Research on the composer Handel Paper Example | Topics and Well Written Essays - 2000 words

On the composer Handel - Research Paper Example Not only the uniqueness of his music but peoples attitude and his popularity made him an important figure of the Baroque period. In fact, this period left a significant imprint on his life as well as career, and it can be traced both in his biography and works. First of all, it is Handels biography that shows he is a representative of a period in which he was living. During the Baroque period, there were two main factors that influenced composers and their music: location and money, with the latter being, perhaps, the most important one. In order to be able to compose music and be heard, composers needed patrons who could support and put them forward as well as sponsor them. In life and work of Handel, such sponsors performed a very important role. The first person who influenced Handels future was the Duke of Saxe-Weisenfels. Despite the fact that he did not support the future composer materially, it was he who recognized the fact that music was Handels true mission even though Handels father felt like his son becoming a lawyer. The Duke once said to the composers father, â€Å"for his own part, he could not but consider it is a sort of a crime against the public to rob the world of such a Genius!† (Kivy 40). It was after Handels v isit to the court of Saxe-Weisenfels that he started taking lessons in playing the organ at Friedrich Wilhelm Zachow (Kivy 40-41). Handel traveled a lot and during his traveling he met quite a significant number of influential people, many of whom were charmed by the composers talent. He spent about four years in Italy (1706-1710) as he was invited there by Prince Ferdinando de Medici of Florence. In Italy, Handel enjoyed great attention of music-loving prelates, such as Cardinal Pamphili and Cardinal Ottoboni. Not only they but other representatives of both aristocracy and clergy were eager to invite Handel to perform music at their palaces for they recognized his talent. Among such people were the Hanoverian Prince Ernst

Group Work vs Alone Essay Example for Free

Group Work vs Alone Essay You could receive useful feedback from group members, and shorten the amount of time you might have originally spent on the project if you had worked alone. Contrary to popular belief, there most certainly is an I in team. It is the same I that appears three times in responsibility. ~Amber Harding When you work in group you will be able to assign each member job that will help the project because of their specialization in that area of expertise, like shy person wouldn’t want to be the presenter and a terrible writer wouldn’t want to have the job of writing down everything. Using each person’s skills and talent to the group’s advantage will make the work easier; everyone has different strengths and can contribute something positive to the group. When all the skills are combined it creates new approaches to solving a problem with better results than if you were to work alone. When working in a group its best to make sure everyone has a job to do so at the end you would know who the slackers were and it’s also important to know your job so at the end of the project there’s no mix up’s at the end causing the entire group to start the project over again. Team means Together Everyone Achieves More! ~Author Unknown When you work in a group you will be able to receive feedback on what you’re doing and help to make the project as a whole better. When you’re working in a group it’s easier to improve your ideas than when you work alone, because you’ll think the idea is really good until someone in your group helps you make the idea better.

Selective Oestrogen Receptor Molecules (SERM)

Selective Oestrogen Receptor Molecules (SERM) Lucy Perry Perry Pharma Development Pipeline Introduction: Perry Pharma Research Development (PP-RD) has been investigating Selective Oestrogen Receptor Molecules (SERM) for potential development that will be effective in both breast and uterine cancer as part of its drug pipeline. Early clinical testing of PKWT and PKWX, for which PP holds Australian patents (66633 –PKWT and 44455 – PKWX) for, indicates significant improvement in their selectivity, clinical outcomes and safety profiles when compared to the current SERMs. Thus, providing an assessment of the development considerations including efficacy, safety, therapeutic indications and potential market share would aid PP in making decisions concerning the development of these molecules. This information is now vital due to a potential infringement of patent 66633 – PKWT, by HCH who manufacture ‘Tamax’, and are about to launch the successor ‘Pro-tam’. PP-RD has analysed samples of ‘Pro-tam’, which has been identified as PKWT. Because of the impending launch, PP-Legal is including recommendations for dealing with this infringement within this review. Selective Oestrogen Receptor Modulators Cancers that grow in response to oestrogen are termed ‘ER-positive’. Oestrogen receptor positive cancers growth is modulated by oestrogen binding at the oestrogen receptor (ER). These ER are located in breast, bone, central nervous system and uterine tissues. SERMs action in the body is through agonism or antagonism at the ER, leading to both positive and negative effects depending on the tissue site. Antagonism of the ER and blocking of the action of oestrogen in a specific tissue such as the breast or uterus is responsible for anti-cancer action of a SERM (Fabian 2005, Maximov 2013). PP is interested in developing PKWT and PKWX for these ER-positive cancers. Treatment of ER-positive cancer: ER positive cancers are one of the most common forms of breast cancer subtype (ACS 2014a). SERMs are used as primary, combination or adjuvant therapy for cancers expressing the ER receptor (Yilmaz 2013, ACOG 2014, Sledge 2014). Compound choice is dependent on the patient population, and the associated treatment period may last up to 10 years (ACOG 2014, Sledge 2014). In uterine and endometrial cancers SERMs are less utilized, (Burke 2003, ACS 2014b,c). Tamoxifen has shown some efficacy, however the Product Information does not list endometrial and uterine cancer within the indications; these are included in the Precautions section (eBS 2014, ACS 2014b, c). Highly selective SERMs are being developed to reduce off target action and improve safety profile, through exploiting the receptor subtypes. (Jordan 2004, Maximov 2013). However biological agent based therapies for breast and uterine cancers (Fabian 2005) make the future for SERMs unclear. Issues in the development of PKWT PKWX: Indications: PP needs to be strategic in the selection of indications to pursue. This will dictate not only the size of the treatable population and the amount of clinical data required for the registration dossier but also potential return on investment. It will also play a significant part in whether the compounds are listed on the Pharmaceutical Benefits Scheme (PBS) PKWT and PKWX both have shown high selectivity as well as good safety and clinical outcomes in women of all ages compared to current SERMs and establish these compounds within an already crowded market. First, PP can position development of a ‘one tablet for both breast and uterine indications for all ages’. Although this will mean a complex and costly clinical development plan, it entails a potentially a larger population to treat due to the wider indications. Second, PP may take a different approach aiming for a specific indication such as the ER positive breast cancer in post-menopausal women, but limiting the treatable population. It is worth noting importantly that there are no SERMs with approved indications for uterine or endometrial cancer, despite phase II trials (Munster 2006), which indicates a potential gap in the market. PP could launch the first SERMs indicated for ER-positive uterine cancer. PP will need rates of ER positive uterine cancer to determine the available market to ensure return on investment and determine any potential competition through patent searches. The third option is to enter the market leveraging the structural novelty of PKWX active metabolite, with improved outcomes and safety. This may provide a compelling case for prescribers to switch treatment options. Efficacy PKWT and PKWX have both shown good clinical outcomes for both breast and uterine cancer. They are also highly selective, which is an important consideration so that off-target action is minimised which responsible for the safety profile of the current SERMs (discussed in Safety section) A consideration for prescribers is the secondary effects of oestrogen treatment. SERMs have been shown to be effective against osteoporosis, keeping lipid profiles favourable, aiding in the reduction in symptoms of menopause, cardio-protectivity and risk prevention of cancer (Maximov 2013, Munster 2006, Pickar 2010). PKWT and PKWX must show some of these positive secondary effects to be competitive. Prescribers will not switch to SERMs which can lead to the same outcome but leave a patient worse off e.g. from loss of bone minerals or exacerbation of menopausal symptoms. Length of treatment with SERMs such as Tamoxifen can be up to 10 years to ensure optimal clinical outcomes for patient (ACOG 2014). PP needs to investigate whether PKWT or PKWX requires the same significant period of treatment to achieve clinical outcomes. Safety Due to the pharmacological action of SERM’s acting as either agonists or antagonists at the ER, negative secondary effects can occur. SERMs safety profile includes development of endometrial abnormalities, increased risk of endometrial cancers, pulmonary venous thromboembolism’s and increased incidence of stroke (Pickar 2010, Qin 2013). PKWT PKWX have been found to have better safety profiles, due to the higher selectivity for breast and uterine ER’s, both acting as antagonists at these receptors. Tamoxifen has agonistic properties at uterine tissue which is linked to its use increasing the risk of uterine/endometrial cancers (Yilmaz 2013). However no information has been provided on the adverse event profile known to date and no animal data on long term use associated with treatment length of current SERMs. Market Share and Market Advantage: ‘Tamax’ is a recognised brand, (first patented 1978) with an established market; it is now the preferred treatment for breast cancer in pre-menopausal women. ‘Pro-tam’ which has reportedly an improved safety profile over the originator ‘Tamax’, already has an established brand and market. PP may become a direct competitor and will require a significant point of difference to change prescribing habits of clinicians. The market advantage within the breast cancer treatment arena may be the improved safety and clinical outcome; however PP needs to consider whether it wants to produce a ‘me-too’ compound. As a SERM to treat uterine cancer specifically, it would be a first. PP should consider pursuing compounds specifically into this new market, especially if there is the added advantage of treating breast cancer. Again PP should consider the structural novelty of the PKWX metabolite as well as improved safety and clinical outcome as a market advantage to attract clinicians and gain some ground in the ER-positive breast cancer market. Regions in which Tamax has been launched needs to be obtained, so PP can determine if there are any new markets, and if there are regional specific factors such as the PBS. Pricing strategy and treatment indications will be important in these markets. Investment Costs As part of the review process there needs to consideration of the level of return on investment. PP need to be sure that if development goes forward they have a treatable population and potential to gain market share or market advantage. PP may wish to consider attempting to out-license the compounds if the development costs prove too much of an investment. Legal: PP-Legal has flagged potential PKWT patent infringement by HCH. The associated legal proceedings may add significant costs to the development budget and also effect development timelines. ‘Pro-tam’: Potential Patent Infringement? HCH is launching ‘Pro-tam’, a prodrug that is claimed to be metabolised into ‘Tamax’. PP-RD have analysed the metabolite and found it to be PKWT. PP-Legal advises pursuing this as a potential infringement by HCH on the PKWT patent and to ensure appropriate legal action is taken to avoid any adverse impact on further development of PKWT. PP-Legal have suggested undertaking the following steps: Review the ‘Pro-tam’ priority date to ensure that it is dated after the PKWT priority date (25 April 2002). If the ‘Pro-tam’ patent does have a priority date prior to 25 April 2002: PP-Legal will review the ‘Pro-tam’ patent to determine any grounds to challenge its validity or navigate around the patent. Applying for a patent on PKWT for uterine cancer. This will require negotiation of a licensing agreement with HCH. PP transfers its efforts to the development of the more novel PKWX. If the patent for ‘Pro-tam’ was lodged after the priority date for PKWT, PP has grounds to pursue patent infringement and attempt to block the ‘Pro-tam’ launch by lodging a request for an interlocutory injunction. This will allow PP to restrain the allegedly infringing actions by HCH until settled in court (IP Australia 2012). The justification would be based on the ‘Pro-tam’ patent not meeting the novelty criteria as the chemical structure of ‘Pro-tam’ is listed as part of the PKWT claim scope (IP Australia 2012). HCH legally can patent the prodrug, but at the point of metabolism, the PKWT patent is infringed. PP-Legal have previously determined PKWT does not exist in published prior art. A patent on a prodrug and its metabolites is only valid if all conditions of patent validity are met. The ‘Pro-tam’ active metabolite structures should therefore be captured in the claims. If the PKWT structure is not listed and the PP-RD can provide evidence that PKWT is the active metabolite, there are grounds to claim falsification of aspects of the patent, as HCH has not disclosed all claim details into the public domain, thus invalidating the patent (IP Australia 2012). Here the emphasis is on HCH proving the case otherwise. PP-Legal suggests creating a further portfolio of surrounding patents for maximum protection of PP intellectual property and allow for further development of the SERM pipeline. The ‘Tamax’ patent has since lapsed, however, for completeness, PP-Legal have provided potential actions for PP to still patent PKWT if the Tamax patent was still valid. The original patent claimed a single isomer structure, which is not PKWT, nor was it described as racemic. The existence of other isomers was not common knowledge at the time of the patent application so HCH were likely unaware that the structure listed in the claim scope had isomers. Between 1996 2000 journal articles were published discussing the discovery of isomers of compounds that may confer improved efficacy and safety profiles. Despite these articles being in the public domain, HCH did not move to patent any potential isomers of ‘Tamax’. If a compound is described as a racemic mix in the aspects and that patent is challenged, court rulings in previous legal cases have stated that it is considered common knowledge that racemic mixtures may contain isomers with different properties and that it is obvious to try to separate these. Considering this information, PP could move to patent the PKWT isomer, on the basis that Existence of different isomers of compounds was not common knowledge at the time of the original ‘Tamax’ patent so the argument of obviousness that the patent would cover the PKWT isomer cannot be made by HCH (IP Australia 2012). If HCH had claimed a generalised formula for ‘Tamax’ type compounds, PP would be infringing (Harris 2013). Information on differences in efficacy and safety of undiscovered isomers has been in the public domain since 1996 and HCH still did not move to patent any isomers. Separation of isomers is possible by skilled practitioners since technological advancements have occurred. Conditions of patent validity can be met by PP – PKWT is novel as it is not described in prior art, it is inventive in that it requires a person skilled in the art (i.e. not obvious) to separate the isomers and it is potentially useful in treating disease (IP Australia 2012). Development Recommendations: PP needs to consider which indications to pursue –as it will affect the size and cost of the clinical development programme. The improved clinical outcome and safety, as well as selectivity, can provide market advantage in both indications. However, a breast cancer ‘me-too’ drug may not be successful in obtaining a PBS listing which is crucial to success of a medicine in the Australian market. The PKWT patent infringement proceedings may affect development schedules and add significant cost. Whereas PKWX has a novel structure that is not subject to patent infringement, so this may be the better compound to pursue to avoid the legal route Word Count 2118 References American Cancer Society (2014a) Breast Cancer http://www.cancer.org/> (Accessed Aug2014) American Cancer Society (2014b) Uterine Cancer http://www.cancer.org/> (Accessed Aug2014) American Cancer Society (2014c) Endometrial Cancer http://www.cancer.org/> (Accessed Aug2014) American College of Obstetricians Gynaecologists (2014) Committee Opinion – Tamoxifen and Uterine Cancer. www.acog.org> (Accessed Aug2014) Burke TW Walker CL (2003) Arzoxifene as therapy for endometrial cancer Gynaecologic Oncology 90 (2003) S40–S46. (Accessed Aug2014) eBS (2014) TGA Nolvadex Product Information. Astra Zeneca 2013 https://www.ebs.tga.gov.au (Accessed Aug2014) Fabian CJ Kimler BF (2005) Selective Estrogen-Receptor Modulators for Primary Prevention of Breast. CancerJ Clin Oncol 23:1644-1655 (Accessed Aug2014) Harris, T., Nicol, D., Gruen, N. 2013 Pharmaceutical Patents Review Report. Commonwealth Government of Australia.http://www.ipaustralia.gov.au/pdfs/2013-05-27_PPR_Final_Report.pdf> (Accessed Aug2014) IP Australia (2012) Pharmaceutical Patents Review: Background issues and suggested Issues Paper. Commonweath Government of Australia www.ipaustralia.gov.au/pdfs/Background_and_Suggested_Issues_Paper_PharmaReview.pdf> (Accessed Aug2014) Jordan VC (2004) Selective estrogen receptor modulation Concept and consequences in cancer. Cancer Cell Volume 5, Issue 3, p207–213. (Accessed Aug2014) Maximov PY,Lee TM,Jordan VC (2013) The discovery and development of selective estrogen receptor modulators (SERMs) for clinical practice. Curr Clin Pharmacol.2013 May;8(2):135-55 (Accessed Aug2014) Munster PN (2006) Arzoxifene: the development and clinical outcome of an ideal SERM. Drug Evaluation March 2006, Vol. 15, No. 3 , Pages 317-326. (Accessed Aug2014) McMeekin DS, Gordon A, Fowler J, Melemed A, Buller R, Burke T, Bloss J, Sabbatini P (2003) A phase II trial of arzoxifene, a selective estrogen response modulator, in patients with recurrent or advanced endometrial cancer. Gynecologic Oncology 90 (2003) 64–69. (Accessed Aug2014) Qin T, Yuan ZY, Peng RJ, Zeng YD, Shi YX, Teng XY, Liu DG, Bai B Wang SS (2013) Efficacy andtolerability of toremifene and tamoxifen therapy in premenopausal patients with operable breast cancer: a retrospective analysis. Curr Oncol, Vol. 20, pp. 196-204; (Accessed Aug2014) Pickar JH, MacNeil T Ohleth K (2010) SERMs: Progress and future perspectives Maturitas Volume 67, Issue 2, Pages 129-138, October 2010 (Accessed Aug2014) Sledge GW, Mamounas EP, Hortobagyi GN, Burstein HJ, Goodwin PJ Wolff AC, (2014) Past, Present, and Future Challenges in Breast Cancer Treatment Journal of Clinical Oncology, Vol 32, No 19 (July 1), 2014: pp 1979-1986 (Accessed Aug2014) Yilmaz S,Gà ¶nenà § IM,Yilmaz E (2014) Genotoxicity of the some selective estrogen receptor modulators: a review. Cytotechnology.2014 Aug; 66(4):533-41.(Accessed Aug2014) Personal Reflection Starting this assignment I had no real knowledge of SERMs- I had a basic understanding of the use of tamoxifen so building background knowledge was a prompt learning curve. However, such events are to be expected in all professional practice and simply enable improvement. When I think about the writing and the researching of this assignment, I can say that I found the intellectual property section the most challenging and intellectually stimulating area, as it resonated with my detail oriented nature and love of deconstructing/reconstructing events and processes. I enjoyed the researching of case law and the practicalities of patents. I always enjoy doing the literature searches and review of papers, and the chance to delve into the legal terminology pushed me outside my comfort zone. The drug development side of the assignment was not so interesting to me. I would put this down to the word limit not really allowing for much exploration of the area. I would have liked to explore market share and the epidemiological basis and strategy of selecting an indication/s for these compounds in a much more detailed review. Because of my work sits strongly in the population health area, this early end of the development pathway is not really something that I am asked to consider often. However from the viewpoint of building a personal knowledge base and being able to provide answers to my direct reports regarding the drug development process in a more holistic manner, this assignment has been of help. Search Strategy Keyword Wildcard Search: PubMed Google Scholar SERM, oestrogen receptor modulator, ER breast cancer, ER uterine cancer, ER endometrial cancer, tamoxifen, hormonal cancer, Obtained literature centred on these wild card searches. Reviewed the literature to build a knowledge base to write the first half of the assignment. Reviewed 9128 course notes to finalise ideas. Keyword Wildcard search: Google Google Scholar Pharmaceutical Patents, enantiomer patents, isomer patents, isomer legal cases, patent portfolios, patent law Australia, pharmaceutical patent cases Australia, intellectual property law Australia, Obviousness, inventiveness. Obtained literature and websites centred around these wildcard searches, Reviewed the literature to build understanding of IP law and previous case law. Referred back to Australian IP law to check proposal was sound. Reviewed 9128 course notes to finalise ideas.

Progressive Movement In America Essay -- essays research papers

There was a great need for the progressives during the early 1900s. In 1900 America’s population was around 76 million, and one out of every seven of those 76 million was foreign. By 1915 there were 13 million more immigrants. If that wasn’t enough of a drastic change in America’s culture, there was another huge change taking place. America was switching from small personal businesses, to the big business type of economy. Newer and bigger businesses meant different working conditions, different working classes as well as economic classes, and completely new jobs that hadn’t even existed before.   Ã‚  Ã‚  Ã‚  Ã‚  Often my parents and I disagree on current events, movies, music, etc. Sometimes I feel like they are both against change. If they see that things aren’t just as they were before, like during the time when they were my age, they see things as bad or wrong. On the other hand, I feel like change is necessary sometimes, and the times of the late 1800s and early 1900s were no exception. In defense of my parents, I don’t always see the need for total changes. After all, as the old saying goes, if it isn’t broke don’t fix it. The progressive movement refused to stick with the status quo and instead welcomed change. However progressives also recognized that some things worked fairly well, like the general form of American government. So they felt a complete change was not necessary, but that some things could use a little work, and that is how progressives forme...

Why Hitler’s Actions, the Treaty of Versailles and the Policy Appeasement Contributed to the Outbreak of War in Sept?

The Policy appeasement contributed to the outbreak of war in sept. 1939 because by appeasing Hitler Britain and France gave him the confidence to believe he could ask for anything he wanted. This only reinforced what they’d already shown him, which was they wouldn’t take action if he wanted him broke the treaty, such as when he took over other parts of Europe, such as Sudetenland in 1938 and reoccupying the Rhineland.This made him stronger and more powerful, which made him more likely to start a war because he thought he was more likely to win or for Britain and France not to react in the first place because even though they said that they’d start war if he attacked Poland, he didn’t believe they would. So he invaded and WW2 broke out as promised. Appeasement couldn’t ever of stopped Hitler; it merely suspended war, which made war more likely in sept. 1939 because it gave Britain and France more time to re-arm which meant they were more likely to de clare a war they could actually win.The treaty of Versailles contributed to the outbreak of war in sept. 1939 because they were overly harsh towards Germany which effected every aspect of life in the country which left the population angry and vengeful. This lead to Hitler’s uprising because he promised to abolish the treaty and get Germany back on its feet, which meant in 1933 he had the power to put in motion his plans for Germany that would lead to War. He Joined with Austria, rearmed and reoccupied the Rhineland, this not only went against the treaty it also made Germany stronger and more ready for War.The treaty of Versailles also contributed to war in sept. 1939 because it made Britain and France more likely to follow the above appeasement policy. Many people after WW1 was fully over started to believe the treaty was way too harsh on Germany, this meant Britain and France felt Germany deserved the land. Which in turn made Germany stronger because of the mineral resource s such as Iron and Coal Hitler could use to fuel his military and country as a hole and also meant more men to fight on Germanys side. Which made war more likely as Germany would be stronger and therefore Hitler would be more likely to start a fight.Hitler’s actions lead to War in Sept. 1939 because he was an aggressive dictator with clear aims to abolish the treaty, get Germany an empire and unit German speakers. In other words make Germany great again. He also wanted to re-arm which would allow him to both break the treaty and expand because he knew other countries weren’t just going to let him walk in and take over, he expected a fight, and so he needed arms. This would also achieve his other aim to create Lebensraum that was living space for German people.These aims lead him to invade Czechoslovakia and Poland, which lead to War in sept. 1939 when they’re allies came to help. Without Hitler’s drive to meet his aims the War might not of happened at all . Another way in which Hitler’s actions contributed to war in Sept. 1939 was because his aims appealed to the German public. He promised a new Germany, better, stronger, without the treaty. Germany were in an economic depression they’d do anything to get out of, this meant they were open to Hitler’s aggressive nature, and this helped bring him to power in 1933.If Hitler wasn’t in power he couldn’t of carried out his actions. In conclusion all three contributed to the war but they all worked together. The treaty of Versailles made Germany want revenge, which lead to Hitler’s popularity because he promised to abolish it, which lead to him gaining power, which meant he could carry out his plans, so Britain and France either had to appease him or start a war. In the end they did both, but by appeasing him first they also made war more likely because it encouraged Hitler’s confidence, so he felt more comfortable taking bigger and bigger ri sks.

Innovation and Change

Innovation and Change Innovation and Change - P G Essay Business Innovation and Creativity Proctor and Gamble (P & G) was established in Cincinnati in 1837 by William Proctor and James Gamble manufacturing Soap and Candles. The partners grew the business from strength to strength through ingenious innovations, with the help of successive generations then through none family management to create the $70 billion enterprise. P & G is a business where innovation flows throughout every sector both internally and externally, from suppliers to distributors. The networks and alliances which have been made allow for channels of communication to be access with ease allowing ideas to be acknowledged and trailed – the lifeblood of innovation. The innovation and creativity practice occurs, and is similarly discouraged by two determining factors: the internal and external environment. Internal Internal factors within an organisation, such as P & G, can foster the creative drive of innovation but likewise can be its own downfall. The Seven Virtues of managing creativity evaluates the areas where ideas can be furthered upon therefore ensuring the organisation continues to be innovative. Culture Politics Learning Generation of ideas Job orientation Architecture Change External The founders of the company have always shown initiative by suppling the needs of the everyday consumer from very early on when the enterprise was established. The first major break through for the company was during the American Civil War in 1862, when the Union Armies contracted the pair to manufacture a soap which was small enough for soldiers to carry everywhere but long lasting. The forward thinking cousins, James Norris Gamble and William Alexander Procter (sons of the founders) purchased a phenomenal amount of rosin (essential in the soap making process) before the war. The purchase stood the company in great stead against its rivals, as supplies ran short P