Monday, September 30, 2019

Benefits of Cost Accounting Information

Cost accounting offers benefits for manufacturing companies. A cost accounting information system offers benefits for many companies. Cost accounting is a type of accounting method concerned with the cost of goods manufactured and /or sold. Many factors are taken into consideration when cost accountants analyze business costs . The information determined by these accountants is used for inventory valuation , financial statements and decision making . Inventory Valuation Cost accounting offers the benefit of having an accurate inventory valuation of all inventories on hand . This includes all raw products used to make goods , all work-in -process inventories and all finished goods ready for sale. Cost accountants take all costs into consideration and are able to determine the value of all of these inventories on hand . This information is useful for financial statements and for management of the company . Managers use this information to determine selling goals and production needs . Maximum Efficiency Cost accounting is beneficial to determine the maximum efficiency production amounts . Cost accountants take all costs into consideration when calculating this amount . Manufacturing costs consist of direct labor , materials and manufacturing overhead. These costs are all calculated and added up to find a per- unit cost price for manufactured items. When the cost price is calculated, these accountants begin determining a hypothesis of production rates . Many times cost accountants determine that if production is increased slightly, overhead costs remain the same. If this is the case, increasing production actually results in a lower per -unit cost for production , and the end result is a higher profit . Decision Making The information determined by cost accountants is used for decision making for future company needs . Short -term goals and decisions are made as well as long-term strategic decisions. The analysis of cost information is used to compare projected costs to actual costs . This is useful for businesses when budgets are created . Often times, unforeseen costs occur with production , and they are determined in this way. Unforeseen costs are added into the future budgets at rates calculated by cost accountants . Cost accounting also helps companies establish approximate future cash flows . Short -term production goals and marketing decisions are set based on this information. Long -term production plans are also calculated.

Review on My Name Is Khan

To write a review about a film which contains not only the magical combo of Shahrukh Khan-Kajol-Karan Johar but also something different from melodramatic love story or usual remake of hardcore commercial film is pleasurable. My Name Is Khan has a excellent point to a class of audience who likes to watch Shahrukh Khan in a different characteristic. But the film does not show the excellence enough to get a perfect worship from all audiences and critics.In the movie Rizwan embarks on a touching journey and gets the true recognition of his love,love for Mandira_we reveal a simple but touchy characteristic of an ordinary man’s love,we go through an extra ordinary journey. The movie has some points for which it can be appreciated. Firstly, though such story is not brand new but it has a fresh and own style of presence. Though it can not pass through the mark, made by movie like Forrest Gump but the point is it is not bullshit in any sence. MNIK also gives you a massage and create a different and sometime authentic feelings while you are watching.Secondly,the script makes you feel for the character. It is not Shahrukh Khan,it is Rizwan Khan for whom you will think. It is not chiffon sarees or bubbly dialogue for which you will adore Kajol,it is Mandira. It is a woman who really reflect the motherly affection, a loving and caring wife. Thirdly, the tempo of the movie. It has many subplot but they are quite interesting. It’s an exceptionally relevant to a concept-the unity of nations is of paramount importance, We are all coming together to fight for a common cause – called humanity.Everyone knows that terrorism has no religion and it will never have a religion. As a film, it tries to show social responsibility and the character tries to fulfill that from their position. Though the specificity of activities is not beyond question. Fourthly, the movie can clear it’s idea. It’s not all about a disabled man’s fight against disabil ity. It’s a disabled man’s fight against the disability that exists in the world—terrorism, hatred, fighting. My Name is Khan is also about Islam and the way the world looks at Islam but it not takes any sides.It only tries to say that there are only good people and bad people. There are no good Hindus, bad Hindus, good Christians, bad Christians. Either you are a good person or a bad person. Religion is not the criterion, humanity is. Fifthly, all the actors and actresses has done well. Specially Shahrukh-Kajal combo has got another dimension in bollywood after this movie. Kajal has done very well. Her maturity is used very consciously. We get Shahrukh in a new and pleasant avatar after Chak De! India and Swades. Zarina Wahab is very good as Rizwan’s mom.Thanks Shahrukh for making the character more closer to the audience. Yes we can say he can act. Sixthly, the director has used the complexity and complication provoked by rational and regional aspect th ough it is not totally agreeable in some sense. Moreover sometimes there are many reasons behind any happenings like- 9/11, which can not be described so easily. Moreover, Indian Film Indusrtry don’t have the trend to take a risk by making film relevant to such touchy issues though films like New York ,Kabul Express,Main hoon Na had made.But they were not totally focused. I am not telling that MNIK is all focused but it has got some solid point to relate with a serious issue. Use of metaphorical shot is also notable. Specially Rizwan holding poster-Repair Almost Anything headlined is a brilliant one. This stands for a meaningful thought. The narrative style of story telling and blending past time and present time is good but continuity error like showing objects which don’t match with the time showed in the movie is not expected.The narrative style may influenced by The Shawshank Redemption and Godfellas. The ending is quite good but it may be more gothic and more auth entic. The journey of Khan may be showed more smartly in accordance with happenings as sometime it has feel us melodramatic. Cinematography is worthy off a hand of applause, specially using the background and wide angle shot. Editing is fine. Thanks Ravi K. Chandran (director of photography) and Deepa Bhatia (editing) Shankar-Ehsan-Loy has done a great job both in soundtrack and background score.Thanks to the lyricist(Niranjan Iyengar and Javed Akhtar) The songs such as â€Å"Noor-e-Khuda† blend western bar blues and techno sounds with Indian classical styles such as Sufi and Hindustani. The soundtrack is thus representative of the â€Å"indie fusion genre†. Unlike Karan Johar's other films, this film has no lip-sync songs. All the songs are in background. â€Å"Tere Naina† is a good one. In short The content of My Name Is Khan is diametrically opposite to whatever Karan Johar done in the past. My Name Is Khan is â€Å"not all about terrorism, or 9/11.Itâ€℠¢s about a relationship between two people, between an individual and the State, and between an individual and the country. In short, there the three important components: love story, Islam and a mild form of autism. You can watch it. Sometime it is impressive, dramatic, a little bit slow, inspiring, may be controversial but enjoyable too. The pick up line is – There are only two kinds of people in this world. Good people who do good deeds. And bad people who do bad. That's the only difference in human beings. There's no other difference.

Saturday, September 28, 2019

Calvin Klein – Brand Audit Questionnaire

Brand Exploratory Research (Consumer perspective) By doing this research, we intend to find the health of the brand, its sources of equity and suggest improvements if any. Name: Age: Gender: How often do you purchase dresses of the brand Calvin Klein? a. < 4 months b. 4-6 months c. 6-10 months d. Once a year e. Other How would you rate the following brand personality elements associated with Calvin Klein Products? (1-lowest and 5-highest) Brand Element| 1| 2| 3| 4| 5| Authentic| | | | | | Excitement| | | | | |Freshness| | | | | | Rich| | | | | | Ruggedness| | | | | | Stylish| | | | | | Smooth | | | | | | Happiness| | | | | | Status symbol| | | | | | Successful| | | | | | Variety| | | | | | Rate the following products of Calvin Klein according to your perception of like/dislike (1-lowest & 5-highest) Product Name| 1| 2| 3| 4| 5| Calvin Klein Collection| | | | | | Jeans| | | | | | Kids Wear| | | | | | Footwear & Shoes| | | | | | Perfumes/fragrances| | | | | | Skinny Jeans| | | | | | Underwear| | | | | |Swimwear| | | | | | Suits| | | | | | Polo T-shirt| | | | | | Accessories (handbags, belts, scarves, umbrella)| | | | | | When you think about the Calvin Klein, what product category immediately comes to mind? a. Calvin Klein collections b. Calvin Klein Menswear c. Calvin Klein Women Wear d. Calvin Klein Kids Wear e. Calvin Klein Sportswear What are the brand promotion elements that you have helped you identify Calvin Klein brand? Brand Element| 1| 2| 3| 4| 5| Logo| | | | | | Tagline/Slogan| | | | | |Television Advertisements| | | | | | CK Symbol| | | | | | Celebrities| | | | | | Online store/Website| | | | | | Billboards| | | | | | QR Codes| | | | | | Please choose a brand that you believe best describes each quality. Choose none if you feel none of the choice apply Trait| 1| 2| 3| 4| 5| Cool| | | | | | Young| | | | | | Contemporary| | | | | | Trendy| | | | | | Charming| | | | | | Upper class| | | | | | Friendly| | | | | | Glamorous | | | | | | Masculine | | | | | | Feminine| | | | | | Wholesome| | | | | |Confidence| | | | | | Cheerful| | | | | | Corporate| | | | | | What is your annual income? a. < 3 lakhs b. 3 to 6 lakhs c. 6 to 10 lakhs d. 10 to 15 lakhs e. > 15 lakhs When you think about your favourite brand of Calvin Klein, does this brand remind you of a person? a. Yes b. No Who makes the majority of purchasing decisions in your household? a. Spouse b. Yourself c. Joint decision d. Other How do you find out the latest product in the market? a. Fashion Magazines b. Television c. Internet d. Shopping Store e. Others

Friday, September 27, 2019

Course Project Research Paper Example | Topics and Well Written Essays - 500 words

Course Project - Research Paper Example This is extremely in contrast with the view of Bueno that companies and organizations that do not carry out an evaluation of the performance of its employees cannot compete well with their rivals (7). This view is further supported by Maslow which describes performance appraisal as the estimation and evaluation of performance of workers during a specific period with the goal of determining their suitability and increasing revenue and profit (24). Evaluation based on results can be done in response to a performance crisis or to find the direction that the skills and knowledge of specific employees have to be developed to increase performance .This will end up helping a company move from a loss making trajectory to a profit making one (Buono 30). The techniques that are used to carry out performance appraisal can be widely grouped into three categories namely the absolute, comparative and the result oriented technique The comparative technique is done to compare performance of employees who work in a group. The result oriented is based on the achievement of a specific goal. Absolute performance evaluation, according to Maslow, is done to evaluate employee performance with respect to a set standard performance (40). The choice of the technique used hugely depends on the nature of the organization and the reason for carrying out the performance appraisal. An analysis of the study of ABC Company reveals that the performance of employees and their work patterns is influenced by four major factors. The first factor is attitude and skills. Employees who have the right skills and knowledge perform their duties as required as compared to the lowly skilled ones. The study reveals that those employees with positive attitude tend to enjoy their work. This directly translates to better performance .The workers with negative attitude do not feel empowered and appreciated and therefore their performance is below

Thursday, September 26, 2019

Who discovered America First Essay Example | Topics and Well Written Essays - 250 words

Who discovered America First - Essay Example On the other hand, the history of Ericksson who is believed to be one of the first Europeans to visit America has not been documented in written form like that of Columbus. It has been mainly recorded in oral form. 2. The discovery of America has had both positive and negative impacts on the western hemisphere. The movement of the Europeans to the western hemisphere resulted in depopulation of the Indian Americans as a result of skirmishes that took place between the Europeans and the native people of America (http://usa.usembassy.de/etexts/history/ch1.htm). This became known as the great dying as they introduced various organisms that caused diseases which lead to death of the native Americans. However, on appositive note, the western hemisphere significantly benefited from the discovery of America. The place witnessed rapid industrialization since it had abundant of resources such as corn which was a staple food in this region. On the other hand, the discovery of America led to religious and civil conflicts between the native Americans and Europeans. As such colonies were established and this led to slavery of the native people. positive benefits were later to be reaped but the early years o f American discovery had negative impacts on the lives of native people in both

Education online system Essay Example | Topics and Well Written Essays - 750 words

Education online system - Essay Example Instead, this mode of study allows one to have the flexibility of time. The students can choose the time that they will be online within 24 hours without interfering with their daily activities. As Rovai, (2003) points out, there are a number of studies there are different measures taken by the instructors to ensure that there is earning similar to those students that are attending face to face classes. Students in this category have to spend much more time with the instructors having to employ some more commitment in setting evaluation questions administering them , marking and guiding the students on the areas of weakness. At the same time, students who are working in groups in different institutions are likely to learn much faster and better than those attending online classes are. Thus, the study establishes that the online studies are of much importance to already established students in various field of specialization. Which, therefore, calls for increased used of the mode of study in offering most of the postgraduate and les of the undergraduate courses. This is so because most graduate students, they can be able to contrite and at the se time comprehend concepts muc h faster because they have some knowledge in the areas of study. Unlike for the other students it will be much difficult to understand new concepts for the first time though an online forum. Hence, this might jeopardize the quality of education in case of poor commitment of instructors while attending to their online students more so the undergraduate students. However, there are number of different student with different preferences. Identifying the unique features of students is key to nearing that the system worked for all the students. For instance, to begin with, one has to identify the student’s ability to comprehend concepts in his or her own. Some students must need an instructor to provide face-to-face educational session to

Wednesday, September 25, 2019

Quit Now Essay Example | Topics and Well Written Essays - 500 words

Quit Now - Essay Example On the other hand it is a deadly poison and when taken in large doses can lead to death. It is of prime importance to take the issue seriously and help smokers get rid of their smoking habits. This requires discipline and dedication from the smokers and everyone around him. The smoker must be convinced that quitting is the only option to avoid injuring his health and those around him. Cigarette smoking involves inhaling nicotine a tobacco extract. This is directly absorbed by lungs. The harmful effect of nicotine on lungs is the high risk of contracting lung cancer. 90% of all the cases of lung cancer are caused due to cigarette smoking. This is because contains carcinogenic factors. The risk of death due to lung cancer is high and is coupled with huge amount of suffering for the patient for long time. The damage to the respiratory system is largely irreversible if smoking is continued for large periods of time. The oxidative stress generated by smoking mutates DNA and promotes atherosclerosis. The long term injury to lungs can be lethal if the smoker does not quit. In addition to lung cancer smoking increases the risk of contracting oral cancer, chronic bronchitis, asthma, and degeneration of all organs involved in respiratory system. The person often feels tired and fatigued.

Tuesday, September 24, 2019

Health history interview Essay Example | Topics and Well Written Essays - 500 words

Health history interview - Essay Example The patient mentioned that he felt relief when he wears warm clothes and drinks warm water. The coughing was worst when he had to do heavy work or walk for a long distance. Kevin was disturbed by the fact that the drugs he had taken for the last one week had not caused substantial relief to his health. Kevin had a severe case of measles at the age of three. He was hospitalized for three days. He received an immunization for pneumonia six months before coming to hospital. Kevin had been diagnosed with HIV a year before and he has been on a daily dose of ARVs. The patient was in the hospital for a CD4 count on 3 Jan 2012. He was on a high vitamin diet to boot his immunity (Reeders, 2001). The mother suffered from varicose veins at the age of sixty-five. There is no history of diabetes, heart problems or tuberculosis. The skin of Kevin was moist, flexible and pink with some skin rashes near the elbow of the left arm. He bears a scar on the knee of the left leg from a fall he had when he was ten years old. The nails of the two toes on the right foot have clubbing. His hair is black and clean. It does not have scales or lice. The cornea is white and clear with no patches. The ears did not have any discharge or tenderness. The nose and sinuses do not have swellings or tenderness. The lips had cracks and there were small white wounds on the lower lip (Irwin, 2003). The lower and upper parts of the mouth were pink and it was not dry. The neck has tender lymph nodes and the lungs have fluid around them (Jamison, 2006). Kevin had a regular heart rate of 69/min. and his sexual health was normal. Kevin was full of confidence and had high expectations that the tuberculosis would be cured. He stopped his morning jog and has not done it for two weeks because he says that it worsens the cough. He sleeps more often because he is more tired than normal. He also said that he felt better after a good rest. He was

Monday, September 23, 2019

Grant Proposal - Pressing Questions Essay Example | Topics and Well Written Essays - 750 words

Grant Proposal - Pressing Questions - Essay Example Therefore, reintroducing the manufacture and use of these tools and furniture will elevate the standards of living in the society in different aspects particularly the economic aspects will elevated immensely. Different cultures that define our origins and societal orientations can be defined or identified by the shapes and styles of tools that our forefathers used in the ancient years (Lane, and Matthew 71). The tools and wares that were used in the early years help in defining the kind of preferences and livelihood that were embraced. However, in the contemporary world, the same tools and wares can be made in their old nature and be sold to museums and to different cultures as means of appreciating the ancient cultures that such tools and wares originate. In this sense therefore, if we reintroduce the modelling and carpentry work in the society that will deal with making such art tools and wares, there will be increased employment opportunities especially to those who will be involved in making such items as well persons who will be doing sales on the same. Many people often tend to identify themselves with ancient items; thus, they are usually concerned with period through which certain tools and wares were made and used. It is very easy to determine periods and dates that the wares and tools that were used. According to Hirth, technologies such as carbon dating have allowed archaeologists to determine the periods that these tools were used (Hirth 39). Vessels were mostly used to represent the artistic orientation of a particular community. There functional characteristics did not apply to the views of the community. Therefore, in cases where people may be having these ancient tools and wares or items we shall install carbon dating systems to help in determining the years that the presented artefact was made. The older the artefact the more value it will earn and the more

Sunday, September 22, 2019

Reliability Essay Example for Free

Reliability Essay The most known and widely used types of reliability are: parallel forms, test-retest, interrater, and internal consistency reliability. Reliability is important because it gives precision, accuracy and dependable answers in researches. Consistency of measurement means there is a reliable measurement. If a method or particular piece of research is not reliable, researchers will and should lack confidence that the results obtained would be obtain again, and can thus hardly be confident that they reflect reality. Even though that several examples of research, which reach similar results, even if the research is not strictly replicable, may still help researchers to increase their confidence in reliability, and perhaps also guide them toward appreciating the range of applicability of a theory (Kurpius Stafford, 2006). Standard scores are the scores that are comparable because they are standardized in units of standard deviation while percentile or a percentile rank is a point in a distribution of scores below which a given percentage of scores fall. It is a particular point within an entire distribution of scores. Percentile ranks have one major disadvantage in comparison to standard scores: percentile ranks have unequal units along their scale. Percentile ranks in the middle of the distribution tend to overemphasize differences between standard scores, where as percentile ranks at the tails of the distribution tend to underemphasize difference performance. The measure of central tendency is a statistical technique wherein a single number is used to represent a group of numbers. Three different central tendency measures that are usually applied in researches are the mean, median and mode. These central tendency measures are significant because they have their own importance in measuring the central tendency. Mean provides the best estimate of average. However median is more reliable because it is clear and fixed on the other hand, mode is used when a quick and approximate measure of central tendency is required.

Saturday, September 21, 2019

Rapamycin And Cisplatin In Breast Cancers

Rapamycin And Cisplatin In Breast Cancers Recent gene expression profiling has identified five breast cancer subtypes, of which the basal-like breast cancers are the most aggressive and possess serious clinical challenges as there are currently no targeted therapies available. Although there is increasing evidence that these tumors confer specific sensitivity to cisplatin, its success is often compromised due to its dose-limiting nephrotoxicity and development of drug resistance. To overcome this limitation, our focus is to maximize the benefits associated with cisplatin therapy through drug combination strategies. Using a well-validated kinase inhibitors library, we showed that inhibition of mTOR, TGFà ¯Ã‚ Ã‚ ¢RI, NFà ¯Ã‚ Ã‚ «B, PI3K/AKT and MAPK pathway sensitized the basal-like MDA-MB-468 cells to cisplatin treatment. Further evaluation demonstrated that combination of mTOR inhibitor, rapamycin, and cisplatin generated significant drug synergism specifically in basal-like cells (MDA-MB-468, MDA-MB-231 and HCC1937). Th ese synergistic effects were not observed in the luminal-like T47D and MCF-7 cells. We further showed that the synergistic effects of rapamycin and cisplatin is mediated through p73. Treatment of rapamycin induced p73 upregulation and synergized cisplatin activity through activation of the p73 pathway. Depletion of endogenous p73 in basal-like cells abolished these synergistic effects suggesting that p73 is required for the rapamycin and cisplatin synergism. In conclusion, combination of mTOR inhibitors and cisplatin may be a useful therapeutic strategy in basal-like breast cancers. INTRODUCTION Recent identification of novel breast cancer subtypes with distinct biological features promises a more specific, effective and less toxic therapies to the patients. Through gene profiling, breast cancer can be categorized into five different subtypes with distinct clinical outcome. The five major subtypes of breast cancer are luminal A, luminal B, human epidermal growth factor receptor-2 (HER2) overexpressing, normal-like and basal-like breast cancer [1, 2]. Of particular important is the basal-like breast cancer which accounts for 15-20% of breast cancers overall and confers a remarkably poor prognosis compared to other subtypes. Majority of basal-like breast cancers exhibit a triple-negative phenotype, characterized by the lack of expression of estrogen receptor (ER), progesterone receptor (PR) or HER2 amplification, and often have high frequency of p53 mutation [3, 4]. Due to the lack of expression of these receptors (ER, PR and HER2), patients with basal-like breast cancers usua lly do not response to hormonal therapy, Herceptin or chemotherapy [5, 6]. As a consequence, the mortality rate of basal-like breast cancer is relatively high in comparison with the non-basal subtype [1]. Numerous clinical studies are currently ongoing to identify novel therapy for treatment of basal-like breast cancers. These include the use of specific targeted therapeutic agents (e.g. Cetuximab, Dasatinib, Bevacizumab, Abraxane and Erlotinib) or conventional chemotherapeutics agents (e.g. cisplatin, doxorubicin, and paclitaxel), either as single agent or in combination, as first line therapy for basal-like breast cancers [7-9]. Cisplatin, a chemotherapeutic agent not commonly used for breast cancer, come to light in the management of basal-like breast cancer on account of evidence that breast cancer cells with basal-like phenotype confer a selective sensitivity towards cisplatin as compared to other chemotherapeutic agents. A variety of evidence suggests that basal-like breast cancers may share defects in BRCA1-associated pathways, of which DNA repair mechanism has been compromised [10]. Indeed, recent clinical studies have demonstrated the clear advantage of cisplatin in treatment of basal-like breast cancer compared to other chemotherapeutic agents [11, 12]. Nevertheless, dose-limiting toxicity including nephrotoxicity, neurotoxicity and ototoxicity have withold the wide-spread use of cisplatin in treating breast cancers in the clinic. To address this problem, we developed a high-throughput screening assay to rapidly identify new therapeutic agents that could synergize the antitumor effects of cisplatin in basal-like breast cancers. Through the use of a small chemical library that targets some of the most relevant oncogenic pathways in basal-like breast cancer, we show that inhibition of mTOR by rapamycin incurred a specific synergistic effect with cisplatin in basal-like breast cancer cells. This synergistic effect is mediated in part through the induction and activation of p73 in the presence of rapamycin and cisplatin, respectively. Together, our findings demonstrate evidence of a synergistic relation between rapamycin and cisplatin in both inhibition of cell growth and induction of apoptosis. This suggests that rapamycin and cisplatin may be a rational combination of a targeted therapy for the refractory basal-like breast cancers. Materials and Methods Cell lines and cell culture The human breast carcinoma cell lines MCF-7, T47D, MDA-MB-231, MDA-MB-468 and HCC1937 were obtained from the American Type Culture Collection (Manassas, VA) and maintained in RPMI 1640 medium containing 10% fetal bovine serum (FBS), 100 IU/ml penicillin and 100 ÃŽÂ ¼g/ml streptomycin (Sigma-Aldrich, St. Louis, MO, USA) at 37 °C with 5% CO2. MTT cell proliferation assay Dose-response curves and IC50 values were determined using the methyl thiazolyl tetrazolium (MTT) cell viability assay as described previously [4, 13]. Cells were seeded into 96-well plates for 24 hours at a density of 5 ÃÆ'- 103 cells/well. Serial drug dilutions were prepared in medium immediately before each assay, and viable cell masses following 3 days of drug exposure were determined by cell-mediated MTT reduction. Cell growth as well as drug activity was determined by measuring absorbance at 550 nm using an Anthos systems plate reader. Construction of IC50 mean graph The IC50 mean graph was constructed as defined by the Developmental Therapeutics Program of the National Cancer Institute (http://dtp.nci.nih.gov). The mean graph consists of positive (more sensitive) and negative (less sensitive) delta values, generated from a set of IC50 values by using a three-step calculation. The IC50 values for each of cell line against the tested compound were converted to log(IC50) values. For each tested compound, the log(IC50) values are averaged. Finally, the individual IC50 value is then subtracted from the average to generate the delta value. Positive delta values project to the right of the vertical line and represent cellular sensitivities to the test agent that exceed the mean. Negative values project to the left and represent cell line sensitivities to the test agent that are less than the average value. Library screening The Inhibitor Select„ ¢ chemical library which consists of 160 well-characterized, cell-permeable inhibitors was purchased from EMD Chemicals, USA. MDA-MB-468 cells at the logarithmic phase of growth were seeded into 96-well plate at a density of 5 ÃÆ'- 103 cells/well. Each compound was added to a final concentration of 10  µM in the absence or presence of 1  µM cisplatin. Plates were incubated for 72h at 37 °C. Cell proliferation was examined using MTT assay as described previously. Combination treatments that induce growth inhibition higher than those of the same doses used alone (p Drug interaction analysis Drug combination analysis was performed by using the method as described by Chou and Talalay [14]. Briefly, cells were seeded at 5 ÃÆ'- 103 cells/well in 96-well plates and treated with various concentrations of cisplatin and compound alone or in combination for 72h. Cell proliferation was measured in each well by MTT assay. Multiple drug dose-effect calculations and the combination index plots were generated using Calcusyn software (Biosoft, Cambridge, UK). Combination index, CI 1 indicate synergism, additive effect and antagonism, respectively. Apoptosis assays Quantitation of apoptosis by annexin V/PI staining was performed as described previously [3, 4]. Briefly, both floating and attached cells were collected 72h after drug treatments. Apoptotic cell death was determined using the BD ApoAlert annexin V-FITC Apoptosis Kit (BD Biosciences, USA) according to the manufacturers instructions, and cells were analyzed on a FACSCalibur flow cytometer using CellQuest Pro software (version 5.1.1; BD Biosciences, USA). Quantitative PCR (qPCR) analysis Total RNA from cells was extracted using Qiagen RNA isolation kit (Qiagen, Valencia, CA, USA) according to the manufacturers protocol. First-strand cDNA was synthesized from total RNA using random hexamer primers and the SuperScript II system for RT-PCR (Invitrogen, Carlsbad, USA). Gene expression levels were measured by qPCR using the iQ SYBR Green Supermix reagent and an Biorad iQ5 real-time PCR detector system (Bio-Rad, Richmond, CA, USA). Data analysis was performed using Opticon Monitor Analysis Software V1.08. The expression of each gene was normalized to ÃŽÂ ²2M as a reference. The relative copy numbers were calculated from an 8-point standard curve generated from a 10-fold serial dilution of full-length cDNA constructs as described previously [3, 4]. Specific forward and reverse primer sequences are as follows : TAp73fwd, 5-GCACCACGTTTGAGCACCTCT-3; TAp73rev, 5- GCAGATTGAACTGGGCCATGA-3; ÃŽÂ ²2Mfwd, 5-AGCTGTGCTCGCGCTACTCTC-3; ÃŽÂ ²2Mrev, 5-CACACGGCAGGCATACTCATC-3; PUMA fwd PUMArev NOXAfwd NOXArev. The conditions for all QRT-PCR reactions were as follows: 3 minutes at 94 °C followed by 40 seconds at 94 °C, 40 seconds at 60 °C, and 25 seconds at 72 °C for 40 cycles. All PCR products were confirmed by the presence of a single peak upon melting curve analysis and by gel electrophoresis. No-template (water) reaction mixtures and no-RT mixtures were performed on all samples as negative controls. All experiments were performed in duplicate. Protein isolation and Western blot analysis Protein lysates from cells were extracted in ice-cold lysis buffer (0.75% NP-40, 1 mM DTT, and protease inhibitors in PBS). Total protein (25 ÃŽÂ ¼g) was subjected to SDS-PAGE followed by immunoblotting with the following antibodies: p73 (diluted 1:1,000, Ab-2; CalBiochem); pS6K (diluted 1:1,000; Cell Signaling Technology); S6K (diluted 1:1,000, Ab9645; Abcam); and ÃŽÂ ²-tubulin (diluted 1:2,500, D-10; Santa Cruz Biotechnology). Lentiviral production and infection The shRNA lentiviral constructs were created by transferring the U6 promoter-shRNA cassette into a lentiviral backbone, and high-titre lentiviral stocks were generated by co-transfection with packaging vectors into 293T cells as described previously [3, 4, 13]. The shRNA target sequences for TAp73 was 5-GGATTCCAGCATGGACGTCTT-3. The TAp73 targeted sequence is found within p73 exon 3. Therefore, this shRNA does not target ΆNp73 [4]. RESULTS Selective sensitivity of basal-like breast cancer toward cisplatin To gain an overview of the selectivity of chemotherapeutic agents for basal-like breast cancer cells, we compared their antiproliferative properties in a panel of basal-like and luminal-like breast cancer cell lines which has been validated previously through gene profiling [15]. All cells were treated with increasing concentrations of cisplatin, paclitaxel or doxorubicin for 72 hours and growth measured using the MTT assay. Figure 1A and B summarizes the results from these breast cancer cell lines in which basal-like breast cancer cells demonstrated selective sensitivity to cisplatin. This selectivity was absence in cells treated with paclitaxel or doxorubicin suggesting that basal-like breast cancer cells confer selective sensitivity towards cisplatin (Figure 1A, B and Supplement Table 1). Small chemical library screening identify rapamycin as synergistic agents for cisplatin Although cisplatin is currently one of the most used agents in the treatment of cancer, the use of cisplatin is hampered by its side effects, especially neurotoxicity, nephrotoxicity and rug resistance [16]. Hence, the present study was aimed to identify chemosensitizers that could synergize the effects of cisplatin for treatment of basal-like breast cancers. To identify small molecules that enhance sensitivity of basal-like breast cancer cells to cisplatin, a cell-based high-throughput screen was performed using MDA-MB-468 cell line and a small chemical library consisting of 160 well validated specific inhibitors. The screens were done in 96-well plates to which compounds were added at 10  µM, followed by cisplatin at 1  µM. Cell viability was measured 72 hours later by MTT assay. Each plate included controls of untreated cells, cells treated with compounds or cisplatin only, and cells treated with a combination of both agents. Combinations of the treatments that induced growth inhibition higher than those of the same doses used alone (p The molecules identified in this screen includes rapamycin, [3-(Pyridin-2-yl)-4-(4-quinonyl)]-1H-pyrazole (LY364947), 4-(3-Chloroanilino)-6,7-dimethoxyquinazoline (AG1478), (E)3-[(4-Methylphenyl)sulfonyl]-2-propenenitrile (BAY11-7082), 2-(4-Morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002) and 4-(4-Fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)1H-imidazole (SB203580). Structures of these compounds and their growth inhibitory effects were shown in Figure 2. The molecular target of these compounds was listed in Table 1. The 6 compounds identified are specific inhibitors of the mTOR, TGF-à ¯Ã‚ Ã‚ ¢, EGFR, NFà ¯Ã‚ Ã‚ «B PI3K/AKT and MAPK pathways which have been previously reported to be upregulated specifically in basal-like breast cancers [7, 17-20]. However, when tested for synergism with cisplatin at fixed concentration ratio, only rapamycin showed synergism when combined with cisplatin in MDA-MB-468 cells using the isobologram method that simulate the median-dose combination index (CI) [14]. The mean combination index at ED50, ED75, and ED90 of rapamycin (10:1 cisplatin:rapamycin) when combined with cisplatin was 0.52 à ¯Ã¢â‚¬Å¡Ã‚ ± 0.06, where combination index Specific synergistic effects of rapamycin and cisplatin in basal-like breast cancer cells Next, we sought to investigate if combination of cisplatin with rapamycin exhibit specific synergism in basal-like breast cancers by comparing their effects in a panel of breast cancer cell lines. The antiproliferative effect of treatment was evaluated using MTT assays and drug interaction was assessed by the isobologram method as described in the previous section. The results demonstrated that combination of rapamysin and cisplatin exhibited selective synergistic effects only in the basal-like MDA-MB-468, MDA-MB-231 and HCC1937 cells, but not in the luminal-like T47D or MCF-7 cells (Figure 3A and Table 2). To ensure that the lack of synergistic effects of rapamycin and cisplatin observed in luminal-like cells is not due the general lack of sensitivity of luminal-like cells to cisplatin per se, we compared the apoptotic effects of cisplatin and rapamycin alone or in combination in MDA-MB-231 and T47D cells using an equal potent dose of cisplatin (IC50 dose). Both cell lines exhibited similar amount of apoptosis following treatment with their respective IC50 dose of cisplatin. Interestingly, when both cell lines were treated with combination of cisplatin and rapamycin, synergistic effects were evidenced only in MDA-MB-231 cells but not in T47D cells. The potentiation effects of rapamycin observed in MDA-MB-231 cells were further enhanced by sequential treatment with rapamycin for 6 hours followed by cisplatin (data not shown). These results demonstrated that rapamycin is capable of sensitizing basal-like breast cancer cells to cisplatin, suggesting that the synergistic effects of rapamyc in and cisplatin may be mediated through a common pathway. Rapamycin sensitizes basal-like cells to cisplatin through p73 up regulation Previous study has shown that inhibition of mTOR by rapamycin up regulate p73 in breast cancer cells [21]. We and others have also demonstrated that p73 is overexpressed in a subset of triple-negative breast tumors and that p73 is required for cisplatin sensitivity in basal-like breast cancer cells [4]. On the basis of these findings, we ask if the synergistic effects of rapamycin and cisplatin combination could be explained by the activation of the p73 pathway. To test this notion, MDA-MB-231 cells were treated with 10  µM of cisplatin and 100 nM rapamycin alone or in combination for 48 hours. mTOR inhibition was confirmed using phospho-S6K as a marker of mTOR activity. Quantitation of the mRNA and protein expression of the TAp73 was performed using qPCR and immunoblotting, respectively. The results showed that treatment of rapamycin or cisplatin alone did not change the expression of TAp73 mRNA but induced significant up regulation of TAp73 protein expression in MDA-MB-231 cells (Figure 4A and B). Next, we evaluated the expression of the two potent pro-apoptotic BH3 only proteins, PUMA and NOXA, which has been identified as specific p73 target genes, using qPCR [22, 23]. As expected, treatment of cells with cisplatin for 48 hours induced mRNA expression of PUMA and NOXA in both MDA-MB-231 and MDA-MB-468 cells. Significant induction of PUMA and NOXA were also observed in MDA-MB-231 cells but not in MDA-MB-468 cells following treatment with rapamycin alone. When cells were treated with combination of cisplatin and rapamycin, the expression of PUMA and NOXA was further enhanced, corroborated with the massive induction of apoptosis as shown in Figure 3B. Together, these results suggest that rapamycin synergize cisplatin activity in basal-like cells through induction of p73 pathway. p73 is required for the synergistic effects of rapamycin and cisplatin in basal-like breast cancer cells To further evaluate whether p73 is the effector of the synergistic effects of rapamycin and cisplatin in basal-like breast cancer cells, we generated a series of isogenic cell lines that have been depleted for TAp73 by stably expressing a shRNA species that target specifically human TAp73. Unlike MDA-MB-231 cells which express one predominant TAp73 isoform (TAp73à ¯Ã‚ Ã‚ ¢) isoform, MDA-MB-468 cells express high levels of two p73 isoforms, TAp73à ¯Ã‚ Ã‚ ¡ and TAp73à ¯Ã‚ Ã‚ ¢ [21]. Figure 5A showed efficient knock-down of TAp73 isoforms in MDA-MB-231 and MDA-MB-468 cells. As expected, treatment of cisplatin alone induced significant amount of apoptosis in MDA-MB-468 vector control cells. This apoptotic effects were further enhanced in the presence of rapamycin, consistent with our previous observations (Figure 3B). In stark contrast, depletion of TAp73 not only reduced the amount of apoptosis following treatment of cisplatin alone but also completely abrogated the synergistic effects of rapamycin (Figure). This result is further supported by the isobologram analysis which showed a lack of synergism of rapamycin-cisplatin treatment in the TAp73 depleted cells. Together, these results suggest that TAp73 is required for the synergistic effects of rapamycin and cisplatin in basal-like breast cancers. DISCUSSION By gene profiling, breast cancers can be classified into 5 molecularly distinct subtypes: luminal A, luminal B, HER2+, basal-like and normal breast cancers. The basal-like subtype, which represents 15-20% of breast cancers, has been subjected to extensive investigation in recent years due to its association with poor patient survival [1, 2, 20, 24]. Unlike many breast cancers, patients diagnosed with basal-like breast cancers are not eligible for molecular targeted therapy that target ER (e.g. tamoxifen, aromatase inhibitors) or HER2 (e.g. Herceptin) as they do not express the estrogen receptor (ER) or progesterone receptor (PR), nor do they have amplified HER2 [1, 24]. The treatment option therefore is relied on aggressive conventional chemotherapies which have limited efficacy, many side effects and often high rate of relapse. Hence, development of an effective therapeutic strategy remains an important goal in the management of basal-like breast cancer. Several lines of evidence has suggested a link between basal-like breast cancers and BRCA1 deficiency [7, 25, 26]. In most cases, the clinical features and outcomes for women with sporadic basal-like breast cancers are broadly similar to those with BRCA1-related cancers including high tendency of developing high grade, high mitotic index tumors, shorter time of relapse, similar pattern of metastatic spread and cytogenetic changes associated with frequent loss of X-chromosome inactivation [7, 27-32]. The majority of BRCA1-associated cancers are also triple-negative (ER, PR and HER2 negative), express basal cytokeratins and other markers commonly seen in basal-like breast cancers (e.g. p53, P-cadherin and EGFR) [7]. Gene expression profiling also demonstrated that BRCA1-associated cancers segregate strongly with basal-like breast cancers [2, 29, 33, 34]. Although BRCA1 somatic gene mutations are uncommon in sporadic basal-like cancers, these tumors have been shown to have a dysfunction al BRCA1 pathway due to BRCA1 gene promoter methylation and/or BRCA1 pathway transcriptional inactivation [7, 25, 26]. The fundamental biological similarities between hereditary BRCA1-related breast cancers and basal-like cancers suggest that strategies targeting the dysfunctional BRCA1 pathway may be effective in basal-like breast cancers. There is increasing evidence that the DNA repair defects characteristic of BRCA1 related cancers, especially defective homologous recombination, confer sensitivity to certain systemic agents, such as platinum-based chemotherapy and poly(ADP-ribose) polymerase (PARP) inhibitors [34-38]. Indeed, recent clinical studies revealed that sporadic basal-like cancers responded to platinum-based chemotherapy and were associated with a high rate of complete pathologic response [9, 11, 38]. Consistent with the clinical data, our in vitro study also reveals that basal-like breast cancer cells confer specific sensitivity to cisplatin as compared to other chemotherapeutic agents (e.g. doxorubicin or paclitaxel) (Figure 1), further support research into the utility of platinum-ba sed agents in basal-like breast cancers. Given the high specificity and response rate of basal-like breast cancers toward platinum-based therapy, our focus is to maximize the benefits associated with this therapy through drug combination strategies. Using a small chemical library consisted of 160 well-validated and specific inhibitors that target the human kinome, we have identified 6 compounds that significantly potentiate the antiproliferative effects of cisplatin in basal-like breast cancer cells. These compounds include rapamycin, LY364947, AG1478, BAY11-7082, LY294002 and SB203580 which targets the mTOR, TGFà ¯Ã‚ Ã‚ ¢RI, NFà ¯Ã‚ Ã‚ «B, PI3K/AKT and MAPK pathway respectively. Of note, these pathways have been reported previously to be over activated in basal-like breast cancers [7, 17, 18, 20]. To further investigate the mode of interaction between these compounds and cisplatin, we performed a drug combination study using the isobologram approach as described previously (Ref). Out of the 6 compounds identified, rapamycin showed the strongest synergistic effects with cisplatin while others (LY364947, AG 1478, BAY11-7082, LY294002 and SB203580) showed mainly additive effects. This result is consistent with other studies which show that inhibition of mTOR by RNAi or small molecules (e.g. rapamycin, CCI-779, RAD001) enhances cisplatin chemosensitivity in ovarian [39-41], endometrial [42], head and neck [43, 44], lung [45], skin [46, 47] and liver [48] cancers. We next compared the synergistic effects of rapamycin in combination with cisplatin in a panel of luminal-like and basal-like breast cancer cell lines that has been previously validated by gene profiling [15]. Intriguingly, the synergistic effects were observed only in MDA-MB-468, MDA-MB-231 and HCC1937 basal-like cells, but not in MCF-7 or T47D luminal-like cells. Several models have been proposed to explain the synergistic effects of rapamycin and cisplatin in cancer cells. Beuvnk et al., 2005 showed that RAD001 (Everolimus), a rapamycin derivative, dramatically enhances cisplatin-induced apoptosis in wild-type p53 but not mutant p53 tumor cells by inhibiting p53-induced p21 expression [49]. Wangpaichitr et al., 2008 demonstrated that inhibition of mTOR by CCI-779 decreased levels of the anti-apoptotic proteins, BCL2/BCLxL, and increasing apoptosis in lung cancer cells that is resistance to cisplatin [50]. Although these models provide important evidence for mTOR inhibition and cisplatin synergism in cancer cells, it fails to explain the specific synergism we observed in basal-like breast cancer cells, as the basal-like cells that we tested are p53 mutated and do not express high level of BCL2/BCLxL (data not shown). This led us to postulate that a common signal transduction pathway inhibited by rapamycin may be an important component that sy nergizes cisplatin sensitivity in basal-like cells. Since p73 has been reported to mediate cisplatin sensitivity in a subset of triple-negative breast cancer cells [4] and that inhibition of mTOR by rapamycin or RNAi lead to upregulation of p73 [21], we postulated that activation of the p73 pathways might be important for the synergistic effects of rapamycin. To test the role of p73 in rapamycin and cisplatin synergism, we first evaluated the expression of p73 mRNA and protein levels following treatment with cisplatin or rapamycin alone or in combination in MDA-MB-231 cells. Consistent with previous studies, treatment of cells with cisplatin or rapamycin alone induces p73 protein expression followed by transcriptional activation of the 2 potent pro-apoptotic p73 target genes, PUMA and NOXA. When MDA-MB-231 cells were co-treated with rapamycin and cisplatin, the elevation of p73 and its pro-apoptotic target genes were synergistically enhanced. The observed changes in p73 protein in MDA-MB-231 cells, however, were not due to parallel changes in p73 RNA levels, suggesting that inhibition of mTOR might lead to inactivation of a yet unknown p73 specific protein degradation pathway. To validate that the rapamycin and cisplatin synergism is mediated by p73, we generated isogenic MDA-MB-231 and MDA-MB-468 cells that were depleted for p73 using a lentiviral-shRNA that target specifically the transactivating isoform of p73 (TAp73). Indeed, depletion of TAp73 in MDA-MB-231 and MDA-MB-468 cells completely abrogated the synergistic effects of rapamycin suggesting that the synergism between rapamycin and cisplatin required p73 function. Although the combination of cisplatin and rapamycin has not been previously investigated in clinical study, it is worth noting that a phase II neo-adjuvant clinical trial of cisplatin and RAD001 (Everolimus), in patients with triple-negative breast cancers has recently open for recruitment (ClinicalTrials.gov Identifier: NCT00930930), and will be able to address the potential of cisplatin and mTOR inhibitors combination therapy directly. It would be equally intriguing to determine the role of p73 related pathway as potential biomarkers that might predict response to treatment given the pivotal role of p73 in the synergistic effects of mTOR inhibition and cisplatin sensitivity. In conclusion, combination of mTOR inhibitors and cisplatin may be a useful therapeutic strategy in basal-like breast cancers.

Friday, September 20, 2019

Impact of Cartoons on Children Research

Impact of Cartoons on Children Research Cartoon or animated movie is a form which uses optical illusion and movements of consecutive performing of many still images. The first cartoon in the world was Fantasmagorie which was made by a France artist, Emile Cohl in 1908. Produced in over 100 years ago, this film had no sound and was called silent film. With white stroke on a black board in class table the film about the adventure of the cartoon character called Stick figure. All are represented by dots and simple strokes. Traditional animated cartoon, developed in early 1900s, was practiced by Ubbe Ert Iwwerks, Walt Disney and others. They had used 24 different pictures for each second of their animated movie. The first complete cartoon was produced in 1991. However, cartoon was not recognized by worldwide audience until 1914 via category animation film Gertie the Dinosaur by producer John Bray. In fact, in 1913, a film studio had producing as ones only occupation and within 5 years, the new entertaining program was born. At that time, a lot of artist took part in animated and got a lot of success. Early 30s of twentieth century, manufactures began to enhance color elements and sound in animation. The most representative works are maximum use of such elements as Snow white and the Seven Dwarfs (1973), this is the long animated the first episode in the history of the genre. Pinocchio (1940) was a cartoon produced by technical systems and the last complete. Frequently, people think cartoons are made by many simple drawing and just put them on order. In most peoples opinion, cartoons are several pictures describe consecutive actions. In fact, the second though is true. However, nowadays, in order to bring out a perfect product; producers have to make a lot of specific things. We have brief proceed about how to make a short cartoon movie. A cartoon movie, even just 30 or 80 minutes also need a number of producer and amount of time to make it completely. Everything starts from the idea, as soon as the script has done, a group of artists begin develop many storyboard which include brief conversations and the sound in the movie. After director checked the storyboard out, they move on to sound recording. Many people whose voice suit with character in the movie will be invited to dub. The sound will be deal with and provided on the number of frame on the movie and written called paper the dope sheet. Next to this step, the main parts of the movie are performed. Rough layout will be drawn first; in this part, artist just only use the pencil for perspective, arrangement of character and design. At the same time, animators make movements and after all of these the producers will make a test of lead draft and move on to check the film composition out. Then, they ad d more colors and theme on movie and move it to computer in order to join the scenes with the sounds. Finally, they check it out again to fix the problems and public. The cartoon making spends a lot of time. It usually takes them, on average, 6 to 12 months or maybe more just only to make a half hour cartoon. It is truly a difficult job. Watching cartoon had many bad effects on children. According to her, even in cartoon, children effected by violence across the screen kicking, killing each other with frequency of about 20 time an hour. Children watch violence images on television many hours a week there will have many violence actions as hitting, punching, biting his parents, sibling and friends. For advertising of food and alcohol, young tend to think the food in advertisements is good for health and not interested in the importance of vegetable in their diet. In addition, kids watch more cartoon are less physically active, easy weight gain leading to obesity while in young ages, children need to play creatively to social development. Finally, cartoon or television also influences a childrens eyesight if they focus on looking at the screen for prolonged periods. Method I. Participants: The researcher chose 100 people from many areas in Hanoi who have different jobs and ages. The participants in this study are: 20 students are working in Banking Academy, Hanoi, Vietnam. 30 kids from Katies living place. (Mage = 15.6 years, age range: 8 18 years) 20 younger parents who have kids (Mage = 27.3 years, age range: 23 35 years) 30 adults live around Hoan Kiem Lake (Mage = 36,3 from 19 45 years) In those participants, researcher chose 3 people to ask them a lot of special question. All of them have kid on school-age: Nguyà ¡Ã‚ »Ã¢â‚¬ ¦n Ngà ¡Ã‚ »Ã‚ c Hoa, 29 years old, lives in Hanoi and she is a business woman. She has two children, one kid is 7 years old and the other one is 10 years old. Nguyà ¡Ã‚ »Ã¢â‚¬ ¦n Phà ºc Là ¢m, 32 years old, lives in Hanoi and works as a director in a Japan Company. He has a son whom is 9 years old. Là ² A Pà ¡o, 27 years old and lives in Hanoi. He works as sale manager on a company. I choose participants of different age living in different area to be objective and results of comprehensive. I focus on those who are kids by age group most influenced by this art. As young adults age is less influenced. I. Procedure: First, the researcher collected the information from some source such as: newspaper, books, Internet and so on. Then, basing on it, the researcher made some relevant questions for adults and people who care about Cartoon. Thirdly, the researcher met them in persons and interviewed to get more information. With the adults, the researcher asked them filling questionnaire or ask and the researcher filled the question list for children. After that, some quotation were cited, analyzed and compared. Finally, the researcher showed the conclusion from studies. Results Many reports have mentioned and researches about the opinion of people about media, including cartoon, and its affect to the peoples life. Stevie Hossler  (August, 2011) said that typically, children begin watching cartoon on television at an early age of six month, and by age two or three, children become enthusiastic audience. This has become a problem because there are too many children are watching TV too much and these programs (even cartoon) become violent and addictive. Children watch cartoon too much on TV are more likely to have mental problems and feelings, along with brain and eyes injuries and unexpectedly the risk of a physical problem increase. Furthermore, because of seeing violent on TV, children become less sensitive to hurting and affliction of others, they are not afraid of violent and easily become aggressive or use harmful action towards other people. Besides above results that I found in references, I also had a survey with 100 people have different ages (from 6 to over 45 years old and come from many different areas around Hanoi) on the question: Do you watch cartoon movie? and if yes: How old are you?. Then, I build on one pie chart that shows us Which are age groups who usually watch cartoon? Nowadays, cartoon movies are very popular and improve very quickly. Variety of cartoon movies were built for every age. From this chart we can see easily that at the period of age from 28 35, the percentage of people watch cartoon is 6 percent, makes up the smallest part of the pie chart. In that period of age, people usually too busy with their job and have no time to watching television, relaxing, even playing with their kids. A few of them spend the weekend to do those things, however it is just a short time. Hoa said that: I work as a business person so I have a lot of things to worry about, such as counting numbers, business, bosses, colleagues and so on. All of them make me crazy to dealing with. However, I still try to spend time playing with my girls, especially watching their favorite animation together. While, children on school age are the ones who watch cartoon the most. On the research, all kids watch cartoon every days, they watch it at home, at school and spend at least 3 hours per day for looking at television screen. It is really a huge number Moreover, we had a survey of a number of people who watch cartoon to find answers of the question: What kind of cartoon movie do you watch? Discussion When we did the research about cartoon with many people, there are two opposite opinions. Nobody can deny that cartoons have many surface advantages. First, watching cartoon movie is a useful entertainment activity for children and adults. A child can lie down quietly on sofa and just watch his favorite cartoon, instead of running around or screaming when his parents are working so they can play with their kid. Moreover, cartoons also have important effect on adults, especially the couples whose young children. After several busy working hours, parents can sit next to their kids and watch cartoon together. Thank to this film, they can relax completely and have a chance to stay their children nearer. These things are better than plunging into job immediately after arriving home and do not spend any time talking to the children. Nguyà ¡Ã‚ »Ã¢â‚¬ ¦n Ngà ¡Ã‚ »Ã‚ c Hoa (29 years old, Hanoi) said that: When my daughter was younger than she is now, after working time, I arrived home and just focused on housework such as cleaning, washing, cooking and so on. Because of my job, I did not have enough time to play with my child and usually took her play by herself or with her friends next door. Recent time, I have spent more time watching Tom and Jerry and other cartoons on Disney channel or Cartoon Network. I realize that when I watching cartoons with my daughter, the conversation between me and my kid become closer than ever. Now, I understand my honey more clearly, know what she wants, what she thinks, what she needs, and how she grows day by day. As a mother, I really feel very happy and so glad to understand her. J.Wolffe, an animation researcher wrote in an article on April, 23, 2012 that the animation is where kids learn how the hero is really, when she was a child, she could learn to pronounce quickly difficult words which make people confusing when listen to them. Smart will help you get almost everything and there is always anybody is more intelligent than you, animation teaches all that. Why? Because, via animation kids can learn and understand quickly when they are entertaining, which is one of the reason why children have difficulty learning from teachers, the pressure makes them liable to remember vocabulary as fast as sing a song in animation. At home, I always buy CD or open a cartoon channel to watch many funny movies with my son. In the past, my child was very active; he always run around house, from a room to another room and never sits quietly on a place within thirty minutes. However, since he has watched cartoon, he can sit on chair with concentration to television without saying any word. Furthermore, after watching a movie, if he does not get anything on this film, he will try to discover by asking me or other ones. He also often dram the characters on cartoon scene, training every day and improves it day by day. I am so proud of my little boy said Nguyà ¡Ã‚ »Ã¢â‚¬ ¦n Phà ºc Là ¢m (32 years old, Hanoi). Not only does cartoon bring happy time for parents with their children, but it also is a special teacher for kids, who is closest and most friendly with younger generation. Nowadays, there are many cartoon series which including educative programs. It teaches children arithmetic, drawing by using beautiful and attractive shape and funny situation. Besides that, via a lot of movies, kids can learn about some knowledge around them, improving their grasp and learning. Some programs teach 7- and 8- years old a little of a foreign language, such as English an international language. Learning English from young is an important step for language ability for children in the future. In addition, animated films have a lot of funny and eye-catching picture which attract the kids so these points will help develop and enrich the childrens imagination. A vast number of people think that watching cartoon is totally good and it does not have any bad influence on children and adults. In fact that opinion is not absolute true. Cartoon is a kind of movie which causes addiction easily. More and more kids have trend toward sitting on room and they prefer watching cartoon to going out and playing with other kids, doing exercise or other activities. Sitting and watching animated movies several hours like that can make the kids sink into the world of many imaginary characters, they can use that time to do more useful work, instead of wasting it only on watching cartoon. Cartoon is just a program used to relax and improve kids brain; it cannot replace healthy activities which will train childrens body. Moreover, base on an unpublished study perform by Mary Fenway, watching cartoon on several hours cause autism for 46% of children who usually do this work and they will find difficult on opening relationship. This is really an unexpected disadvantage of watching cartoon, which nobody is looking forward to. Besides that, nowadays, appeared many animated companies just care about their profit and are insensitive to their products affection for younger generation. Là ² A Pà ¡o (27 years old, Hanoi) said that: I usually let my son watching cartoon himself because he is very interested in this funny program. However, recently, I feel that my son got mad more often than he had been, lazy to eat and sometime he beat his classmate in kindergarten. I felt very nervous and could not explain what the reason was. A few day later, I found that a cartoon channel that my child usually watch for, project an animated movie whose a lot of violent scene. Immediately, I delete that channel because it made much bad influent on my kid. Instead, I let my son watch a lot of educative cartoon and care more about what he watches. In modern life, many parents are busy with their jobs and do not notice what their child watch. Bad animated movies bring a lot of evil effect on young people, teach them things and make them have the wrong view about the lives around. Furthermore, a few animated movies which are made for adults, has unsuitable content with kids and effect on the childrens souls if they watch those movies accidentally.     Ãƒâ€šÃ‚  Ãƒâ€šÃ‚  Ãƒâ€šÃ‚  Ãƒâ€šÃ‚  Ãƒâ€šÃ‚  Ãƒâ€šÃ‚  Ãƒâ€šÃ‚  American Academy of Pediatrics (AAP) and American of Child Psychiatry and adolescents (AACAP) felt that television does not affect the behavior of children as young an age. From  their research, the AACAP countries, Kids watch shows in which violence is very realistic, frequently repeated or unpunished, are more likely to imitate what they see. They also said that childrens parents need to keep a close eye on what their kids watch, and explain for children that the cartoon character was shot was not hurt, but really would be seriously injuries or die in real life. They should tell their kids that violence is not the best ways to deal with a conflict. In conclusion, because of a lot of cartoons affections on childrens life and character in future, choosing a best cartoon for kids is an important work with who are mothers and fathers. In addition, there is an alarm for the industry for kids; they need block the commercial cartoon, give back the innocent, pure and suitable animated movies for the future generation of the world.

Thursday, September 19, 2019

A day at the cubbies game :: essays research papers

Growing up in the suburbs of Chicago and being a sports fan resulted in one and only true outcome; I am the Chicago Cubs’ biggest fan. True, I am not the only person in the greater Chicagoland area who will claim the title, but I stick to my guns and refuse to relinquish the self-appointed title. Every time I go home, I join the thousands of other self appointed â€Å"biggest fans† in the usual afternoon at Wrigley Field. There is nothing quite like a day at a Cubs game. For me, it’s a fun filled day of drinking watered down beer and eating cheap hot dogs and nachos with the guys. Yes, it may sound rather crude to many but to us, its bliss.   Ã‚  Ã‚  Ã‚  Ã‚  The day usually starts early in the morning, an eight o’clock train into Chicago, with the throbbing pain of a hangover after being out too late the night before catching the game at the local sports bar. After the mochas and lattes have crested over the appropriate sets of lips the whole group perks up with anticipation over the days events. Players’ statistics are discussed, along with the usual hopeful, â€Å"Maybe Derek Lee will hit a grand slam today!† and, as always, Nate and Mike get into it at least once over whether Kerry Wood or Richard Prior is a better starting pitcher. Friendly jabs are exchanged in all directions, and by the time everyone agrees to disagree the train is pulling into Union Station and we’re one step closer to the game.   Ã‚  Ã‚  Ã‚  Ã‚  After catching a taxi, the short ride to the ballpark takes far longer then it should due to the hundreds of cars that are assaulting the Wrigley Field parking lots and attacking the local traffic cops. As the taxi creeps impatiently up the street, edging closer and closer to the unmoving vehicle in front of it, Wrigley Field slowly climbs out of the Chicago skyline. A beautiful thing occurs every time this happens†¦silence! Mike, Nate, Nick, Andrew, and James have all stopped their usual â€Å"guy talk† to take in the glory of our team’s home field. The striking red brick of the building, with bold green ivy lazily climbing it’s walls, and the â€Å"WRIGLEY FIELD, Home of the CHICAGO CUBS† sign screaming out from the front, all receive the deserved moment of silence and respect they demand from all who walk within their walls.

Wednesday, September 18, 2019

My First Kiss :: Personal Narrative

My First Kiss â€Å"Kissing a watermelon? No, I’ve never been THAT desperate.† My sister Amy went on to tell me about her friend who dared to do such a feat. â€Å"Did it help?† I asked. â€Å"We don’t know! She hasn’t kissed a real guy yet!† Amy and I burst into a fit of giggles, and I realized how being in the company of my younger sister regressed me to her awkward, girlish high school age. I had forgotten, until this bedside 2:00 a.m. conversation, how I used to be obsessed with popularity and sports cars, and how I daydreamed of my first kiss. But Amy had much more â€Å"experience† than I did at her age. She and her friends had passed their adolescent initiation of first kisses—at least the kind on the lips. â€Å"In the back of the CHURCH van? With everyone watching? Where did he kiss you?† â€Å"On the LIPS!† she squealed. Amy’s excitement and anxiety about kissing ignited a rush of memories. How I used to romanticize about first kissing someone! I thought that I would be in a long flowing gown, and the handsome young man would bring me flowers, and ask to court me. Our kiss would be done on the porch, under an encouraging moon and a harmony of stars. Or maybe I would be in a MacDonalds, and the most good-looking guy I’d ever seen would come to my table, buy me a hot fudge sundae, and he give me a kiss when he walked me to my car. Ah, the kiss was exciting to think about as well. I had no idea what it would be like, but I knew it would feel wonderful. This quick pucker and follow-through would be my initiation into womanhood, somehow setting me apart from other girls who could barely fill a bra or who, as rumors went, practiced kissing by mutilating fruit. A rite of passage, a first romance, yes. But my girlish head had set itself upon one quest: I would be truly in love with the young man I first

Tuesday, September 17, 2019

Intelligence Definition and Measurement

Question a Though the construct of intelligence has been in being for a long period of clip, there has been no acceptable definition of what intelligence really is. Further, the beginning of intelligence remains elusive, merely as is the value and truth of its trials. Assorted governments have attempted to specify intelligence from different positions. One common definition is that it is ‘the capacity to get and use cognition. ‘ ( Gardner, 1999 ) . Another authorization looks at it as the ability that intelligence trials step. Though definitions are by and large used for general intents, there are certain facets that they fail to turn to. In the first topographic point, there are people with histories of autism or those who are mentally retarded, but who are exceptionally talented in specific countries such as music, but hapless in others such as mathematics ( Angela, 2003 ) . Other people are able to make certain things because of the environment in which they stay, and non because they are intelligent. A kid who grows up in a house with a Television set can run it unlike one who does n't cognize what a Television set is. Others are able do carry through certain things because of familial factors, and non because they are intelligent. One ‘s province of wellness can besides impact the manner he acquires and applies cognition, which is non needfully a grade of intelligence. On the other manus, there are people who have been brought up in certain environments, but who are unable to use the cognition f rom the environment to make certain things. These may be presumed to be less intelligent. The theory of multiple intelligences, propounded by Howard Gardner, best tantrums my selected instruments. He identified seven constituents of intelligence which are independent, and each of which is possessed by different persons to different grades. These are the visual-spatial intelligence, the verbal-linguistic intelligence, the bodily-kinetic intelligence, the logical-mathematical intelligence, the interpersonal, and the musical, intrapersonal and realistic intelligence ( Gardner, 1999 ) . Question B The dependability of ACER Test of Reasonability can be tested. Several points which claim to mensurate similar general concepts are tested to see if they produce similar tonss. The campaigner ‘s intelligence and general cognition is tested by each of the 70 points. The trial has been declared 85 per centum reliable. Cogency refers to how strong decisions, propositions and illations on a given issue are ( Oswald, 2001 ) . There should be a correlativity between the instructor ‘s evaluations and the tonss obtained by the pupils. Reasonable dependability and cogency of a trial must accomplish both educational and vocational counsel in establishments of acquisition. The normative process has to make with a choice of a good figure of people whom the trial is to be administered to. The broad country from which the choice is done is likely to do anomalousnesss because of varied geographical, school type, gender, linguistic communication and the societal and economical backgrounds. Bias could be as a consequence of gender. Certain subjects could be better handled by work forces and non adult females, or vise versa. Dependability of The Constructive Thinking stock list could besides be considered. The points on the graduated table must be able to prove what they purport to prove. There should be adequate points proving each variable. Validity relies to a great extent on correlational surveies. A figure of points resting one ‘s emotional and physical fittingness are used. There could besides be instances of prejudice originating from one ‘s age, educational degree, and gender, though these should be curbed if the trial is to hold any significance. Accomplishment trials are used in both academic and professional scenes. They include the Basic Achievement Skills Inventory ( BASI ) and the Test of Academic Performance ( TOAP ) ( Reynolds, 1998 ) . BASI is administered as a group trial. It can assist place larning disablements common in reading, numeracy, choice pupils for particular accomplishments, college arrangement etc. TOAP estimates the academic public presentation of kids topographic points them in classs in footings of accomplishment and analyze how their public presentation has changed over clip. It employs a aggregation of six topics. Two are related to reading while four are administered to persons and groups. The trial is timed, and is meant to be done rapidly and easy. Reliability testing is done to prove the stableness of the consequences on a test-retest footing in the BASI appraisal. The first and 2nd testing of each pupil is computed and correlated. Two hebdomads are allowed between trials. The estimations from test-retest samples are largely reasonably strong. Cogency could besides be tested by looking at the assorted subsets of the pupils to be tested. The norming process could affect random sampling, and attention taken to avoid any prejudice for or against any group. Dependability and cogency for tonss does non come out really clearly in TOAP. However, the test-retest method could still be used. Validity could be looked at by correlativities between subsets. As is the instance with others, possible countries of prejudices need to be avoided for so trials to reflect the true place. Question degree Celsius There are many types of appraisal for proving intelligence degrees. These scope from cognition and abilities of a general nature, to countries and topics that are specific. One of these is the ACER Test of Reasonability. The other one is Constructive Thinking Inventory ( CTI ) . The ACER Test of Reasonability consists of 70 multiple pick points which seek to prove the general ability of scholars between 9 and 11 old ages, and it is largely used in Australia. Focus is on single tonss, whose consequences assist the instructor usher and advocate pupils refering vocational preparation. All inquiries are to be answered, even if the reply is non perfectly known. The Constructive Thinking Inventory ( CTI ) consists of 108 self-reporting points. It is designed for mature people of over 18 old ages. Descriptive statements of idea and behavior are given, where the respondent is supposed to rate himself on a graduated table from 1 ( Absolutely False ) to 5 ( Absolutely True ) ( Simons, 1998 ) . The trial measures one ‘s ability to believe constrictively or destructively. The consequences from this sort of appraisal are used to assist in psychotherapeutics. It is besides used in reding substance maltreaters, pupils in college, human resource choice and work related issues in organisations. Question vitamin D There are a figure of ethical issues associated with accomplishment and intelligence trials in instruction. Consideration should be put to the fact that an test can forever alter person ‘s life. Care should hence be taken when puting and administrating. A low achieving pupil could for illustration be put in a particular category from where his demands can easy be met. One could hold misinterpreted the inquiries and therefore given the incorrect replies, non because he is non intelligent. If the trial is culturally biased, the pupil ‘s public presentation is likely to be affected. Care should hence be taken to avoid this scenario. The pupil ‘s degree ; of success can easy be hindered by IQ trials which are frequently considered biased. Ethically hence, an appraisal of pupils must hold an unquestionable degree of dependability and cogency. The foregoing discourse establishes that the definition of intelligence is varied, and frequently combative. Assorted theories whose purpose nevertheless is to assist in the apprehension of intelligence exists. Measures and trials at the disposal of instructors could be employed to guarantee that proving meets the needed criterions.MentionsAngela, C. ( 2003 ) . Intelligence and Autism. New York. Pride BooksGardner, Howard. ( 1999 ) â€Å" Intelligence Reframed: Multiple Intelligences for the twenty-first Century. † New York: Basic Books. Reynolds, W. ( 1998 ) . Intelligence Theories and Tests. Virginia: Oswald. H. ( 2001 ) . Trials for Research Instruments. Vermouth: Cedar Pine Publishers St. simons, T ( 1998 ) Trials and Measurements of Intelligence. Hollywood: Noel Publications Intelligence Definition and Measurement Critique of the definitions of IntelligenceThere are certainly many definitions of intelligence as there are experts who study it. A Psychologist, R.J. Sternberg (2000), editor of handbook of intelligence offered variety definitions from various writers. Few of these definitions done by the editors of the Journal of Educational Psychology, which I consider fits for this paper are as follows:â€Å"Intelligence is sensory capacity, capacity for perceptual recognition, quickness, range on flexibility or association, facility and imagination, span of attention, quickness, or alertness in response† (p. 8).Intelligence is also defined as â€Å"the ability to learn or having learned to adjust one self to the environment† (p. 8). There are still more definitions but to conserve some space I just chose two. Indeed, all the definitions offered by the editors of the Journal of the Educational Psychology were obviously product of years of studies as most of the definitions were dir ected towards mental ability. The definitions above identify the intelligent person not only in terms of the intellectual ability of the mind but in its ability to quickly adjust to new environment.The Measures of IntelligenceThe Standford – Binet theory of intelligence fits for these two definitions because the measures of intelligence test are more related. The Standford-Binet intelligence tests cover four major areas such as verbal reasoning, quantitative reasoning, abstract/visual reasoning, and short-term memory. Scores include raw scores and scaled scores for each of the 15 subtests, scaled scores and percentile ranks for a composite of the four area scores, a composite of any combination of the four area scores and a profile of all 15 subtests based on scaled scores. A pretest is administered to identify the level at which to begin testing. Scores corresponding to IQ’s are called â€Å"Standford Age Scores†.Meanwhile, the Wide Range Achievement Test (WRAT ) has a number of positive features according to Joseph F. Jastak. He explained that the WRAT is fast and simple to manage and score, the examiner can create choices in the content of the test and in management of the form (Singular or Combined). The prototype of errors that a person has done can be analyzed qualitatively, particularly if the collective form of the test is used, since the WRAT scores are free from the polluting effect or understanding the standard score can be used for comparison with other tests, e.g. the Weschler Scales – in order to determine learning ability or disability, the evidence for construct soundness and dependability is highly regarded and as the literacy sub-tests are untimed, the subject can complete these segment with no time pressures.The WRAT can offer an indicator for the measurement of fundamental reading, spelling and arithmetical skills in individuals with few or no academic qualifications. It can also be used in combination with other tests to present a more wide-ranging picture of the individual academic skills to determine learning ability or disability.Comparing and Contrasting of Selected IntelligenceBoth Kaufman assessment battery for children or K-ABC and the Stanford-Benit theories offered the same areas of concern, cognitive development. They both paid attention to intelligence testing beginning from the child’s early age. However, Kaufman’s ABC development assessment focused on particular groups such as the handicapped group, those with learning disabilities, and cultural minorities. On the other hand, The Stanford-Binet Intelligence Scale presents their test items by age level rather than by particular groupings of special people. Kaupman ABC can also be viewed as rather insufficient in the since that it still needs to be reinforced by other more established, and well studied neuropsychological test such as Stanford-Binet, Wechler scales, and McCarty scales.How the goals are are similar an d differentThe Stanford-Binet theory in contrast with the insufficiency of the Kaufman’s ABC intelligence test is well established and offers a wide range of studies involving all age levels. They have established theories on both language and cognitive development. Kaufman study paid attention on their studies of intelligence on emotionally seriously disturbed children. Their focus is on cognitive development based relationships rather than language skills, while the Stanford-Binet Intelligence Scale offers measures of the person’s general intelligence. In this case, they were on different focus of providing intelligence measurement.How are the Tests Used?In Kaufman’s intelligence scale test is made of sixteen parts. The child then is to complete some task that usually involves placing items in sequence. The child is then evaluated on his or her mathematical, spatial, the ability to mentally process the tasks or problems, and reading skills. The Stanford-Binet intelligence scale Jacquelin Goldman, Claudia L’Engle Stein, and Shirley Guerry (1983) noted that intelligence measurement tests were given at age range from two years old through adulthood. They cited that at each of the age levels there are six items and one alternate item. But from age two through five, test levels are at half-year level intervals, then at age six through fourteen, test levels are at yearly intervals. Goldman, L’Engle and Guerry pointed out that test content conducted for age two, includes form board, delayed response, identifying parts of the body, building blocks, word combinations, and identifying objects by name (p. 148).Purpose of Giving Differing TestIn Kaufman ABC, the purpose of test is for the assessment of the cognitive development, while Stanford-Binet provides the test to measure person’s general intelligence. This is obtained by presenting to the individual a variety of tasks of known increasing difficulty.Examining the Ethical C onsiderations Associated with Achievements and Intelligence Test in EducationAside from children, maybe adult are maybe more liberal in this aspect as long as test that were conducted does not violate any of rights, or as long as it does abuse them. I believe that there is nothing ethically inappropriate with test measures of both Kaufman and the Stanford-Binet. However, test conducted for children should be more cautious especially with use materials. Lead toxicity and choking hazards should be extremely under strict monitoring. Data revealed that prolong exposure to toxic materials may lead to serious renal, hematologic, and neurologic complications (. 117)ReferencesGoldman, J., Stein, C. E., & Guerry, S. (1983). Psychological Methods of Child Assessment. New York. Brunner/Mazel Inc..Sternberg, R.J. (2000). Handbook of Intlligence. U.S.A. Cambrige University Press.Guide to Clinical preventive Services. (1989) U.S. Preventive Task force. U.S.A. Reane PublishingInternet source:Kaufm an Assessment Battery for Childrenwww.cps.nova.edu/~cpphelp/KABC.htmlJastak, Joseph. (1978). Wide Range Achievement Test, Jastak Associates, Incorporated.www.cumc.columbia.edu/dept/sergievsky/cnd/pdfs/ReadingLevel.pdf

Monday, September 16, 2019

Quasar Computers and Different Market Structures

Quasar monopolized the market with the creation of an all-optical imputer known as Neutron. Patents promote innovation for inventors, which allow exclusive rights to do business for a specific duration (McConnell, Bruce, & Flynn 2009). A patent for this new technology allowed Quasar to experience growth in revenues by setting the price as the only provider of an all-optical computer. Quasar established that marginal cost and marginal revenue were equal when selling each Neutron computer at $2,550 with quantities sold was at 5. Units. This helped Quasar determine the need for maximizing future profits to stay competitive with cost reductions in production. Oligopoly In 2006, Quasar was in an oligopolies market because they were already competing with Orion Technologies, a company that recently introduced their own optical notebook computers. During this time of competition, Quasar and Orion mutually stabilized the price for notebooks and both were generating profits.As Orion Technolog y introduced their optical computer to market which resulted In a 50% consumption, Quasar decided that the price of the computer would drop to $1850, creating a profit of $207 and revenues equally $1195 million. Although Orion did make a dent in the optical computer industry they were not able to capitalize on the market. Despite the fact that they were holding the other 50%, they lost profits even though the revenues were equivalent to Quasars. Monopolistic Competition In 2010, Quasar was facing more challenges because of the variety of computer models introduced by other new companies.They were in a monopolistic competition, and Quasar thought of another strategy to keep differentiated from their competitors. They allocated a budget of $200 million to invest in brand development. Because of that Ceres was born, another variation of the optical notebook. Ceres was specifically designed for a new end user, thus distinguishing itself from the Neutron. In a monopolistic competition, b rand development Is vital for maximizing profit higher price for their superior quality products (Fischer, Violence, & Settler, 2010). Pure Competition The final market was the perfect competition.Quasar is well established in the market in 2012. Quasar has obtained controlling interests in Optic for optical display screens (ODDS) technology. The competitive edge with Optic will increase revenues but will require continued innovation to avoid the profit loss. Using a similar strategy that Quasar used in 2005, profits can be maximized by lowering the costs of production. Because Optic operates in a pure competition market, revenue will increase but eventually the competitors will copy Optician's example limiting the economic edge to a short period.Conclusion In each market structure, Quasar made choices that were unique in the structures to maximize profits for each market. The choices made in a monopoly are different from the decisions that needed to be made in other structures. The simulation allowed the opportunity to see how market structure decisions impacted the overall profitability of Quasar over a span of several years. Our findings produced the best exults for Quasar under each organizational change occurring over a span of a few years.

Sunday, September 15, 2019

Written Critique of Drug Therapy in Nursing Practice

According to Wayne K. Anderson, Dean, State University of New York, School of Pharmacy, â€Å"statistically, if you take six different drugs, you have an 80% chance of at least one drug-drug interaction. † The drug regimen of Mrs. Brown includes six drugs that may interact with each other if not administered and monitored carefully. This is the reason why healthcare providers should be aware of the possible adverse affects that may happen related to her drug regimen. Necessary precautions should be observed to get the full benefits of the needed drugs and minimize possible drug-drug interactions. Nursing Management Mrs. Brown has a history of seizure, therefore, necessary measures should be provided to ensure the patient's safety. It is also known that seizure is one of the many side effects of the drug metronidazole (Drugs. com, 2010). To prevent injury to patient, the nurse should provide comfort and safety measures if the CNS effect occurs such as siderails, and assistance with ambulation if dizziness and weakness are present† (Karch, 2006, p. 170). Since Mrs. Brown has numerous risk factors and health conditions, the nurse should â€Å"monitor for drug-drug interactions to arrange to adjust dosages appropriately† (Karch, 2006, p. 47). The drug regimen of Mrs. Brown may present several adverse effects that should be observed, the nurse â€Å"monitor adverse effects and provide appropriate supportive care as needed to help patient cope with these effects† (Karch, 2006, p. 347). To achieve therapeutic effects, it is also important that the nurse is aware how to â€Å"administer the drug as prescribed in appropriate relationship to meals† (Karch, 2006, p. 572). The nurse should provide supportive management to the drug regimen so she should â€Å"monitor the patient's clinical status closely especially during the initial stages of treatment† (Karch, 2006, p. 34). This includes daily monitoring of serum lithium and phenytoin levels, blood glucose, prothrombin time (PT) and hepatic functioning. It is essen tial to promote compliance to the patient. The nurse should â€Å"provide thorough patient teaching, including drug name and prescribed dosage, as well as measures for avoidance of adverse effects, warning signs that may indicate possible problems and the need for monitoring and evaluation to enhance patient knowledge about drug therapy† (Karch, 2006, p. 347). Some of the teaching points that should be included are any sign of blood loss ( petechiae,bleeding gums, bruises, dark colored stools, dark colored urine) to evaluate the effectiveness of warfarin and symptoms of phenytoin toxicity, including drowsiness, visual disturbances, change in mental status, nausea, or ataxia. Indications and Actions The indications and actions of Mrs. Brown's regimen is presented to help verify the purpose of the drugs and their effects on the overall condition of the patient. Metronidazole (Flagyl, MetroGel, Noritate) Metronidazole is used for the treatment of intestinal amebiasis, trichomoniasis, inflammatory bowel disease, H. pylori infection causing peptic ulcers, bacterial vaginosis, and anaerobic infections and perioperative prophylaxis in colorectal surgery† (Kee & Hayes, 2006, p. 470). In this case, it is also used to treat abscesses in the pelvis caused by susceptible anaerobic bacteria. It is classified as â€Å"an antiprotozoal agent that acts to inhibit DNA synthesis in susceptible protozoa, leading it to unable to reproduce and subsequent cell death† (Karch, 2006,p. 169). Paracetamol (Acetaminophen) Acetaminophen is indicated for the treatment of pain and fever associated with a variety of conditions, including influenza; for the prophylaxis of children receiving diptheria-pertussis-tetanus (DPT) immunizations; and for the relief of musculoskeletal pain associated with arthritis† (Karch, 2006, p. 241). Paracetamol was prescribed for the presence of pain in the client's perineal area. Metformin (Glucophage) â€Å"Metformin is a biguanide compound used for the management of type 2 diabetes† (Kee & Hayes, 2006, p. 787). In this case, the patient was known to have diabetes. This medication could be considered as a new mechanism for the management of her type 2 diabetes. This oral diabetic agent â€Å"acts by decreasing hepatic production of glucose from stored glycogen† (Kee & Hayes, 2006, p. 787). It is said to diminish the increase in serum glucose after meals and lessen the degree of postprandial hyperglycemia. Phenytoin (Dilatin) â€Å"Phenytoin is the protoype hydantoin used in the treatment of tonic-clonic seizures and status epilepticus, as well as in the prevention and treatment of seizures after neurosurgery† (Karch, 2006, p. 342). Since the patient has a history of seizure disorder, this medication was prescribed for maintenance. It acts as â€Å"an anticonvulsant drug that works by suppressing sodium influx through the drug binding to the sodium channel when it is inactivated, thus prolonging the channel inactivation and thereby preventing neuron firing† (Kee & Hayes, 2006, p. 341). Warfarin ( Coumadin) â€Å"Warfarin (Coumadin) is an anticoagulant drug in oral form that is used to maintain a state of anticoagulation in situations in which the patient is susceptible to potentially dangerous clot formation† (Karch, 2006, p. 38). The patient was given this medication since she has a history of atrial fibrillation that makes her susceptible to thrombus and embolus formation. The drug Warfarin inhibits the formation of thrombus and embolus formation by decreasing certain clotting factors. â€Å"Warfarin causes a decrease in the production of vitamin K-dependent clotting factors (II [prothrombin], V II, IX and X) in the liver† (Karch, 2006, p. 740). Lithum Carbonate â€Å"Lithium is used as a mood stabilizers which is used to treat bipolar affective disorder† (Key & Hayes, 2006, p. 399). Mrs. Brown has a bipolar mood disorder so this drug was prescribed to control her periods of mania and depression. It is said to function in several ways, â€Å"it alters sodium transport in nerve and musle cells; inhibits the release of norepinephrine and dopamine, but not serotonin, from stimulated neurons; increases the intraneuronal stores of norepinephrine and dopamine slightly; and decreases intraneuronalcontent of second messengers† (Karch, 2006, p. 330). Common Drug Interactions Drug to Drug Interactions Metronidazole (Flagyl, MetroGel, Noritate) This drug is known to produce interactions with phenytoin, oral coagulants and lithium. â€Å"Coadministration with a nitromidazole may increase the serum concentration of phenytoin† (Drugs. com, 2010). It is known to induce microsomal liver enzyme activity such as phenytoin that may accelerate the elimination of metronidazole resulting in reduced plasma; impaired clearance of phenytoin has been reported† (DailyMed, 2009). In this case, pharmacologic responses and serum phenytoin should be checked frequently whenever metronidazole is being administered to the patient. The drug dosage should be adjusted as necessary. Another thing to do is to educate the patient the signs and symptoms of phenytoin toxicity for immediate physician notification. â€Å"Metronidazole has been reported to potentiate the anticoagulant effect of warfarin and other oral coumarin anticoagulants, resulting in a prolongation of prothrombin time† (DailyMed, 2009). Mrs. Brown should be advised to report any signs of bleeding to her physician. INR should be checked frequently for adjustments in warfarin dosage, specifically after starting or discontinuing metronidazole. And lastly, lithium is said to produce interactions when administered with metronidazole. â€Å"Concurrent use of metronidazole with lithium may provoke lithium toxicity due to reduced renal clearance† (Rxlist, 2010). Since Mrs. Brown has a bipolar mood disorder, lithium is a long drug regimen. The serum lithium and creatinine levels should be monitored after the initiation of metronidazole. Phenytoin (Dilantin) Besides the impaired clearance of phenytoin with the use of metronidazole, there are other drug interactions that can happen in reference to Mrs. Brown's drug regimen. It is said that Phenytoin can increase the effects of anticoagulants. â€Å"The hydantoins displace the anticoagulants and aspirin, causing more free drug and increasing their activity† (Kee & Hayes, 2006, p. 342). Still, it is important to check on the prothrombin time (PT), phenytoin level and prothrombin time of the patient during the administration of both drugs. â€Å"Signs of an active bleed include coughing up blood in the form of coffee grinds (hemoptysis), gum bleeding, nose bleeds, cola- or tea-colored urine (hematuria), and black, tarry stools (hemoccult positive)†. Brown should be observed and notified to the physician. It is also said that the use of phenytoin can lead to â€Å"increased hepatotoxicity with acetaminophen† (Karch, 2007, p. 952). Lithium interacting with Phenytoin â€Å"may either increase or decrease the effectiveness of lithium or increase or decrease the effectiveness of the drug† (Raber, 2010). Phenytoin level and lithium serum level should be checked frequently to monitor the effectiveness of these drugs. Warfarin (Coumadin). Aside from the drug interactions of warfarin to both Metronidazole and Phenytoin, there is an existing interaction between Metformin and Warfarin. It is said that Metformin â€Å"oral hypoglycemic drugs for diabetes can displace warfarin or dicumarol from the protein-bound site, causing more free-circulating anticoagulant† (Kee & Hayes, 2006, p. 663). Due to this possible interaction, it is important to monitor the blood glucose level and prothrombin time (PT). The patient should be informed of the signs and symptoms of hypoglycemia and bleeding so that she could report it to the health care team immediately. Warfarin also interacts with paracetamol (acetaminophen); it said that â€Å"some investigators advise that the hypothrombinemic response to warfarin can increase when acetaminophen is taken in a dosage of more than 2 g per day for longer than one week† (Ament, Bertolino & Liszewski, 2000). Since Mrs. Brown has a prescription of 1000mg to be taken four times a day, her dosage is more than 2g per day. â€Å"If acetaminophen therapy is needed, the dosage should be as low as possible, and the drug should be taken for only a short period. In addition, the INR should be monitored closely† (Ament et al. 2000). Metformin (Glucophage) Meformin has moderate drug interaction with the drug Phenytoin. It is said to diminish the efficacy of oral diabetic agents and insulin. â€Å"These drugs may interfere with blood glucose control because they can cause hyperglycemia, glucose intolerance, new-onset diabetes mellitus, and/or exacerbation of preexisting diabetes† (Drugs. com, 2010). There should be close monitoring of Mrs. Brown's blood glucose level in order to observe hypoglycemia in the patient. Lithium (Eskalith) Lithium has drug interactions with Metronidazole and Phenytoin. It is also established that lithium may diminish the therapeutic effects of insulin and oral anti-diabetic agents. â€Å"In one study, 10 psychiatric patients treated with lithium carbonate for 2 weeks demonstrated elevated blood glucose levels and impaired glucose tolerance tests. There have also been isolated case reports of hyperglycemia, impaired glucose tolerance, or diabetes mellitus in patients on lithium, although a causal relationship has not been established† (Drugs. com, 2010). The blood glucose level should be checked frequently after starting or discontinuing lithium therapy. Drug to Food, Drug to Herbal, Drug to OTC drugs Interactions Metronidazole Metronidazole has a significant interaction with ethanol. â€Å"Use of alcohol or products containing alcohol during nitroimidazole therapy may result in a disulfiram-like reaction in some patients† (Drugs. com, 2010). Necessary precautions should be made in relation to use of ethanol and ethanol-containing products. Mrs. Brown should be instructed not to take alcohol beverages and alcohol-containing products. It is said that â€Å"alcohol beverages should not be consumed for at least a day after completion of metronidazole therapy† (Drugs. om). Metronidazole has an interaction to the herb milk thistle. â€Å"Milk thistle has been reported to protect the liver from harm caused by some prescription drugs. While milk thistle has not yet been studied directly for protecting people against the known potentially liver-damaging actions of metronidazole, it is often used for this purpose† (Morazz oni & Bombardelli, 1995). Phenytoin Phenytoin has moderate interaction with alcohol and food. The effects of alcohol on the therapeutic level of Phenytoin depend on the duration of its consumption. â€Å"Acute consumption of alcohol may increase plasma phenytoin levels. Chronic consumption of alcohol may decrease plasma phenytoin levels† (Drugs. com, 2010). Phenytoin (oral drug) could be given with or without food in a consistent manner. Give with food if patient complains of GI upset ( Karch, 2007). The bioavailability of Phenytoin is said â€Å"to decrease to subtherapeutic levels when the suspension is given concomitantly with enteral feedings† (Drugs. com, 2010). Antacids containing calcium may decrease the blood level of phenytoin while aspirin (more than 1500 mg/dl) may increase the blood level of phenytoin (Epilepsy. om, 2010). Phenytoin also will lower the blood levels of other types of medication like acetaminophen (Epilepsy. com, 2010). Warfarin Patients taking Warfarin should not take Vitamin K-rich foods like â€Å"liver, broccoli, brussels sprouts, spinach, Swiss chard, coriander, collards, cabbage, and other green leafy vegetables† (Drugs. com). There are also particular medicines that should not be taken for they m ay cause serious bleeding problems in the stomach and intestines and alterations in blood clotting. These particular medicines are as follows: â€Å"acetaminophen (Tylenol), aspirin, and NSAIDs including celecoxib (Celebrex), diclofenac (Voltaren), ibuprofen (Motrin, Advil), indomethacin, naproxen (Aleve, Naprosyn),and others† (Drugs. com, 2010). It is also said that the patient should â€Å"avoid eating cranberries, drinking cranberry juice, or taking cranberry herbal products† (Drugs. com, 2010). Warfarin can interact with the following herbal products: â€Å"garlics, gingko biloba, ginseng or St. John's wort†. (Drugs. com, 2010). Metformin Drugs that can raise the blood sugar affecting the use of Metformin include medicines to treat colds and allergies while drugs that lower blood sugar include some nonsteroidal anti-inflammatory drugs (NSAIDs), aspirin, and sulfa drugs (Bactrim)† (Drugs. com, 2010). Alcohol should also not be taken concomitantly with this drug. â€Å"Alcohol lowers blood sugar and may increase the risk of lactic acidosis while taking this drug† (Drugs. com, 2010). There could be increased risk for hypoglycemia if the drug is taken with â€Å"juniper berries, ginseng, garlic, dandelion root and celery† (Karch, 2007, p. 58). Lithium Patients taking lithium carbonate should â€Å"avoid drinking large amounts of coffee, tea, or cola, which can cause dehydration through increased urination† (Drugs. com, 2010). Besides having interactions with other drugs in the patient's regimen, lithium also interacts with over-the-counter drugs. â€Å"If Eskalith is taken with certain other drugs, the effects of either could be increased, decreased, or altered such as nonsteroidal anti-inflammatory drugs† (Drugs. com, 2010). â€Å"Patients being treated with lithium should be encouraged not to use the herbal therapy psyllium. If combined with lithium, the absorption of the lithium may be blocked and the patient will not receive therapeutic level† (Karch, 2006, p. 333) Possible Adverse Reactions and Nursing Interventions Metronidazole â€Å"Convulsive seizures have been reported in patient treatment with metronidazole† (DailyMed, 2009). Necessary seizure precautions should be implemented. Mrs. Brown has a history of seizure; this is why the healthcare team should take necessary adjustments to the dosage of metronidazole. Aside from this major adverse reaction, the patient can develop â€Å"unpleasant metalic taste, nausea, vomiting and diarrhea† (Karch, 2007, p. 86). Nursing care for strange metallic taste should be â€Å"frequent mouth care, sucking sugarless candies†, and for nausea, vomiting and diarrhea, the patient should be advised to â€Å"eat frequent small meals† (Karch, 2007, p. 786). In the case of Mrs. Brown, complains of discomfort in her buttocks, pain in per ineal area and offensive odor could mean that she developed cadidiasis as â€Å"known or previously unrecognized candidiasis may present more prominent symptoms during therapy with metronidazole† (DailyMed, 2009). Treatment with candidicidal agent should be instituted to the patient. Other adverse effect can be â€Å"disulfiram-like interaction with alcohol† (Karch, 2007, p. 786). The patient should be always reminded of precautions on ingesting alcohol and alcohol-containing products. Phenytoin â€Å"Nausea,vomiting, diarrhea, constipation and gingival hyperplasia† (Karch, 2009, p. 951) could be present in patients taking Phenytoin. The nurse should â€Å"arrange instruction in proper hygiene technique for long-term patients to prevent development of gum hyperplasia†, â€Å"take drug with food, eat frequent small meals† (Karch, 2007, p. 953). Among the other common adverse effects are â€Å"dizziness ,drowsiness, confusion and headache†. The patient should be advised to â€Å"avoid performing tasks requiring alertness and visual acuity† (Karch, 2007, p. 953). Warfarin The common adverse effects of Warfarin are â€Å"nausea, vomiting, abdominal cramping, diarrhea and hemorrhage† (Karch, 2007,p. 1216). Nurse should advise the patient to â€Å"avoid any situations in which she could be easily injured. † Necessary care should be provided to avoid bleeding in the patient like â€Å"not giving any IM injections† (Karch, 2007, p. 1217). The patient should also be asked to â€Å"report unusual bleeding (from brushing teeth, excessive bruising), black or bloody stools, cloudy or dark urine† (Karch, 2007, p. 1218). Metformin The most significant possible adverse effects of this drug are â€Å"hypoglycemia and lactic acidosis† (Karch, 2007, p. 758). The nurse should â€Å"monitor blood for glucose and ketones† or â€Å"should ask the client any sign of hypo- or hyperglycemic reactions† (Karch, 2007, p. 758). There could also be â€Å"signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat† (Drugs. om, 2010). In this case, it is necessary to â€Å"stop the medication and report to the physician† (Drugs. com, 2010). Lithium The common side effects of Lithium involves CNS manifestions such as â€Å"lethargy, slurred speech, muscle weakness and fine hand tremor; GI manifestions such as nausea, vomiting , diarrhea, thirst; GU effect is polyuria† (Karch, 2007, p. 704). It is important to instruct the client to â€Å"report any signs of toxicity such as diarrhea, vomiting, tremor, drowsiness, muscle weakness† (Karch, 2007, p. 705). The patient should also be prohibited or â€Å"avoid driving or performing tasks requiring alertness† and should be instructed to â€Å"eat frequent small meals† (Karch, 2007, p. 705). Health Education Metronidazole It is impotant to instruct the client to â€Å"not drink alcohol (beverages or preparations containing alcohol, cough syrups)† (Karch, 2007, p. 786). The nurse should also mention to the client that she may experience â€Å"urine with darker color , dry mouth with strange metallic taste, nausea, vomiting and diarrhea† (Karch, 2007, p. 786). Intervention to relieve these side effects should be taught like â€Å"frequent mouth care, sucking sugarless candies for dry mouth; eating frequent small meals for nausea, vomiting and diarrhea† (Karch, 2007, p. 786). Phenytoin Patients taking Phenytoin should be advised to â€Å"take this drug exactly as prescribed with food to reduce GI upset or without food — but maintain the consistency† (Karch, 2007, p. 953). Mrs. Brown should be advised to â€Å"not discontinue this drug abruptly or change dosage, except on advice of health care provider† (Karch, 2007,p. 953). Since Mrs. Brown has diabetes, it should be advised that she should â€Å"monitor blood or urine sugar regularly, and report any abnormality to health care provider† (Karch, 2007, p. 953). She should be advised that she should â€Å"maintain good oral hygiene to prevent gum disease and arrange frequent dental checkups† (Karch, 2007, p. 953). Warfarin It should be advised to the patient to â€Å"not start or stop taking any medication without consulting her health care provider† (Karch, 2007, p. 1217). She should â€Å"carry or wear a medical ID tag to alert emergency medical personnel about the drug† (Karch, 2007, p. 218). She should be instructed to â€Å"avoid situations that may cause injury and have periodic blood tests to check on drug action† (Karch, 2007, p. 1218). Lastly, the patient should be instructed to â€Å"report unusual bleeding, black or bloody stools and cloudy or dark urine† (Karch, 2007, p. 1218). Metformin Some of the instructions t hat should be given to the patient are â€Å"not to discontinue the medication without consulting health care provider and avoid using alcohol while taking the drug† (Karch, 2007, p. 758). She should also be advised to â€Å"monitor blood for glucose and ketones and report any hypo-or hyperglycemia reactions† (Karch, 2007, p. 758). Lithium Health teaching about this drug should include the following: â€Å"take the drug exactly as prescribed, after meals or with food or milk; eat a normal diet with normal salt intake and maintain adequate fluid intake and arrange for frequent checkups including blood tests† (Karch, 2007, p. 705). Mrs. Brown has numerous risk factors and health conditions that may produce drug interactions that may worsen her health. It is known that Metronidazole can produce seizures as its side effect. Considering this, safety precautions should be made since she has a history of seizure. This drug can also impair the clearance of the drug Phenytoin in her system and potentiate the anticoagulant effects of Warfarin. These things should be monitored by the healthcare team for them to make necessary adjustments. Phenytoin can also increase the anticoagulant effect of Warfarin and may either increase or decrease the efficacy of lithium. Necessary drug dosage adjustments should be made to minimize these interactions. Daily blood glucose monitoring should be done and symptoms of hypo- or hyperglycemia should be reported. This is necessary because Warfarin can increase the effects of oral diabetic agents such as Metformin. However, Phenytoin and Lithium can diminish the efficacy of this drug. Thus, it is really important to monitor the client's clinical status and the possible adverse effects of the drug regimen. It is also important to â€Å"offer support and encouragement to help the patient cope with the drug regimen† (Karch, 2006, p. 334).