Challenges to the pharmaceutical industry's blockbuster-driven Research Paper

Challenges to the pharmaceutical industry's blockbuster-driven business model, and the effectiveness of GlaxoSmithKline's st - Research Paper Example After discussing the challenges associated with the use of the Blockbuster-Driven Business Model, the effectiveness of GSK’s strategies to meet these challenges will be tackled in details. 2. About the Company: Business Press and Analyst’s Narratives on GlaxoSmithKline (GSK) and Its Business Performance (i.e. Sales Revenue, Stock Prices, and Market Share) Based in Britain, GlaxoSmithKline (GSK) is a science-based health care company that aims to develop a wide-range of medicines through product researches and innovation (GSK, 2013a). Serving 115 countries worldwide, GSK is one of the top three biggest pharmaceutical companies around the world (GSK, 2013a ; Gilbert, Henske and Singh, 2003). To develop and innovate new drugs, GSK spent as much as ?4 billion in 2002 (GSK, 2013a). Back in July 1986, the share price of GSK was only 7.31 (Yahoo, 2013). Since January 1992, GSK’s share price has been fluctuating due to a series of merger and acquisition, expiry of patent s, heavy investment on new drug innovation, and tight competition in the market. Between 1979 to 1993, GSK filed 6 patents on Augmentin (Community Catalyst, n.d.). As a result, GSK’s share price started to increase in December 1992 at 30.75. ... It was between 1994 to 1995 when GSK contested their point-of-views with the federal appeals court concerning the legal issues behind patent infringement on one of their famous ulcer drug called Zantac (Los Angeles Times, 1995). Since the federal appeals court supported the arguments made by GSK, Novopharm – a Canadian company was not allowed to sell the generic version of Zantac in the U.S. throughout the period when the patent right is still effective (Los Angeles Times, 1995). One of the possible reasons why GSK’s share price significantly decreased from 69.50 in December 1998 down to 48.75 in February 2000 and 35.05 in February 2003 was because of patent litigation of GSK’s Paxil (Evaluate, 2002). In relation to the expiration of GSK’s patent on Advair in 2010, GSK’s share price has also significantly decreased from 42.29 in December 14, 2009 down to the lowest point at 33.46 in May 24, 2010 (Yahoo, 2013). Because of GSK’s business strate gy, this company managed to gradually increase its share price up to 52.51 in December 2013. Since it takes 10 years for GSK to develop new patented drug (Williams et al., 2008), this company has been continuously developing other promising drug that can compete or even better than their existing â€Å"blockbuster† drugs. (See Chart I – Historical Trend of GSK’s Share Price below) Chart I – Historical Trend of GSK’s Share Price Source: Yahoo, 2013 One of GSK’s â€Å"blockbuster† drugs was the Advair Diskus – an inhaler which can be used in the treatment of chronic asthma and chronic obstructive pulmonary disease (COPD) such as bronchitis or emphysema (Kitamura, 2013; Recruiting Experts Worldwide, 2013). Costing roughly US$300 per dose, the selling of

Introduction to Law Enforcement unit 2 DB Essay Example | Topics and Well Written Essays - 250 words

Introduction to Law Enforcement unit 2 DB - Essay Example According to (BLS,2012)Police officers protect lives and property. Detectives and criminal investigators, who sometimes are called agents or special agents, gather facts and collect evidence of possible crimes. The role of the law enforcement authorities should change as the circumstances and threats surrounding a county is always unstable.For eg: Since the September 1 1th terrorist attack the role and responsibilities of law enforcement has changed for good. As per (Walsh,2009)†The field of law enforcement has changed greatly since I became involved in public safety in 1985, and my career in Wenham in 1987†. The main change I would like to make is the abuse of drugs among students and selling of drug on the street.This is because protection of young generation is the foremost duty of the law enforcement agents. According to (Bennett,2010)†Illicit drug abuse is seriously affecting our children, our schools, our workplaces and our society†. Bennett, W. J. (2010, September 4). We ignore rise in drug abuse among kids. In http://articles.cnn.com. Retrieved June 12, 2012, from http://articles.cnn.com/2010-09-24/opinion/bennett.drug.abuse_1_drug-overdose-drug-abuse-illegal-drugs?_s=PM:OPINION Walsh, K. M. (2009, February 18). Walsh: Law enforcement changes over 20 years. In .wickedlocal.com/. Retrieved June 12, 2012, from http://www.wickedlocal.com/ hamilton/news/lifestyle/ columnists/

Pategonias Expansion Strategy Essay Example for Free

Pategonias Expansion Strategy Essay 1. Patagonia’s Current Strategy: Key Processes and Customer Perception In the context of our business model our number one key process is our Rules and Norms (a complete breakdown of Patagonia’s current business model and a to-be-proposed business model are available for review in Exhibit I). This ethos that started with the founding of Chouinard Equipment continued through the creation of Lost Arrow and indeed Patagonia. Our self-proclaimed â€Å"dirtbag† culture has resulted in some unorthodox business practices over the years. We pride ourselves on our efforts to reduce the social and environmental impact of the lifetime of the goods and services we produce. This is something that our competitors recognize but do not focus efforts on; for us it is of the utmost importance. I took this liberty to draft a Customer Value Proposition (CVP) for our current model: â€Å"We provide high quality, durable outdoor athletic clothing and accessories that are produced with a high standard for environmental and social impact. We make the products that we want to use.† To extrapolate on the latter portion of our CVP, we expect our employees to not only share in the environmental and social consciousness that Mr Chouinard has weaved into the culture of Patagonia but we expect employees to be users of our products as well. This gives us an incredible insight into the functionality and durability of our products. This is exemplified in our generous sabbaticals and midday surfing breaks at our corporate headquarters. Additional insight in this regard is provided by our investment in brand ambassadors, who also provide us with the core of our visual marketing in our catalogs, our website, and social media. In order of volume we move our products through three main channels: wholesale, retail, catalog/internet. In order of profitability the channels are arranged as such retail, catalog/internet[1], and wholesale. There is an additional product repair arm of Patagonia’s structure that at the moment is not profitable. Our commitment to the ethical fiber that binds the core of what Patagonia as a brand stands for results in a product that comes at a premium price, however we believe that the money you spend on Patagonia products is a contribution to our commitment for care when it comes to the environments and social spheres within which we operate. So far we have seen success as shown below. 2. Financial Review of Current Business Model The competition analysis in Exhibit III outlines our industries averages for financial health. It would seem that our â€Å"dirtbag† approach to business has boded well for us over the last ten years. While our total market share (annual sales) is far below the industry average over all the company is making money. Our gross profit margin is over 6% higher than the industry average and our pre-tax profit margin is right in line with the industry average. While Patagonia’s ROE and ROA are below the industry average it is not my much and our debt to equity ratio is far below the industry average. So while we holds more equity and assets on hand than our competitors we has enough liquid cash flow to finance operations without having to incur much debt. Our 12 month revenue growth is trending along with the industry however our 12 month net growth income is nearly 13% higher than our competitors. Thus while we are experiencing growth that is on par with the industry we are experiencing a downward turn in our operating and/or material costs. It should be noted that the information here is of companies who compete in our industry but not exclusively. Columbia is the competitor that competes most directly with our niche in the industry and on every account except for debt/equity our numbers are favorable and even in the case of debt/equity the difference is negligible. The standards for philanthropy and an ethical purview for production and material sourcing at Patagonia are much higher than the industry average. We donate 1% of gross sales to environmental initiatives and causes, and our COGS are higher than competitors as a result of our ethical stance. However, once again (as shown in Lost Arrow: Financials, Exhibit III) we have been operating in the black for the last decade. This may also be explained by our company ethic. We focus on a curbing of consumption and that focus has limited how much we are willing to spend on advertizing. Conversely our competition holds advertisement as a high priority when establishing sales and brand. This observation is not trivial and could more than account for the balance between our costs and those of our competitors. 3. Moving Forward As discussed the current model for Patagonia works. You can be a â€Å"dirtbag† and make make money. The question is how do we continue on with the goal of 10% growth per year for the next five years? Whatever we choose we must operate within that moral fiber that helped us to achieve who we are today. Following are two suggestions for how to move forward, one uses our current business model, the other proposes a change. Please reference Exhibit I for business model analysis and Exhibit II for strategy. Strategy: Current Business Model Tactic One: A Focus on Retail – Our best margins are derived from retail sales however this accounts for just one third of our sales volume. The best type of marketing asset we have are our retail employees. Our Dirtbag Ambassadors are out there skiing, snowboarding, climbing, camping, bouldering, and living the life that Patagonia wants to be an integral part of. We must expand our retail channel and focus on those areas where dirtbags convene. A quick review of the 26 stores in the United States can be found in Exhibit V. Portland, Seattle, St. Paul, Chicago, Atlanta, DC. Sure dirtbags live in cities but where are our stores in Telluride, Tahoe, Bend, Cheyenne, or Buffalo? An expansion of our retail stream increases profitability as well as the reach of our marketing, the Patagonia way. These are the places our competitors don’t wants stores for lack of traffic, but our stores are more than commerce they are community centers for dirtbags. Tactic Two: Research and Development – Our industry ethic has produced one of the best research and development laboratories in the industry. We can leverage this in two ways. First and foremost we must fund research to produce material with the ethical and physical integrity that also helps lower our gross margins. We have pioneered ethical durable material in the industry, now we must find a way to do so cheaper. Doing so would open up the market for those dirtbags who dont have as much money and would normally go to a competitor based on price point. Second we hold patents for these materials we could offer to sell material to other outdoor companies, or begin a joint venture. In either of these cases we must make sure that the material we produced is being utilized in an end product that is up to the standards of Patagonia. Strategy Two: A New Business Model There comes a time in a business life when you have to ask: While what we are doing has worked, how long will it work? To achieve the goal of 10% growth per year we may have to think outside of our wheelhouse and think about how committed we are to our ethical and social standards. As long as we continue to produce more clothing people will buy it. As it stands our customer base has expendable income. How can we convince them to only buy what we need? Through an expansion of our clothing repair services and clothing swap market. A case is made for the business model change in Exhibit I. Tactic One: Expansion of Repair and Retail – It is not our goal to abandon what has made Patagonia the company it is today, thus once again we will need to expand retail stores however we do so in a way that will facilitate clothing repair. Each store should have a mending workshop staffed and equipped to repair what comes their way. To really take advantage of this service we must willing to mend non-Patagonia clothing. This will do two things: it will reduce the overall number of unnecessary purchases in our market and it will introduce people to the Patagonia lifestyle through our retail store. These store can also facilitate a recycling program for those articles of gear that are beyond repair. Something as simple as an in store credit can get people who would otherwise go to Nike experience Patagonia CA. Additionally the expanded retail presence will be an opportunity to create a network for clothing swaps Tactic Two: Expansion of Internal Repair – Expand the repair infrastructure behind retail presence. That is to say, as opposed to expanding retail and having repair work centers in-store, invest in larger repair facilities that stores can send garments to. In our current business model we are reaching critical mass with regard to how much clothing repair we can handle. If we strategically place lager facilities near our exiting stores we can handle this work load our selves. This also ensures that the materials and process of clothing repair is within the ethical conduct of our company without having to do audits of our outsourced partners. The clothing repair infrastructure for our market is basically nonexistent at this point and with research and development focused on this new business model we can create and dominate this market. This will once again involve repairing more than just Patagonia products but in the end that’s what this business model is about. To survive and grow into the next decade we must not just reduce the consumption of our customer base but we must reduce the consumption of our competitors as well. When a dirtbag holds on to a coat for another year he helps reduce Patagonias impact on the earth and its inhabitants. When Patagonia repairs a Columbia or North Face coat and it lasts for another year we have slowed the consumption of unethically produced clothes and possibly created another dirtbag. Exhibit I: Four Components of Business Model Framework (Johnson, Christensen, Kagerman) Customer value proposition (CVP): Current: Providing high quality durable outdoor athletic clothing and accessories (CA) produced with a high standard for environmental and social impact. Proposed: In addition to production, engage the consumer in the environmental and social impact of their outdoor athletic CA by involving them in the maintenance/repair/swap of CA. Profit formula: Revenue model: Current: Standard industry mark up on goods sold. Proposed: Lower the price of goods sold and charge a small fee for repairs or continue with current price structure charge cost for repairs of Patagonia clothing/accessories, charge premium repair rates for non-Patagonia clothing and accessory repair. Cost structure: Current: COGS = 80% materials 20% parts with a wholesale margin of 45% and a retail margin of 65% Proposed: A modified cost structure that emphasizes retail sales and profits off of repairs Margin model: Current: Largest channel of sales in wholesale 44%, second retail 33%, and finally Catalog/internet 23% Proposed: Shift focus from wholesale to retail/catalog/internet sales, add additional emphasis on repair cost structure for maximum profitability Resource velocity: Current: In general keeping inventory exhausts resources, something which Patagonia wants to minimize. Thus production should match as close to demand as possible. Assets should be available, although they do not need to be incredibly liquid. Proposed: Same as current model. Key resources. Current: People: There is a certain type of person who works for Patagonia. Ideally a person who works at Patagonia is the ideal consumer of their goods. Brand: With a strong brand associated with high environmental and social standards combined with a strong dislike of standard advertising channels for the industry the reputation Patagonias brand has gained is remarkable (this is achieved through the people they employ as well). Technology: Their ethical commitment to responsible sourcing and production has resulted in some profitable patents of great CA material. Proposed: The current Key Resources should not be lost but the Technology will shift to the new business model – a focus on materials , threads, and substances for repair. Additionally there would be a re-purposing of Facilities to reflect this model change as well. Key processes. Current: Rules and Norms: Patagonias Rules and Norms inform every aspect of their business and it is no different when it comes to their Key Processes. So while manufacturing, service, and training are all important, it all comes down to the Rules and Norms. Propsed: This would not change. When a new business model is needed. 1. The opportunity to address through disruptive innovation the needs of large groups of potential customers who are shut out of a market entirely because existing solutions are too expensive or complicated for them. The product repair market is just this. As it stands now such jackets tend to be luxury purchases as they hobbies they are designed for are not generally cheap ones to keep. 2. The opportunity to capitalize on a brand new technology by wrapping a new business model around it or the opportunity to leverage a tested technology by bringing it to a whole new market Patagonia isn’t capitalizing on a new technology when it comes to CA per se but the market could motivate their RD department to develop a technology that could be incorporated into the repair model. 3. The opportunity to bring a job-to-be done focus where one does not yet exist The expansion of clothing repair for Patagonia and other non-Patagonia CA provides a real opportunity for an existing market that consumers may not know they need. It creates a job to be done (clothing repair as opposed to replacement). 4. The need to fend off low-end disrupters. Patagonia would be a low end disrupter in the repair market; repair is cheaper than replacement. 5. The need to respond to a shifting basis of competition. Patagonia would be shifting the basis of competition.

IOP Spike Control after Intravitreal Anti-VEGF

IOP Spike Control after Intravitreal Anti-VEGF In ophthalmology many ophthalmic procedures are there in which there is a spike of intraocular pressure after the procedures. Cataract surgery, argon laser trabulectomy (ALT), yag laser capsulotomy, yag laser iridotomy, trabulectomy, pars plana vitrectomy are few to be named. The new anti VEGF therapy is an addition to the prior list. Many IOP lowering drugs have been used in different procedures to stop these spikes. For ALT 1% apraclonidine, an alpha agonist has been found to be the most effective against the IOP spikes, but 0.5% has also been found to be equally effective. Brimonidine an alpha 2 adrenergic agonist has also been shown to be effective and safe choice. For cataract surgery different drugs have been used treat the postoperative increase in IOP. These include carbonic anhydrase inhibitors, prostaglandin analogs like latanoprost, alpha agonists like apraclonidine and brimonidine, beta-blockers and miotics (intracameral carbachol and acetylcholine). Similarly intravitreal injection of triamcinolone has been complicated with a rise of IOP and have been controlled effectively by beta blockers, but some may need aggressive treatment. Different researchers have worked on the control of acute spikes after the intravitreal injection of anti-VEGF, showing varied result. Some have advocated the use of IOP lowering medicine while other negating the need all together. Lim Young et al showed that the prophylactic use of fixed dorsolamide/timolol combination eye drops before the intravitreal anti-VEGF injection was a safe method of preventing IOP spikes occurring immediately after the intravitreal injection of anti-VEGF. He showed that the mean IOP at 5 minutes and 30 minutes postoperative was 14.12 Â ± 4.18 mm Hg and 10.87 Â ± 1.58 mm Hg in group 1 using IOP lowering medication while it was 28.21 Â ± 3.16 mm Hg and 17.48 Â ± 2.34 mm Hg in control group 2, respectively.9 He showed that there was a significant lowering of mean IOP at each reading at 5 minutes of interval. Frenkel et al showed the use of IOP-lowering medication prior to injection of pegaptanib, ranibizumab, or bevacizumab had little effect on the IOP spike. The failure of lowering the IOP spike was implicated to be due to the inability of these medications to counteract the volume-related mechanism of the IOP spikes after anti-VEGF injections. However, it was stated that there might be benefit to lower the IOP before intravitreal injection. In their study 2 cases of sudden loss of vision were reported due to the high IOP spike which prompted them to do anterior chamber paracentesis.8 It was also stated that the prophylactic use of medication in patients with advanced glaucoma receiving pegaptanib intravitreal injection or patients receiving 0.1 ml of bevacizumab could be considered because their study showed that it lowered IOP at the 3- to 10-minute interval in these patients. In another study done in 2013 the IOP lowering effect of Dorzolamide/Timolol and Brinzolamide/Timolol were compared with a control group. They measured the IOP after every 5 minutes for the first half hour and the next day and week after that. For all the 3 groups, the changes relative to the baseline at 5 and 30 minutes after intravitreal injection was found to be significant. Also when the groups were broken down as to whether receiving bevacizumab or ranibizumab, again the mean decrease of IOP compared to the control group was found significant. El Chehab et al have also found that the prophylactic use of fixed combination of timolol with brimonidine or dorzolamide and of 1% apraclonidine could not only reduce the IOP spikes but also their duration; and both the combination and 1% apraclonidine had equal effect. However the use of oral acetzolamide 20 minutes prior to the intravitreal injection was not proven to be effective. Evaluating the efficacy of timolol 0.5 % and brimonidine 0.2 % eye drops as a fixed combination in preventing IOP spikes Theoulakis et al found that twice a day instillation on the day before and before the time of injection in eyes which were scheduled for intravitreal ranibizumab was a safe and also effective in controlling the IOP spikes. IOP LOWERING MEDICATIONS Most of the IOP lowering medicines are administered topically. They are absorbed through the cornea and conjunctiva; mainly acting locally on the eye. Many anti glaucoma medicines have been used. The main groups of drugs are as following: BETA- ADRENERGICANTAGONISTS They are the most prescribed drugs of IOP control. There are a total of five topical beta-adrenergic antagonists which are currently FDA approved for managing high intra ocular pressure. They are timolol betaxolol, carteolol, metipranolol, levobunolol. Betaxolol is selective beta1 selective antagonist, and is safe to use this drug in patients with pulmonary and cardiac problems. The mechanism of action is to reduce IOP by decreasing the production of aqueous by inhibiting the production of cyclic adenosine monophosphate (cAMP) in ciliary epithelium. The IOP reduction is upto 20 to 35%. The effects of beta blockers occur within an hour after its instillation. Timolol is available in the market in concentrations of 0.1%, 0.25% and 0.5%. The recommended dosage is 1 drop two times a day. Burning, allergy and corneal epithelial erosions are the main ocular side effects. It can be absorbed systemically and can cause systemic side effects like bronchospasm, bradycardia, hypotension, respiratory failure. Timolol maleate has a molecular weight of 432.50. It is an odorless, white, crystalline powder that is soluble in methanol, water and alcohol. It is compounded as an isotonic, sterile, buffered solution available in two strengths: 0.25% Timolol maleate eye drops contains 2.5 mg of timolol (about 3.4 mg of timolol maleate). It has a pH of approximately 7.0, and an osmolarity of 274-328 milliosmole. And each ml of 0.5% Timolol Maleate eye drops contains 5 mg of timolol (about 6.8 mg of timolol maleate). The Inactive ingredients are usually monobasic and dibasic sodium phosphate and sodium hydroxide to adjust pH. Preservative used is Benzalkonium chloride 0.01%. PARA SYMPATHOMIMETIC AGENTS They act by stimulating sphincter pupillae and ciliary body by acting on the muscarinic receptors. They cause the contraction of the ciliary muscles which thus increases the aqueous outflow through the trabecular meshwork. Pilocarpine is the commercially available drug in this group and is compounded in concentration of 1%, 2%, 3%, and 4% and the recommended dosage is 1 drop 4 times per day. Ocular side effects are miosis, induced myopia with brow ache, retinal detachment, and cataract. Systemic side effects after its absorption can be of diarrhea, vomiting, abdominal cramps and bronchial spasm. CARBONIC ANHYDRASE INHIBITORS (CAIs) The enzyme required for aqueous formation is carbonic anhydrase. The CAIs cause inhibition of this enzyme and thus cause a decrease in the aqueous humor secretion by the ciliary epithelium. Carbonic anhydrase is required for catalyzing the reaction of CO2 to H2CO3 which further splits into HCO3 _ and H+. The bicarbonate ions are pumped along with sodium ions into the posterior chamber along with diffusion of water for the formation of aqueous humor. Carbonic anhydrase is present in ciliary body in excess. 99.9 % of the enzyme must be inhibited before a significant decrease in IOP can occur. Dorzolamide and brinzolamide are the commercially available eye drops in market. They have a good corneal penetration, and are also water soluble. These agents are able to reduce IOP upto 14-17%. Adverse effects of topical CAIs are burning and stinging of eyes on instillation, conjunctivitis, blephritis, corneal allergy, corneal punctuates keratitis and can also cause bitter taste. The systemic used CAIs are methazolamide and acetazolamide. They also cause inhibition of carbonic anhydrase in ciliary epithlium thus reducing the reduction of aqueous humor. As it is taken orally systemic side effects of CAIs include metabolic acidosis, leading to alkaline diuresis which result in hypokalemia. So potassium levels should be regularly checked in patients using CAIs on long term basis and oral potassium supplement should be recommended to all these patients. Other side effects include renal stones formation and central nervous system side effects like numbness and tingling of hands and feet, depression, anorexia, and nausea. Dorzolamide hydrochloride has a molecular weight of 360.91. It is a white to off-white in colour, in a crystalline powder form, which is also soluble in water, methanol and ethanol. ADRENERGIC AGONISTS Adrenergic agonists act by increasing the uveoscleral and trabecular meshwork outflow thus causing decrease in IOP. Epinephrine has a mixed action of being an alpha and a beta agonist. Its effect usually begins at 1 hour and reaches a maximum at 2-6 hours. Topical epinephrine drops usage has been stopped due to frequent systemic side effects of headache, palpitation and cardiac arrhythmias. The main ocular side effect is cystoid macular edema and black pigmentation of conjunctiva. Commercially available topical form is dipivefrin hydrochloride 0.1%eye drops, which is a prodrug of epinephrine. It is converted by the enzyme esterase into epinephrine in the cornea. Because of its high lipid solubility and corneal penetration a low dose is required as compared to epinephrine and thus has less side effects. The selective alpha 2 agonist apraclonidine and brimonidine are indirect acting adrenergic agonist which act by decreasing aqueous production and also the episcleral venous pressure and thus improving the trabecular outflow. Apraclonidine is associated with tachyphylaxis while brimonidine has less of this problem. Brimonidine tartrate is available commercially in 0.25 and 0.15% eye drops. Its reduces IOP by 26% at 2 hour of interval. PROSTAGLANDIN ANALOGUES Prostaglandin analogues are relatively a new class of IOP lowering drugs. Four prostaglandin analogues have been approved by the FDA for clinical use. Latanoprost was the pioneer drug to be developed and used in this group. Others are travoprost, bimatoprost, and unoprostone. Latanoprost is a pro drug which penetrates the cornea and then is turned into active form. It enhances the uveoscleral outflow and thus lowers the IOP upto 25-35%. The dosage is one drop per day which makes the compliance of the patient better. The main ocular side effect is darkening of the iris and the periocular skin, by increase in the number of melanosomes in the melanocytes. Other side effects include conjunctival hyperemia, hypertrichosis, uveitis and cystoid macular edema. Systemic side effects are flu like symptoms, skin rash and uterine bleeding. OSMOTIC AGENTS Osmotic agents act by decreasing the vitreous volume by removing the liquid out of the eye into the circulation. The osmotic agents can be given orally or intravenously. Oral agent is glycerin while urea and mannitol are given intravenously. The osmotic activity is dependent upon the number of particles in the solution which cannot cross over and maintains the osmotic gradient between the compartments. Mannitol is given intravenously because it cannot be absorbed from the gastro-intestinal tract. A rebound increase in IOP and local tissue necrosis limit the use of urea. Glycerin is most commonly used oral osmotic agent which is given along with cracked ice to dilute its nauseating feeling. In patients with diabetes a non-metabolized sugar isosorbide can be used instead. Several fixed combinations have been developed which are available in markets used for IOP-lowering. Most of these fixed combinations contain timolol (dosed once or twice daily) combined with either adrenergic agonists, prostaglandin analogs, and CAIs. COMBINATION Fixed combination timolol maleate 0.5% with dorzolamide hydrochloride 2% was first introduced in market in 1998. Each milliliter of drug consisting of 6.83 mg timolol maleate and 22.26 mg dorzolamide hydrochloride. Timolol inhibits aqueous humor production by down-regulating adenylate cyclase by inhibiting ÃŽ ²2-adrenergic receptor sites on the ciliary process . While dorzolamide acts as a selective inhibitor of Carbonic anhydrase II enzyme, present on the ciliary process. The local bicarbonate production is slowed down, which as a result decreases sodium and fluid transport and, finally, decreases the aqueous humor production thus lowering the IOP. Because the mechanisms of action of both the drugs differ, they provide an additive effect when used together. Fixed combinations of drugs have been found to improve the compliance of the patient by reducing the number of eye drops used daily. Moreover the IOP-lowering effect of fixed combination timolol and dorzolamide was found to be greater than that of either drug instilled as monotherapy. In addition the load of preservative is also reduced along with any wash out of drug when the drugs in monotherapy are instilled one after the other.

Tornado Essay -- Natural Disasters Weather

A tornado is defined as a violently rotating column extending from a thunderstorm to the ground. The most violent tornadoes are capable of tremendous destruction with wind speeds of two hundred and fifty miles per hour or more. Damage paths can be more than one mile wide and fifty miles long. In an average year, eight hundred tornadoes are reported nationwide, resulting in eighty deaths and over one thousand five hundred injuries. In the body of my essay, I will tell you about types of tornadoes, where tornadoes come from, where and when tornadoes occur, the damage they inflict, variations of tornadoes, and how to detect tornadoes. There are many types of tornadoes. The average tornado is usually split up into categories based on the strength of the tornado. Most tornadoes, about sixty nine percent 69%, are considered weak, which means they usually last between one minute and ten minutes, have winds less than one hundred and ten miles per hour, and the percent of deaths that occur during these is less than five percent. Strong tornadoes, about twenty nine percent 29%, may last about twenty minutes, have winds between one hundred and ten and two hundred and five miles per hour, and the percent of deaths that are found are about thirty percent of all tornado deaths. The last category for tornadoes is violent ones. With these comes winds greater than two hundred and five miles per hour, they can last about an hour, and have seventy percent of all deaths from tornadoes. Another type of tornado is known as a waterspout. This is a weak tornado that forms over warm water. They are most common along the Gulf Coast and southeastern states. In the western United States, they occur with cold late fall or late winter storms, during a time when you least expect it to develop. They occasionally move inland becoming tornadoes that can cause a great deal of damage and many injuries. Most tornadoes evolve from energy. Tornadoes come from the energy released in a thunderstorm. As powerful as they are, tornadoes account for only a tiny fraction of the energy in a thunderstorm. What makes them dangerous is that their energy is concentrated in a small area, perhaps only a hundred yards across. Not all tornadoes are the same, of course, and science does not yet completely understand how part of a thunderstorm's energy sometimes gets focused into something as small as a tornad... ...ms using all the information they can obtain from weather maps, modern weather radar’s, storm spotters, monitoring power line breaks, and so on. These are all important tornado facts and reasons of why this phenomenon occurs. Tornadoes are natural disasters that we can not do anything about, we just have to learn to live with them and be smart about how we approach them. There is no preventing a tornado from occurring so we must merely take all the precautions so we will be safe. Bibliography: Rosenfeld, Jeffrey O.; Eye of the Storm: Inside the World's Deadliest Hurricanes, Tornadoes, and Blizzards; HarperCollins Trade Sales Dept, January 1999 Robinson, Andrew,; Earth Shock: Hurricanes, Volcanoes, Earthquakes, Tornadoes and Other Forces of Nature; Themes & Hudson Ltd., September 1993 Tufty, Barbara; 1001 Questions Answered about Hurricanes, Tornadoes, and Other Natural Air Disasters; Dover Publications, Incorporated, August 1987 Verkaik, Arjen; Under the Whirlwind; Whirlwind Books, March 1998 Miller, Norman; "How A Whirlwind Works"; Geographical Magazine, June 1999 Compton's Encyclopedia Online; www.comptons.com SKYWARN Online; www.skywarn.org

New Zealand Early Childhood Curriculum Essay -- Education, elementary

Fleer claims â€Å"there are many theoretical voices within Te WhÄ riki,† the New Zealand Early Childhood Curriculum document (Nuttall, 2003, p.254). However two are predominant and stand symbiotically on the pages and in the intent of the curriculum. Bronfenbrenner’s ecological, system’s theory, which emphasises how the quality and setting of the child’s environment influences the child (Ministry of Education, 1996; Paquette, & Ryan, 2001) and Vygotsky’s ‘sociocultural theory,’ which describes learning as a social process originating in society or culture and passed through generations (UNESCO, 2004). Discussed within this essay will be a review of these theoretical perspectives illustrating their explanations for how each influences the child, how the child learns, how development is explained, and how these theories are reflected within Te WhÄ riki. Bronfenbrenner’s ecological, system’s theory describes how the child and their immediate surroundings are in an innermost layer surrounded, embedded and influenced by layers from the larger environment all impacting upon the child (Ministry of Education, 1996; Paquette, & Ryan, 2001). Of particular interest are the effects to the child of two way relationships towards and away from the child, as defined by Bronfenbrenner as bi-directional influences, these are particularly influential in the child’s inner layer. For instance: the impact to the child of attentive or non-attentive parents affects how the child reacts to a given situation, which in turn affects how the parent behaves. Notwithstanding, the impact of bi-directional influences on the child’s world continues into the outer layers, as in the example of a parent’s workplace demanding more input into the workplace, which means... ... social aspects have a huge influence on these surroundings. This is demonstrated when whÄ nau are involved and supportive in a child’s life, sharing the family’s and their culture’s funds of knowledge, resulting in the positive effect to the child’s environment which will have vast social and educational impacts by ensuring connections are made to children’s lives and experiences. Adding to this is the socio-cultural philosophy of peer tutoring and where knowledge is actively constructed through modelling and scaffolding, with teachers facilitating the learning process. While through the building of relationships between the family and the centre, Te WhÄ riki advocates the importance of the involvement of whÄ nau and family, which encourages a learning community which has interchangeable reciprocal advantages in a safe, positive, fun, caring, learning environment.

Types of Translation

Types of translation. Types of translation classification. Administrative translation The translation of administrative texts. Although administrative has a very broad meaning, in terms of translation it refers to common texts used within businesses and organisations that are used in day to day management. It can also be stretched to cover texts with similar functions in government. Commercial translation Commercial translation or business translation covers any sort of document used in the business world such as correspondence, company accounts, tender documents, reports, etc.Commercial translations require specialiast translators with knowledge of terminology used in the business world. Computer translation Not to be confused with CAT, computer assisted translations, which refer to translations carried out by software. Computer translation is the translation of anything to do with computers such as software, manuals, help files, etc. Economic translation Similar to commercial or bu siness translation, economic translation is simply a more specific term used for the translation of documents relating to the field of economics.Such texts are usually a lot more academic in nature. Financial translation Financial translation is the translation of texts of a financial nature. Anything from banking to asset management to stocks and bonds could be covered. General translation A general translation is the simplest of translations. A general text means that the language used is not high level and to a certain extent could be in layman's terms. There is no specific or technical terminology used. Most translations carried out fall under this category.Legal translation Legal translations are one of the trickiest translations known. At its simplest level it means the translation of legal documents such as statutes, contracts and treaties. A legal translation will always need specialist attention. This is because law is culture-dependent and requires a translator with an exc ellent understanding of both the source and target cultures. Most translation agencies would only ever use professional legal to undertake such work.This is because there is no real margin for error; the mistranslation of a passage in a contract could, for example, have disastrous consequences. When translating a text within the field of law, the translator should keep the following in mind. The legal system of the source text is structured in a way that suits that culture and this is reflected in the legal language; similarly, the target text is to be read by someone who is familiar with another legal system and its language. Literary translationA literary translation is the translation of literature such as novels, poems, plays and poems. The translation of literary works is considered by many one of the highest forms of translation as it involves so much more than simply translating text. A literary translator must be capable of also translating feelings, cultural nuances, humour and other subtle elements of a piece of work. Some go as far as to say that literary translations are not really possible. In 1959 the Russian-born linguist Roman Jakobson went as far as to declare that â€Å"poetry by definition [was] untranslatable†.In 1974 the American poet James Merrill wrote a poem, â€Å"Lost in Translation,† which in part explores this subject. Medical translation A medical translation will cover anything from the medical field from the packaging of medicine to manuals for medical equipments to medical books. Like legal translation, medical translation is specialisation where a mistranslation can have grave consequences. Technical translation A technical translation has a broad meaning. It usually refers to certain fields such as IT or manufacturing and deals with texts such as manuals and instructions.Technical translations are usually more expensive than general translations as they contain a high amount of terminology that only a specialist translator could deal with. According to Brislin (1976: 1) translation is a general term referring to the transfer of thoughts and ideas from one language to another, whether the language is in written or oral form, whether the languages have established orthographies or not; or whether one or both languages is based on signs, as with signs of the deaf.Another expert, Wilss (1982: 3), states that translation is a transfer process which aims at the transformation of a written source language text (SLT) into an optimally equivalent target language text (TLT), and which requires the syntactic, the semantic, and the pragmatic understanding and analytical processing of the source text. Syntactic understanding is related to style and meaning. Understanding of semantics is meaning related activity. Finally, pragmatic understanding is related to the message or implication of a sentence. This definition does not states what is transferred. Rather, it states the requirement of the process.Nid a and Taber (1982: 12) see translating as a process of reproducing in the receptor language the closest natural equivalent of the source language message, first in terms of meaning and secondly in terms of style. In other words, translation is a transfer of meaning, message, and style from one SLT to the TLT. In the order of priority, style is put the last. Here the things to reproduce (transfer) is stated, message. Newmark (1991: 27) defines the act of translating very briefly. It is the act of transferring meaning of a stretch or a unit of language, the whole or a part, from one language to another. The discussion on meaning can be seen at sub-point F. Meaning, Message, and Style. ) According to the purpose, translation can be divided into four types: (a) pragmatic, (b) aesthetic-poetic, (c) ethnographic, and (d) linguistic translation (Brislin, 1976: 3-4). Pragmatic translation is the translation of a message with an interest in accuracy of the information meant to be communicate d in the target language form. Belonging to such translation is the translation of technical information, such as repairing instructions.The second type is aesthetic-poetic translation that does not only focus on the information, but also the emotion, feeling, beauty involved in the original writing. The third is ethnographic translation that explicates the cultural context of the source and second language versions. The last type is linguistic translation, the one that is concerned with equivalent meanings of the constituent morphemes of the second language and with grammatical form. Seen from this classification, the translation of literary work should be the aesthetic-poetic one.The other kinds of translation or translation approach important to review are the ones related to the concept of dynamic translation, semantic translation, communicative translation, and artistic translation. Dynamic translation tries to transfer the messages or ideas into a target language and to evoke in the target language readers the responses that are substantially equivalent to those experienced by the source text readers (Nida and Taber, 1982 :28). A definition of dynamic translation centers on the concept of dynamic equivalence, that is the closest natural equivalence to the source language message.Hohulin (1982: 15) notices that the definition of dynamic translation contains three essential terms: (a) equivalent, which points toward the source language message, (b) natural, which points toward the receptor language, and (3) closest, which binds the two orientations together on the basis of the highest degree of approximation. Dynamic equivalence approach can be used in the level of translating sentences or group of sentences, because the whole message lies here. Similar to the above concept is the idiomatic translation developed by Beekman and Callow (in Gutt, 1991: 68).It resembles the dynamic equivalence approach in the sense that it rejects the form-oriented translation and emphasizes that a translation should convey the meaning of the original. A translation, according to this approach, should be faithful to the ‘dynamics’ of the original, or the SL’s ‘naturalness’ of language use and ease of comprehension. The idea of dynamic translation was first proposed by Nida and Taber and the semantic and communicative translation was by Newmark. He even states that the concepts represent his main contribution to general theory of translation (Newmark, 1991: 10).It seems to be a reaction to the concepts of formal and dynamic equivalence, literal and free translation. In the above dichotomy, the first â€Å"pole† of the dichotomy (formal equivalence and literal translation) seems to be condemned for being not be able to transfer the message. Semantic and communicative translation seem to be in the middle of the two poles formal and dynamic translation. (Here formal translation is understood as translation that pursues the formal equivalence and dynamic translation is the one that seeks for the dynamic equivalence.Discussion on the issue of equivalence can be seen in the next sub-point. ) Semantic translation emphasizes the â€Å"loyalty† to the original text. It is more semantic and syntactic oriented and, therefore, also author-centered. On the other hand, communicative translation emphasizes the loyalty to the â€Å"readers† and more reader-centered. The two concepts are not to be contrasted with literal word-for-word translation which is criticized in the concept of formal translation and literal translation. He sees it as a translation procedure.He states that literal word-for-word translation is not only the best in both communicative and semantic translation, but it is the only valid method of translation if equivalent effect is secured (Newmark, 1991: 10-11). He further maintains that, in fact, there is no pure communicative or pure semantic method of translating a text. The re are overlapping bands of methods. A translation can be more or less semantic as well as more or less communicative. Even a part of a sentence can be treated more communicatively or more semantically.Anyhow he maintains that the more important the language of the text or units of text, e. g. in the sacred texts, the more closely it should be translated. Finally he points out that meaning is complicated, many-leveled, a ‘network of relation’. The more generalization and simplification is done, the less meaning is gotten. From this discussion, it can be argued that the choice between semantic and communicative approach is done in the level of translating sentences or even parts of sentence (Newmark, 1991: 10). In the area of literary translation, Chukovsky (1984) offers the concept of artistic translation.Like the other types of translation, meaning is a very important point to consider. Yet, style is taken as importantly as the other aspects for style is the portrait o f the author; so when a translator distorts his style he also distorts ‘his face’ (Chukovsky, 1984: 20). Besides the meaning, impression on the readers should also be kept the same. This translation expert states that it is essential that the readers of the translation should be carried into the very same sphere as the readers of the original, and the translation must act in the very same nerves (Chukovsky, 1984: 80).To compare, formal and dynamic translation center on the message of the original, the semantic and communicative translation on whether author-centered or reader-centered, and artistic translation does on the consideration of literary aspects: ideas and style. The concepts are based on different ground. It is clear that the concept of dynamic translation is suitable for translating the Bible. It is so because the concept of dynamic equivalence itself was developed from the practice of Bible translation. As it is known, there are many kinds of text some of w hich are with the characteristics different from the Bible.The semantic and communicative ones, on the other hand, can be applied at any kinds of text. The case of style is also discussed by Newmark in his hint that â€Å"the more important the language of the text or units of text, the more closely it should be translated. † Finally, artistic translation is probably most appropriate for translating certain literary works, like poetry. Maintaining the author’ style accurately is very difficult in certain novels as the translator is confronted with the syntactic system as well as literary convention of the target language. 1) Communicative classification of translation ) Genre classification of translation 3) Psycho-linguistic classification of translation 1) Communicative classification of translation is based on the predominant communicative function of the source text or the form of speech involved in the translation process. Translation can be literary and informati ve. Literary translation is the translation of literary texts. The main function of literary translation is to produce an emotional or aesthetic impression upon the reader. The informative translation deals with rendering into target language the non-literary texts.The main purpose of the informative translation is to convey a certain amount of ideas. 2) Literary works fall into genres. The technical translation the main goal is to identify the situation described in the original. In official documents every word must be carefully chosen. Publicistic texts include the translations of newspapers, magazines, ect. To other genres belong the translations of film scripts, where the main problem is to fit pronunciation and the choice of words. The translations of commercials are those, the main goal of which is to attract the attention of the audience. ) The  psycho-linguistic classification  of translation falls into written and oral translation, consecutive and simultaneous translat ion, compression and text development. In written translation the original text is in written form as well as in target language. Written translation is continuous, oral translation is commentary (one time action). There are two main types of oral translation. In consecutive translation the translating starts after the original speech of some part of it has been completed. In simultaneous interpretation the interpreter is supposed to be able to give his translation while the speaker is uttering his message.The difference between consecutive and simultaneous interpretation – in simultaneous interpretation the interpreter is much more limited in time. The length of the text translated is much shorter than in consecutive translation. Unlike consecutive interpretation, were the interpreter may correct mistakes and slips of the tongue, simultaneous has no time for corrections and redoing. Text compression is aimed at saving interpretation time and removing source text redundancy, which allows the interpreter to keep in pace with the source text, not sacrificing the context. It is more often used in simultaneous interpretation.Basic comprehension devices in the Ua-En translation are: 1) Transformation of the nominative structures into the verbal ones 2) Conversion of prepositional constructions into noun clusters 3) Omission of transformation of words and word combinations typical to Ukrainian style and considered redundant according to English speech standards. Compression is more often used in translations from Ukrainian into English because the English way of expression is more concise. And often English text contains no redundant words, which is explained by the analytical structure of the language.Text development is more often used in consecutive translation. It is reflected in the note-taking procedure. Text development in the course of interpretation is the restoration of the full composition of the source sentence, starting from its syntactic and sem antic core, accompanied by compliance with syntactic and semantic standards of the target language. The note-taking procedure includes main ideas (skeleton outline, subject-predicate-object), links and separations, viewpoints of the speaker, tenses and modalities, proper and geographical names, dates and numbers.