Melbourne 2am lockout Case Study Example | Topics and Well Written Essays - 3000 words

Melbourne 2am lockout - Case Study Example Heavy penalties in form of fines were equally designed and implemented where licensees were highly discouraged from breaching the lockout initiative. The failure of the initiative as experienced resulted from various factors, which led to great opposition such as some exceptions that were applied where among the 457 premises that were initial targets of the policy, 115 of them received exception to the policy. Issues The issues raised in the 2am lockout in Melbourne are numerous and spans around supporting as well as discouraging the policy. According to the political as well as the media view, late night violence within the Australian cities was wholly to blame on alcohol (Wilson, 2013, para 1-2). There was therefore the need to introduce a policy, which addressed the increase in violence and such related anti-social behavior as was blamed on use of alcohol within the late night hours. There were many arguments raised in support of the policy which ideally supported curtailing patro ns and licensees to access their premises within the stipulated time and which prohibited those who were within the respective venues to leave within the stipulated time. ... of people hoping from one venue to another after they are kicked out of the venue for such reasons as misbehaviors increased the rate of crime and violence within the country and hence the support of the policy. The reason on the need to curtail and prevent venue hopping was instructed by the fact that many of the related violence occur within the streets and not within the venues as would be expected. The timing of the proposed lockout was informed by the fact that this time represented the key time where the police involvement in curbing violence was on prime and hence the need to have the street movement of persons reduced for effectiveness. The reduction of street movement would be effective in allowing the police manage people and the occurrence of such crimes within the street as against the management of people within night venues. Moreover, the time between 2am and 7am was ample to allow police clear the streets of such drunkards or any resultant mess as well as allow the dru nkards sober up (Melbournepubs.com, 2008, para 5). On the other hand, there were numerous cases raised against the imposition of such a policy, which included the un-fateful punishing of law-abiding majority of the persons as of the irresponsible actions of just a minority segment of persons within the society. The policy framework brought with it curtailing of freedom of choice to the general population besides reducing civil liberties to be enjoyed. The imposition of the ban changed the city from what was so wonderful about it (which served to attract many people into the 24-hour economy city) and the choice of only one venue for a night would never be satisfying to the majority. Imposition of the same reduced the time for persons serving within the hospitality industry to hang out after

Human Resources Essay Example | Topics and Well Written Essays - 750 words - 5

Human Resources - Essay Example An HRD professional assumes the duty of the staff trainer or instructional designer. HRD professionals maintain the organization’s reward system to guarantee fair and equitable pay rates. Administer and design the companys reimbursement program, as well as pensions and health insurance. They report any gaps between outputs and expectations and assess workers performance. They conduct training programs, which improve employees skills and enhance their abilities to function as a group. Finally, HRD professionals evaluate training schemes and propose future options for frequent learning. They serve an extremely crucial role in the development of an organization. Their philosophy is that they need to possess numerous skills, as well as competencies, which will assist them to bring success in the organization they work in. They consider their roles to be more crucial than the actual owners of the organization who, therefore, assume the role of a leader. What I learnt about the HRD field, while conducting this interview, was that the field in extremely critical in determining the success of an organization. This is because people who function in this field are the ones responsible for creating the powerful workforce that will bring success to the company. As a child, my father crafted me in to being a leader. I was amazed of how he handled matters as the head of the family with ease. Therefore, I grew up also hoping to play a critical role in bring success to this world. Through jobs, people are able to be successful; hence, no other field would have suit me better than the HR field. This is a place where a person could shape others to becoming successful people in this world. My strengths as a HR professional are that I work diligently. It is always in me to see a task completed successfully, and after that I find myself coming up with a new task. I also opt to listen to other people’s opinions

Gastronomy And Food Within The Tourism Industry Tourism Essay

Gastronomy And Food Within The Tourism Industry Tourism Essay Over the time, the term of gastronomy was defined in many ways and it is constantly changing. There is wide range of definitions but it was initially used to describe sophisticated dishes prepared for the upper class. As Hjalager Richards (2002) show, a different version of the original definition of gastronomy in the early year, the concept is defined as a process of excellence which involve a reflecting eating, cooking and preparation as well as the general presentation and production. As it is generally agreed food is a vital component of our daily life. But as a tourism product, gastronomy is a distinctive experience which involves food and wine tasting of local food and wine productions (Buhalis and Costa, 2006). A tourist has to eat and somewhat participate in local food experiences; therefore, gastronomy has always been part of a tourist experience. In the recent years, the identification of tourism gastronomy has changed in term of the integration within the tourism industry and as a valued asset. Although, that tourists do not always take part of experiencing local food production due to a lack of interest which lay certain limit on tourism gastronomy experience, its represent a real benefit for some destinations. Tourism gastronomy still a new field of research but as a growing development product, it has opened a new special interest products such as wines routes, food fairs and short breaks. The main keys finding of researches on tourism gastronomy were encompassed in two English literature books, that is Tourism and gastronomy by Hjalager A.M. Richards G. (2002) and Food Tourism Around the world, Development, Management and Markets by Hall M.C. et al (2003). The perspective of food in tourism industry is widely disputed but mostly agreed that tourism product specialised on food experiences ameliorate the possibility of enhancing the destination marketing opportunities, the economic relation between agricultural production and tourism as well as traditional activities (Buhalis and Costa, 2006 Roberts and Hall, 2001). Moreover, studies have demonstrated that the gastronomy is the core of tourist experience and a source of identity for most of the post-industrial societies (Roberts Hall, 2001). Van Westering (1999) describes gastronomy has the key of many features of tourism experience and part of the culture which influence other aspects of culture. Furthermore, gastronomy plays a big role in tourism industry as well as cultural development and sustainability of a tourism heritage. The relation between them is a key motivator which influence tourist to travel. Although, the perception of gastronomy is defined as an identity of culture by many authors (Hjalager Corigliano, 2000) and connected to the tourists who use holiday as a way to discover the insight of different cultures. Corriea et al add that gastronomy is not only the central part of culture but an important element of a traditional portfolio of cultural products such as architecture and monuments. Indeed, gastronomy is ranked on the most important attributes of a destination. Due to the implication of gastronomy in decision making of tourist destination, it has become the attention of the marketing of tourist des tination as well as tourism policies (Kivela Crotts 2006 and Du Rand Heath 2006).The gastronomy is part of the culture, heritage and history of a country and those aspects influence the tourist choice to choose is future destination. Hall (2003) shows, that the traditional source of revenue in occurrence agriculture is not sufficient enough whereas food production and tourism are progressively becoming a possible and sustainable source of economy in rural areas. Boyne Hall (2002) cited in Hall (2003) emphasis the contribution of local community in occurrence businesses which have an important role for the sustainability of the development of food tourism within those areas. Wood (2001) cited in Hall et al (2003) further insists on the role of the food tourism which will benefit economically as well as strengthening local identity and community pride. The WTO (2004) describes the sustainability as values which are connected to tourism development in term of economic, socio-cultural a nd environmental aspects. The regions which adopted gastronomy as culture identity often associated to regional culture are part of sustainable development of tourism destinations. Scarpato (2000) cited in Hjalager Richards (2002) shows that the sustainability of gastronomy is the importance of producing environmentally sensitive food and preparing it with excellence in order to nourish the mind and body. In the book Tourism and Gastronomy by Hjalager Richards (2002), tree cases was critically evaluates by Scarpato and she determines that gastronomy researches could provide great influence on communities policies in order to improve sustainable development. This new form of tourism experience has taken shape during the last decades and emerged with the globalisation of foods products, also known as Macdonaldisation (Hall, 2003). Hall (2003) emphasizes that in the post-modern time gastronomy has been affected by the globalisation in term of blurring the boundary of the cultural and notional identity. In fact, the external food imports influence the local level of gastronomy (traditional cuisine). But Urry (1992) states by defending the post-modernism in term of tourist behaviour than tourists are aware that tourism is a series of games with multiple texts and no single, authentic tourist experience. And tourists allow most of the heritage products to avoid vanishing. Controversy, Cohen and Avieli (2004) stat, that local cuisine should be filtered in accordance to the tourism-oriented culinary establishments in order to become a popular attraction. Moreover, new cultural products are created in tourism cuisine, indeed the local cuisine an d foreign dishes are transformed and adapted to the tourist taste by tourism. However, the sustainability of tourism or responsible tourism is neglected if such processes are undertaken in tourism gastronomy. The authenticity of the food experience should be endorsed by the participation of hotels and restaurants by procurement of locally grown product and produce while respecting the protection of the environment. The degree of integration of gastronomy within the tourism industry could be ameliorate and fully accepted as a tourism and cultural resource as gastronomy contribute already to the sustainability of tourism. The implication of tourism organisation, local communities and producers could take a different approach and all stakeholders should cooperate in order to improve the implantation of sustainable tourism. More research in food and gastronomy tourism will help in the future to identify tourist profiles for each destination or specific region in order to conduct more targeted offers. Annotated Bibliography Buhalis, D., Costa, C. (2006): Tourism business frontiers; consumers, products and industry, Oxford, Elsevier LTD Correia, A.,et al (2008), The determinants of gastronomic tourists satisfaction: a second-order factor analysis 19: 3, 164 176 This article helps to understand the degree of importance of tourist satisfaction and how it affects in a destination. Du Rand, G.E., Heath, E. (2006): Towards a framework for food tourism as an element of destination marketing. Current Issues in Tourism 9:206 34. Hall, C.M., et al. (2003): Food Tourism Around the world, Development, Management and Markets. United Kingdom, Butterworth Heinemann Hjalager, A., Richards, G. (2002), Tourism and gastronomy, London/NewYork, Routedge Kivela, J., Crotts, J.C. (2006): Tourism and gastronomy: gastronomys influence on how tourists experience a destination. Journal of Hospitality and Tourism Research 30:35477. Roberts, L., Hall, D. (2001): Rural tourism and recreation; principle to practice, Wallingford (UK), CABI Publishing Urry, J., (2002): The Tourist Gaze. 2nd Edition, London, Sage Van Westering, J., (1999): Heritage and gastronomy: The pursuits of the new tourist, International Journal of Heritage Studies, 5: 2, 75 81 This article help to understand the relation between gastronomy and heritage and the key motivator which will push the tourist to choose a destination. Xore, A., et al (2006): Tourism quality agro-food products: an opportunity for the Spanish countryside 97: 2, 166 176 This article help to understand the relation between tourism gastronomy and agricultural production and traditional production.

Gothic Art :: essays research papers

Romanesque may first be sensed in new structural developments.. Sophisticated but unsatisfactory attempts to vault the great basilican naves safely, with elements of Roman, Byzantine, or Eastern origin, impelled progressive Romanesque engineers, from about 1090 onward, to invent a new type of ribbed groin-vaulted unit bay, using pointed arches to distribute thrust and improve the shape of the geometric surfaces. Fifty years of experimentation produced vaulting that was light, strong, open, versatile, and applicable everywhere--in short, Gothic vaulting. A whole new aesthetic, with a new decorative system--the Gothic--was being evolved as early as 1145. The spatial forms of the new buildings sometimes caused acoustic difficulties, which may help to account for the concomitant development of the new polyphonic music that supplemented the traditional Romanesque plainsong. Romanesque architecture became old-fashioned, but its heavy forms pleased the Cistercian monks and, likewise, other conservative patrons in Germany, Poland, Hungary, Italy, Spain, and Portugal. Thus, buildings that were essentially Romanesque in spirit continued to be built, even when such extraordinary Gothic works as the Amiens cathedral were under construction (begun 1220). (see also Index: Gothic architecture, music, history of) The development of proto-Romanesque in the Ottonian period culminated in the true Romanesque style represented by five magnificent churches on the international pilgrimage routes leading from central France to the reputed tomb of St. James at Santiago de Compostela in Spain: Saint-Martin at Tours (a huge once wooden-roofed basilica that was rebuilt on the new model beginning about 1050), Sainte-Foy at Conques ( c. 1052-1130), Saint-Martial at Limoges (c. 1062-95), Saint-Sernin at Toulouse (1077 or 1082-1118), and the new cathedral at Santiago de Compostela itself (c. 1075-1211). This was a real family of buildings; each one had a splendid apse with ambulatory (a sheltered place to walk) and radiating chapels, a transept and nave with aisles and galleries, an

Introduction To Top Glove Corporation Berhad Essay

Top Glove Corporation was Started In 1991 In the Beginning Top Glove Company had just 1 Factory 3 Production lines and 100 Staff, but Now it Has Become the Most Successful and Largest Rubber Glove manufacture resulting in 25 factories which they had just 1 one when they started and now has 470 Production lines and a capacity to produce 41.1 Billion Gloves per Annum. Top Glove Corporation has more than 10 Branches Not In Malaysia but has also Spread In China and Thailand The Main Activities of Top Glove are Investment holdings and provision of Management services. Top Glove are one of the largest latex gloves, nitrile, surgical, household, Cleanroom,Vinyl and more types of glove Producer and meets High Quality Products and meets the Increasing expectations of the International Top Glove Corporation was Listed 2nd In Malaysian Bourse and within a year It was promoted to the Capital city of Malaysia Kuala Lumpur Stock Exchange (Bursa Saham) . It consists Shareholder fund worth 1.28Billion with an annual turnover which is almost 2.31Billion as at financial year ended 31 August 2012.Tan Sri Lim the Founder of Top Glove Achievements has A Huge Credit for Company’s Success Not Only Tan sri Lim But the Highly Committed and Motivation of Board of Directors Together with 11000 Strong Work Force. Customers are the Important Factor for Top Glove Company their motive is to Provide High Quality Products with affordable cost and To Provide them the best customer service. The Company is looking forward To Invest IN R&D IT and Automation to make sure to Improve The Quality and Production Efficiency. Looking At the Future Top Glove’s Objective is to Capture 30% of the Global Market share by 2015, (Top Glove, 2013) (EMIS, 2013) 1.1 TOP GLOVE CORPORATION VISION AND MISSION â€Å"We Strive to be the World’s Leading Manufacture with Excellent Quality Glove Products and Service enrich and Protect Human Lives† CORPORATE MISSION: â€Å"To Be World Class Glove Manufacturer by providing top Quality products with Excellent services through continuous Improvements and Innovation† (Top Glove, 2013) 1.2 KEY EXECUTIVES Wee Chai Lim Chairman Kim Meow LeeManaging Director Cheong Guan LimExecutive Director Siew Bee TongExecutive Director Arshad Bin AyubIndependent Non-Executive Director (Company) 1.3 CHAIRMAN LIM WEE CHAI PROFILE: (Top Glove Corporation Berhad, 2012) Lim Wee chai is a Malaysian citizen aged 54; He was graduated in Bachelor of Science degree in physics from University Malaya and completed his master degree in business administration Sul Ross State University in Texas, United States. Lim wee chai was appointed as a chairman at top glove corporation on 4th September 2000. Top glove Corporation Berhad was started with only 3 production lines under the Chairman lim wee chai Leadership and visions top glove have become world’s largest rubber glove producers and has captured 25% of the world market share. The company now has more than 23 factories and 457 production lines in Malaysia and on the other counties which are china and Thailand. The Production capacity is to produce 40 billion pieces of gloves per annum, over thousands of customer’s demand in more than 185 Countries. He has received 10 awards for his achievements success and contribution towards the Glove Industry (Top Glove Corporation Berhad, 2012) 2.0 INTRODUCTION TO HARTALEGA HOLDINGS BERHAD (Hartalega, 2013) Hartalega Berhad Manufacture and sell latex and Nitrile gloves.The company’s latex and Nitrile gloves consists of examination and Surgical, Laboratory, Clean room gloves, atomic power plant etc.It also deals in retail and wholesale of gloves, Property leasing research and development of automation systems. Hartalega was established in 1988 with the vision to produce gloves to protect the important thing which is Life, Hartalega Used to be  One line operation in the beginning but now it is one of the most largest Company with 53 Production lines, and a capability to produce 12 Billion gloves Per Year. Since the Start, Hartalega every single operation is been dedicated to Tradition of Excellence, they are delivering the best quality through state of the art equipment, high quality system and dedicated workers their products are high recognized all over the world Hartalega Success is Because of their loyal customers and Consistent improvements in quality of products, reliable service with efficiency by the culture of open and honest approach to business. Hartalega has Huge Market all over the world which are in North America, Europe, Asia, Australia Malaysia Hartalega is the company which has produced a lot types of products compare of it’s competitors and they are first one who has produced it which are Polymer Coated Powder-Free Examination Gloves, Low Protein Latex Examination Gloves, Robotic glove stripping system which helps to strip gloves off from the production lines, first one to produce high-stress relaxation NBR Examination and Surgical gloves, first industry to use oil Palm Empty fruit bunches as biomass fuel to produce heat for production process and Many More products which had produce 1st the Industry. Hartalega has earned a lot of Awards Because of their hard work, dedication and motivation. (Hartalega, 2013) (Businessweek, 2013) 2.1 BOARD OF DIRECTORS 1. Kuan Kam HonExecutive Chairman and Managing Director 2. Chuah Phaik SimIndependent Non-Executive Director 3. Dato Mohamed ZakIndependent Non-Executive Director 4. Kuan Mun KengNon-Independent Executive Director 5. Kuan Mun LeongNon-Independent Executive Director 6. Liew Ben PohNon-Independent Non-Executive Director (Haralega, 2012) (Hartalega Holding Berhad, 2012) 2.2 HARTALEGA CHAIRMAN PROFILE: (Hartalega Holding Berhad, 2012) Kuan Kam Hon aged 65, Is the Executive chairman and Managing Director at  Hartalega, he was appointed on May 7, 2007. Kuan Kam Hon is responsible for all business strategic plannings and whole operations in the group including research and development, He started his Career in the construction company named kuan Yuen & Sons Company which was a well-known construction company in 1970’s, in 1981 he formed Hartalega Sdn Bhd Under his leadership Hartalega has now become a reputable producers of latex gloves in the industry in Malaysia and is public listed in bursa Malaysia. He has created a set of Management with Higher standards and encourages creativity and innovation to produce highly-skilled personnel. (Hartalega Holding Berhad, 2012) 3.0 RUBBER GLOVE INDSUTRY ANALYSIS The rubber demand has been increased rapidly high after the H1N1 Pandemic in 2010. Rubber glove industry is going to witness Lower demand as there is no Huge Disease found in Humans, Plants or Animals since last year, Rubber Glove Industry totally depends on its usage on medical sector, Industry has been facing recession time to time. Malaysia is the largest Producer and exporter of Rubber gloves at present, Malaysian industry of rubber gloves has high Demand all over the world, Top Producers of Rubber gloves are, Top Glove, Supermax, Kossan rubber industry and Hartalega. Malaysian Industry exports to the US, Europe, Latin America, China and India, Us is the largest Importer of Rubber Gloves as their expenditure on Health Care has gone high as percentage of GDP Since 2000. UK and European Countries are following the same trend of using more hygienic products. And is expected for other countries as well Demand for Rubber gloves Have Increased in Countries like India, China and Brazil in the recent years as they are more concerned to their healthcare and wants to use hygienic Products, Demand for lower-end powdered latex gloves is high in developing countries who are more cost conscious which is cheaper than powder-free latex and nitrile gloves, The Developed countries such as US and Europe prefer to use Powder-free latex and Nitrile gloves. (Koncept Analysis, 2012) 4.0 FUTURE OUTLOOK OF RUBBER GLOVE INDUSTRIES 4.1 HIGH DEMAND OF GLOVES: Rubber Glove Industry will be having long term  demand for their products from the highly developed Countries. Emerging economies may possibly drive high future demand as their population is increasing, they are more aware of the importance of hygienic products in medical sectors as will be having high demand of High quality of Healthcare products and services. Health Care Expenditures is increasing for most developed Countries, which has increased demand for gloves, which may affect increase in cost but still can be manageable. Gas and Labor cost are expected to be increase In 2013, but no sure if that can make a huge impact of Glove market (lee, 2012) 4.2 STABLE MARKET SHARE, CAPACITY TO INCREASE: Top 4 Glove Producers may not become M &A Targets. Kossan Rubber industry may have a chance of being such a target if we pick among the four Largest Producers. The Rubber Glove Companies are increasing their production capacity to remain in the competition. Annual Capacity growth is expected to be about 18% or 14.2BN pieces in 2013 (lee, 2012) 4.3 RISKS INVOVLED IN RUBBER GLOVE INDUSTRIES: Rubber Glove Industries can face various kinds of risks which are as follows: 1. Competitors in this Industry have aggressively expended their capacity plans this can result in an oversupply 2. Sharp instability in latex costs and foreign currencies resulting in near term margin squeeze 3. Political Risk, domestic and regional, Glove manufactures source 50% of their raw material from Thailand. Risk is low production of NR latex and lower supply at glove manufacturers 4. Infrastructural bottle necks and Labor Shortages : Supply of Malaysia’s Natural Gas is reached its maximum point to the Glove industries and new allocations are expected to come, any delay in new allocation will become a huge problem for Glove Industries for that they have to use alternative fuel for production with higher cost (Michelle Foong, 2012) 5.0 FINANCIAL ANALYSIS 5.1 FINANCIAL ANALYSIS FOR TOP GLOVE CORPORATION BERHARD 5.3 PROFITABLITY: Profitability ratios shows that profit earning capacity of a business for the sake of clear understanding profitability ratios classified into two categories general profitability ratios and overall profitability ratios, The gross profit margin ratio (or gross margin ratio) provides clues to the company’s pricing, cost structure and production efficiency. A low profit margin ratio indicates that low amount of earnings, required to pay fixed costs and profits are generated from revenues. (Thukaram, 2007). Top Glove Corporation gross profit margin has been increased as compare with the profit ratio in 2011 and 2012, 2011 it was 11.44% in 2012 its 16.63 same goes for net profit margin, but with less expenses. Top glove Corporation profit earning capacity has been increased impressively Profitability 2012 2011 Gross profit margin Net profit Margin Expenses margin 16,63 – 9,87 = 6.76% 11,44 – 6,57 = 4.87% 5.4 LIQUIDITY: Liquidity ratios provides information on the time structure of debt and the firm’s ability to meet its short term obligation Current ratio is balance-sheet financial performance measure of company liquidity. Current ratio indicates a company’s ability to meet short-term debt obligations. The current ratio measures whether or not a firm has enough resources to pay its debts over the next 12 months. Quick ratio is viewed as a sign of a company’s financial strength or weakness; it gives information about a company’s short term liquidity. The ratio tells creditors how much of the company’s short term debt can be met by selling all the company’s liquid assets at very short notice. (Emilio Colombo, 2006).Liquidity ratios shows ability of the company to pay back its debts which top glove has improved  from 3.12:1 to 2.95:1 in 2012 LIQUIDITY 2012 2011 Current ratio Quick Ratio 5.5 EFFICIENCY: Efficiency ratios measure how efficiently a firm uses its resources. The average collection period shows the average number of days it takes your business to collect payment for sales to customers on credit, The accounts payable turnover ratio shows how quickly your business pays its bills and how often payables turn over during the year. Trends in the accounts payable turnover ratio demonstrates how your business handles its outgoing payments and can help you assess the cash situation of your business. This efficiency ratios shows that top glove fixed asset turnover has been increased from 2.9 in 2011 to 2.93% in 2012 debtors collection time has also slight more efficient compared to 2011 it was 47 days in 2012 it is 46 days meanwhile creditor payment is facing more delays compared to previous year which was 39days in 2011 turn into 44days in 2012 (Emilio Colombo, 2006) EFFICIENCY 2012 2011 Fixed asset turnover Debtors collection Creditor payment Stock Turnover 5.6 CAPITAL STRUCTURE: Capital Structure is a mix of a company’s long term debt, specific short-term debt, and common equity and preferred equity. The capital Structure is how a  firm finances its overall operations and growth by using different sources of funds. The interest coverage ratio indicates the extent of which earnings are available to meet interest payments. A interest cover ratio means less earnings are available to meet interest payments and that the business is more vulnerable to increases in interest rates. Capital Structure 2012 2011 Interest Cover Gearing ratio INVESTORS: Financial ratios are used to analyze company performance, Return of equities investors is much greater than that applied to debentures may be because this investment class have a huge risk, and ordinary shareholder are the best group of investors for an organizations. The Price earning ratio for an organization is used to compare the financial position of a company compare to other organizations, this means the better financial position of a company is according to PE Ratios the lower risks is for its investors and shareholders. Organizations which want to expand their dividends will seek to over a large amount of their earnings; whereas organizations which have high cash holdings are able to pay higher dividends if they wish to, the relation between dividends and earnings are calculated by dividend cover (Woods, 1999). Investors 2012 RM’000 2011 RM’000 ROCE ROE EPS 0,3277 0,1829 Earning Yield Dividend Payout Dividend Retention 1 – 0,478 = 0,52 1 – 0,59 = 0,41 6.0 FINANCIAL ANALYSIS FOR HARTALEGA HOLDINGS BERHAD 6.1 PROFITABLITY: These figures shows that Hartalega’s gross profit margin was 37.15% In 2011and it is Decreased in 2012 to 31.85%, Net profit margin is also decreased in 27.9% 2012 which was 33.4% in 2011 it tell that company is underperforming compared to last year’s performance. But expenses are decreased from 4.75% to 3.95% Profitability 2012 2011 Gross profit Net Profit Margin Expenses Margin 31,85 – 27,9 = 3.95% 37,15 – 32.4 = 4.75% 6.2 LIQUIDITY: This Table shows Liquidity of Hartalega Company their ability to pay their debts is Increased compared to 2011 which was 3.63:1 Now increased to 4.42:1 in current ratio. If we measure that in quick ratio it also shows an Increase from 2.81:1 to 3:28 Liquidity 2012 2011 Current Ratio Quick Ratio 6.3 EFFICIENCY: This table shows The Figures how Efficiently hartalega corporation is using their resources in 2011 their fixed asset turnover was 2.11 which is increased to 2.45% it tells us that and debtors collection period is decreased from 50 days to 46 days so they are collecting their debts earlier compared to previous year and creditor period in also decreased from 45 days to 35 days they are able to pay back their Creditors earlier than 2011 and stock turnover is also increased from 51 days to 56 days. This table tells us that hartalega is using their resources very efficiently Efficiency 2012 2011 Fixed asset turnover Debtors collection period Creditor payment Stock turnover 6.4 CAPITAL STRUCTURE: Capital Structure 2012 2011 Interest Cover Gearing Ratio INVESTORS: Investors 2012 2011 ROCE ROE EPS 0,2765 pence 0,2618 pence Earning Yield Dividend Payout Dividend Retention 1 – 0,43 = 0,57 1 – 0,29 = 0,71 7.0 RECOMMENDATIONS AND CONCLUSIONS Rubber Glove industry has huge demand in market and in future it will be demanded even more Developed Countries and developing countries are very concerned to use Hygenic products in their medical sectors and so their medical care expenditures will be increasing the demand for Gloves will also be increasing. As For Under developed Countries If there is a hope for them to Increase their Economy and they will also be concerned to use hygienic products like other Developed Countries demand for the Rubber Gloves will go even higher. Malaysia has dominated the Rubber Glove Industry and Is the King of rubber gloves. Top Rubber and latex gloves manufacturing companies are In Malaysia So there is a lot more competition with in Malaysia on this Business and all the companies are trying to improve their   capacity top Glove Manufacturing companies In Malaysia are Top Glove and Hartalega which are performing extremely well in this business and their products are demanding all over the world. Malaysian Organizations are the largest world exports of rubber gloves industry where as other countries like Thailand have no Competition with Malaysian Industries the Biggest Strength of Malaysian industries are their labor production each worker in the rubber glove industry are three times more productive than Thailand and Indonesian workers. So there is Nothing to worry about at the moment that some Country Might take over their Market. There are few things Which has to be considered are political relations with other countries, Thailand supplies 50% of Raw Material to make gloves to Malaysia. Any Political Issue can cause a lot of problems to the Rubber Glove manufactures. Bibliography Businessweek, 2013. http://investing.businessweek.com. [Online] Available at: http://investing.businessweek.com/research/stocks/snapshot/snapshot.asp?ticker=HART:MK [Accessed 7 July 2013]. Emilio Colombo, L.S., 2006. Contribution to economics. In M.B. Werner A Muller, ed. Financial Market Imperfections and Corporate Decisions. New york: Physica-Verlag. p.174. EMIS, 2013. http://www.securities.com. [Online] Available at: http://www.securities.com/Public/company-profile/MY/Top_Glove_Corporation_Bhd_en_1663501.html [Accessed 7 July 2013]. Haralega, 2012. Unlocking Potential. Annual Report. Kuala Lumpur: Haralega Holdings Berhad. Hartalega Holding Berhad, 2012. Unlocking Potential. Annual report. Kuala Lumpur: Hartalega Holdings Hartalega Holdings. Hartalega, 2013. Hartalega.com. [Online] Available at: http://hartalega.com.my. [Accessed 7 July 2013]. Koncept Analysis, 2012. http://www.researchandmarkets.com/reports/2097332/global_rubber_gloves_market_an_analysis_2012. [Online] Koncept An alsysis Available at: http://www.researchandmarkets.com/reports/2097332/global_rubber_gloves_market_an_analysis_2012 [Accessed 8 July 2013]. lee, J., 2012. Malaysia Equity. Investment research daily, 1, p.23. Michelle Foong, 2012. Rubber Gloves Gloving the world. Research. Global Market Research Companies. Thukaram, R.M., 2007. Management Accounting. In Management Accounting. 1st ed. New Delhi: New Age International(P) Limited Publishers. p.588. Top Glove

Policy Topic Search and Selection Essay

Policies are everywhere, and have to be followed by all for success. If they are not followed, consequences can occur, which are mostly negative. Policies are also set to ensure the organization’s rules are being followed. Health policy is a statement of a decision regarding goals in health care, and the plan for achieving these goals. Health policy is also known as a field of study and practice where priorities and values dealing with health resource allocation are determined (â€Å"Health Policy,† 2014). In this paper, Women’s Health Policy in regard to the Affordable Care Act will be discussed. The paper will also provide a quick summary of women’s health and the stakeholders affected. Let us begin with the definition of women’s health. Women’s Health Care Women’s health care is hard to define because it is so complex. Women’s health not only deals with adult women, it also deals with young girls and teenagers. If put into words, women’s health care would be defined as the physical and emotional care a woman needs to ensure she has the best quality of life possible. Women’s health care is a new arena in health care that must be clearly stated in the future to improve the health of a population (South Carolina Department of Health, 2013). This is important because women are the child bearers, and the advancement in women’s health care prevents and reduces the burden of illness or disability that affects women at each stage of life, and ultimately improves women health in the United States across the lifespan. Women’s Health Care with the Affordable Care Act Women’s, who includes young and teenage girls are the stakeholders affected by this policy. The Affordable Care Act (ACA) included several measures that are changing the profile of women’s coverage as the law is implemented. In regards to women, the implementation of the ACA will allow 2. 4 million women be insured. For women, the ACA includes caps on out-of pocket spending for certain low-income individuals and coverage for many preventive services without cost-sharing. There are a lot of improvements to the coverage for women because of the ACA implementation. The biggest improvement is that insurance plans were mandated to cover essential benefits like outpatient and hospitalization care, maternity care, and prescription drugs. Along with the essential benefits, the plans have to cover preventive services and vaccines for women; without any co-payments or other cost sharing. Those services are pap smears, mammograms, bone density tests, and HPV vaccine. As of August 2012, plans also have to cover contraceptives as prescribed by a provider, breastfeeding supplies and supports such as breast pumps, screening for domestic violence, well woman visits, and several counseling and screening services (â€Å"Women’s Health Insurance Coverage,† 2013). Even though the changes because of the ACA are extensive, they are needed to ensure women’s health care is at an optimal level because they are the catalyst by which our next generation is born. If this is done correctly and plans follow, the ACA will shape access to coverage and care for millions of women across the nation for years to come.

The eNotes Blog A Writers Haven 5 Authors Writing SpacesReimagined

A Writers Haven 5 Authors Writing SpacesReimagined As bibliophiles can attest, we  are all  intrigued by the private lives of our favorite authors, often wondering  about the ways that they worked creatively, and especially  where  they chose to write. For many, the choice was obvious, their office or bedroom a personal space for reflection and inspiration. At , we are really interested in embracing creativity and developing tips for success in school and work spaces. Time and time again we encounter articles noting the importance of having an organized, inspiring space to get to work. As we meditate on how to improve our own spaces, weve found ourselves wondering  how our favorite authors might  decorate their offices today. With this in mind, we  created todays blog post: A Writers Haven. Weve gone through and selected five  famous authors from various time periods and have translated their individual preferences into modern takes on their offices. We had a lot of fun putting these together, and we hope you enjoy checking them out and finding inspiration for your own space. Check em out below! Jane Austen: For Janes office we imagined a light and airy space with lots of natural light and creature comforts. We acknowledged her English roots and incorporate a tea pot, because we think that if any of our favorite authors would have had a tea pot in their office, it would have been her. We like to imagine that if Jane were here today, she would be a bit of an introvert, anxious to re-read the great number of books in her built-in bookcase. Want to learn more about Jane Austen and her writing? Check out this link:  /topics/jane-austen F. Scott Fitzgerald: We think that good ol Fitz would stay true to his Art Deco roots and draw inspiration from Gatsby, so we added lots of pieces with classic deco influences, and incorporated some rather regal accessories to reflect the Jazz Age in which he lived. (Check the desk clock and chandelier, jadore!) If you want to learn more about F. Scott Fitzgerald, check out this link to his biography:  /topics/f-scott-fitzgerald Ernest Hemingway: Hemingway was a world traveler, but he also enjoyed his alone time and the time he spent in the country, because of this, we felt it was important to incorporate both these things when re-imagining his office. By including a map, a travel trunk, and a painting of a ship we think we were properly able to effectively capture his wanderlust. For more information on Ernest Hemingway and his life, check out this link:  /topics/ernest-hemingway Edgar Allan Poe: We think that Poe would be a miserable hipster today, living in a seemingly effortlessly cool loft featuring some rather bizarre and morbid art. He would definitely be the guy that carries around an old typewriter, claiming that it makes his writing more authentic (we would call him more pretentious than authentic). For more information on Edgar Allan Poe and his writing, check out this link:  /topics/edgar-allan-poe Susan Sontag: Susan Sontag, Queen of the Bohemians! This space pays homage to her appreciation for the surreal and eclectic things in life. Sontag was one of the most devoted intellectuals of her time. Her office features a portrait taken by   Annie Leibovitz, her long time partner and friend. For more information on Susan Sontag and her work, check out this link:  /topics/susan-sontag Now that youve had a peek into our imaginings of these spaces, drop us a line letting us know what you think, and tell us about your space, and what inspires you! All these collages were done using Polyvore. For product information follow this link and click on the collage you are curious about!  http://kttrounds.polyvore.com/

Yield to Maturity Essays

Yield to Maturity Essays Yield to Maturity Essay Yield to Maturity Essay In economics yield to mature is the internal rate of return from the flows of cash of fixed income security, especially from bonds. Yield is paid if the bonds or other securities are to be held until their maturity. Yield to maturity is a measurement of the return from the bonds. Yield to maturity gives investors the opportunity to calculate the fair value of financial instruments. Yield to maturity applies exactly to a zero coupon bond. The reason is that this bond has no interest to be reinvested. (Yield to Maturity) Yield to maturity assumes that all interests and dividends are reinvested. It takes also into account losses and gains in case of difference between the purchase and redemption price. Economists say that yield to maturity is a projection of future performance, because yield to maturity has to assume a reinvestment and the rate of yield to maturity itself. In other words, yield to maturity â€Å"an implicit function that can only be evaluated by the method of successive approximations†. To achieve the quoted yield to maturity is easy when a zero coupon bond is to be help until maturity. Yield to maturity is mostly quoted in terms of â€Å"bond-equivalent yield†. (Yield to Maturity) For example, let’s consider a zero coupon bond that is 30 years. Its face value would be $100. The bond would cost $5.73 today if it is priced at a yield to maturity of 10%. The annualized return would be 10% over the thirty years, because the price would advance to $100. Let’s suppose that during first 10 years the interest rates would decline. In the result the yield to maturity would fall to 7%. After 20 years of maturity the bond price would be $25.84. Nevertheless even in such situation the yield to maturity for bond would be just 7%. The bargained yield to maturity for the moment of bond buying was 10%, the earned return over the 10 years would be 16.26%. But it doesn’t mean that the bond holder will earn 16.26 annually over the remaining 20 years. His annual income would be only 7%. It will be found that over the 30 years period the annual return would be 10%. (Bond Yield to Maturity) References â€Å"Yield to Maturity: Definition†. (2005). Retrieved September, 17, from investorwords.com.

The Best Career Tips No One Told You

The Best Career Tips No One Told You Career advice is common and usually welcome, but some bits of career advice are  seldom mentioned, even though they can help you make large professional strides. Just getting a job and plugging away at it can sometimes get you a promotion, but being proactive can get you there faster. Learning the best career tips can help build your standing and personal growth to become more successful in whatever career you choose. Do What You LoveExamine what your talents are and where your interests lie. That may be a good indicator of what direction you should go when going into a career. Does helping people give you that warm, fuzzy feeling? In that case, maybe you should look into healthcare jobs where you can spend your days helping others. Do you love mathematics and excel  at calculations? Maybe accounting or bookkeeping would be a good career move for you. Whatever your interests, you may be happiest doing what you love.Keep LearningKeeping on top of your profession is what makes your career rewarding. Taking a class, learning a new computer program, or earning a certificate in your field can make you feel as though you’re growing in your career and building toward the future. Learning new things keeps you ahead of the rest and helps if you want to change jobs or want a promotion.Find a MentorNo matter what your job, there is always someone who has been around longer and has much more experience. Observe that individual to see how he or she handles tasks and responsibilities, and then and learn to emulate the best techniques. Someone else’s  proven method can help you learn and grow.Set Goals to Achieve MoreAsk yourself where you want to be in the short-term and in the long term, and set reasonable goals to reach these landmarks. Do you need more training to go into a job you want eventually? Take the time to get that training. Are there responsibilities you don’t have that would benefit you in the future? Ask for more responsibilities at work. Learning other types of jobs can round out your experience and make you more marketable. Setting goals can get you there more quickly.Put in the TimeGo-getters know that working strictly during office hours and being the first one to leave for lunch or in the evening will not get you promoted. Put in extra effort to get the job done, even if it means missing a lunch break or working a little later. It won’t go unnoticed by your boss, and you may end up being assigned more responsibility because of it. This extra duty can lead to a pay raise or promotion.Keep Your Eye on Your GoalsMost people don’t start off in the perfect job. However, by finding a job that will help you get the skills and experience you need to move up on the ladder, you can work your way toward that perfect job. All it takes is perseverance and know-how.It is up to you to reach where you want to be in your career. With hard work and determination, you can reach that job of your dreams. TheJobNe twork helps you in your job search 24 hours per day. After you fill out your qualifications and job interests, we send you emails when jobs matching that description come up. In this way, you won’t miss any opportunities to get a great job doing what you love the most. If you want to, you can also search the job listings yourself, so you know you are being proactive in your search. Sign up for job match alert to start on the path to a new career.

In the UK, ethical businesses are not as successful as less ethical Essay

In the UK, ethical businesses are not as successful as less ethical businesses. Discuss - Essay Example Despite emphasis on ethical business operation in U.K, it has not been consummated to a successful enterprise. Firstly, unethical businesses operate on no moral obligation and thus commonly engage in hoarding of commodities and price manipulation irrespective of the set price standards. Pavelin & Porter (2008. p. 720) admits that â€Å"due to use of dubious means, they often have supernormal profits and their businesses have significantly grown its market share†. While ethical businesses such as Marks and Spencer remain committed in fair price mechanisms, unethical businesses would create artificial shortages and make supernormal profits to the disadvantage of the consumers. Ethics emphasizes on the distinction of wrong and right and unscrupulous businesses have the least concern on morals, their main goal is profits on returns. Secondly, operating ethical businesses in U.K requires compliance to bureaucratic laws and policies. For instance, a business should seek approval by obtaining an up to date operation license. Besides, â€Å"for food industries they must comply with Food and Drug Association (FDA) besides an additional medical certificate of all staff handling food items† (Aras 2012 p.177). It, therefore, provides for a lengthy process that requires time and money. While compliance will create additional time to start and operate a business, non-ethical businesses operations commences almost immediately because they often navigate around requirements. In addition, ethical businesses operate on honest as a fundamental pillar. They, therefore, ensure compliance to stringent taxation requirements. They ensure that there is â€Å"undoubted level of accuracy in the amount of tax remitted to the government tax authority† (Moore 2009 p.183). However, unethical businesses are skeptical on tax payment and often remit fewer taxes than the actual amounts needed. Although they employ an immoral approach in tax evasion, these unethical

Occupational Safety Assignment Example | Topics and Well Written Essays - 2500 words

Occupational Safety - Assignment Example The biggest problem here is that the diseases do not develop immediately but appear after a few years of exposure. The impact of pollution at workplace on productivity has been well investigated. Studies on the impact of pollution at work environment in productivity reveal a tendency of reduction in the economic activity (Marrewijk, 2005). "Sick building Syndrome" (SBS) and 'Building related illness' (BRI) gives rise to employee complaints such as headaches, dizziness, disorientation, fatigue, ear, eye and throat irritations. The world demand for high-speed ferries and LNG tanks is being met with an increase in Aluminium welding and casting production. This has introduced a new health hazard to the Aluminium welders and ways are being probed to protect the welders against the Aluminium fumes. In the U.K, the Control of Substances Hazardous to Health (COSHH) regulations stipulates that the occupational expose limit for Aluminium fume should not exceed 5mgm exp 3 of air. Aluminium fumes during welding also generate quantities of ozone gas, which can cause nausea (Rabin, 1997) and unconsciousness. Welding is a process in which metal or other thermoplastic materials are joined together by the application of heat or pore sure or both. Electric welding was introduced in 1940s. Aluminium welding has been in prominence since 1970. There are several types of welding like Arc welding and Manual metal arc is a common process where the workers are exposed to the fumes. Carbon arc, Cold welding, Electron beam welding, Flux core arc welding, Gas welding, Gas metal arc welding, Gas tungsten arc welding, Shielded metal arc welding, Plasma arc welding, Laser beam welding are the other welding processes where workers are exposed to metal fumes. The welding workers have a high exposure of metal fumes and the exposure depends on place, confined space, workshop or open air. The metal fumes depend on not only the Aluminium but also the process involved, which may produce gases like acetylene, carbon monoxide, oxides of nitrogen, ozone, phosgene and tungsten. The metal fumes primarily enter the human system by inhalation route namely Respiration.. The deposition of these inhaled metallic particles is influenced by its physical and chemical properties and a variety of host factors. In the lungs, these particles produce a variety of reactions depending on the concentration, duration of the exposure of the particles, and degree of exposure. All Metallic particles greater than 10 are deposited on the Mucous membrane in the nose and pharynx. Particles between 3m and 10 m are deposited throughout the trachea of the lungs. Particles less than 3m are deposited in the alveoli and cause serious hazards. These particles have a fair chance of being carried into the blood stream and cause Hepatotoxicity

Sports media advertising Term Paper Example | Topics and Well Written Essays - 2750 words

Sports media advertising - Term Paper Example This "Sports media advertising" essay outlines the impact of the sport advertisement on our society and our behaviour. Sports have been termed as one major currency and I believe it is because of the major investments that these events are accompanied with. Between 1998 and 2008 for example, various broadcasting houses were able to spend massively to ensure that they got broadcasting rights to Olympic events. This represents the economic value that sporting events and their images possess. Many market players have been for years interested in utilizing sporting events for purposes of promoting their business as evidenced by the massive payments they make to advertising agencies in such events. I can argue that this is because of the appeal that sports advertisement has on people who watch the event whether live or via television. Sports are seen by many in my opinion, to be a true reflection of the modern civilized world. Sporting events have the ability to articulate both local and international cultures while at the same time including various aesthetics. Sports form a unique tool for media advertisers because of their ability to draw large audiences through entertainment. They capture people from different cultures and therefore an ideal tool that can be utilized for purposes of advertising. The manner in which sports are structured also serves as a good ground for advertising. Consumers are attracted to sporting events because of uncertainties in their outcome, rules that govern them and commercial breaks in each event. Sports are a depiction of human drama and this is the justification of their popularity amongst people. They appeal to many because originally, some sporting events were reported in the news and that is where they originated. The increase in media complexity has therefore impacted on the way most businesses seek to advertise during sporting events. Sports fans form a larger part of audience that I believe is an idiosyncratic kind of consumers that is targeted by many consumers (Max, 2005). The way fans are loyal to their teams taking part in the sporting event is therefore a clear reflection of how a consumer can be tied to a commodity. In addition, major sporting events throughout the year form part of a fans emotional calendar and this is mostly utilized by business personalities in ensuring that they reach their consumers. Fans have a tendency of making a follow up of their team’s performance whether winning or losing. Apart from their loyalty, most fans in a sporting even t are normally a huge audience that is diverse. They are therefore a recipient of all types of advertisers because of the diversity that they carry with them into the event. The other advantage that sports advertising carries with it is the ability to easily categorize the fans into various sections depending on what they can be able to consume. In line with this, fans in any given sporting event that is targeted by business people can be categorized into their level of education and the income that they earn. People who are educated can participate in a sporting event and thereafter come out with the spillover effect of advertisement, which has an added advantage to business people in the long run. This has been popularly termed as direct sports consumption whereby fans have a tendency to consume something because it was advertised during the time when the sporting event was on. Sports media advertisement is also seen as advantageous because the rate or frequency at which each even t is repeated helps in creating

Show how language use reflects social identity and discuss any Essay

Show how language use reflects social identity and discuss any implications you can draw for second language teaching - Essay Example As the world becomes more global through communication and immigration, teaching a second language begins to have a greater impact on our society. Language not only expresses thoughts and ideas, it creates a representation of the speaker to their audience. As an example, respect is an aspect of that can be gained through speech and illustrates the broader relationship between power and language. Power is the degree to which one agent is able to control the behavior of the other. Physical strength, age, wealth, sex, or profession, are all unspoken ways to convey power. However, the introduction of a second language creates another center of power. That center derives its power from sociolinguistic solidarity. Using non-solidary forms express distance and formality, while solidary forms express intimacy and familiarity. Solidarity can be achieved in cooperation where communicators share some common attribute, such as attending at the same school or working in the same profession. However, to be a successful communicator in a linguistically diverse environment, it is necessary to know the languages, their nuances, and develop an appreciation for the power derived from language solidarity. A member in a community may have several groups with which he wishes to identify and associate with. The identity that the person creates for each group will be associated with their verbal communications, and there are certain linguistic forms that will construct each identity. People create their linguistic systems to resemble those of the in-group with which they wish to identify. A person participates in many different speech communities that vary according to time, place, audience, and participants. In a speech community, each individual has a range of social identities that creates different roles for all of the different subgroups within the community. The range of linguistic varieties expressed by these relationships is called the communicative repertoire. This repertoire, whether oral or written, can include different languages, dialects, or registers. Language serves as a symbol of association on several levels. On the national level, language attachment can serve an impor tant political function. On a local level, language is a symbol of attachment to a community. Within a social setting, language can be an in-group virtue. Foreign languages are a part of our communicative repertoire. When a person learns a second language, they become a member of a new cultural group within a social structure. They not only learn the appropriate linguistic forms, but it also extends their social identity to include other speakers of the new language. For the community as a whole, socialization through language learning creates conformity to social norms and relates the culture of the community. Teaching a second language encompasses more than just conveying the mechanics and the linguistics. It is an opportunity to construct an identity as a social being. In teaching a second language, it becomes vital to present the context, slang, and cultural attitudes that may be a part of the language. A second language is more than just a means of communication. It identifies the learner as a member of a unique cultural group, establishes their

CORPORATE STRATEGY - FITNESS INDUSTRY NEW YORK FITNESS Assignment

CORPORATE STRATEGY - FITNESS INDUSTRY NEW YORK FITNESS - Assignment Example This industry renders the facility of fitness specially gym and health clubs as per membership basis. The benefits provided by this industry include the use of exercise equipments and weights, along with facilitating personal training, group classes and other club amenities. As per the data of IBIS World (2012), the fitness industry especially gym and health clubs have inculcated an estimated figure of around 8.7 million members across the United Kingdom, which is nearly 17% of the adult population. The London Olympics specially provided the extra motivation in this industry; as a result, the revenue increased by around 9.5% over the last five years (IBIS World, 2013). The fitness industry is incredibly successful with innovation and changing technologies which provides the adapting capability of the products for suiting its own requirements. Though there are around 6000 gyms and health clubs in the UK but they cater to the different market segments. These include women only gyms, tr aditional body building gyms, budget model gyms, premium full service health club, and 24-hour gyms among others. In London, there are around 70,200 people employed in the active leisure, learning as well as wellbeing sector among them 5900 are employed in the health and fitness industry. Therefore, the government of the UK also provides help for ensuring sustained growth of this sector. London has a rich mix of active leisure and learning facilities, high profile sporting clubs and also a host of international, national and regional events. Therefore, the industry skills fill the gap of sports specific technical skills and health consciousness (AACS LMI, 2010). Contextually, on the basis of research initiatives on management theory the analysis is done with the help of PESTLE analysis of the external environment. Besides, in this paper, Bowman’s Strategy Clock and application and justification of the Ansoff’s Matrix are also going to be provided as analysing tools for finding out marketing and growth strategy of a new company. Thus, by analysing the external and internal factors a set of recommendations is also drawn on the development options of the business (Jarzabkowski & et. al, 2009). PESTLE Analysis of the Fitness Industry in the UK A PESTLE analysis at times referred to as PEST analysis is one of the imperative and useful tools for analysing and understanding the industry position as a whole and is often used in conjunction with a SWOT analysis to access the situation of an individual business. A PESTLE analysis is one of the most important frameworks regarding to the assessment of macro environmental analysis. Therefore, it is one of the most important frameworks and a key part for designing of strategic management. The term ‘PESTLE’ refers Political, Economical, Social, Technological, Legal and Environmental factors. This analysis enables to draw varied pertinent responses regarding various questions such as what are the po litical factors which likely to affect the industry, important economic factors, cultural aspects, technological innovations, present and imminent legislations of the government as well as environmental considerations. However, it is also needed to highlight that these factors definitely depend and

Today's Architecture Essay Example | Topics and Well Written Essays - 500 words

Today's Architecture - Essay Example The working thesis for the research is that ethics and social responsibility are important for architects. The angle of the research will be finding the benefits and reasons for ethical and social responsibility for architects and the development of strategies that will be effective in meeting the ethical needs of student architects. A study of the ethical and social responsibility of architects is an important undertaking because of the influence of the design choices made by architects on communities, individuals, and the global community. Architecture as a profession spans a lot of issues and the choices made in the course of design has direct and indirect impacts on the air quality, land use, design of public spaces, functions of the buildings, allocation of resources, security and safety of the buildings designed to the current and future generations, and aesthetic delight, among other issues. Being an architecture study, I believe I will be in a good position to capture the main issues to be dealt with in the research. The primary audience includes architects, critics of the architecture profession, and readers of architecture journals, including the Architect’s Newspaper and Architect’s Journal, aimed at dealing with responsible architecture, and the general public (Shobow, March 12, 2014). The secondary audience includes fellow students and professor. The audience believes in the importance of having ethics and social responsibility by architects. Ethical guidelines are present for architects but not followed too much owing to the client requirements that take more precedence. From the research I have noted on the high insistence on having ethical guidelines and following them in the course of architecture to ensure the needs of the client, as well as those of the society, are represented in design (Chan, 2013). I need to

CORPORATE STRATEGY - FITNESS INDUSTRY NEW YORK FITNESS Assignment

CORPORATE STRATEGY - FITNESS INDUSTRY NEW YORK FITNESS - Assignment Example This industry renders the facility of fitness specially gym and health clubs as per membership basis. The benefits provided by this industry include the use of exercise equipments and weights, along with facilitating personal training, group classes and other club amenities. As per the data of IBIS World (2012), the fitness industry especially gym and health clubs have inculcated an estimated figure of around 8.7 million members across the United Kingdom, which is nearly 17% of the adult population. The London Olympics specially provided the extra motivation in this industry; as a result, the revenue increased by around 9.5% over the last five years (IBIS World, 2013). The fitness industry is incredibly successful with innovation and changing technologies which provides the adapting capability of the products for suiting its own requirements. Though there are around 6000 gyms and health clubs in the UK but they cater to the different market segments. These include women only gyms, tr aditional body building gyms, budget model gyms, premium full service health club, and 24-hour gyms among others. In London, there are around 70,200 people employed in the active leisure, learning as well as wellbeing sector among them 5900 are employed in the health and fitness industry. Therefore, the government of the UK also provides help for ensuring sustained growth of this sector. London has a rich mix of active leisure and learning facilities, high profile sporting clubs and also a host of international, national and regional events. Therefore, the industry skills fill the gap of sports specific technical skills and health consciousness (AACS LMI, 2010). Contextually, on the basis of research initiatives on management theory the analysis is done with the help of PESTLE analysis of the external environment. Besides, in this paper, Bowman’s Strategy Clock and application and justification of the Ansoff’s Matrix are also going to be provided as analysing tools for finding out marketing and growth strategy of a new company. Thus, by analysing the external and internal factors a set of recommendations is also drawn on the development options of the business (Jarzabkowski & et. al, 2009). PESTLE Analysis of the Fitness Industry in the UK A PESTLE analysis at times referred to as PEST analysis is one of the imperative and useful tools for analysing and understanding the industry position as a whole and is often used in conjunction with a SWOT analysis to access the situation of an individual business. A PESTLE analysis is one of the most important frameworks regarding to the assessment of macro environmental analysis. Therefore, it is one of the most important frameworks and a key part for designing of strategic management. The term ‘PESTLE’ refers Political, Economical, Social, Technological, Legal and Environmental factors. This analysis enables to draw varied pertinent responses regarding various questions such as what are the po litical factors which likely to affect the industry, important economic factors, cultural aspects, technological innovations, present and imminent legislations of the government as well as environmental considerations. However, it is also needed to highlight that these factors definitely depend and

Penelope Lively & Going Back Essay Example for Free

Penelope Lively Going Back Essay Jane retells the book Going Back for us, and how she, now an adult with a family of her own, is looking back into her childhood memories, she has had to revisit Medleycott, as now her child home is being sold. She recalls her childhood memories of Medleycott, where all summers are one hay making and raspberry time and all winters are one scramble across glass-cold lino to dress quickly. Jane and her elder brother, Edward, live a peaceful life in the country. Their misunderstood father has been sent away to fight in the war and they are loved and cared for by Betty, their motherly figure. The childrens mother died whilst they were young and their father finds it difficult to understand their innocent childish ways. This shows us a strong border between the adult and children world. Lively has also displayed this border through Janes different perspective, how her images of live have changed now she is an adult. Lively has expressed this by describing the different characteristics belonging to child and adult, the different ways in which they speak, the differences in their languages and how adults and children both enjoy different surrounds. We lived in the playroom and in the Garden The way in which Lively uses different territories belonging to different characters, represents a strong border between the Adult and Child worlds. The children like to spend most of their time, when at Medleycott, in the garden. It is a place where they can retreat and live a world of their own. To Jane and Edward their garden is their paradise. Their innocence and naivety makes it seem like the perfect haven, The Garden of Eden. It is a safe place, where they have everything they need and they are free to do what they wish, within the garden borders. The adults within the book also have their territory. Betty has her kitchen, which is where she spends her time cooking, cleaning, washing and other household chores. Lively describes the Fathers territory in terms of the furniture within it. His part of the house, beyond the glass door on the upstairs landing, had thick carpets and smelt of polish, you had to be careful not the knock over flowers There is a substantial difference between his area and the childrens area compared to Bettys kitchen and the childrens territory. The children find it easy to relax when they are in the Kitchen, but they have to be careful and smart when around their father. Lively has done this to show that there is a closer bond between Jane, Edward and Betty than with the Father and his children. This may be due to the death of the childrens mother, but Jane and Edwards father finds it difficult to communicate with them. With the war on, all of the adults are worried and careful, yet the children only see it as a game. Standing on the lawn, staring up at those blue and white skies out of which Germans would come. We would misdirect them. Ah, wed scupper them London pointing west, and send them storming. The children see the war in the one-dimensional view that children do. They take every thing they hear literally, basically believing anything that they have been told. Jane and Edward do not understand the seriousness of the situation around them; all they have noticed is that the war put an end to Bettys Saturdays at the cinema. There was a war on, so you couldnt have lots of sweets anymore, just one sixpenny bar of chocolate a week, and no more oranges or bananas. Jane and Edward are not worried if they get a chocolate bar or not, they have their garden to play in, it is natural and simple, they dont understand why the Adults are worried. The adult world is a very materialistic and ordered world, and they care about what will happen and that everything has to be right.

Haemoglobin-related Diseases Management Strategies

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