Corporate governance and social responsibility investment Essay

Corporate governance and social responsibility investment - Essay Example It is conceivably foreseeable that crises lead to calls for improved regulation of business actors, such as the debate over the world economic predicament. Nevertheless, such methodical crises are unusual. On the other hand, company failure following a wrongdoing is a more frequent occurrence. For illustration, Maxwell and BCCI in the UK, WorldCom and Enron in the United States and Bayerische Hypo- und Vereinsbank of Germany are examples of corporations that have collapsed as a result of wrongdoing. Such corporate scandals have resulted in the establishment and improvement of company governance codes, which are put in place to monitor corporate conduct generally, and act of corporate directors in specificity (London stock exchange, 2012). The codes are either wholly voluntary such as the financial reporting council of 2008 in the United Kingdom, or a mixture of legal and voluntary elements like the 2008 German code. As thus, they may be taken as apparatus of flexible law or a mixture of soft and inflexible law. Within the code elements, individual rules might be flexible or rigid. Advocates of flexible law of explanation assert that it has fundamental flexibility, which is not present in rigid laws and the aspiration to conform to societal norms yields indisputable observance. Flexible laws are the rules of conduct that have no lawful obligatory force, which may have practical upshots. Though corporations and their directors may opt to conform or not match flexible law, a generally held supposition is that actions are more likely to be consistent with codified regulation and declarations of best practice. Since flexible law is not lawfully obligatory, its execution has to solely rest on the goodwill of those agreeing to and affected by it. Apparently, where such goodwill is not present, flexible law may result in flexible observance. Where benevolence and the aspiration to conform subsist, conformance may not be the most practicable alternative for corporations and their directors. They may set out that the doctrine supporting a specific regulation on bets practice will be best served by non-conforming. In addition, they might be safeguarded from conforming for reasons beyond their control (The European voice of directors, 2012; Australian council of super investors, 2010). The use of prudence to establish conformance or non-conformance may be helpful to both regulators and the regulatees. Comply or explain may assume several forms. Compliance means severe observance to every detail of the rule or to the primary rule, or both. Germany advocates the formation of an audit committee to act as the oversight of the entire audit process in a large company. Non conformance is commonly warranted by the resort to firm-or industry level specifics, or against the judgment of definite code terms. The flexibility of the laws, that is, â€Å"explain† might lead to corporate scandal and eventual collapse. For illustration, the yearly report by th e Hypoereinsbank (Germany) vindicated its non-conformance (explain) with the certain rules necessitating that directors’ and officers’ responsibility insurance has a deductible with the plain statement: â€Å"responsible act is an understood obligations of the members, no deductible is needed for that. In the same

Macbeth - The Central Themes of the Play Essay Example for Free

Macbeth The Central Themes of the Play Essay The central themes of the play are highlighted by the sinister statement made by the witches at the very beginning of the play, Fair is foul, and foul is fair: Hover through the fog and filthy air. The whole tone for the play is set as it is a drama about contradictory forces and ideas: light and darkness; good and evil; holy and unholy; loyalty and disloyalty; trust and mistrust; what is natural and unnatural; honesty and deception. The witches mention of Macbeth is significant because he is immediately associated with evil. Duncan decides to appoint Macbeth as the next Thane of Cawdor as the previous one was a traitor, he says, No more that Thane of Cawdor shall deceive Our bosom interest. Go pronounce his present death, And with his former title greet Macbeth. This is ironic as Macbeth has inherited the title of a traitor and the title leads to Duncans killing and ultimately Macbeths downfall. This is also a link to the fair is foul statement as Macbeth seems fair, noble and a good servant for the king but in the end he kills Duncan and is evil. Macbeth has the capacity to kill for both good and evil. Duncan realises that he cant judge people by their appearances and that they can be deceptive, Theres no art To find the minds construction in the face: This is ironic as he about to make the same mistake with the next Thane of Cawdor, the fact that people can be deceptive is reflected by fair is foul as people arent always what they seem. When Macbeth realises that one of the witches prophesies has come true Banquo says, What! Can the devil speak true? This is saying that the witches are the devil and evil but they have spoken the truth which is not expected, this mixes good and evil referring back to fair is foul and one of the themes this statement explores. Macbeth is also immediately liked with evil as he echoes the witches, So foul and fair a day I have not seen. The witches have established their deliberate evil and their powerful presence in the play, Macbeth has become their victim, we can see this where he says Upon the blasted heath you stop our way With such prophetic greeting? Speak, I charge you. This shows that Macbeth is drawn into what they are saying and also indicates the witches power over him as they just vanish. Macbeths echo links him with the themes that these words explore, he uses ironic lines such as, Win us with honest trifles, to betrays In deepest consequence. Macbeth is now liked with the themes such as honesty, betrayal and loyalty all explored by the fair is foul, and foul is fair statement, Macbeth is gradually being drawn more and more towards evil by his own weaknesses. Macbeth and Lady Macbeth share a very close relationship which is based around trust and honesty. Macbeth is ambitious and Lady Macbeth is trying to help him achieve his ambition, All that impedes thee from the golden round, Which fate and metaphysical aid doth seem To have thee crownd withal. This is ironic as although the wealth and power seems very attractive to them once they get it the trust, honesty and closeness they had is lost, this once links back to the fair is foul theme. Lady Macbeth also tells Macbeth to be deceitful and disguise the truth, Look at the time, bear welcome in your eye, Your hand, your toungue: look like the innocent flower But be the serpent undert. This shows that Macbeth looks innocent and fair but inside he is evil and foul. Duncan ironically praises Macbeths castle as pleasant and welcoming, This castle hath a pleasant seat; the air Nimbly and sweetly recommends itself Unto our gentle senses. This shows that fair is foul as the castle looks pleasant from the outside but is evil within and is where Duncan is to be murdered. Duncan also praises Lady Macbeth as the noble, welcoming hostess; she is deceptive and puts on the false face of goodness to Duncan when really she is planning his murder, she says, Your majesty loads our house: for those of old, and the late dignities heapd up to them, Macbeths ambition overpowers his conscience and morality with the help of Lady Macbeth and he commits the murder. Once they find out that Duncan has been murdered Macbeth again plays innocent and is not genuine, for example, You are, and do not knowt: The spring, the head, the fountain of your blood Is stoppd; the very source of it is stoppd. Macbeth conceals what he knows and pretends to be horrified by the murder in contrast to Macduff who is genuine, Macbeths language is over elaborate. The theme of natural and unnatural is created throughout the play, for example when the Old Man says, T is unnatural, Even like the deed thats done. On Tuesday last, A falcon, towering in her pride of place, Was by a mousing owl hawked at, and killed. This means that nature has changed and become strange and unnatural and reflects the murder and unnaturalness of Duncans death. Macbeth holds a Banquet at which Banquo is supposed to be present but Macbeth has murdered him, this shows that fair is foul as everything seems normal but it is not and the ghost of Banquo turns up to haunt Macbeth. When Macbeth goes to visit the witches again they are cunning and employ equivocation, juggling with words to disguise the truth and lull Macbeth into a false sense of security. This is shown where they say, The power of man, for none of woman born Shall harm Macbeth. This is making Macbeth feel safe without them lying as Macduff was cut from his mother when she was dead, the witches are deceiving him showing that foul is fair. When Macduff goes to ask Malcom to raise an army to fight Macbeth and bring order back to Scotland Malcom accuses himself of being evil and foul. He is cautious to make sure Macduff is not trying to leur him back to Macbeth, he says, To make me hunger more, that I should forge Quarrels unjust against the good and loyal, Destroying them for wealth. Malcom is appearing foul but is fair in contrast to Macbeth, Malcom believes in Maduffs integrity and decided to help him. Malcom also says, The night is long that never find the day. This means that every black, evil night comes to a good day, foul is fair. The contrasts become moral contrasts and Macbeth has lost everything, eventually goodness overpowers evil.

Things Fall Apart :: essays research papers

Things Fall Apart Essay   Ã‚  Ã‚  Ã‚  Ã‚  The book Things Fall Apart by Chinua Achebe definitely has a fitting title. It explains how two cultures with different ideas and beliefs can clash and be intolerant towards one another. Most of the theme is developed through the plot of the story and through a man and his struggle against fear and anger (the main character, Okonkwo). Throughout the book he tries to resolve the problems that develop all around him and within himself. As the story progresses, conflict overwhelms him and leads to his downfall and the downfall of the Ibo culture.   Ã‚  Ã‚  Ã‚  Ã‚  One part of the book that shows how the title is developed is when Okonkwo's character is introduced and explained to the reader. The author tells how he is shameful of his father and that he is belligerent and cold-hearted. Pointing out these flaws in Okonkwo's character seems to foreshadow his downfall. Since Okonkwo probably represents the 'intolerant culture';, that culture's downfall is also foreshadowed. Later more obvious instances occur. Okonkwo kills Ikemefuna, who is like a son to him. His decision of killing the boy is definitely unreasonable, and he only acts on what he was told was right. Just like the rest of the clan he follows these customs that seem immoral and unjust to other cultures. In another part of the story, Okonkwo is banished from his fatherland. This incident is the first where he is punished greatly for his actions. It marks a turning point in Okonkwo's downfall, and therefore the downfall of the traditional culture that he stands for. His hopes and aspirations are almost forgotten while he is away from Umuofia, and he desperately tries to regain his status when he returns. During this period of time, Okonkwo also discovers that his son has converted to his enemy's ways and beliefs. He abandons his son, and doesn't want to be his father any longer. This shows that his relationships with family and other people are beginning to 'fall apart';. The most obvious development of the theme and title takes place at the end of the book, when the final clash of cultures occurs.

Succubus Shadows Chapter 11

I was in Seattle. Modern-day Seattle, thankfully. I wanted to be nowhere near the fourth century, even though I dreaded what awful vision the Oneroi would show me now. Not only was I in Seattle, I was with Roman. He had just parked on Cherry Street and was striding toward the heart of Pioneer Square, which was buzzing today with tourists and others enjoying the clear autumn night. This time, I wasn't in the dream. I was an observer only, following along with him like a ghost or maybe a documentary camera. I wanted to talk to him, to communicate in some way, but I had no mouth with which to speak. I had no form whatsoever, only my consciousness watching this vision. His pace was brisk, and he pushed through the meandering crowd with no concern for the dirty looks and occasional comment. He was focused on his destination, one I recognized immediately: the Cellar. Our favorite immortal hangout was crowded with mortals tonight. Yet, for whatever reason, no matter how busy the bar was, Jerome always managed to get the same corner table in the back. He sat there now with Carter but didn't wear the usual unconcerned look we often found him with while drinking. The demon's face was filled with agitation, and he and Carter were arguing about something. Roman's signature was masked, so neither angel nor demon noticed his approach. Jerome shot him a glare, no doubt thinking some human was bothering them. Jerome's expression promptly changed when he saw who it was, and he opened his mouth to say something. He didn't get the chance because Roman spoke first. â€Å"Where is she?† demanded Roman. He sat in a chair and jerked it toward Jerome so that father and son could look eye to eye. â€Å"Where the fuck is Georgina?† The music and conversation covered most of his shouting, but a few nearby patrons gave him startled looks. Roman was oblivious. His attention was all on Jerome. Anger crackled around the nephilim like an aura itself. Jerome had been clearly distressed about something when Roman had entered, but now, in the presence of an underling, the demon put on the cold, haughty expression that was so typical for him. â€Å"Funny,† said Jerome. â€Å"I was going to ask you the same thing.† Roman glowered. â€Å"How the hell would I know? She vanished right before my eyes! You're the one that's supposed to have some sort of divine connection to her.† Jerome's face didn't twitch, but his words were like a gut punch to both me and Roman. â€Å"I can't feel her anymore. She's disappeared for me too.† I might have had no physical form, but cold fear ran through me nonetheless. An archdemon was connected to his subordinates. He always knew where they were and could tell if they were in pain. When Jerome had been summoned, that connection had shattered, cutting us off from our hellish â€Å"gifts.† Now, the opposite had happened. I had been summoned, so to speak, and torn from Jerome. The Oneroi's words came back to me: He won't find you. He can't find you. You no longer exist for him. â€Å"That's impossible,† growled Roman. â€Å"Unless†¦Ã¢â‚¬  A troubled look came over him. â€Å"Someone's hiding her signature?† It would be terribly ironic if the scheme he'd once planned came to be through someone else. Jerome shook his head and gestured to a waiter for another round. â€Å"I wouldn't be able to find her if that happened, but the connection would be there. I'd know she still existed.† You no longer exist for him. â€Å"Is she†¦is she dead?† Some of Roman's initial fury had dimmed a little. It wasn't an unreasonable question, really. I kind of felt dead. â€Å"No. Her soul would have shown up in Hell.† Jerome took a sip of his new drink and narrowed his eyes at Roman. â€Å"But it's not your job to ask questions. What do you know? You said she disappeared. Literally?† Roman's face was downright bleak now. He glanced between Jerome and a grim, thus far silent, Carter. â€Å"Yes. Literally. She's been having these†¦I don't know how to explain it. She couldn't even explain it.† â€Å"I was there,† Jerome reminded him. â€Å"She told me. The music. The colors.† The sneer in his voice made it clear that he regarded those types of things as nuisances. â€Å"It was like this weird force pulling her, enchanting her. It wanted her to come to it.† Roman was repeating known info, possibly to make Jerome take it more seriously. â€Å"She called it a siren song and kept sleepwalking, trying to get to it. And then†¦and then tonight, she went to it.† â€Å"Did you see it?† asked Carter. It was odd to see him so serious and†¦well, confused. The former emotion I'd seen only a handful of times. The latter I'd never seen on him. â€Å"I saw her disappear. Like, vanish into thin air. But I didn't see it exactly. I felt it. I could sense whenever it was around.† â€Å"What did it feel like?† asked Jerome. Roman shrugged. â€Å"I don't know. Just†¦a force. A power. Not an entity exactly. And not something I could identify. Not a greater immortal or anything.† â€Å"That,† declared Jerome, â€Å"is absolutely useless information.† Roman's anger returned. â€Å"It's all I've got! If you'd listened to her more, this wouldn't have happened. You let this happen. You didn't take it seriously, and now she's gone!† Yelling at Jerome. Not a good thing. â€Å"Be careful, lest I revoke your invitation,† hissed the demon, eyes boring into his son. â€Å"And I did listen. I set you to protect her. You, apparently, are the one who ‘let' this happen.† Roman flushed. â€Å"I was in the other room when that thing showed up again. I hurried in as fast as I could, but it was too late. Georgina'd already given herself up, and honestly†¦I'm not sure I could have stopped it anyway.† It was a big concession for Roman. Nephilim could inherit anywhere from none to all of their immortal parent's power. Roman was very close to having as much strength as Jerome but still lagged behind just a little. Additionally, the types of power wielded by greater and lesser immortals differed. As a type of hybrid, Roman might not have been able to fight what Jerome could have. Jerome didn't push that point further. â€Å"So, we still know nothing.† â€Å"We know that whatever did this isn't one of ours,† said Carter quietly, speaking at last. â€Å"Yes,† snapped Jerome. â€Å"Which only leaves a billion other things it could be. Unless†¦Ã¢â‚¬  He glanced over at one of the chairs at their table. One moment it was empty. The next, Simone sat there. Carter didn't seem surprised, but Roman and I certainly were. And she was especially surprised, as shown by her squeal of fear and befuddled expression. Being teleported by a greater immortal was not a pleasant experience. She was blond today, dressed in a plain blouse and pair of jeans. It was a sign of her agitation that she didn't widen her neckline when she saw Carter. â€Å"What – what's going on?† she stammered. â€Å"What'd you do to Georgina?† asked Jerome. Her eyes went wide. He might still wear the guise of John Cusack, but as he stared her down, it was easy to see that he truly was a demon of Hell. â€Å"Nothing!† cried Simone. She cowered back into her chair. â€Å"I don't know what you're talking about!† Jerome was up and out of his chair so fast, he might have teleported himself. He jerked Simone up as well and shoved her against a nearby wall, hand on her throat. I'd been in a similar position with him before and felt pity for the other succubus. No one else in the bar noticed, so Jerome was either glamoring them or making him and Simone invisible. â€Å"Do not lie to me!† he exclaimed. â€Å"What have you done? Who did you get to do this?† I could see his line of reasoning now. What Roman had sensed might not be demon or angel, but it wasn't impossible that someone from our side could have worked with an unknown entity. It wouldn't be the first time. Roman had caught on as well and leapt up to stand beside his father. â€Å"I swear, if you've hurt her even a little, I will rip you apart!† Simone's fear was put on pause as she gave Roman a puzzled look. With his signature hidden, he only came across as a human to her. As far as she was probably concerned, he had no involvement in any of this – and no ability to back up his threat. Little did she know. She turned back to Jerome, cringing when she saw his face once more. â€Å"Nothing,† she said, her voice hard to understand with Jerome choking off her air. â€Å"I didn't do anything to her, I swear it!† â€Å"You were trying to get Seth into bed,† said Roman. â€Å"That's all! I didn't do anything to her. Anything.† Simone's face turned pleading as she spoke to Jerome. â€Å"You have to know why I'm here. It's not to harm her.† Jerome's face was still filled with terrible fury, but there was also a flicker of consideration in his eyes. He said nothing, and it was Carter's voice that filled the tense silence. â€Å"She's telling the truth,† he said. Jerome didn't break his hold on Simone, but that calculating look was still in his gaze. â€Å"Do you know anything about her disappearing? Anything at all?† â€Å"No! No!† Jerome glanced back at Carter, who gave a swift nod. With a disappointed sigh, Jerome released her and stepped back. Roman looked doubtful, but he too had to know that if Carter vouched for her, it was gospel, so to speak. Jerome returned to his chair, downing his drink in one gulp. Roman joined him a moment later, but Simone remained standing, watching the whole group uncertainly as she rubbed her bruised throat. â€Å"I don't know what's going on, but if there's anything – â€Å" â€Å"I'm done with you,† said Jerome harshly. He waved his hand in a type of dismissal, and Simone vanished as quickly as she'd arrived. â€Å"That was mean,† noted Carter, idly stirring his bourbon. â€Å"I sent her back to her hotel,† said Jerome. â€Å"Not to a desert island.† Roman's anger had cooled a little, and he wore a calm, considering expression that looked remarkably like his father's. â€Å"What did she mean when she said you knew why she was here? Why was I following her?† â€Å"I can't report this,† said Jerome. He was speaking to Carter, like Roman wasn't even there. â€Å"Not yet†¦not unless I have to. We can't let any higher authorities know.† â€Å"And I can't do anything at all,† mused Carter. â€Å"This is technically your problem.† He took a long drink, as though that would fix everything. â€Å"But you will,† said Roman boldly. â€Å"You'll try to find her?† â€Å"Of course,† said Carter. One of his trademark cynical smiles lit his lips, replacing the grim expression from earlier. I suspected it was a cover-up for how he truly felt. â€Å"This place would be too boring without her.† For a heartbeat, I kind of liked this invisible watcher thing. Carter had no sense that I was there, and for the first time, I was able to truly study him without him looking back. He might have that annoying levity on now, but he'd already shown concern for my well-being. And I really couldn't believe it was simply because he found me entertaining. What was his game? Those gray eyes revealed nothing. â€Å"Yes,† said Jerome dryly. â€Å"Who knows how we'll get by without her maudlin misadventures.† Carter started to protest, but again, Roman came forward with an interruption. â€Å"Oh. That's the other thing, what we talked to Erik about.† He gave them a brief recap of Erik's observations and how I was only visited when I was depressed. Roman also described each of the incidents in as much detail as possible. Jerome and Carter exchanged looks. â€Å"With as down as she usually is, that's not much to go on,† noted the demon. â€Å"But it might be worth a visit to the old man.† â€Å"Jerome,† said Carter in a warning voice. The two locked eyes again and had some sort of silent communication. When Jerome finally looked away, it was to casually pick up his latest drink. â€Å"Don't worry. I won't scare him. Much.† I wondered if he'd go to Erik right then, but I didn't get a chance to find out. The world dissolved once more, and I found myself back in my prison. Aside from being terribly uncomfortable, I also felt exhausted. Studying the smiling, shining Oneroi, I could guess what had happened. In feeding off my dream, they'd taken some of my energy with it. â€Å"Dream†¦Ã¢â‚¬  I murmured, suddenly confused. I'd braced myself for some terrible outcome, but it hadn't happened. â€Å"That wasn't a dream. That was real. You showed me what was really happening. What my friends are doing.† â€Å"Some dreams are true, and some are lies,† said Two. I really wanted to slap him. â€Å"That one was true.† A story came back to me, the faintest memory from my childhood. Christian priests had long had a foothold in Cyprus when I was born, but old stories and rites had lingered. What were considered myths today had been held as fact back then. One such story said that dreams were sent to humans from one of two gates: one of ivory and one of horn. Those from the ivory gate were false; those from the horn gate were true. I didn't know if that was just a metaphor, but the outcome apparently had some validity to it. â€Å"But why?† I asked. â€Å"Why show me true dreams? You'd torture me a lot more with another stupid nightmare.† That nightmare hadn't been stupid. It had been agonizing, but I didn't want them to know that. What was stupid was me suggesting how they should torment me. â€Å"Because you don't know,† said One. â€Å"Soon you won't know truth from lies. You assume everything that causes pain must be a lie. But you won't know. Soon you won't trust anything at all.† â€Å"I'll know,† I said adamantly. â€Å"I can tell the difference.† â€Å"You believe what you just saw was true?† asked Two. â€Å"Yes. Absolutely.† â€Å"Good,† said One. â€Å"Then you've also learned another truth: it's impossible for anyone to find you. You'll stay here forever.†

Can We Know When to Trust Our Emotions in the Pursuit of Knowledge? Essay

The question advocates that we can from time to time trust our emotions in the pursuit of knowledge. And generally we presume that it may be possible to know when to trust emotions and that emotions can help us in the acquisition of knowledge. And you may challenge these presumptions. Maybe it is not possible to know when to trust our emotions, and maybe our emotions have a limited value in the pursuit of knowledge, but to what I aim to analyse is to what extent do our emotions play a role in the pursuit of knowledge. After being elected as the captain of my house, a post which came armed with heavy responsibilities, my luck struck out in getting the ideal vice captain to assist me. Hence, I was forced to consider replacing my vice captain. Be that as it may, it just so happened that this replacement happens to be a good friend of mine, which led me to question whether or not I was doing the right thing. Am I choosing to replace my current vice captain out of whats best for my house or am I simply replacing him out of the emotional attachment for my good friend. Taking my emotions into consideration, my judgment is affected to some extent, but at the same time it doesn’t mean that it prevents me form making the right decision. While I did want my friend as my new vice captain, there were also facts to support the way I felt about why my current vice captain had to be replaced. Having said that even if my friend turned out to be even worse than his predecessor then I would on some level act rationally and replace my friend as well with someone else. Maybe that someone else might be chosen on the basis of my liking of that person but nevertheless the fact that I was willing to strip that post from him for the good of my house shows that it isn’t always down to our emotions which affect our judgement and how that judgement affects our pursuit of knowledge. The pursuit of knowledge in this case discusses knowing what is truly fair and right, and while I did what I thought was best for my house, I was also simultaneously fulfilling my own personal 1interests by choosing a close friend. The way I look at it, there is no harm in killing two birds with one stone. Then again when I say I did what I did because it was best for my house then the only reason I did what was best for my house was because of the emotional attachment I had towards my house itself and if changing my house captain was what I had to do then either way which ever decision I took was because my of emotions. So how do our emotions pave our path in our understanding of the decisions we make and weather those decisions are ethical or not? And how do those decisions in turn affect the way we pursue knowledge? Decision making requires a very cognitive thinking and conditional to the situation we are in we can classify our decisions as emotional or logical decisions. Making a logical decision requires us to exclude our emotions and seek to use only rational methods in arriving at a resolution. Such a situation could involve solving a simple maths problem. Considering my real life situation where is was supposed reach a verdict by using my emotional and logical thinking, making a choice in my houses best interest was on the basis of my logical thinking which was fueled my emotional attachment towards my house. Essentially to a large extent reason and emotions do go in conjunction with each other. Its been widely proven that the reasoning and emotional centers of our brains are inclined to work together in many situations from choosing which movie to watch to solving mathematical equations, to making ethical choices. In an experiment conducted by Neuroscientist Antonio Damasio, a group of subjects who had sustained brain injuries in the part of the brain where emotions were generated were studied. Everything about them remained the same except for the fact that they lost the ability to feel emotions. In his observations he found that their ability to make decisions was severely impaired. They could logically illustrate what they were doing but in practice found it very difficult to make decisions about what to eat, where to live, etc. Subjects like mathematics through which we use deductive logic to gain certain knowledge and state a valid argument on the basis of a true axiom or premise might seem rather emotionless compared to subjects to like the arts which involve terms like inspiration and expression of oneself through his/her emotions but as different as they seem, they both go hand in hand. When you tell a person he/she is horrible at a particular subject, he/she looses the motivation to push himself/herself to excel in that subject, however if you told that same person that he/she has a lot of potential to transcend in a certain subject, he/she feels obligated to unlock this talent he/she has for this subject that other people claim he/she has. By simply manipulating that persons emotions, you can essentially affect the way that person pursues that particular subject. An ground breaking event in history which incorporates biology and religion would be the time when Charles Darwin came up with the theory of evolution. While various religions have to come to reconcile their beliefs in this theory, there are religions that raise various objections to the concept of evolution. The religion of Christianity for example talks about how the world was created by its god in seven days, and this ideology had stayed strong and had been passed down generations for thousands of years. Even till today young children are acquainted with this story until the eight grade when they learn of Darwin’s theory of evolution. This sudden revelation of the truth can instigate people to deeply question their faith and its teachings which can deeply affect them on an emotional platform. Christianity like all religions give its followers a sense of belonging. They take pride in being a Christian and strictly follow its principals and values which were imbibed into them by their parents and their church, and to a large extent their faith plays a big role in defining their integrity and character. That being the case when they learn that all those years being followers of Christianity could well be a lie, it can cause them to fear and question their values and virtues. Due to the fact that their religion gave them so much happiness and joy, they would come to blindly accept it without casting any aspersions about it. As a result those positive emotions led them to could their reasoning and prevented them from thinking clearly therefore predominantly affecting their way of learning and how they accepted different truths. From the above example people are now forced to fight emotions with reasoning, and instead of blindly accepting any theories or prophecies told to them, people take a larger initiative to believe in these unknown theories only after personally witnessing it or understanding that respective phenomenon from studying rational facts. And yet from this whole phenomenon of evolution which changed the face of the world, millions of people are still strong believers of Christianity. And while they have simultaneously come to terms with the numerous theories which defy their religion, they continue living life by balancing their beliefs with what science throws at them. The fact of the matter is that believing in a greater power gives people a sense of comfort during a time of difficulty, it gives them this sense of safety that they have something or someone they can turn to, to help keep themselves and their emotions sound and under control. And maybe at the cost of escaping the actual truth they may give into their emotions to keep themselves convinced and satisfied in the fantasies which they feel protect them from the harshness of reality. And for that reason yes I do feel that our emotions affect our pursuit of knowledge and not in a way that we can trust them for the fact that our emotions strongly dilute reality to help us humans cope with life’s obstacles. 2 Emotions play a big role in the one of the ways of knowing. In fact emotions can be so powerful that it can sometime change our other ways of knowing, such as the way we perceive the world. It can drive us away from logic and even change the way we use language. In the end I have analysed how our emotions can give rise to us escaping the truth, and notwithstanding the fact that at the same time our emotions are also key to helping us make logical decisions.

Greek Gods essays

Greek Gods essays When you think of Greek Mythology, you think of Zeus, probably, or Hercules (which is Roman). Well, there is A LOT more to it than just him. I mean a lot, a lot. There are dozens upon dozens of gods. But not all of them are worth mentioning, but most are. Because I cant make this very long, I have cut it down to the main three gods: Zeus, Poseidon, and Hades. But, I will start out by telling how the world was created and the gods were born, according to Greek Mythology. It all started with Chaos. It was dark, nothing was around. Out of the darkness came Erebus, which is the unknowable place where death dwells, and Night. It was still dark, when out of nowhere came Love, which brought order. Love brought Light and Day with it. With Light and Day, Gaea, the earth, was born. Gaea gave birth to Uranus, which became the heavens. They mated and produced 3 Cyclopes, 3 Hecatoncheires (beings with 100 pairs of arms, all equally strong), and the 12 Titans. Gaea didnt like Uranus, he was a bad husband and a bad father. So she conspired against him. None of her children, the Titans, would help her, except Cronus. Cronus was the youngest Titan of them all. He attacked him when he was sleeping and castrated him. The blood from Uranus created the Giants, Ash Tree Nymphs, and the Erinnyes. Cronus took over for his father and imprisoned the Cyclopes and the Hecatoncheires in Tartarus (Tartarus is the ultimate prison, worse than the Underworld, where there is no way you are getting out unless you are released.) He married his sister Rhea and all the Titans had many children during his reign. He was told one of his kids would overthrow him when they got older. So, to keep the from happening, he swallowed each of his children, except one. Rhea took her sixth child, Zeus, and hid him in the land of Crete. She then took a stone, wrapped it in a cloth and presented it to Cronus, which he then swallowed, thinking...

Professional Values and Ethics Paper

Professional Values and Ethics Paper Values and ethics are an essential part to human life. They differentiate between right and wrong. To know the difference can keep people where they should be; allowing them to be good example to others. People like to see someone walk out an ethical lifestyle, not just hear about it. What is valued defines character because it shows what is most important. It is the standard people hold themselves accountable to which actions are based on the values they live by. When people have good values, it can carry into other areas of life; both professional and personal.By having good values and ethics in life, it is easier to let that filter into a career. A person will want to show that they have good standards and know how to work in stressful situations and keep their head on straight. This will show any employer that their employee has it under control and can maintain a good work attitude.English: , Prussian philosopher. Portuguà ªs: , fil...It also means that this person can be accou ntable and people can rely on this person to make good choices as well as creating a healthy work environment where everyone feels safe and trusts each other.Whether people are consciously aware of them or not, every individual has a core set of personal values. Dictionary.com defines values as:n: beliefs of a person or social group in which they have an emotional investment (either for or against something); "he has very conservatives values"The key point to keep in mind about values is that implementing them energizes everything concerned with it. For an individual, committing to and applying values releases fresh energies, which always attract success, achievement, and well-being. Similarly, when companies or other institutions adopt values, individuals working at the organization become excited, as do its customers, its products and...

Biography of Kurt Schwitters, German Collage Artist

Biography of Kurt Schwitters, German Collage Artist Kurt Schwitters (June 20, 1887 - January 8, 1948) was a German collage artist who anticipated many later movements in modernist art, including the use of found objects, Pop Art, and art installations. Initially influenced by Dadaism, he created his own style, which he called Merz. He used found objects and items others considered garbage to create aesthetically appealing works of art. Fast Facts: Kurt Schwitters Full Name: Kurt Hermann Eduard Karl Julius SchwittersOccupation: Collage artist and painterBorn: June 20, 1887 in Hanover, GermanyDied: January 8, 1948 in Kendal, EnglandParents: Eduard Schwitters and Henriette BeckemeyerSpouse: Helma FischerChild: Ernst SchwittersSelected Works: Revolving (1919), Construction for Noble Ladies (1919), The Merzbau (1923-1937)Notable Quote: The picture is a self-sufficient work of art. It is not connected to anything outside. Early Life and Career Kurt Schwitters was born into a middle-class family in Hanover, Germany. At age 14, he suffered an epileptic seizure, a condition that recurred throughout much of his life and had a significant impact on the way he looked at the world. Schwitters began studying art at the Dresden Academy in 1909 seeking a traditional career as a painter. In 1915, when he returned to Hanover, his work reflected a post-impressionist style, showing no impact from modernist movements such as cubism. In October 1915, he married Helma Fischer. They had one son who died as an infant and a second son, Ernst, born in 1918. Initially, Kurt Schwitters epilepsy exempted him from military service in World War I, but as conscription expanded late in the war, he faced enlistment. Schwitters didnt serve in battle, but he spent the last 18 months of the war serving as a technical draftsman in a factory. Genja Jonas / Public Domain First Collages The economic and political collapse of the German government at the end of World War I had a profound impact on Karl Schwitters art. His painting turned toward Expressionist ideas, and he began picking up litter in the streets as found objects to incorporate into works of art. Schwitters gained the attention of other artists in postwar Berlin with his first one-person exhibition at Der Sturm Gallery. He created a non-sensical Dada-influenced poem, An Anna Blume, for the event and displayed his first collage works. Through the use of items that others would consider garbage, Schwitters illustrated his idea that art could emerge from destruction. Construction for Noble Ladies (1919). Kurt Schwitters / Wikimedia Commons / Public Domain Kurt Schwitters was suddenly a respected member of the Berlin avant-garde. Two of his closest contemporaries were Austrian artist and writer Raoul Hausmann and German-French artist Hans Arp. Merz or Psychological Collage While he engaged directly with many artists in the Dada movement, Kurt Schwitters devoted himself to the development of his own style that he labeled Merz. He adopted the name when he found a piece of an advertisement from the local bank or kommerz that contained only the last four letters. The Merz magazine first appeared in 1923. It helped solidify Schwitters place in the European art world. He supported lectures and performances by a wide range of Dada artists, musicians, and dancers. He often created collages to help advertise the events. The Merz collage style is also often called psychological collage. Kurt Schwitters work avoids non-sensical construction by trying to make sense of the world with a harmonious juxtaposition of found objects. The materials included sometimes made witty references to current events, and other times were autobiographical including bus tickets and items given to the artist by friends. In 1923, Kurt Schwitters began the construction of the Merzbau, one of the most ambitious of his Merz projects. He ultimately transformed six rooms of his familys house in Hanover. The process was a gradual one and involved contributions of art and objects from Schwitters ever-expanding network of friends. He completed the first room in 1933 and expanded from there into other parts of the house until fleeing to Norway in 1937. A bombing raid destroyed the building in 1943. Merzbau. Sprengel Museum / Wikimedia Commons / Public Domain In the 1930s, Kurt Schwitters reputation spread internationally. His work appeared in two landmark 1936 exhibitions at the Museum of Modern Art in 1936. One show was titled Cubism and Abstract Art and the other Fantastic Art, Dada, and Surrealism. Exile from Germany In 1937, the Nazi government in Germany labeled Kurt Schwitters work degenerate and confiscated it from museums. On January 2, 1937, after finding out that he was wanted for an interview with the Gestapo, Schwitters fled to Norway to join his son who left a week earlier. His wife, Helma, stayed behind in Germany to manage their property. She visited Norway regularly until the outbreak of World War II in September 1939. The last time Kurt and Helma saw each other was a family celebration in Oslo, Norway in June 1939. Helma died in 1944 of cancer before World War II ended. After Nazi Germany invaded and occupied Norway in 1940, Schwitters escaped to Scotland with his son and daughter-in-law. As a German national, he was subject to a series of interments by the U.K. authorities in Scotland and England until he eventually arrived at Hutchinson Square in Douglas on the Isle of Man on July 17, 1940. Dadaists in Germany including Kurt Schwitters. Apic / Getty Images A collection of terraced houses around Hutchinson Square served as an internment camp. Most of those in residence were German or Austrian. It soon became known as an artists camp since so many internees were artists, writers, and other intellectuals. Kurt Schwitters soon became one of the most prominent residents of the camp. He soon opened up studio space and took on art students, many of whom later became successful artists. Schwitters earned release from the camp in November 1941, and he moved to London. There he met Edith Thomas, the companion of his last years. Kurt Schwitters met a number of other artists in London including British abstract artist Ben Nicholson and Hungarian modernist pioneer Laszlo Moholy-Nagy. Later Life In 1945, Kurt Schwitters moved to the Lake District of England with Edith Thomas for the last stage of his life. He moved into new territory in his painting creating what are considered precursors to the later Pop Art movement in a series titled For Kate after his friend, art historian Kate Steinitz. Schwitters spent many of his last days working on what he called the Merzbarn in Elterwater, England. It was a recreation of the spirit of the destroyed Merzbau. To maintain his income, he was forced to paint portraits and landscape pictures that could be sold easily to residents and tourists. These show a heavy influence from his Post-Impressionist past. Kurt Schwitters died on January 8, 1948, from chronic heart and lung disease. This is a cover of a book of 8 lithographs entitled Die Kathedrale, published in Hanover in 1920. This publication was created as response to the Dadaism included in the periodical Dada: Receuil litteraire et artistique by Tristan Tzara. Corbis via Getty Images / Getty Images Legacy and Influence Whether intentional or not, Kurt Schwitters was a pioneer anticipating many later developments in modernist art. His use of found materials anticipated the later collage work of artists like Jasper Johns and Robert Rauschenberg. He believed that art couldnt be and shouldnt be restricted to a frame on a wall. That point of view impacted the later development of installation and performance art. The series For Kate is considered proto-pop art through its use of a comic book art style. Merzzeichnung 47 (1920). Kurt Schwitters / Wikimedia Commons / Public Domain Arguably, the most complete representation of Schwitters artistic point of view was his beloved Merzbau. It allowed those in the building to immerse themselves in an aesthetic environment composed of found objects, autobiographical references, and the contributions of friends and acquaintances. Sources Schulz, Isabel. Kurt Schwitters: Color and Collage. The Merrill Collection, 2010.

Integrated Marketing Communication (IMC) and Marketing Channel Essay

Integrated Marketing Communication (IMC) and Marketing Channel Strategy - Essay Example We need to be selective in choosing from a number of online and offline marketing mediums. Internet marketing, direct marketing, database marketing, and public relations – all mediums seem to be consistent to provide the competitive edge in the market. Internet marketing can help in attracting new customers from the social media sites like Facebook where prospective customers have better chances of viewing the advertisement. Google advertisement through Pay-per-click programs and promotion through email marketing can be beneficial where only customers from the database could be sent promotional mailers, designed by the hired PR agency. Through Internet-TV, relevant audiences’ attention can be captured while their favorite programs are run on television channels. At the same time, using SMS as means of advertisement to the target audience telling the features of customized mobile phones of JF’s Electronics can click the marketing campaign by contacting the right t ouch points to attract wider audiences. Using online media tools judiciously can make the marketing campaigns more effective and relevant (http://en.wikipedia.org/wiki/Integrated_marketing_communications). Print media like radio, television, newspapers, and billboards are components of offline media. JF’s Electronics should combine both Medias in advertising the new product, customized cell phone. Offline media can be a crucial and cheap tool in making the product popular through television and radio advertisement. For television advertisement, there is good scope of showing interesting visuals based on the storyline as per the features of customized cell phones not found available in any other company and popular brand’s cell phones. Banners of the product at the most visible locations at the marketplace will help in generating people’s interest. All promotional initiatives should be made at regular and continuous intervals to create brand

Course Reflection Essay Example | Topics and Well Written Essays - 1000 words

Course Reflection - Essay Example To begin with, my first inquiry assignment talked about the causes of failure of El Hadji, the ruler of the Senegalese after the French rulers left. In this assignment, I put the superfluous reading into practice to enable me to come up with the storyline of the book-Xala. I also learnt that, through forming a proper question of inquiry, one is able to diagnose the whole story by answering the question of inquiry. For instance, by letting my question of inquiry to be, ‘’what led to the failure of El Hadji?’’, I was able to make a critical reading through the novel as I quench to find the answers to my question. In a way, I was able to develop greater meanings of the story rather than just reading the novel to know what it is talking about. From the story of this ruler, my question of inquiry enabled me to know that greed, corruption and inability to perform can make us as leaders to fail in discharging our duties to the people we lead. These are themes from the story that one can only make a good argument about when they form a question of inquiry and answer the question by making a thorough scrutiny of the text to develop some meaning from it that can be a lesson to the whole society. In my endeavors to create much meaning in my learning this semester, I realized that one would just have a superfluous reading at first to enable them to form an inquiry question. The inquiry question I formed had to be holistic in such a way that it had to allow me to be able to diagnose the whole novel as I got to the next assignment which required close reading to give a critical analysis. My first inquiry assignment therefore was only to give me an outline of what I need to do in order to answer my inquiry question. This then led to my second inquiry assignment where I was required to make a closer reading of the novel that would enable me to answer my inquiry question thoroughly. This brings a connection of the two assignments in a very interesting manner. It made me learn that one needs to make the first reading of a text or a novel to find its storyline. I then used the first reading to know what the novel talks about in a nutshell. From there, I was able to form a proper question that could help me scrutinize the whole novel. I was able to answer the formulated question by making a closer and critical reading of the novel as required by the second inquiry assignment. In the second assignment, I only went through certain sections of the novel, reading to find specific points that would give answers to my question. This helped me particularly to know what the author was trying to pass across to his readers. My major aim was to find the authors hidden meaning of the texts through his story and make them become lessons that everyone can use or learn from. Hence, the second part of this assignment really was to identify the author’s messages from the story to his readers and to the whole African society who find themselv es in similar contexts of leadership. I then wrote my writer’s letter which was included the steps that I followed to be able to make a close and critical reading of the novel. It also reflected on the deeper meanings from the author’s point of view, that anyone reading my notes would get from them. When one reads

Does Different Business Strategy Is Indeed a Requirement for Success Essay

Does Different Business Strategy Is Indeed a Requirement for Success - Essay Example According to the research findings, it can, therefore, be said that competition is even more profound in businesses surviving in competitive markets. Companies will, therefore, resort to innovation whereby new untapped markets will be created. However, creating and investing in new markets has its risks and disadvantages. The other option involves applying robust efforts to provide the same services and products better than any other player in the same industry does. However, the benefits cannot be retained for a long time. Therefore, the most successful business organizations resort to a hybrid of the two options. Best market players combine innovativeness and best of service to produce a different business field where competitors will find hard to compete. Most successful global business organizations have indeed survived the torrential market conditions by playing it differently. Apple is one of the leading companies in the production of high-tech electronic gadgets. Due to its su ccess, the company has become envy to most companies that are trying to follow its steps. With Steve Jobs as its current CEO, the company has achieved much success than other companies that have been in the industry for many years. Currently, the company’s market capitalization has exceeded $ 200 billion and this makes Apple find a position in the top ten companies in the globe. Currently, the company is ranked slightly below Microsoft, which is the leading technology company in the world. The most striking thing about the success of the company is how fast the company has achieved the success. Other market players in the industry are hoping to learn the secrets of the company and if possible emulate them. To understand Apple secrets, one needs to make a detailed analysis of its business strategies in order to determine how the same has indeed contributed to its success. Firstly, unlike other companies in the industry, Apple is a vertically integrated company. This implies th at the company control or owns most of the technology required to produce its products.

Business Regulations Essay Example | Topics and Well Written Essays - 3000 words

Business Regulations - Essay Example This code was set up by the Press Compliant Commission in order to regulate the industry. This commission is an independent entity that was set up in the early 1990s following the recommendations of a commission on press regulation that was chaired by Sir. David Calcutt. The commission’s core responsibility is to ensure that the press adheres to the agreed code of practice on sensitive topics such minors and privacy (Fourie 2002: 46). In case of any breach of the code of conduct, the commission will conduct an investigation and either uphold the complaint or dismiss it in its entirety. With the exception of incidents regarding inaccuracies (these are dealt with by the editor responsible) all other cases have to be adjudicated and published by the commission. This commission came to being ultimately because government wanted to come up with measures to ensure protection of individual’s privacy rights against the activities of various media houses. The commission that was set up to give recommendations on how to replace the Press council which was the regulatory body before. This new regulatory body, the PCC had a maximum of one and a half years to have its impact felt or be replaced by a system that was to be statutory based. The defunct Press Council had been set up in the year 1947. This was after the recommendations of the Royal commission into regulation of the press. It was introduced to mainly deal with the ongoing claims of deteriorating standards in the press. It was however not successful and this was evident in the 1980s when the National Union of Journalists withdrew its membership. Many publications were ignoring it due to the fact that it did not any formal code of practice that the press could adhere to. It also did not have any legal means to enforce its resolutions and sanctions.(McNair, 2009) Over the years since the year 2000, events

PR Assignment Essay Example | Topics and Well Written Essays - 250 words

PR Assignment - Essay Example One area where public opinion has been used for positive influence is in the political field. In the United States and most European countries, although public opinion poll results are sometimes not a true reflection of election results, there is a tendency of voters supporting the political candidate who is portrayed as a winner in the polls. On the other hand, public opinion can be used as a negative influence. In the Yugoslav Wars, public opinion in form of propaganda was used to breed hatred and incite the Serbians against other ethnic groups such as the Croats and Albanians (Price 93). There are three main factors that are involved in source credibility (KoEun 112). These are supposed expertise, attractiveness and a source’s trustworthiness. Expertise can be defined as having capability, knowledge and sufficient skills in a given field of specialization. Trustworthiness refers to the capacity of believing somebody as being honest. Attractfulness refers to the motivation towards something or somebody. An example of a product that can be influenced by source credibility is the design of different websites. For any website to appeal to its customers, it must feed them with true and gorgeous information. This cannot be achieved unless skilled and highly qualified personnel are employed to do the web designing. A crisis can be defined as a threat to operations that can have a negative impact if not appropriately handled (Coombs 6). It refers to the probable damage that a crisis can cause on a given organization or industry and its stakeholders. Examples of crises include industrial accidents, industrial product harm and organizational communication breakdown among others. If not properly handled, such crises may result in reduced financial gains and loss of an organization’s reputation. 4.) There are many ways to respond to a crisis on conflict. Timothy W. Coombs offers several

Business Regulations Essay Example | Topics and Well Written Essays - 3000 words

Business Regulations - Essay Example This code was set up by the Press Compliant Commission in order to regulate the industry. This commission is an independent entity that was set up in the early 1990s following the recommendations of a commission on press regulation that was chaired by Sir. David Calcutt. The commission’s core responsibility is to ensure that the press adheres to the agreed code of practice on sensitive topics such minors and privacy (Fourie 2002: 46). In case of any breach of the code of conduct, the commission will conduct an investigation and either uphold the complaint or dismiss it in its entirety. With the exception of incidents regarding inaccuracies (these are dealt with by the editor responsible) all other cases have to be adjudicated and published by the commission. This commission came to being ultimately because government wanted to come up with measures to ensure protection of individual’s privacy rights against the activities of various media houses. The commission that was set up to give recommendations on how to replace the Press council which was the regulatory body before. This new regulatory body, the PCC had a maximum of one and a half years to have its impact felt or be replaced by a system that was to be statutory based. The defunct Press Council had been set up in the year 1947. This was after the recommendations of the Royal commission into regulation of the press. It was introduced to mainly deal with the ongoing claims of deteriorating standards in the press. It was however not successful and this was evident in the 1980s when the National Union of Journalists withdrew its membership. Many publications were ignoring it due to the fact that it did not any formal code of practice that the press could adhere to. It also did not have any legal means to enforce its resolutions and sanctions.(McNair, 2009) Over the years since the year 2000, events

You are an Investment Analyst Essay Example | Topics and Well Written Essays - 2500 words

You are an Investment Analyst - Essay Example Amazon is an American Multinational electronic company and it is the largest online retailers dealing in a variety of products. The company was started in 1994 by Jeff Bezo and it has its headquarters in Seattle, Washington in the US. The company exists in the internet and online retailing industry. The company underwent a rebranding in 1995 when it got renamed to Amazon.com from Amazon River. It started its operations with the main objective of offering online books and it diversified its operations later on (BELEW, 2011). Among its original products we have books sold alongside CDs, MP3 downloads, DVDs, video games and a variety of software. In addition to the above, the company later on started dealing in furniture, food stuff, electronics, toys as well as jewelry. Generally, the company provides consumer electronics such as the amazon kindle e-book reader. The products it provides therefore include; IMDb, LoveFilm, The Book Depository, Zappos.com, Woot, Junglee.com, Amazon Studios, Amazon Web Services, Audible.com, dpreview.com, Endless.com, A2Z Development, A9.com, Alexa Internet, Amazon.com, and Amazon Kindle. The company targets the world market with its main consumers being, students at all levels of studies, corporates such the universities, as well as researchers. To widen their supply chain, Amazon targets major suppliers such as top publishers, manufacturers of books, together with researchers and universities. They also coordinate with manufacturers who are involved in the production of other items. Under the leadership of the company steered by Jeff, the company stresses on the principles of customer obsession, hiring and developing the best, insistence on very high quality, aspect of thinking big, vocally self-critical, invention and simplification as well as delivery of results. These leadership principles apply to everyone in the company irrespective of whether they are

Learning Team Reflection Essay Example for Free

Learning Team Reflection Essay This past week, our team has been going over and reflecting on four main objectives. These main objectives are differentiating between accrual basis and cash basis accounting, the process of creating adjusting entries, and adjusted trial balances. We will also collectively discuss our opinions of what would be the most important skills learned in an accounting position. In accordance to week three’s objectives, I would have to say that everything that we have gone over is essential to our success in future accounting positions, however, we feel that the most important skill is to be able to accurately record the inflow (revenue earned) and the outflow (expenses: utilities, etc. ) of monies. Accural vs. Cash Basis Accounting According to the readings, accrual basis accounting is defined as in which companies record, in the periods in which the events occur, transactions that change a companys financial statements, even if cash was not exchanged. In other words, it means that recorded or un-recorded, all transactions are taken and projected into the overall balance. Cash Basis Accounting basis in which a company records revenue only when it receives cash, and an expense only when it pays out cash. This means that this means of accounting, only takes accountability of the physical cash that is at a physical location. The differences, Accural is all transactions whether recorded, unrecorded, or projected. Cash is the physical monies on hand at a physical location and does not record earnings until payments are actually made. Create adjusting entries This week we have been given a lot of practice on how to create adjusting entries to financial documents and internal financial â€Å"memos† (such as balance sheets). There are five types of adjusting entries: Accrued revenues – making adjustments to a service that has been performed but not billed. 1. Accrued expenses – expenses such as wages paid to an employee. 2. Unearned revenues – payments for goods or services to be delivered at a future date. 3. Prepaid Expenses – assets that are prepaid and gets used up during the accounting period. 4. Depreciation – process of allocating the cost of an asset. When adjusting entries are created, they are created in real time. These entries are important so that the net profit or loss and the financial position can be established. Prepare an adjusted trial balance. Again, we have practiced a lot this week in being able to successfully and accurately adjust entries in many different financial documents and of course, adjusting entries in trial balances have been some of those documents that we have worked on. In order to be a successful accountant, being to be able to successfully adjust entries in a trial balance sheet could be the very life factor in holding in accountant position. If we are unable to accurately record a trial balance the likelihood of us being able to hold our position as accountants is slim to none.

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