title: Mesothelioma

text: Asbestos was known in antiquity, but it was not mined and widely used commercially until the late 19th century. The dangers were not unknown in antiquity. Pliny the Elder, a Roman author and naturalist, observed that quarry slaves from asbestos mines tended to die young. Its use greatly increased during World War II. Since the early 1940s, millions of American workers have been exposed to asbestos dust. Initially, the risks associated with asbestos exposure were not publicly known. However, an increased risk of developing mesothelioma was later found among naval personnel (e.g., Navy, Marine Corps, and Coast Guard), shipyard workers, people who work in asbestos mines and mills, producers of asbestos products, workers in the heating and construction industries, and other tradespeople. Today, the official position of the U.S. Occupational Safety and Health Administration (OSHA) and the U.S. EPA is that protections and "permissible exposure limits" required by U.S. regulations, while adequate to prevent most asbestos-related non-malignant disease, are "not" adequate to prevent or protect against asbestos-related cancers such as mesothelioma. Likewise, the British Government's Health and Safety Executive (HSE) states formally that any threshold for exposure to asbestos must be at a very low level and it is widely agreed that if any such threshold does exist at all, then it cannot currently be quantified. For practical purposes, therefore, HSE assumes that no such "safe" threshold exists. Others have noted as well that there is no evidence of a threshold level below which there is no risk of mesothelioma. There appears to be a linear, dose–response relationship, with increasing dose producing increasing risk of disease. Nevertheless, mesothelioma may be related to brief, low level or indirect exposures to asbestos. The dose necessary for effect appears to be lower for asbestos-induced mesothelioma than for pulmonary asbestosis or lung cancer. Again, there is no known safe level of exposure to asbestos as it relates to increased risk of mesothelioma.


title: Mesothelioma

text: The time from first exposure to onset of the disease, is between 25 and 70 years. It is virtually never less than fifteen years and peaks at 30–40 years. The duration of exposure to asbestos causing mesothelioma can be short. For example, cases of mesothelioma have been documented with only 1–3 months of exposure.


title: Mesothelioma

text: Exposure to asbestos fibers has been recognized as an occupational health hazard since the early 20th century. Numerous epidemiological studies have associated occupational exposure to asbestos with the development of pleural plaques, diffuse pleural thickening, asbestosis, carcinoma of the lung and larynx, gastrointestinal tumors, and diffuse malignant mesothelioma of the pleura and peritoneum. Asbestos has been widely used in many industrial products, including cement, brake linings, gaskets, roof shingles, flooring products, textiles, and insulation.


title: Mesothelioma

text: Commercial asbestos mining at Wittenoom, Western Australia, took place from 1937 to 1966. The first case of mesothelioma in the town occurred in 1960. The second case was in 1969, and new cases began to appear more frequently thereafter. The lag time between initial exposure to asbestos and the development of mesothelioma varied from 12 years 9 months up to 58 years. A cohort study of miners employed at the mine reported that 85 deaths attributable to mesothelioma had occurred by 1985. By 1994, 539 reported deaths due to mesothelioma had been reported in Western Australia.


title: Mesothelioma

text: Occupational exposure to asbestos in the United States mainly occurs when people are maintaining buildings that already have asbestos. Approximately 1.3 million US workers are exposed to asbestos annually; in 2002, an estimated 44,000 miners were potentially exposed to asbestos.


title: Mesothelioma

text: Family members and others living with asbestos workers have an increased risk of developing mesothelioma, and possibly other asbestos-related diseases. This risk may be the result of exposure to asbestos dust brought home on the clothing and hair of asbestos workers via washing a worker's clothes or coming into contact with asbestos-contaminated work clothing. To reduce the chance of exposing family members to asbestos fibres, asbestos workers are usually required to shower and change their clothing before leaving the workplace.


title: Mesothelioma

text: Many building materials used in both public and domestic premises prior to the banning of asbestos may contain asbestos. Those performing renovation works or DIY activities may expose themselves to asbestos dust. In the UK, use of chrysotile asbestos was banned at the end of 1999. Brown and blue asbestos were banned in the UK around 1985. Buildings built or renovated prior to these dates may contain asbestos materials.


title: Mesothelioma

text: Therefore, it is a legal requirement that all who may come across asbestos in their day-to-day work have been provided with the relevant asbestos training.


title: Mesothelioma

text: In a recent research carried on white American population in 2012, it was found that people with a germline mutation in their BAP1 gene are at higher risk of developing mesothelioma and uveal melanoma.


title: Mesothelioma

text: Erionite is a zeolite mineral with similar properties to asbestos and is known to cause mesothelioma. Detailed epidemiological investigation has shown that erionite causes mesothelioma mostly in families with a genetic predisposition. Erionite is found in deposits in the Western United States, where it is used in gravel for road surfacing, and in Turkey, where it is used to construct homes. In Turkey, the United States, and Mexico, erionite has been associated with mesothelioma and has thus been designated a "known human carcinogen" by the US National Toxicology Program.


title: Mesothelioma

text: In rare cases, mesothelioma has also been associated with irradiation of the chest or abdomen, intrapleural thorium dioxide (thorotrast) as a contrast medium, and inhalation of other fibrous silicates, such as erionite or talc. Some studies suggest that simian virus 40 (SV40) may act as a cofactor in the development of mesothelioma. This has been confirmed in animal studies, but studies in humans are inconclusive.


title: Mesothelioma

text: The mesothelium consists of a single layer of flattened to cuboidal cells forming the epithelial lining of the serous cavities of the body including the peritoneal, pericardial and pleural cavities. Deposition of asbestos fibers in the parenchyma of the lung may result in the penetration of the visceral pleura from where the fiber can then be carried to the pleural surface, thus leading to the development of malignant mesothelial plaques. The processes leading to the development of peritoneal mesothelioma remain unresolved, although it has been proposed that asbestos fibers from the lung are transported to the abdomen and associated organs via the lymphatic system. Additionally, asbestos fibers may be deposited in the gut after ingestion of sputum contaminated with asbestos fibers.


title: Mesothelioma

text: Pleural contamination with asbestos or other mineral fibers has been shown to cause cancer. Long thin asbestos fibers (blue asbestos, amphibole fibers) are more potent carcinogens than "feathery fibers" (chrysotile or white asbestos fibers). However, there is now evidence that smaller particles may be more dangerous than the larger fibers. They remain suspended in the air where they can be inhaled, and may penetrate more easily and deeper into the lungs. "We probably will find out a lot more about the health aspects of asbestos from [the World Trade Center attack], unfortunately," said Dr. Alan Fein, chief of pulmonary and critical-care medicine at North Shore-Long Island Jewish Health System.


title: Mesothelioma

text: Mesothelioma development in rats has been demonstrated following intra-pleural inoculation of phosphorylated chrysotile fibers. It has been suggested that in humans, transport of fibers to the pleura is critical to the pathogenesis of mesothelioma. This is supported by the observed recruitment of significant numbers of macrophages and other cells of the immune system to localized lesions of accumulated asbestos fibers in the pleural and peritoneal cavities of rats. These lesions continued to attract and accumulate macrophages as the disease progressed, and cellular changes within the lesion culminated in a morphologically malignant tumor.


title: Mesothelioma

text: Experimental evidence suggests that asbestos acts as a complete carcinogen with the development of mesothelioma occurring in sequential stages of initiation and promotion. The molecular mechanisms underlying the malignant transformation of normal mesothelial cells by asbestos fibers remain unclear despite the demonstration of its oncogenic capabilities (see next-but-one paragraph). However, complete in vitro transformation of normal human mesothelial cells to a malignant phenotype following exposure to asbestos fibers has not yet been achieved. In general, asbestos fibers are thought to act through direct physical interactions with the cells of the mesothelium in conjunction with indirect effects following interaction with inflammatory cells such as macrophages.


title: Mesothelioma

text: Analysis of the interactions between asbestos fibers and DNA has shown that phagocytosed fibers are able to make contact with chromosomes, often adhering to the chromatin fibers or becoming entangled within the chromosome. This contact between the asbestos fiber and the chromosomes or structural proteins of the spindle apparatus can induce complex abnormalities. The most common abnormality is monosomy of chromosome 22. Other frequent abnormalities include structural rearrangement of 1p, 3p, 9p and 6q chromosome arms.


title: Mesothelioma

text: Asbestos has also been shown to mediate the entry of foreign DNA into target cells. Incorporation of this foreign DNA may lead to mutations and oncogenesis by several possible mechanisms:


title: Mesothelioma

text: Several genes are commonly mutated in mesothelioma, and may be prognostic factors. These include epidermal growth factor receptor (EGFR) and C-Met, receptor tyrosine kinases which are overexpressed in many mesotheliomas. Some association has been found with EGFR and epithelioid histology but no clear association has been found between EGFR overexpression and overall survival. Expression of AXL receptor tyrosine kinase is a negative prognostic factor. Expression of PDGFRB is a positive prognostic factor. In general, mesothelioma is characterized by loss of function in tumor suppressor genes, rather than by an overexpression or gain of function in oncogenes.


title: Mesothelioma

text: As an environmentally triggered malignancy, mesothelioma tumors have been found to be polyclonal in origin, by performing an X-inactivation based assay on epitheloid and biphasic tumors obtained from female patients. These results suggest that an environmental factor, most likely asbestos exposure, may damage and transform a group of cells in the tissue, resulting in a population of tumor cells that are, albeit only slightly, genetically different.


title: Mesothelioma

text: Asbestos fibers have been shown to alter the function and secretory properties of macrophages, ultimately creating conditions which favour the development of mesothelioma. Following asbestos phagocytosis, macrophages generate increased amounts of hydroxyl radicals, which are normal by-products of cellular anaerobic metabolism. However, these free radicals are also known clastogenic (chromosome-breaking)


title: Mesothelioma

text: and membrane-active agents thought to promote asbestos carcinogenicity. These oxidants can participate in the oncogenic process by directly and indirectly interacting with DNA, modifying membrane-associated cellular events, including oncogene activation and perturbation of cellular antioxidant defences.


title: Mesothelioma

text: Asbestos also may possess immunosuppressive properties. For example, chrysotile fibres have been shown to depress the in vitro proliferation of phytohemagglutinin-stimulated peripheral blood lymphocytes, suppress natural killer cell lysis and significantly reduce lymphokine-activated killer cell viability and recovery. Furthermore, genetic alterations in asbestos-activated macrophages may result in the release of potent mesothelial cell mitogens such as platelet-derived growth factor (PDGF) and transforming growth factor-β (TGF-β) which in turn, may induce the chronic stimulation and proliferation of mesothelial cells after injury by asbestos fibres.


title: Mesothelioma

text: Diagnosis of mesothelioma can be suspected with imaging but is confirmed with biopsy. It must be clinically and histologically differentiated from other pleural and pulmonary malignancies, including reactive pleural disease, primary lung carcinoma, pleural metastases of other cancers, and other primary pleural cancers.


title: Mesothelioma

text: Primary pericardial mesothelioma is often diagnosed after it has metastasized to lymph nodes or the lungs.


title: Mesothelioma

text: Diagnosing mesothelioma is often difficult because the symptoms are similar to those of a number of other conditions. Diagnosis begins with a review of the patient's medical history. A history of exposure to asbestos may increase clinical suspicion for mesothelioma. A physical examination is performed, followed by chest X-ray and often lung function tests. The X-ray may reveal pleural thickening commonly seen after asbestos exposure and increases suspicion of mesothelioma. A CT (or CAT) scan or an MRI is usually performed. If a large amount of fluid is present, abnormal cells may be detected by cytopathology if this fluid is aspirated with a syringe. For pleural fluid, this is done by thoracentesis or tube thoracostomy (chest tube); for ascites, with paracentesis or ascitic drain; and for pericardial effusion with pericardiocentesis. While absence of malignant cells on cytology does not completely exclude mesothelioma, it makes it much more unlikely, especially if an alternative diagnosis can be made (e.g., tuberculosis, heart failure). However, with primary pericardial mesothelioma, pericardial fluid may not contain malignant cells and a tissue biopsy is more useful in diagnosis. Using conventional cytology diagnosis of malignant mesothelioma is difficult, but immunohistochemistry has greatly enhanced the accuracy of cytology.


title: Mesothelioma

text: Generally, a biopsy is needed to confirm a diagnosis of malignant mesothelioma. A doctor removes a sample of tissue for examination under a microscope by a pathologist. A biopsy may be done in different ways, depending on where the abnormal area is located. If the cancer is in the chest, the doctor may perform a thoracoscopy. In this procedure, the doctor makes a small cut through the chest wall and puts a thin, lighted tube called a thoracoscope into the chest between two ribs. Thoracoscopy allows the doctor to look inside the chest and obtain tissue samples. Alternatively, the cardiothoracic surgeon might directly open the chest (thoracotomy). If the cancer is in the abdomen, the doctor may perform a laparoscopy. To obtain tissue for examination, the doctor makes a small incision in the abdomen and inserts a special instrument into the abdominal cavity. If these procedures do not yield enough tissue, an open surgical procedure may be necessary.


title: Mesothelioma

text: Immunohistochemical studies play an important role for the pathologist in differentiating malignant mesothelioma from neoplastic mimics, such as breast or lung cancer that has metastasized to the pleura. There are numerous tests and panels available, but no single test is perfect for distinguishing mesothelioma from carcinoma or even benign versus malignant. The positive markers indicate that mesothelioma is present; if other markers are positive it may indicate another type of cancer, such as breast or lung adenocarcinoma. Calretinin is a particularly important marker in distinguishing mesothelioma from metastatic breast or lung cancer.


title: Mesothelioma

text: There are three main histological subtypes of malignant mesothelioma: epithelioid, sarcomatous, and biphasic. Epithelioid and biphasic mesothelioma make up approximately 75-95% of mesotheliomas and have been well characterized histologically, whereas sarcomatous mesothelioma has not been studied extensively. Most mesotheliomas express high levels of cytokeratin 5 regardless of subtype.


title: Mesothelioma

text: Staging of mesothelioma is based on the recommendation by the International Mesothelioma Interest Group. TNM classification of the primary tumor, lymph node involvement, and distant metastasis is performed. Mesothelioma is staged Ia–IV (one-A to four) based on the TNM status.


title: Mesothelioma

text: Mesothelioma can be prevented in most cases by preventing exposure to asbestos. The US National Institute for Occupational Safety and Health maintains a recommended exposure limit of 0.1 asbestos fiber per cubic centimeter.


title: Mesothelioma

text: There is no universally agreed protocol for screening people who have been exposed to asbestos. Screening tests might diagnose mesothelioma earlier than conventional methods thus improving the survival prospects for patients. The serum osteopontin level might be useful in screening asbestos-exposed people for mesothelioma. The level of soluble mesothelin-related protein is elevated in the serum of about 75% of patients at diagnosis and it has been suggested that it may be useful for screening. Doctors have begun testing the Mesomark assay, which measures levels of soluble mesothelin-related proteins (SMRPs) released by mesothelioma cells.


title: Mesothelioma

text: Mesothelioma is generally resistant to radiation and chemotherapy treatment. Long-term survival and cures are exceedingly rare. Treatment of malignant mesothelioma at earlier stages has a better prognosis. Clinical behavior of the malignancy is affected by several factors including the continuous mesothelial surface of the pleural cavity which favors local metastasis via exfoliated cells, invasion to underlying tissue and other organs within the pleural cavity, and the extremely long latency period between asbestos exposure and development of the disease. The histological subtype and the patient's age and health status also help predict prognosis. The epithelioid histology responds better to treatment and has a survival advantage over sarcomatoid histology.


title: Mesothelioma

text: The effectiveness of radiotherapy compared to chemotherapy or surgery for malignant pleural mesothelioma is not known.


title: Mesothelioma

text: Surgery, by itself, has proved disappointing. In one large series, the median survival with surgery (including extrapleural pneumonectomy) was only 11.7 months. However, research indicates varied success when used in combination with radiation and chemotherapy (Duke, 2008), or with one of the latter. A pleurectomy/decortication is the most common surgery, in which the lining of the chest is removed. Less common is an extrapleural pneumonectomy (EPP), in which the lung, lining of the inside of the chest, the hemi-diaphragm and the pericardium are removed. In localized pericardial mesothelioma, pericardectomy can be curative; when the tumor has metastasized, pericardectomy is a palliative care option. It is often not possible to remove the entire tumor.


title: Mesothelioma

text: For patients with localized disease, and who can tolerate a radical surgery, radiation can be given post-operatively as a consolidative treatment. The entire hemithorax is treated with radiation therapy, often given simultaneously with chemotherapy. Delivering radiation and chemotherapy after a radical surgery has led to extended life expectancy in selected patient populations. It can also induce severe side-effects, including fatal pneumonitis. As part of a curative approach to mesothelioma, radiotherapy is commonly applied to the sites of chest drain insertion, in order to prevent growth of the tumor along the track in the chest wall.


title: Mesothelioma

text: Although mesothelioma is generally resistant to curative treatment with radiotherapy alone, palliative treatment regimens are sometimes used to relieve symptoms arising from tumor growth, such as obstruction of a major blood vessel. Radiation therapy, when given alone with curative intent, has never been shown to improve survival from mesothelioma. The necessary radiation dose to treat mesothelioma that has not been surgically removed would be beyond human tolerance. Radiotherapy is of some use in pericardial mesothelioma.


title: Mesothelioma

text: Chemotherapy is the only treatment for mesothelioma that has been proven to improve survival in randomised and controlled trials. The landmark study published in 2003 by Vogelzang and colleagues compared cisplatin chemotherapy alone with a combination of cisplatin and pemetrexed (brand name Alimta) chemotherapy in patients who had not received chemotherapy for malignant pleural mesothelioma previously and were not candidates for more aggressive "curative" surgery. This trial was the first to report a survival advantage from chemotherapy in malignant pleural mesothelioma, showing a statistically significant improvement in median survival from 10 months in the patients treated with cisplatin alone to 13.3 months in the group of patients treated with cisplatin in the combination with pemetrexed and who also received supplementation with folate and vitamin B. Vitamin supplementation was given to most patients in the trial and pemetrexed related side effects were significantly less in patients receiving pemetrexed when they also received daily oral folate 500mcg and intramuscular vitamin B 1000mcg every 9 weeks compared with patients receiving pemetrexed without vitamin supplementation. The objective response rate increased from 20% in the cisplatin group to 46% in the combination pemetrexed group. Some side effects such as nausea and vomiting, stomatitis, and diarrhoea were more common in the combination pemetrexed group but only affected a minority of patients and overall the combination of pemetrexed and cisplatin was well tolerated when patients received vitamin supplementation; both quality of life and lung function tests improved in the combination pemetrexed group. In February 2004, the United States Food and Drug Administration (FDA) approved pemetrexed for treatment of malignant pleural mesothelioma. However, there are still unanswered questions about the optimal use of chemotherapy, including when to start treatment, and the optimal number of cycles to give. Cisplatin and pemetrexed together give patients a median survival of 12.1 months.


title: Mesothelioma

text: Cisplatin in combination with raltitrexed has shown an improvement in survival similar to that reported for pemetrexed in combination with cisplatin, but raltitrexed is no longer commercially available for this indication. For patients unable to tolerate pemetrexed, cisplatin in combination with gemcitabine or vinorelbine is an alternative, or vinorelbine on its own, although a survival benefit has not been shown for these drugs. For patients in whom cisplatin cannot be used, carboplatin can be substituted but non-randomised data have shown lower response rates and high rates of haematological toxicity for carboplatin-based combinations, albeit with similar survival figures to patients receiving cisplatin. Cisplatin in combination with premetrexed disodium, folic acid, and vitamin B12 may also improve survival for people who are responding to chemotherapy.


title: Mesothelioma

text: In January 2009, the United States FDA approved using conventional therapies such as surgery in combination with radiation and or chemotherapy on stage I or II Mesothelioma after research conducted by a nationwide study by Duke University concluded an almost 50 point increase in remission rates.


title: Mesothelioma

text: In pericardial mesothelioma, chemotherapy – typically adriamycin or cisplatin – is primarily used to shrink the tumor and is not curative.


title: Mesothelioma

text: Treatment regimens involving immunotherapy have yielded variable results. For example, intrapleural inoculation of Bacillus Calmette-Guérin (BCG) in an attempt to boost the immune response, was found to be of no benefit to the patient (while it may benefit patients with bladder cancer). Mesothelioma cells proved susceptible to in vitro lysis by LAK cells following activation by interleukin-2 (IL-2), but patients undergoing this particular therapy experienced major side effects. Indeed, this trial was suspended in view of the unacceptably high levels of IL-2 toxicity and the severity of side effects such as fever and cachexia. Nonetheless, other trials involving interferon alpha have proved more encouraging with 20% of patients experiencing a greater than 50% reduction in tumor mass combined with minimal side effects.


title: Mesothelioma

text: In October 2020, the FDA approved the combination of nivolumab (Opdivo) with ipilimumab (Yervoy) for the first-line treatment of adults with malignant pleural mesothelioma (MPM) that cannot be removed by surgery. Nivolumab and ipilimumab are both monoclonal antibodies that, when combined, decrease tumor growth by enhancing T-cell function. The combination therapy was evaluated through a randomized, open-label trial in which participants who received nivolumab in combination with ipilimumab survived a median of 18.1 months while participants who underwent chemotherapy survived a median of 14.1 months.


title: Mesothelioma

text: Hyperthermic intrathoracic chemotherapy is used in conjunction with surgery, including in patients with malignant pleural mesothelioma. The surgeon removes as much of the tumor as possible followed by the direct administration of a chemotherapy agent, heated to between 40 and 48 °C, in the abdomen. The fluid is perfused for 60 to 120 minutes and then drained. High concentrations of selected drugs are then administered into the pleural cavity. Heating the chemotherapy treatment increases the penetration of the drugs into tissues. Also, heating itself damages the malignant cells more than the normal cells.


title: Mesothelioma

text: Multimodal therapy, which includes a combined approach of surgery, radiation or photodynamic therapy, and chemotherapy, is not suggested for routine practice for treating malignant pleural mesothelioma. The effectiveness and safety of multimodal therapy is not clear (not enough research has been performed) and one clinical trial has suggested a possible increased risk of adverse effects.


title: Mesothelioma

text: Large series of examining multimodality treatment have only demonstrated modest improvement in survival (median survival 14.5 months and only 29.6% surviving 2 years). Reducing the bulk of the tumor with cytoreductive surgery is key to extending survival. Two surgeries have been developed: extrapleural pneumonectomy and pleurectomy/decortication. The indications for performing these operations are unique. The choice of operation namely depends on the size of the patient's tumor. This is an important consideration because tumor volume has been identified as a prognostic factor in mesothelioma. Pleurectomy/decortication spares the underlying lung and is performed in patients with early stage disease when the intention is to remove all gross visible tumor (macroscopic complete resection), not simply palliation. Extrapleural pneumonectomy is a more extensive operation that involves resection of the parietal and visceral pleurae, underlying lung, ipsilateral (same side) diaphragm, and ipsilateral pericardium. This operation is indicated for a subset of patients with more advanced tumors, who can tolerate a pneumonectomy.


title: Mesothelioma

text: Mesothelioma usually has a poor prognosis. Typical survival despite surgery is between 12 and 21 months depending on the stage of disease at diagnosis with about 7.5% of people surviving for 5 years.


title: Mesothelioma

text: Women, young people, people with low-stage cancers, and people with epithelioid cancers have better prognoses. Negative prognostic factors include sarcomatoid or biphasic histology, high platelet counts (above 400,000), age over 50 years, white blood cell counts above 15.5, low glucose levels in the pleural fluid, low albumin levels, and high fibrinogen levels. Several markers are under investigation as prognostic factors, including nuclear grade, and serum c-reactive protein. Long-term survival is rare.


title: Mesothelioma

text: Although reported incidence rates have increased in the past 20 years, mesothelioma is still a relatively rare cancer. The incidence rate varies from one country to another, from a low rate of less than 1 per 1,000,000 in Tunisia and Morocco, to the highest rate in Britain, Australia and Belgium: 30 per 1,000,000 per year. For comparison, populations with high levels of smoking can have a lung cancer incidence of over 1,000 per 1,000,000. Incidence of malignant mesothelioma currently ranges from about 7 to 40 per 1,000,000 in industrialized Western nations, depending on the amount of asbestos exposure of the populations during the past several decades. Worldwide incidence is estimated at 1-6 per 1,000,000. Incidence of mesothelioma lags behind that of asbestosis due to the longer time it takes to develop; due to the cessation of asbestos use in developed countries, mesothelioma incidence is expected to decrease. Incidence is expected to continue increasing in developing countries due to continuing use of asbestos. Mesothelioma occurs more often in men than in women and risk increases with age, but this disease can appear in either men or women at any age. Approximately one fifth to one third of all mesotheliomas are peritoneal. Less than 5% of mesotheliomas are pericardial. The prevalence of pericardial mesothelioma is less than 0.002%; it is more common in men than women. It typically occurs in a person's 50s-70s.


title: Mesothelioma

text: Between 1940 and 1979, approximately 27.5 million people were occupationally exposed to asbestos in the United States. Between 1973 and 1984, the incidence of pleural mesothelioma among Caucasian males increased 300%. From 1980 to the late 1990s, the death rate from mesothelioma in the USA increased from 2,000 per year to 3,000, with men four times more likely to acquire it than women. More than 80% of mesotheliomas are caused by asbestos exposure.


title: Mesothelioma

text: The incidence of peritoneal mesothelioma is 0.5–3.0 per million per year in men, and 0.2–2.0 per million per year in women.


title: Mesothelioma

text: Mesothelioma accounts for less than 1% of all cancers diagnosed in the UK, (around 2,600 people were diagnosed with the disease in 2011), and it is the seventeenth most common cause of cancer death (around 2,400 people died in 2012).


title: Mesothelioma

text: The connection between asbestos exposure and mesothelioma was discovered in the 1970s. In the United States, asbestos manufacture stopped in 2002. Asbestos exposure thus shifted from workers in asbestos textile mills, friction product manufacturing, cement pipe fabrication, and insulation manufacture and installation to maintenance workers in asbestos-containing buildings.


title: Mesothelioma

text: Although life expectancy with this disease is typically limited, there are notable survivors. In July 1982, Stephen Jay Gould, a well-regarded paleontologist, was diagnosed with peritoneal mesothelioma. After his diagnosis, Gould wrote "The Median Isn't the Message", in which he argued that statistics such as median survival are useful abstractions, not destiny. Gould lived for another 20 years, eventually succumbing to cancer not linked to his mesothelioma.


title: Mesothelioma

text: Some people who were exposed to asbestos have collected damages for an asbestos-related disease, including mesothelioma. Compensation via asbestos funds or class action lawsuits is an important issue in law practices regarding mesothelioma.


title: Mesothelioma

text: The first lawsuits against asbestos manufacturers were in 1929. Since then, many lawsuits have been filed against asbestos manufacturers and employers, for neglecting to implement safety measures after the links between asbestos, asbestosis, and mesothelioma became known (some reports seem to place this as early as 1898). The liability resulting from the sheer number of lawsuits and people affected has reached billions of dollars. The amounts and method of allocating compensation have been the source of many court cases, reaching up to the United States Supreme Court, and government attempts at resolution of existing and future cases. However, to date, the US Congress has not stepped in and there are no federal laws governing asbestos compensation.


title: Mesothelioma

text: In 2013, the "Furthering Asbestos Claim Transparency (FACT) Act of 2013" passed the US House of representatives and was sent to the US Senate, where it was referred to the Senate Judiciary Committee. As the Senate did not vote on it before the end of the 113th Congress, it died in committee. It was revived in the 114th Congress, where it has not yet been brought before the House for a vote.


title: Mesothelioma

text: The first lawsuit against asbestos manufacturers was brought in 1929. The parties settled that lawsuit, and as part of the agreement, the attorneys agreed not to pursue further cases. In 1960, an article published by Wagner et al. was seminal in establishing mesothelioma as a disease arising from exposure to asbestos. The article referred to over 30 case studies of people who had had mesothelioma in South Africa. Some exposures were transient and some were mine workers. Before the use of advanced microscopy techniques, malignant mesothelioma was often diagnosed as a variant form of lung cancer. In 1962, McNulty reported the first diagnosed case of malignant mesothelioma in an Australian asbestos worker. The worker had worked in the mill at the asbestos mine in Wittenoom from 1948 to 1950.


title: Mesothelioma

text: In the town of Wittenoom, asbestos-containing mine waste was used to cover schoolyards and playgrounds. In 1965, an article in the British Journal of Industrial Medicine established that people who lived in the neighbourhoods of asbestos factories and mines, but did not work in them, had contracted mesothelioma.


title: Mesothelioma

text: Despite proof that the dust associated with asbestos mining and milling causes asbestos-related disease, mining began at Wittenoom in 1943 and continued until 1966. In 1974, the first public warnings of the dangers of blue asbestos were published in a cover story called "Is this Killer in Your Home?" in Australia's "Bulletin" magazine. In 1978, the Western Australian Government decided to phase out the town of Wittenoom, following the publication of a Health Dept. booklet, "The Health Hazard at Wittenoom", containing the results of air sampling and an appraisal of worldwide medical information.


title: Mesothelioma

text: By 1979, the first writs for negligence related to Wittenoom were issued against CSR and its subsidiary ABA, and the Asbestos Diseases Society was formed to represent the Wittenoom victims.


title: Mesothelioma

text: In Leeds, England the Armley asbestos disaster involved several court cases against Turner & Newall where local residents who contracted mesothelioma demanded compensation because of the asbestos pollution from the company's factory. One notable case was that of June Hancock, who contracted the disease in 1993 and died in 1997.


title: Mesothelioma

text: The WT-1 protein is overexpressed in mesothelioma and is being researched as a potential target for drugs.


title: Mesothelioma

text: There are two high-confidence miRNAs that can potentially serve as biomarkers of asbestos exposure and malignant mesothelioma. Validation studies are needed to assess their relevance.


title: Anticholinergic

text: Anticholinergics (anticholinergic agents) are substances that block the action of the neurotransmitter called acetylcholine (ACh) at synapses in the central and peripheral nervous system.


title: Anticholinergic

text: These agents inhibit the parasympathetic nervous system by selectively blocking the binding of ACh to its receptor in nerve cells. The nerve fibers of the parasympathetic system are responsible for the involuntary movement of smooth muscles present in the gastrointestinal tract, urinary tract, lungs, sweat glands, and many other parts of the body.


title: Anticholinergic

text: In broad terms, anticholinergics are divided into two categories in accordance with their specific targets in the central and peripheral nervous system and at the neuromuscular junction: antimuscarinic agents, and antinicotinic agents (ganglionic blockers, neuromuscular blockers).


title: Anticholinergic

text: The term "anticholinergic" is typically used to refer to antimuscarinics which competitively inhibit the binding of ACh to muscarinic acetylcholine receptors; such agents do not antagonize the binding at nicotinic acetylcholine receptors at the neuromuscular junction, although the term is sometimes used to refer to agents which do so.


title: Anticholinergic

text: Anticholinergics generally have "antisialagogue" effects (decreasing saliva production), and most produce some level of sedation, both being advantageous in surgical procedures.


title: Anticholinergic

text: Until the beginning of the 20th century anticholinergic drugs were widely used to treat psychiatric disorders.


title: Anticholinergic

text: Clinically the most significant feature is delirium, particularly in the elderly, who are most likely to be affected by the toxidrome.


title: Anticholinergic

text: Long-term use may increase the risk of both cognitive and physical decline. It is unclear whether they affect the risk of death generally. However, in older adults they do appear to increase the risk of death.


title: Anticholinergic

text: Possible effects in the central nervous system resemble those associated with delirium, and may include:


title: Anticholinergic

text: An acute anticholinergic syndrome is reversible and subsides once all of the causative agents have been excreted. Reversible acetylcholinesterase inhibitor agents such as physostigmine can be used as an antidote in life-threatening cases. Wider use is discouraged due to the significant side effects related to cholinergic excess including seizures, muscle weakness, bradycardia, bronchoconstriction, lacrimation, salivation, bronchorrhea, vomiting, and diarrhea. Even in documented cases of anticholinergic toxicity, seizures have been reported after the rapid administration of physostigmine. Asystole has occurred after physostigmine administration for tricyclic antidepressant overdose, so a conduction delay (QRS > 0.10 second) or suggestion of tricyclic antidepressant ingestion is generally considered a contraindication to physostigmine administration.


title: Anticholinergic

text: Plants of the family Solanaceae contain various anticholinergic tropane alkaloids, such as scopolamine, atropine, and hyoscyamine.


title: Anticholinergic

text: Physostigmine is one of only a few drugs that can be used as an antidote for anticholinergic poisoning. Nicotine also counteracts anticholinergics by activating nicotinic acetylcholine receptors. Caffeine (although an adenosine receptor antagonist) can counteract the anticholinergic symptoms by reducing sedation and increasing acetylcholine activity, thereby causing alertness and arousal.


title: Anticholinergic

text: When a significant amount of an anticholinergic is taken into the body, a toxic reaction known as acute anticholinergic syndrome may result. This may happen accidentally or intentionally as a consequence of either recreational or entheogenic drug use, though many users find the side effects to be exceedingly unpleasant and not worth the recreational effects they experience. In the context of recreational use, anticholinergics are often called deliriants.


title: Anticholinergic

text: The most common plants containing anticholinergic alkaloids (including atropine, scopolamine, and hyoscyamine among others) are:


title: Anticholinergic

text: Several narcotic and opiate-containing drug preparations, such as those containing hydrocodone and codeine are combined with an anticholinergic agent to deter intentional misuse. Examples include Hydromet/Hycodan (hydrocodone/homatropine), Lomotil (diphenoxylate/atropine) and Tussionex (hydrocodone polistirex/chlorpheniramine). However, it is noted that opioid/antihistamine combinations are used clinically for their synergistic effect in the management of pain and maintenance of dissociative anesthesia (sedation) in such preparations as Meprozine (meperidine/promethazine) and Diconal (dipipanone/cyclizine), which act as strong anticholinergic agents.


Teenage Mutant Ninja Turtles: Out of the Shadows is a 2016 American superhero film directed by Dave Green, written by Josh Appelbaum and André Nemec. It is the sequel to "Teenage Mutant Ninja Turtles" (2014), and the second and final installment in the "Teenage Mutant Ninja Turtles" reboot film series. The film stars Megan Fox, Will Arnett, Laura Linney, Stephen Amell, Noel Fisher, Jeremy Howard, Pete Ploszek, Alan Ritchson, Tyler Perry, Gary Anthony Williams, Brian Tee, and Sheamus.


title: Teenage Mutant Ninja Turtles: Out of the Shadows

text: Principal photography on the film began on April 27, 2015, in New York City. It was released on June 3, 2016, by Paramount Pictures. The film received generally mixed reviews from critics, with some deeming it a slight improvement over its predecessor. However, it was not financially successful and grossed only $245 million against a $135 million budget, resulting in a planned third film being scrapped. A reboot is being planned.


text: One year after stopping Shredder, the Teenage Mutant Ninja Turtles are informed by April O'Neil that scientist Baxter Stockman is working for Shredder and plans to bust him out of prison. As the Shredder is transferred between prisons alongside Bebop and Rocksteady by corrections officer Casey Jones, the Foot Clan attack their convoy. Despite the turtles' interference, Shredder escapes when Stockman uses a teleportation device. Shredder is hijacked mid-teleport, winds up in another dimension, and meets the alien warlord Krang, who reveals his plans to invade Earth. He gives Shredder a mutagenic compound in exchange for finding three components of a machine that Krang sent to Earth long ago which will open a portal to his dimension when united, as Shredder and Stockman have the first piece. Casey tells NYPD chief Rebecca Vincent what happened to Shredder, but is met with disbelief, and decides to go on his own.


text: Shredder recruits Bebop and Rocksteady, and Stockman uses Krang's mutagen to transform them into a humanoid warthog and rhinoceros, respectively. April witnesses their transformation and steals the remaining mutagen vial from the TCRI lab. Pursued by the Foot, she is rescued by Casey, who later meets the turtles, but the vial is taken into police custody. In the lair, Donatello deduces that the mutagen could be used to turn the turtles into humans, but Leonardo refuses and orders Donatello to keep it a secret from the others. However, Michelangelo overhears and tells Raphael, which enrages Raphael and leads to a fierce argument between him and Leo. Raphael then recruits Mikey, April, Casey, and Vern Fenwick to break into the NYPD headquarters and retrieve the mutagen, but the Foot arrive ahead of them. In the ensuing battle, the turtles' existence is revealed to the police, who start a manhunt for them, and April and Casey are arrested while helping the brothers escape with the mutagen.


text: After recovering the second component of the machine, Bebop and Rocksteady go to the rainforests of Manaus, Brazil, for the final component. The turtles follow them and board Bebop and Rocksteady's jet in midair. In the resulting battle, the jet is critically damaged after Rocksteady fires a tank-mounted Mark 19 grenade launcher, and crashes into a river, though Bebop and Rocksteady are ultimately able to escape with the component. Shredder and Stockman complete the device and open a portal to Krang's dimension through which his war machine, the Technodrome, begins to emerge. Shredder betrays Stockman and his men take him to their headquarters in Tokyo. When entering the Technodrome, Krang likewise betrays Shredder, freezing him and locking him with his collection of other defeated foes.


text: Unable to reach the Technodrome as the police pursue them, the turtles debate over taking the mutagen to become human and fight openly. While Leonardo agrees, Raph shatters the vial. Upon April's request, Vern recovers the security footage from a hidden TCRI camera that proves Stockman and the Shredder's collaboration and secures April and Casey's release. April arranges a meeting between the turtles and Vincent, and convinces her that they are not enemies. With the help of the police, the turtles are able to jump from the Chrysler Building and confront Krang aboard the still-assembling Technodrome. Krang is defeated when Donatello short circuits his robotic body. April, Casey and Vern raid the Foot Clan facility, defeat Bebop, Rocksteady and the Shredder's lieutenant Karai and take control of the device. The turtles are able to hurl the ship's beacon back through the portal, taking Krang and the rest of the Technodrome with it, as April, Casey, and Vern shut the portal down.


text: Bebop and Rocksteady are back in custody, while Stockman remains at large. The turtles are honored by Vincent and the NYPD along with April, Casey, and Vern. Vincent offers to introduce the turtles to the public, but the turtles opt to keep their existence a secret while still helping as they always have. On top of the Statue of Liberty, the turtles celebrate their victory over the vanquished Krang.


text: Dean Winters appears as a bartender. Supermodel Alessandra Ambrosio has a cameo appearance. NBA players Carmelo Anthony, DeAndre Jordan, Lou Amundson, JJ Redick, Austin Rivers, Matt Barnes, and Spencer Hawes also made cameos in the film. Series co-creator Kevin Eastman makes a cameo appearance as a pizza delivery man named after himself in the film's opening. Jill Martin also made a cameo appearance in the basketball scene in the film. Judith Hoag, who previously played April O'Neil in the 1990 film, appeared in a cameo as Rita, April's boss, in a deleted scene. Jane Wu plays Jade, a police officer.


text: After the 2014 film exceeded box office expectations, Paramount and Nickelodeon officially announced a sequel was greenlit, and set to be released in theatres on June 3, 2016, with plans to incorporate the characters Casey Jones and Bebop and Rocksteady. Jonathan Liebesman and Bradley Fuller were also interested in doing a storyline that involved Dimension X and Krang. "Earth to Echo" director Dave Green helmed the sequel, replacing Jonathan Liebesman. Known briefly as "Teenage Mutant Ninja Turtles: Half Shell", Paramount revealed that the title had officially been changed to "Teenage Mutant Ninja Turtles: Out of the Shadows".


text: Megan Fox and Will Arnett returned as April O'Neil and Vern Fenwick respectively; also confirmed were the Shredder's return, and Bebop and Rocksteady debut in the movie. In an interview, William Fichtner stated that he would be returning as Eric Sacks, but for unknown reasons, he ultimately did not appear in the final film. However, he could have returned for the third installment, considering he (along with the turtle actors, Noel Fisher, Jeremy Howard, Alan Ritchson and Pete Ploszek) signed on for three TMNT films at the time. Production was confirmed to start in April 2015, along with the casting of Alessandra Ambrosio, and several members of the Los Angeles Clippers. Stephen Amell was cast as Casey Jones, after test reading alongside several different actors. Amell acknowledged the character bore similarities to his Oliver Queen from "Arrow". He stated the characters are "fundamentally different" from one another, but that Casey did resemble Oliver from older versions. Tyler Perry was cast as scientist Baxter Stockman, replacing K. Todd Freeman, who played the role in the 2014 film. Brian Tee joined the cast as the Shredder, replacing Tohoru Masamune from the first film. Laura Linney was cast in an unspecified role. Gary Anthony Williams was cast as Bebop, while WWE wrestler Sheamus was confirmed to play Rocksteady. Minae Noji was replaced with Brittany Ishibashi in the role of Karai. CM Punk revealed that he lost the role of Rocksteady to Sheamus. Fred Armisen was originally chosen to voice Krang in the film, but, in May 2016, shortly before the film's release, Brad Garrett voiced Krang instead due to Armisen having schedule conflicts. While promoting "Elvis & Nixon", Johnny Knoxville revealed that he was not asked to return for the sequel as the voice of Leonardo.


text: Filming began in April in New York City and Buffalo, New York, spending about $70 million in the state. Filming began on April 27, 2015, when the film crew was spotted filming in Midtown Manhattan and moved out to Foz do Iguaçu, Brazil, with filming in Buffalo beginning on May 4, along the Kensington Expressway and ended May 17. Filming wrapped up in August 2015. Additional filming occurred in New York City on January 30 following year, and ended on February 1. Farrelly and Williams recorded additional dialogue for the film in February 2016.


text: Steve Jablonsky composed the music score, replacing Brian Tyler from the first film. Mexican teen boy band CD9 performed an updated version of the original show's theme song for the film. The film score soundtrack was released on June 3, 2016, on digital platforms but excluded compact discs.


text: The film premiered in New York City on May 22, 2016, and was released in the United Kingdom on May 30 and the United States on June 3.


text: "Out of the Shadows" was released on Digital HD on September 6, 2016, and on 4K Ultra HD, Blu-ray, Blu-ray 3D and DVD on September 20. The film debuted in first place on the overall home video sales chart and in second place on the Blu-ray sales chart for the week ending on September 25.


text: "Out of the Shadows" grossed $82.1 million in the United States and Canada and $163.6 million in other territories for a worldwide total of $245.6 million, against its production budget of $135 million. It made around 50% less than its predecessor, which had grossed $493 million. In October 2016, in response to the film's poor commercial performance, producers Andrew Form and Brad Fuller said they loved the movie, and they loved making it, but they were surprised by the film's performance and "it just didn't find an audience. We really don't know why" "The Hollywood Reporter" estimated the film lost the studio at least $75 million, when factoring together all expenses and revenues.


text: In the U.S. and Canada, the film was projected to gross around $30–40 million from 4,071 theaters in its opening weekend, with some estimates going as high as $49 million. It received a one-week special run across 331 IMAX and IMAX 3D theaters from June 2 up to June 9. The film made $2 million from Thursday night previews which began at 5 p.m., compared to the first film's $4.6 million. On its opening day it earned $12.5 million (including previews), with $4.4 million (36%) coming from 3D showings. In its opening weekend, it grossed $35.3 million, finishing first at the box office. However, its opening was down 45% from the first film's $65.6 million debut. Paramount vice chairman Rob Moore said that while the studio was hoping for a stronger opening, he believed that the film could make up some ground in the coming weeks since most films aimed at younger audiences play at better multiples.


text: Outside North America, the film was released in about 30 overseas IMAX markets, beginning Wednesday, June 1, with additional markets throughout the summer, including China on July 2. It opened across 40 markets the same weekend as its U.S. release, including big markets like the United Kingdom, Mexico and Russia, which is about 39% of its total international marketplace, and was projected to make around $36 million. It ended up grossing $33 million, which is down 11% when compared to the first film's same suite of markets, and had No. 1 debuts in 21 markets out of the 40. The top openings were in China ($26.1 million), the UK ($5.1 million), Russia ($4.8 million) and Mexico ($4.5 million). In the United Kingdom, it came in second place – behind "Warcraft" – with a £3.49 million ($5 million) seven-day opening from 513 theaters.


text: In China the film was granted a rare July release date, along with "The Legend of Tarzan", where it grossed an estimated $26.1 million from 6,600 screens in two days. It had a limited opening on Friday, July 1 and opened wide the following day. It faced competition from local film "Bounty Hunters" which had the advantage of opening wide right from Friday. Yet, "Out of the Shadows" emerged victorious at the end of the weekend ahead of the latter's $18 million opening. As a result, "Out of the Shadows" became the ninth consecutive Hollywood import film to debut atop the chart beginning from May 6, 2016. In comparable to Saturday releases, the figure is almost double the launch of "Big Hero 6"; 41% above the first film; and 18% higher than "The Angry Birds Movie". It fell precipitously in its second weekend by 74%, earning $6.6 million and thereby slipped in to fourth place. It opened in key markets such as Germany and Austria on August 11 as well as Japan on August 26, 2016.


text: On Rotten Tomatoes, the film has an approval rating of based on reviews, with an average rating of . The site's critical consensus reads: ""Teenage Mutant Ninja Turtles: Out of the Shadows" is a slight improvement over its predecessor, but still lacks the wit or anarchic energy of the comics that birthed the franchise." On Metacritic, the film has a weighted average score of 40 out of 100, based on 30 critics, indicating "mixed or average reviews". Audiences polled by CinemaScore gave the film an average grade of "A−" on an A+ to F scale, an improvement over the first film's "B".


text: Glenn Kenny of "The New York Times" gave the film a positive review writing: "This movie is, it happens, easier to sit through than the 2014 film", while also adding that "the 3-D action, overseen by the director Dave Green, is not wholly incoherent. The production values (showcasing new mutants and many gear-heavy extra-dimensional machines undreamed of in any actual engineering philosophy) are ultrashiny. And there are even a couple of amusing, albeit unmemorable, sight gags and one-liners". Edward Douglas of "New York Daily News" gave the film three out of five stars: "As with the best popcorn flicks, "Out of the Shadows" offers plenty of mindless entertainment and mind-numbing silliness that somehow works well enough to leave even the Ninja Turtles' biggest detractors shell-shocked". Michael O'Sullivan of "The Washington Post" praised the film's action sequences and story while overall writing that, ""Out of the Shadows" is, at least, deliciously silly, even if it is also decidedly forgettable. Like a well-plated but nutrition-free meal, it registers on the senses while being bad for you".


text: Peter Hartlaub of "San Francisco Chronicle" gave the film a negative review: "Your 11-year-old is going to love this film. Then he'll grow up and wonder what he was thinking". Sara Stewart of "The New York Post" gave the film two out of four stars and wrote, "despite the title, the wisecracking turtles named for Renaissance painters are never allowed to shine... It’s a bummer, dude". Lindsey Bahr of the "Associated Press" gave the film one star out of four and said, ""Teenage Mutant Ninja Turtles: Out of the Shadows" is a Saturday morning cartoon on Michael Bay steroids. For the under 12 set, that's fine. For the rest of us? It's something to actively avoid".


text: Noel Fisher stated in an interview that he and the other Turtle actors had signed on for three films. Megan Fox had also signed on for three films. Tyler Perry said that if a third film was made, his character, Baxter Stockman, would probably mutate into his fly form during the movie. Pete Ploszek also expressed his interests in reprising his role in a third film as Leonardo. In October 2016, in light of the film's mixed reception and financial underperformance, producer Andrew Form indicated that a third film was unlikely.


text: In June 2020, it was reported that Nickelodeon Animation Studio was developing a computer-animated "Teenage Mutant Ninja Turtles" film for Paramount Pictures. Seth Rogen, Evan Goldberg, and James Weaver would produce the film through their company, Point Grey Pictures. Jeff Rowe was set to direct the film, with Brendan O'Brien writing the screenplay. It is scheduled for release on August 4, 2023.


text: In June 2018, Paramount Pictures announced a new reboot in the series with Bay, Fuller and Form returning to produce the film and Andrew Dodge writing the script. Fuller and Form said at the 24th Critics' Choice Awards that production on the reboot was set to start in 2019, but in July, co-creator Kevin Eastman revealed that the film was still in development and believed that Paramount took the reactions to the 2014 and 2016 films "to heart", and that "its going to be a next-level type of stuff".


text: In August 2021, it was announced that a new live-action film was in the works with Colin Jost and Casey Jost penning the script and Michael Bay, Andrew Form, Brad Fuller, Scott Mednick and Galen Walker signing on as producers.


title: London Stock Exchange

text: London Stock Exchange (LSE) is a stock exchange in the City of London, England, United Kingdom. , the total market value of all companies trading on LSE was £3.9 trillion. Its current premises are situated in Paternoster Square close to St Paul's Cathedral in the City of London. Since 2007, it has been part of the London Stock Exchange Group (LSEG, that it also lists ()). The LSE was the most-valued stock exchange in Europe from 2003 when records began till Autumn 2022, when the Paris exchange was briefly larger, until the LSE retook its position as Europe’s largest stock exchange 10 days later.


title: London Stock Exchange

text: The Royal Exchange had been founded by English financier Thomas Gresham and Sir Richard Clough on the model of the Antwerp Bourse. It was opened by Elizabeth I of England in 1571.


title: London Stock Exchange

text: During the 17th century, stockbrokers were not allowed in the Royal Exchange due to their rude manners. They had to operate from other establishments in the vicinity, notably Jonathan's Coffee-House. At that coffee house, a broker named John Castaing started listing the prices of a few commodities, such as salt, coal, paper, and exchange rates in 1698. Originally, this was not a daily list and was only published a few days of the week.


title: London Stock Exchange

text: This list and activity was later moved to Garraway's coffee house. Public auctions during this period were conducted for the duration that a length of tallow candle could burn; these were known as "by inch of candle" auctions. As stocks grew, with new companies joining to raise capital, the royal court also raised some monies. These are the earliest evidence of organised trading in marketable securities in London.


title: London Stock Exchange

text: After Gresham's Royal Exchange building was destroyed in the Great Fire of London, it was rebuilt and re-established in 1669. This was a move away from coffee houses and a step towards the modern model of stock exchange.


title: London Stock Exchange

text: The Royal Exchange housed not only brokers but also merchants and merchandise. This was the birth of a regulated stock market, which had teething problems in the shape of unlicensed brokers. In order to regulate these, Parliament passed an Act in 1697 that levied heavy penalties, both financial and physical, on those brokering without a licence. It also set a fixed number of brokers (at 100), but this was later increased as the size of the trade grew. This limit led to several problems, one of which was that traders began leaving the Royal Exchange, either by their own decision or through expulsion, and started dealing in the streets of London. The street in which they were now dealing was known as 'Exchange Alley', or 'Change Alley'; it was suitably placed close to the Bank of England. Parliament tried to regulate this and ban the unofficial traders from the Change streets.


title: London Stock Exchange

text: Traders became weary of "bubbles" when companies rose quickly and fell, so they persuaded Parliament to pass a clause preventing "unchartered" companies from forming.


title: London Stock Exchange

text: After the Seven Years' War (1756–1763), trade at Jonathan's Coffee House boomed again. In 1773, Jonathan, together with 150 other brokers, formed a club and opened a new and more formal "Stock Exchange" in Sweeting's Alley. This now had a set entrance fee, by which traders could enter the stock room and trade securities. It was, however, not an exclusive location for trading, as trading also occurred in the Rotunda of the Bank of England. Fraud was also rife during these times and in order to deter such dealings, it was suggested that users of the stock room pay an increased fee. This was not met well and ultimately, the solution came in the form of annual fees and turning the Exchange into a Subscription room.


title: London Stock Exchange

text: The Subscription room created in 1801 was the first regulated exchange in London, but the transformation was not welcomed by all parties. On the first day of trading, non-members had to be expelled by a constable. In spite of the disorder, a new and bigger building was planned, at Capel Court.


title: London Stock Exchange

text: William Hammond laid the first foundation stone for the new building on 18 May. It was finished on 30 December when "The Stock Exchange" was incised on the entrance.


title: London Stock Exchange

text: In the Exchange's first operating years, on several occasions there was no clear set of regulations or fundamental laws for the Capel Court trading. In February 1812, the General Purpose Committee confirmed a set of recommendations, which later became the foundation of the first codified rule book of the Exchange. Even though the document was not a complex one, topics such as settlement and default were, in fact, quite comprehensive.


title: London Stock Exchange

text: With its new governmental commandments and increasing trading volume, the Exchange was progressively becoming an accepted part of the financial life in the city. In spite of continuous criticism from newspapers and the public, the government used the Exchange's organised market (and would most likely not have managed without it) to raise the enormous amount of money required for the wars against Napoleon.


title: London Stock Exchange

text: After the war and facing a booming world economy, foreign lending to countries such as Brazil, Peru and Chile was a growing market. Notably, the Foreign Market at the Exchange allowed for merchants and traders to participate, and the Royal Exchange hosted all transactions where foreign parties were involved. The constant increase in overseas business eventually meant that dealing in foreign securities had to be allowed within all of the Exchange's premises.


title: London Stock Exchange

text: Just as London enjoyed growth through international trade, the rest of Great Britain also benefited from the economic boom. Two other cities, in particular, showed great business development: Liverpool and Manchester. Consequently, in 1836 both the Manchester and Liverpool stock exchanges were opened. Some stock prices sometimes rose by 10%, 20% or even 30% in a week. These were times when stockbroking was considered a real business profession, and such attracted many entrepreneurs. Nevertheless, with booms came busts, and in 1835 the "Spanish panic" hit the markets, followed by a second one two years later.


title: London Stock Exchange

text: By June 1853, both participating members and brokers were taking up so much space that the Exchange was now uncomfortably crowded, and continual expansion plans were taking place. Having already been extended west, east, and northwards, it was then decided the Exchange needed an entire new establishment. Thomas Allason was appointed as the main architect, and in March 1854, the new brick building inspired from the Great Exhibition stood ready. This was a huge improvement in both surroundings and space, with twice the floor space available.


title: London Stock Exchange

text: By the late 1800s, the telephone, ticker tape, and the telegraph had been invented. Those new technologies led to a revolution in the work of the Exchange.


title: London Stock Exchange

text: As the financial centre of the world, both the City and the Stock Exchange were hit hard by the outbreak of World War I in 1914. Due to fears that borrowed money was to be called in and that foreign banks would demand their loans or raise interest, prices surged at first. The decision to close the Exchange for improved breathing space and to extend the August Bank Holiday to prohibit a run on banks, was hurried through by the committee and Parliament, respectively. The Stock Exchange ended up being closed from the end of July until the New Year, causing street business to be introduced again, as well as the "challenge system".


title: London Stock Exchange

text: The Exchange was set to open again on 4 January 1915 under tedious restrictions: transactions were to be in cash only. Due to the limitations and challenges on trading brought by the war, almost a thousand members quit the Exchange between 1914 and 1918. When peace returned in November 1918, the mood on the trading floor was generally cowed. In 1923, the Exchange received its own coat of arms, with the motto "Dictum Meum Pactum", My Word is My Bond.


title: London Stock Exchange

text: In 1937, officials at the Exchange used their experiences from World War I to draw up plans for how to handle a new war. The main concerns included air raids and the subsequent bombing of the Exchange's perimeters, and one suggestion was a move to Denham, Buckinghamshire. This however never took place. On the first day of September 1939, the Exchange closed its doors "until further notice" and two days later World War II was declared. Unlike in the prior war, the Exchange opened its doors again six days later, on 7 September.


title: London Stock Exchange

text: As the war escalated into its second year, the concerns for air raids were greater than ever. Eventually, on the night of 29 December 1940, one of the greatest fires in London's history took place. The Exchange's floor was hit by a clutch of incendiary bombs, which were extinguished quickly. Trading on the floor was now drastically low and most was done over the phone to reduce the possibility of injuries.


title: London Stock Exchange

text: The Exchange was only closed for one more day during wartime, in 1945 due to damage from a V-2 rocket. Nonetheless, trading continued in the house's basement.


title: London Stock Exchange

text: After decades of uncertain if not turbulent times, stock market business boomed in the late 1950s. This spurred officials to find new, more suitable accommodation. The work on the new Stock Exchange Tower began in 1967. The Exchange's new 321 feet (96 metre) high building had 26 storeys with council and administration at the top, and middle floors let out to affiliate companies. Queen Elizabeth II opened the building on 8 November 1972; it was a new City landmark, with its trading floor.


title: London Stock Exchange

text: 1973 marked a year of changes for the Stock Exchange. First, two trading prohibitions were abolished. A report from the Monopolies and Mergers Commission recommended the admittance of both women and foreign-born members on the floor. Second, in March the London Stock Exchange formally merged with the eleven British and Irish regional exchanges, including the Scottish Stock Exchange. This expansion led to the creation of a new position of Chief Executive Officer; after an extensive search this post was given to Robert Fell. There were more governance changes in 1991, when the governing Council of the Exchange was replaced by a Board of Directors drawn from the Exchange's executive, customer, and user base; and the trading name became "The London Stock Exchange".


title: London Stock Exchange

text: FTSE 100 Index (pronounced "Footsie 100") was launched by a partnership of the "Financial Times" and the Stock Exchange on 3 January 1984. This turned out to be one of the most useful indices of all, and tracked the movements of the 100 leading companies listed on the Exchange.


title: London Stock Exchange

text: On 20 July 1990, a bomb planted by the Provisional Irish Republican Army (IRA) exploded in the men's toilets behind the visitors' gallery. The area had already been evacuated and nobody was injured. About 30 minutes before the blast at 8:49 a.m., a man who said he was a member of the IRA told Reuters that a bomb had been placed at the exchange and was about to explode. Police officials said that if there had been no warning, the human toll would have been very high. The explosion ripped a hole in the 23-storey building in Threadneedle Street and sent a shower of glass and concrete onto the street. The long-term trend towards electronic trading platforms reduced the Exchange's attraction to visitors, and although the gallery reopened, it was closed permanently in 1992.


title: London Stock Exchange

text: The biggest event of the 1980s was the sudden de-regulation of the financial markets in the UK in 1986. The phrase "Big Bang" was coined to describe measures, including abolition of fixed commission charges and of the distinction between stockjobbers and stockbrokers on the London Stock Exchange, as well as the change from an open outcry to electronic, screen-based trading.


title: London Stock Exchange

text: In 1995, the Exchange launched the Alternative Investment Market, the AIM, to allow growing companies to expand into international markets. Two years later, the Electronic Trading Service (SETS) was launched, bringing greater speed and efficiency to the market. Next, the CREST settlement service was launched. In 2000, the Exchange's shareholders voted to become a public limited company, London Stock Exchange plc. London Stock Exchange also transferred its role as UK Listing Authority to the Financial Services Authority (FSA-UKLA).


title: London Stock Exchange

text: EDX London, an international equity derivatives business, was created in 2003 in partnership with OM Group. The Exchange also acquired Proquote Limited, a new generation supplier of real-time market data and trading systems.


title: London Stock Exchange

text: The old Stock Exchange Tower became largely redundant with Big Bang, which deregulated many of the Stock Exchange's activities: computerised systems and dealing rooms replaced face-to-face trading. In 2004, LondonStock Exchange moved to a brand-new headquarters in Paternoster Square, close to St Paul's Cathedral.


title: London Stock Exchange

text: In 2007, the London Stock Exchange merged with Borsa Italiana, creating London Stock Exchange Group (LSEG). The Group's headquarters are in Paternoster Square.


title: London Stock Exchange

text: The Stock Exchange in Paternoster Square was the initial target for the protesters of Occupy London on 15 October 2011. Attempts to occupy the square were thwarted by police. Police sealed off the entrance to the square as it is private property, a High Court injunction having previously been granted against public access to the square. The protesters moved nearby to occupy the space in front of St Paul's Cathedral. The protests were part of the global Occupy movement.


title: London Stock Exchange

text: On 25 April 2019, the final day of the Extinction Rebellion disruption in London, 13 activists glued themselves together in a chain, blocking the entrances of the Stock Exchange. The protesters were all later arrested on suspicion of aggravated trespass. Extinction Rebellion had said its protesters would target the financial industry "and the corrosive impacts of the ... sector on the world we live in" and activists also blocked entrances to HM Treasury and the Goldman Sachs office on Fleet Street.


title: London Stock Exchange

text: The main market is home to over 1,300 large companies from 60 countries. The FTSE 100 Index ("footsie") is the main share index of the 100 most highly capitalised UK companies listed on the Main Market.


title: London Stock Exchange

text: The Alternative Investment Market is LSE's international market for smaller companies. A wide range of businesses including early-stage, venture capital-backed, as well as more-established companies join AIM seeking access to growth capital. The AIM is classified as a Multilateral Trading Facility (MTF) under the 2004 MiFID directive, and as such it is a flexible market with a simpler admission process for companies wanting to be publicly listed.


title: London Stock Exchange

text: Through the Exchange's Italian arm, Borsa Italiana, the London Stock Exchange Group as a whole offers clearing and settlement services for trades through "CC&G" (Cassa di Compensazione e Garanzia) and Monte Titoli. is the Groups Central Counterparty (CCP) and covers multiple asset classes throughout the Italian equity, derivatives and bond markets. CC&G also clears Turquoise derivatives. "Monte Titoli" (MT) is the pre-settlement, settlement, custody and asset services provider of the Group. MT operates both on-exchange and OTC trades with over 400 banks and brokers.


title: London Stock Exchange

text: Their previous trading platform TradElect was based on Microsoft's .NET Framework, and was developed by Microsoft and Accenture. For Microsoft, LSE was a good combination of a highly visible exchange and yet a relatively modest IT problem.


title: London Stock Exchange

text: Despite TradElect only being in use for about two years, after suffering multiple periods of extended downtime and unreliability the LSE announced in 2009 that it was planning to switch to Linux in 2010. The main market migration to MillenniumIT technology was successfully completed in February 2011.


title: London Stock Exchange

text: LSEG provides high-performance technology, including trading, market surveillance and post-trade systems, for over 40 organisations and exchanges, including the Group's own markets. Additional services include network connectivity, hosting and quality assurance testing. MillenniumIT, GATElab and Exactpro are among the Group's technology companies.


title: London Stock Exchange

text: The LSE facilitates stock listings in a currency other than its "home currency". Most stocks are quoted in GBP but some are quoted in EUR while others are quoted in USD.


title: London Stock Exchange

text: On 3 May 2000, it was announced that the LSE would merge with the Deutsche Börse; however this fell through.


title: London Stock Exchange

text: On 23 June 2007, the London Stock Exchange announced that it had agreed on the terms of a recommended offer to the shareholders of the Borsa Italiana S.p.A. The merger of the two companies created a leading diversified exchange group in Europe. The combined group was named the London Stock Exchange Group, but still remained two separate legal and regulatory entities. One of the long-term strategies of the joint company is to expand Borsa Italiana's efficient clearing services to other European markets.


title: London Stock Exchange

text: In 2007, after Borsa Italiana announced that it was exercising its call option to acquire full control of MBE Holdings; thus the combined Group would now control Mercato dei Titoli di Stato, or MTS. This merger of Borsa Italiana and MTS with LSE's existing bond-listing business enhanced the range of covered European fixed income markets.


title: London Stock Exchange

text: On 9 October 2020, London Stock Exchange agreed to sell the Borsa Italiana (including Borsa's bond trading platform MTS) to Euronext for €4.3 billion (£3.9 billion) in cash. Euronext completed the acquisition of the Borsa Italiana Group on 29 April 2021 for a final price of €4,444 million.


title: London Stock Exchange

text: On 12 Dec 2022, Microsoft buys nearly 4% stack in LSE(London Stock Exchange Group) as part of 10-Year cloud deal.


title: London Stock Exchange

text: In December 2005, London Stock Exchange rejected a £1.6 billion takeover offer from Macquarie Bank. London Stock Exchange described the offer as "derisory", a sentiment echoed by shareholders in the Exchange. Shortly after Macquarie withdrew its offer, the LSE received an unsolicited approach from NASDAQ valuing the company at £2.4 billion. This too it rejected. NASDAQ later pulled its bid, and less than two weeks later on 11 April 2006, struck a deal with LSE's largest shareholder, Ameriprise Financial's Threadneedle Asset Management unit, to acquire all of that firm's stake, consisting of 35.4 million shares, at £11.75 per share. NASDAQ also purchased 2.69 million additional shares, resulting in a total stake of 15%. While the seller of those shares was undisclosed, it occurred simultaneously with a sale by Scottish Widows of 2.69 million shares. The move was seen as an effort to force LSE to the negotiating table, as well as to limit the Exchange's strategic flexibility.


title: London Stock Exchange

text: Subsequent purchases increased NASDAQ's stake to 25.1%, holding off competing bids for several months. United Kingdom financial rules required that NASDAQ wait for a period of time before renewing its effort. On 20 November 2006, within a month or two of the expiration of this period, NASDAQ increased its stake to 28.75% and launched a hostile offer at the minimum permitted bid of £12.43 per share, which was the highest NASDAQ had paid on the open market for its existing shares. The LSE immediately rejected this bid, stating that it "substantially undervalues" the company.


title: London Stock Exchange

text: NASDAQ revised its offer (characterized as an "unsolicited" bid, rather than a "hostile takeover attempt") on 12 December 2006, indicating that it would be able to complete the deal with 50% (plus one share) of LSE's stock, rather than the 90% it had been seeking. The U.S. exchange did not, however, raise its bid. Many hedge funds had accumulated large positions within the LSE, and many managers of those funds, as well as Furse, indicated that the bid was still not satisfactory. NASDAQ's bid was made more difficult because it had described its offer as "final", which, under British bidding rules, restricted their ability to raise its offer except under certain circumstances.


title: London Stock Exchange

text: In the end, NASDAQ's offer was roundly rejected by LSE shareholders. Having received acceptances of only 0.41% of rest of the register by the deadline on 10 February 2007, Nasdaq's offer duly lapsed.


title: London Stock Exchange

text: On 20 August 2007, NASDAQ announced that it was abandoning its plan to take over the LSE and subsequently look for options to divest its 31% (61.3 million shares) shareholding in the company in light of its failed takeover attempt. In September 2007, NASDAQ agreed to sell the majority of its shares to Borse Dubai, leaving the United Arab Emirates-based exchange with 28% of the LSE.


title: London Stock Exchange

text: On 9 February 2011, London Stock Exchange Group announced it had agreed to merge with the Toronto-based TMX Group, the owners of the Toronto Stock Exchange, creating a combined entity with a market capitalization of listed companies equal to £3.7 trillion. Xavier Rolet, CEO of the LSE Group at the time, would have headed the new enlarged company, while TMX Chief Executive Thomas Kloet would have become the new firm president. London Stock Exchange Group however announced it was terminating the merger with TMX on 29 June 2011 citing that "LSEG and TMX Group believe that the merger is highly unlikely to achieve the required two-thirds majority approval at the TMX Group shareholder meeting". Even though LSEG obtained the necessary support from its shareholders, it failed to obtain the required support from TMX's shareholders.


title: London Stock Exchange

text: Normal trading sessions on the main orderbook (SETS) are from 08:00 to 16:30 local time every day of the week except Saturdays, Sundays and holidays declared by the exchange in advance. The detailed schedule is as follows:


title: London Stock Exchange

text: SETSqx (Stock Exchange Electronic Trading Service – quotes and crosses) is a trading service for securities less liquid than those traded on SETS.


title: London Stock Exchange

text: Holidays are currently: New Year's Day, Good Friday, Easter Monday, May Bank Holiday, Spring Bank Holiday, Summer Bank Holiday, Christmas Day, and Boxing Day. If New Year's Day, Christmas Day, and/or Boxing Day is on a weekend, the following working day is a holiday.


title: Narcissus (mythology)

text: In Greek mythology, Narcissus (; Ancient Greek: Νάρκισσος "Nárkissos") was a hunter from Thespiae in Boeotia (alternatively Mimas or modern day Karaburun, Izmir) who was known for his beauty. According to Tzetzes, he rejected all romantic advances, eventually falling in love with his own reflection in a pool of water, staring at it for the remainder of his life. After he died, in his place sprouted a flower bearing his name.


title: Narcissus (mythology)

text: The character of Narcissus is the origin of the term narcissism, a fixation with oneself. This quality, in turn, contributes to the definition of narcissistic personality disorder, a psychiatric condition marked by grandiosity, excessive need for attention and admiration, and an inability to empathize.


title: Narcissus (mythology)

text: Like the myth of Laius and Chrysippus, the myth of Narcissus is a Boeotian pederastic cautionary tale, a story meant to teach by counter-example.


title: Narcissus (mythology)

text: The name is of Greek etymology. According to R. S. P. Beekes, "[t]he suffixes [-ισσος] clearly points to a Pre-Greek word." The word narcissus has come to be used for the daffodil, but there is no clarity on whether the flower is named for the myth or the myth for the flower, or if there is any true connection at all. Pliny the Elder wrote that the plant was named for its fragrance ( , "I grow numb"), not the youth.


title: Narcissus (mythology)

text: In some versions, Narcissus was the son of the river god Cephissus and nymph Liriope, while Nonnus instead has him as the son of the lunar goddess Selene and her mortal lover Endymion.


title: Narcissus (mythology)

text: Several versions of the myth have survived from ancient sources. In appreciation of one from a Greek traveler and geographer of the second century AD named Pausanias and a more popular one by Ovid, (supposably rewritten from Pausanias version as a Roman myth) found in Book 3 of his Metamorphoses. This is the story of Echo and Narcissus. When Liriope gave birth to the handsome child Narcissus, she consulted the seer Tiresias, who predicted that the boy would live a long life only if he never discovered himself. One day Narcissus was walking in the woods when Echo, an Oread (mountain nymph) saw him, fell deeply in love, and followed him. Narcissus sensed he was being followed and shouted "Who's there?". Echo repeated "Who's there?" She eventually revealed her identity and attempted to embrace him. He stepped away and told her to leave him alone. She was heartbroken and spent the rest of her life in lonely glens until nothing but an echo sound remained of her. Nemesis (as an aspect of Aphrodite), the goddess of revenge, noticed this behaviour after learning the story and decided to punish Narcissus. Once, during the summer, he was getting thirsty after hunting, and the goddess lured him to a pool where he leaned upon the water and saw himself in the bloom of youth. Narcissus did not realize it was merely his own reflection and fell deeply in love with it, as if it were another young man. Unable to leave the allure of his image, he eventually realized that his love could not be reciprocated and he melted away from the fire of passion burning inside him, eventually turning into a gold and white flower.


title: Narcissus (mythology)

text: An earlier version ascribed to the poet Parthenius of Nicaea, composed around 50 BC, was discovered in 2004 by Dr Benjamin Henry among the Oxyrhynchus papyri at Oxford. Unlike Ovid's version, it ended with Narcissus who lost his will to live and committed suicide. A version by Conon, a contemporary of Ovid, also ends in suicide ("Narrations," 24). In it, a young man named Ameinias fell in love with Narcissus, who had already spurned his male suitors. Narcissus also spurned him and gave him a sword. Ameinias committed suicide at Narcissus's doorstep. He had prayed to the gods to give Narcissus a lesson for all the pain he provoked. Narcissus walked by a pool of water and decided to drink some. He saw his reflection, became entranced by it, and killed himself because he could not have his object of desire. A century later the travel writer Pausanias recorded a novel variant of the story, in which Narcissus falls in love with his twin sister rather than himself. In all versions, his body disappears and all that is left is a narcissus flower.


title: Narcissus (mythology)

text: The myth of Narcissus has inspired artists for at least two thousand years, even before the Roman poet Ovid featured a version in book III of his "Metamorphoses". This was followed in more recent centuries by other poets (e.g. Keats and Alfred Edward Housman) and painters (Caravaggio, Poussin, Turner, Dalí (see "Metamorphosis of Narcissus"), and Waterhouse).


title: Narcissus (mythology)

text: In Stendhal's novel "Le Rouge et le Noir" (1830), there is a classic narcissist in the character of Mathilde. Says Prince Korasoff to Julien Sorel, the protagonist, with respect to his beloved girl:


title: Narcissus (mythology)

text: During the two or three little outbursts of passion she has allowed herself in your favor, she has, by a great effort of imagination, seen in you the hero of her dreams, and not yourself as you really are.<br>


title: Narcissus (mythology)

text: The myth had a decided influence on English Victorian homoerotic culture, via André Gide's study of the myth, "Le Traité du Narcisse" ('The Treatise of the Narcissus', 1891), and the only novel by Oscar Wilde, "The Picture of Dorian Gray".


title: Narcissus (mythology)

text: Paulo Coelho's "The Alchemist" also starts with a story about Narcissus, found (we are told) by the alchemist in a book brought by someone in the caravan. The alchemist's (and Coelho's) source was very probably Hesketh Pearson's "The Life of Oscar Wilde" (1946) in which this story is recorded (Penguin edition, p. 217) as one of Wilde's inspired inventions. This version of the Narcissus story is based on Wilde's "The Disciple" from his "Poems in Prose (Wilde) ".


title: Narcissus (mythology)

text: Author and poet Rainer Maria Rilke visits the character and symbolism of Narcissus in several of his poems.


title: Narcissus (mythology)

text: Seamus Heaney references Narcissus in his poem "Personal Helicon" from his first collection "Death of a Naturalist":To stare, big-eyed Narcissus, into some spring<br>


title: Narcissus (mythology)

text: In Rick Riordan's "Heroes of Olympus series," Narcissus appears as a minor antagonist in the third book "The Mark of Athena".


title: Narcissus (mythology)

text: William Faulkner's character "Narcissa" in "Sanctuary", sister of Horace Benbow, was also named after Narcissus. Throughout the novel, she allows the arrogant, pompous pressures of high-class society to overrule the unconditional love that she should have for her brother.


title: Narcissus (mythology)

text: Hermann Hesse's character "Narcissus" in "Narcissus and Goldmund" shares several of mythical Narcissus' traits, although his narcissism is based on his intellect rather than his physical beauty.


title: Narcissus (mythology)

text: A. E. Housman refers to the 'Greek Lad', Narcissus, in his poem "Look not in my Eyes" from "A Shropshire Lad" set to music by several English composers including George Butterworth. At the end of the poem stands a jonquil, a variety of daffodil, "Narcissus jonquilla", which like Narcissus looks sadly down into the water.


title: Narcissus (mythology)

text: Herman Melville references the myth of Narcissus in his novel Moby-Dick, in which Ishmael explains the myth as "the key to it all," referring to the greater theme of finding the essence of Truth through the physical world.


title: Narcissus (mythology)

text: On Sophia de Mello Breyner Andresen's A Fada Oriana, the eponymous protagonist is punished with mortality for abandoning her duties in order to stare at herself in the surface of a river.


title: Narcissus (mythology)

text: Joseph Conrad's novel The Nigger of the 'Narcissus' features a merchant ship named "Narcissus". An incident involving the ship, and the difficult decisions made by the crew, explore themes involving self-interest vs. altruism and humanitarianism.


title: Narcissus (mythology)

text: Naomi Iizuka's play "Polaroid Stories", a contemporary rewrite of the Orpheus and Eurydice myth, features Narcissus as a character. In the play he is portrayed as a self obsessed, and drug addicted young man who was raised on the streets. He is alluded to being a member of the LGBT+ community (a wider LGBT community, that may include non-binary and intersex activities) and mentions his sexual endeavours with older men, some ending with the death of these men due to drug overdoses. He is accompanied by the character Echo, whom he continuously spurns.


title: Narcissus (mythology)

text: Scottish-Canadian animator Norman McLaren finished his career with a short film named "Narcissus", re-telling the Greek legend through ballet.


title: Narcissus (mythology)

text: Narcissus appears in the Disney adaptation of "Hercules". In the film, he is portrayed as an Olympian god with purple skin.


title: Narcissus (mythology)

text: In the film Bab'Aziz, directed by Nacer Khemir, a Narcissus like character was portrayed by an ancient prince who sat by a pond for days after days and looked at the reflection of his own soul. He was referred to as 'The prince who contemplated his soul'.


title: Narcissus (mythology)

text: The Neon Demon, a 2016 psychological horror film by Nicolas Winding Refn, is loosely based on the story of Narcissus.


title: Narcissus (mythology)

text: In the TV series Boardwalk Empire, a Dr. Narcisse (Valentin Narcisse) is introduced as a condescending intellectual.


title: Narcissus (mythology)

text: Narcissus is the name of the host club in the 2018 Japanese drama Todome no Kiss. The lead character, Otaro Dojima (Kento Yamazaki), works in the nightclub as a sought-after host under the stage name Eight and just like Narcissus, he is narcissistic and disregards the feelings of others; he uses women for money and power.


title: Narcissus (mythology)

text: Narcissus has been a subject for many painters including: Caravaggio, Poussin, Turner, Dalí, Waterhouse, Carpioni, Lagrenée, and Roos.


title: Narcissus (mythology)

text: Sculptors such as Paul Dubois, John Gibson, Henri-Léon Gréber, Benvenuto Cellini and Hubert Netzer have sculpted Narcissus.


title: Baby Face Nelson

text: Lester Joseph Gillis (December 6, 1908 – November 27, 1934), also known as George Nelson and Baby Face Nelson, was an American bank robber who became a criminal partner of John Dillinger, when he helped Dillinger escape from prison, in Crown Point, Indiana. Later, the Federal Bureau of Investigation (FBI) announced Nelson and the remaining gang of bank robbers were collectively "Public Enemy Number One."


title: Baby Face Nelson

text: The "Baby Face Nelson" nickname derived from Gillis being a short man with a youthful appearance; however, in the professional realm, Gillis's fellow criminals addressed him as "Jimmy". A violent bank robber, Lester Joseph Gillis killed more agents of the FBI than has any other criminal. FBI agents fatally wounded and killed Baby Face Nelson in the Battle of Barrington (27 November 1934), fought in a suburb of Chicago, Illinois.


title: Baby Face Nelson

text: Nelson was born Lester Joseph Gillison December 6, 1908 in Chicago, Illinois. He was arrested on July 4, 1921 at the age of twelve, after he accidentally shot a playmate in the jaw with a pistol that he had found. He served over a year in the state reformatory. Nelson was arrested again for car theft and joyriding at age 13 and was sent to a penal school for an additional 18 months and released on April 11, 1924.


title: Baby Face Nelson

text: He joined a gang during his mid-teens and became its leader. In 1928, he married Helen Wawrzyniak, and they had two children.


title: Baby Face Nelson

text: By the time he met Wawrzyniak, Nelson was working at a Standard Oil station in his neighborhood which doubled as the headquarters for a group of young tire thieves, known colloquially as "strippers". Nelson fell into association with the strippers, and acquainted himself with a number of local criminals, including one who employed him to drive bootleg alcohol throughout the Chicago suburbs. Nelson became associated with members of the suburb-based Touhy Gang.


title: Baby Face Nelson

text: Within two years, Nelson and the gang were involved in organized crime, especially armed robbery. On January 6, 1930, the associates forced entry into the home of magazine executive Charles M. Richter. After trussing him up with adhesive tape and cutting the phone lines, they ransacked the house and made off with approximately $205,000 worth of jewelry (equivalent to approximately $ million in dollars). Two months later, they carried out a similar robbery at the bungalow of Lottie Brenner Von Buelow (on Sheridan Road). This job netted approximately $50,000 worth of jewelry. After the crime, Chicago newspapers nicknamed the group "The Tape Bandits".


title: Baby Face Nelson

text: On April 21, 1930, Nelson robbed a bank for the first time, making off with approximately $4,000. A month later, he and his gang netted $25,000 worth of jewelry from home invasions. On October 3, Nelson robbed the Itasca State Bank of $4,600; a teller later identified him as one of the robbers. Three nights later, he stole the jewelry of the wife of Chicago mayor Big Bill Thompson, valued at $18,000. She described her attacker, saying "He had a baby face. He was good looking, hardly more than a boy, had dark hair and was wearing a gray topcoat and a brown felt hat, turned down brim." Nelson and his crew were later linked to a botched roadhouse robbery in Summit, Illinois, on November 23, 1930. In the ensuing gunfight, three people were killed and three wounded. Three nights later, Nelson's gang robbed a tavern on Waukegan Road, and Nelson committed his first murder of note when he fatally shot stockbroker Edwin R. Thompson.


title: Baby Face Nelson

text: Throughout the winter of 1931, most of the Tape Bandits were rounded up, including Nelson. The "Chicago Tribune" referred to their leader as "George 'Baby Face' Nelson" who received a sentence of one year to life in the state penitentiary at Joliet. Nelson escaped during a prison transfer in February 1932. Through his contacts within the Touhy Gang, Nelson fled west to Reno, where he was harbored by William Graham, a known crime boss and gambler. Using the alias "Jimmy Johnson", Nelson went to Sausalito, California, where he worked for bootlegger Joe Parente. During his San Francisco Bay area criminal ventures, Nelson met John Paul Chase and Fatso Negri, who later became close associates. In Reno the next winter, Nelson first met the vacationing Alvin Karpis, who in turn introduced him to Midwestern bank robber Eddie Bentz. Teaming up with Bentz, Nelson returned to the Midwest the next summer. He committed a major bank robbery in Grand Haven, Michigan, on August 18, 1933; his first in the area. The robbery was not lucrative, though most of those involved made a full escape.


title: Baby Face Nelson

text: The Grand Haven bank robbery convinced Nelson he was ready to lead his own gang. Through connections at the Green Lantern Tavern in St. Paul, Nelson recruited Homer Van Meter, Tommy Carroll, and Eddie Green. With these men and two other local thieves, Nelson robbed the First National Bank of Brainerd, Minnesota, of $32,000 on October 23, 1933 (equivalent to approximately $ in dollars). Witnesses reported that Nelson wildly sprayed sub-machine gun bullets at bystanders as he made his getaway. After collecting his wife Helen and four-year-old son Ronald, Nelson left with his crew for San Antonio, Texas. While there, Nelson and his gang bought several weapons from underworld gunsmith Hyman Lehman. One of those weapons was a .38 Super Colt pistol that had been modified so it was fully automatic. Nelson used this gun to kill Special Agent W. Carter Baum at Little Bohemia Lodge several months later.


title: Baby Face Nelson

text: On December 9, 1933, a local woman tipped off San Antonio police regarding the presence nearby of "high-powered Northern gangsters". Two days later, Tommy Carroll was cornered by two detectives and opened fire, killing Detective H.C. Perrin and wounding Detective Al Hartman. All the Nelson gang, except Nelson, fled San Antonio. Nelson and his wife traveled west to the San Francisco Bay Area, where he recruited John Paul Chase and Fatso Negri for a new wave of bank robberies the following spring.


title: Baby Face Nelson

text: On March 3, 1934, John Dillinger made his famous "wooden pistol" escape from the jail in Crown Point, Indiana. Although the details remain in some dispute, the escape is suspected to have been arranged and financed by members of Nelson's newly formed gang, including Homer Van Meter, Tommy Carroll, Eddie Green, and John "Red" Hamilton, with the understanding that Dillinger would repay some part of the bribe money out of his share of the first robbery. The night Dillinger arrived in the Twin Cities, Nelson and his friend John Paul Chase were cut off by another car driven by local paint salesman Theodore Kidder. Nelson lost his temper and gave chase, crowding Kidder to the curb. The salesman exited his vehicle to protest, whereupon Nelson shot him dead.