Asylums in Massachusetts McLean and Northampton Essay Example

Refuges in Massachusetts: McLean and Northampton Paper Conceptual Asylums, for example, The McLean Asylum for the Insane situated in Boston, The Worcester Lunatic Asylum, and The Northampton Lunatic Hospital have been around for a long time. Since the 1800s through the 1950s refuges have definitely changed in appearance, treatment, conclusion and numerous parts of the haven, for example, the food patients are given to eat, and what work the patients get the opportunity to do while being dealt with. The grounds and structures of refuges have made critical enhancements. Treatment has gotten increasingly good and precise as the decades progress. Every haven has various types of amusement and work that the patients are permitted to do while being treated in the early refuges. Haven Changes in Massachusetts The fundamental and most punctual refuges in Massachusetts all together incorporate the McLean Asylum for the Insane situated in Boston, The Worcester Lunatic Asylum, and The Northampton Lunatic Hospital. McLean Asylum for the Insane was established in 1818 initially situated in Somerville, at that point moved to Belmont, Massachusetts. In 1895. It is well known for its earth shattering neuroscience research and for the huge number of celebrated individuals who have been treated there, for example, Ray Charles and James Taylor. We will compose a custom exposition test on Asylums in Massachusetts: McLean and Northampton explicitly for you for just $16.38 $13.9/page Request now We will compose a custom article test on Asylums in Massachusetts: McLean and Northampton explicitly for you FOR ONLY $16.38 $13.9/page Recruit Writer We will compose a custom article test on Asylums in Massachusetts: McLean and Northampton explicitly for you FOR ONLY $16.38 $13.9/page Recruit Writer This refuge was the primary mental medical clinic In the U. S to ensure it had fundamental clinical research facilities. The emergency clinic considered natural factors in dysfunctional behavior patients. The McLean Asylum was additionally a division of the Massachusetts General Hospital and followed the Quaker standards of good treatment. The Worcester Lunatic Asylum was established in 1832 in Worcester, Massachusetts. It was the first of its sort in Massachusetts. During the primary year that it was opened 164 patients were gotten. The Northampton Lunatic Hospital was established in 1858 and situated in Northampton, Massachusetts. This clinic was later added to the National Register of Historic Places. The Northampton Lunatic Hospital and Worcester Lunatic Asylum were both piece of the Kirkbride Plan. This arrangement was a nineteenth century building style that was placed into impact for some shelters. There have been numerous upgrades since the 1800’s until the 1950’s in structures and grounds, analyze, socioeconomics including relaxation, work, food, and patient treatment in these refuges in Massachusetts. Past to the 1800s, patients experiencing psychological instability were covered up and housed in prisons before havens. Benjamin Rush, otherwise called â€Å"The Father of American Psychiatry. † contributed an incredible add up to the treatment of patients. Patients were controlled to Benjamin Rush seats; His treatment strategies likewise included dying, cleansing, and hot and cold showers. (Ozarin, L, 2006). 1800s: Buildings Grounds The Worcester Lunatic Asylum comprises of an inside structure and two wings, the cellar is intended for storerooms, a kitchen and pantry. Channels have been laid for water flexibly. The structures were plain, solid and made of block with a zinc rooftop. The structures had separate condos for patients, which were warmed in winter and exceptionally ventilated. They had spaces for occupants just as cooking foundations. For the grounds, exhuming and stoning for the basement done just as development of a street. High fences were put up to isolate the various yards. (Massachusetts General Court Senate, 1837). Diversion Patients are urged to take practice in the ranches accessible in the reason for them. They are permitted to meander in the carpenters’ shop, stroll in the nurseries, take outings, and take an interest in-entryway games just as different types of amusement. American Psychiatric Association, 1895). Treatment Bloodletting was not generally utilized in rewarding the crazy patients (American Psychiatric Association, 1895). At the Worcester Lunatic Asylum, regarding arrangement of treatment, representatives of the refuge need to give unique consideration to neatness, substantial wellbeing of patients, clean air and appropr iate eating regimen. Moral treatment was utilized and profoundly remembered, they used to accept that humankind is the law of adoration. (Massachusetts General Court Senate, 1837). Patients are inspected for fixes yearly. The patients at Worcester have been all the more exceptionally chose. Those considered â€Å"incurables† have no choice of slim down and get minimal clinical treatment and nursing help. Anyway they do require a considerable measure of food. 1850s Buildings Grounds In 1888, The Northampton Lunatic Hospital rolled out numerous improvements and enhancements in their structures and grounds. Yards of solid walk have been laid by the patient just as uncovering. for the creatures were raised. The stable for bovines and cows are presently in the cellar. The horse shelters were constructed in light of the fact that the interest in milk expanded from the approaching measure of patients being admitted to the emergency clinic. A chilly stockpiling building was included also, this stockpiling building for the most part containing apples, potatoes, dairy items and vegetables. As far as progress, the expansion toward the south wing of the medical clinic was taken a shot at. There was a significant requirement for the expansion in light of latrine and shower purposes. An extensive structure with a huge chimney for the most part for the utilization of the patients was developed on the emergency clinic grounds. This structure was an endowment of Miss Martha Eastman of Amherst. A considerable lot of the patients utilized the structures and justification for a brief home, a situation to work in and for recreational and practice reasons. (Northhampton Lunatic Hospital, 1907). Numerous different enhancements have been made, for example, people are presently in discrete agreeable quarters in their own structures. The pantry is currently substantially more extensive and present day. The kitchen offices were currently multiplied in size. The inside of the female wing had been reconstructed. The wing has bigger windows for light just as new wire-strip roofs that are defensive from flames. Another house of prayer was built; it would be over multiple times bigger than the one they right now had. Treatment as far as treatment, Most of the patients, eighty-two percent, are viewed as serious Taking the normal of the patients that currently present themselves in Massachusetts, eighteen percent should be reparable, and need dynamic treatment, and eighty-two percent, hopeless, and require mainly broad administration and alleviating custodial guardianship. It is accepted that good and clinical treatment is fundamental. (Jarvis, E. 1855). Food At The Northampton Lunatic Hospital, the dozing, eating, individual cleanliness, exercise, diversion and occupation schedules are profoundly requested and observed. Private patients get the chance to eat from a bigger assortment of food. The patients are served bread, oats, cheddar, eggs, natural product, meats, beans, tea, espresso, and vegetables with their dinners. (Northampton Lunatic Hospital, 1907). In another model, if the food isn't considered ‘good’ numerous patients will be come furious or harder to control and oversee. The patients likewise require great consideration and checking from the hospital’s workers. Jarvis, E. 1855). Work At The Northampton Lunatic Hospital, patients help out in zones, for example, in the kitchen, sewing, clothing, carpentry shops, painting, brick work, power work, plumbing and in the nurseries horse shelters and pens. The patients make brushes, tin product, garments, sleeping pads, and bedding and upholster seats. These movem ent are for the most part completed in the modern room, wards, their exercises have even been in displays at the medical clinic for everybody's viewing pleasure. The work people accomplish for the haven and during their off hours are very different. Men were permitted to work in the ranches, accomplish garden work, evaluating, and fencing. For ladies, it was not unexpected to accomplish family work, sew shoes, stockings, making floor coverings, basketry, and cultivating too. Representatives of the shelter should figure out how to accomplish the work and show the patients the right ways before the patients are required to do it. (Northampton Lunatic Hospital 1907). These exercises are done for the fundamental reason for giving the patients a kind of treatment, many are considerably more joyful on the grounds that they are given work which makes the thought a triumph. 1900s Buildings Grounds Since the 1900s, a lot more enhancements and changes have been made in the structures and grounds. For instance for the Northampton Lunatic Hospital in 1910, the structures were rebuilt and numerous increments were made. The â€Å"Day Barn† had been redesigned to help suit 30 calves and the storm cellar floor was principally to house the 40 cows. Eight sections of land of land was cleared, furrowed, and fenced for the homestead. The hospital working for ladies was just a single story high. Ways between the structures on each floor were vital. A sunroom on each floor was likewise being given. Concrete strolls from the thruway up until the passageway of the medical clinic have been laid making openness simpler for patients. (Hurd, Drewry, Dewey, Pilgram, Blumer, 1916). Another kitchen was assembled; it was currently large enough for the representatives to prepare nourishment for a bigger measure of patients. Is it all around ventilated, and has all the advanced enhancements. There is an exceptional butcher’s room, where the meat is gotten and cut up. The food, when cooked, is carried on vehicles through sections in the cellar at that point went to the ward where the food is then set up in the feasting lobbies. In 1898, dynamic changes and augmentations have been made. Another structure to suit the warming plant, machine shop, and craftsman shop, accounted for e

The Theme of Escape in The Glass Menagerie Essay examples -- essays re

The Theme of Escape in The Glass Menagerie In The Glass Menagerie, Tennessee Williams utilizes the topic of getaway to help drive the play forward. None of the characters are fit for living in reality. Laura, Amanda, Tom and Jim utilize different strategies to get away from the brutalities of life. Laura withdraws into a universe of glass creatures and old records. Amanda is fixated on living from quite a while ago. Tom escapes into his universe of verse composing and motion pictures. Jim additionally returns to his past and recollects the days when he was a secondary school legend. Mr. Wingfield is alluded to regularly all through the play. He is a definitive image of departure. This is on the grounds that he has figured out how to expel himself from the edgy circumstance that the remainder of the family is as yet living in. The emergency exit builds up the topic of the story. This passageway into the condo gives an alternate reason to every one of the characters. The emergency exit permits Tom the chance to get away from the loft and escape from his pestering mother. Amanda sees the emergency exit as an open door for respectable man guests to enter their lives. Laura's view is not quite the same as her mom and her sibling. Her break is by all accounts covering up inside the loft, not out. Laura winds up getting away every step of the way. She instigates ailment in her composing class and even as a man of his word guest holds up in the front room. Another getaway for Laura is her glass zoological display. Her assortment of glass speaks to her own private world set apart from the real world, a spot wh...

Creativity Tools for Every Entrepreneur

Creativity Tools for Every Entrepreneur Creativity is something that has become closely associated with entrepreneurs, in the sense that those who engage in entrepreneurship are already presumed to have creative-thinking skills, that they are artistic or imaginative. Otherwise, they would not be able to come up with brilliant ideas and turn them into profitable ventures.But being creative is not the only thing that entrepreneurs have going on, because all those ideas and that “innate brilliance” will amount to nothing by themselves. They need reinforcements and support, and these come in the form of various tools and techniques that entrepreneurs can use. © Shutterstock | Rawpixel.comIn this article, we explore 1) creativity in entrepreneurship, 2) tools for increasing entrepreneurs motivation, 3) tools for gaining improving ones expertise, and 4) tools for boosting ones creative thinking.CREATIVITY IN ENTREPRENEURSHIPCreativity has several meanings, all of which point to one thing: coming up with something new and fresh, or something that no one has seen before. First, it is the ability that is inherent among individuals, making them capable of coming up with fresh and innovative ideas. It can also be described as the way that these individuals do things, or their approach towards a problem that needs a solution. Finally, creativity also refers to that process that starts with the identification of a problem until the completion of the work involved in bringing the ideas to reality.From those definitions alone, it is clear the entrepreneurs simply cannot exist without at least the smallest degree of creativity. An entrepreneur need s to have all of the following components of creativity:Motivation:  Let us say, for example, that the individual has the two basic ingredients of an entrepreneur: creative thinking and expertise. There is still a high probability that nothing will come out of it, if the individual is not motivated to do anything about. One thing is for sure: an unmotivated individual can never become an entrepreneur.Expertise: This covers everything that the entrepreneur knows, particularly in the field or area that he works in. An entrepreneur is expected to have more than basic knowledge about the line of business that he is planning to set up. Expertise may be acquired through formal education, trainings and seminars, or even actual or practical experience.Skills on creative thinking: While expertise is largely obtained from external sources, creative thinking is more attributed to one’s personality and character. It refers to the capability of the individual to come up with ideas and putting them together to arrive at combinations that provide their desired results or goals.These three are deemed to be the main components of creativity. Without any one of them, creativity simply could not exist. But those are not the only elements that are required in order to fully tap or utilize the full potential of an entrepreneur’s creativity. We will now try to look into the various creativity tools that are required.TOOLS FOR INCREASING ENTREPRENEUR’S MOTIVATIONThere are two types of motivation, and both have an effect on a person’s creativity, albeit in varying degrees.Extrinsic motivation: The source of motivation is external, meaning outside of the person. This could include circumstances or situations that he or she is subjected to. They often come in the form of incentives â€" both tangible and intangible â€" and you’ve probably heard of the saying that says money is the best motivator. There is more than a grain of truth to that when taken in a corporate or workplac e setting. Employees go to work and perform their job well in order to get paid for it. Businessmen think of what products to make and sell in order to earn revenue and make profit.Intrinsic motivation: In contrast to the extrinsic motivation, this type is spurred by an individual’s internal desire to do or make something. He is interested about it; it can even be said that he is passionate about it. There are a lot of people who perform their job well because it gives them satisfaction to get very good results. They also find enjoyment in dealing with the challenges of their jobs.Accordingly, we can classify the tools for motivation into two categories:Tools for external motivationPhysical work environment designIf you have been exposed in more than a couple of work places before, you have probably noticed that you do better work in one workplace than in the others. This is most likely because of the work environment in general.Environment can boost creativity; the flow of the cr eative process is greatly affected by what goes on. In a simple office setup, employees will feel better about going to work every day when they can expect to spend the workday in a clean office with good ventilation and lighting, and a comfortable seat and table.Of course, that design does not work for all work settings, because the design of the work space will mostly depend on the nature of work that is going to be performed. Thus, the first thing that entrepreneurs should do is to make sure that they will be working in a physical environment that is designed for working. This includes focusing on the location, the lighting, the building design and floor plan, and even the furniture, fixture and equipment to be used, as well as their placement around the work area.Aside from lighting and ventilation, here are some more points to consider:Use of colors. In a 2009 study conducted by a team of psychologists at the University of British Columbia, subjects were made to take a series o f tests using computer screens with different colors (blue and red) as background. Results show that those who had the blue background scored higher on creative thinking, while those with a red computer screen showed more analytical prowess. The reasoning behind this was that blue was associated with peace, tranquility and free thinking, whereas red brings about feelings of urgency and danger signs, forcing people to think in a more analytical manner.Sound levels. Noise conditions also have an effect on creativity. Again, depending on the nature or type of work being performed, the noise or sound levels could either be distracting or creativity-inducing. Of course, those who would like to play it safe would prefer to take the middle ground: making sure that the workplace is subjected to a moderate level of noise, just enough to prevent distractions and induce creativity.Supportive TeamTeamwork is one of the crucial factors for productivity, and it goes without saying that it also wo rks for creativity. Ideas tend to flow more freely if there are unhindered and unencumbered channels for sharing and exchange. Group flow, which can only be achieved when creative people get together, is an excellent way to foster creativity.It is not enough for entrepreneurs to be aware that they are capable of coming up with creative and good ideas. Having a team that provides solid support behind and alongside them is also good for motivation. Getting assurance and reassurance that you are doing something right, or that you are on the right track, will definitely boost creativity.To ensure group flow that will boost motivation, make sure to:Choose the right people for the teamMatch the skills of the team members to the right taskMake the goal of the group clear, and be sure they understand itTools for internal motivationOften, motivation becomes stronger when induced internally. Entrepreneurs have to take the actions themselves to keep their motivations high and, consequently, th eir creativity.Time managementScheduling is important when you want to achieve effectiveness and efficiency in business. In business lingo, you can often hear the phrase “time is money” and, in many ways, it is true. Many brilliant ideas amounted to nothing because of wrong timing; some other entrepreneur beat them to it, for example, or they spent too much time working on an innovation that the best time for the output to be launched or introduced to the market has already passed.There are many time management tools that can be adapted by entrepreneurs, from using traditional planners and calendars tomodern or digital versions. A good application you can use to manage time and tasks is Flow, your online “team task managers” that lets you list down the tasks to be accomplished, prioritize them, and be reminded when you missed something.Health and wellness activitiesFor an entrepreneur, health and well-being is very important. They have to remain healthy and vigorous to be ab le to carry out their tasks. Poorly health and sickly bodies will certainly make it difficult for anyone to go on working. They will feel unmotivated to go to work or get on thinking about new ideas. Even ongoing projects may be put on hold or delayed because of health concerns.In order to take care of their health, the following activities are encouraged:Engaging in sports. Any sport that requires physical activity and exertion is advised in order to keep their energy levels up and build strength and endurance.Healthy and balanced nutritional meal plan. This is basically about watching what you eat: eating the proper type of food, at the right amounts, and at the right time. It’s not necessarily going to a professional dietician to create a meal plan for you to stick to. It’s all about finding the right balance.Meditation as a method of relaxation. Being stressed out all the time is not good for anyone, much less an entrepreneur. Relaxing every once in a while, especially throu gh meditation, is highly recommended even by the most seasoned business people.Vision boards.  Sometimes it is not enough to just think you can do something; it will also help if you are constantly being visually reminded about it. Making a vision board, or a simple poster containing pictures, words and mantras that will push you forward is already a good way to affirm what you visualize as an entrepreneur.TOOLS FOR GAINING AND IMPROVING ONE’S EXPERTISEOne great thing about expertise is that you can gain it from various sources, in various ways. The most common way, obviously, is through formal education. Taking courses in college or extra classes certainly never hurt in making sure that an entrepreneur is armed with the basics, but there are other tools to hone his expertise.Additional trainingsDo not confine yourself within the four corners of a classroom, or restrict your learning after you have graduated or earned your degree. There are organizations that conduct separate trai nings, seminars and workshops related to the line of work that you are involved in. You will also find aspiring entrepreneurs taking on internships or doing volunteer work in order to gain hands-on experience and use what they learn later on when they start their own venture.Use of platformsFortunately for entrepreneurs â€" aspiring and veterans alike â€" there are now several platforms that they can take advantage of in order to improve their skills and expertise. Some examples include:Coursera. Massive open online courses, also known as MOOCs, are now being offered by many educational technology companies, and one of them is Coursera, a firm that is connected with top universities and learning institutions. Through Coursera, entrepreneurs can take the courses that they want and need online, choosing from a wide range of subjects and classes.SkillShare. This platform utilizes a “learning community” setup, where creators, entrepreneurs, and anyone looking to learn can take onlin e classes that are taught and handled by industry experts. The approach is more interactive, because they are more focused on the completion of a project rather than just reading up loads of literature or listening to long lectures. This is particularly recommended for entrepreneurs, since the courses are focused on skills in advertising, business, fashion and design, audio-visual production, food technology, and more.Codecadamy.  Programmers are always on the lookout for new information and learning, for the simple reason that coding and programming is fast-paced and changes rapidly as technology also advances. Codecademy specializes in providing free coding classes of the various programming languages currently in use. There is also a community where everyone can converge to discuss further about programming.CREATIVITY TOOLS FOR BOOSTING ONE’S CREATIVE THINKINGOne would say that creative thinking is something you are born with, not learned. True, it is innate in most of us. Howe ver, there is no reason to think that it, too, cannot be acquired. In fact, there are a lot of things one can do in order to get ideas, get inspired, and become a more creative thinker.A notebookThis is as traditional as any creative person could get. It could be in the form of a simple notebook where you can write down ideas as they come to you. Artists or designers are usually seen carrying a sketchpad around with them, and this is where they put their ideas into writing or a simple representation.There is also a more modern option: digital devices such as tablets and digital notepads. Even smartphones are now seen as excellent note-takers.  Evernote is a widely-used note-taking application that also allows entrepreneurs to sync with their other devices, so they can check their notes and get to work anywhere they are in the world.BrainstormingThere are several brainstorming techniques that you can use. You just have to choose the one that you are most comfortable with.SCAMPER. The word stands for Substitute, Combine, Adapt, Modify, Put to Another Use, Eliminate and Reverse. Entrepreneurs use this technique by looking at current or existing products or services and asking questions about them, using the seven words as prompts.Six Thinking Hats. In this brainstorming technique developed by Edward de Bono, the participants of a group discussion are guided towards six different directions, marked by six colors: Managing (blue), Information (white), Emotions (red), Discernment (black), Optimistic Response (yellow), and Creativity (green). Using the strategy of Parallel Thinking, the members of the group start by focusing in one direction, and donning the metaphorical hats as the discussion moves forward, depending on the direction they are taking.Mind-mapping. This is one of the tried-and-tested brainstorming techniques, where a central idea branches out to more ideas and sub-ideas. There are several Mind Maps templates that can be obtained online to get you star ted.Trend spotting toolsBy looking at trends, you will easily spot patterns that will inspire you to come up with a good idea for a new product or service. In the past, entrepreneurs used to largely rely on their powers of observation or wait for official statistics to be released by regulatory agencies before they can establish and analyze trends and patterns. However, in today’s technology age, there are now several tools that can be used to learn about current trends, as they happen.Of course, in this day and age where everything works online (well, almost everything), you want to keep your pulse on the trends that really matter. LinkedIn Pulse makes that happen.Pinterest. More than a social media platform, Pinterest is a good place to start spotting trends. In fact, many people (even the non-entrepreneurs) readily claim to have found inspiration when checking out images “pinned” on Pinterest. You will be amazed at the amount of creativity found on this website, and how eff ective they are in inspiring anyone to be just as creative, or even more so.Fab. Creativity was often used synonymously with design, so that is one of the first things that people who are looking for inspiration seek out. Fab.com is a flash sale website that focuses on design items, so it contains unique and fresh design ideas that will definitely inspire anyone.You can probably name more creativity tools that specifically focus on motivation, creative thinking and expertise. Entrepreneurs need not be concerned that they will have trouble finding these tools, however, because they are now more accessible and readily available.

St. Dismas Assisted Living Facility Project Action Plan --...

1. Draw a Gantt chart for the construction phase of the program. What is the completion date if construction starts in March? What is the completion date of the project if construction is started in November? If the project is started on March 1st, 2012, the finish date is July 30th, 2013. For the November start date, the case does not mention exactly what date the project should start but rather mentions that it should start after the elections. We do not have the election date so I will assume a start date of November 14th, 2011, which is a Monday. In this case, the end date of the project would be April 11th, 2013. However, the case states that if the project starts in November, bad weather could affect the outside operations,†¦show more content†¦A February start might not cause the 2 months delay, as would a November start. 3. When will the project be completed based on your recommendation? Start date of January 30th, 2012. The first 45 units would be ready May 23rd, 2013 with the entire project being completed June 27rd, 2013. The Gantt chart displayed in Annex, chart c). 4. Develop a Gantt Chart of the Marketing Plan and Implementation Phase of the Program. Determine the start date of the Marketing Plan project in order to meet your recommended facility ready for occupancy date? I will consider the project dates stated in question 3 for this question and also consider that occupancy may begin when the first 45 units are ready, which is May 23rd, 2013. This means that the Marketing Plan and Implementation must be completed by this date. The Marketing VP states that she needs 5 months lead time for the implementation of the plan and thus, must begin 5 months prior to May 23rd, 2013. With the Gantt chart, found in Annex, chart d), this gives us a start date of September 14th, 2012. 5. What is the next step the team members must take in order to complete their project plans? The must allocate resources and must compile the different projects into one, making sure that predecessor are accurate in respect to the different phases. Just as the Marketing dates are affected by the Construction dates, LegalShow MoreRelatedPractices in Project Management: The St. Dismas Medical Center4115 Words   |  17 Pagesï » ¿ Practices in Project Management MSPM 6102 April 25, 2014 Abstract The St. Dismas Medical Center (SDMC) Assisted Living Facility (ALF) Project was authorized to create a new service line to counteract a decline of inpatient activity. The project objectives are to build 100 light- and heavy-assist units in a standalone residential facility with a sheltered connection to SDMC by late-July 2001 and within an $11 million budget. The particular deliverables, constraints, assumptionsRead MoreChapter 64943 Words   |  20 PagesChapter 6 Allocating Resources to the Project This chapter extends the previous one on scheduling into the area of allocating resources among the activities of a project, or among multiple projects competing for the same resources. The chapter begins with a discussion of expediting project completion times and highlights that by selectively choosing which activities to crash and by how much, we can determine the minimum cost for all possible project completion time. The use of Excel’s SolverRead MoreHelp4989 Words   |  20 PagesChapter 6 Allocating Resources to the Project This chapter extends the previous one on scheduling into the area of allocating resources among the activities of a project, or among multiple projects competing for the same resources. The chapter begins with a discussion of expediting project completion times and highlights that by selectively choosing which activities to crash and by how much, we can determine the minimum cost for all possible project completion time. The use of Excel’s Solver

Finding the Best How to Write a Personal Essay about Yourself

Finding the Best How to Write a Personal Essay about Yourself Know your objectives, know your objectives and do not switch off the intended path. Based on your dream, the tools you will need will either be simple to find or extremely difficult to get. Before you begin a project, consider why you would like to do it. As soon as it's important to select a project that isn't results-dependent, that doesn't indicate you should ignore metrics. Prayer Prayer deserves a tremendous shout-out. Creating unique blog ideas may not be simple in the start. Finding an intriguing blog post topic isn't always simple. Choosing How to Write a Personal Essay about Yourself Is Simple In fact, a seasoned writer can get the job done much faster than any student as they've been writing academic assignments during their entire life. Analyze what you have to write in the essay and the way you want the readers to react to it. Nowadays it's very difficult to locate a trustworthy essay writing service. Ask three distinct experts what a personal essay is and you'll probably get three distinct answers. The degree of marketing required in your career can change from job to job, but regardless, it's important to get a strong comprehension of the marketing and advertising targets and relationship behind what you're designing. It's essential that the statement portrays the applicant's personality when keeping up a professional tone. Actually, the personal statement is the one most important part of your whole application. As opposed to using a conventional thesis statement you can set forth a societal observation that ties into first topic of your essay. The elements of your topic will ascertain the subparagraphs of the principal body. Among the biggest misconceptions about the personal essay is that it's a chance to compose your entire life's story. Whether you're a novice writer or an experienced one, you always will need to begin with a structured strategy. You develop into a contributor rather than a consumer. New Step by Step Roadmap for How to Write a Personal Essay about Yourself It is possible to write about whatever you want, but do make sure it's an excellent article. The simplest approach to specify the sort of an essay is to realize the writer's point of view. So, as soon as you are sitting down to compose an essay, you will need to keep in mind that you need to express your personality there. An essay involve a great deal of thinking and self-analysis. Recall unpleasant moments that you discover very beneficial for your private improvement. Possessing a plan before starting to compose a piece is almost always a very good idea. You don't wish to waste time seeking your notes, research or buying supplies online when you may be working on a huge idea. Your project will acquire stale at some point should you do the very same thing over and over again. You've got every possibility of fulfilling somebody's dream if you may be bold enough to show up and share yourself. Deciding to write about the death or illness of a relative or pet, a close call in a vehicle, or an account of the huge game may make it simpler for you to conjure up and establish the emotions you would like to express, but you should be careful. You're able to list bits of your private life, but you should be cautious not to overshare. Be aware that personal should attempt to avoid repeating key words. There's no ideal solution about how to compose an effective essay. In fact, prior to making an order you may find a price quote on your essay. Writing a strategies and tricks' post is an excellent mixture of fun and useful. To structure an essay, you should simply follow the above mentioned format. If you discover that the writer did not provide just what you expected, request a revision, and we'll make the corrections. When you inform us about all of the paper information, we'll begin searching for an ideal writer for your paper. Today you can develop a thorough structure of the writing piece. The creative procedure is sometimes sloppy and disorganised.

Making Best Use of Windows Server 2003 Free Essays

The basis of technology development lies in bettering the older systems and coming to terms with enhanced functions in our information systems, etc.   Without the operating system, however, the information system technology would barely come to anything.   Hence, the Windows Server 2003 was developed as an enhancement to the Windows Server 2000, taking â€Å"the best of Windows 2000 Server technology and make it easier to deploy, manage, and use. We will write a custom essay sample on Making Best Use of Windows Server 2003 or any similar topic only for you Order Now †   Ã¢â‚¬Å"The result,† as described by Microsoft, is â€Å"a highly productive infrastructure that helps make your network a strategic asset for your organization.†Ã‚   The world’s leading company for operating systems, once charged with near-monopolistic practices in an anti-trust trial, further reported on the new addition to the operating system family that Microsoft continues to be famous for: As of March 28, 2005, all Windows Server 2003 operating systems ship with  Windows Server Service Pack 1 (SP1).   Windows Server 2003 SP1 provides enhanced  security, increased reliability, and a simplified administration to help enterprise  customers across all industries†¦Ã‚   In addition, in December 2005, Standard, Enterprise,  and Datacenter editions of Windows Server 2003 R2 were released, offering Active  Directory, storage, and branch office enhancements for customers (â€Å"Introducing the  Windows,† 2006). Released only recently, the Windows Server 2003 has become the talk of every computer technician today.   One of its key features is its enhanced availability through improved â€Å"clustering support.†Ã‚   Microsoft reports that â€Å"clustering services† are very important to trade, where inputs and outputs, imports and exports must be clustered so as to ease organizational functioning.   Windows Server 2003 allows for just that.   Besides, it helps in â€Å"scalability,† and not just â€Å"manageability.†Ã‚   Also according to the maker of the new operating system: Clustering installation and setup is easier and more robust in Windows Server 2003,   while enhanced network features in the product provide greater failover capabilities  and high system uptime.   The Windows Server 2003 operating systems supports server  clusters for up to eight nodes.   If one of the nodes in a cluster becomes unavailable  because of failure or maintenance, another node immediately begins providing service,  a process known as failover.   Windows Server 2003 also supports network load  balancing (NLB), which balances incoming Internet Protocol (IP) traffic across nodes  in a cluster (â€Å"Introducing†). As far as support and training are concerned, it has been confirmed that Windows Server 2003 is meant to make communications easier than before, not just between the organization and the users of the operating system, but also between the organizational users of the system and the customers of the organization.   The R2 Standard Edition of the Windows Server 2003 was made by collaboration between â€Å"third-party hardware and software partners† of Microsoft (â€Å"Overview of Windows,† 2005). Similarly, the company ensures that there are experts (Microsoft Certified Consultants) available to guide people through the process of installing any one of the following: (1) Windows Server 2003, Standard Edition; (2) Windows Server 2003, Enterprise Edition; (3) Windows Server 2003, Datacenter Edition (for highest availability); and (4) Windows Server 2003, Web Edition (Microsoft Certified Consultants). Seeing as Microsoft’s Windows Server 2003 is targeting businesses for the most part, the operating system – truly one of its kind – is packaged with sure technical support and training.   Microsoft’s business is tough, and the abundance of Microsoft experts in every nation in the world proves that the Windows Server 2003 would survive in firm business. Windows Server 2003 has training courses available with it (â€Å"Windows Server 2003,† 2007).   What is more, it is Microsoft’s intention to sell more of its countless software amenities to businesses after giving the new operating system to many of them for free.   Given that no other operating system company has thus far been able to meet or match the practices of the giant (â€Å"near-monopoly†) – the Windows Server 2003 would capture its unique market until a more advanced operating system, with better availability, support, and training, arrives out of Microsoft to substitute and complement the Server 2003. References Introducing the Windows Server 2003. (2006, January 24). Microsoft. Retrieved 26 May 2007, from http://technet.microsoft.com/en-us/windowsserver/bb429524.aspx. Overview of Windows Server 2003 R2 Standard Edition. (2005, December 6). Microsoft. Retrieved 26 May 2007, from Microsoft.com. Microsoft Certified Consultants. Microsoft Windows Server 2003 Help: Consulting, Support, Troubleshooting.Retrieved 26 May 2007, from http://www.progent.com/microsoft_windows_server_2003.htm. Windows Server 2003. (2007). Symantics. Retrieved 26 May 2007, from http://www.systematix.co.uk/mstech/windows-2003-training. How to cite Making Best Use of Windows Server 2003, Essay examples

Parallel Distributed Processing (PDP) In Brain

The nature of declarative memory and the possibility of its use in parallel distributed processing (PDP) regarding formation affects the perception of this complex and potentially threatening scene in a number of ways. The following analysis will help in understanding the scenario whereby a person sees a barely visible human as he/she is approaching an isolated ranch house at twilight.Advertising We will write a custom research paper sample on Parallel Distributed Processing (PDP) In Brain specifically for you for only $16.05 $11/page Learn More Declarative memory is often referred to as the conscious memory. It has two main components, namely the semantic and episodic memory (Goldstein, 2005). The episodic memory is concerned with those memories that an individual had once experienced in his/her lifetime. Such events could be traumatizing in nature and at times leading to poor perception and memory loss, especially when someone is engaged in deep thinki ng for a long time. The mental stress associated with such deep thinking would lead to memory lapse and poor vision. Precisely, episodic memories are focused on specific events, place and time (Banich, 2004). On the other hand, semantic memory has little to do with specific events since its knowledge is not linked to any personal experience. Though, semantic memory concerns mainly the concepts, numbers, facts, and vocabulary, it can as well find its relevance in this case. It is the semantic memory that has scripts that enable an individual to visualize what happens in a given situation. Semantic memory also shares a close link with the parallel distributed processing (PDS) in the brain. The PDS in the brain is a concept that is correlated with the semantic networks and motor neurons, which are photosensitive and can help in visualizing pictures (Antonio, 2005). Failure to enhance these parallel distributed activities would prevent someone from creating mental images and visualizing pictures. It is through the help of parallel distributed processing in the brain that vision is enhanced via the spreading activation mechanism. This is facilitated through the PDP because image processing occurs along parallel lines. Consequently, the distribution of the processed images for visual output occurs in many units, which require a proper psychomotor coordination of the whole process (Dominowski Dallob, 2005). The parallel distributed processes (PDP) augment memory can aide natural memory in evaluating the potential risk in this and other potentially threatening situations in a number of ways as highlighted in the discussion that follows. The PDP in the brain is very essential in representing knowledge (Robert Frank, 2001).Advertising Looking for research paper on psychology? Let's see if we can help you! Get your first paper with 15% OFF Learn More It is through the PDP system that individuals are able to make visual generalizations and create similar p atterns that aide the visualization process. As an aide to the natural memory, the parallel distributed processing in the brain is capable of recognizing and visualizing similar images and patterns. After having the knowledge of one image, the PDP system is capable of predicting how the consequent images and patterns would look like. The system has proved to be quite reliable and can help the natural memory since it is highly protected and cannot totally breakdown. Single wreckage in the PDP system can only delete patterns whose units are affected. Often, such mental problems mainly occur among the patients who suffer brain lesions (Zimbardo, 1995). Even though PDP has several advantages, it suffers some limitations as well. The parallel distributed processing (PDP) explains various elements about knowledge representation in an organized and elaborated fashion. However, it fails to provide some detailed explanations on complex processes such as rapid learning. And, it is through suc h weaknesses that PDP can at times fail to explain such threatening situations. References Antonio, R. D. (2005). Descartes’ Error: Emotion, Reason and the Human Brain. Oxford: Penguin Books. Banich,M.T. (2004). Cognitive Neuroscience and Neuropsychology. New York, NY: Housthon Mifflin Company. Dominowski, R. L. Dallob, P. (2005). Insight and Problem Solving: In The Nature of Insight. USA: MIT Press.Advertising We will write a custom research paper sample on Parallel Distributed Processing (PDP) In Brain specifically for you for only $16.05 $11/page Learn More Goldstein, E.B. (2005). Cogntive Psychology. Connecting Mind, Research, and Everyday Experience. Belmont: Thomson Wadsworth. Robert, A. W. Frank, C. K. (2001). The MIT Encyclopedia of Cognitive Sciences (MITECS). New York, NY: Bradford Book. Zimbardo, P. G. (1995). Psychology and Life. Inc. Glenview, Illinois: Scott, Foresman and Company. This research paper on Parallel Distributed Processing (PDP) In Brain was written and submitted by user PrinceofOrphans to help you with your own studies. You are free to use it for research and reference purposes in order to write your own paper; however, you must cite it accordingly. You can donate your paper here.

8 Bad Habits that Make You Look Unprofessional

8 Bad Habits that Make You Look Unprofessional Everyone has some bad work habits. You might be the most punctual, inoffensively friendly person around, but there’s always something that occasionally causes colleagues to roll their eyes. It’s a fact of life- none of us is perfect. However, recognizing these bad habits, and working hard to correct them, can do a lot to keep your work reputation as high as possible. Here are 8 bad habits that make you look unprofessional. 1. Being a Debbie DownerYou know the type- the other shoe is always about to drop, the successful completion of one project just means another one is around the corner, everyone else is just so incompetent all the time. You may not even realize how much you’re complaining, but it’s definitely something to keep an eye on.2. ProcrastinatingCounterintuitively, multitasking makes it so much easier to procrastinate: â€Å"I’ll do these three things now, and that other thing later.† Then that fourth thing gets pushed back, and pu shed back until it’s a week later and you’re still not done with it. This is especially problematic if the delayed task is something needed by someone else, because then it makes you look undependable.3. OverpromisingOverpromising is dangerous, because either you set yourself up for an onslaught of extra work, or you fail to deliver, which means your professionalism takes a hit. Colleagues and bosses need to know they can depend on you to deliver on time, and part of that is knowing the limits of what you can and can’t do within a certain timeframe.4. Trying to please everyoneBeing a people-pleaser is an impulse that comes naturally to a lot of us†¦after all, you want everyone to think you’re awesome at delivering awesomeness. But that can easily shift over into Pushoverville, where people take advantage of your eager nature. It can also come off as sucking up, or cause frustration when you’re trying to placate one boss who wants things one wa y, a colleague who wants them another way, and someone from a different department who needs things done a third way. It’s much better to use your judgment find the best way to handle something, and make sure that everyone knows why you’re doing it your way.5. Swearing like a pirateMany workplaces have become more casual in dress and attitude in general, but that doesn’t mean it’s okay to swear up a storm, especially when you’re talking about work. Everyone has slip-ups when they’re especially frustrated, but if you drop the f-bomb in front of coworkers more than a few times, it shows a lack of professionalism and care about how you present yourself in public. In terms of self-restraint, think broadcast network standards, not HBO.6. Running lateThere’s always a reason- traffic on the commute, dog ate the car keys, your favorite TV chef was showing you how to make bacon soufflà ©s on the Today Show. Chronic lateness just never makes y ou look good, even if you have one of those jobs where it doesn’t really matter if you’re at your desk at 9:00 or 9:20. Being there on time (except in those times when there really is a terrible commute) shows everyone that you’re ready to get things done.7. Making excusesWhen things go wrong, don’t be that guy/gal who always has a bunch of excuses ready to go. Excuses sound exactly like what they are, and when you use them, everyone around knows it. If things go wrong, own it and resolve to move on, and people will respect your honesty and drive to get things right.8. Being too flirtyBoundaries? What boundaries? Even if the flirting is harmless, you don’t want to run afoul of any sexual harassment policies your company has- especially if you don’t know the flirtee very well. Also, if it seems like you’re flirting to get ahead at work, that won’t endear you to your colleagues. Complimenting coworkers is fine, but try to keep it brief, friendly, and professional.Do any of these sound uncomfortably familiar to you? If so, don’t worry- we all have stuff to work on when it comes to workplace behavior. And there’s always time to recognize, correct, and start fresh!

Profile of Prince Henry the Navigator of Portugal

Profile of Prince Henry the Navigator of Portugal Portugal is a country that has no coast along the Mediterranean Sea, only the Atlantic Ocean, so the countrys advances in worldwide exploration centuries ago may come as no surprise. That said, it was the passion and goals of one man who truly moved Portuguese exploration forward, the man known as Prince Henry the Navigator (1394–1460). Formally, he was Henrique, duque de Viseu, senhor da Covilh. Fast Facts: Prince Henry the Navigator Known For:  He founded an institute for explorers, and people from around the world visited to learn about the latest discoveries in geography and navigation technology.Born:  1394 in Porto, PortugalParents:  King John I of Portugal, Philippa of Lancaster, of EnglandDied:  1460 in Sagres, PortugalSpouse: NoneChildren: None Although Prince Henry never sailed on any of his expeditions and rarely left Portugal, he became known as Prince Henry the Navigator because of his patronage of explorers, who increased the worlds known geographic information through the sharing of knowledge and by sending expeditions to places previously uncharted. Early Life Prince Henry was born in 1394 as the third son of King John I (King Joao I) of Portugal. At the age of 21, in 1415, Prince Henry commanded a military force that captured the Muslim outpost of Ceuta, located on the south side of the Strait of Gibraltar, on the northern tip of the African continent and bordering Morocco. It became Portugals first overseas territory. On this expedition, the prince learned about gold routes and became fascinated with Africa. The Institute at Sagres Three years later, Prince Henry founded his navigational institute at Sagres on the southwestern-most point of Portugal, Cape Saint Vincent- a place ancient geographers referred to as the western edge of the earth. The institute, best described as a 15th-century research and development facility, included libraries, an astronomical observatory, shipbuilding facilities, a chapel, and housing for staff. The institute was designed to teach navigational techniques to Portuguese sailors, to collect and disseminate geographical information about the world, to invent and improve navigational and seafaring equipment, and to sponsor expeditions. Prince Henrys school brought together some of the leading geographers, cartographers, astronomers, and mathematicians from throughout Europe to work at the institute. When people returned from voyages, they brought back with them information about currents, winds- and could improve existing maps and seafaring equipment. A new type of ship, called a caravel, was developed at Sagres. It was fast and was much more maneuverable than prior types of boats, and though they were small, they were quite functional. Two of Christopher Columbus ships, the Nina and the Pinta, were caravels (the Santa Maria was a carrack). Caravels were dispatched south along the western coast of Africa. Unfortunately, a major obstacle along the African route was Cape Bojador, southeast of the Canary Islands (located in Western Sahara). European sailors were afraid of the cape, for supposedly to its south lay monsters and insurmountable evils. It also hosted some challenging seas: tough waves, currents, shallows, and weather. Expeditions: Goals and Reasons Prince Henrys expeditionary goals were to increase navigational knowledge along the western coast of Africa and find a water route to Asia, to increase trade opportunities for Portugal, to find gold to provide the trips own funding, to spread Christianity around the world, and defeat Muslims- and perhaps even to find Prester John, a legendary wealthy priest-king thought to reside somewhere in Africa or Asia. The Mediterranean and other ancient East sea routes were controlled by the Ottoman Turks and Venetians, and the breakup of the Mongol Empire made some known land routes unsafe. Thus came the motivation to find new water routes heading East. Exploring Africa Prince Henry sent 15 expeditions to navigate south of the cape from 1424 to 1434, but each returned with its captain giving excuses and apologies for not having passed the dreaded Cape Bojador. Finally, in 1434 Prince Henry sent Captain Gil Eannes (who had previously attempted the Cape Bojador voyage) south; this time, Captain Eannes sailed to the west prior to reaching the cape and then headed eastward after passing the cape. Thus, none of his crew saw the dreadful cape, and it had been successfully passed, without catastrophe befalling the ship. This was the first European expedition to sail past this point and successfully return. Following the successful navigation south of Cape Bojador, exploration of the African coast continued. In 1441, Prince Henrys caravels reached Cape Blanc (the cape where Mauritania and Western Sahara meet). The expedition brought back some blacks as exhibits of interest to show the prince. One negotiated his and his sons release by promising several slaves upon their safe return home. And so it began. The first 10 slaves arrived in 1442. Then it was 30 in 1443. In 1444, Captain Eannes brought a boatload of 200 slaves back to Portugal. In 1446, Portuguese ships reached the mouth of the Gambia River. They were the first Europeans to sail that, too. In 1460 Prince Henry the Navigator died, but work continued at Sagres under the direction of Henrys nephew, King John II of Portugal. The institutes expeditions continued to venture south, then rounded the Cape of Good Hope, and sailed to the east and throughout Asia over the next few decades. The European Age of Discovery and Its Aftereffects The 100-year period from the mid-15th century to the mid-16th is called the European Age of Discovery or Age of Exploration, when Portugal, Spain, Great Britain, the Netherlands, and France sent out voyages to previously unknown lands and claim their resources for their country. The cheapest labor to work on plantations for crops such as sugar, tobacco, or cotton were slaves, brought on a triangular trade route, one brutal leg of which was known as the middle passage. Countries that are former colonies still suffer the aftereffects today, especially in Africa, where there is poor or inconsistent infrastructure in many areas. Some of the countries just gained their independence in the 20th century. Sources Dowling, Mike. Prince Henry the Navigator. MrDowling.com. https://www.mrdowling.com/609-henry.html.â€Å"Henry the Navigator.†Ã‚  Biography.com, AE Networks Television, 16 Mar. 2018, www.biography.com/people/henry-the-navigator.Henry the Navigator.  Encyclopedia of World Biography.  Encyclopedia.com.  https://www.encyclopedia.com/people/history/spanish-and-portuguese-history-biographies/henry-navigator.Henry the Navigator Facts. YourDictionary.com. http://biography.yourdictionary.com/henry-the-navigator.History. Sagres.net. Allgarve, Promo Sangres, and Municipia do Bispo. sagres.net/history.htm.Nowell, Charles E., and Felipe Fernandez-Armesto. â€Å"Henry the Navigator.†Ã‚  Encyclopà ¦dia Britannica, Encyclopà ¦dia Britannica, Inc., 12 Nov. 2018, www.britannica.com/biography/Henry-the-Navigator.The Portuguese Role in Exploring and Mapping the New World. Library of Congress. loc.gov/rr/hispanic/portam/role.html.Prince Henry the Navigator. PBS. https://www.pbs.org /wgbh/aia/part1/1p259.html.

Gender and History in Modern South Asia Term Paper - 1

Gender and History in Modern South Asia - Term Paper Example It is worth considering what other people perceive as being Chinese citizenship as opposed to the perspective of the Chinese themselves. Some of the ancient practices by Chinese people have faced stiff rejection especially over the course of the twentieth century by citizens who are believed to be from China. During the empire rulings, traditional rituals and practices were common among Chinese communities but cultural erosion has been greatly evident especially during the first half of the twentieth century. In the nineteenth century, Chinese were seen to uphold and respect their cultural practices such as marriage and burial rituals. However, things have significantly changed during the twentieth century where traditions have been greatly rejected by the Chinese. Instead, they are turning to modern life by abandoning indigenous ways of dressing and practices for the modern way of life. Chinese people have encountered a number of challenges as they try to transform from imperialism to modern way of life but by the help of educated people in the society, effective techniques have been used to liberate China from imperialism. The nation of China was a long time ago composited of small communities until when transformation took place over the nineteenth and twentieth centuries. The kind of leadership that was in place was quite different from the current one since centralization was in practice as opposed to decentralized leadership practiced today. The ruler of the state was an emperor the Son of Heaven who held the central position of cosmos (Harrison 2). Besides the emperor, there existed a bureaucracy education which, had characteristics that clearly portrayed the existence of modern China. However, it is worth noting the emperor was then perceived as a world but not as a country. Nevertheless, this did not mean that the Qing courts did not recognize the presence of other nations since they could have a negotiation with foreigners only that the negotiations could never be allowed to erase Chinese culture.  

Business and Management Essay Example | Topics and Well Written Essays - 1500 words - 1

Business and Management - Essay Example Recently UK government tried to privatise the royal mail partially. According to Lord Peter Mandelson, the business secretary of the country, it is required to have a strategic partner for bringing a gale-force fresh air in the culture and management of the organisation (Tyler, February 3 2009). The main objective of privatising the organisation is to modernise it and improve its financial condition. UK government found that there is significant declination in royal mail’s popularity and demand as there is other advanced mode of communication like email has emerged. According to some analysts there is almost 7 billion euro pension deficit in Royal mail. UK government provide various attractive benefits to royal mail so it stays ahead in the competition. But according to experts the decision of making it modernise and atomise it by bringing a private sector company as the strategic partner might result to 40,000 to 50,000 job cut. As a consequence Communication Workers Union (C WU) asked the workers to go for a strike till the decision is reconsidered. The union claimed that over 12,000 postal employees would go for strike in different cities like London, Edinburgh, Plymouth and Bristol (Hope, July 15 2009). In UK postal industry this is worker’s strike is a historical problem which is actually badly affecting the future of UK postal industry. Proper understanding and implementation of strategic human resource management would be the ultimate solution for this type of situation. Strategic human resource management is such a complex process that is continuously evolving and being discussed and studied by academic experts. There is no proper definition of Strategic human resource management as different people have different opinion regarding the topic. According to Wright and McMahan SHRM is â€Å"The pattern of planned human resource deployments and activities intended to enable the forms

Causes, Symptoms and Treatments of Anaemia

Causes, Symptoms and Treatments of Anaemia 1. Introduction Anaemia is a syndrome characterised by a lack of healthy red blood cells or haemoglobin deficiency in the red blood cells, resulting in inadequate oxygen supply to the tissues. The condition can be temporary, long-term or chronic, and of mild to severe intensity. There are many forms and causes of anaemia. Normal blood consists of three types of blood cells: white blood cells (leucocytes), platelets and red blood cells (erythrocytes). The first generation of erythrocyte precursors in the developing foetus are produced in the yolk sac. They are carried to the developing liver by the blood where they form mature red blood cells that are required to meet the metabolic needs of the foetus. Until the 18th week of gestation, erythrocytes are produced only by liver after which the production shifts to the spleen and the bone marrow. The life of a red blood cell is about 127 days or 4 months (Shemin and Rittenberg, 1946; Kohgo et al., 2008). The main causes of anaemia are blood loss, product ion of too few red blood cells by the bone marrow or a rapid destruction of cells.   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Haemoglobin, a protein, present in the red blood cells is involved in the transport of oxygen from the lungs to all the other organs and tissues of the body. Iron is an important constituent of the haemoglobin protein structure which is intimately involved in the transport of oxygen. Anaemia is generally defined as a lower than normal haemoglobin concentration. The normal blood haemoglobin concentration is dependent on age and sex, and, according to the World Health Organisation (WHO) Expert Committee Report, anaemia results when the blood concentration of haemoglobin falls below 130 g/L in men or 120 g/L in non-pregnant women (WHO, 1968). However, the reference range of haemoglobin concentration in blood could vary depending on the ethnicity, age, sex, environmental conditions and food habits of the population analysed. According to Beutler and Warren (2006), more reasonable benchmarks for anaemia are 137 g/L for white men aged between 20 and 60 years and 132 g/L for older men. The value for women of all ages would be 122 g/L. Also, the lower limit of normal of haemoglobin concentrations of African Americans are appreciably lower than that of Caucasians (Beutler and Warren, 2006).   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Besides the well recognised iron deficiency anaemia, several inherited anaemias are also known. These are mostly haemoglobinopathies. Adult haemoglobin is a tetrameric haeme-protein. Abnormalities of beta-chain or alpha-chain produce the various medically significant haemoglobinopathies. The variations in amino acid composition induced genetically impart marked differences in the oxygen carrying properties of haemoglobin. Mutations in the haemoglobin genes cause disorders that are qualitative abnormalities in the synthesis of haemoglobin (e.g., sickle cell disease) and some that are quantitative abnormalities that pertain to the rate of haemoglobin synthesis (e.g., the thalassemias) (Weatherall., 1969). In SCD, the missense mutation in the ÃŽ ²-globin gene causes the disorder. The mutation causing sickle cell anemia is a single nucleotide substitution (A to T) in the codon for amino acid 6. The substitution converts a glutamic acid codon (GAG) to a valine codon (GTG). The form of haemoglobin in persons with sickle cell anemia is referred to as HbS. Also, the valine for glutamic acid replacement causes the haemoglobin tetramers to aggregate into arrays upon deoxygenation in the tissues. This aggregation leads to deformation of the red blood cell making it relatively inflexible and restrict its movement in the capillary beds. Repeated cycles of oxygenation and deoxygenation lead to irreversible sickling and clogging of the fine capillaries. Incessant clogging of the capillary beds damages the kidneys, heart and lungs while the constant destruction of the sickled red blood cells triggers chronic anaemia and episodes of hyperbilirubinaemia.   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Fanconi anaemia (FA) is an autosomal recessive condition, and the most common type of inherited bone marrow failure syndrome. The clinical features of FA are haematological with aplastic anaemia, myelodysplastic syndrome (MDS), and acute myeloid leukaemia (AML) being increasingly present in homozygotes (Tischkowitz and Hodgson, 2003). Cooleys anaemia is yet another disorder caused by a defect in haemoglobin synthesis.   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Autoimmune haemolytic anaemia is a syndrome in which individuals produce antibodies directed against one of their own erythrocyte membrane antigens. The condition results in diminished haemoglobin concentrations on account of shortened red blood cell lifespan (Sokol et al., 1992).   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Megaloblastic anaemia is a blood disorder in which anaemia occurs with erythrocytes which are larger in size than normal. The disorder is usually associated with a deficiency of vitamin B12 or folic acid . It can also be caused by alcohol abuse, drugs that impact DNA such as anti-cancer drugs, leukaemia, and certain inherited disorders among others (Dugdale, 2008).   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Malaria causes increased deformability of vivax-infected red blood cells (Anstey et al., 2009). Malarial anaemia occurs due to lysis of parasite-infected and non-parasitised erythroblasts as also by the effect of parasite products on erythropoiesis (Ru et al., 2009).   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Large amounts of iron are needed for haemoglobin synthesis by erythroblasts in the bone marrow. Transferrin receptor 1 (TfR1) expressed highly in erythroblasts plays an important role in extracellular iron uptake (Kohgo et al., 2008). Inside the erythroblasts, iron transported into the mitochondria gets incorporated into the haeme ring in a multistep pathway. Genetic abnormalities in this pathway cause the phenotype of ringed sideroblastic anemias (Fleming, 2002). The sideroblastic anemias are a heterogeneous group of acquired and inherited bone marrow disorders, characterised by mitochondrial iron overload in developing red blood cells. These conditions are diagnosed by the presence of pathologic iron deposits in erythroblast mitochondria (Bottomley, 2006).    2. Classification of anaemia Anaemia can be generally classified based on the morphology of the red blood cells, the pathogenic spectra or clinical presentation (Chulilla et al., 2009). The morphological classification is based on mean corpuscular volume (MCV) and comprises of microcytic, macrocytic and normocytic anaemia.   Ã‚  Ã‚  Ã‚  Ã‚  (a) Microcytic anaemia refers to the presence of RBCs smaller than normal volume, the reduced MCV ( 15 would probably indicate IDA (Chulilla et al., 2009).   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  In macrocytic anaemia, erythrocytes are larger (MCV > 98 fL) than their normal volume (MCV = 82-98 fL). Vitamin B12 deficiency leads to delayed DNA synthesis in rapidly growing hematopoietic cells, and can result in macrocytic anemia. Drugs that interfere with nucleic acid metabolism, such as.hydroxyurea increases MCV (> 110 fL) while alcohol induces a moderate macrocytosis (100-110 fL). In the initial stage, most anaemias are normocytic. The causes of normocytic anaemia are nutritional deficiency, renal failure and haemolytic anemia (Tefferi, 2003). The most common normocytic anaemia in adults is anaemia of chronic disease (ACD) (Krantz, 1994). Common childhood normocytic anaemias are, besides iron deficiency anaemia, those due to acute bleeding, sickle cell anemia, red blood cell membrane disorders and current or recent infections especially in the very young (Bessman et al., 1983). Homozygous sickle cell disease is the most common cause of h aemolytic normocytic anemias in children (Weatherall DJ, 1997a).   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  In practice, the morphological classification is quicker and therefore, more useful as a diagnostic tool. Besides, MCV is also closely linked to mean corpuscular haemoglobin (MCH), which denotes mean haemoglobin per erythrocyte expressed in picograms (Chulilla et al., 2009). Thus, MCV and MCH decrease simultaneously in microcytic, hypochromic anemia and increase together in macrocytic, hyperchromic anemia.   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Pathogenic classification of anaemia is based on the production pattern of RBC: whether anaemia is due to inadequate production or loss of erythrocytes caused by bleeding or haemolysis. This approach is useful in those cases where MCV is normal. Pathogenic classification is also essential for proper recognition of the mechanisms involved in the genesis of anaemia. Based on the pathogenic mechanisms, anaemia is further divided into two types namely, (i) hypo-regenerative in which the bone marrow production of erythrocytes is decreased because of impaired function, decreased number of precursor cells, reduced bone marrow infiltration, or lack of nutrients; and (ii) regenerative: when bone marrow upregulates the production of erythrocytes in response to the low erythrocyte mass (Chulilla et al., 2009). This is typified by increased generation of erythropoietin in response to lowered haemoglobin concentration, and also reflects a loss of erythrocyt es, due to bleeding or haemolysis. The reticulocyte count is typically higher.   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Sickle cell disease is characterised by sickled red cells.   The first report of SCD was published a century ago noting the presence of peculiar elongated cells in blood by James Herrick, an American physician (1910). Pauling et al. (1949) described it as a molecular disease. The molecular nature of sickle haemoglobin (Hb S) in which valine is substituted for glutamic acid at the sixth amino acid position in the beta globin gene reduces the solubility of Hb, causing red cells to sickle (Fig. 1). Sickling of cells occurs at first reversibly, then finally as a state of permanent distortion, when cells containing HbS and inadequate amounts of other haemoglobins including foetal haemoglobin, which retards sickling, become deoxygenated (Bunn, 1997). The abnormal red cells break down, leading to anaemia, and clog blood vessels with aggregates, leading to recurrent episodes of severe pain and multiorgan ischaemic damage (Creary et al., 2007). The high levels of inflammatory cytokines in SCD may promote retention of iron by macrophage/reticuloendothelial cells and/or renal cells. SCD care commonly depends on transfusion that results in iron overload (Walter et al., 2009). 3. Pathogenesis of anaemia Anaemia is a symptom , or a syndrome, and not a disease (Chulilla et al., 2009). Several types of anaemia have been recognised, the pathogenesis of each being unique. Iron deficiency anaemia (IDA) is the most common type of anaemia due to nutritional causes encountered worldwide (Killip et al., 2008). Iron is one of the essential micronutrients required for normal erythropoietic function While the causes of iron deficiency vary significantly depending on chronological age and gender, IDA can reduce work capacity in adults (Haas Brownlie, 2001) and affect motor and mental development in children (Halterman et al., 2001). The metabolism of iron is uniquely controlled by absorption rather than excretion (Siah et al., 2006). Iron absorption typically occurring in the duodenum accounts for only 5 to 10 per cent of the amount ingested in homoeostatis. The value decreases further under conditions of iron overload, and increases up to fivefold under conditions of iron depletion (Killip et al., 2008). Iron is ingested as haem iron (10%) present in meat, and as non-haem ionic form iron (90%) found in plant and dairy products. In the absence of a regulated excretion of iron through the liver or kidneys, the only way iron is lost from the body is through bleeding and sloughing of cells. Thus, men and non-menstruating women lose about 1 mg of iron per day while menstruating women could normally lose up to 1.025 mg of iron per day (Killip et al., 2008). The requirements for erythropoiesis   which are typically 20-30 mg/day   are dependent on the internal turnover of iron (Munoz et al., 2009) For example, the amount of iron required for daily production of 300 billion RBCs (20-30 mg) is provided mostly by recycling iron by macrophages (Andrews, 1999).   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Iron deficiency occurs when the metabolic demand for iron exceeds the amount available for absorption through consumption. Deficiency of nutritional intake of iron is important, while abnormal iron absorption due to hereditary or acquired iron-refractory iron deficiency anemia (IRIDA) is another important cause of unexplained iron deficiency. However, IDA is commonly attributed to blood loss e.g., physiological losses in women of reproductive age. It might also represent occult bleeding from the gastrointestinal (GI) tract generally indicative of malignancy (Hershko and Skikne, 2009).   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Iron absorption and loss play an important role in the pathogenesis and management of IDA. Human iron disorders are necessarily disorders of iron balance or iron distribution. Iron homeostasis involves accurate control of intestinal iron absorption, efficient utilisation of iron for erythropoiesis, proper recycling of iron from senescent erythrocytes, and regulated storage of iron by hepatocytes and macrophages (Andrews, 2008). Iron deficiency is largely acquired, resulting from blood loss (e.g., from intestinal parasitosis), from inadequate dietary iron intake, or both. Infections, for example, with H pylori, can lead to profound iron deficiency anemia without significant bleeding. Genetic defects can cause iron deficiency anaemia. Mutations in the genes encoding DMT1 (SLC11A2) and glutaredoxin 5 (GLRX5) lead to autosomal recessive hypochromic, microcytic anaemia (Mims et al., 2005). Transferrin is a protein that keeps iron nonreactive in the circulation, and delivers iron to cells possessing specific transferrin receptors such as TFR1 which is found in largest amounts on erythroid precursors. Mutations in the TF gene leading to deficiency of serum transferrin causes disruption in the transfer of iron to erythroid precursors thereby producing an enormous increase in intestinal iron absorption and consequent tissue iron deposition (Beutler et al., 2000). Quigley et al. (2004) found a haem exporter, FLVCR, which appears to be necessary for normal erythroid development. Inactivation of FLVCR gene after birth in mice led to severe macrocytic anaemia, indicating haem export to be important for normal erythropoiesis.   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  The anaemia of chronic disease (ACD) found in patients with chronic infectious, inflammatory, and neoplastic disorders is the second most frequently encountered anaemia after iron-deficiency anaemia. It is most often a normochromic, normocytic anaemia that is primarily caused by an inadequate production of red cells, with low reticulocyte production (Krantz, 1994). The pathogenesis of ACD is unequivocally linked to increased production of the cytokines including tumour necrosis factor, interleukin-1, and the interferons that mediate the immune or inflammatory response. The various processes leading to the development of ACD such as reduced life span of red cells, diminished erythropoietin effect on anaemia, insufficient erythroid colony formation in response to erythropoietin, and impaired bioavailability of reticuloendothelial iron stores appear to be caused by inflammatory cytokines (Means, 1996;2003). Although iron metabolism is characterist ically impaired in ACD, it may not play a key role in the pathogenesis of ACD (Spivak, 2002). Neither is the lack of available iron central to the pathogenesis of the syndrome, according to Spivak (2002), who found reduced iron absorption and decreased erythroblast transferrin-receptor expression to be the result of impaired erythropoietin production and inhibition of its activity by cytokines. However, reduced erythropoietin activity, mostly from reduced production, plays a pivotal role in the pathogenesis of ACD observed in systemic autoimmune diseases (Bertero and Caligaris-Cappio, 1997). Indeed, iron metabolism as well as nitric oxide (NO), which contributes to the regulation of iron cellular metabolism are involved in the pathogenesis of ACD in systemic autoimmune disorders. Inflammatory mediators, particularly the cytokines, are important factors involved in the pathogenesis of the anaemia of chronic disease, as seen in rheumatoid arthritis anaemia (Baer et al., 1990), the cyt okines causing impairment of erythroid progenitor growth and haemoglobin production in developing erythrocytes.     Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Anaemia is also commonly found in cases of congestive heart failure (CHF), again caused by excessive cytokine production leading to reduced erythropoietin secretion, interference with erythropoietin activity in the bone marrow and reduced iron supply to the bone marrow (Silverberg et al., 2004). However, in the presence of chronic kidney insufficiency, abnormal erythropoietin production in the kidney plays a role in the pathogenesis of anaemia in CHF.   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  The myelodysplastic syndromes (MDS) are common haematological malignancies affecting mostly the elderly as age-related telomere shortening enhances genomic instability (Rosenfeld and List, 2000). Radiation, smoking and exposure to toxic compounds e.g., pesticides, organic chemicals and heavy metals, are factors promoting the onset of MDS via damage caused to progenitor cells, and, thereby, inducing immune suppression of progenitor cell growth and maturation. TNF- and other pro-apoptotic cytokines could play a central role in the impaired haematopoiesis of MDS (Rosenfeld and List, 2000). Premature intramedullary cell death brought about by excessive apoptosis is another important pathogenetic mechanism in MDS (Aul et al., 1998).     Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Sickle cell disease (SCD) arising from a point mutation in the ÃŽ ²-globin gene and leading to the expression of haemoglobin S (HbS) is the most common monogenetic disorder worldwide. Chronic intravascular haemolysis and anaemia are some important characteristics of SCD. Intravascular haemolysis causes endothelial dysfunction marked by reduced nitric oxide (NO) bioavailability and NO resistance, leading to acute vasoconstriction and, subsequently, pulmonary hypertension (Gladwin and Kato, 2005).    However, a feature that differentiates SCD from other chronic haemolytic syndromes is the persistent and intense inflammatory condition present in SCD. The primary pathogenetic event in SCD is the intracellular polymerisation or gelation of deoxygenated HbS leading to rigidity in erythrocytes (Wun, 2001). The deformation of erythrocytes containing HbS is dependent on the concentration of haemoglobin in the deoxy conformation (Rodgers et al., 1985). It has been demonstrated that sickle monocytes are activated which, in turn, activate endothelial cells and cause vascular inflammation. The vaso-occlusive processes in SCD involve inflammatory and adhesion molecules such as the cell adhesion molecules (CAM family), which play a role in the firm adhesion of reticulocytes and leukocytes to endothelial cells, and the selectins, which play a role in leukocyte and platelet rolling on the vascular wall (Connes et al., 2008). Thus, inflammation, leucocyte adhesion to vascular endothelium, and subsequent endothelial injury are other crucial factors contributing to the pathogenesis of SCD (Jison et al., 2004). 4. Current therapies for clinical management of sickle cell diseaseincludingacritical appraisal of transfusion Between 1973 and 2003, the average life expectancy of a patient with SCD increased dramatically from a mere 14 years to 50 years thanks to the development of comprehensive care models and painstaking research efforts in both basic sciences especially molecular and genetic studies, and clinical aspects of SCD (Claster and Vichinsky, 2003). The clinical manifestations of SCD are highly variable. Both the phenotypic expression and intensity of the syndrome are vastly different among patients and also vary longitudinally within the same patient (Ballas, 1998). New pathophysiological insights available have enabled treatments to be developed for the recognised haematologic and nonhaematologic abnormalities in SCD (Claster and Vichinsky, 2003). The main goals of SCD treatment are symptom alleviation, crises avoidance and effective management of disease complications. The strategy adopted is primarily palliative in nature, and consists of supportive, symptomatic and preventative approaches to therapy. Symptomatic management includes pain mitigation, management of vasoocclusive crisis, improving chronic haemolytic anaemia, treatment of organ failure associated with the disease, and detection and treatment of pulmonary hypertension (Distenfeld and Woermann, 2009). The preventative strategies include use of prophylactic antibiotics (e.g., penicillin) in children, prophylactic blood transfusion for prevention of stroke in patients especially young children who are at a very high risk of stroke, and treatment with hydroxyurea of patients experiencing frequent acute painful episodes (Ballas, 2002). Currently, curative therapy for sickle cell anaemia is only available through bone marrow and stem cell transplantation. Hematopoietic cell transplantation using stem cells from a matched sibling donor has yielded excellent results in paediatric patients (Krishnamurti, 2007). Curative gene therapy is still at the exploratory stage (Ballas, 2002). Current and potential therapies The potential treatment strategies basically target cellular dehydration, sickle haemoglobin concentrations, endothelial dysfunction, and abnormal coagulation regulation (Claster and Vichinsky, 2003). HbS concentrations are essentially tackled through transfusions while approaches to reduce HbS polymerisation which is the main mechanism for the development of vaso-occlusion include (a) increasing foetal haemoglobin (HbF) concentration using hydroxyurea (Fig. 2), butyrate, or erythropoietin, and (b) preventing sickle cell dehydration using Clotrimazole (Fig. 3) or Mg2+pidolate. Hydroxyurea therapy increases the production of HbF in patients with sickle cell anaemia, and, thereby, inhibits the polymerisation of HbS and alleviates both the haemolytic and vaso-occlusive manifestations of the disease (Goldberg et al., 1990). Recombinant erythropoietin also increases the number of reticulocytes with HbF. Additionally, it has been observed that administration of intravenous recombinant eryt hropoietin with iron supplementation alternating with hydroxyurea enhances HbF levels more than hydroxyurea alone (Rodgers et al., 1993). As SCD is essentially characterized by an abnormal state of endothelial cell activation   that is, a state of inflammation, a pharmacologic approach to inhibit endothelial cell activation has proved clinically beneficial (Hebbel and Vercellotti, 1997). Thus, administration of sulfasalazine which is a powerful inhibitor of activation of nuclear factor (NF)-B, the transcription factor promoting expression of genes for a number of pro-adhesive and procoagulant molecules on endothelium to humans has been found to provide transcriptional regulation of SCD at the endothelium level (Solovey et al., 2001). Red blood cell transfusion : a critical appraisal A key therapy that is applied regularly in the clinical management of patients with SCD is packed red blood cell transfusion. RBC transfusion improves the oxygen-carrying capacity which is achieved by enhancing the haemoglobin levels, causes dilution of HbS concentration thereby, reducing blood viscosity and boosting oxygen saturation. Furthermore, RBC transfusion is helpful in suppressing endogenous production of sickle RBCs by augmenting tissue oxygenation ( Josephson et al., 2007). There are two major types of RBC transfusion therapy: intermittent and chronic which are further classified as prophylactic or therapeutic. Intermittent transfusions are generally therapeutic in nature and administered to control acute manifestations of SCD whereas chronic transfusions are performed as general preventative measures to check complications of SCD. RBC transfusion given as a single dose is termed as simple transfusion. Exchange transfusion involves administration of a larger volume of RBCs replacing the patients RBCs that are simultaneously removed. Details of the various types of RBC transfusion and the major clinical indications for the same in SCD patients are listed in Table 1.   Ã‚  Ã‚  Ã‚  Ã‚  SCD (Source: Josephson et al., 2007) Indications for Intermittent transfusions Indications for intermittent transfusions include acute manifestations of SCD, as indicated in Table 1, that require redressal through therapeutic transfusions. However, under certain circumstances intermittent transfusions could be prophylactic such as for instance, when SCD patients are transfused before specific surgeries viz., those related to pregnancy complications or renal failure (Table 1).   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Acute Chest Syndrome (ACS) describes a manifestation of SCD in which, due to sickling, infectious and noninfectious pulmonary events are complicated, resulting in a more severe clinical course. The diagnosis is the presence of a new infiltrate on chest radiography that is accompanied by acute respiratory symptoms. ACD accounts for nearly 25% of all deaths from SCD (Vichinsky, 2002). Repeated episodes of ACS are associated with an increased risk of chronic lung disease and pulmonary hypertension (Castro, 1996). The severe pulmonary events occurring in SCD may be precipitated by any trigger of hypoxia (Vichinsky, 2002). Transfusions are very efficacious and provide immediate benefit by reversing hypoxia in ACS. Transfusion of leucocyte-poor packed red cells matched for Rh, C, E, and Kell antigens can curtail antibody formation to below 1% (Vichinsky, 2002). Simple transfusions suffice for less severe cases; however, exchange transfusion is recomm ended to minimise the risk of increased viscosity. Also, chronic transfusion appears promising for prevention of recurrence in selected patients (Styles and Vichinsky, 1994). In a multicentre ACS trial, prophylactic transfusion was found to almost completely eliminate the risk of pulmonary complications (Vichinsky, 2002).   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Acute Symptomatic Anaemia arises in SCD as a result of blood loss, increased RBC destruction, suppression of erythropoiesis etc. and is effectively treated with intermittent transfusion of RBCs to relieve symptoms of cardiac and respiratory distress (Josephson et al., 2007).   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Aplastic Anaemia is commonly caused in SCD on account of infection of haematopoietic precursors in the bone marrow by Parvovirus B19 leading to a steep fall in RBCs. According to Josephson et al. (2007), therapeutic intermittent transfusion of RBCs is again the recommended first-line of treatment to improve total haemoglobin count and prevent cardiac decompensation. However, in those patients who are prone to fluid overload on account of cardiac or renal dysfunction an alternative transfusion strategy is to remove the whole blood and replace it with packed cells while avoiding the addition of excess volume (Josephson et al., 2007).   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Acute Stroke is a high risk especially in paediatric SCD cases because of elevated cerebral flow. Enormous decline in stroke rate have occurred in children receiving intermittent simple transfusion (Adams et al., 1998). However, the identification of the stroke type would be necessary in all SCD patients in order to determine the appropriate treatment approach since the occurrence of infarctive strokes is higher in children as opposed to a higher incidence of haemorrhagic strokes in adults (Adams, 2003). Indications for Chronic Transfusions Prophylactic chronic RBC transfusion every 3 to 4 weeks to maintain HbS levels lower than 30% is crucial for preventing first as well as recurrent strokes in children (Johnson et al., 2007). The transfusions could either be chronic simple transfusion or prophylactic chronic RBC exchange transfusion. Prophylactic chronic transfusions are recommended for patients with chronic renal failure so as to avoid severe symptomatic anaemia and for those patients with SCD undergoing pregnancy with complications. However, prophylactic transfusion is not indicated for SCD patients with normal pregnancy (Tuck et al., 1987). Controversial and indeterminate indications for intermittent or chronic transfusion According to Hankins et al. (2005), chronic transfusion therapy is helpful in reducing the incidence of strokes in children but not the severity of strokes. In the case of acute priapism, improvement in patients has been observed after exchange or simple transfusion (Rifikind   et al., 1979). Yet, due to the ASPEN syndrome, transfusion currently is only a second-line therapy in the management of priapism ( Miller et al., 1995).   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  RBC transfusion is a vital component in the management of symptoms and complications of SCD. It has drastically reduced the morbidity and mortality of SCD. Yet, immune-related effects such as FNHTRs and alloimmunisation to HLAs,   and nonimmune-related effects e.g., iron overload and transfusion-transmitted infections are serious adverse effects of the transfusion therapy that need to be attended to in SCD patients receiving transfusion (Johnson et al., 2007). Chronic transfusions could result in an inexorable accumulation of tissue iron that could become fatal if not treated (Cohen, 1987). Excess iron damages the liver, endocrine organs, and heart and may be fatal by adolescence (Engle, 1964). 5. Critical review of thalassemias : (i) Molecular pathogenesis The large number of inherited haemoglobin disorders known today include (a) those related to anomalies in the haemoglobin structure e.g., sickle cell disease, and (b) the thalassemias whose hallmark is globin-chain deficiency of one or other of the globin chains of adult haemoglobin in erythroid cells. ÃŽ ²-Thalassaemias These are a set of genetic disorders inherited as simple codominant traits affecting haemoglobin synthesis. Depending on the haemoglobin chain affected, 2 types of thalassemia are recognised: ÃŽ ±-thalassaemia and ÃŽ ²-thalassaemia. Homozygous ÃŽ ²-thalassaemia is marked by a quantitative deficiency of the ÃŽ ²-globin chains in the erythroid cells. A complete absence of the ÃŽ ²-globin chains occurs in homozygous ÃŽ ²o-thalassaemia whereas in homozygous ÃŽ ²+-thalassaemia the ÃŽ ²-globin chains are present at less than 30% of normal. Accounting for nearly 90% of the cases, ÃŽ ²+-thalassaemia is the most commonly observed form of ÃŽ ²-thalassaemia. The condition is termed thalassaemia major when there is microcytic hypochromic anaemia with severe haemolysis, hepatosplenomegaly, skeletal deformities and iron overload. ÃŽ ²-thalassaemia homozygotes exhibit severe transfusion-dependent anaemia in the very first year of life. Homozygotic individuals having a relatively benign clinical phe notype and surviving with or without transfusion are described as thalassaemia intermedia (Weatherall, 1969). The thalassaemias, thus, encompass a wide gamut of clinical disability from intrauterine death to a mild anaemia with no overt symptoms (Weatherall, 1997b). The coexistence of   ÃŽ ± -thalassaemia leading to reduction in the synthesis of ÃŽ ±-globin chains, and a genetic predisposition to produce high levels of HbF, could be important factors for the extensive p Causes, Symptoms and Treatments of Anaemia Causes, Symptoms and Treatments of Anaemia 1. Introduction Anaemia is a syndrome characterised by a lack of healthy red blood cells or haemoglobin deficiency in the red blood cells, resulting in inadequate oxygen supply to the tissues. The condition can be temporary, long-term or chronic, and of mild to severe intensity. There are many forms and causes of anaemia. Normal blood consists of three types of blood cells: white blood cells (leucocytes), platelets and red blood cells (erythrocytes). The first generation of erythrocyte precursors in the developing foetus are produced in the yolk sac. They are carried to the developing liver by the blood where they form mature red blood cells that are required to meet the metabolic needs of the foetus. Until the 18th week of gestation, erythrocytes are produced only by liver after which the production shifts to the spleen and the bone marrow. The life of a red blood cell is about 127 days or 4 months (Shemin and Rittenberg, 1946; Kohgo et al., 2008). The main causes of anaemia are blood loss, product ion of too few red blood cells by the bone marrow or a rapid destruction of cells.   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Haemoglobin, a protein, present in the red blood cells is involved in the transport of oxygen from the lungs to all the other organs and tissues of the body. Iron is an important constituent of the haemoglobin protein structure which is intimately involved in the transport of oxygen. Anaemia is generally defined as a lower than normal haemoglobin concentration. The normal blood haemoglobin concentration is dependent on age and sex, and, according to the World Health Organisation (WHO) Expert Committee Report, anaemia results when the blood concentration of haemoglobin falls below 130 g/L in men or 120 g/L in non-pregnant women (WHO, 1968). However, the reference range of haemoglobin concentration in blood could vary depending on the ethnicity, age, sex, environmental conditions and food habits of the population analysed. According to Beutler and Warren (2006), more reasonable benchmarks for anaemia are 137 g/L for white men aged between 20 and 60 years and 132 g/L for older men. The value for women of all ages would be 122 g/L. Also, the lower limit of normal of haemoglobin concentrations of African Americans are appreciably lower than that of Caucasians (Beutler and Warren, 2006).   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Besides the well recognised iron deficiency anaemia, several inherited anaemias are also known. These are mostly haemoglobinopathies. Adult haemoglobin is a tetrameric haeme-protein. Abnormalities of beta-chain or alpha-chain produce the various medically significant haemoglobinopathies. The variations in amino acid composition induced genetically impart marked differences in the oxygen carrying properties of haemoglobin. Mutations in the haemoglobin genes cause disorders that are qualitative abnormalities in the synthesis of haemoglobin (e.g., sickle cell disease) and some that are quantitative abnormalities that pertain to the rate of haemoglobin synthesis (e.g., the thalassemias) (Weatherall., 1969). In SCD, the missense mutation in the ÃŽ ²-globin gene causes the disorder. The mutation causing sickle cell anemia is a single nucleotide substitution (A to T) in the codon for amino acid 6. The substitution converts a glutamic acid codon (GAG) to a valine codon (GTG). The form of haemoglobin in persons with sickle cell anemia is referred to as HbS. Also, the valine for glutamic acid replacement causes the haemoglobin tetramers to aggregate into arrays upon deoxygenation in the tissues. This aggregation leads to deformation of the red blood cell making it relatively inflexible and restrict its movement in the capillary beds. Repeated cycles of oxygenation and deoxygenation lead to irreversible sickling and clogging of the fine capillaries. Incessant clogging of the capillary beds damages the kidneys, heart and lungs while the constant destruction of the sickled red blood cells triggers chronic anaemia and episodes of hyperbilirubinaemia.   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Fanconi anaemia (FA) is an autosomal recessive condition, and the most common type of inherited bone marrow failure syndrome. The clinical features of FA are haematological with aplastic anaemia, myelodysplastic syndrome (MDS), and acute myeloid leukaemia (AML) being increasingly present in homozygotes (Tischkowitz and Hodgson, 2003). Cooleys anaemia is yet another disorder caused by a defect in haemoglobin synthesis.   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Autoimmune haemolytic anaemia is a syndrome in which individuals produce antibodies directed against one of their own erythrocyte membrane antigens. The condition results in diminished haemoglobin concentrations on account of shortened red blood cell lifespan (Sokol et al., 1992).   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Megaloblastic anaemia is a blood disorder in which anaemia occurs with erythrocytes which are larger in size than normal. The disorder is usually associated with a deficiency of vitamin B12 or folic acid . It can also be caused by alcohol abuse, drugs that impact DNA such as anti-cancer drugs, leukaemia, and certain inherited disorders among others (Dugdale, 2008).   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Malaria causes increased deformability of vivax-infected red blood cells (Anstey et al., 2009). Malarial anaemia occurs due to lysis of parasite-infected and non-parasitised erythroblasts as also by the effect of parasite products on erythropoiesis (Ru et al., 2009).   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Large amounts of iron are needed for haemoglobin synthesis by erythroblasts in the bone marrow. Transferrin receptor 1 (TfR1) expressed highly in erythroblasts plays an important role in extracellular iron uptake (Kohgo et al., 2008). Inside the erythroblasts, iron transported into the mitochondria gets incorporated into the haeme ring in a multistep pathway. Genetic abnormalities in this pathway cause the phenotype of ringed sideroblastic anemias (Fleming, 2002). The sideroblastic anemias are a heterogeneous group of acquired and inherited bone marrow disorders, characterised by mitochondrial iron overload in developing red blood cells. These conditions are diagnosed by the presence of pathologic iron deposits in erythroblast mitochondria (Bottomley, 2006).    2. Classification of anaemia Anaemia can be generally classified based on the morphology of the red blood cells, the pathogenic spectra or clinical presentation (Chulilla et al., 2009). The morphological classification is based on mean corpuscular volume (MCV) and comprises of microcytic, macrocytic and normocytic anaemia.   Ã‚  Ã‚  Ã‚  Ã‚  (a) Microcytic anaemia refers to the presence of RBCs smaller than normal volume, the reduced MCV ( 15 would probably indicate IDA (Chulilla et al., 2009).   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  In macrocytic anaemia, erythrocytes are larger (MCV > 98 fL) than their normal volume (MCV = 82-98 fL). Vitamin B12 deficiency leads to delayed DNA synthesis in rapidly growing hematopoietic cells, and can result in macrocytic anemia. Drugs that interfere with nucleic acid metabolism, such as.hydroxyurea increases MCV (> 110 fL) while alcohol induces a moderate macrocytosis (100-110 fL). In the initial stage, most anaemias are normocytic. The causes of normocytic anaemia are nutritional deficiency, renal failure and haemolytic anemia (Tefferi, 2003). The most common normocytic anaemia in adults is anaemia of chronic disease (ACD) (Krantz, 1994). Common childhood normocytic anaemias are, besides iron deficiency anaemia, those due to acute bleeding, sickle cell anemia, red blood cell membrane disorders and current or recent infections especially in the very young (Bessman et al., 1983). Homozygous sickle cell disease is the most common cause of h aemolytic normocytic anemias in children (Weatherall DJ, 1997a).   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  In practice, the morphological classification is quicker and therefore, more useful as a diagnostic tool. Besides, MCV is also closely linked to mean corpuscular haemoglobin (MCH), which denotes mean haemoglobin per erythrocyte expressed in picograms (Chulilla et al., 2009). Thus, MCV and MCH decrease simultaneously in microcytic, hypochromic anemia and increase together in macrocytic, hyperchromic anemia.   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Pathogenic classification of anaemia is based on the production pattern of RBC: whether anaemia is due to inadequate production or loss of erythrocytes caused by bleeding or haemolysis. This approach is useful in those cases where MCV is normal. Pathogenic classification is also essential for proper recognition of the mechanisms involved in the genesis of anaemia. Based on the pathogenic mechanisms, anaemia is further divided into two types namely, (i) hypo-regenerative in which the bone marrow production of erythrocytes is decreased because of impaired function, decreased number of precursor cells, reduced bone marrow infiltration, or lack of nutrients; and (ii) regenerative: when bone marrow upregulates the production of erythrocytes in response to the low erythrocyte mass (Chulilla et al., 2009). This is typified by increased generation of erythropoietin in response to lowered haemoglobin concentration, and also reflects a loss of erythrocyt es, due to bleeding or haemolysis. The reticulocyte count is typically higher.   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Sickle cell disease is characterised by sickled red cells.   The first report of SCD was published a century ago noting the presence of peculiar elongated cells in blood by James Herrick, an American physician (1910). Pauling et al. (1949) described it as a molecular disease. The molecular nature of sickle haemoglobin (Hb S) in which valine is substituted for glutamic acid at the sixth amino acid position in the beta globin gene reduces the solubility of Hb, causing red cells to sickle (Fig. 1). Sickling of cells occurs at first reversibly, then finally as a state of permanent distortion, when cells containing HbS and inadequate amounts of other haemoglobins including foetal haemoglobin, which retards sickling, become deoxygenated (Bunn, 1997). The abnormal red cells break down, leading to anaemia, and clog blood vessels with aggregates, leading to recurrent episodes of severe pain and multiorgan ischaemic damage (Creary et al., 2007). The high levels of inflammatory cytokines in SCD may promote retention of iron by macrophage/reticuloendothelial cells and/or renal cells. SCD care commonly depends on transfusion that results in iron overload (Walter et al., 2009). 3. Pathogenesis of anaemia Anaemia is a symptom , or a syndrome, and not a disease (Chulilla et al., 2009). Several types of anaemia have been recognised, the pathogenesis of each being unique. Iron deficiency anaemia (IDA) is the most common type of anaemia due to nutritional causes encountered worldwide (Killip et al., 2008). Iron is one of the essential micronutrients required for normal erythropoietic function While the causes of iron deficiency vary significantly depending on chronological age and gender, IDA can reduce work capacity in adults (Haas Brownlie, 2001) and affect motor and mental development in children (Halterman et al., 2001). The metabolism of iron is uniquely controlled by absorption rather than excretion (Siah et al., 2006). Iron absorption typically occurring in the duodenum accounts for only 5 to 10 per cent of the amount ingested in homoeostatis. The value decreases further under conditions of iron overload, and increases up to fivefold under conditions of iron depletion (Killip et al., 2008). Iron is ingested as haem iron (10%) present in meat, and as non-haem ionic form iron (90%) found in plant and dairy products. In the absence of a regulated excretion of iron through the liver or kidneys, the only way iron is lost from the body is through bleeding and sloughing of cells. Thus, men and non-menstruating women lose about 1 mg of iron per day while menstruating women could normally lose up to 1.025 mg of iron per day (Killip et al., 2008). The requirements for erythropoiesis   which are typically 20-30 mg/day   are dependent on the internal turnover of iron (Munoz et al., 2009) For example, the amount of iron required for daily production of 300 billion RBCs (20-30 mg) is provided mostly by recycling iron by macrophages (Andrews, 1999).   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Iron deficiency occurs when the metabolic demand for iron exceeds the amount available for absorption through consumption. Deficiency of nutritional intake of iron is important, while abnormal iron absorption due to hereditary or acquired iron-refractory iron deficiency anemia (IRIDA) is another important cause of unexplained iron deficiency. However, IDA is commonly attributed to blood loss e.g., physiological losses in women of reproductive age. It might also represent occult bleeding from the gastrointestinal (GI) tract generally indicative of malignancy (Hershko and Skikne, 2009).   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Iron absorption and loss play an important role in the pathogenesis and management of IDA. Human iron disorders are necessarily disorders of iron balance or iron distribution. Iron homeostasis involves accurate control of intestinal iron absorption, efficient utilisation of iron for erythropoiesis, proper recycling of iron from senescent erythrocytes, and regulated storage of iron by hepatocytes and macrophages (Andrews, 2008). Iron deficiency is largely acquired, resulting from blood loss (e.g., from intestinal parasitosis), from inadequate dietary iron intake, or both. Infections, for example, with H pylori, can lead to profound iron deficiency anemia without significant bleeding. Genetic defects can cause iron deficiency anaemia. Mutations in the genes encoding DMT1 (SLC11A2) and glutaredoxin 5 (GLRX5) lead to autosomal recessive hypochromic, microcytic anaemia (Mims et al., 2005). Transferrin is a protein that keeps iron nonreactive in the circulation, and delivers iron to cells possessing specific transferrin receptors such as TFR1 which is found in largest amounts on erythroid precursors. Mutations in the TF gene leading to deficiency of serum transferrin causes disruption in the transfer of iron to erythroid precursors thereby producing an enormous increase in intestinal iron absorption and consequent tissue iron deposition (Beutler et al., 2000). Quigley et al. (2004) found a haem exporter, FLVCR, which appears to be necessary for normal erythroid development. Inactivation of FLVCR gene after birth in mice led to severe macrocytic anaemia, indicating haem export to be important for normal erythropoiesis.   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  The anaemia of chronic disease (ACD) found in patients with chronic infectious, inflammatory, and neoplastic disorders is the second most frequently encountered anaemia after iron-deficiency anaemia. It is most often a normochromic, normocytic anaemia that is primarily caused by an inadequate production of red cells, with low reticulocyte production (Krantz, 1994). The pathogenesis of ACD is unequivocally linked to increased production of the cytokines including tumour necrosis factor, interleukin-1, and the interferons that mediate the immune or inflammatory response. The various processes leading to the development of ACD such as reduced life span of red cells, diminished erythropoietin effect on anaemia, insufficient erythroid colony formation in response to erythropoietin, and impaired bioavailability of reticuloendothelial iron stores appear to be caused by inflammatory cytokines (Means, 1996;2003). Although iron metabolism is characterist ically impaired in ACD, it may not play a key role in the pathogenesis of ACD (Spivak, 2002). Neither is the lack of available iron central to the pathogenesis of the syndrome, according to Spivak (2002), who found reduced iron absorption and decreased erythroblast transferrin-receptor expression to be the result of impaired erythropoietin production and inhibition of its activity by cytokines. However, reduced erythropoietin activity, mostly from reduced production, plays a pivotal role in the pathogenesis of ACD observed in systemic autoimmune diseases (Bertero and Caligaris-Cappio, 1997). Indeed, iron metabolism as well as nitric oxide (NO), which contributes to the regulation of iron cellular metabolism are involved in the pathogenesis of ACD in systemic autoimmune disorders. Inflammatory mediators, particularly the cytokines, are important factors involved in the pathogenesis of the anaemia of chronic disease, as seen in rheumatoid arthritis anaemia (Baer et al., 1990), the cyt okines causing impairment of erythroid progenitor growth and haemoglobin production in developing erythrocytes.     Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Anaemia is also commonly found in cases of congestive heart failure (CHF), again caused by excessive cytokine production leading to reduced erythropoietin secretion, interference with erythropoietin activity in the bone marrow and reduced iron supply to the bone marrow (Silverberg et al., 2004). However, in the presence of chronic kidney insufficiency, abnormal erythropoietin production in the kidney plays a role in the pathogenesis of anaemia in CHF.   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  The myelodysplastic syndromes (MDS) are common haematological malignancies affecting mostly the elderly as age-related telomere shortening enhances genomic instability (Rosenfeld and List, 2000). Radiation, smoking and exposure to toxic compounds e.g., pesticides, organic chemicals and heavy metals, are factors promoting the onset of MDS via damage caused to progenitor cells, and, thereby, inducing immune suppression of progenitor cell growth and maturation. TNF- and other pro-apoptotic cytokines could play a central role in the impaired haematopoiesis of MDS (Rosenfeld and List, 2000). Premature intramedullary cell death brought about by excessive apoptosis is another important pathogenetic mechanism in MDS (Aul et al., 1998).     Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Sickle cell disease (SCD) arising from a point mutation in the ÃŽ ²-globin gene and leading to the expression of haemoglobin S (HbS) is the most common monogenetic disorder worldwide. Chronic intravascular haemolysis and anaemia are some important characteristics of SCD. Intravascular haemolysis causes endothelial dysfunction marked by reduced nitric oxide (NO) bioavailability and NO resistance, leading to acute vasoconstriction and, subsequently, pulmonary hypertension (Gladwin and Kato, 2005).    However, a feature that differentiates SCD from other chronic haemolytic syndromes is the persistent and intense inflammatory condition present in SCD. The primary pathogenetic event in SCD is the intracellular polymerisation or gelation of deoxygenated HbS leading to rigidity in erythrocytes (Wun, 2001). The deformation of erythrocytes containing HbS is dependent on the concentration of haemoglobin in the deoxy conformation (Rodgers et al., 1985). It has been demonstrated that sickle monocytes are activated which, in turn, activate endothelial cells and cause vascular inflammation. The vaso-occlusive processes in SCD involve inflammatory and adhesion molecules such as the cell adhesion molecules (CAM family), which play a role in the firm adhesion of reticulocytes and leukocytes to endothelial cells, and the selectins, which play a role in leukocyte and platelet rolling on the vascular wall (Connes et al., 2008). Thus, inflammation, leucocyte adhesion to vascular endothelium, and subsequent endothelial injury are other crucial factors contributing to the pathogenesis of SCD (Jison et al., 2004). 4. Current therapies for clinical management of sickle cell diseaseincludingacritical appraisal of transfusion Between 1973 and 2003, the average life expectancy of a patient with SCD increased dramatically from a mere 14 years to 50 years thanks to the development of comprehensive care models and painstaking research efforts in both basic sciences especially molecular and genetic studies, and clinical aspects of SCD (Claster and Vichinsky, 2003). The clinical manifestations of SCD are highly variable. Both the phenotypic expression and intensity of the syndrome are vastly different among patients and also vary longitudinally within the same patient (Ballas, 1998). New pathophysiological insights available have enabled treatments to be developed for the recognised haematologic and nonhaematologic abnormalities in SCD (Claster and Vichinsky, 2003). The main goals of SCD treatment are symptom alleviation, crises avoidance and effective management of disease complications. The strategy adopted is primarily palliative in nature, and consists of supportive, symptomatic and preventative approaches to therapy. Symptomatic management includes pain mitigation, management of vasoocclusive crisis, improving chronic haemolytic anaemia, treatment of organ failure associated with the disease, and detection and treatment of pulmonary hypertension (Distenfeld and Woermann, 2009). The preventative strategies include use of prophylactic antibiotics (e.g., penicillin) in children, prophylactic blood transfusion for prevention of stroke in patients especially young children who are at a very high risk of stroke, and treatment with hydroxyurea of patients experiencing frequent acute painful episodes (Ballas, 2002). Currently, curative therapy for sickle cell anaemia is only available through bone marrow and stem cell transplantation. Hematopoietic cell transplantation using stem cells from a matched sibling donor has yielded excellent results in paediatric patients (Krishnamurti, 2007). Curative gene therapy is still at the exploratory stage (Ballas, 2002). Current and potential therapies The potential treatment strategies basically target cellular dehydration, sickle haemoglobin concentrations, endothelial dysfunction, and abnormal coagulation regulation (Claster and Vichinsky, 2003). HbS concentrations are essentially tackled through transfusions while approaches to reduce HbS polymerisation which is the main mechanism for the development of vaso-occlusion include (a) increasing foetal haemoglobin (HbF) concentration using hydroxyurea (Fig. 2), butyrate, or erythropoietin, and (b) preventing sickle cell dehydration using Clotrimazole (Fig. 3) or Mg2+pidolate. Hydroxyurea therapy increases the production of HbF in patients with sickle cell anaemia, and, thereby, inhibits the polymerisation of HbS and alleviates both the haemolytic and vaso-occlusive manifestations of the disease (Goldberg et al., 1990). Recombinant erythropoietin also increases the number of reticulocytes with HbF. Additionally, it has been observed that administration of intravenous recombinant eryt hropoietin with iron supplementation alternating with hydroxyurea enhances HbF levels more than hydroxyurea alone (Rodgers et al., 1993). As SCD is essentially characterized by an abnormal state of endothelial cell activation   that is, a state of inflammation, a pharmacologic approach to inhibit endothelial cell activation has proved clinically beneficial (Hebbel and Vercellotti, 1997). Thus, administration of sulfasalazine which is a powerful inhibitor of activation of nuclear factor (NF)-B, the transcription factor promoting expression of genes for a number of pro-adhesive and procoagulant molecules on endothelium to humans has been found to provide transcriptional regulation of SCD at the endothelium level (Solovey et al., 2001). Red blood cell transfusion : a critical appraisal A key therapy that is applied regularly in the clinical management of patients with SCD is packed red blood cell transfusion. RBC transfusion improves the oxygen-carrying capacity which is achieved by enhancing the haemoglobin levels, causes dilution of HbS concentration thereby, reducing blood viscosity and boosting oxygen saturation. Furthermore, RBC transfusion is helpful in suppressing endogenous production of sickle RBCs by augmenting tissue oxygenation ( Josephson et al., 2007). There are two major types of RBC transfusion therapy: intermittent and chronic which are further classified as prophylactic or therapeutic. Intermittent transfusions are generally therapeutic in nature and administered to control acute manifestations of SCD whereas chronic transfusions are performed as general preventative measures to check complications of SCD. RBC transfusion given as a single dose is termed as simple transfusion. Exchange transfusion involves administration of a larger volume of RBCs replacing the patients RBCs that are simultaneously removed. Details of the various types of RBC transfusion and the major clinical indications for the same in SCD patients are listed in Table 1.   Ã‚  Ã‚  Ã‚  Ã‚  SCD (Source: Josephson et al., 2007) Indications for Intermittent transfusions Indications for intermittent transfusions include acute manifestations of SCD, as indicated in Table 1, that require redressal through therapeutic transfusions. However, under certain circumstances intermittent transfusions could be prophylactic such as for instance, when SCD patients are transfused before specific surgeries viz., those related to pregnancy complications or renal failure (Table 1).   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Acute Chest Syndrome (ACS) describes a manifestation of SCD in which, due to sickling, infectious and noninfectious pulmonary events are complicated, resulting in a more severe clinical course. The diagnosis is the presence of a new infiltrate on chest radiography that is accompanied by acute respiratory symptoms. ACD accounts for nearly 25% of all deaths from SCD (Vichinsky, 2002). Repeated episodes of ACS are associated with an increased risk of chronic lung disease and pulmonary hypertension (Castro, 1996). The severe pulmonary events occurring in SCD may be precipitated by any trigger of hypoxia (Vichinsky, 2002). Transfusions are very efficacious and provide immediate benefit by reversing hypoxia in ACS. Transfusion of leucocyte-poor packed red cells matched for Rh, C, E, and Kell antigens can curtail antibody formation to below 1% (Vichinsky, 2002). Simple transfusions suffice for less severe cases; however, exchange transfusion is recomm ended to minimise the risk of increased viscosity. Also, chronic transfusion appears promising for prevention of recurrence in selected patients (Styles and Vichinsky, 1994). In a multicentre ACS trial, prophylactic transfusion was found to almost completely eliminate the risk of pulmonary complications (Vichinsky, 2002).   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Acute Symptomatic Anaemia arises in SCD as a result of blood loss, increased RBC destruction, suppression of erythropoiesis etc. and is effectively treated with intermittent transfusion of RBCs to relieve symptoms of cardiac and respiratory distress (Josephson et al., 2007).   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Aplastic Anaemia is commonly caused in SCD on account of infection of haematopoietic precursors in the bone marrow by Parvovirus B19 leading to a steep fall in RBCs. According to Josephson et al. (2007), therapeutic intermittent transfusion of RBCs is again the recommended first-line of treatment to improve total haemoglobin count and prevent cardiac decompensation. However, in those patients who are prone to fluid overload on account of cardiac or renal dysfunction an alternative transfusion strategy is to remove the whole blood and replace it with packed cells while avoiding the addition of excess volume (Josephson et al., 2007).   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Acute Stroke is a high risk especially in paediatric SCD cases because of elevated cerebral flow. Enormous decline in stroke rate have occurred in children receiving intermittent simple transfusion (Adams et al., 1998). However, the identification of the stroke type would be necessary in all SCD patients in order to determine the appropriate treatment approach since the occurrence of infarctive strokes is higher in children as opposed to a higher incidence of haemorrhagic strokes in adults (Adams, 2003). Indications for Chronic Transfusions Prophylactic chronic RBC transfusion every 3 to 4 weeks to maintain HbS levels lower than 30% is crucial for preventing first as well as recurrent strokes in children (Johnson et al., 2007). The transfusions could either be chronic simple transfusion or prophylactic chronic RBC exchange transfusion. Prophylactic chronic transfusions are recommended for patients with chronic renal failure so as to avoid severe symptomatic anaemia and for those patients with SCD undergoing pregnancy with complications. However, prophylactic transfusion is not indicated for SCD patients with normal pregnancy (Tuck et al., 1987). Controversial and indeterminate indications for intermittent or chronic transfusion According to Hankins et al. (2005), chronic transfusion therapy is helpful in reducing the incidence of strokes in children but not the severity of strokes. In the case of acute priapism, improvement in patients has been observed after exchange or simple transfusion (Rifikind   et al., 1979). Yet, due to the ASPEN syndrome, transfusion currently is only a second-line therapy in the management of priapism ( Miller et al., 1995).   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  RBC transfusion is a vital component in the management of symptoms and complications of SCD. It has drastically reduced the morbidity and mortality of SCD. Yet, immune-related effects such as FNHTRs and alloimmunisation to HLAs,   and nonimmune-related effects e.g., iron overload and transfusion-transmitted infections are serious adverse effects of the transfusion therapy that need to be attended to in SCD patients receiving transfusion (Johnson et al., 2007). Chronic transfusions could result in an inexorable accumulation of tissue iron that could become fatal if not treated (Cohen, 1987). Excess iron damages the liver, endocrine organs, and heart and may be fatal by adolescence (Engle, 1964). 5. Critical review of thalassemias : (i) Molecular pathogenesis The large number of inherited haemoglobin disorders known today include (a) those related to anomalies in the haemoglobin structure e.g., sickle cell disease, and (b) the thalassemias whose hallmark is globin-chain deficiency of one or other of the globin chains of adult haemoglobin in erythroid cells. ÃŽ ²-Thalassaemias These are a set of genetic disorders inherited as simple codominant traits affecting haemoglobin synthesis. Depending on the haemoglobin chain affected, 2 types of thalassemia are recognised: ÃŽ ±-thalassaemia and ÃŽ ²-thalassaemia. Homozygous ÃŽ ²-thalassaemia is marked by a quantitative deficiency of the ÃŽ ²-globin chains in the erythroid cells. A complete absence of the ÃŽ ²-globin chains occurs in homozygous ÃŽ ²o-thalassaemia whereas in homozygous ÃŽ ²+-thalassaemia the ÃŽ ²-globin chains are present at less than 30% of normal. Accounting for nearly 90% of the cases, ÃŽ ²+-thalassaemia is the most commonly observed form of ÃŽ ²-thalassaemia. The condition is termed thalassaemia major when there is microcytic hypochromic anaemia with severe haemolysis, hepatosplenomegaly, skeletal deformities and iron overload. ÃŽ ²-thalassaemia homozygotes exhibit severe transfusion-dependent anaemia in the very first year of life. Homozygotic individuals having a relatively benign clinical phe notype and surviving with or without transfusion are described as thalassaemia intermedia (Weatherall, 1969). The thalassaemias, thus, encompass a wide gamut of clinical disability from intrauterine death to a mild anaemia with no overt symptoms (Weatherall, 1997b). The coexistence of   ÃŽ ± -thalassaemia leading to reduction in the synthesis of ÃŽ ±-globin chains, and a genetic predisposition to produce high levels of HbF, could be important factors for the extensive p