Analysis Of A Midsummer Night s Dream - 1052 Words

Savannah Dunn Miss Sibbach English IV 10 December, 2014 Endless Love Faults exist when love and law attempt to coincide. In A Midsummer Night’s Dream, Hermia comes head to head with unfairness, the fault which arises after her father disapproves of her marrying who she loves. According to the Athenian Law she must serve a punishment for disobeying her father. By this law, she should treat him like a god or her ruler. What he says goes and he intends for her to marry Demetrius, but she loves Lysander. In the play, if she does not marry who her father has chosen for her, several punishments may occur. Hermia has a few options she must quickly choose by the wedding of Theseus and Hyppolyta. Ultimately, law should not factor into a person’s†¦show more content†¦Although the Athenian law states that death should occur, Theseus takes it upon himself to give her an alternative punishment. â€Å"†¦question your desires, know your youth, examine well your blood, whether if you yield not your father’s choice you can endure th e livery of a nun, for aye to be in shady cloister mewed, to live a barren sister all your life†¦Ã¢â‚¬  (Skakespeare4). Theseus gave her the option to move away, so she would not have to die. This decision will also keep Egeus from having to kill his daughter. Although this alternative is not the best thing, it makes for a better punishment than dying. Theseus gives her the safest and smartest choice, marrying Demetrius and obeying her father. It would be the safest due to the fact her father has no problem getting rid of her. â€Å"As she is mine, I may dispose of her, which shall be either to this gentlemen or to her death according to our law immediately provided in that case† (Shakespeare3). Choosing this option would cause a lot less problems and make things easier for everyone, but Hermia loves Lysander too much, so she takes the harder road out and decides to run off with Lysander and get married, putting a big risk on many things in her life. â€Å"She is even prepared to give up her family and way of life to marry Lysander, agreeing to elope with him into the forest† (Hermia). The love she shares with Lysander seems much stronger than the

Concept Of An Advancing Leadership Style - 1660 Words

In this research paper, my endeavor is to explain my concept of an Advancing Leadership Style. I will identify the characteristics of a leader, and the external and internal environments that would play a part in any leadership style. Additionally, I will demonstrate how this leadership model assists in moving the organization forward in the direction of the mission or goal and assist in defining the organizational culture. Finally, I will show how this model is useful to the leader and followers by comparing other leadership models and their effects on the organization and followers. The Advancing leadership style is flexible to the demands, constraints, and resources available to the leader. It is the model in which one would use to†¦show more content†¦Key Terms: Advancing, Ethical, Followers, Goal, Leadership, Leadership Model, Organization, Organizational Culture. Literature Review The intention of this research paper is to define what an Advancing Leadership Style is and explain with examples and research how a leader would apply this style. To explain leadership and its relationship to the organization and the organizational culture. I will also discuss the importance of every leadership style having a foundation of an ethical leader. An ethical leader is what assists in motivating followers, and defining the purpose or the process of reaching a set goal or mission of an organization. Van Wart (2011), â€Å"Because leadership is a large social phenomenon as well as highly complex, we should not be surprised that many theories have been advanced to explain it† (p.72). Van Wart writes â€Å"†¦.a bewildering number of theories have been advanced to explain a variety of aspects of leadership, each with its own partial wisdom or advantages† (p.72). Leadership style can be define as a leader s style of providing direction, implementing plans, and motivating people. There are many different styles that can be used, exhibited and implemented by leaders. In literature, there are various definitions of leadership with many concentrating on influence processes used in pursuing a goal or set of goals (Sashkin, 1988; Yukl, 2002). Rauch and Behling (1984) provides additional insight into the definition of leadership as a â€Å"process

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Jesus and muhammed Essay Example For Students

Jesus and muhammed Essay Jesus and Muhammad have been held in high respect, if not respected, by the billions who have belonged top the religions that these two greats founded. Although both men thought of them of selves as spokes people of the same God not very much attention has been given to their similarities and differences. It is hard to find people through the ages that appreciate what Muhammad did. It seems that a lot of people degrade the rival leader to promote their won religious leader. In spite of these similarities, a comparison of the two men is somewhat uneven in the eyes of the Muslims and Christians. Muhammad spent his life in a region known as Hijaz, an arid plateau in western Arabia and also he lived the end of his life in Medina, where as Jesus spent his life in Nazareth located less than a thousand miles northwest of Mohammed homeland He also spent some time if his younger life in Egypt once Jesus was kicked out of Nazareth he moved to the lakeside town Capernium. Most of the young live s of the two are not very well documented all biographical information is held within the bible and the Koran. Islam and Christianity are the most widely studied religions. Jesus belonged to a religion which some women were given respect, as in the Islamic religion the women are given very much less respect that Christianity The bible and the Koran are both the most widely read books in the history of the world. In the Koran the word of god became divine in the Koran but in Christianity Jesus became divine not the bible. Both Jesus and Muhammad believed they they could converse directly with god in public or private. It was believed that mecca is the holiest place in the Islamic religion, in Christianity there is no such area or city, the closest place to mecca would be Bethlehem which is the birthplace of Jesus. In the last years of Mohammed life he was treated in an awesome way that distinguished him from others in his area. In the last years of Jesus life he was treated terribly by all who didnt follow his ways. In Islam it is said when Jesus was crucified that he said My god have you forsaken me , but Christianity there is no place where it says that Jesus gave up on god in the way the Koran says. In Islam the Koran was given to Mohammed by Allah directly. In Christianity the bible was written by many other people and not given to Jesus by god. Jesus is spoken of and is featured in the Koran and he is known as somewhat of a saint in the Koran, but in the bible Mohammed is never spoken of. Muhammad said that he was merely just a mortal man , but Jesus was brought back to life after he died. In the Koran it says that people are either good or evil and that has to kind of do with Adam and Eve and Abel. Jesus said that his religious tradition had long encouraged love toward other Israelites while going with hatred toward foreigners who had been unfriendly to his people. Jesus conveyed him self as knowing that he was gods suffering servant. I thought that this book was very informative but it really doesnt go along the lines of the kind of books that i usually read. It was a really hard book to read and it was hard to stay interested in. I gave up on this book about three or four times but i am glad i read it and i learned a lot.

Japanese Colonialism In Korea Essays - , Term Papers

Japanese Colonialism in Korea North and South Korea are nations that while filled with contempt for Japan have used the foundations that Japan laid during the colonial period to further industrialization. Japan's colonization of Korea is critical in underezding what enabled Korea to industrialize in the period since 1961. Japan's program of colonial industrialization is unique in the world. Japan was the only colonizer to locate various heavy industry is in its colonies. By 1945 the industrial plants in Korea accounted for about a quarter of Japan's industrial base. Japan's colonization of Korea was therefore much more comparable to the relationship between England and Ireland then that of European colonization of Asia or Africa. Japan's push to create colonial industry lead Japan to build a vast network of railroads, ports, and a system of hydro-electric dams and heavy industrial plants around the Yalu River in what is now North Korea. The Japanese to facilitate and manage the industrialization of a colony also put in place a strong central government. Although Japan's colonial industrialism in Korea was aimed at advancing Japanese policies and goals and not those of the Korean populace; colonization left Korea with distinct advantages over other developing countries at the end of World War Two. Korea was left with a base for industrializing, a high level of literacy, experience with modern commerce, and close ties to Japan. Japan's colonial heavy industrial plants were located primarily around the Yalu River in North Korea. Because of this the North had an edge in industrialization. For many years the North had the fastest growth rates of the communist countries, and its cities were on par with those of Eastern Europe. It was not until the early 1970's that the South surpassed the North in levels of industrialization. Because most of the heavy industrial plants were either located in North Korea or destroyed by the Korean War the groundwork for industrialization that South Korea received from Japanese colonialism consisted mostly of social changes. During colonialism Korea's populace in increasing numbers moved to cities and became urbanized these new urbanites worked in factories and were used to the organization of modern commerce. The Japanese also let a small number of Koreans develop into a semi-elite. Although this group never held powerful positions many of them were educated in Japanese schools, and became either involved in the military or worked as businessmen, bureaucrats, lawyers, and doctors. This elite provided much of the leadership and framework for post World War Two Korean Government in Korea. They had an intimate knowledge of Japanese companies, language, organizational structure, and government. The Korean elites that emerged after the liberation of 1945 and helped steer Korea's economic policies under Park Chung Hee had an intimate knowledge of Japan. Some of them like Park had been educated in Japanese schools, some had worked for the Japanese, and nearly all of them spoke fluent Japanese. It was this closeness to Japan both geographically and culturally that made it natural for the Koreans to use the Japanese model of industrialization when Japan's economy boomed in the 1960's and 1970's. The leaders of Korea were ambivalent about relying on Japan, on one hand they felt a profound respect for Japan and its successes and on the other a deep hatred for what Japan had done to Korea in the past. But Japan still served as a model for Park Chung Hee who normalized relations with Japan in 1965 and turned to Japan for technology, equipment, and a model for development. Some nationalistic Korean scholars say that Japan's colonialism slowed Korea's growth by exploiting Korea and disturbing its economy. But these views of Korea ignore the fundamental role that Japan's policies of industrial colonialism played in allowing Korea to Industrialize during the 1960's. Japan's colonialism improved infrastructure, urbanized the nation, educated much of the populace, gave the pubic experience with modern commerce, and indoctrinated Korean elites in the Japanese language and culture. It was Korean elites history and close ties with Japan that made them turn naturally to Japan to provide a development model. Japan's legacy of colonialism in Korea is felt not only in the many graves and monuments that attest to Japanese brutality but also

Free Essays on OSPF Terminology

OSPF Terminology Neighbor – A neighbor refers to a connected (adjacent) router that is running an OSPF process with the adjacent interface assigned to the same area. Neighbors are found by Hello packets. Adjacency - An adjacency refers to the logical connection between a router and its corresponding designated routers and backup designed routers. Link – In OSPF, a link refers to a network of a router interface assigned to any given network. Within OSPF, link is synonymous with interface. Interface – An interface is a physical interface on a router. When an interface is added to the OSPF process, it is considered by OSPF as a link. If an interface is up than a link is up. Link State Advisement – (LSA) is an OSPF data packet containing link state and routing information that is shared among OSPF routers. Designated router – (DR) is only used when the OSPF router is connected to a broadcast (multi-access) network. Backup Designated router – (BDR) is a hot standby for the DR on broadcast links. OSPF areas – OSPF areas are similar to EIGRP Autonomous Systems. Areas are used to establish a hierarchical network. It uses four types of areas. Area boarder router – (ABR) is a router that has multiple area assignments. An interface may belong to only one area. If a router has multiple interfaces and if any of these interfaces belong to different areas, the router is considered ABR. Autonomous system boundary router – (ASBR) is a router with an interface connected to an external network or a different AS. An external network or AS refers to an interface belonging to a different routing protocol. Non-broadcast multi-access – (NMBA) networks are networks such as Frame Relay, X.25, and ATM. This type of network allows for multi-access but has no broadcast ability like Ethernet. Broadcast (Multi-access) – Networks such as Ethernet allow multiple access as well as provide broadcast ability. Point-to-Point – This t... Free Essays on OSPF Terminology Free Essays on OSPF Terminology OSPF Terminology Neighbor – A neighbor refers to a connected (adjacent) router that is running an OSPF process with the adjacent interface assigned to the same area. Neighbors are found by Hello packets. Adjacency - An adjacency refers to the logical connection between a router and its corresponding designated routers and backup designed routers. Link – In OSPF, a link refers to a network of a router interface assigned to any given network. Within OSPF, link is synonymous with interface. Interface – An interface is a physical interface on a router. When an interface is added to the OSPF process, it is considered by OSPF as a link. If an interface is up than a link is up. Link State Advisement – (LSA) is an OSPF data packet containing link state and routing information that is shared among OSPF routers. Designated router – (DR) is only used when the OSPF router is connected to a broadcast (multi-access) network. Backup Designated router – (BDR) is a hot standby for the DR on broadcast links. OSPF areas – OSPF areas are similar to EIGRP Autonomous Systems. Areas are used to establish a hierarchical network. It uses four types of areas. Area boarder router – (ABR) is a router that has multiple area assignments. An interface may belong to only one area. If a router has multiple interfaces and if any of these interfaces belong to different areas, the router is considered ABR. Autonomous system boundary router – (ASBR) is a router with an interface connected to an external network or a different AS. An external network or AS refers to an interface belonging to a different routing protocol. Non-broadcast multi-access – (NMBA) networks are networks such as Frame Relay, X.25, and ATM. This type of network allows for multi-access but has no broadcast ability like Ethernet. Broadcast (Multi-access) – Networks such as Ethernet allow multiple access as well as provide broadcast ability. Point-to-Point – This t...

Upgrading of the Public Safety System of Rosa County Case Study - 1

Upgrading of the Public Safety System of Rosa County - Case Study Example Under the circumstance that the action of county authorities is influenced by changing circumstances around them, it can be said that the common strategic consideration that has necessitated the current action is that of market demand. The rationale for selecting market demand is that under this common strategic consideration, the need for change is always triggered by external and macro factors rather than internal and micro factors (Moore 32). Under this circumstance, the external factors calling for the change in the safety system of the county is the need to ensure that the county comes to such a level that can be standardized with global demands. Other macro factors including the need to advance in terms of the use of technology in the provision of safety and security have also triggered this change. As with all other market demand factors, once there is a response to what is needed by the market, stakeholders can expert growth and improvement (Moore 34). Such growth and improve ment are thus expected in the safety and security system of Rosa County. For the proposed project, a formal business requirement can be given as, â€Å"The Rosa County Public Safety Upgrading system requires the capacity to conform to modern technological demands for rapid response to safety issues. This system must bring to the people a guaranteed safety environment to go about their duties.† Value for money is a very important consideration for any form of the project, be it large, small or medium (Keen, 21). But to attain value for money, cost-benefit analysis plays the very crucial role. There are several ways of measuring cost-benefit, including quantitatively and qualitatively. In the instance of Rosa County, both methods can be applied to make a point as to whether the upgrading system will bring value for money. Once it brings value for money, then it can be said that the project is recommended for initiation.  Ã‚  

Latino Culture is Growing Research Paper Example | Topics and Well Written Essays - 1750 words

Latino Culture is Growing - Research Paper Example Latino culture is certainly changing, but it is the aim of this essay to provide evidence that Latino culture is growing within the United States and as such is becoming more influential and powerful than ever before. The hypothesis of this paper is that the literature will support the notion that Latino culture is growing within the United States, and as such the operational definition will seek to define the statement above by describing the number of Latin Americans in the United States and the areas in which their culture is growing. We will define the weight of the Latin American culture in terms of number and evidence provided within the literature that it is becoming more and more influential in all areas of cultural interest. According to our hypothesis, Latino culture is growing and as such we will expect the tests we do (in this case measuring qualitative and quantitative evidence for the growth of Latino culture) to support this, providing us with an operational definition . To understand the growth of Latino culture, it is important to understand what exactly comprises it. Latino culture at its most basic level involves anything cultural that can be found predominantly amongst those within the Latin American ethnic group. It also generally refers to movements that have come from Latin America directly, or modern adaptations of this. For example, Roman Catholicism is generally thought to be a large part of Latin American culture (Phol, 1998). Music is found within all cultures, and Latino culture is no different. Latino music generally refers to music made by those of a Latin American origin, whether it be traditional forms such as salsa or adaptations of more modern American trends such as hip-hop or rock music with a distinctly Latin flavour, such as involving traditional rhythms or singing in Spanish. Language is often associated with culture too, and we will look at how the Spanish language is the most important growing language in the United Stat es and how Spanglish (a fusion of Spanish and English) is becoming more common amongst Latin American and Anglo American teens. It is hard with Latino culture, as with any culture, to pin down exactly what makes it unique, as culture changes so rapidly. However, it is safe to assume that Latino culture can be attributed to those of Latin American origin and as such most of the cultural elements discussed within this essay will be those directly formed under the influence of people of this ethnic origin. It is widely recognised that Latino culture is growing, particularly within adolescent groups. Latino teenagers now have more spending power than Anglo teens, spending over $320 a month, which is 4% more than the average American teenager (Stapinski, 1999). This means that advertising companies have had to adapt and begin to target Latino adolescents to improve profit margins, and new advertising companies such as Lazos Latinos have started to appear, primarily targeting the Latino Y outh. With this increased targeted advertising, more elements of Latino culture have been reaching a wider audience, meaning that Anglo teenagers pick up on the trends that are currently defining Latino culture and as such the trends are spreading to a wider

Language and Autism Essay Example | Topics and Well Written Essays - 1000 words

Language and Autism - Essay Example In 1908, Eugen Bleuler a Swiss psychiatrist coined the word "autism" in schizophrenic patients who screened themselves off and were self-absorbed. Leo Kanner, while at Johns Hopkins, was first to describe autism in 1943 (Yazbak, 2003, 103-107). Leo Kanner described children with the following common traits: impairments in social interaction anguish for changes, good memory, belated echolalia, over sensitivity to certain stimuli (especially sound), food problems, limitations in spontaneous activity, good intellectual potential, often coming from talented families. He called the children autistic (Certec, 2004). A German scientist in 1944, Dr. Hans Asperger, described a milder form of the disorder that is now known as Asperger Syndrome. Asperger Syndrome (AS) (Asperger, 1944) is a subgroup on the autistic spectrum. People with AS share many of the same features as are seen in autism, but with no history of language delay and where IQ is in the average range or above (Baron-Cohen, 2004, 73-78). For a very long time, autism and psychosis continued to be confused and to this day parents are accused of causing the serious disabilities their autistic children have. For many years, researchers searched for the underlying cause of contact and language disorders, but they realized that the disability was more complex (Certec, 2004). Just et al. (2004, 1811–1821) suggest neural basis of disordered language in autism entails a lower degree of information integration and synchronization across the large-scale cortical network for language processing.

Tuberculosis: Prevention and Treatment

Tuberculosis: Prevention and Treatment Tuberculosis (TB) is an airborne infectious disease which is caused by strains of mycobacteria, mainly Mycobacterium tuberculosis1. There are roughly one third of the worlds population are infected with tuberculosis where nine millions of new cases reported annually2. Although tuberculosis can be prevented and treated, it continues to cause millions of deaths every year2. When infected individual coughs, sneezes or spits, M. tuberculosis is propelled into the air and infected those who breathed in the bacteria that existed in droplets of saliva3. Primarily, tuberculosis will affect the lungs, known as pulmonary tuberculosis3. It will also affect other parts of body, for instance lymph nodes, bones, brain and kidneys3. Once a person is infected with tuberculosis, there are basically three possible ways may occur. Firstly, the immune system plays a vital role and strong enough to kill the bacteria3. Secondly, immune system is not strong enough to fight off the bacteria but is able to b uild a defensive barrier against the bacteria3. Individuals who are latently infected with M. tuberculosis show asymptomatic where these bacteria lie dormant in the lungs and able to reactivate after years1. The disease is often reactivated in those who are immunocompromised or generally weakened. Lastly, the immune system fails to kill bacteria causing the bacteria to grow and spread towards other parts of body which is called active tuberculosis3. In the fight of tuberculosis, World Health Organisation (WHO) recommends universal Bacille Calmette-Guà ©rin (BCG) vaccination in the countries with high TB burdens4. BCG vaccine contains weakened form of M. tuberculosis which will induce human antibodies to fight against this type of bacteria. The efficacy of BCG vaccination can be ranging from 0% to 84%5. This may be due to the frequency of TB exposure and quality of vaccine used, leading to arguments on BCG vaccination efficacies4. One of the greatest arguments is that BCG vaccination causing positive reactions to tuberculin skin testing and hence interfere with the diagnosis of latent TB4. Existence of evidences showing the rates of efficacy also depends on geographical location, age at vaccination and form of TB further complicate the situation. Currently, TB chemotherapy is made up of combination of a list of first-line drugs isoniazid (INH), rifampicin (RIF), pyrazinamide (PZA) and ethambutol (EMB) 6. If the treatment fails d ue to bacterial drug resistance, or patient unable to tolerate, second-line drugs for instance para-aminosalicylate (PAS), fluoroquinolones, ethionamide and cycloserine are introduced6. These are considered as second line drugs generally either less potent with larger doses regimen or more toxic with serious side effects6. Tuberculosis is presently treated in two phases, namely initial phase and continuous phase7. In initial phase, the patient will be treated with concurrent use of four first line drugs, with the aim to eradicate or control bacteria population to replicate in rapid motion and also avoid the emergence of bacteria resistance7. The treatment choices available for initial treatment include isoniazid, rifampicin, pyrazinamide and ethambutol7. Streptomycin is used rarely but can be used in patients who infected with bacteria that are resistant to isoniazid before the therapy is commenced7. The duration for initial phase is 2 months whereas the continuous phase takes 4 months7. During the four months of continuous phase, patients are treated with isoniazid and rifampicin at same doses7. Most of the TB treatment is supervised where drug administration needs to be fully supervised by healthcare professions since lengthy duration of treatment causing incompliance in patients7. These patients who are unlikely to be compliance will be given the drugs three times a week until the course is completed while patients who able to comply with the treatment will not be supervised7. Despite the chemotherapy treatment and BCG vaccine, TB remains as a significant infectious disease due to increasing emergence of drug resistant TB and co-infection with Human Immunodeficiency Virus (HIV) 6. Since the host defense in HIV patients is suppressed, they are more susceptible to TB infections. Moreover, drug- drug interactions between antiviral therapy and anti-TB also causing complications in treating co-infected patients6. Drug resistant TB has evolved mainly because of improper treatment or incompliance in patients who stop taking their medications before the bacteria is being fully eradicated since the duration of treatment is lengthy which takes 6-9 months8, 9. The mechanism involved includes chromosomal mutations in genes that responsible for drug targets encoding9. When there is a sequential accumulation of mutations, multi-drug resistant tuberculosis (MDR-TB) emerges where the M. tuberculosis strains will resistant to two of the most commonly used drugs, Isoniazid and Rifampicin9. Patients with MDR-TB are then relying on the second-line drug classes, fluoroquinolones and the three injectable agents namely amikacin, capreomycin, and kanamycin10, 11. The chances to cure would dramatically be reduced for patients who infected with extensively drug-resistant tuberculosis (XDR-TB), a situation where the isolated strains are resistant against any one of fluoroquinolones and at least one of three injectable drugs6. In order to combat with the MDR-TB or XDR-TB and optimize the tuberculosis drug regimen, it is crucial to understand the mechanism of action of current using first-line drugs and how resistance is developed against these drugs. Isoniazid (INH) or isonicotinic acid hydrazide is discovered in 1952, a bactericidal agent which active against organism of the genus Mycobacterium, especially M. tuberculosis, M. bovis and M. kansassi6, 12. In vivo, INH has shown to be bactericidal in culture over the first 48 hours which become bacteriostatic after this particular time frame12. This indicates that INH is bacteriostatic for slow replicating bacilli but is bactericidal against rapidly dividing mycobacterium. The minimal tuberculostatic concentration is 0.025 to 0.05ug/ml13. INH is a prodrug that needs to be activated by catalaseperoxide hemoporotein, KatG before acts by inhibiting mycolic acid synthesis and cell wall disruption in susceptible mycobacterium13, 14. This inhibitory action is only targeted to mycobacteria since other bacteria do not contain mycolic acid in the cell wall13. INH acts by inhibit enoyl acyl carrier protein (ACP) reductase, InhA, and a beta-ketoacyl-ACP synthase, KasA that are crucial in fatt y acid synthesis system for mycolic acid15. Resistance to INH is believed due to mutations in gene encoding catalaseperoxidase katG or InhA or lacking KatG 9, 14. Isoniazid is metabolised in the liver, mainly by acetylation and dehydrazination where slow acetylator may experience higher concentration leads to potential toxicity before excreted in the urine within 24 hours13. Rifampicin (RIF), discovered in 1963, is a lipophilic semisynthetic derivative of rifamycin antibiotic which is produced by the fermentation of a strain of Amycolatopsis mediterranei6, 9, 16. RIF has bactericidal activities against a broad spectrum of microorganisms including gram-positive and gram-negative. RIF will inhibit the action of DNA-dependent RNA polymerase of mycobacteria that is encoded by rpoB through formation of a stable drug-enzyme complex9. This will suppress the initiation chain formation in RNA synthesis and hence prohibit protein synthesis in M. tuberculosis9. Development of resistance to RIF is mostly due to mutation in 81 base pair region of rpoB gene thus facilitate a straightforward approach to detect MDR-TB since 85-90% RIF-resistant strains are also resistant to INH9. RIF produces peak plasma concentration of 7ug/mL in 2 to 4 hours after ingestion of 600mg17. It also distributed well to most of the body tissues and fluids, including cerebrospinal fluid since it is lipophilic17. Following absorption from the gastrointestinal tract, RIF is eliminated rapidly in the bile with fewer amounts excreted through urine17. Pyrazinamde (PZA) is discovered in 1954 and it produces excellent sterility effects against semidormant tubercle bacilli at slightly acidic pH6, 9. The antimicrobial activity of PZA is through interference with mycolic acid synthesis in M. tuberculosis by pyrazinoic acid, an active moiety of PZA9. Conversion of PZA to pyrazinoic acid is mediated by pyrazinamidase enzyme that is encoded by pncA gene in M. tuberculosis, thus indicating that these bacilli are sensitive to PZA9. Resistance against PZA evolved when mutation occur at pncA gene that is responsible for pyrazinamidase, hence affecting the activity of this enzyme9. PZA is well absorbed from gastrointestinal tract and is widely distributed to most tissues and fluid too17. The oral administration of 500 mg PZA produces plasma concentrations of 9-12ug/ml after two hours and 7ug/ml after 8 hours17. PZA is metabolized in liver whereas the metabolites are excreted through renal glomerular filtration17. Ethambutol (EMB) is discovered in 1962, acts as bacteriostatic agent and is active against undergoing cell division6, 18. EMB primarily targets on impairment of cell wall polymerization by inhibits arabinosy transferase, a vital enzyme responsible for mycobacteria cell wall biosynthesis9, 18. Since arabinosy transferase enzyme is encoded by embC-embA-embB genes, resistance against EMB evolved is believed due to mutation of these genes9. EMB is currently used as one of the first-line treatment for tuberculosis mainly because of its synergistic effect with other front-line drugs and its low toxicity property18. There is roughly 75-80% of an oral dose of EMB is rapidly absorbed in gastrointestinal tract with absorption unaffected when administered with foods19. In addition, EMB is distributed widely to body tissues and fluid, including cerebrospinal fluid before being metabolized in the liver and excreted in urine19. Streptomycin (SM) is an aminoglycoside antibiotic, used as first line treatment for TB when it first discovered in 19441, 6. Streptomycin is isolated from the bacteria Streptomyces griseus and its antimicrobial effects against M. tuberculosis is highly effective when use in combination with other first line agents20. However, SM is no longer considered as first line treatment as resistance against it has developed rapidly1. The optimum pH for SM is at pH8 where its bacteriostatic activity will reduce with increasingly acidic environment20. SM acts by binding tightly to A site of 16S ribosomal RNA subunit, interferes with mRNA translation, causing faulty protein being produced1, 9. Resistant emergence when the mutation occurs at gene rpsL and rrs that encoded for 16S and S12 ribosomal protein1, 9. Upon administration, SM is poorly absorbed from gastrointestinal tract and mostly administered parentally1. SM is mostly excreted in urine and patients with low renal profile might experienc e toxicity such as neurotoxic reactions1. When the first line treatment is no longer suitable for patients or patients develop multi-drug resistance TB, second line drugs will then be introduced in combating the TB. Second line drugs that are mostly used include Ethionamide (ETH), Cycloserine (CS), Para-Aminosalicylic Acid (PAS) and Fluoroquinolones (FQ). ETH has been in use since 1960s, is a structural analogue of INH and it targets at inhibition of mycolic acid biosynthesis in tubercle bacilli9, 21. INH however is much more potent than ETH since the minimal inhibitory concentration for ETH is 0.5-5.0ug/mL21. Resistance evolved due to mutation at gene InhA and ethA which encode for oxygenase enzyme in activation of ETH 9. In vitro, CS has inhibitory effect on M. tuberculosis at 5-200ug/mL and there is no cross resistance occurred between CS and other drugs13. CS acts by interfereing the biosynthesis of bacterial cell wall13. CS is well absorbed in gastrointestinal tract and also widely distributed to body tissues and fluid including cerebrospinal fluid13. PAS was first introduced as first line drug but being replaced by Ethambutol in 1960s1. It acts bacteriostatically with possessing inhibitory effect at concentration less than 1mg/ml by interfere with folic acid metabolism in bacteria1. PAS is readily absorbed from gastrointestinal tract and distributed well throughout the body. Approximately 80% of the drugs will be excreted via kidney after being metabolized to acetylated form1. Moxifloxacin and Gatifloxacin are both been synthesized and evaluated as excellent bactericidal agents through inhibiting DNA gyrase, an ATP-dependent enzymes topoisomerase II which is responsible in bacteria DNA transcription9. DNA gyrase is consisted of two subunits that is arranged in a complex, is encoded by two different genes, gyrA and gyrB where mutations at gyrA will normally cause bacteria resistance to these new generation of flouroquinolones9. Due to the increasing incidence of multidrug resistance TB, it is highly desirable to develop new drugs that are not only potent and effective against current resistant strains of M. tuberculosis but also possess shorter treatment duration since most of the incompliance of patients is brought up by lengthy TB treatment. Most of the mechanisms of action of current treatments are involved in interfering the bacterial DNA synthesis, protein and mycolic cell wall biosynthesis. The enzymes that participate in these pathways could also be the target of newly designed drugs such as TMC207, one of the new drugs which are currently under investigations and clinical trials. TMC207 is a member of diarylquinoline class of compound which target at adenosine triphosphate (ATP) synthase by binding to subunit C of the synthase, blocking the energy pathway of mycobacteria22, 23. In vitro, TMC207 not only possesses ability to inhibit both drug sensitive and resistant M. tuberculosis isolates, but also able to sterilize the patient through killing the dormant bacilli bactericidally22. TMC207 showed a minimum inhibitory concentration of 0.03ug/mL against M. tuberculosis, suggesting a more potent agent compared to current first- line treatments such as isoniazid and rifampicin23. Apart from that, its synergistic effect with pyrazinamide could promise as effective drug combination for sterilizing the patients against TB22. A phase I clinical trials which involved short terms administration of TMC207 in healthy individuals showing no adverse effects and the subjects are well tolerated with it23. However, it is essential to investigate the selectivity of TMC207 again st mammalian ATP synthase with longer periods to ensure the patients safety when administered with TMC207. Thiacetazone (TAC) is widely used as second line anti-TB agent against multiresistant tuberculosis at present24. TAC acts by interferes the biosynthesis pathway of mycolic acid in tubercle bacilli24. The fact that M. tuberculosis has been difficult to eradicate and remains persistent is due to its cell wall that composed of mycolic acid which is resistant against chemical injury, dehydration and also has low permeability to antibiotics24. Mycolic acid contains cyclopropane rings that is activated through cyclopropane mycolic acid synthase (CMASs), has a significant contribution to tuberculosis24. By inhibiting the cyclopropanation, the cell wall biosynthesis will then be interrupted, introducing the bactericidal effects24. The aim of this research is to synthesis and evaluates the analogues of Thiacetazone which might be potential anti tuberculosis agents. The analogues will be tested against different strains of mycobacteria in lab. The target actions of these analogues will also be identified based on the structure of the analogues. The above analogue is synthesized when a benzylaldehyde reacts with a primary amine. This is a condensation process and an imine is produced. The changes at position R1 to R3 with different electron withdrawing groups are first planned to be evaluated. However, the plan is prohibited since the corresponding structures are either unavailable or too expensive that falling outside the budget. After revised on the previous analogues that were discovered and their respective MIC values obtained from lab, the structures of new analogues that are going to be evaluated are finally sorted out. The R1 to R3 positions would be replaced by either a -chloro or a -methoxy with R8 position would either be an amine, a methyl or a benzene ring. A chloro is used at position R1 to R3 since it is electron withdrawing, big and lipophilic molecule whereas the methoxy group is electron donating, small and quite lipophilic. For R8 position, an amine is selected because it is electron withdrawing and small. A methyl is also selected since it is quite lipophilic, small and electron donating. On the other hand, benzene ring which is highly lipophilic, neither electron donating nor withdrawing group might have a different effect on the analogue synthesized. References: Patrick Brennan, Douglas Young (2008). Tuberculosis. 88(2), 85-86, 137-138, 162-163. Health Protection Agency. http://www.hpa.org.uk/HPA/ National Health Services. http://www.nhs.uk/Pages/HomePage.aspx Zaida Araujoa, Jacobus Henri de Waard, Carlos Fernà ¡ndez de Larrea, Rafael Borges, Jacinto Convit (2008). The effect of Bacille Calmette-Guà ©rin vaccine on tuberculin reactivity in indigenous children from communities with high prevalence of tuberculosis. Vaccine 26, 5575-5581. Hart and Sutherland (1977). BCG and vole bacillus vaccines in the prevention of tuberculosis in adolescence and early adult life. Br Med J2(6082), 293-295. Global Alliance for TB Drug Development. http://www.tballiance.org/home/home.php 57th edition of British National Formulary: Section on Tuberculosis drugs, 316-317. Blumberg, H. M. et al. (2003). American Thoracic Society/ Centers for Disease and Prevention/ Infectious Disease Society of American: treatment of TB. Am.J.Respir.CareMed.167, 603-662. Suhail Ahmad and Eiman Mokaddas (2009). Recent advances in the diagnosis and treatment of multidrug-resistant tuberculosis. Respiratory Medicine 103(12), 1777-1790. Frieden TR, Sherman LF, Maw KL, et al. (1996). A multi-institutional outbreak of highly drug-resistant tuberculosis: epidemiology and clinical outcomes. JAMA 276, 1229-1235. Mukherjee JS, Rich ML, Socci AR, et al. (2004). Program and principles in treatment od multi-drug resistant tuberculosis. Lancet 363, 474-481. Zhang Y. et al. (2003). Isoniazid. Tuberculosis 2, 739-758. Hardmn, J.G., L.E. Limbird, P.B Molinoff, R.W. Ruddon, A.G. Goodman (2006). Goodman and Gilmans The Pharmacological Basis of Therapeutics. 9, 1164-1165. Zhang Y, Heym B, Allen B, Young D, Cole S (1992). The catalase-peroxidase gene and isoniazid resistance by Mycobacterium Tuberculosis. Nature 358, 591-593. Richard A. Slayden, Richard E. Lee and Clifton E. Barry (2002). Molecular Microbiology 38(3), 514-525. Rup Lal, Sukanya Lal (2005). Recent trends in rifamycin research. BioEssays 16(3), 211-216. Hardmn, J.G., L.E. Limbird, P.B Molinoff, A.G Gilman (2001). Goodman and Gilmans The Pharmacological Basis of Therapeutics. 10, 1278-1281. Raghunandan Yendapally and Richard E. Lee (2008). Design, synthesis and evaluation of novel ethambutol analogues. Bioorganic and Medical chemistry Letters 18(5), 1607-1611. McEvoy, G.K. (2007). Admerican Hospital Formulary Service. Besthesda, 551. Selman A. Waksman (1953). Streptomycin: Background, Isolation, Properties and Utilisation. Science, 118(3062), 259-266. Sampson AE, Barry CE (1999). Abstract General Meeting American Society Microbiology. 99, 635. Andreas H.D., Alexander Pym, Martin Grobusch et al. (2009). The Diarylquinoline TMC207 for Multidrug- Resistant Tuberculosis. 360(23), 2397-2405. Anna C. Haagsma, Rooda Abdillahi-Ibrahim, Marijke J. Wagner, Klaas Krab, Karen Vergauwen, Jerome Guillemont, Koen Andries, Holger Lill, Anil Koul, and Dirk Bald (2009). Selectivity of TMC207 towards mycobacterial ATP synthase compared with that towardsthe Eukaryotic homologue. Antimicrobial Agents and Chemotherapy, 53(3), 1290-1292. Anuradha Alahari, Xavier Trivelli, Yann Guà ©rardel, Lynn G. Dover, Gurdyal S. Besra, James C. Sacchettini, Robert C. Reynolds, Geoffrey D. Coxon, Laurent Kremer (2007). Thiacetazone, an Antitubercular Drug that Inhibits Cyclopropanation of Cell Wall Mycolic Acids in mycobacteria. PloS ONE, 2(12): e1343. Mycolic acids are a complex mixture of branched, long-chain fatty acids, representing key components of the highly hydrophobic mycobacterial cell wall. Pathogenic mycobacteria carry mycolic acid sub-types that contain cyclopropane rings. Double bonds at specific sites on mycolic acid precursors are modified by the action of cyclopropane mycolic acid synthases (CMASs). The latter belong to a family of S-adenosyl-methionine-dependent methyl transferases, of which several have been well studied in Mycobacterium tuberculosis, namely, MmaA1 through A4, PcaA and CmaA2. Cyclopropanated mycolic acids are key factors participating in cell envelope permeability, host immunomodulation and persistence of M. tuberculosis. While several antitubercular agents inhibit mycolic acid synthesis, to date, the CMASs have not been shown to be drug targets. We have employed various complementary approaches to show that the antitubercular drug, thiacetazone (TAC), and its chemical analogues, inhibit mycolic acid cyclopropanation. Dramatic changes in the content and ratio of mycolic acids in the vaccine strain Mycobacterium bovis BCG, as well as in the related pathogenic species Mycobacterium marinum were observed after treatment with the drugs. Combination of thin layer chromatography, mass spectrometry and Nuclear Magnetic Resonance (NMR) analyses of mycolic acids purified from drug-treated mycobacteria showed a significant loss of cyclopropanation in both the ?- and oxygenated mycolate sub-types. Additionally, High-Resolution Magic Angle Spinning (HR-MAS) NMR analyses on whole cells was used to detect cell wall-associated mycolates and to quantify the cyclopropanation status of the cell envelope. Further, overexpression of cmaA2, mmaA2 or pcaA in mycobacteria partially reversed the effects of TAC and its analogue on mycolic acid cyclop ropanation, suggesting that the drugs act directly on CMASs. This is a first report on the mechanism of action of TAC, demonstrating the CMASs as its cellular targets in mycobacteria. The implications of this study may be important for the design of alternative strategies for tuberculosis treatment.

The Euthyphro Dilemma Essay -- Philosophy Plato Euthyphro

The Euthyphro Dilemma In Plato's dialogue, 'Euthyphro', Socrates presents Euthyphro with a choice: `Is what is pious loved by the gods because it is pious, or is it pious because it is loved [by the gods]?' Euthyphro responds by asserting that piety is that which is approved [loved] or sanctioned by the gods; whence impiety is whatever is disapproved of by the gods. However, as Socrates points out, the question poses a dilemma for those who believe as Euthyphro does that Truth is revealed by divine authority alone. Now, a dilemma is an argument forcing a choice of two unfavourable alternatives. The important point here is that the alternatives must be equally unfavourable. Simply to be faced with two alternatives is not to be faced with a dilemma. To appreciate why each of the options set out above are unpalatable for Euthyphro, we need to unpack the import of each alternative carefully. In drawing out the implications of Socrates' argument, I intend to substitute the word `God' for Plato's `gods'; this change will not affect the potency of the argument, and will make the dilemma more topical and relevant to the modern reader. Essentially, the dilemma faced by Euthyphro is this: If it is maintained that certain actions and dispositions are good simply because God favours them, then it seems that the distinction between good and evil, right and wrong, is purely arbitrary; for no reason can be given why God should favour one kind of action rather than another. The distinction is solely a matter of God's `taste', just as it is a matter of my taste that I prefer prawns to oysters. As no reason can be given why God should favour, say, justice and kindness, he might equally have favoured their opposites. In which case ... ...d so, the dilemma has not been resolved completely after all. Undoubtedly, anyone holding a theistic conception of morality must find some place for divinely revealed moral commands; but it may be that in so doing the theist weakens their resolution of the dilemma. On the one hand, they want to say that the question of whether an alleged special revelation concerning moral matters comes from God is to be answered in the light of our rationally established criteria of good and evil. This suggests that morality has no need of revelation. On the other hand, they want to say that, for the theist, ultimate questions of good and evil cannot be answered apart from reference to special revelation. This suggests that, in the final analysis, our reason is inadequate as a source of the knowledge of good and evil. It is hard to see how the theist can have it both ways.

Royal Wedding Media Coverage

Example of a great media coverage The Royal wedding in 2011 Many PR specialists define the Royal Wedding of Kate Middleton and prince William as the PR event of the year. It is a proof that a well- managed event can resonate for months or even years. It has set the beginning of the reputation building of this new family. As Pagefield's founder and senior partner Mark Gallagher argues, the event not only promoted the young couple, but also gave the monarchy, London and the UK a boost. Before the event, there was an estimated number of 8500 journalists expected to arrive in London from abroad.More than 36 broadcasters, such as BBC, Sky News, ABC, NBC, CBS, Al-Jazeera etc. ; were housed in a special structure, built close to the Westminster Abbey, where the wedding took place. Apart from nearly 2000 guests, 40 broadcast cameras, 12 photographers and 28 reporters from national, international and regional media were expected. More than 100 overseas broadcasting organizations were transmit ting the event. BBC had the biggest broadcasting presence with around 550 people staff at a cost of ? 2 million. The US networks have begun their coverage at 3 a. m. n the west coast. 64% of Americans said that they believe that the event has received too much attention in the media, however 28% of US citizens have admitted that they have followed the wedding very closely. The wedding’s audience has reached 2 billion people worldwide. According to Google, there are over 162 million web pages mentioning the wedding. It was estimated to bring ? 630 million into the economy. All these facts are a proof that the event has received great, or even excessive media ; editorial coverage worldwide and has reached a huge number of people.This has probably turned it into the TV (PR) event of the century. An example of the number of articles that only CNN has concerning the Royal wedding: http://edition. cnn. com/SPECIALS/2011/royal. wedding/ . —————â₠¬â€Ã¢â‚¬â€Ã¢â‚¬â€Ã¢â‚¬â€Ã¢â‚¬â€Ã¢â‚¬â€Ã¢â‚¬â€Ã¢â‚¬â€Ã¢â‚¬â€Ã¢â‚¬â€œ [ 1 ]. http://www. prweek. com/uk/features/1124547/the-power-books-top-5-pr-campaigns-2011/ [ 2 ]. http://www. guardian. co. uk/uk/2011/apr/28/royal-wedding-media-tv-audience [ 3 ]. http://www. guardian. co. uk/news/datablog/2011/apr/29/royal-wedding-numbers-figures

Claudio Monteverdis Orfeo and the development of Baroque Op essays

Claudio Monteverdis Orfeo and the development of Baroque Op essays Any aspiring musician in this day and age should expect certain things from opera productions; drama, lyricism, and sensitive instrumental accompaniment. But if we observe operas written in the 16th century, we will find a very different style of vocal drama, a formality and dryness that has all but vanished in operas developing past the baroque, classical, and romantic eras. Then, is it possible to trace the seeds of expressive opera back to a specific work or composer at the dawn of the baroque? When asked to consider this question, the opera Orfeo, and its composer, Claudio Monteverdi, inevitably comes to mind, as possessing these seeds for future growth. But how can one justify giving credit to Orfeo, and to Monteverdi, for such radical change in the opera world over the years to follow? _____Before Monteverdi entered the baroque opera scene (which was early in the 17th century), opera was established as a lavish and extravagant, although not entirely refined art. Evolving from the intermedi and the madrigal-cycles of the late 16th century, opera was reserved for royalty and their special events, and was more theatrical than musical. Opera relied on costumes and scenery to bedazzle the audience, rather than the expressive lines that Monteverdi would later write into his recitatives (Grout 277-278). Instrumentation was sparse, and usually unspecified. Composers and scholars alike could not agree on the extent to which Greek theatre (almost exclusively emulated in opera and theatre at the time) should be sung, or performed. A Florentine scholar named Girolamo Mei theorized that the entire drama should be sung, in his books De Modis Musicis. Most of Mei's research took place in the 1560s, and was later discussed by an informal gathering of scholars in Florence kn own as the Camarata, lead by Giovanni Bardi (Grout 279-180). At the same time in Mantua, Cesare Gonzaga (Duke of Guastalla) founded the Mantuan Academy (the group...

Het Behouden Huis essays

Het Behouden Huis essays Ik heb dit boek gekozen nadat ik de achterkant had gelezen, hierop stonden een paar uitspraken over dit boek die mij nieuwsgierig maakten, zoals bijvoorbeeld: het behouden huis heeft zeker niets kinderlijks en dient zeer nadrukkelijk voor volwassenen te worden voorbehouden. Jos. Panhuysen, Het Binnenhof 10-5-52. of Het is in het geheel niet aangenaam om te lezen . Het boek van Anne de Vries zal dat voor de meeste meer zijn. Jos. Panhuysen, De Gelderlander 21-5-52. Ik had nog nooit van deze mensen gehoord maar toch wilde ik graag weten wat ze met deze uitspraken bedoelden. Ook is het een boek dat over de oorlog gaat, wat ik altijd een interessant onderwerp vindt om over te lezen. Ik verwachtte een spannend boek waar veel in gevochten zou worden, maar na het lezen bleek het een vrij saai boek te zijn dat eigenlijk helemaal niet leuk is om te lezen, net als verteld werd in de recensies. Als soldaat in een partizanen leger ergens in Oost Europa bevrijdt de hoofdpersoon een dorp, In het leger zelf heeft hij geen vrienden, hij kan de meeste mensen zelfs niet verstaan. De enige waar hij een beetje contact heeft is een Spanjaard die hij Yesero noemt, ook al is dat niet zijn echte naam. In het dorp krijgt hij van zijn sergeant opdracht te gaan zoeken naar boobytraps, en tijdens zijn tocht door het dorp ziet hij een mooi huis staan. Hij gaat naar binnen en verbaast zich erover dat alles nog zo netjes en onderhouden is, er is zelfs nog warm water. Als hij een tijdje in het huis is en een warm bad genomen heeft besluit hij dat hij hier blijft wonen en zich uitgeeft voor de eigenaar van het huis. Op een gegeven moment staat er een Duitse officier bij hem aan de deur die hem vraagt of er Duitse soldaten in het huis gestationeerd mogen worden. Hij stemt toe om zichzelf niet te ve ...

CLIMATE CARS MARKETING REPORT Essay Example | Topics and Well Written Essays - 2500 words

CLIMATE CARS MARKETING REPORT - Essay Example and also, for rented cabs in the country. At the end of the research, the paper would comment on the tactical ways through which climate cars can augment their performance in the next three years. The learnt from the essay would help to analyze the significance of marketing and its development over time. The essay will also give a detailed view of the nature of the automobile industry in U.K. Contents Growth of science and technology over time has proved to be advantageous for modernization in the world. Living standards of the individuals have radically improved with the contribution of modern technologies. However, with time, ecological balance of the environment is depleting substantially. This paper would try to focus on ‘Climate Cars’, which is a company engaging in providing eco-friendly transport services in United Kingdom (U.K.). The report would perfectly analyze the market for eco-friendly transportation in U.K. and also, for rented cabs in the country. At the end of the research, the paper would comment on the tactical ways through which climate cars can augment their performance in the next three years. The learnt from the essay would help to analyze the significance of marketing and its development over time. The essay will also give a detailed view of the nature of the automobile industry in U.K. ... Educated individuals in the contemporary world are taking prompt initiatives to ensure protection and preservation of environment. This report would try to focus on the business of ‘Climate Cars’, which is a company engaging in eco-friendly transportation services in United Kingdom (U.K.). At the end of the research, the paper would comment on the strategic ways through which climate cars can enhance their performance in the next three years (Hakim, 2000). The learnt from the essay report would help to examine the importance of marketing and its evolution over time. However, the paper would also put some emphasis on the growing consciousness of environmental protection nowadays (Casals and Garcia, 2013). History of Eco-Friendly Transportation in United Kingdom After the World War, Industrial Revolution had increased the aggregate demand and wealth thresholds in the market. From 1950 to 1979, number of vehicles in U.K. had increased by 500%. It was at this point of time w hen Transport Planning became a crucial segment of engineering in U.K. After the global oil crisis in 1973 and the global energy crisis in 1979, the market analysts in U.K. had started understanding the importance if Sustainable Transportation (Parker, 2009). Since then, many private companies had started to contemplate manufacturing hybrid cars in U.K. Figure 1: First Electric Car (Source: Parker, 2009) The above picture is of the first electric car built by a Victorian inventor, Thomas Parker. Over time, there were many companies who have engaged in the manufacture of electric cars in the market. Analysis of the Present Market At present, there are many multinational companies that operate in the market of U.K. for

Innovation and Tradition in French Music since 1920 Essay

Innovation and Tradition in French Music since 1920 - Essay Example The various elements which began to be incorporated into this style worked with new sounds and methodologies of the works while adding in a sense of innovation that broke from the musical traditions of the past. French Music in the 1920s The importance of Les Six in the 1920s of France was important not only because of the changes in classical music. There were also attempts to express the political and social changes that were occurring within France and at a global level. France was currently experiencing the political movements of revolution and war, specifically which began to emerge in the late 1800s. The time period which led to more experimentation was after World War I. The general ideology of those that were in France during this time was based on finding a sense of freedom from the past of politics with an understanding of the complexities from the suffering of war as well as the new philosophies based on freedom. This led to the exploratory nature of the music and the new expressions which showed the modern complexity of the time. The war, as well as the corruptions in politics was then able to guide in new philosophies and ideologies into a sense of modernism1. With the changes in politics, were also alterations in identity among the French culture. This was based on the ideas of nationalism, specifically which expressed a new ideology by understanding that France needed to regain an identity outside of the wars that were being fought. The ideal of patriotism of France, as well as the identity of changing the cultural aspects that were associated with France became the main objectives. This was combined with the concept of modernity, specifically which came from the growth of the industrial era. France created an ideology of identity based on moving into innovation and modernity, as well as placing this around the pride for the country. The reflection in the music was then based on the ideals of innovation and experimentation that could represent th e new French style2. Background of Les Six Les Six began to develop in 1917, with the leader of the group, Jean Cocteau. This French composer took the names from the Russian and German movements which were also interested in experimentation and innovation. However, the ideals moved against the other experimentation aspects, such as from Richard Wagner. The individuals who made this group included Georges Auric, Louis Durey, Arthur Honegger, Darius Milhaud, Francis Poulenc and Germaine Taillefaire. It was noted that the importance of this group was based not only on the ideal of composition with a rebellion of other types of music. More important, there was a creation of commercial advertising and an understanding that the music made would be French and for those interested in creating a specialized type of music that represented the nation3. The basics of Les Six not only were based on the six individuals who held specific relationships to the music and what was occurring. There was also a direct association with the outside influences, which the group began to accept or reject as a part of their works. The first way in which this was done was through the outside influences and theories that began to enter Paris as it became a world – renowned place for travel. The World fair of 1894 as well as the fluctuation of individuals visiting the region from around the world began to move those interested in music into new theories. American, Russian and German influences were three of the strongest areas which began

Animal welfare Research Paper Example | Topics and Well Written Essays - 1000 words

Animal welfare - Research Paper Example ey use physiological measures such as plasma cortisol, endorphins, and the heart rate to determine the ability of the animal to cope with the environment. Seeing animal welfare in terms of the body has limitations such as (a) environment and genetics can create wanted physical outcomes but the animal’s mental state is in jeopardy, (b) some physical parameters such as plasma cortisol and heart rate are difficult to interpret because they can be influenced by the negative and positive experiences (Hewson 496). Animal welfare thus integrates the state of the animal’s body and the feelings. Feelings such as fear and frustration form the basis of the animal welfare; if the animal is feeling well then it is faring well. Feelings in animal welfare measures the outcomes like behavior; behavioral outcomes entail things such as the willingness to work and behavioral signs such as frustration and fear (Hewson 496). One of the biggest problems in the animal welfare is how animals are transported and slaughtered. For many years people have been transporting and slaughtering animals. Animals have provided everything mankind has needed like food, and clothing. The modes of transport and slaughter have been inhumane with some of the people subjecting the animals into situations that were unbearable. The animals are left or die in devastating situations; terror, exhaustion, and injury are the outcome of such brutality (Council of Europe 55). It is very difficult and tiresome to convince large animals to go into a certain direction particularly up in a ramp. On the other hand, smaller animals such as the chicken are not exceptional and they can be frustrating. Bone fractures and bruises are common when the meat birds are being harvested for slaughter; they are usually grabbed by the legs and a number of them get injured or bruised in the process (Spedding 51). The major problems in the slaughtering of animals are the lack of pre-slaughter stunning in kosher (schechita) and

Chronology in ‘A Rose for Emily’ Essay Example for Free

Chronology in ‘A Rose for Emily’ Essay William Faulkner takes into account the ever-complicated concept of time in â€Å"A Rose for Emily†. It is a manifestation his contemplation on the nature of time. It lacks a standard chronology. Faulkner ensnare almost three quarters of century in a few page story. He does it superbly by avoiding a proper chronological order. Faulkner skillfully put the story up to demonstrate the indefinable and intangible character of time. He constructs it in such a subtle manner that it is hard to detect any chronological order of the plot. Time does not flow in a linear direction but take a circular direction with the progress of story. Fault consciously or unconsciously does not concern himself with specific dates. A handful of explicit dates are cited in the story. But these indications reveal as plenty of information about the linear chronology of the vents. For example, it is quite clear that remittance of Emily’s taxes by Colonel Sartoris takes place in 1894. It is further provided that he is dead for the last ten years and this the time Emily meets the new aldermen. Story further discloses that Emily died at 74. This hint capacitates us to construct a linear chronology of the events. The linear sequence of events in Emily’s life is as follow; Section 4 illustrates her birth during civil war. Section 2 describes a joint ride with her father in an old wagon. Her father dies. Homer Barron appears on the scene and an amorous affairs starts with Emily in section 3. She purchases male lavatory set and outfits for him in section 4. We are again forced to revert back to section 3 when town people degrade him and reverted back and summon her cousin. Section 4 is marked with the arrival of cousins and departure of Homer from the town. He returns back after the exit of her cousins. We again slip back to section 3 where Emily purchase poison from a local vendor and Homer disappears in the next section. Section 2 illustrate stink from her house indicating his death and four aldermen are shown sprinkling water on her grave. Faulkner has used a novel narrative technique as story starts with Emily’s funeral (the end) and concludes with the finding of Homer’s rotten dead body. Faulkner’s concept of time and its effective utilization does not weaken the story but it is the most obvious strength of its plot, construction and thematic expressions. Although presentation of time in this manner is mostly related is subject to philosophical orientation of the author but it had deep impact on the plot. He merges past into present and present into past and this feature of the story captivates the reader. â€Å"Faulkner gives the story a chronology, but as with so many of his stories, we have to sort it out† (McGlynn 461); Furthermore, it hinders the formulation of reader’s judgment about Emily till the end. The effects of this non-linear chronology on the story are beautifully summed up by McGlynn (1969). He says that â€Å"A chronology of ‘A Rose for Emily’ is useful for at least two reasons: it makes the plot more easily comprehensible, and it helps clarify the function of time in the story† (461). By evading a clear and linear chronological order of events, Faulkner attempts to provide his reader a riddle comprised of various bits. However, he provides clues to facilitate this puzzle-solving. The motive behind this exercise seems to involve his reader more deeply in the story. So above-mentioned arguments and supported evidence clearly suggest that time is not present in a simple chronological way in the story but it is manifested in random manner and plot flows with the flow of the consciousness of the narrator and does not follow the rules and principle of chronological time. Works Cited Faulkner, William. 1970. A rose for Emily. Columbus; Merrill. McGlynn, Paul D. 1969. William Faulkner: An Interpretation; The Chronology of A Rose for Emily, Studies in Short Fiction. 6.

Chronic Opiod Use after Hysterectomy

Chronic Opiod Use after Hysterectomy Specific Aims The rapid increase in the incidence of opioid-related overdoses and deaths has become a big public health threat in the United States. This opioid epidemic affects more women than men due to higher opioid prescribing and dose, longer period use, and more opioid dependence in women.1 From 1999 to 2010, the rate of opioid overdose caused death increased 5-fold among women.2 Besides the illicit purchase for some women, the initial exposure to opioids for many others may likewise come from the regular medical treatment as prescription opioids are widely used for pain management after surgery.3 As such, the critical research gap on opioids use is that the evidence is insufficient to draw conclusions about optimal strategies for initiation and titration of opioid therapy.4 Several observational studies have investigated the patterns of opioid use for noncancer pain in patients pre and post-surgery, and identified the risk factors of chronic opioid use post-surgery.5-11 Most of these studie s examined the prediction of baseline demographic and clinical characteristics of patients for prolonged opioid postoperative use and suggested that surgery is a risk factor for chronic opioid postoperative use.5-9 Only two studies examined the initial opioid exposure within 6 or 7 days of the surgery date and results are controversial.10,11 One study reported that initial exposure of opioid poses 44% increase risk of chronic postoperative opioid use and another one suggested that this risk would be low and statistically insignificant.10,11 Similar investigation has not been done specifically for hysterectomy, the most frequently performed non-obstetric surgeries in the United States for women of reproductive age.3,12 Pain has been demonstrated as a common symptom before and after hysterectomy.13,14 A small cross-sectional study has examined the predictors for opioid prescription in women of productive age and identified that opioid use was significantly associated with hysterectomy status and pain-related dysfunction.15 Another cross-sectional survey study reported that 32% patients had chronic pain after hysterectomy.14 Neither chronic opioid postoperative use nor initial opioid exposure for acute surgery pain was examined in these two studies.14,15 Filling this gap in knowledge is critical since identifying the risk factors of chronic opioid postoperative use could lead to optimized initial opioid prescribing for acute pain management and reduced chronic opioid postoperative use and improved women health. Our long-term goal is to help reduce chronic use of opioids and optimize the pain management in women after obstetric and gynecologic surgery through identification and dissemination the safer initial opioid prescribing for acute post-operative pain. Our objective here, which is the next step in our long-term goal, is to compare the patters of opioid use pre and post hysterectomy and determine the important risk factors that associate with chronic use of opioids in women post hysterectomy. The national OptumInsight Clinformatics data offers an essential resource to investigate these aims. The availability of clinical diagnoses and pharmacy medical dispensing offers a significant advantage for investigating drug utilization with corresponding clinical conditions in large population. Our team is well suited to conduct this research given extensive expertise in contemporary pharmacoepidemiology, many years of experience on opioid abuse research, prior drug utilization studies using large claims data, and clinical expertise from obstetric and gynecologic physicians. Our specific aims are to investigate patterns and predictors of chronic opioid use in women pre and post hysterectomy with the following analyses: Aim 1: To characterize the patterns of chronic opioid use in women after hysterectomy. Aim 2: To determine the significant risk factors for chronic use of opioids in women after hysterectomy. The first specific aim for this study is to identify patients who chronically take opioids during six months post hysterectomy, and investigate the time and geographical patterns of chronic opioid use in women after hysterectomy. The pattern of chronic opioid use pre- and post-surgery will also be compared in women with varied age, comorbidities, co-medications, as well as types and doses of initial opioid prescribing. The second specific aim is to determine the risk factors that significantly relate to chronic opioid use, and determine if characteristics of initial filled opioid prescriptions significantly associate with the chronic use of opioids after adjusting for other potential risk factors. Many pain related studies have demonstrated that long term opioid prescribing was significantly predicted by patients clinical characteristics and psychosocial factors, including pain conditions, psychiatric disorders, frequency of medical visits, smoking, and pain-related dysfunction.16-18 Therefore, the adjusted covariates in this study would include both demographic and clinical characteristics. B. Significance and Innovation Currently the United States is experiencing an unprecedented opioid epidemic. According to the Centers for Disease Control and Prevention (CDC), opioid-related deaths increased 200% overall from 2000 to 2014.19 During 2014, about 1.9 million people had an addiction of opioids, with overall 47,055 overdose deaths, 18,243 overdose deaths in women, and 18,893 overdose deaths related to prescription pain relievers.20,21 Based on the data reported by the CDC, women are more likely to have chronic pain, be prescribed opioids with higher dose and longer period, and hence progress to dependence.22 Although opioid abuse is a public health crisis, opioid analgesics are still the mainstay for treatment for acute pain after major surgery. In 2014, total 245 million prescriptions for opioids were dispensed from U.S. retail pharmacies.23,24 During 1998-2010, approximately 7.4 million hysterectomies were performed, making hysterectomy one of the most frequently performed surgeries for women in the United States.25 With over 60% of hysterectomies performed abdominally and up to 85% of patients experiencing moderate-to-severe pain after hysterectomy, postoperative pain management becomes very important.26,27 Evidence suggests that intense and long-lasting postsurgical pain can increase postsurgical morbidity, delay recovery, and lead to chronic pain.28 Opioids such as morphine, meperidine, and oxycodone are widely used postoperatively to reduce and manage pain in patients after hysterectomy.29 Women with hysterectomy and high levels of pain-related dysfunction were almost twice as likely to have opioid prescription. More than 85% of women with hysterectomy and a high level of pain-related dysfunction were found to use opioid.15 Hormonal disturbance, hyperalgesia, and iatrogenic effects are potential adverse effects from op ioid use in women after hysterectomy.14,15 The interaction of opioid-induced adverse effects and post-hysterectomy hormonal dysregulation may intensify pain and promote continued use of opioids.15 There are no known studies that evaluate the connection between acute and chronic postsurgical opiate prescription in women experienced hysterectomy. In consideration of the current opioid epidemic it is important to understand how post-surgical pain is managed, and if this setting presents increased risk of opioid addiction among certain groups, or related to particular prescribing practices. The goal of this proposed study is to examine whether opioids prescribed in women following hysterectomy is associated with chronic use of opioids, and to evaluate which factors may predict patterns of opioid use that indicate overuse or addiction. Accordingly, this study first aims to describe the incidence pattern of chronic opioid use in women post hysterectomy. The second aim is to explore the significant risk factors and determine if the characteristics of initial opioid prescribing significantly associate with chronic opioid use after adjusting for other potential risk factors. This study will reveal important insights regarding post-surgical pain management for a common procedure, and determine if certain patient or treatment characteristics increase the risk of chronic opioid use in this setting. We expect that this research will provide evidence for the need to improve clinical practice towards optimized pain management and reduced chronic opioid use in women after hysterectomy through identification the specific opioid, drug type (short-acting or long-acting), and doses that significantly associate with chronic opioid use in women after hysterectomy. Our study will provide sufficient evidence to draw conclusion about optimal strategies for initiation and titration of post-surgery opioid therapy, and enhance evidence-based medicine for opioid use in Rhode Island, and also the United State. This award would enhance my capabilities on handling interdisciplinary studies and further help me to develop my own research projects and seek for external funding. Innovation Our proposed observational studies based on the administrative claims data will allow for investigation of time trends and geographic variation of drug use in large population and address for well-characterized clinical conditions. Our approach will employ state of the art, innovative pharmacoepidemiologic study designs and statistical models, to improve the precision of outcome definition and minimize measured and unmeasured confounding and bias in our estimation of significant predictors for chronic opioid use after hysterectomy. The unintended outcomes from adverse drug effects make the prospective trials unethical. In this circumstance, a well-designed, retrospective observational study with sufficient sample size offers an efficient design to determine if there is an adequate signal for impropriate opioid prescribing to women post obstetrics and Gynecology surgery. The generalizability of study results are guaranteed due to the nationwide large health plan data that the analyses are based upon. C. Approach Data Sources Study data will be derived from the national OptumInsight Clinformatics Data MartTM, a research database spanning January 01, 2010 through December 31, 2013. The Optum Research Database includes about 23 million beneficiaries from the nationwide commercial health insurer, United Healthcare. The data contains health care utilization with transactional reimbursement data from outpatient pharmacy dispensing, inpatient and outpatient services.30 It links administrative enrollment data with the important medical codes including the national drug code (NDC) for pharmacy dispensing, the Current Procedural Terminology (CPT) code for medical procedure, and International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code for diagnosis. The claims data in this database have been adjudicated, ascertained, and deidentified for research purpose. The University of Rhode Island (URI) and OptumInsight Inc have approved utilization of these data. URI already licenses thi s database that it is freely available for faculties to use. Study Population This study will include adult women who receive the hysterectomy surgery between July 01 2010 and June 31 2013 and have at least 6 months of continuous prior coverage under this health insurance plan. This continuous 6-month coverage provides a baseline for defining new drug users, as well as baseline clinical characteristics, such as comorbidities and co-medications. The hysterectomy procedures will be derived from the ICD-9-CM diagnostic codes 68.3x-68.7x, and 68.9x, where 68.3x indicates a subtotal abdominal hysterectomy, 68.4x indicates a total abdominal hysterectomy, 68.5x indicates a vaginal hysterectomy, 68.6x indicates a radical abdominal hysterectomy, 68.7x indicates a radical vaginal hysterectomy, and 68.9x indicates other and unspecified hysterectomy.13,31 Patients with pelvic evisceration (ICD-9-CM: 68.8x) will be excluded. We also will exclude patients with any cancer diagnoses, including malignant neoplasm of the female genitourinary organs-cancer (ICD-9-CM: 179-184), a nd carcinoma in situ of female genitourinary system (ICD-9-CM: 233). Exposure Assessment Opioids in this study include the following medications: codeine, fentanyl, hydrocodone, hydromorphone, meperidine, methadone, morphine, oxycodone, and oxymorphone. Tramadol and propoxyphene, considered as weak opioids or already off market, will not be included.11,15 The exposure group involves adult women who receive the hysterectomy surgery and fill more than one prescription for opioids on the day of hospital discharge or within 7 days after hysterectomy surgery, provided that they have no exposure to opioids for at least 6 months prior to hysterectomy.11 The 7 days of window is based on the assumption that a filled prescription during this period would likely to treat acute postoperative pain caused by hysterectomy. A comparison group, defined as the patients with no opioids use on the day of hospital discharge or within 7 days after hysterectomy surgery, will serve as a control to make a comparison of risks for chronic use of opioids. The control patients also have no exposure to opioids for at least 6 months prior to hysterectomy. The exposure of opioids will be identified using NDC codes from pharmacy claims data. In this study, exposure assessment includes all characteristics of the initial filled opioid prescription at the day of hospital discharge from hysterectomy or during 7 days post-hysterectomy. The different type of opioids (classified as long or short acting), number of supply days, and oral morphine equivalent daily dose (milligrams) will be assessed and analyzed. Outcome Assessment Since the study focuses on the risk of chronic opioid use after initial exposure to opioids following hysterectomy, patients were followed from the 8th day after hysterectomy to the first day of outcome occurrence. The outcome, chronic use of opioids after hysterectomy, will be defined using trajectory models.11 in which patients with similar patterns of medication filling during follow-up will be grouped together. The trajectory model was initially generated for the purpose of the assessment of medication adherence.32,33 In order to classify the trajectory groups for opioid use during the defined follow-up window, we first generate 6 dichotomous variables to indicate if a study participant fills a prescription of an opioid medication during each of 6 consecutive 30 day follow-up periods.11 we then model these 6 binary indicators of using opioids in each 30 day follow-up period as a longitudinal response in a logistic group-based trajectory.34,35 With a trajectory model, we will estimate the probability of membership of patients in each group, and the probability of the certain opioid exposure over time as a smooth function of time. We will fit the model using 2 to 4 opioid exposure groups with comparison of the Bayesian Information Criterion.36 The number of groups will be chosen based on the value of the Bayesian Information Criterion. In each group, a third-order polynomial (including linear, squared, and cubic terms) of time will be used to model the probability of being exposed to opioids. Patien ts will be assigned to different trajectory groups, which are generated from these models and have highest probability of the membership. Based on the model results, the group of patients with the highest probability of filling opioids over time will be defined as the chronic use. Other trajectory groups were classified as nonchronic users. The trajectory models provide new advanced approaches to utilize the observed data to determine distinct filling patterns of opioids in our study population during the year after hysterectomy surgery. It classifies patients into groups with similar opioid exposure patterns without relying on a priori and subjective cutoff line for the definition of chronic opioid use. The trajectory models will be conducted using SAS Proc Traj (SAS, version 9.4, SAS Institute Inc., Cary, NC, USA). Patterns of Chronic Opioid Use After chronic opioid use is defined using trajectory models, we will compare the frequency of the incidence of chronic opioid use over time from 2010 to 2013. The secular trend will be analyzed using Joinpoint regression program (National Cancer Institute, Calverton, MD) to identify the joint points and slopes. The rates of chronic opioid use in women post hysterectomy will also be compared with varied age, comorbidities, co-medications, as well as characteristics of initial opioids exposure, including opioid types and doses. The geographic variation of chronic opioid use will be mapped and analyzed using ArcGIS 10.5 geographic information systems software (ESRI, Redlands, CA). The opioid prescription policies and socioeconomic status in different states will be compared with the geographic variation of chronic opioid use. Predictors of Chronic Opioid Use We will identify the predictors of chronic opioid use at baseline or the time of the initial opioid prescription. A previous study demonstrated that hysterectomy, older age, and higher levels of pain-related dysfunction were associated with opioid prescription.15 Potential predictors in this study would include age, year of surgery, smoking, illicit substance abuse, alcohol abuse, hysterectomy type, psychotropic medication use, pre-operative depression, pre-operative pain condition, primary indication for hysterectomy, co-medications, and characteristics of the initial opioid exposure. Although the benefits of minimally invasive surgical procedures have been documented,37 hysterectomies performed for benign indications in 2010 in the US still consisted of 40.1% total or subtotal abdominal hysterectomies, 30.5% laparoscopic hysterectomy, 19.9% vaginal hysterectomy, and 9.5% robotic-assisted hysterectomy.21,25 Hysterectomy type has been related to the initial opioid prescription,15 how ever, the results from randomized clinical trials showed that abdominal hysterectomies didnt increase postoperative chronic pain.38,39 The primary indication for hysterectomy is defined based on the following algorithm: (i) precancerous conditions will be assigned the primary indication if endometrial cystic hyperplasia or carcinoma in situ of female genitourinary system is listed as an indication associated with hysterectomy surgery; (ii) whichever is listed first of endometriosis, uterine prolapse, or uterine leiomyoma will be assigned the primary diagnosis associated with hysterectomy if cancer or a precancerous condition is not listed; (iii) endometrial cystic hyperplasia is combined with in situ under precancerous and that pain and bleeding were included as reported reasons for hysterectomy, and (iv) other was assigned the leading for the remaining diagnoses.19 Over 60% of patients have reported pain as pre-operative symptoms for hysterectomy.39 After hysterectomy, the prevalent pain was reduced to 4.7% to 31.9% during 1-2 years after surgery, while new onset pain at follow-up was reported in 1-14.9% patients and increased pain was in 2.9-5% of patients with pre-operative pelvic pain.39 Therefore, in our study, we plan to assess pre- and post-operative pain, as well as the pain conditions, including pelvic pain, back pain, fibromyalgia, and migraine or other headache syndromes using ICD-9-CM codes. Patients with pharmacy claims for opioids or diagnoses for opioid abuse (ICD-9-CM: 304.xx) during the 6-month baseline period will be identified as opioid users prior to hysterectomy. Preoperative depression that has been found significantly associated with postoperative chronic pain,40 will be identified using diagnoses, as well as medication use at baseline. Antipsychotropic medication use will be obtained using prescription information. The psychiatric comorbidity, will be assessed using prescription information instead of ICD-9-CM codes for greater specificity.11 Co-medications refer to the use of other medications on postoperative pain management. The postoperative use of Nonsteroidal anti-inflammatory drugs (NSAIDs) or Acetaminophen with opioids has been found safe and effective on pain relieve with reduced opioid dose.41 All potential predictors, including characteristics of initial opioid use, will be adjusted in multivariate analyses to identify the significant predictors for chronic use of opioids in patients post hysterectomy. Statistical Analysis Statistical tests and modeling will be conducted to identify potential significant risk factors for chronic use of prescribed opioids in women post-hysterectomy. Categorical variables will be examined and compared using Chi square or the Fisher exact test. Continuous variables will be compared using the student t test. The covariates will be selected from all demographic and clinical variables using statistical modeling. A univariate analysis will be performed with the initial opioid exposure variable and then with each covariate added one at a time to monitor the change of the estimate of the major exposure variable. The covariates that modify the estimate of opioid exposure (variable >5%) or significantly predict the chronic use of opioids will be selected for further multivariate analysis. To account for many confounding factors, we will also utilize propensity score matching method to combine all confounding factors into a propensity score. The patients with initial opioid exposu re will be 1:5 matched with the patients without initial opioid exposure using the propensity score with a caliper of 0.01. A multivariate conditional logistic regression model will be utilized to measure the adjusted odds ratio of initial opioid exposure on chronic opioid use in two matched groups. A probability of type 1 error (alpha) = 0.05 will be considered to be the threshold of statistical significance. Tukey-Kramer method will be applied to correct the inflated p value due to multiple comparisons. Statistical analysis will be performed using SAS software (version 9.4, Cary, NC). Sensitivity Studies In order to address unmeasured confounding factors, sensitivity analyses will be conducted in two sections: subgroup analyses and instrumental variables. Subgroup analysis In order to investigate the effects of initial opioid exposure in women post hysterectomy, multivariate analysis will be conducted in the following subgroups: women with postoperative chronic pain, women without postoperative chronic pain, women with postoperative NSAIDs use, women without postoperative NSAIDs use, women with postoperative Acetaminophen use, and women without postoperative Acetaminophen use. Interactions between the drug exposure and the important factors will be examined in the multivariate analyses. Subgroup analyses will likewise be conducted if the interaction is statistically significant. Instrumental Variable We plan to use propensity score matching to address all measurable confounding factors and generate two balanced comparison groups. However, the unmeasurable confounding factors, like confounding by indication, may still impact the study validity. Instrumental variable is an advanced methodology that has been utilized in pharmocoepidemiological studies to control for the unmeasurable confounding factors, such as confounding by indication. In the sensitivity study, we will use the physicians preference as an instrumental variable and reexamine the initial opioid exposure on chronic use of opioids post hysterectomy. D. Timeline Table. Study Timeline of the Study. Time Period Study Progress Before 07/01/2017 Obtain IRB approval and Optum data use permission 07/01/2017 08/01/2017 Complete data cleaning, manipulating, and variable editing. 08/01/2017 10/01/2017 Complete analyses for demographic and clinical characteristics 10/01/2017 01/31/2018 Complete trajectory modeling to determine chronic opioid use. Analyze the time and geographic trends. 02/01/2018 02/28/2018 Submit an abstract to the annual meeting of International Society of Pharmacoepidemiology (ISPE) 03/01/2018 06/30/2018 Complete analyses for specific aim 1 07/01/2018 01/31/2019 Complete predictive modeling as described in specific aim 2 02/01/2019 02/28/2019 Submit an R21 to NIH, and an abstract to the annual meeting of ISPE 03/01/2019 06/30/2019 Compete analyses for specific aim 2, including all sensitivity studies. Submit a final paper to a high impact journal 09/01/2017 12/15/2017 Complete course PHP 2090 01/01/2018 05/15/2018 Complete course PHP 2470