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Inborn errors of metabolism Essays

Inborn errors of metabolism Essays Inborn errors of metabolism Essay Inborn errors of metabolism Essay Congenital mistakes of metamorphosis occurs 1 in 5000 births jointly. They can be treated if the congenital mistake is diagnosed decently and early. They are manfully caused by a cistron defect that blocks critical metabolic tracts. The can be server, which is chiefly due to amount of enzymes that is doing the block or lack of the reaction merchandise. This can impact the variety meats and besides have local consequence such as lysosomal storage disease. The symptoms can change, from mild to severe. They affect any variety meats and occur at any clip. To recognize the Inborn Errors of Metabolism, the physician must be leery ; for illustration a babe that show marks of antecedent maternal febrility should undergo a blood civilization and besides undergo simple trials such as Amino acids, Organic acids, Glucose, Electrolytes, Lactate, and Ammonia ; which is done in the research lab. 2.0 Abstraction Congenital mistakes of metamorphosis ( IEM ) are a group of familial upsets that are rare. These upsets are familial diseases that are involved in metamorphosis upsets. A big subdivision of these upsets arise from individual cistrons that encodes for enzymes ; that have been faulty. These enzymes are of import that they catalyses chemical reactions change overing substrates to merchandises indispensable for mundane life. Congenital mistakes of metamorphosis upsets can originate from a figure of conditions such as prolong exposure and accretion of substances which are toxic, and the intervention of normal maps and the inability to bring forth and synthesise indispensable compounds. Congenital mistakes of metamorphosis has related to defects in or damage to a developing fetus that may hold been caused to familial alterations, that is why Congenital mistakes of metamorphosis is sometimes referred as inborn metabolic diseases. Congenital mistakes of metamorphosis have besides been linked to heritable upsets within biochemistry, for illustration PKU ( PKU ) . That is why some times it is referred as familial metabolic diseases every bit good. In the position of alterations of normal mechanical, physical, and biochemical maps, IEM can split into three utile groups that can be analysed diagnostically. Group 1: Disorders which causes poisoning. Group 2: Disorders affecting energy metamorphosis. And Group 3: Disorders affecting complex molecules. 1.0 Introduction 1.1 Congenital Mistakes of Metamorphosis In the early 1900s, a research worker called Sir Archibald Garrod s based his surveies on familial metabolic upsets and discovered IEM [ 1, 2 ] . He was known for his work on the one cistron, one enzyme hypothesis, based on his surveies on the nature and heritage of alcaptonuria. And gave the name and wrote a book on IEM ( The Incidence of Alkaptonuria: a Study in Chemical Individuality. ) [ 1, 2 ] . IEM can originate from a figure of causes, but the major cause is change of a specific metabolic reaction [ 1, 2 ] . IEM has been shown to develop at a really immature age, where epidemiology findings indicated that 100s of IEM affects about 1 in every 5000 born babes [ 2 ] . But as engineering progresss and improved techniques such as metabolomics, has been easy to develop newborn showing that improves early diagnosing and intervention in a figure of IEM upsets [ 2 ] . But as these new techniques cost a batch to run and clip additions, turn outing to be undependable [ 2 ] . The survey and the cognition about congenital mistakes of metamorphosis ( IEM ) have improved due to the latest promotion in engineering and techniques [ 2, 3 ] . These betterment have led us to the decision, for illustration urea rhythm upsets and organic acidemias may and will take to the accretion of ammonium hydroxide, which is a toxic merchandise of aminic acerb metamorphosis [ 2, 3 ] . Besides the latest findings are that congenital mistakes of metamorphosis ( IEM ) may impair encephalon map due to defects in the mitochondrial respiratory concatenation and upsets in gluconeogenesis [ 4 ] . There are 10 facts that need to take inconsiderateness when people with IEM undergo clinical diagnosing [ 5 ] . Common status such as, poisoning, phrenitis and encephalon tumors in older patients and besides sepsis have to be analysed decently and ever see IEM in the same field [ 5 ] . Symptom that persists and that are unexplained even earlier, during and after initial intervention and usual probes has been performed, have to be taken to consideration that it could be IEM [ 5 ] . Newborn babes that have organ disfunction, hypo-perfusion, or hypotension can develop sepsis, which can be caused by IEM. So any babes in neonatal intensive attention unit that dice, the first cause that has to be taken to account is IEM [ 5 ] . Have to take excess attention in reexamining all autopsy findings [ 5 ] . The tester must non confound a symptom for illustration peripheral neuropathy ; or syndrome such as sudden baby decease with etiology [ 5 ] . IEM can develop and show at any age, for illustration from fetal life to old age [ 5 ] . The tester must take to account that non all familial metabolic mistakes causes are due to familial and familial recessive upsets, but a big subdivision of single instances are sporadic [ 5 ] . Always consider congenital mistakes of metamorphosis are unfastened to intervention for illustration with patients that have inborn mistakes of metamorphosis due to intoxication [ 5 ] . In server state of affairss, the tester will necessitate to take a few patients with IEM that are able to name and handle the patient with IEM [ 5 ] . The tester must be unfastened to obtain aid from specialized Centres that specialise with IEM [ 5 ] . The metabolic upsets can be set into three utile groups that can easy be distinguished from each other [ 5, 6, 7 ] . These three groups are sorted from a pathophysiological point of position [ 5, 6, 7 ] . The groups are ; Group 1: Disorders which is caused by poisoning [ 5, 6, 7 ] . Group 2: Disorders affecting energy metamorphosis [ 5, 6, 7 ] . And Group 3: Disorders affecting complex molecules [ 5, 6, 7 ] . 1.2 Group 1- Disorders which is caused by poisoning In this group, it describes congenital mistakes of intermediary metamorphosis. These congenital mistakes cause ague of progressive poisoning from long exposure and addition of toxic compounds, organizing a metabolic block [ 5, 6, 7 ] . In group 1 the congenital mistakes are manfully aminic acerb katabolism [ 5, 6, 7 ] . These include PKU, where there is a lack in the enzyme phenylalanine hydroxylase ( PAH ) ; which is needed to metabolize the amino acid phenylalanine to the amino acerb tyrosine [ 5, 6, 7 ] . Homocystinuria is an familial upset of the metamorphosis of methionine [ 5, 6, 7 ] . Tyrosinemia is where organic structure can non interrupt down the amino acerb tyrosine [ 5, 6, 7 ] . Besides organic acidurias such as methylmalonic acidemia, and propionic acidemia [ 5, 6, 7 ] . Sugar intolerances are besides classified in group 1 [ 5, 6, 7 ] . These include familial fructose intolerance caused by a lack of liver enzymes that metabolise fructose. Metal toxication besides falls under group 1 ; such as iron-storage disease, where the patient has accumulated a batch of Fe [ 5, 6, 7 ] . All these metabolic upsets have something in common, in that they do non impact the embryo development, and besides show similar symptoms of clinical poisoning [ 5, 6, 7 ] . A patient with group 1 upsets may demo an acute marks of purging, coma and liver failure ; or chronic marks which are cardiomyopathy, developmental hold and failure to boom. Acute symptoms that can decline are katabolism, febrility, and nutrient intake [ 5, 6, 7 ] . The analysis in group 1 is easy, and without any complications [ 5, 6, 7 ] . It needs the usage of chromatography in which the plasma and urine amino acid. Most of group 1 upsets are treatable. Treatment is normally involves particular diets and cleansing drugs such as Na benzoate and Cuprimine, to take the toxins [ 5, 6, 7 ] . The congenital mistake of amino acerb synthesis is besides included to this group, as they have the same or similar characteristics [ 7, 8 ] . They are congenital mistakes of intermediary metamorphosis ; the analysis requires the plasma and piss where upsets are able to be treated even when the upset starts with in the womb, for illustration 3-phosphoglycerate dehydrogenase lack [ 5, 6, 7, 8 ] . 1.3 Group 2- Disorders affecting energy metamorphosis In this group congenital mistakes are mistakes of intermediary metamorphosis every bit good. The symptoms are chiefly caused by a deficiency of energy production or use. This will affect the liver, myocardium, musculus, and encephalon [ 5, 6, 7 ] . There are two types of upsets affecting energy metamorphosis. 1. involves mitochondrial energy defects. 2. involves cytoplasmatic energy defects [ 5, 6, 7 ] . Mitochondrial energy defects are more aggressive and are non to the full treatable [ 5, 6, 7 ] . Mitochondrial energy defects cause lactic acidemias where there is dextrorotary lactic acid in the circulating blood, ensuing to defects of the pyruvate transporter ensuing to PKU, pyruvate carboxylase this causes lactic acid to roll up in the blood, pyruvate dehydrogenase where the patient can demo symptoms of terrible lassitude, and defects in the Krebs rhythm [ 5, 6, 7 ] . But some defects such as fatty acerb oxidization and ketone organic structure defects are partially treatable [ 5, 6, 7 ] . Cytoplasmic energy defects are non every bit much aggressive so mitochondrial energy defects. A cytoplasmatic energy defect causes upsets of glycolysis, animal starch metamorphosis and gluconeogenesis [ 5, 6, 7 ] . And recent survey showed it causes upsets of creatine metamorphosis which it is partially treatable by unwritten creatine supplementation [ 5, 6, 7 ] . Cytoplasmic energy defects can do upsets that are untreatable, such as mistakes of the pentose phosphate tract which will be described in farther inside informations [ 5, 6, 7 ] . In group 2, the common symptoms are bosom musculus disease, hypoglycemia, myopathy which is a muscular disease, cardiac failure, specific failure of the circulation, sudden decease particularly in babyhood [ 5, 6, 7 ] . Mitochondrial upsets and every bit good as the pentose phosphate tract defects can blockade embryo-foetal development and give rise to dysmorphism, dysplasia doing an abnormalcy in ripening of cells within a tissue and inborn upset [ 5, 6, 7, 9 ] . The analysis and the diagnosing are difficult to set through as it requires 4 different trials [ 5, 6, 7 ] . 1. Function trials [ 5, 6, 7 ] . 2. Enzymatic analyses necessitating biopsies [ 5, 6, 7 ] . 3. Cell civilization [ 5, 6, 7 ] . 4. Molecular analyses [ 5, 6, 7 ] . 1.4 Group 3- Disorders affecting complex molecules. Group 3 involves cellular cell organs [ 5, 6, 7 ] . The diseases that fall under group 3 modify the synthesis or the katabolism of complex molecules [ 5, 6, 7 ] . There are symptoms that are lasting and progressive, and some symptoms free from intercurrent events [ 5, 6, 7 ] . In this group there are upsets such as lysosomal storage upsets, peroxisomal upsets and congenital mistakes of cholesterin synthesis etc. In this group intervention is hard would necessitate enzyme replacing therapy, particularly for lysosomal upsets [ 5, 6, 7, 10 ] . 2.0 General Symptoms and Signs There is a manner for proving newborn babes for congenital mistakes [ 11 ] . This procedure is called Newborn showing. This tests babes at a really early age for four types of diseases that are treatable: familial, endocrinologic, metabolic and haematological diseases [ 11 ] . Dr Robert Guthrie was a microbiologist who designed a dried blood topographic point testing, and used it to test for PKU [ 12 ] . To this present twenty-four hours that descrying trial is still being used. As techniques have improved so hold the showing [ 12 ] . A doctor who is testing a newborn babe for a metabolic upset has follow four groups of clinical fortunes: The doctor must happen early symptoms, particularly in the antenatal and neonatal period of development. In the ulterior stages the doctor must happen symptoms that are server and repeating. Symptoms such as coma and emesis. If the physician finds any symptoms that are chronic and aggressive, they could be due to three things: 1 ) Gastrointestinal. 2 ) Muscular. 3 ) Neurological. These will be described in more item below The doctor must happen any marks of myocardiopathy, hepatomegaly etc. This could take to organ failures. The three groups have symptoms that are chronic and aggressive that can be easy ignored or misinterpreted. 2.1 Gastrointestinal Symptoms. If a patient has inborn mistakes of metamorphosis ( IEM ) , the individual might hold symptoms that autumn under the Gastrointestinal Symptoms ( GI ) group [ 13 ] . These symptoms include Anorexia, which is an eating upset [ 5, 13 ] . Osteoporosis which untreated could take to castanetss fracturing. Chronic emesis, feeding troubles, and failure to thrive are besides symptoms of ( GI ) . But they are besides associated with chronic diarrhea [ 5, 13 ] . This could take to false and the incorrect diagnosing [ 5, 13 ] . There are two groups that have been described to hold caused chronic diarrhea and failure to boom within congenital mistakes of metamorphosis: These upsets include mistakes of the enteric mucous membrane or the exocrine map of the pancreas, for illustration inborn chloride diarrhea, glucose- galactose malabsorption a status in which the cells run alonging the bowel can non take in the sugars. Lactase and sucrose-isomaltase lacks where the individual is unable to metabolize milk sugar or saccharose. Abetalipoproteinemia type II upset that interferes with the normal soaking up of fat and fat-soluble vitamins from nutrient [ 5, 13 ] . Enterokinase lack ; Enterokinase is an enzyme involved in human digestion. Acrodermatitis enteropathica, a status that affects that soaking up of Zinc. Etc [ 5, 13 ] . Systemic upsets such as diabetes mellitus, diabetes, reaping hook cell disease, sarcoidosis, etc can besides give rise to GI abnormalcies. A job has risen in separating systemic abnormalcies and congenital mistake of metamorphosis and frailty versa [ 5, 13 ] . 2.2 Muscle Symptoms. There are a figure of symptoms that autumn under this group. For illustration: Hypotonia, where there is a upset that causes low musculus tone and strength [ 5, 14 ] . Muscular failing and hapless musculus mass [ 5, 14 ] . These symptoms are common with many congenital mistakes of metamorphosis. These symptoms can be caused by urea rhythm defects and many amino acid metamorphosis upsets [ 5, 14 ] . Recent surveies have shown that the cause of musculus symptoms can be due to mutants in the monocarboxylate transporter 8 cistron, which can develop Allan-Herndon-Dudley syndrome [ 14 ] . Allan-Herndon-Dudley syndrome falls under the musculus symptoms group as it causes hypotonus, general failing of the musculus, reduced musculus mass and delayed development [ 14 ] . Further surveies showed that this X-linked mental deceleration syndrome is involved in the conveyance of liothyronine into neurones and disrupts the blood degrees of thyroid endocrine [ 14 ] . 2.3 Neurological Symptoms. Patients with congenital mistakes frequently have neurological symptoms. These include of neurological abnormalcies, in the cardinal and peripheral system. Surveies have shown that these neurological symptoms are really frequent with congenital mistakes [ 5, 15 ] . These symptoms include hapless eating, hypotonus, ataxy, and even autistic characteristics [ 5, 15 ] . The analysis of congenital mistakes, due to the showing of neurological symptoms is really hard due to symptoms that are non specific marks ; sings that include for illustration developmental hold, and hypotonus [ 15 ] . 3.0 Screening Newborns for Inborn Error of Metabolism 3.1 Newborn showing Newborn showing is a technique, used to observe congenital mistakes [ 17, 12 ] . It was foremost used to observe PKU ( PKU ) by a bacterial suppression check, developed in the 1961 by Dr Robert Guthrie as already stated. His technique in utilizing dried blood sample was further developed in the mid 1975, where a scientist called Dussault used a method to testing for inborn hypothyroidism [ 16 ] . A batch of clip and money has been invested into the showing programme, and now they have uncovered new upsets that are related to congenital mistakes [ 17, 12 ] . Disorders such as cystic fibrosis, inborn adrenal hyperplasia, which is a form mutant of cistrons that produces enzymes that interceding production of hydrocortisone from cholesterin by the adrenal secretory organs. Glucose-6-phosphate dehydrogenase lack and many more [ 5 ] . To this present twenty-four hours, for testing neonates, tandem mass spectroscopy is used [ 18 ] . It is a batch easier for showing and diagnosing. The application of tandem mass spectroscopy to newborn showing was first described in 1990 [ 18 ] . The primary purpose of newborn showing is to place patients, manfully infants with serious upsets that are treatable [ 18 ] . This will do it easy to forestall or better clinical symptoms of the disease [ 18 ] . Tandem mass-spectrometry is really utile in observing more than one upset at one clip [ 18 ] . This can be used to observe early untreatable upsets and besides can be good if the showing was non limited to merely single babes, but the whole household every bit good [ 18 ] . The showing procedure uses MSMS [ 18 ] . MSMS is the method used to mensurate analytes by both mass and construction [ 18 ] . First the compounds are ionised, where the first mass spectrometer selects the ion of involvement, where it is sorted by weight [ 18 ] . Then the compounds travel through a hit cell, are dissociated to signature fragments, and so go through into a 2nd mass spectrometer where ions are selected for sensing. [ 18 ] . 3.2 Method for testing Research have been done where most newborn testing programmes use simplifying sample readying, alternatively derivatisation of the sample which is the old method [ 18 ] . When investigation, the sample might demo more than one upset. But the usage of ratio of analytes improves sensitiveness and specificity [ 19 ] . Specialized biochemical familial testing is ever done to verify which type of upset the patient has [ 18 ] . Theses familial trials include aminic acerb analysis, organic acid analysis by gas chromatography/mass spectroscopy, and plasma acylcarnitine profile by MSMS [ 18 ] . 4.0 Screening for Individual Inborn Errors of Metabolism Well over 40 congenital mistakes of metamorphosis can now be detected by newborn testing [ 20 ] . This subdivision will look at three congenital mistakes. 4.1 Pentose Phosphate Pathway The pentose phosphate tract ( PPP ) is an anabolic tract where is uses a 6 C glucose to bring forth a 5 C sugars and cut downing equivalents, as shown in Fig. 1. There are three primary maps of this tract [ 21 ] : To bring forth cut downing equivalents, such as NADP organizing NADPH. NADPH allows decrease biogenesis reactions to happen within cells [ 21 ] . To bring forth ribose-5-phosphate ( R5P ) for the cell, for the synthesis of the bases and nucleic acids [ 21 ] . Can metabolize dietetic pentose sugars that are derived from digestion of nucleic acids [ 21 ] . These besides rearrange the C skeletons of dietetic saccharides into glycolytic/gluconeogenic intermediates [ 21 ] . 4.1.1 Disorders of the Pentose Phosphate Pathway There are three congenital mistake in the pentose phosphate tract that have been identified [ 21 ] . 4.1.2 Glucose-6-phosphate dehydrogenase lack The enzyme glucose-6-phosphate dehydrogenase ( G6PDH ) , catalyses the reaction that converts glucose-6-phosphate to 6-phosphogluconate. This creates one mole of NADPH each for every mole of glucose-6-phosphate ( G6P ) that enters the PPP [ 21 ] . A lack would take to an mistake to the first irreversible measure of the tract [ 21 ] . This would take farther to a lower production in NADPH, doing the cell more acceptable to oxidative emphasis [ 21 ] . G6PDH is really of import for Red blood cells metabolism [ 21 ] . A lack could take Persons to nonimmune haemolytic anemia which can be caused by, infection or exposure to certain medicines or chemicals [ 21 ] . G6PDH lack is besides linked to favism [ 21 ] . It is thought to be an X-linked recessionary familial disease [ 21 ] . 4.1.3 Ribose-5-Phosphate Isomerase Deficiency A recent survey have shown that a patient with of ribose-5-phosphate isomerise lack, had developed progressive leucoencephalopathy and, developmental and speech hold [ 21 ] . They did farther surveies utilizing NMR and found that polyols ribitol and D-arabitol concentration was unnatural in organic structure fluids [ 21, 22 ] . They did their surveies on fibroblasts and found that the enzyme gene-sequence analysis showed a frame-shift and a missense mutant [ 22 ] . 4.1.31 Metabolic Derangement Ribose-5-phosphate isomerase lack would intend that the reversible reaction change overing ribose-5-phosphate to ribulose-5-phosphate and frailty versa will hold [ 22 ] . If there was no lack ribulose-5-phosphate would be converted to xylulose 5-phosphate, which will supply the substrates for transketolase and farther transition into glycolytic intermediates [ 22 ] . Surveies have found that there are two mutant allelomorphs one from each parents that consequences in ribose-5-phosphate isomerise cistron that causes the lack [ 22 ] . So it could be an autosomal recessionary heritage upset [ 22 ] . The best manner to make a diagnostic trial for Ribose-5-phosphate isomerase lack would be to take a urine sample [ 22 ] . Polyols ribitol and D-arabitol would be analysed [ 22 ] . Besides enzyme checks can be used to sequence the ribose-5-phosphate isomerise cistron [ 22 ] . 4.1.4 Transaldolase Deficiency Some surveies have been done where three unrelated households had Transaldolase lack [ 23 ] . One patient had aortal constriction where the aorta narrows [ 23 ] . During the patient s life they found that ammonium hydroxide was lifting. But neurological and rational development has been normal. Another patient had HELLP syndrome ( haemolysis, elevated liver enzymes and low thrombocyte count ) [ 23, 24 ] . Children with transaldolase lack have been diagnosed have found that the development of rational and neurological showed no abnormalcies [ 23, 24 ] . But there is a strong nexus to liver cirrhosis which consequences from increased cell decease of hepatocytes and bilious epithelial cells [ 23, 24 ] . 4.1.41 Metabolic Derangement Transaldolase catalyses the reaction: Sedoheptulose 7-phosphate + glyceric aldehyde 3-phosphate erythrose 4-phosphate + fructose 6-phosphate [ 59 ] . It is a reversible reaction in the pentose phosphate tract. The lack lead to the accretion of polyols derived from the tract intermediates: erythritol, arabitol and ribitol [ 59 ] . Surveies have shown that all patients were homozygous for these specific mutants, proposing autosomal recessionary heritage [ 23, 24 ] . A simple urine trial can be done to name of transaldolase lack, chiefly because there is a high concentration of arabitol and ribitol in piss. Besides enzyme checks can be used to sequence the cistron [ 23, 24 ] . Liver graft would be the lone option with patients that have severe liver cirrhosis [ 23, 24 ] . 4.2.0 Insulin secernment by the pancreatic A ; szlig ; -cell In the production of insulin glucose enters the A ; szlig ; -cell through a GLUT2 transporter where it is phosphorylated to glucose-6-phosphate by the enzyme glucokinase [ 58 ] . The enzyme is used as a control, where it monitors the degree of glucose [ 58 ] . As blood glucose raises the rate of glucose metamorphosis besides increases, where the cell will undergo glycolysis bring forthing ATP [ 58 ] . This addition of ATP concentration causes K+ channels to shut, doing the membrane depolarised [ 58 ] . This depolarization causes the electromotive force sensitive Ca2+ channels to open and Ca ions inundation in, exciting insulin secernment by exocytosis from storage granules ; this is shown in Fig. 2. 4.2.1Persistent Hyperinsulinemic Hypoglycaemia Hyperinsulinism has been diagnosings in all ages but it is really common in childhood [ 25 ] . Persistent hyperinsulinemic hypoglycemia ( PHHI ) is the 1 of the chief cause of hypoglycemia particularly in immature kids. Patients who are older, that develop PHHI are due to pancreatic adenoma [ 25 ] . Hypoglycemia when there is an overrun of insulin by the A ; szlig ; -cells in the pancreas [ 25 ] . Hypoglycaemia can bring forth a assortment of symptoms the most unsafe is encephalon harm which can take to decease, and that is why intervention is critical [ 25 ] . PHHI has two histopathological lesions that can be easy distinguished, doing PHHI a heterogenous upset [ 25 ] . Focal hyperinsulinemic hypoglycemia ( FoPHHI ) is caused by loss of heterozygosity which is a bodily event [ 25 ] . This causes focal adenomatous hyperplasia, which is a pancreatic lesion [ 25 ] . They are treated with pancreatectomy, where they surgically remove portion of the pancreas. Diffuse hyperinsulinemic hypoglycemia ( DiPHHI ) is besides a heterogenous upset, in that fact that it is unable to encode for proteins needed for insulin secernment [ 25 ] . This can besides be caused autosomal recessive and dominant cistrons which are rare [ 25 ] . Positron emanation imaging ( PET ) is used to separate between focal and diffuse PHHI [ 25 ] . This gives a 3D image or image of functional procedures in the organic structure [ 25 ] . Once a patient is diagnosed with PHHI, they are on intervention straight off with glucose and glucagon [ 25 ] . 4.2.12Metabolic Derangement Hyperinsulinemic hypoglycemia is due to insulin hypersecretion by the pancreas [ 25 ] . The Action insulin causes a lessening in plasma glucose by suppressing hepatic glucose release from animal starch and gluconeogenesis, and by increasing glucose consumption in musculus and fat [ 25 ] . PHHI is a upset that is caused by a assortment of defects, either in ordinance of insulin secernment, unable to transcribe the enzymes needed of even a modified receptor [ 26 ] . For illustration diseases that can impact the ion channels like ictuss [ 27, 28, 29 ] . Besides deficiency of enzyme production of glucokinase ( GK ) , and glutamate dehydrogenase ( GDH ) [ 30, 31 ] . Epidemiology has found that 1/50,000 patients are born with PHHI [ 32, 33 ] . Focal hyperinsulinemic hypoglycemia is strongly linked to mutant of the sulfonylurea-receptor and the K+ channels, both used to depolarize the cell [ 32, 33 ] . Both are found to be located on the chromosome 11p15 [ 32, 33 ] . To place these mutants they would necessitate to be tested in a fetus or embryo before it is born. Sulfonylurea-receptor cistron ( SUR1 ) will non react to diazoxide, which is used as a K+ channels activator [ 34 ] . Surveies have found that a high activity of the enzyme glutamate dehydrogenase ( GDH ) has resulted to hyperinsulism/hyperammonemia syndrome. This would do sense as GDH is needed to bring forth insulin and this would impair detoxification of ammonium hydroxide in the liver [ 31 ] . The enzyme glucokinase ( GK ) is besides expressed extremely, where the affinity is increased for glucose, doing high degrees of insulin secernment [ 30 ] . 4.2.13 Diagnostic Trials Diagnostic of HI is easy, in the fact that, it can be indicated by the degrees of glucose in the blood. Treatment varies from age [ 35 ] . Hyperammonemia should be treated as another disease, when a patient has PHHI, when handling hyperinsulism/hyperammonemia syndrome. This can be done by analysis of urine organic acids and plasma acylcarnitines [ 36 ] . Patients who show the FoPHHI can hold lesion runing from 2.5 to 7.5 millimeters in diameter [ 37, 38 ] . Peoples who have DiPHHI found that there was A ; szlig ; -cells that were unnatural [ 39 ] . Pancreatic venous catheterisation ( PVS ) and pancreatic arteriography have proven really utile in turn uping the site of insulin secernment [ 40, 41 ] . PVS process will hold to able to keep blood glucose degree, which is between 2 and 3 mmol/l. Blood sample would so be taken from the pancreas to mensurate 3 things 1.plasma glucose, 2.insulin and 3.C-peptide degrees [ 40, 41 ] . Surveies have shown that people with FoPHHI tend to hold high concentration of plasma insulin and C-peptide degrees in some samples and low concentration in others [ 40, 41 ] . Peoples who have DiPHHI tend to happen that all their sample have high concentration of plasma insulin and C-peptide [ 40, 41 ] . The usage of [ 18F ] -labelled fluoro-L-DOPA whole-body antielectron emanation imaging ( PET ) , has proved to be really utile in observing hyperfunctional islet pancreatic tissue, where this can be used on patients with focal lesion [ 42 ] . Recent surveies have shown that a new technique have been use to turn up focal lesion and separate focal from diffuse signifiers of HI ; this is the tolbutamide trial [ 44, 45 ] . 4.2.14 Treatment and Prognosis Brain harm can happen if you are hypoglycemic, so intervention demands to be speedy. Glucagon would be given, where the patient would hold to take 1 to 2 milligrams per twenty-four hours if blood glucose degrees are unstable [ 35 ] . To handle PHHI, Hyperstat would be given, normally at a dosage of 15-10 mg/kg/day depending on your age [ 35 ] . Normal blood glucose degrees should be between 4 and 7 mmol/l, before and after a repast [ 56 ] . This could necessitate to be look into every clip one time taking diazoxide [ 35, 56 ] . Octreotide intervention, can besides be used as it is a endocrine inhibitor [ 46 ] . But a high could take to a more terrible hypoglycemia, as it can suppress glucagon and growing endocrine [ 46 ] . Patients will happen that after intervention with octreotide, they might purge or hold diarrhoea [ 46 ] . Calcium-channel blockers could be used, such as Lercanidipine and Pranidipine [ 46 ] . These interventions that have been mentioned are really effectual in commanding blood sugar [ 46 ] . If a patient is diagnosed with FoPHHI, the intervention tends to be surgical as drugs are uneffective [ 46 ] . They would undergo pancreatectomy. This process has its hazard as the patient might develop diabetes mellitus [ 46 ] . DiPHHI patients have been found to hold big karyons in the A ; szlig ; -cells [ 35, 47 ] . And patients with FoPHHI showed no unnatural s-cell karyons but did demo shriveled cytol [ 49, 50 ] . 4.3 Glucose Transporter Deficiency Monosaccharide s such as glucose and fruit sugar have the belongingss of being hydrophilic [ 59 ] . The lipid bilayer has hydrophilic caputs and hydrophobic dress suits, prevent polar molecule such as glucose from spreading across the membrane [ 59, 60 ] . So transport mechanisms are needed. These are hydrophilic pores leting polar molecules to spread in and out of the cell [ 59, 60 ] . There are two types of glucose transporters. 1. Sodium-dependent glucose transporters ( SGLT ) , which have been found to be located in the little bowel and the proximal tubule [ 59, 60 ] . SGLT uses the difference in concentration of Na to transport glucose [ 59, 60 ] . From high to low concentration of Na causes the conveyance of glucose against its ain concentration gradient [ 59, 60 ] . 2. Facilitative glucose transporters ( GLUT ) , which has been found throughout the organic structure, but manfully in musculus and pancreas cells [ 59, 60 ] . These transporters transport glucose from high to low concentration [ 59, 60 ] . Surveies have shown that there are four defects in the conveyance of monosaccharoses [ 59, 60 ] . These defects can depend on where the transporters are located within the o

Urban planning & landscape architecture in Jeddah Saudi Arabia Essay

Urban planning & landscape architecture in Jeddah Saudi Arabia - Essay Example By the mid-fifties, the vital requirement for new lodgings has already led to the manufacture of the first houses in Jeddah and substitute of concrete for the customary coral blocks as the rudimentary construction material.As in less than three decades of unassuming dealing village was turned into a gigantic rambling metropolis, the outstanding development, regrettably, is regulated only by morsels and parts from diverse designing principles.When these new building components were presented, the buildings of customary residences have halted, and architecture took a distinct form. For the most part easily answer to the claims and stresses of up to date life, and in the system precious and viable value of old Jeddah have been disregarded. Turker, M. and E. Derenyi, 2000 There was no time to recognize that the evaluation of old and new and purposeful integration and can have its advantages. Instead of the customary localities of the town were either taken or left to worsen, while Wester n-style residential and financial localities of the town were constructed on the periphery. Now Saudi Arabia is seeking to retrieve these balances previous time, what additional can be save, and hold not less than some of the customary quarter of the old City until it was too late. Jeddah After Riyadh Jeddah is the second biggest town in the Kingdom of Saudi Arabia with a community of over three million people. Jeddah is situated on the west seaboard area of the Kingdom of amalgamation latitude 29.21 north latitude and 39.7 east in the center of the to the east Red Sea seaboard area and the surrounding flat lands Tahoma from the east. Jeddah has seen a pointed boost in community due to migration from villages and suburbs of the town in seek of work and a better life. In supplement, the decrease in death in the UK directed to a natural boost of population. Where there were only 700,000 inhabitants in 1975, by 2006 this number had increased to more than three million people. According to 2004 plan of Jeddah Structure, there was a boost in the mean yearly community development rate from 0, 9% in 1940 to 6, and 3% in 2002. There were an boost in the Saudi community is about 50% in 1995 to about 70% in 2001 and declines in non-Saudi community of about 50% in 1995 to about 30% in 2001 (Municipality of Jeddah 2004). With fast community development, Jeddah built-up localities have increased. In specific, the mass of Jeddah town expanded from 56 sq km in1968 to 1,378 rectangle kilometers in 2002 (Municipality of Jeddah 2004). Urban development has been important to the south and north. This development was the outcome of natural obstacles, while at ocean in the west and hills to the east. Turker, M. and E. Derenyi, 2000 Various undertakings have been evolved and developed in the city. Earth was conceived five milestones in Jeddah: four functional designs taken up in: 1948, 1972, 1979 and 1987 and Structure Plan 2004. City outlook of the town was considerably influenced by these plans. As an outcome, localized administration, Jeddah town, its designing department, in specific, faces trials in supervising and updating of built-up land cover. Traditional procedures for getting facts and numbers for built-up remedy will need a important allowance of time, effort and cash to quickly increasing towns for example Jeddah. However, the span to which isolated feeling can be utilized for the extraction of built-up cover should be investigated. Land use planning In land use designing, these facts and numbers are very apt for supervising the implementation of land use designs, thus, a huge locality of jurisdiction of the whole boundary town of Jeddah. It is conspicuous that the tendency of built-up development and

Ibn Sinna Essay Example | Topics and Well Written Essays - 3000 words

Ibn Sinna - Essay Example Ibn Sina’s supreme work includes the monumental Al Qanun, the Canon and Kitab-al-Shifa (The Book of Healing). The Canon discusses medical completely in order to classify all the present medical knowledge.  While, Kitab-al-Shifa being a philosophical encyclopedia, covers huge areas of knowledge from philosophy to science. The Sheikh al-Ra’is Sharaf al-Mulk Abu Ali al-Husayn Abd Allah al-Hasan Ali Ibn Sina, generally known as Avicenna, is among the most celebrated and original Muslim philosophers in the history of philosophy (Al Naqib, 1993). He is the actual creator of a scholastic system in the Islamic world and is described as the leader of Islamic philosophy. The most famous works of Avicenna are on philosophy and medicine. His philosophical visions have intrigued the interest of Western thinkers over a number of centuries, and his writings have been among the most significant sources in philosophy. His other major contributions were in the fields of metaphysics, poetry, animal physiology, minerals, rhetoric, and mechanics of solids, Arabic syntax and meteorology (Ahmed, 1990). Ibn Sina birth took place in the village of Afshana in the surrounding areas of Bukhara, now known as in Uzbekistan, in 980 AD (370 AH) in an Islamic family interested in intellectual sciences and philosophy which proved to be extremely influential later in his life (Al Naqib, 1993). His early schooling was done in Bukhara and became knowledgeable in the study of the Quran and various sciences by the age of ten.  His teacher, Abu Abdallah Natili, a renowned philosopher, taught him logic and many other subjects (Ahmed, 1990). Furthermore, he began reading philosophy by studying numerous Greek, Muslim and other books related to this subject. He accomplished a degree of expertise in medicine at a very young age due to which he gained immense popularity. After curing the King of Bukhara, Nooh Ibn Mansoor, at the age of 17, he was

Consumers are Passive Victims Manipulated Into Buying Commodities They Essay

Consumers are Passive Victims Manipulated Into Buying Commodities They Cannot Resist - Essay Example This essay discusses and investigates the topic on why the purchasing habits of the consumers are heavily dependent on certain market parameters. Consumer power in the current marketing system is always a controversial one. Majority of the consumers all over the world are passive elements rather than active elements as far market is concerned. In fashion industry, the passive nature of the consumers is more evident. This essay refers to several examples such as: people normally take inspirations from celebrities while they take purchasing decisions in fashion industry. Products endorsed by the celebrities are moving rapidly towards the market than the products which do not have any such backing. In other words, the researcher states that people are blindly trusting the words of the celebrities and product manufacturers and they are not bothering much to research more about the authenticity of the offers put forward by the advertisers and marketers. However, no two individuals are ali ke: either physically or mentally and therefore it is not necessary that a product suited to one person may be suited to another person. To conclude the research, the author suggests his opinion on the topic that modern customers are not ready to accept such claims and they try to boost their image with the help of expensive products that were successfully advertised by celebreties. Long story short, majority of the current consumers are passive in nature while they take their purchasing decisions.

Building Positive Relationships with Children

Building Positive Relationships with Children Jodi Allan Unit 3: Building Positive Relationships Task 1) All children deserve the best start in life, to be provided with endless support which will enable them to fulfill their potential and make the most of their individual talents and abilities as they continue to grow. Between birth to five years, children develop very quickly and their experiences through this time will have a major impact on their future. Enabling a happy, safe and secure childhood along with good parenting and high quality learning, all children will have the start they need for a successful future. The Childcare Act 2006 was introduced as a key piece of legislation and is the first ever Act to be exclusively for early years and childcare (which spans from birth to the 31st August that falls after the child’s 5th birthday). This means that all pre-school childcare providers, including reception classes in primary schools, are all governed by this Act. The legal requirements for any of those operating within the child care setting are in the Ofsted publication , ‘Statutory Framework for the Early Years Foundation Stage’ which sets out the learning and development requirements, welfare requirements, all legal requirements as well as the legal adult to children ratios. The law requires specific duties to be carried out by various authorities, including: Providing an information service for parents; Providing training and advice for providers of child care; Providing working parents with child care as required; Achieving a reduction in equalities in children ages 0-5 through close work with Job Centre Plus, associated partners and the NHS; Providing positive outcomes for any child at risk of poverty; Bridging the inequalities that may exist between children, with particular reference to deprivation. Learning and Development Requirements must be provided by the child care provider and all staff operating under any child care provision and any diversity of children within that provision. All resources are available to providers to ensure everyone required to is able to meet the outcomes, no exceptions. â€Å"The Childcare Act 2006 provides for the Early Years Foundation Stage learning and development requirements to include these 3 elements: The early learning goals-the required knowledge, skills and understanding which young children should have acquired by the end of the academic year in which they reach the age of 5; The educational programmes- the matters, skills and processes which are required to be taught to young children within the provision; The assessment arrangements for assessing young children to ascertain their achievements†. The six areas covered under the learning goals are: Personal, Social and Emotional Development- A group activity such as Show and Tell encourages a child to speak in front of their peers and for other children to learn to respect and listen to each other. Understanding the World- If the provision has a large diversity of children, encouraging them to bring in something from their home that they are able to share with their peers, such as clothing or food, can help children explore and learn different aspects of their community. Physical Development- A fun outside game, such as an obstacle course for the children to participate in would be a perfect opportunity for them to develop movement and co-ordination, or simple dancing games such as ‘head, shoulders, knees and toes’. Mathematics- Practicing counting, shapes and measures together as a group whenever possible is always a perfect opportunity, eg: How many apple slices can count on your plate? How many letters are in your name? Ensuring there are plenty of images around them for them to look and question over. Literacy- the provision has to ensure there are plenty of books and other reading materials around for children to explore whenever they want to. Group reading time is always positive and helping each child to recognise and write their own names. Expressive Arts and Design- plenty of opportunities for children to explore and express themselves, such as role play, creative media, dance, music, arts and crafts. Providing the right materials so they are available to children all the time is the best way to ensure they can express themselves this way whenever they want to. Task 2) Teaching children from an early age to respect and value individuality enables them to learn that these values are very important within their society and for their future as these values will enable them to be decent young adults. Children learn these values from early on by observing everyday situations and mimicking the adults they interact with. The child care setting should be a positive, safe place for children to learn this respect for one another and should be filled with positive images, toys and electronic equipment that promote individuality and diversity as well as a positive perception of the world around them. The child care setting can easily focus entirely on each individual child by devising a plan which helps promote each child’s individuality and includes the parents or carers to participate in this plan too. This also helps other children to watch and listen to their peers and learn to understand, respect and value each others individuality. This can be a à ¢â‚¬Ëœshow and tell’ chart or ‘achievement days’, where once a month, a child gets given a day where they can bring in anything from outside the child care setting that they have done to show and talk about to their child minder and peers, then after they are finished they are awarded a sticker to put onto the chart next to their name. Name of Child Date Activity Stickers Max 28/09/2014 Brought in yummy cakes that he helped make with his Polish Grandma Evie 30/09/2014 Brought in a beautiful painting she did over the weekend and told us about all of the colours that she used George 1/10/2014 Went on holiday to Spain and brought in photos for us to see! Task 3) Children need consistency and the earlier they are given this the better, as it will benefit their ability to learn about respect and also to distinguish from right and wrong, otherwise they could become very confused in situations when beginning to learn about the outside world. Consistent routines at home and their child care setting helps children to keep calm and feel safe, but . Children need to learn that all actions will have a consequence, whether it is good or bad. This helps the children with establishing good and bad behaviour skills and embedding this in their every day life will promote their knowledge as they grow older. Initially to promote positive behaviour in the child care setting, the aim is to help them to want to be consistent in their own positive behaviour themselves by rewarding such behaviour, slowly making the rewards smaller and then taking them away, this will begin to let them realize that behaving well creates a happier environment for them and their pe ers. This is always a simple and effective way to teach them to not want to behave in a negative manner. Sticker charts, books or handing stickers out are always a popular treat for rewarding children, as well as asking them what activity they would like to do next, or which book they would like to read with the class? High appraisal from staff and peers gives children a positive feeling about themselves and their positive attitude. Negative behaviour must also have consequences, such as time out, but it is also important to sit the child down and discuss the situation to ensure the child isn’t left feeling confused or alone. Talking in a calming tone and keeping eye contact whilst letting the child know how they have made others feel when they have behaved in a negative manner will not only help them want to make positive choices but they will begin to understand empathy as well. Task 4) Conflicts between children and adults are common, particularly within a child care setting. There are various triggers that can create conflict which are listed below, such as the child having unmet needs resulting in them craving extra attention from their parent or teacher which can easily build into a heated conflict. Children find it very hard to be selfless at such a young age and often only see their point of view and find it difficult to understand someone elses views in a conflict situation. Due to their lack of social skills, children can easily escalate a small argument, such as over a toy, into a harsher argument as they don’t have the necessary communication skills to solve a conflict in a positive manner. Some children having a lack of suitable role models can easily give children a biased view in ways in which conflict can be handled and this can be very difficult to mend. Another trigger that can affect conflict is that when children are tired or hungry it can h ave a very suppressing effect on their mood and they may engage in conflicting behaviour. Often at home or any child care setting, a parent or teacher intervenes and solves an argument. Sometimes it’s simple when the conflict is between children and their peers but sometimes a child can create conflict with an adult and dealing with this in a positive way can be very distressing for both the child and the adult, making any reasoning very difficult. Many behavioural Theorists have contrasting views when it comes to whether conflict has a positive or negative effect on a childs development. Some feel that conflict helps to shape a child’s social skills for when they become adults and that learning to solve conflicts in a positive way equips them with the skills to continue this skill in their adult lives. Behavioural Theorist B.F Skinners believes in the system of positive and negative reinforcements. His theory is that reinforcers are used to strengthen both positive an d negative behaviour and that humans of all ages respond to verbal operants such as taking advice, listening to the warnings of others and obeying given rules and laws. His theory suggests that without personally experiencing any negative consequences from disobeying, the child simply knowing what could happen when they decide to pursue negative behaviour will be enough for them to want to make positive choices instead. From this they can begin to learn from each incident for any future conflicts and they will want to repeat positive behaviour willingly. Ways of dealing with conflict in a positive manner could start with sitting down with the child and asking them questions about the conflict in question can make them feel like they do have a say in the situation, especially as some children find authority difficult. Letting a child know there is a positive solution to the conflict can calm them down and get them to sit down and think about the situation properly. Ask them what it i s they are feeling, â€Å"are you angry? But also feeling hurt because you have had to wait for me to come and play?† Tell them how the other person could also be feeling, â€Å"I’m sad that you shouted at me, because I didn’t mean to ignore you, but I was very busy with the rest of the children too.† Ask them what they would now like to do, which would be the best way for everybody, a way for both of you to fix the situation in a positive way for a positive outcome. This strategy can let children feel safe and confident, but they may also see that conflict can most definitely be solved in a positive way.

Euthanasia and Assisted Suicide - Eliminate the Pain or Eliminate the P

Eliminate the Pain or Eliminate the Patient? Â   Â   Proponents of euthanasia argue that "mercy-killing" is necessary because patients, particularly those with terminal illness, experience uncontrollable pain(1). They argue that the only way to alleviate the pain is to eliminate the patient. But is there a better way? This essay proves that there is a better way, and this medical opinion is backed up by the best medical opinion available. Â   The better response to patients in pain is not to kill them, but to make sure that the medicine and technology currently available to control pain is used more widely and completely. According to a 1992 manual produced by the Washing ton Medical Association, Pain Management and Care of the Terminal Patient, "adequate interventions exist to control pain in 90 to 99% of patients."[2] The problem is that uninformed medical personnel using outdated or inadequate methods often fail in practice to bring patients relief from pain that today's advanced techniques make possible. Â   Doctor Kathleen Foley, Chief of Pain Services at the Memorial Sloan-Kettering Cancer Center in New York, explained in the July 1991 Journal of Pain and Symptom Management how proper pain management has mitigated patient wishes for assisted suicide: We frequently see patients referred to our Pain Clinic who request physician-assisted suicide because of uncontrolled pain. We commonly see such ideation and requests dissolve with adequate control of pain and other symptoms, using combinations of pharmacologic, neurosurgical, anesthetic, or psychological approaches.[3] Â   In treating "Total Pain" [4], it should be remembered that the social and mental pain suffered by terminally ill patients may exace... ...tional Cancer Institute, "Questions and Answers about Pain Control," (1992), pp. 43-51. 9. Matthew Conolly, M.D., letter to author, August 2, 1993. 10. Louis Saeger, "Patient Controlled Analgesia (PCA) in Caner Pain Management," Supra Note 1, pp. 149-53. 11. Ibid. 12. Chuck Michelini, "Patients Put in Control of Their Pain Medication," Medical Tribune (October 29, 1986): p. 46. 13. Gene Bylinsky, "New Gains in the Fight Against Pain," Fortune (March 22, 1993): p. 116. 14. Matthew Conolly, M.D., letter to author, August 2, 1993. 15. Jane M. Anderson, "Pain Management: Challenging the Myths," Medical World News (April 1992): p. 20. 16. David E. Weissman, June L. Dahl, and John W. Beasley, "The Caner Pain Role Model Program of the Wisconsin Cancer Pain Initiative", Journal of Pain and Symptom Management v. 8 (January 1993): p. 29.

Son of the Morning Star

Son of the Morning Star Analysis Evan S. Connell has a unique writing style. While most stories are told from beginning to end, Son of the Morning Star: Custer and The Little Bighorn (North Point Press, 1984) begins with the aftermath of The Battle of the Little Bighorn. It is then followed by numerous events which led up to this battle. Connell chose this non-linear writing style in order to distribute the details he finds most fascinating and interesting to share with his audience. Using the conclusion of the battle as the introduction of the narrative creates a suspenseful tone.In the beginning of the story, the setting is the battle field which The Battle of the Little Bighorn had taken place a few days earlier. Lieutenant James Bradley has led his troops to the land where they discover the corpses of which they believe are General George Armstrong Custer’s troops. Custer himself was nowhere in sight. Even after a reward was offered upon his retrieval he could not be found . The deserted battle field raised questions and the men began to imagine what had happened days prior to their arrival.The author writes, â€Å"While discussing the day’s events around a campfire most infantrymen predicted more unpleasant news†¦Ã¢â‚¬  (pg. 3) The troops discovered a woman who was present during the battle and described to them what she had witnessed. The woman’s recollection of her experience opens up the story to a chronicle of the events which happened during the battle. The reader is given details regarding to Custer’s entrance and also each opponent’s fighting style: â€Å"Instead, Reno’s men dismounted and formed a skirmish line. Then they began to retreat. They ran very fast, she said, dropping guns and cartridges.She was disgusted by the conduct of these whites, saying they must have been seized with panic worse than that which seized her own people. † (pg. 7) As the plot approaches its conclusion, the reader is taken back to the aftermath of the battle and receives a tale told by a Cheyenne woman named Kate Bighead. She delivered a short story about the corpses she saw laying on the battlefield, one in particular she identified as General Custer: She said two Southern Cheyenne women were at the Little Bighorn and when the fighting ended they went to the battlefield.They saw Custer. They knew him well†¦they recognized him even though his hair was short and face was dirty. (pg. 422) Although the plot of this story does not have a chronological structure, it develops a more personal connection because the characters in the story are directly speaking to the audience as they give their personal accounts on the battle. For example, it had already been said that Reno was dead; however, an outburst made by Reno himself is mentioned shortly after. â€Å"The major was swigging at a flask when DeRudio splashed by. What are you trying to do? ’ Reno asked. ‘Drown me before I am k illed? ’† (pg. 50) Evan S. Connell’s work, Son of the Morning Star is an extraordinary and captivating narrative. He has an acquiring mind and was not afraid to step away from the traditional form of writing. Behind the chaos there is meaning. The writing style presented in this story is untraditional which could possibly lose the attention of the reader; however, this was a valid decision. ? Based on its cover the reader might think that the entire story is about General Custer and his troops.Despite expectations, the audience actually catches a glimpse of both the lives of Custer as well as his opponents. The author gives the reader a little information on the background of Crazy Horse, formerly known as Curly. â€Å"Curly did not reveal this manifestation to anybody until he was sixteen and ready to become a warrior†¦Except for moccasins and breechcloth he rode naked. † (pg. 67) The author also gives the reader the opportunity to read a few journal entries about Crazy Horse. These entries come from the diary of Jesse Lee, â€Å"Saturday, Sept. th, 1877. Everything is quiet and I think will remain so. Crazy Horse’s body was brought to this agency and put on a little platform, Indian fashion, on the hill overlooking the post, not half a mile away. † (pg. 75) He also includes a background on Chief Gall as well, providing facts about his birthplace and family. For example, he writes, â€Å"He was not a hereditary chief. The family seems to have been undistinguished, and because his father died at an early age the boy was regarded more with sympathy than respect.So it appears that not through any legacy did he become a chieftain†¦Ã¢â‚¬  (pg. 376) Throughout the story, the audience develops an idea of the motives of the Native Americans during the battle. The reader becomes aware of what Sitting Bull was thinking: If Sitting Bull did indeed call off the attack it was not because of any affection for whites, who , he hated with abiding and impenetrable rancor, but because he understood how vindictive they could be. If all the soldiers were slaughtered the whites would insist upon another battle†¦ (pg. 6) The audience was not only given an idea of what they were thinking before the battle. The author also makes a point to include a song that the Indians wrote after they had defeated General Custer and his men, â€Å"At that time the Indians did not realized they had fought Custer†¦when they found out, they sang about him. David Humphreys Miller transcribed one such kill-song†¦Ã¢â‚¬  (pg. 54) With the erudition given in the story, the reader concludes that the Native American leaders were fully developed human beings. Connell includes information regarding Chief Crazy Horse’s smart battle technique.For example, there are quotations given from a journalist: At critical moments Crazy Horse would dismount before shooting: â€Å"He is the only Indian I ever knew who did t hat often†¦he didn’t like to start a battle unless he had it all planned out in his head and knew he was going to win. (pg. 63) Chief Gall was compared to other great leaders and his leadership skills are described by his people including Lieutenant Godfrey, â€Å"He perceived Gall as a man of tremendous character natural ability, and great common sense, a chief whose massive physiognomy reminded him of Daniel Webster. (pg. 375) The comments made about these two leaders in particular demonstrate their equality of humanity compared to Custer’s men. Not only does he give details about the lives of the Native Americans but Connell also gives insight on the lives of those who fought with General Custer. The reader is given an idea of the reputation and trial of Benteen. For example, â€Å"In this, that Major Frederick W. Benteen, Ninth Calvary when in command of the Post of Fort Du Chesne, Utah, was found drunk†¦Specifications 2nd, 3rd, 4th, 5th and 6th were id entical, only the dates changed. (pg. 34) The reader also gathers information about Major Marcus Reno regarding his leadership and his behavior thus similar to that of Benteen’s. â€Å"Reno got demerits easily, almost deliberately†¦Ã¢â‚¬  (pg. 40) He also writes, â€Å"At least it failed to mollify the exasperated colonel because Reno found himself saddled with another charge†¦Ã¢â‚¬  (pg. 45) Although a great deal of this piece is devoted to the lives and motives of the Native Americans, the author also takes time to write about Custer’s men as well.Including battle experience as well as family history, Connell captures the importance of The Battle of the Little Bighorn. Throughout the non-linear story, the reader is taken back and forth between stories about Custer’s challengers and his troops. The author’s objectivity is apparent because the reader is given the opportunity to capture the battle from both perspectives. ? Before The Battle o f the Little Bighorn, General Custer had celebrated many victories; however, this battle ended in tragedy.Unaware of what caused the downfall at Little Bighorn, many have speculated possible causes of Custer’s defeat. These possibilities include Custer’s sanity, his confidence and other stereotypes. In the story, Connell’s collection of stories told by Sioux woman and other survivors give the reader ideas of what might have been the cause of this disastrous downfall. When looking back on the battle a discussion between an Indian and General H. L. Scott reveals a possible cause of this defeat.For example, Connell writes: During subsequent conversations Feather Earring emphasized that if Custer had approached diplomatically the Indians would have gone back to the reservations†¦General Scott observed that such a method of dealing with the hostiles had not occurred to anybody. (pg. 414) Shortly after this discussion more information about Custer’s skewed communication with the Indians is unveiled. If this miscommunication had never occurred the battle would have been avoided altogether.A Sioux chief gives his recollection on the events occurring prior to the battle: He asked Custer to promise that he would not fight the Sioux. Custer promised†¦After we got through talking, he soon left the agency, and we soon heard that he was fighting the Indians and that he and all his men were killed. If Custer had given us time we would have gone out ahead of him, but he did not give us time. If we had gone out ahead of Custer he would not have lost himself not would his men have been killed. (pg. 415) The attack had been approved by his officers, however, there had been some objections.Some of his troops did not believe the plan was logical but Custer’s confidence does appear to take over his mentality. He ignores a suggestion made by Gibbon, â€Å"Custer, instead of proceeding at once into the valley of the Little Big Horn, even should the trail lead there, should continue on up the Rosebud, get closer to the mountains†¦Ã¢â‚¬  (pg. 255-256) Losing touch with reality Custer continues to explain his plan to attack, â€Å"the combined forces would count coup on Sitting Bull, Crazy Horse, Gall†¦and all the rest† (pg. 56) Custer’s plan includes a victory rather than an alternative in case of any misfortune, he left no room for the unexpected. Although Custer’s plan seemed a little unrealistic his stubbornness was not the only thing to lead to the downfall at Little Bighorn. Many troops give their comments regarding Major Reno’s choice of leadership, â€Å"several military analysts believe Reno should have stayed there instead of doing what he did. They point out that his battalion so near the village would have engaged a great many warriors, thus allowing Custer’s plan to unfold. † (pg. ) It is also mentioned that Reno had an altercation with one of the Indian s which he encountered, â€Å"Reno misunderstood a figure of speech, taking I as an insult, and threatened to shoot High Bear-who responded by drawing a knife. Another scout, invoking Custer’s name, jumped between them and managed to prevent a bloody settlement. † (pg. 10) Not only was Reno’s lack of intuition a cause of defeat but it is also possible that his belligerent temperament lead to Custer’s labefaction. After analyzing the attitudes and actions of Custer and his troops, the reader can infer many causes that led to this disastrous defeat.Based on the strategic analysts’ comments, Reno could have used better instincts when leading his men into battle. It is possible that if the major would have had stronger intuition Custer’s men would not have suffered as much as they did. The reader can conclude that there was a sense of overconfidence made not only by Major Reno but Custer as well; however, if Custer had kept his promise to Sioux the entire battle could have been avoided. Custer and his five companies certainly underestimated their Native American opponents.

Steamboat Bill Jr. essays

Steamboat Bill Jr. essays "Steamboat Bill Jr." produced in 1928 stars one of the best silent comedians of all time, Buster Keaton. This film contains some of the best and most spectacular sight gags that have ever been performed before. It is the story of Keaton playing a college-educated young man (Willie or Bill Jr.) who comes home to help his father (Bill Sr.) work on his Mississippi River steamboat. Bill Sr. soon realizes that his son is complete let down only being half the man he is, yet Bill Sr. is still determined to make a man out of his son. What is worse, the woman he falls for is the daughter of his father's worst rival, a rich bully by the name of J.J. King, who wants to drive Bill Sr.s steamboat out of business. Keaton's slapstick is inspired and precise, particularly during an amazing sequence in which he tries to walk across town during a hurricane. The film, "Steamboat Bill Jr." has many comically pleasing techniques that Keaton brings to the screen, however it can be questionable if th is film is a part of classical cinema. Unlike Chaplins "Little Tramp," Keaton avoids the pathos, as he never cries out for sympathy. The audience does not need to be charmed into identifying with him. The peaceful blankness of his face is like an empty screen onto which the viewers can project their own hopes and fears. Like the audience, Keaton himself is an observer. He does not seem to rush blindly into action, he waits, watches, considers, taking in everything around him; this was his secret within the movie. This is shown while Keaton waits patiently in the jail to inform his father (Bill Sr.) of his plan to break him out of jail by using the files and the saws that he baked within the bread. As Keaton finally gets the attention of his father, and informs him of the plan, things just fall apart (especially the bread) leaving his future plans in disaster and leaving the audience in tears. It is scenarios like these within the film t...

Peets Coffee and Tea

Peets Coffee and Tea Industrial background Peet’s Coffee and Tea is a restaurant with international operations across the world. With its headquarters located in California, the business has a chain of coffee houses located at various parts of the world. The restaurant business deals in a range of products consisting of diversified coffee and tea beverages.Advertising We will write a custom proposal sample on Peet’s Coffee and Tea specifically for you for only $16.05 $11/page Learn More Problem statement Following the recent business evaluation, there has been a need to establish strategies that will propel the company towards success. In this regard, the following strategies will be included in the company’s marketing proposal. New marketing strategies According to Ataman, Harald and Carl, Peet’s Coffee and Tea restaurant requires new marketing strategies that are effective in a food and beverage industry (866). The use of a suite of services and loy alty programs among others is deemed an effective marketing strategy. Suites of services Customer-friendly suite of services includes installation of free internet services inside the restaurant. When customers access free Wi-Fi internet connections, they would be happy to spend time and enjoy coffee and tea for hours. This means that free internet connection requires installation of electrical cables near the coffee tables for laptop connectivity. Another form of a suite of services includes book live entertainment, where customers engage in poetry reading and other forms of readings that complement relaxation. People who prefer taking coffee and tea do so for purposes of relaxation. Suites of services offer an ambient environment that promotes relaxation mood in a coffee and tea restaurant. Moreover, the suite of services may be viewed by customers as value additional services. This strategy will promote sales once regular customers invite their friends to see the difference (Atam an, Harald and Carl 869). Loyalty programs Loyalty programs are considered as incentive programs for loyal customers (Ataman, Harald and Carl 871). In this respect, Peet’s Coffee and Tea restaurant will use punch cards redeemable for free coffee drinks and snacks after every 10th cup of coffee at any of the business restaurants. In this regard, the loyalty program is deemed to encourage more loyal customers to visit the restaurants and enjoy free drinks.Advertising Looking for proposal on business economics? Let's see if we can help you! Get your first paper with 15% OFF Learn More This program increases sales volume and promotes business-customer relationship (873). Another form of loyal program is to have punch cards that track a client’s amount of purchases done at any of the business restaurants. This would be used to determine discounts given to such loyal clients, as well as the value of freebies given to same customers. On-premises adver tising Advertising is integral for any restaurant business, especially a coffee and tea business. The current Peet’s Coffee and Tea restaurant is to distinguish itself from other competitors through on-premise advertising. This means that the business needs to have creativity in having large windows, glass doors, exotic paintings and interior designs. The set-up of the sitting area is critical on how people view the business premises compared to other competitors with similar products and services. The visibility of the restaurant premises from outside is important. This means that the organization management has to make sure all other restaurant’s outlets are located at highly-visible locations. Promotional advertising In order to boost sales, it is important to incorporate sales promotion initiatives after every 4 months. A better way to ensure promotional advertising takes effect is placing coupons at local daily newspapers (876). To capture the attention of interne t users, the same can also be replicated on social media sites like Facebook and Twitter. Promotional advertising is critical in ensuring that the restaurants experience new visits from potential customers. Sales programs Peet’s coffee and Tea restaurant requires a sales program that seeks to promote the business from various perspectives. An example of sales programs would be special events like music events. Inviting artists in the music industry would be crucial in holding live performances at restaurant entertainment halls. This will promote the popularity of artists, as well as that of the restaurant business. Pricing strategy With a need to have repeat business as an attractive profit margin, establishing effective pricing strategies is imminent. Peet’s Coffee and Tea restaurant will use penetration pricing, promotional pricing, competition pricing and premium pricing strategies (880).Advertising We will write a custom proposal sample on Peet’s Cof fee and Tea specifically for you for only $16.05 $11/page Learn More Penetration pricing strategy Peet’s Coffee and Tea restaurants products and services are known as high quality products, but will be offered at a lower price while entering new markets. This strategy will aid the restaurant business in countering harsh competition from other industrial players. Promotional pricing This pricing strategy is a long-term initiative used to attract potential customers. In this regard, the restaurant business will sell some of its products at a lower price without getting significant profits. This strategy is deemed to attract customers to access and explore other products and service provide by the business. Promotional pricing entails the use of discounts like price and product discounting. Competition pricing This strategy is focused to counter competitor’s prices. The business will identify prices of similar products and services from other competitors and provide a lower price on the same. This strategy can deliver narrow profits, but in long-term can be effective in neutralizing competition. Premium pricing Coffee and tea business are common among middle income earners and the wealthy because of the prestige and luxurious services from the businesses. In this regard, Peet’s Coffee and Tea restaurant business will target high-end consumers by providing high-quality products and services at premium prices. This strategy delivers high profit as it targets high spender with premium prices. Marketing programs Peet’s Coffee and Tea will establish a marketing program with an annual budget of $500,000. The marketing program will be responsible for the establishment and implementation of the mentioned strategies. Strategic alliance Peet’s Coffee and Tea restaurant business requires more than marketing strategies to succeed in a highly competitive industry. The business requires strategic alliances such as human reso urce, reliable suppliers, financial institutions and distributors. In this regard, the business requires having strategic pool of personnel as human resource. The department in charge of human resource management will have policies on hiring qualified personnel, general management, training and development of the same (877). In addition, the business will have strategy alliance with suppliers of essential supplies like coffee beans and food stuffs. A policy on supplier selection is critical for a strong-supplier relationship.Advertising Looking for proposal on business economics? Let's see if we can help you! Get your first paper with 15% OFF Learn More Peet’s Coffee and Tea business operates in perishable products and having reliable suppliers is necessary for business success. The business capacity to distribute determines the decision on the mode of distribution of its products and services to its outlets. In this regard, the company can outsource distributorship of its products from distribution vendors if does not have the capacity to do so. Financial strategic alliances with credible creditors are essential for a business survival. In this respect, the business requires partnership for financial stability with local banking institutions. The financial institutions are helpful in terms of credit control measures and financing new ventures. Auditing financial portioning and financial consultations of the business requires an independent auditor like bank institutions. Ataman, M. Berk, Harald J. Van Heerde, and Carl F. Mela. â€Å"The long-term effect of marketing strategy on brand sales.† Journal of Marketing Res earch 47.5 (2010): 866-882. Print.

Play (Sophocles Antigone) Essay Example | Topics and Well Written Essays - 500 words

Play (Sophocles Antigone) - Essay Example This never comes too well for the elder son a factor that draws them into war. As a result of the war, the two sons die meaning that none wins the battle (Brian 1). Kingship is taken by their uncle who is biased over, the two sons substantiated, by his refusal, to bury the body of one son. This neglect leads to numerous consequences with the death his son, wife and the daughter in law. In my opinion, Creon appears to have been in support of the younger king, Eteocles. This is because he shows no intentions of burying the older son. He seems in support of the younger son being the king even though in the real sense, it is wrong for the young son to obtain kingship in the presence of the elder son. Creon talks about honoring the younger son even though in the real sense, he is the cause of the war between him and his older brother. Providing with such recognition has no basis provided these two sons did something wrong in engaging in the war. Creon has personal reasons for not burying Polyneices, and this is the same reason he prevents Antigone, and Ismene from burying Polyneices. Bearing these personal matters makes Creon show more concern to the Eteocles than to Polyneices. Creon wants to make the populaces believe that the elder son is on the wrong although this is not true in the real sense. Creon feels offended, by Antigone and Ismene offering, to bury their brother contrary to his directions. Creon feels insulted since the two go in front of Thebes, and try to bury their brother even after he has provided a final judgment concerning, the burial of Polyneices. Further to that, Ismene disobeys her and she is a woman a thing that makes Creon so angry that he decides to execute the two. In my view, the younger son would have surrendered kingship to the elder son as traditions assume instead of using force and influence to lead the populace in which one is not chosen by

Commercialism And Advertising On The Internet Essay

Commercialism And Advertising On The Internet - Essay Example The bombardment of advertisement makes the users lose focus of their real intention of work on the internet and annoys them by frequent reinforcement messages. The younger internet users get awareness regarding inappropriate merchandizes and services, such as alcohol, adult bars etc. Online commercialism is aggravating the concepts related to materialistic ideas since these advertisements cannot be ignored by internet users. The Internet has made the whole world come onto a single platform where businesses have the opportunity to access their local, as well as international clients with ease. The attraction of reaching a greater segment of customers on a global scale attracts the companies to prefer the online medium of advertising. According to an article in Business Wire by Goldberg and Silber, the first half of the year 2011 saw an increase of 23.2% in the internet ad revenues which amounted to approximately $15 billion. This figure identifies the inclination of companies towards the online commercialism and the degree to which it is increasing. The cheapness of online advertisements has given way to extensive forms of commercialism on the web. Such instances may result in making the user lose focus from his work and may simply waste his precious time. The problem does not end at the point of being annoyed by the frequent emergence of advertisements; it becomes a data storage issue for some users sinc e they receive hefty emails regarding ad campaigns and promotional messages on their personal email addresses. It is due to such constant spam that people may not receive important emails since their inbox might reach maximum storage capacity.