemias : (i) Molecular pathogenesis The large number of inherited haemoglobin disorders known today include (a) those related to anomalies in the haemoglobin structure e.g., sickle cell disease, and (b) the thalassemias whose hallmark is globin-chain deficiency of one or other of the globin chains of adult haemoglobin in erythroid cells. ÃŽ ²-Thalassaemias These are a set of genetic disorders inherited as simple codominant traits affecting haemoglobin synthesis. Depending on the haemoglobin chain affected, 2 types of thalassemia are recognised: ÃŽ ±-thalassaemia and ÃŽ ²-thalassaemia. Homozygous ÃŽ ²-thalassaemia is marked by a quantitative deficiency of the ÃŽ ²-globin chains in the erythroid cells. A complete absence of the ÃŽ ²-globin chains occurs in homozygous ÃŽ ²o-thalassaemia whereas in homozygous ÃŽ ²+-thalassaemia the ÃŽ ²-globin chains are present at less than 30% of normal. Accounting for nearly 90% of the cases, ÃŽ ²+-thalassaemia is the most commonly observed form of ÃŽ ²-thalassaemia. The condition is termed thalassaemia major when there is microcytic hypochromic anaemia with severe haemolysis, hepatosplenomegaly, skeletal deformities and iron overload. ÃŽ ²-thalassaemia homozygotes exhibit severe transfusion-dependent anaemia in the very first year of life. Homozygotic individuals having a relatively benign clinical phe notype and surviving with or without transfusion are described as thalassaemia intermedia (Weatherall, 1969). The thalassaemias, thus, encompass a wide gamut of clinical disability from intrauterine death to a mild anaemia with no overt symptoms (Weatherall, 1997b). The coexistence of   ÃŽ ± -thalassaemia leading to reduction in the synthesis of ÃŽ ±-globin chains, and a genetic predisposition to produce high levels of HbF, could be important factors for the extensive p Causes, Symptoms and Treatments of Anaemia Causes, Symptoms and Treatments of Anaemia 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‚  Ã‚  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‚  Ã‚  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 (GTG). 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‚  Ã‚  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‚  Ã‚  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‚  Ã‚  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‚  Ã‚  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‚  Ã‚  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.   Ã‚  Ã‚  Ã‚  Ã‚  (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‚  Ã‚  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 hematopoietic cells, and can result in macrocytic anemia. 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 anaemia of chronic disease (ACD) (Krantz, 1994). Common childhood normocytic anaemias are, besides iron deficiency anaemia, those due to acute bleeding, sickle cell anemia, 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 h aemolytic normocytic anemias in children (Weatherall DJ, 1997a).   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  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 anemia and increase together in macrocytic, hyperchromic anemia.   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  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 erythrocyt es, due to bleeding or haemolysis. The reticulocyte count is typically higher.   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  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 (Hb S) in which valine is substituted for glutamic acid at the sixth amino acid position in the beta globin gene reduces the solubility of Hb, 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‚  Ã‚  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 (GI) tract generally indicative of malignancy (Hershko and Skikne, 2009).   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  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 delivers 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‚  Ã‚  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 characterist ically impaired in ACD, 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 cyt okines causing impairment of erythroid progenitor growth and haemoglobin production in developing erythrocytes.     Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  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‚  Ã‚  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‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Sickle cell disease (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 monocytes 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 diseaseincludingacritical 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). 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). Red blood cell transfusion : a critical appraisal 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.   Ã‚  Ã‚  Ã‚  Ã‚  SCD (Source: Josephson et al., 2007) 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).   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  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. ACD 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 recomm ended 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‚  Ã‚  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‚  Ã‚  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‚  Ã‚  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). 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). Controversial and indeterminate indications for intermittent or chronic transfusion 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 currently is only a second-line therapy in the management of priapism ( Miller et al., 1995).   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  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 and alloimmunisation to HLAs,   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 (Engle, 1964). 5. Critical review of thalassemias : (i) Molecular pathogenesis The large number of inherited haemoglobin disorders known today include (a) those related to anomalies in the haemoglobin structure e.g., sickle cell disease, and (b) the thalassemias whose hallmark is globin-chain deficiency of one or other of the globin chains of adult haemoglobin in erythroid cells. ÃŽ ²-Thalassaemias These are a set of genetic disorders inherited as simple codominant traits affecting haemoglobin synthesis. Depending on the haemoglobin chain affected, 2 types of thalassemia are recognised: ÃŽ ±-thalassaemia and ÃŽ ²-thalassaemia. Homozygous ÃŽ ²-thalassaemia is marked by a quantitative deficiency of the ÃŽ ²-globin chains in the erythroid cells. A complete absence of the ÃŽ ²-globin chains occurs in homozygous ÃŽ ²o-thalassaemia whereas in homozygous ÃŽ ²+-thalassaemia the ÃŽ ²-globin chains are present at less than 30% of normal. Accounting for nearly 90% of the cases, ÃŽ ²+-thalassaemia is the most commonly observed form of ÃŽ ²-thalassaemia. The condition is termed thalassaemia major when there is microcytic hypochromic anaemia with severe haemolysis, hepatosplenomegaly, skeletal deformities and iron overload. ÃŽ ²-thalassaemia homozygotes exhibit severe transfusion-dependent anaemia in the very first year of life. Homozygotic individuals having a relatively benign clinical phe notype and surviving with or without transfusion are described as thalassaemia intermedia (Weatherall, 1969). The thalassaemias, thus, encompass a wide gamut of clinical disability from intrauterine death to a mild anaemia with no overt symptoms (Weatherall, 1997b). The coexistence of   ÃŽ ± -thalassaemia leading to reduction in the synthesis of ÃŽ ±-globin chains, and a genetic predisposition to produce high levels of HbF, could be important factors for the extensive p