Post Traumatic Stress Disorder ( Ptsd ) - 1584 Words

Introduction The military serves as a major component in our nation s security. Everyone around the country continues to rely on them each day to defend our freedom. Undeniably, the responsibilities of military members comes along with large amounts of anxiety, self-less service, and occasionally terrifying events that can have a negative influence on the individuals life. Post-traumatic Stress Disorder (PTSD) is a serious illness among the men in our military. Gates et al. (2012) defines PTSD as, a psychiatric condition that is experienced by a subset of individuals after exposure to an event that involved life threat and elicited feelings of fear, helplessness, and/or horror in the individual (p.361). In some environments, this is a†¦show more content†¦14). This is a large number of people impacted by the disease and these statistics must change. There is an obligation as Americans to provide the best care for those that put their lives on the line for us each day. We must all work together to limit the severity of the disorder and assess individuals at a deeper level to improve the lives of those who suffer from it. Due to the significant harm that PTSD inflicts on the men serving our country, the military must persist in reforming the tests and evaluations used to diagnose the tragic illness. Challenges Deployments play a major role and are a real part of serving in the military. Some men deploy for a few months, most leave for over a year, and others deploy at higher rates, but for shorter amounts of time. During and after these times away from home, Foran et al. (2013) notes that it is crucial in making close relationships with fellow military member and to reach out to family to ensure an increase in personal conflict is less likely (p 154). According to Riggs and Sermanian (2012), the strength of the leadership within the unit and how they handle the various traumatic circumstances the service members encounter, may significantly contribute to the degree of the individuals PTSD severity over time (p 18). But when it comes to service members seeking help while deployed, it is very unlikely. While I was deployed to Afghanistan, nothing was ever mentioned to us

Centers for Disease Control and Prevention - 629 Words

CDC Centers for Disease Control and Prevention Weam Khadim PBHE501-American Public University May 21, 2013 Dr. Shalah Watkins-Bailey Centers for Disease Control and Prevention Center for Disease Control and Prevention is a national public health federal agency under Department of Health and Human Services headquartered in Atlanta, Georgia. It is division of Department of Health and Human Services responsible for managing national programs for control and prevention of communicable diseases and Vector born pathogen. CDC also is in charge of implementing strategies and plans to deal with environmental health problems. It also controls quarantine activities and performs epidemiological research, and it provides consultation on†¦show more content†¦This created the need to rename it to Center for Disease control and Prevention (CDC) to reflect this wider scope of activity. â€Å"Today, CDC is the nation†²s premier health promotion, prevention, and preparedness agency and a global leader in public health. It remains at the forefront of public health efforts to prevent and control infectious and chronic diseases, injuries, workplace hazards, disabilities, and environmental health threats† (Centers for Disease Control and Prevention, 2013). Tom Frieden, MD, MPH, is the current director of CDC. Dr. Frieden has worked to control infectious diseases threats to public health, respond to emergencies, and has fought the major causes of suffering and death whether in the United States or around the world. Based on the duties and mission of different subdivisions of Department of Health and Human Services, Two or more of these agencies can be joined together. As example, The Agency for Healthcare Research and Qualitys (AHRQ) main responsibility and mission is to improve the quality, safety, efficiency, and effectiveness of health care for all Americans. Can be joined with the Health Resources and Services Administration (HRSA) where the latter mission and responsibility is to improve heal th and achieve health equity by making sure people are getting quality services, a skilled health workforce and pioneer programs. The agency goal is to provide health care toShow MoreRelatedThe Center For Disease Control And Prevention1497 Words   |  6 Pages1. The Center for Disease Control and Prevention (CDC) had many key audiences it was required to communicate with during the Ebola outbreak. Most importantly, the CDC needed to be communicating with employees within the CDC. 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The document highlights the steps that organizations providing HIV testing and services must follow, upon receiving a HIV positive test result. This process includes uniting the medical and social aspects of HIV care for patients. The documentRead MoreCenters For Disease Control And Prevention Essay753 Words   |  4 Pages1. Centers for Disease Control and Prevention. CDC-Funded HIV Testing: United, States, Puerto Rico and the U.S. Virgin Islands. Atlanta, Georgia 2014. An 85-page, 2014, Center for Disease Control (CDC) issued guidelines for HIV funding and testing. The document highlights the steps that organizations proving HIV testing and services must follow, upon receiving a positive HIV test results. 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Ethics and power in organizations

Questions: 1. What did you learn from thus topic? 2. What do think this topic is important? 3. How would you apply thus topic in your life? Answers: Ethics and power in Organizations - why power corrupts and absolute power corrupts absolutely 1. I have learnt from the understanding of the topic that humans are hungry for power and this is natural. In organisations, bureaucrats and even lower subordinates demand more power as a result of this nature. Greater power enables an individual to make decisions quickly and efficiently; however, the dangers are more in such cases. I have worked in two organisations and have come across people from different domains and having different characters. I believe that corruption is a pragmatic attitude for gaining power without considering ethical views and the outcomes of the deeds. One does not think of what is right and wrong, and places own advantage above justice to others. When someone gains authoritive power and starts exercising control over others, they exhibit wicked behaviours which begin to dominate their minds and eventually destroy it (Fincham and Rhodes 2005). People having the believe that absolute power does not lead to absolute corruption are very mislead (Zimbardo 2007 ). I belief power corrupts since the growth opportunity is destroyed. Power inflates ego and gives rise to erroneous ideas and thoughts. It can be thus said that by way of power one corrupts and by way of absolute power one becomes absolutely corrupted. I have developed an understanding that corruption is to be avoided at all costs even if power is at hand. 2. The topic is important since power and corruption are two integral elements of all organisations. Ethical issues constantly interfere with the functioning of an organisation, and since power and corruption are inevitably related to ethics, the topic is of utmost importance. 3. I would apply this concept of power and corruption in my professional life to maintain a balance between power and ethical concerns. It would be my aim to not walk in the path of corruption and rather utilise the power I would have in a positive way to achieve better professional outcomes. References Fincham, R. and Rhodes, P. 2005.Principles of organizational behaviour. 1st ed. Oxford: Oxford University Press. Zimbardo, P. 2007. The Lucifer Effect. How good people turn evil. Ebury/Random House, pp. 258-293.

Psychosocial Essay free essay sample

The purpose of this essay is to demonstrate knowledge and understanding of both psychological and sociological factors that may impact on the patient/client and also relate to psychological and sociological theories and National Policies. The real name of the client has been changed to protect the patients confidentiality (Nursing and Midwifery Council 2008) NMC. The patient I will be discussing is Mark, a 42 year old man who has worked for a construction company for the past 20 years. Mark is married and has three children ages 3, 4, and 8. Following an incident at home in which Mark fell 15 feet off a roof, he has had persistent chronic lower back pain. Two surgeries over the past 12 months have failed to alleviate his pain. Mark is currently out of work because of this and his wife has had to take on a second job working evening and weekends to make ends meet. Mark has no previous medical history and he classifies himself as being generally healthy. We will write a custom essay sample on Psychosocial Essay or any similar topic specifically for you Do Not WasteYour Time HIRE WRITER Only 13.90 / page Prior to his accident, Mark was very active; playing football with his mates on weekends, jogging every morning, going to the pub, holidays with family and having fun with the kids. Presently Mark is unable to stand for long periods of time; this has affected his quality of life as a whole. The reason I have chosen this patient is because he has a condition that I may encounter in my own personal life and I am highly interested to learn about the impact it may have psychologically and sociologically on individuals. Psychological Aspects The psychological factors that Mark may encounter because of his physical condition may include depression, anxiety/anger, sleep disturbances and possibly low self-esteem. According to Abramson et al (1989), depression is caused by internal stable and global attributions for bad events and external unstable and specific attribution for good events. Depression may occur with mark because of the lowered pain tolerance and may decrease his willingness or ability to comply with medical advice. Mark may also be heightened with his perception of pain; he may become reluctant to carry out treatment modules provided to him because of fear of encountering more pain or injury. The combination of immobility and depression can lead Mark to be irritable, nervous or anxious and have an unhealthy desire for isolation; marital conflicts may also develop and escalate. As the depression sets in, Mark may become more angry, easily frustrated, moody, and plagued with feelings of hopelessness. Anxieties may interfere with Marks ability to concentrate; he may find himself worrying about his health and other life stressors such as finances, providing for his family etc. Anxious thoughts such as catastrophizing (e. g. uminating about the negative impact of pain and worrying about whether the pain will get worse), may increase his pain further and encourage disability. After having two unsuccessful operations on his back, Mark may also have doubts about recovering and therefore may also lose hope. As pain often prevents sleep, Mark may also be affected with constant state of tiredness because of sleep deprivation. According to Lamberg (1999), sleep disorders and persistent pain mutually interact, and it is often a clinical challenge to determine if the pain is due to poor sleep quality or whether sleep disturbance is due to night pain. For example, sleep deprivation can trigger a decrease in pain tolerance and pain thresholds (Onen et al 2001). Conversely, chronic pain may lead to non-restorative sleep and sleep fragmentation, as well as unpleasant consequences such as impaired thinking and greater proneness to accidents. Mark may also experience low self-esteem, having feelings of being unworthy or not measuring up to others and feeling incapable of achievements or successes in life. Body image disturbances such as weight gain may also be a contributing factor to Marks psychological well being. Weight gain can be a side effect of many medications, physical changes combined with an inability to exercise or perform physical tasks can have a negative impact on his body image, in extreme cases this may lead to eating disorders, but much more commonly it affects a person’s self-esteem (Burton et al1995). According to Burton et al (1995), self esteem can have negative consequences such as attempted suicide or withdrawal from friends and family. In relation to my client’s condition, I believe the Behaviourist theory most applies to him. Schwartz et al (1982) mentioned that, Behaviourism is a learning theory that only focuses on objectively observable behaviours and discounts any independent activities of the mind. Behaviour theorists define learning as the acquisition of new behaviour based on environment conditions. Experiments by behaviourists identify conditioning as a universal learning process. There are two different types of conditioning, each yield a different behavioural pattern. The first is Classic Conditioning discovered by Pavlov (1903), which occurs when a natural reflex responds to a stimulus. According to Pavlov (1903), we are all biologically â€Å"wired† so that a certain stimulus will produce a specific response. The second is Operant Conditioning by Skinner (1931). This occurs when a response to a stimulus is reinforced. Operant Conditioning is a feedback system in which a reward or reinforcement follows the response from a stimulus, and then the response becomes more probable in the future (Skinner 1931). Behaviourists tried to show that all behaviour could be shaped, altered, weekend or strengthened as a direct of environmental manipulations. Fordyce et al (1968) were the first to apply the behaviour model to pain. It was thought that there was a simple casual connection between pain and its rein-forcers. The respondent acute pain was seen as a reflexive response to antecedent stimulus and the respondent pain may eventually evolve into operant and persisting pain if the environment offers pain contingent reinforcements. According to Gamsa (1994), pain behaviour may also be learned by observing â€Å"pain models† i. e. individuals who exhibit such behaviour or more complex factors such as personal dynamics, emotional state, physical vulnerability and numerous psycho-social variables that have not been addressed. Fordyce et al (1968) proposed that operant pain persisted because of the behaviour of others (family, friends and healthcare providers) during the acute pain stage, which reinforced the pain to return secondary gains, such as permission to avoid chores or obtain otherwise unobtainable attention and care. The relation between the Behaviourist theory and my client is, the stimulus may be the intake of analgesia (pain relief) and associating that with being pain free, feeling more comfortable, being less irritable and having a better concentration level every time he consumes some. This in turn can activate the response (being pain free) from the stimulus (intake of analgesia). However, if the analgesia were to be eliminated, he may associate that with more pain, discomfort and irritability etc. Hubplace (2010) mentioned that the intake of analgesia may have negative impact on individuals as it can become addictive. Mark may be prone to addiction of pain relief because of the chronic pain he is experiencing on his back. Under the Classic Conditioning, Mark’s fear and anxieties about his condition can trigger a natural reflex which may create a response (pain) from a stimulus (fear/anxieties). Marks pain may also increase because of his environmental factors, not being able to do the things he used to do, for example playing with the kids, recreation activities, bathing, socialising etc. Family members, friends and his children may reinforce his pain also by the way they treat him, talk to him, and behave around him. Conditioning of pain is the main relation of the theory to my client; Mark may condition his pain with his behaviour of being in constant pain when in actual fact the presence of pain may actually be absent. Sociological Aspects The Sociological factors that Mark may encounter include loss of identity, daily activities, employment status, intimacy/sexual activity, social isolation, marital/family relations and financial strain. As Mark is currently out of work, he is faced with a financial strain; the family may experience a loss of wages and fuel a financial burden on the couple, causing conflicts and disagreements within the marriage and possibly altering their life style from what it used to be. Prior to Marks onset accident, his identity may have revolved around his job, hobbies and family. His condition could have significant consequences, such as limiting the range of enjoyable activities, for example, going to the pub, holidays, playing with his kids, working and providing for his family. Chapman et al (1993) mentioned that, individuals who were unable to work because of chronic pain found that their conception of themselves as a hard-working provider for their family was severely challenged, which can perpetuate feelings of guilt, depression and social isolation. According to the Organisation for Economic Co Operation and development (OECD 2005), Social isolation is characterized by a lack of contact with other people in normal daily living, in the work place, with friends, and social activities. OECD (2005) define social isolation has being a symptom and cause of social distress. It may follow a difficult event in a person’s life, for example, the loss of a job, the breakdown of a marriage, illness or financial difficulties. Feelings of isolation can occur in Mark making it difficult or him to reintegrate socially, this can affect moral, and the lack of contacts with other people may reduce both social and economic opportunities for him. The chronic pain in his back may be linked with the concept of suffering which includes; threats to ones integrity, ones wholeness, predominance of negative emotions, overwhelming helplessness and decreased ability to cope. This can be partly because resources are depleted by the persistence of the pain and accumulated losses including appearance, way of life and quality of life (Chapman et al 1993). The loss of intimacy is central to a decreased quality of life. Marks family may become irritated by his constant complaining of pain; his wife may be constantly hearing about the type of pain he is having, where the pain is occurring, and how he is attempting to cope with the pain. Some family members and friends may become desensitized to the pain, and consequently ignore his request for attention and support of pain relief. Marks children may also try to avoid him as he may become less loving, tender and nurturing as he used to be, he may even vent his frustrations and anger on his children and may not be able to tolerate noise, discomfort or even the very presence of his children. Chronic back pain constrains the expression of intimacy in many activities, for example, sex (Schlesinger1996). With regards to sex, Mark may have fears of increasing pain, therefore varying the amount of willingness to learn non-painful/less painful intimate behaviours which in turn can affect his sexual desires. For example, something as rewarding as sex is not going to be seen as desirable if it always involved pain or if the pain makes the person unable to function well in their sexual behaviours, for instance, obtaining and maintaining an erection. The Sociological theory that relates to my client is the Role Theory. Role Theory suggests that human behaviour is guided by expectations held by individuals and other people (Biddle 1986). The expectations involve different roles individuals perform or enact in their daily lives; for example a father, friend or son. The Role Theory implies that if individuals have information about the role and expectations for a specific status, for example a doctor, accountant or dentist, a portion of the behaviour of the persons occupying that position can be predicted. For instance, a doctor is expected to diagnose an illness and prescribe medications, this can be predicted from individuals. There are several extensions of the Role Theory; one that relates to my client is the â€Å"impression management† which is a theory and process developed by Goffman (1961). This theory argues that individuals are constantly engaged in controlling how others perceive them. This process refers to the influence of other people’s perceptions by regulating and controlling information in social interaction. If an individual tries to influence the perception of their own image, it is called self-perception (Goffman 1961). He suggested that individuals were like actors if placed on a face to face situation. It implied that individuals were aware of how they were being perceived by their audience. With relation to my client’s physical disability, Mark may be faced with the alteration of his roles, for example, as the provider for his family, a father to his children, a husband to his wife, a friend and colleague to his work mates. Having been off from work for some time, Mark is faced with the loss of earnings therefore losing the role of the provider or head of the family. Under the Impression Management Theory, Mark may be aware of how his family may perceive him due to his unemployment status. The role of a friend may also be absent has he may isolate himself from friends and society as a result of being restricted on doing the things he used to do prior to his accident. The role of a father may also be affected as he may lose all interest in interacting with his children, playing games or bonding with them. The pain that he may be experiencing on his back may take all of his attention, making it hard for him to focus on anything else. The role of a lover and husband may also be affected; his libido may decrease due to the fears and anxieties of acquiring further harm or pain and the closeness he used to have with his wife may also be affected due to her always working and not having enough time together as a family. This may cause conflicts within their marriage and may possibly lead to divorce, causing Mark to lose the role of a husband. National Policies The Department of Health (2006) suggest that information about life style choices that promote good musculoskeletal health should be available to the public from the education, health and community services in a range of languages and formats. The information should be evidence based of consistent equality and should include information on physical activities, diet and nutrition, exercise, self management and the prevention of injuries. It should be available in settings such as the work place, primary nd secondary care services, schools, leisure facilities, pharmacists and centres for further education and specialist musculoskeletal clinics. This policy would help Mark to manage his condition if and when he eventually returns back to work. Having the knowledge of the risk factors and the prevention of further harm to his back may help to minimise his pain and discomfort in the future. To conclude, chronic back pain can have many consequences to an individual’s quality of life, these may include; social activities, mental state and sexual relations. The management of chronic back pain doesn’t only rely on the physical side of it but also the psychological being of the individual. If both the physical and psychological management of pain is achieved, the chances of the individual overcoming their condition/disability are much higher. However, there are no guarantees that the pain will be alleviated completely. This assignment has helped me to gain the understanding of the psycho-social factors that illnesses can influence on individuals. Individuals need to be treated as a whole, for their physical/physiological, social and psychological well being to ensure that the best quality of care and treatment is being implemented. I hope to put this knowledge into practice in the near future as a qualified nurse. When assessing patients with their illnesses and conditions, I hope to recognise the psycho-social implications that may affect their everyday life and give them as much support as I can and if necessary refer them to the relevant people. ,

Society is becoming over-regulated

Society is becoming over-regulated Society These Days Does Society Really Need Regulation? It is impossible to make generalizations about whether society is or is not becoming over-regulated, as all societies require some forms of regulation in order to function, but not all regulations are of equal value. Instead, rather than trying to assess whether society as a whole is over-regulated, which is too sweeping an assertion to be either proven or disproven, we should unpack the problem of which sorts of regulations are excessive or superfluous and which are needed, and how the issue of the degree to which regulations are enforced is just as important as their existence on the books. Regulations: from Absurd to Necessary The first category of regulations we might consider are obsolete statutes that still remain part of the legal code despite having been rendered obsolete by either changing customs or new technology. In Missouri, for example, it is illegal to drive with an uncaged bear in ones car. Other laws date back to the time when horses and carriages were common modes of transportation. More relevant to todays students are what are sometimes called blue laws that regulate what is considered moral behavior, including sexual acts, and alcohol and drug use. Many of these, such as those concerning what sexual acts are permitted between consenting adults, are impossible to enforce and anyway seem to many people an intolerable limitation on what should be purely personal decisions. Others, such as the laws against pedophilia, seem to be morally justifiable. Another category of laws that in some peoples view constitute forms of over-regulation are those concerning the private use of alcohol, marijuana, and other addictive or mind-altering substances. While most people would agree that some regulation is needed, especially regulations that prohibit young children from accessing such substances, everything from the age at which people should be allowed to make their own decisions to which substances should be regulated in what manner are matters of controversy. My own position on this is that these substances are both over- and under-regulated. On the one hand, making substances illegal or limiting the days on which one can buy alcohol in stores is ineffective in preventing substance abuse. On the other hand, some forms of regulation, such as laws against drunk driving. have saved many lives and strengthening such regulations along with making public transit affordable and widely available might save even more lives. Legalizing recreationa l drugs but closely regulating them for quality and safety might also save lives; in this case, I would argue that many drugs are both over-regulated, in so far as personal use is criminalized, and under-regulated in the sense that quality and safety are not adequately monitored. The Nanny State While many people have issues with what the British term the nanny state that regulates many aspects of personal choice or behavior, peoples opinions vary on what specific regulations are justified. The attempt of New York City to prohibit the sale of soft drinks in servings of over 16 ounces was eventually overturned but still serves as an example of regulatory overreach. Although drinking a 32-ounce soda is not good for ones health, if someone wants that quantity of soda, that is a matter of personal choice. Moreover, as people could have bought two 16-ounce containers under the law, it would not have been a particularly effective way to encourage healthy eating habits. On the other hand, regulations that insist that accurate nutritional labels be made clearly visible to customers seem a legitimate form of regulation, as such labels allow us to make informed choices about our own health. What these examples show is that regulations in our society can be either beneficial or harmful. Some regulations are excessive or absurd, while others are necessary. In some areas, especially ones relating to health and safety, more comprehensive regulations and stricter enforcement would be desirable. Food should be safe to eat and water safe to drink. In other areas, though, regulations can be intrusive or even harmful. Thus our society can neither be said to be over-regulated or under-regulated, but rather we can conclude that we should look at each individual regulation on its own merits.

Understanding Aber and Sondern in German

Understanding Aber and Sondern in German ​Conjunctions are words that link two sentences. In German, they belong to the group of non-declinable words, which means that they never change, no matter what case you think you should use or what gender a following noun has. However, while in English you might only have one option, in German you will often find several possibilities to choose from.  Such is the case with aber and sondern, which your dictionary will most certainly translate both as but. Using but in German Take a look at the following sentences: The child didnt want to go home, but to the park. Das Kind will nicht nach Hause gehen, sondern zum Park. I dont understand what you say, but you will certainly be right. Ich verstehe nicht, was Sie sagen, aber Sie werden schon Recht haben. She is exhausted but doesnt want to go to sleep. Sie ist erschà ¶pft aber will nicht schlafen gehen. As you can see, both aber and sondern mean but in English. How do you know which but conjunction to use? It is actually quite simple: Aber, which means but or however,  is used after either a positive or negative clause. On the other hand, sondern is only used after a negative clause when expressing a contradiction. In other words, the first clause of the sentence must contain either nicht or kein, and the second part of the sentence must contradict the first part of the sentence. Sondern can be best translated as  but rather. Carusos Little Brother Helps You to Create Better Sentences One last thing: aber and sondern are so called ADUSO-words. ADUSO is an acronym for: Aaber (but)Ddenn (because)Uund (and)Ssondern (contradicting but)Ooder (or) Those conjunctions all take position zero in a sentence. To remember that, you might want to think of ADUSO as the little brother of Enrico Caruso, the great opera singer. But he never grew out of his famous brothers shadow and remained quite a loser. Imagine the o in loser as a zero to remember position zero. A Little Quiz Lets test your knowledge. Which German version of but would you use in the following sentences? Ich komme nicht aus England _____ aus Schottland. I dont come from England but from Scotland. Ich bin hungrig, _____  ich habe keine Zeit etwas zu essen. I am hungry, but I dont have time to eat something. Sie spricht drei Sprachen: Englisch, Russisch, und Arabisch, _____ leider kein Deutsch. She speaks three languages: English, Russian, and Arabic, but unfortunately no German. Wir htten gerne drei cheeseburger _____ ohne Zwiebeln. We would like (to have) three cheeseburgers but without onions. Er hat keinen Kartoffelsalat mitgebracht, _____  Nudelsalat. He didnt bring potato salad, but noodle salad. Er hat gesagt, er bringt Kartoffelsalat mit, _____ er hat Nudelsalat mitgebracht. He said, hed bring potato salad, but he brought noodle salad. Answers to the Quiz Ich komme nicht aus England,  sondern  aus Schottland.Ich bin hungrig,  aber  ich habe keine Zeit etwas zu essen.Sie spricht drei Sprachen: Englisch, Russisch und Arabisch  aber  leider kein Deutsch.Wir htten gerne drei Cheeseburger,  aber  ohne Zwiebeln.Er hat keinen Kartoffelsalat mitgebracht, sondern  Nudelsalat.Er hat gesagt, er bringt Kartoffelsalat mit,  aber  er hat Nudelsalat mitgebracht.

Cultural Awareness of Israel Essay Example | Topics and Well Written Essays - 1750 words

Cultural Awareness of Israel - Essay Example Similarly, the culture of Israel is unique in the sense that it is the only country in the world with a majority of Jewish community. Culture, as defined by Anderson and Taylor, is ‘a complex system of meanings and behavior that defines the way of life for a given group or society. It includes beliefs, values, knowledge, art, morals, law, customs, habits, language and dress’ (Anderson and Taylor, pp. 54). 1. Culture is shared: the culture of people living as part of a group is similar with each other to a great extent. The values and belief of the group have been developed through an agreement or principles defined through decades or even centuries; 2. Culture is learned: Culture is not a birth acquired part of a human; but is rather inbred in the person through his parents, guardian, friends and family. A person is taught the way of the society by people around him to such an extent that his thought process is also aligned with the other people in a similar culture; 3. Culture is taken for granted: Since the culture is inbred in a person since his birth, he accepts it as a part of life without questioning the rationality behind the continuance of certain traditions or laws. A person is aware of his cultural differences but most do not usually deviate from their cultural makeup; 4. Culture is composed of symbols: There are always symbols in a society that are unique from other society. A symbol may hold special reverence for one community but may mean nothing for another. The meaning that people give to certain symbols is actually what makes them unique from others. 5. Culture is dynamic: As people migrate from one area to another, they take their cultural belongings with them. Their thoughts, ideas and opinions travel with them and infuse in the thoughts, ideas and opinions of the people they meet. In this manner, cultures continue evolving and are dynamic in nature (Anderson and Taylor, pp. 54-48). Israel, officially names

Zeitgeist Movie Review Example | Topics and Well Written Essays - 500 words

Zeitgeist - Movie Review Example The first part of the movie was more or less based on the birth of Jesus Chris, stating that he wasn’t infact born on this date. Here again, the director has to prove the fact that the birth date of Jesus Christ is not actually the 25th of December and that it should be in the season of winter solstice but the director has yet again avoided the theories which point otherwise. The next topic being discussed in the video is regarding the cross. The director claims that the cross is actually the symbol of the zodiac and is persistent on proving that the symbol is somewhat astrological by origin. The author has done this by discussing the myths. But it could be easily said that the cross has no relation whatsoever from astrological point of view rather it is used because Jesus Christ was crucified on the cross because crucifixion was the conventional method of punishing someone by law. Similar things can be said about the claim the author makes regarding the crown of thorns. The author also makes claim that the Bible is not actually a work of God and the stories of various prophets such as Noah, Moses mentioned in the Bible are actually again similar to other stories of the past. But the one thing that is problematic here is if the director is trying to prove wrong of the Bible why he is not trying to prove the reliability of the stories which he mentions in order to contradict the teachings of the Bible. The author also says that Horus was the God of the sun in Egypt, this shows that the author has a lack of understanding regarding the topic being discussed and he needs to do research regarding them. Every one, particularly Egyptians know that Horus was infact the God of the sky and Ra was the Sun God. This is one of the many examples which show the baseless facts that the director has mentioned in the entire video. The main conclusion that can be drawn from this video is that the religion, especially Christianity is the basis of

Technical Communication Essay Example for Free

Technical Communication Essay Chapter 1. Introduction to Technical Communication. Communication is the exchange of thoughts, message or information, as by speech, visuals, signals, writing, or behavior. Derived from the Latin word â€Å"communis†, meaning to share. Communication requires a sender, a message, and a recipient, although the receiver need not be present or aware of the sender’s intent to communicate at the time of communication; thus communication can occur across vast distance in time and space. Communication requires that the communicating parties share an area of communicative commonality. The communication process is complete once the receiver has understood the message of the sender. Technical Communication would mean a communication specific to the sender and the recipient and both would be from the same field of knowledge. This communication may not be understood by any others in the sense that the messages passed across are in a language that can be understood by persons from once field of knowledge. Here the importance subset of such a communication. Technical Communication is the flow or exchange of information within people or group of people sharing a common platform of similar knowledge or people from the same field with or without the technical knowledge. Means of Communication 1. Verbal Communication: Spoken and pictorial languages can be described as a system of symbols (sometimes as known lexemes) and the grammars (rules) by which the symbols are manipulated. The word â€Å"language† also refers to common properties of languages. Language learning normally occurs most intensively during human childhood. Most of the thousands of human languages use patterns of sound or gestures for symbols which enable communication with others around them. Languages seem to share certain properties although many of these include exceptions. There is no defined line between a language and a dialect. Constructed languages such as Esperanto, programming languages and various mathematical formalisms are not necessarily restricted to the properties shared by human languages. Communication should also include the display of text, Braille, tactile communication, large print, accessible multimedia, as well as written and plain language, human –reader, augmentative and alternative modes, means and formats of communication, including accessible information and communication technology. Manipulative Communications are intentional and unintentional ways of manipulating words, gestures, etc. to â€Å"get what we want â€Å", by demeaning, discounting, attacking or ignoring instead of respectful interaction. Sarcasm, criticism, rudeness and swearing are examples. 2. Non Verbal Communication: A variety of verbal and non-verbal means of communicating exists such as body language, eye contact, sign language. Nonverbal communication describes the process of conveying meaning in the form of non – word messages. Research shows that the majority of our communication includes chronemics (use of time) , haptics (using the sense of touch),gesture, body language or posture; facial expression and eye contact, object communication such as clothing , hairstyles, architecture, symbols infographics, and tone of voice as well as through an aggregate of the above. Speech also contains nonverbal elements known as paralanguage. These include voice lesson quality, emotion and speaking style as well as prosodic features such as rhythm, intonation and stress. Likewise, written texts include nonverbal elements such as handwriting style, spatial arrangement of words and the use of emoticons to convey emotional expression in pictorial form. 3Oral communication: Oral communication, while primarily referring to spoken verbal communication, can also employ visual aids and non verbal elements to support the discussion, and aspects of interpersonal communication. As a type of face-to face communication, body language and choice tonality play a significant role, and may have communication also garners immediate feedback. Historic Stages in Written Communication: 1. Pictograms in the form of stone graphics hence immobile. 2. Written form on papyrus, paper, clay tablets. Introduction of common alphabets and also the invention of printing in the 15th century made the written form a very strong means. 3. Transfer of information through controlled waves and electronic signals. Effective Communication All communication, intentional or unintentional, has some effect. This effect may not be always in communicator’s favor or as desired by him or her. Communication that produces the desired effect or result is effective communication. It results in what the communicator wants. Effective communication generates the desired effect, maintain effect increase effect. Effective communication serves its purpose for which it was planned or designed. The purpose could be to generate action, inform, create understanding or communicate a certain idea/point etc. Effective communication also ensures that message distortion does not take place during the communication process.

The Effectiveness Of Sport Drinks Essay example -- essays research pap

The major reason anyone drinks fluid before, during and after physical activity is to replace the water that is lost through sweat. If the water isn't replaced dehydration will occur and performance will be hampered. The purpose of sports drinks is to help rehydrate your body quickly and help improve performance and productivity. This is accomplished through a well-balanced mix of water, sugar (carbohydrates) and salts (electrolytes), the major ingredients in most sports drinks. These ingredients, combined with a variety of fruit flavours, create pleasant tasting drinks that, according to the companies, are suppose to help your athletic performance. Results prove that commercial sport drinks generally accomplish what they set out to do. That is, they make fluids available for the body, and increase endurance, but at the same time they can create unwanted gastroesophageal reflux. Sport drinks make fluids available to the body and are consequently very effective in preventing dehydration. One tactic sport drinks use in order to accomplish this is by adding sodium and glucose to the drink. These ingredients stimulate fluid consumption by the body, causing the athlete to drink even more, and become rehydrated (Rehrer 45). Another way that sport drinks maintain hydration in the body is by having less than or equal to 10% Carbohydrates (CHO) and small amounts of electrolytes in the beverage. This composition makes fluids available for dilution of body fluids at similar rates, thu...

English Original Writing Coursework

Wake up, Awaken every tingling inch of your body to engage in an experience so saturated with nirvana that you'd think you were dreaming. The ocean sparkling like a gallery, putting its most prized gems in the reach of the common man. The sun shines like a perpetual red carpet, spread out across the entire beach. Absorb the sun. Taste the tranquillity. Savour the serenity. A slow burn scorches your feet, but there's always a price to pay even for the unexplored nirvana exposed in it's purest form. The heat merely pushes you forward by means of a slow blistering pain. Seeing through the veil of sunshine, you spot a series of rocks huddled together, forming a cliff; the very cliff that you will release yourself from. Release your demons, forsake them, and cast them into the sea. No more writhing sense of loneliness. No more craving for a deciphering of your soul. The real world does not exist here, neither do your problems. All that exists now is the sunshine that warms you up from the harsh cold of life. The serene sight of a thousand diamonds scattered over blue plains. The smell of salty seas will soon to leave you dripping and soaked with euphoria. You hear the seas calling with its thundering waves. The sacramental sea of happiness gently cleanses all your traumas. Though you don't seem to be the only one who stumbled on this goldmine, you are the only one that can comprehend its beauty. You were chosen, to feel the exquisite chills down your spine that none of your peers ever will. Welcome to your very own pseudo-narcotic experience. Side effects may include a possessing urge to never leave. You may leave the experience, but it will never leave you. Preying on your mind, this memory will be your most constant cause for procrastination. Transfixed and hypnotised, you make yourself a primitive bed-like stage of consciousness as you cross the bridge of clarity, built with time. As you watch the sky turn from merry to melancholy; from illuminating blue to mesmerizing orange and before it gets a chance to turn pitch black, you hear the sound of a barrage of cleansing bullets. Stretch out your hands, open your mouth, embrace nature in its truest form. Prepare yourself. The rain creeps up into you, injecting you from all sides with a high you've never felt before. As you lie on the cliff, embracing Mother Nature, free of troubles, the sun takes refuge. Behind the blanket of clouds at first and gradually the supposedly everlasting bed of light disappears beyond the horizon. The waves crash through the silence of the dead night like a wrecking ball through the crumbling pillars of tranquillity. Every wave crashing down is yet another chant calling for you to be enveloped in the mysticism of a nocturnal paradise. Every raindrop to bless your tormented skin is another reason for you to stay. Your feet reap the reward for bearing the burden of heat soothing itself in the cool soothing sand. So soothing, you couldn't dream of achieving this in a hyper-real lucid dream. The rain had done its job, showering its blessings on you, making yourself one step closer to transcending into a state of consciousness that acts as nothing less than a gold-mine of serenity. You rise up, and let go of everything that you've ever known. All that guides you now, is animalistic instinct. You're literally soaked in bliss and this will be a moment that you remember, your tongue tasting the rain and your feet embracing the cold mix of hard rock and sand. Unclench your fists; let the colour come back to your palms. And holding your hands out to all of the Earth, you run. Your feet thudding and leaping between tiny gaps between rocks, spaces big enough to let your foot get trapped there; yet, unsurprisingly, nothing happens. And reaching the peak of this sacramental cliff, your adrenalin reaches inhumane levels as you take one last dive into the never-ending abyss of serenity. You wish you could slow down the sensation that travelled ferociously through your entire body as it welcomes the cold water. Mere words can only do so much to describe it; and this is where it's magnitude of peacefulness is one undefined by vocabulary.

There are many reasons why you could argue the ‘Class Structure’ is changing in the Contemporary UK

Firstly, up until the 1980's wealth was becoming more fairly distributed across the population, however since the 1980's this trend has reversed and the gap between rich and poor has rocketed. Now a days, most wealth remains in the hands of a tiny minority whilst the majority float above the fine line of poverty. New Right sociologists claim that the old ruling class has disintegrated and a share owning expanded middle class has emerged. Peter Saunders now claims minority rule by a minority class has been replaced with a nation of stakeholders. However the continued existence of a ‘power elite' controlling the majority of wealth and power has been well documented by John Scott. Manual work patterns have changed also, i.e. in the primary and secondary industry manual jobs have declined significantly, whilst service sector jobs have increased. The expansion of the Welfare state has caused professional and non manual jobs to increase, results in a bloated middle class. The traditional working class has also changed, with women becoming a more influential and important member of the work force. Part time work has increase too. As a result of a rising global economy a geographical shift in the traditional working class has emerged. In the West there has been a growth in non manual employment with an extension of state services, in particular teachers, nurses, clerks etc There has also been an increase the employment of women and part time low insecure employment. Roberts claims the middle class has expanded but also ‘fragmented' into a number of distinct groups, i.e. professionals, managers, self employed. Roberts call these strata within the middles class ‘class fractions' each with its own culture, norms and values. Professionals tend to employ internally, therefore if your father is a professional you are much more likely to be employed. Savage suggest that professionals have a strong sense of class solidarity as evidence of their willingness to take collective action to protect their values, i.e. Occupational Associations-BMA, law society and lower down the NUT There has been a significant increase in self employed people, especially in the areas of consultancy in the finance, ICT areas. Large numbers of employed managers have their own consultancy business too. It is understood that Henry Ford shaped the traditional working class with his first moving assembly line in the 1914. Work was divided up into much more manageable loads and presented to a much lower skilled work force in return for lower labour costs. Fordism shape both working class and its sense of solidarity. However with manufacturing in decline this class has also begun to decline. Henry Braveman argues that Fordism still impacts working class as workers are constantly de-skilled with the introduction of technology. This introduction of technology has also dented the middle class occupations as white collar clerical/ technical are subject to proletarianisation by the impending application of technology. Marxists suggest that revolutionary class consciousness will be the result of such trends. Daniel Bell suggests that we are now living in a post fordist or post industrial age where work is based intellectual creativity rather than physical effort. Businesses also take more care of their workforce through better conditions, pay and concern for professional development. To support these claims by Bell the primary and secondary industries have declined whilst tertiary have expanded, as a result fewer people in Western Europe now work more with their brains than with their hands. Service sector workers lack the old structures of union and solidarity, thus seemingly becoming more privatised. There has been a growth of highly skilled new technology workers (wired workers) whom work from home, enjoying increased flexibility, challenge and autonomy. However there is strong evidence against Bell's theory, i.e. some sociologists argue that manual work has simply followed market conditions to low labour costing parts of the world. Also some argue the point that most computer workers sit in fact sit front of computers to input simple repetitive data, in poor conditions and for low pay.

Data Structures Example

Data Structures Example Data Structures – Coursework Example Data Structures Data Structures A Queue A Queue refers to a list of tasks waiting to be processed. When a task is sent to a queue, it implies that it has been added to the list of tasks waiting to be processed. It is worth denoting that computer programs frequently function with queues as a manner of ordering tasks. For example, when a computer is through with one computation, it goes ahead to process the next task on the queue. Furthermore, another example is the printer queue that refers to a list of files waiting for printing. An Array On matters of data storage, an array refers to a mechanism for storing data on several devices. It is worth mentioning that arrays are oldest and most imperative data structures used by nearly every program. Additionally, another major use of arrays is in the implementation of other numerous data structures such as lists because they play a key role in exploiting computers; logic (Humphris, 2014). The main use of data arrays is in the implementation of both mathematical vectors and matrices. They also play an imperative role in implementing several data structures such as stacks and queues. Array allows one to store a series of correlated variables of the same kind and often referred to as a list. New int[10] is an example that best illustrates the use of arrays in computer technology. In Random access memory, an array refers to the organization of memory cells (Humphris, 2014).A Stack A stack refers to a kind of data structure used to store data in a computer. Apparently, when a fresh object enters into a stack, it remains on top of other previously entered objects. This essentially implies that when one decides to remove a certain object from a stack, the one that is at the top leaves first leaving the previously entered objects.Comparison between an Array, stack and queue The stack and queue are closely related data structures. The definition of each lies on two main operations that is enter a new object and eject an objec t. Apparently, the rule mainly used in the queue data structure is to ensure that one removes the item that has stayed for a long time thereby leaving the new items. The stack rule ensures that one removes the item that has spent minimal time in the collection. In an array, an individual can access the elements at any time but a stack does not allow for random access.ReferencesHumphris, C. (2014). Computing and Information technology. New York, NY: Eptsoft

The Rules of Engagement in English

The Rules of Engagement in English The Rules of Engagement in English The Rules of Engagement in English By Mark Nichol In the same day, this site received, among readers’ responses to my recent post Courtesy Titles and Honorifics, two diverse email messages: One was a reasonable, well-written support of the writer’s opinion that, as she was taught, because the courtesy title Ms. is an artificial designation that doesn’t abbreviate anything, it should not include a period. The other correspondent wrote, â€Å"hey watch out your website looks like a rule book, and we all know rule books are fascist.† Whether one’s convictions are adept or absurd, however, one must accept the incontrovertible fact that although one is free to write in any style or manner one chooses, this choice has consequences. Linguistic anarchy is inimical to language, by virtue of the fact that language, as a form of communication, is essential to family, to society, to civilization. Just as abiding by rules of personal and community conduct (the latter extending in scope from the smallest village to the United Nations) helps protect the fragile coexistence of humans, adhering to guidelines for language use enable at least sizeable blocs of humanity to agree on common signals for cooperation (or conflict). Language evolves, constantly and relentlessly, but precepts and attitudes about it prevail for a time before they slowly respond to changes in usage. Therefore, for example, though one of the correspondents I referred to above is correct that the period following Ms. is not logically justified and that for that reason, early in the term’s life span, many writers omitted the punctuation it is now standard, for the sake of consistency, to treat Ms. the same as Mr. and Mrs. One’s gender and gender politics are irrelevant: Those are the facts, ma’am er, ms. Do you write simply for pleasure, or to share your thoughts and ideas with a small coterie of readers? Do you self-publish, whether in print or online? Knock yourself out you are hereby granted a dispensation to write in any fashion that pleases you and anyone who chooses to read your work. You are akin to a homesteader or a survivalist, staking out your own terrain on your own terms and accepting the terms that go with those terms. But if your intent is to identify yourself as a professional writer or if your employment status is predicated on the fact that your writing is intelligible to your colleagues and perhaps even consistent with distributed guidelines certain standards apply, and your ability to adhere to those standards is inextricably linked to your professional success or survival. If that’s fascist, then I proudly represent the New World Order. I don’t mean to get all serious on you. I respect the point about the unpunctuated Ms., and for all I know, the comment about the â€Å"rule book† may be a goof. But both comments inspire this tip: When it comes to composition, let your unfettered freak flag fly. But if you submit the flag to be unfurled atop a highly visible flagpole, expect it to be redesigned to suit that flagpole or to be refolded and respectfully returned for you to do with what you wish. Want to improve your English in five minutes a day? Get a subscription and start receiving our writing tips and exercises daily! Keep learning! Browse the General category, check our popular posts, or choose a related post below:Regarding Re:How to Play HQ Words: Cheats, Tips and TricksTypes of Plots

Molecular basis of circadian rhythms Article Example | Topics and Well Written Essays - 500 words

Molecular basis of circadian rhythms - Article Example In a fast growing world where travelling is essential to many individuals, jet lag is a common denominator among those individuals. Scientifically speaking, this was mainly because of the disruption of the circadian clock. According to the study of Glossop, Lyons & Hardin, the circadian clock worked in an interlocked feedback loops that is further divided into two: a per-tim loop which is activated by dCLK-CYC and repressed by PER-TIM and a dClk loop which is repressed by dCLK-CYC and depressed by PER-TIM (766). Through these loops, it has been identified that there are five genes necessary for effective circadian rhythm, among of which include the period (per), timeless (tim), Drosophilia Clock (dClk), Cycle (Cyc), and double-time (dbt) (Glossop, Lyons & Hardin, 766). However, nothing can be observed without going through the gene level and oscillating the anatomical structures for sleep and wakefulness. Clock-controlled genes consist of input pathways, oscillator or pacemaker, and output pathways (Cermakian & Corsi, 59). As stated earlier, initiating circadian rhythm requires oscillation and this can be done only through a pacemaker or oscillator. Oscillation occurs automatically as this is a temporal program. A well-oscillated circadian clock has self-sustained rhythm during its long period, compensated with respect to the abrupt changes in the environment, predominantly exposed to cycles of light, temperature, food availability and predator, and has various difference in the assembly of cellular clocks (Merrow, Spoelstra & Till, 931). Without this pathways and oscillation, the rhythm of the circadian clock will definitely be disrupted. The study of circadian clock will not only help humans in adaptation but the agriculture and animal industry as well. Experts would be able to condition the organism to environmental changes. Farmers can manipulate the pthosynthetic activity of the plants to match the appropriate

The Role of Media in National and International Development Essay

The Role of Media in National and International Development - Essay Example This essay stresses that the role of media in national and international development is best described in relation to the community development theories. The community development theories give a guideline on the practicability of the community development plan. They also analyse various aspects of development such as the forms and processes it takes. Some of the most common community development theories include the diffusion theory, the decentralisation theory, group development theory, group behaviour theory and the growth pole theory among others. This paper makes a conclusion that the contribution of the media to the national and international development cannot be underestimated. An active and unbiased media is needed so as to maintain democracy, good leadership and equality in a country. It helps educate, inform, sensitise and mobilise the public among other functions. By carrying out the above functions, the media facilitates growth and development. National development is achieved through the positive change in the social, political and economic sectors of a country. On the other hand, international development is achieved thorough the creation of a developed world community. The dissemination of information portraying a positive image of the whole world has been the key factor in community development. The theory of community development helps in determining and understanding the role of media in development. The theories have been conceptualised to guide the implementers of policies focused to national and international development.

Music World Culture Assignment Example | Topics and Well Written Essays - 1250 words

Music World Culture - Assignment Example On discovering the legends and history behind the nation’s cultural heritage, it is possible to know how these iconic symbols got associated with its culture and society. The discussion here commences with the historical, sociological, and geographical information of Scotland regarding its people, culture, and society; and particularly focuses on the music world culture that includes cultural information about the country’s unique music, dance, and instruments of the Scottish people. The geographical location of Scotland lies approximately in the northern end of United Kingdoms mainland, encompassing about 7.5 million hectares of land. The country is surrounded by the Atlantic Ocean in the west, with the North Sea in the east and the North Channel and Irish Sea in the south-west. In addition to the mainland, the country is made up of around 790 small islands, including the Hebrides and the Northern Isles. Scotland’s population is estimated to be more than 5 million, as per the census 2011, with a population of 62 percent identified as being purely Scottish, 18 percent as Scottish and British, 8 percent as British only, and 4 percent as other national identities. (â€Å"Analysis: National Identity†). The diverse national identities in Scotland have contributed to the culturally divergent heritage of the land. Scotland has a complex yet engrossing history that can be stretched back to some thousands of years, from the Kingdom of Alba to the modern Scotland of today. The emergence of Scotland can be dated back to the Prehistoric period, when the Kingdom of Alba emerged after the primitive immigrants’ colonization of the land. After the invasion of British colonialism and the subsequent agreement Treaty of Edinburgh-Northampton in 1328, Scotland was recognized as an independent sovereign state and got merged with Great Britain in the seventeenth-century. Scotland

Treating Cystic Fibrosis with Gene Therapy

Treating Cystic Fibrosis with Gene Therapy 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. 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 SJ  1997) 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 cell’s 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 â€Å"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 â€Å"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 â€Å"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 Duan’s original paper (et al 2000) and theauthors describe what they call a â€Å"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 Yan’s 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 the  CFTR 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 IB3–1 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 â€Å"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 â€Å"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