Development of Anti-Idiotype Vaccine for Human Follicular Lymphoma

Non-Hodgkin’s lymphomas (NHL) constitute a heterogeneous group of malignancies whose incidence has significantly increased in recent decades. In the year 2000, more than 145,000 cases of NHL were diagnosed in developed countries, representing thus the sixth most common cancer occurring among men and the eighth among women. Low-grade B-cell NHLs, in particular, are incurable diseases characterized by relatively slow growth and excellent initial responsiveness to chemotherapy but also by continuous relapses. In particular, for patients with follicular lymphoma, median overall survival (7-10 years) has not improved over the past 30 years. Although in the vast majority of patients complete or partial remissions can be obtained with either single agents or combination chemotherapy, the clinical course is characterized by a high relapse rate. After relapse, both the response rate and relapse-free survival after subsequent salvage treatment regimens steadily decrease, resulting in a median survival of only 4-5 years after the first relapse. These clinical findings, coupled with the substantial toxicities of standard treatments, have stimulated the search for novel and more tumor-selective therapies.Follicular lymphoma is a clonal B cell malignancy that expresses a unique antigen that is formed by the immunoglobulin light and heavy chains that possess highly variable regions at their amino termini. These variable regions combine to form the antigen recognition site, which can itself be recognized as an antigen, termed the idiotype. The antigen-binding site is a structural feature of each immunoglobulin that distinguishes it from other immunoglobulins. The idiotype of a particular clonal B cell lymphoma represents a tumor-specific antigen. Idiotype is a target of interest in human lymphoma.Therapeutic vaccines targeting B cell lymphoma idiotype (Id) represent a promising immunotherapeutic approach for a better clinical control of these malignancies.Immunoglobulin (Ig) molecules are composed of heavy and light chains that possess highly variable regions at their amino termini. B-cell malignancies are clonal proliferations of Ig-producing cells. The idiotypic determinants of the surface Ig can thus serve as a tumor-specific marker for the malignant clone.Indeed, both protein- and dendritic cell-based vaccines that use the patient-specific Id have resulted in clinically significant tumor-specific cellular responses with very little toxicity. A broad use of Id-based vaccination for B cell lymphomas, however, is hampered by the fact that these approaches are patient-specific so that the vaccine must be individually produced for each patient. On these grounds, new strategies obviating the need to produce customized vaccines would further simplify clinical applications of idiotypic vaccines.Goals:Goal 1:Establishment of a large database including sequences of idiotypic VH and VL genes expressed by a variety of lymphoproliferative disorders, includ ing low grade B-NHL, autoimmunity-associated lymphoproliferations, and chronic lymphocytic leukemia. This will allow the identification of candidate Id proteins for â€Å"cross-reactive† immunotherapy.Goal 2:Pre-clinical characterization of the immunogenicity of selected natural Id proteins, with particular regard to their ability to induce immune responses against lymphoma cells expressing molecularly correlated Id proteins. The characterization will include the identification of B cell epitopes and HLA Class I-restricted cytotoxic T cell epitopes using innovative approaches and will allow the development of dedicated assays for immunomonitoring.Goal 3:Design and validation of optimized Id vaccine.Goal 4:Evaluation and validation of new adjuvants and innovative delivery systems for improved Id vaccine formulations and administration.Goal 5:â€Å"Clinical-grade† production and purification of optimized Id proteins for patient vaccination.IntroductionThere are approxima tely 65,000 new cases of non-Hodgkin’s lymphoma diagnosed each year in the US with a comparable number in Europe. Despite the use of aggressive chemotherapy and recent advances in therapy such as monoclonal antibodies (Rituxan, TM), the disease is almost invariably fatal. Follicular lymphoma (FL) patients, in particular, can have an indolent but ultimately fatal clinical course. The median relapse time for FL patients is three years, with 90% of patients dying of a tumor-related mortality within 7 years of the date of diagnosis.The clinical course is usually characterized by a series of remissions and relapses. Good response rates are seen with treatments such as chemotherapy, radiation, lymphocyte transplantation, and monoclonal antibodies. However, following initial response to treatment, the cancer invariably returns and the majority of patients relapse with resistance to all available therapy. Related B-cell derived neoplasms include multiple myeloma (approx. 15,000 cases /year in the US and chronic lymphocytic leukemia (approx. 10,000 cases/year in the US).Isolation of tumor-specific antigens (TSAs) has been a long sought-after goal for scientists involved in both basic and clinical research. Whereas tumor-associated antigens (TAAs) are localized on both normal and tumor cells, TSA are peculiar to tumor cells. This characteristic makes TSA a very desirable target for immune therapy strategies aiming to spare normal cells, or at least the indispensable ones.As regards effectors mechanisms, although some indirect evidence exists for participation of both natural killer (NK) cells (especially those activated by IL-2, known as lymphokine- activated killer, or LAK cells), and TNF-secreting macrophages in tumor immunity, most interest has been focused on the role of antigen-specific antibodies and T lymphocytes. This is particularly true among scientists developing anti-Id vaccines for human FL, even though no substantial agreement has yet been reached on which of the two main effectors pathways is most important.FL conforms to the general rule that tumors have several mechanisms to escape the attention of the immune system. The risks that Ig somatic hypermutations could result in aminoacid residue replacements leading to substantial changes within the fine immunogenic structure of the Id do not seem to be so relevant. Indeed, no such occurrence has been reported in any of the several dozen patients who have been immunized over the last decade. A much more relevant issue is the very limited ability of FL cells to present their own antigens.Although ontogenetically very close to normal mature B-lymphocytes, with respect to their normal counterparts FL cells are very poor as antigen presenting cells (APCs). This makes it rather difficult to evaluate any vaccine-induced, tumor-specific cytotoxicity even in vitro. On the other hand, no such problems exist for ELISA-based detection of the tumor-specific and vaccine-induced humoral respon se.The first study of anti-Id vaccinations in humans dates only from 1992. Until then, all the work had obviously been confined to animal models. However, the accumulation of experimental data has led to the development of several promising strategies that are currently being investigated in clinical trials. These include the utilization of the Id in the form of a soluble protein or as a DNA sequence, either used to pulse dendritic cells (DCs) or else to be administered in combination with immunologic adjuvants.Soluble protein Id vaccine production is based on a hybridoma technique, which in vitro allows production of exactly the same Ig as that present on the surface of the clonal B cells of FL, or in other words the tumor-specific Id. The suspension of single cells obtained from a biopsy specimen almost invariably contains a residual population of normal B-lymphocytes alongside the tumor cells. Screening of the hybridomas by means of Ig heavy chain CDR3 PCR identification is there fore required in order to make sure that the Ig of the selected hybridoma is truly identical to the tumor- associated one.31 Once the cultured hybridoma has yielded enough purified Id, the TSA needs to be made far more immunogenic than it is in its free form. For this purpose, it may either be conjugated with a highly immunogenic carrier such as keyhole limpet hemocyanin (KLH), or else used to pulse autologous DCs.The association of a soluble protein Id vaccine with immunologic adjuvants monocyte colony-stimulating-has also proved extremely important. Granulocyte factor (GM-CSF) currently seems to be the best such adjuvant both in animal models and humans, probably because of its capacity for local recruitment of DCs in vivo at the site of vaccine injections. This step would appear to be superfluous when autologous DCs are loaded with Id ex vivo and then re-injected into the patient.A completely different alternative approach involves administration of the patients’ Id-encodi ng DNA sequence. With the rise of molecular technology, such DNA vaccines are beginning to come into their own. For instance, exploitation of appropriate molecular vectors (ie containing both a leader and promoter sequence) for insertion of the nucleotide sequences responsible for biosynthesis of both the Ig heavy and light chains variable regions is now relatively easy.Between the heavy- and light-chains variable regions sequences, an intertwined linker peptide must also be inserted to allow the ultimate Id-containing molecule (scFv) to fold properly. Furthermore, the vaccine can be further strengthened by adding other DNA sequences encoding for immunologic adjuvants or powerful immunogens to the vector. Finally, intramuscular injections allow progressive release of the Id following synthesis by muscular cells. In addition, this administration route seems to be associated with prolonged conservation of the genetic information within the cells without any apparent signs of integrati on into their genome.Experimental DesignGoal 1:Establishment of a large database including sequences of idiotypic VH and VL genes expressed by a variety of lymphoproliferative disorders, including low grade B-NHL, autoimmunity-associated lymphoproliferations, and chronic lymphocytic leukemia. This will allow the identification of candidate Id proteins for â€Å"cross-reactive† immunotherapy.In establishing a database, there will be steps to follow in order to support the evidences claimed.I. Finding the cases and the occurrence of VH and VL in lymphoproliferative disorders in different hospitals and institutions that could provide valuable information for the said disorders. The facts and information should have the confirmed consent of the persons involved.II. Subjecting the cases to thorough analysis to provide the essential information needed in documenting the cases.III.   Testing the subject under the identification of Id proteins.IV. Organizing the information and est ablishing the database.Methods:Establishing a database to easily organize information and data needed in making the information available readily whenever they will analyze situation in which there is a suspected occurrence of lymphoproliferative disorder. By providing the information needed, they could develop system that would make things easier for them to do actions required in addressing such situation.Primary step is consolidating all the available facts and information provided that they have the consent from the owner of the information. By having the desired facts available for the reorganization of it, they could classify it according to the general category they want to use in creating their database. It could be based on severity of the case or could be base on gender or any factor that could greatly affect the situation.Then, by gathering the information they needed, the analysis of the data should be carefully done for them to eliminate excess and negligible data for a n easier organization of the structure of their available resources. By implicating the main thrust of the database to the core concept of having advance cases of NHL, the higher chance they could get the information and the data based on the clinical findings of actual patients and people who suffered from that.By simply opening the way of introducing different vaccines in addressing the situation, they could develop a system of transferring and managing information that could make things easier especially in developing new technology and medicinal advancement in creating a better and more effective ways of treating such disease. By making the information more manageable, they could likely innovate an advance communication that would lead them in establishing better information and data management for the use of the development of vaccines and cures.Since they have the information but they should examine carefully every bit of information that will be a part of their set of data an d facts. By looking closely to the subjects result and the specification of the action done, the development of such process in introducing a new finding on the matter should be considered. Since the goal is to establish a database that will focus on the information that could provide the facts needed on the cases diagnosed with a NHL, it is important to screen the cases as important and not negligible for them to be able to use it as a case.At the end of the process, they would go back to their primary goal and that is to establish a functional database that the core information and the key factors are integrated in a way that it would make the processing of facts and vital data would be efficient and effectively handled.Also, it will introduce technology that would compensate the fast rising of development in technological advancement even in the field of medicine. Because there are ready to use valuable information for them to handle and initialize their desired action, they woul d be able to commend the different opportunities in which they could get specimens and studied it for future discoveries and researches.In all, by their incorporation of the cases of NHL and their desired goal of making the information available for them to be able to easily study and review the situations and cases they previously have for them to execute and evaluate the validity of the existing tests in the current occurrence of the disease in the real place.Goal 2:Pre-clinical characterization of the immunogenicity of selected natural Id proteins, with particular regard to their ability to induce immune responses against lymphoma cells expressing molecularly correlated Id proteins. The characterization will include the identification of B cell epitopes and HLA Class I-restricted cytotoxic T cell epitopes using innovative approaches and will allow the development of dedicated assays for immunomonitoring.In dealing with the pre-classification of the immunogenicity of selected natu ral Id proteins, the processes involved are:I.   Accumulating soluble proteins to be tested.II. Testing them with hybridoma essential in testing the equivalence of the tumor inducing material that leads to development of the tumor.III.   Inducing the effect of the proteins and identifying its effect on B cells.IV. Using advance technique in analyzing the result and implicating with the use of the modern testing equipment and processes.Accumulation:Testing the proteins for it to be classified will be the first step. From the patients who are suffering from FL, different samples will be getting for the medical technology to be applied. Then by cultivating natural proteins, they will use it to further test the capacity of the natural cell in penetrating and deeply interacting with other Id proteins in the development of resistance to such substance.By eradicating some external factors such as the presence of other organisms, they could screen the protein level for them to be able t o produce and test the Id proteins by exposing it to toxoids that could develop resistance on the desired solution. Then, the Id proteins gathered will be stored for further testing.Testing:Then, preparation of the Id protein to be tested will be carefully done in a controlled environment. Since the tumor development can not be detected by the immune system, the development of inducing material will be necessary for them to penetrate the basic defenses of the tumor.By exposing it to NKL, tumor will exhibit a different behavior but will not be extinguished. Since B cells epitope derived multiply myeloma that had been the major cause of the return of the behavior of the tumor cells, the gradual exposing it to be classified by soluble Id proteins will be dedicated.The allowance of certain percent productivity will be the basic goal of the clinical testing for them to be able to derive the pre-classification scheme that will determine substances that induce immunity on certain level wit h the use of soluble and Id protein present in the environment.Effect and its IdentificationAfter the testing had been carefully done, they will examine its effect on various elemental positions by trying the substance on the possible outcome. Then, FL cells will be isolated then proteins will be added to see the effect on the neoplasms produced by B-cells. Since the outcome would produce certain behavior that will exhibit a different expected one, the process will be repeatedly associated with soluble proteins to target the development of TSA since it target tumor cells.Analyzing the ResultThen, the result will be analyzed in a way that it consistently produces same output. Then after looking closely and making sure that no other substance induced the effect, the validity of the result will be the next concern in analyzing the data. For it to be valuabe, the result should consist the scientific analysis of the vaccine to be introduced for them to be able to adopt a real one.Goal 3: Design and validation of optimized Id vaccine.Since the protein had been introduced in TSA that would target tumor cells, it is important to develop the next stage wherein it will pay attention to that. Tumor cells, after being extinguished by some other methods, always come back and provide a worse situation that before. It is a common problem of the development of cure because as soon as they introduce stronger antigens and antibiotics, the cells develop stronger immunity to them, making them more powerful and gave them the power to come back and come back whenever they are defeated.The result of the previous testing of the material will be used as the raw data in determining the precise development of the vaccine needed for the tumor cells. Toxoids produced by microorganisms will be introduced to the tumor cells for them to create an astounding reaction with the cells to help the antigens produce a better shield to the tumor cells.They would also address the production of its own immunity by targeting the B cells epitopes produced by the tumor cells for them to be able to weaken the effect of the tumor cells in the body. By simply having the same effect on the cells, they would establish the immunity desired.In addition, since soluble proteins produces amino acid residue, the effect of it to the development of various outgoing tumor cells will be beneficial in the sense that it would catch up the screening proves by a hard core stimulation of heavy chain CDR3 PCR. Then, the use of material that would likely predict the behavior will also introduce for the existing antigen to determine it.Goal 4:Evaluation and validation of new adjuvants and innovative delivery systems for improved Id vaccine formulations and administration.After having the result of the vaccine being tested hand-on on the tumor cells, the activation of the production of antigens will be manipulated for those to be able manage the outcome of the result. By having the systematic chain of micr o toxoids that will enter the entire system of the body, they would likely produce different kinds of reactions that would benefit the production of self stimulating antigens.By exposing it to different procedures that would attest the certainty and validity of the desired production, after introducing different sets of toxoids and NK cells, the development of the self inducing multiple protein will help in eradicating the symptoms and the effect of FL.It is known that FL is fatal in terms of its effect on the human entire system. So it is important to devise a precise way of handling and dealing with it for them to be able to have an outer perspective of the natural phenomena.Id proteins will act as binders to the solutions that will be used in strengthening NK cells and TSA to promote the development and inhibit the further production of malignant development of tumor cells. By preventing the further growth of it, they would have larger revenue in which they could satisfy the need s and the improvement for having a stronger antigen.Then, natural growth of TSA will be affected by the inducing of soluble protein to target dendritic cells for them to be able to manifest the basic function of fighting foreign toxins that could affect the development of the tumor as a vital implication of the vaccine. The use of different methods in determining the feasibility of inducing the growth and the development of natural antigens that would be sufficient enough to fight the invading tumor cells will be of great use for them to be able t produce more antigens that will prevent the further worsening of the situation.Validating the use f the vaccine as one of the potential sources of defense against the foreign material invading the system would be beneficial if the could handle the needs of having a more systematized and organized level of founding a solution that would focus on the elimination of cell processes that inhibits the growth of malignant tumor like FL that is fa tal to humans.Subjecting enough NK cells to further strengthening process will help them in making the process worthwhile I making a protein Id that would address the situation as founding solution to the antigen development.Goal 5:â€Å"Clinical-grade† production and purification of optimized Id proteins for patient vaccination.After developing the vaccine the process would involve the following:I.   Purifying the Vaccine to be prepared.II.   Final VerificationIII. Mass ProductionIV.   Patient VaccinationPurificationAfter devising the vaccine, the next step is purifying it by eliminating microorganisms that would have effects on the vaccine. By continuously subjecting the vaccine into different microorganism killing environment, they would lessen the potential of having such. Radiating and constantly developing processes will be sufficient in terminating such microorganisms.Final VerificationAfter the purification of the vaccine, a method will be done for them o be abl e to test if the results are really valid by having it tested for final verification. It is important to deal with it because the importance f verifying the vaccine would greatly affects its validity in the medical society. By having it tested trough lab rats or animals that have developed FL tumors; they would be injected with such vaccine for them to see if the previous results will e the same.Mass ProductionAfter the verification process, the next process will involve producing the vaccine enough for human consumption. The proteins that deal with the development of TSA would have a various report on it validity and essentialism for them to be able to have a developed system of introducing vaccines.VaccinationAfter the production and the vaccine is ready to use, it would be given to the patients, as long as it is approved by the medical board, to be sued as vaccine against the development of FL into malignant tumors that endangered the lives of many people. Then, by having the sys tem of production of certain involvement of the NK cells within the hybridoma of dendritic cells, the vaccine will be of much use since it will introduce antigens that will prepare the body for the possible FL development.Since there are certain kinds of toxoids that will be introduced, there will be a harsh reaction at first to the place where it is injected because of the behavior of the toxoids and the T cells of the body. This is a sign that the vaccine is effective and doing a reaction that would strengthen the immune system of the body.DiscussionAfter the development of the vaccine in FL, it is important to understand the need of developing such because of its adverse effect on the development of humans. It endangered the lives of many people without having the prior notification of the said disease. This is a vital step in the clinical world.Considering the existence of the natural antigens present in the environment, by the use of Id proteins that inhibits the growth of tumo r cells; it would be beneficial to mankind if the continuous development will take place. By exploring the kind of the interaction ventured in this kind of process, the elemental composition of the vaccine would be developed to address the needs of the people in having the desired implication of the subject process.The processing of vaccine would include the development of stages in which it would acknowledge the presence of the cells responsible for the development of the disease. In effect, they would have a better understanding on the subject, matter and would increase the possibility of having a curable state.By implicating the notion of having a different technique in addressing the development of the vaccine, the question left for it is how long would it last for them not only to develop vaccine but also to develop a cure that would forever block the negative effects of the disease. By using and ensuring the safety of the user, they would have a proper citation of the needed p lan for them to be able to execute the importance of the vaccine and its use in the modern life.Furthermore, by examining the application of the vaccine in the curing of the disease, we would see the importance of development and use of innovating techniques in determining the possible outcome of the curing of the disease.Finally, the consideration of the process if it fits the standards of the medical consideration despite the fact that there exist different processes that involve much medicinal advancement should take into consideration the impact of the introduction of this vaccine prior to the ethical understanding of the matter.   Since FL can be considered as one of the deadliest disease that one can have, the help of having a vaccine against it is beneficial to the human industry.

Small Scale Industries

Small-Scale Industries in the Globalization Era: The case of Jordan Basem M. Lozi, Assistance Professor, Al-Balqa Applied University, [email  protected] com Abstract The research examines the role of SSI in the economic development of Jordan by showing the effects of the SSI on the unemployment rate, production, and sales. The research concludes with policy recommendations to ensure the sustained and competitive growth of small-scale industries in Jordan. The results of the study show that the growth of SSI in Jordan in terms of employment, production and sales has increased due to globalization and domestic liberalization.However, it is still not as significant as planned. The SSI sector should be encouraged to make a sustainable contribution to the national income, employment, and exports. Keywords: Small scale industries, policy, globalization, Jordan, competitiveness. Introduction The development of small-scale industries (SSI) has been one of the major planks of Jordan’ s economic development strategy since Jordan's independence. The SSI sector occupies a place of strategic importance in the Jordanian economic structure due to its considerable contributions in terms of output, exports and employment.SSI play a key role in the industrialization and development of any country. This is because SSI provides an immediate large scale employment, ensure a more equitable distribution of national income, and facilitate an effective mobilization of resources, capital, and skills which might otherwise remain underutilized. It is possible to determine the concept of the SSI in accordance with two measures: the size of the labor force employed; and the amount of invested capital in this industry. Jordan has adopted the first concept to distinguish between the SSI and other industries.An establishment is considered small if it employs not more than 10 workers, while industry employing between 15-30 workers is considered a medium scale industries, and when having more than 30 workers the industry is considered large scale industry's category. Although many countries have adopted this criterion, other, countries determined the higher ceiling of the number of the labor in this industry to become 15 workers as it is in Iraq and Ghana, while Egypt, Belgium and Denmark adopted the criterion that the number of workers should not exceed 50 workers.In contrast , countries such as France and Italy adopted the criterion of 500 workers to distinguish between small-scale and other industries But in Japan and in the United States the total number of workers working in small scale industries was set at 300 in Japan and 1000 workers in the United States(Subramanian 1995). Furthermore , the SSI are characterized by their degree of spread as show in table (2), the SSI in Jordan comprise nearly 84% of the established industries during the period of 19901998 and increased to nearly 90% of the total industries established during the period of 1999-2006 (Hachur e 2004).Moreover, most of these industries were characterized as being environmentally friendly. The possibility of establishing these industries in different regions is favorable because they do not need a special infrastructure, once these industries are well established then the encouragement of their spread in the rural regions will help to achieve many of the social and economic goals, such as increasing income in rural areas, controlling the migration from rural areas to cities and controlling demographic growth.Objectives of the study The main objective of this paper is to highlight the importance of SSI in the Jordanian economy as SSI occupies a place of strategic importance in the Jordanian economy due to their considerable contributions in terms of production, sales and employment. These 1 contributions have emerged despite of the fact that this sector has been exposed to intensifying competition. Research Questions This paper is also attempting to answer the following res earch questions.The answers to these questions are part of the objectives of this study. †¢ Why should global and national policy development affect SSI in Jordan? How? What are its implications? †¢ How far have SSI been able to cope with the competitive environment? What was their growth performance in the last decade? †¢ What was their effect on employment, production, and sales? †¢ What policies need to be taken to strengthen SSI to ensure their sustained contribution to the Jordanian economy?Methodology This study is based on the primary and analysis of secondary data. The data was gathered from published studies and reports available in both English and in Arabic languages. Relevant statistics were obtained from the Central Bank of Jordan and the Department of Statistics. These data were then analyzed to describe and explain the objectives of the study. Review of literature The literature review indicated that the numbers of studies which have examined SSI i n Jordan are very limited.The most notable studies are: A special report was conducted by the International Bank in the Middle East and North Africa (2005). This report shows that the financial gap which is the difference between the capitals offered and the capital needed has decreased, which means the SSI influenced part of the financing problem. Another study was conducted by the Royal Scientific Society (2001), concluded that if the SSI control the cost of needed materials for production, then the role of these industries in the economic development of Jordan will be significance.Additionally, N. Khalil (2004) reported on his paper â€Å"The role of SSI in decreasing the poverty and unemployment rate in Jordan†, that the SSI has a minor effect on the poverty and unemployment especially in the rural areas. While, I. Krabiliah (2002) in his paper â€Å"Relation between the no. of SSI and the unemployment rate in south Jordan†, that the no. of SSI in south Jordan is l imited compared to other districts. Therefore, the SSI in the south has a minor effect on the unemployment rate.Ironically, Almeyda (1996) reports that commercial banks role in SSI finance is significant even when compared to large and developed non-governmental organizations. It was found that 70 percent of the outstanding value of microfinance and SSI loans was extended by the 25 banks, whereas 150 non-governmental organizations were responsible for 4 percent only. A world Bank survey of 206 microfinance intermediaries world wide (2001), finds out that many area of the world – unlike the Middle East and North Africa and contrary to perceived barriers – banks are becoming a major player in microfinance.This report states that â€Å"banks may be the most efficient channel for providing microfinance to the entrepreneurial poor†. Global and national changes implications for small scale industries Last decade was a remarkable period in terms of policy changes natio nally as well as internationally. Since the beginning of 1990s, policy changes have been taking place at two different levels: global and national. Both have implications for the functioning and performance of SSI in Jordan. Globalization refers to free movement of factor inputs as well as output among countries.However, the developments that have been taking place since the early 1990s are mostly reference to the movement of capital, commonly known as Foreign 2 Direct Investment (FDI), and the free movements of goods, particularly from the developed not the developing economics. The liberalization of FDI regimes and the strengthening of international standards for the treatment of foreign investors give foreign firms greater freedom in making internationally location decisions. More than 58 countries have annually introduced changes in their investment regimes during the 1991-2006.In 2001 alone, 70 countries made a total of 150 regulatory changes, of which 147 were more favorable t o foreign investors (Stiglitz 2002). As a result, global FDI increased from US $ 209 billion in 1990 to US $ 1591 billon in 2000. The increased flow of FDI has led to its greater share in gross capital formation in all industries as well as manufacturing industries (Table 1). The increase was more significant in developing countries. This would have led to intensifying competition in the national as well as international markets for small firms.Table (1): FDI in capital formation (1980, 1990, and 2005) Region FDI as a percentage of Gross capital Formation ( All industries ) World 1980 1990 2005 Developing countries 1980 1990 2005 Source: UNCTAD The formation of the World Trade Organization (WTO) in 1995 has only accelerated the process of scaling down tariff and non-tariff restrictions on imports. Jordan, as a member of the WTO, had substantially done away with its quantitative and non-quantitative restrictions by 2000. The process of removal of quantitative and non-quantitative res trictions across countries has led to a greater movement of goods between countries, including Jordan.However the reduction of restrictions on the movement of goods between countries and the subsequent increase in world exports have benefited Multinational Corporations (MNC) much more than small enterprises. This situation has not been examined along with the process of economic reforms launched by the government of Jordan at the national level. This has resulted in considerable freedom for enterprises – domestic as well as foreign – to enter, expand or diversify their investments in Jordanian industry.Jordan's economic reforms have two major outcomes. Firstly, the growth of the public sector decreased considerably since 1988 compared to the earlier period, in terms of not only investment and employment but also production. Secondly, there has been a rapid increase in FDI inflow, into diverse sectors of Jordanian industry. This economic reform in Jordan has treated the small scale industries in two ways: first is due to opening the door for intensified competition for non-durable consumer goods industries.The second way is by providing an opportunity for outsourcing to small enterprises in durable consumer goods and capital goods industries. Performance of small scale industries in the globalization era SSI is considered as the backbone of the private sector all over the world, which assures their role in production, employment and sales. In addition to their role in economic development, 1. 2 4. 0 8. 3 11. 7 22. 3 29. 8 2. 3 4. 7 9. 7 9 14 22 FDI as a percentage of Gross capital Formation In manufacturing 3 they play a vital role in social, political, and cultural development as well.However, the notable spread of SSI contributed to the increased severity of competition between these industries that often leads to the failure of these industries. Most SSI fail during the first year of establishment, and 90% of these industries are subject to fai lure during a period not exceeding their first 5 years. On the other side, the Mexican experience illustrates of the 200,000 small projects entering the market annually, no more than 70,000 projects continue in the market by the second year (Bencivenga, V. Bruce, S. and Starr, R. 1995).Table (2): The relative importance of the SSIs in Jordan (1990-2006) Year 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 No. of SSIs 52496 54696 64752 66160 66100 74896 76468 78580 81856 92923 106730 103753 105662 130149 126196 132166 135732 No. of all industries 58984 61388 74369 75920 80363 91520 93432 95856 98768 109532 118271 115820 118492 140338 141944 145699 150222 Relative importance 89% 89% 87% 87% 81% 82% 82% 82% 83% 84% 90% 89% 89% 92% 88% 90% 90% Source: Department of statistics, yearly statistical bulletins, various issues.As shown in table (2) the number of the SSI increased from 52496 projects in 1990 to 135732 projects in 2006. These numbers illustr ates the relative importance of the number of SSI of the total number of industries in Jordan is more than 80%. The SSI was distributed in Jordan into three districts as follows (Department of Statistics 2005): The northern district: 22% of the total small scale industries in Jordan. The middle district: 68% of the total small scale industries in Jordan. The southern district: 10% of the total small scale industries in Jordan.Furthermore, discrepancy in the relative importance of the spread of the SSI in the districts can be attributed to many factors. The most important factor is the demographic distribution that characterizes Jordan's districts, as well as to the nature of the concentration of the economic activities in these districts. However, the geographic distribution of the spread of the SSI may not relate to other economic indicators, but it is possible to accept it as an indicator to express the strength of most of these indicators in favor of the middle district.On the ot her hand, the lack of data and information about the geographic distribution of all the economic and social indicators concerning the SSI – such as investment , employment , production , sales †¦.. etc. – led to making the analysis inclusive for all of Jordan without dealing with details at the district level. 4 The investment Investment is the major driving force for the development process in any country. For instance, the greater the size of capital invested, the more its positive effects on the national economy. Table (3): Total amount of capital invested in the SSIs in Jordan (1990-2006) JD.Thousands* Year Small scale All industries Relative importance industries 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 26205 39347 44981 39149 46413 51345 47886 56048 54268 55355 57889 58322 60142 63324 65589 66639 67174 551811 591426 647104 751231 976636 947662 1208362 1354252 1429333 1438452 1457334 1467441 1492211 1521123 1543189 1551132 1561114 4. 7% 6. 7% 7. 0% 5. 2% 4. 8% 5. 4% 4. 0% 4. 1% 3. 8% 3. 8% 3. 9% 3. 9% 4. 0% 4. 1% 4. 2% 4. 2% 4. 3% Source: Department of statistics, yearly statistical bulletins, various issues. JD. 0. 71 = 1 $ From table (3), it can be noticed that the average of the relative importance for capital invested in the SSI is nearly 4% of the total capital invested in all industries during the period 1990 -2006. This illustrates that the SSI are characterized by the relative reduction in the capital needed to establish these industries compared to other industries. Such characteristics encourage and attract the investor's savings towards this category of industries because it achieves faster and bigger revenues compared to medium and large scale industries.Adding to such attractiveness the autonomy, flexibility and the accommodation the SSI are enjoying. Furthermore table (4) indicates that the average of the available capital for the SSI does not exceed 3. 6% of the total available capital for the different industries during the period 19902006. This is notably less than the average of the relative importance of capital invested in the SSI compared to the total invested capital. In other words, this category of industries depends on its financial resources from its own capital and from the circulated revenues more than the medium and large scale industries do. Table (4): Total value of fixed assets in the SSIs in Jordan (1990-2006) JD. Thousands Year Small scale All industries Relative importance industries 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 32641 45784 61329 48069 54317 72196 56977 69985 72803 73985 73376 72987 73324 73297 74122 75032 76125 980996 1007398 1030155 1062687 1603036 1698525 2084144 2471266 2480713 249687 250991 251543 257198 256244 259822 258970 259765 3. 3% 4. 5% 6. 0% 4. 5% 3. 4% 4. 3% 2. 7% 2. 8% 2. 9% 2. 9% 2. 9% 2. 8% 2. 8% 2. % 2. 8% 2. 9% 2. 9% Source: Department of statistics, yearly stati stical bulletins, various issues. It is important to notice that it is not realistic to explain the aforementioned result on the basis that the financial institutions did not perform their duties towards the SSI in financing their investment activities. The justification must be linked by knowing the nature of the fixed assets for this category of industries. Despite the attractiveness of SSI for investment, financial institutions seem hesitate to finance this industry.This situation can be explained by the fact that SSI are characterized as being traditional assets, handmade in many instances, and their low prices when comparing the capital assets of the medium and large scale industries. Also, the SSI does not conduct systematic studies for the benefits of their capital expenditure in the field of fixed assets. Therefore, financial institutions appear not willing to finance these industries at the current interest rate in the market because of the high risk.But the financial insti tutions could provide the finance for this category of industries at low interest rates only if these industries could provide more guarantees to the financial institutions. There is another alternative to financing SSI so as to receive the needed finance for their operations without bearing any additional financial burdens through loan guarantee's program. In order to over come this dilemma, the Central Bank of Jordan and the financial institutions established the Jordanian Company for Loans Guarantee in 1994, with the aim of providing the needed guarantees to cover the risk of the provided loans for SSI.This company guaranteed 5269 loans with JD. 140 million during the period 1990-2006. The financial institutions are characterized by their wide spread, as there are 17 banks providing the finance for this category of industries, and they accredited more than 24 programs. Some programs were oriented towards a specific age category such as the youth. While others oriented toward a sp ecific districts or specific geographic regions. Moreover the number of the institutions and the differences in financial programs for SSI, created a big discrepancy in the nature of the small loans terms.For instance, the interest rates ranged from 0% as in the case of the National Aid Fund into 22% for the Jordanian 6 Woman Department Establishment. The term of these loans extended from 3 months for the Women Loan Fund to15 years in the Agricultural Credit Corporation. On the other hand, the volume of the small grant reached JD. 192 million during the period 1990-2000. The first stage of the Social Security bundle program (1998-2000) provided loans backed by JD. 14 million for the SSI. The American Agency for the International Development (USAID) worked during the end of the last century to provide JD. 8 million as a grant to finance the SSI. This illustrates the relative sufficiency for the small financial grants compared to the needs to finance the activities of these industries during the past decade. To support this, one study conducted by the International Bank in the Middle East and several North African countries during the year 2005, showed that the financial gap for industries with less than 10 labors in Jordan reached nearly JD. 38 million, while the previous estimates for the financial gap for the SSI, and was JD. 48 million.Through this comparison it is evident that the financial gap was lowered, which means that the financial intuitions notably contributed in financing the SSI and the growth rate for the financing needs for these industries was lowered which contributed in reducing this gap. On the other side, the results of a field survey conducted recently by the Royal Scientific Society confirmed this indirectly as the study concluded that the cost reduction of the needed materials for production is one of the major factors that contribute to solving the problem.Employment The capability of the SSI to attract a large labor force is one of the most prominent aspects that characterized these industries. Also, the possibility of establishing these industries in all regions is considered an added function of the SSI to limit the unemployment in these regions. Table (5) indicates that the SSI provided opportunities for 18% of employment during the period 1990-2006. This percentage clearly demonstrates that the SSI contributes in alleviating the unemployment rate in Jordan.Table (5): Total no. of employees in the small scale industries in Jordan (1990-2006) Year Small scale All industries Relative importance industries 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 80134 83522 855121 88991 90115 93145 96244 98100 98541 100241 103788 93269 82008 123248 97340 100541 105211 421191 455621 479131 482231 491522 501993 521177 539981 544189 563131 585140 575930 573243 617466 705838 706111 706233 19. 0% 18. 3% 17. 8% 18. 4% 18. 3% 18. 5% 18. 4% 18. 2% 18. 1% 17. % 17. 7% 16. 2% 14. 3% 20. 0% 14. 0 % 14. 0% 15. 2% Source: Department of statistics, yearly statistical bulletins, various issues. 7 The importance of SSI for employment in Jordan was similar to their role in other countries. In the African countries SSI reached nearly 40% of the total labor force during the 1980s, while this rate was more than 50% for the developing countries during the 1970s and 1980s. The SSI in the United States contributed no less than 50% of the employment in the private sector during 1970s.In addition to the aforementioned, percentages one study conducted by the International Bank in 2005 pointed out that the rate of the labor force in the small and middle projects increased in developing and developed countries, such as Indonesia (79%), South Korea (78%),Turkey (62%),Brazil (59%),and the United State (52%). Also noted by comparing the contents of table (5) to the contents of table (3) is that the average capital density for each worker in the SSI reached JD. 2146 during the study's period 199 0-2006.This means that providing an additional job opportunity in this category of industries needs an investment of nearly JD. 2100, while average capital investment needed to provide a job during the same period reached JD. 1118, which is equal to the average of the capital density for each worker according to the industrial survey's data for the years 1984, 1988 and 1994. The result was surprising when it was noticed that the average of the relative importance for the number of the females working in the SSI during the research period was no more than 2% of the total labor force in these industries.In addition to what was mentioned above, the data by the Department of Statistics for the period 1990-2006, pointed out that the percentage of the labor force in the small scale industries was 92% of the total industrial sector. The average of the relative importance of working women in small scale industries did not exceed 5% of the total female labor force in the total industries dur ing the same period of the study. Some of SSI depends on employing foreign labor because low wages and salaries in this industries.Therefore, employment policies have to be geared to force the SSI to give domestic labors the first priorities for employment. However, the capability of these industries to eliminate poverty in Jordan is relatively limited. Production The SSI is characterized by their relative large contribution to the GDP. For instance, the average contribution of the SSI to the gross domestic product in Malaysia is 21%, the United States 40%, Spain 64%, Canada 52%, and France 54%. Table (6) shows the contribution of SSI to Jordan GDP is about 8. 5%. the significance of SSI to GDP could be noticeable by relating their ontribution to GDP ( 8. 5%) to their need for capital (4%) from the total invested capital. Table (6): Value added of the SSIs in Jordan (1990-2006) JD. Thousands Year Small scale industries 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 4955 2 56307 84191 76133 73393 85987 73277 84163 93049 94154 93690 95050 638955 643299 738460 766819 916853 1001738 988548 1089376 1145344 1149805 1116732 1140964 7. 8% 8. 8% 11. 4% 9. 9% 8. 0% 8. 6% 7. 4% 7. 7% 8. 1% 8. 2% 8. 3% 8. 3% All industries Relative importance 8 2002 2003 2004 2005 2006 96248 96119 98546 99187 100235 169870 1161779 1179806 1169901 1206509 8. 2% 8. 2% 8. 4% 8. 5% 8. 3% Source: Department of statistics, yearly statistical bulletins, various issues. This characterized can be explained by the nature of SSI as extensive use of labor which is considered the major element in the production process compared to the capital element. On the other hand, comparing the contents of table (6), to those of table (5), revealed that the average annual labor productivity for SSI during the period of the study reached nearly JD. 3600. While before 1990 the average was JD. 3300 annually.Additionally, the data of tables 5 and 6 showed that increase in the average of no less than 9%, which indicates an increase in the labor productivity in the SSI. Table (7): Total sales of SSIs in Jordan (1990-2006) Year Small scale industries 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 67272 89472 149612 115469 104037 113891 115675 117988 136515 130665 135788 137430 140870 142997 143065 144087 148980 1499371 1637914 1947837 2030058 2482996 2769218 2766048 3029266 3094727 3278654 3199054 3304530 3587861 3689954 3788293 3803572 4006590 4. 5% 5. % 7. 7% 5. 7% 4. 2% 4. 1% 4. 2% 3. 9% 4. 4% 4. 0% 4. 2% 4. 1% 3. 9% 3. 7% 3. 7% 3. 8% 3. 7% All industries JD. Thousands Relative importance Source: Department of statistics, yearly statistical bulletins, various issues. Table (7) shows that the average contribution of the SSI total sales for all industries did not exceed 4. 8% during the period 1990-2006. This average is considered â€Å"neutral† because it is completely equal to the small scale industries share of the total capital investe d in these industries. Analyzing the sales structure of the SSI in Jordan demonstrates that 99. % of total sales were directed into domestic markets. In other words, the share of these industries for international market did not exceed 0. 06% of the total sales. 9 Conclusion The findings of this study revealed: 1- Generally, the SSI plays an important role in achieving social and economic development. The average invested capital in these industries reached 4. 8% of the total invested capital in all industries, during the period 1990-2006. Also, the SSI provided 22% of the total job opportunities and contributed in achieving nearly 8. % of the total value added. Lastly, their share of the total sales in the industrial sector was 4. 8%, and most of the sales were in the domestic market. 2- Despite the positive effects of the SSI in the Jordanian economy, the SSI still suffer from many weaknesses such as low average employment of women which is due to the socioculture. The percentage of women working in the SSI was only 1. 7%. Also, the percentage of foreign labor in the SSI is relatively high. 3- The financial institutions are characterized by their wide spread.There are 17 banks providing finance for this category of industry and more than 24 programs have been accredited. Some programs are oriented towards a specific age category such as youths, and some institutional activities are exclusively for specific district or specific geographic regions. 4- There is an increase in the productivity of labor in the SSI, which indicates that the training programs directed towards these industries have increased. 5- Increasing the investment in SSI by 1% lead to an increase of the value added by 0. 78%, production growth by 0. 81%, and employment by 0. 7%. 6- All the results of the statistical analysis of the SSI were statistically acceptable and no differences were noticed between the effect of SSI and other industries on the economic development of the Jordanian econo my. 7- Marketing has been identified as one of the major problem areas of the small scale industries and it has been ranked as the second most important reason for the closure of small scale businesses. Accordingly, small firms will not be able to penetrate markets, national or international, even if marketing support is given by government agencies.Recommendations Based on this study's analysis and results, the following recommendations may contribute to increasing the role of development of SSI in the Jordanian economy. 1- Establishing government centers in all districts in Jordan to provide the needed services and facilities to SSI in order to increase their role in the economic development of the Jordanian economy. 2- Establishing specialized training centers for SSI to provide special training programs on how to establish a project and how to maintain the continuity of that project. – Fostering technology development through either technology transfer or technological in novations or inter-firm linkages should be emphasized in the light of dimensions of global competition and its negative fall out as well as positive opportunities, to SSIs entrepreneurs through seminars and workshops, at the local level.4- The financial infrastructure is needs, and an adequate inflow of credit to the sector should be ensured, taking into consideration the growing investment demands including the requirements of technological transformation. – Limiting the establishment of small scale industries to designated industrial areas for better monitoring and periodic surveys, enabling the Ministry of Industry to make policy corrections from time to time. 10 6- Establishing strong relations between small and large firms. One of the major objectives of this scheme would be to provide reliable information by large-scale industries to the smallscale industries about new methods of marketing and how to participate in the international market. 7- Increasing exports of smal l- scale industries with governmental aid by exhibiting their productions in International Exhibitions. – To reap the benefits of SSI, Jordanian policy and decision makers have to enact and enforce the employment of Jordanian workers in the SSI. 9- It is highly recommended that Jordanian policy and decision makers to work in cooperation with other interest groups to train and encourage SSI to employ more Jordanians women. It is obvious that a large portion of unemployed in Jordan is among women.

Hayleys Consumer HR policy

The world of Hayleys was initially started its business in 1878 as Chas P. Hayleys and company in Sri Lanka, was incorporated as Hayleys Ltd in the year 1952. Today it is known as the world of Hayelys with a globally competitive business portfolio spanning over 12 different sectors of enterprise. The main business portfolio of world of Hayleys fall under seven broad categories such as: Global market and manufacturing Agriculture and plantation Logistics and transportation Leisure and aviation Consumer products Power and energyOut of the sectors under consumer products comes the Hayleys Consumer Products Limited and the Consumer lighting, Consumer products contributes about 7% of the group's total turnover. Hayleys Consumer Products limited hosts home for many of the world renown brands in Sri Lanka such as Downy, Gillette, Olay, Whispers, Tide, Pantene, Kiwi, Pringles, Fujifilm, GP Batteries, 3M, Head and Shoulders, Philips and etc. These brands are basically operated under few divis ions such as Consumer Lighting, Consumer Imaging and Information, Consumer Healthcare, P;G products, New Business development.There is a supermarket channel owned by the Hayleys consumer named Haymart and there are outlets owned by Hayleys for perspective brands such as Hayleys Caf © Pixel for consumer imaging and information and Lighting craft for consumer lighting. Hayleys consumer products have reached a range of 70, 000 outlets throughout the country and expanding their business day by day as the corporate leader of the Sri Lankan market. During the last two years the group has delivered an increase in turnover of Rs. . 1 bn from the previous financial year. The group over the years has experienced a steady growth in terms of ncreased operations and simultaneously increased and favorable numerals. The share prices of the Hayleys group have also increased despite facing tough competition and rapidly changing market conditions. Investments made by the group has also rapidly incr eased within the past few years, this has especially been true for the leisure sector. 2.Examination on the five HR roles at Hayleys Consumer World of Hayleys has a proper Human resource management system under it, the world of Hayleys has a group HR department to control the HR activities of the companies under the group and each daughter company of the group has a separate HR department to control the HR activities going on inside the company. So does the Hayleys Consumer Products Limited, it has a separate HR department headed by a HR manager and HR executives under the manager.Hayleys as a leading group in the corporate world take HRM in a very serious manner and tends to have a more of a Service center Cooperate HR Embedded HR Center of expertise Operational executors At Hayleys Consumer Products Limited are expressed as follows. 2. 1 Service Center The HR department at Hayleys Consumer Products Limited has about 1 50 administrative and executive staff working within the compan y and in the outlets and number of employees working outside the company.There are permanent staff and also contract staff working under Hayleys consumer. Service center is providing all these people with a maximum service for their betterment. All the HR functions are computerized at Hayleys consumer and the news and information is passed through email to the administrative and senior executive staff, including their pay role and other relevant information every month, those information for the other Junior staff with no company email address is given manually. The HR system is outsourced atHayleys Consumer and all the details of every employee working under Hayleys consumer is inserted into the system where all the necessary details could be taken in a few seconds at the finger tips. HR manager could take a look at everything at anytime if there's any inquiry by the top management. Any employee at anytime can use the technology to contact the service center through email or otherw ise via calling the HR manager or any HR executive at anytime to solve their problems and issues regarding HR perspective. Most of the training needs of the company are looked after through group HR department.When the service center identifies any such need they inform the group HR department and arrange the necessary training programs, so the group HR decides whether the training should be given by an outsource company or it could be given within the organization. That is the main time where outsourcing comes in for the service center, and the evaluation is done through the company HR department. The provident fund at Hayleys consumer is the same as the group it is a private provident fund not like many of the other private companies in the country and the employees have quick access to their fund through he HR service center. . 2 Corporate HR Corporate HR usually lies on building a connection between the company's strategic goals and the flow of Human resource objectives. Since t he Hayleys Consumer is fully operated via the World of Hayleys group the strategic goals are made by the top management and the CEO and the Managing Director is instructed to work accordingly. Because of that the HR activities of Hayleys consumer is always monitored by the group HR department and the needed instructions are given in order keep in track with the Corporate Strategic goals.The recruitments are done Hayleys to achieve their objectives and that is mainly done through the consumer HR department with the guidance of the group HR department. And the direct communication channel with the consumer HR department along with the group HR department give the information flow a quick access and the relevant actions could be taken much quicker. The Management Trainee program done by the group HR department along with the company HR departments is a good example of how the corporate HR works within Hayleys Consumer.Even when hiring interns for the consumer the group HR gives a bette r help in selecting the best to succeed towards he strategic goals of the corporate. When a division in the company ask for a new recruitment the HR division goes through their information bases and do the surveys to select the best fit for the position to make the path easier to achieve strategic goals. The recruitments training and development is done and the objectives of HR are set in a way which the group strategic goals can be achieved.But also there some points where the corporate HR comes in the way, where there was an incident happened lately where there was a new recruitment was done at a shop and the hop manager requested the HR department to give an increment to the current employee since the new employee was also bought in with the similar package, even though the company HR manager agreed on it the CEO didn't since the policy of the corporate is not that. So there are both pros and cons in the Corporate HR at Hayleys Consumer. 2. Embedded HR Embedded HR is basically th e HR department building up a direct link with the departments in the organization and discussing with the managers what needed to be done in order to achieve the organizational goals. At Hayleys consumer the mbedded role in HR is not identified as vital and important and not given much of an attention by the HR department of the company. The HR manager has direct links with the managers and the staff of the organization and opens up to discuss any issue or matter regarding their work but the discussions needed to be done to acknowledge the managers are not done properly.Sometimes the HR manager doesn't know the vital situations in the company where there are threats for some employees Jobs where there are threats that some divisions could be closed down in the near future and the HR manager should have a clear understanding about such ituations to provide those employees with Job opportunities at least in some other company in the group but apparently the HR manager in the consumer products is not well aware of such facts, but the manager should be aware and should be able to provide necessary guidance for the employees in such situations. . 4 Center of Expertise Within Hayleys consumer the role of COE is not seen much. The training for the employee is usually given on the Job and there are some instances where employees are sent for training outside the organization such as outbound training done every ear for the employees and some training throughout the year for employees.Interns working for consumer are given much of a care by the managers and other the training given for the management trainees is anyways monitored by the group HR since they are part of group HR plan. The analysis on the Job satisfaction and the job evaluations are not done with a great effort but always the employees are given the priority in the organization. 2. 5 Operational Executor This role is basically to check whether the other five roles are going in order to achieve the goals both HR and strategic for the organization.This role is done by the group HR for the consumer products limited and given much of a notice where the HR roles are carried through well within the organization. Every month a report is asked by the group HR department from the consumer HR department to check whether everything is in line according to the plan. The group HR in that regard plays a major role in monitoring the company's carrying out on HR roles. 3.Conclusion Hayleys Consumer Products Limited has a more of a soft approach towards the human resource management where the freedom is given to the employees to carry n the work on their will to achieve strategic goals and company mission but there are some loop holes in the HRM in the Hayleys consumer products also like every other business organization the world and the loop holes can be overtaken if the HR department pays a little bit more attention towards them and make the work easier for the employees and make a safe and soun d environment to work for all the employees in the organization.

Byronic Hero The term Byronic hero was coined to describe a specific Essay

Byronic Hero The term Byronic hero was coined to describe a specific type of hero found in many of Lord Byron's works, arguably based on the author himself - Essay Example The historian and essayist Thomas Babington Macaulay said it best when he described the Byronic hero as â€Å"A man proud, moody cynical, with defiance on his brow, and misery in his heart, a scorner of his kind, implacable in his revenge, yet capable of deep and strong affection† (qtd Breen 155). This dark, highly mysterious gloomy hero can be found in the works of many romantic writers like Edward Rochester of the Jane Eyre novel by Charlotte Bronte in 1847 and Heathcliff of Wuthering Heights written by Charlotte’s sister Emily Bronte, also in 1847, and; Erik of the Phantom of the Opera, a 1910 novel by Gaston Leroux. Today, the Byronic hero continues to show up in many literary genres like the novel, short story, movie and even the comics. In Anne Rice’s Chronicles of the Vampire, for example, the characters of Louise and Lestat both approximate the qualities and characteristics of the Byronic hero (Hoppenstand & Browne 82). In the comic book genre, the fictio nal character of Spawn created by Todd McFarlane in 1992 embodies the dark, brooding, mysterious and the combined evil-good nature of the Byronic character. The plot of the comic story of Spawn revolves around a character named Albert Simmons who was once a decorated officer of the United States Marines and eventually also became a decorated US Secret Service. His act of saving the US president in an assassination attempt paved the way for his promotion as a Central Intelligence agent specifically in a high-level task force called US Security Group. However, Simmons was in a constant conflict with his boss with respect to operational strategies used by the group, believing that they unnecessarily involve innocent civilian lives. The conflict eventually came to a head and Simmons resigned and went home to his wife whom he beat out of his frustration and rage, an act which would later come to haunt him. His boss sent out an assassination order to end Simmons’

History Essay Example | Topics and Well Written Essays - 250 words - 2

History - Essay Example It is no wonder that hardly the first serious book on Progressive Era history was The Search for Order. Its author, Robert Wiebe, viewed this search as replacing such mores and values of small town community life as promptness, frugality, efficiency and foresight† with such assumptions of bureaucracy as rationality and functionality, management and administration, regularity and continuity. According to Wiebe Americans traded the values that had been regulating individual relationships for those oriented towards bureaucratic order because new interconnected industrial economy needed to be centralized and professionalized. As a result Americans have assumed bureaucratic Weltanschauung. Wiebe argues that such a worldview allowed for giving adequate responses to complicated problems unlike previous era narrow-minded, community-centered moralistic mind. As Wiebe puts it the Progressivism in fact was ambition of the new born middle class to realize its predestination through the mea ns of bureaucracy Work Cited Wiebe, Robert. The Search for Order, 1877-1920. New York: Hill & Wang, 1967. Print.

Justifying an evaluation Essay Example | Topics and Well Written Essays - 1000 words

Justifying an evaluation - Essay Example Griffith’s work in the film is fascinating both in the adverse and affirmative dimensions. The characterization features from different angles. For instance, the general scene development of the film is very accurate and authentic with reference to the music played, archives featuring and the natural landscapes that existed in the times of civil wars. The major theme of culture and racial prejudice forms part of the epic story of the film. Initially, what fascinates me about the film is the general presentation of reality with regards to the society. Some of these preside the film with defined warnings regarding the heuristic nature of war amongst different races. For instance, the film tends to seek clarity and relevance from the Biblical directives and Shakespeare works. Most of the scenes of the film disentangle the inappropriate trends of life and give way to light where darkness features most. The issue here is about virtues. It is thrilling to find a film that tries to establish the necessity of liberty. The â€Å"birth of a nation film† is a good pace setter. The first impressive instance about the film is that it takes a representation of the superior culture and the slave’s cultures. The actual history in America is that the whites dominate the northern region, and the African Americans dominate the south. The first part of the film features the introduction of the Africans into the American territory. The underside of disunity in the territory remains well established in the film. The film does not complicate the entire situation of hatred amongst the Africans cultural backgrounds and the American cultures. The film features two distinct families from the Cameroonian and American backgrounds. The film also features intensive political trends where some sides of the national house support intense need for the demolition of civil wars. Others support the need for safety and respect for the African culture thus

Comparative and interactional Aspect of Hinduism and Buddhism Religion Essay

Comparative and interactional Aspect of Hinduism and Buddhism Religion - Essay Example One thing common about the two, they emanated from India thus sharing common ideologies and roots (Elliot 16). Buddhism, in its origin at least is an offshoot of Hinduism. Though ranked amongst the profound religions in the world, Hinduism comes third and is much more popular than Buddhism. The founder of Buddhism known as Guatam Buddha had in early life brought up in posh life of Hindu society. This gives reference for Hinduism that it interconnects with Buddhism. Hinduism, better known as ‘Sanatan Dharma’, according to the Hindu people, it forms the indigenous life of the society, though its origin is still not certain. Factual studies have concluded that Buddhism grew because of the intricate nature involving Hinduism. Despite these differences, the two share a lot in common. This paper will draw the comparative analysis of the two religions, as well as how they differ from each other. On ritual dimensions, Buddhism and Hinduism belief and in practice of meditation. B uddhism does follow some rituals like meditation, bowing to the ground in worship while offering their prayers in their Buddhist holy places. Buddhist practices and rituals do not require any priest. On the side of Hindus, their rituals are complex as they vary from birth to death of that particular person. Unlike in Buddhism, priest on the part of the Hindus plays a major role in practice of these rituals (Elliot 140). This aspect form part of their ethical teachings. Despite this difference in them, meditation as a ritual has influenced their life. The two religions believe that meditation brings them close to nirvana. In Hinduism, someone has to intone in repetition the words ‘OM’ for focus and extol himself to higher realm. Through meditation, the worshipper drives to deep link to the holy deity. This comes due to the continual practice of this focusing technique; it brings them closer to eventual certainty and close to the proximity of more knowing. Equally, Buddha went through this thorough deep meditation. In their belief, through Buddha’s meditation He realized the power within, the deity of Dharma. This makes the ritual important to the followers of Buddhism. In order to reach nirvana, Buddha learned that inward reflection was the only way thus encouraged others to do so by practicing meditation (Elliot 270). Therefore, the two faiths delve on meditation. s Buddhism and Hinduism have universal understanding on the concepts of soul recreation. They differ on the value of sacred texts. As for the Hindus, Vedas is their pinnacle Smriti writings. It is part of the old age drafts, the times of Aryans. There are four divisions on Vedas . They contain over a thousand hymns, prescriptions on customs and fairy-tale stories on their gods. The writings travel around cyclical ideas as in other religions such as sustaining tranquility and normalcy in the world we live in. On contrary, Buddhism does not believe in such doctrines, or any other Hi ndu scriptures. They have they own scriptures known as the Tripitaka. This highlighted Buddha’s tradition. Rules of basic living and moral modalities as well as Buddha’s teachings and sermons abound there. They teach philosophical collections as well (Elliot 214). These comparisons highlight the nature of these two world religions and their etymological ratings. On the issue of Samsara, Hinduism and Buddhism converge to it. To both, living never ends for there exist circle of birth, death, and re-birth. For the Hindu’s, life is recurring, having neither the beginning nor demise. On point of death, away from the world we are reborn in another life but in very unimaginable form. These forms can vary. This successive rebirth allows one to continue learning, and live in respect of the personal dharma. Hinduists believe living in

The Media and Our Children Research Paper Example | Topics and Well Written Essays - 1500 words

The Media and Our Children - Research Paper Example Television and the media that it displays can bring about physical, mental, emotional, and intellectual implications. The negative ramifications and influences of television on children can result in permanence if the problem is not solved while they are still young. The more time that a child spends in front of the television, the less time they spend participating in anything else. Of all the things shunted aside and neglected for the sake of the television, exercise is often at the top of the list. The most favored activity while watching television, however, is eating sugary and starchy snacks. As such, obesity has become an increasing concern in young children due to the amount of time spent watching television in comparison to the time spent exercising or playing. Children that watch over four hours of television on a daily basis are more likely to weigh more than children who spend less time in front the television (Bryant & Thompson 128). When children combine constant immobi lization with continuous eating, they risk gaining an excessive, unhealthy weight. Unhealthy weight gain for a child carries with it the potential of other health consequences, such as diabetes, heart strain, which can lead to heart failure, and health complications as the child reaches adulthood (Liebert & Sprafkin 94). While some of these health issues can be prevented and even reversed if the weight is lost in a safe and timely fashion, if it is not taken care of, children can experience them for the rest of their lives. Media exists as entertainment, providing children with many shows and movies to exercise their imagination and to simply entertain. Unfortunately, there are just as many shows and movies that are not made for children but are just as easily accessible given the ease of using the television and navigating through the various stations and programs. Quite a lot of this media consists of graphic violence, sexual activity, and great quantities of drugs and alcohol. Th e younger that children are, the more impressionable and influenced they are by the things that they are subjected to by media. The graphic images and ideas that are presented to children can leave a lasting impression or negatively influence the way they view the world and respond to issues in their lives. A startling correlation has been found between media violence and aggressive behaviors and children displaying violent acts and behaviors (Kelemwork 29). As children witness these negative and often dangerous behaviors in the media, they feel that they are being condoned. Children become more willing to participate in these actions because they saw them on television, and then they apply them to situations in their own lives where they see fit. Instead of talking out their problems or seeking help from an adult, they allow the anger that they have learned to become solutions. Similarly, children engage in the risky behavior that is so openly displayed in media, such as promiscuit y, drug and alcohol abuse, and rebellion against authoritative figures. If children see these activities in the media, yet nobody is there to explain the difference between right and wrong, fact and fiction, the children are apt to experience the actions for themselves.

Why is terrorism difficult to define Essay Example | Topics and Well Written Essays - 500 words

Why is terrorism difficult to define - Essay Example Terrorism, as Oxford dictionary describes, is (1) "government by intimidation as directed and carried out by the party in power in France during the Revolution of 1789-94 . . . " and (2) "policy intended to strike with terror those against whom it is adopted." It is interesting to see that both definitions hold a common viewpoint for those people who resort to threats and violence that is outside the normal oppositional struggle against their enemies. Although this definition is easy to understand, if we look deeper we can find that this definition is vague. The question that this definition fails to answer is ‘How do we measure what extent of violence is considered ''outside the normal oppositional struggle'’? As we begin to understand this problem, we find that there is no objective criterion available to us to gauge what extent of violence and threat can be called as an act of 'terrorism'. This difficulty to find what qualifies as an act of terrorism is even more diff icult since ‘terror’ is used to describe a strategy rather than an act. The strategy is to send a message to the higher ups in the government that they and their policies are vulnerable, that there is common voice in the public that are against government’s policies and that public has the capacity to attack the government in case those policies aren’t removed. The most common type of terrorism in the world is religion related. Multitude organizations all over the globe fight to uphold their religion.

The benefits associated with exercising Essay Example for Free

The benefits associated with exercising Essay 1. Exercising lowers your risk for disease There’s no question losing weight is good for your health, and kicking your fitness up a notch has even greater benefits. Regular exercise has been shown to boost mood and banish anxiety, and lower your risk for stroke, Type 2 diabetes and certain types of cancer. It can also help you fall asleep quicker, and into a deeper sleep (just don’t exercise too close to bedtime). All great reasons to get your body moving on a daily basis! * It burns off blood sugar Recent Czech research showed that three months’ strength training improved insulin sensitivity in men with insulin resistance. A British study confirmed that exercise was linked to reduced metabolic syndrome—and that people who were unfit to start with benefited even more from the physical activity than those who were reasonably fit when they started. * It controls weight Exercise burns calories so you lose, or at least don’t gain, weight. A recent study showed that among people whose BMI averaged 41 (that’s morbidly obese) those who lost just 7 percent of their body weight through regular exercise regained healthy blood pressure and triglyceride levels, and the inflammation in their arteries dropped by between a quarter and a third, even though their BMI still averaged 38 (still too high). Numerous studies have confirmed that you don’t need to be skinny to be physically fit. * It cuts total cholesterol The major and most important effect of exercise is to raise levels of â€Å"good† cholesterol, thus reducing total cholesterol levels. An international review of multiple studies revealed that adding exercise to a weight-loss diet not only raised the good cholesterol but also increased the benefits of the weight-loss program and reduced triglycerides and blood pressure. * It reduces your heart rate Every 60 seconds, the average couch potato’s heart beats 70 to 75 times. An active person’s heart, on the other hand, is so strong that it can pump the same amount of blood in only 50 beats. That’s 36,000 fewer beats every day and 13 million fewer by the end of just one year. Exercise strengthens your heart and saves it having to work at a higher rate all the time. * It breaks bad habits In a study of 280 women, U.S. researchers found that those who gave up smoking were twice as likely to stay smoke-free—and gained half as much weight—as those who gave up without exercising. * It lifts stress and sadness The positive effects of exercise on mood were demonstrated in a British study where sedentary adults were randomly assigned to moderate intensity aerobic exercise, stretching exercises or none at all, for 12 weeks. Those in the moderate intensity group reported reduced tension, anxiety and confusion. The others did not. Additionally, a Berlin study revealed that just 30 minutes a day of exercise can be more effective than antidepressant drugs in treating depression. Exercise stimulates the brain to produce endorphins—the body’s â€Å"feel good† hormones. It has two other advantages: it acts immediately and has few harmful or dangerous side effects. * It could save your life According to the World Health Organization, inactivity causes 2 million deaths worldwide annually and is a major factor in breast and colon cancer, diabetes and heart disease. The World Hear Federation believes that inactivity is as bad for you as smoking a pack of cigarettes a day. 2. Be a good role model Child obesity is becoming a serious problem. Approximately 26 percent of Canadian kids aged 2-17 are overweight or obese. Even scarier, stats show that for the first time ever, today’s children will have a shorter life expectancy than their parents. With school gym programs being reduced and  screen time on the rise, we need to be our kids’ fitness role models. Encourage fitness by taking family walks after dinner, or trying out the Family Circus class. 3. Exercise boosts energy Winded by grocery shopping or household chores? Regular physical activity can improve your muscle strength and boost your endurance. Exercise and physical activity deliver oxygen and nutrients to your tissues and help your cardiovascular system work more efficiently. And when your heart and lungs work more efficiently, you have more energy to go about your daily chores. 4. Fully enjoy the things you love The more fit you are, the easier it will be for you to take part in the activities you enjoy. Whether it’s going for a hike and experiencing the outdoors, or playing with the kids, you’ll find yourself more able to keep up, and less short of breath. 5. Ease back pain and improve your posture A daily regimen of stretches and exercise can also do wonders for your back. By strengthening your core abdominal muscles, you’ll increase your overall strength, taking the pressure away from your back and helping to alleviate any existing back pain. 6. Take some time for yourself Whether it’s an early morning jog, an afternoon cycle class or a late night walk with the dog, solo exercise gives you the opportunity to have a few moments of peace and quiet, think about future goals, and take some much-deserved â€Å"you† time. It’s also the perfect excuse to listen to your favourite soundtrack while you work out!

Non Steroidal Anti Inflammatory Drugs (NSAID): Effects

Non Steroidal Anti Inflammatory Drugs (NSAID): Effects Non steroidal anti inflammatory drugs or NSAIDs are inhibitors of prostaglandin, they have several key therapeutic effects, anti-inflammatory, antipyretic (reduces fevers) and analgesic. NSAIDs prevent the synthesis of prostaglandins; theses are made from the enzyme cyclo-oxygenase (COX) which supports inflammation, pain and fever, there are two cyclo-oxgenase COX-1 and COX-2. NSAIDs block the enzyme COX thus reducing the amount of prostaglandins and therefore reducing inflammation, pain and fevers. The main mechanism of action of NSAIDs is the inhibition of enzyme cyclo-oxygenase (COX). COX converts the fatty acid arachidonic acid into endoperoxide, prostaglandins and thromoxanes. The prostanoids have many physiological functions such as protecting the gastrointestinal tract, renal, homeostasis responses, platelet aggregation, contraction of uterine smooth muscle etc. There are two isoforms of COX, COX-1 and COX-2. COX-1 produces prostaglandin that support platelets and protect the stomach therefore has the most adverse side effects. COX-2 is inducible and found is inflammatory conditions and some types of carcinoma. Some drugs only inhibit COX-2 which reduces adverse effects that are associated with COX-1, such as the irritation of the stomach lining. Prostaglandins have numerous tasks to play as mediators of inflammation. They enhance the action of histamine and other natural compounds causing vasodilatation and increasing vascular permeability to fluids. These two factors re sult in the symptoms of inflammation. As well prostaglandins they relay pain messages to the brain. This journal article supports my essay on NSAIDs  [i]  Salicylic acid and salicylates, obtained from natural sources, have long been used as medicaments. Salicylic acid was chemically synthesized in 1860 and was used as an antiseptic, an antipyretic, and an antirheumatic. Twenty-five years ago, it was proposed that the mechanism of action of NSAIDs was through their inhibition of prostaglandin biosynthesis. Since then, there has been general acceptance of the concept that these drugs work by inhibition of the enzyme cyclo-oxygenase (COX), which we now know to have at least two distinct isoforms: the constitutive isoform, COX-1, and the inducible isoform, COX-2. COX-1 has clear physiologic functions. Its activation leads, for instance, to the production of prostacyclin, which when released by the endothelium is antithrombogenic and when released by the gastric mucosa is cytoprotective. COX-2, discovered 6 years ago, is induced by inflammatory stimuli and cytokines in migratory and other cells. It is therefore attractive to suggest that the anti-inflammatory actions of NSAIDs are due to inhibition of COX-2, whereas the unwanted side-effects, such as irritation of the stomach lining, are due to inhibition of COX-1. Drugs that have the highest COX-2 activity and a more favourable COX-2: COX-1 activity ratio will have a potent anti-inflammatory activity with fewer side-effects than drugs with a less favourable COX-2: COX-1 activity ratio. The identification of selective inhibitors of COX-2 will therefore lead to advances in therapy. NSAIDs are highly lipophilic substances, adsorption occurs through the gastrointestinal tract, as NSAIDs are weak acids they are less ionised in the gastric juices and therefore are absorbed by the mechanism of ionic or diffusion tapping. Most NSAIDs are given as oral tablets or capsules; others are given by injection to avoid gastric irritation. The main use of anti-inflammatory drugs is in the treatment of pain resulting from rheumatoid arthritis and osteoarthritis. Rheumatoid arthritis is an inflammatory condition of connective tissue especially within the joint capsule; it may be described as an autoimmune disease, whereby the bodys own immune system starts to destroy the synovial membrane. This may lead a complete destruction of the joint. Osteoarthritis is due to a mechanical damage to the joint which leads to degeneration of the articular cartilage the hip joint is commonly affected. Prostaglandins are found in the hypothalamus are involved in raising the temperature of the body during infection, therefore NSAIDs are useful in inhibiting prostaglandins and reducing body temperature, this is called antipyretic . Most prostaglandin inhibitors are acidic drugs that can directly irritate the gastric mucosa. Prostaglandins in the stomach lead to a decrease in gastric secretions; therefore, inhibiting the synthesis of prosta glandins leads to an increase in sections which may lead to ulcers. Aspirin is an irreversible inhibitor of COX-1 but has adverse side an effect, most side effects of NSAIDs is related to their action on the gastrointestinal tract. In the stomach prostaglandins are normally involved in the protection of the gastric mucosa (lining of the stomach) against the corrosive actions of the gastric acid; prevention of prostaglandin synthesis by NSAIDs therefore remove this protection and make the stomach open to irritation and ulceration. NSAIDs themselves are irritant chemicals which have a direct effect on the gastric mucosa. Other Problems of NSAIDs such as aspirin have an effect the kidneys, because the role of prostaglandins in the maintenance of blood flow to the kidneys, NSAIDs often cause kidney damage and disorders of salt and fluid balance. This article shows the adverse effects and mechanism of NSAIDs on the gastrointestinal tract. Mechanisms of gastrointestinal (GI) injury NSAIDs injure the gut by causing topical injury to the mucosa and systemic effects associated with  mucosal prostaglandin depletion derived from COX-1. The systemic effects of NSAIDs appear to have  the predominant role. Because of that the use of enteric-coated aspirin preparations and parenteral or rectal administration of NSAIDs in order to prevent topical mucosal injury has failed to prevent the development of ulcers. Topical injury The acidic properties of most NSAIDs (included ASA) initiate mucosal damage. These weak acids remain in their non ionised lipophilic form in the highly acidic gastric environment. These conditions favour migration into surface epithelial cell, where NSAIDs are dissociated into the ionised form that traps hydrogen ions, inducing mucosal injury. Systemic effects NSAIDs inhibit cyclooxygenase (COX), a key in the biosynthesis of prostaglandins. There are two isoforms, COX 1 and COX 2. Traditional NSAIDs (tNSAIDs) and ASA inhibit both isoforms. Selective NSAIDs (COXIBs) spare COX 1 and primarily inhibit COX 2. COX 1 isoform is expressed in most tissues, producing prostaglandins that play an important protective role in the gut by stimulating the synthesis and secretion of mucus and bicarbonate, increasing mucosal blood flow and promoting epithelial proliferation. When NSAIDs inhibit this enzyme create a gastric environment that is more susceptible to topical attack by endogenous and exogenous factors. Besides, the inhibition of the COX 1 blocks platelet production of thromboxane, which increases bleeding when an active GI bleeding site is present .On the other hand, COX2 isoform is induced inmost tissues in response to inflammatory stimuli. Prostaglandins derived from COX-2 can be generated at the ulcer margin and appear to play an important ro le in ulcer healing through triggering the cell proliferation, promotion of angiogenesis and restoration of mucosal integrity .This isoform is the primary target for anti-inflammatory drugs. Therefore selective COX-2 NSAIDs while having little to no effect on COX-1 should result in effective pain relief with reduced adverse GI effects. This COX2 hypothesis has been challenged by data from animal studies. Wallace et al reported that inhibition of both COX-1 and COX-2 is required for NSAID-induced gastric injury in the rat. Aspirin (acetylsalicylic acid) was first isolated in 1829 by Leroux from willow bark. It can cause irreversible inactivation of cyclo-oxygenase, acting on both COX-1 and COX-2. Aspirin has many pharmacologic effects for example it has antipyretic action it reduces fevers and is rapidly effective in febrile patients, yet has little effect on normal body temperature. It has many effects on the body; prostaglandin PGE2 is produced in the brain and causes the temperature regulatory centre in the hypothalamus to raise the body temperature, Aspirin inhibits PGE2 production so body temperature falls. Aspirin also has anti-inflammatory action, during inflammation, prostaglandin and other arachidonic acid are produced and contribute to the pain, swelling and tissue damage, and aspirin inhibits the production of arachidonic acid thus reducing inflammation. It is a very good anti-inflammatory effects it helps in condition for example the treatment of musculoskeletal disorders, such as rheumatoid arthritis, osteoarthritis and ankylosing spondylitis. The ability of aspirin to control pain occurs both through a peripheral and central action when aspirin inhibits the synthesis of prostaglandins in inflamed tissue, and it prevents the prostaglandin from sensitising the nociceptors, by inhibiting prostaglandin synthesis in the brain. Aspirin is also thought to also modify transmissions in the pain conducting pathways. Aspirin has other analgesic effects which is usually effective for low- to moderate-intensity pain. Integument pain is relieved better than the pain from hollow visceral areas. Relief of pain occurs through both peripheral and central mechanisms. In the peripherally, it inhibits the synthesis of PGs in inflamed tissues, thus preventing the sensitisation of pain receptors to both mechanical and chemical stimuli. Also in the centrally, the analgesic site exists in close proximity to the antipyretic region in the hypothalamus. Its analgesia action is not associated with mental alterations, such as hypnosis or changes in se nsation other than pain. EFFECTS OF ASPIRIN ON PROSTAGLANDIN SYNTHESIS Both COX-1 and COX-2 enzymes are inhibited by aspirin, but not by opioids, acetaminophen, or tramadol. The active site of both enzymes appears to be at the end of a long, tubular channel in the molecule. Aspirin block arachidonates entrance to this channel (as seen in picture below). Aspirin does this by irreversibly acetylating a specific serine molecule (serine 530 for COX-1 and serine 516 for COX-2) When blocked by aspirin, COX-1 becomes completely inactive. COX-2, on the other hand, converts arachidonate to 15-R-hydroxyeicosatetraenoic acid (15-R-HETE). Neither enzyme is capable of producing prostaglandin H2, the necessary precursor of prostaglandin and thromboxane synthesis. Aspirin causes damage to the gastric mucosa partly by inhibiting the formulation of prostaglandins that protect stomach wall from gastric acids. Aspirin in addition has Gastrointestinal effects such as It can cause epigastric distress, nausea, and vomiting by irritating the gastric mucosal lining and stimulating the chemoreceptor trigger zone in the CNS. It may cause a dose-related gastric ulceration, bleeding, and erosive gastritis because of inhibiting the formation of PGE2, which inhibits gastric acid secretion and has a cytoprotective effect. Salicylates-induced gastric bleeding is painless and may lead to an iron deficiency anemia. Aspirin is used in restricted situation for the symptomatic relief of fever. Because of an increased incidence of Reyes syndrome in children who previously were given aspirin for the relief of viral fevers, it is now recommended that a child with any fever be given paracetamol instead, if medication is required. It is useful as analgesics for certain categories of pain, such as headache, arthritis, and dysmenorrhea. It remains the standard, first-line drug in the therapy of rheumatoid arthritis, and can provide relief of symptoms in acute rheumatic fever. Some clinicians recommend small daily doses of aspirin for prophylaxis of thromboembolism, stroke, or myocardial infarction because of its antiplatelet activity. Some adverse effects of aspirin when uses in large repeated dosages are headache, mental confusion, lassitude, and drowsiness, tinnitus and difficulty in hearing, hyperthermia, sweating, thirst, hyperventilation, vomiting, and diarrhea. Contraindications Aspirin, non-steroidal anti-inflammatory drugs and anticoagulants should be avoided in all patients with liver disease because of the risk of altering platelet function, causing gastric ulceration and bleeding. NSAIDs have also been implicated in precipitating renal dysfunction and vericeal bleeding in patients with end-stage liver disease. Although COX-2 inhibitors may cause a lower incidence of bleeding complication, currently they are avoided in patients with liver disease as their still pose a risk. Paracetamol is an analgesic agent. It does not have ant-inflammatory or anti-platelet activities, but it is a useful analgesic in febrile illnesses such as influenza. As paracetamol has no anti-inflammatory properties it does not inhibit prostaglandin thus have no affect on the gastric mucosa. As an analgesic, paracetamol is best taken on an empty stomach for fast action, as it gets absorbed faster. As it is not associated with Reyess syndrome, it is the preferred analgesic in the symptomatic treatment of children with viral infections. The mechanism of action of paracetamol is now thought to be via COX-3 inhibition. This enzyme is present in the brain and spinal cord and is selectively inhibited by paracetamol. Paracetamol has no action on COX-1 and COX-2, thus does not have any gastric side effects. The central action of paracetamol explains it antipyretic effects and its lack of other peripheral adverse effects associated with NSAIDs. Paracetamol has few adverse side effects as it is tolerated by the stomach because inhibition of prostaglandin in the periphery is weak; allergic reactions and skin rash sometimes occur. Heavy, long term daily use may predispose chronic renal disease.