Coley’s Toxins Essay Example

Coley’s Toxins Essay Coley’s Toxins Name: Course: Date: We will write a custom essay sample on Coley’s Toxins specifically for you for only $16.38 $13.9/page Order now We will write a custom essay sample on Coley’s Toxins specifically for you FOR ONLY $16.38 $13.9/page Hire Writer We will write a custom essay sample on Coley’s Toxins specifically for you FOR ONLY $16.38 $13.9/page Hire Writer Coley’s Toxins Coley’s Toxins are the invention of William B. Coley, a bone surgeon at a cancer hospital in New York, who developed a vaccine that he used in cancer treatment after he witnessed a patient of his succumb to sarcoma. The development of the vaccine, Coley’s Toxins, is well mapped out as well as its effectiveness in treating some of the cases that Coley and others handled (Nauts, 1953). The effectiveness of his treatments was critiqued by his peers. The advancement of other methods of cancer treatment like radiotherapy and subsequently chemotherapy continued to undermine the relevance of Coley’s Toxins. The outcome of Coley’s life work is the motivation it inspired to further research in the field of cancer immunotherapy. Born in 1862, William B. Coley attended college at Yale before being admitted into Harvard Medical School in 1888. He was drawn into cancer treatment by a patient that was referred to him, Bessie Dashiell, who was suffering from bone cancer and eventually succumbed to it despite radical surgery. He trudged through hospital records trying to find cases that had different outcomes to his patient’s case and came across a case study of a patient Fred Stein. This German immigrant’s tumor disappeared after the fever from an erysipelas infection caused by the bacteria Streptococcus pyrogens. His interest sparked, Coley found this patient and verified that his cancer had gone into remission. Coley knew that anecdotal theories that connected tumor remission with concurrent bacterial infections existed in antiquity. The renowned Egyptian physician Imhotep recommended the treatment of tumors (swellings) as the application of a cataplasm followed by an incision (Ebbell, 1937). Diedier reported in 1725 that patients suffering from syphilis developed few tumors, if any (Diedier, 1725). Sir James also mentioned the same (Hobohm, 2001). Coley did further research and stumbled into other medical pioneers such as Koch and Pastuer, who had made similar observations. He was convinced of this line of thought and decided to act on it. In 1891, Coley made the courageous move to infect his patients intentionally with live Streptococcus pyrogens bacteria. The first patient to receive this treatment had throat cancer, and the erysipelas infection improved his condition. His findings related to similar ones made by a German physician W. Busch (Busch, 1867). The patient lived for additional eight and a half years without any further recurrence of metastases. Bolstered by his outcome, Coley continued to infect a further nine of his patients with erysipelas. He noted that the results were either an active immune response to the infection or a fatality due to the infection. History is replete with examples of spontaneous regression of tumors after fever inducing infections. One such example is Peregrine Laziosi (1265-1345), the canon saint of cancer patients. He has a tumor on his tibia that was diagnosed malignant by the best physicians of his time (Pack, 1967). Just before his leg was amputated, the only option available to him, the lesion grew and broke through his skin becoming severely infected. This infection coincided with the spontaneous regression of the cancerous tumor. Such cases reported in literature (Coley, 1893) served to bolster Coley’s research and strengthened his belief in the methods he used, coupled with own findings (Coley, 1906). Coley’s assessment of the responses was that the live Streptococcus bacteria produced erysipelas but, unfortunately, not on all the patients given the treatment. In some, the administration of the bacteria gave no response due to the patient forming immunity to the bacteria. In other instances, the patient would succumb to the bacterial infection because of his or her own immune system inadequacies (Coley, 1896). His second attempt involved the use of heat sterilized Steptococcus bacteria. The reason is that Coley needed to find a way to control the virulence of the bacteria Streptococcus pyrogens while still maintaining its purpose which was to produce a fever inducing infection but it did not provide the expected results. He combined the use of the sterilized streptococcal bacteria with a second organism, Serratia marcescens, and this concoction is known as Coley’s Toxins. This proved successful in cancer treatment and documented the cases he had treated using this approach (Coley, 1914). Coley injected his preparation directly into the tumor or in the surrounding area in several doses. These treatment courses would last even for weeks but the outcome was positive. For years to come, physicians used Coley’s Toxins to treat inoperable cases with high success rates. A compiled review to these cases was published by Coley’s daughter, Helen Coley Nauts, where 896 cases were documented (Nauts, 1982). In spite of Coley’s success rates and high profile as a bone surgeon, he came under great criticism due to various inconsistencies. These included, poorly-documented follow up that was also not well control casting doubts on the supposed success of these treatments; the number of different preparations of Coley’s Toxins and their associated efficiencies; the mode of administration varied from intravenous injections to injections directly in the tumor (McCarthy, 2006). This meant that not every doctor got the same results as Coley did. The Journal of the American Medical Association (JAMA) issued a stern review of Coley’s Toxins. It held the view that the toxin was a complete failure as a remedy for sarcomas and carcinomas based on the toxins’ failure to produce satisfactory results when used by various oncologists. It disputed Coley’s reported findings ignoring the reports submitted by other physicians using the same regimen on their patients and showing favorable results (JAMA, 1894). Cancer treatment was not a clearly understood process in the turn of the century, and naturally, some practitioners favored certain modes of treatment to others. Coley’s Toxins were not one of the better-understood treatments available. Furthermore, advances made in radiation therapy provided a better alternative since it was a more predictable regimen. The mode of action of Coley’s Toxins was not, and still is not well understood. This served to marginalize Coley’s Toxins even further despite the fact that some doctors were able to report the successful use of this regimen. Coley’s Toxins faced further resistance after the establishment of the Bone Sarcoma Registry whose role was to standardize bone cancer therapeutics (McCarthy, 1995). It proved difficult to have some of Coley’s cases accepted by the registry because members of the registry believed that the toxins did not work or claimed that some of the successful cases were misdiagnosed. His work slowly fell out of favor, and the Park Davis Company halted production of Coley’s Toxins. By 1962, the U.S. Food and Drug Administration had accredited Coley’s Toxins as a â€Å"new drug† meaning it could no longer be used in cancer treatment (Hoption, 2003). Although Coley’s ideas were no longer acceptable by most doctors to treat cancer, he continued to believe in his methods until the end of his career. Some doctors were willing to welcome the notion that the toxins may be beneficial after all. In fact, in 1934, JAMA changed its position and acceded that Coley’s Toxins might be valuable. It praised the ingenuity of the combined erysipelas and prodigious toxins (Coley’s Toxins) and retained them in New and Unofficial Remedies with an aim of promoting more research on the toxins (JAMA, 1934). Additional acceptance of Coley’s research and treatment methods was brought about by his own children. Bradley Coley, an orthopaedic surgeon, succeeded Coley as the head of the Bone Tumor Service at his father’s former residency at Memorial Hospital in New York (now Memorial Sloan Kettering Cancer Center). Bradley published a textbook on bone tumors and reinforced Coley’s Toxins use as auxiliary treatment to prevent micro-metastasis (Coley, 1949). Helen Coley Nauts, a cancer researcher, dedicated her life to studying her father’s work, documenting his cases and publishing them (Coley-Nauts, 1990) The mechanism of action of Coley’s Toxins has generated great interest leading to research with the aim of identifying the â€Å"active† ingredient of the toxins and their role in cancer regression. The increased understanding of the factors involved in an immune response led to suggestions that cytokines like tumor necrosis factor (TNF), interleukins (IL) and interferons played a significant role (Old, 1988; Oettgen,1990; Nethersell,1990). This, supported by the observations, made after treatment of superficial bladder cancer by bacillus Calmette-Guerin (BCG), a bacterial vaccine used in conventional therapy (Hoption, 2003). A random clinical trial carried out in the late 1980s proposes the mode of action of Coley’s Toxins in the following way: interferons induce augmentation of natural killer cell activity, stimulation of lymphoid tissues, induction of serum factor that causes necrosis of tumors, activation of macrophages, as well as stimulation of interleukin-2. (Tang et al., 1991) Interleukin II, or IL-2, is a well-known conventional immunotherapy and Bacillus Calmette Guerin (BCG), another vaccine, is used in conventional immunotherapy for bladder cancers. (Zlotta et al., 1998). Some proposals of the immune response elicited by the administration of Coley’s Toxins are that the cell-mediated immune (adaptive) response is the key moderator of cancer regression (Lucey, 1996) although animal studies involved infections that evoke a humoral immune response: aspergillus (Tzankov, 2001), malaria (Nauts, 1980), trichella (Molinari, 1979), and trypanosome (Cabral,2000). Besides, tumor regression occurred within a few hours of injection with Coley’s Toxins while adaptive immune response takes a few days to a week (Medzhitov, 2001). This supports the theory that the immune response elicited in the non-specific innate immune response. Because of the immune stimulating nature, treatment with Coley’s Toxins induces other conventional regimens that cannot be used simultaneously. Radiotherapy and chemotherapy suppress the immune system, killing the cancerous cells in the process. Coley’s Toxins, on the other hand, trigger an immune response with the macrophages destroying the cancer. An increased vivacity of the immune system and enhancement of lymphocyte activity due to the biologically active lipopolysaccharide result in the high fevers, typical of Coley’s Toxins therapy. Tests conducted on mice showed that mixed bacterial toxins caused regression of tumors with 15% or less lethal effects compared to the use of purified lipopolysaccharide (Havas, 1990). Non-immune mechanisms have been postulated to be responsible for the mechanism of action of Coley’s Toxins. This has been documented by Helen Coley Nauts as being derived from bacterial enzymes like streptokinase (Nauts, 1953). This theory was further developed, and streptokinase was proposed to act as a bacterial plasminogen to activate the host’s plasminogen. Plasminogen is then converted to the potent enzyme plasmin to initiate protease precipitation reactions capable of breaking down various plasma proteins (Zacharski, 2002; Zacharski, 2005). The efficacy of Coley’s Toxins is not a blanket treatment as evidenced by the various success and failure cases. It is believed or even extrapolated from a study of the cases documented that different types of cancers respond differently to this mode of treatment. The most successful cases have stemmed from the regimen being administered to patients suffering from sarcomas compared to carcinomas. The difference between a carcinoma and a sarcoma is the tissue showing malignancy. Tissue types of mesenchymal origin like bone, muscular, cartilaginous or adipose tissue, are considered to be sarcomas if they form malignant tumors while those of epithelial cells, such as colon and lung, are carcinomas. The possibility of toxicity of Coley’s Toxins means that doses should be adjusted and care given to support such patients. This treatment is patient specific but not to be recommended to all, but at the doctor’s own discretion. Some instances require special mention: patients with severe hepatic insufficiency, patients with severe cardiac conditions, or patients near death since the regimen will not help them (Nauts, 1975). The finished product needs to be tested using modern methods to assay the lipopolysaccharide and exotoxins presence and levels. Since it is evident that tumors secrete proteins that can stimulate an immune response, it is imperative that ways isolate the tumor-reactive T-cells from the tumor-bearing host. Attempts are made to up-regulate the chances of an immune response by modifying tumor cell to exhibit immunoregulatory proteins such as cytokines, interferons, streptokinase, and tumor necrosis factor (TNF) (Chang, 1996). These advancements in the understanding of immunobiology in relation to cancer are stimulating research into vaccines for treatment in different types of cancer, specifically colon cancer and melanoma (Chamberlain, 2004) The American Cancer Society’s Guide to Complementary Alternative Cancer Methods attests, â€Å"Scientific evidence suggests Coley toxins or the mixed bacterial vaccine (MBV) may have a therapeutic role in the treatment of cancer, in a combined treatment approach.† (American Cancer Society, 2000). This is followed by the disclaimer that much has been learned about the science of immunology and practice of immunotherapy since Coley’s time and that modern immunotherapy is likely to be of greater value. The toxins are used outside the United States, for example, a Canadian company MBVax Bioscience produces Coley’s Fluid for use in clinical trials and research purposes. The biotech company Coley Pharmaceutical Group is involved in research on the DNA sequences that enable Coley’s Toxins to be efficient in producing regression of certain types of cancers. In addition, laws in Germany permit physicians to use any therapy he or she considers most appropriate in light of the patient’s medical condition and their medical knowledge. By 2006, there had been thirty human studies conducted and published in peer-reviewed literature databases but only two articles were relevant to Coley’s Toxins (Zacharski, 2005; McCarthy, 2006). Case studies involving this cancer-treating regimen have been well documented by Helen Coley Nauts and proved the success rate of her father’s treatment. Still, these cases are not usually cited by modern researches due to the advancement in modern clinical trials methods. The procedures followed now are more rigid and require adequate and consistent follow-up of patients, something Coley’s reports did poorly or lacked entirely. All this cancer research requires large amounts of resources, and the National Cancer Institute is the main agency that coordinates the national cancer research program. It is also responsible for disbursing funds received from Congress, federal agencies, voluntary organizations private institutions and corporations. Coley’s first patient Bessie Dashiell was reportedly John. D. Rockefeller Jr.’s childhood friend, and her death stimulated his contribution to cancer research funding. Pharmaceutical companies such as Pfizer are involved in research in the hopes of developing their own drugs and vaccines. The use of Coley’s Toxins has brought to light the significance played by fever-inducing infections (Hoption, 2003). The modern use of antibiotics has suppressed the natural immune mechanisms resulting from evolution, and antipyretic use to manage fever has resulted in the neglect of the significance of fever as the body’s response to an infection. The onset of fever usually accompanies multifarious physiological changes, namely increase in metabolic rates which facilitates leukocyte proliferation, maturation, and activation (Aubert, 1999; Hasday, 2000). Historically, fevers were considered important and even encouraged. Perhaps, a return to these previously held practices may help boost our weakened immune systems, which in turn would fight some of the incurable diseases faced by mankind today (Hoption, 2003). Coley’s Toxins have a place in the future despite being designated â€Å"new drug† status by the U.S. Food and Drug Administration. The successful use of this regimen by Coley and other physicians during his time proves that it is a useful area of research. This widely documented method of treating spontaneously occurring tumors has been instrumental in instigating further investigation into the significance of the role of the innate immune response to cancerous tumors. Modern cancer treatments repress the immune system. Although they are the conventional modes of therapy, they do not provide a definite cure. The nature of Coley’s work, his dedication, and the extensive case studies documented on the use of the toxins have granted him the epithet â€Å"Father of Immunotherapy†. Although he did not discover a new therapeutic method, his research and creation of Coley’s Toxins were not only useful to his patients but stimulated a change in the way that the immune system is viewed. His life’s work brought to light the role immunotherapy can have not only for managing cancer but also for curing it. Using the methods of study including but not limited to extensive clinical studies, the principles of Coley’s Toxins can be established with respect to the exhaustive human data in existence. Resurgence in interest, in Coley’s Toxins and the mechanism of action, may seem like retrogression in the field of cancer research. Clearly, Coley was a man before his time in terms of finding innovative to tack an ancient scourge that has plagued humanity with more severity in recent times. The slow progression of orthodox cancer therapy has lent a closer look into the medical past to chart the way forward (Hoption, 2003). References American Cancer Society, (2000). American Cancer Society’s Guide to Complementary Alternative Cancer Methods, 366-67. Aubert A., (1999). Sickness and behaviour in animals: a motivational perspective. Neuroscience and Biobehavioural Review, 23, 1029–1036. Busch W., (1867). â€Å"Aus dersitzung der medicinichen†. Berliner Klinische Wochenschrift 5: 137 Cabral HR., (2000). The tumoricidal effect of Trypanosoma cruzi: its intracellular cycle and the immune response of the host. Medical Hypotheses, 54, 1–6. Chamberlain RS, Kaufman H., (2000). Innovations and strategies for the development of anticancer vaccines. Expert Opinion Pharmacotherapy, 1(4), 603–614. Chang AE, Shu S., (1996). Current status of adoptive immunotherapy of cancer. Critical Review in Oncology/Hematology. 1996;22:213–228. Coley B.L., (1949). Neoplasms of bone. Medical Book Department of Harper Brothers, New York, 565–570. Coley W.B., (1906). Late results of the treatment of inoperable sarcoma by the mixed toxins of Coley W.B., (1893). The treatment of malignant tumors by repeated inoculations of erysipelas: with a report of ten original cases. American Journal of Medical Science. May; 105, 487–511 Coley W.B., (1896). Further observations upon the treatment of malignant tumors with the toxins of erysipelas and Bacillus prodigiosus with a report of 160 cases. John Hopkins Hospital Bulletin. 7, 175 Coley W.B., (1914). The treatment of malignant inoperable tumors with the mixed toxins of erysipelas and bacillus prodigiosus. Brussels: M Weissenbruch. Coley-Nauts H, McLaren J.R., (1990). Coley Toxins – The First Century. Advanced Expanded Medical Biology, 267, 483 Deidier A., (1725). Dissertation medicinal et Chirurgical sur les Tumeurs. Paris. Ebbell B., (1937). The Papyrus Ebers: the greatest Egyptian medical document. London. Oxford University Press. Erysipelas and bacillus prodigiosus. American Journal of Medical Science, 131, 375–430. Erysipelas and Prodigiosus Toxins (Coley) JAMA. (1934). Oct 6, 103(14), 1067–1069. Editorial. Falcone R. Adjuvant, (1994). Vaccine Therapies: The Complete Guide to Alternative Cancer Therapies: What You Need to Know to Make an Informed Choice. 166-169. Hasday JD, Fairchild KD, Shanholtz C., (2000). The role of fever in the infected host. Microbes and Infection, 2, 1891–1904. Havas H.F,, Schiffman G., Bushnell B., Dellaria M., Axelrod R.S., Shanahan T., et al., (1990). The effect of bacterial vaccine on tumors and immune response of ICR/Ha mice. Journal of Biological Response Modifiers. 9, 194-204 Hobohm U., (2001). Fever and cancer in perspective. Cancer Immunology, Immunotherapy, 50, 391–396 Hoption-Cann S.A., van Netten J.P., et al., (2003). Dr William Coley and tumor regression: A place in history or in the future. Postgraduate Medical Journal, 79(938), 672–680. Lucey D.R, Clerici M., Shearer G.M., (1996). Type 1 and type 2 cytokine dysregulation in human infectious, neoplastic, and inflammatory diseases. Clinical Microbiology Review, 9, 532–562. McCarthy E.F., (2006). The toxins of William B. Coley and the treatment of bone and soft- tissue sarcomas. Iowa Orthopaedic Journal, 26, 154-158 McCarthy E.F., (1995). The Registry of Bone Sarcoma: A History. Iowa Orthopaedic Journal.15:74–78. Medzhitov R., (2001). Toll-like receptors and innate immunity. National Review of Immunology, 1, 135–45. Molinari J.A., Carrick L. Jr, Lubiniecki A.S., (1979). Influence of Trichinella spiralis infection on development of sarcoma-180 ascites tumors. Tropenmed Parasitol, 30, 429–433. Nauts H.C., (1975). Beneficial effects of immunotherapy (bacterial toxins) on sarcoma of the soft tissues, other than lymphosarcoma: end results in 186 determinate cases with microscopic confirmation of diagnosis, 49 operable, 137 inoperable. Cancer Research Institute, Inc. Monograph #16. Nauts H.C., Fowler G.A., Bogatko F.H., (1953). A review of the influence of bacterial infection and of bacterial products (Coley’s toxins) on malignant tumors in man. Acta Medica Scandinavica. 145 (Supplementary 276) Nauts H.C., (1982). Bacterial products in the treatment of cancer: Past, present and future. International Colloquium on Bacteriology and Cancer. Pack G.T., (1967) St Peregrine, OSM—the patron saint of cancer patients. CA: A Cancer Journal for Clinicians, 17, 83-84 Tang Z.Y., Zhou H.Y., Zhao G., Chai L.M., Zhou M., Lu J.Z., et al., (1991). Preliminary result of mixed bacterial vaccine as adjuvant treatment of hepatocellular carcinoma. Medical Oncology Tumor Pharmacotherapy, 8, 23- 28 Tzankov A., Ludescher C., Duba H.C., et al., (2001). Spontaneous remission in a secondary acute myelogenous leukaemia following invasive pulmonary aspergillosis. Ann Hematology, 80, 423–425. Zacharski L.R., Ornstein D.L., Gabazza E.C., D’Alessandro-Gabazza C.N., Brugarolas A., Schneider J., (2002). Treatment of malignancy by activation of the plasminogen system. Seminar of Thrombosis and Hemostasis, 28, 5-17. Zacharski L.R., Sukhatme V.P., (2005). Coley’s toxin revisited: Immunotherapy or plasminogen activator therapy of cancer? Journal of Thrombosis and Haemostasis. 3. 424-427. 1-103. Zlotta A.R., Drowart A., Van Vooren J.P., et al., (1998). Superficial bladder tumors and increased reactivity against mycobacterial antigens before Bacillus Calmette-Guerin therapy. Journal of Urology, 159(6), 1885-91

Steroids in Baseball

Steroids in Baseball Something that has a dominate force in American and International sports for the past 10 years has been one thing, Steroids. Steroids are in the news now more than ever due to one man, Barry Bonds. Barry is now 9 home runs away from tieing The Babe for second on the all time list to only Hank Aaron. All of the major sports have implemented stricter drug testing programs in hopes of slowing down the use of steroids. However, these drug tests are out dated and do not test for every kind of steroid or HGH (Human Growth Hormone). These tests are more expensive and require a blood sample instead of urin. Steroids are destroying sports as we know it, there is wide spread doubt in major league baseball if a player has a breakout year or is now not as great a player as they were a few years ago.English: Barry Bonds in actionSteroids are chemicals that act like hormones. Anabolic steroids are the ones that are abused to build muscle mass or to make your workout longer and recovery time less. They are chemicals of artificial testosterone, which is a male hormone. With higher testosterone you can have more physique, less body hair, and a deeper voice. Why take steroids if you already know that it is not good for you? Most of the steroid users are injecting for better performance and strength for their sports, but, other users are simply juicing to build more muscle mass or to look better, physically. This reminds us of another LEGAL drug, ciggerettes.Inside their bodies they are actually ruining themselves. Taking steroids is a big threat to your health. You could have severe acne, genital changes, water retention, and yellowing eyes and skin. Its not only your appearance that could be at...

Electronic Monitoring System Implementation Case Study

Electronic Monitoring System Implementation - Case Study Example I have been appointed as the consultant and my responsibility is to carry out a research-oriented study for management Board of an organization, for the implementation of the electronic monitoring system for the better management and handling of the employee’s activities and daily tasks on the job. This report will provide a deep insight into the overall organizational implementation new electronic monitoring system. Companies desire to be persuading their personnel are carrying out a first-class job; on the other hand, employees don't desire their every trip or sneeze to the water-cooler logged. That's the fundamental conflict or clash of office observation (Workplace? 2009). Up-to-date technologies put together it feasible for organizations to view numerous activities of their worker’s occupation, predominantly on computer terminals, telephones in the course of voice mail, electronic as well as when workers are making use of the Internet. This sort of monitoring is practically unregulated. As a result, except business strategy purposely position otherwise, our company can listen, observe as well as read the majority of our place of work communications (Workplace? 2009). From the perspective of workers, electronic monitoring through companies engages considerable isolation distress. Electronic monitoring allows an organization to check what staff is performing on the duty as well as investigation of worker communications, encompassing Internet activity and e-mail, frequently confining as well as evaluation of communications that workers judge privately. Since electronic monitoring as well comprises utilize of computer forensics, a comparatively innovative discipline as well as a significant progression in the wider areas of computer evidence and electronic monitoring (King, 2009). There are numerous business reasons for organizations to electronically monitor employees in the place of work encompassing the judgment of employee’s effectiveness, defending organization’s property from mistreatment, as well as making sure and fulfilment through the place of work  strategies.

Mummers Parade Essay Example | Topics and Well Written Essays - 2500 words

Mummers Parade - Essay Example Historians believe that Mummers Parade is the only tradition that has lasted for a long time running fork festival in the United States. The parade usually consists of thousands of performers who spend months developing and rehearsing so that it will be enjoyable. They build costumes and scenery and make the parade to be perfect preparing for entire day moving their way up Broad Street where day drinking marks the event. For those who do not go for the parade choose to keep drinking the whole night and in the morning while others use the New Year Eve to move to other countries for leisure. People usually come to the parade by train, bike and others on foot carrying glasses and thermoses of beer so that they can wear their costumes which will depict foreign cultures. Some people who do not like to be associated with racism do not let their children to go to the parade since they say that the parade is a racist tradition that is usually carried from one generation to the next despite t he parade being banned. The participant of the parade dress like a person or a thing that they are not, where they colour themselves and others depicts creatures which are colourful though they are white men they present simplistic cartoons which depicts foreign people and their culture showing that the parade is usually prepared to mark racist agendas in each and every year. During the 18th and 19th century   the slaves who were transported to United States and later employed in the plantation used to play instruments in the plantations.

West Meets East an Exchange of Royal Letters Essay

West Meets East an Exchange of Royal Letters - Essay Example In his letter, King Louis seems to be interested in personal achievements rather than the general good of France citizens. Motivation to him appears to originate from the concept of punishing sinners and not propagating his religion, as stated in his letter to the King of Tonkin (Spielgovel 431). On the contrary, the King of Tonkin recognized the virtue of fidelity as held by King Louis as well as emphasizing the importance of justice. In his perspective, King of Tonkin notably believes that fidelity and justice would not produce worthy results. The King of Tonkin upholds the custom of his kingdom rather than that of private friendship. He also seems not to have belief and trust in King Louis following the long war that had persisted for several years between the two nations. However, the sense of sincerity from King Louis constitutes the source of his motivation. In addition, the feelings of justice and fidelity also motivate the King of Tonkin (Spielgovel 431). In writing to King o f Tonkin, King Louis had a wooing voice towards capturing the consideration by the King on accepting his request to propagate his religion. In the letter, the voice and language used presents numerous praises with the motive of irony. This would be evidenced by the use of certain praise words that seem to portray an opposite meaning to the King of Tonkin to what he really intends. King Louis also advocates a motive of expanding his personal ambitions and territory of operation. Furthermore, in the letter, King Louis gives reference to his subjects who once received protection under the Realm of the King of Tonkin. This inclusion of the protection accorded to his subjects indicates a point of reference by him in convincing the King of Tonkin to accept his request (Spielgovel 431). The letter by King Louis reveals certain personality traits about him. He does not exist as a theologian but instead uses the virtue of religion in seeking to achieve his personal associations. Also, he rem ains to be an eminent figure in France’s history during the western civilization period. Moreover, King Louis practices an authoritarian leadership style. This becomes evident in his letter when he informs the King of Tonkin about his commands for the Royal Company and Messrs to establish itself in Tonkin soonest possible. In presenting the gifts to the King of Tonkin, the language used in writing does not reflect the willing and free choice of giving, but rather a command. This, thus, portrays a sense of customary formality in his way of appreciation through gifts and not a heartfelt appreciation. King Louis may be a hypocrite in the sense that he pretends to have moral virtues and opinions that he does not actually have. The idea of Christian missionaries reveals this personality in him (Spielgovel 431). In his response to King Louis, the King of Tonkin refused to accept Christian missionaries in his kingdom. He justified his position by asserting that some authorities or e dicts had already introduced a custom that forbids Christian missionaries. In addition, the King of Tonkin justifies his position by way of asking a straight forward question indicating that he could disregard a well-established custom in satisfying private friendship.

GHR Gene Variant Influence on Craniofacial Morphology

GHR Gene Variant Influence on Craniofacial Morphology â€Å"I526L† Growth hormone receptor gene variant and its effect on craniofacial morphology. Abstract OBJECTIVES: To investigate the influence of GHR (Growth Hormone Receptor) gene variant (I526L) on craniofacial morphology. SETTING AND SAMPLE POPULATION: The department of orthodontics, D.A.P.M.R.V.Dental College and Hospital, Bangalore, India. 30 randomly selected subjects, aged 20-30 years who were patients at D.A.P.M.R.V.Dental College Hospital, Bangalore. MATERIALS AND METHODS: DNA was extracted from venous blood samples of all the subjects. The extracted DNA samples were subjected to polymerase chain reaction, where amplification of the selected gene segments was done and later these amplified products were subjected to restriction fragment length polymorphism using HpyCH4V restriction enzyme. Results were documented in specific bands with gel documentation centre. The effects of the gene variant on the 4 craniofacial morphologic parameters of anterior cranial base length, maxillary length, mandibular ramus length/height and mandibular length were obtained from lateral cephalograms and tabulated. Appropriate statistical analysis was carried out. RESULTS: The results indicated that the subjects with I526L variant of GHR gene had a significantly greater mandibular ramus height. GHR gene variant I526L could be a genetic marker for mandibular ramus height. KEY WORDS: Craniofacial morphologic parameters, Growth hormone receptor, Polymerase chain reaction, Restriction fragment length polymorphism. CLINICAL RELEVANCE: The key to the determination of the etiology of malocclusion, and its treatability lies in the ability to differentiate the effect of genes and environment on the craniofacial skeleton in a particular individual. There are numerous ways in which the variant I526L could affect GHR activity. In addition to potentially causing direct changes in protein function, the variants could affect regulation of GHR, and in either case the variant could act singly or in combination with other single nucleotide polymorphisms (SNPs). The effect of these SNPs on GHR function and downstream gene expression should be clarified by further study. A study of gene polymorphisms in GHR would be useful in understanding genetic influences on craniofacial morphological determinants and helps in diagnosis and treatment in orthodontics to be delivered at a molecular level. INTRODUCTION: Growth hormone (GH) is a craniofacial morphologic determinant. Genetic influences are important in the determination of mandibular morphology, and growth hormone receptor (GHR) is believed to have an important influence on the growth of craniofacial bones. Responses to systemic GH therapy are time and site dependent in the craniofacial region, increasing growth, particularly in mandibular ramus. The growth hormone receptor gene is located on chromosome 5p13.1-p12 and is 87 Kb long, with 10 exons encoding 620 amino acids .1 Cartilage-mediated growth in the mandibular condyle is known to play an important role in the determination of growth and morphology of the mandible. GH treatment accelerates craniofacial growth, especially in the mandibular condyle where cartilage-mediated growth occurs. GH receptors have been shown to be present in the mandibular condyle.2 A single-nucleotide polymorphism (SNP) or a gene variant or a missense mutation is a DNA sequence variation occurring when a single nucleotide A, T, C, or G in the genome differs between members of a species or between paired chromosomes in an individual.Sequence analysis showed that 6 SNPs/gene variants were identifiable in the GHR gene in Chinese population, out of which C422F, P477T, I526L, and P561T are SNPs with significant effects.1 The purpose of this study was to investigate the single nucleotide polymorphisms (SNPs) (I526L) in GHR gene and examine the relationship between GHR gene variant I526L and craniofacial morphology. MATERIALS AND METHODS: The sample consisted of 30 randomly selected subjects, aged 20-30 years who were patients at D.A.P.M.R.V.Dental College Hospital, Bangalore. After clearance from ethical committee, venous Blood samples (2ml) were obtained from the subjects with informed consent. Lateral cephalograms of these subjects obtained as a part of routine treatment protocol were used. Method of Polymerase Chain Reaction and Restriction fragment length polymorphism was employed to deduce the genotypes. After collection and storage of blood samples, genomic DNA was isolated and Polymerase Chain Reaction Test was performed using specific primers (rs6180). This was followed by digestion with Restriction Enzymes HpyCH4V.Cephalometric measurements were carried out on standardized lateral cephalograms using Burstone analysis norms3 to measure the craniofacial parameters of anterior cranial base length, maxillary length, mandibular ramus length/height and mandibular length. The results were computed by correlating PCR results with the cephalometric craniofacial measurement values. Statistical analysis using Z test for proportions was carried out to test the level of significance. The Statistical software namely SPSS 11.0 and Systat 8.0 were used for the analysis of the data. RESULTS: The initial PCR product of the GHR gene variant I526L was obtained for the thirty subjects. The size of this PCR product was 602bp. Photograph 1: Initial PCR Product of GHR gene variant I526L (602bp). This was then subjected to digestion with the specific restriction enzyme HpyCH4V for I526L. After digestion, the 602 bp products were completely digested in 16 subjects whereas 14 subjects showed incomplete/no digestion. So the presence of variant I526L was shown in 14 subjects and absence of variant I526L in 16 subjects. Association of the presence or absence of variant I526L with increased, normal and decreased measurements (when compared with norms) of all four craniofacial parameters were tabulated. Table 1: Table comparing the P-values of samples with presence of I526L variant with respect to normal v/s increased, normal v/s decreased and increased v/s decreased mandibular ramus length Graph 1:Presence and absence of variant I526L in samples with normal,increased and decreased ramus height. Out of the four craniofacial parameters investigated association of presence of variant with mandibular ramus height was found to be statistically significant(P=0.002,P DISCUSSION: In the Human Gene Mutation Database, 56 different GHR gene mutations, including 32 missense and nonsense mutations, have been registered.4 In a few reports concerning the effect of GHR gene mutations on craniofacial growth, Chinese Han individuals with a genomic polymorphism at codon 526 of the GHR gene had a greater mandibular ramus length. Presence of variant I526L was seen in 46.67% of the samples. This is in accordance with a study done in Chinese population which showed I526L to have the highest heterozygosity of all the variants i.e 47.6%.1 A significant association was seen with presence of I526L variant and increased ramus height. (P=0.002, 1,5 Evaluation of site specific relationship between various craniofacial morphological determinants and the variant I526L showed significant association of increased ramus height with presence of I526L and this is in accordance with the study done by Zhou et al in Chinese population.1,5 This is also in accordance with a study done on 39 cephalometric variables which are under strong genetic control which showed strong genetic correlation with the vertical parameters.6Since mandibular ramus is the only vertical parameter included in the study it is seen to have a significant correlation with the variants. Further studies with all the four SNPs i.e. C422F, P477T, P561T and I526L can be carried out for a more detailed analysis of their influence on craniofacial morphology . CONCLUSION: This study indicates that subjects with I526L variant of GHR gene had a significantly greater mandibular ramus height. Influence of I526L is site specific as presence of I526L has an influence on increasing ramus height out of the four craniofacial parameters.GHR gene variant I526L could be a genetic marker for mandibular ramus height.

Does College Help :: essays research papers

College or technical schools are supposed to be the gateway to higher paying careers, but most are not all that they are cracked up to be. The standards and goals that society wants met are continually not being met by the students today. Also, many higher learning facilities lack the funds to provide positive learning environments for students. For these reasons and many more are keeping the students of today from benefiting fully from schools.   Ã‚  Ã‚  Ã‚  Ã‚  Society today has to make some new choices for the students of tomorrow, choices that will carry them into the next millennium. Society can either “lower standards so that everybody “passes'; in a way that looses all meaning in the real world'; or “ raise standards and then meet them'; (Barber 479). I personally believe in raising our expectations and doing whatever is needed to meet them. Our countries standards are among the lowest in the world and “ at the same moment as we are transferring our responsibilities to the shoulders of the next generation, we are blaming them for our own generation’s most conspicuous failures'; (Barber 472). Every election year the candidates use something about education as one of their platforms, but few ever carry through with them once they are elected. Most education bills die in congress in some shape or another and the ones that actually make it through congress, are usually ineffective because t hey have been changed and modified to the point of ineffectiveness.   Ã‚  Ã‚  Ã‚  Ã‚  Also, many of the learning facilities today lack the funding to provide adequate, positive learning environments for students. Underpaid teachers and professors who “ make less than accountants architects, doctors, lawyers, engineers, judges, health professionals, auidiors, and surveyors'; and thus many student disregard teachers as role models. If people see someone who can score touchdowns or dunk a basketball making millions while their teachers are scraping bottom to survive, then how can an educator possibly motivate them to learn (Barber 470). Many people chase after their “dreams'; of money instead of seeing the reality of learning. Although society today rates an education as one of their top priorities, they still allow learning facilities to become broken and run down. Like animals, children and adults file into buildings with bad floors, horrible plumbing, leaky roofs and ceilings, and pack into desk, usually 35+ per educator. Today the gove rnment spends $35,000 a year to keep someone behind bars and only a fraction of that to keep them in school (Barber 475).

Political Inquiry Terms and Definitions

Research Design * Good research, bad research * Involves connecting theory and data. * Maximising leverage by using very few variables to explain many effects. * Reports on the degree of certainty of results. * Shows true causal relationship, not just correlation. * Provides accurate data and accounts for other variables. * Determines if the relationship is unidirectional. * Purpose of research * To establish a relationship between two or more variables * To demonstrate that the results are generally true in the real world and not in just a particular context. To reveal whether one phenomenon precedes another in time, establish time order * To eliminate as many alternative explanations for the observed finding as possible * Choice of design * What affects * Is research exploratory, descriptive or explanatory * What are the practical limitations in investigating hypothesis. * Experimental design: * Classical experimental design, 2 groups, pre and post test, randomisation, * Simple pos t test: only post test * Repeated measure design, measure how long effect takes to start. Multiple pre and post tests. Multigroup design, more than 2 groups, can compare different levels of experimental variable. * Randomised Field experiments, applies logic of randomisation and variable manipulation * Non-randomised quasi-experiments. Purposeful selection, target a certain group. * Non-experimental design: single group, no control over assignment and application of IV, inability to measure DV. * Case study: small N designs. Provide detailed explanation * Comparative analysis: compare two or several units in relative detail * Focus group: gather information about reaction to certain IV. Surveys: large number of people measured to find causal relationships. * Aggregate data analysis: variables are averages or percentages of geographical areas, find causal relationships. * Longitudinal designs, time span. * Trend analysis: measurement on same variables at different time periods to exa mine changes. * Panel analysis: follows a group of participants. * Intervention analysis: measurement of change in the DV is observed and taken before and after. No interaction, mere observation. * Ethnographies: form of data collection through participant observation, interviews and questionnaires.Field studies * Content analysis: textual analysis, study of recordings, written. * What they have in common * They all share the basic objectives of research design despite having different levels of internal and external validity. Using several designs together will cover each other’s shortfall. * They all attempt to draw sound conclusions supported by observable evidence * Terms * Causal vs spurious * Both show correlation between IV and DV, but in spurious the change in DV because 3rd factor caused changed in both. Causal is a direct relationship. 5 different relationships. Multiple causes without chain.Multiple causes with chain. Multiple causes that affect DV, but are changed with the introduction of another variable. Spurious causality with antecedent variable. Chain causality with intervening variable. * Covariation * Demonstrates that the IV does in fact covary with DV. Not causal relationship yet. * Time order * Show that the IV precedes DV. Effect cannot appear before cause. * Alternative causes * Confounding factors. Factors that possible cause a change in DV as well. * Randomised controlled experiments * Experiments that allow the researcher to control the exposure to the IV through assignments to groups.Selection and grouping all randomised. * Experimental design * The way in which the researcher controls exposure to test IV. 5 different designs. * Control group * The group of subjects that does not receive experimental treatment or test stimulus. * Pre-test * Measurement of the DV prior to administration of IV or experimental treatment. * Post test * Measurement of the DV after administration. * Internal vs external validity * Internal validity is the ability to show that manipulation or variation of the IV actually causes change in DV. * External validity is the ability to generalise from one set of research findings to other situations. History * A threat to internal validity. Events other than the experimental stimulus that occur between pretest and posttest measurements. * Along with maturation * Testing * When measuring the DV prior to the stimulus alerts the subjects of the research objectives. * Selection bias * Bias due to the assignment of subjects to experimental and control groups according to some criterion and not randomly. A threat to internal validity. * Experimental mortality * A differential loss of subjects from experimental and control groups that affects the equivalency of groups; threat to internal validity * Instrument decay A change in the instrument used to measure the DV, like different researcher conducting pretest and posttest. * Demand characteristics * Aspects of the research situation that ca use participants to guess at the investigators goals and adjust their behaviour or opinions accordingly. Trying to â€Å"help†. * Simple post test * Similar to classical. Experimental group exposed but control not, only post test is conducted. * Repeated measure design * Contains several pre and post test measurements to know exactly how quickly the effect of the independent variable should be observed or how reliable pretest measurement of DV should be taken. Multi-group design * There are more than one experimental r control group created so different levels of the IV can be compared. Can involve both pre and post test or just one. * Field experiments * They are experimental designs that are applied in a natural setting. Adopts logic of randomisation and variable manipulation. * Non-experimental design * They are designs that do not follow the experimental model of two groups and have controlled exposure to IV. They are more practical to do but are not as strong in terms of establishing causal relationships. * Case study * Comprehensive and in depth study of a single case or several cases.Provide detailed explanations * Comparative analysis * Comparing between two or several units in relative detail * Focus group * Often use to observe reactions to the introduction of the IV. Has a group of people who meet at a single location * Surveys * Measurement of DV and IV at the same time. Respondents report their exposure to various factors. No assignment to groups, examines groups basd on values of IV, measurement of DV to see differences between groups. * Aggregate data analysis * Variables that are displayed as averages or percentages, to find causality. Trend analysis and longitudinal design * Measurements on same variables at different time periods to see the changes caused by the IV on the DV. No manipulation of variables. Multiple measurements. * Panel study * A study that follows a group of participants where the same units are measured at different t imes. * Panel mortality * Refers to the participants in the panel study who drop out. Rate? * Intervention analysis. * Looks at the occurrence of the IV as an observation. Looking at the DV before and after IV. Works best when IV happens in a brief period in time and brief in nature.Measure only before and after event. Literature Review * Purpose of Literature review, 7 * To see what has and has not been investigated * To develop general explanations for observed variations in a behaviour or a phenomenon * To identify potential relationships between concepts and to identify researchable hypothesis * To learn how others have defined and measured key concepts * To identify data sources that other researches have used * To develop alternative research designs * To discover how a research project is related to the work of others. * What constitutes a literature review It is made of different relevant articles that provide more insight into topic * It should help arrive at a good researc h topic * It should show what has and has not been researched * It provides a general explanation for variations in behaviour or phenomenon * It identifies researchable topics * It should help develop alternative research designs * Best methods for collecting literature * Using electronic databases like JSTOR, Web of Science and Google Scholar. * Searching by topic and key words, slowly limiting results, read the articles and find new words to narrow down the search. Searching by starting with a single article. Use data base to find more relevant articles or other articles written by the same author. Use the citations in that first article. Find articles that have cited the first article. * Best ways to write a literature review * It should rely on scholarly sources * It must relate directly to topic * Have to become familiar with as much of the research before selecting the final sources. * Summarising of relevant literature that focuses on over-arching topics rather than single ar ticles. * Compiling all articles into something that makes sense. * Organising the topics ased upon the research question. * Identifying common themes or methodologies across the articles. * Discussion of conventional wisdom, illustrating how current politics has changed and identifying the flaws in past research. Sampling * Terms * Population * all case or observations covered by a hypothesis, all the units of analysis to which a hypothesis applies. * Sample * A subset of observations or cases drawn from a specified population. * Sample statistics * The estimator of a population characteristics or attribute that is calculated from sample data * Advantages and disadvantages of samples Advantages * It is cheaper and less time consuming as compared to using population * More convenient. * Disadvantages * They can be less accurate or more prone to error * Some studies do not use sampling, like case studies. * Population parameter * A characteristic or attribute of a population that can be quantified. * Estimator * A statistic based on sample observations that is used to estimate the numerical value of an unknown population parameter. * Element * A particular case or entity about which information is collected, the unit of analysis. When to use a sample * Practicality. When data from an extremely large population is required, it is impossible to interview or approach each and every subject. Thus sampling is require because although the sample statistics will not exactly equal the corresponding values, they will be reasonably close if sampling is done correctly. * Sampling frame * The particular population in which the sample is actually drawn from. * Random digit dial: purpose of and how and why it works * It is a procedure used to improve the representativeness of telephone amples by giving both listed and unlisted numbers a chance of selection. * It is used to overcome the problem of cell phone numbers which are unlisted * It works by randomly dialling numbers. * It works because it gives all numbers, whether listed or not a chance to get dialled. * Sampling unit * The entity listed in a sampling frame. Maybe same as an element or group. * Sample bias * The bias that occurs whenever some elements of a population are systematically excluded from a sample. It is usually due to an incomplete sampling frame or a non-probability method of selecting elements. Probability sample: types, pros and cons * Sample for which each element has a known probability of being included in the sample * Types: * Simple random samples: each element has an equal chance of being selected. * Pros: each element has an equal chance of being selected. * Cons * It is not truly random, small patterns of selection might appear. * Obtaining a list of the entire population is not possible, reducing the probability. * Systemic samples: elements are selected from a list at predetermined intervals * Pros It is easier to apply than simple random. * Useful when dealing with a v ery large population size. * Cons * May result in biased sampling: if elements on the list have been ranked according to a characteristic. The list contains a pattern that corresponds to the sampling interval. * Stratified samples: elements sharing one or more characteristics are grouped and elements are selected from each group in proportion to the group’s representation in the total population * Pros * Homogeneous populations, smaller sample seize is needed to achieve accuracy. * Cons Heterogeneous populations need a much larger sample to be accurate. * Proportionate samples: stratified samples where each stratum is represented in proportion to its size in the population. * Pros * Very representative of the population * Cons * Not good with heterogeneous populations * Disproportionate samples: stratified samples in which elements sharing a characteristic are under-represented or over-represented. * Pros * When the sample size is too small, can be used to increase it easily. * Cons * May not be representative of the population if weight factor is not used. Cluster samples: the sampling frame initially consists of clusters of elements * Pros * Used when no list of elements exists and to create one would be too expensive. * Reduces field work costs * Cons * There is greater imprecision. Samples are not representative of population. * Non-probability samples: types, pros and cons * Each element has an unknown probability of being included in the sample * Types * Purposive samples: when a researcher exercises considerable discretion over what observations to study. * Pros * Can learn more from carefully selected unusual cases. Cons * Not accurately representative of population. * Convenience sample: elements are included because they are convenient and easy for the research to select * Pros * Convenience * Large numbers easy to get * Cons * Unknown accuracy * Quota sample: elements are sampled in proportioned to their representation in the population. * Pr os * Similar to proportionate sampling, but subjects chosen purposefully. * Cons * Selection bias * Snowball sample: respondents are used to identify other persons who might qualify for inclusion into the sample * Pros Good for relatively selective and rare populations * Relationship between samples and statistical inferences * Statistical inferences is the mathematical theory and techniques for making conjunctures about the unknown characteristics of the population based on samples. Making inferences about a population. * Trying to define more clearly what supportable means * Samples provide an estimate of population attributes and may be off from the true population parameter. The difference is the level of precision lost. * 3 types of errors in inference Expected values or sampling error * Expected value is the average value of a sample statistic based on repeated samples of the population. * Sampling error is the difference between a sample estimate and a corresponding populatio n parameter that arises because only a portion of the population is observed * Standard errors * The standard deviation or measure of a variability or dispersion of a sampling distribution * Provides a numerical indication of the variation in sample estimates * Sampling distributions. A theoretical non-observed distribution of sample statistics calculated on samples on size N that, if known, permits the calculation of confidence intervals and the test of statistical hypothesis * Describes the mean, variation and shape of the distribution that is based on an independently and randomly drawn population. * It allows researchers to calculate the probability that sample statistics fall within certain distances of the population parameter. * Sampling error * the difference between a sample estimate and a corresponding population parameter that arises because only a portion of the population is observed * Standard error The standard deviation or measure of a variability or dispersion of a sampling distribution * Provides a numerical indication of the variation in sample estimates * Confidence * How much error this is in a sample. The degree of belief or probability that an estimate range of values includes or covers population parameter. * Sample distribution * Describes the mean, variation and shape of the distribution that is based on an independently and randomly drawn population. * Sample size. * 100 (11% +/-) * 600 (5% +/-) * 1000 (4% +/-) * 1500 (3% +/-) 4000 (2% +/-) Observations * Terms * Quantitative vs qualitative data * Quantitative data involves a large amount of data and its involves numeric manipulation * Qualitative data involves small number of cases, more in depth and it relies on quotations, comments, anecdotes and other written evidence to support arguments * Both seek to explain trends or patterns through systematically collected data. * Data collection, how do we choose the best way, characteristics of * How to choose the best way * Depends on th e question * Depends on the sample Depends on which constitutes the best measures, validity of the measurements that a particular method will allow. * Depends on cost and availability, some are more observable than others, some less expensive. * Depends on the reactivity to the collection by the population. * Consider ethical implications. * Characteristics * Primary and secondary data * IRB, what role it plays and the significance of it * Institutional review board, a must for any test involving human subjects. * It is guided by 3 principles: respect for persons, beneficence and justice. The role it plays s to ensure that all research conducted will not harm any individuals, recognise that they are autonomous and there is distribution of benefits to participants. To ensure that no ethical boundaries are crossed. * Its significance is that it has removed all unethical research to be done, but this limits the way data is collected. Thus researchers must consider the benefits vs the b urden of the research. * Observation, types and pros and cons: basic distinction is direct and indirect. * Direct * Allows researchers to view things in natural setting more often than laboratory. Field study or ethnography. Observation in lab gives more control over environment ‘ * Pros * Natural settings allow people to act normally, increases validity * Researchers can observe for longer periods of time * Lab can give more control. * Cons * Lab can also mean that subjects know they are being observed and thus alter behaviour, low validity * Natural setting cannot control external effects and variables. * Indirect * Observation of physical traces of behaviour, essentially detective work. Inferences are made based on physical traces * Two types of measures * Erosion Created by selective wear on some material. Looking at what has been eroded or removed, looking at what is left. * Accretion * Measures a phenomenon a manifested through the deposition and accumulation of material s. Seeing what has built up. * Pros * It raises less ethical issues than direct * Some materials or traces of them are more/less durable than other, making them more/less easy to measure, depending on the method. * Less obtrusive, much cheaper than alternatives * Cons * There are many threats to validity, prone to measurement problems * Can be difficult to make strong inferences * Participant Most field studies involve this, proverbial fly on the wall. Observing people for long periods of time. Assume a role or identity within the group. * Pros * Gain deep access into the group through informants * Natural setting * Observe for long periods so changes in behaviour can be studied * Has a degree of accuracy and completeness that other methods cannot provide. * Cons * It is not viable for every question, some things are just unobservable, like voting * Lack of control over the environment, inability to isolate factors * May be invalid or biased, going native.Becoming part of the enviro nment, perceived biased. * Difficulties with replication of study * Non participant * Same as direct. * Overt * Participants are aware of the investigators presence and intentions * Covert * Investigators presence is hidden or undisclosed. * Structured * Investigator looks for and systematically records the incidence of specific behaviours * Unstructured * All behaviour is considered relevant, at least at first, and recorded. * Ethical issues and how to avoid * Negative repercussions from associating with researcher because of the researcher’s sponsors, nationality or outsider status. Invasion of privacy * Stress during research interaction * Disclosure of behaviour or information to the researcher resulting in harm to the observed during or after the study. * How to avoid: ethical proofreading * Assume everything and all identities will be discovered * Look at actual words in manuscript * When describing potentially unflattering things go from general to specific * Be genera l about community at hand * Realise that data and research will be used again * Know what perspective and attitude is towards subject * Caution subjects multiple times Know study limitations and agreement are in advance * Have other people edit sensitive portions. Document analysis * Types of records, pros and cons of utilization * Two types of records * Running: produced by organisations rather than private citizens, carefully stored and easily accessed and is available for long periods of time. * Pros * Low cost in terms of money and time. * Accessibility * Covers more extensive period in time. * Extensive amounts of records * Many records are digitalised * Cons * At the mercy of those who keep the records, may or may not be biased. Questions on recording keeping practices, may not be kept properly. * Episodic: records that are produced and preserved in a more casual, personal and accidental manner. Diaries and memoirs. Important to political historians. * Pros * Used to illuminat e phenomena rather than generate large sample * Provides different perspectives on certain phenomena. * Use qualitatively. * Cons * Gaining access to episodic records can be difficult, locating suitable materials is the most time consuming aspect of data collection * Many are not digitalised. Content analysis, procedures, pros and cons, intercoder reliability * Refers to the use of excerpts, quotes, and examples from recorded documents to support and observation. * Can be both qualitative and quantitative in nature. * Procedures * Decide on appropriate sample, what materials to include in the analysis. * Define the recording or coding units, decide what is actually going to be measured. * Choose categories of content that are going to be measured, deciding the recording unit. How to measure what you want. Code words? Devise a system of enumeration for the content being coded, a numeric system based on what is being coded. Code for number of times X appears. * Pros * Gives researcher s access to subjects that would otherwise be difficult to attain. * Raw data are usually nonreactive, no undesired influences on behaviour. * Written records like newspapers have existed over long periods in time * They can be easily attained * It often enables us to increase sample size above what would be possible though either interviews or direct observation . * The cost of keeping records are borne by the keepers, it is low cost for those using them. Cons * Selective survival, record keepers may not preserve all pertinent materials, only selectively. Gaps may exist * Incompleteness. Gaps may exist due to fires losses of other types * Content may be biased. May be incomplete, selectively preserved, inaccurate or falsified * Unavailable to researchers because they are classified. * They lack a standard format because it is kept by different people. * Intercoder reliability * Refers to when two or more coders, using the same procedures, agree on how the content is analysed.The mor e times the coders make the same conclusions the same way, the more claims can be made. * Written records, pros and cons * Pros * Can be used when other means like direct observation or interviews are not possible. * Able to use for large scale collective behaviour, cannot possibly interview all. * Raises fewer ethical issues than observation or interviewing. * No risk to individuals as long as they are not identified in records. * Cheaper than other forms. * Not affected by time or history, what is recorded cannot be changed. * Cons * Gaining access may be difficult, classified Records not kept properly, or purposefully changed Survey research and interviews * definition and difference * surveys are a method of data collection that acts as an alternative to experiments or simulations. * Instead of manipulating an independent variable to view its effects, survey design examines the relationship between variables, better at establishing correlation rather than causation. * Types of s urveys, pros and cons, * Personal, face to face * High cost * High to medium completion rate * Potentially high sample congruence * Long to medium length * High data processing cost * Telephone Medium cost * Medium completion rate * Medium sample congruence * Medium to short length * High to low data processing cost * Mail * Low cost * Low completion rate * Medium sample congruence * Medium to short length * Medium data processing costs * Email * Low cost * Depends but low completion rate * Low sample congruence * Medium to short length * High to low data processing costs * Internet * Low costs * Depends but low completion rate * Low sample congruence * Medium to short length * High to low data processing costs * Group administration * Very low costs * High once group is convened completion rate Depends on group selection process, sample congruence * Variable length * High to low data processing costs * Drop off/pick up. * Very low costs * Low completion rate * Low sample congruence * Short length * Low data processing costs. * Completion and response rates, significance of * Refers to the proportion of persons initially contacted who actually participate. * When the proportion of the persons contacted who actually participate is too low, the ability to make statistical inferences about the population is limited * Too little responses, cannot make inferences. * Cost * Time and money. Have to balance between costs and completion rate. * Data processing * Answers of the surveys still have to be tabulated. All data need to be coded in a way that a computer can process them. * Problem with open ended questions. Have to be transcribed and coded. * A major reason for adopting internet and telephone surveys. * Sample-population congruence * Refers to how well the sample subjects represent the population from which they are drawn * Biases can enter through the initial selection of respondents or through incomplete responses. * The closer the congruence, the more repre sentative the sample, higher validity. Length * Too long and respondents lose interest or start answering without care, get distracted. * Too short and not enough data is collected. * Well motivated participants can help with the problem. * Response quality * Cannot take the responses at face value. * Participants may not have the same interests or familiarity with certain topics. * People may be reluctant to express their opinions to strangers. * Busy people won’t answer truthfully. * Interview bias * Occurs when the interviewer influences the respondent’s answers, may have a larger effect on telephone surveys than in person surveys. Question types and wording, what to be careful for and why, pros and cons * Close-ended questions * Pros * Easier for people to answer and takes little time * Easier to sort and tabulate data * Sensitive issues are better paired with close ended questions * Cons * Force respondents to choose from a list they may not agree with * Single si ded and double sided questions that can affect responses * Single side, agree or disagree with a statement * Two sided, gives two alternative statements to choose. Problems of recall versus recognition, can prompt answers that would have otherwise been blank. People don’t know the answer but recall when seeing the choice. * Oversimplified and distorted picture of public opinion * Open-ended questions * Pros * Allows respondents to state what they know and think. * Good for situations where likely answers are not known. * Cons * Respondents may respond too much or too little. * Problem with recording answers, tedious and difficult to code, interpretations vary as well. * Processing data is time consuming. * Wording Wording is important, question clarity is vital to get valid responses. Objectivity and clarity * Avoid * Double barrelled questions * Two questions in one. Sometimes participants might not agree with first question but is made to in order to answer the second. * Am biguous questions * One that contains a concept that is not defined clearly. * Participants may interpret the question wrongly. * Leading questions * Reactive question. Encourages respondents to choose a particular response because the question indicates that the researcher expects it. * Giving what the researcher wants, validity is off. Push polls. * Question order and effects * The order in which questions are presented may influence the reliability and validity of answers. Participants any answer differently or stop when they see certain questions. Can solve response set. * Branching questions * A question what sorts respondents into subgroups and directs them into different parts of the questionnaire * Filter questions * A question that screens respondents from inappropriate questions. * Response set * Straight line responding. * May occur when a series of questions have the same answer choices.Check the first few, then blindly check the rest. * Archives surveys, pros and cons * Existing surveys that have been designed in the past and are readily available to use. * Pros * Very cheap, for those with no access to funding. * Less time is spent designing the surveys. * More reliable and higher quality, widely used thus more reliable. * Well written questions. * Cons * The questions are not what you want. * Interviews, definition, pros and cons. * Interviewing is the act of asking individuals a series of questions and recording their responses.May be face to face or over the phone. * Pros * Sometimes asking questions is the only way * Elites can provide valuable information, but only through interviews. Focused interviews. * Can provide more comprehensive and detailed information, rich variety of perspectives. * Excellent form of data collection in exploratory studies. * Cons * Can be difficult to administer * Have to take into account non-verbal cues and be willing to go off topic * Detailed note taking * face to face, strong necessity for interpersonal skill s.

How to Handle Dry Ice Safely

How to Handle Dry Ice Safely The solid form of carbon dioxide is called dry ice. Dry ice is the perfect ingredient for fog, smoking volcanoes, and other spooky effects! However, you need to know how to transport, store, and use dry ice safely before you get it. Here are tips to help keep you safe. How To Get and Transport Dry Ice You can obtain dry ice from some grocery stores or gas companies. Its important to be prepared to transport dry ice before you purchase it. This will help it last longer and prevent accidents. Plan to get enough dry ice. It will sublimate at the rate of  five to ten pounds each 24 hours (for pellets or chips), so if you wont be using the dry ice right away, plan for the loss of product. The rate of sublimation also depends on the exposed surface area. Dry ice pellets will convert to gas more quickly than a solid chunk of dry ice.  Bring a cooler or a cardboard box. Your goal is to insulate the dry ice from warmer temperatures. Its also helpful to have a blanket or sleeping bag to wrap around the container to protect it from temperature changes.Usually dry ice is sold in paper bags. Set the paper bag inside the box or cooler. Close the lid to insulate the dry ice, but make sure it does not seal. This is important, because dry ice sublimates from its solid form into carbon dioxide vapor. The gas builds up pressure and could cause an explosion if it doesnt have a way to escape.As sublimation occurs, the level of carbon dioxide in the vehicle will rise. Make sure new air c irculates into the vehicle to prevent carbon dioxide poisoning. Storing Dry Ice The best way to store dry ice is in a cooler. Again, make sure the cooler is not sealed. You can add insulation by double-bagging the dry ice in paper bags and wrapping the cooler in a blanket. Its best to avoid putting dry ice in a refrigerator or freezer because the cold temperature can cause your thermostat to switch the appliance off, carbon dioxide levels could build up inside the compartment, and gas pressure could force open the door of the appliance. Using Dry Ice Safely The 2 rules here are (1) dont store dry ice in a sealed container and (2) avoid direct skin contact. Dry ice is extremely cold (-109.3 °F or -78.5 °C), so touching it can cause immediate frostbite. Use gloves or tongs to handle dry ice.Be aware cold carbon dioxide sinks, so risks from too much carbon dioxide are highest close to the ground or in any enclosed space. Make sure there is good air circulation.If youre using dry ice in drinks to produce fog, be careful you dont ingest the dry ice fragment. Ingesting dry ice is a medical emergency because of the tissue damage from frost bite and the pressure buildup from the release of gas. Dry ice sinks in a glass or bowl, so the risk of ingestion normally is very low. However, do not allow intoxicated people to drink dry ice cocktails or work with dry ice. How To Treat a Dry Ice Burn Treat a dry ice burn the same way as you would treat frostbite or a burn from heat. A red area will heal quickly (day or two). You can apply burn ointment and a bandage, but only if the area needs to be covered (e.g., open blisters). In cases of severe frostbite, seek medical attention (this is extremely uncommon). More Dry Ice Safety Tips Never leave children or pets unattended around dry ice.Be aware of symptoms of carbon dioxide poisoning and make sure there is good air circulation where dry ice is used and stored. Ordinarily, slightly elevated levels of carbon dioxide dont pose a significant health risk. The levels of carbon dioxide are most likely to become too high near the ground.If youre using dry ice to chill food, youll get the best results if you put the dry ice on top of the food. This is because cold sinks.Avoid setting dry ice directly onto counter tops or placing it in empty glass containers. The temperature shock could crack the material.Some airlines will allow you to carry dry ice, but not more than 2 kilograms. Expect the dry ice to sublimate at a slightly faster rate than usual because cabin pressure may be lower than normal pressure. Pack the dry ice with crumpled paper or a blanket to reduce loss.

Magwitch-a criminal Essay Example

Magwitch Magwitch-a criminal Paper Magwitch-a criminal Paper Dickens uses of short, descriptive sentences help to achieve these visions. Magwitch is a colourful, cunning and manipulative character, yet he loosens up his anger slightly towards Pip, when he learns that he is an orphan. It may show that Magwitch is an orphan too, and so shows slight sympathy towards him. Dickens may also be implying that Magwitch was provoked to turn to crime, as a result of becoming an orphan- fending for his self. This signifies a (very) subtle change in a relationship that was full of fear and intimidation, to one with a form of dependence, and some sympathy attached alongside it too. Pip agrees to follow the commands of Magwitch-a criminal, and therefore despite not really knowing, performing a noble act. In chapter 2, Dickens delves deeper into investigating the life of a typical orphan; in the era. We learn more about the harsh realities of life for an orphan. If you werent killed by the numerous epidemics around, then you were considered lucky. Ironically, the situation is written about quite comically to lessen the impact of the powerful opening chapter. Pip lives with his abrupt, and shrewish sister, Mrs Joe Gargery-who now looks after him, and her husband, Joe Gargery, who is a blacksmith. Pip is regularly the victim of angry beatings delivered by his sister, who has established a reputation by bringing Pip up by hand. Knowing her to have a heavy hand and to be much in the habit of laying it upon her husband as well as upon me, I suppose that Joe Gargery and I were brought up by hand. The channelling of problems faced in childhood evokes feelings of sympathy from the reader towards Pip- Dickens successfully does this to make the reader see that society was unjust, he explores this further through out the story. Mrs Joe isnt afraid to let Pip know that she thinks of his as a burden, and so uses him as a cannonball, she regrets looking after him. If it wasnt for me youd have been to the churchyard long ago, and stayed there. Who brought you up by hand? And why I did it, I should like to knowId never do it again! I know that. Mrs Joe believes that Pip should be grateful to her for what she has done for him. She is also quick to say that she is ashamed of her situation. It is bad enough to be a blacksmiths wife (and him a Gargery), without being your mother. This shows that Mrs Joe feels burdened by her position-looking after Pip, she is continuously working. Pip and Joe are in understanding of each others situations and so try to make the best of their situation. Joe tries to protect Pip, rather than lashing out on him too. When Pip hides some bread for Magwitch, Joe thinks that he has been bolting (swallowing without chewing). Mrs Joe makes both Pip and Joe drink repulsive tar-water (disinfectant mixture-wood tar); the cruel conditions of childhood are again depicted. In Dickens view of childhood, he felt that children have certain needs: guidance in a nurturing home, to be free from emotional and physical abuse, to have a good education, and to be allowed to be happy. Lack of parental love and support; in these circumstances have inclined Pip to long for a better future for himself, thinking it be possible if he can become a gentleman, he tries to pursue this ambition. Firing from the Hulks announces the escape of another convict. At dawn he steals food and a file, and hurries to meet the convict, despite his conscious questioning him-he feels that this is a criminal act, although he still carries it out. Chapter 3 opens to a rimy (frosty), miserable morning, where key events are about to occur. Pips guilty conscience is exposed, he thinks that his surroundings are talking to him, everything seemed to run at me and accusing him of crime. The gates and the dykes and banks came bursting at meA boy with somebody-elses pork pie! Stop himThe Cattle came upon me with like sadnessHolloa young thief! Dickens shows through the narrative, that he knew how children thought, and so the reader is able to enter Pips mind and see the world through the eyes of a child. Pip sees another convict in the dangerous fog and escapes from him, assuming that he is the murderous young man Magwitch mentioned was with him. The first convict-Magwitch is waiting for Pip. He devours the food with animal relish, and works to remove the leg iron with the file. He shows a different side of emotions when Pip comes back to meet him, and gives him food, something clicked in his throat as if he had works like a clock, and was going to strike. The usage of a metaphor tries to convey the fact that his burst of softer emotions is surprising, as he has presented his intense, and angry side, the narrative suggests that his presence is not human like, more like a machine. Alliteration helps to pinpoint this And he smeared his ragged rough sleeve over his eyes. Pips fear of him is mixed with pity, pitying his desolation, and watching him as he gradually settled down. The convict had obviously invented the young man to frighten Pip. Their relationship has shifted at this point-its a landmark. Magwitch doesnt act violently towards Pip (although he when he hears about another convict he gets angry-suggesting a mysterious connection between them), although the element of violence is still mentioned. He shivered all the while so violently and He was already handling mincemeat down his throatmore like a man putting it away somewhere in a violent hurry, than a man eating it. This shows us that Magwitch has indecisive violent qualities. Magwitchs almost unsettled state is highlighted again. His manners are compared to that of dogs. The politeness of Pips sympathetic conversation with the convict is an attempt to normalise an abnormal situation, but also, as recognition of the convict as a fellow human being. He is becoming somewhat comfortable with the situation now. Pip: I was glad you enjoyed it (the food Pip bought for Magwitch). Magwitch even thanks Pip, thus creating a noticeable change in their relationship-it is significant. Pips initial referral to Magwitch as my convict shows that an emotional bond/relationship between them is felt and has formed incomparison to previous fear. Pip leaves Magwitch to work on his leg-iron with the file, whilst he runs back home (for Christmas). In Chapter 4, at the forge an abundant dinner is held. Pip has got a guilty conscious, and is feeling terrified that his theft will be discovered. The tar-water that Pip substituted for the stolen brandy is drunk, and the pork pie cant be found. When Pip finally runs for the door but is met by a soldier bearing a pair of handcuffs. We are faced with the worrying question will Pip be arrested for his act? This end on a note of suspense reminds us that Dickens was writing to please a wide audience. In chapters 5-6, we learn that Joe is asked to repair the broken handcuffs. Everyone is forced to follow the soldiers on the search for the convicts, although Pip is reluctant-and worried about what Magwitch will think. Would he believe that I was both imp and hound in treacherous earnest, and had betrayed him? Pip is clearly feeling anxious and guilty about the situation, he is unsure about what may happen to both himself and Magwitch. The convicts are eventually found. Our curiosity about the convicts is aroused when one of them is called a gentleman-a topic that is at the core of the story is questioned. We see Joes humanity when he recognises Magwitch as a poor miserable fellow-creatur. Joe says We dont know what youve done, but we cant have you starve to death for itCould we Pip? to Magwitch. The reader learns that Pip gains his good morals and humanity from Joe, and his teachings. Dickens tries to bring into view of the audience that many convicts like Magwitch) werent necessarily bad people, you should consider that they may have been driven to commit crimes. Before being rearrested and taken back to the Hulks, Magwitch admits that he has stolen food from the forge, but doesnt reveal that Pip helped him; this public spew of protection shows gratitude and reassurance between the pair. Their relationship is still developing, and there has been a rapid shift since their first encounter the previous day, where a whirlwind of violence, and tension was displayed. Since the morning their relationship and attitude has turned into something more meaningful-loyalty has been conjured up; Proving that Magwitch must have been really touched when he was shown kindness from Pip. Criminals like Magwitch were pushed to the bottom of society. It was rare to see any affection shown towards them, as they were treated so badly. Magwitch shows emotion when kindness is shown to him from Pip and Joe. The something I had noticed before, clicked in the mans throat again, and he turned his back. Magwitchs turn around implies that he doesnt really want to show his softer emotions, this may be because criminals were believed to be hard and their emotions werent taken into consideration, as if they lacked them. Pip decides not to confide in Joe about his own part in the theft either; this signifies the start of a break between them.

Virginia's winery business plan example Essay Example | Topics and Well Written Essays - 1000 words

Virginia's winery business plan example - Essay Example The sustainability of the winery to competitive advantage will be to seek and attract younger generation wine consumers2. The main source of market will be analysed through internet perceptive marketing methods that will apply the use of flashy websites. The primary use of this marketing method is that it allows sales of wine through the internet3. Moreover, there shall be a 5K wine run that will incorporate the county’s clubs especially the Augusta County Track Club. This initiative will run or operate for the three years with the aim of supporting local area runners thereby publicizing the name of the new company among the locals4. Additionally, the Virginia’s Winery will host a series of events including business meetings and weddings among other festivals that will be conducted throughout the year. In the beginning of the operation, the winery will have three distribution channels. These channels will mainly provide retail services for the product within the company and outside the company as well as internet sales. Notably, these three channels will provide the business with the most accessible and effective primary and secondary markets5. Additionally, competitive pricing strategies where prices slightly below other local premium wineries will be applied to these new products in order attract younger generation among other wine consumers6. Finally, profit generation and maximizing of profit will be achieved through the analysing of different operational costs to ensure that the company will be generating a modest profit to cover all its expenses. To start the operation of the company, Virginia’s winery will need a long-term loan that will be operated in line with credit as the amount that will help cover the start up operational costs of the winery. By the ninth year of operation, the Winery will get switched to a net income corporation. At this point, the management will establish customer based

International Involvement Paper Essay Example | Topics and Well Written Essays - 750 words

International Involvement Paper - Essay Example In principle, each state must mind its own business and must respect the business of other independent states. However, in practice, this was not as easy as it seemed because these states related to each other in matters of commercial, political, cultural or humanitarian interests. Pickett (p. 13-14) added that the educational training and mental biases of historians of international relations affected their analysis of how America’s government behaved during the period. Pickett’s short article covered the whole period from the success of the American Revolution in the late 18th century to the collapse of the Soviet Union in the late 20th century. Having gained independence from England, the young American state continued to be concerned with the matter of how to guarantee its survival against European nations that were always intent on imperialism or the expansion of their respective empires through conquest. Newly independent from imperialist England, America faced a quandary throughout most of the nineteenth century that touched on the young state’s conscience: since conquest meant having to go against the freedom of other peoples and their governments, how could America justify its involvement in international affairs that may involve going to war? Pickett (1992, p. 14) cited the importance of the Monroe Doctrine as â€Å"the first and – in the nineteenth century – the most important American diplomatic principle. Through the Doctrine the United States first asserted interests in the Western Hemisphere.† The Monroe Doctrine, based on an 1823 Congressional address by President James Monroe, called for U.S. indifference to European affairs and for European powers not to interfere in the Western Hemisphere or the Americas. Thus, until the late nineteenth century, America’s policy was not to engage other nations, i.e., to be internationally isolationist. Several events in the