Secondary Malignancies in Pediatric Population

Secondary Malignancies in Pediatric Population Secondary malignancies in pediatric population: a case series and literature review Introduction Advances in medical care therapies and early diagnosis has fulfilled the hope for normal life expectancy in many cancerous patients with a 5 year survival rate for at least 75% in childhood (1). Although expecting 70% long-term survive in children with diagnosed cancer, 60-70% of them will develop a consequential disability by the primary cancer treatment as a cost(2). Development of second cancer (a new cancer following the first after a complete treatment , whether the onset is in childhood or as an adult, however histologically different from the origin) is a grieving expected side- effect embracing 6% of all diagnosed cancers in Unites states (3), as a result of the carcinogenic effects of chemotherapy drugs and radiation on both normal and cancerous cells (4). When major risk factors for developing the secondary malignancies in childhood survivors such as the primary origin, early diagnosis , onset age, duration of therapy , dose received and familial history of the cancer are c onsidered , radiation associated solid tumors as well as hematologic malignancies account for the most probable types in secondary cancers (5-8). Despite the excellent prognosis for long-term survival in childhood acute lymphoblastic leukemia, retinoblastoma and Hodgkin lymphoma , radiation associated secondary solid tumors almost covers two-thirds of all cases in long term (4, 9, 10). The increased risk of the incidence persists for at least 30 years after the primary treatment of Hodgkin lymphoma (11). Chemotherapy agents, such as alkylating agents have been proposed to play role in secondary cancers incidence. Although studies in field of secondary cancers and their relationship with administered treatment protocols have been a field of interest for researchers, data regarding this topic is rather inconclusive because of variety of factors involved (12, 13). In present case series study, a series of pediatric secondary malignancies with different primary cancers and subsequent treatment protocol are presented. Methods: In this case series study, 11 samples were selected retrospectively from patients attending at Mahak Pediatric Cancer Treatment and Research Center (Tehran, Iran) from 2007 to 2016, who were diagnosed with a secondary cancer. All a patients had been already diagnosed with a primary cancer and had received standard treatment protocol of primary cancer. Clinical information was obtained by the authors or provided by referring physicians. Using patients records, past medical history, type of primary and secondary cancer including method of diagnosis, cumulative doses of cytotoxic drugs and treatment outcome was extracted. In case of any missing records, patients were contacted to acquire required data. All patients had already undergone required diagnostic modalities to diagnose malignancies properly. A literature search in Ovid, Medline and PubMed was carried out using the terms secondary cancer, chemotherapy and radiotherapy to provide enough material to discuss findings. A medical in formation scientist performed the literature retrieval and the initial screening of relevant studies. Statistical analysis was performed using SPSS version 16. Quantitative data was expressed as mean  ± standard deviation and frequency (percentage). Case history Patients primary malignancies type and administered therapy are shown in Table 1. Patients Secondary cancer type and features of therapy administered is shown in Table 2. Patients No.1 was a 15 years old girl, who presented with pain in buttocks when she was 4 years old, then following bone marrow biopsy. She was first diagnosed with Ewing sarcoma. During 1 year of treatment, She underwent VAC/IE (vincristine (VCR) + doxorubicin (ADR) + cyclophosphamide (CPA) alternating with ifosfamide (IF) + etoposide) regimen. This treatment protocol led to complete remission. After 1 year, during a routine laboratory test, elevated levels of white blood cell was detected. Following flow-cytometry and cytogenetic studies, pre-B cell precursor ALL diagnosis was confirmed, which was associated with central nervous system involvement according to lumbar puncture examination. During 3 years, she was administered with X regimen. Also, complete CNS prophylaxis protocol was also administered. Complete remission was confirmed for her after treatment. During 6 years of follow-up, she has not had any signs of relapse. Patient No.2 was a 12 years old boy, who attended clinic presenting with balance disorder. Following 24-hour urine catecholamine test and MIBG scan neuroblastoma diagnosis was made. He underwent OPEC regimen (vincristine, cisplatin, etoposide and cyclophosphamide) and daunorubicin, which led to remission. When he was 6 years old, in a routine laboratory test, elevated white blood cells were detected. Flow-cytometry studies indicated ALL(L1), so the patient was administered with standard regimen and intrathecal chemotherapy. This treatment led to complete remission. During 2 years of follow-up patients has no sign of relapse. Patient No.3 was a 14 year old, who had first presented with headache. Following imaging, meduloblastoma diagnosis was made. After 10 months of chemotherapy and radiation, patient had complete remission. Patient had a history of heart failure. Two years later, an elevated white blood cells were detected in complete blood count. Flow-cytometry studies revealed non-M3 AML. Despite chemotherapy, patient was expired after 12 days of treatment initiation. Patients No.4 was 12 years old girl, who presented with intermittent coughs. So, bronchoscopy was performed, which revealed small cell lung tumor. She underwent 4 months of chemotherapy , radiotherapy and pulmonary lobectomy. During this period, when she had been receiving chemotherapy for 3 months, she presented altered level of consciousness. Following lumbar puncture and cerebrospinal fluid flowcytometry AML diagnosis was made. She underwent CNS prophylaxis. Despite 3 months of treatment, patient was expired. Patient No.5 is a 21 year old girl, who first presented with right sided pre-orbital swelling when she was 12 years old. Following biopsy, histiocytosis X diagnosis was made. After treatment she was in complete remission, but two years later a brain CT scan revealed signs of disease relapse. when 15 years old, due to the elevated white blood cells count and flow-cytometry AML(M1) diagnosis was made. Although patient underwent 2 years of chemotherapy, she did not continue the treatment process, so she was lost to follow-up. Patient No.6 is a 13 year old girl, who was first diagnosed with retinoblastoma when she was 4 months old. She underwent VEC (vincristine+etoposide+carboplatin) chemotherapy protocol and radiotherapy. Enucleation was performed for both eyes when she was 2 years old. At last, patient had complete remission. When she was 11 years old, she attended clinic with right-sided face pain. After biopsy, osteosarcoma diagnosis was made. She underwent MAP protocol (High-dose methotrexate, cisplatin, and doxorubicin), ifosfamide and etoposide for 40 weeks. After complete remission, she has had no sign of relapse so far. Patient No.7 is a 12 years old boy, who was first diagnosed with actrocytoma grade II-III shown as a supratentorial mass in brain imaging which was confirmed by biopsy. Then, patient underwent PCV (lomustine + procarbazine + vincristine) plus temozolomide protocol and radiotherapy. After 6 courses of chemotherapy, patients underwent gross total resection of tumor. One year after complete remission, patient presented with backache. Biopsy indicated gliosarcoma. So far patient has undergone radiotherapy and surgery, also he is still going through chemotherapy. Based on the literature review, Discussion Based on information from the U.S. Surveillance Epidemiology, about 16 percent of cancers are in persons with a prior history of cancer. It is thought that the main point behind this phenomenon is that patients after treatment of cancer, patients live long enough to have second cancer (14). But as matter of fact, the cancer experience does not finish as treatment does. Cancer and the administered treatment (including radiation, chemotherapy, surgery, hormonal therapy, and newer drug therapies) can affect almost every aspect of an individuals life. Besides, not considering the secondary cancers as a part of natural incidences of time course, secondary cancers might be due to the treatments received by the patients at time of primary cancer treatment (15). Most of the therapies used in cancer, aim at destroying cancerous cells by affecting their genetic structures, but in therapy process normal cell are also involved just as malignant cells. This involvement will consequently lead to a poptosis, mutation or recovery. Mutations are tried to be minimized by the corrective mechanisms defined in cells and immune system (16). When these mechanisms fail a newly established malignancy is unavoidable. Current study presents 7 patients with secondary cancers (5 hematological malignancies, 1 osteosarcoma and 1 gliosarcoma). All secondary malignancies in current study had mesanchymal components, also both localized secondary malignancies (gliosarcoma and osteosarcoma) were in previous radiotherapy field. Vincristine, etopside and alkylating agents (such as ifosfamide and cyclophosphamide) were the most used cytotoxic drugs. Both patients No.3 and 4 who were expired, had undergone chemotherapy and radiotherapy. Based on the literature review, alkylating agents such as ifosfamide and cyclophosphamide are know of mainstays of treatments for hematologic malignancies, solid tumors and preconditioning regiments for hematologic stem cell transplantation, but it has been shown that they are important risk factors for development of secondary malignancies as they increase in the relative risk for a secondary malignancy of 1.5-2.5 (17-21). Especially, exposure to alkylating agents has been associated with an increased risk hematologic malignancies development, often referred to as therapy-related acute myelogenous leukemia (22, 23). Therapy-related AML seems to have an onset within 5-7 years after therapy for primary cancer, and this risk appears to increase further with the concomitant use of epipodophyllotoxins such as etopside (24). In present case series, patients No. 1,2 and 4 had also received a combination of alkylating agents and etopside, which could have been a major risk factor for the se condary malignancy. In a study by Bhatia et al. investigating Therapy-related myelodysplasia and acute myeloid leukemia after Ewing sarcoma and primitive neuroectodermal tumor of bone, it was concluded that exposure to ifosfamide from 90 to 140 g/m2, cyclophosphamide from 9.6 to 17.6 g/m2, and doxorubicin from 375 to 450 mg/m2 increased the risk of tharapy related myelodysplasia and acute myeloid leukemia significantly (25). Patient No. 1 had also received doxorubicin, ifosfamide and cyclophosphamide , but the cumulative doses were not that much of what Bhatia et al.(25) mentioned. In a study by Granowetter et al. about comparing dose-Intensified with standard chemotherapy for non-metastatic Ewing sarcoma, it was concluded that dose escalation of alkylating agents do not improve the outcome for patients with Ewing sarcoma of bone or soft tissue (25). So, by taking this into account, more cautious approaches should be chosen when deciding about chemotherapy doses, especially alkylating agents. Topoisomerase II inhibitors as another well-known chemotherapeutic agents are widely used treatment of pediatric malignancies. This category includes anthracyclines (e.g. doxorubicin) , anthracenediones as well as epipodophyllotoxins (e.g. etoposide and tenoposide)(26). Therapy related AMLs due to topoisomerase II inhibitors are known as an entity of therapy and incidence varies in literature, but has been reported as high as 9% (27-29). In contrast to the latency period after exposure to alkylating agents which was about 5-7 years, therapy related AMLs after topoisomerase II exposures have a more early onset, usually within 2-3 years after primary malignancy chemotherapy (24). In present case series, the time interval between secondary AMLs and primary therapy were less than 2 years, which is less than what mentioned for alkylating agents and topoisomerase II inhibitors; this might be due to the combination of these categories in our therapy protocols. Based on studies, the most eff ective agents against secondary hematologic malignancies due to top topoisomerase II inhibitors are cytarabine, dactinomycin, daunorubicin, docetazel, mitoxantrone, gemcitabine, mitomycin C, etoposide, teniposide, topotecan, triethylnemelamine, and vinblastine (30-32). Also, in present case series, following agents were used for secondary malignancy chemotherapy. Ionizing radiation as a standard of care for many pediatric malignancies is used in many conditions such as CNS malignancies, Hodgkins lymphoma, solid tumors and as part of preconditioning regimens for hematologic stem cell transplantation (33). Carcinogen role of ionizing radiation is reported in detail in the literature. According to The Childhood Cancer Survivor Study, ionizing radiation exposure was accompanied with a relative risk of developing secondary malignancy of 2.7, and was also the strongest independent risk factor for secondary malignancy development (34). In a study based on German Childhood Cancer Registry, it was concluded that ionizing radiation after adjustment for various chemotherapy was associated with an odds ratio of developing a secondary malignancy at 2.05 (35). For the development of secondary malignancy after radiation the latency period is typically 10-15 years after primary treatment is typically 10-15 years after primary treatment (36). Common secondary malignancies seen in pediatric population with prior cancer history include bone tumors, breast and thyroid carcinoma, non-melanoma skin cancer and benign CNS tumors. These tumors are often associated with previously irradiated treatment region (4, 37-39); in present case series, patients No. 3, 4, 6 and 7 had received radiotherapy, and in patients No. 6 and 7 had the secondary malignancies where the prior field of radiotherapy was, although incidence of these malignancies are far less than the latency period mentioned. Radiotherapy is the most important therapeutic modality in the treatment of many primary CNS tumors, so this have brought secondary malignancies as an undeniable component of this modality (40). In a study by Packer et al. studying survival and secondary tumors in children with medulloblastoma receiving radiotherapy and adjuvant chemotherapy, reported on 359 children with medulloblastoma treated with 2,340 cGy of craniospinal radiation with 5,580 cGy of posterior fossa radiotherapy and chemotherapy, also it was reported that 5 percent of patients developed a secondary malignancy, with a majority of them being highly aggressive gliomas. The median time to a secondary malignancy was 5.8 years, with an estimated cumulative incidence rate at 5 and 10 years of 1.1 percent and 4.2% percent, respectively (41); similar to this study, in present case series, patient No. 7 who had undergone radiotherapy due to astrocytoma, developed gliosarcoma as the secondary tumor. Fortunately this patients is currently under treatment and his condition is improving. Conclusion Present case series study, presented a series of patients with secondary neoplasms with their administered cumulative doses of chemotherapy and radiotherapy. Considering this , these information might lead to a more cautious approach in selecting chemotherapy and radiotherapy protocols. Further studies should focus on comparing different treatment protocols with adequate follow-up period not also to evaluate treatment efficacy, but to assess long term consequences. Also, studies with more detailed treatment protocol of patients with secondary malignancies should be performed to make a more precise conclusion. References: 1.Bhatia S, Sklar C. Second cancers in survivors of childhood cancer. Nature Reviews Cancer. 2002;2(2):124-32. 2.Hall EJ. Intensity-modulated radiation therapy, protons, and the risk of second cancers. International Journal of Radiation Oncology* Biology* Physics. 2006;65(1):1-7. 3.Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. 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Early secondary acute myelogenous leukemia in breast cancer patients after treatment with mitoxantrone, cyclophosphamide, fluorouracil and radiation therapy. Annals of oncology. 2000;11(10):1289-94. 24.Hijiya N, Ness KK, Ribeiro RC, Hudson MM. Acute leukemia as a secondary malignancy in children and adolescents: current findings and issues. Cancer. 2009;115(1):23-35. 25.Bhatia S, Krailo MD, Chen Z, Burden L, Askin FB, Dickman PS, et al. Therapy-related myelodysplasia and acute myeloid leukemia after Ewing sarcoma and primitive neuroectodermal tumor of bone: a report from the Childrens Oncology Group. Blood. 2007;109(1):46-51. 26.Hande KR. Topoisomerase II inhibitors. update on cancer therapeutics. 2008;3(1):13-26. 27.Hijiya N, Hudson MM, Lensing S, Zacher M, Onciu M, Behm FG, et al. Cumulative incidence of secondary neoplasms as a first event after childhood acute lymphoblastic leukemia. Jama. 2007;297(11):1207-15. 28.Pui CH, Relling MV. Topoisomerase II inhibitorà ¢Ã¢â€š ¬Ã‚ related acute myeloid leukaemia. British journal of haematology. 2000;109(1):13-23. 29.Ezoe S. Secondary leukemia associated with the anti-cancer agent, etoposide, a topoisomerase II inhibitor. International journal of environmental research and public health. 2012;9(7):2444-53. 30.Hoeksema KA, Jayanthan A, Cooper T, Gore L, Trippett T, Boklan J, et al. Systematic in-vitro evaluation of the NCI/NIH Developmental Therapeutics Program Approved Oncology Drug Set for the identification of a candidate drug repertoire for MLL-rearranged leukemia. Onco Targets Ther. 2011;4:149-68. 31.De Boer J, Walf-Vorderwà ¼lbecke V, Williams O. In focus: MLL-rearranged leukemia. Leukemia. 2013;27(6):1224-8. 32.Bernt KM, Armstrong SA. Targeting epigenetic programs in MLL-rearranged leukemias. ASH Education Program Book. 2011;2011(1):354-60. 33.Brenner DJ, Doll R, Goodhead DT, Hall EJ, Land CE, Little JB, et al. Cancer risks attributable to low doses of ionizing radiation: assessing what we really know. Proceedings of the National Academy of Sciences. 2003;100(24):13761-6. 34.Friedman DL, Whitton J, Leisenring W, Mertens AC, Hammond S, Stovall M, et al. Subsequent neoplasms in 5-year survivors of childhood cancer: the Childhood Cancer Survivor Study. Journal of the National Cancer Institute. 2010;102(14):1083-95. 35.Kaatsch P, Reinisch I, Spix C, Berthold F, Janka-Schaub G, Mergenthaler A, et al. Case-control study on the therapy of childhood cancer and the occurrence of second malignant neoplasms in Germany. Cancer causes control. 2009;20(6):965-80. 36.Goldsby R, Burke C, Nagarajan R, Zhou T, Chen Z, Marina N, et al. Second solid malignancies among children, adolescents, and young adults diagnosed with malignant bone tumors after 1976. Cancer. 2008;113(9):2597-604. 37.Constine LS, Tarbell N, Hudson MM, Schwartz C, Fisher SG, Muhs AG, et al. 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VCR 9 mg CPA 3.5 gr VP16 400 mg ADR 60 mg Cisplatin 160 mg 3 Meduloblastoma 10 10 months VCR 24 mg CCNU 320 mg 360 Gy and 180 Gy (posterior fossa) 4 Small round cell tumor 12 4 months VCR 12 mg IF 60 gr VP16 3.9 gr 8 Gy 5 Histiocytosis X 12 1 year Vinblastine 135 mg 6 Retinoblastoma 4 mo. 14 months VCR 14 mg VP16 700 mg Carboplatin 3.5 gr 60 Gy 7 Astrocytoma 2 months 6 months months<

Loneliness In Of Mice And Men Essay -- English Literature

Loneliness In Of Mice And Men John Steinbeck’s Of Mice & Men: Loneliness ========================================== Loneliness is a state of being alone in sadness, resulting from being isolated or abandoned. As I understand it, loneliness is when a person has no one to talk to, no one to confide in, nor anyone to keep companionship with. Loneliness also makes a person slip into a desolate state, which they try to conceal under a tough image, and is an emotion even the strongest cannot avoid. In his novel, Of Mice and Men, John Steinbeck deals with loneliness by looking for comfort in a friend, but settling for the attentive ear of a stranger. Although they seem at ease and friendly on the surface, a deep sense of loneliness lingers in the hearts of Crooks, George, and Curley's wife, to which they are desperate to find an escape from to cope with their seclusion from the rest of society. Crooks, a lively, sharp-witted, black stablehand, who takes his name from his crooked back, leads a lonely life. He lives according to the rule that no black man is allowed to enter a white man's home. Crooks’ loneliness is a result of rejection from everyone else on the ranch. He is forced to live alone in a barn, where he lives his life in isolation because of his colour, which was an issue in those days. When Lennie visits him in the room, Crooks' reactions reveal the fact that he is lonely. As a black man with a physical handicap, Crooks is forced to live on the border of ranch life. He is not even allowed to enter the white men's bunkhouse, or join them in a game of cards. His resentment typically comes out through his bitter, sad, and touching vulnerability, as he tells Lennie: â€Å"†¦A guy needs somebody to be nea... ...ch seems to disappear when narrating the story of the farm to Lennie. Curley's wife's loneliness is covered behind the mask of a portrayed prostitute, but the mask falls off during her conversations with strangers, including Lennie. I think John Steinbeck's message about loneliness and people's attempts to overcome loneliness in the novel is to reveal to us the nature of human's true existence. One cannot escape from being lonely, and the characters' attempts to overcome their loneliness is to seek the desire and comfort of a friend, but settle for the attentive ear of a stranger. I feel that Steinbeck is not completely successful in delivering his message across because for a full realization, one has to dig deep into the story, as well as place themselves in the shoes of a character to emphasize with, as well as relate to them and perceive their misery.

Ralph Waldo Emerson Essay

Ralph Waldo Emerson, who led the transcendentalist movement of the mid-19th century, once wrote, â€Å"The virtue in most request is conformity. Self-reliance is its aversion. † The Transcendentalist were a group of people who believed that everyone was equal and had power inside them as an individual. In the mid-19th century Emerson, Henry David Thoreau, and Walt Whitman were the main writers and thinkers of the transcendentalist movement. In the 1960’s as African American’s fought for civil rights in a cruel society. William Melvin Kelly combines the two in the book â€Å"A Different Drummer. † This book tells the story of Tucker Caliban, a black farmer who encourages a huge amount of blacks to leave the south when he decides to salt his crops and burn down his house and leave. Tucker embodies the characteristics of a Transcendentalist according to Emerson, Thoreau, and Whitman in three ways: he does what he wants without an explanation, he’s self-reliant, and he fights a corrupt system in his own way. Tucker does what he wants without an explanation or logic. Tucker stays out all night to teach Dewey how to ride a bike, even though his grandfather would be mad. Tucker also burned his house down and salted his crops without explaining this to his wife or to anyone else. Tucker writes Dewey a letter in college, he ask about the bike he taught him to ride. Dewey doesn’t understand why because Tucker really didn’t explain what he wanted to know about the bike. This shows Tucker really doesn’t tell anyone his logic behind his actions. â€Å"To be great is to be misunderstood†, Emerson. This quote refers to Tucker because he is misunderstood by the whites. This shows he’s also self-reliant and free spirited. Tucker Caliban is self-reliant and unique. Tucker self taught himself to farm and ride a bike. He also doesn’t believe in the civil rights movement which most other blacks strongly believe in. He also believes everyone has to free themselves or else there not really free. This shows that Tucker Caliban is not just any other black, he’s unique. But he also fights the south’s corrupt system in his own one of a kind way. â€Å"We but half express ourselves, and are ashamed of that divine idea which each of us represents. † This quote refers to Tucker because he is different and others are afraid to be different. Tucker Caliban is a rebel and he fights the system. He burned down his house and salted his crops because that’s where the slaves worked for the Willsons. He broke the grandfather clock because it was bought the same day as the African. He cut down the tree that separated his land from the Willisons, that was there from the days of slavery. He did all of this to cut his ties from slavery and from the south.† Society everywhere is in conspiracy against the manhood of everyone of its members. † This refers to the south and other blacks like Tucker. Therefore Tucker Caliban embodies the characteristics of a Transcendentalist according to Emerson, Thoreau, and Whitman in three ways: he does what he wants without an explanation, he’s self-reliant, and he fights a corrupt system in his own way. Tucker’s movement from the south is a strong step in the right direction for racism in the south. To me what Tucker did was strong and no else was strong enough to leave before Tucker did it.

Nelson Mandela - A Biography

Nelson Mandela - A Biography Nelson Mandela was elected the first black president of South Africa in 1994, following the first multiracial election in South Africas history. Mandela was imprisoned from 1962 to 1990 for his role in fighting apartheid policies established by the ruling white minority. Revered by his people as a national symbol of the struggle for equality, Mandela is considered one of the 20th centurys most influential political figures. He and South African Prime Minister F.W. de Klerk were jointly awarded the Nobel Peace Prize in 1993 for their role in dismantling the apartheid system. Dates: July 18, 1918- December 5, 2013 Also Known As: Rolihlahla Mandela, Madiba, Tata Famous quote:   I learned that courage was not the absence of fear, but the triumph over it. Childhood Nelson Rilihlahla Mandela was born in the village of Mveso, Transkei, South Africa on July 18, 1918 to Gadla Henry Mphakanyiswa and Noqaphi Nosekeni, the third of Gadlas four wives. In Mandelas native language, Xhosa, Rolihlahla meant troublemaker. The surname Mandela came from one of his grandfathers. Mandelas father was a chief of the Thembu tribe in the Mvezo region, but served under the authority of the ruling British government. As a descendant of royalty, Mandela was expected to serve in his fathers role when he came of age. But when Mandela was only an infant, his father rebelled against the British government by refusing a mandatory appearance before the British magistrate. For this, he was stripped of his chieftaincy and his wealth, and forced to leave his home. Mandela and his three sisters moved with their mother back to her home village of Qunu. There, the family lived in more modest circumstances. The family lived in mud huts and survived on the crops they grew and the cattle and sheep they raised. Mandela, along with the other village boys, worked herding sheep and cattle. He later recalled this as one of the happiest periods in his life. Many evenings, villagers sat around the fire, telling the children stories passed down through generations, of what life had been like before the white man had arrived. From the mid-17th century, Europeans (first the Dutch and later the British) had arrived on South African soil and gradually taken control from the native South African tribes. The discovery of diamonds and gold in South Africa in the 19th century had only tightened the grip that Europeans had on the nation. By 1900, most of South Africa was under the control of Europeans. In 1910, the British colonies merged with the Boer (Dutch) republics to form the Union of South Africa, a part of the British Empire. Stripped of their homelands, many Africans were forced to work for white employers at low-paying jobs. Young Nelson Mandela, living in his small village, did not yet feel the impact of centuries of domination by the white minority. Mandelas Education Although themselves uneducated, Mandelas parents wanted their son to go to school. At the age of seven, Mandela was enrolled in the local mission school. On the first day of class, each child was given an English first name; Rolihlahla was given the name Nelson. When he was nine years old, Mandelas father died. According to his fathers last wishes, Mandela was sent to live in the Thembu capital, Mqhekezeweni, where he could continue his education under the guidance of another tribal chief, Jongintaba Dalindyebo. Upon first seeing the chiefs estate, Mandela marveled at his large home and beautiful gardens. In Mqhekezeweni, Mandela attended another mission school and became a devout Methodist during his years with the Dalindyebo family. Mandela also attended tribal meetings with the chief, who taught him how a leader should conduct himself. When Mandela was 16, he was sent to a boarding school in a town several hundred miles away. Upon his graduation in 1937 at the age of 19, Mandela enrolled in Healdtown, a Methodist college. An accomplished student, Mandela also became active in boxing, soccer, and long-distance running. In 1939, after earning his certificate, Mandela began his studies for a Bachelor of Arts at the prestigious Fort Hare College, with a plan to ultimately attend law school. But Mandela did not complete his studies at Fort Hare; instead, he was expelled after participating in a student protest. He returned to the home of Chief Dalindyebo, where he was met with anger and disappointment. Just weeks after his return home, Mandela received stunning news from the chief. Dalindyebo had arranged for both his son, Justice, and Nelson Mandela to marry women of his choosing. Neither young man would consent to an arranged marriage, so the two decided to flee to Johannesburg, the South African capital. Desperate for money to finance their trip, Mandela and Justice stole two of the chiefs oxen and sold them for train fare. Move to Johannesburg Arriving in Johannesburg in 1940, Mandela found the bustling city an exciting place. Soon, however, he was awakened to the injustice of the black mans life in South Africa. Prior to moving to the capital, Mandela had lived mainly among other blacks. But in Johannesburg, he saw the disparity between the races. Black residents lived in slum-like townships that had no electricity or running water; while whites lived grandly off the wealth of the gold mines. Mandela moved in with a cousin and quickly found a job as a security guard. He was soon fired when his employers learned about his theft of the oxen and his escape from his benefactor. Mandelas luck changed when he was introduced to Lazar Sidelsky, a liberal-minded white lawyer. After learning of Mandelas desire to become an attorney, Sidelsky, who ran a large law firm serving both blacks and whites, offered to let Mandela work for him as a law clerk. Mandela gratefully accepted and took on the job at the age of 23, even as he worked to finish his BA via correspondence course. Mandela rented a room in one of the local black townships. He studied by candlelight each night and often walked the six miles to work and back because he lacked bus fare. Sidelsky supplied him with an old suit, which Mandela patched up and wore nearly every day for five years. Committed to the Cause In 1942, Mandela finally completed his BA and enrolled at the University of Witwatersrand as a part-time law student. At Wits, he met several people who would work with him in the years to come for the cause of liberation. In 1943, Mandela joined the African National Congress (ANC),  an organization that worked to improve conditions for blacks in South Africa. That same year, Mandela marched in a successful bus boycott staged by thousands of residents of Johannesburg in protest of high bus fares. As he grew more infuriated by racial inequalities, Mandela deepened his commitment to the struggle for liberation. He helped to form the Youth League, which sought to recruit younger members and transform the ANC into a more militant organization, one that would fight for equal rights. Under laws of the time, Africans were forbidden from owning land or houses in the towns, their wages were five times lower than those of whites, and none could vote. In 1944, Mandela, 26, married nurse Evelyn Mase, 22, and they moved into a small rental home. The couple had a son, Madiba (Thembi), in February 1945, and a daughter, Makaziwe, in 1947. Their daughter died of meningitis as an infant. They welcomed another son, Makgatho, in 1950, and a second daughter, named Makaziwe after her late sister, in 1954. Following the general elections of 1948 in which the white National Party claimed victory, the partys first official act was to establish apartheid. With this act, the long-held, haphazard system of segregation in South Africa became a formal, institutionalized policy, supported by laws and regulations. The new policy would even determine, by race, which parts of town each group could live in. Blacks and whites were to be separated from each other in all aspects of life, including public transportation, in theaters and restaurants, and even on beaches. The Defiance Campaign Mandela completed his law studies in 1952 and, with partner Oliver Tambo, opened the first black law practice in Johannesburg. The practice was busy from the start. Clients included Africans who suffered the injustices of racism, such as seizure of property by whites and beatings by the police. Despite facing hostility from white judges and lawyers, Mandela was a successful attorney. He had a dramatic, impassioned style in the courtroom. During the 1950s, Mandela became more actively involved with the protest movement. He was elected president of the ANC Youth League in 1950. In June 1952, the ANC, along with Indians and colored (biracial) people- two other groups also targeted by discriminatory laws- began a period of nonviolent protest known as the Defiance Campaign. Mandela spearheaded the campaign by recruiting, training, and organizing volunteers. The campaign lasted six months, with cities and towns throughout South Africa participating. Volunteers defied the laws by entering areas meant for whites only. Several thousand were arrested in that six-month time, including Mandela and other ANC leaders. He and the other members of the group were found guilty of statutory communism and sentenced to nine months of hard labor, but the sentence was suspended. The publicity garnered during the Defiance Campaign helped membership in the ANC soar to 100,000. Arrested for Treason The government twice banned Mandela, meaning that he could not attend public meetings, or even family gatherings, because of his involvement in the ANC. His 1953 banning lasted two years. Mandela, along with others on the executive committee of the ANC, drew up the Freedom Charter in June 1955 and presented it during a special meeting called the Congress of the People. The charter called for equal rights for all, regardless of race, and the ability of all citizens to vote, own land, and hold decent-paying jobs. In essence, the charter called for a non-racial South Africa. Months after the charter was presented, police raided the homes of hundreds of members of the ANC and arrested them. Mandela and 155 others were charged with high treason. They were released to await a trial date. Mandelas marriage to Evelyn suffered from the strain of his long absences; they divorced in 1957 after 13 years of marriage. Through work, Mandela met Winnie Madikizela, a social worker who had sought his legal advice. They married in June 1958, just months before Mandelas trial began in August. Mandela was 39 years old, Winnie only 21. The trial would last three years; during that time, Winnie gave birth to two daughters, Zenani and Zindziswa. Sharpeville Massacre The trial, whose venue was changed to Pretoria, moved at a snails pace. The preliminary arraignment alone took a year; the actual trial didnt start until August 1959. Charges were dropped against all but 30 of the accused. Then, on March 21, 1960, the trial was interrupted by a national crisis. In early March, another anti-apartheid group, the Pan African Congress (PAC) had held large demonstrations protesting strict pass laws, which required Africans to carry identification papers with them at all times in order to be able to travel throughout the country. During one such protest in Sharpeville, police had opened fire on unarmed protestors, killing 69, and wounding more than 400. The shocking incident, which was universally condemned, was called the Sharpeville Massacre. Mandela and other ANC leaders called for a national day of mourning, along with a stay at home strike. Hundreds of thousands participated in a mostly peaceful demonstration, but some rioting erupted. The South African government declared a national state of emergency and martial law was enacted. Mandela and his co-defendants were moved into prison cells, and both the ANC and PAC were officially banned. The treason trial resumed on April 25, 1960 and lasted until March 29, 1961. To the surprise of many, the court dropped charges against all of the defendants, citing a lack of evidence proving that the defendants had planned to violently overthrow the government. For many, it was cause for celebration, but Nelson Mandela had no time to celebrate. He was about to enter into a new- and dangerous- chapter in his life. The Black Pimpernel Prior to the verdict, the banned ANC had held an illegal meeting and decided that if Mandela was acquitted, he would go underground after the trial. He would operate clandestinely to give speeches and gather support for the liberation movement. A new organization, the National Action Council (NAC), was formed and Mandela named as its leader. In accordance with the ANC plan, Mandela became a fugitive directly after the trial. He went into hiding at the first of several safe houses, most of them located in the Johannesburg area. Mandela stayed on the move, knowing that the police were looking everywhere for him. Venturing out only at night, when he felt safest, Mandela dressed in disguises, such as a chauffeur or a chef. He made unannounced appearances, giving speeches at places that were presumed safe, and also made radio broadcasts. The press took to calling him the Black Pimpernel, after the title character in the novel The Scarlet Pimpernel. In October 1961, Mandela moved to a farm in Rivonia, outside of Johannesburg. He was safe for a time there and could even enjoy visits from Winnie and their daughters. Spear of the Nation In response to the governments increasingly violent treatment of protestors, Mandela developed a new arm of the ANC- a military unit that he named Spear of the Nation, known also as MK. The MK would operate using a strategy of sabotage, targeting military installations, power facilities, and transportation links. Its goal was to damage property of the state, but not to harm individuals. The MKs first attack came in December 1961, when they bombed an electric power station and empty government offices in Johannesburg. Weeks later, another set of bombings were carried out. White South Africans were startled into the realization that they could no longer take their safety for granted. In January 1962, Mandela, who had never in his life been out of South Africa, was smuggled out of the country to attend a Pan-African conference. He hoped to get financial and military support from other African nations, but was not successful. In Ethiopia, Mandela received training in how to fire a gun and how to build small explosives. Captured After 16 months on the run, Mandela was captured on August 5, 1962, when the car he was driving was overtaken by police. He was arrested on charges of leaving the country illegally and inciting a strike. The trial began on October 15, 1962. Refusing counsel, Mandela spoke on his own behalf. He used his time in court to denounce the governments immoral, discriminatory policies. Despite his impassioned speech, he was sentenced to five years in prison. Mandela was 44 years old when he entered Pretoria Local Prison. Imprisoned in Pretoria for six months, Mandela was then taken to Robben Island, a bleak, isolated prison off the coast of Cape Town, in May 1963. After only a few weeks there, Mandela learned he was about to head back to court- this time on charges of sabotage. He would be charged along with several other members of MK, who had been arrested on the farm in Rivonia. During the trial, Mandela admitted his role in the formation of MK. He emphasized his belief that the protestors were only working toward what they deserved- equal political rights. Mandela concluded his statement by saying that he was prepared to die for his cause. Mandela and his seven co-defendants received guilty verdicts on June 11, 1964. They could have been sentenced to death for so serious a charge, but each was given life imprisonment. All of the men (except one white prisoner) were sent to Robben Island. Life at Robben Island At Robben Island, each prisoner had a small cell with a single light that stayed on 24 hours a day. Prisoners slept on the floor upon a thin mat. Meals consisted of cold porridge and an occasional vegetable or piece of meat (although Indian and Asian prisoners received more generous rations than their black counterparts.) As a reminder of their lower status, black prisoners wore short pants all year-round, whereas others were allowed to wear trousers. Inmates spent nearly ten hours a day at hard labor, digging out rocks from a limestone quarry. The hardships of prison life made it difficult to maintain ones dignity, but Mandela resolved not to be defeated by his imprisonment. He became the spokesperson and leader of the group, and was known by his clan name, Madiba. Over the years, Mandela led the prisoners in numerous protests- hunger strikes, food boycotts, and work slowdowns. He also demanded reading and study privileges. In most cases, the protests eventually yielded results. Mandela suffered personal losses during his imprisonment. His mother died in January 1968 and his 25-year-old son Thembi died in a car accident the following year. A heartbroken Mandela was not allowed to attend either funeral. In 1969, Mandela received word that his wife Winnie had been arrested on charges of communist activities. She spent 18 months in solitary confinement and was subjected to torture. The knowledge that Winnie had been imprisoned caused Mandela great distress. Free Mandela Campaign Throughout his imprisonment, Mandela remained the symbol of the anti-apartheid movement, still inspiring his countrymen. Following a Free Mandela campaign in 1980 that attracted global attention, the government capitulated somewhat. In April 1982, Mandela and four other Rivonia prisoners were transferred to Pollsmoor Prison on the mainland. Mandela was 62 years old and had been at Robben Island for 19 years. Conditions were much improved from those at Robben Island. Inmates were allowed to read newspapers, watch TV, and receive visitors. Mandela was given a lot of publicity, as the government wanted to prove to the world that he was being treated well. In an effort to stem the violence and repair the failing economy, Prime Minister P.W. Botha announced on January 31, 1985 that he would release Nelson Mandela if Mandela agreed to renounce violent demonstrations. But Mandela refused any offer that was not unconditional. In December 1988, Mandela was transferred to a private residence at the Victor Verster prison outside Cape Town and later brought in for secret negotiations with the government. Little was accomplished, however, until Botha resigned from his position in August 1989, forced out by his cabinet. His successor, F.W. de Klerk, was ready to negotiate for peace. He was willing to meet with Mandela. Freedom at Last At Mandelas urging, de Klerk released Mandelas fellow political prisoners without condition in October 1989. Mandela and de Klerk had long discussions about the illegal status of the ANC and other opposition groups, but came to no specific agreement. Then, on February 2, 1990, de Klerk made an announcement that stunned Mandela and all of South Africa. De Klerk enacted a number of sweeping reforms, lifting the bans on the ANC, the PAC, and the Communist Party, among others. He lifted the restrictions still in place from the 1986 state of emergency and ordered the release of all nonviolent political prisoners. On February 11, 1990, Nelson Mandela was given an unconditional release from prison. After 27 years in custody, he was a free man at the age of 71. Mandela was welcomed home by thousands of people cheering in the streets. Soon after his return home, Mandela learned that his wife Winnie had fallen in love with another man in his absence. The Mandelas separated in April 1992 and later divorced. Mandela knew that despite the impressive changes that had been made, there was still much work to be done. He returned immediately to working for the ANC, traveling across South Africa to speak with various groups and to serve as a negotiator for further reforms. In 1993, Mandela and de Klerk were awarded the Nobel Peace Prize for their joint effort to bring about peace in South Africa. President Mandela On April 27, 1994, South Africa held its first election in which blacks were allowed to vote. The ANC won 63 percent of the votes, a majority in Parliament. Nelson Mandela- only four years after his release from prison- was elected the first black president of South Africa. Nearly three centuries of white domination had ended. Mandela visited many Western nations in an attempt to convince leaders to work with the new government in South Africa. He also made efforts to help bring about peace in several African nations, including Botswana, Uganda, and Libya. Mandela soon earned the admiration and respect of many outside of South Africa. During Mandelas term, he addressed the need for housing, running water, and electricity for all South Africans. The government also returned land to those it had been taken from, and made it legal again for blacks to own land. In 1998, Mandela married Graca Machel on his eightieth birthday. Machel, 52 years old, was the widow of a former president of Mozambique. Nelson Mandela did not seek re-election in 1999. He was replaced by his Deputy President, Thabo Mbeki. Mandela retired to his mothers village of Qunu, Transkei. Mandela became involved in raising funds for HIV/AIDS, an epidemic in Africa. He organized the AIDS benefit 46664 Concert in 2003, so named after his prison ID number. In 2005, Mandelas own son, Makgatho, died of AIDS at the age of 44. In 2009, the United Nations General Assembly designated July 18, Mandelas birthday, as Nelson Mandela International Day. Nelson Mandela died at his Johannesburg home on December 5, 2013 at the age of 95.

How to Say No in German, With Explanations and Examples

How to Say No in German, With Explanations and Examples Even people who dont study German know that Nein means no in German. But of course thats only the beginning to German negation. The German adverb nicht and adjective kein can be used to negate a sentence as well. Nicht is the English equivalent of not. Kein, on the other hand, can have different nuances depending on the sentence: no, not any, not a, none, no one, nobody. The rules for applying kein and nicht are actually quite simple. (really!) They are as follows: WhenNichtIs Used in a Sentence The noun to be negated has a definite article. Er liest das Buch. Er liest das Buch nicht. (He is not reading the book.) The noun to be negated has a possessive pronoun. Er liebt seine Freundin. Er liebt seine Freundin nicht. (He does not love his girlfriend.) The verb is to be negated. Ich will schlafen. Ich will nicht schlafen. (I dont want to sleep.) An adverb/adverbial phrase is to be negated. Sie rennt schnell. Sie rennt nicht schnell. (She does not run fast.) An adjective is used with the verb sein. Das Kind ist geizig. Das Kind ist nicht geizig. (The child is greedy.) WhenKeinIs Used in a Sentence The noun to be negated has an indefinite article. Ich will einen Apfel essen. Ich will keinen Apfel essen. (I dont want to eat an apple.) The word kein is in fact k ein and is positioned where the indefinite article would be. The noun has no article. Ich habe Zeit dafà ¼r. Ich habe keine Zeit dafà ¼r. (I dont have time for that.) Please note that though ein has no plural, kein does and follows the standard case declension pattern. The Position of Nicht The position of nicht is not always so clear-cut. However, generally speaking, nicht will precede adjectives, adverbs and either precede or follow verbs depending on its type. Nicht and Sondern, Keinand Sondern When nicht and kein negate only a clause, then usually the second clause that follows will begin with the conjunction sondern. Ich will nicht dieses Buch, sondern das andere.To put particular emphasis on nicht, positioning it at the beginning of the sentence is acceptable: Nicht Karl meinte ich, sondern Karin.

Minerals Essay Example | Topics and Well Written Essays - 500 words

Minerals - Essay Example Crespo et al., (2004) reported that disseminated graphite only occurred in metamorphic rocks of the La Umbria series and Fuente del Oro in the â€Å"Aracena Metamorphic Belt†. The deposits of graphite are weathered at 50 to 65 feet in depth. Coherence between graphite and other minerals is lessened due to weathering. Subsurface mining needs the cutting of multiple shafts to access the graphite deposits. Sometimes, tunneling equipments are used to remove the rock. Both, crystalline, and flake Graphite are graded as per carbon contents, and size of particles. Graphite with a high purity is only achieved through heating in the electric furnaces. Ash chemistry and likely applications are applied to grade the Flake carbon (80-99%), crystalline graphite (90-99%) and amorphous carbon (70-85%). Graphite’s purity is determined on the basis of Carbon contents and size of particles while amorphous Graphite is classified only on the basis of the carbon contents. Both, synthetic and natural graphite are heated up to 2500 °C that produces the graphite of a high purity 99.9%. Silicon and Boron are used as promoter elements for the graphite structure. Introduction of these elements enhances the consistency, conductivity and lubricant properties of the graphite (Crossely, 2000). Usually two techniques named as open pit mining and underground mining are used for graphite mining. Open pit mining is the method for the extraction of rocks from the open pits. This technique is useful when graphite ore lies close to the surface of the earth. On the other hand, underground mining involves the mining of graphite placed at the depth under the surface of the earth. Drift mining, slope mining, shaft mining and hard rock mining are the important methods for the underground mining (Crusher in China, 2012). Mining process of Graphite requires the power operations at the mining locations. The construction, decommissioning and operations

Talent Dry Cleaners Service Operational Challenges Case Study

Talent Dry Cleaners Service Operational Challenges - Case Study Example The business`s capacity utilization is 85.94% with an average turnaround time of 3-4 hours and it is a profitable as per the returns. The study will examine the challenges this business is currently experiencing and the possible solutions that have been drafted to counter such challenges. The understanding of such challenges will lead to appropriate recommendations that would help the company achieve the desired growth, goals, and objectives. Background This case study evaluates and analysis many perceptions in the service operation administration. It shows the business satiation of Patrick Eze who is trying so much to expand his business but he hardly got capital for the expansion and building of an institution to train dry cleaners. Problem Statement During the operation of the business, it took longer to register one client’s clothes. The company did not have a system of doing the registration hence wasting a lot of time in the registration of customers. Talent dry cleaners do not have strict payment tracks methods. The client is the one to decide when to pay either when dropping off or when picking the clothes. This can lead to wastage of resources because other clients can avoid paying their fees if strict laws of payment are not in place. The business has only two collection points. Moreover, it is not well marketed and the owner feels that there are needs to advertise his dry cleaner (Yelowitz, 2011). The dry cleaner has one dry-cleaning machine that takes five kilograms of garments and takes twelve minutes to wash. This is a long time and lead to time wastage. Therefore, the owner should buy a machine with a bigger capacity. The company is usually overwhelmed during peak season when there are many customers. Analysis The most essential solution towards the growth and development of this business is that the owner needs to notice that in small businesses, there need ensure that the level of hard work matches the complexity needed for the intended growth (Takaki, 2008). The owner did not consider this before the establishment of his business. Eze`s previous business had a well experienced manager who made the vital business decision that were essential for the success of his business. Eze has no experience in planning and handling business venture because prior to him starting the business, he did not take his time to study operational challenges he was likely to experience in running the business. Analysing from his background, Eze worked for fifteen years in his the previous employment; however, this did not equip him with strong management and leadership skills for successfully running a personal business. Notably, he only has basic skills for operating business since he no experience in marke ting that could have led to the growth of his small business. Additionally, he had no experience in planning large business ventures; thus, whenever he had a large number of customers, his problems increased (Takaki, 2008). Lack of experience and information are major problems in any business venture. Furthermore, poor planning usually leads to waste of time and this is experienced in the