Italy Tax System free essay sample

Faculty of Business and Management, Brno University of Technology INTERNATIONAL AND EUROPEAN BUSINNES LAW Tax system in Italy 2009/2010 Taxation in Italy The taxation system in Italy is administered by the Agenzia delle Entrate (Revenue Agency) which is the national legal authority for taxation. Taxation of an individuals income in Italy is progressive. In other words, the higher the income, the higher the rate of tax payable. There are reduced rates of tax and tax exemptions available to certain income earners. The liability for Italian income tax depends on where a person is domiciled. A domicile is usually the country we regard as the permanent home and where we live most of the year. A foreigner working in Italy for an Italian company who became resident in Italy and has no income tax liability abroad is considered to have a tax domicile in Italy. A person can be resident in more than one country at any time, but can be domiciled only in one country. We will write a custom essay sample on Italy Tax System or any similar topic specifically for you Do Not WasteYour Time HIRE WRITER Only 13.90 / page The country of domicile is important regarding inheritance tax, as there’s no longer any inheritance tax in Italy. Generally, person is considered to be an Italian resident and liable to Italian tax if any of the following applies: †¢The person has permanent home in Italy; †¢He/She stays at least 183 days in Italy during any calendar year †¢Person carries out paid professional activities or employment in Italy, except when secondary to business activities conducted in another country; †¢The centre of person’s economic interest in in Italy If the person is registered as a resident in a comune, he/ she is liable to pay income tax in Italy. If a person moves to Italy to take up a job or start a business, he/she must register with the local tax authorities soon after the arrival. This is done at a local tax office. An individual is also liable for tax on his income as an employee and on income as a self-employed person. Tax will be payable on income earned in Italy and overseas by an individual who meets the test of a permanent resident of Italy. A foreign resident who is employed in Italy pays tax only on income earned in Italy. It is important to point out as regards taxable income from outside Italy, that a tax credit is granted for tax deducted outside Italy. In the case of income from a salary, the employer is obligated to deduct the amount of tax payable on a monthly basis. A self-employed person must prepay income tax that will be offset on filing an annual return. The advance payment is determined on the basis of the return made for the previous year. In the event of a new business, the advance will be calculated on the basis of estimates made by the owner of the business. The taxation system in Italy is divided into two categories: Direct taxes * IRPEF or IRE: Imposta sui Redditti delle Persone Fisiche ( Personal Income Tax) * IRPEG or IRES: Imposta sur Redditi delle Persone Giuridiche (Corportation Tax on the Income of limited liability and joint-stock companies SRL or SpA) * IRAP: Imposte Regionale sulle Attivita Produttive (Regional Tax which applies to the value of goods and services) Italy Personal Income Tax rates in year 2009 * 23%0 15,000(EUR) * 27%15,001-28,000(EUR) * 38%28,001-55,000(EUR) * 41%55,001-75,000(EUR) 43%75,001 and over (EUR) Capital Gains Tax in Italy For individuals capital gains are generally added to the regular income. †¢The rate of tax payable on capital gains from shareholding is 12. 5% for non-qualifying shareholding of up to 25% in a company. †¢For the purpose of calculating a capital gain, the gain is decreased in line with the rate of increase in inflation, from the date of purchase to the date of sale. In r egard to capital gains in a corporation, identical relief is allowed at the rate of increase in the Index. †¢Companies pay 27. 5% tax on capital gains. In sale of participation, 95% is tax exempt, subject to certain conditions. Italy Reporting Dates and Payment The tax year in Italy ends on December 31st. Advance payments of tax are made on the following basis. †¢ An Individual An individual whose only income is from a salary is not obligated to file an annual tax return. His employer deducts tax from the employee and transfers the payment immediately to the tax authorities on a monthly basis. †¢ A Self-Employed Individual is obliged to pay 100% of the tax forecast for a year, or an amount that is the equivalent of 98% of the tax paid in the previous year. The pre-payment is made in two installments. 40% of the total is paid by June 20th and the remaining 60% is paid on November 30. The date for filing an annual return for an individual is July 31. Fines are imposed for arrears in filing an annual return at the rate of 120% 240% of the tax, depending on the length of time that the return is in arrears. †¢ A Limited Company A limited company is obligated to submit Financial Statements within 30 days of the date of approval of the Statements. Up until the date of approval of the Statements, the Company is obligated to pay the amount of tax due for the previous year as well as 40% of the advance on account of the tax forecast for the current year. Italy Deduction of Tax at Source Italy Taxation of Employees As regards employed persons, the employer is obligated to deduct tax at source from an employee and to make additional contributions to social security. Italy Social Security †¢An employed person the employers contribution is around 30% of the salary and the employees contribution is around 10% of the salary. A self-employed person the rate of payment is between 17%-25. 7% with an upper limit that changes from year to year. Indirect taxes * IVA (VAT) * Imposta di Registro (Registration Tax) * Imposte Ipotecarie e Catastali (Mortgage and Land Registration) * Imposta di Bollo (Revenue Stamps) * Accise o Imposte di Fabbricazione e consumo (Inland Duties) IVA (VAT) * Standard Rate 20% (since Oct 1997) Reduced Rate 10% Italy VAT Recovery Time: 18 months Italy VAT Registration Threshold Non-Resident: Nil Inheritance Tax ; Gift Tax There is no longer any tax on inherited property, regardless of its value and the relationship between the deceased and the heirs. On immovable property and real property rights, the catastral tax (imposta catastale) and land registry tax (imposta ipotecaria) must be paid at the rates of one percent and two percent, respectively, of the cadastral value of the property or the real property rights included in the inheritance. If one of the beneficiaries satisfies the conditions for the main or only residence (prima casa), the cadastral and land registry taxes due on an inheritance or a gift are a fixed amount of â‚ ¬168 each. In relation to gifts, the rules vary depending on the degree of kinship and the value of the gift. There are no taxes payable on gifts in favour of a spouse, descendants or other relatives up to the fourth degree. Gifts in favour of persons other than those mentioned above are subject to taxes on the transfer if the value of the share due to each beneficiary is greater. Other Taxes There are other taxes payable to central, regional, provincial or local governments. These are usually paid once a year. Bollo Auto (Car Tax), which includes the tax on your car radio and the stamp duty on your Italian driving licence * Bollo Moto (Motorbike Tax) * Bollo Motorino (Scooter Tax) * Canone RAI (TV Tax) * Tassa Rifiuti (Garbage Tax) * Imposta Comunale Sugli Immobili ICI (Municipal Property Tax) Deductible Burdens and Tax Allowances Tax allowances include the so-called no-tax area, (a deduction of between â‚ ¬3,000 and â‚ ¬7,500 to avoid taxing those on low incomes), as well as allowances for dependant family members (dependant wife and/or children). Some deductible burdens (oneri deducibili) are expenses which can be used to reduce the total income. For example: some types of medical expenses, national insurance contributions, donations to religious institutions, donations to universities, research bodies and associations for the protection of assets of artistic interest, the cadastral income (income deriving from the value of any land owned) of the main residence are considered to be deductible burdens. Some deductible burdens are expenses which can be used to reduce the amount of the gross tax due. Again by way of example: medical expenses, passive interest on mortgages, education expenses, donations to Bodies or Foundations for research, for performing arts, for social purposes, donations to political parties. Each type of expense has its own rules for the deductions. For example: from rental property income a fixed amount of 15 percent of the income is deducted for expenses, while from business and self-employed income the expenses sustained for the carrying out of the activity are deducted. Some unearned incomes are taxed only on 40 percent of the amount. The majority of these burdens are not deductible from the income of non-residents. Other deductions in Italy Deductions must be made from the following payments to nonresidents according to this table: * Dividend27 (1. 375% to EU and EEA residents) * Royalties22. 5% * Interest12. 5 / 27% * Directors Remuneration20% Deduction at source in the case of a dividend, royalties and interest paid to foreign residents is subject to the Double Taxation Prevention Treaty. Double Taxation Treaties Double taxation treaties contain rules that determine in which country an individual is resident. Italian residents are taxed on their world-wide income, subject to certain treaty exceptions. Non-residents are normally taxed only on income arising in Italy. Citizens of most other countries are exempt from paying taxes in their home country when they spend a minimum period abroad, e. g. a year. Double taxation treaties are designed to ensure that income that has already been taxed in one treaty country isn’t taxed again in another treaty country. The treaty establishes a tax credit or exemption on certain kinds of income, either in the country of residence or the country where the income was earned. Where applicable, a double taxation treaty prevails over domestic law. Italy has double taxation treaties with over 60 countries, including all members of the EU, Australia, Canada, China, the Czech Republic, Cyprus, Estonia, Hungary, Iceland India, Israel, Japan, Latvia, Lithuania, Malaysia, Malta, Mexico, New Zealand, Norway, Pakistan, the Philippines, Poland, Romania, RSA, Russia, Singapore, the Slovak Republic, Sri Lanka, Switzerland, Turkey, and the US. Bibliography: SOCR. CZ. Pravidla pro volny pohyb sluzeb a svobodu usazovani v  EU- Italie. [online]. [cit. 2010-04-12]. URL:http://www. ocr. cz/images/prirucka/pdf/it. pdf, cit. 1 BUSINESSINFO:CZ. Italie: Financni a danovy sektor [online]. [cit. 2010 012]. URL:http://www. businessinfo. cz/cz/sti/italie-financni-a-danovy-sektor/5/1000683/ ANGLOINFO. COM. Personal Taxes Income Tax, Capital Gains Inheritance Tax in Italy. [online]. [cit. 2010 012]. URL: http://rome. angloinfo. com/countries/italy/tax. asp CANADINTERNATIONAL. GC :CA. Income and Other Taxes in Italy. [online]. [cit. 2010 012]. http://www. canadainternational. gc. ca/italy-italie/consular_services_consulaires/tax_italy-italie_taxes. aspx? lang=eng

Controlling Point Sources To Reduce Pollution An Environmental Sciences Essays

Controlling Point Sources To Reduce Pollution An Environmental Sciences Essays Controlling Point Sources To Reduce Pollution An Environmental Sciences Essay Controlling Point Sources To Reduce Pollution An Environmental Sciences Essay Point beginnings pollution is the fouling substance is emitted straight into the waterway. Point beginning pollution is taint that enters the environment through any discernable, confined, and distinct conveyance, such as a smokestack, pipe, ditch, tunnel, or conduit. Point beginning pollution remains a major cause of pollution to both air and H2O. Point beginnings are differentiated from non-point beginnings, which are those that spread out over a big country and have no specific mercantile establishment or discharge point.A National Pollutant Discharge Elimination System ( NPDES ) a license system to command outflowing releases from direct industrial discharges and POTWs ( Publicly Owned Treatment Works ) . The licenses province exactly what the outflowing restrictions are every bit good as the monitoring and coverage demands. Technology-based Effluent Restriction The purpose of technology-based wastewater bounds in NPDES licenses is to necessitate a minimal degree of intervention of pollutants for point beginning discharges based on available intervention engineerings, while leting the discharger to utilize any available control technique to run into the bounds. For industrial ( and other non-municipal ) installations, technology-based wastewater bounds are derived by: Using national outflowing restriction guidelines and criterions established by EPA Using best professional opinion ( BPJ ) on a individual footing in the absence For municipal installations ( publically owned intervention works or POTWs ) , technology-based wastewater bounds are derived from national secondary Standards to command discharges from point beginnings based chiefly on technological capableness. License authors must see the possible impact of every proposed surface H2O discharge on the quality of the receiving H2O. A license author may happen that technology-based wastewater bounds are non sufficient to guarantee that H2O quality criterions, designed to protect the H2O quality, will be attained in the receiving H2O. Water Quality Based Effluent Limitation ( WQBEL ) means an outflowing restriction, which may be more rigorous than a engineering based outflowing restriction, that has been determined necessary by the Department to guarantee that H2O quality criterions in a receiving organic structure of H2O will non be violated. Analysis of the Effluent Limitation Imprecise Statutory definition Meeting the Zero Discharge Goal Lack of an Efficiency Standard Cost-Ineffective Decision Making THE POTWs support plan Federal grant plan: provided major support from the federal authorities for a portion of the building costs of POTWs. Clean Water State Revolving Fund ( CWSRF ) Plan: Establishes province loaning plans to back up POTW building and other undertakings. The replaced the federal grant plan is to supply loans for POTW building every bit good as for other environmental undertakings. CWSRF plans provided more than $ 5 billion yearly in recent old ages to fund H2O quality protection undertakings for effluent intervention, nonpoint beginning pollution control, and watershed and estuary direction. CWSPFs have funded over $ 74 billion, supplying over 24,688 low-interest loans to day of the month. Offers low involvement funding understandings for H2O quality undertakings. Annually, the plan disburses between $ 200 and $ 300 million to eligible undertakings. Nonpoint beginnings Pollution Nonpoint beginning pollution is besides known as overflow pollution . It occurs when rainfall or snowmelt tallies over land or through the land, picks up pollutants, and deposits them into rivers, lakes, wetlands, and coastal Waterss or present them into groundwater. Some of the primary activities that generate nonpoint beginning pollution include agriculture and graze activities, lumber harvest home, new development, building, and recreational yachting. Manure, pesticides, fertilisers, soil, oil, and gas produced by these activities are illustrations of nonpoint beginning pollutants. Even single families contribute to nonpoint beginning pollution through improper chemical and pesticide usage, landscape gardening, and other family patterns. Runoff pollution mean H2O from rain ( besides called storm H2O, urban overflow, and storm drain pollution ) , irrigation, garden hosieries or other activities that picks up pollutants ( coffin nail butts, rubbish, automotive fluids, used oil, pigment, fertilisers and pesticides, lawn and garden cuttings and favored waste ) from streets, parking tonss, private roads and paces and carries them through the storm drain system and heterosexual to the ocean. Nonpoint beginnings pollutants include: Fertilizers, weedkillers, and insect powders from agricultural lands and residential countries ; Oil, lubricating oil, and toxic chemicals from urban overflow ; Sediment from improperly managed building sites, harvest and forest lands, and gnawing stream Bankss ; Bacterias and foods from farm animal, pet wastes, and defective infected systems Nonpoint Source Pollutants and Their Effectss Nonpoint beginning pollution is the taking cause of H2O quality jobs. The effects of nonpoint beginning pollutants on specific Waterss vary. Nonpoint beginning pollutants have harmful effects on imbibing H2O supplies, diversion, piscaries, and wildlife. The illustrations of nonpoint beginning pollutants include: Foods which are compounds that stimulate works growing. The two most common foods making our Waterss are nitrogen and phosphoric. Nitrogen taint of imbibing H2O can do wellness jobs. Excess foods running off the land and making surface Waterss can do monolithic algae blooms, the decay of which can make olfactory properties and utilize up most of the dissolved O, which can ensue in fish putting to deaths. Foods in contaminated overflow can come from a assortment of beginnings such as agricultural fertilisers, infected systems, place lawn attention merchandises, and yard and carnal waste. Sediment which is the silt, sand, soil, and crushed rock eroded by overflow normally ends up in watercourses and lakes. Deposit can change watercourse flow and diminish the handiness of healthy aquatic home ground. Ill protected building sites, agricultural Fieldss, and roadways can be major beginnings of deposit. Pathogens which are beings as bacteriums, viruses, and protozoon, coming from untreated sewerage, storm drains, infected armored combat vehicles, and overflow from farms. Pathogens cause unwellnesss such as enteric fever and dysentery. Watershed A watershed is the country of land where all of the H2O that is under it or drains off of it goes into the same topographic point. It is a basin-like landform defined by highpoints and ridgelines that descend into lower lifts and watercourse vales. A watershed carries H2O shed from the land after rain falls and snow thaws. Drop by bead, H2O is channeled into dirts, groundwaters, brook, and watercourses, doing its manner to larger rivers and finally the sea. Water is a cosmopolitan dissolver, affected by all that it comes in contact with: the land it traverses, and the dirts through which it travels. The of import thing about water partings is: what we do on the land affects H2O quality for all communities populating downstream. Watershed attack is the most effectual model to turn to today s H2O resource challenges. Four chief characteristics are typical of the Watershed Approach: 1 ) Identifying and prioritizing H2O quality jobs in the water parting, 2 ) Developing increased public engagement, 3 ) Organizing activities with other bureaus, and 4 ) Measuring success through increased and more efficient monitoring and other informations assemblage. An extra feature of the Watershed Approach is that it complements and coordinates other environmental activities. This allows for close cooperation with local citizen groups, local authoritiess, other province bureaus, and federal bureaus. When all permitted dischargers are considered together, bureaus are better able to concentrate on those controls necessary to bring forth mensurable betterments in H2O quality. This besides consequences in a more efficient procedure: It encourages bureaus to concentrate staff and fiscal resources on prioritized geographic locations and makes it easier to organize between bureaus and persons with an involvement in work outing H2O quality jobs. The Targeted Watershed Grant Program The targeted watershed grant plan is a competitory grant plan to promote the protection and Restoration of the state s H2O resources. The plan supports environmental stewardship and action by supplying needed support to watershed organisations for on-the-ground Restoration and protection attempts designed to accomplish quick, mensurable, environmental consequences. The end is to construct on the successes of bing partnerships and alliances that have evaluated and assessed their water partings, devised a technically sound watershed program, and are ready to ship on stairss to implement their program. Watershed-based NPDES Permitting is an attack to developing NPDES licenses for multiple point beginnings located within a defined geographic country. Through this attack, NPDES allowing governments consider watershed ends and the impact of multiple pollutant beginnings and stressors, including nonpoint beginning parts. This attack can embrace a broad assortment of activities, from synchronising license issue within a watershed to developing water-quality based outflowing bounds for a group of point beginnings, aimed at accomplishing new efficiencies and environmental consequences. Water Quality Trading is an advanced manner for H2O quality bureaus and community stakeholders to develop cost-efficient solutions to turn to H2O quality jobs in their watersheds.A

Financial Statment Analyasys Case Study Example | Topics and Well Written Essays - 1000 words

Financial Statment Analyasys - Case Study Example was established in the year 1980 for retail sale of â€Å"natural and organic foods† (Edgar Online 1). It became the first grocer enterprise to receive national organic certification among grocers. The organization’s history has been based on its mission of quality products towards high health standards and supports national movements for natural and organic foods. The organization floated its initial public offer in the year 1992 and currently operates more than 300 stores globally. Most of its stores have many years of existence in the market, with an average of ten years in their respective locations. Most of the stores are in the United States but subsidiaries exist in Canada and the United Kingdom. Retail in natural and organic foods is the organization’s core operation. Focus on social responsibility such as environmental consciousness and the need to improve health through quality product, despite nature of competition, are the most interesting features of the organization. I preferred the company to others because of its prominence in the industry. 2. The purpose of the ‘management discussion and analysis section’ is to offer the management’s position on its organization’s financial features on a times series scale. ... The section also explains existence of competition, describes the entity’s products, and offers a summary of financial data over the past three accounting periods. Its clear and outlined organization is the most interesting thing and it communicates high prospects and stability of the entity. 3. Ernst & Young LLP is the organization’s independent auditor. 4. The auditor’s opinion validates reported information by the management. The auditor’s opinion, in the form, approved the company’s statement to be a fair representation of the company’s financial position. The opinion is unqualified because it offers no reservation on reliability of the financial statements. 5. The company did not change its auditors. 6. The 10-K includes certification statement required by Sarbanes-Oxley and John Mackey signed the certification. The certification qualifies the report’s compliance with sections 13(a) and 15(d) of the Security Exchange Act and that the report is a fair representation of the organization’s financial position and operational outcomes and means the management’s adoption of the financial statements. 7. The lowest stock price for the last financial year was $ 60.39 while the highest price was $ 100.5. The following table summarized trend in data for the period ended 2012. Graph 1: Stock daily closing stock prices 8. The stock prices had a generally decreasing trend with a level of volatility, politics is a major factor as the nation headed for presidential elections in November 2012, and the management did not associate the decline with economic factors. 9. The industry identifies positive prospects based on accounting rations such as revenue growth, return on equity, and long-term

Legal System of UK Essay Example | Topics and Well Written Essays - 4000 words

Legal System of UK - Essay Example By the sixteenth century the legal profession in the UK had branched into two categories. The first one was barristers and the other is collective of attorneys and solicitors. The local "common law" was formulated by a specialised legal society known as the Inns of Court, in London. It was in these inns that through lectures and apprenticeship individuals were admitted to practise before the royal courts. With the passage of time these practitioners became sergeants who were considered as the most distinguished among the advocates. These dignitaries were later on appointed as royal judges. The "attorneys," who were authorised by the legislation initially, shared the life of the Inns with the "apprentices" in advocacy, till they acquired the title of barrister. (Branches of the Legal Profession, http://www.pravo.hr/_download/repository/ LEGAL_PROFESSION_IN_ENGLAND_08web.ppt, viewed on 9th April, 2009) In its ultimate growth the English legal profession resembled the European professions, particularly the northern France, where the parliaments (courts) were considered as corporate, and apprentices were trained like that of the Inns. Growth of the law was mainly through precedents based on the judgments of the courts, rather than through legislation. In England, senior practicing professionals were appointed as judges. Apart from this, the partition between barristers and solicitors eventually became more rigid in England. Moreover, England never acquired the profession of notaries and thus the whole burden of transactional work was carried out by the present solicitors with legal advice from the bar. David H. Goodchild, in his work on History of the English Legal Profession in Paris 1850-2000 says, ".in 1880 the picture had changed quite considerably by which time as a result of the Judicature Act 1873 all attorneys at law and solicitors had been merged into one single profession of "solicitor" and those practising abroad were listed under the somewhat charming section entitled "Solicitors practising in foreign parts". (Page 1, http://72.14.235.132/searchq= cache:dhmu KhIOD2YJ:fbls.org/pages/FR/ publications/assets/articles/ English_legal_profession.pdf+History+of+UK+legal+profession&cd=15&hl=en&ct=clnk&gl=in, viewed on 9th April, 2009) Change in Status of the Law Professionals Even before the Judicature Act 1873 the status of the solicitors has undergone radical changes. They became the legal advisors of the wealthy feudal and businessmen. In the year 1804 they acquired the monopoly of conveyancing, and just before the end of the 19th century they started dealing with divorce and admiralty cases and obtained the rights of audience in County Courts. The progress they earned since then was tremendous, and at present over 97000 solicitors practise all over UK. Many of them are practising in private firms and governmental bodies as legal advisors doing advocacies, drafting legal documents etc. However, they cannot appear in every court, whereas the barristers are entitled to have appearance in courts. More than 11500 barristers are engaged in practice in England and Wales, now. Some of them are in employed practice. They only represent their employers. Other

Willingness to Pay Essay Example | Topics and Well Written Essays - 250 words - 1

Willingness to Pay - Essay Example The contingent valuation methodology was adopted in drafting the questionnaires that were used in collecting the data to be used in the analysis. An approximate 72% of all the participants who responded to the questionnaires indicated willingness to pay for the conservation though at varying levels. This therefore pointed out that the public in many instances are willing to contribute towards the improvement of the quality of the environment. The study employed use of logistic regression procedures in comparison of the persons who were willing and not willing to contribute actively in improving the environmental quality. Through the contingent valuation analysis, the use value as well as non-use value of natural resources and environmental quality can be established. This method therefore involves a hypothetical scene to establish the willingness to pay of individuals on such natural resources and quality of environment. Hypothetical case studies are often used in such a situation where after describing such a case to the respondent, he/she is then expected to quote the amount of money he/she would be willing to pay for the environmental quality. Reasons expressed for willingness to pay would therefore form the basis of policymaking especially as regards to legislation on environmental conservation and management. In often cases such as was revealed through the case study, non-use values like existence value were cited most as reasons why many people would be willing to pay for conserving natural environment or such a natural park. This study therefore shows that valuation of gains from natural reso urces and environment would contribute greatly towards efforts and willingness of people to pay for such conservations. Han, F., Yang, Z., Wang, H., & Xu, X. (2011). Estimating willingness to pay for environment conservation: A contingent valuation study of kanas nature reserve, xinjiang, china. Environmental Monitoring and Assessment,

Advanced breast cancer

Advanced breast cancer Background Cancer accounts for 13% of all deaths in 2007, making it the largest cause of mortality worldwide and is the leading cause of premature death in Scotland. 2,22 Out of the staggering figure of 27,500 new cases that were diagnosed on that same year in Scotland, 4044 of them are breast cancer cases, making breast cancer the most commonly diagnosed cancer among Scottish women.3 In the UK, 16-20% of women have advanced breast cancer and approximately 40-50% of those diagnosed with early or localised breast cancer may eventually develop metastatic disease. Breast cancer is usually defined using a staging system known as the Tumour, Node and Metastasis Staging System (TNM) and stage III and IV are known as advanced stages of the disease with stage III being locally advanced and or has spread to regional lymph nodes and stage IV describing the presence of metastases at distant sites such as the bone, brain, or lung.23 In the elderly group of female cancer patients, the prevalence of breast cancer is highest at 4% and these post-menopausal women make up 80% of all breast cancer patients, hence proving that the risk increases with age.1 Apart from age, other factors like family history, uninterrupted oestrogen exposure, early menarche, late menopause, late first pregnancy, hormone replacement therapy, obesity, not breast feeding, taking oral contraceptives and past breast cancer may all attribute to a higher risk of developing breast cancer.9 Over the last decade, mortality rates from breast cancer have dropped by almost 14%, despite having more women diagnosed with the disease. In 2000-2004, the survival rate for breast cancer patients has also bumped up to 84% compared to a mere 64% 20 years earlier.4Improvement in prognosis, screening techniques such as mammography, ultrasound and Magnetic Resonance Imaging(MRI), earlier diagnosis of cancers in women participating in the Scottish Breast Screening Programme, a myriad of new hormonal and chemotherapy treatments, and better organisation and patient care plans has attributed to the substantial increase in incidence and survival rate of breast cancer patients. Women today are also encouraged to perform self breast examinations, hence are familiar with the shape and feel of their breasts, as well as to look out for abnormities like a new discrete lump, nipple discharge, unilateral persistent pain especially in post-menopausal women or pain associated with a lump and skin changes comprising of skin tethering, ulceration, abscess or inflammation.However, there is still a disparity between women from different social classes in terms of combating this disease. Women from more affluent backgrounds are more likely to have their breast cancer diagnosed earlier, have slower disease progression from the time of diagnoses and higher survival rates compared to women from poorer socioeconomic backgrounds. Women from more deprived communities are more likely to be diagnosed with the advanced stage of the disease. Pathogenesis Cancer or malignant neoplasm which literally means new growth is a disease manifested in the form of uncontrolled cell proliferations, dedifferentiation and loss of function, invasiveness and metastasis.6 Breast cancer usually forms from the inner lining of milk ducts or the lobules that supply the ducts with milk. In patients with Breast Cancer, women who inherit a single defective copy of tumour suppressor genes BRCA1 or BRCA 2 have a marked higher risk of developing breast cancer in their lifetime. The presence of a defective BRCA1 or BRCA 2 gene can invoke changes in several cellular systems including the signaling pathways and receptors of growth factors and cell cycle tranducers, the apoptotic machinery which responsible for programmed cell death that normally disposes of abnormal cells, the secretion of telomerase, and local blood vessels which results in tumour-directed angiogenesis to supply nutrients to these tumours both aids the proliferation of cancer cells.7,8 Breast cancer cells are able to invade other tissues like the lymph nodes as they no longer exercise the same restraints as the normal cells and they also secrete enzymes like metalloproteainase to break down the extracellular matrix, conferring them mobility. Metastases are secondary tumours normally found in the advanced stage of breast cancer formed by cells released from the primary tumour and have reached and have established themselves at other sites like the lung brain or the bones which are common sites for metastatic cancers of breast origin through blood vessels and lymphatics. The tissues of lung, brain and bone origin express high levels of CXR4 chemokine receptors produced by the breast cancer cells, facilitating the selective accumulation of the cells at these sites.6 Treatment Options There are three main approaches to treating breast cancer, namely surgical excision, irradiation and a host of systemic disease-modifying therapies or a combination and is chosen based on the stage of breast cancer. However, when caring for patients with advanced breast cancer, the goal of treatment of advanced breast cancer is to palliate symptoms, improve survival and quality of life. There are notably three types of systemic disease-modifying therapies to treat advance breast cancer namely endocrine therapy, chemotherapy and biological therapy. Endocrine Therapy Oestrogen exposure has been instrumental in inducing mutations that can lead to breast cancer as they can stimulate cell growth in most of human breast cancer cell lines expressing Oestrogen Receptor (ER) ÃŽÂ ± .8 Clinical studies have proven that more than half of breast carcinomas are ER ÃŽÂ ± positive and respond fairly well to endocrine therapy. Drugs are aimed either to change the ER signaling pathways or prevent estrogen synthesis.7 Tamoxifen and 3rd generation Aromatase Inhibitors (AI) have been used for advance breast cancer with the former being effective in premenopausal, perimenopausal and post menopausal women. Pre-menopausal and perimenopausal cancer patients with ER positive tumours should be offered Tamoxifen tablets 20 mg daily, an oestrogen -receptor antagonist and ovarian ablation or the administration of LHRH agonists such as Buserelin or Goserelin as first-line treatment.5,12 Both options are just as effective in terms of tumour response and overall surviva l rates. The latter group of drugs, AI, are the preferred choice for post-menopausal women only with no prior history of endocrine therapy or have been previously been treated with Tamoxifen. AI work predominantly by suppressing oestrogen levels in post-menopausal women by blocking the conversion of androgens to oestrogens in the peripheral tissues. However, they do not inhibit ovarian oestrogen synthesis, hence can cause an elevation in oestradiol levels in pre-menopausal women. Anastrozole and Letrozole are non-steroidal AIs are known to be as efficacious as Tamoxifen as first -line treatment of metastatic breast cancer. 14Exemestane is a steroidal AI used as second-line treatment in advanced breast cancer in post-menopausal women in whom anti-oestrogen therapy has failed. Fulvestrant, an oestrogen receptor antagonist also confers short term benefits in the clinical setting for post-menopausal women who was previously prescribed a non-steroidal AI, delaying the need for chemotherapy. 13AI h ave been associated with an increased progression-free survival and 13% decrease risk of mortality and lower incidence of vaginal bleeds and blood clots. However, patients given AI are more prone to hot flushes and gastro-intestinal symptoms. 5 Other endocrine therapies available include older and less popular therapies such as progestogen and androgen for pre-menopausal women and stilboesterol and trilostane for post-menopausal women. 5 Chemotherapy Both ER positive and negative patients with advanced breast cancer would benefit from either a choice of two or three regiments of chemotherapy and classes of drugs commonly prescribed includes antharacyclines, taxanes, capecitabine, vinorelbine, gemcitabine, alkylating agents like cyclophosphamide and platinum based drugs like carboplatin.5 Anthracyclines such as Epirubicin, Mitoxantrone and Doxorubicin are prescribed as first line chemotherapy as they boost modest survival advantage in patients with advanced breast cancer and are superior to non-anthracycline regimens.1,5Doxorubicin is commonly given via injection into a fast running infusion at 21 day intervals as extravastation can cause severe tissue damage. It exerts a cytotoxic effect by interfering with DNA and RNA synthesis by inhibiting DNA toposiomerase II action. The metabolites are excreted through the bile, hence elevated bilirubin levels are indicative of a need to reduce the dosage. 6,12 Higher accumulation of doses may result in cardiopathy precipitating to heart failure, hence cardiac monitoring is deemed important in managing cancer patients taking it and a limit of total cumulative doses is set at 450 mg/m2.Other symptoms of toxicity includes myelodysplasia and neutropenic sepsis. Doxorubicin is also available in liposomal formulations which are safer in terms of reduced incidents of cardiotoxicity and local necrosis but is not recommended by the Scottish Medicines Consortium for treatment of metastatic breast cancer.1,12 Both Epirubicin,an anthracycline derivative, and Mitoxantrone ,an anthracenedione derivative,are structurally related to Doxorubicin, hence similar drug activity could be predicted for all three drugs.12 Mitoxantrone given intravenously is licenced to treat metastatic breast cancer and has been well tolerated by patients.However, side effects like myelosuppression and cardiotoxicity are evident and cardiac examinations are recommended after a cumulative dose of 160 mg/m2.12When both drugs are compared in a clinical trial, Epirubicin boosts higher response rates despite demonstrating a higher percentage of toxicity related side effects.20Clinical trials suggest the efficacy of Epirubicin in treating advanced breast cancer is comparable to Doxorubicin as similar response rates were recorded when equal doses were given. These trials also indicated that patients taking Epirubicin had fewer episodes of congestive heart failure and other complications resulting from cardiotoxicity. Therefo re, it could be surmised that Epirubicin is the drug of choice in this regimen .However,a limit of 0.9-1 g/m2 was still imposed when Epirubicin is given to avoid cardiotoxicity. 1,12 Due to the ineffectiveness of single-agent anthracycline therapies in impeding disease progression, combination therapies are often considered for the treatment of advanced breast cancer after failure of with anthracycline monotherapy, provided that the patient is able to tolerate additional toxicity and have a higher chance of response.5 There are clinical evidence suggesting that a combination of anthracycline and taxanes like Doxorubicin and Docetaxel have resulted in better tumour response, delayed progression time compared and reduce risk of mortality to anthracycline monotherapy. The benefits of this synergistic combination, however, did not include improved survival and side effects experienced were more numerous such as thrombocytopenia, alopecia in 75% of these patients,a 10% increase in peripheral neuropathy and neutropenia in 40 to 68% of these patients.1,5 A combination of Epirubicin and Docetaxel would be a better choice as it is just as potent as the Doxycycline and Pac litaxel combination but deemed free of side effects like cardiotoxicity and fluid retention whereas neutropenia was the dose-limiting toxicity .21 Systemic chemotherapy should be offered to patients whom antrhracyclines are contraindicated in cases of cardiac disease hypertension,the elderly, those who have received myocardial irradiation ,those receiving radiotherapy for breast cancer or had receive prior adjuvant treatment with anthracycline. Docetaxel monotherapy is prescribed as the first-line drug followed by single-agent Vinorelbine or Capecitabine as the second-line treatment. Third-line treatment encompasses the use of either Vinorelbine or Capecitabine of which was not offered previously.5 Docetaxel, a member of the taxane group derived from a naturally occurring compound from the bark of yew trees, is licensed to treat locally advanced or metastatic breast cancer. It acts by stabilizing microtubules in the polymerized state, preventing cell division. Side effects associated with Docetaxel are myelosupression, peripheral neuropathy, cardiac conduction defects with arrhythmias, alopecia, muscle pain, nausea and vomiting . Patients currently on Docetaxel are also susceptible to leg oedema and hypersensitivity reactions, which can be ameliorated by taking Dexamethasone orally.1,6,12 Antimetabolites like Capecitabine is a rationally designed tumour-activated and tumour-selective fluoropyrimidine carbamate thatis metabolized to generate 5-fluorouracil at the tumour site which would then be converted to fluorodeoxyuridine monophosphate (FDUMP), a fraudulent nucleotide and interact and inhibit thymidilate synthetase,preventing the synthesis of 2-deoxythymidilate (DTMP),which is vital for DNA synthesis.17Capecitabine has a role in second-line or third-line treatment of chemotherapy for patients of locally advanced or metastatic breast cancer either in combination with Docetaxel or given orally alone at a dose of 1250 mg/m2 twice daily for a forthnight and subsequent courses are repeated after a 7-day interval. Vinorelbine is a semi-synthetic analogue of vinblastine, a vinca alkaloid derived from Madagascar periwinkle. Unlike taxanes, it is targeted at tubulin of mitotic microtubules to form tubulin dimers which prevents spindle formation in dividing cells leading to mitotic arrest at metaphase resulting in cell death. 6 Besides inhibiting mitosis, its effects are also significant in inhibiting leucocyte phagocytosis, chemotaxis and axonal transport in neurons. Hence, side effects includes neutropenia which was found to be the dose-limiting, peripheral or autonomic neuropathy which manifests as peripheral paraestesia, loss of deep tendon reflexes and motor weakness,constipation and abdominal pain. Neurotoxicity caused by Vinorelbine is considered relatively mild compared to other vinca alkaloids even at maximum tolerated dose as it preferentially binds to mitotic over axonal microtubules. 6,12 Vinorelbine is an option to anthracycline or taxane pre-treated patients with advanced breast canc er as second-line or third-line chemotherapy given via intravenous administration at a dose of 30mg/m2 in 250 ml of normal saline over 1 hour. Alternatively, Vinorelbine can be given orally at a dose of 60 mg/m2 for 3 weeks and can be increased if the patient shows good tolerance to the regime to maximum dose of 160 mg once weekly. A clinical response rates of 16-60% was seen with Vinorelbine as a single agent, 28-77% in combination chemotherapy.5, 16 A study comparing Vinorelbine in intravenous(i.v.) form used in combination with Capecitabine given orally and a combination therapy of Vinorelbine and Capecitabine both in oral formulations was done to observe the efficacy of both combinations in anthracycline and taxane pretreated patients with metastatic breast cancer. Despite showing a marginally higher percentage in control of the disease in the oral group,improved survival rates and lower incidence of neutropenia and thrombocytopenia were associated with the i.v. group.17 This study has also shown that a combination of Vinorelbine with Capecitabine therapy may confer advantages as both have unique mechanisms of action, different proposed mechanism of drug resistance and relatively non-overlapping toxicity profiles. However, this combination has yet to be recommended by the NICE or SIGN guidelines as it has yet to be proven to be cost-effective. The recommendation for systemic chemotherapy by NICE is done following a cost-utility analysis which compares chemotherapy regiments in terms of survival, quality of life and associated costs of 17 different strategies drawn up. From the table below, strategies that gives the best survival rates and quality of life are combinations 3,4,13 and 15.However,combinations 3 and 4 that offer Gemcitabine and Docetaxel as the first line are somewhat more costly by approximately  £ 10 000 in total costs compared to combinations 13 and 15.It is also proven here that offering Docetaxel as a first-line drug is also superior to Paclitaxel as survival rates and quality of life are slightly poorer in combinations 8 and 10. 5 Biological Therapy New agents to specifically target molecular processes have been developed over the last decade like Tratuzumab, Bevacizumab and Lapatinib which are all used to treat advanced breast cancer. Tratuzumab, the sole drug of its kind recommended by NICE for use in the UK, is a recombinant humanized monoclonal antibody which binds to Human Epidermal Growth Factor (HER2) on the cancer cells with HER2 over expression and impedes the growth. Hence, HER2 status should be assessed before commencing this therapy as only a quarter of patients with advanced breast cancer have HER2 positive tumours. Tratuzumab is given intravenously in combination with Paclitaxel, Docetaxel or Vinorelbin has been well tolerated. 5,11However, once disease progression occur outside the central nervous system, Tratuzumab should be discontinued. Bevacizumab is another monoclonal antibody aimed at affecting the growth of tumour blood vessels and Lapatinib affects the metabolic pathways of the HER2 and Epidemal Growth Fac tor Receptor (EGFR). 5,23. Surgery Surgical intervention comprises of conservation surgery which involves the removal of the tumour with a rim of surrounding breast tissue with retention of the breast followed by radiation therapy and mastectomy which is usually followed by breast reconstruction. However, these surgical procedures are limited to patients diagnosed with primary operable breast cancer or as palliative surgery for locally advanced breast cancer as they may not confer much benefits to patients diagnosed with later stages of breast cancer.1,11,19 Some patients may have already underwent surgery which was not very successful in eliminating the disease.1 Treatment Recommendation Hormonal therapies are the recommended first-line therapy for patients with an ER positive tumour, are widely used and are said to be appropriate for 70 % of patients who have hormone receptor -positive advance breast cancer. However, in circumstances whereby the disease is life-threatening or the patient has an ER negative tumour, the hormonal therapy would be of no benefit to these patients. At the time of initial diagnosis, the oestrogen receptor (ER) was accessed and the results came out positive before considering commencing on endocrine therapy. Several factors like previous endocrine therapy including adjuvant therapy, the extent and period of response to the therapy and menopausal status have to be taken into account before prescribing hormonal therapy. 5The patient is 62 years of age and is considered to be post-menopausal, hence would benefit tremendously when given aromatase inhibitors(AI),regardless of whether she is tamoxifen naÃÆ' ¯ve. A choice of non-steroidal AIs o f either Anastrozole 1 mg daily or Letrozole 2.5 daily could be given orally. However, if she has a prior history of non-steroidal AIs and she failed to respond well to it, she should be given either Exemestane 25 mg orally or Fulvestrant 250 mg via intramuscular injection into the gluteal muscle every 4 weeks.5,12 Chemotherapy would be the second choice of treatment following failure to respond to hormonal therapy. If anthracyclines are not contraindicated for this patient, Epirubicin would be a good choice. Initial doses of 75 mg/m 2 of Epirubicin could be given intravenously every three weeks.20The addition of Docetaxel 75 mg/m2in combination with Epirubicin 90 mg/m2 both by intravenous infusions could be given should Epirubicin monotherapy fails. Docetaxel monotherapy could also be given as an intravenous infusion at a dose of100 mg/m2 as a 1-hour intravenous infusion every 3 weeks should anthracyclines be contraindicatedas first-line chemotherapy. Vinorelbine monotherapy could be given intravenously at a dose of 30 mg/m2 for days 1 and 8 of a cycle or whereares Capecitabine monotherapy could be given orally at a dose 1250 mg/m2 twice daily for two weeks. If the patient fails to respond to the entire treatment, the last resort would be to offer support and palliative care to this patient. Pain Management Pain is usually associated with progression of cancer with three quarters of patients with advanced cancer reporting pain during treatment. The principles for treating pain in cancer patients are outlined by the World Health Organisation (WHO) analgesic ladder: Patients are the prime assessor of pain and should have treatment outcomes monitored regularly using visual analogue scales, numerical rating scales. Patients usually start with non-opioids and then progress stepwise to step 2 and step 3. However, critics have debated that the progression to step 2 analgesics was obsolete as inadequate pain control was an issue despite having to endure similar adverse effects when given step 3 analgesics and recommended a immediate step up to step 3. Most patients with advanced breast cancer will be on step 3 for pain control. Oral morphine with an initial dose of 5-20 mg every four hourly, adjusted according to patients response, would be the first-line therapy to treat severe pain in cancer before switching to a modified release preparation once the patient is stabilized on it. Breakthrough pain should be managed while on a modified release preparation by prescribing oral morphine at 1/6th of the total daily dose to be taken when necessary. The use of adjuvants such as antidepressants like Venlafaxine and anticonvulsants like Gaba-pentin are recommended for neuropathic pain. 18 Managing Complications Complications that may arise from treating patients with advance breast cancer includes lymphoedema,cancer-related fatigue,uncontrolled local disease,bone metastases and brain metastases. Lymphoedema may occur due to damage to lymph nodes and vessels following surgery and radiotherapy or as a sign of loco-regional disease progression. This condition can be managed through manual lymphatic drainage, multi-layer lymphoedema bandaging,goos skin care and remedial exercise. Cancer-related fatigue may be well managed by identifying the factors causing lethargy which may be a host of psychological, nutritional and cognitive factors apart from the cancer itself and them treating them accordingly. Patients may also develop local disease characterized by ulceration on the chest wall and axilla, fungating tumours that may bleed and exude discharge, causing pain and giving off repulsive odours. Hence, good wound management should be adopted in relation to preventing dire consequences when wounds are left unattended. Out of the three categories, cancer with distant metastases is the hardest to treat and is considered an incurable disease with palliative care being the sole priority in treatment plans. A diagnosis of metastatic disease could be confirmed with the use of positron emission tomography fused with computed tomography (PET-CT) and bone scintilography.1As bone metastases may be a long-term condition, management involves prevention of skeletal events, pain control with Biphosphonates,radiotherapy and cementoplasty and treating complications such as fractures,immobility and spinal cord compression.5,18 Brain metastases may develop in multiple sites in these patients as most drugs used in chemotherapy cannot penetrate the blood brain barrier, especially in women with HER2-overexpressing tumours. Diagnosis of brain tumours ultimately mean a loss of independence, physical deterioration, communication difficulties,psychological distress and issues regarding body image.Treatment regimens includ es surgery for patients who have solitary metastasis, corticosteroids for symptomatic relief of inflammation and radiotherapy.

Discomfort, Irritation, and Confusion of The Bath Essay -- Wife of Bat

Discomfort, Irritation, and Confusion of The Bath People are living robots. They follow the norm. They go with the latest trend. They walk the latest walk and talk the latest talk. Even the "brilliant ideas" that sprout from people's minds are a combination of other people's thoughts and ideas; friends, family and the media are the greatest influences. When a situation that is out of the norm confronts people, they are suddenly caught off guard, and instead of dealing with the situation, they shy away from it in attempt to return to their protective glass case; the norm. Raymond Carver forces his readers to face discomfort, irritation, and confusion through reading "The Bath". His language is dry, and the story is short. The characters do not have names, the language does not flow well, and the ending leaves the reader hanging. The message of the story is vague, and the plot lacks depth; however, the details that this story reveals through the concise language surpasses any detail that "A Small, Good Thing" reveals through its abund ance of words. To begin with, "The Bath" lacks much usage of adverbs. Adverbs typically help describe an action so that the reader better understands either the character or the situation. Clearly, the point of not including adverbs in this short story is to force the reader to focus on what happens instead of how something happens. A short story is "something glimpsed from the corner of the eye, in passing" (Carver 558). A reader should not feel connected with the characters in the story because that is not the author's main concern. An author simply attempts to convey a message through some words in a page that is arranged in ... ... intentions for "A Small, Good Thing" differ from his intentions for "The Bath". Throughout "The Bath" the reader struggles with many uncomfortable feelings, and although the reader may not immediately realize that he/she can relate to the story more than he/she knows, a relationship is present. "The Bath" does a good job of putting the reader in the characters' shoes. "A Small, Good Thing," on the other hand, provides a comforting feeling of knowing everything that happens, and knowing that everything works out at the end. Since there is a beginning and an ending to the story, the reader can conclude a meaningful message from the story and relate or apply it to his/her life. Overall, "The Bath" sets the mood of the story better than "A Small, Good Thing" because of its concise language and its focus on "the glimpse" instead of the "big picture".