Discovery to Debacle Essay Example

Discovery to Debacle Essay Introduction: The outgrowth of the monoclonal antibodies as regulative T cell activators raised a great ardor among research workers to develop them as potent go-betweens for immunotherapy. Although many of these monoclonal antibodies have been marketed for the intervention of assorted diseases [ 1 ] ( Bhogal, 2007 ) , some of them were unable to make this finish due to their discontinuance in the clinical phases. One such model theoretical account is TGN1412. TGN1412 is an IgG4 type of monoclonal antibody which acts as superagonist for CD28, a co-stimulatory receptor required for T-cell activation. Since TGN1412 activates the T cell without anterior activation of the T cell antigen ( TCR ) receptor it was designated as a superagonist [ 2 ] ( Bhogal, 2006 ) . However, the vision of using TGN1412 as an anti-inflammatory agent was crashed when it failed in the first measure of the clinical surveies. The stage 1 clinical test of this promising drug emerged to be a catastrophe taking to dangerous effects in the voluntaries. This reappraisal focuses on the find, presymptomatic development and ethical concerns related to the drug and the possible mistakes made during the period from its find to the ruin. All the above factors had a cascading consequence and contributed greatly to the drug s failure. This fiasco of TGN1412 demands the important change in the current drug testing form for the advancement of the hereafter development of drugs. Development: -To promote the activation of immunosuppressive regulative T-cells, TeGenero, a German Pharmaceutical company developed TGN1412, a wholly humanized monoclonal antibody by protein technology of the non-human species generated antibody ( mice antibody ) to obtain belongingss specific to worlds. Protein technology involved the transportation of the complementary determining parts of a mouse anti-human CD28 ( 5.11.A1 ) antibody into human antibody concatenation proteins derived from Chinese hamster ovary ( CHO ) cells [ 1 ] ( Bhogal, 2007 ) . Autoreactive T-cells doing redness and autoimmunity against certain cells and organic structure tissues are kept in changeless cheque by regulative T cells. Normal T cell activation requires both the T cell receptor and CD28, a receptor protein on surface of T cells for its proliferation and activation [ 3 ] ( Vitetta, 2006 ) . Harmonizing to surveies conducted by TeGenero, TGN1412 can trip the T cells of all specificities and release c ytokines by aiming an antigenic determinant of CD28, a extremely conserved part of CD cringle which is exposed on the extracellular surface of T-cell membranes, therefore short-circuiting the demand to T cell receptor specificity. With this hope of stamp downing the immune system by activation of regulative T cells, TGN1412 was developed as a fresh therapy for autoimmune and inflammatory diseases. In Rheumatoid Arthritis, an autoimmune disease, TGN1412 reduced the degrees of inflammatory go-betweens by activation of the T-cells. B-CLL, most common type of chronic leukaemia is associated with a high white blood cell count and slow accretion of a peculiar type of B-cell. TGN1412 is effectual in intervention of B-CLL by non merely triping and exciting the growing of lymph cells but besides heightening the antigen showing ability of B-cells associated with the B-CLL. [ 2 ] ( Bhogal, 2006 ) We will write a custom essay sample on Discovery to Debacle specifically for you for only $16.38 $13.9/page Order now We will write a custom essay sample on Discovery to Debacle specifically for you FOR ONLY $16.38 $13.9/page Hire Writer We will write a custom essay sample on Discovery to Debacle specifically for you FOR ONLY $16.38 $13.9/page Hire Writer After complete development, pre-clinical and carnal testing, TeGenero decided to continue with first in human clinical test to measure the safety, tolerability and pharmacokinetics of TGN1412 and supervise its immunogenicity and effects on T cells, B cells and on cytokine degrees in blood serum. For this intent TeGenero recruited Parexel, a separate clinical test unit. The test protocol submitted by Parexel was authorized by Medical wellness regulative bureau ( MHRA ) on 27th January 2006 approved by Medical Ethics commission on 14th February 2006. [ 2 ] ( Bhogal, 2006 ) Phase 1 Clinical test failure: Harmonizing to the test protocol designed, on 13 March 2006, the first group of 6 voluntaries received a dosage of 0.1mg/kg on and was scheduled to have farther escalating doses over three-week period. However, the test turned ruinous and had to be suspended when these voluntaries developed cytokine release syndrome with an unmanageable addition in tissue cytokine concentrations finally taking to multiple organ failure. [ 4 ] ( Schraven, 2008 ) Preclinical: The probe conducted by MHRA and the European governments after the clinical test stated that there were no mistakes in fabrication, preparation and no marks of taint in the batch TGN1412 administered to the voluntaries [ 4 ] ( Schraven,2008 ) . With the purpose of forestalling such fatal events in future, the expert groups were recruited by Secretary of the province for wellness to look into the mistakes taking to failure of the test. The presymptomatic surveies with regard to the species choice, invitro and exvivo testing, appropriate dose choice and carnal surveies were points subjected to re-examination. In-vitro testing: Sing the species choice, non human Primatess are most frequently considered for the presymptomatic testing due to their close familial and pharmacological similarity to worlds. In instance of TGN1412, Rhesus macaques and the cynomolgus monkeys were used as the theoretical account for surveies on the footing that the 6 amino acid epitope on the C D loop of CD28 to which the drug appears to adhere is wholly similar and conserved in both the macaques and the worlds. [ 5 ] ( Stebbings, 2009 ) After careful designing of the TGN1412 based on the conserved sequence of the non-human Primatess, it could place the recombinant human cells showing CD28 with high adhering affinity. Specificity of TGN1412 for CD28 was confirmed with adhering surveies on the human cells showing CD-28, Cytotoxic T lymphocyte antigen-4 ( CTLA-4 ) and the inducible co-stimulator ( ICOS ) , in which TGN1412 did non expose cross-reactivity with the CTLA-4 and ICOS with the fact that both these proteins have high grade of amino-acid sequence homology with CD28. In order to further synergize the species selectivity, adhering ability of TGN1412 in the human, Macaca mulatta and cynomolgus monkeys and gnawers and marmoset T-cells was evaluated. It was found that nanomolar concentration of TGN1412 could adhere specifically to human and Macaca mulatta and cynomolgus monkeys but non with marmoset and rodent T-Cells due to difference in the antigenic determinant of the marmoset and human CD28. In marmoset species , 2 of the amino acids out of 6 differ as compared to rat in which all 6 amino acids are different, therefore impacting the binding of the TGN1412 to CD28 of these species. All these surveies prompted the research workers to continue with the surveies on the Macaca mulatta and cynomolgus macaques. [ 1 ] [ 2 ] ( Bhogal, 2006, 2007 ) Along with pre-dominant look in human lien, CD28 is besides expressed in the lymphatic, respiratory, connective and female generative tissues. Even though being cognizant of this fact, the cross-reactivity surveies in cynomolgus monkeys were performed with limited tissues non accounting for complete tissue distribution of TGN1412. In add-on to this, cross-reactivity was observed with the respiratory CD28 which was unexplained in the redirect examination of presymptomatic trials since respiratory disfunction was observed in the voluntaries who participated in the test. [ 2 ] ( Bhogal, 2006 ) . Thus it was suggested that executing such surveies with wider assortment of tissues would greatly assist in the hereafter development of immunobiologics. In add-on to binding and the cross responsiveness surveies, invitro trials with human peripheral blood mononuclear cells ( PBMC ) were performed for foretelling the invivo specificity and the species sensitiveness for TGN1412 [ 5 ] ( Stebbings, 2009 ) . Since most maps of the antibodies are mediated by adhering of their Fc part to Fc receptor incorporating cells [ 4 ] ( Schraven,2008 ) , in-vitro trials finding specificity, with Fc immobilized TGN1412, which mimicked the Fc binding were performed in cynomolgus monkeys and adult male, due to high grade of similarity in their sequence homology of the Fc receptor. It displayed that TGN1412 could arouse the response merely when it was immobilized onto a surface, or coupled via immobilized Fc-specific antibody. In contrast to the above consequences, immobilisation of TGN1412 in the cynomolgus monkeys did non demo its action as a superagonist [ 5 ] ( Stebbings, 2009 ) . Alternatively it acts as conventional CD28 agonist necessitating T-cel l receptor and CD28 activation for T cell stimulation and above all that it did non trip the cytokine production as seen in the voluntaries in the clinical tests [ 2 ] ( Bhogal, 2006 ) . All these consequences indicated hapless species choice for the presymptomatic trials. Animal Trials: Pharmacokinetic and toxicological issues have been taken into consideration in correspondence with carnal surveies. Pharmacokinetic appraisals made during the comparative survey of the TGN1412 with its variant TGN1112 in Macaca mulatta macaques, indicated that after their IV disposal, both the drugs were present in the blood serum for 20 yearss, with the peak concentration of the T-cells and no indicant of the increased cytokine degrees. Due to the overestimate of these effects in invitro surveies, 28 twenty-four hours surveies were performed in the cynomolgus monkeys. The half life of TGN1412 in these surveies was found to be 8 yearss with ascertained addition in the expansion of the lymph nodes and enlargement of the CD4+ T-cells. Furthermore, 50mg/kg was set as the no-observed-adverse consequence degree ( NOAEL ) even though these surveies indicated 5mg/kg as an optimum dosage for TGN1412. With respects to the 28 twenty-four hours toxicologic surveies conducted in the cynomolgus monkeys, there was no indicant of the drug related toxicity and half life was similar to the pharmacokinetic trials. All the above consequences supported TeGenero in continuing with the clinical tests in homo for proving the safety and efficaciousness of the drug. [ 2 ] ( Bhogal, 2006 ) Methodological and Ethical concerns: -The calamity of the TGN1412 alerted the field of immunotherapeutics, to non merely meticulously study presymptomatic trials but besides safeguard the ethical regulations associated with each procedure in drug development. Sing the methodological concern, the disposal of appropriate dosage is really important. The dosage of 50mg/kg of TGN1412 for the disposal into the voluntaries was selected on footing of no-observed-adverse consequence degree ( NOAEL ) which was a high dosage [ 5 ] ( Stebbings, 2009 ) . However, the dosage selected should be of optimum concentration, optimum signifies that it should be low plenty to protect the safety of the voluntaries and high plenty to arouse the response for which it is tested. Thus the choice of the dosage should be based on use of all relevant information known about the drug including the freshness, species specificity and mark distribution, in vivo dose response curve and receptor tenancy with regard to concentration. From the invivo dose response curve obtained from the surveies on the Human PBMC, bell shaped dose response curve was obtained with optimal responses between 2-10ug/ml. These consequences stated that the dosage should be selected from the scope of doses falling within this curve and implied the usage of MABEL ( minimal anticipated biological consequence degree ) attack for choosing the safe and optimum dosage for the tests [ 5 ] ( Stebbings, 2009 ) . Second, the design of TGN1412 test required the disposal of the drug to six voluntaries within short clip continuance of two proceedingss. Since monoclonal antibodies have fresh mechanism of action, disposal into fewer voluntaries with sufficient clip intervals is recommended. A better method would be detecting the consequence of such drug in one voluntary before continuing with the test. A good pattern of documenting the medical history of voluntary was non followed in the instance of TGN1412 by the test carry oning grou p, Parexel. [ 6 ] ( Ferguson, 2009 ) Sing the ethical issues, each test performed must be in concurrency with the Helsinki s declarations to safeguard the rights and safety of each take parting voluntary. Conversely all take parting groups including the voluntaries and the research groups must follow the ethical guidelines. The inside informations of the approved survey by the Ethics commission must be given to the voluntaries. Consent signifier must be short, concise and comprehensive and each voluntary should be given adequate clip to analyze and do determination sing take parting in the test. In instance of any inauspicious events, the test groups must describe it instantly to the moralss commission to avoid put on the lining the life of participants. In instance of TGN1412 each voluntary was given a big amount of money as compared to other stage 1 tests. In add-on, the clip given to analyze the long consent signifier was limited [ 6 ] ( Ferguson, 2009 ) . Therefore, attention should be taken that none of the regulat ions are breached under any fortunes. The chief aim of the investigational survey on failure of TGN1412 was to better the drug development procedure and cut down its clinical failure. However, even after this catastrophe in 2006, many of the late developed drugs have undergone failure. Taranabant ( MK-0364 ) was developed by Merck A ; Co. for intervention of fleshiness, which is frequently associated with increased hazard of developing cardiovascular diseases, diabetes and malignant neoplastic disease [ 8 ] . Taranabant is a fresh reverse agonist of cannabinoid-1 receptors ( CB1R ) , which are of import in ordinance of organic structure weight, energy usage and lipid and glucose metamorphosis [ 9 ] ( Pacher, 2009 ) . The thought of cannabinoid exciting appetency was based on utmost hungriness experienced by hemp tobacco users [ 8 ] . This observation led to the birth of Taranabant which stimulates weight loss by adhering to cannabinoid receptors and forestalling their activation. The presymptomatic surveies indicated th at acute disposal of Taranabant inhibited the food-intake and weight addition in dose dependent form, therefore taking to weight loss and lessening in organic structure fats which were non observed in smasher mice deficient in the CB1R cistron. Based on these surveies it was found that merely 30-40 % CB1 receptor tenancy was required to advance weight loss. These consequences from presymptomatic surveies inspired the research workers to continue with clinical tests. The first clinical survey was carried out in 24 healthy voluntaries as random, double-blind and placebo controlled test. This survey was successful as it displayed additive and dose dependent addition in AUC0 and Cmax values, long half life of 38 to 69 hours and mild inauspicious events [ 10 ] ( Addy, 2008 ) . Phase II test carried out for 12 hebdomads in 533 patients confirmed that effectivity of Taranabant in bring oning weight loss as compared to the placebo. Phase III test was initiated in 2400 patients and was inten ded to be continued for 2 old ages. Even after 1 twelvemonth of stage III survey in March 2008, Taranabant was found effectual in cut downing dual sum of weight by dosage of 2mg of drug with combination of exercising and diet. However, in October 2008 it was withdrawn due to GI and CNS side effects associated with it. [ 8 ] ( www.drugdevelopment-technology.com ) . Gastrointestinal side effects associated were chiefly sickness, purging concern, drowsiness abdominal uncomfortableness, and increased intestine motion. Other drug associated symptoms observed were mood alteration, fatigue and increased sudating [ 9 ] ( Addy, 2008 ) . Happening of all these inauspicious events compels the research workers to retreat a specific drug from the clinical test. Many other drugs which appeared to be innovators in development of assorted diseases have faced the failure during their clinical testing continuance either due to their toxic effects in worlds or due to unsatisfactory degree of consequence for intervention of the disease. Flurizan ( tarenflurbil ) , developed by Myriad Pharmaceuticals was intended for the intervention of Alzheimer s disease by selective take downing the Amyloid degrees. However, it was withdrawn from Phase III clinical test since it was found to be unproductive in bettering the cognitive signals and everyday activities in Alzheimer s disease patients. [ 11 ] ( www.drugdevelopment-technology.com ) Decision: Since monoclonal antibodies have evolved to be one of the promising drugs in intervention of countless diseases owing to their novel mechanism, a argus-eyed reappraisal of the presymptomatic surveies before their disposal into worlds is critical. The presymptomatic surveies of the antibody based drugs should be performed in Primatess possessing wholly matched antigenic site with that in worlds. Apart from the detailed the analysis of the presymptomatic consequences and appropriate species choice, it is important to guarantee that these methods are validated. Standardization of these methods will assist in more accurate extrapolation of the similar effects in worlds and prevent such tragic events in future. Besides elaborate analysis of the comparative measurings of the binding affinities should be done for both human antigen and archpriest antigen, to command the unforeseen structural fluctuations of the proteins. If all these stairss were followed in instance of TGN1412, the awful event might hold been predicted and life of the voluntaries would non hold been on the hazard. A valuable lesson was learnt in the field of research that even a little faux pas in any portion of drug development might take to a large blooper and therefore careful hazard analysis and examination of each measure in the drug development in hereafter will greatly heighten the field of drug find, development and cut down the failure of possible drugs. Mentions: [ 1 ] N.Bhogal and R. Combes, Toxicology in Vitro Vol 21:1227-1232, 2007 [ 2 ] N.Bhogal et.al, ATLA 34,225-239, 2006 [ 3 ] E. Vitetta et.al, Perspective Immunology, Vol 313: 308-309, July 2006 [ 4 ] B. Schraven et.al, Immunity Vol 28:591-595, May 2008 [ 5 ] R. Stebbings et. Al, Current Opinion in Biotechnology, Vol 20: 673-677, 2009 [ 6 ] P.R. Ferguson, The SciTech Lawyer, Vol 5 ( 4 ) , 2009 [ 7 ] MJH Kenter and A F Cohen, Lancet, Vol 368:1387-1391, October 2006 [ 8 ] hypertext transfer protocol: //www.drugdevelopment-technology.com/projects/taranabant/ [ 9 ] Pacher et. al. , Arteriosclerosis, Thrombosis A ; Vascular Biology, Vol 29 ( 1 ) :7-9, Jan 2009 [ 10 ] C. Addy, Journal of Clinical Pharmacology, Vol 48: 418-427, 2008 [ 11 ] hypertext transfer protocol: //www.drugdevelopment-technology.com/projects/flurizan/

Do not miss these cities while exploring Europe

Do not miss these cities while exploring Europe The lesser-known European cities which are worth tourist attention Paris, Amsterdam, Copenhagen, Florence, Berlin†¦All these famous cities have become the visiting cards of Europe. However, there are many other European cities which deserve our attention as well. They have a lot of interesting things to offer. These underrated cities are full of hidden cultural and historic treasures. So, it is high time to explore them.   The charming, cobblestone city of Maastricht This Dutch city will definitely impress you with its French and Belgian twists in the architecture, Roman and Spanish ruins, and sophisticated drink and food. It is considered to be one of the oldest cities in the Netherlands. Maastricht is a lively and energetic place with beautiful historic streets and a distinct international spirit. The biggest attractions of Maastricht are the underground tours to the casemates. It would be very interesting to walk through the tunnels and listen to the stories about the life underground. You can also enjoy the stunning Limburg landscapes during a boat ride over the river Meuse. Don`t forget to visit the annual European Fine Art Fair and enjoy the artworks of contemporary and modern artists. The ancient, Arabic-inspired city of Cadiz The Andalusian city of Cadiz is almost entirely surrounded by water. It has no shortage of breathtaking views and tourist attractions. White houses, open plazas, cobblestone streets, wonderful beaches and seafood, and charming old center – all these things will definitely impress every visitor of Cadiz. This city is well known for its fabulous seafood and fish. At El Faro restaurant you can enjoy some delicious local dishes. Don`t forget to take an excursion to Castillo San Sebastian, which is a magnificent historic fortress, linked to the sea by a tidal causeway. Hamburg – a Germany`s Gateway to the World Hamburg is the second largest city in Germany, the biggest port, and the centre of international trade. It is one of Germany`s wealthiest cities. There are a lot of attractions in Hamburg which are really worth your attention. There is always something to marvel at the Fish Market, HafenCity, and Port of Hamburg. You can visit the century-old Speicherstadt, which is the world-largest contiguous warehouse complex. Elbphilarmonie in HafenCity is a new cultural and urban landmark of Hamburg. It is one of the ten best concert halls in the world, where you can enjoy the classical music culture, music of the 21st century and sophisticated light music. The Portugal city of Porto will become your love at first sight Its higgledy-piggledy medieval centre, charismatic locals, divine food and wine, beautiful monuments and bridges, tiles, shopping streets, hipster bars, flowering balconies, baroque churches, and colorful cliffs will definitely leave you breathless. This city looks like it has emerged from the pages of a storybook. The River Douro on the Gaia side and the historic centre of Porto belong to the World Heritage. Don`t miss to visit Casa do Infante, by Riberia, enjoy the great beaches and cafà © terraces at the mouth of the river Douro, explore Porto by night, try a francesinha, which is one of Porto`s specialties, and stroll through the Parque da Cidade, down the seafront. Perugia – the picturesque Umbrian city with rich history Perugia is a substantial town city with good transport links and a number of historical attractions. It is a medieval, hilltop city that rises above the lush vineyard and hills. It is a major center of medieval art and a major producer of chocolates. It is a home of the Eurochocolate Festival and Umbria Jazz Festival. The Saint Peter`s Basilica is one of the most significant and symbolic landmarks of the city. Fontana Maggiore is the main symbol of Perugia. It is a perfect holiday destination with the beauty of the architecture and active leisure active ideas. The charming city of Aarhus has plenty to offer Aarhus is the second-largest city in Denmark, which is full of opportunities for tourists. It is surrounded by beautiful nature. Here you will find wonderful areas for running, walking, and biking. It has several attractions that are renowned internationally. Den Gamle By, ARoS Aarhus Art Museum, Musikhuset Aarhus, Moesgaard Museum, and Tropical Houses at the Botanical Garden are the absolute best attractions in Aarhus. You should definitely visit this city if you are interested in art and architecture.

Political Science - Global Warming Essay Example | Topics and Well Written Essays - 500 words

Political Science - Global Warming - Essay Example The most prevalent of these gases is carbon dioxide. There has always been a natural layer of greenhouse gases in the Earth’s atmosphere, but the present augmentation is widely held to be the result of human activities, primarily the burning of fossil fuels and environmental alterations, especially deforestation. The burning of fossil fuels – coal, oil and natural gas – is mainly done in industrial processes, in energy production, and also in transport. Because fossil fuel consumption is much greater in industrialized and more economically developed countries, North America, Europe and Asia are responsible for over 90% of global fossil fuel output. Deforestation, meanwhile, is most serious in South America, and especially in the Amazon basis. Furthermore, if current trends continue, fossil fuel consumption will continue to increase, especially as countries with large populations, such as India and China with a combined population of over 2 billion, rapidly indust rialize. All of this is causing the temperature of the Earth to increase at a much faster rate than is usual, and perhaps at a rate faster than it has been for thousands of years. The increasing blanket of greenhouse gases traps heat from solar radiation in the Earth’s atmosphere, and as the temperature within becomes higher, water stored as ice in glaciers or the ice caps is melting, causing sea levels to rise.

Health and Safety Strand Essay Example | Topics and Well Written Essays - 6500 words

Health and Safety Strand - Essay Example However, they may not know the immediate cause. It is indicated that most of them may not actually know that the vibration exposure may be the main cause. Hands to arm vibration on the other hand occur when individuals hold vibrating machines. However, such vibrations are not of high magnitude compared to that causing whole body vibration. Nevertheless, it has effects on the body especially when it is uncontrolled. It may cause loss of decreased grip and hand sensation. It has also been said to cause carpel tunnel syndrome. This happens when pressure on the median nerve causes numbness and weakness on fingers and hands. Apart from the above mild health problems, research conducted in the Europe and Australia have indicated presence of some of the fatal ailments. Both studies agree that mental disorders, cardiovascular diseases and occupational cancer as some of the most likely health problems. With lack of legal measures controlling the exposure to vibrations, it has become difficult to control these effects. However, many critics agree it is almost impossible to prevent machines from vibrating. It will therefore be difficult to protect employees from these harmful exposures. However, the researchers have indicated job rotation and reduced duration of exposure as some of the ways to mitigate this effect. (i) Describe the nature of occupational vibration exposure and the health effects of exposure to vibration; provide researched examples of affected workers or groups of workers Literature review Vibration exposures as indicted above should not be taken for granted. Majority of employees are not aware of the health effects of exposure to vibrations (Seidel 2000, p.26). Through they may experience complications from time to time; they might note relate them to vibrations. There are several studies, which have been carried out in a view to study the relationship between vibration exposure and health effects (VIBRISKS 2007, p.89). Most of those studies agree on one issues; that exposure to constant and persistent vibrations can result in fatal ailments. In 2008, the Australian Safety and Compensation Council (ASCC) decided to find out how its workers were being affected in terms of health due to vibration exposures. The council decided to carry out a survey with the help of National Hazard Exposure Worker Surveillance (NHEWS) team. The main target subjects were workers in the farming, fishing, transport, industrial and the shipping sectors. These are the main occupations where individuals are more likely to be exposed to some kind of vibration (Macias 2007, p.90). The main reason for conducting the study was to find out whether the increased number of diseases such as occupational cancer and cardiovascular was in any way linked to the continued exposure (Paoli 2001, p.57). A sample of about 4,500 workers from the sectors indicated above was selected for the study. The researchers used the random sampling method to ensure that all subjects wer e given equal chance to participate in the study. Telephone calls were made randomly to the employees where they were asked questions about their occupation and how long they had worked. Secondly, the researcher wanted to know whether individuals understood the effects of vibrations on their health. Thirdly, subjects were asked to state some of the ailments they had been diagnosed with in the recent past. The research findings found that all the subjects were involved in one form of

Social Marketing Assignment 2 Example | Topics and Well Written Essays - 1000 words

Social Marketing 2 - Assignment Example There is need to sensitise the population about the need to seek professional medical services and also avail the services to the people (Lee & Kotler 2011). The campaign will be targeting various stakeholders who can be involved in delivering the communication and the services within the programme. The campaign will be seeking to sensitise the aboriginals on the need for seeking professional medical assistance when faced with health complications (Neiger et al. 2003). This campaign’s objective will be achieved through ensuring the active participation of the various groups of people being targeted by the campaign. The targets will include the following The fundamental focus of the campaign will be on the change of behaviour among the aboriginals to begin using healthcare facilities rather than relying on their traditional medicine in the treatment of various ailments. A change in the behaviour will be initiated by the campaigns which will be sensitising the people on the importance of visiting healthcare facilities (Lefebvre 2011). The campaign will be aimed at educating the people on the importance of depending on the professional healthcare services offered at institutions. The target groups will be informed through the media and direct communication delivered through social organisations providing other services to the community. The application of these methods will ensure that the target populations are reached by the campaign message in order to achieve the objectives of the campaign. Freedom from diseases will be the name of the campaign which will be undertaken in seeking to achieve the objectives that have been defined within the plan. This name of the campaign will be communicating the target for the whole campaign as well as the benefits which people will be getting from the product. Active involvement will be leading people

The role of family power structure

The role of family power structure Family Power structure plays a critical role in family health functioning. Power has been defined as the ability to control, influence or change another persons behavior (Friedman, 1998). Power is related to resources. Control over resources (eg. money) infers power. In most families, parents control these resources. There are three types of family power namely chaotic power, symmetrical power and complementary power (Hanson, 2001). The power structure in my family is complementary power. It is defined as requiring dominion-submission dynamic within the family structure. In this family-power type, healthy families are characterized by parents having a clear family advantage that their children recognize and accept. Although my father brings home the bacon every month, power is mainly shared between my parents. The decision-making in my family is highly dependent on my parents. Although my sister and I are involved in the decision-making, my parents are mainly responsible for making all sorts of decisions in the family from purchasing household furniture to deciding on a holiday destination to the meals we have together. Family power structure is not fixed. As I turned 18 this year, my parents recognize me as an adult and would listen to more to what I have to say and how I feel. My parents are not as power-dominant as they were 10 years ago. 1.2 Subsystems All families develop networks of co-existing subsystems formed on the basis of gender, interest, generation or function that must be performed for the familys survival. Each member of a family may belong to several subsystems. Each subsystem can be thought of as a natural coalition between participating members. Subsystems in a family relate to one another according to rules and patterns. There are three types of subsystems in my family namely spousal, parental and sibling subsystems. For example, the spousal subsystem educates children about male-female intimacy and commitment by providing a model of marital interaction. Ways of accommodating one anothers needs, making decisions together and managing conflict etc. Another example, my parents define the boundary of a parental subsystem by telling me as the oldest child to not interfere when they are reprimanding my younger sister. Parental subsystem also includes child guidance, nurturing, limit-setting and discipline. 1.3 Boundaries Boundaries are invisible barriers that keep subsystems separate and distinct from other subsystems. They are maintained by rules that differentiate the particular subsystems tasks from those of other subsystems. Boundaries may either be rigid, diffuse or clear. Disengaged families have rigid boundaries which leads to low levels of effective communication and support among family members. Enmeshed families have diffuse boundaries which make it difficult for individuals to achieve individualization from family. Clear boundaries are more of a balance as they do not fall on either extreme ends of rigid or diffuse. Clear boundaries are firm yet flexible, permitting maximum adaptation to change. The boundary in my family is clear. For example, my parents temporarily redefine the boundaries of the parental subsystem when she tells me to be in-charge of the house when they are away from home. Many years ago, my parents would ask my aunt to come over to care for my sister and I while they are away. This shows that the parental subsystem is flexible enough to include other people temporarily. 1.4 Triangulation Triangulation is used to describe a situation in which one family member will not communicate with another family member unless a third family member is present, forcing the third family member to then be part of the triangle. In this triangulation, the third person will either be used as a messenger to carry the communication to the main party or as a substitute for the direct communication. Usually this communication is an expressed dissatisfaction with the main party. For instance, my family used to be very united until a year ago when my sister who was one of the top PSLE students in her primary school dropped out from secondary school at secondary two suddenly. She stopped attending lessons and was extremely rebellious towards my parents and me. My parents having high expectations from my sister were absolutely furious and upset when she decided to quit school. Numerous attempts to persuade her to attend school failed again and again until a point when my parents gave up convincing her. However, they still talk about my sister to me all the time, mentioning how stubborn/ignorant she is and that she would regret her decision later in life. 2. Communication patterns McLeod and Chaffee (1972) came out with a scheme to analyze family communication patterns (FCP) to examine the role of family communication. In this model, the family communication environment is characterized by the extent to which the family emphasizes on socio-orientation and concept-orientation. Socio-orientation stresses the importance of harmony in the family and avoidance of conflicts. Concept-orientation encourages children to think about and discuss political and social issues. In a highly socio-oriented family, children should not argue with parents and should not express opinions different from other family members so as to maintain social harmony. On the other hand, in a highly concept-oriented family, parents believe that children should look at both sides of issues and talk freely about these issues. Using these two dimensions, McLeod and Chaffee (1972) introduced a four-fold typology of family communication patterns as seen in Figure 1. Figure 1 High on both dimensions of socio-orientation and concept-orientation, the communication pattern in my family is consensual. Consensual families emphasize both relational harmony and free communication exchange. Every member in my family is able to express our ideas freely as long as internal harmony in the family is maintained. Since young, my parents have encouraged both my sister and I to voice out displeasures in the family openly but stresses the importance of logical reasoning behind it. Like most traditional Asian families, my family tends not to express affectionate behaviors in the form of hugging or kissing towards or saying mushy words to one another. Instead, my parents would constantly ask me questions regarding about my school life, the friends that I go out with, among many others that revolve around my daily life. I suppose these are ways of displaying affectionate behaviors in my family. There are few conflicts in my family. Nevertheless, whenever one arises, we tend to face each other openly and voice out our concerns. My father would always play the middle-man whenever I had an argument with my sister and he would always ensure both parties are treated fairly and just. 3. Family environment Based on Olson, Russell and Sprenkles (1979) Circumplex Model, the Circumplex Model assumes that the difference between functional and dysfunctional families is determined by two interrelated dimensions: cohesion and adaptability. Cohesion is defined as the degree of attachment and emotional bonding among family members. There are four various degrees to the cohesion dimension namely disengaged, separated, connected, and enmeshed. Families that are disengaged lack family bond and loyalty, and are characterized by high independence. On the other hand, families identified as enmeshed are characterized by high levels of closeness, loyalty, and/or dependency. Adaptability is the ability of the family to change power structure, roles, and relationships in order to adapt to various situational stressors. It too has four degrees namely rigid, structured, flexible, and chaotic. Families with low levels of adaptability are considered inflexible or rigid. Rigid family types are characterized by authoritarian leadership, infrequent role modification, strict negotiation, and lack of change. Families with high levels of adaptability are considered chaotic as it is changing too frequently. Chaotic family types result from a lack of leadership, dramatic role shifts, erratic negotiation, and are characterized by frequent change. Based on the Circumplex Model, my family environment is balanced. It has moderate level of both adaptability and cohesion. Power structure is not fixed and there are times when there is a temporary shift in power to adapt to various situations. For example, I am responsible for taking care of my sister when my parents are out. Another example is when an deciding on a holiday getaway, power is shared among each family members to be involved in decision making. 4. Family Rules Family rules help family members to get along better, and make family life more peaceful. Effective rules are positive statements about how family members want to look after and treat one another. I have become so accustomed with my own family rules that sometimes I do not even realize that some of my daily activities are actually in fact, family rules. Dos and donts rules regarding family members safety, manners and daily routines were set up in my family since I was young. Of course these rules are constantly changing as my sister and I grew older with more responsibility in our hands. Rules such as be home by 10pm and do not lock the doors at home are a thing of the past when I was much younger. Today, the rules are much more flexible. For instance, if I were to return home late or spend the night at a friends house, all I have to do is to call home to inform my parents. There are also fewer family rules as my sister and I are expected to be able to care for ourselves. Moreover, rules set when we were young are already deep-rooted in our daily life. 5. Family values and attitudes Family values are political and social beliefs that hold the nuclear family (parents and children) to be the essential ethical and moral unit of society. 5.1 Money From a very young age, my parents have taught me the importance of saving up money and spending them wisely. Every week, I was to slot in leftover coins in a piggy bank. Years passed by and today I still have the habit of keeping all my loose change in a piggy bank and when it became full, I would then deposit the money into the bank. My parents are prudent in spending money; they only buy what is deemed necessary and seldom splurge on luxury goods. However, there are times when my parents think that it is worthwhile to spend more money such as holding birthday celebrations or Chinese new year celebrations at home. 5.2 Religion My family is a little religious. My parents are Buddhists and they made an effort to pay their respects to the deities at temples annually. However, my sister and I do not have a religion but our parents do not force us to join a religion too. There are no altars at home and my parents do not carry religious charms either like a pendent or a talisman with them. 5.3 Education Like most parents in Singapore, my parents take education very seriously. My father stresses that education is the key to survival in Singapore and this is especially more true since Singapore has been ranked the most competitive country in the world in 2010 by Time. Although my parents view education as important, they also know that each individual has their own limitations towards studying. My parents want my sister and me to have a positive mindset towards studying but yet at the same time not to overwork ourselves. The ideal model is to strike a balance between work and recreation. 5.4 Success/failure My parents are rather reasonable and they know that success and failure are part and parcel of life. My parents view success as achieving ones goals. For instance, one of my goals in secondary school was to get into Singapore Polytechnic (SP) and I did well enough during my O levels to enroll in SP. My parents were very happy and proud of me. On the other hand, I did not get into the course of my choice so I felt disappointed because it felt like I had succeeded and failed at the same time. My parents told me that one couldnt always get what we have aimed for and as long as I have tried my best, thats all that counts. 6. What I have learnt from my parents relationship What I learnt about marriage from my parents relationship is to treat your partner as a friend. Marriage is a lifelong process full of ups and downs. My parents are both committed to overcome obstacles and being the best spouse and friend to each other. My parents are always joking around. My mother loves my fathers sense of humor and they always laugh at the silliest things. This taught me that being playful is a crucial part of marriage and nothing should be taken too seriously in a family. My parents also speak kindly of each other. My mother always told me that my father was a good father and a hardworking man. In addition, they also give each other nicknames as some term of endearment. I learnt the significance of having interests/hobbies different from your spouses too. My father and mother have different interests. My father enjoys watching detective crime television programs while my mother loves watching Korean Dramas serials. My mother would never last an episode of detective crime programs but that seems okay because they respect each others alone time as well. This also taught me that it is fine to have a degree of independence in a marriage too. 7. Attitude towards authority I have a positive attitude towards institutional authority (parents, teachers, police, and the law). I tend to respect the rules and abide by it. I held many student leader positions in schools too. Positions such as class monitor in primary school, student counselor and National Police Cadet Corp (NPCC) non-commissioned officer (NCO) in secondary school and class chairperson in my polytechnic life. This is mainly due to my strict upbringing from early childhood. My father was a very strict man. I still remember the times when my father would cane me whenever I got into trouble in primary school. Furthermore, I would have to write a reflection about my wrongful actions. I used to be very afraid of my father when I was very young. However looking back in time, I realized that my father just wanted me to grow up to be a good person and I am grateful for what my father had done to make me the person I am today. 8. Attitude towards sibling My relationship with my sister has definitely seen better days. We used to be very close and play with each other a lot. However in recent months, my sisters attitude has grown worst. She became very temperament and gets annoyed very easily. We had a lot of quarrels with each other and soon grew distant. Nowadays, we seldom speak to one another. 9. Level of differentiation from family Level of differentiation refers to the degree of ones ability to distinguish his own thoughts and emotions from that of his own family. Individuals with low level of differentiation are more probably to become reliant on others approval and acceptance. They either conform themselves to others in order to please them, or attempt to force others to conform to themselves. Thus, they are more vulnerable to stress and they struggle more to adapt to life changes. Individuals with high levels of differentiation recognize that they need others, but they rely less on others acceptance and approval. They do not only adopt the attitude of those around them but take into account their principles thoughtfully. These enable them decide significant family and social issues, and resist the feelings of the moment. Thus, despite conflict, criticism, and rejection they can stay calm and clear-headed to differentiate thinking rooted in a careful assessment of the facts from thinking clouded by emotion. Well differentiated individuals choose thoughtfully and act in the best interests of the group. I think my level of differentiation from my family is balanced. I have my own thinking and my own point of view. I am not afraid to have a different mindset from my family members. My parents also encouraged my sister and I to become more independent, to be ourselves and not conform for the sake of pleasing others. 10. Family strengths 10.1 Caring and Appreciation I think I am very fortunate to have a family who is caring and appreciative. Even if a family member makes mistakes, other members would to encourage and support one another. My parents notice and share positive qualities of each other. For example, they pay attention to another persons polite behavior or something nice he or she did or said. They notice the characteristics, skills, achievements and special qualities that make the other person unique. My father would write encouragement messages on his red packet during Chinese New Year. These messages are inspirational and reassured me that my family members do care about me. 10.2 Good Communication Furthermore, there is communication between me and my parents. We talk and share our feelings, hopes, dreams, joys, sorrows, and experiences. I would tell the daily happenings in school or with my friends just to update my parents about whats going on in my life. My parents take the time to listen and respond to what I have to say. 10.3 Openess to change There is a set of family rules in my family. These rules are ways to deal with daily life. Some of the more obvious rules consist of who does the cooking, who washes the dishes, who does the laundry or who clean the toilet. Other less obvious forms include: Who has the authority to make what decisions? How are differences of opinion handled? How are anger, affection, or other emotions expressed at home? 10.4 Working together Most of the time, my family make decisions, solve family problems, and do family work together. Everyone participates. Parents may be in charge of the decision-making at home but the childrens opinions and efforts are invited, encouraged, and appreciated. For example, whenever my parents decided to buy a new television set, they would always ask for opinions about which television is suitable for the family. It makes my sister and I involved in the shopping as well and let us know that what we say counts. I learnt that if parents allow their children to make real decisions, it enables children to grow up to be responsible adults. Children need opportunities to make decisions, to be involved in family decisions, and to observe the parents decision-making process and outcomes. Children are more motivated to carry out their responsibilities if they have some say as to what those responsibilities are and can see how these particular activities help the family. Teenagers are keener to go along on a family vacation if they help decide the destination and itinerary. 11. How has my family affected my personality? What are the weaknesses you want to improve and what are the strengths you want to maintain in yourself. Based on a study on more than 100 children conducted by psychologist Diana Baumrind, she identified four important dimensions of parenting which affects the childs personality. They are disciplinary strategies, warmth and nurturance, communication styles and expectations of maturity and control. Based on these dimensions, Baumrind suggested that the majority of parents display one of three different parenting styles. Further research by also suggested the addition of a fourth parenting style (Maccoby Martin, 1983). The four parenting styles include authoritarian parenting, authoritative parenting, permissive parenting and uninvolved parenting. My parents parenting style suit authoritarian the most. My parents establish house rules and guidelines and expect my sister and I to follow them. However, my sister and I were also involved in the rules setting so we were able to find them realistic. This parenting style is much democratic. When children fail to meet the expectations, authoritative parents are more nurturing and forgiving rather than punishing. Although my father punished me whenever I broke the house rules; he would always end it off with nurturing and kind words. My parents are assertive, but not intrusive and restrictive. Their disciplinary methods are supportive, rather than punitive. I think I grew up to be a socially responsible and cooperative person. I tend to avoid conflicts with people and adopt the make more friends than enemies mindset. I lean more towards the extrovert scale as I enjoy the company of my friends. My friends told me that I am a good-tempered person too. They dont see me get angry because I am not bothered by the slightest issues. Another strength that I have is being persistent and committed. Once I set my mind on a target or a goal. I would thrive to achieve it. My parents have been teaching me the importance of goal-setting since young. I also gain a huge sense of pride and satisfaction whenever I accomplished my goals. One weakness that I have is being perfectionist. I am very attentive to details and would not be satisfied unless I get the exact results that I wanted. Most of the time striving for perfection is tiring and time consuming. My project members would sometimes find me a pain in the neck when I was not satisfied with their research work. Another weakness I have is laziness. I think I have been too pampered from young. I seldom do household chores because my mother is a housewife and she does all the housework. Well, almost all, my father did his part too. As such I became reliant on my parents to do my own laundry, to wash my dishes etc. I have been trying to increase my contribution to my family by doing some household chores but its hard to do so especially since I have done almost no housework since young but Im not giving up easily. In summary, family relationships are one of the longest relationships we would ever have in our life. We should never take our family members for granted but should cherish them instead.

What Sort Of A King Was Duncan? :: essays research papers

We were not told an awful lot about Duncan in Shakespeare’s Macbeth. He had very few lines, and appeared on only a few occasions. Despite this, I was able to gather a fair idea of Duncan’s character, through the interpretation of messages hidden within the text.Duncan was a kind and good man. There are several segments of the play that show this; as I have demonstrated below.Duncan is an extremely trustworthy King of his fellow men. He trusts his men with his life, his children, his throne, and most highly, his kingdom. He has no other choice but to trust these men. "The service and loyalty†¦ throne and state, children and servants, Which do but what they should by doing everything Safe toward your love and honour†¦"Macbeth [I.iv.22-27]We see how he surpasses a blind eye to the people who serve him. He cannot judge them in anyway, for he thinks of them as pure and good as himself. He also thought that Macbeth is a true man to him. Later on, we see how his judgment has not served him well."†¦He was a gentleman on whom I built An absolute trust†¦" [I.iii.14-15]Duncan regards his fellow men rather highly. He often praises their work and service to himself and his kingdom:(1) "Welcome hither. I have begun to plant thee, and will labour To make thee full of growing. -Noble Banquo, That hast no less deserved, nor must be known No less to have done so, Let me infold thee, And hold thee to my heart." [I.iv.27-32](2) "My worthy Cawdor" [To Macbeth I.iv.49](3) "True, worthy Banquo; he is full so valiant, And his commendations I am fed: It is a banquet to me. Let’s after him, Whose care is gone before to bid us welcome. It is a peerless kinsman.(4) "Give me your hand; Conduct me to mine host. We love him highly, And shall continue our graces towards him†¦" [Talking about Macbeth I.iiv.28-30](5) "†¦How you shall bid God ‘ield us for your pains, And thank us for your trouble†¦" [I.vii.13-14]Duncan represents the purest of all beings.