Wednesday, October 30, 2019

International Marketing Strategies of Pepsi and Apple Inc Essay - 7

International Marketing Strategies of Pepsi and Apple Inc - Essay Example This research will begin with the statement that PepsiCo and Apple Inc are two renowned international companies making a name while employing international marketing activity across the world. These companies have instituted what is vital to marketing in the international context. They employed the essential activities for them to be able to surpass a very tough competition in their industry around the world. Apple Inc has become popular with its capacity to innovate not just in marketing activities, but almost all components of its operation. PepsiCo, on the other hand, has become trendy with its ability to initiate the high level of market performance with a purpose, allowing it to rank next to Coca-Cola.   Ã‚  Ã‚  These two companies are therefore mostly studied because of their innovative approach and contribution to modern marketing techniques, allowing them to employ marketing strategies that at some point are cut above the other while adhering to the basics. They eventually do not just settle for less, but above all are market leaders willing to substantially innovate and create a difference in their respective industry.PepsiCo, for instance, has become the wide competitor of Coca-Cola, and in this situation, it is necessary for the firm not only to contend but create its brand as something worthy to be considered unique and one of a kind in its industry. On the other hand, Apple Inc is experiencing the same scenario, because of the linked many players in its industry. It is going to be hard for the company to compete in an industry where there are relevant key players mushrooming and aiming to get a substantial market share and a sustainable competitive advantage. However, Apple Inc has eventually proven its worth, allowing it to be as one of the top key players in its industry. In 2012, the firm was voted as the winner of the 2012 CMO Survey Award for Marketing Excellence.

Monday, October 28, 2019

Development levels and record Essay Example for Free

Development levels and record Essay To observe Lydia during a creative choosing session. I will try to observe her development levels and record how she interacts with other children and the adults around her.  Setting  The primary school, in which I am working in, is situated on a campus with a sports centre, a community school and a 6th form college. It has 6 junior classes and 3 infant classes. There is a class room assistant and a teacher for each class. On a Thursday and a Friday there are 2 students working in the infants. There are a various number of parent helpers in on different days of the week. Lydia is 6 years 11mths old and is in yr. 2. She has just completed her SATS. She is in the 1st (higher) set for math and in the 2nd (middle) set for literacy. She has many friends and enjoys school, learning new things. Lydia has 3 friends who she usually plays with and works with in class. They are all girls and all in year 2. Hannah, Shannell Erica and Lydia always do the same activity even if they dont all agree. English is Shannells second language and she sometimes has trouble with the language barrier between the girls in the group. I will observe Lydia on the 27th of July 2002 for 45mins during a creative choosing session. There are several activities set up in the class rooms and the children may choose which activity they wish to participate in. Some of these activities include painting, drawing, junk models and collage work. Observation  I will make notes during my observation, then copy it up into a written report.  Lydia heads straight for the art table at the far end of the classroom where a painting session has been set up. Her and many of the yr2 girls start collecting sheets of paper. Lydia, Hannah, Erica and Shannell ask me what they can paint as I sit down at the end of the table. I suggest that they draw each other. So the girls pair up. Hannah and Lydia start to paint Shannell and Erica. Lydia looks closely at Ericas features and tries to copy down all the details. She notes the freckles, the dimples the small earrings and the way her hair is put up. She miss judges the size of Ericas nose and as a consequence the picture looks out of place. She mixes up the colour to fill in for Ericas skin tone. Erica sits slightly impatiently fidgeting slightly. Lydia still concentrates on the painting and ignores Erica impatience and continues to concentrate hard on the colour mixing. I ask her some questions. Lydia, what colours make green?  Thats easy, you just mix blue with yellow   But you have to put yellow in first cause blue is darker and you have to put loads of yellow in to make it a lighter colour.  Ok, how about purple?  Oh Miss Carr, that is well easy, dont you know?  Im just seeing if you do, so that if you dont know I can teach you.  Oh, -thinks hard- ok. Its blue and red. Isnt it?  Yes well done, How about brown?  Yellow, blue and red! I learnt a lot from with class 1 / 2 K and this was a typical session. Everyone in the class has different view on things and even though there are definant social groups every one is friends with everyone else. The teachers and other staff need to practice anti-discriminatory and anti-bias practice. It is important to portray equal opportunities.  Children are to be treated equally but at the same time their personal needs need to be taken into consideration. In class 1 / 2 K there are friends who are in definite social groups then there are groups that inter-change and mix with the whole of the infants school. This observation points out how the girls work together to the get tasks completed. They all work together to form a good team. It is a clear that the team works well; they all have roles to play. Theres the team leader Hannah, the quick thinker Erica and the do-er Lydia who always works hard to complete necessary tasks. Shannell is a hard worker and tries to fit in even if she doesnt always understand. I learnt to set up and clear away activities with the childrens help how to encourage exploration of colour and creativity. I managed to gain the childrens confidence and by helping them to reach their full potential.  All four girls developed their fine motor skills and creativity in this exercise. They practice painting techniques and different colours and styles. They learned how to co-operate and communicate with each other. They learn to trust opinions of the adults they work with, they learn to respect their knowledge and experience. I think that in the future the children could be put into groups to help them to mix into different social groups and form new relationships. Lydia could have, in the future, extra help during tasks which involve thinking though complicated theories, and she has trouble understanding some complicated concepts.

Saturday, October 26, 2019

Editing, Cinematography, and Sound in Gladiator Essay -- Papers

Editing, Cinematography, and Sound in Gladiator The film that I have chosen to analyse is Gladiator. I have chosen to analyse the scene where the gladiators are battling in the Middle East. The scene contains many features and editing techniques which make the fight sequence exciting and thrilling. The scene begins with a medium high angle shot of a goat with blood dripping down its body. This shot frames the body of the goat and gives it a sense of vulnerability. The shot creates meaning to the viewer who can predict that the scene might contain violence or bloodshed of some sort. The camera then zooms outward into an establishing shot to give the viewer an idea of the setting. The mise en scene conveys the setting, which is in the desert, the costumes are distinctive of the Middle East and to accompany this there is non diegetic Middle Eastern music. All of these aspects of mise en scene and the camera shot completely give the viewer an idea of the setting. The title of the film is Gladiator, from this the viewer would expect the film to be set in Rome, but these features are put together to highlight that the setting is not in Rome. The desert and Middle Eastern music are not typical features of Rome. The props and setting also convey the genre of the film. The genre is a historical adventure and although the scene is not set in Rome there are features such as the coliseum and chariots which suggest to the audience that the film is set in that particular time period. The props i.e. the armour plating, swords, and battle axes are also distinctive to the genre. The establishing camera shot in which all of this is shot is al... ...feels the battle as a haze. The music then begins to go quieter and at this stage the 360ËÅ ¡ shot turns to the crowd instead of Russell Crowe and here the camera begins to become dark and unclear, this is where the next scene begins. This use of the 360ÂÂ ° is effective as it ends the scene mysteriously. The shot is fast and distorted leaving the viewer longing for more exciting and thrilling battles. And because the scene is early on in the film, the viewer could predict more battles to come after the mysterious and distorted ending. In conclusion, the scene contains many camera and editing techniques such as low and high angle shots, quick speed and order of editing and the camera shot behind the netting. All of these shots created a specific meaning to the audience and are intended to create a specific response.

Thursday, October 24, 2019

According to Cormack

As reflected in his painting `Hay Wain`, Constable had naturalist concerns   as compared to the more romanticist elements of Turners work, as exemplified in his painting The Slave Ship. Constable made all the efforts towards rebellion against the cultures of the artists in the application of imagination for the purpose of representation of their art in favor of nature.He stresses the need to forget having seen any picture in the process of making a sketch. His studies are based on the spot of action in contrast to following any formula. According to Cormack, â€Å"The world is wide†, no two days are similar, nor even two hours; neither were there ever two leaves of a tree alike since the creation of all the world; and the genuine productions of art, like those of nature, are all distinct from each other.† (Cormack, 2006).  In comparison to the work of Turner, he had a less extensive range as well as aspirations. The most suitable definition of Constable is a ‘n aturalist’ which through his correspondence, he has successfully as so. However, the stylistic variety of Constable is marred with instability with regard to the perception of the constituent of nature. Further the sites intimately known to him have been the focus of his paintings.There is no strict uniqueness of the indisputable approach of Constable in as far as the concern of the local scenery is concerned. This is evidenced by the participation of the contemporary artist of the Norwich as well as the conformation to the work of Thomas Christopher, who is an artist of 1777-1843 (Fleming-Williams, 2006). The common practice is the application of oil to sketch from nature.Turner has made his contribution to in the establishment of a landscape to represent a historical painting although he widely disputes the idea. The single mindedness of Constable is responsible for the portrayal of site of limited range in a unique way producing unprecedented oil sketching of a brilliance capacity (Fraser, 2006).On the other hand, Turner has a subjective reflection that surpasses far beyond the romantic contemporaries that he possesses with the capacity to foreshadow an image in dissolution in a painting of the 20th century. According to Bailey, the best description of the work of Turner is â€Å"airy vision painted with tinted steam† (Bailey, 2007).As has been visualized in the Slave Ship in an instance that a description is offered of the sharks following the slave ship in reaction to a storm. The sharks react to the scent crowds that steam due to rank diseases as well as death.There is also an existence of a realistic event involving a slave ship captain dumping human cargo in the sea as result of a disease outbreak below decks. The work of Turner has a clear demonstration of romanticism elements through the employment of disjoint diagonals. The consequence is composition fragmentation (Kelder, 2000).Turner, the terrific creator had the potential for the ap plication of unique invention for the purpose of liberating color from line definition for the purpose of the expression of the natural forces for the purpose of its unity to the stirring response of the artists.This leads to uniting emotions reality to the color reality. Used as an abstract media, the work of Turner was associated with unpredictable effects. This is seen in the nature of ultimate painting element evident in his innovations due to the emotive as well as aesthetic strength of his application of pure color (Leslie, 2005).

Wednesday, October 23, 2019

Airport Security Essay

Every upstanding individual who lays a foot onto the airport floor wants to remain safe. Consequently, that devastating day of September 11, 2001 instilled the fear of flying in many Americans. This gave our nation the need to reevaluate airport checkpoints in order to secure the safety of the people of our country from those who are not sympathetic to our American ways. Some find that the measures the Transportation Security Administration (TSA) has taken in the recent years are unjust and a violation of many rights that we have by living in our free country. The reason that some of these rights have been taken away is only beneficial to the protection of our homeland. I propose that in order to give passengers a better experience, the up and coming technologies such as Thermal Lie Detection and â€Å"all in one screening† need to be implemented as soon as they become available. With these new methods, passengers will become more understanding of the safety the government is providing rather than viewing it as a violation of privacy. The sole purpose of this writing is to persuade and inform the society on the necessity of the security equipment, despite the hassle, and to educate those about the rising developments. Presently, high tech x- ray machines, metal detectors, body scanners, and pat downs are the methods implemented in order to greatly decrease the possibility of anything catastrophic happening within the airports or on board the aircraft. I have personally had to partake in this bothersome process, and I’m going to have to deal with the annoyance more often after I graduate as a Hospitality Management major. The annoyance of the current process is not only cumbersome to me but especially to frequent flyers, nonetheless it remains extremely necessary. The aim of my extended argument examines the possible changes within airports so they can further protect us, the people, and lead to a more satisfactory client base. My proposition will mainly be directed towards my ENC1102 professor and my fellow classmates, as well as other common travelers, school teachers, adults, and our upcoming generation. After extensive research for my exploration of both sides of the argument, I have found many reasons as to why we must partake in the elongated processes of airport check-ins, however, I foresee more effective, simpler, less violating new systems that are currently birthing. An airline officials reveals that â€Å"prior to 9/11, an average of 350 people would normally go through a checkpoint in an hour. Now the number is down to about 150 in one hour† (Jim Barnett). This background knowledge shows how evident of a change that needs to be instilled in the TSA’s methods. The up and coming technology on the horizon is thermal lie detection which has the ability to detect different facial temperatures towards those who seem suspicious. Another enhancement is the â€Å"all in one† screening, a series of detectors equipped with eye-scanners, x-ray machines, metal and liquid detectors, which will surely speed up the process. These innovations will further be explained in detail in my upcoming extended writings. My further works will start off with explaining the controversy over airport security and its benefits and disadvantages. First, there will be brief overview of the entire subject and an explanation as to why people are angered by this subject. Then, I will lead into further investigation on the topic and go into detail about the two different advances that will better help our airports. I will use research articles and descriptions of the product to better inform my reader. Finally, I will persuade readers that with less compromising systems travelers will soon turn understanding and be thankful towards the officials trying to keep them safe. This brings me to the conclusion of this plan leading to a better-rounded more satisfied consumer base. This paper encumbers a full understanding of why a percentage of the population feel like their civil rights are being stripped away. In the past I would have agreed with them, but our world is a dangerous, frightening place, and all citizens must stand up to the plate and understand the actions taken by our government, like our parents, they do whatever they must do to protect us, their children. This act actually ensures us our freedom, to cross boarders freely with piece of mind; it definitely doesn’t take away our freedom or take away our civil rights. One must get off their high horse and face reality. If we can implement this technology to make our processing time through the airport, more convenient, less harassing, less time consuming, and less degrading, most individuals will not feel so violated anymore. Eventually the process will be so simplistic and common that the negative feelings towards the TSA and our government will disappear and travelers will soon accept that the extensiveness of security and come to the realization that it’s only for their own good. With these security measures just on the horizon, we will no longer feel compromised and therefore become more comfortable and accustomed with the measures that need to be taken in today’s world to continue living in the land of the free. The goal is to work towards a safer tomorrow for us and generations to come yet still maintaining the integrity given to us by our forefathers. Works Cited â€Å"American Civil Liberties Union. † American Civil Liberties Union. N. p. , n. d. Web. 14 July 2013. Bajoria, Jayshree. â€Å"The Debate Over Airport Security. † Council on Foreign Relations. Council †¦.. on Foreign Relations, 28 Dec. 2010. Web. 16 July 2013. â€Å"BalancedPolitics. org. † – Civil Liberties/Patriot Act in Wartime (Pros & Cons, Arguments For †¦.. and Against, Advantages & Disadvantages). N. p. , n. d. Web. 11 July 2013. Barnett, Jim. â€Å"A Speedier Trip through Airport Security Could Come within a Decade. â€Å"CNN. †¦.. Cable News Network, 01 Jan. 1970. Web. 22 July 2013. â€Å"Flying With Fish The Blog for Those Who Fly & Those Who Want to Fly Smarter. â€Å"Flying With †¦.. Fish RSS. N. p. , n. d. Web. 22 July 2013. PBS. Drastic Changes in Airport Security After 9/11 Stir Controversy. PBS, n. d. Web. 11 July †¦.. 2013 Shachtman, Noah. â€Å"Passenger Screening Policies Violate Privacy and Do Not Ensure †¦.. Security. † US Airport Security. Ed. Margaret Haerens and Lynn M. Zott. Detroit: †¦.. Greenhaven Press, 2013. Opposing Viewpoints. Rpt. from â€Å"Has Airport Security Gone Too †¦.. Far? † Wall Street Journal 17 Nov. 2010. Opposing Viewpoints In Context. Web. 10 July †¦.. 2013. â€Å"The Patriot Act: Security Tool or Big Brother 2011. † Berkeley Political Review. N. p. , n. d. Web. †¦.. 14 July 2013. â€Å"The Usa Patriot Act, a Controversial Public Policy, Julius Taka. † – Term Papers. N. p. , n. d. †¦.. Web. 16 July 2013. Webster, George. â€Å"The Future of Airport Security: Thermal Lie-detectors and Cloned Sniffer †¦.. Dogs. † CNN. Cable News Network, 25 Nov. 2011. Web. 22 July 2013 â€Å"Where Do You Stand on the Usa Patriot Act? † – Essay. N. p. , n. d. Web. 16 July 2013.

Tuesday, October 22, 2019

Calculate the Expected Value in Roulette

Calculate the Expected Value in Roulette The concept of expected value can be used to analyze the casino game of roulette.  We can use this idea from probability to determine how much money, in the long run, we will lose by playing roulette.   Background A roulette wheel in the U.S. contains 38 equally sized spaces. The wheel is spun and a ball randomly lands in one of these spaces. Two spaces are green and have numbers 0 and 00 on them. The other spaces are numbered from 1 to 36. Half of these remaining spaces are red and half of them are black. Different wagers can be made on where the ball will end up landing. A common bet is to choose a color, such as red, and wager that the ball will land on any of the 18 red spaces. Probabilities for Roulette Since the spaces are the same size, the ball is equally likely to land in any of the spaces.  This means that a roulette wheel involves a uniform probability distribution. The probabilities that we will need to calculate our expected value are as follows: There are a total of 38 spaces, and so the probability that a ball lands on one particular space is 1/38.There are 18 red spaces, and so the probability that red occurs is 18/38.There are 20 spaces that are black or green, and so the probability that red does not occur is 20/38. Random Variable The net winnings on a roulette wager can be thought of as a discrete random variable. If we bet $1 on red and red occurs, then we win our dollar back and another dollar. This results in net winnings of 1. If we bet $1 on red and green or black occurs, then we lose the dollar that we bet. This results in net winnings of -1. The random variable X defined as the net winnings from betting on red in roulette will take the value of 1 with probability 18/38 and will take the value -1 with probability 20/38. Calculation of Expected Value We use the above information with the formula for expected value. Since we have a discrete random variable X for net winnings, the expected value of betting $1 on red in roulette is: P(Red) x (Value of X for Red) P(Not Red) x (Value of X for Not Red) 18/38 x 1 20/38 x (-1) -0.053. Interpretation of Results It helps to remember the meaning of expected value to interpret the results of this calculation. The expected value is very much a measurement of the center or average. It indicates what will happen in the long run every time that we bet $1 on red. While we might win several times in a row in the short term, in the long run we will lose over 5 cents on average each time that we play. The presence of the 0 and 00 spaces are just enough to give the house a slight advantage. This advantage is so small that it can be difficult to detect, but in the end, the house always wins.

Monday, October 21, 2019

Reparations Granted to the Descendents of Slaves essays

Reparations Granted to the Descendents of Slaves essays "If you have two people running in a mile race around a track and one has a ball and chain tied around his leg for three laps, you can't take the ball and chain off for the final lap and still expect him to win" Jesse Jackson's aide, Frank Watkins once stated. Many African Americans in the United States have demanded that our nation must confront and render reparations for the past injustices of slavery. The U.S. government has not yet awarded reparations to African Americans or made a formal apology for the involvement of this act. Essentially, this topic has arisen controversy for numerous years. Reparations cannot truly make up for past injustices Dealing with a highly complex and contended issue, many key factors contribute to my opposition of reparations. This complicated issue brings up many questions. For example, the last slave ship that arrived in the U.S. was in 1808. It is statistically likely that an individuals white ancestor immigrated to the U.S. post 1808. Should white immigrants that arrived after 1808 exclude themselves from helping pay for reparations? Should descendants of blacks that arrived in the U.S after 1808 be exempted from the reparations granted? Should all taxpayers bear the cost of reparations, or only those who are descendents of slave owners or from those who lived in the slave states? Although the United States was, in fact, a large contributing region for the housing of slavery, African tribes sold their neighbors in to the trade and sailors of the Spanish and Portuguese transported the slaves. This horrendous crime had other contributing factors than just the U.S., which received most of the blame for this crime. The payment of reparations would logically not make sense because how would anyone be able to divide the blame of slavery into the different contributing countries, regions, and tribes. Also, if reparations did exist, how would the decedents of slave owners or...

Sunday, October 20, 2019

Easy Methods to Arrange a Classroom

Easy Methods to Arrange a Classroom Classroom arrangement is one of the key decisions that teachers need to make when they begin a new teaching year. A few of the items that need to be decided include where to place the teacher desk, how to place the student desks, and whether or not to use seating charts. Where to Place the Teacher Desk Teachers typically place their desk to the front of the classroom. However, there is nothing that says that this is the way it has to be. While being in the front of the class affords the teacher a good view of the students faces, there are advantages to placing the desk in the back of the classroom. For one thing, by being in the back of the classroom, the teacher has less of a chance of blocking the students view of the board. Additionally, less motivated students will choose to sit in the back of the class even though the teachers desk is placed in the back. Finally, if a student needs help from the teacher, they might feel less intimated by not being on show in front of the classroom. Classroom Arrangement of Student Desks After placing the teachers desk, the next step is to decide how you will arrange student desks. There are four main arrangements that you can choose from. You can set up desks into straight lines. This is the normal way in which student desks are set up. In a typical class, you might have five rows of six students. The benefit of this is that it affords the teacher the ability to walk between the rows. The negative is that it doesnt really allow for collaborative work. If you are going to have students often work in pairs or teams you will be moving the desks a lot.A second way to arrange desks is in a large circle. This has the benefit of providing ample opportunity for interaction but hinders the ability to utilize the board. It can also be challenging when having the students take quizzes and tests in that it is easier for students to cheat.Another method of classroom arrangement is to have students sit in pairs, with two desks touching each other. The teacher can still walk down the rows helping students, and there is a greater chance for collaboration to occur. The board is still available for use. However, a couple of issues can arise including interpersonal problems and cheating concerns. The fourth method to arrange student desks is in groups of four. Students face each other, providing them ample opportunity for teamwork and collaboration. However, some students might find they are not facing the board. Further, there can be interpersonal issues and cheating concerns. Most teachers opt to use rows for their students but have them move into the other arrangements if a specific lesson plan calls for it. Just be aware that this can take time and can be loud for adjoining classrooms. Seating Charts The final step in classroom arrangement is to decide how you are going to deal with where students sit. When you dont know the students coming in, you typically do not know which students should not be seated next to each other. Therefore, there are a couple of ways to set up your initial seating chart. One way that you can arrange students is alphabetical. This is a simple way that makes sense and can help you learn student names.Another method for seating charts is to alternate girls and boys. This is another simple way to divide out a class.One way that many teachers choose is to allow students to choose their seats. Then you as a teacher mark this down and it becomes the seating chart.The final option is to have no seating chart at all. Realize, however, that without a seating chart you lose a bit of control and you also lose a powerful way to help you learn student names. No matter which seating chart option you choose, make sure that you reserve the right to change the seating chart at any time in order to keep order in your classroom. Also, realize that you start the year without a seating chart and then decide partway through the year to implement one, this can cause some issues with students.

Saturday, October 19, 2019

The American Red Cross Humanitarian Organization Essay

The American Red Cross Humanitarian Organization - Essay Example In 2005, the American Red Cross played a critical role in providing humanitarian assistance to thousands of Americans who were affected by the Hurricane Katrina. Jones (2012) indicate the Red Cross assisted in the evacuation of the affected families as well as proving first aid services to the injured, as well as food and temporary shelters to those who were affected by the disaster. The American Red Cross also assisted greatly during the 9/11 terrorist attacks, where the organization provided emergency assistance to the affected people. In fact, the American Red Cross is currently synonymous with humanitarian assistance. This document will conduct a review of the Red Cross business model, lobbying efforts, leadership profile of CEO, SWOT analysis, strategic planning, administration, and operations. The American Red Cross is the largest humanitarian organization in the country. The organization was founded in 1881 to assist those who were injured during the Civil War. The American Red Cross main areas of operation are the provision of humanitarian assistance to those affected by disasters and emergencies. The first major area of Red Cross operation is the provision of disaster response services. America is one of the countries that are prone to natural and manmade disasters most of which are devastating. However, the American Red Cross has always played a key role in providing disaster response services. In fact, the American Red Cross has provided many response services, which has helped save lives of thousands of people affected by disasters. Some of the disaster incidences where the Red Cross has provided effective response services include Hurricane Katrina, 9/11 terrorist attacks, Comair Flight 5191, the Kansan tornadoes, and the Florida tornadoes just to name but a few (Am erican Red Cross, 2006). In all these incidences, the Red Cross responded by assisting in the provision of evacuation services, first aid to the injured, food, temporary shelter, clothes and bedding.American Red Cross also provides blood services in the form of donations to hospitals in need of blood. The Red Cross works closely with community centers that help in the donation of blood. The Red Cross then supplies the blood to hospitals and health facilities that require blood.  

Friday, October 18, 2019

Exclusive interview with E. H. Sutherland Essay Example | Topics and Well Written Essays - 750 words

Exclusive interview with E. H. Sutherland - Essay Example The theory also had a structural element positing that conflict and social disorganization are the underlying causes of crime because they determine the patterns of people associated with. This latter element was dropped when the fourth edition was published in 1947. But he remained convinced that social class was a relevant factor, coining the phrase white-collar criminal in a speech to the American Sociological Association on December 27, 1939. In his 1949 monograph White-Collar Crime he defined a white-collar crime as approximately as a crime committed by a person of respectability and high social status in the course of his occupation. Sutherland's Response. Criminology is a fascinating field and because of my curious nature and natural passion for intrigue. I joined this profession and as you are already aware that the distinctive feature of criminology since the 1930s has been the dominance of sociology among the various disciplines studying crime and criminal justice. My humble contributions to the sociology of crime and delinquency came from his teaching, scholarship, and involvement in criminal justice policy and this field has helped me to pioneer, innovate and provide significant contributions to the study of organized crime, prisons, and criminological theory. I have also made central and lasting contributions to the sociology of criminal law and white collar crime and my ideas in each of these areas are reviewed to produce a portrait or profile of what he added to criminology, to remind those who know it already and also to those who have no knowledge about this field. Q2 Being an expert criminologist do you think that money and greed are the reasons w

Ls week7 Essay Example | Topics and Well Written Essays - 1500 words

Ls week7 - Essay Example This contains extensive involvement on the part of American professionals, who, as contributors far exceed those from elsewhere. This has been has been credited to the fact that it is closely associated with Cornell Business School, as well as other American business schools. Organisational theory is a major focus of Clegg’s argument. Considering the writing of Hinings and Greenwood (2002) questions are asked about such things as organisation theory. Such things as the effect and impact of large organisations upon wider society, and the role they should play are discussed, and how these place controls upon the organisations concerned. There is also discussion of the place power plays within organisations, as well as the importance played by schools of business, a topic I have myself discussed earlier. This brought me to an understanding of how research must aim to produce findings that are both capable of being utilized by companies and which can be comprehended by industry le aders. This provides links between the schools and the businesses they seek to serve. . As stated by Bennis and O’Toole (2005) business schools need to benefit from knowledge which is already available as well as new data. However within the work place environments this can become especially complex. to arrive at a better comprehension of ways in which knowledge can be used in order to increase the competitive edge, (Syvertsen, 2008) It was thus recommended by Bennis and O’Toole in 2005 that the schools of business need to place more emphasis on research. Also important, state the authors, is the use of undergraduate programmes, because in the search for new knowledge it is such programmes which produce questions and to overturn or discard knowledge already in place. The creation of fresh knowledge needs theories to be arrived at, requires theory building as well as the ability to form and analyse

Thursday, October 17, 2019

What is terrorism Essay Example | Topics and Well Written Essays - 1750 words

What is terrorism - Essay Example There are many other similar definitions of terrorisms used by scholars and research institutions and thus, there isn`t a consensus on the exact definition as yet. Thus, it may be concluded that it is not an easy task to define it with one single definition. In fact, the true definition of terrorism can be given by looking at the nature of conflict and role of media. Since both of these are determining factors for classifying an act as a terrorist activity or the war of freedom it is crucial to study various definitions and thus find out recurring patterns. Thus, despite of the variety of definitions, there are some factors that are common to all of them (Duncan 2013). These factors are: b) Perpetrator: constitutes the person who is responsible for the terrorist attack. It can be anyone; even the state itself uses violence against its own public which is referred to as state terrorism c) Motive: in other words the aim of the terrorist attack. There is always a goal behind any terrorist activity which may be political or social. In the absence of any such motive, the act is not a terrorist attack, it is simply a crime. d) Victims: Who is a victim of terrorist activity is a very controversial issue. According to many definitions of terrorism, victim is generally the common people. Terrorists’ activities are carried on the masses in order to pressurize the government of that particular country. The term terrorism was first coined during the French revolution in 1790`s for the insurgents using violence against the state (Lacqueur 1977). However, over the years, such terrorist groups have been found inflicting violence if different forms all over the world. The concept of terrorism was historically treated as religious extremism, i.e. religious extremism could interchangeably be used for terrorism. One of the aspects

The problems caused by the cereal-cyst nematode (CCN) in many wheat Essay

The problems caused by the cereal-cyst nematode (CCN) in many wheat fields and Saudi Arabias huge amount of loss of underground water due to the attempt of becoming a major agriculture producer of wheat - Essay Example The writers determined the genetic basis of meloidoyne incognita –fusarium exosporium lycopersici disease which affected tomatoes as from the inoculations of progeny F2. The paper demonstrated the role of nematode in the disease interactions through resistance breakdown to F Oxysporum lycopersici in the presence of M. It showed that the cysts have a significant effect in the productivity of the important food crops. This paper evaluates the impact of the H.avenae on the spring wheat yields in Northwest Pacific. The condition had been observed on the fields but had not been quantified. It was motivated by the variation in infestation between the fields in dry land and irrigated fields. Heterodera avenae is widely distributed in the western US. These are the regions where wheat is grown in the non-irrigated winter wheat and summer fallows in the regions of low rainfall. The social and economic pressures have motivated growers to pursue a transition into the summer fallow rotation to the no till annual spring cereals. These cereals are also grown in the irrigated fields. Spring wheat was, therefore, planted without aldicarb in determining the relationship between H.avenae and the yields under the irrigated and dry land in moderately infested lands. From the research, the spring wheat productivity was negatively correlated with the initial H.avenae populations. This research paper aims to present valuable information and figures related to agricultural development plans in Saudi Arabia. This is done despite the unsuitable and harsh climate as well as other conditions for normal production in agriculture. This is because of the limited and deteriorating water availability for agricultural productivity. The paper focuses on the condition of Saudi Arabia in improving and increasing the production of agricultural products. The

Wednesday, October 16, 2019

What is terrorism Essay Example | Topics and Well Written Essays - 1750 words

What is terrorism - Essay Example There are many other similar definitions of terrorisms used by scholars and research institutions and thus, there isn`t a consensus on the exact definition as yet. Thus, it may be concluded that it is not an easy task to define it with one single definition. In fact, the true definition of terrorism can be given by looking at the nature of conflict and role of media. Since both of these are determining factors for classifying an act as a terrorist activity or the war of freedom it is crucial to study various definitions and thus find out recurring patterns. Thus, despite of the variety of definitions, there are some factors that are common to all of them (Duncan 2013). These factors are: b) Perpetrator: constitutes the person who is responsible for the terrorist attack. It can be anyone; even the state itself uses violence against its own public which is referred to as state terrorism c) Motive: in other words the aim of the terrorist attack. There is always a goal behind any terrorist activity which may be political or social. In the absence of any such motive, the act is not a terrorist attack, it is simply a crime. d) Victims: Who is a victim of terrorist activity is a very controversial issue. According to many definitions of terrorism, victim is generally the common people. Terrorists’ activities are carried on the masses in order to pressurize the government of that particular country. The term terrorism was first coined during the French revolution in 1790`s for the insurgents using violence against the state (Lacqueur 1977). However, over the years, such terrorist groups have been found inflicting violence if different forms all over the world. The concept of terrorism was historically treated as religious extremism, i.e. religious extremism could interchangeably be used for terrorism. One of the aspects

Tuesday, October 15, 2019

Human resource management in UK government Essay

Human resource management in UK government - Essay Example The financial stringencies of recent years have combined with growing anxieties about seemingly inflated local authority staff numbers to persuade local authorities to make increasing efforts to make better use of their existing staff, in order to reduce demands for extra posts. The pressure imposed by compulsory competitive tendering to reduce labour costs in order to retain service contracts within the local authority have also produced major changes in human resource management in local government (Fenwick, Shaw and Foreman, 2003). Since a long time, methods of improving human resource management and establishment control have expanded greatly in UK. Work study and organisation and methods techniques have developed rapidly. Computers have made the task of collecting, storing and analysing human resource records easier and quicker, a development which alarmed some trade union leaders because of the fear of job losses, as well as possible threats to privacy. In 1984 the Data Protection Act both improved the legal protection of confidentiality and gave data subjects the right to see information held about themselves on computers and correct it where it is inaccurate (Elcock, Stephenson 1996). The development of these and other new management techniques led the Fulton Committee to urge the speedy development of systematic human resource management in the civil service. Similarly, the Bains Committee (1972) urged local authorities to recognise that: The human problems of management in local government are in no way different from those in industry or the civil service. The resources devoted to the solution and more important the prevention of those problems in local government are in our view generally inadequate. (Bacon, Eltis, 2001) Local government had not, in the Bains Committee's view, made adequate use of the techniques available for improving its efficiency in the use of personnel. However, concern about human resource management is relatively new in local government. In the mid-1960s, the Mallaby Committee was charged with investigating the staffing of local government and its report was hardly a recipe for a radical change of approach to human resource management. In the chapter devoted to this subject, the committee made frequent references to the previous inquiry into local government staffing carried out by the Hadow Committee and it did little more than endorse the recommendations of the earlier committee. Thus the Hadow Committee had recommended that local authorities should create establishment committees responsible for human resource matters, including controlling the size of the authority's departments and vetting requests for new posts. This was establishments work as traditionally understood in the public services: a concern to restrain the size of departments and ensure that new posts are created only when they are absolutely necessary. The establishments committee should be advised by the authority's clerk, a member of whose staff should take responsibility for human resource matters. This approach was largely supported by the Mallaby Commi

Monday, October 14, 2019

Death Penalty Essay Example for Free

Death Penalty Essay Death penalty has been an inalienable part of human society and its legal system for centuries, regarded as a necessary deterrent to dangerous crimes and a way to liberate the community from dangerous criminals. However, later on this type of punishment came to be regarded as a crime against humanistic ideals by many, and its validity in the legal system has been questioned. Until now, the debate rages on. But I’m here to tell you that the death penalty is the right thing to do !! Background: The first established death penalty laws date as far back as the Eighteenth Century B.   C. E. in the Code of King Hammurabi of Babylon, which codified the death penalty for 25 different crimes. The death penalty was also part of the Fourteenth Century B. C. E. s Hittite Code; in the Seventh Century B. C. s Draconian Code of Athens, which made death the only punishment for all crimes; and in the Fifth Century B. C. s Roman law of the Twelve Tablets. Death sentences were carried out by such means as crucifixion, drowning, beating to death, burning alive, and impalement. In the Tenth Century A. D. , hanging became the usual method of execution in Britain. In the following century, William the Conqueror would not allow persons to be hanged or otherwise executed for any crime, except in times of war. This trend would not last, for in the Sixteenth Century, under the reign of Henry VIII, as many as 72,000 people are estimated to have been executed. Some common methods of execution at that time were boiling, burning at the stake, hanging, beheading, and drawing and quartering. Executions were carried out for such capital offenses as marrying a Jew, not confessing to a crime, and treason. The number of capital crimes in Britain continued to rise throughout the next two centuries. By the 1700s, 222 crimes were punishable by death in Britain, including stealing, cutting down a tree, and robbing a rabbit warren. Because of the severity of the death penalty, many juries would not convict defendants if the offense was not serious. This lead to reforms of Britains death penalty. From 1823 to 1837, the death penalty was eliminated for over 100 of the 222 crimes punishable by death. And in America over 38 states use the death penalty. Now that tells me that almost 50% of the United States uses he death penalty and even john Haynes from the book â€Å"the death penalty† even agrees with me..!!! Mistakes  now let’s move on to mistakes , as we all know back then several ages ago we didn’t have the technology that we do have now. But wait now that we have the world’s smartest people, well at least some. They can assure you that we will give correct D. N. A. answers!!! And if I was to give you a percentage of how many we have gotten correct I would say 100%. Cost of death vs. life in prison: So in the case for money which is better, I would say that the death penalty is a lot better and it’s cheaper than keeping the prisoner there and going through trial after trial after trial, I mean this could go on for weeks and even up to months!!! The death penalty cost the government 1. 5 million- 5. 1 million dollars. The cost of keeping the prisoner $22,218 to 50,000 per year ! In conclusion I know that the death penalty may cost more but do we really want to have our citizen’s life in danger, I know I don’t. Any consideration of the crime rate cancellation would become viable if the crime rate at least for murders goes sharply down. At present, however, capital punishment serves as an important barrier on the way of criminals ready to take another persons life.

Sunday, October 13, 2019

Significance Of Site Layout Planning Construction Essay

Significance Of Site Layout Planning Construction Essay Site layout planning can affect productivity and is crucial to project success. However, as construction is heterogeneous in the nature of its organizations, project designs, time constraints, environmental effects, etc., site layout planning for each project becomes unique. Affected by many uncertainties variables! And variations, site layout planning is a typical multi objective problem. Introduction Problem solving requires representing the problem in a language that problem solvers can understand. However, solutions of most construction problems rely on empirical Knowledge about the site layout that can be as a site space allocation for material storage, working areas, units of accommodation, plant positions, general circulation areas, and also access and egress for deliveries and emergency services. Furthermore, conflicting objectives and the uniqueness of construction projects like bad site layout make the problems difficult to conceptualize and define. In this report presenting, a routine task for many site staff in both precontract and postcontract stages of site layout planning of the typical multi criteria and multi objective construction problems. It is very much influenced by types of construction, density of development, and whether the site is bad or in a good layout. Significance of Site Layout Planning Site layout shows the relationship of the proposed site with its surroundings with respect to communication, approaches, and existing facilities. Good site layout planning assists in minimizing the traveling time and movement costs of plant, labor, and materials, activity interference during construction work, and site accidents, and ensures that work on buildings and other construction positions is not impeded by the thoughtless storage of materials on these locations. So site layout can thus either enhance or adversely affect construction productivity and progress. It is important to acquire the knowledge of the project site before setting out the site layout. The knowledge about the project site can be obtained from: Site Investigation Site investigation is a process of site exploration consisting of boring, sampling and testing so as to obtain geotechnical information for a safe, practical and economical geotechnical evaluation and design. Generally it is an exploration or discovery of the ground conditions especially on untouched site. In other words the main purpose of site investigation is to determine within practical limits, the depth, thickness, extent and compositions of each subsoil stratum, the depth and type of rock, the depth and composition of groundwater, the strength, compressibility and hydraulic characteristics of soil strata required by geotechnical engineers. Sometimes it is also known as geotechnical investigation. Wok Procedure for SI Steps of work involved in site investigation: 1.Desk study to collect all the relevant data and information, 2.Reconnaissance of site works, 3.Planning program after reviewing the above, 4.Ground or soil exploration includes boring, sampling and testing, 5.Laboratory testing (also field if necessary), 6.Preparation and documentation of SI report, 7.Engineering design stages, 8.Review during construction and monitoring. Steps of Soil Exploration Soil exploration consists of: Boring: Refers to drilling or advancing a hole in the ground. The test would include hand auger, motorized hand boring (wash boring), deep boring (rotary drilling), and/or trial pits. Sampling: Refers to removing soil from the hole. The samples can be classified as disturbed or undisturbed sampling. Disturbed samples are usually used for soil grain-size analysis, determination of liquid limit, specific gravity of soil as well as compaction test and California bearing ratio (CBR). The undisturbed samples are collected at least every 1.5 m and if changes occur within 1.5 m intervals, an additional sample should be taken. Testing: Refers to determining the properties from the soil. The test can be performing either at laboratory or at field. Laboratory testing would normally be moisture content, sieve analysis, liquid limit, compaction test, CBR and so forth. Field test would include Standard Penetration Test (SPT), Cone Penetration Test (CPT) and Vane test. Record of Soil Exploration It is important to keep complete and accurate records of all data collected. Boring, sampling and testing are often costly. A good map giving specific locations of all boring should be available. All boring should be identified and its location documented by measurement to permanent features. And all pertinent data should be recorded in the field on a boring log sheet. Soil data obtained from a series of test boring can best be presented by preparing a geologic profile: Arrangement of various layers of soil, Ground water table, Existing / proposed structures, Soil properties data (e.g., Standard Penetration Test values). The profile was prepared with data obtained from the boring, sampling and testing of each borehole from selected points. Summarizing Scope of site investigation works when planned by different engineers tend to be varied because there are an infinite number of conditions to be met and the process of planning also leaves many areas where individual judgment and experiences must be applied. It is also impossible to attempt to provide an exhaustive step by step guideline applicable to all possible cases. It should be realized that there is a possibility that any site investigation may leave some area unexplored or overlooked. The main risk in foundation design is the uncertainty involving in predicting soil conditions which may change with environment. The more site investigation the more it will reduce the margin of uncertainty but the time and cost requirement will be exorbitant. Therefore the extent and the cost of Site Investigation should be such that risk is at an established acceptable level to the designer and also comply to the accepted code of practice. Decision Criteria and Site Facilities Adopted in Site Layout Planning Although each site layout is unique, site layout planning can be resolved into a repetitive selection-evaluation process. Several analysis techniques can be used for the selection process for example, the dominant factor analysis and Parker s judgment technique, which can be used to screen out available decisions in choosing facilities, and identify key decision factors and locations for each particular facility. All space-planning problems consist of a set of activities to be located and a space in which to locate them. Site layout planning consists of identifying the facilities needed to support construction operations, determining their size and shape, and positioning them within the boundaries of the site. So, the most temporary facilities are classified into six important categories, which are tabulated in Table 1. Table1. General Classification of Temporary Facilities Temporary facilities Description Access road and exit Needs vary with the type of project and the stage of the job. It will normally be linked with the plan of construction and in some cases may actually control the progress of construction. Ideally, short direct routes and one-way traffic are encouraged. Location of plant and equipment Choice of the major items of the plant is of real consequence on most sites. Correctly chosen and well operated and maintained equipment enables a construction project to be completed efficiently and economically. Material storage and handling area Areas must be set aside for the storage and handling of material. The objective here is to minimize waste and losses arising from careless handling, bad storage, or theft, and to reduce costs by obviating double handling or unnecessary movement. Site accommodations and welfare facilities Consideration should always be given to the possibility of ensuring that the site accommodations are kept at a suitable distance from the construction work and are in such a position to enable the site staff to conduct their duties (welfare facilities also) Temporary services This includes water supply, electricity supply, gas, telephones, and drainage the requirements of which may vary between different projects. Workshop position Position should be indicated to enable the site supervisor to arrange for the erection of the following types of workshops: 1) fitter s shops and work area; 2) joinery shop and machinery area; 3) Reinforcement and bar bending areas; and 4) Concrete mixing. Bad site layout planning Bad site layout is usually a multi criteria problem involving in construction site without any or less temporary facilities regarding to the type of project. Fig1.Bad site layout Figure1 shows one of the bad site layouts occurs daily in construction site that the Decision makers made mistake. As you can see there are some missing temporary facilities like: 1. There is no enough access road to use. Only have two main entries that all type of vehicles can access. 2. No female toilet for any side of the site layout. 3. They don t provide any temporary office place 4. There is no storage for steel, timber and other facilities. 5. No temporary services including water supply pipes and waste storage like septic tank. According to all that things, we can say the site layout planning is bad layout. Cause for the lake of or missing of some important facilities that leads the hall project to be fulfilled. Conclusion Site investigation product plane such as space allocations and material transportations need a lot of experience and knowledge. The planning of a site layout in practice will depend upon a number of factors such as the time and money. The need for careful site layout and site organization planning becomes more relevant as the size and complexity of the construction operation increases, and especially where spare site space is very limited.

Saturday, October 12, 2019

Fictional Newspaper Article about Medevial Tournaments -- essays resea

The Medieval Joust This morning I witnessed a tournament held in town. As I was watching I realized that I wasnà ¢Ã¢â€š ¬Ã¢â€ž ¢t exactly certain about all the rules. This is why I decided to write this article about the history, rules, and guidelines of this riveting sport. The words "tournament" and "joust" are frequently used interchangeably. Strictly speaking "joust" describes single combat between two horsemen. "Tournament" refers to mounted combat between parties of knights, but also is used to refer to the whole proceeding. The first written tournament guidelines are credited to a Frenchman named Geoffroi de Purelli in 1066. I would have interviewed this man but he was unfortunately killed, ironically in one of these very tournaments for which he made rules. Jousting is a way of gaining respect. It is what is done when there is no war to fight. Jousting is essentially a way of à ¢Ã¢â€š ¬Ã…“playingà ¢Ã¢â€š ¬? war. Tournaments were, at first, merely battles arranged on some pretext at an appropriate appointment between parties of knights. From these bloody conflicts there developed the tourn... Fictional Newspaper Article about Medevial Tournaments -- essays resea The Medieval Joust This morning I witnessed a tournament held in town. As I was watching I realized that I wasnà ¢Ã¢â€š ¬Ã¢â€ž ¢t exactly certain about all the rules. This is why I decided to write this article about the history, rules, and guidelines of this riveting sport. The words "tournament" and "joust" are frequently used interchangeably. Strictly speaking "joust" describes single combat between two horsemen. "Tournament" refers to mounted combat between parties of knights, but also is used to refer to the whole proceeding. The first written tournament guidelines are credited to a Frenchman named Geoffroi de Purelli in 1066. I would have interviewed this man but he was unfortunately killed, ironically in one of these very tournaments for which he made rules. Jousting is a way of gaining respect. It is what is done when there is no war to fight. Jousting is essentially a way of à ¢Ã¢â€š ¬Ã…“playingà ¢Ã¢â€š ¬? war. Tournaments were, at first, merely battles arranged on some pretext at an appropriate appointment between parties of knights. From these bloody conflicts there developed the tourn...

Friday, October 11, 2019

Cystic Fibrosis

————————————————- Introduction Cystic fibrosis  (also called  CF  or  mucoviscidosis) is an  autosomal  recessive  genetic disorder  that affects most critically the  lungs, and also the  pancreas,  liver, and  intestine. It is characterized by abnormal transport of  chloride  and  sodium  across an  epithelium, leading to thick, viscous secretions. The name  refers to the characteristic  scarring  (fibrosis) and  cyst  formation within the  pancreas that was first recognized in the 1930s.Difficulty in breathing  is the most serious symptom and results from frequent  lung infections  which are treated with  antibiotics, therapies and several other medications. Other  symptoms, including  sinus infections,  poor growth, and  infertility affect other parts of the body. A breathing treatment for cystic fibrosis, usi ng a mask nebulizer and a ThAIRapy Vest A breathing treatment for cystic fibrosis, using a mask nebulizer and a ThAIRapy Vest CF is caused by a  mutation  in the  gene  for the  protein  cystic fibrosis trans-membrane conductance regulator  (CFTR).This protein is required to regulate the components of sweat,  digestive  juices, and  mucus. CFTR regulates the movement of  chloride  and  sodium ions across epithelial membranes, such as the alveolar epithelia located in the  lungs. Although most people without CF have two working copies of the CFTR gene, only one is needed to prevent cystic fibrosis due to the disorder's recessive nature. CF develops when neither gene works normally (as a result of mutation) and therefore has  autosomal recessive  inheritance.CF is most common among  Caucasians; one in 25 people of European descent  carries one  allele  for CF. The  World Health Organization  states that â€Å"In the European Union, 1 in 200 0–3000 new-borns is found to be affected by CF†. Individuals with cystic fibrosis can be diagnosed before birth by  genetic testing or by a  sweat test  in early childhood. Ultimately,  lung transplantation  is often necessary as CF worsens. ————————————————- Signs and symptomsThe hallmark symptoms of cystic fibrosis are salty tasting skin,  poor growth and poor weight gain despite a normal food intake,  accumulation of thick, sticky mucus, frequent chest infections, and coughing or shortness of breath. Signs and symptoms often appear in infancy and childhood, such as  bowel movement obstruction  in new-born babies. As the children grow, they must exercise to release the mucus present in the alveoli. Ciliated  epithelial cells present  in the patient have a mutated protein that leads to abnormally viscous mucus production.The poor growth in children typically presents as an inability to gain weight or height at the same rate as their peers and is occasionally not diagnosed until investigation is initiated for poor growth. The causes of growth failure are multifactorial and include chronic lung infection, poor absorption of nutrients through the gastrointestinal tract, and increased metabolic demand due to chronic illness. In rare cases, cystic fibrosis can manifest itself as a coagulation disorder. A double recessive allele is needed for cystic fibrosis to be apparent.Young children are especially sensitive to vitamin  malabsorptive disorders because only a very small amount of vitamin K crosses the placenta, leaving the child with very low reserves. Because factors II, VII, IX, and X (clotting factors) are vitamin K–dependent, low levels of vitamin K can result in coagulation problems. Consequently, when a child presents with unexplained bruising, a coagulation evaluation may be warranted to determine whet her there is an underlying disease. Lungs and sinuses Lung disease results from clogging of the airways due to mucus build-up, decreased  mucociliary clearance, and resulting  inflammation.Inflammation and infection cause injury and structural changes to the lungs, leading to a variety of symptoms. In the early stages, regular incessant coughing along with copious  phlegm  production, and decreased ability to exercise are common. Many of these symptoms occur when  bacteria that normally inhabit the thick mucus grow out of control and cause pneumonia. In later stages, changes in the architecture of the lung, such as pathology in the major airways (bronchiectasis), further exacerbate difficulties in breathing.Other symptoms include coughing up blood (hemoptysis), high  blood pressure  in the lung (pulmonary hypertension),  heart failure, difficulties getting enough  oxygen to the body (hypoxia), and respiratory failure requiring support with breathing masks, such asà ‚  bi-level positive airway pressure  machines or  ventilators. Staphylococcus aureus, Haemophilus influenzae, and  Pseudomonas aeruginosa  are the three most common organisms causing lung infections in CF patients. In addition to typical bacterial infections, people with CF more commonly develop other types of lung disease.Among these is  allergic bronchopulmonary aspergillosis, in which the body's response to the common  fungus  Aspergillus fumigatus  causes worsening of breathing problems. Another is infection with Mycobacterium avium  complex (MAC), a group of bacteria related to  tuberculosis, which can cause a lot of lung damage and does not respond to common antibiotics. Mucus in the  paranasal sinuses  is equally thick and may also cause blockage of the sinus passages, leading to infection. This may cause facial pain, fever, nasal drainage, and  headaches.Individuals with CF may develop overgrowth of the nasal tissue (nasal polyps) due to inflammati on from chronic sinus infections. Recurrent sinonasal polyps can occur in as many as 10% to 25% of CF patients. These polyps can block the nasal passages and increase breathing difficulties. Cardiorespiratory complications are the most common cause of death (~80%) in patients at most CF centers in the United States. Gastrointestinal Prior to prenatal and  newborn screening, cystic fibrosis was often diagnosed when a newborn infant failed to pass feces (meconium).Meconium may completely block the  intestines  and cause serious illness. This condition, called  meconium ileus, occurs in 5–10%  of newborns with CF. In addition, protrusion of internal  rectal  membranes (rectal prolapse) is more common, occurring in as many as 10% of children with CF, and it is caused by increased fecal volume, malnutrition, and  pressure due to coughing. The thick mucus seen in the lungs has a counterpart in thickened secretions from the  pancreas, an organ responsible for provi ding digestive  that help break down food.These secretions block the  exocrine  movement of the digestive enzymes into the  duodenum and result in irreversible damage to the pancreas, often with painful inflammation (pancreatitis). The  pancreatic ducts  are totally plugged in more advanced cases, usually seen in older children or adolescents. This causes atrophy of the exocrine glands and progressive fibrosis. The lack of digestive enzymes leads to difficulty absorbing nutrients with their subsequent excretion in the feces, a disorder known as malabsorption. Malabsorption leads to  malnutrition  and poor growth and evelopment because of calorie loss. Resultant hypoproteinemia  may be severe enough to cause generalized edema. Individuals with CF also have difficulties absorbing the fat-soluble vitamins  A,  D,  E, and  K. In addition to the pancreas problems, people with cystic fibrosis experience more  heartburn, intestinal blockage by  intussusception , and constipation. Older individuals with CF may develop  distal intestinal obstruction syndrome  when thickened feces cause intestinal blockage. Exocrine pancreatic insufficiency occurs in the majority (85% to 90%) of patients with CF.It is mainly associated with â€Å"severe† CFTR mutations, where both alleles are completely nonfunctional (e. g. ?F508/? F508). It occurs in 10% to 15% of patients with one â€Å"severe† and one â€Å"mild† CFTR mutation where there still is a little CFTR activity, or where there are two â€Å"mild† CFTR mutations. In these milder cases, there is still sufficient pancreatic exocrine function so that enzyme supplementation is not required. There are usually no other GI complications in pancreas-sufficient phenotypes, and in general, such individuals usually have excellent growth and development.Despite this, idiopathic  chronic pancreatitis  can occur in a subset of pancreas-sufficient individuals with CF, and is a ssociated with recurrent abdominal pain and life-threatening complications. Thickened secretions also may cause liver problems in patients with CF. Bile  secreted by the liver to aid in digestion may block the  bile ducts, leading to liver damage. Over time, this can lead to scarring and nodularity (cirrhosis). The liver fails to rid the blood of toxins and does not make important  proteins, such as those responsible for  blood clotting. Liver disease is the third most common cause of death associated with cystic fibrosis.Endocrine Clubbing in the fingers of a person with cystic fibrosis Clubbing in the fingers of a person with cystic fibrosis The  pancreas  contains the  islets of Langerhans, which are responsible for making insulin, a hormone that helps regulate blood  glucose. Damage of the pancreas can lead to loss of the islet  cells, leading to a type of diabetes that is unique to those with the disease. This cystic fibrosis-related diabetes  (CFRD) shares characteristics that can be found in  type 1and  type 2  diabetics, and is one of the principal non-pulmonary complications of CF.Vitamin D is involved in  calcium  and  phosphate  regulation. Poor uptake of vitamin D from the diet because of malabsorption can lead to the bone disease  osteoporosis  in which weakened bones are more susceptible to  fractures. In addition, people with CF often develop clubbing  of their fingers and toes due to the effects of chronic illness and  low oxygen  in their tissues. Infertility Infertility  affects both men and women. At least 97% of men with cystic fibrosis are infertile, but not sterile and can have children with assisted reproductive techniques.The main cause of infertility in men with cystic fibrosis is congenital absence of the vas deferens  (which normally connects the  testes  to the  ejaculatory ducts  of the  penis), but potentially also by other mechanisms such as causing  azoospermia,  te ratospermia  and  oligoasthenospermia. Many men found to have congenital absence of the vas deferens during evaluation for infertility have a mild, previously undiagnosed form of CF. Some women have fertility difficulties due to thickened cervical mucus or malnutrition. In severe cases, malnutrition disrupts  ovulation  and causes  amenorrhea. ———————————————— Cause CF is caused by a  mutation  in the  gene  cystic fibrosis trans-membrane conductance regulator  (CFTR). The most common mutation,  ? F508, is a deletion (? signifying deletion) of three nucleotides  that results in a loss of the amino acid  phenylalanine  (F) at the 508th position on the protein. This mutation accounts for two-thirds (66–70%) of CF cases worldwide and 90% of cases in the  United States; however, there are over 1500 other mutations that can produce CF.Althou gh most people have two working copies (alleles) of the CFTR gene, only one is needed to prevent cystic fibrosis. CF develops when neither allele can produce a functional CFTR protein. Thus, CF is considered an  autosomal recessive disease. The  CFTR gene, found at the q31. 2  locus  of  chromosome 7, is 230,000  base pairs  long, and creates a protein that is 1,480  amino acids  long. More specifically the location is between base pair 117,120,016 to 117,308,718 on the long arm of chromosome 7, region 3, band 1 and sub-band 2, represented as 7q31. . Structurally, CFTR is a type of gene known as an  ABC gene. The product of this gene (the CFTR) is a chloride ion channel important in creating sweat,  digestive  juices and  mucus. This protein possesses two  ATP-hydrolyzing  domains, which allows the protein to use  energy  in the form of  ATP. It also contains two domains comprising 6  alpha helices  apiece, which allow the protein to cross the cell membrane. A regulatory  binding site  on the protein allows activation by  phosphorylation, mainly by  cAMP-dependent protein kinase.The  carboxyl terminal  of the protein is anchored to the  cytoskeleton  by a  PDZ  domain interaction. In addition, there is increasing evidence that  genetic modifiers  besides CFTR modulate the frequency and severity of the disease. One example is  mannan-binding lectin, which is involved in  innate immunity  by facilitating  phagocytosis  of microorganisms. Polymorphisms in one or both mannan-binding lectin alleles that result in lower circulating levels of the protein are associated with a threefold higher risk of end-stage lung disease, as well as an increased burden of chronic bacterial infections. ———————————————— Pathophysiology Molecular structure of the CFTR protein Molecular structure of the CFTR protein There are several mutations in the  CFTR  gene, and different mutations cause different defects in the CFTR protein, sometimes causing a milder or more severe disease. These protein defects are also targets for drugs which can sometimes restore their function. ?F508-CFTR, which occurs in >90% of patients in the U. S. , creates a protein that does not  fold  normally and is degraded by the cell.Other mutations result in proteins that are too short (truncated) because  production  is ended prematurely. Other mutations produce proteins that do not use energy normally, do not allow  chloride iodide  and  thiocyanate  to cross the membrane appropriately,  or are degraded at a faster rate than normal. Mutations may also lead to fewer copies of the CFTR protein being produced. The protein created by this gene is anchored to the  outer membrane of  cells  in the  sweat glands, lungs, pancreas, and all other remaining exocrine glands in the body.Th e protein spans this membrane and acts as a  channel  connecting the inner part of the cell (cytoplasm) to the  surrounding fluid. This channel is primarily responsible for controlling the movement of halogens from inside to outside of the cell; however, in the sweat ducts it facilitates the movement of chloride from the sweat into the cytoplasm. When the CFTR protein does not work, chloride and thiocyanate  are trapped inside the cells in the airway and outside in the skin. Then  hypothiocyanite, OSCN, cannot be produced by immune defense system.Because chloride is  negatively charged, this creates a difference in the electrical potential inside and outside the cell causing  cations  to cross into the cell. Sodium is the most common cation in the extracellular space and the combination of sodium and chloride creates the  salt, which is lost in high amounts in the sweat of individuals with CF. This lost salt forms the basis for the sweat test. Most of the damage in CF is due to blockage of the narrow passages of affected organs with thickened secretions.These blockages lead to remodeling and infection in the lung, damage by accumulated digestive enzymes in the pancreas, blockage of the intestines by thick faeces, etc. There are several theories on how the defects in the protein and cellular function cause the clinical effects. One theory is that the lack of halogen and pseudohalogen (mainly, chloride, iodide and thiocyanate) exiting through the CFTR protein leads to the accumulation of more viscous, nutrient-rich mucus in the lungs that allows bacteria to hide from the body's  immune system.Another theory is that the CFTR protein failure leads to a paradoxical increase in sodium and chloride uptake, which, by leading to increased water reabsorption, creates dehydrated and thick mucus. Yet another theory is that abnormal chloride movement  out  of the cell leads to dehydration of mucus, pancreatic secretions, biliary secretions, etc. Chr onic infections The lungs of individuals with cystic fibrosis are colonized and infected by bacteria from an early age. These bacteria, which often spread among individuals with CF, thrive in the altered mucus, which collects in the small airways of the lungs.This mucus leads to the formation of bacterial microenvironments known as biofilms that are difficult for immune cells and antibiotics to penetrate. Viscous secretions and persistent respiratory infections repeatedly damage the lung by gradually remodeling the airways, which makes infection even more difficult to eradicate. Over time, both the types of bacteria and their individual characteristics change in individuals with CF. In the initial stage, common bacteria such as  Staphylococcus aureus  and  Hemophilus influenzae  colonize and infect the lungs.Eventually,  Pseudomonas aeruginosa  (and sometimes  Burkholderia cepacia) dominates. By 18 years of age, 80% of patients with classic cystic fibrosis harbor  Ps eudomonas aeruginosa, and another 3. 5% harbor Burkholderia cepacia. Once within the lungs, these bacteria adapt to the environment and develop  resistance  to commonly used antibiotics. Pseudomonas  can develop special characteristics that allow the formation of large colonies, known as â€Å"mucoid†Ã‚  Pseudomonas, which are rarely seen in people that do not have CF. One way infection spreads is by passing between different individuals with CF.In the past, people with CF often participated in summer â€Å"CF Camps† and other recreational gatherings. Hospitals grouped patients with CF into common areas and routine equipment (such as  nebulizers)  was not sterilized between individual patients. This led to transmission of more dangerous strains of bacteria among groups of patients. As a result, individuals with CF are routinely isolated from one another in the healthcare setting and healthcare providers are encouraged to wear gowns and gloves when examining p atients with CF to limit the spread of virulent bacterial strains.CF patients may also have their airways chronically colonized by filamentous fungi (such as  Aspergillus fumigatus,  Scedosporium apiospermum,  Aspergillus terreus) and/or yeasts (such as  Candida albicans); other filamentous fungi less commonly isolated include Aspergillus flavus  and  Aspergillus nidulans  (occur transiently in CF respiratory secretions), and  Exophiala dermatitidis  and Scedosporium prolificans  (chronic airway-colonizers); some filamentous fungi like  Penicillium emersonii  and  Acrophialophora fusisporaare encountered in patients almost exclusively in the context of CF.Defective mucociliary clearance characterizing CF is associated with local immunological disorders. In addition, the prolonged therapy with antibiotics and the use of corticosteroid treatments may also facilitate fungal growth. Although the clinical relevance of the fungal airway colonization is still a ma tter of debate, filamentous fungi may contribute to the local inflammatory response, and therefore to the progressive deterioration of the lung function, as often happens with allergic broncho-pulmonary aspergillosis (ABPA) – the ost common fungal disease in the context of CF, involving a Th2-driven immune response to Aspergillus. ————————————————- Diagnosis and monitoring CFTR gene on chromosome 7 CFTR gene on chromosome 7 Cystic fibrosis may be diagnosed by many different methods including  newborn screening,  sweat testing, and genetic testing. As of 2006 in the United States, 10 percent of cases are diagnosed shortly after birth as part of newborn screening programs.The newborn screen initially measures for raised blood concentration of immunoreactive trypsinogen. Infants with an abnormal newborn screen need a sweat test to confirm the CF diagnosis. In many cases, a parent makes the diagnosis because the infant tastes salty. Trypsinogen  levels can be increased in individuals who have a single mutated copy of the  CFTR  gene (carriers) or, in rare instances, in individuals with two normal copies of the  CFTR  gene. Due to these  false positives, CF screening in newborns can be controversial.Most states and countries do not screen for CF routinely at birth. Therefore, most individuals are diagnosed after symptoms (e. g. sinopulmonary disease and GI manifestations) prompt an evaluation for cystic fibrosis. The most commonly used form of testing is the sweat test. Sweat-testing involves application of a medication that stimulates sweating (pilocarpine). To deliver the medication through the skin, iontophoresis  is used to, whereby one  electrode  is placed onto the applied medication and an electric current  is passed to a separate electrode on the skin.The resultant sweat is then collected on filter paper or in a capi llary tube and analyzed for abnormal amounts of  sodium  and  chloride. People with CF have increased amounts of sodium and chloride in their sweat. In contrast, people with CF have less thiocyanate and  hypothiocyanite  in their saliva and mucus. CF can also be diagnosed by identification of mutations in the CFTR gene. People with CF may be listed in a  disease registry  that allows researchers and doctors to track health results and identify candidates for  clinical trials. PrenatalCouples who are pregnant or planning a pregnancy can have themselves tested for the CFTR gene mutations to determine the risk that their child will be born with cystic fibrosis. Testing is typically performed first on one or both parents and, if the risk of CF is high, testing on the  fetus  is performed. The  American College of Obstetricians and Gynecologists  (ACOG) recommends testing for couples who have a personal or close family history of CF, and they recommend that carrie r testing be offered to all Caucasian couples and be made available to couples of other ethnic backgrounds.Because development of CF in the fetus requires each parent to pass on a mutated copy of the CFTR gene and because CF testing is expensive, testing is often performed initially on one parent. If testing shows that parent is a CFTR gene mutation carrier, the other parent is tested to calculate the risk that their children will have CF. CF can result from more than a thousand different mutations, and as of 2006 it is not possible to test for each one. Testing analyzes the blood for the most common mutations such as ? F508—most commercially available tests look for 32 or fewer different mutations.If a family has a known uncommon mutation, specific screening for that mutation can be performed. Because not all known mutations are found on current tests, a negative screen does not guarantee that a child will not have CF. During pregnancy, testing can be performed on the  pla centa  (chorionic villus sampling) or the fluid around the fetus (amniocentesis). However,  chorionic villus sampling  has a risk of fetal death of 1 in 100 and amniocentesis of 1 in 200;  a recent study has indicated this may be much lower, approximately 1 in 1,600.Economically, for carrier couples of cystic fibrosis, when comparing pre-implantation genetic diagnosis (PGD) with natural conception (NC) followed by prenatal testing and abortion of affected pregnancies, PGD provides net economic benefits up to a maternal age of approximately 40 years, after which NC, prenatal testing and abortion has higher economic benefit. ————————————————- Management While there are no cures for cystic fibrosis there are several treatment methods. The management of cystic fibrosis has improved significantly over the past 70 years.While infants born with cystic fibrosis 70 years ag o would have been unlikely to live beyond their first year, infants today are likely to live well into adulthood. Recent advances in the treatment of cystic fibrosis have meant that an individual with cystic fibrosis can live a fuller life less encumbered by their condition. The cornerstones of management are proactive treatment of  airway infection, and encouragement of good nutrition and an active lifestyle. Management of cystic fibrosis continues throughout a patient's life, and is aimed at maximizing organ function, and therefore quality of life.At best, current treatments delay the decline in organ function. Because of the wide variation in disease symptoms treatment typically occurs at specialist multidisciplinary centers, and is tailored to the individual. Targets for therapy are the  lungs,  gastrointestinal tract  (including pancreatic enzyme supplements), the  reproductive organs  (including (ART) and psychological support. The most consistent aspect of therapy in cystic fibrosis is limiting and treating the lung damage caused by thick mucus and infection. Intravenous,  inhaled, and oral antibiotics are used to treat chronic and acute infections.Mechanical devices and inhalation medications are used to alter and clear the thickened mucus. These therapies, while effective, can be extremely time-consuming for the patient. One of the most important battles that CF patients face is finding the time to comply with prescribed treatments while balancing a normal life. In addition, therapies such as  transplantation  and  gene therapy  aim to cure some of the effects of cystic fibrosis. Gene therapy aims to introduce normal CFTR to airway. Theoretically this process should be simple as the airway is easily accessible and there is only a single gene defect to correct.There are two CFTR gene introduction mechanisms involved, the first use of a viral vector (adenovirus, adeno-associated virus or retro virus) and secondly the use of  lipo some. However there are some problems associated with these methods involving efficiency (liposomes insufficient protein) and delivery (virus provokes an immune response). Antibiotics Many CF patients are on one or more  antibiotics  at all times, even when healthy, to  prophylactically  suppress infection. Antibiotics are absolutely necessary whenever pneumonia is suspected or there has been a noticeable decline in lung function, and are usually chosen based on the results of a putum analysis and the patient's past response. This prolonged therapy often necessitates hospitalization and insertion of a more permanent  IV  such as a  peripherally inserted central catheter  (PICC line) or  Port-a-Cath. Inhaled therapy with antibiotics such as tobramycin,  colistin, and  aztreonam  is often given for months at a time to improve lung function by impeding the growth of colonized bacteria. Oral antibiotics such as ciprofloxacin or  azithromycin  are given to hel p prevent infection or to control ongoing infection. The  aminoglycoside  antibiotics (e. g. obramycin) with long-term use can cause  several side effects such as hearing loss, damaging the  balance system  present in the  inner ear  and producing many chronic kidney problems  . To prevent these  side-effects, the amount of antibiotics in the blood are routinely measured and adjusted accordingly. Other treatments for lung disease Several mechanical techniques are used to dislodge sputum and encourage its expectoration. In the hospital setting, chest physiotherapy (CPT) is utilized; a respiratory therapist percusses an individual's chest with his or her hands several times a day, to loosen up secretions.Devices that recreate this percussive therapy include the  ThAIRapy Vest  and the  intrapulmonary percussive ventilator  (IPV). Newer methods such as  Biphasic Cuirass Ventilation, and associated clearance mode available in such devices, integrate a cough a ssistance phase, as well as a vibration phase for dislodging secretions. These are portable and adapted for home use. Aerosolized medications that help loosen secretions include  dornase alfa  and  hypertonic  saline. Dornase is a  recombinant  human deoxyribonuclease, which breaks down DNA in the  sputum, thus decreasing its  viscosity.Denufosol  is an investigational drug that opens an alternative chloride channel, helping to liquefy mucus. As lung disease worsens, mechanical breathing support may become necessary. Individuals with CF may need to wear special masks at night that help push air into their lungs. These machines, known as  bi-level positive airway pressure  (BiPAP) ventilators, help prevent low blood oxygen levels during sleep. BiPAP may also be used during physical therapy to improve sputum clearance. During severe illness, a  tube  may be placed in the throat (a procedure known as a  tracheostomy) to enable breathing supported by a  ven tilator.For children living with CF, preliminary studies show pediatric massage therapy may improve patients and their families’ quality of life, though more rigorous studies must be done. Transplantation Lung transplantation  often becomes necessary for individuals with cystic fibrosis as lung function ceases and  exercise tolerance  declines. Although single lung transplantation is possible in other diseases, individuals with CF must have both lungs replaced because the remaining lung might contain bacteria that could infect the transplanted lung.A pancreatic or liver transplant may be performed at the same time in order to alleviate liver disease and/or diabetes. Lung transplantation is considered when lung function declines to the point where assistance from mechanical devices is required or patient survival is threatened. Other aspects Intracytoplasmic sperm injection can be used to provide fertility for men with cystic. .fibrosis Intracytoplasmic sperm injection c an be used to provide fertility for men with cystic. .fibrosis New-borns with intestinal obstruction typically require surgery, whereas adults with  distal intestinal obstruction syndrome typically do not.Treatment of pancreatic insufficiency by replacement of missing digestive enzymes allows the duodenum to properly absorb nutrients and vitamins that would otherwise be lost in the faeces. So far, no large-scale research involving the incidence of  atherosclerosis  and  coronary heart disease  in adults with cystic fibrosis has been conducted. This is likely due to the fact that the vast majority of people with cystic fibrosis do not live long enough to develop clinically significant atherosclerosis or coronary heart disease.Diabetes  is the most common non-pulmonary complication of CF. It mixes features of  type 1and  type 2  diabetes, and is recognized as a distinct entity,  cystic fibrosis-related diabetes (CFRD). While oral  anti-diabetic drugs  are somet imes used, the only recommended treatment is the use of  insulin  injections or an  insulin pump,  and unlike in type 1 and 2 diabetes, dietary restrictions are not recommended. Development of  osteoporosis  can be prevented by increased intake of vitamin D and  calcium, and can be treated by  bisphosphonates, although  adverse effects  can be an issue.Poor growth may be avoided by insertion of a  feeding tube  for increasing  calories  through supplemental feeds or by administration of injected  growth hormone. Sinus infections are treated by prolonged courses of antibiotics. The development of nasal polyps or other chronic changes within the nasal passages may severely limit airflow through the nose, and over time reduce the patient's sense of smell. Sinus surgery is often used to alleviate nasal obstruction and to limit further infections. Nasal steroids such as  fluticasone  are used to decrease nasal inflammation.Female infertility may be overc ome by  assisted reproduction  technology (ART) with the help of embryo transfer  techniques. Male infertility caused by absence of the  vas deferens  may be overcome with  testicular sperm extraction  (TEST), collecting sperm cells directly from the testicles. If the collected sample contains too few sperm cells to likely have a spontaneous  fertilization,  intracytoplasmic sperm injection  can be performed. Third party reproduction  is also a possibility for women with CF. ————————————————- PrognosisThe prognosis for cystic fibrosis has improved due to earlier diagnosis through screening, better treatment and access to health care. In 1959, the median age of survival of children with cystic fibrosis in the United States was six months. In 2008, survival averaged 37. 4 years. In Canada, median survival increased from 24 years in 1982 to 47. 7 in 2007 . Of those with cystic fibrosis who are more than 18 years old as of 2009; 92% had graduated from  high school, 67% had at least some college education, 15% were disabled and 9% were unemployed, 56% were single and 39% were married or living with a partner.In Russia  the overall median age of patients is 25, which is caused by the absence or high cost of medication and the fact that lung transplantation is not performed. Quality of life Chronic illnesses can be very difficult to manage. Cystic fibrosis (CF) is a chronic illness that affects the â€Å"digestive and respiratory tracts resulting in generalized malnutrition and chronic respiratory infections†. The thick secretions clog the airways in the lungs, which often cause inflammation and severe lung infections. Therefore, mucus makes it challenging to breathe.If it is compromised, it affects the quality of life of someone with CF, and their ability to complete such tasks as everyday chores. It is important for CF pati ents to understand the detrimental relationship that chronic illnesses place on the quality of life. Havermans and colleagues (2006) have shown that young outpatients with CF that have participated in the CFQ-R (Cystic Fibrosis Questionnaire-Revised) â€Å"rated some QOL domains higher than did their parents†. Consequently, outpatients with CF have a more positive outlook for themselves.Furthermore, there are many ways to improve the QOL in CF patients. Exercise is promoted to increase lung function. The fact of integrating an exercise regimen into the CF patient’s daily routine can significantly improve the quality of life. There is no definitive cure for Cystic Fibrosis. However, there are diverse medications used such as, mucolytics, bronchodilators, steroids and antibiotics that have the purpose of loosening mucus, expanding airways, decreasing inflammation and fighting lung infections. ————————— Ã¢â‚¬â€Ã¢â‚¬â€Ã¢â‚¬â€Ã¢â‚¬â€Ã¢â‚¬â€Ã¢â‚¬â€-Epidemiology Mutation| Frequency worldwide| ?F508| 66%–70%| G542X| 2. 4%| G551D| 1. 6%| N1303K| 1. 3%| W1282X| 1. 2%| All others| 27. 5%| Cystic fibrosis is the most common life-limiting autosomal recessive disease among people of  Caucasian heritage. In the United States, approximately 30,000 individuals have CF; most are diagnosed by six months of age. In  Canada, there are approximately 3,500 people with CF. Approximately 1 in 25 people of European descent, and one in 30 of Caucasian Americans, is a carrier of a cystic fibrosis mutation.Although CF is less common in these groups, approximately 1 in 46  Hispanics, 1 in 65  Africans  and 1 in 90 Asians  carry at least one abnormal CFTR gene. Ireland has the world's highest incidence of cystic fibrosis, at 1:1353. Although technically a  rare disease, cystic fibrosis is ranked as one of the most widespread life-shortening genetic diseases. It is most common among nations in the Western world. An exception is  Finland, where only one in 80 people carry a CF mutation. In the United States, 1 in 4,000 children are born with CF. In 1997, about 1 in 3,300 Caucasian children in the United States was born with cystic fibrosis.In contrast, only 1 in 15,000 African American children suffered from cystic fibrosis, and in Asian Americans the rate was even lower at 1 in 32,000. Cystic fibrosis is diagnosed in males and females equally. For reasons that remain unclear, data has shown that males tend to have a longer  life expectancy  than females,  however recent studies suggest this gender gap may no longer exist perhaps due to improvements in health care facilities,  while a recent study from Ireland identified a link between the female hormone, estrogen and worse outcomes in CF.The distribution of CF alleles varies among populations. The frequency of ? F508 carriers has been estimated at 1:200 in northern Sweden, 1:143 in Lithuanians, and 1 :38 in Denmark. No ? F508 carriers were found among 171  Finns  and 151  Saami people. ?F508 does occur in Finland, but it is a minority allele there. Cystic fibrosis is known to occur in only 20 families (pedigrees) in Finland. Hypotheses about prevalence The  ? F508  mutation is estimated to be up to 52,000 years old. Numerous hypotheses have been advanced as to why such a lethal mutation has persisted and spread in the human population.Other common autosomal recessive diseases such as  sickle-cell anemia have been found to protect carriers from other diseases, a concept known as  heterozygote advantage. Resistances to the following have all been proposed as possible sources of heterozygote advantage: * Cholera: With the finding and discovery that  cholera toxin  requires normal host CFTR proteins to function properly, it was hypothesized that carriers of mutant CFTR genes benefited from resistance to cholera and other causes of diarrhea. Further studies have not confirmed this hypothesis. Typhoid: Normal CFTR proteins are also required essentially for the entry of  Salmonella typhi  into cells,  suggesting that carriers of the mutant CFTR genes might be resistant to  typhoid fever. No  in vivo  study has yet confirmed this. In both cases, the low level of cystic fibrosis outside of Europe, in places where both cholera and typhoid fever are  endemic, is not immediately explicable. * Diarrhea: It has also been hypothesized that the prevalence of CF in Europe might be connected with the development of cattle domestication. In this hypothesis, carriers of a ingle mutant CFTR chromosome had some protection from diarrhea caused by lactose intolerance, prior to the appearance of the mutations that created lactose tolerance. * Tuberculosis: Another explanation is that carriers of the gene could have some resistance to TB. ——————————————à ¢â‚¬â€Ã¢â‚¬â€- History It is supposed that CF appeared about 3,000 BC because of migration of peoples, gene mutations, and new conditions in nourishment. Although the entire clinical spectrum of CF was not recognized until the 1930s, certain aspects of CF were identified much earlier.Indeed, literature  from Germany and Switzerland in the 18th century warned  Wehe dem Kind, das beim Ku? auf die Stirn salzig schmekt, er ist verhext und muss bald sterbeor â€Å"Woe to the child who tastes salty from a kiss on the brow, for he is cursed and soon must die,† recognizing the association between the salt loss in CF and illness. Dorothy Hansine Andersen Dorothy Hansine Andersen In the 19th century,  Carl von Rokitansky  described a case of fetal death with  meconium peritonitis, a complication of meconium ileus associated with cystic fibrosis.Meconium ileus was first described in 1905 by  Karl Landsteiner. In 1936,  Guido Fanconi  published a paper describing a conn ecting link between  celiac disease, cystic fibrosis of the pancreas, and bronchiectasis. In 1938  Dorothy Hansine Andersen  published an article, â€Å"Cystic Fibrosis of the Pancreas and Its Relation to Celiac Disease: a Clinical and Pathological Study,† in the  American Journal of Diseases of Children. She was the first to describe the characteristic cystic fibrosis of the pancreas and to correlate it with the lung and intestinal disease prominent in CF.She also first hypothesized that CF was a recessive disease and first used pancreatic enzyme replacement to treat affected children. In 1952 Paul di Sant' Agnese discovered abnormalities in  sweat  electrolytes; a  sweat test  was developed and improved over the next decade. The first linkage between CF and another marker (Paroxonase) was found in 1985, indicating that only one locus exists for CF  Hans Eiberg. In 1988 the first mutation for CF,  ? F508  was discovered by  Francis Collins,  Lap-Che e Tsui  and  John R. Riordan  on the seventh chromosome.Subsequent research has found over 1,000 different mutations that cause CF. Because mutations in the CFTR gene are typically small,  classical genetics  techniques had been unable to accurately pinpoint the mutated gene. Using protein markers,  gene-linkage  studies were able to map the mutation to chromosome 7. Chromosome-walking and  -jumping  techniques were then used to identify and  sequence  the gene. In 1989 Lap-Chee Tsui led a team of researchers at the Hospital for Sick Children  in  Toronto  that discovered the gene responsible for CF.Cystic fibrosis represents the first genetic disorder elucidated strictly by the process of  reverse genetics. ————————————————- Research Gene therapy Gene therapy  has been explored as a potential cure for cystic fibrosis. Ideally, gene therapy places a normal copy of the  CFTR gene into affected cells. Transferring the normal CFTR gene into the affected epithelium cells would result in the production of functional CFTR in all target cells, without adverse reactions or an inflammation response.Studies have shown that to prevent the lung manifestations of cystic fibrosis, only 5–10% the normal amount of CFTR  gene expression  is needed. Multiple approaches have been tested for gene transfer, such as liposomes and viral vectors in animal models and clinical trials. However, both methods were found to be relatively inefficient treatment options. The main reason is that very few cells take up the vector and express the gene, so the treatment has little effect. Additionally, problems have been noted in cDNA recombination, such that the gene introduced by the treatment is rendered unusable.With the help of the  Cystic Fibrosis Trust, which has a league of highly professional gene therapists, both somatic and Adeno -associated viral vector have made advances. The  Adenoviridae, or more commonly known as the cold virus, is genetically altered, allowing the CFTR gene to enter lung cells. Small molecules A number of  small molecules  that aim at compensating various mutations of the CFTR gene are under development. One approach is to develop drugs that get the ribosome to overcome the  stop codon  and synthesize a full-length CFTR protein.About 10% of CF results from a premature stop codon in the DNA, leading to early termination of protein synthesis and truncated proteins. These drugs target nonsense mutations  such as G542X, which consists of the amino acid  glycine  in position 542 being replaced by a stop codon. Aminoglycoside antibiotics interfere with DNA synthesis and error-correction. In some cases, they can cause the cell to overcome the stop codon, insert a random amino acid, and express a full-length protein.The aminoglycoside  gentamicin  has been used to treat lun g cells from CF patients in the laboratory to induce the cells to grow full-length proteins. Another drug targeting nonsense mutations is  ataluren, which is undergoing Phase III clinical trials as of October 2011. BIBLIOGRAPHY 1. BIOLOGY TEXTBOOK FOR CLASS – XII (NCERT) 2. TRUEMAN’S BIOLOGY FOR CLASS – XII 3. SCIENCE REPORTER (September, 2007) 4. THE NEWYORK TIMES (December 22, 2009) 5. www. google. co. in/cysticfibrosis 6. en. wikipedia. org/wiki/Cystic_fibrosis 7. www. ncbi. nlm. nih. gov 8. www. cff. org/ 9. www. cysticfibrosis. com/ 10. www. cftrust. org. uk/