Introduction. A Resounding “Thank You” Is Directed Toward

Introduction A resounding â€Å"thank you† is directed toward former President, George W. Bush for mandating the â€Å"No Child Left Behind† Act in 2002, which consists of the Common Core State Standards (CCSS) Initiative. CCSS is set of quality academic standards in math and English for grade levels K-12 that outlines what a student should have learned at the successful completion of each grade. Ultimately, the CCSS levels the learning field for students across America, regardless of social class, race, or disability by requiring all students to meet the same standards of quality education. Statement of the Problem The popularity of the CCSS falls onto a spectrum. One end favors the CCSS and is a part of the population that resides in†¦show more content†¦The Future of Education Looking forward, enforcing nationwide K-12 education standards will shrink the earning gap and increase the earning potential of everyday Americans. Those persons who cannot afford the luxury of college would be able to earn a livable wage with just a high school diploma because there will be job market opened for them. In contrast to today’s job market, where minimal a graduate degree is needed to gain competitive employment. The job market’s affinity to post-graduate degrees is a direct result of the lack of faith in the public school system. Employers do not believe that incoming recent high school graduates are prepared for the workforce. Current Issues in Education High-stakes Testing Test-based accountability systems, the application of tests to hold individuals or institutions accountable for achievement and to reward accomplishment, have transformed into the cornerstone of United States federal education policy. The past decade has observed a nationwide adoption of test-based accountability systems in the U.S. Consider just one essential manifestation of this burgeoning trend: test sales have grown from roughly $260 million yearly in 1997 to nearly $700 million now—almost a threefold increase (Supovitz, 2017). Where was the money spent? Research tells us that high-stakes assessments can and doShow MoreRelatedHow Social Media Has Changed Our Life1937 Words   |  8 Pagesshare their stories, identify themselves, but an online market – where products are popularized by famous people’ broadcast. As a part of it, the advertising campaign between Taylor Swift, a musician-singer, and the pop brand Coca-Cola achieved resoundin g success. The commercial, with the participation of tons of cat, brings to the audience great, happy, and enthusiastic feeling as well as introducing Taylor Swift’s coming album. 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Postmodernism and the Matrix - 952 Words

Postmodernism in The Matrix Postmodern writing evolved around WWII in response to Modernism that dominated the 19th c. The two writing styles share many characteristics, but the defeated modernist wallows in his realizations whereas the postmodernist offers a light or hope in conclusion. There is still a sense of foreboding for the postmodernist concerning science and technology. However, they are able to forge past their distrust, accept it as a logical progression, and begin to embrace some elements of advancement. Postmodernists have also lost faith in transcendence and spirituality, but to counter this loss they search and find hope in mystical forces or worldly treasures. Objective reality doesn’t exist for them either, but†¦show more content†¦This man will lead and succeed in the war against the machines. When the real population believes that Neo is their savior, they find a new hope they never had before. 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Taxation Core Tax Legislation

Question: Describe about the Taxation for Core Tax Legislation. Answer: Introduction This is a write-up that critically analyses the income tax implication between Bronx lighting pyt ltd and Mrs. Gilling who is the sole proprietor. Mrs. Gilling is in discussion and have reached a bargain with an Italian system manufacturer regarding a sole agency agreement. In order for Mrs Gilling to get the final contract, she had to travel to Italy. Mrs. Gilling transactions and actions during this period had tax implications and these are what we are emphasizing upon hereafter. Agency contract Agreement The business agent is defined in section 10 of the Agent Act 2003 as buying, selling, echanging or disposing of goods or providing a service n behalf of the principal in lieu of a reward (Barkoczy 2016). Mrs. Gilling had an agreement on being a sole agency contact with the Italian lighting company. The agreement states that in the next 5 years it is only the Bronx who could supply Allese lighting systems. However, the Bronx would have to pay for the sole distribution and sales right an amount to the tune of $205000.00. We can clearly conclude that as per section 10 of the Agent Act 2003, the business agent in this case is the Bronx. The section 8-1 of the ITAA 1997 states that a taxpayer can deduct loss or expenses from the assessable income if such expenses are incurred for earning the assessable income (Saad and Udin 2016). It goes ahead to state income that is not allowed as deduction and these would include in the act that the capital expenses, private expenses and expenses incur red for earning an exempted income. Under section 8-1 of the act it is quite clear that the expense for sole agency for distributorship of $205000.00 that the Bronx is subjected to is actually part of the business income and is an accepted deduction under section 8 of the ITAA 1997. Travelling expenses paid to Mrs. Gilling by Alesseto During the trip to Italy, the Bronx spent $9500.00 as travelling cost and $10500.00 for legal fees while bargaining for the agreement of sole agency. The company earned some measurable income from dales of lighting in as much as they had expenses while bargaining for the final contract. section 8 of the ITAA 1997 states that measurable income was attained despite some expenses incurred and these are also deductions as part of what the business spent. (Taylor and Richardson 2013). Mrs. Gillings visit to Italy also cost Allese money. During the bargaining period, there were several formal dinners that took place as the preparations for the legal agreement for sale agency of lighting was to be signed. These dinners were all paid for by Allese. Alesse also appreciated Mrs Gilling and provided her with a leather bag as a present and ensured she had tours around the city. These totaled to $2500.00. Mrs Gilling expenses will not be taxed under her name (Richardson et al. 2013). It is well noted that on normal occasions gifts are not taxed. In the case at hand the $2500.00 that was spent on the gift, will have to undergo taxation as it was received by Mrs. Gilling in matters relating to business thus is a business income. Cost of attending the launch that is paid by Bronx Business Travel expenses include expenses in travelling that have measurable income according to the section 900-95 of the ITAA 1997. Business travel is not a periphery to employees and it is not a benefit. As per section 8-1 of the ITAA 1997 deduction is made on any expense that is related to the business travel. Subsequently, every 12 months Mrs. Gilling, her son and daughter are to travel to Itally for the launch of the product. The upkeep of this family is to be incurred by Bronx. Since under section 8-1 of the ITAA 1997 (Binning and Young 2015) , these are treated as general business expenses as they were incurred during business. Expense payment fringe benefit is considered if a payment is made in to a person as they do the duty that was meant for another person. This is in accordance to The section 20 of the Fringe Benefit Tax Assessment Act 1986. Mrs Gilling, her son and daughter will be visiting Itally for the product launch. While there, they will tour the city. The expenses they will occur during these tours are taken as expense payment fringe benefit as section 20 of the FBTA 1986 clearly states.(Taylor and Richardson 2012). Hence Bronx will pay for the FBT expense of the tours. Product support Payment made by Bronx to Alesse Under section 8-1 of the ITAA 1997 deduction can be claimed on the expenses made from the measurable income. These expenses are the operating and capital expenses (Morse and Deutsch 2016). For information and marketing material that Alesse provide, Bronx is required to pay them a monthly fee of $5000.00. Under section 8-1 of the ITAA 1997 this monthly fee is allowable deduction incurred by Bronx under measurable income. Mrs. Gilling selling of Bronx Share capital From section 100-35 in ITAA 1997 usually states that the amount which is always received from CGT event usually exist any costs that its associated with in such event. Thus its a gain in capital, while id the CGT event exceeds the received amounts from CGT asset sale. It will be refereed to us capital loss. Loss and capital gain usually arise thus its important we we understand the section 100-25 of 1997 ITAA (Lanis and Richardson 2012). The CGT list provides shared capital. The section 1004-135 in 1997 ITAA provides payment for share capital which is treated as a payment made by owning a share within the company where payment is not included Discount method can be used to calculate the profit if the payment is held for more than 12 month. Section 115 in ITAA 1997 provides for discounting method to be used where it can only be applied where CGT will be required after 1999 September. With a discount rate of 50% as provided under 115-100 act. Division 114 of the act also provides the formula to be used in calculating capita income. Any asset acquired before 1999 September indexation method will be applied. The share capital was purchased in 2000 for $256000 thus the capital gain discount method is used. For the new room shares, which were sold for $1,500,000.The net capital gain is $710200 which is taxable income .The following are the calculations. Capital gain using discount method Particulars Amount Profits from sale of shares $ 1,500,000.00 Less: cost of acquisition $ (51,200.00) sale of shares $ (21,900.00) purchase Legal fees Share $ (6,500.00) capital Gain from sale of shares $ 1,420,400.00 less: Deduction@50% $ (710,200.00) Net Capital Gain $ 710,200.00 CGT cost base in purchase of the show room Mrs. Gilling bought the showroom for $ 1,500,000. This is the cost base for the showroom. According to section 112-25, the cost attributable to Australian tax should be adjusted to include other miscellaneous costs relevant to the property. In this case, the miscellaneous costs include $ 7,600 for paint and $ 16,600 which totals to$ 7,600+ $16,600= $ 24,200. Therefore, the total cost base attributable to tax will be $1,500,000+ $ 24,200 =$ 1,524,200. Statement showing Calculation of Cost Base Particulars Amount purchase price of show room $ 1,500,000.00 painting cost $ 7,600.00 New flooring cost $ 16,600.00 Total Cost Base $ 1,524,200.00 The new show room is $1524200.00.CGT Insurance Payment According to the Australian Tax regulations, payment of insurance premiums is tax exempt in an attempt to reduce the cost of premiums so as to motivate more individuals to acquire insurance packages. Due to this on the occurrence to insured risk, payment of damages is also tax exempt. This is because if they are taxed, the value of the damages will be too high for the insurance companies which will prevent them from meeting their obligations (Ostergren, 1970). As such, Mrs. Gilling will not be taxed on her payment of insurance premiums. Even though the insurance company negated her claim for the need of compensation, on payment for the damaged the company could not be taxed. This could have motivated the company to pay the damages but still negated the claims. Calculation of the expenses incurred Particulars Amount Cost of Repairing $ 85,000.00 Structural job $ 180,000.00 insurance received $ (85,000.00) Total Cost Base $ 180,000.00 Silvio to leave in Australia Silvio visited Australia and fell in love with the place to the point of quitting his job. Due to this he can obtain Australian citizenship and be eligible to taxes based ITAA 1936 in section 995-1 on his source of income and assets acquired (Tiley, 1992).The amount of money that he receives yearly from his former employer as a means of preventing him from working for rival companies is subject to income tax regulations according to Australian regulations. Thus Silvio satisfying the domicile test is considered to pay taxes from the amount receivable of $90000.00 in Australia. Conclusion On signing the contract, Bronx Company paid $ 205,000. For tax purposes, the Agency contract agreement will be taxed on this amount (Braun et al, 2004). Alesse agreed to offer product support, information and marketing at a fee of $ 5,000 payable by Bronx Company. However, these payments will be in support of activities of operations in Australia. The Australian government is entitled to tax a certain amount. The fees will be paid to Alesse net of the tax payable to the government (Brown et al, 2001). Reference Barkoczy, S., 2016. Core tax legislation and study guide.OUP Catalogue. Binning, C. and Young, M., 2015.TALKING TO THE TAXMAN ABOUT NATURE CONSERVATION_Proposals for the introduction of tax incentives for the protection of high conservation value native vegetation. Brown, K. Ke, Y. (2001) Agreements and Tax Avoidance.SSRN Electronic Journal. https://dx.doi.org/10.2139/ssrn.2715879 Jones, D., 2016. Capital gains tax: The rise of market value?.Taxation in Australia,51(2), p.67. Lanis, R. and Richardson, G., 2012. Corporate social responsibility and tax aggressiveness: a test of legitimacy theory.Accounting, Auditing Accountability Journal,26(1), pp.75-100. Morse, S.C. and Deutsch, R., 2016. Tax Anti-Avoidance Law in Australia and the United States. Richardson, G., Taylor, G. and Lanis, R., 2013. The impact of board of director oversight characteristics on corporate tax aggressiveness: An empirical analysis.Journal of Accounting and Public Policy,32(3), pp.68-88. Saad, N. and Udin, N.M., 2016. Public Rulings as Explanatory Materials to the Income Tax Act 1967: Readability Assessment.Advanced Science Letters,22(5-6), pp.1448-1451. Snape, J. and De Souza, J., 2016.Environmental taxation law: policy, contexts and practice. Routledge. Taylor, G. and Richardson, G., 2012. International corporate tax avoidance practices: evidence from Australian firms.The International Journal of Accounting,47(4), pp.469-496. Braun, J. Fuentes, D. A (2004) Legal and Economic Analysis of Austria's Double Tax Treaty Network with Developing Countries.SSRN Electronic Journal. https://dx.doi.org/10.2139/ssrn.2516308 Taylor, G. and Richardson, G., 2013. The determinants of thinly capitalized tax avoidance structures: Evidence from Australian firms.Journal of International Accounting, Auditing and Taxation,22(1), pp.12-25.

The Crucible Essays (389 words) - Culture, Religion, Literature

The Crucible The witch trials in Salem, Massachusetts in the early sixteen hundreds was a time of uneasiness and suspicion. Anyone could easily turn in his or her neighbor on the ground of witchcraft. Someone could merely say their neighbor's spirit had attacked them during the night, which no man can prove. Nevertheless, as a God-fearing community, they could not think of denying the evidence, because to deny the existence of Evil is to deny the existence of Goodness, which is God. The most important scene in the play was act two, scene three, where John Proctor is able to talk with his wife, Elizabeth, one last time. He decides that he will "confess" to the crime of witchcraft, thereby avoiding being hung. However, to accept what he said, the judge also requires him to sign a written confession which states that he confessed to the crime of witchcraft. Judge Danforth would post it on the church door, to use Proctor as an example to get other people to confess. That upset Proctor greatly, because people would look down on him with disdain, and it would blacken forever his name. What was most important to him was to make a stand against the insanity of the town, for himself and for God, and using that as a last resort to make people aware of what was happening. This last stand for righteousness is an example of proctor's great character and rationale. Arthur Miller wrote his play, The Crucible, a story about the Salem witch trials, and the panic resulting from it, as an allegory to show people the insanity of the McCarthy hearings. He wrote it as an allegory so that, if tried by McCarthy, he could say, "it's just a play about the witch trials in Salem. How do you get this communist idea from it?" The story illustrates how people react to mass hysteria, created by a person or group of people desiring fame, as people did during the McCarthy hearings. Arthur Miller, acting as a great visionary, warned us that if we did not become aware of history repeating itself, our society would be in danger. At the same time, he had to do this in a matter that would not get him arrested, hence the witch-trial mechanization.

Enduring Issues In Criminology Essays - Criminology,

Enduring Issues In Criminology Enduring Issues in Criminology, by Boomstrom, ed., is written in a debate style that allows the reader to compare and contrast major philosophical views such as the rehabilitation debate. This book contains articles of opposing viewpoints on various issues, but we will concentrate on those dealing with rehabilitation. The articles on rehabilitation generally reflect an ideological left or right point of view. Bartollas, a liberal, takes a positivistic approach and supports rehabilitation of criminals and blames factors outside the control of the offender for causing criminal behavior. Enduring Issues is meant to provide insight into these theoretical concepts and allow the reader greater understanding of one's own perspective. The popular opposing views are to explain the different perspectives that exist in criminology as to the function, purpose and problems of the criminal justice system. Sociology Essays

Individual And Family Assessment Case Study Social Work Essay Essay Example

Individual And Family Assessment Case Study Social Work Essay Essay Example Individual And Family Assessment Case Study Social Work Essay Essay Individual And Family Assessment Case Study Social Work Essay Essay This paper will look at the instance survey of Ruth, Joseph and their household. They are Human-centered Entrants in Australia and face many issues. Their past life in Southern Sudan was fraught with war, force and supplanting. As a societal worker measuring their instance there are several factors which need to be taken into history which can impact greatly on their hereafter. These include the dominant discourse which as a societal worker we will take to work from. The biomedical discourse trades with many factors which are apparent in the work with Ruth and Joseph. Factors such as anguish and injury and the reverberations psychologically which this has had and how it continues to impact on the household. This paper will besides look at how the western biomedical theoretical account may restrict mental unwellness as merely a encephalon disease and non look at all the factors which are related. When working with seeking to resettle a refugee household in a new state which is so far removed from what they know, a societal worker demands to cover with wide scope of undertakings. Choosing the right theory is important. The theory which would outdo work for Ruth and Joseph would be Anti-oppressive. Looking at the anti-oppressive theory when working with new migrators can assist us to understand their history and assist them get the better of the subjugation which they have felt for so long. It is our function as societal workers to assist incorporate refugee people into local communities and adjust to a new civilization. I will necessitate to measure my ain values and attitudes when working with my CALD ( Culturally and Linguistically Diverse ) clients. My focal point will be on how these differences may impact or suppress my work with Ruth and Joseph viz. our cultural differences. GENOGRAM Measuring clients and step ining as a Social Work practician it is indispensable that we choose the best discourse relevant to our clients inevitably. As Healy ( 2008 ) provinces the biomedical discourse is one of the most powerful discourses determining pattern contexts, peculiarly in wellness services such as infirmaries, rehabilitation services and mental wellness services ( p20 ) . Healy discusses how societal work practicians need to learn to understand some signifier of the biomedical nomenclature ( 2005, p22 ) . When working with clients such as Ruth and Joseph whom both have post-traumatic symptoms in changing grades the biomedical discourse seeks to turn to the complexness of their jobs. Both Ruth and Joseph appear to endure from some signifier of mental unwellness related to their post-traumatic experiences. Penhale and Parker ( 2008 ) say that troubles with mental unwellness can be deepened if the person/s comes from black or minority cultural community ( p103 ) . The symptoms which Ruth and Joseph are sing are in the signifier of flashbacks, anxiousness and fright. The National Centre for PTSD province that refugees often experience repeating losingss, challenges, and alterations during the exile/acculturation and resettlement/repatriation periods ( Bolton,2010 ) . When measuring Ruth and Joseph, we have to be careful non to exteriorize them every bit merely their unwellness. As a societal worker we need to look at a client from changing grades non merely one. We need to look at a client and their past history in a holistic biopsychosocial manner. With Ruth and Joseph, turn toing their mental unwellness is merely one of the multidimensional factors which they are sing. Looking at them as people instead than as an unwellness can assist with measuring their instance. STARTTS luxuriant stating that It is necessary for societal workers in this field to develop an apprehension of organized force and its effects on persons, households and societies, and besides of the refugee experience of flight and lasting in refugee cantonments ( Bowles, n.d. ) . The biomedical discourse can besides hold restrictions. Healy discusses how there is possible for biomedical cognition to lend to societal subjugation ( 2005, p26 ) . When working with Ruth and Joseph our pattern must be about authorising them and assist them get the better of any subjugation which they have experienced. The deductions which we as practicians may confront when working with refugees from the biomedical theoretical account is as Healy ( 2008, p.25 ) suggests in struggle with the holistic attack . As societal workers it is our function to look at a client in a societal context. Ruth and Joseph present with a scope of jobs that stem from the injury which they have encountered. This branches into countries of societal, economic and emotional demands that need to be addressed. Ruth faces seeking to voyage her manner around the bureaucratism of Centrelink, Medicare and other bureaus merely to acquire their simplest demands met. We will necessitate to work with Ruth to get the better of her fright of authorization which stems from her injury which she experienced in Southern Sudan. In the instance analyze it mentions that Ruth appears afraid of all the inquiries sing acquiring a occupation and the fright of authorization coupled with the language/cultural barrier which she experienced has led to her self-doubting. We need to look at the instance of Ruth and Joseph from more of societal degree instead than a medical degree. This theoretical account does non see the function, such as household and community play in development of unwellness ; therefore, diagnosing and intervention are narrowly defined ( Pardeck and Yuen,2001, as cited in Pardeck,2002, p.4 ) . Measuring clients whom have trauma related symptoms such as Joseph, being cognizant of his status and all facets appear to be from physical to emotional to psychological will assist us to do determinations of referrals to other bureaus which may necessitate to be done. It appears as though Joseph will necessitate to see a physical therapist, tooth doctor and a GP to assist get the better of his physical hurting. His emotional and psychological jobs range from problem concentrating to going violent towards his household. The safety of Ruth and the kids will be made in the initial appraisal. It will necessitate to be decided whether Ruth feels safe plenty to hold Joseph in the house with her and her kids if he continues with his violent behavior. Referrals may necessitate besides to be made to a psychologist or a mental wellness bureau for Joseph. Healy places anti-oppressive pattern between strengths perspective and the postmodern patterns to reflect the common historical line of descent of theories for pattern, all which have emerged as important influences in the formal base of societal work since 1990 s ( 2005, p173 ) . Adopting an anti-oppressive model whilst working with Ruth and Joseph, testimonial must be paid to the past battles and forfeits which they have faced. Ruth and Joseph have suffered great subjugation in Southern Sudan. This subjugation included imprisonment, relatives killed, being taken from their place, hungriness, and deficiency of safety. OHara and Weber ( 2006 ) maintain that an anti-oppressive or extremist model encourages practicians to understand the structural context of their appraisal pattern ( p,141 ) . Some critical constituents of the anti-oppressive model are the isms . These are anti-racism, anti-sexism, anti-heterosexism, anti-ablism, and anti-ageism ( Moore,2003, n.d ) . Addressing these constituents of the anti-oppressive model when measuring Ruth and Joseph will let pattern to authorise and enable and back up them to derive more control over their lives. As Milner and OBryne reference †¦..social work should do a difference so that those oppressed may recover control of their lives and re-establish their right to be full and active members of society ( 2009, p.23 ) . In an initial appraisal with Ruth and Joseph factors to be considered include whether an translator is needed as interlingual rendition will play a critical function in the appraisal procedure. Ruth and Joseph have evidently sought freedom from persecution because of war, assault and anguish and/or other degrading intervention. STARTTS province that Social workers in this field are exposed to narratives of gross human rights misdemeanors, and can non keep impersonal sentiments refering the actions of assorted groups and governments. Conversely, one is besides exposed to the complexnesss of civil and international struggles ; one s ain political political orientations, stereotypes and beliefs are all challenged in this work . Culture plays a important portion in anti-oppressive pattern when working with Ruth and Joseph. Penhale and Parker ( 2008, p.197 ) points out: Cultural competency stems from an anti-oppressive attack to pattern and concerns the competency and apprehensions to work with diverse groups, esteeming and admiting difference whilst working with people to consequence alterations that have been agreed and negotiated together. There is no demand to be a cultural expert as such but consciousness of cultural differences and how this may impact on pass oning efficaciously with Ruth and Joseph is of import. By making some research if possible of Ruth and Joseph s Dinka civilization will assist when working with measuring their demands. For illustration the WYDA provinces that Dinka household members provides an indispensable support web ( 2008, para 5 ) . This is of import when speaking to Ruth and Joseph about their household life and functions in the household etc. Another consideration to do would be to inquire them what some of their outlooks may be and inquire them how things were done in their state. Interrupting down this cross-cultural barrier in the initial appraisal can take to a more positive result for both the societal worker and Ruth and Joseph. . Thompson s PCS synergistic theoretical account of subjugation ( Penhale and Parker, 2008, p.155 ) shows subjugation to be the builder of personal, cult ural and social positions and that the personal bias entirely does non explicate racism. Furthermore it is of import that a societal worker understands how these facets of life interact can make and animate forms of subjugation and favoritism. It is of import besides to observe that Ruth and Joseph s kids appear to be acculturating faster hence may hold to take over the function of transcribers in official kingdom. This reversal of functions can make emphasis in both parents and kids and can sometimes take to intergenerational struggle. Parents can experience like their kids have lost regard for them and that that their authorization may hold been undermined. Social work pattern must turn to a myriad of issues when covering with refuge searchers and refugees. In set uping themselves in the community Ruth and Joseph they will necessitate a figure of services with which to entree which will play a critical function in supplying a safe community. Offering on-going support and following an anti-oppressive pattern Working with CALD ( Culturally and Linguistically Diverse ) clients as a societal work practician this can raise several issues with values and attitudes which I may hold. I am white, Australian and a societal work pupil. I have a different cultural individuality and am from a different state which holds different positions and thoughts to Ruth, Joseph and their household. Bing a female and a female parent I can sympathize with Ruth in respects to running a family and lovingness for kids. Ruth has had to take over as head of the household as Joseph appears to be mentally ailing and non suit to take his household for the clip being. She besides has a big household and lovingness for seven kids can be a struggle Lashkar-e-Taiba entirely being in a new state and seeking to voyage our public assistance and schooling systems. Having different cultural individualities could restrict my capacity when working with Ruth and Joseph. I need to recognize that refugees have similar societal, emo tional, religious and fiscal demands to everyone else and be work in a culturally sensitive manner. As I am from the Australian civilization this is another subgroup which I have rank. With all the negative media attending environing asylum searchers or boat people it has been hard non to organize an attitude. My attitude is that I believe that I do nt understand, and I neer will, the despair that refuge searchers must experience to hold to set themselves and their household in such insecure environments such as a rickety boat from Indonesia merely to get away the persecution and fright which they must see in their ain state to hold to fly. I know that Ruth and Joseph are Human-centered Entrants intending that Ruth s sister sponsored them to come and populate here but they still were in fright of persecution and subjected to torment and trauma in their ain state. As I am citizen of a state that lives in democracy I will neer to the full understand but my values of regard, honestne ss and Another subgroup I am portion of is that of a household. I have two kids of my ain and I know personally that my household is my initial support web. As mentioned, the Dinka civilization respects their immediate household as their initial support web besides. When working with Ruth and Joseph my values and attitudes towards household support can heighten my capacity with turn toing their demands. I feel that it is of import to work with the positives of Ruth and Joseph s state of affairs and in this instance it is their household is together in the one topographic point. Offering some household reding would let a safe infinite for the household to turn to any issues which have arisen, such as Joseph s deficiency of connection with the household. Along with Joseph having some therapy in respects to his mental wellness this would set the household on the way to mending together. Oommen, Brian, Stephen and Komersee ( 2008, p.6 ) province that An every bit of import construct when working in culturally diverse scenes is the demand for a wellness professional to suspend their personal prejudices and opinions about those for whom he or she may be be aftering wellness plans . As with so many countries affecting values, brooding pattern and self-awareness are cardinal. I need to analyze and oppugn the beginnings and nature of my ain power and the ways in which this is exercised in my dealingss with kids and my household. By utilizing brooding pattern when working with Ruth and Joseph can assist me keep a degree of self-awareness so as to use my attitudes in an appropriate mode. As there is a domestic force issue this could be one of the countries where my value of regard could restrict my capacity when working with Ruth and Joseph. I could get the better of this restriction by looking at the all the factors and understanding that the domestic force is something that is perpetuated from their history as displaced individuals and the injury and anguish which they have experienced. Working with a non-judgmental attitude will besides assist with struggles such as domestic force. Decision

Note Taking on the Current issues and the potential future of GM foods Essay

Note Taking on the Current issues and the potential future of GM foods - Essay Example They have various beneficial traits key among them being their herbicide e, and insect and viral resistance. Additionally, they also have some nutritional enhancements. Food allergy has been a major concern to most people on the use of the GM crops. This has related much to the amount, type and synthesis of the proteins in these GM crops. There are other risk issues but these too have had little to do with most of the technologies applied (Baram, and Bourrier, 2014, p.10). Summary; Risks and safety issues relating to the use of the GM food and feed have been of particular concern to the masses. Allergic reactions have been experienced by some users and thus safety assessments must be carried out for these foods and the technologies used in producing them. Based on these concerns, critics of the technology have engaged in various activities to dissuade consumers of the products using facts that are not true and whose results are pegged on misinterpreted data sets from inappropriate test systems (Goldstein, 2014, p.195). Goldstein, D. A., (2014). Tempest in a Tea Pot: How did the Public Conversation on Genetically Modified Crops Drift so far from the Facts?. Springerlink.com, x(1), p. 194–201.

Video Games and Artificial Intelligence Research Paper

Video Games and Artificial Intelligence - Research Paper Example Artificial Intelligence (AI) and the gaming arena together, have been a sought after area of research since the discovery of AI. Even though, the main objective of the domain of AI which is of creating an interactive human like robot is far from the reality but the field has definitely revolutionized the world of video games, making them more life like and innovative ( Calero & Martin vii). Furthermore, the authors state that the video games provide an interactive real world environment to the player by depicting complex behavior, where perceptions are under total control, through the utilization of enhanced resolution of photo realization and state of the art multiprocessor architecture (vii). Before delving into the crux of AI and the components that drives this phenomenon, it would be a better idea to configure concept of what AI actually is and how it came about. Millington and Funge states that AI enables computers to perform task that human and animals are exclusively capable o f for instances, tasks such as sorting, arithmetic etc are solved easily by a computer system but for it to perform tasks such as face recognition, decision making and language compatibilities needs AI to develop algorithms to give the instructions to the underlying hardware as to what to do next (4). They further add that these algorithms are developed using either using the philosophical notion by retracing the trail of human thoughts or by using the psychological technique, through the process of understanding the human brain and the processes therein. Thirdly, the algorithms can also be engineered by configuring them to perform human-like tasks (4). Millington and Fudge say that the AI in game is divided into three sections: Movement, Decision making and strategy (4). Shedding light into the movement segment of an AI model, gives us a clear indication that in most of the games except the combat ones, the movement is related to path finding. Jones explain that in most of the game s integrating the path finding strategy, the main objective is to find a path between an arbitrary point A to another point B. In many game, multiple pathways exist between the two required points so constraints such as finding the shortest path or least cost exists (123). The authors illustrate this point by laying out a scenario in which multiple paths exists by considering two points separated by a hill, it is faster to take the path that round the hill that the one that goes up it, however it may prove to be an advantage for the player to go up the hill in terms of general progress of the game (123). Path finding, at certain times is actually searching for the shortest path that exists in a graph, in terms of games, a graph is a particular land route a gamer has to pass through. It consists of edges and nodes. Nodes are the points A and B that we discussed above and the path joining them are called edges, most of the time, these edges are weighted, giving them a measure of the d istance that they cover. In a graph we have multiple nodes and edges and to find a shortest path between two particular

Clara Schumann Essay Example | Topics and Well Written Essays - 1500 words

Clara Schumann - Essay Example In fact she has made a unique world of music which was unknown to the public till that time. The contributions of Clara Schumann to the world of music remain unique, especially when we consider the fact that most of the ancient musicians were from the dominant male community and females had many restrictions in the society during her life period. â€Å"In an era when women, apart from singers, almost never performed in public or composed, Clara Schumann did both† (Clara Schumann (1819-1896)). This paper analyses the life and contributions of Clara Schumann and answer the question "Why did Clara Schumann have great success during a time when women had many restrictions in society?" As in the cases of other regions and countries, the conditions of German women in the nineteenth century were not so encouraging. German women forced to work hard for finding livelihood, especially poor women. German women forced to work in domestic services and in shops during this period and it was difficult for them to concentrate on recreational areas like music because of the over burden of looking after their family and the male dominance in the society. Historically, German women faced severe discrimination in the society mainly because of the Christian prejudice against women. They were excluded even from church participation in till the beginning of the nineteenth century.   Ã¢â‚¬Å"As late as 1700, women were not allowed to sing in churches.  In the Middle Ages, women were still subordinate to men. They could not be active in the political life of the society† (Gordeeva). However, Clara Schumann’s father was a brave person who had liberal views about social life. He never believed in traditions and customs even though he studied theology. He was a musician by profession and did everything needed to encourage his daughter Clara to learn music. However, Clara’s father was cruel at times which forced her to concentrate fully on her profession and l earn more and more topics in piano playing. Clara slowly gained popularity and started to mesmerize the audience with her immense talents on Piano. She was able to play piano from her memory which was a rare sight during that period. In 1830’s, she met several famous musicians of that time, including Ludwig van Beethoven, Franz Schubert, and Robert Schumann. The meeting with Robert Schumann made lot of changes in her life. â€Å"By 1836, Clara had become completely infatuated with Robert Schumann and her father’s concern over the suitability of the match was apparent†Ã‚  (Clara Schumann (1819-1896)). But her father was against this relationship. Robert Schumann was comparatively an unknown composer while Clara was already a famous and accomplished performer. â€Å"On March 15, 1838, at the age of 18, she received the greatest honor Austria could bestow: She was named Royal and Imperial Chamber Virtuosa, even though she was a protestant, foreigner and a femaleâ €  (Reich, p.3). In other words, Clara’s popularity and fame was not limited to the boundaries of Germany alone. She became world famous even at the age of 18 which forced her father to try and break her love affair with Robert Schumann. Clara’s father tried to prevent Clara from meeting Schumann, but they strengthened their love affair through secret romantic letters. German laws during that period prevented a woman from marrying without her father’s consent. The battle between Clara’

Management of Melanoma Brain Metastases (MBM)

Management of Melanoma Brain Metastases (MBM) Abstract: Melanoma is the third most common cause of brain metastases, after lung and breast cancer. Common clinical manifestations include headache, neurologic deficits, cognitive impairment and seizures. The management of melanoma brain metastases (MBM) can be broadly divided into symptom control and therapeutic strategies. Supportive treatment includes corticosteroids to reduce peritumoral edema, antiepileptics for seizure control and medications to preserve cognitive function. Until recently the therapeutic strategies focused on local treatment including surgery, whole brain radiation therapy (WBRT), and stereotactic radiation (SRS). Historically, systemic therapy has had limited utility. Immunotherapeutic drugs like anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and anti-programmed cell death protein 1 (PD1) and agents targeting BRAF- MEK pathway have revolutionized the systemic treatment of MBM. Recent clinical trials with these agents have shown activity against MBM and incre asingly being used in clinical practice. In this article, we will discuss epidemiology, biology of MBM and the role of surgery, WBRT, SRS in this patient population. An overview of the currently available systemic therapeutic agents that includes immunotherapy and targeted tyrosine kinase inhibitors (TKIs) and a practical multidisciplinary management algorithm to guide the practicing oncologist will be outlined. Introduction: Recent advances in the management of advanced melanoma have resulted in improved 5-year survival rates, however, MBM remain a significant cause of morbidity and mortality. Approximately 20% of metastatic melanoma patients have brain metastases at diagnosis.   Overall about 50% of stage IV melanoma patients will develop symptomatic brain metastases (1-3). Cerebral hemispheres are the site of 80% of brain lesions from melanoma followed by the cerebellum (15%) and brainstem (5%)(4).Common clinical manifestations include headache, neurologic deficits, cognitive impairment and seizures. Until recently, patients with MBM had a dismal prognosis with a median overall survival (OS) of 6 months (5). The management of MBM can be broadly divided into supportive management and therapeutic strategies. Supportive treatment includes steroids to reduce peritumoral edema, antiepileptics for seizure control and medications to preserve cognitive function. Traditionally, therapeutic strategies focused on local treatment including surgery, WBRT, and SRS. Historically, systemic therapy has had limited utility in the management of MBM. However, the treatment paradigm has changed considerably with the advent of targeted therapy and immunotherapy. Approximately 50% of advanced melanoma patients harbor a BRAF mutation and a number of targeted agents for this mutation and downstream pathway have shown promise in the management of metastatic melanoma. Immunotherapeutic agents like anti- CTLA-4 and anti- PD-1 have shown clinical efficacy in MBM and now constitute first line treatment options for metastatic melanoma. Biology of brain metastases: Until recently MBM were believed to have the highest mutational discordance compared to the primary site (6).   However, Chen et al. reported molecular profiling that included hot spot mutations, global mRNA expression patterns, quantitative analysis of protein expression and activation by reverse protein array (RPPA) analysis of 16 patients (7). In this study, authors reported complete concordance in mutational profile between intracranial and extracranial sites. Despite these similarities crucial differences in the expression of PI3K/AKT pathway were noted by RPPA. Another study compared the expression of BRAF mutation in different sites of metastases in advanced melanoma and showed greater mutational concordance (16/20 patients) in brain compared to other visceral/subcutaneous metastases (8). These studies provide an initial understanding of the molecular characteristics of MBM. With the advent of immunotherapy, tumor microenvironment and immune infiltration has been a focus of intense research. Brain has been traditionally thought of as an immune privileged organ but recent studies have established the existence of a neuro-immune axis and questioned this belief(9). Our understanding of this unique interplay between the immune system and central nervous system has dramatically evolved over time. Berghoff et al. investigated the expression of PD-1, PD-L1, CD3, CD8, CD45RO, forkhead box protein 3 (FoxP3), CD20, and BRAF V600E by immunohistochemistry in MBM samples (10). Varying degrees of tumor infiltrating lymphocytes (TILs) were reported in this study, 33 out of 43 specimens stained positive for CD3(+) T-lymphocytes, 39 for CD8(+) T-lymphocytes, 32 for CD45RO (+)memory T-lymphocytes, 27 for PD-1(+), 21 for FoxP3(+) T regulatory lymphocytes, and 19 for CD20(+) lymphocytes.   Significant tumoral PD-L1 expression (>5%) was observed in 9 specimens while 22 sam ples stained positive for PD-L1 suggesting role of immunotherapeutic agents in MBM. Prognostic indices Although the median OS of MBM is dismal, approximately 5% patients are long term survivors(2). Hence prognostic factors that predict outcomes and can guide the treatment decisions and enrollment in clinical trials are of value. Several large single center series have examined various primary tumor, brain metastases, and patient characteristics predictive of survival (2, 11, 12). Age, performance status, number of brain metastases, extra-cranial metastases, time from primary tumor diagnosis, presence of neurologic symptoms and elevated LDH are factors that determine survival. (13). Sperduto et al proposed a new disease basedscoring index based on 483 newly diagnosed MBM patients from 8 different centers (14). On multivariate analysis, performance status and number of BMs were prognostic for survival in MBM. The outcomes of ds-GPA MBM varied from GPA class I with survival of 3.4 months to GPA class IV with survival of 13.2 months. These prognostic indices have inherent limitations. All of them were evaluated retrospectively, had only overall survival as the end point, did not include molecular and genetic profile of the primary malignancy, and did not take systemic therapy into consideration (15). A large single institutional experience of 366 patients treated to 1,336 brain metastases has also shed some light on the interplay of important prognostic variables in patients with MBM. In this series, characteristics associated with survival included younger age, lack of extracranial metastases, performance status, and treatment with BRAF inhibitors or immunotherapies. This work specifically highlights the importance of modern out outcomes in patients who are eligible for and receive newer targeted therapies. For example, the 12-month survival estimate for patients treated with BRAF inhibitors was 37% compared to 23% for those patients who did not receive these therapies (p=0.01). Moreover, the 12-month survival e stimate for patients treated with immunotherapies was 47% compared to 22% for those patients who did not receive these therapies (p=0.04). Clearly, further work is needed to define the impact of mutation, targeted drugs and immunotherapy in the current era. Diagnosis: The neurologic symptoms associated with brain metastases include headaches, seizures, cranial nerve deficits to motor or sensory deficits. All melanoma patients with neurologic symptoms worrisome for MBM should undergo a gadolinium enhanced magnetic resonance imaging (MRI) of the brain, if no contraindications exist. Guidelines recommend routine MRI of brain with and without gadolinium contrast for patients with stage IV melanoma due to the high prevalence of asymptomatic brain metastases(16). Computed tomography of brain with and without contrast can be used as an alternate imaging. Management: The options available for management of brain metastases include surgery, WBRT, SRS, systemic therapy and symptom management. The management plan to treat these patients should take into account the overall prognosis, performance status and morbidity associated with the treatment. 5.1 Management of symptoms: Supportive care for patients with brain metastases is typically to control the cerebral edema with steroids. Due to minimalmineralocorticoid effect and long half-life, dexamethasone is the steroid of choice, however, other steroids at an equivalent dose can be used and tapered gradually over a two week period(17). A randomized trial in 1990s compared different doses of dexamethasone ranging from 4 mg/day to 16 mg/day and concluded that 4-8 mg/day would provide same degree of clinical improvement in 1 week (18). Routine use of prophylactic anti-epileptics in patients with brain metastases is not recommended(19). When patients have seizures several anti-epileptics are available including phenytoin, carbamazepine, valproic acid and levetiracetam. Non-enzyme inducing agents like levetiracetam are preferred to avoid interactions with systemic agents. 5.2 Neurosurgical Options: Surgery has traditionally been used for management of solitary brain metastases, or large symptomatic brain lesions. Multiple retrospective studies have reported improved survival with surgery compared to best supportive care(13, 20-22). Younger patients with good performance status, fairly well-controlled extracranial disease, solitary brain metastasis, lesions in accessible locations and of small size generally have better outcomes with surgery (21, 23). Surgery is usually followed by radiation boost to the surgical bed by either WBRT or SRS, with an intention of sterilizing the surrounding tissues and preventing local recurrence. Two randomized trials comparing adjuvant WBRT to surgery alone have shown improvement in outcomes(24, 25). Patchell et al. evaluated the role of WBRT post-resection of a single brain metastasis compared to surgery alone(25). Postoperative WBRT resulted in a significant reduction in local and distant intracranial failure. However, no difference in the over all survival or time duration of functional independence was noted. Similar results were seen in the EORTC 22952-26001 study with decreased 2-year intracranial and resection site recurrence without significant survival benefit. Multiple retrospective reports of post-operative SRS have shown improved patient outcomes however prospective data is awaited (26, 27). Bindal et al. showed benefit of resection in select group with multiple metastases in a retrospective review of 56 patients(28).   In practice, surgery plays an important role in debulking or removal of life-threatening lesions. Surgery also provides immediate relief from intracranial hypertension by eliminating the mass effect, and symptomatic hydrocephalus by reestablishing the flow of cerebrospinal fluid (CSF). 5.3 Whole brain radiation therapy: Melanoma brain metastases lesions are generally considered radio-resistant compared to other histologies (29). Randomized trials with WBRT have reported survival in the range of 2.4 to 4.8 months.(30) The ideal dose and number of fractions, balancing the intracranial control and cognitive decline, has been subject to intense debate.   WBRT fraction sizes of ≠¤ 3 Gy do not lead to significant neuro-cognitive decline. A retrospective study compared higher dose of radiation, 40 Gy in 20 fractions with 30 Gy in 10 fractions(31). The 40 Gy group had overall survival of 5.6 months compared to 3.1 months. However most of these trials were not melanoma specific and included patients with all tumor types. Patients who are symptomatic with change in mentation, headaches and seizures but are deemed unfit for surgery or SRS due to large number of metastases, poor performance and uncontrolled extracranial metastases are generally treated with WBRT(32). 5.4 Stereotactic radiation therapy: Stereotactic radiation has been increasingly used in the management of MBM in the last two decades. SRS in MBM results in local control rates of 50-75% at 1 year(33-35). SRS is generally limited to lesions smaller than 4 cm in diameter (36).   In a retrospective review of 333 patients treated with SRS showed a sustained tumor control rate of 73%(35). The 12-month cumulative incidence of local failure was 14% in another single institution experience of 191 patients treated to 793 MBM.   Number of brain metastases that can be treated with SRS has been intensely investigated. SRS for solitary brain metastasis was compared to surgery plus WBRT in a phase III trial that closed prematurely due to poor accrual. The overall survival, freedom from local recurrence and neurological death rates were similar in both groups(37).   Several studies have evaluated the role of SRS in patients with 1-3 brain metastases (38, 39). Aoyama et al. compared SRS alone with SRS followed by WBRT in patie nts with 1-4 brain metastases(38). No difference in neurocognitive function and survival was observed. SRS-alone arm had increased local and distant intracranial failure. A phase III trial compared WBRT followed by SRS to WBRT alone, in 333 patients with 1-3 brain metastases from different histologies that included only 13 MBM patents (40). Performance status at six months improved significantly with addition of SRS to WBRT. SRS for patients with 5-10 brain lesions was evaluated in a multi-institution prospective observational Japanese study of 1194 patients(41). The overall survival, neuro-cognitive function and post SRS complications did not differ for patients with 5-10 brain lesions compared to 2-4 brain lesions(42). 5.5 Systemic therapy: Traditional systemic therapy had a limited role in MBM due to challenges of drug delivery in the brain from blood brain barrier (BBB) with its tight junctions and efflux pumps (P-gp and MRP transport proteins) (43). The concept of localized disruption of BBB at the site of brain metastases has been proposed, as demonstrated on MRI by contrast enhancement (44). Chemotherapy: Chemotherapy agents have not shown good activity in MBM. Dacarbazine which is the approved chemotherapy for metastatic melanoma does not cross the BBB(45). A number of studies evaluated the role of alkylating agents with good BBB penetration such as temozolomide (TMZ), lomustine and fotemustine in MBM patients. In a phase II trial Agarwala et al. enrolled 151 MBM patients with no local radiation therapy for BM to receive TMZ (46). TMZ use showed a modest intracranial response of 6%, median PFS of 4.3-5.2 weeks and median OS of 3.2 months. Two phase II trials of WBRT with TMZ(47, 48); or thalidomide, WBRT with TMZ (49) failed to improve the response rates significantly. Lomustine in combination with TMZ showed modest efficacy in a phase I/II study(50).   Intracranial activity of fotemustine was first reported in a phase III trial of fotemustine versus dacarbazine for metastatic melanoma (51). This led to a randomized phase III trial that compared fotemustine plus WBRT to fotemustine alone in MBM (52). The response rates were 7.4% for fotemustine alone and 10% for fotemustine plus WBRT. Fotemustine is not currently approved by FDA for use in MBM due to delayed thrombocytopenia and leukopenia(53). Targeted therapy: BRAF, NRAS and KIT are three common, mutually exclusive driver mutations seen in metastatic melanoma (54, 55). Of these three, BRAF mutation is the most common mutation seen in approximately 40-50% of patients with advanced melanoma. The presence of BRAF, NRAS increases the risk of CNS metastases seen in patients with   advanced melanoma. Prior studies have reported 24% CNS metastases rate in BRAF and 23% CNS metastases incidence in NRAS mutant melanoma compared to 12% rate in those who lack these mutations(56). Dabrafenib and vemurafenib target BRAF V600 mutation and FDA approved for metastatic melanoma. A phase I trial of dabrafenib in ten patients with untreated asymptomatic brain metastases, intracranial response was seen in 8 patients (four CR, four PR) (57). This impressive 80% response rate prompted the phase II trial of dabrafenib in BRAF mutant melanoma brain metastases (BREAK-MB) (58). This multicenter open label study accrued 172 patients asymptomatic brain metastases with BRAFV600E or BRAFV600K mutation and one measurable lesion (defined as atleast 1 cm in diameter). Cohort A consisted of 89 patients who were radiation naive and cohort B consisted of 83 patients who had failed prior radiation therapy for BM. BRAFV600E patients had an intracranial response rate (IRR) of 39% (29/74) in cohort A and 31% (20/65) in cohort B, PFS of 16.1 weeks in cohort A and 16.6 weeks in cohort B with OS of 33.1 weeks in cohort A and 31.4 weeks in cohort B. BRAFV600K patients had a lower IRR of 7%(1/15) in cohort A and 22% (4/18) in cohort B. This trial supports the efficacy of dabrafenib in BRAF mutant MBM patients, especially those with BRAFV600E mutations with acceptable toxicity. In an open label study of 24 non-resectable, untreated MBM patients harboring BRAFV600 mutation, treatment with vemurafenib resulted in tumor regression of more than 30% (7/19)and partial response was seen in 3 patients. Median PFS and OS was 3.9 and 5.3 months respectively in this study. In a phase II study, 146 BRAF mutant MBM patients were treated with vemurafenib(59). The first cohort included 90 patients with untreated BM, the second cohort comprised of 56 patients with previously treated BM.   Complete response was noted in 2 patients, with 14 PRs, and a best objective response rate of 18%. In previously untreated MBM, the median intracranial PFS and OS were 3.7 months and 8.9 months respectively. Previously treated MBM had similar PFS and OS of 4.0 months and 9.6 months respectively. There is no prospective data of safety and efficacy of combination of BRAF inhibitors and radiation therapy. Most reports are retrospective in nature with increased incidence of dermatitis seen in extracranial skin associated with concurrent use of BRAF inhibitors and radiation (60). Rompoti et al. reported five patients with MBM treated with combined radiation and BRAF inhibitor(61). Two patients underwent SRS and three received WBRT. Patients treated with SRS did not experience any skin adverse effects while all three patients treated with WBRT noted grade1/2 dermatitis. A retrospective analysis evaluated effectiveness of vemurafenib and radiation in BRAFV600 MBM (62). All of them received vemurafenib, six patients underwent SRS, two received WBRT, one received SRS and WBRT and three underwent surgery and radiation. Thirty-six of the 48 index lesions responded with 23 (48%) CRs and 13(27%) PRs. Major limitations were the retrospective nature of the study, small number, and pretreat ed patients with radiation and systemic therapy including ipilimumab. Several small retrospective case series have reported outcomes of MBM treated with targeted agents and SRS/WBRT (Table-1). A recent study of 19 patients with BRAF mutations undergoing SRS and concurrent BRAF directed therapies has shown impressively few local failures (12-month cumulative incidence of 1%). Additional studies of combination therapy are clearly warranted. Immunotherapy: Melanoma is an immunogenic malignancy (63) with a high mutational burden that results in high number of neo-antigen(64). It has been proposed that the relatively high neo-antigen burden makes this malignancy more susceptible to immunotherapy. However, the brain has traditionally been considered an immunologically privileged site due to the presence of the BBB. Recent studies on the intracranial tumor microenvironment as elucidated above have suggested otherwise, showing CD8 T-cells, CD 20+ cells, T-regulator cells and PD-L1 expression within intracranial tumor(10). The intracranial activity of interleukin-2 (IL-2, one of the first immune modulatory agents) was reported in two retrospective reviews(65, 66).   A response rate of 5.6% was seen in 37 patients with untreated brain metastases within a larger group of 1069 metastatic melanoma and renal cell carcinoma patients treated with high dose IL-2(65). In a second report, two of the 15 brain metastases patients treated with high dose IL-2 showed CR (66). No prospective trials were initiated with high dose IL-2 due to concerns for cerebral edema and neurotoxicity. Two pathways that have revolutionized the management of advanced melanoma are those involving CTLA-4 and PD-1/PD-L1.   The CTLA-4 receptor is expressed exclusively on T-cells and downregulates the interaction between antigen presenting cells and T-cells. Ipilimumab is a fully human monoclonal antibody against the cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4)(67). The pivotal phase III trial that compared ipilimumab with or without gp 100 peptide vaccine to gp 100 vaccine as a single agent allowed enrollment of patients with asymptomatic and/or previously treated MBM (68). A non-significant trend towards better survival in the MBM subgroup was noted among the patients treated with either ipilimumab alone or ipilimumab plus gp 100 compared to gp 100 alone(69). In an expanded access program (EAP) in Italy, 146 MBM patients received ipilimumab and a global response rate of 12% was seen (70). An American EAP reported a 1-year overall survival rate of 20% among 165 MBM patients tr eated with ipilimumab (71). Margolin et al. conducted an open label phase II clinical trial of ipilimumab for MBM (72). The trial enrolled 72 patients 51 patients in cohort A (those who were not on steroids for cerebral edema) and cohort B of 21 patients (on treatment with steroids). According to the WHO criteria, the response rate was 18% (9/51) in cohort A compared to 5% (1/21) in cohort B, and by immune-related response criteria the response rate was 25% (12/51) in cohort A and 10% (2/21) in cohort B. The median OS was 7.0 months and 3.7 months in cohort A and cohort B respectively. The study concluded that ipilimumab can be used safely in MBM patients. An Italian phase II trial tested a combination of ipilimumab and fotemustine in patients with advanced melanoma including asymptomatic MBM patients (73). A total of 20 patients (out of 83 patients) had asymptomatic MBM, and among these patients the study reported a PFS of 3.0 months and 3-year OS rate of 27.8% (74). A randomized, 3 arm, phase III trial of fotemustine, versus fotemustine plus ipilimumab, versus ipilimumab plus nivolumab (NIBIT-M2) is currently recruiting patients (75). Several retrospective studies have evaluated the safety of combining ipilimumab and radiation therapy (SRS or WBRT), and prospective trial data is forthcoming (76-78). PD-1 receptors are expressed on several cells including T-cells and antigen presenting cells. Their interaction with PD-L1 ligands on tumor cells leads to T-cell exhaustion and downregulation of tumor-specific immune response(79). Nivolumab and pembrolizumab are two anti-PD-1 antibodies that are currently approved for the management of advanced melanoma, and several others are under evaluation. An open label, single-center, phase II clinical trial is currently enrolling patients with untreated brain metastases from melanoma or non-small cell lung cancer (80). In a published early analysis, a response rate of 22% (4 patients) was reported in a total of 18 MBM patients and the responses were durable. Authors noted a high concordance between systemic and brain metastasis responses. Additionally, 11% (2 patients) had stable disease. Intriguingly all responders lacked a BRAF mutation. Relatedly, 4 patients were not evaluable either due to rapid progression necessitating BRAF-targeted ther apy (3 patients), or intralesional hemorrhage (1 patient). Toxicities in the MBM cohort included grade 3 transaminitis (1 patient), as well as grade 1-2 seizures (3 patients) and grade 3 cognitive dysfunction (1 patient) from peritumoral edema. Leptomeningeal disease in melanoma   Leptomeningeal disease (LMD) is a subset of metastatic with extraordinarily poor prognosis and median survival of 8 weeks(81, 82). About 5% of malignant LMD originates from melanoma (Kesari) and up to 23% of melanoma cases develop LMD(1, 83). Primary leptomeningeal melanoma also exists as a separate clinical entity and should be a consideration in the context of a person with multiple congenital melanocytic nevi(84). Diagnosis of LMD is usually made based on the combination of neurologic symptoms along with corresponding leptomeningeal enhancement on MRI. While cytology from cerebrospinal fluid (CSF) is considered to be the gold standard for LMD diagnosis, sensitivity of this testing ranges from 50% to 80%, depending on number of lumbar punctures performed (85). Like with MBM, treatment of LMD with chemotherapy has low response rates(86). The clinical course of LMD is more treacherous in melanoma in other malignancies given the propensity for melanoma LMD to hemorrhage(87). Molec ular characterization of melanoma LMD suggests a higher percentage of BRAF mutations in comparison to the general melanoma population (68% v 45%), based on a single center melanoma LMD cohort of 60 patients(76). Several case reports have been published highlighting complete and partial responses as well as prolonged ongoing survival beyond 15-18 months with BRAF inhibitors (86). Immunotherapy approaches, including intrathecal IL-2, adoptive cell therapies with tumor infiltrating lymphocytes (TILs) and cytotoxic T-lymphocytes (CTLs), and immune checkpoint inhibitors, have also reported prolonged survival in comparison to historic medians (86). A single center study of 38 patients with melanoma LMD who were treated with intrathecal IL-2 reported a median survival of 9.1 months, and the best 15% of patients reached a median survival over 24 months(88). Ongoing survival over 18 months in a melanoma LMD case was reported with WBRT followed by ipilimumab, an immune checkpoint CTLA-4 inhib itor; in this case, treatment with ipililumab resulted in complete radiologic response(89). A phase II trial of combination immunotherapy with ipilimumab and nivolumab, a PD-1 inhibitor, in melanoma LMD has recently opened to accrual(90). In summary, these early data suggest that both targeted therapy and immunotherapy have efficacy in melanoma LMD and can result in durable responses well over a year. Upcoming trials addressing melanoma LMD with newer therapies will likely yield significantly improved survival data over the next decade. Conclusion: Despite significant recent improvement in the outcomes of patients with melanoma, brain metastases remain a major determinant of mortality and morbidity in melanoma patients, and patients with MBM remain in the worst prognostic category. The vast majority of clinical trials with newer agents exclude patients with MBM, thus data on the effectiveness of new drugs in the context of MBM is still lacking. Understanding the biology of MBM and its clinical response to newer agent and particularly combinations of agents and strategies is crucial to increasing the longevity of the poorest-risk melanoma. Appropriate care of MBM begins with diagnosis. In melanoma, the brain is a common site of metastatic spread, both early and late. It is crucial to begin screening patients for MBM at diagnosis, and NCCN guidelines have recently been updated to reflect this changing diagnostic paradigm. The frequency at which to repeat imaging is still not known. Several therapeutic options now exist for the treatment of MBM (A proposed algorithm is provided in Figure-1). Surgical resection, radiation therapy, targeted therapy and immunotherapy all show some degree of efficacy with MBM.   Even in cases of LMD, perhaps the worst subset of MBM in terms of survival, treatment with targeted therapy and immunotherapy can induce prolonged survivals from historic means. Initial reports involving combinations of these therapies, such as radiotherapy with either targeted therapy or immunotherapy, appear promising, but will need to be systematically studied in cohorts with larger numbers. Equally important will be the parallel investigation of predictive markers in MBM with these therapies and combinations. Thus, whenever possible, patients with a new diagnosis of brain metastases should be enrolled in appropriate clinical trials. If an appropriate clinical trial is unavailable, treatment decisions should be made with input from a multidisciplinary t eam including radiation oncologists, neurosurgeons, and medical oncologists.

Putting an End to School Violence †Is Zero Tolerance the Solution? :: Argumentative Persuasive Essays

Putting an End to School Violence – Is a Zero Tolerance Policy the Solution? There are very few people today who are unaware of the violence in schools. As college students we live in a world that is desperate to find prevention methods against violence. That makes this issue important to today's college students, considering the fact that we are the generation that could have been involved and directly effected by a school shooting like Columbine. Is this how we want our school systems to be when our children enroll? A school is defined as "an institution for teaching and learning". However, today's educational institutions include punishment, violence, and misbehavior. When we find ourselves glued to the television because of another school shooting, obviously something needs to be done about violence in schools. Unfortunately, the solution causes creates more problems. Schools around the world have recently adopted revolutionary solution and prevention methods. The controversy over school violence prevention is not "yes we should or, "no we shouldn't", because you will probably be hard pressed to find someone who thinks we shouldn't get involved. The debate lies in the method we use to prevent and solve school violence. The zero tolerance policy is one suggestion to implement punishment in schools. The zero tolerance policy is strict and devises rules for students and faculty alike. It is a policy that doesn't ask questions when a rule is broken which often results in suspension and expulsion. The policy also addresses the possession of weapons, drugs, and alcohol. Many schools have adopted this policy and have observed both positive and negative results. If the zero tolerance program is installed in the educational system, schools must decide when and how it should be enforced. This is a very complex issue and when open to debate you see three approaches to it. First, advocates of zero tolerance policies concentrate on positive changes in school security, ways of punishment, and change in student behavior. Those who oppose the policies argue that zero tolerance should be eliminated due to its lack of rationale and logic. Finally, the opposing viewpoint criticizes the zero tolerance policy for being too extreme and inappropriate for schools. The first group, those who favor the policy, dwell on school improvement due to zero tolerance. One positive change is reinstated safety in schools giving students, parents, teachers, and the community a breath of relief. Advocates of this positive change believe that schools should be a place of learning without safety concerns.

Risk Assessment & Safe Systesm Of Work

Whitelee Wind Farm is a Scottish Power facilities situated on Eaglesham Moor, some 17 miles from Glasgow city centre. This is the largest wind farm in Europe boasting 140 wind turbines. Scottish Power have introduce a guided tour of this site, where visitors are shown the turbines and the many ponds that a spread throughout the site. Some of the water from the ponds is used to supply the surrounding area with drinking water. Scottish Water who previously owned the moor stipulated that pollution of the water course was not acceptable, and if Scottish Power were to introduce a tour then a pollution free method of transport was required. Scottish power purchased one of three electric buses which were built for Strathclyde Public Transport (SPT) by Smiths Electric Vehicles. SPT never made full use of these buses. The bus used on the Whitelee site is powered by 54 lead acid gel batteries, arranged in two parallel banks of 27. These batteries are located within the bus chassis. Mechanically the bus is a standard design, with the typical front wishbone and rear trailing arm suspension. The braking system is air over hydraulic, incorporating an air activated spring loaded fail safe parking brake. It is the power-train that is powered by the lead acid gel batteries and the ancillary systems are powered by two 12V heavy duty commercial vehicle batteries which connected in series will give the required 24V to power the ancillary systems, Table 1 shows the power requirements and consumption rates of these components. Risk Assessment The following pages incorporate a hazard checklist, risk assessment and safe systems of work for the use of the bus at the Whitelee facility. The hazard checklist was completed to form a qualitative risk assessment highlighting the where and why an incident was likely to occur. The information gathered from the checklist was then used to compile the risk assessment. The risks were classified according the likelihood of occurrence and the severity of the possible injury. The risks were scored from 1 to 25, where 1 shows there is no inherent risk involved in the task, and 25 shows this task to be highly dangerous and could result in fatal or debilitating injury. The risk register has a copy of the scoring mechanism at the bottom of the page. From this a Safe System of Work was complied to sever as an aid memoir. This highlight the salient points of the risk register to ensure risk of injury is kept to a minimum. Safe System of Work In compiling any Safe System of Work, the following steps give a good example of what points need to be reviewed. * The task o What is the work being carried out o What specialist tools are used o Who will do the task * Hazards associated with the task o From tooling o From plant and other equipment o From substances * Risk Assessment o Assess risks arising from the task * Define a safe method of work o Break task down into individual parts o Specify safe method o Produce documented work instructions * Implementation & operation o Ensure members of staff carrying out the task are adequately trained o Record training o Carryout regular checks and re-assess as appropriate In the case of the bus, I have identified two different tasks, the first being the daily maintenance, the other being the actually driving of the bus on the tour. The hazards associated with the tasks are dependent on which task is being carried out. The following pages are exemplar Safe Systems of Work for the daily maintenance of the bus and for driving the bus on a tour.

Introducing LinkedIns New Home and Profile Pages

Introducing LinkedIns New Home and Profile Pages On Thursday, December 11th, LinkedIn ® started rolling out its latest Home and Profile page design changes. For those of you who arent yet seeing the redesign when you log in, you can email LinkedIn ® to get a sneak peak at SeeNewHP@linkedin.com. Home Page Across the top of your Home page you will now enjoy instant access to the most important information regarding your account, including a quick link to your profile page, your stats and your Keep in Touch feed. Directly below this section, you will find the latest news and updates from Pulse. You can even sort your Pulse feed by the most popular or most recent. You will then see your regular feed of activity from your groups and connections, aesthetically revamped for quick connection identification, content preview, following, joining and connecting. Throughout your news feed you will notice suggestions by LinkedIn ® regarding connections you might like to make and jobs that might interest you. Profile LinkedIn has updated all profile pages to automatically appear in edit mode when accessed by the owner of the profile. After all, when we visit our own profile page, it is usually to make edits, so LinkedIn ® is saving us a step! To see your profile the way a connection would see it, click the View profile as button. In this view, you will notice a new option at the top of the page. Similar to Google+ or Facebook, you can choose to view your profile as a connection or non-connection (or a connection who is not logged into LinkedIn ®) would. LinkedIns suggestions for including additional sections are now located directly below the top portion of your profile. This information used to appear in the right-hand column in Edit Profile mode. Old: New: Your notification setting are also now available in the right-hand column so that changes to your profile can easily be hidden or shared with your network with the click of a button. Note the redesigned sections. For example, Recommendations no longer have 2 access points, but one. Old: (Profile mode) (Profile Edit mode) New: LinkedIns new streamlined design was created to enhance our experience as members and will likely be further enhanced in the future based on our response to these updates. I hope you enjoy the new changes. They are certainly presenting challenges to me as the author of a book about LinkedIn ®! But look for updates in the 11th edition of How to Write a KILLER LinkedIn ® Profile, still slated for release in January! Save Save

About the U.S. Department of State

About the U.S. Department of State The United States Department of State also referred to as â€Å"the State Department† or simply â€Å"State,† is the executive branch department of the United States federal government primarily responsible for administering U.S. foreign policy and consulting with the President of the United States and Congress on international diplomatic issues and policies. The mission statement of the State Department reads: â€Å"To advance freedom for the benefit of the American people and the international community by helping to build and sustain a more democratic, secure, and prosperous world composed of well-governed states that respond to the needs of their people, reduce widespread poverty, and act responsibly within the international system.† The primary functions of the State Department include: Provide protection and assistance for U.S. citizens traveling or living abroad;Assist U.S. businesses and industries operating in the global marketplace;Coordinate and provide support for international activities of other U.S. agencies, official visits overseas and at home, and other diplomatic efforts;Inform the public about U.S. foreign policy and relations with other countries and provide feedback from the public to administration officials. Similar the foreign ministries in other nations, the State Department conduct international diplomatic relations on the part of the United States by negotiating treaties and other agreements with foreign governments. The State Department also represents the United States in the United Nations. Created in 1789, the State Department was the first executive branch department established after final  ratification of the U.S. Constitution. Headquartered in the Harry S Truman Building in Washington, D.C., the State Department currently operates 294 U.S. embassies around the world and oversees compliance of more than 200 international treaties. As an agency of the president’s Cabinet, the State Department is led by the Secretary of State, as nominated by the president and confirmed by the U.S. Senate. The Secretary of State is second in the line of presidential succession after the Vice President of the United States. In addition to assisting with the international activities of other U.S. government agencies, the State Department provides many important services to U.S. citizens traveling and living abroad and to foreign citizens trying to visit or immigrate to the United States. In perhaps its most publicly noticeable role the State Department issues U.S. Passports to U.S. citizens allowing them to travel to and return from foreign countries and travel visas to U.S. citizens and non-citizen residents. In addition, the State Department’s Consular Information Program informs the American public of conditions abroad that may affect their safety and security while traveling abroad. Country-specific travel information and global Travel Alerts and Warnings are vital parts of the program. The State Department also oversees all U.S. foreign aid and development programs such as the U.S. Agency for International Development (USAID) and the President’s Emergency Plan for AIDS Relief. All activities of the State Department, including foreign assistance programs, representing the U.S. abroad, countering international crime and human trafficking, and all other services and programs are paid for through the foreign affairs component of the annual federal budget as requested by the president and approved by Congress. On average, the total State Department expenditure represents just over 1% of the total federal budget, projected to exceed  $4 trillion in 2017.  Ã‚   Brief History of the State Department On July 27, 1789, President George Washington singled a bill passed by the House of Representatives and Senate on July 21, 1789, creating the Department of Foreign Affairs as the first federal agency created under the new Constitution. A law enacted on September 15, 1789, changed the name of the agency to the Department of State and assigned it oversight of a variety of domestic, rather than foreign issues. For example, the law made the Department of State responsible for running the United States Mint and conducting the decennial U.S. census. During the 19th century, these and most of the Department of State’s other domestic duties were turned over to other federal agencies and departments. Appointed by President Washington on September 29, 1789, Thomas Jefferson of Virginia, then serving as Minister to France became the first Secretary of State. Appointed before Washington had taken office, John Jay had been serving in as Secretary of Foreign Affairs and continued to function as de-facto Secretary of State until Jefferson returned from France several months later.

Fashion Designer Employment Status Report Assignment

Fashion Designer Employment Status Report - Assignment Example Realistically, since I am still a starter on this career, I will take on any opportunity that I will be offered to be able to showcase my ability. This will entail attending any beauty pageant that I am able to so that I can sharpen my designing skills. I am constantly seeking growth as an artist while trying to enjoy the process as much as I can. I feel that if I enjoy myself while working on a piece that I am designing, the pleasure will help me put in that extra effort that is necessary to make the piece truly polished. Even though I am so passionate, there are moments when I feel there is something holding me back. This often happens when I have conversations with my parents regarding my future. They always ask me questions that I do not want to answer due to the fact that they consider I do not take my life seriously. However, I am motivated to pursue my career in the fashion design industry due to the fact that this industry has grown up a lot in the past 20 years. It has become a large part of the creative industry hence competitive; as such there is no guarantee that one can be successful. Despite the fact that it is extremely hard to get established in this industry, there are some things that I can do to make myself get a better chance of getting noticed. I believe that I can work hard and produce great work at college hence recognition. The quality of my work is my biggest philosophy; I believe that this is the greatest tool that I have to boost me to achieve my goals. Currently, I am a student in the Academy of Art University majoring in Costume Design. Since joining this university, I have seen how to design in my own way so that I am comfortable designing each piece in the shortest amount of time but still keep developing my own style. In order to gain my own style is to take the next step. According to Careers in Fashion, p.1, fashion marketing careers are highly competitive, so the more you can learn from fashion school, the better prepared you will be.  At the moment I am a student and my next step is to gain experience in the business field.  

Ethical Breakdown and Leadership Essay Example | Topics and Well Written Essays - 500 words

Ethical Breakdown and Leadership - Essay Example Although the vice has changed dramatically in the past decade, consider the past infamous Ford Pinto case which was produced during the 1970s. The car brand became disreputable for its tendency to leak fuel and explode into flames. Many deaths and injuries were recorded due to the manufacturing faults before they were recalled to correct the hitch. Investigations revealed that due to competition from Volkswagen, and other manufacturers the production of the cars was rushed, although the engineers noticed the mishaps during the reproduction crash tests, they went on with the production (Bazerman & Tenbrunsel, 2011). The main reason for the leaders of Ford to go on with the production is mere greed rather than a marketing decision which was highly unethical. US Secretary of Defense Chuck Hagel recently commented on the unethical behavior of the military, after it emerged that 30 officers of the US navy cheated on an exam for nuclear reactor instructors. The test in question is expected to gauge knack by launch officers in handling â€Å"emergency war orders†. The Pentagon describes the scandal as an ethical issue, although others may view it differently. Others may see the problem as more of a cultural problem (Ortiz, 2014). Personally, the breakdown mainly occurs due to the high standards that have been put by the system for the officers to achieve. The pressure to get good grades and a zero tolerance for wrong answers can be one of the reasons that the officers decided to cheat during exams. The failure by the authorities to notice the breakdown also raises some questions about their leadership abilities (Ortiz, 2014). This is due to the fact that it took one sailor who saw this as unethical to report the matter to the seniors.