Plasmodium: The Malaria Parasite

Plasmodium: The Malaria Parasite An endoparasitic protozoan that causes malaria, Plasmodium, requires two hosts to complete its life cycle in; usually a mosquito and a vertebrate. Female Anopheles mosquito is responsible in the transmission of malaria in human beings. Human malaria is caused by four identified species of Plasmodia, namely Plasmodium falciparum, Plasmodium vivax, Plasmodium malariae and Plasmodium ovale. Recently, in addition to these four species, the simian parasite Plasmodium knowlesi have been identified to infect humans in Malaysia (Cox-Singh, Singh, 2008). Malaria can be treated in just 48 hours; however the delay in diagnosis and treatment can cause fatal complications. Malaria caused by P. falciparum is also called malignant or falciparum malaria (Rich et al., 2009), which is observed to be the most dangerous form of malaria with the highest rates of complications and mortality. A dormant stage in the life cycle of P. vivax and P. ovale may results into relapses long afterwards. The malaria d ue to P. knowlesi can also cause life threatening symptoms(Cox-Singh et al., 2008). P. malariae is associated with milder clinical manifestations in comparison to other species. The systematic position of malaria parasite described by (Mhelhorn H. and Walldorf V., 1988) is as follows: Kingdom Protista Sub Kingdom Protozoa Phylum Apicomplexa Class Sporozoa Sub Class Coccidia Order Haemosporidae Sub Order Aconoidina Family Haemosporidae Genus Plasmodium 1.2 History of Malaria The term malaria is derived from Italian word mala bad and aria air. Italians used this word to refer the cause of intermittent fevers associated with exposure to marsh air or miasma. In the first century A.D., Roman scholar Marcus Terentius Varro (116-27 BC) suggested that swamps breed certain animalcula which is not visible with naked eyes and we breathe it through our mouth and nose into the body, where they cause grave maladies. Later, about 30 A.D., two types of tertian fevers were described by Celsus. He concurred with the views expressed by Varro. In 1716, Italian physician Giovanni Maria Lancisi, first demonstrated a characteristic black pigmentation of the brain and spleen in the victims of malaria. In 1816, Giovanni Rasori (1766-1837) of Parma suggested microorganism as a cause for the disease. Later, in 1847, a German physician, Heinrich Meckel, identified round, spindle-shaped or ovoid structures containing black pigment granules in protoplasmic masses in the microscopic slides of blood from a patient with fever and observed similar entities in the spleen of an insane person during the autopsy. In 1848 Schutz observed these pigments in the internal organs of patient who had died of malaria. Soon afterwards, Virchow (1849) observed these pigmented bodies in the blood of a patient who had died from chronic malaria and specifically associated it with malaria. Finally, Charles Louis Alphonse Laveran in 1888 named a living organism as Oscillaria malariae and suggests it as the malaria parasite. In 1885 Camillo Golgi, established that there were at least two forms of the disease, one with tertian periodicity (fever every other day) and one with quartan periodicity (fever every third day). He demonstrated that the rupture of shizoints and release of merozoites into the blood stream coincided with the fever and correlated the severity of symptoms with parasite load in the blood. In 1906, Nobel Prize was awarded in Medicine for his discoveries in neurophysiology. In 1897, the sexual cycle of malaria parasite was demonstrated by Dr. McCallum, William G and Opie of Johns Hopkins Hospital. In the same year, Ronald Ross demonstrated the presence of oocysts in the midgut of female anopheline mosquito and soon afterwards, he (1898) demonstrated the sporozoites infection in salivary glands of the mosquito and also carried out transmission of malaria in birds with an infected mosquito. He was awarded the Nobel Prize in 1902 for establishing the fact that infected mosquitoes are respons ible for transmission of malaria. In 1907, Charles Louis Alphonse Laveran, was awarded the Nobel Prize for Medicine and Physiology for his discovery of the malarial parasite and other significant contribution to parasitology. In 1975 William Trager cultured P. falciparum in a medium of red blood cells. In 1987, a Colombian biochemist named Dr. Manuel Elkin Patarroyo developed the first synthetic Spf66 vaccine for P. falciparum infection. In 2002, the genome of parasite Plasmodium falciparum and the vector Anopheles gambiae were successfully sequenced. 1.3 Public and Global Health Burden Malaria is one of the oldest infectious diseases known to mankind. Malaria influenced outcomes of many wars and fates of many kings would have been different. It has competently forced many military defeats and responsible for decline of nations, often caused casualties more than the weapons could have. For centuries it has been responsible in preventing economic development in various regions of the earth. Malaria occurred in more than 100 countries and affects more than 2400 million people in the tropics, from South America to the Indian peninsula. Human malaria in tropical and subtropical areas accounts approximately 40% of the world at risk for the disease. The cause of this distribution in tropics is because of ideal breeding and living conditions for the anopheles mosquito. About 300 million to 500 million people suffer from malaria annually. Most lethal form of malaria infection is focused in the African continent, especially among children under five. In total, sub- Saharan A frica show most (90%) of the malarial cases and two thirds of the remaining 10% cases occur in six countries- India, Sri Lanka, Colombia, Vietnam, Brazil and Solomon Islands (Figure 1.1). WHO forecasts a 16% augmentation in malaria cases annually and about 1.5 million to 3 million deaths due to malaria every year (85% of these occur in Africa), accounting for about 4-5% of all moartality in the world. One child dies every 20 sec. due to malaria somewhere in Africa and there is one malarial death every 12 sec somewhere in the world. 50 million peoples have died of malaria. Among the major infectious diseases, malaria ranks third in cause of martality- after pneumococcal acute respiratory infections and tuberculosis (WHO., 2005). A brief account stated that ~ 30000 visitors who visited endemic countries developed malaria; where as 1% may succumb to the disease. Malaria can be accounted for 2.6 % of the worlds overall burden of diseases, thus raising expectations that it can climb to n umber one of the highest killer infectious diseases by the end of the century. Total global estimates of the annual expenditure (in 1995) showed a whooping US$ 2 billion directed towards malaria. World Health Organization reported it as a re-emerging infectious disease, and specify as infectious killer and number 1 priority tropical disease (WHO., 2005). The recent WHO World Malaria Report registers a global impact of approximately 225 million new clinical malaria infections associated with 781,000 deaths (WHO., 2010). Particularly, in the tropical countries, malaria is a health problem that setbacks social and economical developments. Malaria is commonly associated with poverty, and represents a major burden to economic and social development, costing an estimated sum of greater than US$ 6 billion for the year 2010 (Sachs. J and Malaney. P, 2002; WHO., 2010). Early diagnosis and prompt treatment are two basic elements in easing the impact of malaria. While progress in these areas h as been remarkable, the emerging insecticide resistant vectors, population movements, environmental disturbances, disintegrative health services and wide spread antimalarial drug resistance have constrained this mission. In early 60s, under the guidance of the Figure 1.1 Global distribution of malaria. (Reprinted from Nat Rev Microbiol.) (Bell et al., 2006) World Health Organization, malaria was nearly eradicated from most parts of the world owing to well planned anti malarial campaigns over the world. However, soon after, a resurgence of malaria took place in 1970s, which could be due to several reasons described below. Man made complacency and laxity in anti malarial campaigns; conflicts and wars; migrations; deteriorating health systems; poverty Drug resistance in parasite Insecticide resistance in vector and ban on use of DDT Environment global warming causing increased breeding and life span of the vector Jet age shrinking world spread of malaria from endemic areas to all other parts of the world. 1.4 Life Cycle of Malaria PARASITE The complex life cycle of malaria parasite involves two hosts; an insect vector (anopheles mosquito) and a vertebrate host (human). In search of a blood meal, a malaria-infected female Anopheles mosquito inoculates the infectious sporozoites into the human host. The malaria infection begins as these viable sporozoites invade liver cells and develop into mature schizonts, which in turn rupture and release invasive merozoites into blood stream. In P. vivax and P. ovale an arrested phase [hypnozoites] can remain dormant in the liver and re-invade the bloodstream after weeks, or even years later and cause infection, this delayed primary blood infection is termed as relapse. The initial asexual replication in liver is termed as exo-erythrocytic schizogony. In the normal developing exo-erythrocytic schizont, the cytoplasm of the parasite becomes subdivided and the ensuing invasive merozoites develop. These emergent merozoites are then released upon rupture of the mature schizont and invade the erythrocyte. The parasites undergo asexual multiplication in the erythrocyte, termed as erythrocytic schizogony. Redifferentiation of intra-erythrocytic merozoites into the feeding trophozoites occurs then. The ring stage Figure 1.2 Life cycle of malaria parasite (Plasmodium falciparum) trophozoites mature into schizonts and when rupture releasing merozoites to begin another cycle of red blood cell infection. However, the majority of merozoites entering an erythrocyte will develop into asexual schizonts, a small fraction can develop into the first sexual stage of life cycle (gametocytes). The rupture of mature schizont also releases the metabolic debris, which is toxic to the host and play a role in stimulating the clinical manifestations of the disease. The female anopheles mosquito must take blood meals on regular basis to support the development of eggs in successive batches. When biting malaria infected vertebrate host, she will take up infected erythrocyte and the gametocytes. Both female (macrogametocytes) and male (microgametocytes) are ingested by female anopheles mosquito during a blood meal. The asexual division of parasites in the mosquito is termed as sporogonic cycle. While in the mosquitos gut gametocytes are triggered by the fall in temperature and begin the formation of gametes. The microgamete penetrates the macrogamete generating zygote. Soon after the zygotes become motile and elongated structure termed as ookinetes, which invade the midgut wall of the mosquito where they develop into oocysts. The sporozoites emerge from ruptured oocysts make their way to reside in the mosquito salivary glands. Inoculation of these viable sporozoites into a new human host to maintain the malaria life cycle (Figure 1.2) (Bannister, Mitchell, 2003). 1.5 THE PLASMODIUM GENOME SEQUENCE The genome sequences of six Plasmodium species have now been published. The complete sequences of the P.falciparum 3D7 strain and the rodent malaria P.y. yoelii 17XNL clone (Carlton et al., 2002; Gardner et al., 2002) appeared in 2002 and the genomic data of two more rodent malaria species, the P.berghei ANKA clone and P. chabaudi AS clone, were published in 2005 (Hall et al., 2005). Recently, the genome sequences of the human malaria P.vivax Salvador 1 strain and the human/simian malaria P.knowlesi H strain, along with a comparative analysis with P.falciparum, were released (Carlton et al., 2008; Pain et al., 2008). Thus, this genus has the highest number of sequenced species of any eukaryotic organism yet (Birkholtz et al., 2008). Comparative analysis of the publicly of the available Plasmodium genomes revealed that they are all haploid with a standard size of 23-27 Mb, which is distributed among 14 linear chromosomes between 0.5-3.0 Mb in size. The base composition varies among the different species, with the rodent and P.falciparum genomes being extremely A+T rich (80.6% on average and close to 90% in introns and intergenic regions in P.falciparum) in contrast with the more G+C rich P.knowlesi and P.vivax genomes (37.5% and 42.3% respectively) Each Plasmodium genome has in the order of 5000-6000 predicted genes, most of which (51%) contain at least one intron and ~60% are orthologus among the different species (Hall, Carlton, 2005; Hall et al., 2005). The difference in gene number is the result of the differential gene expansion in distinct lineages and the presence of large variant gene families that are involved with antigenic variation (Hall, Carlton, 2005). The unique genes of the different species are o ften localised within the subtelomeric regions and code for immunodominant antigens (Hall, Carlton, 2005). The mean gene length of the three sequenced human malarias (including P. knowlesi) is~ 2.2 to 2.3 kb, compared to the average of 1.3 to 1.6 kb in other organisms (Gardner et al., 2002). The reason for these long gene lengths is not known and this is compounded by the fact that these long genes usually encode hypothetical proteins with unknown function (Gardner et al., 2002). Gene-mapping studies of conserved genes have shown that gene location, order and even exon-intron boundaries have been preserved over large regions across the three sequenced rodent Plasmodium species and P.falciparum(Hall, Carlton, 2005). In addition to the nuclear genome , the parasites also have a liner mitochondrial genome of ~6 kb in the case of P.falciparum , which is smallest mitochondrial genome known (Painter et al., 2007) and a ~35 kb circular apicoplast genome (Gardner et al., 2002). The P.falciparum nuclear genome exhibits minimal redundancy in transfer RNA (tRNA) and encodes 43 tRNAs (Gardner et al., 2002) compared to the ~30 of Homo sapiens (Strachan T and Read A, 1998). The parasite tRNA bind all 64 possible codons except TGT and TGC that both specify cysteine (Cys). As no other codons specify Cys, it is possible that these tRNA genes are located within the currently unsequenced regions , since Cys is incorporated into P.falciparum proteins (Gardner et al., 2002). The small P.falciparum mitochondrial genome does not encode any tRNAs (Vaidya et al., 1989) compared to the 22 tRNA of the circular 16.6 kb human mitochondrial genome (Anderson et al., 1981). The P.falciparum mitochondrion therefore imports tRN As from the cytoplasm , whereas the apicoplast genome encodes sufficient tRNAs for protein synthesis within the organelle (Wilson et al., 1996). The P.falciparum genome does not contain tandemly repeated ribosomal RNA (rRNA) gene clusters as seen in many other eukaryotes, but it contains individual 18S-5.8S-28S rRNA units at loci on seven of the chromosomes(Gardner et al., 2002). The sequence of the particular rRNA genes is distinct in the different units and the expression of each unit is developmentally regulated, depending on the stages of the parasite life cycle It is anticipated that by transcribing different rRNAs at different life stages, the parasite could change its ribosomal properties and the translation rate of all or specific messenger RNA (mRNA), which could alter the cell growth rate or cell development pattern. Previously , the rRNA expressed in the mosquito was described as S(sexual)-type and that expressed in the human host as A (asexual) type(Gardner et al., 2002). Parasite rRNA is also species-specific and can be assessed for diagnostic purposes (Singh et al., 2004). More than 60% of the predicted 5268 ope n reading frames (ORFs) of P.falciparum have no sequence similarity to genes from other sequenced organisms (Gardner et al., 2002). The absence of sequence similarity complicates characterization of the unknown ORFs, but might hold the answer to finding selective drug targets (Bozdech et al., 2003). There is currently a dedicated initiative aimed at improving the annotation status of P.falciparum led by the Plasmodium database, PlasmoDB (www.plasmodb.org). 1.6 Malaria Incidence in Different States of India The malariometric index evaluated as annual parasite incidence (API) indicates the number of malaria cases per thousand of population. As per the National Vector Borne Disease Control Programme (NVBDCP) incidence records, in most part of India, the API was 5 API were scattered in the states of Gujarat, Goa, Rajasthan, Madhya Pradesh, Chhattisgarh, Jharkhand, Orissa, the northeastern states and Karnataka (Kumar A et al., 2007). The proportion of occurrence of P. falciparum and P. vivax differs in various parts of India. Most of the indo-gangatic plains, northwestern India, northern hilly states, and southern state like Tamil Nadu have > 90% P. vivax infections, and the rest are P. falciparum. This situation is reversed in forested areas inhabited by ethnic tribes, where the proportion of P. falciparum is 30-90%. In the remaining areas P. falciparum prevail between 10% and 30%. Although Orissa has a population of 36.7 million (3.5%), it contributed most (25%) of a total of 1.5-2 milli on reported annual malaria cases, 39.5% of total P. falciparum malaria, and 30% of deaths caused by malaria in India (Source NVBDCP, India). Similarly, in the other states, forest ecosystems inhabited by ethnic tribes lives mainly in Figure 1.3 Prevalance of Plasmodium falciparum in India meso to hyperendemic conditions of malaria, where the preponderance of P. falciparum exist upto the extent of 90% or even more (Kumar et al., 2007) (Figure 1.3). 1.7 MALARIA Control and Prevention A global strategy for malaria control was developed by W.H.O. in a ministerial conference at Amsterdam, held in October 1992. The strategy broadly suggests emphasis on diagnosis and treatment in place of earlier trend of emphasis on vector control as a strategy for malaria control. The salient aspects of this strategy were early diagnosis and treatment; prevention of malarial deaths; promotion of personal protection measures like use of ITMs; forecasting, early detection and control of malaria epidemics; monitoring, evaluation and integration of activity in primary health centres; and operational research in field sites. Malaria prevention was classified at the level of personal protection, the prophylaxis and the malaria vaccines. Protective measures adopted at individual level and at family level not only help in protection of the individual against mosquito bites but also prevents spread of malaria in locality. These measures indirectly helped in reducing the mosquito population b y denying the blood meal which is an essential for nourishment of the mosquito eggs in the female anopheles. Protection measures at personal level against mosquitoes includes: Prevention of mosquitoes from entering the house, protection from mosquito bites and prohibiting the mosquitoes from resting inside house. All these prevention activities need the following; i. Protective Clothing ii. Mosquito Repellents iii. Insecticide vaporizers iv. Mosquito nets v. Air conditioning The absence of vaccines necessitates the use of drugs against malaria. All visitors from non-endemic area to a malarious area should have presumptive antimalarial drugs which offer protection against clinical attacks of malaria in that particular malaria endemic area (www.who.int/malaria). The practice of anti-malarial drugs to prevent the development of malaria is known as chemoprophylaxis. The choice of chemoprophylaxis differs depending on the species and drug resistance prevalence in a country. It must be remembered that no chemoprophylaxis regime provides 100% protection. Therefore it is essential to have personal protection from mosquito bites as well as to practice the chemoprophylaxis. Drugs used for chemoprophylaxis include: chloroquine, sulfadoxine, pyrimethamine, atovaquone plus proguanil, proguanil, halofantrine, doxycycline and mefloquin (www.ncbi.nlm.nih.gov/antimalarialdrug.html). The effective way to control any infectious disease is indeed to have a safe and effective vaccine, but even after decades of malaria research, an effective malaria vaccine is still elusive. The major culprit in not having an effective malaria vaccine is complex life cycle of the parasite which involves vector mosquitoes and human. In turn, parasites allelic diversity and antigenic variations make the development and implementation of effective malaria control intervention more problematic. In the present scenario of increasing resistance against antimalarials by parasite and the insecticide resistance shown by the anopheles mosquito, it is evident that an intervention at multiple stages of life cycle will be an appropriate way of combating malaria. Malaria vaccines for different stages of life cycle will therefore play a major role in future malaria interventions. Evaluation of new malaria vaccine candidates in malaria endemic countries is required. The present situation demands suf ficient sites in malaria endemic countries for testing potential malaria vaccines in future. 1.8 Antimalarial drug resistance One of the major control strategies against malaria is prompt treatment of malaria patients with effective antimalarial drugs; however one of the major challenges in the battle against malaria in recent years is the development of drug resistance in the malaria parasites. A continuous research and monitoring is crucial when trying to control and diminish this development. Antimalarial drug resistance in the malaria parasite, both in vitro and in vivo has been related to changes at molecular level in the malaria parasite (P. falciparum and P. vivax).

Revenge and Downfall Essay -- essays research papers

Yasmin Nunez   Ã‚  Ã‚  Ã‚  Ã‚  In Shakespeare’s Hamlet, it is the desire for revenge that lies behind the motives of young Hamlet. His moral struggle towards revenge becomes an obsession leading to a change in character. His actions strongly imply that madness has overcome him. However, there are hints present in the text that implies his madness was feigned in order to achieve his revenge.   Ã‚  Ã‚  Ã‚  Ã‚  Immediately following the appearance of old King Hamlet’s ghost, Hamlet warns Horatio that he may act mad, which foreshadows a change in Hamlet’s character. The reader is prepared that any abnormal acts may be a result from Hamlet’s acting. As the play continues, more questions are raised that involve his sanity.   Ã‚  Ã‚  Ã‚  Ã‚  Ophelia, who was the first to witness his madness, offered an insight as she described Hamlet’s actions to her father. Hamlet, who was described as being mad, was speechless and only stared into Ophelia’s eyes. The bizarre actions of Hamlet are presumed to be an act, but the strong visualization of the scene can create doubt in a reader’s mind. If Hamlet was feigning his madness, then why would he want to frighten his girlfriend that he cared for so much?   Ã‚  Ã‚  Ã‚  Ã‚  As more events led to the questioning of Hamlet’s sanity, the reader was given a glimpse into the mind of Hamlet in the famous â€Å"To be or not to be† soliloquy. Hamlet’s questions of life and contemplation of suicide revealed h...

Contract Formation

Part A Contracts are an integral part of business and everyday life, and are fundamental to construction as the industry relies on the formation of contracts for business agreements. â€Å"Contracts are based on the idea of a bargain, where each side must put something into the bargain. A contract may be defined as ‘an agreement which is binding on the parties’† (Galbraith, 1998, pg78). There are a number of key components which must be present in the formation of such contracts. Firstly, there needs to be an initial offer made by one party for the formation to begin. An offer exists when one party effectively declares his readiness to be bound by a set of terms without any further negotiation† (Galbraith, 1998, pg79). It is interesting to note also that there is generally no requirement that the offer be made in any particular form, it may be made orally, in writing or by conduct (McKendrick, 2007, pg33). The exception to this is with speciality contracts s uch as the sale of land or estates or when deeds are formed between parties giving them twelve years liability instead of the six on simple contracts, and are frequently used within construction (Owen, 1998, pg47).However there is a fine line between what constitutes an offer, and an invitation to treat. â€Å"An invitation to treat is simply an expression of willingness to enter into negotiations which will lead to the conclusion of a contract at a later date† (McKendrick, 2007, pg33). There is much confusion between the two, as shown in the cases of Gibson v. Manchester City Council [1978] and Pharmaceutical Society of Great Britain v Boots Cash Chemists (Southern) Ltd [1953].An example of an invitation to treat in construction is the tendering process, in which the employer will invite contractors to make an offer based on the project information, which the employer can then choose to accept to form a binding contract. In terms of the enforcement of contract law, when case s are examined McKendrick (2007, pg32) states â€Å"the courts adopt the ‘mirror image' rule of contractual formation, that is to say they must find a clear offer which is matched by an equally clear acceptance†.Acceptance is also defined as â€Å"an unqualified expression of assent to the terms proposed by the offeror† (McKendrick, 2007, pg43). Therefore a contract can only be legally binding if the offer includes clear terms and is declared to the offeree, with communication of a clear and firm acceptance to be bound by these terms given back to the offeror. These two factors combined culminate in the agreement of the contract. However contract formation is rarely simple, and often the offeree will wish to introduce their own terms to the agreement as part of the negotiations, communicating this back to the offeror.This is known as a counter offer. Galbraith (1998, pg80) points out that â€Å"the offer – counter offer situation arises frequently in busi ness where each side in the negotiations may be trying to make the contract on the basis of their own ‘pro forma' standard documents. This gives rise to what us known as battle of the forms† The battle of the forms scenario succinctly defines the rules of offer and acceptance, in that any counter offer destroys the original offer making it irretrievable, with agreement of contract resulting when the last offer is accepted by the offeree.An example of this is evident in the case of Butler Machine Tool Ltd v Ex-Cell-O Corp [1979]. It is also important that there is an element of certainty to the terms of the contract, with the parties expressing their agreement in a form sufficiently certain for the courts to enforce (McKendrick, 2007, pg57). If there is an element of vagueness in the terms of the contract, it could be judged there is no valid contract at all, an example being the vague use of the term ‘hire-purchase' in the case Scammell v Ousten [1941].However if t he parties have contracted with each other previously, it could be deemed as stated by Owen ( 1998, pg55) â€Å"a previous course of dealings will control some of the matters not expressly agreed in the present case, e. g. the amount of pay which could be the same as that paid on a prior occasion†. One particular problem in construction is the ‘letter of intent', widely used between employers and contractors as a form of pre-contract agreement. Following on from the tendering negotiations, Adriaanse (2010, pg55) writes â€Å"the purpose of a letter of intent is to express an intention to enter into a contract at a future date†.These are the result of failing to negotiate on certain terms in time for the project start date, and are introduced to allow the commencement of work, keeping within the projects' completion target. As these are often not legally binding contracts they cause disputes in the future if one of the parties does not carry out their duties, as i n British Steel Corporation v. Cleveland Bridge & Engineering Co. Ltd (1981). Owen ( 1998, pg50) writes that â€Å"all simple contracts must have consideration given by each party to the other as the price of each other's promises.It may take the form of money, goods, services, promises not to sue etc. † For example party A must receive something from party B, in return for party A providing something to party B. However McKendrick (2007, pg88) states that â€Å"consideration must be sufficient but does not need to be adequate†, meaning for example something must be offered to the other party in return to satisfy the rules of consideration, but does not need to be of an equal value as shown in the cases Chappell & Co Ltd v Nestle Co Ltd [1960] and Thomas v Thomas [1842].Consideration given also cannot be past, stated by Owen ( ) in that â€Å"you cannot make a contract in which one person promises to do something for another in exchange for a consideration which has a lready been performed†. This is clear in the cases of Lampleigh v Brathwait [1615] and Roscorla v Thomas [1842].Consideration is of huge importance in the construction industry, as Adriaanse writes this is due to â€Å"a number of factors such as the length of the contractual chain stretching beyond the parties to their subcontractors and suppliers, as well as the system of competitive bidding meaning one party may under-price the cost of the work, raising the possibility that one party may wish to renegotiate the agreement†. This can lead to the question of whether consideration was given when the contract was formed and whether the party is legally entitled to expect renegotiation to occur.However even when consideration has been given by parties and agreement reached this does not mean there is an enforceable contract in place. For a contract to be valid there must also be present the intention of all parties to enter legal relations with one another. Galbraith (1998 , pg91) explains there are two categories, â€Å"commercial arrangements where the parties are presumed to have intended to create a contract, and family, domestic and social arrangements where they are presumed to have not†.In the field of construction only the former is relevant, where the courts would initially look at a case between the parties and presume an intention to enter a contract exists. Conflict can occur when one of the parties seeks to rebut the presumption, in which the party will need to show evidence no contract was intended. An example of such a rebuttal is the case of Rose and Frank Co. v. Compton Bros where it was indicated the written document drawn up was merely a ‘gentleman's agreement' and not a legally binding contract (Galbraith, 1998, pg92). The legal capacity of the parties to enter into a binding agreement also must be present.Minors under the age of 18, and the mentally incapacitated are not able to enter into contracts to protect them fr om their own inability or inexperience (McKendrick, 2007, pg348). Companies are deemed to have full capacity to enter into legal contracts and are not restricted in any way. In conclusion, in order for the formation of a legally binding contract to occur there must be an offer from a party which is followed by acceptance from another party. Certainty must exist within the terms of the agreement, and due consideration must be given by both parties for the price of the promises received.The intentions of all parties to enter into legal relations must be present, as well as the capacity to qualify as valid party to the agreement. Part B a. ) When determining if there is a legal contract agreed between two parties there needs to be examination of whether the key elements of contract formation have been satisfied. In the case of Caroline v. A. W Electrical, the question is if at any point an offer was accepted and therefore a contract agreed between the two parties on the terms given. Wh en A. W Electrical placed the advertisement in the newspaper for the ZR250 Smart Television at ? 80 via mail order, this is a clear invitation to treat and should not be classed as an offer. As discussed in part A, an invitation to treat is where a party will indicate they wish to enter into negotiations which may lead to receiving an offer and an agreement if they choose to accept. Advertisements are a prime example of an invitation to treat as they are an indication of what goods or services that party may be willing to negotiate over, with the price of ? 480 an estimate to invite offers. Subsequently when Caroline saw the advertisement and sent in a cheque for the ? 80, this equates to an offer being made to A. W Electrical. As Galbraith (1998, pg79) states â€Å"an offer exists when one party effectively declares his/(her) readiness to be bound by a set of terms without any further negotiation†. Caroline has effectively done this by sending the cheque for the amount on th e advertisement, the terms being if she gives ? 480, A. W Electrical will send the item without any further negotiation if they accept Caroline's offer. Due to the nature of the terms, A. W Electrical will be judged to have accepted if they go ahead and send Caroline the ZR250 Smart Television.As explained in part A above, there needs to be communication of a clear and firm acceptance to be bound by these terms given back to the offeror. This will be deemed to be communicating via accepting by conduct, in which their actions equates to acceptance of the terms. However instead of sending Caroline the ZR250 model, A. W Electrical sent a ZR200 and a letter the following day with a cheque for ? 80 explaining the ZR250 was not available and unless Caroline returned the item within two weeks they would assume she was satisfied with the deal. A.W Electrical have not accepted Caroline's offer, but introduced a counter offer which is binding to their terms and not Caroline's. As explained by McKendrick (2007, pg43) â€Å"a purported acceptance which does not accept all the terms and conditions proposed by the offeror but which in fact introduces new terms is not acceptance but a counter-offer, which is then treated as a new offer which is capable of acceptance or rejection†. Due to not being able to reply as she was departing on a two week holiday, upon her return Caroline returned the item with a note explaining it was not what she ordered, however A.W Electrical refused to accept the item or provide any further refund as she had not returned the item within two weeks. This raises the question whether Caroline did actually accept the offer by not returning the item within two weeks. For this to be enforceable, the law of contract needs to govern that acceptance by silence is a valid form of coming to agreement. Galbraith states (1998, pg82) â€Å"the rule that acceptance must be communicated means that silence cannot usually amount to acceptance† This ma y mean that in the context of this case, Caroline did not accept the offer made by A. W Electrical and therefore is not bound by the terms.However, full clarity on the matter can be taken from a case law example of Felthouse v. Bindley [1862], where it was judged accepting by silence cannot equal a clear communication of acceptance, unless it is totally clear the offeree intended to do so. In Caroline's case, it is most definitely not clear she wished to accept, due to A. W Electrical not providing the item she requested on the terms given in her original offer. Therefore, there was no contract formed between the two parties as at no point an offer was accepted, rendering the contract void and no terms binding on either party. . ) If however we were to assume a contract was formed between Caroline and A. W Electrical at the point the two week period elapsed, there would be terms binding and these can be separated into two types, express terms and implied terms. McKendrick (2007, pg1 84) explains that â€Å"express terms are the terms agreed specifically by the contracting parties and implied terms are those not specifically agreed but which are implied into the contract by the courts or by Parliament†. The express terms of Caroline’s contract included the price being ? 00 for a ZR200 television given that she sent a cheque initially for ? 480 with an ? 80 cheque sent to Caroline with the item, and that A. W Electrical reserve the right to repair or replace the goods at its discretion if any dispute over the quality of goods were to arise. The implied terms of the contract will include elements of the Sale of Goods Act 1979, which will enforce A. W Electrical to adhere to certain conditions relating to the quality of goods and defects, and the description of the goods sold. S. 4(2) of the Act states there is an implied condition that goods supplied under the contract are of satisfactory quality. This is clearly contradicting the express term made b y A. W Electrical regarding the right to repair or replace the goods, however in order to protect consumers rights the Unfair Contract Terms Act 1977 means that implied terms cannot be excluded in contracts with consumers (McKendrick, 2007, pg205). Therefore the express term is not valid in the contract, and A. W Electrical have broken this implied term by stating this.Furthermore the Sale of Goods Act 1979 s. 13(1) states an implied condition that goods sold by description shall correspond with the description. The advertisement was for a ‘smart’ television however the item provided to Caroline did not possess any ‘smart’ features, therefore this term has been broken due to the item not matching the description advertised. In relation to the right to return the item, when Caroline sent this back to A. W Electrical they refused to accept stating the two week period has passed.We are assuming the contract came in effect and was accepted by Caroline’s silence at the end of this period however the Consumer Protection (Distance Selling) Regulations 2000 s. 10 and s. 11(1-2) explains she has the right to a seven day cancellation period starting from the date the contract was concluded, expiring seven days later. This is another implied term of the contract A. W Electrical have broken in refusing to accept the returned goods. c. ) There are remedies available to Caroline in order to resolve the fact A. W Electrical have broken the terms of the contract.The main issue to her is she is not able to return the television either in exchange for the model she asked for, or for a full refund. This breach of contract is likely to be classed as a breach of warranty, where a warranty is a term in the agreement not fundamental to its existence and therefore the contract cannot simply be terminated due to the breach. However Caroline could recruit the services of a lawyer or solicitor to take legal action against A. W Electrical in the form of a specific performance order, which will require A.W Electrical to perform their primary obligations under the contract (McKendrick, 2007, pg451). This would enforce the implied term from the Consumer Protection (Distance Selling) Regulations 2000. Caroline could also contact the Office of Fair Trading to make a complaint, which could lead to an application to the courts for an injunction against A. W Electrical, ultimately resulting in the same effect of enforcing the contract (Office of Fair Trading, 2012). Bibliography Reference list Adriaanse, J. (2010). Construction Contract Law (3rd ed. Basingstoke: Palgrave Macmillan. Davenport, A. , Galbraith, A,. Stockdale, M. , Wilson, S. (1998). Galbraith’s Building & Land Management Law For Students (4th ed. ) Oxford : Butterworth-Heinemann 1998. McKendrick, E. (2007). Contract Law (7th ed. ) Basingstoke : Palgrave Macmillan 2007. Office of Fair Trading. (2012). Relevant Legislation – The Office of Fair Trading. Retrieved 28 November 2012, from http://www. oft. gov. uk/about-the-oft/legal-powers/legal/#. ULY4v8UTDwM. Owen, S. (1998). Law For The Construction Industry (2nd ed. ) Harlow : Longman 1998. Cases Gibson v.Manchester City Council [1978]. Pharmaceutical Society of Great Britain v Boots Cash Chemists (Southern) Ltd [1953]. Butler Machine Tool Ltd v Ex-Cell-O Corp [1979]. Scammell v Ousten [1941]. British Steel Corporation v. Cleveland Bridge & Engineering Co. Ltd (1981). Chappell & Co Ltd v Nestle Co Ltd [1960]. Thomas v Thomas [1842]. Lampleigh v Brathwait [1615]. Roscorla v Thomas [1842]. Rose and Frank Co. v. Compton Bros [1925]. Felthouse v. Bindley [1862]. Statutes Sale of Goods Act 1979 Unfair Contract Terms Act 1977 Consumer Protection (Distance Selling) Regulations 2000

Henry V Free Essay Example, 1500 words

War and Conflict Wars have their own deep realities which are characterized by individual interests, Kingdom policies, and conspiracies. The complexities of war are well explained in several historical and literary texts which aim to bring the lesser known realities into spotlight. The concept of war and conflict is thematically expressed in Henry V where the previously rash prince claims the throne after the death of father in a chaotic environment. As Henry V assumes the responsibilities of a King, further issues await him including rebuilding the trust of his people and settling disagreements with his neighbors. As he declares war with France, Henry V finds himself in the midst of conspiracies where his enemies try to ensure his absolute defeat against the French. The whole play excellently represents the environment in which wars occur and the realities behind wars including conspiracies, interests of individuals and kingdoms, and so on. As Man realizes, the realities of war are actually far from what it seems from a distance. As armies celebrate their victories and historians praise leaders, the reality is that most wars are marked by indifferent brutalities which often go unreported or ignored. We will write a custom essay sample on Henry V or any topic specifically for you Only $17.96 $11.86/pageorder now War settings have also been very well explained in the poetry Dulce et Decorum Est by Wilfred Owen who explains the conditions in which World War I was fought and how the war impacted millions of lives as they struggled between death and life. Wartimes are often symbolized by unjust and forced recruitment of civilians into the armed forces and The Conscript by Wilfred Gibson reflects the period of war where this process occurred and how these conscripts were involuntarily pushed to the threats of war. The plot of Henry V, written by William Shakespeare, addresses a very central issue of power, politics, and war in 15th century England. The story is set in a time when England was going through severe political upheaval as a result of power struggle and civil wars. Henry IV had just died and following his death, the young prince Henry V had claimed the throne to become the king. In between several harsh civil wars, the people of England are left distr essed and dissatisfied with the regime. In an attempt to build trust with his people, Henry V tries to come to terms with his rash past which he spent with a bad company of thieves and alcoholics. Amidst all these attempts, Henry V also has to attend to several of his responsibilities as a King where he has to decide about his relations with his neighbors, particularly France.