Reflective journal Essay Example | Topics and Well Written Essays - 2000 words - 2

Intelligent diary - Essay Example Through Sainsbury’s 2014 Christmas Advert, I got the chance to comprehend the clashing messages which can be through past messages. From the job of History as an asset of the residents, I had the option to fathom the job of history when both national and global occasions. The above can be applied in my future scholarly just as genuine interest while visiting new places and seeing how their current culture is impacted by history. I met the destinations of the talk through understanding the importance of History and its different implications to current life1. Dr Andrea Mammone addressed the subsequent Lecture, and its essential target was to educate on the verifiable formation of Identities with the significant spotlight being on autocracy. I had the option to meet the goals of the lecture.In the talk, I had the option to develop by understanding characters identified with autocracy across various social viewpoints. The teacher showed the relative verifiable characters from legislative issues to game and how they are utilized and reconsidered to legitimize present day political and nearby circumstances. Through the incorporation of memory and history, the various vectors of memory, for example, verifiable examinations, broad communications, recognitions and exhibition halls among others are built up. This prompts different sorts of recollections, for example, group and individual memory, individual and open among others. Mussolini is with despotism and after his fall pictures even in sports were utilized to imply his fall. One party rule is from different nations, for example, Austria and France. From the class, I had the option to see how the characters straightforwardly tested the acknowledgment of expansion, just as vote based systems around the globe. I was accordingly ready to accomplish the lecture’s objective through seeing how previous chronicled exercises had prompted the formation of characters on practically all social aspects2. The third talk on making characters concerning

The power of optimism Essay Example | Topics and Well Written Essays - 750 words

The intensity of positive thinking - Essay Example One additionally understood that through close to home encounters, just as the encounters transferred by others, there are substantial backings to the dispute that the intensity of positive thinking is genuine as it could open more open doors that could prompt achievement. As a matter of first importance, one avows that I am a positive thinker, essentially. Nonetheless, I am likewise a pragmatist. In confronting various circumstances, I accept a positive position that everything would come out right. On the off chance that they don’t, I accept that the difficulties are made to be experienced to discover some new information and great from them †subsequently, as yet improving us at long last. I have demonstrated the intensity of positive thinking through the experience of my auntie. Following a time of profitable vocation as a bank chief, she lost her position at the middle of an extraordinary money related strain since her significant other had been determined to have diabetes and interminable kidney disappointment and they have six youngsters to help. Luckily, she was additionally a hopeful person. As opposed to being discouraged, on edge, and upset, she tried to discover other business openings that would empower her to work at home and t ake care of both her husband’s and children’s needs. She recognized that since more open doors are being made accessible through the online medium, she could utilize her abilities in turning into an independent author. She in the long run got a new line of work as an independent author; multiplied and even significantly increased her income, and had the option to do everything without leaving the solaces of their home. All things considered, the loss of one employment was seen, not as a finish of a profession; yet as a surprisingly positive development. Through the intensity of idealism, she didn't lose trust in finding an increasingly profitable work which empowered her to address their budgetary needs, the wellbeing necessities of her significant other, and the instructive help for their six kids. Obviously, the intensity of good faith delivers new

Sales Associate Resume Examples, Template Resume Tips

Sales Associate Resume Examples, Template Resume Tips We all have different things that worry us â€" from family, job, education up to all the personal matters that bother us.However, there is one thing we have to admit we all have in common â€" no matter the age, experience or skills. That one thing is called getting a new job.In our pursuit of finding a new opportunity for us (preferably the best one on the market), there are some important steps and milestones we need to complete in order to get where we want.The first step is writing and sending an outstanding CV.So how should you do it?That is the most stressful part and the part we are going to help you with!You are a salesperson, so you are completely aware of the ways to take your sales skills and invest them in the process of creating your CV, as although it sounds harsh â€" this is the ultimate way to sell yourself as the best candidate to the company.Without further ado, we will focus now on the instructions and guide you on your way from no CV to the best possible one! You c an expect that we cover the following topics:What are the things your CV needs to haveDONT Dos that will help you avoid common mistakes and stand out amongst all the candidatesVisual representation â€" yes, your CV needs to catch HR’s eyes firstContent readabilityWe’ll explore each of this topic with great details until it becomes completely known to you what you should do, when and how.We will even give you a special tool you can use to generate your CV, guaranteeing that all of the things mentioned above are followed.So, we advise you to sit tight, take notes and enjoy the process of making the best cv ever that will let know every HR in the world that you are the best sales associate out there.Lets begin this journey of finding you a perfect teaching job!Sales Associate Resume Example Right Sales Associate Resume Sample Right Create your own resumeDo you see what we did here? We have two different CVs for two different positions. Yer, they have one thing in common. Can you imagine what?Its that they show you the most important information in a best-stylized way just by throwing your eyes on it.We want to do the san with your CV, so let’s dig into the guide!These two resumes contain different information but have at least one thing in common.Let’s go, your perfect resume is waiting to be written!GUIDE ON WRITING THE PERSONAL INFO SECTIONPersonal information â€" such a wide concept.You are aware of your personal information and what does that mean but of course you dont know which information actually to include and show in your CV.There are some strict guidelines, and we’re gonna teach you now how to write personal info section in the right way:?our name â€" it is important for them to know who you are and how to call so make sure you write your full name and surname correctly: and remember to alway s EXCLUDE nicknames, as it is unprofessionalYour field of expertise â€" this is where you are supposed to write your profession, to let them know your qualifications; TIP if the job opening is for the Junior Sales Associate, then your profession should be Junior Sales AssociateYour contact information â€" a phone number that is valid and in useYou e-mail address â€" first round of applications usually goes through e-mail so make sure you write down the valid e-mail addressAdditional things you need to considerA professional photo of you â€" (depending on the country so DO check what is expected from a candidate in the country you are applying for a job) â€" a portrait of you, with a one-color backgroundYour address â€" for some jobs it is necessary for people to live in a specific area, so if asked in the application, you should add your address to your CVYour social media profile â€" really questionable, a there should be a line between personal and professional life, at least on s ocial media. The only social media profile we advise you to link is your profile on LinkedIn as it is a platform for professionals and a longer version of your CV.The most common mistakes and the correct versions:Personal Infoalexa.richardson@gmail.com https://www.linkedin.com/in /alexa-richardson + 1 030-586-9339 RightPersonal Infoalexa.miss.beauty93@gmail.com https://www.linkedin.com/in/ alexa-richardson-998345/ 0305869339 WrongBtw, did you know that there’s a program that can make your CV creation twice as easy and triple as fun?Check out clverism site for more information!GUIDE ON WRITING THE SUMMARY SECTIONHow to sum up your entire life in 5 sentences?Difficult, but not impossible, especially if you follow our guide on writing the summary section!First thing you have to bear in your mind that this is a summary of your professional life â€" exclude any stories about your family or other parts of personal life.This is your 5 sentences to shine, so youve gotta use them wisely! Lets take a look at this example and compare two summaries of the same CV:Summary?xperienced sales person with a career in the business development department for the past 10 years. Throughout this period, I have got to know and develop my own sales process, which enabled me to have a closing rate higher than 95%. I dont find sales only as a job, but my life mission to connect people with products and services that will make their lives better. Currently, I am looking for a new job â€" a new opportunity to bring people what they need in life while I push my own limits and continue to improve. RightSummaryI’ve been working in sales for the past 10 years. Now it is time for me to change the job. Im looking for a dynamic position where I could work with a lot of clients and have a good salary. WrongTo be honest, we don’t have to say which one is good and which one is a bad example. You see it by yourself.The sad truth is that people usually send CVs with a summary similar to the one in the right box, as they are either unfamiliar with the correct way or just don’t know from where to start.That’s why we will guide you know and teach how to do it exactly!Bear in mind these simple rules:Focus on your strengths â€" it might be your years of experience, fresh energy of a recent graduate, or anything else you believe should be the first thing HR reads about youKnowledge and skills â€" experience is nothing if you didn’t learn anything from it, so make sure that you highlight your main learnings in the sales areaAchievements â€" don’t brag about everything you’ve done in your life, but do mention key achievements (and let them be measurable and based on facts)Current status â€" where you are right now, why you are looking for a new job and how is the job you are applying for relevant for your longterm ambitions and goalsNow that you know main rules, it’s time you get familiar with main mistakes, so you avoid them!SummaryThroughout this period, I have g ot to know and develop my own sales process, which enabled me to have a closing rate higher than 95%. RightSummaryIn the past 10 years, I became really good at sales and developed my sales process, which helped me have a better closing rate. WrongTo ensure correctly written resume, use our resume builder and let HRs see the best version of you!GUIDE ON WRITING THE EXPERIENCE SECTIONFirst thing first â€" the way you write your experience should always be reverse-chronological, meaning that you always start from the latest experience you’ve had. Take a look: Right WrongThe necessary information you need to include:time periodyour rolethe company youve worked forIf you want somebody to read your resume, first you’ve gotta make it readable. It is important that your information is structured like the example above, so you can show your best version of yourself.Not to scare you or anything but this is just beginning. Now it’s time to explain what you go out of these experiences, as that is what matters.Remember, without learnings, the experience is nothing!These are the main rules on how to write a kicking resume:always rely on facts and highlight measurable actionsspecify your area of expertise â€" job title doesn’t say much, you have to write down concrete tasks youve had while on this jobhighlight your biggest achievements â€" for example, sales growth 64%, returning customers ration improved from 1 to 5, etc.show your unique contributionâ€" this is what the company will be looking for, so dont be shy to mention your unique contributio n to the companies youve worked previously forNow let’s see common mistakes and how to avoid them:Experience description examplesImproved the ratio of returning customers from 1 to 3Organized promotional activities in 14 different facilities with a result of 20% higher salesReceived 3 years in a row an award Next generation sales   killer from the company RightExperience description mistakesMore returning customersPromotionsNext generation sales killer WrongJust a friendly reminder that you can always use our resume builder to create a perfect size and design for your CV, that every HR will love!GUIDE ON WRITING THE SALES ASSOCIATE EDUCATION SECTIONPeople often confuse education and experience section and merge them instead of specifying them. Thats wrong as there are two completely different things.No matter how different they are, they have a similar concept, so it will be easy for you to write this down correctly!One thing remains definitely the same â€" the data you should p rovide:a lasting period of your educationdegreethe university youve attendedstill, only enlisting this information will not be enough. Let’s see how it should be done: Right WrongFor our extra ambitious friends that finished more than one university, heres the thing: mention it, as it will definitely make you stand out.Again, in a reverse-chronological way. Starting with the latest one you have attended or finished.Important note: if you are still a student (it happens really often that sales associates focus on work and career path a bit earlier than supposed to and find themselves still on college while looking for a new job), you have to mention it by stating current as the finish date.Be prepared as this question about your current status might pop up at the interview!We live in an age where non-formal education is taking more and more impact over the formal one.With the internet, came the knowledge, accessibility, and a privilege people before us never had.That’s why it’s very valuable if you’re attending any additional courses, seminars, webinars, etc. even researches, essays and extracurricular activities you took during your studies count .A quick tip: dont forget to mention them all!When you get all of this into your resume, you will definitely shine on your job application, especially if you allow our Resume builder to be your personal assistant!GUIDE ON WRITING THE SKILLS SECTIONThis is the trickiest part as you might find yourself on two possible sides:I have too many skills, I can’t write them allI can’t name even one skill, why am I even applyingEither way, its bad, and you need some guidance.That’s why we have prepared this guide to help you understand which skills to put down in your CV, so you dash each HR that takes a look at it!These are the rules you should follow:Priorities on what you want to show â€" not every skill is relevant for the job you’re applying toSpecify the skill â€" if its not concrete, its irrelevant, and you appear like an amateurAdd facts and numbers â€" if it’s not measurable, it’s irrelevantDetermine the level of development of your skills â€" by using bars, charts, grades â€" its up to you. Our resume builder program could definitely help you out with it!Go into details â€" only when a 5-year-old child can understand your biggest strengths is your application ready to go!SkillsOrganizational skills High capacity for organizing and coordinatingTime managementAdvanced communication skills RightSkillsOrganizingPunctualGood with people WrongFINAL TIPS TRICKSMake sure you convert your CV to PDF before sending it to keep the same format and design.The PDF version of your CV should be named as Your Name_Your Surname_Position you’re applying for.Always have a custom CV for each job application â€" many people apply for a dozen different job and fail to get it, as they always send the same CV.Remember that LinkedIn is a longer version of your CV and that it should be updated before sending the application. Don’t forget to include the link to your profile in your CV!Ensure that the format and design of your CV support your application and contribute t o HRs loving you. Success is guaranteed with our cleverism custom templates!FINAL THOUGHTSAnd, that’s a wrap! It may sound unbelievable, but right now, you have everything you need to create THE perfect CV that will help you get your dream job!Just follow every step from the guide, and we guarantee you-you will be on your way to your new job shorter than you think it’s possible!Don’t finish this process here when it gets most useful.Go to our website and check out the custom CV templates made by our resume designer program, that will make you have yure desired cv in no time, better than you can imagine!Few wish you the best of luck and can’t wait to see how many closed deals await you in the future! Create your own resume

Essay about José Martí - 568 Words

Josà © Martà ­: A Cuban Hero The nineteenth century introduced several great leaders into this world, many recognized by historians today. These men, Thomas Jefferson, Abraham Lincoln, and others, have all been honored and commemorated for their contributions. One such leader, Josà © Martà ­, continues to remain anonymous outside the Hispanic community, and hidden in the shadows cast by these men. His name does not appear in the history books or on the tongues of many proud Americans, for he was neither a citizen of America nor an American hero. Josà © Martà ­, born in Havana, Cuba in 1853, experienced many hardships throughout his lifetime. All through his adolescence, Josà © Martà ­ struggled against poverty. He would not have attended primary or†¦show more content†¦Unfortunately, many totalitarian governments of Hispanic descent found his ideas and literary inclinations rather alarming and dangerous to the community. As a result, Josà © Martà ­ was exiled from Cuba, Mexico, Guatemala, and Venezuela. While exiled from these countries, he spent several years in New York. While there, he wrote for the New York Sun, taught school, and founded the Cuban Revolutionary Party. Josà © Martà ­ focused the majority of his energy towards this party. He brought together Cuban people from all over the nation in the hope of establishing independence and finding freedom for the people of Cuba. He educated many people of his party for over ten years. He alone toiled away to keep their interests focused during the long wait towards independence. He accumulated money weekly from the many Cuban members and persuaded people to join together harmoniously under the influence of the Cuban party. Planning each aspect of the Revolution, he compiled shipments of arms without the knowledge of neither the United States nor Cuban governments. He placed his heart and soul into the organization and preparations of the Revolution without complaint. As the Revolution dawned, he fought with dignity and purpose, serving his followers well into the revolution even after death. Josà © Martà ­ fought for the independence and freedom of the Cuban people. He contested the tyranny of despotic and unruly governments through the written andShow MoreRelatedNuestra America: Josà © Martà ­ Essays601 Words   |  3 Pageshermanos celosos, que quieren la misma tierra, o el de casa chica, que le tiene envidia al de la casa mejor, han de encajar, de modo que sean una, las dos manos.† Josà © Martà ­ enero de 1891 â€Å"Nuestra Amà ©rica† expresa como Hispanoamà ©rica debe de empezar de liberarse de los gobernantes de otros paà ­ses, como los europeos o estadunidenses. Martà ­ nos da a entender que amà ©rica latina TIENE que empezar a luchar por sà ­ misma y darse a conocer. Para poder hacer esto, todos los paà ­ses han de unirse para poderRead MoreThe Plaza ( Jose Marti Memorial )1032 Words   |  5 Pagesin the country. 1. Revolucion of the Plaza (Jose Marti Memorial),Havana The Revolucion of the Plaza should be the first stop for lovers or students of history interested in the country. In the middle, features a gray tower, 109 meters in height, a memorial of Jose Marti who was a Cuban national hero. To get a better view , you can ascend to the top of Havana city,which is the capital city of the country. Beneath the monument is the Memorial of Jose Marti that is the home of a museum on the hero. TheRead MoreThe Cuban National Hero Jose Marti, A Precursor Of Latin American Modernism2567 Words   |  11 Pages My concentration in this comparison is on how ethnicity and race are illustrated. The first nationalist thinker whose ideas I intent to discuss is the Cuban national hero Josà © Martà ­, a precursor of Latin American modernism. I will contrast Martà ­Ã¢â‚¬â„¢s ideas and writings with the Peruvian journalist and political philosopher Josà © Carlos Marià ¡tegui, the representative and advocator of twentieth century Latin American Marxist ideas. T here are some similarities between the offered social solutions betweenRead MoreSocial Science Teacher That Educates Students At Jose Marti Mast 6-12 Academy1201 Words   |  5 PagesChristy Llanes is an AP Biology, Biology, and AP Environmental Science teacher that educates students at Jose Marti MAST 6-12 Academy; she works with 8th-12th graders. Christy is also the head of the SECME Club, as well as the Head Chair of the Science Department. She believes her Science department offers an innovative and cutting edge program. Students learn to be critical thinkers, problem-solvers, and decision making citizens about the science and technology issues that encounter our societyRead More Cuban Revolution Essay945 Words   |  4 Pages nbsp;nbsp;nbsp;nbsp;nbsp;Fidel Castro, inspired by Josà © Martà ­ who first dreamt of a Cuban Revolution who died a martyr before he could succeed, wanted to overthrow the corrupt government under Fulgencio Batista. Castro gathered an army of revolutio naries known as the Fidelistas who were driven by nationalism, idealism, patriotism, and the thought of possibly becoming a martyr, a historical glory of Cuba. The result of this revolution in Cuba was an overthrow of the government and the startRead MoreThe s Concept Of Cuban Nationalism Essay2021 Words   |  9 PagesChase Marx IAH 203 Prompt #1 Martà ­ s concept of Cuban nationalism was broad as it encompassed a strong national Latin American identity while still tying in cultural aspects of Spain and North America that he had picked up during his time spent in exile. Josà © Martà ­Ã¢â‚¬â„¢s vision for an independent Cuba united Latin Americans all over the world and incited a revolution that would define a new future Cuban National Identity for better or for worse. Josà © Martà ­ spent the majority of his life in exileRead MoreThe Spanish American War During The 19th Century1391 Words   |  6 Pagesmajor leaders for the Cuban struggle was Jose Marti Jose Marti was born in Havana in 1853, to Spanish parents. As a child his teachers stirred a motivation in him for the cause of freedom. As a teenager he had written many stories and poems and so impressive were they that he was hired to write for a newspaper in Havana when he was only 16. In 1869 he was critical of the Ten Years War in Cuba, which was between landowners and former slaves. Marti wrote passionately about the plight of theRead MoreThe Historical And Intellectual Trends1746 Words   |  7 Pagesblack Cuban population. The purpose of this paper will be to explore the historical and intellectual trends that have simultaneously perpetuated and condemned racism and racial inequality, ranging from the institution of slavery to the writings of Jose Marti. These paradoxes have l ed to the contradictory social and systematic responses to the Afro-Cuban population, especially with regard to their role in the shaping of national Cuban culture and music. Cuban Transculturation Cuban historian, philosopherRead More10 Best Places Visit Of Cuba1090 Words   |  5 Pagescountry. 1. Plaza de la Revolucion (Jose Marti Memorial), Havana The Plaza de la Revolucion should be the first stop for lovers or students of history interested in the country. The center of the Plaza de la Revolucion features a gray tower, 109 meters in height, a memorial of Jose Marti who was a Cuban national hero. You can ascend the tower to get better view of the city of Havana, which is the capital city of the country. Beneath the monument is the Jose Marti Memorial that is the home of a museumRead MoreChronicle Of A Death Foretold By Gabriel Garcia Marquez1492 Words   |  6 Pagespromise for her. In contrast to her hope Latin American author Jose Marti states that â€Å"that land for them, go and live with the English during the years when he saw the English marching against his own land? These incroyables who drag their honor across foreign soil, like the incroyables of the French Revolution, dancing, smacking their lips, and deliberately slurring their words!†(Marti,1982,para.2). Using these words it is clear that Marti is wr iting in a way that does not express that he has faith

Horses Of The Night Stage Notes - 1896 Words

Horses of the Night Stage notes First Stage Second Stage Brick House Quite literally, a brick house. The location of which a lot of the story happens. Owned by Vanessa’s grandfather. â€Å"Looked huge and cool from the outside†¦ inside it wasn’t cool at all.† Could possibly represent Grandfather Conner’s cold, ignorant, arrogant attitude and demeanor. Grandfather Connor Very aggressive, cold demeanor similar to the bunkhouse. Always tries to find a reason to get mad like the train being late or Grandmother not making potato salad, etc. Appears to have a poor/uneasy relationship with her daughter, Beth. As noted by â€Å"I can’t bring myself to ask father about it, Ewen. I simply cannot do it.†Ã¢â‚¬ ¦ â€Å"There wouldn’t be much point in asking†¦ when the†¦show more content†¦Believing that he can do anything if he puts his mind to it, could believe that his fantasies are real by following the theory. Chris One of the main characters. He is from Shallow Creek where his family runs a farm and he believes to have his own ranch. Apparently he was known to be violent as noted by his mother before going to the Brick House. There is a great age difference between Vanessa and himself as he starts highschool as Vanessa is 6 years old. Believes in his own fantasies throughout the story (Duchess and Firefly, becoming and engineer, etc). A child-like mind allows easy communication with the children that run around his house but not with the others in his household, absorbing their words like he did when facing Grandfather Connor. Story always seems to mention his clothing when he returns after disappearing for a while. (When Vanessa and Chris first meet, when he comes back as a salesman, hospital clothes, etc.) Suffers from a mental breakdown after 6 months in WWII. Goes back to his delusions after being discharged. (I could not know whether the land he journeyed through was inhabited by terrors, the old monster-kings of the lake, or whether he had discovered at last a way for himself to make the necessary dream perpetual.†) Slowly detaches himself from the real world to hole up in his own little world. Vanessa picks upShow MoreRelatedAll Quiet on the Western Front: Themes1023 Words   |  5 PagesAll Quiet On the Western Front: Themes All Quiet on the Western Front is a graphic depiction of the horrors of war. In the short note before Chapter One, Remarque lets the reader know exactly what themes he intends. War is a savage and gratuitous evil, war is unnatural, and war is responsible for the destruction of an entire generation. Remarque is very clear on the strength of his themes, and uses graphic imagery to convey to the reader the physical and psychological impact that warRead MoreStuggles Of Neil Young Essay1317 Words   |  6 Pagesunit to Sample and Hold, made This Note for You, and Lived with War. However, through it all, he has been able to make original music for more than 40 years. The Needle and the Damage Done first appears of Neils 1972 solo release of Harvest. The song mainly is dedicated to Youngs late band mate Danny Whitten (McDonough 329). Whitten was the guitarist for Crazy Horse and appeared on several albums.Read MoreThe Role of the Chorus in Henry V by William Shakespeare Essay1172 Words   |  5 Pagesoccur in the play, to really imagine the royal courts of England and France, and to really imagine the battle scenes with all the horses and men. The prologue to the beginning of this play calls upon the Muse to help present the play. 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The reason I specify the definition of animation is because the origin of animation is dependent on the definition that you follow -- the definition of animation is very abstract. This means that even the simple flipping of a series of sticky notes that represent different frames can be considered an animation, as long as the intent is to show movement through those frames. So, following this definition the very first glimpse of animation that humanity produced originated from the early EgyptiansRead MoreWilliam Shakespeares Biography903 Words   |  4 PagesWilliam Shakespeares Biography On an April night unknown, in 1564, at a humble home in Henley St. in the quiet town of Stratford, England Isle of Wight, John and Mary Shakespeare gave birth to a poet. William Shakespeare was born on what is believed to be the 23rd of April the feast day of patron saint the dragon-slayer St. George, and though there are no known records either to confirm or deny, this date was subsequently accepted, has been established, and is widely celebrated as the day ofRead MoreThe Book I Read For This Project Was The Complete Psychological2063 Words   |  9 Pagesdeveloping theory on infantile sexuality (Stanford). Evidence for psychosexual stages and theories of gender development were collected through this study. Even though Freud did not actually work directly with Hans, Hans’ phobia was cured by Freud’s application of Freudian psychosexual concepts and revealing the unconscious and repressed reasons for this fear. The aim of this case study was to understand Hans’ fear of horses and treat it while collecting information Freud could use for his developingRead MoreHow Magical Realism Is Achieved1398 Words   |  6 Pagesfaraway world and let [himself] be pulled along by the current,† meaning Preciado felt overwhelmed and confused, given that previously, Eduviges had also told him that his mother was the one who voiced her about his trip to Comala (Rulfo 11). One notes the use of broken time in Preciado’s and the reader’s confusion when he mentions â€Å"my mother? 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This breed is bred at the Turkmenbashi Stud Farm, six miles south of the city of Ashgabat. The races themselves take place in the Hippodrome in Ashgabat. I chose this event because I am an avid equestrian and I have always been fascinated with the racing portion of the sport. I think that it would be amazing to watch a breed of horse, who is said to be one

New Zild Free Essays

? New Zealand English (NZE) which is now known as â€Å"New Zild† is an exciting and newfangled language they speak in New Zealand. New Zild is forever evolving-forming new, abbreviated ways of speech. Their shared language – Te Reo/English makes up their unique, lucid dialect, which unites them as a country and distinguishes them from the rest of the world, this is a great aspect as their language will be fancied in the future. We will write a custom essay sample on New Zild or any similar topic only for you Order Now New Zealand English is the newest most fascinating language in the world today. New Zild is the only language that can be tracked since its birth over two centuries ago. The dialogue is forever evolving, changing and advancing. New Zealand English is a continuously developing speech. What makes this language so exclusive is that you can use available resources to show the developing and unfurling of it. Although characteristic features of New Zealand English have evolved from British English, there are no longer any dominant influences. New Zild forms and illustrates a Kiwi, who creates their own language, being New Zild. Their strong accent is greatly noticed overseas. Foreigners find New Zild bizarre, as they talk faster than, they do. Although New Zealand English is closely related Australian English also known as ‘strine’ but they have their individuality, as New Zealanders do. America has major influence in all the languages, including New Zild. American English is the most influential language of the world. The trends it sets are spread by mass communications around the globe, for example, television, movies and music. American English can have a negative impact depending on the kind of influence being portrayed, for example, teenagers listening to rap music, the lyrics or words expressed may have meaning, but would their parents like them talking like the rapper? American English also has a positive impact on New Zild as it creates new characteristics and majorly influences the development of New Zealand English. The American English greatly affects young New Zealanders as they may speak an even stranger language than their elders. Their speech has been hugely influenced which all contributes to the future. The dialect of the younger population is different, therefore change naturally occurs. New Zealand’s younger generation being teenagers forms many, new colloquialisms, increasing yet decreasing their vocabulary. According to Jennifer Hay in Denis Welch’s Listener article, â€Å"By the time someone is seven or eight, it doesn’t matter where their parents came from, they’re speaking like their friends at school. † Older New Zealanders are trying to adapt to the teenage dialect, after all they are the voices of the future. Their dialogue will be the future New Zealand’s English, as the new vocabulary, colloquialisms work their way from the bottom of the social heap to the top. The tremendous variety of languages composed in New Zealand is another impact. New Zild is an exciting language as it includes an assortment of influences from these solitary vocal influences. Maori have changed the way New Zealanders speak because words and sayings from Te Reo have been absorbed into the vocabulary spoken today. There are some Maori who can speak both English and Maori beautifully. Years ago only 1/1000 Maori words spoken were fully understood in New Zealand English, now 6/1000 Te Reo words spoken are understood in New Zealand English. Could this be renaissance? Including Te Reo, there is also one other contributing factor to New Zealand English, such as Pacific Island dialect. Te Reo and the pacific input combined, greatly influence New Zealanders speech and pronunciation of different words. New Zild is the most innovative, peculiar language. New Zealand English is the only language in the world that can be documented from the beginning which helps predict future dialect. Along with the growing Te Reo pronunciation New Zild is evolving into something that is very interesting and distinctly theirs. How to cite New Zild, Papers

Spinal Injuries In Sports Essay Research Paper free essay sample

Spinal Injuries In Sports Essay, Research Paper More late than of all time on the intelligence we re hearing narratives of participants having serious blows to the caput and spinal column which force them to be carried off on a stretcher. The crowd is soundless and participants stand on the out of boundss with an empty expression in their eyes. This is the state of affairs that arises during the clip of crisis and while medical attending trades with the victim. All the stairss of safeguard must be taken to guarantee the jocks safety. The crowd rises to its pess and gives a loud cheer for the participant s wellness as he is carried off from the game. Millions of ideas race through a participant s caput, Am I traveling to walk once more? Is this traveling to impact my mental ability? Cipher should hold to be in that state of affairs at all. We will write a custom essay sample on Spinal Injuries In Sports Essay Research Paper or any similar topic specifically for you Do Not WasteYour Time HIRE WRITER Only 13.90 / page Sports are supposed to be a friendly competition that is safe and gives a great trade of enjoyment. Head and Spinal hurts are the most unsafe hurts that can be produced in athleticss and that is besides why we must do safeguards. Many people today don T understand what can be done to work out the job. Some say that participants should be suspended every bit long as the participant is hurt and others say that they should set a halt mark on the dorsum of a participants helmet/jersey. What needs to be done is a better regard for 1s opposition. Today with participants have oning every bit much equipment as they, cipher has regard for their opposition. They swing their sticks, hit hard as possible without thought of what harm you can make to a participant. When there were no helmets and no cushioning, participants had a common regard for each other and freak accidents were the lone 1s that happened. Today in the inflationary universe of participant wages and winning is the lone consequence ; drama Ers take their aggressiveness to another degree. I believe that merely one time a participant regard 1s opposition, can a common regard be made to care for the other participants wellness, because to an jock, that could ever be you lying on the ice next inquiring if you ll of all time be able to walk once more. To me, playing athleticss is one of the greatest gifts that anyone could give me. Not being able to walk would take that off from me as it would any other professional jock. Though it may non be my occupation or I m doing 1000000s of dollars to make it, I still have the bosom and desire to play athleticss whenever I can. Possibly my organic structure isn t worth a billion dollars like Jennifer Lopez, but to me my organic structure is all I have and without, I wouldn t be able to work or bask life to its maximal possible. Though the athletics I play, which is hoops is less likely to supply hurts, safety in athleticss where contact is made is really of import. It s really of import to set aside the self-importance of have oning helmets and do it for the safety of the jock and everyone around you. What you can make as an jock is have a greater regard for the opposition you play against and possibly they ll return the favor. Sports International Relations and Security Network T about concern, the existent athleticss are about fairplay and enjoyment. Traveling out at that place in a merriment game and seting your organic structure on the line is instead silly since you might play hockey one time a hebdomad, but you walk mundane of your life. The STOP plan, which was mentioned before in this study, is extremely promoted by celebrated analyst Don Cherry. He claims that the mark should be moved to the following degree, being the NHL. Hopefully the marks will move as a deterant to any type of hitting when a participant comes hotfooting in.

Employees’ Perception of Selection Systems The WritePass Journal

Employees’ Perception of Selection Systems Introduction Employees’ Perception of Selection Systems IntroductionArticle 1: â€Å"Applicants Perceptions of Selection Procedures and Decisions: A Critical Review and Agenda for the Future†.Article 2: â€Å"Fairness Reactions to Selection Methods: An Italian Study†.Conclusions and RecommendationsReferencesRelated Introduction This paper summarises the views of two authors on how job applicants or potential employees perceive selection procedures. Both articles focus on employees’ perceptions of selection methods. Article 1: â€Å"Applicants Perceptions of Selection Procedures and Decisions: A Critical Review and Agenda for the Future†.    The first article is written by Ryan and Plolyhart (2000) and is titled â€Å"Applicants’ Perceptions of Selection Procedures and Decisions: A Critical Review and Agenda for the Future†. This article is motivated by the fact that low unemployment rates have increased the competition for employees, which has forced organisations to review the various components used in selecting job applicants and how job applicants’ perceptions of those procedures can affect the attractiveness of the organisation to potential employees. Another motivation for this study is the fact that there is lack of better research on applicant perspectives. Thirdly, the article notes that social justice theorists are looking for ways to apply social justice theory concepts to applicants’ perceptions of selection methods. Moreover, there is an increasing diversity in the workforce as well as racial differences in perception of selection procedures which can affect the manner in which j ob applicants perceive organisations and thus the attractiveness of those organisations to potential employees. The article notes that one of the main assumptions of most research in this area is that the manner in which job applicants perceive selection procedures and processes affects the manner in which the applicant views the organisation and thus the decision on whether to apply for a job vacancy to that organisation or not. The article also suggests that differences in perceptions between minority and majority groups on certain selection procedures can account for some of the differences in job performance that is often observed between these two groups. The article begins by reviewing the works of Schimittand Gilliland (1992) and Gilliland (1993). These studies develop a model which provides a link between between applicants’ perceptions of selection systems and situational factors and their subsequent â€Å"attitudes and behaviours† towards those organisations. The model postulates that applicants’ perceptions of the procedural justice system are influenced by situational characteristics. These characteristics include the type of test administered during the selection process, the human resource policy of the organisation and the behaviour of the human resource staff of the organisation. The overall fairness of the selection system is influenced by the degree to which the applicants’ perceptions of the procedural justice of the selection system meet the expectations of applicants. The framework further stipulates that applicants’ prior experiences with a selection system would affect the evaluatio n of the system. Distributive justice rules of equity, equality, and need have an impact on the perceptions of the distributive fairness of the final decision reached through the selection system. Distributive justice rules are in turn influenced by performance expectations and the salience of discrimination. In a nutshell, the framework concludes that there should be a relationship between outcomes such as â€Å"job application decisions, test motivation, self-esteem, self-efficacy, endorsement of the company’s products, job acceptance decisions, job satisfaction, and performance among others† and applicants’ perceptions of fairness of the selection process. After reviewing the framework, the authors then move on to provide a critical review of the empirical literature and evaluating how they conform to the framework. The review focuses on four key areas including: The perceptions that have been studied; The factors that determine applicants’ perceptions; The consequences of holding more positive or negative perceptions; and The theoretical frameworks that have been presented. With respect to the applicants’ perceptions that have been studied, the article notes that the most commonly researched perceptions include applicants’ feelings regarding degree to which the selection system is related to the job, feelings about the fairness of various aspects of the selection system and its associated outcomes, as well as feelings about test taking motivation. The authors provide a critical review in this area and conclude that a major concern with most of these studies is that their constructs are imprecise with respect to the manner in which they are defined as well as the variability with which they are operationalised. As a result, the authors conclude that a better conceptualisation of research on test behaviours and on fairness is required to improve understanding. The authors however, admit that the work of Chan et al (1998) to a certain extent provides a link between test attitudes and perception of fairness although the study focused only on two concepts from each line of research. According to the authors, lack of an improved integration of studies on test attitudes on fairness and test attitudes makes understanding difficult. For example, it is difficult to determine whether potential employees who are more anxious perceive procedures are more unfair as opposed to those who are less anxious. In addition, it is difficult to deter mine whether beliefs about testing have a higher impact on perceptions of fairness of a procedure than characteristics of the procedure and selection situation itself. The author notes that notes that most test-taking attitude measures are perceptions of oneself (including motivation, anxiety, etc) while justice-related perceptions typically focus on the fairness of the test used in making hiring or rejection decisions. The authors argue that there should be a relationship between applicants’ motivation and anxiety and the justice-related perceptions. The authors also suggest that it is important for other perceptions to be tested. Basically most of the studies under review focus on how the motivation or perceptions of applicants influence their perceptions of fairness. This approach neglects the impact of other perceptions of fairness that may be critical for the improvement of selection systems. Article 2: â€Å"Fairness Reactions to Selection Methods: An Italian Study†. This article is written by Bertolino and Steiner (2007). Like the first article, this article begins by reviewing the works of other authors who provide different conceptual frameworks on the relationship between applicants’ perceptions of fairness of selection systems and their attitudes and behaviours towards the organisations. This article cites the work of Schuler (1993) whose framework suggests that the reaction of applicants to a selection process is a function of the key characteristics of the selection techniques employed. In addition, the article reviews the work of Anderson and Ostroff (1997) who focus on the socialisation impact of selection methods. Like the first article, the second article also reviews the work of Gilliland (1993) who employ organisational justice theory to comprehend the reaction of applicants to selection systems. Unlike the first article, which is based solely on a critical review of empirical literature on the reaction of applicants to selection systems as well as the underlying models of selection systems, the second article is based on both primary and secondary information. It begins by reviewing literature, and then conducts and exploratory study on the reaction of applicants to selection systems using a sample of 137 Italian students. The study is motivated by the fact that despite the presence of evidence on selection systems, most of the studies have been conducted in other countries with no attention given to Italy. The article notes that cultural differences may play an important role in the manner in which applicants perceive selection systems and thus their reaction to those systems as well as their attitudes towards the organisation. Based on the four dimensions of culture proposed by Hofstede (1980, 1991) (individualism vs collectivism, uncertainty avoidance, masculinity vs femi ninity, and power distance), the article suggests that it is possible for selection systems to be avoided by these four dimensions. For example, the article reviews the work of Ryan et al. (1999) who show that uncertainty avoidance can affect the selection practices of many countries. In addition, the study reviews the work of Triandis (1990) who argue that people from countries with high uncertainty avoidance prefer predictability, knowing what others will do, and having clear instructions and expectations. This means that employees who work in countries with high uncertainty avoidance should be more inclined towards engaging in structuring activities, including the standardisation of practices. On the contrary, those in countries with low uncertainty avoidance should be less committed to formal structures and should be prepared to accept spontaneous changes in practices. The study employed a survey questionnaire to study the reaction of Italian student to selection systems. The questionnaire used in the study is the one developed by Steiner and Gilliland (1996) which presents 10 different selection methods used in the U.S or Europe. The questionnaire asked students to think about a job they would apply for upon completion of their course Using a within-subject analysis of variance (ANOVA) the ratings of process favourability was compared across 10 selection methods. The evidence suggests that there are significant differences across the 10 selection methods. The selection method that received the most favoured rating was â€Å"work-sample test†. Resumes, written ability tests, interviews and personal preferences had the second favourable rating. Personality tests and biographical information blanks received a neutral rating while honesty tests and personal contacts received negative ratings. The authors conclude that their results are similar to those obtained from other countries. In particular, they observe that employer’s right, opportunity to perform and face validity are the procedural dimensions that had a high correlation with process favourability for all four countries that were studied. The two articles are similar in that they both begin by providing a theoretical framework on selection methods. Both articles provide the same theory which shows that there is a relationship between applicants’ perceptions and their reactions to selection systems. However, the first article differs from the second one in that it is based solely on the review of secondary literature. The article does not arrive on any conclusions with respect applicants reactions to selection systems. Rather, it identifies weaknesses in the literature and provides recommended procedures for improvement in future studies. On the contrary, the second article employs primary data to study how employees’ perceptions of selection systems affect their reactions to those systems. It compares findings to previous studies and concludes that culture has no significant impact on employees’ reaction to selection systems in Western countries. The study observes that the findings from France, I taly and other Western countries are similar to those obtained in studies from the United States. This shows that the different cultural dimensions mentioned in Hofstede (1981, 1990) do not influence the manner in which employees perceive selection systems which means that it does not affect the manner in which the react to those systems. The foregoing suggests that other factors may be affecting employees’ perceptions rather than culture. Conclusions and Recommendations Based on the discussion of the two articles above, one can conclude that employees’ perception of selection procedures influences the manner in which they behave towards the organisation and the decision to accept or reject an offer to work for a particular company. These perceptions may even influence the applicants other interactions with the company such as deciding to buy or not to buy the company’s products. The main difference between the two articles is that one focuses on criticising research on selection systems while one focuses on understanding how employees perceive selection systems across countries and how those systems affect their reaction. Based on this conclusion, it is important for organisations to note that the manner in which they design their selection system can affect the perception of applicants and as such affect the attractiveness of vacancies to potential applicants. Selection systems can even influence the ability of a company to attract qu alified applicants. If employees have a negative perception about a particular company, they may not be motivated to apply for a vacancy in that company and this may make it difficult for the company to fill the vacancy with a qualified applicant. Consequently, employers should seek the most favourable selection systems so as to increase their ability to attract qualified applicants to their jobs. The first article shows that research on selection systems is limited. Therefore, this paper recommends that more research should be conducted on selection systems and how employees perceive those systems. By so doing one can provide better recommendations to employers to aid them in designing their selection systems. References Bertolino, M., Steiner, D. D. (2007) â€Å"Fairness Reactions to Selection Methods: An Italian study†, International Journal of Selection and Assessment, 15, Number 2 Ryan, A. N., Ployhart R. E. (2000) â€Å"Applicants Perceptions of Selection Procedures and Decisions: A Critical Review and Agenda for the Future†, Journal of Management, 26, 565-606

Last Time Consecutive Democratic Presidents Were Elected

Last Time Consecutive Democratic Presidents Were Elected Political analysts and Beltway pundits can debate the obstacles facing Democrats in the 2016 presidential election. But theres one inescapable truth facing the partys nominee, no matter if its Hillary Clinton or Elizabeth Warren or Julian Castro: Voters rarely elect someone from the same party for consecutive terms. â€Å"Mostly, the White House flips back and forth like a metronome. Voters just get tired after eight years,† the writer Megan McArdle wrote. Explains political analyst Charlie Cook: They tend to conclude that it is time for a change, and they trade the in party for the out party. In fact, since American politics evolved into what we know as the current two-party system, the last time voters elected a Democrat to the White House after a president from the same party had just served a full term was in 1856, before the Civil War. If thats not enough to scare of presidential hopefuls in the Democratic Party who want to succeed two-term President Barack Obama, what is? Last Democrat to Succeed a Democrat The last Democrat elected to succeed a Democratic president was James Buchanan, the 15th president and the only one ever to come from Pennsylvania. Buchanan succeeded President Franklin Pierce. Youd have to go back even further in history to find the most recent instance of a Democrat being elected to succeed a two-term president from the same party. The last time that happened was in 1836 when voters elected  Martin Van Buren to follow  Andrew Jackson. This, of course, does not include the four terms of Democrat Franklin Delano Roosevelt; he was elected to the White House in 1932 and re-elected in 1936, 1940 and 1944. Roosevelt died less than a year into his fourth term, but he is the only president to have served more than two terms. Why It's so Rare There are very good explanations for why voters rarely choose a president from the same party for three consecutive terms. The first and most obvious one is fatigue with and unpopularity of the president who is completing his second and final term at the time of the election for his successor. That unpopularity often sticks to the candidate of the same party. Just ask some of the Democrats who sought unsuccessfully to succeeded Democratic presidents including  Adlai Stevenson in 1952) Hubert Humphrey in 1968 and, most recently, Al Gore in 2000.   Another reason is distrust of people and parties who hold power for too long. The distrust of people in power ... dates back to the age of the American Revolution and the mistrust of hereditary rulers with no curbs on their powers, wrote the National Constitution Center. What It Meant in 2016 The rarity of presidents from the same party being elected consecutively is not lost on political analysts when it came to the 2016 presidential election. Many believed the success of Hillary Clinton, who was the most likely contender for Democratic nominee, hinged on who the Republicans chose. Opined the New Republic: The Democrats could benefit if the Republicans nominate a relatively inexperienced right-winger or someone who possesses the temperament of a high school football coach rather than a president ... If they opt for an experienced centrist in 2016  -   Florida’s Jeb Bush is the obvious example  -   and if the party’s right wing doesn’t demand he toe the line, they could stand a good chance of reclaiming the White House and of confirming Americans’ reluctance to keeping the same party in the White House three terms in a row.

Marketing Communications Assignment Example | Topics and Well Written Essays - 3000 words

Marketing Communications - Assignment Example There are several marketing tools that are used by the companies for the purpose of promotional activities. Campaign is one of the techniques that are often used by the companies to promote a brand or product. The following report is based on the Vodafone and its operations in the UK market. It is seen that the present situation of Vodafone in the market is not too good as from a market position of third place in the market it will be falling back to the last place. This has happened due to the decision of BT to take over EE and decision of Hutchison whampoa the owner of three to take over O2. This will be causing a major change in the mobile landscape of the country and the company needs to change the marketing strategy that the company uses. The company must make use of integrated marketing communication and a new campaign should be launched in order to increase the market share of the company. The present scenario and the application of the integrated marketing communication are studied based on the application of SOSTAC model. SOSTAC model is an important tool which is utilized for planning campaigns. Marketing strategies are designed on basis of this model in order to evaluate current situation properly and formulate plans for future growth. Different planning activities can be easily structured through SOSTAC model. SOSTAC planning model was developed during 1990 to facilitate easier accomplishment of tasks by marketing practitioners. This model encompasses certain factors such as situation, objectives, strategy, tactics, actions and control. Situation indicates the current marketing scenario. Objectives reflect upon key tasks to be accomplished through marketing strategies. Strategy relates to the path which needs to be followed in order to achieve set goals or objectives. Tactics outlines the method that can help in reaching set targets. Action is the plan framed by

Mcdonaldization and it's effect on globalization Essay

Mcdonaldization and it's effect on globalization - Essay Example Therefore, the process of McDonalization obliviously predates the starting and the proliferation of McDonald’s restaurant. The system of McDonald and the standard on which it spread so successful across the world is a representation of the example of modern development of rationalization. Whereas the fast food restaurant is the paradigm of the McDonaldization process, the process by now has affected many if not all of the social structures as well as institutions in the US. The same has penetrated many countries across the world. Therefore, the term ‘McDonaldization’ is not limited to just the fast food industry or the US. Instead, it refers to far reaching distinctive process of social change (Ritzer, 121). The model of McDonalization has been used well beyond the industry of fast food restaurant and even daily intake to such disparate phenomenon as higher education, vegetarianism, theme parks, southern fork art and politics. This process is a wide social development. Not all systems are the same as McDonalization which may be a matter of extent, with some situations being more McDonalized than others. Nevertheless, few modern social situations or institutions have managed to escape its impact altogether (Ritzer, 105). The relevance of the thesis of McDonalization to the issue of globalization ought to be apparent, both explicitly and implicitly. It asserts that social systems in the modern society are increasing in McDonalization and more so, that the fundamental principles of efficiency, predictability, accountability and control by the replacement of nonhuman for human technology that undergird it have been brought in from America to most of the rest of the world. This is to the degree that these principles have been adopted and turned to be defining characteristics of institutions in other countries and it can be stated that they are undergoing the process of McDonaldization (Richland WA

Measuring The Impact Of Given Hrm Strategy Commerce Essay

Measuring The Impact Of Given Hrm Strategy Commerce Essay Human resource is seen as one of the most critical differentiators contributes to the organizations competitive advantages. All the other assets, such as products, markets, cash, buildings and equipment are passive require human application to generate value (Caliskan, 2010). It is the manpower that plays the key factor to sustaining the productivity for the organizations. How people being managed effectively and the behaviours of theirs can tell an organizations performance. In other words, the organizational performance can be explained by productivity, efficiency, effectiveness and competitiveness made by the employees. INTRODUCTION This essay will discuss why work ethic principles and values are part of the human resources strategy, how training and further education can enhance employees behaviours therefore to offer more to the organizations performance, and how human resources impacts on corporate performance. THE FACTORS INVOLVED IN MEASURING THE IMPACT OF GIVEN HRM STRATEGY Every organization is powered by its people. And the organizational effectiveness is viewed by the quality of services deliver to their customers who develop the organizations reputation. HR strategies play to role to help to organizations to delivery excellent services. Successful organizations see HR strategy formulation and execution as a continuous and dynamic process. In fact, effective HR strategies are essential to ensure productivity and maximum success for organizations. Effectiveness is one way of measuring the impact of HRM strategy implantation. The true success of the human resources management could not be just measured by the organizations financial targets. We should not treat strategies isolated, they need to be bundled. Therefore, to measure the effectiveness of strategic contribution of human resource management should focus on the overall contribution to the success of the organization, in terms of added value, competitive advantage and the impact on business performance (The Association of Business Executives , 2008). And typically, ways in which this contribution has been made will include: Develop a positive and healthy working environment Enhance positive motivations and commitment Increase employee skills and extended the skills base Provide employees with extended responsibilities so they can make full use of their skills and abilities Provide career opportunities and define competence requirements Provide career development and job security to employees Instituting processes of performance management and continuous development Use reward management system to convey messages about what the organization believes to be important. Share information and management transparent. Provide employees with invoice. Treat employees as partners instead of team players. (The Association of Business Executives , 2008) THE AVAILABLE TOOLS USED FOR MEASURING THE EFFECTIVENESS OF HRM STRATEGY Organizations need to have a complete system for the followings: Identify what process should achieve (i.e. its objectives), then measure what is actually being achieved, compare what is actually being achieved against what should have been achieved, then provide required corrective actions if necessary, last implement new actions. By doing all these can measure weather the HRM strategy being effective or not. The popular concept for measuring the effectiveness of human resources strategy these days are: Balance scorecard and Benchmarking. Balance scorecard is comprehensive management tools to measure and share the organizations progress towards its achievement of the strategic goals. More specifically, the balance scorecard is a strategic planning management system that consists of people, strategy, process and technology to align the organization to share a version of achieving its success and getting the people working on the right tracks. Added value, it is people who develop visions, define and set goals, develop strategic plans and implement them (The Association of Business Executives , 2008).This right organization structure is to develop employees being motivate and managed effectively, gain their commitment therefore to deploy them effectively, productively. For example, traditional measures of performance such as value of sales per salesperson, With this strategic management scorecard system, the organizations operational performance such as financial status, customer results, operational efficiency and capacity building can be measured and valued. The balance scorecard is also a communication system through the whole organization to provide better aligning strategic objectives with resources. It sets goals and drives all the employees to adopt and adjust their attitudes and behaviours/actions to achieve them. The balance scorecard helps people within the organization to come to a better understanding regards the interrelationships between different organizational functions. Therefore the top management can avoid the functional barriers and improve decision-making and problem solving. Ultimately enhance the organizations performance. Last but not least, the balanced scorecard helps the organization focus on the future not simply the past or present. Another popular tool of measuring organizations performance is Benchmarking. In fact benchmarking has long been recognized in industry as an effective means of improving business performance. Benchmarking is frequently cited as the second most popular global technique (after business planning) for performance improvement (Bencharmarking, 2006). The shortest definitions of benchmarking is Finding and implanting best practice (Camp, 1995). It means searching for industry best practice that lead to superior performance. Benchmarking is the process of comparing ones business process and/or best practices from other industries. Organizations benchmark themselves in quality, time and cost etc. against their real peers therefore to improve their performance. Benchmarking process diagram (Bencharmarking, 2006) There are two types of benchmarking: Informal and Formal benchmarking. Here I would only talk about formal benchmarking, which consists: Performance and best practice benchmarking. Performance benchmarking involves comparison of the organizations financial status (such as expenditure, cost of labour, adherence to budget, cash flow, revenue collected etc.) and non-financial measures (such as staff turnover, budget processing time, complaints etc.). Through benchmarking, the organization can recognize whether is being a leader or it is far behind in the market. For example, by comparing the income with the organization itself to the industry, the organization can know whether it is making too small profits or there is still more rooms to grab more profits. These processes involve identifying, capturing, analysing and comparing, the organization gains knowledge to know its status well enough which leads to better business strategies and responding human resources practices. The CONNECTION BETWEEN HRM STRATEGY AND ORGANIZATIONAL PERFORMANCE Human resource is considered the most important factors to gain and sustain competitive advantages for organizations. In order to achieve this, the human resource management practices need to be aligned within themselves (internal fit). The human resource management also need to be aligned with the organizations strategy (strategic fit) (Lamboij, Sanders, Koster and Zwiers, 2006). Human resources strategy should always match the business strategy. It should be flexible, compatible, adoptive, integrated, and effective to the organizational changes. The goals of HR strategy process are strictly concerned with the managing people effectively which can assist in the achievement of organizational objectives. The best fit human resource strategies that help the organizations to gain and sustain competitive advantages should be: Invest in people to increase capability and align skills to the organizational needs through on-the job and off-the job training and further educations. Providing training and development, job security and satisfaction are key human resource techniques essential for high performance. Acknowledge the organizations identifies and the knowledge/attitudes that require to meet the organizational goals and satisfy the customers. Define and promote the behaviours and positive attitudes required for organizational success and encouraged, valued and rewarded them. The better employees know what to expect from them, the more they behave cooperatively towards their co-workers and their supervisors. HRM provides professional conduct guides that apply to from hourly employees up to top management to determine business related acts or behaviours are right or wrong. Appoint right employees with the right skills/abilities to do the right jobs to let them feel fulfilled and challenged. Gain employees commitment and loyalty to the achieve organizations missions and goals. ETHICAL CODES OF CONDUCT/BEHAVIOUR IN HRM STRATEGY There are a number of reasons why developing a workplace code of ethics is crucial. Workplace ethics is the moral conducts of behaviours developed by a place of business to determine what is expected of employees in a particular settings. Managers play the key role to take responsibility for determining and enforcing the acceptable and expected standards within their organizations. Workplace ethics set the rules of conduct for everyone at a particular business environment. It helps everyone to know what is encouraged/expected or inappropriate at work. If everyone is clear on what kind of behaviours are expected and what is unacceptable, employees are able to be point out when there are some actions are out of the lines. Workplace ethics also ensures that employees are treated equally and they always have rights to speak for themselves. Workplace ethics helps to enhance reputation by gaining consumers to think that the organizations are somehow better than their competitors. More impo rtantly, the ethical standards/values are shared and known within the organizations by the entire staff, the environment will be conductive to values-driven behaviours, such as values that can guide decision making and discussion and information sharing; values can help to enhance a sense of commitment to the organizations and therefore, are an important part of high commitment management. Values can improve the all the relationships within and outside the organizations. For example, within the organization, between the organization and its workforce, values and ethics codes identify the attitudes towards equal opportunities and diversity; Between management and employees, value and code ethics guide the managers to maintain a professional relationships with employees, and to identify the importance of trust, respect and equality; Between employees, values and ethics codes identify what sort of behaviours are expected among employees. Outside the organization, values and ethics and make an organization stand out among other competitors to its customers and consumers (The Association of Business Executives , 2008). Indeed an organization that has good value and ethics code can impress its customers with their attitudes, the responsibilities they have towards the social responsibility and the views of the environment, etc. THE ETHICAL IMPLICATIONS OF STRATEGIC HUMAN RESOURCE MANAGEMENT Human resource managers are in a key position to ensure that ethics codes management is applied through the whole organization. Communications and training programmes are essential. And managers need to make decisions ethically to determine business-related acts or behaviours are right or wrong. Business ethics can provide businesses with moral guidelines in conducting their affairs. Managers often face ethical dilemmas in the workplace but they may not aware of it. On reason is the manager is not trained in ethics so it is difficult to know when an ethical issue exists (Mintz, 2011). The first step in making ethical decisions is to be sensitive to identify the unethical signposts in question. Determine whether your decision harms one or more parties while benefiting others. Managers need to be aware that ethical decision making causes the consequences of the actions on others the stakeholders in the specific situation. The next step is to identify alternative choices and actions to evaluate them in the ethical way. Be sure to follow the laws, regulations, practices and company policy including the code of conducts. From an ethical perspective certain guidelines apply such as dont violate anyones rights; be fair-mined in deciding how best to resolve the dilemma, always follow basic virtues including honesty, integrity, reliability and being responsible and accountable for ones actions (Mintz, 2011). After evaluating the alternatives from the ethical perspective, managers need to know for certain how the potential decision might affect the stakeholders. It should create trusting or even legal problems/reputation damage among employees and top management. The last step in ethical decision-making is the most difficult one. It takes a lot to carry out an ethical decision with ethical action. It could be the case that the ethical decision and ethical action would actually do harm to the company reputatio n or other employees image among the organization. For example, if sales A found out that sales B, one of the top sales in the company, misleading customers a bit regarding the product (not a serious mistake) in order to get more sales. In this case, should sales A reports to the top management straight away or just pretend nothing happen? If reports to the top management, they may likely not do anything. Or they would think sales A is just getting jealous with sales B, which will lead them to think that sales A is not the type of guy that they want to keep for long term. Or the top management invest in the detail and find out the truth and they have to fire sales B, which the consequence will be the company lost a top sale and some big customers therefore it effects the organizations reputation and selling targets. One of the the rational way to deal with this unethical issue will be whistle-blowing. Sales A could make an anonymous complain or letter to report this unethical behavi our explain the behaviour or issue in detail as well as how the issue should be resolved. Nowadays organizations have employees from different culture background. One thing managers need to ensure that they do not discriminate unfairly in their decisions or actions towards employees, either before or during the employment. Organization should provide equal opportunities to everyone within the organization. Managing cultural diversity is never easy. Recognising the behaviours of discrimination is the first step towards establishing equal treatment working environment. All in all, the responsibilities of good managers in making ethical decisions are: Be sensitive with the ethical issues in working environment Be clear with the responding consequence followed by the ethical decisions/actions Identify company policy, code of ethics conducts and carry out the ethical actions TRAINING METHOD IN WORK PLACE Training in an organization can be divided to two broad types. They are on-the-job trainings and off-the job trainings. With on-the-job trainings, employees receive trainings while they are at work. In this way, employees are conducting and learning when they are working. On-the-job training gives employees motivation to start the job. Some reports indicate that people learn more efficiently if they learn hands on rather than just listening to the instructors. Example: New engineers could work with experienced engineers. They could ask questions about the machines and the tools they are operating on, the problems they may come across the usual solutions to them etc. Instructors need to make the plan for what should be taught, and how much time spend on it, and after the trainings employees will informed about their progress. The main methods of on-the-job/off-the-job training included: Demonstration / Instruction Showing on site to the trainers specifically how to get the job done. Coaching a more detailed and intensive method of training that involves a close working relationship between the experienced trainers and the trainees. Coaching gives trainees the chance to ask questions and receive honest answers. Lectures Lectures usually take place in a classroom-format. Giving lectures supply huge amount of information to a lot of people in a short amount of time. But lectures could get boring and trainees lose interest in it. Group discussion Group discussion is most likely to take place in a classroom where a group of people discuss issues. Group discussion can allow employees to ask questions and provide ideas for the management. Comparing to lecture, it gets more involvement from the employees, and managers can heave the voice from the employees. Role playing Role playing allows employees to act out issues that could occur in the work place. Role playing can be effective in connecting theory and practice. There are many methods of trainings. The key is to find the best training method to suit the actual situation. Assess each training method implemented in the organization and get feedbacks from trainees. Then decide to adopt the most effective method to specify the training programme (Silva, 2011) FURTHER TRAINING AND DEVELOPMENT These days for every business their goal is to stay competitive in the market. And highly skilled, motived and committed staff is the key factor to achieve that goal. Further-training widens employees skills and acknowledge, and therefore enable their personal advancement to contribute more to the organizations performance. Providing career development helps to motive employees and gain their commitment. In details, firstly, training and development helps in maximizing the human resource which further helps the organization to achieve organization goals as well as their personal goals. Secondly, training and development helps to provide opportunities to broaden employees knowledge, increase their skills, improve their personality even. Thirdly, training and development helps in increasing the productivity of the employees that helps the organization further to achieve its long-term success. Fourthly, training and development helps building the positive attitudes, good team spirits, and friendly working environment among the organization. It also helps improving the quality of work and work-life. Last but not least, training and development helps in the organization development. For example, the organization gets more effective decision making and problem solving with dedicated and skilled staff. Training and development helps in developing leadership skills, employee motivation, loya lty, positive attitudes, good perceptions between managers and employees. CONCLUSION Human resource is the most valuable resource to gain and maintain competitive advantage for organizations. From above we know that HRM impacts greatly on organizational performance. There are available tools such as balanced scorecards and benchmarking to measure the effectiveness of HRM. In workplace, unethical issues are inevitable and ethical codes of principles are necessary for every company. Mangers need to make ethical decisions and act on them ethically. Training and further education improves employees skills and abilities therefore enhance the organizations performance greatly.

Song of Roland

The textbook displays Charlemagne as an astounding and great military leader but examines a few of his flaws as well. The Song of Roland creates the image of Charlemagne that is an extraordinary, legendary leader. They both tell about what great things he accomplished in his life, the many wars he won and how his bravery carried him through everything. The Song of Roland praised him in such a legendary way to create the impression of a heroic leader.By doing this it establishes a strong positive view of the Frankish Empire. In the ninth chapter of the Making of the West, the authors describe the Carolingian king, Charlemagne and the various views of his life that historians have. While admiring his greatness the authors analyze a few negatives about Charlemagne. For example, he liked the Pope but hated that the Pope crowned him emperor. He liked being king and calling himself king but at first didn’t want the title of Emperor.Another criticism to Charlemagne’s great wor k as a military leader is that he did all of his work winning wars and conquering lands that he destroyed the states surrounding his original empire and gaining control of them but by doing that, he lost his buffer. So soon after all the wars were finally over for Charlemagne, hew invasions started occurring on the borders of his new kingdoms. One more concern historians claim he did was what he had done when he arrived at the Saragossa Town after the winning the war with the Saxons.Apparently when he got to the city, the citizens were resisting conversion to Christianity and he wasn’t happy about it. He forced mass conversion of the Muslim citizens with the threat of his sword. This act goes against the whole idea of Christianity to be accepting of other faiths and tolerant of them. These examples only demonstrate a few criticisms to Charlemagne’s leadership but still explain that he was a great emperor overall. The Song of Roland describes Charlemagne as an amazing m ilitary leader.He had Counts and Bishops in charge of leading wars to gain lands for the Franks in every direction and he was successful in doing so. He was a very emotional man, he wept over the deaths of fellow comrades and warriors, friends and relatives. Charlemagne was also a spiritual man in that he prayed everyday and asked for God to protect the bodies of the fallen soldiers and keep them safe. The angel St. Gabriel came down to him many times to give Charlemagne advice or to encourage him to continue his missions and to fight.He fought with courage and bravery, he was afraid of nothing. After his victory against Emir, he still felt the need to serve God and all his kingdom respected him for that and obeyed his power. Charlemagne is described as a courageous, spiritual, loyal and extraordinary emperor and leader full of pride for his kingdom. All of the words Charlemagne can be indentified with help bring about the view of the Frankish Empire. Because of the things Charlemag ne did and more importantly they way he went about them, the Frankish kingdoms were viewed as prestigious and in control.They gave off the impression of high power and other kingdoms were going to have a challenge if they wanted to fight the Franks. The Making of the West textbook and the book The Song of Roland discuss how great Charlemagne was and how what he did made a difference in the view of the Frankish Empire. Although he had some flaws or contradictory actions, he was still an astounding emperor. He expanded his kingdoms and defeated many enemies. He had become a heroic military leader for the Franks and the Frankish Empire.

The Treatment of Cystic Fibrosis using gene therapy, in particular Adeno-Associated Viruses

Sample details Pages: 25 Words: 7507 Downloads: 4 Date added: 2017/06/26 Category Statistics Essay Did you like this example? In this dissertation we shall consider the field of gene therapy in specific relation to cystic fibrosis. We examine the different delivery vector mechanisms that have already been explored and concentrate primarily on the adeno-associated vectors. We examine the current state of research and consider the advantages and drawbacks of the various methods considered. Don’t waste time! Our writers will create an original "The Treatment of Cystic Fibrosis using gene therapy, in particular Adeno-Associated Viruses | Physics" essay for you Create order We conclude with a discussion and analysis of our findings and make anumber of assumptions relating to the future direction of the researchin the field. The rate of progress in the field of gene therapy has been enormous. We must remind ourselves that the first clinical gene transfer experiment took place in 1989 when a patient with malignant melanoma received genetically modified auto logous T cells. (Rosenberg SA et al1990) Gene therapy encompasses two major areas. The in vivo field, where genes are incorporated into the target cells of the living body and the ex-vivo field where the target cells themselves are genetically modified outside the body and then re-implanted. Medical science has been using the basic techniques of gene transfer for a long time. The technique has been exploited when viral genes are introduced to human cells when a viral vaccine is administered. The key technologies that allowed the transition from vaccination to gene therapy were the evolution of methods that allowed the genes to be isolated and replicated (cloned) and manipulated (engineered) prior to transfer into human cells (Freeman SM et al 1996) The key principle in this process is the efficient transfer of the manipulated therapeutic genes into the nuclei of target cells usually be means of various vectors. This dissertation will be considering the utilisation of these vectors in some detail. In broad terms, the new or modified genetic material is able to produce new proteins which can restore deficient or abnormal functions of genetically diseased tissues, to generate tissues that have entirely new properties or to create transplantable tissues for the controlled release of therapeutic proteins. (Russell SJ1997) In terms of viral vectors, prior to 1996 science was dependent on the use of modified retroviral vectors (eg.MMLV) to effect gene transfer into the chromosomes of a target cell and the adenovirus vectors when such integration was not needed. Neither vector was particularly successful as the intact nuclear membrane (in then on-dividing state) was a major barrier for chromosomal gene integration. (Sikorski R et al 1998). A breakthrough came with the realisation that lentiviruses (e.g. HIV) have the same ability to transfer genetic coding into the cellular genome but could do this in the non-dividing or dormant phase cells. (Amado R G et al 1999) In vitro, lentiviruses have been shown to change the target cells expression of proteins for up to six months. importantly, they can be used for terminally differentiated cells such as respiratory epithelium. The only cells that the lentivirus cannot penetrate the nucleus are those in the quiescent (G0) state as this blocks the reverse transcription stages of protein synthesis. (Amado R G et al1999) Cystic fibrosis Cystic fibrosis is the most commonly lethal inherited recessive inthe caucasian population. It affects about 1 per 2,500 livebirths. Thetreatment of cystic fibrosis has improved enormously in the last fiftyyears with the life expectancy increasing from an average 10 years to30-40 years now. The prime cause of death in affected individuals is the repeatedcycle of infection, inflammation and fibrosis of the respiratory tractwhich eventually culminates in respiratory failure and death. The disease itself is caused by mutations in the single gene forthe cystic fibrosis transmembrane conductance regulator (CFTR) whichproduces a protein found in sweat and pancreatic ducts, gut,seminiferous tubules, lungs and many other tissues. The mutationsresult in an abnormal protein which, when expressed in the lungs,produces thick viscous and dehydrated secretions. This does not allow for the efficient expulsion of bacterial pathogensfrom the lungs and a number of highly resistant forms of bacteria arecommonly found in cystic fibrosis (viz pseudomonas aeruginosa)(Porteous DJ et al 1997). An individual must receive a defective copy of the cystic fibrosisgene from each parent in order to develop the clinical picture ofcystic fibrosis. Following normal genetic principles, if two carriersconceive a child, there is a 25% chance that it will have cysticfibrosis, a 50% chance that it will be a carrier and a 25% chance thatit will have two normal cystic fibrosis genes. Viral and non viral vectors Viruses have an ability to enter a host cell and combine their owngenetic material with that of the host cell. This is the basicrationale behind the science of gene transfer therapy. As we shalldiscuss in some detail in this dissertation, there are a number ofpotential viral vectors that have been explored, evaluated andexploited in the search for an efficient and safe form of therapy.Viruses are not the only vector that can be utilised . Simply placingDNA in the nasal mucosa will produce some incorporation into theepithelial cells (Knowles MR et al 1998). This absorption can bedemonstrably enhanced further by the combination of the DNA withvarious plasmid or lipid complexes(Zabner et al 1997) The advantages of lipid or plasmid assisted transfer mechanisms arethat they do not appear to generate the immunological responses thatare seen with the viral vectors. They can also be used to facilitatethe transport of much larger pieces of DNA which would otherwise belimited by the packaging consideration incumbent on the viral vectors.(Felgner P 1997). The use of retroviral vectors is far from straightforward. The heavilypublicised case in April 2000 brought some of the problems to theattention of the media. A retroviral manipulation of a case of X-SCID(X linked severe combined immunodeficiency) was treated by gene therapywith an apparent degree of success (BBC 2002). This particular diseaseprocess is caused by a mutation on the gene which codes for the C chainof the cytokine receptors which is situated on the X chromosome andvital for the functional development of T Killer lymphocytes which aretherefore completely absent in the condition A multinational team used a retroviral vector to insert a functionalcopy of the gene into bone marrow stem cells which were thenre-transfused back into the patient. (Cavazzana-Calvo M et al 2000).This particular case resulted in a return to normal levels of T cellsin a comparatively short period of time. This was hailed in both thepopular media and the peer reviewed journals as a major success and itcan indeed be considered a landmark as it pioneered the successful useof an ex-vivo procedure that avoided direct in vivo transfer of thevector. The reason for specifically highlighting this particular case isthat following the initial optimism of the clinical team, two of thefirst ten patients with this condition who were treated in the same waysubsequently developed a leukaemia-like illness. Genetic analysis ofthe malignant cells suggested that the retroviral vector used in thetransfer had also activated an oncogene LIM-only2 (LMO2) which is knownto be associated with some forms of leukaemia. The clinicians reviewingthe situation felt that, although it was not the only cause of themalignancy it was one of the events that triggered it. Similar concernshave been raised in respect of other clinical trials. (Lehrman S 1999) The prime reason for presenting these events is to demonstrate thefact that there is both a theoretical and practical risk of insertionalmutagenesis. Reduction of the risk requires greater specificity of thetargeting of the genetic deficit perhaps by directing the expressionof the therapeutic genes to various specific tissues utilising bothtransductional and transcriptional targeting. Relph K et al 2004), In terms of specific considerations of the arguments in favour of theuse of retroviral vectors, one can cite the fact that they have ahighly efficient mechanism of gene transfer together with lowimmunogenicity. It is a well researched and well studied system and isknown to selectively infect actively dividing cells. The conversearguments reflect their disadvantages including their ability todisturb or activate oncogenes, the fact that they are difficulty tospecifically target and it is difficult to obtain high titres in theclinical situation (after Olsen, J. C. 1998). In broad terms, the principles behind the use of retroviral vectorsare that they must be modified in order not to be able to transmit anyovertly pathological coding. This involves the deletion of viral helpergenes such as gag, pol and env to render the replication processinvalid. This is done by utilisation of a producer or packaging cellline. (Nichols, E. K 1998). An example of a commonly utilised and extensively researched vector isthe MoMuLV. It is an engineered vector which can store 8 kb of RNAwithout compromising packaging efficiency. It is a hybrid cell lineeasily grown in mouse fibroblast cells There is a subdivision of the retroviral vectors known as thelentivirus, which is the only retroviral vector capable of integratinginto the chromosomes of non-dividing cells. This has been effectivelydemonstrated in vitro (Naldini L et al 1996). The biggest problem with the lentivirus vectors is that theyappeared to only produce very low titres. Some recent researchsuggested that a modification to a amphotropic envelope protien wascapable of allowing higher titre levels. (Rolls M et al 1999) At about the same time that the scientific press was learning aboutthe problems with retroviral transfer (see above) other investigatorswere working with adeno-associated viruses (AAVs). A similar processwas invoked using adeno-associated viruses to correct a genetic defectinvolving coagulation factor IX. The adeno-associated viruses were usedas they were considered to be amongst the safest candidates for genetransfer. They do not naturally cause disease processes in humans andhave only rarely been found to incorporate in a random fashion into thehuman genome. Although it is noted that adenoviruses do cause oncogeneactivation in rodents although it has not been found in humans(Blacklow NR 1988). The trial had a very positive outcome. (Kay MA et al 2000), but thetrial author (in later research work) published a study which suggestedthat, in study mice, the vector used in the trials actually integrateditself into gene containing regions of DNA more frequently that it didinto non-coding regions (Kay MA et al 2003). The findings were reportedas the fact that new genetic material was randomly distributed amongstall of the chromosomes particularly at sites of gene activity. On thisbasis, there appears to be at least a theoretical basis for thepossibility of similar cellular defects such as occurred in the X-SCIDpatients. Adenoviruses are comparatively simple structures. They arecategorised as double stranded DNA viruses. They have icosahedralcapsids with twelve vertices and seven surface proteins. The virionitself is spherical and non-enveloped and in the region of 70-90 nm insize. Their natural history is that they are spread easily in the naturalstate by the faeco-oral route and also by respiratory inhalation whichclearly has great implications for the treatment of cystic fibrosis. A theoretical analysis would immediately suggest that the adenovirus should be a suitable candidate for gene therapy as they can codefor specific proteins and they do not produce infection pathogenicviral offspring. The early trials into this particular area were reviewed by Griesenbach(Griesenbach U et al 2002) who pointed out that the cystic fibrosisgene was first cloned in 1989 and in the subsequent years, 18different trials were carried out, all with rather low degrees ofsuccess. They collectively trialed three different vectors, namelyadenoviruses, adeno-associated viruses 2 and cationic liposomes, andalmost universally found that each vector had a very low rate ofclinically significant gene transfer and none was sufficient to achieveclinical benefit Plasmid Complexes At its most basic level, a plasmid is a small accessory collection ofDNA which is found in the cytoplasm outside of the nucleus. They arecapable of independent replication and can be manipulated with rathermore ease than nuclear DNA. Early investigations into the field of gene transfer explored thepossibility of plasmid vectors and demonstrated the feasibility of themethod to effect CFTR gene transfer in vitro (Alton EW 1993). Otherteams had demonstrated the fact that, in clinical use theplasmid-liposome is both nontoxic and non-immunogenic (Hyde,SC et al1993). This appeared to raise the possibility that many of theimmunological problems encountered by teams working with viral mediatedgene transfer mechanisms might be circumvented. In vivo work (Yoshimura,K et al. 1992) had demonstrated that genescould be transferred into the cytoplasm by this method and Stribling, R(et al 1992) demonstrated that, once there, they would then replicatenormally. Alton experimented with a CFTR-plasmid preparation in miceand demonstrated that it was capable of correcting the chloride levelsin cystic fibrosis mice back to normal levels (Alton EW 1993) Although the initial results were encouraging, clinical trials weredisappointing as the plasmid complex could not easily penetrate thethick mucous residues in the diseased lungs of patients with cysticfibrosis. (Erickson,R 1993) The plasmids typically have a positively charged head-group which isable to bind to the DNA strand and a hydrophobic tail group whichfacilitates the transfer of the complex across the cellular membranes.Initial studies suggest that between 100-1000 times more DNA isrequired to effect successful gene transfer when this method iscompared to viral vectors. (Santis,G et al 1994). One alternative adaptation has been reported by Stern M (et al 2003)who points out that one of the solution of delivery is to ensure thatthe respiratory epithelium is exposed to the DNA over a long period.Their solution was to encapsulate the CFTR-plasmid in a slow releasebiocompatible polymer. Clinical trials are underway but not yetreported. The adeno-associated vectors appear to have (at least on atheoretical basis) a number of advantages over the vectors that we havealready discussed. They are based on a virus vector that is alreadynon-pathogenic (Berns, KI et al 1995) and has a mechanism that allowsit to be a long-term persistent entity in human cells (Blacklow, NR etal 1989). The adeno-associated vectors are particularly useful indealing with disease process that involve single gene mutations. This,therefore makes it particularly suitable for single gene disorderssuch as cystic fibrosis and alpha 1 antitrypsin deficiency. (Flotte, TRet al 1998). In addition, some workers have also developed vectors which are capableof producing either inducible or constitutive expression of thecytokine, interlukin-10 (IL-10) which is an importantanti-inflammatory protein which, on a theoretical basis, could beuseful not only in cystic fibrosis but in other disease process whichhave chronic inflammation as their prime manifestation (viz Type Idiabetes mellitus or inflammatory bowel disease) (Egan, M et al 1992).These manifestations have been studied and have now reached the stageof early clinical trials (Wagner J et al 2002). With specific reference to the implications of cystic fibrosis, wecan point to trials which have resulted in the expression of cysticfibrosis transmembrane conductance regulator (CFTR) from rAAV(recombinant adeno-associated vectors) in cell cultures (Flotte, TR etal 1993), in animal models (primates) (Afione, SA et al 1996), andagain in early phase I clinical trials (Wagner, J et al 1998) The rAAV-IL-10 model has been studied in bronchial cell culturesfrom cystic fibrosis patients, to determine the functional consequencesof CFTR complementation. This has not yet been demonstrated in vivowith humans but in both mice (Song, S et al 1998), and monkeys (Conrad,CK et al 1996) The overall results of these (and other) studies have shown that itis possible to achieve long term gene transfer and functionalexpression of the replaced gene (some studies for as long as 18 months)without any overt pathological findings. The histological findings are something of a surprise however, as,at least in both primate and mouse studies, the vector-introduced DNAin this form does not appear to be assimilated into the geneticmaterial of the chromosome, but persists in log strings or concatemersthat are episomal, which is in complete contrast to what happens whenthe naturally occurring agent infects the cell. There is some evidenceto suggest that host cell intrinsic factors such as DNA-dependentprotein kinase play some role in this process (Song, S 2001). The significance of this finding could be that the exclusion of thefunctional, newly introduced DNA from the rest of the nuclear gene poolmay be less likely to produce effects that could be either potentiallydisruptive to the host cell and less likely to activate oncogenes.Phase I trials have demonstrated significant rises of CFTR levels inboth sinus and lung tissue with no evidence of vector-related toxicity.(Wagner, JA et al 1999) The adeno-associated vectors are constructed from proviraladeno-associated vectors plasmids, which have the Rep and Cap proteinsdeleted and substituting the appropriate gene (CFTR or equivalent)between the rAAV2 inverted terminal repeats together with other signalsequences such as promoter and polyadenylation sequences (Flotte, TR etal 1994) The packaging processes allows for about 5 kb of rAAV genomes to becarried in the vectors which are prepared using a cotransfectiontechnique utilising human embryonic kidney cells (HEK-293) where thevector plasmid is cotransfected into the cells with helper agents(plasmid pDG) being used to encode the rAAV2-rep and -cap genestogether with the adenovirus helper functions (Grimm, D et al 1998).These are incubated for between 48 and 72 hrs. The cells are then lysedand the resultant agents are then separated by ultracentrifugationagainst a density gradient and affinity chromatography (Zolotukhin, Set al 1999). The vectors are thereby amenable to being separated by both theirphysical characteristics and also their biological characteristics(infectious units). They are carefully screened to ensure the absenceof any possible contamination from non-modified (replication competentAAVs) prior to clinical usage. (Muzyczka N 1994) The comparatively small payload of the adeno-associated vectorsis proving to be a significant problem. The vector itself is small whencompared to the comparatively large size of the CFTR gene. (Flotte TRet al 1993) It does not leave any room to manoeuvre to manipulate thevector-specific sequences in the way that we have described with theretroviral and adenoviral groups. (Flotte TR et al 2001). A number of authors have characterised the problem with theobservation that the rAAV is typically about 20 nm across which allowspackaging of about 4.7 kb (kilobases) of transferable modified gene(exogenous DNA). (Dong JY et al 1996), If it is combined with otherenhancers such as the promoter, the polyadenylation signal, thisclearly reduces the capacity for the DNA component. (Duan D et al2000). The Yan paper (Yan Z et al 2000) has outlined a novelexploitation of the unique ability of the rAAV genomes to link togetherin strings which appears to have the ability to bypass this particularlimitation.( Flotte TR 2000). The mechanism itself is the capacity of two distinct rAAV genomes thathappen to simultaneously infect the same target cell to undergo anintermolecular recombination insider the transduced nucleus of thetarget cell. This was a chance finding which arose from work involvingrAAV-derived episomes (Kearns WG et al 1996) in primate airways. It wasfound that some of these episomes were configured as circular head totail concatemers (Duan D et al 1999). This could have been either froma rolling circle replication from a single vector or alternatively,from an intermolecular recombination of material from multiple cellularpenetrations which combined within the palindromic inverted terminalrepeat sequences that are an intrinsic part of the AAV genomestructure. The authors were of the opinion that it was likely to be thelatter eventuality (Duan D et al 1998) It was a logical progression to try to exploit this phenomenon andthereby bypass the limitations imposed by the relatively smallpackaging capacity of rAAV. The adeno-associated vectors capsid onlyhas a capacity of about 5 kb. If we consider that the 145 nucleotidestretch of the AAV-ITR (inverted terminal repeat) sequence has to be inplace at both ends of the single-strand DNA for the vector DNA to beboth replicated and packaged, this only leaves in the region of 4.7 kbof genetically active material in each rAAV particle. As we have cited earlier in relation to the Dong paper (Dong JY et al1996) the CFTR gene accounts for about 4.5 kb which leaves very littlespace for other enhancing material. Because of this, the actual CFTRvector that has been used in the clinical trials to date uses only theminimal promoter activity of the AAVs-ITR itself to actually activateand drive the CFTR expression (Flotte TR et al. 1993). To look at this potentially important development in a little moredetail we can consider Duans original paper (et al 2000) and theauthors describe what they call a superenhancer. They describe acombination of a potent simian virus (SV40) and CMV immediate earlyenhancer elements as being packaged in one rAAV vector and a luciferasegene assisted by a small minima;l promoter in another rAAV vector. Invitro experiments suggested that either the SV40 or the intrinsicpromoter activity of the AAV-ITR was sufficient for this purpose. Theintermolecular recombination described above, was found to occur inboth vitro and in vivo experiments and was found to be sufficient tohave a greater than additive effect. Initial results from these varying methods are encouraging insofaras they are producing results of transgene expression which are 100-600times greater than with the unenhanced vector alone. (Yan, Z et al2000) Although not directly referable to our considerations of cysticfibrosis, we should note that Yans group and other workers have doneexperimental work which has culminated in the long term expression offunctional levels of erythropoetin with this two vector method in micein vivo. (Naffakh N et al 1995), This basic principle has been further enhanced by Sun (Sun L et al2000) with an ingenious manipulation of the system. They triedinserting the promoter and the first half of the coding sequence in onerAAV vector, immediately followed by a splice donor and then theupstream half of an intron. In the other rAAV vector was the downstreamhalf of the intron, the splice acceptor, the second half of the geneand the polyadenylation signal. To quote the author verbatim: This strategy is efficient enough to mediate high-level expressionand the intermolecular junctions are apparently stable enough tomediate expression for several months in vivo. Although this is clearly an ingenious augmentation of the sameprinciple , we should note that there are both advantages anddisadvantages to both pathways. The strategy that adopts the superenhancer takes its strengths fromthe fact that the recombination mechanisms optimise theposition-independent and orientation-independent functions of theenhancers. Consideration of the options would suggest that there arefour potential recombination outcomes from the process described.Either of the two vectors could be on the 5 end of the heterodimericmolecule and clearly either molecule could be in either orientation. With the superenhancer option, all four of these possibleintermolecular recombination outcomes should be functional fortransgene expression whereas if compared to the split intron strategy,by using the same reasoning, it is clear that only one out of the fourcould work. On the other side of the argument, the superenhancer option has thedisadvantage that the actual coding sequence of the gene to betransferred must still fall within the packaging capacity of the vectoritself whereas the split intron allows for a greater functionalexpansion of the packaging capacity. (after Flotte TR et al 2000) In either event it can be seen that these ingenious modificationseffectively eliminate the main size limitation of the rAAV deliverysystem. Although initial pre-clinical work is encouraging it appearsthat there is still some potential for a degree of immune responseparticularly if the host organism has not experienced the newlyproduced protein before. A number of studies have been done on animal (vertebrate andprimate) with only minimal success. Different administration methodshave been studied including direct administration into the lung (WagnerJ et al 1999), IM injection (Song, S et al 2001 B) and hepatic portalvein infusion (Song, S et al 2001 A) Human clinical trials have taken place with these vectors (Flotte T etal 1996)(Wagner J et al 1998) (Virella-Lowell, I et al 2000). Thestudies were done on adult male and female patients (18-47 yrs) whowere pseudomonas free and had recently been hospitalised for IVantibiotic infusions The disappointing results were probably a reflection of the factthat the CFTR defect is also interconnected in some way with aproinflammatory phenotype which appears to be triggered by the abnormalprotein via an unfolded protein response. The authors were able to showevidence that the rAAV-CFTR mechanism was able to correct the proteinproduction defect, they found it clinically difficult to transduce asufficient number of cells in the airway to reverse the inflammatoryresponse. It is proposed to run further experimental work which combines theCFTR expression with an anti inflammatory gene such as the IL-10.There is some in vitro work to suggest that this may be a possibleworkable approach (Teramoto, S et al 1998). Other work on ways ofenhancing the phenotypic expression of the modified genotype hassuggested that the use of various promoters and the rAAV-CMV/beta-actinhybrid promoter (CB-AAT) was found to be tone of the most efficient, atleast when it was compared to the other tested options such as the CMV,E1, U1a and U1b promoter constructs (Teramoto, S et al 1998) Overall, the initial results appear to be encouraging. A singleinjection of an rAAV-CB-AAT vector in animal studies has resulted inhigh level, stable transgene expression which has persisted over thelife span of the experimental animals and that there was no detectableinflammatory response in the animals who had received this form oftreatment (Flotte TR 2002) Flotte (et al 2002) reports that four human clinical trials at bothPhase I and Phase II level are currently underway examining the effectsof the rAAV-CFTR vector. They had an entry cohort of seven patientswith the vector being applied to the nasal lining, the maxillary sinusand the bronchus. The authors report no adverse effects being found andthat they have observed transgene expression at doses of 6 x 108 drp inthe sinus or 1 x 1013 drp in the lung. There are no reported interimfindings from the Phase II trials as yet. There is clearly a potential for clinical benefit on the basis of theresults found to date if one can extrapolate from in vitro and animalexperiments. The authors comment that, in contrast to the adenovirusvectors there is a marked lack of inflammatory toxicity with the rAAVvectors. Despite these positive comments, we should not, however, overlook thepotential limitations of this particular delivery system. These havebeen identified by various authors as: The inhibitory effect of preexisting airway inflammation on rAAV transduction in the lungs (Virella-Lowell, I et al 2000) A relative paucity of receptors on the apical surface of airway epithelial cells (Summerford, C et al 1998), The relatively weak nature of the minimal promoters used in the first-generation rAAV-CFTR vectors(Flotte, TR et al 1993), The potential for adverse long-term effects from rAAV vector DNA persistence. (Wu, P et al 2000) The Flotte group are currently investigating this problem by examiningthe hypothesis that the barriers in the airways of the cystic fibrosissufferer are primarily due to the neutrophil-derived -defensins (HNP1and HNP2) and are actually reversible by the mechanism of AAT proteindelivery (Virella-Lowell, I 2000) Wu and his co-workers have been looking at ways of manipulating thegenetic make up of the rAAV2 capsid and thereby trying to enhance thetargeting ability so that the vector specifically targets the serpinenzyme complex receptor on IB31 cells which is virtually specificfor the Cystic fibrosis bronchial cells Zabner, J (et al 2000), have considered alternative rAAV serotypesin the hope of finding one that will bind more specifically to thebronchial cells Other peripheral adjuncts have also been explored includingpromoters to enhance the effects of complementation and superenhancerswhich have been shown to improve the ability of the rAAV toconcatermerise with the help of smaller amounts of promoter agents(Duan, D et al 2000). Perhaps it is appropriate to conclude this section on considerationof adeno-associated vectors with a critical analysis of a very recentmulticentre, double-blind, placebo-controlled trial (Moss RB et al2004) This was a well constructed, fully statistically significant anddouble blinded trial which considered both the safety and thetolerability of repeated doses of adeno-associated serotype 2 vectorrepeatedly given by aerosol inhalation. The vector contained cysticfibrosis transmembrane conductance regulator (CFTR) complementary DNA(cDNA) [tgAAVCF], an adeno-associated virus (AAV) vector encoding thecomplete human CFTR cDNA. The entry cohort was comparatively small with 42 patients, of whom20 received the active agent. A number of indices of airway functionwere measured. Of particular interest to our considerations in thisdissertation was the fact that vector shedding was found in alltreated subjects up to 90 days after inoculation. And that all subjectswho received the active agent exhibited at least a fourfold increase inthe serum AAV2 neutralising antibody levels. Of the 20 treated patients, six subsequently underwent bronchoscopy.Of those six, gene transfer but not gene expression was demonstrated inall of them. On this basis, it would appear that the actual transfermechanism is effective, but there are other factors present whichappear to interfere with the subsequent expression of the gene in termsof protein production. The study did not comment on the possiblereasons for this. The authors were able to conclude that the delivery system workedwell with no evidence of adverse effects and that treated patientsdemonstrated an encouraging trend in improvement in pulmonary functionin patients with CF and mild lung disease. Lipid 67 We have discussed the various shortcomings of the virus-associatedvectors and this has prompted researchers to explore and consider otheroptimising options for facilitating gene transfer. Zabner (J et al1997) considered the use of cationic lipids in this process and foundone GL-67:DOPE (colloquially known as lipid 67) which appeared to beparticularly helpful in the process. Cationic lipids appear to show a degree of promise as possible vectorsfor CFTR cDNA transfer into respiratory epithelial cells of cysticfibrosis patients. Zabners group developed a preparation of plasmidencoding CFTR (pCF1-CFTR) and cationic lipid (GL-67:DOPE) whichappeared to facilitate the gene transfer to a significantly greaterextent than previously tested lipid complexes. They performed in vivostudies which compared the gene transfer rate to the epithelial cellsof the nasal mucosa of DNA-lipid complex and DNA alone. In generalterms, their findings indicated that the DNA-lipid complex was far moreeffective in achieving gene transfer than was simply giving DNA. Theauthors felt able to conclude that: These results indicate that nonviral vectors can transfer CFTR cDNAto airway epithelia and at least partially restore the Cl- transportdefect characteristic of CF. However, improvements in the overallefficacy of gene transfer are required to develop a treatment for CF. In this dissertation we are primarily considering the issues ofgene therapy in direct relation to cystic fibrosis. Inevitably, thishas meant considering the issues on a wider front, as many areasoverlap on a theoretical or practical basis. The prime biochemical cellular defect in cystic fibrosis is anabnormality in the cystic fibrosis transmembrane conductance regulator(CFTR). From a theoretical perspective it should be obvious thatreplacement of the defective gene with a working alternative would bebest achieved in the neonatal period before the body had time todevelop substantial fibrotic changes in the lungs that were secondaryto repeated episodes of infection (Dark J et al 1996). If successful, this could be expected to reduce both morbidity andmortality for cystic fibrosis. We have been able to cite evidence thatgene transfer has been accomplished both in vitro and in vivo. We havediscussed the results of a number of research groups who haveinvestigated various delivery systems which, to varying extents, haveproved able to deliver at least a small quantity of functional respiteto the cystic fibrosis sufferer. It is also important to be fully aware of the possibility ofinadvertent side effects in the field of gene manipulation. We havehighlighted the problems with oncogene activation. But this appears tobe associated with some vectors more than others. In short, it wouldappear that the problems and limitations that appear with this type ofprocedure are a function of the parent virus. The initial work with adenoviruses appeared promising as genetransfer could be accomplished but the major drawback was the doselimiting inflammatory effects which arose primarily as a result of thelarge amount of viral protein which was required to achieve atherapeutic dose. The subsequent modifications which had a greaternumber of coding sequence deletions appeared to be more effective inanimal experiments as they generated a lesser response from the cellmediated immunity mechanisms and therefore had a greater duration ofaction. (Caplen NJ et al 1995). It seemed a logical step from there to produce vectors that had noviral genes at all. This did not produce any significant benefits orimprovements from the previous agents. A number of research teamsacross the world tried different subsidiary strategies including druginduced immunosuppression or modifications of various immunogenicepitopes. The plasmid-lipid complexes appeared to have a number of clinicallyimportant advantages insofar as they did not appear to generate anyimmunological response which is in distinct contrast to many viralvectors. Initial optimism did not appear to be translated intopractical application as the delivery systems explored appeared to beunable to deliver sufficiently large quantities through thepathological mucous layer that is the main feature of the cysticfibrosis patient. (Crystal RG 1992). The adeno-associated vectors have received a large amount of attentionwhen it became clear that alternative vectors were needed to optimisethe therapeutic effect. They have now reached the stage where animaltesting has lead to human Phase I and II clinical trials. As a group,they appear to have the advantage that they dont trigger theinflammatory reaction in the same way, or to the same extent as theadenovirus group. The major practical difficulty with this grouphowever, is the fact that because they are so small compared to thecomparatively large size of the CFTR gene it leaves no space forvector-specific sequences on which to base assays to help todistinguish the endogenous RNA from the vector-expressed RNA. (FlotteTR et al 2001) All the evidence that we have seen appears to suggest thatadeno-associated vectors have a satisfactory safety profile andcertainly appear to produce a longer duration of clinical effect thanthe other modalities. Another variable, and indeed challenge, in the field of genetherapy, is to find the optimum delivery vehicle. We have cited studiesthat have tried direct insufflation to the bronchial epithelium. Thisappears to be a superior mode of delivery to the aerosol which appearsto have the ability to cause agent specific reactions in the alveolarmembranes. There is continuing work which is currently looking at therelative merits of nebuliser delivery mechanisms as compared toconventional aerosol delivery systems. Others that have tried avoidingthe bronchial tree and utilising the respiratory epithelium byintroduction to the maxillary sinuses through intranasal antrostomies. Conclusion including future of gene therapy. In this dissertation we have presented evidence of from a number ofdifferent approaches to the problem of gene therapy in tacklingmonogenic conditions such as cystic fibrosis. As with most areas ofscientific exploration many blind alleys have to be explored beforean appropriate avenue of research becomes apparent. The initial enthusiasm the greeted the exploration of theplasmidDNA vector did not appear to be well founded although it isclear that further exploratory work is continuing in the field. The area of adeno-associated vectors appears to be currently themost promising with, at least in vitro, suggestions that many of thecurrent limiting problems may be on the verge of being solved. The major stumbling blocks at the moment are the difficulties ofproducing a high vector titre in the clinical situation and the longterm safety considerations, particularly those relating to mutagenesisof ongogenes. On this point the Flotte group are optimistic and feelable to make the comment: The data from our laboratory strongly indicate that the bulk of rAAVDNA in the lung, muscle, and liver is episomal and that rAAV genomesinteract with host cell proteins such as the DNA-dependent proteinkinase in the formation of stable high-molecular weight concatemers. It is the episomal situation of the gene that is currently thoughtto be the best insurance against inadvertent iatrogenic oncogenesis(Flotte et al 2002) but this is clearly no substitute for long termcareful and rigorous safety studies. It is often assumed, quite incorrectly, that the field of genetherapy is a discrete and academically isolated field. Progress in thisarea, as in so many other areas of research, is completely dependent ofdiscoveries and improvements in other areas of science. The future direction of research will be determined, to a degree,by improvements in our ability to manipulate cell types and cell linesoutside of the body as this will inevitably aid our ability to implantgenetically engineered agents. Reflection over the advances inknowledge from just the last decade indicates that new and innovativedelivery mechanisms will be developed, explored and evaluated. 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