Sickle Cell Disease: Causes, Effects and Treatment

Sickle Cell Disease: Causes, Effects and Treatment Abstract Sickle cell disease is a genetically inherited hematological (blood) disorder that results from a mutation in the beta globin gene that is responsible for the development of hemoglobin. Hemoglobin is the protein that delivers oxygen to the red blood cells throughout the body. In the disease, a mutated variant of normal hemoglobin generates an abnormal structure of the cells, leading to the development of symptoms. Sickle cell anemia and beta thalassemia are two common types of sickle diseases that are discussed in this review. The symptoms, complications, and therapies are also highlighted in the context of the pathophysiology of the disease. Sickle Cell Disease: An Overview Sickle cell disease is a genetically inherited blood disorder and it is characterized by an abnormal structure or production of hemoglobin. Hemoglobin is the protein in red blood cells that transports oxygen to cells throughout the body (National Institutes of Health, 2014). The disease results from a mutation in the beta globin gene causing a class of sickle diseases, such as sickle cell anemia and beta thalassemia (Thein, 2008). Together, they are often referred to as the beta hemoglobinopathies and present a range in disease severity (Thein, 2008). Beta globin is a protein that produces hemoglobin and the gene mutation in both diseases produces abnormal variants of hemoglobin in the blood. This results in either a predominance of abnormal hemoglobin molecules in red blood cells or an absence of normal hemoglobin, and thus, normal red blood cells (Edwards et al., 2005). There are a number of available therapies that manage sickle cell disease and the only curative treatment is hema topoietic cell transplantation. Pathophysiology of Sickle Cell Disease The National Institutes of Health reports that sickle cell disease is the most common inherited blood disorder in the United States and it affects 70,000 to 80,000 Americans (National Institutes of Health, 2014). It is estimated to occur in 1 in 500 African Americans and 1 in 1,000 to 1,400 Hispanic Americans (National Institutes of Health, 2014). The disease affects 30 million people worldwide and it is most common among people who have ancestors from Africa, Mediterranean countries, the Arabian Peninsula, India, parts of South America, Central America and the Caribbean (Khoury, Musallam, Mroueh, Abboud, 2011; National Institutes of Health, 2014). As it is an inherited disease, the sickle gene is presumed to have a genetic advantage in which it protects from the development of malaria infection (Stuart Nagel, 2004). There are many types of sickle diseases, such as sickle cell anemia and beta thalassemia. Sickle cell anemia is considered the most commonly occurring type of sickle c ell disease (National Institutes of Health, 2014). In sickle cell anemia, hemoglobin S replaces both beta-globin and the sixth amino acid is changed from glutamic acid to valine (National Institutes of Health, 2014; Rees Gibson, 2011). Sickle cell trait is not considered a disease and it is found in approximately 1 in 10 African Americans (Edwards et al., 2005). When both parents have the sickle cell trait, there is a one in four chance with each pregnancy that the child will have sickle cell anemia (Edwards, et al., 2005). Today, many health organizations offer newborn screenings that can determine if a child has either the disease or trait (National Institutes of Health, 2014). The development of the disease occurs due to the polymerization of deoxygenated hemoglobin S (Chirico Pialoux, 2012). The polymer formation modifies the normal red blood cell disc shape into a rigid, irregular-shaped, unstable cell and causes intravascular hemolysis, or rupture of the cells, to release hemoglobin into the plasma of the blood (Chirico Pialoux, 2012). The repeated polymerization leads to sticky blood cells (blood cell adhesion), obstruction of blood vessels (vasocclusion), and restriction of blood supply to tissues and organs in the body (ischemia) (Chirico Pialoux, 2012). Additionally, the endothelium and leukocyte, or white blood cells, are also found to play a role in disease mechanisms. Studies have found a connection between the endothelium, a thin layer of cells that line the interior surface of blood vessels, and sickled red blood cells (Stuart Nagel, 2004). The red blood cell receptors that are associated with cell adhesion are present in increased numbers on sickled immature red blood cells and mature sickle cells compared to normal red blood cells (Stuart Nagel, 2004). This finding demonstrates a structure-function abnormal activity that leads to coagulation on cell surfaces, leading to anemia (Stuart Nagel, 2004). Like cell adhesion, leukocytes have an impact in disease activity. White blood cells are found to be at an increased baseline in sickle cell disease, which serves as an independent risk factor for pulmonary and cardiac complications (Stuart Nagel, 2004). The size of the white blood cell, its rigidity, and adhesive characteristics are implicated in microvascular blood flow, vascular inflammation, and vasocclusion (Stuart Nagel, 2004). Clinical Symptoms of Sickle Cell Disease The clinical manifestation of sickle cell disease can lead to inflammatory responses and may result in acute chest syndrome, pulmonary hypertension, and stroke (Chirico Pialoux, 2012). People with sickle cell disease may also encounter several physical complications, such as delayed growth, fatigue, headaches, and cerebral vascular damage (Edwards et al., 2005). Acute chest syndrome is considered the second most common cause of hospital admissions and a leading cause of death in patients with sickle cell disease (Khoury, Musallam, Mroueh, Abboud, 2011). It involves the presence of a pulmonary infiltrate on a chest X-ray and the symptoms may include chest pain, a temperature of more than 38.5 degrees Celsius (101.3 degrees Fahrenheit), tachypnea (rapid breathing), wheezing or cough ((Khoury, Musallam, Mroueh, Abboud, 2011). The symptoms at clinical presentation vary with age as wheezing, cough, and fever are common in children 10 years or younger (Khoury, Musallam, Mroueh, Abboud, 2011). Pain in the arms and legs and shortness of breath are more commonly presented in adults with the disease (Khoury, Musallam, Mroueh, Abboud, 2011). It is believed that there are three mechanisms involved in acute lung injuries, which include infection, fat embolization (clotting) from bone marrow, and sequestration of sickled red blood cells (Khoury, Musallam, Mroueh, Abboud, 2011). People with sickle cell disease have an increased risk for developing infections, particularly pneumonia. Treatment for acute chest syndrome is primarily supportive and includes supplemental oxygen to keep the saturation above 92% (Khoury, Musallam, Mroueh, Abboud, 2011). Pain is considered the most frequent complication associated with the disease and acute chest syndrome stimulates this crisis (Edwards et al., 2005; Khoury, Musallam, Mroueh, Abboud, 2011). Repeated episodes of acute chest syndrome predispose patients to chronic pulmonary disease, such as pulmonary hypertension (Stuart Nagel , 2004). The occurrence of asthma is also associated with the increased incidence of acute chest syndrome, which is considered a comorbid condition found in people with sickle cell disease (Khoury, Musallam, Mroueh, Abboud, 2011). Beta Thalassemia Beta thalassemia is a common genetic blood disease that reduces hemoglobin production (National Institutes of Health, 2014). The hemoglobin gene mutation results in an unusually low level of beta-globin (National Institutes of Health, 2014). There are different levels of thalassemia based on the number of copies of beta thalassemia alleles or different copies of the same gene (Thein, 2008). The variety in alleles impacts the deficit in beta globin production, which, in turn, impacts disease severity (Thein, 2008). Carriers, for example, who have inherited a single copy of the beta thalassemia allele are clinically asymptomatic and may demonstrate mild anemia (Thein, 2008). Unlike a globin imbalance that is found in sickle cell anemia, variants of beta chains are broken down and result in ineffective red blood cell production in beta thalassemia (Thein, 2008). Physical complications involve cardiac and bone disease, bilirubin metabolism, and iron metabolism. Such symptoms may include jaundice and a predisposition to gallstones (Thein, 2008). Treatment for Sickle Cell Disease Several complications may emerge from sickle cell disease, whether it is in sickle cell anemia or in beta thalassemia. The purpose of therapies for sickle cell disease is to prevent and treat complications (Inati, Chabtini, Mounayar, Taher, 2009). The treatment of sickle cell disease is best achieved by decreasing the amount of hemoglobin S through the prevention of its production (Inati, Chabtini, Mounayar, Taher, 2009). People with severe sickle cell disease are treated with three validated therapies: hydroxyurea, transfusion and chelation therapy, and a hematopoietic or stem cell transplant (Inati, Chabtini, Mounayar, Taher, 2009). Hydroxyurea has been shown to be an effective form of treatment for children and adults with the disease. It has been demonstrated to reduce pain and acute chest syndromes, and it decreases the frequency of hospitalizations and the need for transfusions. This therapy has also been found to play a role in stroke prevention (Inati, Chabtini, Mounayar, Taher, 2009). At a molecular level, hydroxyurea reduces the adhesion of sickle red cells to endothelial cells. It also modulates endothelial cell activation and nitric oxide generation (Inati, Chabtini, Mounayar, Taher, 2009). Nitric oxide has been found to affect acute and chronic complications of sickle cell disease (Stuart Nagel, 2004). Nitric oxide, on a normal functioning level, induces relaxation of smooth muscle and dilation of blood vessels. In sickle cell disease, the bioavailability of nitric oxide is impaired, resulting in an imbalance between endothelial production and consumption (Stuart Nagel, 2004). The lungs are most affected by a reduction of nitric oxide and tend to constrict, which predisposes an individual to acute chest syndrome (Stuart Nagel, 2004). No adverse effects have been thus far reported on the usage of hydroxyurea and any toxicity is typically reversible (Inati, Chabtini, Mounayar, Taher, 2009). Transfusion therapy is currently considered a standard of care treatment for primary and secondary stroke prevention in children with sickle cell disease (Inati, Chabtini, Mounayar, Taher, 2009). It is used for short and long term management, preventing a first stroke in high-risk children as well as preventing against a recurrent stroke (Inati, Chabtini, Mounayar, Taher, 2009). Transfusions are also used for chronic and severe pain or in cases when patients with acute chest syndrome do not respond to hydroxyurea (Inati, Chabtini, Mounayar, Taher, 2009). Chelation therapy is used for patients who experience iron overload. Iron overload is a serious and inevitable outcome from receiving regular transfusion therapy (Inati, Chabtini, Mounayar, Taher, 2009). Unless treated, iron overload may result in severe organ damage and other life threatening complications and this treatment mediates this by removing excess metals from the body (Inati, Chabtini, Mounayar, Taher, 2009). While hydroxyurea, tranfusions, and chelation therapy aim to prevent and treat complications, they do not cure sickle cell disease (Inati, Chabtini, Mounayar, Taher, 2009). The currently available curative treatment is a stem cell transplant. A transplant is indicated in those patients who experience complications, such as recurrent severe pain, acute chest syndrome, and stroke (Inati, Chabtini, Mounayar, Taher, 2009). Only one-third of affected children meet the criteria for a stem cell transplant as it is an aggressive and serious procedure (Inati, Chabtini, Mounayar, Taher, 2009). The goal of a stem cell transplant is to replace the host’s marrow with normal cells, resulting in a new immune system (Stuart Nagel, 2004). Studies on stem cell transplant as a curative option for patients with severe sickle cell disease are demonstrating mean overall survival and event-free survival rates between 95 and 85% (Inati, Chabtini, Mounayar, Taher, 2009). Significant advancements have been made for pediatric patients who have beta thalassemia and were treated with a stem cell transplant. Over the last three decades, disease-free survival rates have exceeded 80% in patients who received transplants from biologically compatible family donors (Mehta Faulkner, 2013). Sickle cell disease is a genetically inherited blood disorder that is primarily diagnosed in people who have ancestors from Africa, Mediterranean countries, the Arabian Peninsula, India, parts of South America, Central America and the Caribbean (Khoury, Musallam, Mroueh, Abboud, 2011; National Institutes of Health, 2014). The disease results by a mutation in the gene that creates beta globin, which is the protein that is responsible for producing hemoglobin. Hemoglobin is the protein in red blood cells that transports oxygen to the body’s organs and tissues. When the mutation occurs, a hemoglobin variant is produced, resulting in a structural and functional change in the red blood cells. Several physical complications emerge in both children and adults who have the disease. These may include, but not limited to, pain, acute chest syndrome, cerebral and vascular damage (Edwards et al., 2005). There are three primary therapies for managing and/or treating the disease. These inc lude the drug, hydroxyurea, transfusion and chelation therapy, and hematopoietic cell transplantation (Inati, Chabtini, Mounayar, Taher, 2009). More research is underway in the development of additional treatment options, such as gene therapy and clinical trials are exploring this possibility. References Chirico, E. N., Pialoux, V. (2012). Role of oxidative stress in the pathogenesis of sickle cell disease. International Union of Biochemistry and Molecular Biology Life, 64 (1), 72-80. Edwards, C. L., Scales, M. T., Loughlin, C., Bennett, G. G., Harris-Peterson, S., De Castro, L. M., Whitworth, E., Abrams, M., Feliu, M., Johnson, S., Wood, M., Harrison, O., Killough, A. (2005). A brief review of the pathophysiology, associated pain, and psychosocial issues in sickle cell disease. International Journal of Behavioral Medicine, 12 (3), 171-179. Inati, A., Chabtini, L., Mounayar, M., Taher, A. (2009). Current understanding in the management of sickle cell disease. Hemoglobin, 33 (S1), S107-S115. Khoury, R. A., Musallam, K. M., Mroueh, S., Abboud, M. R. (2011). Pulmonary complications of sickle cell disease. Hemoglobin, 35 (5-6), 625-635. Mehta, P. A., Faulkner, L. B. (2013). Hematopoietic cell transplantation for thalassemia: a global perspective BMT tandem meeting 2013. Biology of Blood and Marrow Transplantation, 19, S70-S73. National Institutes of Health (2014). Genetics home reference: beta thalassemia. U.S. Department of Health and Human Services, Retrieved from http://www.ghr.nlm.nih.gov/condition/beta-thalassemia. National Institutes of Health (2014). Genetics home reference: sickle cell disease. U.S. Department of Health and Human Services, Retrieved from www.ghr.nlm.nih.gov/condition/sickle-cell-disease. Rees, D. C., Gibson, J. S. (2011). Biomarker in sickle cell disease. British Journal of Haematology, 156, 433-445. Stuart, M. J., Nagel, R. L. (2004). Sickle-cell disease. Lancet, 364, 1343-1360. Thein, S. L. (2008). Genetic modifiers of the ÃŽ ²-haemoglobinopathies. British Journal of Haematology, 141, 357-366.

Theseus Or Hercules? :: essays research papers

Theseus or Hercules? Theseus is most worthy of emulation. He was a great hero in Athens. "Theseus was, of course bravest of the brave as all heroes are, but unlike the other heroes he was as compassionate as he was brave." (p. 159). Theseus also was a man of bravery, intellect and bodily strength. Hercules on the other hand was what all Greece except Athens most admired. He was very strong but wasn't too smart. Hercules never thought of the consequences that his actions would bring about before he followed through with them. First, Theseus was very strong. He fought many terrible horrendous monsters such as the Minotaur, "..a monster, half bull, half human.." (p.151), and went on many great ventures such as the Quest for the Golden Fleece. Theseus showed his great strength in adventures such as the one with the Minotaur. Hercules was also involved in many great adventures in which his great strength was shown. Hercules was much stronger than Theseus, but Theseus made up for this small loss in other ways. Second, Theseus was very smart. Because of his great intellect the Athenians, people who valued thought and ideas, chose him and not Hercules as their hero. Theseus escaped from the Labyrinth and killed the Minotaur. Neither of these tasks were easy and required someone with aptitude unlike Hercules. Theseus always thought things through and made good decisions. Hercules' foolishness was shown on many occasions such as when he killed his family and his music teacher. Theseus' intellect is one very valuable quality which makes him more worthy of emulation. Third, Theseus was very brave. In fact he went on so many great excursions that a saying grew up in Athens "Nothing without Theseus!" (p. 149). When it was time for Theseus to seek his father he would not go by water " But Theseus refused to go by water because the voyage was safe and easy." (p. 149). Theseus insisted to take the way by land. His idea was to become a hero as quickly as possible, and he accomplished his goal by ridding the land of all the banns to travelers on his way to find his father. Theseus had many other adventures. He was on the Argo, in the Caledonian hunt, as well as many others. Hercules also had many adventures but his were often the result of his own

Economics The Russian Experience Essay

The economy of the Soviet Union was based on a system of state ownership and administrative planning which meant that the state was the single decision organ in economic matters. The economic growth was guided by what was then called Five Year Plans crafted by the national decision makers appointed by the state. This approach made it easy for the resources to be harnessed to achieve set objectives. The economic set up concentrated more in building capital goods, machine manufacture and the chemical industry. The economic setup was top down model that offered little option for feedback to move to the decision makers. This made it hard for the decision makers to assess the effects of their decisions with a view to eliminate destructive ones. It therefore made it hard for the decision makers to abandon earlier decisions that failed to work or that produced negative results. (http://www. answers. com/toic/history-d-the-soviet-union-1985-1991). The economic setup, otherwise called communism, often resulted into the problem of over or under production of goods. The system paid little attention to the production of consumer goods and this led to black markets thriving. This black market had a counter effect on the economic agenda of the planners. The system was also very bureaucratic delaying issues that required urgent decisions. This scenario led to a back logging of decisions, which overwhelmed the decision makers with time. Middle level managers began to agitate for freedom to deal with customers and suppliers directly for them to more effectively respond to the economic laws of demand and supply. This agitation built up to eventually break the Soviet Union because the decision makers and the political leaders of the time failed to respond to these demands responsibly. (http://www. answers. com/toic/history-d-the-soviet-union-1985-1991). The economic setup of the Soviet Union had made some big gains, which enabled them to become industrialized faster than other economic fronts. Failure to respond to arising issues was what contributed to its downfall. Strong institutions had already been setup such as the agricultural sector, foreign trade as well as the financial sector. All capital goods were collectively owned with little exceptions. Individual property ownership was minimal. The ownership controversy also contributed to the Soviet Union breakup. Since then Russia has had to undergo intensive reform program to enable them to respond to the largely capitalistic world economy (Moszczynska, undated) A key sector that is the focus of the reform process is the financial sector. The Russian economy is reliant on oil and the fluctuations of prices affect the economy adversely. To alleviate such adverse effects, the financial sector needs reforms because it offers smoother transition into the envisioned economic setup. A challenge facing Russia and other countries as they transit from command economy to the free market economy is imbalance created by foreign trade. These countries have begun to import goods that were in short supply but on the other hand exports have began to decline. This slows down the recovery process since exports spurred growth previously. When the exports are more than the imports, a country is performing well economically and this is reverse for these former Soviets. Consumption growth had for a time led to an increment is real wages but productivity growth has stagnated those gains. This again is due to the heavy reliance on the oil industry for economic growth (Barnard, 2000). In addition, there is little investment outside the oil and metal industries. This means that as much as the motive is to create wealth for the citizenly, there cannot be much success if no considerable investment is made. In fact investments in other areas has been declining over time. The investment climate in Russia is still hostile which slows down the ability of the reform process to spur growth. The economic system only favor large business establishments leaving small and medium sized enterprises struggling. The government’s authorization requirements are stringent while corruption has been rife. This has led to more resources being allocated to large firms. With the medium sized enterprises grounded, no much growth can be achieved. The banking system is also inefficient since it only lends to the large establishments. The reform of the banking sector has largely depended upon political climate but a legal framework is needed to effectively reform this sector. A better framework to regulate the banking industry has to be put in place (Kahan, 2001). The reform process of the Russian and other former Soviet countries are on the right track. There are enough challenges in the implementation process of the proposals but they are gaining ground. Under performing areas have shown indications of growth. The recovery process, though, calls for political will among the leaders to drive the process. No much progress would be realized if political will is lacking. The effects of the Cold War need to be eliminated from the fore. The Russian economy has great potential and if the strategies respond appropriately to upcoming issues, the Russian economy would perform better. The Russian economy performance had put Russia ahead of other countries. It was not entity based on wrong principles. The major problem was the bureaucratic system that had been set that made it difficult to respond to rising issues. If the economy is to acquire the envisioned status it once had, it has to respond to arising issues.

Karl Marx And Karl Polanyi - 1668 Words

Adam Smith, Karl Marx and Karl Polanyi are writer of capitalism, that have influenced capitalism in different ways to making capitalism what it is today. Adam Smith known as the father of the political economy, developed the concept of the invisible hand; which explains how self-interest and competition in a free market economy, would allow economy prosperity. Another concept Smit developed is division of labour which say that jobs a business should be specialised, instead of one person having to carry out all the processes. Karl Marx, on the other hand, demonstrates to us the negative impact of the capitalist system upon workers and society in general. As Marx believed that workers gain nothing, instead get exploited by the capitalist who†¦show more content†¦However, critics of the invisible hand say that it is not as strong as it was in the time of Smith, due to large powerful cooperation, effective marketing system and inefficient financial market blocks the mechanism of the invisible hand which does not allow the scare resources to be used at their best use. An example is of the invisible hand in works is, say if a candle maker sells one candle stick for  £1 but, another candle maker sells 3 sets of candles for  £2, it would mean he would get all the business making the other candle maker lose out and make even run out of business. So, to compensate the lose the candle marker would be forced lower his prices to survive and not get out of business, therefore, the candle maker is guided by the invisible hand being his self-interest to gain profit to lower his prices. Division of labour another, one of Adam Smith’s concepts explains that productive power of workers would increases each worker would have a specialised job to carry out and in turn would allow increase number of output to be produced. Smith further, says that division of labour is not something that is regulated by an authority, instead it is human nature. As what make us human is our propensity to truck, barter and exchange items, which gives us assurance to be able to trade what we have produced goes on to encourage division of labour. Smith gives 3 reasons as to why division of labour increase’s productivity. First, divisionShow MoreRelatedKarl Marx And Karl Polanyi1805 Words   |  8 PagesAdam Smith, Karl Marx and Karl Polanyi, have influenced different parts of capitalism. Adam Smith known as the father of the political economy, developed the concept of the invisible hand; which explains how self-interest and competition in a free market economy, would allow economy prosperity. 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