Implementation and Modification IP 4 Essay Example | Topics and Well Written Essays - 1000 words

Implementation and Modification IP 4 - Essay Example This report gives an account of the effectiveness of the Medicare program and provides a futuristic approach towards the program and systems of implementing the changes (Moon, 2006). The topic "Strengthening and Improving Medicare" elicited various views from both public and private entities and individuals. The congressional subcommittee of health held a forum for persons of concern to give their witness accounts on the topic. Some of the prime witnesses who stood before the subcommittee include among others, Robert Berenson, the senior consultant officer at Academy Health, Foster, Richard, Buddy Robert, a beneficiary of the Medicare + Choice health plan and Grealy, Mary, the President of Healthcare Leadership Council. All these witnesses gave individual accounts of the success of the current Medicare system and gave recommendations on ways of improving it. According to Berenson, the well-established and effective Medicare program is being replaced by the Medicare + Choice program, which shifts focus from the government provided healthcare to private health insurance. There is no evidence to prove that shifting to such a system will reduce the program’s expenditure or improve on its financial position. The only entities to benefit from the new program will be private health insurance institutions, which will only serve to segment adversely the insurance pool and increase costs of maintaining the traditional program. Through her statement, Grealy, advocates for the introduction of a prescription drug benefit to boost the financial as well as healthcare quality of the Medicare program. According to the Healthcare Leadership Council (HLC), the 50 percent increase from $6,200 to $9,500 in cost of Medicare for one beneficiary by the year 2013 will have no significant improvement in the program’s quality of an outpatient prescription drug coverage is not included in the program. The HLC advocates for the establishment of a Medicare delivery module that incorporates the aspects of competition, flexibility and invests in beneficiaries who have consumer choice power. Through such a measure, Medicare would be able to provide similar benefits to employer-sponsored programs, which offer benefits such as outpatient prescription drugs, the ability to choose a health program that best suits individual needs and reduce out-of-pocket costs and. The Medicare + Choice plan reduces the number of services offered to Medicare beneficiaries because it receives lower payments than the previous fee-for-service Medicare program. Through this, the Medicare + Choice plan has increased beneficiary cost sharing, which squashes the chance of fair competition in healthcare provision (CEC, 2003). Robert Buddy, a beneficiary of the Medicare + Choice health program gave his account of the benefits of the Medicare Program and the Medicare + Choice plan, which he joined after the privatization of the Medicare program. According to Robert, the Medicare program did not offer comprehensive benefits thus had to spend at least $2,000 on a Medicare Supplement policy to gain more healthcare benefits. Emphasis of the Medicare + Choice plan is early detection and treatment, which affords better healthcare to its beneficiaries. Robert recounted the case of his father, who was on the Medicare prog

Marketing Mix Essay Example for Free

Marketing Mix Essay 1.1 Background to the Report Strategic management refers to analysing the important initiatives which are taken by the top management of the company on behalf of the owners. It successfully keeps a track of day- to- day activities which are going into an organization to organise the resources and plan a strategy which the organization should follow in order to get benefit in the business. It provides a direction to the organization and is closely related to the field of organizational structure. (Hambrick, 2007) In this report, strategic management of Singapore Airlines is critically evaluated on the basis of several strategies used by them. This not only helped the company in achieving the results but also enabled SIA to expand itself in the global market as well as establish a new base in the new expanding countries. 1.2 Aims of the research are – To develop a good understanding about what involves in Strategic management. To develop knowledge about constituents of strategic management process. Critical assessment of strategies of a selected organization. To throw some light on the internal and external environment of selected organization. Gap analysis for Singapore Airlines – 2. Analysis of internal framework of Singapore Airlines – Capability to restore competency in order to attain similarity with the change in business environment are termed as dynamic capabilities. This is done by reconfiguring, mixing and adjusting external and internal resources, skills and abilities (Teece et al., 1997). 2.1 Resources – Connecting strategic resources and core strategies is defined as ‘configuration’ by Hamel where core competencies and assets, process and assets are organized and combined in order to maintain strategies (Hamel, 2002). Resources are divided into two categories, tangible and intangible resources of Singapore Airlines. They are further divided into sub categories on the basis of which it can be assessed that core strategies and strategic resources were well connected. 2.2 Capabilities – On the basis of broad variety of competency and technological expertise in newly invented planes, Singapore Airlines effectively fascinated more airlines clients to its fleet management industry, securing its place as major fleet management facility providers of the world. It also persists on expanding its potential by means of strategic joint ventures. For instance, a joint venture agreement is signed by SIA with Panasonic Avionic Corporation in order to prepare a facility for maintenance, repair and operation of communication and in-flight entertainment. Facility will be based in Singapore and components will be generated by Panasonic Avionics (Singapore Airlines, 2011). 2.3 Core Competencies – Core competencies of Singapore Airlines consist of the interpersonal talents of its flight assistants and ability of its top level management in planning strategies for marketing. They endeavour to make flights as relaxing as possible (Singapore Airlines, 2011). 3. Analysis of external framework of Singapore Airlines – PESTEL Analysis FactorsSingapore Airlines PoliticalUnpredictable, SIA reject Air India offer EconomicSIA offer created trouble in Hong Kong SocialSIA Airplane crash in Taiwan TechnologicalQuick technology implementation EnvironmentalLaunch of A380 Air career LegalPassengers safety 4. Five forces of porter – Porter’s five forces model deliver a well-liked external analysis framework for Singapore Airlines. After analysing the internal and external framework of Singapore Airlines, S.W.O.T analysis is performed in order to assess SIA’s capabilities, followed by the critical analysis of corporate and business level strategies. 5. S.W.O.T. Analysis – Strengths – Singapore Airlines has an expanded geographical reach. They operate in a number of reasons like US, West Asia, Europe, Africa, South west Pacific and East Asia. They run flights to 63 cities globally, whereas its division Silk Air is offering flights in 12 countries with 39 cities. Considerable amount of revenue is generated by SIA group with its airline operations around the globe. Equally spread and diversified revenue base guarantees that group is not dependent on single geographic market for most of its profits, by which business risk decreases significantly. Though, SIA is basically a passenger airline, but the group is also offering various specialized services like engineering services, airline operations, cargo operations, etc. which are providing them stability by diversifying business threats. Additionally, SIA group has a policy of maintaining young aircraft fleets, which emit lower carbon emissions and have less burning of fuel per kilometres. This is also strength of SIA group as this factor helps in keeping maintenance costs less, along with reducing performance related security concerns (Heracleous, 2006). Weaknesses – SIA faced extremely competitive market in its initial phases. Many countries restricted air-route access to protect national airlines from other competitions. SIA worked hard to get access rights for many important airports (eg. Heathrow, Manchester) (Reddy, 2004). Various competitive authorities keep on investigating about Singapore airlines and its subsidiaries. For example, South Korea, Canada, Australia, South Africa and European Union investigated about SIA group in order to determine whether the rates, surcharges, and other characteristics of cargo service were determined lawfully or not. In financial year 2012, SIA paid administrative penalty to South African competition commission (2.8millionUSD) as settlement. Legal expenses connected with the inquiry and court case and time spent on this issue left an impact on SIA’s business and operations. Opportunities – Singapore Airlines with its well-built base of operations and proficiency, is well placed to reap advantages from the worldwide boom in tourism industry. This would help SIA Group to produce extra profits. Also, group is focusing on joint ventures and strategic operational alliances to add opportunities for growth and sales. SIA entered into partnerships (jetblue Airways) and code-sharing agreements (Virgin Australia/ Virgin America) in order to increase growth opportunities. For instance, SIA signed code share agreement with Virgin America in December 2012 (SIA, Virgin America reach code-sharing agreement, 2012). SIA will add its ‘SQ’ airline code to flights of virgin which are America-operated serving Washington DC, Las Vegas, Seattle, Chicago, etc Furthermore, SIA group has launched ‘Scoot’ which is a low cost carrier in order to grow its existence in low cost flight market. This step will enable SIA group to attract more groups of customers which will in crease its growth and revenues. Threats – Competition is very high in the airline industry. Reputation, safety records, customers service, flight schedules, fares, code-sharing relations are few parameters of competitions. SIA faces straight competition with other carriers on its route. Cathay Pacific, Japan airlines, United Continental,  AMR are few of its competitors. Extreme competition on the basis of price matching, promotions, discounting, capacity, etc. affects operating margins of SIA. Also, Natural disasters can have affect on SIA’s operations effecting the cash flows and financial state. Moreover, hike in the prices of jet fuel can increase operating costs, which can affect the profitability (Heracleous, 2006). 6. Strategies used by Singapore Airlines – 6.1 Corporate level Strategies – Diversification – Companies tend to grow their full potential in economies which are developing, with the help of strategic diversification. Strategy of diversification is followed by SIA at the corporate level. SIA group has number of primary companies with key companies being SIA Cargo, SIA Engineering Company and Silk AIR. They also have number of associated companies. Its Airlines divisions which consist of 49% ownership of Virgin Atlantic, 32 % of Tiger Airways and entire ownership of local carrier Silk Air cover basic segments of customer in the industry. This was a long-term strategy (Singapore Airlines, 2008). Benefits of using diversification by Singapore Airlines is to enable passing of learning and control quality and side by side reaping cost synergies. Subsidiaries serve as sources of learning; and also as progress arena for skills of management and corporate rather than divisional viewpoint through job rotation. Profit margins are better in related operations (like aircraft maintenance and catering) on comparison with airline business itself as structure of industry in those sectors is more favourable. (Singapore Airlines, 2008). Strategic Alliances – In April 2000, SIA joined Star Alliance as a step of its internationalization strategy. In the three main airline alliances, Star alliance hold its place  with Oneworld and Skyteam. Also, In India and China, SIA Group were investing through planned deals during this time. Deals were done with local services like engineering services, cargo85 divisions, catering and airport services. SIA is also under a code share contract with Malaysian Airlines. These airlines are offering up to 14 flights in a day between Kuala Lumpur and Singapore (Doganis, 2006). For the expansion of the company, strategic alliances are becoming more common tool. SIA used strategic alliances for increasing competitiveness in the global and domestic markets. This helped SIA in developing new business opportunities with the help of new services and products. This resulted in the expansion and growth of company globally. An alliance is a business-to-business relationship (Jeffrey, 2004). 6.2 Business level strategies – Differentiation strategy – Premium services were successfully delivered by Singapore Airlines to those customers who are very demanding and this can be termed as achieving differentiation strategy. This helped Singapore Airlines in identifying that different customers are broadly scattered, with varied needs and sufficient spending power. If an organization is unique in something which is valuable to its customers at the same time, it differentiates itself in the marketplace (Chamberline Robinson, 1996). If an offer is valuable for the customers, they tend to be less sensitive to characteristics of competing suggestions where cost may not be one among these characteristics. This accomplishment of SIA challenges viewpoint of Porter that cost leadership and differentiation strategies are equally exclusive strategies (Porter, 1985). Differentiation strategy allowed Singapore Airlines to insulate itself partially from rivalry competitors of same industry. Customers of differentiated services were less sensitive to prices and they started preferring SIA over other airlines, that is, SIA succeeded in gaining customer loyalty (Hitt et al., 2007). SIA carefully applied this strategy and played safe by delivering premium services appropriately without over-proliferating them. leadership strategy – Singapore Airlines has considerably greater effectiveness than its peer group, which is a crucial aspect of an effective leadership strategy. They have young fleets which have lower maintenance costs; they are fuel efficient and have effective hedging of fuel. Labor cost of SIA is comparatively low (16.6%) than average of all prime airlines (20.1%) (Singapore Airlines, 2008). Singapore Airlines have youngest fleets in the airline industry, which is worth considering. Their fleets have average age of 75 months, and average age of half of airline industry fleets is 163 months. SIA’s fleets are much efficient. Younger planes are quiet, comfortable and fuel efficient. They have low repair, service and maintenance costs which are all part of its leadership strategy. 7. Recommendations – Keeping in mind the weaknesses discussed above, some recommendations for Singapore Airlines come into light like keeping company information confidential. SIA paid huge fine as various companies successfully investigated about SIAs internal facts and figures. Also, they need to keep a close eye on its competitors who try to gain lead in the competition on the basis of price matching, promotions, discounting and capacity. 8. Conclusion – A variety of strategies were executed by Singapore Airlines by which the company is successful for a considerable time. By keeping a track on industrial environment and the macro environment, Singapore Airlines can uplift its capabilities to secure future success. However, as there are uncertainties in the environment and market keeps on altering quickly, it is crucial to monitor and carefully consider all the strategies before implementation. Singapore Airline’s potential to become accustomed to change will positively help the company..to..strive..on..with..competitors..in..the..future. 9. References – Chamberline. E, Robinson, J. (1996). â€Å"Theory of Monopolistic Competition, What is Perfect Competition ? † Quarterly Journal of Economics, Vol. II, no. 4, 431- 433 Doganis, R. (2006). Outlook, The Airline business ed. 2, Routledge, Abingdon. Hambrick, D. C., (2007). What is strategic management really? Hamel, G. (2002). Leading the Revolution: How to Thrive in Turbulent Times by Making Innovation a Way of Life. New York: Plume Books. Heracleous, L. (2006). Flying high in competitive industry: Cost effective service at SIA. Mc Graw hill. Hitt, M., Hoskisson, R., Ireland, R. (2007) Management of Strategy: Concepts and Cases.7th ed., Thomson South-Western, USA Jeffrey, R., (2004). Strategic alliances: Theory and evidence, Oxford university press, US, 2004. Porter, M.E.(1985). Competitive Advantage. New York: Free Press, 6-22. Reddy, A. (1994). Total quality marketing: the key to regaining market shares. Westport, CT: Quorum Books. SIA, Virgin America reach code-sharing agreement (2012, December 15, Saturday). Business pg30..Retrieved..from http://imcmsimages.mediacorp.sg/CMSFileserver/documents/006/PDF/20121215/1512BZC032.pdf SIA (2012). Virgin America reaches code-sharing agreement, December 15, 2012. Singapore Airlines, (2008). Annual Report, Singapore. Singapore Airlines, (2011). Annual Report, Singapore. Teece, D., Pisano, G., and Shuen, A.(1997). Dynamic capabilities and strategic management, Strategic Management Journal , 18, 509-533. reaches code-sharing agreement (2012, December 15, Saturday)

The Creative Classroom :: Education Teaching Teachers Essays

The Creative Classroom When I was three years old, my parents and I made the most significant move of our lives– we moved from northern Ohio to my mother’s hometown in southern West Virginia. Many things about my life changed because of our relocation, but most significantly was my mom’s job. While in Ohio, she had stayed home with me, but once we came to West Virginia, she resumed her career as a teacher. Immediately, I was thrown into the school system. I remember being so proud that my photograph had been included in the 1987 Man Junior High School Yearbook– and I was just four. Since then, I have viewed the teaching profession through my mother’s eyes and consequently, the eyes of a teacher. I have seen the joy that comes with teaching as well as the frustrations, and I look forward to them all in my future as an educator. I consider my views of teaching to be realistic. I have seen firsthand the paperwork, confrontations with students, extra hours required, and the stress that comes with teaching. But, I have also seen a teacher’s entire day be turned around just because one student grasped a new concept. I have seen a student’s eyes sparkle when they discover something new. And beyond that, I have seen a teacher’s eyes sparkle when his or her pupil rejoiced in their newfound knowledge. I welcome all these experiences into my life, and cannot wait to make my own discoveries in my secondary mathematics classroom. Because of my observations of the education field and my own personal style, I feel that my classroom will best be served with a diverse group of philosophies including essentialism, perennialism, behaviorism, and social reconstructionism. Essentialism is the "back to basics" approach to education that concentrates on teaching primary skills to students. Essentialism tugs at the very heart of mathematics: in order to understand the more complex theorems and algorithms, you must first have a firm grasp of the basic principles of mathematics. I believe learning mathematics is both a step-by-step and conceptual process. With essentialism, I hope to highlight the step-by-step approach. In this, I will be constantly reviewing elementary mathematical concepts, building to a better understanding of the given concept and further building up to a more complex mathematical understanding. Perennialism emulates the belief that ideas that have lasted over centuries should be the concentration of the classroom.

Camus: On and In Action :: Camus Essays

Camus: On and In Action ABSTRACT:In this paper I wish to examine the position of Camus regarding social change, namely his concepts of rebellion and revolution. I in no way question his well-deserved status as a major twentieth-century French writer, nor do I wish to suggest that he may have been someone caught in a Sartrean notion of 'bad faith.' I am concerned with what one might call his theory of social action. I do wish to assert that Camus was a good man who seriously wrestled with the events of his time. Yet his claims on behalf of suffering humanity, while honest, are not sufficient when faced with complex social issues. That his move toward the right that today might well be taken for a supposed liberalism was undoubtedly bound up with his continued misunderstanding of the dialectic of history. A Series of Critical Observations Camus continually stresses the break from Christianity (God is dead—the world is without order) whether in speaking of the French Revolution or what he calls the new absolutism of the communist revolution. In the first case there is a degree of confusion on the issue when speaking of Rousseau, St. Just, and the divine right monarchies. Camus obviously holds to one traditional view of the king as God's representative on earth and from this lays the groundwork for his future project. I would like to suggest that there are at least two alternate interpretations of divine right monarchy that vie for our attention. First, there is the view forwarded by Reinhart Koselleck in his 1959 book Kritik und Krise. There in he suggests that rather than a union of the sacred and the secular, divine right monarchy already announced the triumph of the secular over the sacred. Before this period there had been the two worlds of religion and politics. With the Reformation Christianity no longer w as unified under the pope but broke into various factions. The divine right of kings, whether it is in England or France, certainly allowed for an absolutism, but relegated the religious partner to the outer fringe of politics where it was left to argue matters of theology and direct the religious faithful while recognizing the supremacy of the King in all matters political, or even, as in England, recognizing the King as leader in both matters. When Camus points to Marx's observation that the beginning of a radical critique of society is a radical critique of religion, he believes his own critical project to be partly vindicated.

Informative Speech on Leukemia Essay

Hope, denial, anger, fear, and worry are words that come to mind when we think of the word cancer. Cancer is a word we never want to hear. I’m sure at some point in your life, everyone in here knows someone who has been affected by cancer. On September 19th of this year, not even a month ago, I did one of the hardest things I was ever faced to do†¦ I attended one of my best friend’s funeral. Kali suffered from Leukemia since the young age of 10 and fought her battle until the age of 24. This topic is so dear to my heart because it was not until after she passed away that I found out exactly what she suffered from. So today, I would like to inform you about Leukemia’s symptoms, treatments, and who can be affected by it. So, what exactly is Leukemia and what are some symptoms to be aware of? Leukemia is characterized by an increase of abnormal white cells in the blood and bone marrow. In lamer terms, â€Å"Cancer of the blood cells.† If you have Leukemi a, the first thing affected are your white blood cells that fight infections. If you have Leukemia, your white blood cell count becomes almost non-existent making it extremely difficult to fight any infection. A simple cold would feel like pneumonia to a Leukemia patient. Kali told me that her immune system was equal to a 6 month old baby. In addition to your white blood cells, your red blood cells are also affected. Red blood cells help carry oxygen from your lungs throughout your entire body. If you lack red blood cells, you will most likely experience shortness of breath. This explains why at times Kali would speak very slowly in order to catch her breath. Lastly, your platelets are affected. Platelets help control bleeding and bruising on the body. When affected you are more likely to experience excessive bleeding and easily bruised. When the oncologist, a doctor that specializes in cancer, suspects that you have cancer he or she will question your symptoms. Common symptoms include fever, paleness of the skin, fatigue, pain in the bone and joints, weight loss, discomfort in the abdomen, and night sweats. Furthermore, the oncologist will perform a bone marrow biopsy. If the patient is not put to sleep, this procedure can be extremely painful. They take a 12 inch needle, stick it into your hip, and extract the bone marrow. The bone marrow is then tested to determine if you have Leukemia and wha t type of treatment is best for you. This brings me to my next point. Medicinenet states there are three major types of treatment: Chemotherapy,  steroid therapy, and stem cell transplant. With the stem cell transplant, doctors use high dosages of chemotherapy and basically remove your entire immune system and replace it with someone else’s. This person can be a related or unrelated donor. If it is a related donor, this person is usually someone very close to the patient such as a parent, sibling, or close relative. Kali was given the stem cell transplant and had new blood in her body. She informed me that her childhood vaccine shots were no longer in her bloodstream and she could not get them again because they could work against her in a negative way sort of putting her between a rock and a hard place. Like Kali, once a patients transplant is complete, they are given lots of medicine to help support the body and pain in hopes of preceding with a normal life. This brings me to my final point. Are you at risk? Can you be affected? According to the Leukemia and Lymphoma society, approximately every 3 minutes someone in the United States is diagnosed with a blood cancer and approximately every 10 minutes someone dies from a blood cancer. There were an estimated 310,000 people living with or in remission from Leukemia in th e United States. In this year alone, roughly 52,000 people were diagnosed and 24,000 are expected to die- 14,000 males and 10,000 females. While there is no known ways to prevent Leukemia, the National Cancer Institute states that developing Leukemia increases with several factors such as: smoking cigarettes and air pollution. Why should this be important and relevant to you? According to the Washington Post, Louisiana has been given the name â€Å"Cancer Alley† because of the 150 petrochemical companies and 17 refineries that line the Mississippi River from New Orleans to Baton Rouge releasing dangerous levels of toxins in the air we breathe in every day. We live in a state where cancer rates are to the roof. Leukemia is most frequent in Caucasian males than in any other population. Kali was an African American female. This lets me know, no one is susceptible. I’m sure after listening to me, you are more knowledgeable about Leukemia, its symptoms, treatments, and risks. Although it may not affect you directly, I encourage each and every one of you to get regular check-ups, stay healthy, and give to those who are affected. I’ll leave you with this quote by John F. Kennedy, â€Å"When written in Chinese, the word crisis is composed of two components, one represents danger, the other represents opportunity.†

Movie Evaluating Criteria and Standards †Humanities Informal Essay

Movie Evaluating Criteria and Standards – Humanities Informal Essay Free Online Research Papers Movie Evaluating Criteria and Standards Humanities Informal Essay The evolution and widespread use of the genre in feature films, along with the tremendous amount of releases now offered to the movie-going public has now instilled in me a sense of standards for evaluating each film I view. With the many genres, however, I find myself using a different set of sub-standards that evaluate a particular genre. The particular genres that I enjoy viewing, and, hence evaluating, are science fiction / fantasy, action, comedy, horror, and drama. I am currently writing a script for a science fiction story that could easily be used as a movie, book, or even video game. Thus, I find myself being the most scrutinizing with this genre. When I see a science fiction or fantasy movie, I usually look for projected realism. This is a term I have created for myself to evaluate the ideas and actions presented within the framework of the universe created. Obviously, science fiction or fantasy movies with magic, space warp, etc, are not going to be â€Å"realistic† in the classic sense. Projected realism means, in a direct definition, â€Å"Ok, we have this galaxy (or this magical world or whatever). Given the physical laws (magic, light sabers, etc.) that are given to us with the film, would this particular scene really happen?† For example, the Force is supposed to be this mystical controlling power that can move objects with the mind. Would Darth Vader really want to toss large metal objects at Luke if he could rationally do something else? It is unfair to discard a science fiction story by the merits of its physical laws (i.e. Bavmorda couldn’t really turn people into pigs- magic doesn’t exist!) because, by virtue of its genre, that is what the writer has created for us. What I, as a viewer, have to do is put myself into that created world and become involved with its fictional physical laws to truly evaluate it. For a comedy, it is obvious what specific constraints I put on that genre- it has to make me laugh. Although there are a few areas of gray matter, for the most part, comedies fall into two major categories: dumb comedies and smart comedies. Dumb comedies are those that are centrally slapstick, normally require breakage of the laws of physics and of chance, and do not require any sophistication to laugh at. Dumb and Dumber, the Airplane series, The Naked Gun sequels, and most spoofs are considered to be in this category. It must be understood that I enjoy most of these very much. The criterion for these, however, is unique. They must make me laugh, and must not be so poorly written that I look at it and mutter, â€Å"what the heck was that in there for?† The majority of movies that cause me to say that are those with numerous sexual jokes. Although I do admit that some sexual jokes make me laugh, for the most part, they contain very little humor and rely more on the sexuality o f the situation than the humor to cause the laughter. For the perverse, the goal is accomplished, but for myself, it does need to contain some actual humor. The sophisticated, or â€Å"smart comedies† include those that are funny, but realistic fiction- given those circumstances and those characters, the laws of nature and physics would allow that story to actually happen. Most romantic comedies, e.g. My Best Friend’s Wedding, While You Were Sleeping, are smart comedies. Unless the humorous situations are poorly written (which is essentially my central criterion), I find that the romantic comedies I dislike are few and far between. Other comedies, such as Greedy, Clue, Trapped in Paradise, and the Father of the Bride movies are also â€Å"smart† movies. They have a realistic base, and are intelligently planned out. In truth, these are the most difficult comedies to make, which is why I have such great admiration and respect for them. Horror movies must scare me; suspense movies must put me in suspense. These criteria are obvious and apply to essentially all the movies in those genres. However, I do have a set of criteria that I apply to basically all of the films I see. The first aspect of a screenplay that I notice is its meaning. If a film has no meaning, then it is merely entertainment. I do not frown on entertainment for its own sake, and, as such, enjoy many a motion picture devoid of any purpose. However, the movies that I do not mind seeing and evaluating numerous times are those that the writer intended to display a greater meaning or purpose than normally granted to the public. Additionally, when I look at a film that has a message or a purported meaning, I try to dissect the symbolism. Several years ago, I used to over-evaluate movies and try to find symbols in almost every single aspect of the screenplay, but now, with my increased maturity, I have narrowed my view to those aspects of a film that truly attempt to express a point of human truth. It is not often that I see a meaningful movie that aims to express an eternal principle and does it very well. However, this July, a film was released that exemplified that criterion and did it so well that have I gladly paid to see it three times. This was the movie, Contact, with Jodie Foster. This film expressed the eternal principle of God with such skill that I left the theater with an altered personal philosophy. â€Å"Is there a God?† The movie poses the question very directly and never attempts to definitively answer the question but displays the many complications and truths inherent in maintaining either a theistic or an atheistic point of view towards this matter. This is why I liked the movie. It denounces the classic scientific principle of â€Å"if there is no evidence, then it is not true† without denouncing science as a holistic concept. It shows that things can be true without physical evidence. The movie showed that some things just cannot be proven with our limited methods of expression and explanation. Contact definitely had a meaning. It vindicated belief without true knowledge (i.e. human impression) and vindicated a liberal view of science as the study of wholeness of the universe, including God and the scientific laws inherent in such a higher power. I sincerely doubt there was anyone who walked out of the theater without being touched in some aspect. It is a film with direct elements and symbolism to be praised and emulated. Research Papers on Movie Evaluating Criteria and Standards - Humanities Informal EssayWhere Wild and West MeetHarry Potter and the Deathly Hallows EssayHip-Hop is ArtMind TravelComparison: Letter from Birmingham and CritoHonest Iagos Truth through Deception19 Century Society: A Deeply Divided EraRelationship between Media Coverage and Social andStandardized TestingResearch Process Part One

Biochemical investigations Essay Example

Biochemical investigations Essay Example Biochemical investigations Essay Biochemical investigations Essay Ameliorating consequence of ethanolic infusion ofBrassica oleraceaL. volt-ampere. italica against aflatoxin B1 induced hepatic harm in mice. Faculty of Science Abstraction Background Brassica oleraceaL. volt-ampere. italica besides known as Brassica oleracea italica is a cruciferous vegetable belongs to household that protects against malignant neoplastic disease. Its flowerets have been used in many states as salad. It contains phytochemicals that helps to make unsusceptibility and antioxidant support in the organic structure by bring oning excess protection of the organic structure s enzymes. The present probe purposes at measuring the hepatoprotective consequence ofBrassica oleraceaL. volt-ampere. italica ( Brassica oleracea italica ) infusion on aflatoxin B1 induced hepatic harm in mice. Methods Aflatoxins are powerful hepatotoxic and hepatocarcinogenic agents. Reactive O species and attendant peroxidative harm caused by aflatoxin are considered to be the chief mechanism taking to hepatotoxicity. In present survey, aflatoxin ( 66.6 A µg/kg bw/day ) treated animate beings showed a important addition in lipid peroxidation degree with attendant lessening in enzymatic and non enzymatic antioxidants as compared to controls. Consequences Broccoli, a cruciferous veggie which contains a assortment of polyphenolic antioxidants, showed hepatoprotective consequence at a dose regimen of 0.2 g/kg organic structure weight per twenty-four hours by take downing lipid peroxidation and heightening the degree of decreased glutathione ( GSH ) and protein contents in comparing to aflatoxin treated group. The hepatoprotective consequence was besides shown by the important addition in the activities of enzymatic antioxidants such as glutathione-S-transferase ( GST ) , glutathione peroxidase ( GPx ) , glutathione reductase ( GR ) , superoxide dismutase ( SOD ) and catalase ( CAT ) when compared to controls. Histopathological analysis of liver samples further confirmed the protective consequence of the infusion. Decisions All these findings demonstrated that, ethanolic infusion of Brassica oleracea italica has strong antioxidant and hepatoprotective effects and accordingly may relieve liver harm caused by aflatoxin B1 induced hepatotoxicity in mice. Background Fruits and veggies are good beginnings of natural antioxidants for the human diet, incorporating many different antioxidant constituents include carotenoids, vitamins, flavonoids, other phenolic compounds, dietetic glutathione and endogenous metabolites, which provide protection against harmful free groups [ 1,2 ] . These antioxidants besides have been strongly associated with decreased hazard of chronic diseases, such as cardiovascular disease, malignant neoplastic disease, diabetes, Alzheimer s disease, cataracts and age-related functional diminution in add-on to other wellness benefits [ 3 ] . Cruciferous veggies, belong to household Cruciferae in specific of theBrassicagenus such as Brassica oleracea italica, Brassica oleracea botrytis, boodle and Bruxelless sprouts, have important malignant neoplastic disease preventative effects, as shown in epidemiological and carnal carcinogenesis surveies [ 4 ] . They contain significant measures of isothiocyanates ( largely in the signifier of their glucosinolate precursors ) some of which ( e.g. , sulforaphane or 4-methylsulfinylbutyl isothiocyanate ) are really powerful inducers of stage 2 enzymes [ 5 ] .Brassica oleraceaL. volt-ampere. italica ( Brassica oleracea italica ) is a good beginning of wellness advancing compounds since it besides contains a assortment of polyphenolics [ 6 ] . The malignant neoplastic disease protective belongingss of Brassica oleracea italica ingestion are most likely mediated through bioactive compounds that induce a assortment of physiologic maps including moving as direct or indirect antioxidants, m odulating enzymes and commanding programmed cell death and the cell rhythm [ 7 ] . Broccoli besides contains other protective components like beta-carotene, vitamin C and vitamin E, which can assist to cut down reactive O species, degree and prevent malignant neoplastic diseases [ 8 ] . Broccoli showed its antioxidant and cytoprotective efficaciousness against many diseases such as alzheimer s disease [ 9 ] , Parkinson s disease [ 10 ] , chest malignant neoplastic disease [ 11 ] , vesica malignant neoplastic disease [ 12 ] , prostate malignant neoplastic disease [ 13 ] , lung malignant neoplastic disease [ 14 ] , nephritic malignant neoplastic disease [ 15 ] , hepatic malignant neoplastic disease [ 16 ] , skin malignant neoplastic disease [ 17 ] , encephalon hurt [ 18 ] and cholestrol [ 19 ] . Ascorbic acid ( vitamin C ) is an negatron giver, and this belongings histories for all its known maps. As an negatron giver, vitamin C is a powerful water-soluble antioxidant in worlds. Antioxidant effects of vitamin C have been demonstrated in earlier surveies[ 20 ] . Vitamin C plays an of import physiological function in cells as a reduction agent and antioxidant, free extremist scavenger and enzyme cofactor. Glutathione and vitamin C show a strong functional mutualityin vivo. Vitamin C protects endothelial cells from oxidative emphasis by neutralizing the effects of oxidative species and diminishing blood cell-endothelial cell interactions, while glutathione modulates the oxidation-reduction belongingss of vitamin C in endothelial cells. Clinical surveies have revealed that vitamin C can change by reversal endothelial disfunction under different pathological conditions such as hypercholesteremia, high blood pressure, smoke, diabetes and coronary artery disease [ 21 ] .Aflatoxin B 1 ( AFB1 ) is a powerful hepatocarcinogen, which may play a major function in the etiology of human hepatic and extrahepatic carcinogenesis [ 22, 23 ] . An increased incidence of hepatocellular carcinoma has been associated with dietetic exposure to AFB1, peculiarly in population that is normally exposed to hepatitis B virus [ 24, 25 ] . The toxicity and carcinogenicity of AFB1 is thought to be straight linked to its bioactivation, ensuing in a extremely reactive AFB1 8, 9-epoxide ( AFBO ) . This bioactivation of AFB1 occurs chiefly by a microsomal cytochrome P450 ( CYP450 ) dependent epoxidation of the terminal furan ring of AFB1 and is responsible for adhering to cellular supermolecules such as DNA, RNA and other protein components [ 26 ] . Recent findings have demonstrated that oxidative harm is one of the underlining mechanisms for the aflatoxin B1 ( AFB1 ) -induced cytotoxicity and carcinogenicity [ 24 ] . An addition in the formation of reactive O species ( ROS ) was detected by Shenet Al. [ 26, 27 ] utilizing a fluorescent investigation, 2V,7V-dichlorofluorescin diacetate, in civilized rat hepatocytes following AFB1 exposure. These reactive O species ( ROS ) may assail soluble cell compounds every bit good as membranes, finally taking to the damage of cell operation and cytolysis [ 28 ] . Peroxidative amendss induced in the cell are encountered by luxuriant defence mechanisms, including enzymic and non enzymic antioxidants [ 29 ] . It has been implicated that oxidative emphasis following aflatoxin metamorphosis, together with hepatotoxicity or hepatocarcinogenesis was inhibited by the usage of food-associated antioxidants and/or free extremist scavengers [ 30, 31, 32, 33, 24 ] . The overall purpose of this survey was to measure the ameliorating consequence ofBrassica oleraceaL. volt-ampere. italica infusion in Restoration of enzymatic and non enzymatic antioxidants and decrease of lipid peroxidation in aflatoxin induced liver harm in mice. Methods Materials Aflatoxin B1 ( AFB1 ) C17H12O6 EC No. 214-603-3, 1-chloro-2,4-dinitrobenzene ( CDNB ) , dithio-bis-2-nitrobenzoic acid ( DTNB ) , glutathione reductase ( GR ) nicotinamide adenine dinucleotide phosphates ( NADPH ) , oxidized glutathione and decreased glutathione were obtained from Sigma Aldrich Co. , St. Louis, MO, USA ) . Ascorbic acid, ethylene diamine tetraacetic acid ( EDTA ) , thiobarbituric acid ( TBA ) and trichlororoacetic ( TCA ) acid were obtained from Merck. Nitroblue tetrazolium salt ( NBT ) was purchased from Himedia Labs, Mumbai, India, while other chemicals were obtained from S. D. Fine Chemicals. Animals The survey was conducted in maleSwiss albinomice ( 30 A ± 2 g ) provided by Central Animal House Facility of Jamia Hamdard. A anterior blessing was obtained from the Animal Ethics Committee of Hamdard University ( JHAEC ) for the survey protocol. The animate beings were maintained under the standard conditions of humidness, temperature ( 25 A ± 2oC ) and light ( 12 H light/12 H dark ) , and fed with commercial pellet diet and H2Oad libitum. Plant infusion ( PE ) Plant stuff,Brassica oleraceaL. volt-ampere.italica, ( Brassica oleracea italica ) was purchased from the local market, New Delhi, India and authenticated by the taxonomer, Department of Botany, Hamdard University. Ethanolic infusion of Brassica oleracea italica ( EEB ) was prepared by soxhlet method utilizing 500 ml ethyl alcohol ( 95 % ) for 100 g ( dry weight ) of works stuff. Extract was concentrated in H2O bath to semisolid signifier [ 34 ] . The output of infusion was 19.80 % . Chemical profile of Brassica oleracea italica infusion has been described by assorted research workers and chief identified components are glucocynolates, vitamin Es, carotenoids, polyphenolics, etc.A [ 35, 6 ] . Animal theoretical account and in vivo intervention regimen Animals were divided into six groups. Each group consisted of 15 mice. Control mice ( Group I ) were administered normal saline ( 0.9 % NaCl ) orally for 90 yearss. Group II mice were administered aflatoxin B1 ( 66.6 A µg/kg/ bw/0.2ml/day, [ 36 ] which was dissolved in dimethyl sulfoxide ( DMSO ) and diluted farther with normal saline to the needed concentration. The concluding forced feeding solution of AFB1 contained 1 % DMSO. Group III mice were administered orally with a dosage of 0.2g/kg bw/0.2ml/day ethanolic infusion of Brassica oleracea italica ( EEB ) [ 37 ] . Ethanolic infusion of Brassica oleracea italica and ascorbic acid were dissolved in normal saline. Group IV ( AFB1+ EEB ) micewere administered with ethanolic infusion of Brassica oleracea italica after 30 proceedingss of aflatoxin disposal. Group V mice were administered with ascorbic acid dose ( Asc, 0.1g/kg bw/0.2ml/day, [ 38 ] . Group VI ( AFB1 + Asc ) mice were administered orally after 30 proceedingss of aflato xin disposal. The dosage of ethanolic infusion of Brassica oleracea italica and ascorbic acid were selected on the footing of above cited literature. The interventions were given during the full period of survey i.e. three months. Biochemical probes During the survey five animate beings from each group were sacrificed by cervical disruption on 30th ­ , 60th, and 90th twenty-four hours. Liver tissues from the sacrificed mice were rapidly removed and cleaned to do them free of immaterial stuff and perfused with ice-cold saline. The tissues were homogenized in chilled phosphate buffer ( 0.1 M, pH 7.4 ) utilizing a Potter Elvehjem homogenizer. The homogenate was filtered through muslin fabric and centrifuged at 800g for 5 min at 4oC to divide the atomic dust. The supernatant was centrifuged at 10,500g for 30 min at 4oC to obtain the station mitochondrial supernatant ( PMS, [ 39 ] ) for the biochemical measurings as described below. Lipid Peroxidation ( LPO ) LPO was measured by the method of Utleyet Al. ( 1967 ) [ 40 ] . The assay mixture consisted of 0.67 % thiobarbituric acid ( TBA ) , 10 % chilled trichloro acetic acid and homogenate ( 10 % ) in a entire volume of 3 milliliter. The rate of LPO was expressed as nmoles of Thiobarbituric acid reactive substance ( TBARS ) formed/h/g tissue, utilizing a molar extinction coefficient of 1.56A-105 M-1cm-1. Reduced glutathione ( GSH ) GSH content was measured by the method of Jollowet Al. ( 1974 ) [ 41 ] . PMS ( 1.0 milliliter ) was precipitated with 1.0 milliliters of sulfosalicylic acid ( 4.0 % ) . The samples were kept at 4oC for 1 H and so subjected to centrifugation at 1200g for 15 proceedingss at 4oC. The assay mixture contained 0.5 milliliter of filtered aliquot, 2.3 milliliter of Na phosphate buffer ( 0.1 M, pH 7.4 ) and 0.2 milliliter DTNB in a entire volume of 3.0 milliliter. The optical density of reaction merchandise was measured instantly at 412 nanometer and consequence expressed as nmoles GSH/g tissue. Protein contents Protein contents in assorted samples were estimated by the method of Lowryet Al. ( 1951 ) [ 42 ] . 0.1 milliliter of PMS was diluted with 0.9 milliliters of DDW and precipitated with equal sum of 10 % TCA and subjected to centrifugation at 1,200g for 5 proceedingss at 4oC.A Precipitate was saved and dissolved in 0.5 milliliter of 1 N NaOH. The reaction mixture contained 0.1 milliliter aliquot of sample, 0.9 milliliter of DDW, 2.5 milliliter alkaline Cu reagent and 0.25 milliliter of Follin s reagent in a entire volume of 3.75 milliliter. Then optical density was taken after 20 proceedingss at 680 nanometers and protein content was calculated in footings of milligram protein/g tissue. Antioxidant enzyme measurings Glutathione-S-transferase ( GST ) activity was assayed by the method of Habiget Al. ( 1974 ) [ 43 ] . The reaction mixture consisted of 1.675 milliliters sodium phosphate buffer ( 0.1 M, pH 7.4 ) , 0.2 milliliter reduced glutathione ( 1 millimeter ) , 0.025 milliliter of 1 CDNB ( 1 millimeter ) and 0.1 milliliter PMS ( 10 % ) in a entire volume of 2 milliliter. The alteration in optical density was recorded at 340 nanometers and the enzyme activity calculated as nmoles CDNB conjugates formed/min/mg protein, utilizing a molar extinction coefficient of 9.6A-103 M-1cm-1. Glutathione peroxidase ( GPx ) activity was assayed by the method of Mohandaset Al. ( 1984 ) [ 39 ] . The assay mixture consisted of 1.44 milliliters sodium phosphate buffer ( 0.1 M, pH 7.4 ) , 0.1 milliliter EDTA ( 1 millimeter ) , 0.1ml Na azide ( 1 millimeter ) , 0.05 milliliter of glutathione reductase ( 1 IU/ml ) , 0.1 milliliter GSH ( 1 millimeter ) , 0.1 milliliter NADPH ( 0. 2 millimeter ) , 0.01 milliliter H2O2 ( 0.25 millimeter ) , and 0.1ml PMS ( 10 % ) in a entire volume of 2 milliliter. Oxidation of NADPH was recorded at 340 nanometer. The enzyme activity was calculated as nmoles NADPH oxidized/min/mg protein, utilizing a molar extinction coefficient of 6.22A-103 M-1 cm-1. Glutathione reductase ( GR ) activity was assayed by the method of Mohandaset Al. ( 1984 ) [ 39 ] . The assay mixture consisted of 1.68 milliliters sodium phosphate buffer ( 0.1 M, pH 7.4 ) , 0.1ml EDTA ( 0.5 millimeter ) , 0.1ml NADPH ( 0.1 millimeter ) , 0.05 milliliter oxidized glutathione ( 1 millimeter ) , and 0.1 milliliter PMS ( 10 % ) in a entire volume of 2 milliliter. Oxidation of NADPH was recorded at 340 nanometer. The enzyme activity was calculated as nmoles NADPH/min/mg protein, utilizing a molar extinction coefficient of 6.22A-103 M-1 cm-1. Superoxide dismutase ( SOD ) activity was assayed by the method of Dhindsaet Al. ( 1981 ) [ 40 ] . The reaction mixture dwelling of 1.5 milliliters phosphate buffer ( 0.1 M, pH 7.4 ) , 0.1 milliliter NBT ( 2.25 millimeter ) , 0.1 milliliter PMS ( 10 % ) , 0.1 milliliter Na carbonate ( 1.5 M ) , 0.2 milliliter methionine ( 200 millimeter ) , 0.1 milliliter EDTA ( 3mM, ) , 1 milliliter DDW and 0.1 milliliter riboflavinA ( 60 A µM ) in the entire volume of 3 milliliter was incubated in visible radiation for 60 proceedingss at room temperature. The rate of reaction was measured by entering alteration in optical density at 560 nanometers due to formation of Formosan, a reaction merchandise of NBT. The enzyme activity was calculated as units/mg protein/h Catalase ( CAT ) activity was assayed by the method of Claiborne ( 1985 ) [ 41 ] . The reaction mixture was consisted of 1.95ml phosphate buffer ( 0.1 M, pH 7.4 ) , 1 milliliter H2O2 ( 0.09 M ) and 0.05 milliliters 10 % PMS in the concluding volume of 3 milliliter. Change in optical density was recorded at 240 nanometer. Catalase activity was calculated in footings of A µmoles H2O2 consumed /min/mg protein. Histopathological analysis Histopathological analysis of liver tissue was carried out by the method of Luna, 1968 in Maulana Azad Medical College ( MAMC ) , New Delhi, India to measure the hepatoprotective consequence [ 42 ] . The tissues were fixed in impersonal buffered formol ( 10 % methanal in phosphate buffered saline ) , a fixative that stabilized the tissues to forestall decay. The samples were so immersed in multiple baths of increasingly more concentrated ethyl alcohol to desiccate the tissue, followed by a glade agent such as xylol or Histoclear, and eventually hot molten paraffin wax ( impregnation ) . During this 12 to 16 hr procedure, paraffin wax replaced the H2O and soft, damp tissues were turned into a difficult paraffin block, which was so placed in a mold incorporating more liquefied wax ( embedded ) and allowed to chill and indurate. The tissue was so sectioned into really thin ( 2 8 micron ) subdivisions utilizing a microtome. These pieces, thinner than the mean cell, was so placed on a gl ass slide for staining. To see the tissue under a microscope, the subdivisions were stained with one or more pigments. This was done to give contrast to the tissue being examined. Hematoxylin and eosin ( abbreviated H and E ) discolorations and used in histopathology. Hematoxylin colours nuclei blue, eosin colours the cytol. After staining the tissue were examined under negatron microscope. Statistical analysis All values were expressed as average A ± SE. Statistical analysis was performed byA one manner analysis of discrepancy ( ANOVA ) to see the differences in consequences of assorted groups. A value of P lt ; 0.01 and p lt ; 0.05 were considered important. Dunnett trial was besides applied for analysing the significance between different groups. Consequences Consequence of EEB on Lipid peroxidation Aflatoxin intervention resulted in a important ( p lt ; 0.01 ) addition in lipid peroxidation by 43 % , 61 % and 86 % severally on 30th, 60th and 90th twenty-four hours inA group II mice every bit compared to command group ( group I ) .A Group IV ( AFB1 +EEB ) showed important ( p lt ; 0.01 ) lessening in LPO degree by 13 % , 25 % and 40 % severally at 30th, 60th and 90th twenty-four hours as compared to the aflatoxin treated group ( Figure 1 ) . Group VI ( AFB1 + Asc ) besides showed important ( p lt ; 0.01 ) lessening in LPO degree by 9 % , 26 % and 43 % as compared to the aflatoxin treated group ( group II ) severally on 30th, 60th and 90th twenty-four hours. Consequence of EEB on Reduced glutathione Figure 2 shows cellular GSH information of mice liver. A important ( p lt ; 0.01 ) lessening by 35 % , 56 % and 64 % severally on 30th, 60th and 90th twenty-four hours were observed in group II mice every bit compared to command group. Besides, there was a important ( p lt ; 0.01 ) addition by 14 % , 80 % and 180 % severally on 30th, 60th and 90th twenty-four hours in Group IV ( which was treated by EEB after 30 proceedingss of aflatoxin disposal ) as compared to group II which received aflatoxin entirely. Similar consequences were obtained in group VI ( AFB1 + Asc ) with a important increased by 50 % , 143 % and 217 % in comparing to the group II. Protein contents Protein contents decreased in group II by 28 % , 41 % and 60 % severally on 30th, 60th and 90th twenty-four hours during aflatoxin intervention as compared to the group I. Groups, which received ethanolic infusion of Brassica oleracea italica and ascorbic acid entirely showed protein contents comparable to group I. While, groups which received ethanolic infusions of Brassica oleracea italica and ascorbic acid in several groups alongwith aflatoxin intervention showed significantA ( p lt ; 0.01 ) addition in protein contents by 9 % , 37 % , 114 % and 23 % , 60 % and 149 % severally on 30th, 60th and 90th twenty-four hours in several groups as compared to the group II ( Table 1 ) . Consequence of EEB on Antioxidants enzymes GST activity significantly ( p lt ; 0.01 ) decreased in aflatoxin treated mice liver by 40 % , 49 % and 69 % severally on 30th, 60th and 90th twenty-four hours during aflatoxin intervention as compared to command groups. While groups ( III and V ) which received Brassica oleracea italicas extract and ascorbic acid entirely showed consequences comparable to command group ( group I ) . Whereas other groups ( IV and VI ) which received ethanolic infusion of Brassica oleracea italica and ascorbic acid alongwith aflatoxin showed significantly ( p lt ; 0.01 and p lt ; 0.05 ) increased GST activity by 16 % , 53 % , 199 % and 29 % , 74 % and 239 % in several groups on 30th, 60th and 90th twenty-four hours ( Table 1 ) , in comparing to aflatoxin treated group. GPx activity significantly ( p lt ; 0.01 ) decreased in aflatoxin treated mice liver by 20 % , 48 % and 66 % on 30th, 60th and 90th twenty-four hours during aflatoxin intervention as compared to command groups. Groups ( III and V ) which received Brassica oleracea italicas extract and compounds entirely showed normal GPx activity comparable to command groups. Whereas group which received ethanolic infusion of Brassica oleracea italica ( EEB ) alongwith aflatoxin showed increased GPx activity by 19 % , 87 % and 192 % severally on 30th, 60th and 90th twenty-four hours. Group VI, which received ascorbic acid alongwith aflatoxin, showed increased in GPx activity by 27 % , 82 % and 215 % severally on 30th, 60th and 90th twenty-four hours ( Table 1 ) . Glutathione reductase ( GR ) activity significantly ( p lt ; 0.01 ) decreased in aflatoxin treated group of mice by 41 % , 52 % and 73 % severally on 30th, 60th and 90th twenty-four hours during intervention. Groups ( III and V ) , which received Brassica oleracea italicas extract and compounds entirely, showed normal GR activity comparable to command groups. Group IV showed addition in GR activity by 23 % , 60 % and 228 % severally on 30th, 60th and 90th twenty-four hours. Group VI which received ascorbic acid alongwith aflatoxin besides showed significantly ( p lt ; 0.01 ) increased GR activity ( Table 1 ) . Aflatoxin treated mice liver showed lessening in superoxide dismutase activity by 39 % , 58 % and 77 % severally on 30th, 60th and 90th twenty-four hours as compared to command group ( group I ) . Groups, which received ethanolic infusion of Brassica oleracea italica and ascorbic acid entirely showed SOD activity comparable to aflatoxin treated group. Group, which received ethanolic infusion of Brassica oleracea italica alongwith aflatoxin, showed significantly ( p lt ; 0.01 ) enhanced SOD activity by 10 % , 88 % and 268 % severally on 30th, 60th and 90th twenty-four hours. Group VI which received standard compound ascorbic acid alongwith aflatoxin showed addition in SOD activity by 28 % , 95 % and 286 % severally on 30th, 60th and 90th twenty-four hours as compared to group II ( Table 1 ) .A Aflatoxin treated mice group which received aflatoxin entirely showed important lessening in catalase activity by 25 % , 46 % and 62 % severally on 30th, 60th and 90th twenty-four hours as compared to command group ( group I ) . Groups, which received Brassica oleracea italicas extract and ascorbic acid entirely, showed catalase activity comparable to command group in several groups. Group, which received ethanolic infusion of Brassica oleracea italica alongwith aflatoxin, showed important sweetening in catalase activity by 11 % , 70 % and 173 % . Treatment of ascorbic acid alongwith aflatoxin besides showed important ( p lt ; 0.01 and p lt ; 0.05 ) sweetening in catalase activity by 8 % , 66 % and 129 % severally on 30th, 60th and 90th twenty-four hours as compared to group II ( Table 1 ) .A Consequence of EEB on Histopathological analysis Histopathological analysis of liver subdivision of aflatoxin treated mice after 90th twenty-four hours showed marked vacuolar devolution of hepatocytes ( Figure 3b ) while mice treated with aflatoxin and Brassica oleracea italica infusion at the same time showed kupffer cells hyperplasia and regeneration activities in cells ( Figure 3c ) as compared to command group, which was normal ( Figure 3a ) . Discussion A figure of groundss suggest that oxidative harm caused by aflatoxin B1 ( AFB1 ) might be one of the mechanism behind aflatoxin B1 induced cell hurt and DNA harm, finally taking to carcinogenesis [ 43, 27 ] . AFB1 induced free extremist production or ROS production has been referred to as a possible ground for hepatotoxicity [ 44 ] . When ROS production overcomes the legion antioxidant barriers of defence it amendss a scope of cellular constructions and maps is produced. This procedure, known as oxidative emphasis, leads to pathologies such as coronary artery disease and malignant neoplastic disease, and finally to cell decease [ 45 ] . Lipid peroxidation ( LPO ) is one of the chief manifestation of oxidative harm initiated by ROS and it has been linked with altered membrane construction and enzyme inactivation. It is initiated by abstraction of H atom from the side concatenation of polyunsaturated fatty acids in the membrane [ 46 ] . Present information reveals that AFB1 disposal pr oduced pronounced oxidative impact as evidenced from important ( P lt ; 0.01 ) addition in LPO. The addition in LPO might consequences from increased production of free groups and lessening in antioxidant position. The oxidative emphasis observed in our survey is in conformity with the other studies where it has been implicated in AFB1 induced hepatotoxicity [ 47, 48, 49 ] .A In this survey intervention of animate beings with ethanolic infusion of Brassica oleracea italica ( EEB ) after 30 proceedingss of AFB1 disposal significantly reduced the AFB1 induced LPO ( Figure 1 ) by their ability to scavenge the free groups due to the presence of vitamin C, caretenoides and polyphenols etc in the Brassica oleracea italica infusion [ 50 ] . An of import function in the protection of tissues from the hurtful consequence of activated AFB1 is besides played by GSH and GST [ 51 ] . The enzymatic antioxidant defence systems are the natural defenders against lipid peroxidation. SOD, CAT and GPx enzymes are of import scavengers of superoxide ion and H peroxide. These enzymes prevent coevals of hydroxyl extremist and protect the cellular components from oxidative harm [ 52 ] . GPx is a cytoplasmatic and mitochondrial enzyme that detoxifies H2O2 in most cells. Glutathione-S-transferase ( GST ) is a household of the enzymes that catalyze the add-on of the tripeptide glutathione to endogenous and xenobiotic substrates, which have electrophilic functional groups. They play an of import function in detoxification and metamorphosis of many xenobiotic and endobiotic compounds. Superoxide dismutase is a really of import enzyme that maps as a cellular antioxidant. It is present in cell cytol and in chondriosome in order to keep a low concentration of superoxide anions. The important decrease in the activities of antioxidant enzymes ( GPx, GST, GR, SOD and CAT ) and non- enz ymatic antioxidant system ( GSH ) in aflatoxin treated mice liver ( group II ) as compared to the control group ( group I ) could be responsible for increased lipid peroxidation degrees observed during aflatoxin induced oxidative emphasis. Similar consequences have besides been reported antecedently for liver of mice [ 33 ] . GSH is a tripeptide containing cysteine that has a reactive -SH group with reductive authority. It can move as non enzymic antioxidant by direct interaction of -SH group with ROS or it can be involved in the enzymatic detoxification of ROS as a coenzyme [ 53 ] . GST catalyzes the junction of AFB1-8,9-epoxide with GSH to organize AFB1 -epoxide- GSH conjugates thereby diminishing the intracellular glutathione content [ 54 ] . This observation supports our findings where we observed a important diminution in degree of GSH ( Figure 2 ) and GST ( Table 1 ) in AFB1 induced animate beings. The Restoration of intracellular GSH contents and GST activity to normal degrees by Brassica oleracea italica infusion and ascorbic acid indicates that they play a critical function in extenuating AFB1 induced oxidative emphasis and subsequent harm to liver. Protein contents besides significantly decreased in aflatoxin treated mice liver. While groups which received ethanolic infusion of Brassica oleracea italica or ascorbic acid alongwith aflatoxin showed important addition in protein contents, this consequence is supported by old findings which demonstrated that aflatoxin lowers the protein contents [ 55 ] . It is already reported that Brassica oleracea italica is a good beginning of wellness advancing compounds since it contains many antioxidants such as vitamins, vitamin Es, caretenoids, polyphenolics and more specifically the compound glucoraphanin, which can metabolize to an anticancer substance sulforaphane [ 6 ] . In present survey the Restoration of GSH degree by broccoli infusion may be due to the polyphenolic antioxidants particularly flavonoids. Our findings is supported by the old surveies related to the protective consequence of antioxidants such as carotenoid, oltipraz, ebelsen against the cytotoxicity, hepatotoxicity and genotoxicity of aflatoxin B1 [ 56 ] . Antioxidants enzymes like GPx, GR, SOD and CAT form the first line of defence Against ROS and a lessening in their activities was observed with aflatoxin B1 disposal [ 49 ] . The above findings corroborates with our consequences where we observed a diminution in GPx, GR, SOD and CAT activities.A Selenium dependant GPx removes both H2O2 and lipid peroxides by catalysing the transition of lipid hydroperoxide to hydroxyl acids in the presence of GSH. The activity of GPx which is a component of GSH redox rhythm decreased during AFB1 disposal. This lessening in GPx activity may be due to the lessening in the handiness of substrate ( GSH ) and besides because of their change in their protein construction by ROS [ 29 ] . The increased intracellular GSH content following broccoli infusion and ascorbic acid intervention in several groups after aflatoxin disposal may trip GPx by forestalling the accretion of H2O2. The lessening in the degree of glutathione metabolising enzyme GR activity in AFB1 administered rats occurs as a consequence of reduced supply of reduced nico tinamide A dinucleotide phosphate ( NADPH ) for the transition of GSSG to GSH in the presence of GR. Under oxidative assault, NADP+ /NADPH ratio will exchange in favor of NADP+ , bespeaking lessening in the activity of enzymes [ 49 ] . Treatment with infusion of Brassica oleracea italica ( EEB ) and ascorbic acid ( Asc ) significantly increased the activity of GR ( Table 1 ) . This determination is besides supported by the work ofA Eberhardtet Al. ( 2005 ) [ 57 ] who reported the antioxidant capacity of Brassica oleracea italica on cellular oxidative emphasis. SOD is a household of metalloenzymes that is known to speed up the dismutation of endogenous cytotoxic superoxide groups to H2O2 which are hurtful to polyunsaturated fatty acids and structural protein of plasma membrane [ 58 ] . The H peroxide produced by SOD is farther removed by CAT. Decline in the activities of these enzymes after AFB1 disposal might be due to the inactivation of these enzymes ROS. Broccoli infusion increases the GSH position ensuing in the addition in SOD activity thereby forestalling the hurtful effects of superoxide groups. Therefore broccoli infusion indirectly influences the activities of SOD and CAT ( Table 1 ) . Histopathological analysis of liver samples shows vacuolar devolution of hepatocytes in aflatoxin treated liver of mice ( Figure 3b ) , while mice treated with aflatoxin and Brassica oleracea italica infusion at the same time showed kupffer

The Relationship between Unilateralism and Multiculturalism essays

The Relationship between Unilateralism and Multiculturalism essays The Relationship between Unilateralism and Multiculturalism in the United States Foreign Policy Now that the world has gone into the 21st century, the theme of globalism and world peace has become stronger than ever before. The world has become a smaller place with the inventions of fast transportation and fast communication such as telephones and internet. There has never been a better chance to unite the world. Instead, as years pass by, the world is facing deeper and deeper separation because of one superpower that seems as if it is going to take over the world in the near future. Why is this happening? The answer is unilateralism and multiculturalism in the U.S. society and the government. Unilateralism being the doctrine a nation should conduct their foreign affairs individualistically without the advice or involvement of other nations, and multiculturalism being the doctrine that several different cultures (rather than one national culture) can co-exist peacefully and equitably in a single country. In this report, I would like to write about the relationship between the unilateralism and the multiculturalism that lies in the U.S. government and how it affects the world. Since the Cold War conclusion, American unilateralism has become evident. The terminology of unilateralism was started being used from the time of the Clinton administration, relating to the circumstance that America reigned in worldwide politics as a superpower. Although unilateralism existed in the Clinton administration, they were more concerned about the cooperative relationship with the ally countries so the thought of unilateralism did not reach up to where it is now. When the Bush administration appeared, it reached to the point where unilateralism was pursued extensively. This became the American basis principle which said for America to assemble all policies based on its self-interests, and with this, the relationship with its allies was going to be...

The influence of senior management involvement on the effectiveness of Essay - 1

The influence of senior management involvement on the effectiveness of management training in selected Saudi Arabia (KSA) SMEs - Essay Example rpose of this study the effectiveness of the transfer of training within organization is defined by factors such as consensus between training participants and their senior management, better communication, team work, high spirit, move involvement of their work and faster decision making and problem solving. These factors are used as indicators of the effectiveness of the transfer of learning, because they are the ultimate aims of the management. It is important to note however that this research is based on the effectiveness of training in the workplace and effectiveness is not measured with a cost effective approach. Factors given above are used to define the effectiveness of training. From a cost effectiveness point of view, a counter argument will arise: will the senior management attending training program lead to reduced efficiency and effectiveness in their job, as they have less time to devote to their other roles. Some may suggest analyzing the cost-and-benefit of the action taken by the senior management. However this research is to study the effectiveness of training programs with or without the senior management participation. The reasons for the researcher to leave out cost-and-benefit factor are: firstly, the aim of the research is to study the human behavior after attending training; secondly, the researcher presumes the cost incurred by the whole group members of an organization is probably larger than the cost incurred by the senior management. Further complementary research could be conducted into a full cost-benefit analysis. This research concerns the relationship between the senior management and the transfer of management training effectiveness to the workplace of selected small and medium sized enterprises (SMEs) in Saudi Arabia (KSA). In this country, â€Å"SMEs† mean manufacturing companies provide manufacturing related services with annual sales revenue not greater than Saudi Arabian Riyal (SAR) 25 million and with full-time employees

The Main Selling Point of Globalization and E-Commerce Research Paper

The Main Selling Point of Globalization and E-Commerce - Research Paper Example Among all the developments today in globalization, it is the explosion of retail channels that are fueling the most excitement. The idea of being able to sell to the whole world is the main selling point of globalization and e-commerce however retailers are now realizing the constraints of these expanded channels. With the deluge of buyers and the stress on the company’s selling infrastructure, there is a need to evaluate and redevelop retail management policies. Fashion retailing whether online or not and whether selling globally or not are among the industries that need to asses its position and strategies. Since the industry usually entails actual perusal of the product, sellers need to communicate on a personal level with its buyers. Since the selling strategy targets this level of appeal, companies need to realize that they need to understand better who they are selling to culturally and psychologically stay competitive (Johansson, 2001). According to Perner (2004), "A le arned, shared, compelling, interrelated set of orientations for members of society". Culture influences goals, beliefs, attitudes and values and ultimately buying behaviour. In the development of the essential strategies for competing effectively in today’s globalized retail markets, it can be concluded that several factors are essential to success. Among them are extensive and relevant market research, responsive and sensitive marketing strategies, focus and creativity to execute plans and strategies, attentiveness changes in society and the social and political environment, flexibility to cope with the critical situation effectively and efficiently.

The role of the International monetary fund (IMF) in helping poor and Essay

The role of the International monetary fund (IMF) in helping poor and debt-troubled countries - Essay Example Consequently, the institution offers advice on investments in the public sector. The IMF supports United Nations policies on development. A good illustration can be derived from the fact that IMF is primarily concerned in financing services that raise public welfare such as education and health. IMF finances various aspects of the economies of debt ridden countries to achieve general Equilibrium. Stability of the economy benefits civilian populace both economically and socially. Moreover, stability in the economy enhances security and sound governance. If IMF intervention does not stabilize the economy, a crisis is imminent, which often yield to violence in poor countries. Such conditions are evident in African countries. IMF is a financial institution obliged to offer development loans to countries. However, countries must fulfill asset of condition before their application can be granted. The eligibility conditions or criteria are several. The first condition is that the IMF should have a direct link to the program that is being rolled out with its money. The condition is aimed at enhancing accountability and control of the economic direction by the IMF. Consequently, the condition acts as security for the MF funds by avoiding misallocation or squandering by government officials. Second, the project that is supposed to be financed must be stated clearly, with the requirements. This information can be found on the IMF factsheet. In addition, the government must accompany the information with the reasons that caused of the problem and the efforts that are being made to ensure that the situation is resolved in the future. The factors that led the government to request funds from the IMF must have a proposed solution in the loan application details. The IMF can approve the proposal, reject them or offer alternative policies that can achieve similar or better results (IMF). In cases where the economic policies of the

Current Recession Impacts on the Construction Industry Dissertation

Current Recession Impacts on the Construction Industry - Dissertation Example This resulted in reduction of the average disposable income. The overall negative implications were on the demands of products and goods. The economic cycle was disturbed. One of the most affected sectors by this recession was constructions and engineering sector. Globally the construction industry was at its peak in 2008, when the recession hit it. At this time, the demands of houses and infrastructure were increasing and there was consistent flow of funds within the sector. The demands of housing and new infrastructures and the flow of funds within the construction sector changed (Barrell and Kirby). The reduction in the expected flow of funds and unavailability of the predicted clients reduced the profitability and chances of survival for may construction companies across the world (Property Wire). Research Background According Jakovljevic the construction industry has a worth of nearly $5 trillion globally in terms of total output. This sector is one of the sectors providing high est employment. As per the estimation, there are nearly 100 million people employed in this sector at various levels of jobs. At the same time, contribution of the construction sector to the Global GDP is nearly 10%. This figure is considerably higher than the estimated annual spending in 2008. According to Zeiss (2008) the US$ 2.3 Trillion was the estimated spending of the Global Construction Industry. Global construction industry reached to the peak before recession. PropertyWire (2009) argues that the recession of 2008 was the hardest hit on this sector in last 60 years. Construction industry as such operates in highly complex business environment. The business environment is characterised by high regulations, coordination of various authorities, departments and skill sets, impact of the changing climatic and weather conditions on the construction process, lagging productivity or other issues linked with workforce (Bosch and Phillips). The recession at one hand reduced the dispos able income of the consumers by salary cuts and loss of jobs; on the other hand, this reduced the funds flow in the construction sector. All the intermediaries like equipment suppliers of the construction sector, transport companies, intermediaries and others have experienced the repercussions of the recession. The business environment of the construction sector became more pessimistic. However by the mid of 2009, the impact of recession was reduced and industry started being optimistic again. This was revealed in a global survey conducted by KPMG that by the end of 2009, the Global construction industry started expecting positive growth. This was an important survey that covered more than two-third construction companies of the globe and from the 30 different countries. The study reported that the majority of the construction companies were having positive growth or consistent business performance. However it was evident in the study that the companies working on the long term proj ects have minor impact of recession as compared to the companies who were expecting returns at the shorter duration (Molly). The recession resulted in reducing

LEADERSHIP Essay Example | Topics and Well Written Essays - 3000 words

LEADERSHIP - Essay Example stitutions and hospitals to recruit nurses, who have efficient leadership skills that would be beneficial to provide good quality health care to the patients (The Faculty of Medical Leadership and Management, 2015). Possessing a powerful and effective leadership skill is very essential for the nurses, especially who are in the top most positions. The role of a nurse is to provide care to the patients and provide medicines to the patients as being prescribed by the doctor. Sometimes, in the absence of doctor or registered practitioner, the nurses are required to take decisions regarding the medicines to be provided to the patient in case of emergency. It is very essential for a nurse to be a good decision maker that is an important element of leadership skill, which would help to take important decisions in emergency situations (Cherie & Gebrekidan, 2005). Therefore, a nurse should possess effective leadership skills as well as styles that would help in leading, controlling, organizin g and planning their activities, which would serve beneficial in delivering effective healthcare services to the patients (National Academy of Sciences, 2011; CNA, 2010). From my past experience in a well-known healthcare organization, helped me to understand how the quality of nursing is being influenced by the leadership styles and skills possessed by the nurses. I was being appointed as a trainee in the healthcare centre from where I gained practical experience regarding the leadership qualities possessed by the nursing professionals working in the healthcare centre. The leadership skills possessed by the head nurse of the organization inspired me the most. She was prominent and experienced in every aspect of decision making that are required for providing good quality healthcare in the organization. Moreover, she was highly cooperative with the team members and the junior nurses and supported them to carry out their activities in an effective manner. She always tried to make sure

Current Recession Impacts on the Construction Industry Dissertation

Current Recession Impacts on the Construction Industry - Dissertation Example This resulted in reduction of the average disposable income. The overall negative implications were on the demands of products and goods. The economic cycle was disturbed. One of the most affected sectors by this recession was constructions and engineering sector. Globally the construction industry was at its peak in 2008, when the recession hit it. At this time, the demands of houses and infrastructure were increasing and there was consistent flow of funds within the sector. The demands of housing and new infrastructures and the flow of funds within the construction sector changed (Barrell and Kirby). The reduction in the expected flow of funds and unavailability of the predicted clients reduced the profitability and chances of survival for may construction companies across the world (Property Wire). Research Background According Jakovljevic the construction industry has a worth of nearly $5 trillion globally in terms of total output. This sector is one of the sectors providing high est employment. As per the estimation, there are nearly 100 million people employed in this sector at various levels of jobs. At the same time, contribution of the construction sector to the Global GDP is nearly 10%. This figure is considerably higher than the estimated annual spending in 2008. According to Zeiss (2008) the US$ 2.3 Trillion was the estimated spending of the Global Construction Industry. Global construction industry reached to the peak before recession. PropertyWire (2009) argues that the recession of 2008 was the hardest hit on this sector in last 60 years. Construction industry as such operates in highly complex business environment. The business environment is characterised by high regulations, coordination of various authorities, departments and skill sets, impact of the changing climatic and weather conditions on the construction process, lagging productivity or other issues linked with workforce (Bosch and Phillips). The recession at one hand reduced the dispos able income of the consumers by salary cuts and loss of jobs; on the other hand, this reduced the funds flow in the construction sector. All the intermediaries like equipment suppliers of the construction sector, transport companies, intermediaries and others have experienced the repercussions of the recession. The business environment of the construction sector became more pessimistic. However by the mid of 2009, the impact of recession was reduced and industry started being optimistic again. This was revealed in a global survey conducted by KPMG that by the end of 2009, the Global construction industry started expecting positive growth. This was an important survey that covered more than two-third construction companies of the globe and from the 30 different countries. The study reported that the majority of the construction companies were having positive growth or consistent business performance. However it was evident in the study that the companies working on the long term proj ects have minor impact of recession as compared to the companies who were expecting returns at the shorter duration (Molly). The recession resulted in reducing

Quality Assurance & Control in the Procurement Chain (Oil & Gas Dissertation

Quality Assurance & Control in the Procurement Chain (Oil & Gas Industry) - Dissertation Example This concern can be stated as quite vital for the oil and gas companies as the products offered by the industry is termed to be inelastic providing minimum opportunity to the customers to switch to substitute products (Slocum, 2006). The research study proposed in this paper shall emphasise on this aspect of quality assurance and control measures as considered by the oil and gas companies. Further description of this paper will thereby focus on identifying the particulars of the research process intended to be executed. In other words, a comprehensive and detailed outline of the research planning shall be provided in this paper with due consideration to the research problem, research questions and the research methodology to be followed in the study. II. Literature Review Various measures had been considered in concern to the aspect of quality assurance and control in the oil and gas companies. These include environmental regulations and procurement rules imposed by the government wi th the intention to standardise the operations of the industry players. ... Companies should also intend maintaining a community standard in their operations as directed in the programme (Gao, 1998). In the current day context, gas and oil industry plays a significant role for an economy. The industry nearly contributed 24% to the total GDP earning of the UK in 2008. The industry also witnessed a significant rise in the investors’ interest. This in turn significantly enhanced the profitability of major industry players with inelastic consumer demand and increased financial strength (UK National Statistics, 2009). However, from an in-depth perspective it can be observed that the taxation charges were increased in the recent years. To be illustrated, the budget planned in 2011 stated a hike in revenue tax charges from 20% in the prior fiscal year, i.e. 2010-2011, to 32% in the current fiscal year, i.e. 2011-2012. It is worth mentioning that the UK oil and gas industry was recognised to be one of the most stable industries in comparison to the energy ind ustries of other economies. With strong barriers to the price hike in the industry, the UK government also focussed on relatively secure tax regimes that provided the investors in the industry with certainty assurance (Energy and Climate Change Committee Inquiry, 2011). On the similar context, it can be stated that with strict regulatory barriers the oil and gas industry in the UK is likely to face various challenges in maintaining its profit. According to the report forwarded by Energy and Climate Change Committee (2011), there are various challenges likely to be faced by the oil and gas industry in the economy due to the increase in tax charges. For instance, the industry is likely to witness decelerated investment operations that in turn shall

Comparison of Heroin Lies with The Basketball Diaries Essay Example for Free

Comparison of Heroin Lies with The Basketball Diaries Essay Heroin is a deadly drug, which kills approximately one million people every year. In this essay I will be comparing two dramatic acts. Heroin Lies, which I acted out. The other is a 1995 hit called The Basketball Diaries. I chose this particular film to compare with my act because they have several similarities but also a number amount of differences. The beginning of the film The Basketball diaries starts with an ordinarily boy waking up in bed on a normal day. Instantly you see that he has got a type of book in his hand, which later on we see that it is his diary which he occasionally writes in. In the block opposite him we see a strong religious woman constantly shouting out what seems to be a prayer. We then witness the boy by the name of Jimmy Carroll change from an innocent being to a horrifying beast as he tells this religious woman to Shut up! We now see that Jimmy has a horrible side to him. As we watch on we see that Jimmy Carroll is a star basketball player on his New York City Catholic school team. Fellow basketball team mates Mickey and Neutron and unofficial cheerleader Pedro are Jimmys closest friends, and whenever trouble stalks one, it invariably affects them all. So, when the drug cycle starts, it quickly spreads to each of the four corners of the friendship. What begins as casual use first becomes a weekend habit, then an everyday obsession. Grades plummet, on-court performance becomes unreliable, and crime looms as the only means to pay for a seemingly endless supply of uppers, downers, cocaine, and heroin. Heroin Lies is a play written by Wayne Denfhy. The story is about a young teenage girl that is having problems with friends. Later on she finds her self addicted to heroin and soon after dies at an early age. We chose a scene from the play and we made changes to the scene as apart of our task, for example we added monologues and dialogues. I learnt a lot about the characters in our scene. Vicki was a young stubborn teenager who had a lot of confusing things going on in her life, although she finally decided to make a decision and start taking drugs to solve her problems. Mandy had been involved with drugs longer than Vicki. So obviously Mandy would be more confident about it. Mandy can easily loose her temper as we showed in the play when Vicki hits the drugs all over the floor. Mandy ends up slapping Vicki. This implies that Mandy is quite violent and doesnt know how to control her emotions very well. My character (Jason) wears corded trouser and an old knitted woollen jumper to sho w that he bought them from Oxfam, since what he wears is mentioned in the script. I believe that Jason is quite immature watching playschool and pretending to grow into a big tree. However this end scene Mandy got what she came for. Jason, my character, was an older brother of Vicki, as it says in the script however I had played him younger then Vicki. As Mandy was flirting with me I used a stuttering voice to emphasize the fact that I was shy. This tells us that Jason is growing up as the tree is growing, and Vicki is stuck, still having problems with friends and drugs. This scene Mandy probably would like to know more about Jason. Not only does the relationship between Mandy, and Jason but the relationship with Vicki later on in the scene. Vicki seems more dominating with Jason since she scares him off. I dont believe that Vicki feels very comfortable having Mandy in her house. This results in Vicki snatching the drugs off Mandy and Mandy hitting Vicki. After Vicki has been hit. Mandy comes to her senses and tells her she regrets hitting her and asks Vicki to take some drugs. I believe that this is the most important part of the scene because this is the first step of Vicki ending her life. Heroin Lies and The Basketball Diaries in my opinion had interesting but defiantly very similar characters. Vicki Brown (Heroin Lies) who is a drug addict who gets thrown out of her house. Jimmy Carroll (The Basketball Diaries) is a drug addict and like Vicki Brown gets thrown out of his house. This is an example of a similarity. However after becoming a drug addict Vicki Brown then leads to a tragic ending. Whilst Jimmy Carroll then realises his mistakes, then fights his addiction to drugs. I have researched Heroin to find out more about this drug. Heroin is a highly addictive drug, and its use is a serious problem in America. Recent studies suggest a shift from injecting heroin to snorting or smoking because of increased purity and the misconception that these forms of use will not lead to addiction. (From a website discussing drugs) The play that I did Heroin Lies and the film The Basketball Diaries had several similarities and differences. The main similarity that I picked up was that these two plays were based on drugs. This is also the main reason I chose to compare these two plays. Heroin Lies was set in the 90s, which is modern time. These days it tends to be teenagers that are addicted to these drugs. The film The Basketball Diaries was also set in the 90s, which again the teenagers are pushed towards Heroin.

Accelerated Pathways for Authorisation of Drugs

Accelerated Pathways for Authorisation of Drugs Mary Treasa Lohan Abstract and Summary Every year, thousands of chemical and biological entities are developed in the hope of making it to the shelf. The drug development process is the progression by which drugs will either be approved or not approved for use, and spans from discovery and preclinical testing to Phase IV of Clinical Trials (post marketing surveillance). The underpinning aim is to ensure the safety and efficacy of a drug before it can be approved for use. Given that only one in every 5,000 to 10,000 compounds that enter preclinical testing are approved for marketing, and that an average of 15 years is required to take a drug through the complete process, the drug development process is a long and costly one. The two main regulatory bodies in the world are the FDA (USA) and the EMA (EU) and while the drug approval process varies from the EU to the USA, the basic regulation process remains the same. Figure 1 Basic drug development regulation       (Kashyap et al., 2013) 1.1. Drug approval process in the US In brief, the process of drug approval in the US first involves the submission of an Investigational New Drug application by the Sponsor. This allows the Clinical Trials to commence once the data from the Preclinical trials shows that the drug is safe. Once the drug is shown to be safe and effective (Clinical Trials data), a New Drug Application is filed which is essentially an application to manufacture and sell the drug (Rick, 2009). 1.1. Drug approval process in the EU The application process for the EU, similar to the US, requires two steps. The first step is a clinical trial application to an individual member state, and then a marketing approval. The marketing approval in the EU can take one of three approaches The centralised procedure The mutual recognition procedure The decentralised procedure As mentioned before, the purpose of the drug development process is to ensure safe and effective drugs are available to the patient. However, both the US and EU processes are very lengthy procedures and often do not provide rapid patient access to drugs. There is of course a balance to be struck between providing patients with rapid access to medicines and ensuring adequate information is available regarding the risk-benefit factors of the drug, sometimes termed the evidence versus access challenge (Eichler et al., 2015). 1.2. Improvements In recent times however, much has been done to try and improve the situation (Baird et al., 2014). In the EU, there are two means to fast track approval of a drug; Accelerated assessment and Conditional marketing authorisation. The Conditional marketing authorisation process allows the approval of a medicine that address unmet medical needs of patients on the basis of less comprehensive data than normally required. The available data must indicate that the medicines benefits outweigh its risks and the applicant should be in a position to provide the comprehensive clinical data in the future (EMA, 2015). In 2014, the EMA initiated a pilot project for a new model of drug testing and marketing called Adaptive Pathways (also known as Adaptive Licensing, or more recently the terms Medicines Adaptive Pathways (MAPs) or Medicines Adaptive Pathways to Patients (MAPPs) have been used). This concept allows new drugs that would treat unmet medical needs to be launched on the market faster, based on an incomplete data set (Davis et al., 2016). This project aims to discuss Adaptive Pathways in general, the different types of Adaptive Pathways, as well as the types of drugs that are suitable for these pathways. Finally, the Adaptive Pathway approval strategies in the EU and the US will be discussed. 2.1. Adaptive Pathways 2014 saw the introduction of a pilot program by which drugs could potential to make it to the market faster in order to fulfil unmet medical needs, the Adaptive Pathway. The idea was to ensure timely patient access to new drugs, while ensuring adequate risk benefit information was available. The Adaptive Pathways model presented by the EMA is not a new route of marketing authorisation but rather makes use of existing regulatory approaches such as the conditional marketing authorisation or the standard marketing authorisation. Using this pilot program, drugs could be authorized conditionally or in a staggered fashion using data gathered throughout the life of the product. The three key principles of Adaptive Pathways are; Iterative development Gathering real-life evidence Early involvement of stakeholders Bearing in mind that drugs are approved through adaptive pathways based on incomplete data and are given market approval earlier in the development process, iterative development refers to the gathering of data to increase knowledge after authorisation. It is a staggered approach to widen the target population or expand the indication. The data collected can also be used to reduce any uncertainties that were present at the early approval stage. A key component of Adaptive Pathways is a well-defined prospective plan for collecting real-life data that can be used in conjunction with the Clinical Trials data to enhance the risk benefit ratio (Eichler et al., 2012). Communication between stakeholders is critical and helps to decide what medicines are suitable, and are also responsible for creating an agreed prospective plan required for data gathering throughout the lifecycle of the product. Stakeholders are involved from a very early stage and can include health technology assessment (HTA) bodies, patients, as well as regulators and healthcare professionals. 2.2. Benefits and challenges of Adaptive Pathways The obvious advantage of the Adaptive Pathway is that the patient can potentially have access to a drug in a much shorter time period than if the drug had to go through the standard application process. If the drug shows a good risk benefit outcome, the drug can be approved at an earlier stage, while real-life data is gathered at predefined intervals from patients to confirm effectiveness. There is also the opportunity for drugs to be fully approved within a shorter timeframe than normal.   Eichler also suggests that this process may reduce the overall cost of development by allowing better-informed decisions on product viability to be made earlier in the development process (Eichler et al., 2012). Eichler has published an article detailing the enablers of this new concept (Eichler et al., 2015). However, since the publication of the EMAs final report in July following the completion of the pilot program, a number of articles have been published which criticise the new concept (Eichler et al., 2012) (Woodcock, 2012). Unlike the standard authorisation, the Adaptive Pathway uses preliminary data and omits a number of steps that were designed to protect patients from unsafe and ineffective drugs and, this raises concerns as to whether this can potentially lead to increased risk to the patient. For adaptive Pathways to work, it is critical that evidence obtained after initial approval be taken into consideration. However, it has been found that healthcare professionals are often slow to abandon unsafe methods (Tatsioni et al., 2007). This is worrying as the basis of Adaptive Pathways is that reliable data is generated after authorisation that will shed more light on the risk benefit to the patient. Another serious concern relates to the life cycle management of the new drug (Davis et al., 2016). As mentioned earlier, a key principle of the Adaptive Pathway is gathering real-life evidence in post-marketing studies that would be used to update the risk benefit information. However, it would seem that in the case of conditionally approved drugs, the regulatory bodies have failed to ensure post-marketing study commitments are followed through (Banzi et al., 2015). It has also been suggested that where undesirable findings are encountered, companies may dispute these as unreliable results (McCabe et al., 2010) or may discount them because there are large financial gains or reputations at risk (Prasad et al., 2012). Moreover, the willingness of stakeholders to participate in a program that involves more uncertainty, and correspondingly perhaps more risk, than before will be one of the greatest challenges to the Adaptive Pathway. 2.3. Suitable drugs for Adaptive Pathways The report issued by the EMA suggests that drugs that treat infectious diseases, Alzheimers disease, degenerative diseases and rare cancers are potential candidates for this process with the objective of furthering their development and that suitable for the Adaptive Pathways would be those that treat rare diseases, where clinical data is not that common. The EMA have provided a flowchart to help companies determine if a product is an appropriate candidate or not, (Figure 2). Based on this, the key features of a drug that could be deemed suitable for this Adaptive Pathways approach are; iterative development, collaboration with HTA, and the use of real time data for regulatory purposes. Figure 2 Adaptive Pathway product eligibility flowchart While there is no strict restriction on what type of drugs are eligible for the Adaptive Pathways, the EMA states that this route is not to be applicable to all medicines, but only to medicines that are likely to address an unmet medical need(EMA, 2016). During the pilot, 62 applications were received from a variety of therapeutic areas with cancer therapies accounting for a large proportion (33%). It is worth noting that Orphan designated drugs are suitable candidates, with 5 making it through to Stage 1 Meetings (15 drugs had been given Orphan drug designation by the European Commission at the time of submission) (EMA, 2016). (EMA, 2016) 2.5. Adaptive Pathway approval strategy in the USA Within the USA, there are four approaches to getting drugs on the market as rapidly as possible, and in each case the drug must be intended to treat a serious condition. A serious condition is defined as a disease or condition associated with morbidity that has a substantial impact on day-to-day functioning Fast Track Breakthrough Therapy Accelerated Approval Priority Review Fast Track refers to the process, approved in 1992 under the Prescription Drug User Fee Act, by which drugs needed to treat serious conditions or to fulfil unmet medical needs are rapidly approved. According to the FDA, filling an unmet medical need is defined as providing a therapy where none exists or providing a therapy which may be potentially better than available therapy (FDA, 2014). This strategy means more communication with the FDA regarding the drug development plan, data collection and clinical trials design. In addition, a Fast Track designated drug is potentially eligible for Accelerated Approval and Priority Review if it meets the applicable criteria. Breakthrough Therapy designation accelerates the development of drugs needed to treat serious conditions that have shown substantial advantages over existing treatments in early clinical studies (Poirier and Murphy, 2016). This strategy utilises a surrogate endpoint. A surrogate endpoint is a marker used to determine effectiveness of a drug, such as the shrinking of a tumour and is often used rather than actual clinical endpoints, such as survival rates. Another example would be a significantly improved safety profile compared to available therapy (FDA). In addition to the Fast Track designation benefits, Breakthrough Therapy drugs receive a vast amount of guidance with the drug development program. References   BAIRD, L. G., BANKEN, R., EICHLER, H. G., KRISTENSEN, F. B., LEE, D. K., LIM, J. C. W., LIM, R., LONGSON, C., PEZALLA, E. SALMONSON, T. 2014. Accelerated access to innovative medicines for patients in need. Clinical Pharmacology Therapeutics, 96, 559-571. BANZI, R., GERARDI, C. GARATTINI, S. 2015. Approvals of drugs with uncertain benefit-risk profiles in Europe. European journal of internal medicine, 26, 572-584. DAVIS, C., LEXCHIN, J., JEFFERSON, T., GØTZSCHE, P. MCKEE, M. 2016. Adaptive pathways to drug authorisation: adapting to industry? BMJ: British Medical Journal, 354. EICHLER, H. G., BAIRD, L. G., BARKER, R., BLOECHLà ¢Ã¢â€š ¬Ã‚ DAUM, B., BØRLUMà ¢Ã¢â€š ¬Ã‚ KRISTENSEN, F., BROWN, J., CHUA, R., DEL SIGNORE, S., DUGAN, U. FERGUSON, J. 2015. From adaptive licensing to adaptive pathways: Delivering a flexible lifeà ¢Ã¢â€š ¬Ã‚ span approach to bring new drugs to patients. Clinical Pharmacology Therapeutics, 97, 234-246. EICHLER, H. G., OYE, K., BAIRD, L. G., ABADIE, E., BROWN, J., L DRUM, C., FERGUSON, J., GARNER, S., HONIG, P. HUKKELHOVEN, M. 2012. Adaptive licensing: taking the next step in the evolution of drug approval. Clinical pharmacology and therapeutics, 91, 426. EMA. 2015. Fast track routes for medicines that address unmet medical needs [Online].   [Accessed]. EMA 2016. Final report on the adaptive pathways pilot. FDA. Breakthrough Therapy [Online]. Available: http://www.fda.gov/ForPatients/Approvals/Fast/ucm405399.htm [Accessed]. FDA. 2014. Fast Track [Online]. Available: http://www.fda.gov/ForPatients/Approvals/Fast/ucm405399.htm [Accessed]. KASHYAP, U. N., GUPTA, V. RAGHUNANDAN, H. V. 2013. Comparison of Drug Approval Process in United States & Europe. J Pharm Sci Res, 5, 131-6. MCCABE, C., CHILCOTT, J., CLAXTON, K., TAPPENDEN, P., COOPER, C., ROBERTS, J., COOPER, N. ABRAMS, K. 2010. Continuing the multiple sclerosis risk sharing scheme is unjustified. Bmj, 340, c1786. POIRIER, A. F. MURPHY, W. R. 2016. The Impact of Breakthrough Therapy Designation on Development Strategies and Timelines for Nononcology Drugs and Vaccines. Clinical Pharmacology Therapeutics, 100, 603-605. PRASAD, V., CIFU, A. IOANNIDIS, J. P. A. 2012. Reversals of established medical practices: evidence to abandon ship. Jama, 307, 37-38. RICK, N. 2009. Drugs from discovery to approval., John Wiley & Sons, Inc. TATSIONI, A., BONITSIS, N. G. IOANNIDIS, J. P. A. 2007. Persistence of contradicted claims in the literature. Jama, 298, 2517-2526. WOODCOCK, J. 2012. Evidence vs. Access: Can Twentyà ¢Ã¢â€š ¬Ã‚ Firstà ¢Ã¢â€š ¬Ã‚ Century Drug Regulation Refine the Tradeoffs? Clinical Pharmacology Therapeutics, 91, 378-380. staggered or conditional marketing authorization AL is expected to involve a trade-off between earlier access for some patients vs. an increased level of acceptable uncertainty about benefits and risks, although the degree of uncertainty is expected to diminish with additional evidence generation. One of the main purposes of the AL scheme is to get more robust and more relevant data earlier and throughout product development. Any attempt to move toward a more adaptive approach would have to be complemented by appropriate communications to key stakeholders and assurance that the appropriate post-initial authorization capabilities exist for ongoing monitoring of medical products for which AL has been applied