Shiseidos Brief History Essay Example for Free

Shiseidos Brief History Essay In 1902, Arinobu was inspired to introduce the American culture to the Japanese public by bringing the Japan’s first soda fountain. The fortune was on his side as it later grew into the Shiseido Parlour restaurant business which makes him introduce another rare production in Japan at the time, ice cream. The foundation of Shiseido laid over a century ago, its pioneering spirit that combines eastern aesthetics with western science and business technology, continues to live on today to serves as the underlying philosophy of Shiseido’s corporate activities. Shiseido established it Five Management Principles in 1921. Quality First: Shiseidos constant quest for the highest possible quality standards has supported its activities for close to a century. Coexistence and Co-prosperity: Shiseido seeks to share its benefits with all companies and individuals associated with Shiseido. Respect for Consumers: Shiseido pursuits must be thoroughly consumer-oriented. Corporate Stability: Shiseido must be built on a firm infrastructure with long-range goals. Sincerity: Shiseido business transactions must be conducted loyally, honestly, and respectfully. In 1923, Shiseido began forming its chain store network. To meet its five management principles, the storeowners were provided special training to assure that consumers across the nation could enjoy products and service of consistent high standards. With their high spirit and commitment, the network has grown to approximately 25,000 outlets today. On June 14th of 1927, Shiseido, formerly a limited partnership, became a joint stock company under Arinobu Fukuhara’s third son, Shinzo’s leadership. Shiseidos first president, Shinzo Fukuhara graduated from Columbia Universitys Faculty of Medicine. During his stay in the United States, from 1908, he worked at a suburban New York drugstore and later a cosmetics factory of an American pharmaceutical manufacturer. Under his leadership, the groundwork for a distinctive Shiseido approach to business and creation was formed. To serve Shiseido’s loyal customers better, they have formed the Camellia Club in 1937. Corresponding with formation of the club, Shiseido issued a fashion periodical, HANATSUBAKI (Camellia). The magazine takes its roots from Japan’s first cultural magazines by a cosmetics company, which were issued by Shiseido from 1924 for distribution to customers through the nationwide network of chain stores. This magazine offered articles on domestic and overseas fashion, travel, and the arts. Essays and commentaries by leading literary figures of the time were also featured in this magazine, which is still issued on a monthly basis by Shiseido today. The Japanese Camellia Club has grown to boast a membership of approximately 9 million members presently. In the year of Malaysia’s independence, 1957, Shiseido has taken their first step overseas in Taiwan with exports to Singapore and Hong Kong following closely after. In 1962, Shiseido expanded to Hawaii and in 1965; it established Shiseido Cosmetics America to commence sales in the mainland. European sales began with Italy in 1968 and officially in Oceania with New Zealand in 1971. Stepping into 1980’s, Shiseido has realized the importance of brand image and Serge Lutens from France was being appointed as its international image creator in order to support its expanding global distribution network. Shiseido’s history of advertising and image creation has always been one of evolution and renewal. When Shiseido sought new global imagery for its international marketing it turned in an entirely advanced direction, that of a collaboration with Serge Lutens who established a reputation as a hair and makeup artist for Vogue. As we can see from the brief background of Shiseido in the early years, they have diversified their business from pharmacy to restaurant and gradually into cosmetics and toiletries. Today, Shiseido sales are mainly generated from its main business category of cosmetics, which makes up about 78. 4% of total sales with toiletries at 10. 7% and other categories such as salon, products, foods and pharmaceuticals at 10. 9%. 26% of total consolidated sales were generated by Shiseido’s international activities in fiscal year 2004. Individual shareholders constitute more than 97% of the total number of shareholders, an exceedingly high percentage for a major Japanese company. Marketing its products in 65 countries and regions globally including Europe and Americas as well as Asia/Oceania, Shiseido aims to become â€Å"a global player representing Asia with its origins in Japan. † To become a â€Å"global player†, Shiseido has taken the international business challenges integrating with the operations performance objectives into their global operations in the early years. Reviewing their 5 management principles written in 1921, it was pretty similar with the operation performance objectives in trend today.

Mycobacterium Marinum Treatment Literature Review

Mycobacterium Marinum Treatment Literature Review Abstract Background Mycobacterium marinum is an atypical mycobacterium that can be found in water environment. It is the agent of a characteristic skin disease known also as fish tank granuloma. In some occasions it can spread as a nodular lymphangitis, extend to deep structures as well as in exceptional cases disseminate systemicaly . The infection is adquired after contact with fish or contaminated water mainly from aquaria or swimming pools. Although the real incidence is understimate, it is a uncommon infection that needs high clinical suspicion to be diagnosed. As a consequence, delay in the diagnosis is common. Mycobacterium marinum is intrinsically a multidrug resistant mycobacterium.There is no clear consesus in the management of this infection. Usually it is managed either with monotherapy or with combination of antibiotics plus surgery in selected cases. Methods Retrospective study of cases of fish tank granuloma collected from 2000 to 2009 in the dermatology surgery of The Hospital of Tropical Diseases (HTD) of the University College London Hospitals. Systematic review of the literature with the terms Mycobacterium marinum and fish tank granuloma from 1999 to 2009. Results From the HTD dermatology surgery were collected 7 cases. Identification of M. marinum was possible only in 5. The response to treatment was good at least in 5 of them. In the literature review there were reported a total of 516 cases. From those 133 could be analyzed as individual cases. Identification was possible in 89.5% of the cases. Cured was reported in 82% of the cases. Conclusion The key of the diagnosis is to collect accurately the history of exposure. Histology, although no pathognomonic, will rise the suspicion if granuloma formation are found and will facilitate the differential diagnosis. Identification is done after culture with classical biochemical tests. Molecular biology techniques have the advantage of accelerate the procedure. There is not enough evidence to propose any specific treatment. Currently, recommendations are based in experts opinions. A prospective, randomized controlled clinical trial would be valuable to propose a base evident treatment. Contents Pages Introduction M. marinum is an environmental atypical mycobacterium ubiquitous in fresh, salt, and brackish water. It is known that infects temperate and tropical species of fish of at least 150 species, including ornamental fish. But also affects frogs, eels, oysters, aquatic mammals, toads and snakes [2, 11]. It cause tuberculosis-like disease in fish, its natural host [129]. The infection in fish has an average incubation period of 3 months. It affects viscera and produce anorexia with emaciation, skin defects, distension of the abdomen, being cause of sudden death [11, 12, 66]. In 1904, Alexander described for first time lesions in a cod fish that were associated with acid fast bacilli. But it was Aronson in 1926 that isolated the bacteria from tubercles of fish that died in an aquarium of Philadelphia. He described the bacilli as acid fast, chromogenic, pleomorphic and growing best at 18 º-20 ºC. Aronson suggested the name of Mycobacterium marinum [130]. M. marinum is as well the causative agent of the human disease called fish tank granuloma, also known as swimming pool granuloma or fish fancier ´s finger syndrome. In 1951 Norden and Linell reported for the first time the human disease in a swimming pool outbreak in ÃÆ'–rebro, Sweden. They described the lesions as chronic papulous ulcerations, usually located in the elbows. The pathogen was isolated from the walls of that swimming pool as well as from the lesions of the patients. They called the pathogen isolated Mycobacterium balnei [131]. It was not until 1959 when Bojalil demonstrated that M. marinum and M. balnei were in fact, the same mycobacterium [132]. M. marinum is the most frequent cause of skin infection among the environmental mycobacterium that affects humans [86, 133]. Nowadays the frequency of human infections is mainly sporadic. But in the past, outbreaks related with swimming pools were not uncommon [134]. As an example, one of the biggest epidemics was in Glenwood springs pool, Colorado in 1956 with 262 cases reported [135]. That was before chlorination became a common practice. Chlorination makes water safer. As was seen recently in Bologna, were water from swimming pools were free of M. marinum. But still could be isolated in 4.5% of the samples from the shower floor of the same [136]. The real global incidence of the disease is not know because the number of cases are underreported, due probably to the difficulties in the diagnosis [94]. It is world wide distributed but with a tendency to aggregate geographically [137]. Like in Chesapeake bay, Maryland, where there is an incidence of 4 cases per 100000 population per year [138]. Meanwhile in California was estimated in 0.27 cases per 100000 adults [139]. Or in Satowan, Micronesia, with an estimated prevalence of 10% of the population [115]. Apparently the global annual incidence remains small and stable [140]. Even though an increase number of reported cases has been noticed in The United States, going from an average of 40 cases per year in the 80s to an average of 198 cases per year in the 90s [141]. What seems clearer is that differing from other atypical mycobacteria the prevalence of M. marinum has not increased with the HIV epidemic [140]. Opposite to humans, the incidence in fish is increasing in hatchery fish, probably due to the high population density of fish. Transmission is possible fish to fish and between fish and amphibians. In addition it has been proposed transmission through eggs and through practice of feeding fish with fish carcasses [140]. There are 2 groups or clusters of M. marinum with different pathogenicity. Cluster I is characterized by producing acute disease and death in fish and also for affecting humans. On the contrary, cluster II only affects fish producing the classical chronic disease with granuloma formation [9]. This is also supported by a study done in Israel were it was seen that only certain strains of M. marinum affected humans. They also demonstrate that in Israel strains affecting humans came from ornamental fish and not from local fish for consumption [5]. The mode of transmission to humans is mainly waterborne and fish borne. Person to person transmission has not been documented [137]. However, It has been described indirect transmission via fomites in at least 3 cases. Two very small children and one infant who acquired the infection after bathing in containers that were previously used to clean the family fish tanks of tropical fish [27, 40, 142]. As other environmental mycobacterium, M. marinum has commonly low pathogenicity. For this reason in normal conditions only affects disrupted skin [8]. The main risk factor to contract the infection consists in having lesions or abrasions in the skin with exposure to non chlorinated water or marine animals infected [140]. The most frequently nowadays is the exposure to private aquaria. But some times the source of exposure is unknown. As a consequence, after the description of cases following injuries with plants, it has been suggested the possibility that could be other reservoirs different from water and fish. Although at the present moment this possibility has not been demonstrated [30, 43]. The incubation period is usually 3 to 4 weeks [135]. Following, the most common manifestation is a cutaneous lesion at the site of inoculation. It initiates as a solitary nodule or pustule that eventually evolutes to an ulcer , abscess or verrucous plaque [143]. It affects more frequently the extremities, probably because the pathogen grows better at low temperatures [144]. The severity of the disease depends, among other factors, on the number of microorganisms inoculated [134] In 20% of the cases the cutaneous lesions spread along ascending lymphatic vessels. This is called sporotrichoid spread or nodular lymphangitis [143]. As a result of direct extension invasion of deep structures as tendons, articulations and bones occurs in 29% of the cases [144]. Systemic dissemination is unusual but has been described in immunocompromised patients [140]. Spontaneous resolution , usually with scaring , has been documented from months after the infection up to 2 years [133, 135]. The diagnosis is based on the history of exposure and risk factors along with the characteristic clinical features. It is supported with histopathology, culture and bacteriological identification that in some cases require molecular biology techniques [94, 120]. The fact is that the diagnosis is not easy and in most of the cases is either delayed or remain being presumptive based in the history and response to treatment. The objective of the treatment is to increase the speed of resolution and prevent progression of the disease [1]. With this purpose different combinations of antibiotics plus the support, in selected cases, of surgery are the common practices in the treatment of this infection. Although the election of the drugs still depends of the preference of individual authors and is not based on controlled evidence [143]. Aims and Objectives The overall aim of the project is to determine the current state of evidence for the diagnosis and treatment of M. marinum infection. Being the specific objective to review the literature and the series of HTD cases with the purpose of suggest appropriate diagnosis and case management of Mycobacterium marinum infection. Material and Methods Cases with diagnosis of fish tank granuloma were review. The cases were diagnosed and treated from 2000 to 2009 in the dermatology surgery of The Hospital of Tropical Diseases of the University College London Hospitals. There were included patients with either culture positive for M. marinum or clinical diagnosis plus response to appropriate treatment. The files of those patients were reviewed and data were collected in a questioner that included: anthropological data, past medical and drug history, risk factors and exposure, description and location of the lesions, spread or deep extension of the infection, incubation period , delay in diagnosis, diagnosis, treatment and evolution (see questioner in annex). Additional information considered relevant was as well collected. A literature review in Medline and Cochrane databases was done. The review included the combination of the following terms: Mycobacterium marinum or fish tank granuloma. It was limited to papers from 1999 to July 2009, English and Spanish literature and humans. The papers obtained in the search were divided in 3 categories. First, case reports in which it was possible to collect data from individual cases. Information of those papers was collected in the questionnaire previously mentioned. Second, case series of 14 or more cases in which data from individual cases was not reported. And finally, a miscellaneous category of papers that were considered relevant for the diagnosis and treatment of this infection. The information gathered in the questioners was computerized in Microsoft Excel 2007. No statistical analysis was done in view of the cases were publish not with this purpose. As a consequence probably important reporting bias would invalidate any statistical outcome. Simple description of the results was done. Results Cases of The Hospital of Tropical Diseases From 2000 to July 2009 there were collected 7 cases with diagnosis of Mycobacterium marinum infection. The 7 cases included 6 males and 1 female and their ages ranged form 31 to 65 years. All the cases admitted to have had contact with an aquarium. In two cases the exposure was occupational. One of them worked in the London Zoo being responsible of the management of the aquaria. The second was a cook in a restaurant that store crustacean in an aquarium. All the cases presented nodular lesions located in one of the upper limbs, six of them with sporotrichoid spread and one with a solitary nodule (see photos is annex). One patient that was taking oral prednisolone due to severe atopic eczema presented with tenosynovitis of the left hand, sporotrichoid spread and palpable regional lymphonodes. The rest of the patients were not immunosuppressed. Biopsy of the lesions was performed in all the cases. However AFB were found just in one case. Whereas cultures were positive in 5 cases for M. marinum. In the other two cases the diagnosis was done based on history of exposure, clinical characteristics and positive response to treatment. Different combinations of antibiotics were used with no clear advantage of any regimen in particular. In 4 patients it was need to change the regiment. The reasons were drug intolerance in one case and lack of improvement in the rest. There was also one case that initially was improving with a regimen of rifampicin plus minocycline. But after simplification of the regiment to clarithromycin monotherapy presented worsening of the lesions. This case was eventually controlled switching to minocycline plus ethambutol. There was one patient who presented a relapse after one year of the previous infection. Finally it was cured with 6 months of rifampicin plus clarithromycin. Susceptibility test was done in 3 cases. It was detected resistance to trimethoprim-sulfamethoxazole and rifampicin in one case and susceptibility to clarithromycin, ethambutol and doxycycline in 3 cases. The average time of duration of the treatment was 6 months with a range of 2 to 9 months. Surgery was not required in any patient. The final outcome was good in 5 patients being the other 2 lost of follow up (see table 1). Case No Age(y) /Sex Medical history Drug history Exposure Location Clinical characteristics Histology AFB results Culture Treatment Duration (months) Evolution 1 9/M No Aquarium Upper limb Multiple nodules sporotrichoid spread Granulomatous inflammation AFB + 1-RIF+DOX 2-RIF+EMB+DOX 3-RIF+EMB+CLR 7 Cured 2 61/F Psoriasis Chronic paronychia Aquarium Upper limb 3 nodules Sporotrichoid spread AFB + 1-MIN 2 Improving Lost of follow up 3 64/M No Aquarium Upper limb Multiple nodules Sporotrichoid spread Noncaseating granuloma 1-EMB+TET 2-RIF+EMB+INH 9 Relapse after 1year 3(*) 65/M Fish tank granuloma Aquarium Upper limb Multiple nodules Sporotrichoid spread 1-RIF+CLR 6 Cured 4 59/M Severe atopic eczema Systemic steroids Aquarium Upper limb Multiple nodules Sporotrichoid spread Tenosynovitis AFB + 1-DOX 2-RIF+EMB 3-RIF+EMB+CLR 4-ERI+MIN ? Lost of follow up 5 44/M No Aquarium Upper limb 5 nodules Purulent discharge Sporotrichoid spread Necrotizing granulomatous inflammation AFB- + 1-RIF+MIN 2-CLR 3-MIN+EMB 3.5 Cured 6 31/M No Aquaria (London Zoo) Finger Solitary nodule AFB + 1-CLR+EMB 4 Cured 7 49/M No Aquarium (Restaurant) Upper limb 5 nodules Sporotrichoid spread + 1-RIF+EMB 5 Cured (*) Notice that case number 3 is repeated. It belongs to the same patient that the one above but one year later. The patient presented a relapse after one year of being cured. Results from the literature review From 1999 to July 20009 there were found 233 results in Medline database and zero In Cochran Library. From those, 127 were considered relevant and consequently analysed in this review. From the 127 papers reviewed, 108 contained case reports and the 19 remaining were a miscellaneous of reviews or original articles covering issues related with diagnosis and treatment. No clinical trials or randomized control trials were found. In those years the literature reported a total of 516 cases of M. marinum infection. From those cases reported only 133 could be analyzed as individual cases. The rest of cases were reported as series of cases (See figure 1). The number of cases reported per year since 1999 up to July 2009 have been variable with a minimum of 6 cases per year in 2004 to a maximum of 88 cases in 2000. No clear tendency to increase neither decrease has been notice (see Figure 2). The majority of the cases have been reported in Europe, North America and South East Asia. No cases have been reported in Africa and only one case in South America (see Figure 3). Results from papers that could be analyzed as individual cases The reports included 82 men and 51 women. The average age was 46.7 years with a minimum of 18 months and a maximum of 87 years (see Figure 4). 70% of the patients had no relevant past medical history. 9% of the patients were immunosuppressed: 5 patients had HIV infection, 4 were recipients of solid organ transplant, 1 patient had a myelodisplastic syndrome, 1 had Non-Hodking Lymphoma and 1 had Chronic Lymphocytic Leukaemia. Among other relevant pathologies were reported 12 diabetic patients, 11 with rheumatic diseases and finally 5 that were suffering from other problems as: asthma, bullous pemphigoid, myasthenia gravis, Cronh ´s disease and sarcoidosis. The majority of the patients were not taking any relevant drug. However, 20 of them were on systemic steroids, 12 had received steroids as local injection, 10 took methotrexate and 9 TNF-blockers. The most frequent exposure referred was the contact with an aquarium usually of tropical fish, it was reported in 51% of the cases. It was followed in 26 cases (20%) by other kind of contact with fish mainly referred as contact while cooking or cleaning fish. Finally 16 cases (14%) had other kind of contact with water environment. That included mostly fishermen or recreational sailors. Opposite to papers from the 60s, only in 2 patients referred contact with swimming pools. In 15 cases (11%) the source of exposure was not recall or reflected in the papers. Injury related with plants was reported in 3 cases. In one case the exposure was a bucket. The bucket was used to bath a child of 18 months after being used to put fish from an aquarium. As a result the child got infected [40]. History of trauma with skin barrier impairment was referred in 46 cases (71%) of the patients. Among those, 18 cases (39%) recall direct injury with either fin fish, fish hook or crab bite. Occupational exposure was reported in 20 cases (15%). The most frequent occupational risk was to be cook and have injuries while cleaning fish. Another common job of high risk was to work in a pet shop, with the duty of cleaning aquaria. Finally fishermen are evidently in direct contact with water and fish and prone to suffer injures with fish hooks. The incubation period was documented only in 30 patients. It went from 1 day up to 4 months with and average of 48.9 days. The cases that presented an incubation period less than two weeks had in common to have suffered penetrating injuries with fish (figure 5). The upper limbs were affected in 120 case (90.2%), being the fingers the most frequent location. The lower limbs were affected in 11 cases (8.3%). The face in 7 cases (5.3%) and that included delicate locations as nostrils, eyelid and cornea. Finally, cutaneous dissemination was reported in 7 cases (5.3%). Sporotrichoid spread was found in 53 cases (39.8%). Lymphonodes affectation was recorded in only in 7 cases (5.3%) of the cases. The lesions were described as nodules in 63 cases (7%), plaques in 23 (17.35%), papules in 13 (9.8%) and ulcers in 22 (16.5%). There was purulent discharge in 32 cases (24.1%), as well as swelling and tenderness in 37 (27.8%) and 42 (72.4%) cases respectively. Involvement of deep structures was referred in 45 cases (33.8%) of the cases being the most frequent tenosynovitis with 34 cases (75.6%), followed by arthritis with 12 (26.7%) and osteomyelitis with 6 (13.3%). Systemic dissemination with documented bacteraemia was reported in 3 cases. The 3 of them were males from 66 to 87 years. In 2 cases the patients were on systemic steroids, due to myasthenia gravis[103] in one case and polymyalgia rheumatica[62] in the other. Sadly the third case that initially was not taking drugs, after being misdiagnosed as rheumatoid arthritis was put on systemic steroids, infliximab (TFN blocker) and methotrexate [59]. From the patients with invasive disease, including involvement of deep structures or systemic dissemination, 21 (46.6%9 were taken some kind of immunosuppressive drug. Meanwhile only 13 (15.5%) of the rest of the patients were taken them (see figure 6). Other interesting characteristic of the patients with invasive disease was that 15 (33.3%) of them referred direct fish injury. Only 3 (3.4%) of the rest had this exposure (see figure 7). Patients that for any reason were taken immunosuppressive drugs presented different characteristics from the rest of the patients. More than half of them presented invasive disease compared with only 20% of the rest (see table 2). Patients taking immunosuppressive drugs (*) Patients no taking any drugs Number of patients 36 91 Average age (years) 53.2 44.9 Female % 14 / 38.9% 36 / 39.6 % Sporotrichoid spread 13 / 36.1% 39 / 42.8% Involvement deep structures 21 / 58.3% 19 / 20.8% Systemic dissemination 3 / 8.3% 0 AFB positive 19 / 52.7% 33 / 36.3% Culture 33 / 91.6% 75 / 82.4% Bad evolution 2 / 5.5% 3 / 3.3% (*)Immunosuppressive drugs including: TNF-Blockers, systemic steroids, local injectable steroids, methotrexate and azathioprine. The time of evolution until the patients presented for consultation was as short as 4 days and as long as 18 years with an average of 8.6 months. The time until the diagnosis was finally done was only reflected in 17 patients. However the delay went from 21 days to 2 years with an average of 6.3 months. Tuberculosis skin test was only done in 19 patients. From those 86.4% were positive. Biopsy of the lesions was done in 120 cases (90.2%). Aspirate was reported only in 19 cases (1 4.3%). Histology characteristics suggestive of mycobacterial infection with granuloma formation were found in 45.5% of the biopsies. However, only 21% of those were described as caseating granulomas. Other frequent finding reported was mix infiltrates with chronic and acute inflammatory cells. In some cases a wrong diagnosis was done due to confusion with rheumatoid nodules, Sweetà ¢Ã¢â€š ¬Ã¢â€ž ¢s syndrome, foreign body granuloma or interstitial granuloma annulare (See table 3). Table 3: Histology Findings Histology description Number of patients Non caseating granuloma 19 Caseating granuloma 12 Granuloma( type not specified) 26 Infiltrates of chronic and acute inflammatory cells (lymphocytes , neutrophils, histiocytes) 18 Granulation tissue 6 Abscess formation 9 Necrotizing folliculitis 1 Focal dermal necrosis 3 Fibrinoid degeneration 1 Necrotizing paniculitis 2 Cystic degeneration 1 Pseudoepitheliomatous hyperplasia 4 Acute suppurative paniculitis 1 Fibrinous exudates 3 Lichenoid inflammation 1 Acanthosis in epidermis 2 Necrotic Corneal Stroma 1 Dermal fibrosis 2 à ¢Ã¢â€š ¬Ã‚ ¢ Pseudocarcinomatous hyperplasia of follicles à ¢Ã¢â€š ¬Ã‚ ¢ Nodular and perifollicular infiltrate of neutrophils and histiocytes à ¢Ã¢â€š ¬Ã‚ ¢ Dermal fibrosis à ¢Ã¢â€š ¬Ã‚ ¢ Collections of neutrophils within follicles 1 patient with lesions of 18 years evolution Confusion with other pathologies Rheumatoid Arthritis ( rheumatoid nodule) 2 Sweet ´s syndrome 2 Foreign body granuloma 2 Interstitial gra nuloma annulare 2 In the samples collected AFB was found in 41.7%, was negative in 34.6% and was not reported in 23.6%. In total identification of M. marinum was possible in 119 cases (89.5%). Culture was positive in 114 cases (85.7%). The time until the cultures grew went from 8 to 56 days, with an average of 23.3 days. Identification with PCR was done in 19 cases (14.2%). The imaging techniques were useful to diagnose extension of the infection. Radiographies were used in 25 cases (18.7%) to rule out bone involvement. Magnetic resonance imaging was used in 16 cases (12%) resulting in the diagnosis of tenosynovitis, abscess, join effusions or osteomyelitis. About the treatment, 126 patients were treated with antibiotics; in the rest of the cases the management is not mentioned. Surgery was need in 38 patients (84.4%) with affectation of deep structures and in 21 patients (25%)with cutaneous lesions. Monotherapy was used in 54 cases (42.8%), bitherapy in 38 cases (29.4%), triple therapy in 20 cases (15%) and combination of 4 or more drugs in 5 cases (4%). Finally combinations of drugs that included classical tuberculosis treatment were used in 10 cases (8.7%). In 41 patients the regimen of drugs needed to be change, either for non effectiveness or non tolerance. The regiment was change one time in 29 cases (21.8%), two times in 10 cases (7.5%), and up to 3 times in 2 patients (1.5%). The drug more frequently used as monotherapy was clarithromycin, followed by minocycline, doxycycline, ciprofloxacin and trimethoprim-sulfamethoxazole. The combinations of drugs more frequently used were rifampicin + ethambutol followed by clarithromycin + rifampicin and clarithromycin + ethambutol. (Effectiveness of the different regimens depending of the extension of the disease can be seen in table 4) Susceptibility test were reported in 34 patients. Rifampicin was susceptible in 86.4% of the test, ethambutol in 91.3%, clarithromycin in 95% and minocycline in 62.5%. Isoniazid was resistant in 100% of the tests done and streptomycin in 66.6% (see table 5). The average time of duration of antibiotic treatment was 5.4 months, with a range of 12 days to 15 months. After completion of the treatment the final evolution of 109 patients (81.9%) was reported as good outcome or cured. Only in 8 patients (6%) the evolution was reported as bad outcome. No mention about the evolution was done in the rest of cases. Among 12 patients in which long follow up was reported, only one patient presented recurrence of the infection after 3 months course of doxycycline. (Characteristics of the cases with bad outcome are resumed in table 6. Table 4:: Antibiotic Combinations Used Depending On The Extension of The Disease Patients with only cutaneous lesions Patients with Invasive disease Number of patients Effectiveness Number of patients Effectiveness Monotherapy 38 52.5% 16 75% CLR 8 75% 5 100% MIN 10 70% 1 100% DOX 8 50% 1 100% CIP 4 25% 2 50% CTX 2 100% 3 33.3% AZI 3 0% 0 AMK 1 0% 0 ERI 0 1 0% LEV 0 1 0% MOX 1 0% 0 OFL 1 0% 2 50% Combinations of 2 drugs 26 92% 11 83.3% CLR + EMB 6 100% 2 100% CLR + CIP 1 100% 0 CLR + MIN 1 100% 0 CLR + RIF 5 80% 0 CLR +CTX 1 100% 0 RIF + EMB 9 100% 5 60% RIF + CTX 0 1 100% RIF + INH 0 1 100% CIP +DOX 1 100% 0 CIP + EIR 1 0% 0 DOX +CTX 0 2 100% CIP + EMB 1 100% 0 Combinations of 3 drugs 13 72.7% 7 66.6% CLR + EMB + CIP 0 1 0% CLR + EMB + RIF 2 100% 5 100% CLR + EMB +RFB 0 1 0% CLR +CTX + CIP 1 0% 0 EMB + AZI + MIN 1 0% 0 RIF + CLR + AMK 1 100% 0 RIF + INH + CLR 1 0% 0 RIF + EMB + CTX 5 100% 0 RIF + EMB + DOX 1 0% 0 RIF + EMB + MOX 1 0% 0 Combinations of > than 3 drugs 2 100% 3 33.3% CIP+RIF + EMB + CLR + RFB + AMK 0 1 100% CLR + DOX + RIF + EMB 0 1 0% RIF + EMB + CLR + AMK + IMP 0 1 0% RIF + EMB + AZ I+ CTX 1 100% 0 RIF + EMB + CLR + CIP 1 100% 0 Combinations with TB treatment 1 100% 9 55.5% INH + RIF + EMB + CLR 1 100% 1 0% INH + RIF + EMB 0 3 100% INH + RIF + EMB + PZA 0 4 50% INH + RIF + EMB + PZA + CLR 0 1 0% TABLE 5: PATTERN OF SUSCEPTIBILITY Drug Number of patients Susceptible Resistant Indeterminate Isoniazid 9 9 Rifampicin 22 19 3 Ethambutol 23 21 2 Pyrazinamide 1 1 Streptomycin 6 1 4 1 Rifabutin 2 2 Azithromycin 4 1 3 Clarithromycin 20 19 1 Minocycline 8 5 1 2 Doxycycline 6 6 Tetracycline 2 1 1 Trimethoprim-sulfamethoxazole 6 5 1 Ciprofloxacin 11 6 1 Levofloxacin 1 1 Moxifloxacin 4 4 Gatifloxacin 1 1 Amikacin 9 9 Linezolid 1 1 Imipenem 2 2 Erythromycin 2 1 1 Cefotaxime 2 1 1 Kanamycin 3 3 Ethionamide 3 3 Ansamycin 1 1 The table reflects in how many patients each drug was tested and in how many it resulted as susceptible, resistant or indeterminate. TABLE 6: CHARACTERISTICS OF CASES WITH BAD OR POOR OUTCOME References Age Sex Past medical history Type of infection Treatment Duration treatment (months) Evolution [25] 67/M DM Cutaneous disseminated RIF+EMB+CLR+CIP 3.7 Deceased Secondary bacterial infection [26] 50/M No Tenosynovitis RIF+EMB Synovectomy 3 Dysfunctional index finger [46] 62/F No Tenosynovitis CLR 4 debridements 6 Amputation index finger [46] 26/M No Tenosynovitis DOX+CTX 4 debridements 3.5 Persistent infection Need of grafting [73] 56/M No Tenosynovitis Local gentamicin Synovectomy 3 drainages ? Deformity [83] 47/M HIV infection Osteomyelitis 1-INH+RIF+EMB+PZA 2-Avobe + Fluoroquinolone 3-RFB+EMB+CIP 4-RFB+CIP ? Amputation Knee [88] 60/F NHL Systemic steroids Cutaneous disseminated 1-Ofloxacine 2-RIF+EMB+LEV+CLR 3-Above+STR+IG 4-CTX+MOX ? Continue with signs of active infection [103] 81/M Myasthenia gravis Systemic steroids Cutaneous and systemic dissemination 1-CIP 2-Hyperthermia 3-DOX intravenous 5 Deceased Bone marrow infected by M.marinum Results from papers that contain series of 14 or more cases There were 14 papers that contained series of cases with no available information of individual cases. As a consequence, individual cases could not be analyzed separately. There were 2 papers that reported the same series of cases in different years, the cases were counted just once. The principal characteristics of the papers are described in the table 7. There were 363 cases reported, 68% were males with an average of 44.3 years. In most of the cases the past medical history was not relevant; only 4 cases of HIV infection were reported. The most frequent exposure was to own an aquarium in 134 cases (37%). There was other kind of contact with fish in 37 cases (10%), swimming pool contact in 7 cases (2%) and other kind of contact with water in 58 cases (16%). In the rest of cases exposure was not mention. Finally occupational exposure was referred in 68 cases (19%). The incubation period was not reported. The upper limbs were affected in 245 cases (67%), the lower limbs in 78 cases (21%), the face in 3 cases (0.8%) and there was cutaneous dissemination in 10 cases (3%). Sporotrichoid spread was reported in 46 cases (12%). The lesions were described as plaques in 92 cases (25%) and nodules in 54 cases (15%). Deep structures were affected in 45 cases (12%): 41 tenosynovitis (91%), 8 arthritis (18%) and 3 osteomyelitis (6%). There were no cases of systemic dissemination described in any of the series. The average in the delay until the diagnosis was done was 3.8 months. The drugs more commonly used as monotherapy were doxycycline, minocycline, trimethoprim-sulfamethoxazole and clarithromycin. The combinations more prescribed were rifampicin plus ethambutol, rifampicin plus clarithromycin and clarithromycin plus ethambutol. The effectiveness of the treatments were not frequently reported. Consequently is not possible to point the advantage of any concrete regimen (see table 8). The average duration of the treatment was 5 months. Surgery was reported in 73 cases (20%). The evolution was good in 225 cases (62%), poor in 15 cases (4%) and not mention in the rest. There were 5 papers that contained series of cases of atypical mycobacterial infecti

Tom Sawyer Essay -- essays research papers

AN IMAGINATIVE AND MISCHIEVOUS BOY named Tom Sawyer lives with his Aunt Polly and his half-brother, Sid, in the Mississippi River town of St. Petersburg, Missouri. After playing hooky from school on Friday and dirtying his clothes in a fight, Tom is made to whitewash the fence as punishment on Saturday. At first, Tom is disappointed by having to forfeit his day off. However, he soon cleverly persuades his friends to trade him small treasures for the privilege of doing his work. He trades these treasures for tickets given out in Sunday school for memorizing Bible verses and uses the tickets to claim a Bible as a prize. He loses much of his glory, however, when, in response to a question to show off his knowledge, he incorrectly answers that the first two disciples were David and Goliath. Tom falls in love with Becky Thatcher, a new girl in town, and persuades her to get â€Å"engaged† to him. Their romance collapses when she learns that Tom has been engaged before—to a girl named Amy Lawrence. Shortly after being shunned by Becky, Tom accompanies Huckleberry Finn, the son of the town drunk, to the graveyard at night to try out a â€Å"cure† for warts. At the graveyard, they witness the murder of young Dr. Robinson by the Native American â€Å"half-breed† Injun Joe. Scared, Tom and Huck run away and swear a blood oath not to tell anyone what they have seen. Injun Joe blames his companion, Muff Potter, a hapless drunk, for the crime. Potter is wrongfully arrested, and Tom’s anxiety and guilt...

Comparing The Adventures of Huckleberry Finn and A&P :: comparison compare contrast essays

Huck Finn and A+P Â   In the novel Huckleberry Finn, Huck goes through many adventures on the Mississippi River. He escapes from Pap and sails down a ways with an escaped slave named Jim. Huck goes through a moral conflict of how wrong it is to be helping Jim escape to freedom. Eventually Huck decides he will go against what society thinks and help Jim by stealing him from a farmer with the help of Tom Sawyer, a friend. In A+P the young man, Sammy, is confronted with an issue when he sees his manager expel some girls from the store he worked in simply because of their defiance to its dress code. In his rebellion against the owner, the boy decides to quit his job and make a scene to defend the rights he feels are being violated. In these stories, both the boys are considered superior to the authority that they are defying because of the courage that it took for Huck to free Jim, and for Sammy to quit his job for the girls because it was what they believed in. Â   Why would anyone in his or her right mind even think about freeing a slave? Everyone in the society was telling Huck that slaves were no more than ones property, but Huck began to question this belief when he got to know the property for who it really was. During the story there are many times when Huck feels an obligation to turn Jim in to the authorities and just get on with his life, but his conscience kept telling him that this man is a real person. Near the end of the story, Jim was stuck in a holding cell, since he had run away. After much consideration of the situation, Huck decides that he wants to free Jim because he believes that he shouldn't be treated that way. Even though the entire town believes that Jim should be contained and treated like property, Huck still sticks to his morals and goes along with the plan that could get him in trouble or even killed. At the end of the story we find out that Jim had always been free, and we now find Huck's actions to be heroic and noble.

Major Market Structures Essays -- Economics

During the initial phase of starting up a business, there are many factors to weigh in. If you desire a particular kind of lifestyle, then one of the major factors to consider is what kind of market you would like to be in. There are four major market structures, perfect competition, monopolistic competition, oligopoly, and monopoly. All of these markets have positive and negative attributes, including but not limited to, barriers to entry, how many sellers are in a particular market, and the stress of running a business while keeping a keen eye on product pricing. Many entrepreneurs may not want to agonize over anything at all, and participate in a perfect competition market where they know exactly what the prices are and what they expect to make at all times. Then there are some investors that enjoy the competition and would rather be in a monopolistic competition market. However, it’s no secret that the majority of the public, if given the absolute choice, would choos e to be in a monopoly. This kind of market of course, is very hard to acquire, so a very fine choice would be an oligopoly. Both a monopoly and an oligopoly are at the top of the list as far as profit is concerned. No matter which market one chooses to participate in, they all have similar goals, and that is to minimize costs and maximize profits. In a monopoly, there is only vendor with a product or service, meaning there are no close substitutes, so there is no competition to be concerned about and the barrier for others to enter is virtually inaccessible. One may have an exceptionally large control on the market, and can also dictate it as much as they would like, other than being limited by market demand, depending on the elasticity of one’s product... ...& 211†. Mason, OH. : CENGAGE Learning. Bade, Robin; Michael Parkin (2001). â€Å"Foundations of Microeconomics†. Boston, Massachusetts. : Addison-Wesley. Colander, David (2008). â€Å"Microeconomics, 7th Edition†. New York, NY. : McGraw-Hill Paperback. Eaton, B. Curtis; Eaton, Diane F.; and Douglas W. Allen (2002). â€Å"Microeconomics, 5th Edition†. Saddle River, NJ. : Prentice Hall. Frank, Robert A. (2006). â€Å"Microeconomics and Behavior, 6th Edition†. New York, NY : McGraw-Hill/Irwin. Mankiw, N. Gregory. (2000). â€Å"Principles of Microeconomics, 2nd Edition†. Oklahoma City, OK. : South-Western Pub. Pindyck, Robert S.; and Daniel L. Rubinfeld. (2008). â€Å"Microeconomics, 7th Edition†. Saddle River, NJ. : Prentice Hall. Ruffin, Roy J.; and Paul R. Gregory. (2000). â€Å"Principles of Microeconomics, 7th Edition†. Boston, Massachusetts. : Addison-Wesley.

Frankenstein Research Paper

Anastasia Shevchenko Professor Patricia Barker English 1302 15 November 2013 Frankenstein In Marry Shelleys Frankenstein, Victor and the monster share similar nature. Throughout the story, Victor Frankenstein and his creation share hatred towards one another. The two characters have the same objective that they are trying to achieve. They each not only value their learning through reading, but appreciate the natural world to help them cope, and have a craving for revenge when they feel it is necessary. While reading the story, the reader can see similarities betweenFrankenstein and the monster's eagerness for knowledge, gratefulness for nature, and devotion for revenge. As a young boy Frankenstein enjoyed learning new things. Victor's determined character was what begins his disintegration. In Victor's younger days, he enjoyed reading the books of Cornelius Agrippa. After reading these books, Victor had a different view of the world. Victor's parents thought that he should attend the University of Ingolstadt to expand his cultural knowledge, although Victor at the time was attending the schools of Geneva. When I had attained the age of seventeen, my arents resolved that I should become a student at the University of Ingolstadt. I had hitherto attended the schools of Geneva; but my father thought it necessary, for the completion of my education, that I should be made acquainted with other customs than those of my native country' (Shelley 25). This inspired the young Victor to attend the University of Ingolstadt to study science. â€Å"His mother's death causes him to delay his departure by many months, but once at the university, Victor spends two years studying chemistry under the direction of M. Waldman and M. Krempe† (Guyer).In addition, the monster himself enjoyed to learn new things. From the very first day of being created, the monster had a desire to understand the way the world worked. Just as Victor had once done, the monster came upon three book s. The Sorrows of Werter, a volume of Plutarch's Lives, and Paradise Lost were the three books that helped the monster open up his mind to the knowledge that these books had to offer him. â€Å"l learned from Werter's imaginations despondency and gloom: but Plutarch taught me high thoughts; he elevated me above the wretched sphere of my own reflections, to admire and love the heroes of past ages†¦But Paradise Lost excited ifferent and far deeper emotions† (89-90). These books shaped how the monster viewed the world around him. The monster did not only learn through reading but from the cottagers as well. â€Å"It impressed me deeply. I learned, from the views of social life which it developed, to admire their virtues, and to deprecate the vices of mankind† (88). Victor and his creation both had the passion for learning; this is what would eventually lead to their destruction. Similar to Victor, the monster appreciated nature.They both enjoyed the views of nature; it had the effect to be able to calm them down in the awful situations. After he murder ot Victor's son, William, Victor still tound peacetulness upon looking at the mountains. â€Å"Dear mountains! My own beautiful lake! how do you welcome your wanderer? Your summits are clear; the sky and lake are blue and placid. Is this to prognosticate peace, or to mock at my unhappiness? † (55). â€Å"The call–a version of the lyric gesture of addressing the earth with the assumption that it can respond– establishes a relation of nativity and origination: Victor is the mountains' as they are his.He identifies the calm landscape as a response, but an enigmatic response that he is unable to interpret† (Guyer). Also, after gazing out the window for hours Victor â€Å"felt the silence, although I was hardly conscious of its extreme profundity' (120). â€Å"The sublime mountainscape gives Victor a feeling of potential freedom and of mastery; however, in order to live t hat freedom he will have to free himself from the dead who haunt him, a freedom that may be possible only in death. Victor calls upon the dead and presents them with an alternative–give me happiness or death† (Guyer).Victor's creation always lived alone, and in that state of loneliness he found comfort in the natural environment he resided in. Soon after the creature was created he had a ifficult time remembering the original era of his being. All of a sudden â€Å"a strange multiplicity of sensations seized me, and I saw, felt, heard, and smelt, at the same time†¦ † (70). At first, the monster was surprised when spring came and he saw nature begin to bloom. His senses heightened and became revived. â€Å"It surprised me, that what before was desert and gloomy should now bloom with the most beautiful flowers and verdure.My senses were gratified and refreshed by a thousand scents of delight, and a thousand sights of beauty' (80). Victor and the creature shar ed a love for nature and the way it could soothe them. While loneliness filled their hearts and souls, Victor and the monster both turned to nature for refuge. As the reader gets deeper in to the story, one begins to notice that both Victor and his creation were filled with a voracious reprisal. After the monster found victor in his room he was filled with anger miou have destroyed the work which you began; what is it that you intend? † (120).In addition, the monster asked â€Å"endured incalculable fatigue, and cold, and hunger; do you dare destroy my hopes? † (120). Subsequent to the monster braking in to Victor's room and escaping in his own boat, Victor was filled with rage. The night passed away, and the sun rose from the ocean; my feelings became calmer, if it may be called calmness, when the violence of rage sinks into the depths of despair† (121). One main event that started the quench for the undying hatred and sorrow was the death of Victor's son, Willia m. The monster decided to give the humans one last chance.When he stumbled upon a child, â€Å"suddenly, as I gazed on him, an idea seized me, that this little creature was unprejudiced, and had lived too short of a time to have imbibed a horror of deformity' (100). Soon after his encounter with the child, the monster realized that the young boy was Just like veryone else he has met. â€Å"Hideous monster! Let me go; my papa is a Syndic-he is M. Frankenstein-he would punish you. You dare not keep me† (100). The creature also learned that the child he gave one last chance to was the son of Victor Frankenstein. â€Å"Frankenstein! ou belong then to my enemy-to him towards whom I have sworn eternal revenge; you shall be my first victim† (100). Soon after the creature strangled the child, he saw something on his chest, it was a picture of a beautiful woman â€Å"For a few moments I gazed with delight on her dark eyes, fringed by deep lashes, and her lovely lips; but pres ently my rage returned:† (100). This is when the monsters downfall began. â€Å"It is thus that, too often in society, those who are best qualified to be its benefactors and its ornaments, are branded by some accident with scorn, and changed, by neglect and solitude of heart, into a scourge and a curse† (Shelley).The creation wanted revenge on Victor because he felt neglected and abandoned. â€Å"Frankenstein's moral failure is his heedless pursuit to know all that he might about life without taking any responsibility for his acts. His â€Å"sin† is not solely in creating the monster, but in abandoning him to orphanhood at his birth† (Griffith). As a result, the ctions of the two characters in the course of the novel become very apparent to the reader that both Victor and his creation live for revenge.After reading the literature the reader can effortlessly identify the similar characteristics between Victor Frankenstein and his creation. They both had the desire to expand their knowledge and learn new things. Each one of them read different books that changed the way they viewed the world. They were each mesmerized by the world's natural beauty and what it could bring them. Victor and his creation both turned to nature that helped them during the most gloomy time. Even though they were able to see the beauty in the world, each one of them had a dark side.Victor abandoned his creation right after he was created. The monster himself later killed a lot of people do to neglect. They both sought revenge. Victor wanted to kill the monster for destroying his family, the monster after being neglected by his creator and all the people he had met, decided he wasn't going to give the human raise another chance after being rejected by the little boy who he thought was unprejudiced. With as many differences that Victor and the monster have, knowledge, nature, and revenge will always be common factors that they hare.

The Vampire Diaries: The Awakening Chapter Sixteen

Elena hurried toward Robert E. Lee, feeling as if she'd been away from it for years. Last night seemed like something from her distant childhood, barely remembered. But she knew that today there would be its consequences to face. Last night she'd had to face Aunt Judith. Her aunt had been terribly upset when neighbors had told her about the murder, and even more upset that no one seemed to know where Elena was. By the time Elena had arrived home at nearly two in the morning, she had been frantic with worry. Elena hadn't been able to explain. She could only say that she'd been with Stefan, and that she knew he had been accused, and that she knew was innocent. All the rest, everything else that had happened, she had had to keep to herself. Even if Aunt Judith had believed it, she would never have understood. And this morning Elena had slept in, and now she was late. The streets were deserted except for her, as she hurried on toward the school. Overhead,, the sky was gray and a wind was rising. She desperately wanted to see Stefan. All night, while she'd been sleeping so heavily, she'd had nightmares about him. One dream had been especially real. In it she saw Stefan's pale face and his angry, accusing eyes. He held up a book to her and said, â€Å"How could you, Elena? How could you?† Then he dropped the book at her feet and walked away. She called after him, pleading, but he went on walking until he disappeared in darkness. When she looked down at the book, she saw it was bound in dark blue velvet. Her diary. A quiver of anger went through her as she thought again of how her diary had been stolen. But what did the dream mean? What was in her diary to make Stefan look like that? She didn't know. All she knew was that she needed to see him, to hear his voice, to feel his arms around her. Being away from him was like being separated from her own flesh. She ran up the steps of the high school into the nearly empty corridors. She headed toward the foreign-language wing, because she knew that Stefan's first class was Latin. If she could just see him for a moment, she would be all right. But he wasn't in class. Through the little window in the door, she saw his empty seat. Matt was there, and the expression on his face made her feel more frightened than ever. He kept glancing at Stefan's desk with a look of sick apprehension. Elena turned away from the door mechanically. Like an automaton, she climbed the stairs and walked to her trigonometry classroom. As she opened the door, she saw every face turn toward her, and she slipped hastily into the empty desk beside Meredith. Ms. Halpern stopped the lesson for a moment and looked at her, then continued. When the teacher had turned back to the blackboard, Elena looked at Meredith. Meredith reached over to take her hand. â€Å"Are you all right?† she whispered. â€Å"I don't know,† said Elena stupidly. She felt as if the very air around her was smothering her, as if there were a crushing weight all around her. Meredith's fingers felt dry and hot. â€Å"Meredith, do you know what's happened to Stefan?† â€Å"You meanyou don't know?† Meredith's dark eyes widened, and Elena felt the weight grow even more crushing. It was like being deep, deep under water without a pressure suit. â€Å"They haven't†¦ arrested him, have they?† she said, forcing the words out. â€Å"Elena, it's worse than that. He's disappeared. The police went to the boarding house early this morning and he wasn't there. They came to school, too, but he never showed up today. They said they'd found his car abandoned out by Old Creek Road. Elena, they think he's left, skipped town, because he's guilty.† â€Å"That's not true,† said Elena through her teeth. She saw people turn around and look at her, but she was beyond caring. â€Å"He's innocent!† â€Å"I know you think so, Elena, but why else would he leave?† â€Å"He wouldn't. He didn't.† Something was burning inside Elena, a fire of anger that pushed back at the crushing fear. She was breathing raggedly. â€Å"He would never have left of his own free will.† â€Å"You mean someone forced him? But who? Tyler wouldn't dare-† â€Å"Forced him, or worse,† Elena interrupted. The entire class was staring at them now, and Ms. Halpern was opening her mouth. Elena stood up suddenly, looking at them without seeing. â€Å"God help him if he's hurt Stefan,† she said. â€Å"Godhelp him.† Then she whirled and made for the door. â€Å"Elena, come back! Elena!† She could hear shouts behind her, Meredith's and Ms. Halpern's. She walked on, faster and faster, seeing only what was straight ahead of her, her mind fixed on one thing. They thought she was going after Tyler Smallwood. Good. They could waste their time running in the wrong direction. She knew what she had to do. She left the school, plunging into the cold autumn air. She moved quickly, legs eating up the distance between the school and the Old Creek Road. From there she turned toward Wickery Bridge and the graveyard. An icy wind whipped her hair back and stung her face. Oak leaves were flying around her, swirling in the air. But the conflagration in her heart was searing hot and burned away the cold. She knew now what a towering rage meant. She strode past the purple beeches and the weeping willows into the center of the old graveyard and looked around her with feverish eyes. Above, the clouds were flowing along like a lead-gray river. The limbs of the oaks and beeches lashed together wildly. A gust threw handfuls of leaves into her face. It was as if the graveyard were trying to drive her out, as if it were showing her its power, gathering itself to do something awful to her. Elena ignored all of it. She spun around, her burning gaze searching between the headstones. Then she turned and shouted directly into the fury of the wind. Just one word, but the one she knew would bring him. â€Å"Damon!† [The End]