The Connection Between Culture And Learning - 934 Words

1. What is the connection between culture and learning? Provide an example from your own teaching or learning experiences. As educators we are responsible for teaching children from all races, ethnicity, and cultures. We are to tailor our instructions and lessons to fit the needs of the children. Pollock (2008) states that â€Å"Every individual participates in many cultures that affect, to varying degrees, how he or she â€Å"achieves† in school† (p. 370). All children learn differently and their cultural background can have an effect on their learning process. Goski (2014) stated â€Å"The most important skill for equity-literate teachers is the ability to recognize subtle and not-so-subtle biases and inequities† (para. 5). Educators need to be†¦show more content†¦371). I work with two and half year old children. They all come from a wide selection of ethnic groups and cultures. A few years ago I had a student who had moved to the United States from China. This particular student had a limited English vocabulary, so for the first few weeks we communicated through g estures and me physical showing this child what she needed to be doing. After a month of being immersed in her new school setting she started to come out of her shell and interact with her peers as well as the teacher. As I was going over notes from my observations of her I notice that she would always sit at the table until I gave her instructions on what to do. The other children in the class would move freely around the classroom picking which interest area they wanted to play in. Then it dawned on me that she was always taught to follow instruction by an adult. Her cultural background was to be obedient to adults and follow directions. I had to ask this child’s parent to let her know that it is ok to freely play in the classroom as well as follow directions. In my mind, I had already formed an opinion on how she learned based on her culture. Dunn, Dunn, Price (1989) noted â€Å"Only by examining each individual’s multidimensional characteristics, can we iden tify that person’s learning style† (as cited by Howe, 2012, p. 33). I had to think about her educational needs and find new ways to facilitate

The Six Most Common Forms of Anxiety Essay - 1069 Words

Everyday we experience anxiety. Normally, it’s the feeling you get right before a test, recital, or an interview, but sometimes and for some people it can be a whole lot worse. It can even result in terrible panic attacks that affect the way they live. Anxiety is defined as a general term for several disorders that cause nervousness, worrying,, and fear. Severe anxiety is the most common mental illness and affects 40 million people in the U.S. That’s about 18% of our population. We all get mild anxiety from time to time, but there are more severe cases, types, and forms to this illness. I will tell you about the type of anxiety that could be harmful to your everyday life. Today I will tell you about the types of anxiety, the different†¦show more content†¦People with this disorder are normally aware that they have OCD, but are still unable to control their fear. To get rid of their anxiety, they will clean obsessively and make sure everything is in place and o rderly. Posttraumatic Stress disorder or PTSD, is a very common anxiety disorder that a lot of people who have served in the military get this disorder. PTSD is a form of anxiety that results from a previous trauma like hostage situations and military combat. As a result, this disorder leads to flashbacks and behavioural changes in order to get rid of some of these causes. Panic Disorder is a type of anxiety that leads to severe panic attacks that cause dizziness, shaking, confusion, and nausea. These attacks normally last 10 minutes, but can last for hours. They can occur after a traumatic event or can be spontaneous. Normally after a person has one, they expect more, which can lead to drastic life changes. Extreme anxiety is a very serious mental illness that needs to be diagnosed and treated. We all get nervous in stressful situations, but what causes this disorder? Anxiety can be caused by numerous environmental and brain changes. Anxiety can be passed down through parents, but that is not very likely to happen. Anxiety is more likely to be triggered by a very traumatic event that causes extreme stress. An event like losing a loved one or changing schools can trigger the start of this disease. ThisShow MoreRelatedAll About Anxiety Essay788 Words   |  4 Pages The six most common forms of anxiety are Generalized Anxiety Disorder, Panic Disorder, Phobias, Social Anxiety Disorder, Obsessive Compulsive Disorder, and Posttraumatic Stress Disorder. Generalized Anxiety Disorder, or GAD, is characterized by excessive worries about nonspecific life events, objects, and situations. People with GAD often have trouble identifying that specific fear and controlling it. That said fear is often unreasonable and not in proportion with what is expected in a normal situationsRead MoreSymptoms And Symptoms Of Anxiety Disorders Essay1352 Words   |  6 Pages10 Sept 2016 Did you know that anxiety disorders are the most common mental illness in the U.S.? Affecting more than 40 million adults nationwide. Here is my next question. What exactly is a anxiety disorder? Anxiety is a mental illness that creates constant fear and worry which can be overwhelming or debilitating. There is a difference between normal, everyday anxiety and an actual anxiety disorder. Normal anxiety is caused by stress, usually this kind of anxiety can be helpful by motivating youRead MoreGeneralized Anxiety Disorder Is A Mental Disorder That1410 Words   |  6 PagesGeneralized anxiety disorder is a mental disorder that affects approximately four to five percent of the general population. This disorder can be illustrated by excessive anxiety and worry that lasts a minimum of six months and deals with various events or activities. People who struggle with this disorder have difficulties controlling their worry; this worry can permeate into every action or thought which leads to increased anxiety. Moreover, people with generalized anxiety disorder exhibit at leastRead MoreHow Anxiety Affects Student Performance1346 Words   |  6 PagesHow Anxiety Affects Student Performance Sloan E. Williams Greenville Technical College 10-18-16 â€Å"Surpassing even depression, anxiety is the most common form of mental illness in the United States. It’s estimated that approximately 10 percent of teenagers and 40 percent of adults suffer from an anxiety disorder of some kind† (11 Facts About Anxiety). Anxiety is a feeling of worry, nervousness, or unease, typically about an imminent event or something with an uncertain outcome.You may feel worriedRead MoreFear And Angst Disorder ( Gad )931 Words   |  4 Pagesspecific, then it’s possible you have an anxiety disorder. While there are seven to eight different forms of anxiety disorders, Generalized Anxiety Disorder (GAD), which is an anxiety disorder in which one has constant, overwhelming anxiety over†¦ everything, and Social Anxiety Disorder (SAD), which is an anxiety disorder where one has anxiety only over social situations (such as public speaking, parties, going to school or work, etc.) are the two most common. Despite the fact that they are o ften viewedRead MoreCognitive Behavioral Therapy1111 Words   |  5 PagesThe most cost effective interventions for adults with anxiety disorder appears to be individual forms of Cognitive Behavioral Therapy. The mean total societal costs were lower for Cognitive Behavioral Therapy as compared to Selective serotonin reuptake inhibitors and Cognitive Behavioral Therapy and Selective serotonin reuptake inhibitors (Apeldoorn et al, 2014). In particular, self-help books are cost effective compared with other forms of treatment options. Drugs and group based psychologicalRead MoreSeparation Anxiety : A Normal Part Of Childhood Development1463 Words   |  6 Pages Separation Anxiety often known as SAD refers to a developmental stage in which a child experiences anxiety due to separation from the primary caregiver (usually the mother). It is considered to be a normal part of childhood development. The normal stage occurs around eight months of age and can last up until the child is fourteen months old. Babies and toddlers are not the only ones that suffer from this disorder. When people would see children crying once their parents would hand them to someoneRead MoreGeneralized Anxiety Disorder1142 Words   |  5 PagesGeneralized anxiety disorder (GAD) is a disorder of shared self-reported symptoms. It goes with tension, uncontrollable worrying, sometimes muscle pain, trouble sleeping, and irritability that all together impair work ability, relations, and leisure activities. It is a common condition and there are psychological and pharmacological treatment options are available for anxiety disorders but not all patients respond to the same treatment as others. Finding a good treatment can take many months or sometimesRead MoreGeneralized Anxiety Disorder1632 Words   |  6 PagesGeneralized Anxiety Disorder Research Paper I choose to research Generalized Anxiety Disorder for my research topic. This disorder is one of the most arguably common faced encounters clinicians deal with today. Because of this I choose to focus much of my emphasis on the difficulties one face, that’s diagnosed with GAD and the hard ship of building and maintain a good client relationship. Generalized anxiety disorder begins at the onset of a worry and or tension that carries on into more severeRead MorePsychology Is The Study Of Human Behavior1447 Words   |  6 Pagesa great number of avenues to explore the mind. There are different types of psychology, both normal and abnormal as the overarching distinctions. There are also many disorders associated with abnormal behavior psychology such as schizophrenia, anxiety disorders, antisocial personality disorders, and borderline personality disorders. Of course, there are also many therapies from each respective perspective of psychology to treat these disorders as well. Normal psychology is the study of the behaviors

The Soothing Sensation That Is Bath Salts Free Essays

string(116) " room by the local police after they received multiple phone calls reporting an assailant breaking into their home\." The Soothing Sensation That is Bath Salts Introduction â€Å"Oh yeah, me and my girlfriend have a big bag of lavender bath salts sitting at home,† was the initial reaction when I asked a fellow engineer to portray as a testimonial for our borderline inappropriate bath salts infomercial. Contrary to popular belief, this new synthetic drug is far away from producing any effects that are similar to that of a relaxing bath. Until recently, bath salts were popularized to be a â€Å"legal high. We will write a custom essay sample on The Soothing Sensation That Is Bath Salts or any similar topic only for you Order Now In order to tip toe around the federal drug regulatory laws, bath salts were marked with a warning label that mentioned â€Å"not for human consumption. † In South Carolina, before the ban on October 24th 2011, bath salts could be purchased at one of the many head shops, gas stations, and even online. The appearance of the drug itself is usually in a powdered form that is sold within a package that is very aesthetically pleasing. These packages are sold under a variety of appealing names such as Ivory Wave, Vanilla Sky, Bliss, Blue Silk and etc. The composition of the synthetic drug bath salts can vary from dealer to dealer. Sometimes you may find traces of other stimulant drugs such as cocaine, amphetamines, or ecstasy, but the most important culprit in bath salts is 3,4-methylenedioxypyrovalerone (MDPV). MDPV falls under the category of phenethylamines and it is structurally related to synthetic cathinones. Synthetic cathinones are a group of drugs that are derivatives of the natural plant Catha edulis (also known khat), that contain the chemical phenylalkylamine alkaloid (Coppola, 2011). The remainder of the paper will provide some of the current available information such as pharmacokinetics, neurophysiology, and a brief discussion about MDPV as the primary active ingredient in bath salts. Pharmacokinetics The routes of administration of bath salts are similar to that of drugs in the â€Å"salt† class. The most common method is insufflation which results in faster onset of the effects but does not have a long duration. There are also other routes of administration preferred by drug enthusiasts; these mechanisms include parietal injections, intravenously, â€Å"bombing,† and also rectal administration. The â€Å"bombing† method involves putting the salt crystals in to cigarette paper to form a capsule and then simply swallowing it. The rectal administration requires an individual to dissolve the salt crystals in a type of liquid vehicle (i. e. water) and then introduce the liquid to the rectum via the anus. The absorption of MDPV is primarily dependent on the route of administration. The nasal route obviously has the quickest absorption. On the other hand, the oral administration is absorbed poorly because when taken orally, the rate of absorption compares to that of cocaine. The metabolism of MDPV in the human liver occurs similarly to that of other synthetic cathinone. The process involves multiple steps and the last of which is where the catechol ring of MDPV is methylated by COMT (Prosser, 2011). COMT is one of several enzymes that are involved in the degradation of catecholamines (i. e. dopamine, norepinephrine, and epinephrine). Finally, after the metabolism, the excretion of MDPV waste occurs through the urine of feces. Since there are no published, the duration of the effects of MDPV must be recorded with the word of mouth from experienced users. The drug effects start presenting themselves approximately 10-20 minutes after nasal administration and duration is close to 2. 5 hours. With oral administration, users report the effect to set in between 15-45 minutes after ingestion and the duration can last anywhere from 3-4 hours (in rare cases as much as 12 hrs) (Psychonaut, 2009). Neurophysiology As mentioned previously, due to the limited amount of available information for understanding the mechanism of physiological action of MDPV, the neurophysiology is theorized to have a similar mechanism to that of amphetamines and MDMA. This comparison is highly based on the structural similarities between amphetamines and synthetic cathinones (Prosser, 2011). The effects of amphetamines and their derivatives are produced by the three-fold effect on monoamine synapses. First, amphetamine-like drugs cause a leakage of neurotransmitters (NTs) from the presynaptic vesicles into the synaptic cleft. Second, they also increase the amount of NTs released in response to an action potential. Finally, there is an inhibition of monoamine reuptake from the synaptic cleft. As a result of the three-fold effect, there is an increase in concentration of NTs in the synaptic cleft which prolongs and enhances the effect of MDPV. Effects of MDPV on the Mind and Body Similar to most highly abused substances, MDPV has a laundry list of physical and psychological effects, including both desired and undesired. This data of effects is generated from first hand users and from the thousands of hospital admissions. With initial administration of MDPV, users can feel some desired effects that are not necessarily harmful (including but not limited to): increased energy, increased sociability, mild euphoria, increased concentration, sexual arousal (Coppola, 2011 Psychonaut 2009). Individuals that experience these non-harmful side effects are considered to be very lucky because on the other side of the coin are some very serious undesired psychoactive side effects. These undesired effects include extreme paranoia, delusional thinking, visual auditory hallucinations, self-mutilation, insomnia, violence, and restlessness (Prosser, 2011). Side effects of MDPV travels in pairs, if it affects the mind it will also have an effect on the body. Effects on the body include hypertension, tachycardia, chest pains, vasoconstriction, muscle twitches, bruxism, insomnia, and lack of appetite (Psychonaut, 2009). Currently, there is no effective treatment against MDPV overdose. The only method that is considered is to treat the physiological symptoms as they rise in order to prevent the individual from cause harm to themselves or others. To integrate all of the information I have provided in the paper thus far, I will present one of the many case studies that were published by medical doctors after this dramatic increase in hospital admissions as a consequence of MDPV psychosis. A 27-year-old female named J. H was brought to the emergency room by the local police after they received multiple phone calls reporting an assailant breaking into their home. You read "The Soothing Sensation That Is Bath Salts" in category "Essay examples" Upon arrival of the police, they were notified that there was a dead body in the hallway and that the homeowners were next for being killed. The police soon deduced that J. H. as suffering from paranoid delusions. In the emergency room, J. H. presented with hypertension, tachycardia, diaphoresis, and extreme fear but there were no sign of a physical disorder. When the results for her complete blood count, the comprehensive metabolic panel and the drug urine test returned completely unremar kable, she was transferred to the hospital’s psychiatric unit. The psychiatric staff recorded that she had a disorganized thought process, poor memory and was still convinced that she was in imminent danger. The only option for the doctors that was available was to start J. H. n treatment for Schizophrenia. The following day, her condition mildly improved and she was able to inform the doctors about the events that resulted with her being hospitalized. Apparently, she had a past history of opiate dependence, and one day, her and her boyfriend discovered bath salts, under the name of â€Å"Powdered Rush,† at a local head shop. They admitted to being on a binge period by insufflation for about five to six days prior to admission. The doctors concluded that paranoid psychosis from MDPV developed very much like that seen with methamphetamines and other psychostimulants. After three to four days of sleep deprivation, there was an onset of paranoid psychosis symptoms. She was released from the hospital a few days later after she was able to recover from sleep exhaustion (Antonowicz, 2011). Discussion As of November 2011, it was reported that there is currently no research that focuses on addiction and withdrawal related to synthetic cathinones (Prosser, 2011). This means that conclusions about MDPV related addiction, dependence, and withdrawal must be extrapolated from other drugs that are similar in structure and mechanism of action. As discussed previously, the mechanism of MDPV is by inhibiting the reuptake of catecholamines to produce strong stimulant effects. MDPV stimulates the ventral tegmental area to release more dopamine, which in turn will project to multiple areas of the brain: prefrontal cortex (PFC), nucleus accumbens (NAcc), and the hippocampus. All of these structures contribute to the conditioning and reinforcing behavior of MDPV. Since the reuptake of dopamine is inhibited, there is going to be an increase in the concentration of dopamine in the synaptic cleft. One can imagine the addictive, dependence, and tolerance properties of MDPV to be a combination of the properties of morphine, cocaine, and ecstasy. To elaborate, the pattern of administration of MDPV resembles to morphine because there is a slow increase in the dose over time required to acquire the necessary effect. Then the administration pattern of ecstasy also factors in because of cravings it causes. When an individual abuses ecstasy the serotonin will become scarce over time due to overstimulation. The low levels of serotonin will cause the individual to crave more ecstasy, but no amount of ecstasy will help. Similarly, the over production of MDPV causes the catecholamines to run low in supply and cause the addict to crave more. Finally, the other pattern that contributes to MDPV resembles the administration pattern of cocaine. The components of cocaine administration pattern that is relative to MDPV are the binge and exhaustion periods. Individuals will abuse MDPV for a period of time and due to sleep deprivation the individual will crash. In conclusion, when we integrate the three patterns together, the overall pattern of MDPV will show an increase in dose of administration until the individual either crashes from exhaustion or passes away due to an event that occurred in psychosis. When viewing the overall pattern of MDPV use, it is easy to see that majority of the time this drug can be extremely harmful. But, some users report that when MDPV is ingested at low doses, it produces a stimulant effect that is similar to methylphenidate. This glimpse of reported user experiences can make MDPV a candidate for ADD/ADHD treatment (Psychonaut, 2009). One of the factors that can increase the frequency of abuse of MDPV is the marketing of the bath salts themselves. The overall design and nomenclature that the bath salts are sold under are very aesthetically pleasing. Through personal experience, prior to the ban of bath salts, the price was very affordable when compared to the quality of effect (approximately $18 for 50 mg). Now after the federal ban, the price of some bath salts online range from $900 to $2200 for a large quantity. Many news reports suggest that there is a common misconception of harm when it comes to substances such as bath salts or other similar â€Å"legal† substances. Just because there are substances that seem to sneak around the drug regulations, they should be assumed as being safe. Statistics from the American Association of Poison Control Centers state that there were 1782 calls nationwide to poison centers about designer drugs labeled as â€Å"bath salts† just during the first four months of 2011. This was an exponential increase when compared to just 302 calls in all of 2010 (AAPCC). Mark Ryan, director of the Louisiana Poison Center, writes a quote for an article on Drugs. com that said: â€Å"If you ake the very worst effects of the illegal drugs LSD and Ecstasy with their hallucinogenic, delusional type properties, and combine them with the extreme agitation, superhuman strength and combativeness of PCP, as well as the stimulant properties of cocaine and methamphetamines, you have summarized the potential negative effects of bath salts use. † In conclusion, there has been a dramatic increase in the abuse of bath salts with the primary ingredient being MDPV. The current approach of gathering information for the mechanism of action of MDPV is mostly done by modulating the internet. Despite the lack of research on synthetic cathinones, individuals still take the risk to abuse MDPV. But based on similarities found between MDPV and other stimulants, we can theorize the mechanisms of action in the central nervous system. In my opinion, if you have not exposed yourself to MDPV it would be a wise decision to keep it that way because, metaphorically speaking, MDPV is like your girlfriend; it not only screws with your body but also your mind. 🙂 (I thought I would put a smiley face so that I can actually get to see it). References 1. American Association of Poison Control Centers. . Antonowicz, J. , Metzger, A. , Ramanujam, S. (2011). Paranoid psychosis induced by consumption of methylenedioxypyrovalerone: two cases. General Hospital Psychiatry, 33, 640. e5-640. e6. Retrieved December 4, 2011, from the SciVerse ScienceDirect database. 3. Coppola, M. , Mondola, R. (2011). 3,4-Methylenedioxypyrovalerone (MDPV): Chemistry, pharmacology, and toxicology of a new d esigner drug of abuse marketed online. Toxicology Letters, 208(1), 12-15. Retrieved December 4, 2011, from the ScienceDirect database. 4. Hallucinogens Legally Sold as ‘Bath Salts’ a New Threat – Drugs. om MedNews. (n. d. ). Drugs. com | Prescription Drug Information, Interactions Side Effects. Retrieved December 6, 2011, from http://www. drugs. com/news/hallucinogens-legally-sold-bath-salts-new-threat-2 9344. html 5. Prosser, J. , Nelson, L. (2011). The Toxicology of Bath Salts: A Review of Synthetic Cathinones. American College of Medical Toxicology, 7, 1-10. Retrieved December 4, 2011, from the SpringerLink database. 6. Psychonaut: Psychonaut WebMapping Research Group, MDPV Report, Institute of Psychiatry, King’s College London, London, UK (2009). How to cite The Soothing Sensation That Is Bath Salts, Essay examples

Modern Managers Certain Skills Leadership †Myassignmenthelp.Com

Question: Why Is An Understanding Of Paradox Important To Modern Managers? Answer: Introducation Modern mangers must be a leader first then be a manger in the organization. The modern managers should have certain skills of leadership which will take them and the organization to the height of efficiency and help the organization to run effectively. The leaders or the managers of the organization should have the quality to sense that what is happening in their environment. Managers are the directors of the organization who guide and direct others to achieve the organizational goals. The companies in the recent economic era are facing significant discontinuous changes with the changes in the market structure and consumer dealings. The leaders in this atmosphere need to be more flexible to meet the continuous changes in the market structure. Paradoxes are clear inconsistencies that in the beginning it seems to conflicting but looking into it closely and deeply they turn out to be simple and non-conflicting. Leaders should be open to overseeing many-sided quality, they comprehend that their destinations offer ascent to contending partner needs, as well as that they should accomplish their goals through the compelling administration of the pressures emerging from these necessities. Leaders can take a gander at circumstances from various focal points, distinctive perspectives and to comprehend their interdependencies. Complex issues must be comprehended and overseen through complex structures. Viable leaders comprehend associations as mind boggling versatile frameworks (Johnson, 2014). The Competing Values Framework rose up out of a progression of exact investigations on the idea of hierarchical adequacy. These endeavors were an endeavor to comprehend viability criteria. The study has found two measurements of adequacy. The primary measurement is identified with authoritative concentration, from an interior accentuation on individuals in the association to an outside concentration of the association itself. The second measurement speaks to the difference amongst soundness and control and adaptability and change. The Competing Values Framework got its name on the grounds that the criteria inside the four models appear at first to convey clashing messages. We need our associations to be versatile and adaptable, yet we additionally need them to be steady and controlled. The system has four quadrants: Inward Process Model: in view of progression, accentuation on estimation, documentation and data administration. These procedures bring solidness and control. Progressive systems appear to work best when the undertaking to be done is surely knew and when time is not an imperative factor. Open Systems Model: in view of a natural framework, accentuation on flexibility, preparation, development, asset securing and outside help. These procedures bring development and innovativeness. Individuals are not controlled but rather propelled. Reasonable Goal Model: in light of benefit, accentuation on balanced activity. It accept that arranging and objective setting comes about into profitability and effectiveness. Assignments are cleared up; goals are set and move is made. Human Relations Model: in view of union and resolve with accentuation on human asset and preparing. Individuals are seen not as secluded people, but rather as collaborating individuals from a typical social framework with a typical stake in what happens. While the models appear to be four completely alternate points of view or areas, they can be seen as firmly related and entwined. They are four sub domains of a bigger develop: authoritative and administrative adequacy. Thus with the help of CVF the leaders are able to handle the paradoxes. The leaders can bring changes to the issues with new transformations. I am the Legal manager of the XYZ Company dealing with insurance business. I look after the legal claims arising from the motor vehicles accident in the XYZ Company. I got an assignment to mitigate the loss of the company by bringing strong policy framework and reduce the number of claims. I have am talking about the doing an policy development of the company through inter-departmental cooperation. The task has been assigned to me i.e. the legal department and to my fellow colleague who is the Area Manager of Risk And Loss Mitigating Unit. We shall be responsible to complete the assignment and implement the policy framework within the company. I made an idea which if successfully implemented within the company will be best suited. The legal team and the RLM team both will frame certain policies which will make a check point for both the team performance that is to say that the legal team will frame policies that will have a check on the team performance of RLM and RLM team will frame policies to check the performance of the Legal Team. In this way, the objective of framing the policies will be served and help the company to mitigate more losses and give the company a good economic growth. The assignment will be performed by me and my fellow college in the department of Risk and Loss Mitigation Unit. Before starting the assignment we need to discuss the areas we should share regarding completion of the assignment. Therefore, we have a discussion with each other regarding the possibilities in completing the assignment successfully and areas in which we should work. The RLM unit is being specialized in investigating into the legal claims and gives report to the Legal unit to track the court proceedings associated with the claims. Therefore, I have an idea that the RLM should put more emphasis on the investigation and bringing out facts. There is a lack with the RLM unit to provide appropriate and completed report within the stipulated deadlines and the unit does not adhere to the regular deadlines at all. This led to the conflict with my colleague that the unit works harder and it should be the legal unit who should support them to investigate into the claims. The barrie r between us that obstruct both of us to resolve the conflict is our position in the company. I am the Zonal legal manger of the company and he being the National Head of the RLM Unit of the company working in two different verticals as well as two different levels of the organization. My ideas of tracking the investigation process and finding the loopholes in the investigation process hurts the professional ego of my fellow colleague and gave rise to the conflict between me and him. Moreover, the work pressure in our job roles is very high which is becoming an obstruction in resolving the conflict between us. We are not getting enough time to resolve the conflict in our ideas and go through the assignment. The only thing that I cannot understand throughout the conflict that if an department of the same organization comes up to help in developing other vertical of the organization what is the problem in it? The other vertical should have come forward and coordinate to achieve the goals set forth by the organization. After all we are all working towards the same goal that the organization has set forth. My fellow colleague should be more outward towards this small conflictions and clashes of interest and should think about the broader goals of the organization. My fellow colleague is egoistic and does not believe in the realistic and practical approaches to reach the goal. Coordination between the departments enhances the productive capacity of the organization wh ereas confliction creates separation. Therefore, I thought to make an investigation form my side into the claims and will put before the management to showcase the departmental lacking of the RLM in their process of work. Dear Colonel Williams, Meeting with you this morning was a pleasant and will be glad if we meet like this at regular intervals. The discussion which we started in our meeting regarding micronization was a successful and an informative one but one thing I must discuss with you is regarding the due date for implementing such. The due date which you have set for micronization process is very short and there is a possibility of failing the due dates. Moreover, if we ry to implement the process within this short period there might be various loopholes in the process and afterwards may not work properly as per the process. So this is my request to you to extend the due date for the implementation of the process so that enough time for decision making and other process related informations can be adhered and we can stick to our success. Whereas if we run fast to adhere the deadline set by you it may happen that we may miss various important aspects of the process which may lead ro unsuccessful implementation. I will be highly obliged t you if you grant y proposal and extend the due date by a week more so that we are able to check the suitability of the process in our organization. The theories of management are as follows: Scientific management School Classical Organizational Theory School Behavioral School Theory X Theory Y I found that scientific management theory as more effective than any other model of theory. The scientific management theory believes in the rule of the thumb and replaced the outdated theories of management. The scientific management theories advocates systematic training if the workers in an organization and believes it to be the best managerial practice. Moreover, this theory believes in sharing the workload evenly across the workers in the organization and division of labor should be such that each one is doing the task which is suitable for it (Barkema et al., 2015). The theory states that a complex task should be breakdown into various sub tasks so that the performance of the subtask can be optimized effectively and meet the deadlines. Moreover, the theory is interesting as it says to do through a task before attempting it and visualize the completion of the task. The task will be easier if you visualize each and every step of the task that is how it should be done and who shou ld do it. Thus, according to me scientific management theory is the effective way in the managerial functioning. Reference: Barkema, H. G., Chen, X. P., George, G., Luo, Y., Tsui, A. S. (2015). West meets East: New concepts and theories.Academy of Management Journal,58(2), 460-479. Johnson, B. (2014). Reflections: A perspective on paradox and its application to modern management.The Journal of Applied Behavioral Science,50(2), 206-212.

10 Highest Paying Jobs for College Graduates

10 Highest Paying Jobs for College Graduates A a college degree is not a guarantee for the big bucks the way it used to be. and law school and medical school are always a good idea for making good money over the course of a career, but they can be prohibitively expensive- and take far too long. Here are 10  of the highest paying jobs  for college graduates  that don’t require any additional schooling.1. Investment banker – $100kIt’s not the most altruistic career, but starting salaries are often over $100k on average, and if you’ve got a degree in economics, business, or math, this could be a great way to set yourself up nicely right out of the gate.2. Software developer – $80kIf you’ve got a degree in computer science, math, or engineering, and you’d like to make over $80k in your first year, plus you’re interested in getting in a field with a 30% growth rate, this career may be for you.3. Actuary – $79kActuaries work for insurance companies, assessing risk a nd helping to determine rates. You’ll need a strong math background, plus you’ll have to pass a few professional exams, but the money is good- an average of $79k per year.4. Engineer – $72kYou’ll need a BS in engineering, and to pass two different state licensure exams, but if you’re the problem-solving type and you’d like to make an average of $72k your first year, you might want to go to work- literally- fixing the world.5. Network systems admin – $70kWith an average first-year salary of just under $70k per year, network systems administrators need a degree in computer science (sometimes even an associate’s degree plus experience!). It’s got good growth potential (23%) and if you love computers and helping people, this could be a great fit.6.  Internet marketer – $70kWith more companies turning to the internet and social media for marketing, this is a good ground-floor career to get in on. Best pursued with a bachelor’s degree in marketing, you’ll likely make just under $70k in your first year.7. Financial analyst – $66kIf you have a degree in business, finance, economics, accounting, or statistics, and you feel you can give sound advice to business about expanding their growth, then you could make an average of $66k in your first year.8. Pharmaceutical rep – $60kYou’ll need a degree in chemistry, pharmaceutical science, or marketing, plus some training, but the pay is almost $60k in the first year, and you’ll be interacting with people for a good chunk of your workweek.9. Web designer – $58kIf you have a degree in computer science, graphic design, and/or some programming knowledge (i.e. HTML, CSS, java, flash, PHP, or MySQL), and you’d perhaps like to set your own schedule and workplace location, then you could be making around $58k in your first year designing and building websites.10. RN – $45kRegistered nurses make over $ 45k in their first year. You’ll need a degree in nursing, plus you’ll have to pass a national licensure exam, but there’s good growth (22%), and you’ll be helping people for a living!

Daniel Websters Seventh of March Speech

Daniel Websters Seventh of March Speech As the United States struggled with the deeply divisive issue of slavery a decade before the Civil War, public attention in early 1850 was directed to Capitol Hill. And  Daniel Webster, widely regarded as the nations greatest orator, delivered one of the most controversial Senate speeches in history. Websters speech was widely anticipated and was a major news event. Crowds flocked to the Capitol and packed the galleries, and his words traveled quickly by telegraph to all regions of the country. Websters words, in what became famous as the Seventh of March Speech, provoked instant and extreme reactions. People who had admired him for years suddenly denounced him as a traitor. And those who had been suspicious of him for years praised him. The speech led to the Compromise of 1850 and helped to hold off open warfare over slavery. But it came at a cost to Websters popularity. Background of Websters Speech In 1850, the United States seemed to be splitting apart. Things seemed to be going well in some regards: the country had concluded the Mexican War, a hero of that war, Zachary Taylor, was in the White House, and newly acquired territories meant the country reached from the Atlantic to the Pacific. The nations nagging problem, of course, was slavery. There was a strong sentiment in the North against allowing slavery to spread to new territories and new states. In the South, that concept was deeply offensive. The dispute played out in the U.S. Senate. Three legends would be the major players:  Henry Clay of Kentucky would represent the West;  John C. Calhoun of South Carolina represented the South;  and Webster of Massachusetts would speak for the North. In early March, John C. Calhoun, too frail to speak for himself, had a colleague read a speech in which he denounced the North. Webster would respond. Websters Words In the days before Websters speech, rumors circulated that he would oppose any sort of compromise with the South. A New England newspaper, the Vermont Watchman and State Journal, published a dispatch credited to the Washington correspondent of a Philadelphia newspaper. After asserting that Webster would never compromise, the news item lavishly praised the speech Webster had not yet delivered: But Mr. Webster will make a powerful Union speech, one which will be a model of eloquence, and the memory of which will be cherished long after the orators bones shall have mingled with the kindred of his native soil. It will rival Washingtons farewell address, and be an admonition to both sections of the country to fulfill, through union, the great mission of the American people. On the afternoon of March 7, 1850, crowds struggled to get into the Capitol to hear what Webster would say.  In a packed Senate chamber, Webster rose to his feet and gave one of the most dramatic speeches of his long political career. I speak today for the preservation of the Union, Webster said near the beginning of his three-hour oration. The Seventh of March Speech  is now considered a classic example of American political oratory. But at the time it deeply offended many in the North. Webster endorsed one of the most hated provisions of the compromise bills in Congress, the Fugitive Slave Act of 1850. And for that, he would face withering criticism. Public Reaction On the day after Websters speech a leading newspaper in the North, the New York Tribune, published a brutal editorial. The speech, it said, was unworthy of its author. The Tribune asserted what many in the North felt. It was simply immoral to compromise with slave states to the extent of requiring citizens to become involved in capturing fugitive slaves: The position that Northern States and their Citizens are morally bound to recapture fugitive Slaves may be good for a lawyer, but is  not good for a Man. The provision is on the face of the Constitution. True, but that does not make it the duty of Mr. Webster nor any other human being, when a panting fugitive presents himself at  his door begging for shelter and the means of escape, to arrest and bind him and hand him over to the pursuers who are hot upon his trail. Near the end of the editorial, the Tribune stated: We cannot be converted into Slave-catchers, nor  can Slave-catchers operate freely among us. An abolitionist newspaper in Ohio, the Anti-Slavery Bugle, blasted Webster. Quoting the noted abolitionist William Lloyd Garrison, it referred to him as the Colossal Coward. Some northerners, especially business people who preferred tranquility between the regions of the nation, did welcome Websters appeal for compromise. The speech was printed in many newspapers and was even sold in pamphlet form. Weeks after the speech, the Vermont Watchman and State Journal, the newspaper which had predicted that Webster would deliver a classic speech, published what amounted to a scorecard of editorial reactions. It began: As to Mr. Websters speech: it has been better praised by his enemies and better condemned by his friends than any speech ever before made by any statesman of his standing. The Watchman and State Journal noted that some northern papers praised the speech, yet many denounced it. And in the South, the reactions were considerably more favorable. In the end, the Compromise of 1850, including the Fugitive Slave Act, became law. And the Union wouldnt split until a decade later when the slave states seceded.

HRM in Organisations Coursework Example | Topics and Well Written Essays - 3750 words

HRM in Organisations - Coursework Example Ulrich’s foundation to HR model was based on his statement, â€Å"HR should be defined not by what it does but by what it delivers – the results that enrich the organization’s value to customers, investors, and employees† (1998; p.29). To underpin this proposition, Ulrich has proposed the four-role model of HRM that clearly defines the roles of human resource professionals in creating value for the organization. The present work is an attempt to understand both models from a critical perspective through respective advantages and disadvantages. These models have been studied based on few examples derived from organizations that have successfully adopted them; demerits have also been explored based on some unsuccessful attempts. Four-role model of HR: Identification of various roles that HR professionals performed has led Ulrich to organize these multiple roles in a more systematic and understandable fashion that resulted in the four-role model. In the four-role model, Ulrich has emphasized the business-partnership roles that HR professionals play in terms of focus on long-term/strategic to short-term/operational functions, and activities ranging from managing processes through HR tools and systems to managing people. Based on these two dimensions, focus and activities, Ulrich has identified four key roles for HR professionals that include, management of strategic human resources, management of firm infrastructure, management of employee contribution, and management of transformation and change (Ulrich, 1997; p.25). Ulrich (1997) has referred to each of these functions with specific metaphors that are identical with respective role or function, namely, strategic partner, administrative expert, employee champion, and change agent. As strategic partners, HR professionals are involved in framing HR strategies in line with organizational goals and objectives; specific operational objectives are also considered while framing the strategies. For instance, Ulrich (1997) cites the example of Marriott Hotel’s initiative while starting their operations in Hong Kong. This strategic initiative included introduction of five-day working schedule for its staff, which was unlike most other competitors in that sector. This initiative was meant to attract the best talent in the industry, as well as a step to retain them. Ulrich stated, â€Å"The five-day workweek became a cornerstone of Marriott’s strategy for achieving high-quality service, enabling the company to advertise, solicit, and secure the talented employees who would provide that service in Hong Kong market† (1997; p.26). It has been proven in many organizations that appropriate HR strategies are very effective in achieving organizational objec tives. Critiques, which include Ulrich also, have argued that the HR roles in this model literally mean HR functions, and not limited to specific roles. However, many organizations that adopted the Ulrich model had misinterpreted the model and its adoption. Adoption of this model had lead to division of HR functions based on roles, which was not the original intention or idea embedded in this model. Moreover, HR functions and structures cannot be fixed, and need to be changed based on

Case study(BMW Films) Essay Example | Topics and Well Written Essays - 1250 words

Case study(BMW Films) - Essay Example BMW is very clear in fulfilling its consumer’s needs and expectations; therefore they installed the features the target audience demanded from their luxury cars. As said by McDowell the vice president for marketing of BMW, company has lots of products to offer and it yet possesses a very small market share; therefore they need to have a strong influential and creative marketing plan to advertise its campaign and maintain its share. Because of its wild unconventional and creative advertising campaigns the company has survived tough times. Through the introduction of new concepts in advertisements, BMW films have managed to maintain its market share successfully in business. Sales increased rapidly which encouraged the company to invest in this department. Market is very narrowly segmented for the luxury cars business. According to BMW’s marketing head BMW is master at understanding the psychographic demands of its consumers. The target audience of BMW is around 46 years old with an income around $150,000, majority males. These are people who eye for perfection and are willing to pay for the best. They enjoy the attitude that the car enriches their personalities with which makes them loyal to its products. They focus in serving their consumers only with specific demands and to approach them. It is important to have a proper consumer segmentation model because different consumers have different needs and expectations. The company have its primary focus on fulfiling the demands of the existing customers and further on creating awareness to expand the range of consumers. Because if the luxury products it offer there is a specific niche market who can only afford it therefore all the strategies are implemented keeping them in mind. (Durker) Peter Drucker believes that there are two basic function of a business; marketing and innovation. BMW have keenly followed the innovation path to make successful marketing plan. There are three parts of being

Philosophy of Science Coursework Example | Topics and Well Written Essays - 250 words - 2

Philosophy of Science - Coursework Example These research methods include philosophical assumptions such as ontology, epistemology, and philosophical assumptions. While ontology is the claim about what knowledge is, epistemology refers to how a researcher recognizes the knowledge (Creswell, 2013). Additionally, how investigators write the facts is referred to as rhetoric while the study procedure is the methodology. Dr. Patton explains epistemology as the investigation of learning taking a deep insight on how we distinguish what we know. The meaning of this is how human differentiate between what they know and what they do not know. On the other hand, ontology refers to the address of the issue that someone is examining, what makes up the world. Philosophy of science refers to the study of theoretical fundamentals of scientific investigation. It is important for a researcher to be familiar with the philosophy of science to study and offer disapprovals for scientific ideas.

Haemoglobin-related Diseases Management Strategies

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