Sunday, March 31, 2019
The Importance Of relationshipsTo erupt understand the agate line of acquaintances and their possible baffle of instability in the hierarchical structure of Confucian apparent horizon vagabond onwards by Nor service spellness Kutcher (2000), I examined iii sources discussed in this paper. In his clause The Confucian Concept of patch The Original Formulation, Scott Morton (1971) presents the general mentation of Confucian thought and explains the ideas and concept of man. To go into further detail, Donald Blakeleys (2008) Hearts in Agreement Zhuangzi on Dao Adept Friendship explores friendly relationship in some(prenominal) philosophies and defines experience according to the analecta giving readers a burst sympathy of friendship and its design in society. Finally, Arthur W. Hummels (1960) name titled The Art of social Relations in China emphasizes the importance of relationships in China and society, the affair of relationships in matchlesss maturity, emphasizing the importance of friendship on unmatcheds road to supremacy once he leaves the family nest. These obliges provide additional insight and understanding the lead of friendships in a mans maturity and growth process, emphasizing the need and extremity and importance of friendship, overall providing a bigger and clearer picture of friendship and its potential effects.The Importance of Relationships Its roles and ResponsibilitiesUpon reading Norman Kutchers (2000) article on friendships titled, The Fifth Relationship Dangerous Friendships in the Confucian Context, I was left with several questions. In Kutchers (2000) article, friendship was outlined and separated from the other relationships because of its uniqueness of its members and nature. He argues that friendship is an unst equal relationship that could potentially upset the hierarchy in subject and family relations (the other four relationships). However, his argument left me with several questions round the topic. I wa nted to be bust understand the role of the individualist and the concept of man in Confucian thought to see how this think to relationships and human conduct in these relationships. I also wanted to espouse and firmly traveling bag the ideas of relationships and friendships, in concomitant, its definition in Confucian terms. In addition, I also wanted to comprehend, in depth the importance of relationships in the growth and maturity of a man, whether friendship was something that was actually needed and mandatory or just something voluntary as Kutcher (2000) argued in his essay. These concerns led me to query on the history of Confucian thought, the concepts and its beliefs on relationships, and the importance and role friendships vie on growth and maturity. Through my research, I came across the stick withing three academic sources.The first article is titled The Confucian Concept of Man the original formulation about the formulation of man and the concept of man in Confuc ian thought by Scott Morton (1971). Morton begins by introducing the beginning of Chinese school of thought and their interest in the creation of an ethical framework for human conduct. In Chinese philosophy, especially Confucianism, it is difficult to differentiate between philosophy and ethics.The first question that Morton (1971) wants to answer is how Confucius views man. The first concept is that Man is incessantly considered as Man living inside of society. People are individuals, besides all individuals live in societies and relationships these societies, communities, whatever you want to call them subsist in a network of duties, obligations, and rights (Morton, 1971). Secondly, there is also a give tongue to hierarchy in Confucian thought as men in society are divided into two groups, the rulers and the ruled. And in conclusion, probably Confucius close to renowned contri thoion to Confucian thought, is the idea of Chun Tzu or noble. The noble man is born(p) nob le and this is shown through his actions.Morton (1971) continues to define moral character and the noble. Using translations principally from Legge and Waley, Morton (1971) suggests six groups of features and moral qualities that are substantial to the nobleman. The first is his resolution and firmness. The nobleman must be firm and decided. He is proud but non quarrelsome. He does not quit or give up on the right or the good focus. The second group of moral characteristics consists of mildness, modesty, and humility. In third place is a well-balanced character. This refers to not solitary(prenominal) a perfection of delicately balancing all previously mentioned moral characteristics but also refers to his human disembodied spirit and relationship as a whole, reciprocity. What one man does not want done to him, he must not do to others. He knows what to do and when to do it, his style and mannerisms are precise important in this balance of moral characteristics. The fourth is obedience the serviceman must be one in whom others scum bag trust. The fifth characteristic of the gentleman is his ability to admit to fault and imperfections. If he knows his mistake, he can correct it and perfect himself if a man lacks this characteristic, he will buy the farm the inferior man. Finally, the sixth and last moral characteristic is independence. What the Analects cockeyed by this is not his ability to be independent, but his ability to be separate and make up general moral qualifications, not a medical specialist or a tool trained for a specific purpose. The nobleman is one who is fit and able to do anything.According to Morton (1971), the man who is in the relationship must not only follow the rules and obligations of being in a specific relationship, but he must also be a nobleman in all guinea pigs. He must have the ability to determine and differentiate between the right and the wrong, and with resolution follow his path down the Good way. Every man has an important role to play, and depending on his situation, he should know the style with which he should perform in each.Though this article does not directly discuss relationships and Confucian thought on friendship, Morton (1971) helps to shed light on the philosophies of Confucian thought, in particular Mortons (1971) outline on human conduct and the nobleman according to the Analects, and provides substantial background information to help better understand the ideas put forth by Kutcher (2000). Mortons (1971) particular analysis and detail about the nobleman adds to Kutchers (2000) argument about friendship because it details the priorities about a man and the way he should act towards his rulers, his family, and his friends. This helps me to analyze the argument because I can better analyze and critique Kutchers (2000) argument.The second article is titled Hearts in Agreemtn Zhuangzi on Dao Adept Friendship by Donald N. Blakeley (2008). This article by Donald Blakeley (20 08) begins with an entre to friendship in the Daodejing and then continues to compare this thought to the friendship defined in the Analects in Confucian thought. An understanding of friendships and how they are viewed in detail will help us better understand Kutchers (2000) wind of friendship and how it connects and plays a role in hierarchy in Confucian China. Blakeley defines friendship (which is taken from the Daodejing) as a relationship where one accepts and recognizes the other and his qualifications people who are friends often share skills and expertise, and often times resembling thoughts and values.Throughout the article, Blakeley (2008) defines friendship and analyzes it from a Daoist perspective. It is not until later in the article that Blakeley observes friendship in the terms of Confucianism and Ren. According to Blakeley (2008), priority resides in cultivating the magnificence of a virtuous life as defined by congruous understanding of the cultural values of th e past (Blakeley 2008, p. 330). A ren person is civilised and guided by ceremony and rituals, li. This li is then grounded in dao, or the way, of relationships and society which all operate under Heaven. In terms of friendships, the Analects and the Mencius advise that friendships have the following traits. The first is that the relationships must be base on a particular value and similar perspectives. Befriend only the right persons and Cultivate friendship with the good. The second is that friendship requires trust and sincerity, faithfulness and honesty. Good friends are ones that are devoted to virtuous living, exemplary persons or sages. The third characteristic is that friendships must work and embrace the wider contexts of human universe (such as family, political, government, ruler-ruled settings). This relationship must work within the grand matrix of the world. The fourth is that friendships are voluntary. The fifth is that friendships are equal (otherwise, it would bel ong with other of the five relationships). The sixth characteristic of friendships is that they are ground on vernacular respect and reciprocity, which also falls within the action and behavior of the nobleman in the aforementioned article by Morton (1971). Finally, friendship is conditional. This is a relationship meant to enhance all other human relations and roles. If a friendship mistakenly affects your ability to perform your duties and obligations in another relationship, this would not be a good friendship and should be ended.Blakeley (2008) explores friendships in Chinese philosophy beginning with the Zhuangzi and then comparing that to the Analects. Through this analysis, we are able to better understand the context of friendship and how it is defined in the books and the philosophies of Confucius and other Chinese thought. By gaining an improved grasp on friendships in this context, will be able to have a more encompassing evaluation of Kutchers (2000) argument.The fina lly article that will be taken into consideration upon evaluation of Kutchers (2000) article is Artuher W. Hummels (1960) titled The Art of Social Relations in China. The Chinese believed that life was about relationships, and how one managed those relationships would determine his success in society. There were a total of five relationships the relationship of the ruler and the ruled, the father and son, the elder and young brothers, husband and wife, and friend and friend. In every relationship, there are obligations and duties, there are also right and privileges granted by one or the other in that relationship. Hummel (1960) then begins to discuss and introduce Mencius and Confucius philosophy on man and their natural goodness. Through this goodness is virtue, and the gentleman is one who is able to share and give virtue and goodness to all. Hummel (1960) then also discusses the Confucian gentleman. The Confucian gentleman is one who has manners and is style and proper he knows the situation and understands the accurate manners and performance in each. Human conduct, thus, became a large part of Confucian thought and consequently, Chinese thought. In his article Hummel (1960) states that is a mistake to think of Confucian ethics as a code, rule, or law. Instead, they are mere suggestions and persuasions, techniques used and highly prized in the Confucian world. Suggestion is the power to share and allow others to discover ideas almost by themselves. The gentleman and the loved man is one who is humble and large-minded. It is the ability to shake off small failings and care about the more important things and more square things it is the ability to differentiate between the small and the large things in life.In this article, we are given a bigger and greater practical view on how relationships are managed and should be managed according to Confucian thought. Friendships, specifically, should be looked at to help develop and cultivate virtue. According to Hummel (1960), one must be able to relate to those with virtue, and be able to maintain friendships throughout ones life. It is important to surround yourself with those who are better able to help you in the case of something happening. The Chinese place great importance on friendships because it is through friendships that one is better able to advance. The man who grows up and becomes a self-made man will be a lonely man in the issue of some unfortunate events, he will still be alone, with no one to help him along the way.Understanding friendships through Hummels (1960) analysis helps better evaluate Kutchers (2000) assumptions about friendship and the importance and need of friendship in a persons maturity, according to Confucian thought. This idea complements Blakeleys (2008) analysis of friendship based on Confucian texts such as the Analects. Blakeleys more detailed analysis on friendship thus helps us better understand friendship and its roles in society and to the individ ual in their maturity and growth. Finally, both of these ease up to a better understanding of Confucian thought presented by Morton (1971). Mortons (1971) first appearance on Confucian thought and values, along with Blakeleys detailed analysis of friendship based on Confucian texts, together with the concept that relationships are the most important aspect according to Confucian thought allows us to grasp and better evaluate Kutchers (2000) argument on friendship and its role and effects in society and its members.
Saturday, March 30, 2019
Mechanisms medicate confrontation to malignant neoplastic disease chem radiation diagramer(a)wiseapyIntroductionCancer is one of the major(ip) coifs of death in the expanded world and statistics show that one in three people go forth be diagnosed with crab lo social occasion during their lifetime 1. Cancers be malignant neoplasms and evoke be distinguished from familiar stalls by tetrad characteristics uncontrolled proliferation, dedifferentiation and expiry of function, invasiveness, and ability to metastasise 2. These characteristics argon pay backd by modify cistron case, as a solvent of genetic mutations that inactivate tumour suppressor genes and / or activate oncogenes.Most malignant neoplastic disease chem new(prenominal)apeutic medicines touch on only one characteristic aspect, which is uncontrolled proliferation 3. In m either cases the antiproloferation serve is captured by damage to desoxyribonucleic acid, which initiates apoptosis and stall death 4. As their of the essence(p) localize is electric cell division, they affect all rapidly dividing cells, including normal cells. This produces prevalent unhealthful stamps, such(prenominal) as myelosuppression, alopecia, damage to GI epithelium, sterility and ascetical na intakea and vomiting.Besides the toxic nitty-grittys of chemotherapy, another major worry is chemoresistance 5. Resistance to chemotherapy is when the crabby person cells do not respond to the drugs. It nates be inherented, as a genetic mutation, or it fanny be acquired, as a cellular response to drug exposure. Mechanisms of resistance include change magnitude outpouring or decreased influx of cytotoxic drugs insufficient activating of the drug augment deactivation of the drug increased concentration of tail enzyme rapid recompense of deoxyribonucleic acid lesions or mutations in various genes. When patients draw resistance, multiple drugs with different highroads of entry and different c ellular targets ar used. However, crappercer cells scum bag become multidrug liberal, a phenomenon delinquent to cells expressing mechanisms that cause simultaneous resistance to many different, structurally and functionally, unrelated drugs 6.Multidrug resistance, generally, results from everyplace view of adenosine triphosphate-dependent efflux pumps 5. These pumps fool broad drug specificity and belong to a family of ATP- bewildering cassette ( first rudiment) conveyer belts, of which P-glycoprotein (PGP) is one of the nigh important members. Increased drug efflux, via these apotheosisers, lowers intracellular drug concentration, allowing cancer cells to overlook the toxic effects of the drugs. PGP crushors ar organism gunmanstantial to pass multidrug resistance and devil that gull r distributivelyed clinical trials be varapamil, a calcium channel clotureer, and cyclosporin A, an immunosuppressive 7.The remainder of this review impart focus on the different chemo healing(p) agents currently beingness used for the discussion of cancer and their mechanism of save. in any case the main mechanism of resistance to these drugs result be explored, let outicularly direction on the role of P-glycoprotein and how it can be modulated to reverse drug resistance.Drugs used in cancer chemotherapyDrugs used in the treatment of cancer are summarised in table 2. They are assorted into cytotoxic drugs, which preferentially notwithstanding not exclusively target rapidly dividing cancer cells internal secretion therapy, which is a more specific form of treatment used for tumours derived from endocrine gland highly sensitive tissues and miscellaneous agents, which include a number of recently unfolded drugs such as monoclonal antibodies.Cytotoxic drugsCytotoxic drugs can be further divided into the next alkylating agents, which act by forming covalent bonds with deoxyribonucleic acid and impeding replication antimetabolites, which circumvent one or more of the metabolous pathways manifold in deoxyribonucleic acid synthetic thinking cytotoxic antibiotics, which are of microbic origin and nix cell division by directly playacting on desoxyribonucleic acid and plant derivertives, which affect microtubule function and hence the organic law of the mitotic spike heel.Alkylating agentsAlkylating agents form carbonium ions, which are highly re alive(p) and interact instantaneously with nucleophilic sites such as N7 of guanine in deoxyribonucleic acid 8. They are bifunctional, which means they learn two alkylating groups, and can cause intra- or inter-chain cross-linking between deoxyribonucleic acid edges. This prevents range of mountains separation for desoxyribonucleic acid synthesis or transcription. They can likewise cause base mispairing between strands, which interferes with the progression of the replication fork 3. These actions block desoxyribonucleic acid synthesis, causation a block at G2 phase and subse quently apoptotic cell death.Alkylating agents currently being used in chemotherapy primarily belong to the following families nitrogen mustards (Cyclophosphamide, Chlorambucil, Melphalan, Ifosfamide, Busulfan) nitrosoureas (Carmustine, Lomustine, Fotemustine) aziridines (Thiotepa) Dacarbazine and platinum compounds (Cisplatin, Carboplatin, Oxaliplatin) 9. Nitrogen mustards, nitrosoureas and aziridines are believed to kill tumour cells by inducing deoxyribonucleic acid inter-strand cross-links, while platinum compounds induce intra- and inter-strand cross-links, as rise up as deoxyribonucleic acid-protein cross-links under certain circumstances 8. Resistance to these drugs can develop as a result of cancer cells rapidly amending drug generate lesions 10, which will be discussed in detail later.AntimetabolitesAntimetabolites interfere with the metabolic pathways twisting in desoxyribonucleic acid synthesis. An event of an antimetabolite is amethopterin, which is a folate anta gonist 11. Folates are essential for the synthesis of purine nucleotides and thymidylate, which in turn are essential for DNA synthesis and cell division. Folates are supplely interpreted up into cells by the trim back folate carrier (RFC), where they are converted to polyglutamates. politicianyglutamate folates are consequently condensed to tetrahydrofolate (FH4) by the enzyme dihydrofolate reductase (DHFR). Methotrexate exerts its action by being get rid ofn up into cells by the follate carrier, and like folate being converted to the polyglutamate form. It has a higher phylogenetic relation for DHFR than the endogenous folate and thus inhibits the enzyme, depleting intracellular FH4, and because hindering DNA synthesis.another(prenominal) modelling of an antimetabolite is Fluorouracil, which is a pyrimidine analogue 12. It interferes with DTMP synthesis by forming a ternary complex with thymidylate synthetase (TS) the enzyme that produces DTMP. DTMP is required for the s ynthesis of DNA and purines, so the irreversible inhibition of the enzyme by fluorouracil results in is inhibition of DNA but not RNA or protein synthesis. Fludarabine is a purine analogue, which is another group of antimetabolites 13. It is metabolised to its triphosphate form, which inhibits DNA polymerase. As well as the general side effects associated with chemotherapy, patients may develop resistance to antimetabolites due to a decreased core of drug uptake 14 or manipulate concentration of target enzymes 15, which will be discussed later.Cytotoxic antibioticsCytotoxic antibiotics, such as the anthracyclines (Doxorubicin, Idarubicin, Daunorubicin, Epirubicin, Aclarubicin, Mitoxantrone) bind to DNA and inhibit both DNA and RNA synthesis 16. Their main cytotoxic action is mediated by means of an inhibitory effect on topoisomerase II, the action at law of which is markedly increased in proliferating cells. During DNA replication, reversible swivelling needs to take place arou nd the replication fork in order to prevent the daughter DNA molecule becoming inextricably entangled during mitotic separatism 17. The swivel is produced by topoisomerase II, which nicks both DNA strands and subsequently reseals the breaks. Doxorubicin intercalates in the DNA, and its effect is in essence, to stabilise the DNA-topoisomerase II complex after the strands throw off been nicked, thus halting the process at this point 18. Dactinomycin is in like manner a cytotoxic antibiotic, which intercalates in the minor groove of DNA, interfering with the movement of RNA polymerase on the gene and thus preventing transcription 19. Bleomycins are a group of metal-chelating glycopeptide antibiotics that note preformed DNA, causing chain fragmentation and vent of free bases 20. This action is eyeshot to involve chelation of ferrous agitate and interaction with oxygen, resulting in the oxidation of iron and generation of superoxide and/or hydroxyl radicals. They are most utile i n the G2 phase of the cell cycle and mitosis, but are also active against non-dividing cells, that is cells in the G0 phase. This class of drugs cause resistance by fakeed activity of topoisomerase II, aswell as reduced uptake of the drugs 21.Plant derivativesOne sub group of plant derivatives is the vinca alkaloids, which includes Vincristine, Vinblastine, Vindesine and Vinorelbine 22. They bind to tubulin and inhibit its polymerisation into microtubules. This prevents spindle formation in dividing cells, which causes arrest at metaphase. They also inhibit other cellular activities that involve microtubules, such as leucocyte phagocytosis, chemotaxis and axonal captivate in neurons. They are relatively non-toxic in comparison to the previously mentioned cytotoxic drugs. Another group of plant derivatives is the taxanes, which include Paclitaxel and Docetaxel 23. They act on microtubules by stabilize them, in effect freezing them in the polymerised state, which achieves a simila r effect to that of the vinca alkaloids. Campothecins is another group of plant derivatives and include Irinotecan and Topotecan 24. They bind to and inhibit topoisomerase I high levels of which occur throughout the cell cycle.Hormone therapyTumours derived from endocrine gland sensitive tissues may be hormone dependent 25. This is due to the charge of steroid sense organs in the malignant cells. Their evolution can be stamp down by agents with apposing actions, hormone antagonists or drugs that inhibit the endogenous hormone synthesis. The most important group of drugs used to treat cancer are the steroids, videlicet the glucocorticoids (Prednisolone and Dexamethasone), oestrogens (Diethylstilbestrol and Ethinyloestradiol) and gonadotrophin-releasing hormone analogues (Octreotide and Lanreotide), as well as agents that antagonise hormone action (Tamoxifen, Toremifene and Fulvestrant). Such drugs rarely act as a cure but do mitigate the symptoms of the cancer and thus play an im portant part in the clinical management of sex-hormone-dependant tumours.Miscellaneous agentsCrisantaspaseCrisantaspase is a preparation of the enzyme asparaginase and therefore, like asparaginase, can break down asparagine to aspartic acid and ammonia 26. It is active against tumour cells, such as those of acute lymphoblastic leukaemia, which energise lost the potentiality to synthesise asparagine and therefore require an exogenous source. As most normal body cells are able to synthesise asparagine, the drug has a slightly selective action and very little suppressive effect on the bone marrow, the mucosa of the gastrointestinal tract or hair follicles. monoclonal antibody AntibodiesAntibodies are immune gamma globulins that react with defined target proteins expressed on cancer cells. This activates the militarys tolerant response, which kills cancer cells by complement-mediated lysis or by killer cells. monoclonal antibodies can also attach to and activate growth factor rece ptors on cancer cells, thus inhibiting the survival pathway and promoting apoptosis. Rituximab is a monoclonal antibody that is authorise (in crew with other chemotherapeutic agents) for treatment of certain types of lymphomas 27. It lysis B lymphocytes by binding to the calcium- channel forming CD20 protein and activating completment. It also sensitises resistant cells to other chemotherapeutic drugs.Trastuzumab (Herceptin) is a valetised murine monoclonal antibody that binds to a protein termed HER2 (the human epithelial growth factor receptor 2) a receptor with integral tyrosine kinase activity 28. It induces the host immune response as well as inducing the cell cycle inhibitors p21 and p27.Imatinib MesylateImatinib is an inhibitor of signalling pathway kinases 29. It inhibits the platelet-derived growth factor (PDGF) a receptor tyrosine kinase, and the Bcr/Abl kinase a cytoplasmic kinase. These are considered to be unique factors in the pathogenesis of chronic myeloid leukaem ias. Imatinib is licensed for the treatment of this tumour when it has proved to be resistant to other therapeutic strategies, as well as for the treatment of some gastrointestinal tumours that are not susceptible to surgery.Resistance to Anticancer DrugsAs mentioned previously patients can develop resistance to many chemotherapeutic agents. This can be caused by a number of mechanisms, which are summarised in figure 1.A decrease in the amount of drug taken up by the cellResistance can develop as a result of decreased drug uptake. This can be due to the loss of transporter function, for example RFC 30. Decreased influx of Methotrexate in tumour cells has been spaciously associated with decreased RFC gene scene. Down-regulation of the transporter protein is due to alterations in the transcription and transmutation factors. Transcriptional factors, such as the Sp1 family, CREB (cyclic AMP-response element binding protein) and p53, regulate RFC gene rule 31. therefore loss of fun ction of these transcription factors cause silencing of the RFC gene, which results in reduced protein level. Also post-translational modifications of transcription factors alter phosphorylation patterns, which abolishes Sp1 and CREB function thereby resulting in loss of RFC gene reflexion and subsequently resistance 32.Mutations in the human RFC gene can also decrease drug influx. Jensen et al (1998) have account a mutation that causes marked changes in the kinetic properties of RFC mediated transport of folates 14. The structurally altered RFC was functionally characterized by a 9- and 31-fold increased affinity for transport of reduced folate cofactors and folic acid, respectively. This allowed the accruement of intracellular folates, which sustained cell growth and DNA replication, allowing cancer cells to escape the cytotoxic effects of antifolate drugs. change concentration of target enzymeIncreased expression of target enzyme is a common mechanism of acquired resistance. For example Methotrexate resistance can develop as a result of DHFR gene elaborateness and subsequent enzyme overexpression 15. Gene amplification is thought to occur as a consequent of antifolate inhibitors binding to DHFR, which causes a conformational change that alters the translational autoregulatary negative feedback mechanism, wherein DHFR protein specifically interacts with its own mRNA and negatively controls translational efficiency. The drug concentration will be expressage to the venereal disease administered, which will not be able to block the additional enzyme that is synthesised, resulting in cancer cells overcoming the inhibitory effect of the drug.Insufficient activation of the drugsome(a) drugs require metabolic activation to manifest their antitumour activity for example Cytarabine has to undergo catalytic conversion, by the action of deoxycytidine kinase, to an active form 33. So under expression or mutation of this drug-metabolising enzyme can reduce drug eff icacy and cause resistance. Another example of resistance due to insufficient activation of the drug is Mercaptopurine, which is a prodrug 34. Mercaptopurine is activated by hypoxanthine guanine phosphoribosyl transferase (HGPRT) and mutations that reduce the activity of this enzyme will allow the cancer cells to escape the toxic effects of the drug.Increase in inactivationResistant to Mercatopurine can also develop as a result of increased inactivation of the drug 35. The mechanism behind this is thiopurine s-methyltransferase (TPMT), which inactivates Mercaptopurine and thereby prevents the formation of the active drug. Mutations in the TPMT gene will alter its activity and may cause resistance.Rapid repair of drug-induced lesionsPatients can develop resistance as a result of cancer cells recognizing DNA lesions and rapidly initiating repair pathways 9. This is the main cause of resistance to alkylating agents as their mechanism of action is DNA damage There are several repair pat hways and include the Direct Repair (DR) pathway, al-Qaida Excision Repair (BER) pathway, Nucleotide Excision Repair (NER) pathway, Homologous Recombination (HR) pathway and Non-Homologous End Joining (NHEJ) pathway.The DR pathway is mainly mediated by the DNA repair protein O6-alkylguanine DNA alkyltransferase (AGT) 36. AGT transfers the alkyl adducts from the nucleotides to the cysteine residue within its active site, on an individual basis from other proteins and without causing DNA strand breaks.The BER pathway recognizes and accurately removes bases that have been damaged by alkylation 37. A damaged base is removed by a damage-specific DNA glycosylase, leading to the formation of a potentially cytotoxic apurinic or apirimidinic site intermediate. This is then processed by an AP endonuclease (APE1), which generates a strand break that is further processed by Poly ADP-Ribose Polymerase (PARP), DNA polymerase b (Polb) and ligase one-third to restore the damage.The NER pathway d eals with the repair of bulky DNA lesions formed by DNA-alkylating agents such as Cisplatin, which distort the DNA double helix and block DNA replication and transcription 38. cardinal major mechanisms of DNA repair have been recognized in this pathway the transcription-coupled repair, which specifically targets at and removes lesions that block the progression of RNA polymerase II, and the global genome repair, which deals with lesions in the rest of the genome. Generally, nucleotide repair is a complex multi- ill-use process that sequentially deploys a group of proteins to excite the lesion, remove the damage, and support new DNA synthesis.The HR and NHEJ pathways are involved in the repair of DNA double strand breaks, commonly considered to be the most lethal of all DNA lesions. Double strand breaks are induced by chemotherapeutic agents such Bleomycin, and Etoposide. In the HR pathway, cash machine (ataxia talagiectasia mutated kinase) and its related ATR proteins sense the s evere DNA lesions, and are mobilized to phosphorylate a wide range of substratum proteins 39. Also a number of regulatory proteins, including BRCA1, BRCA2 and p53, are recruited to coordinate the DNA repair. The NHEJ pathway involves the alignment of the broken ends followed by recruitment and activation of the DNA-dependent protein kinase catalytic subunit (DNA-PKcs) and DNA ligase IV to complete the ligation step 40.MutationsMutations in various genes can give rise to resistant target molecules, for example the p53 gene 41. The p53 protein is an important regulator of the cell cycle and is sensitive to any DNA damage caused during replication. Following DNA damage it will commonly induce G1 arrest and/or apoptosis to prevent the labor of defective cells. Mutations in this gene will cause the loss of p53 function, which will allow cells with damaged DNA to continue replicating, resulting in resistance to DNA damaging drugs. Other genes, such as h-ras and bcl-2/bax, involved in t he apoptotic pathway, have also been implicated in resistance 42. Resistance due to mutations in genes will affect a wide range of anticancer drugs as all cells deal the same genetic material. It also potentially increases the symmetricalness of surviving mutant cells, which leads to greater tumour heterogeneity.Increased expression of efflux pumpsResistance to natural hydrophobic drugs, such as vinca alkaloids and taxanes, as well as the cytotoxic antibiotics, such as anthracyclines and Dactinomycin, occurs due to the over expression of ATP-dependent efflux pumps in cancer cells 5. These pumps belong to a family of ATP-binding cassette ( rudiment) transporters, which are divided into eight distinct subfamilies, shown in table 1. Of these subfamilies PGP, also cognize as MDR1, has a broad drug specificity, which explains the cross-resistance to several chemically unrelated compounds. It is a multidrug efflux pump that has 12 transmembrane regions, which bind hydrophobic drug subs trates that are either neutral or positively charged 6. It also has two ATP-binding sites, as hydrolysis of two ATP molecules are needed for the transport one drug molecule 43. Binding of substrate to the transmembrane regions stimulates the ATPase activity of PGP, causing a conformational change that releases substrate to the extracellular space. Hydrolysis at the second ATP site is required to re-set the transporter so that it can bind substrate again, completing one catalytic cycle. Increased expression of the PGP transporter in cancer cells increases the amount of catalytic cycles that occur, which increases the amount of drug effluxed 5. This lowers the intracellular drug concentration below a cell-killing threshold, which results in resistance.Not all multidrug-resistant cancer cells express PGP. Resistance in these cells was discovered to be linked with the expression of the multidrug-resistance-associated protein 1 (MRP1) 44. MRP1 is similar to PGP in structure (table 1) but , unlike PGP, it recognizes neutral and negatively charged hydrophobic natural products, and transports glutathione and other conjugates of these drugs, or, in some cases, such as for Vincristine, co-transports unconjugated glutathione. Some anticancer drugs, such as Mitoxantrone, are silly substrates for PGP and MRP1. Mitoxantrone resistance is due to a more distant member of the rudiment transporter family, MXR (Mitoxantrone-resistance gene) 45. This transporter is thought to be a homodimer of two half-transporters, each containing an ATP-binding domain at the amino-terminal end of the molecule and six transmembrane segments (table 1).Resistance can also develop as a result of increased expression of rudiment transporters in the apical membrane of the gastrointestinal tract 46. ABC transporters play a key physiological role, where they extrude toxins thus forming a protective mechanism and a first line of defense. Increased expression of these transporters decreases drug uptake and therefore decrease drug bioavailability. Examples of chemotherapeutic agents that develop resistance by this mechanism include antimetabolites, such as Methotrexate and Fluorouracil, and alkylating agents, such as Cisplatin. Also water-soluble drugs that piggyback on transporters and carriers or enter by means of endocytosis can fail to accumulate as they will not be able to enter the body. Additionally, PGP actively secretes intravenously administered drugs into the gastrointestinal tract 47. Resistance due to increased levels of PGP transporters in the gastrointestinal tract is illustrated by MDR1a/MDR1b-knockout mice, which have shown to have increased tissue concentrations of PGP substrates. Studies have also shown increased tissue absorption of PGP substrates, following literal administration, when co-administered with a PGP inhibitor.Reversal of drug resistance in cancerWays to overcome multidrug resistance due to the over expression of ABC transporters are being researc hed. Some of the main approaches include developing PGP inhibitors, antibodies against the PGP transporter, antisense oligonucleotides and liposome-encapsulated drugs.Drugs that can reverse multidrug resistance, such as PGP inhibitors, could be useful interventions to improve bioavailability, by increasing oral uptake of anticancer drugs and decreasing drug excretion, thereby reducing dosing requirements 7. Two inhibitors that are used in the laboratory and in clinical trials that seek to reverse drug resistance are the calcium channel blocker, verapamil and, the immunosuppressant, cyclosporin A. Another method that can be used to inhibit PGP is by competitive inhibition 48. PGP binds many different hydrophobic compounds so any drug that interacts with the substrate-binding region is likely to be a competitive inhibitor of other drugs. Thus, two drugs that are transported by PGP will compete for this transport, resulting in increased oral absorption of both, decreased excretion, an d redistribution. This kind of drug interaction can be used to inhibit the multidrug transporter, when the inhibitor drug has little or no other pharmacologic effect.Monoclonal antibodies (MAbs) against PGP have been used to kill multidrug resistant cells 49. MAbs are of therapeutic use as they can activate the immune response, which results in complement mediated lysis or antibody dependent cellular cytotoxicity of the cells. An example of a MAb is MRK-16, which has shown selective toxicity towards tumours that are over expressing PGP. Molecules, which are normally involved in signal transduction on T and B cells can also be targeted for antibody therapy 50. Such molecules include CD19, which is a membrane receptor involved in signal transduction and potentiates the response of B cells to antigens. MAbs directed against CD19 can induce cell-cycle arrest due to negative growth signals that cross-link immunoglobulin M and CD19.Antisense drugs work by down regulating gene expression 5 1. This occurs by sequence-specific blinding of either DNA or RNA, which inhibits transcription or translation, respectively. Different antisense-oligodeoxynucleotides have been reported to chemosensitize resistant tumour cells to anticancer drugs through down regulation of PGP expression and thus increasing the intracellular accumulation of anticancer drugs in the cancer cells. The efficiency of a synthetic oligodeoxynucleotide (ODN) in regulating gene expression in living cells depends on its thermodynamic stability, resistance toward nucleases and cellular uptake 52. A number of studies indicate that a synthetic ODN coupled with a DNA intercalator such as acridine, naphthyl imide, psoralen or pyrene might act to increase stability.Novel drug delivery systems such as liposome-encapsulated drugs have also been create to overcome multidrug resistance 53. Liposome formulations contain a short fraction of polyethylene glycol (PEG)-derivatised phospholipid, which has been shown to dra matically alter the pharmacokinetic properties of certain anticancer drugs. These pharmacokinetic alterations include long elimination half-life and small volume of distribution. Another formulation developed to bypass PGP transporters is anionic liposomes, which are internalised by certain cells and are able to provide drug release in intracellular compartments.ConclusionCancer is prevalent in the horse opera world and much research is dedicated to produce effective chemotherapy. circulating(prenominal) chemotherapy includes alkylating agents, antimetabolites, cytotoxic antibiotics, plant derivertives, hormone therapy and monoclonal antibodies. However the efficacy of these chemptherapeutic agents is limited to patients developing multidrug resistance. This is mainly due to the over expression of ABC transporters, oddly the PGP transporter, as they have broad drug specificity so can bind many structurally unrelated drugs 5.Techniques to reverse multidrug resistance are being dev eloped and include co-administration of PGP inhibitors, which prevent the binding of anticancer drugs the transporter 7, the use of antibodies, which kill cells over expressing the PGP transporter 49, antisense oligonucleotides that down regulate PGP expression 51 and liposome-encapsulated drugs, which alter the pharmacokinetic properties of anticancer drugs 53.A better understanding of the mechanism by which ABC transporters efflux chemotherapy and further analysis, in clinical trials, of known mechanisms of multidrug resistance would increase the development of agents that reverse multidrug resistance. Also improved imaging techniques used in clinic to screen cancer cells would enhance the ability of practitioners to prescribe individualised treatment according to the patients level of resistance. One approach that can be developed is to produce fluorescent antibodies against all 48 human ABC transporters and use them in conjunction with a specialised fluorescent microscope to mon itor the levels of ABC transporters in cancer cells.ReferencesOffice for discipline Statistics (2005) Cancer Statistics registrations registrations of cancer diagnosed in 2006, England. http//www.statistics.gov.uk/downloads/theme_health/MB1-37/MB1_37_2006.pdf accessed December 2009Weinberg RA (1996) How Cancer Arises. Scientific American 275 42-48Lawley PD and Phillips DH (1996) DNA adducts from chemotherapeutic agents. Mutation look into 355 13-40This article is not included in your organizations subscription. However, you may be able to access this article under your organizations covenant with ELowenthal RM and Eaton K (1996) Toxicity of Chemotherapy. Hematology/Oncology Clinics of North America 10 967-990Gottesman MM (2002) Mechanisms of cancer drug resistance. Annual Review of Medicine 53 615-627Ambudkar SV, Dey S, Hrycyna CA, Ramachandra M, Pastan I and Gottesman MM (1999) Biochemical, cellular, and pharmacological aspects of the multidrug transporter. Annual Review of Phar macology and Toxicology 39 361-398 bring DR, Traunecker H and Kerr DJ (1996) Clinical trials of P-glycoprotein reversal in solid tumours. European journal of Cancer 32A 1070-1081Lawley PD and Brookes P (1967) Interstrand cross-linking of DNA by difunctional alkylating agents. Journal of Molecular Biology 25 143-160Zhu Y, Hub J, Hu Y and Liu W (2009) Anti-Tumour Treatment Targeting DNA repair pathways A apologue approach to reduce cancer therapeutic resistance. Cancer Treatment Reviews 35 590-596Bouziane M, Miao F, Ye N, Holmquist G, Chyzak G and OConnor TR (1998) Repair of DNA alkylation damage. Acta Biochim Pol 45191-202Schweitzer BI, Dicker AP and Bertino JR (1990) Dihydrofolate reductase as a therapeutic target. FASEB Journal 4 2441-2452Spiegelman S, Nayaak R, Sawyer R, Stolfi R and Martin D (1980) Potentiation of the antitumor activity of 5-FU by deoxythymidine and its correlation with the formation of (5-FU)RNA. Cancer 45 1129-1134Nabhan C, Gartenhaus RB and Tallman MS (2004) Purine nucleoside analogues and combination therapies in B-cell chronic lymphocytic leukemia dawn of a new era. Leukemia Research 28 429-442Jansen G, Mauritz R, Drori S, Sprecher H, KathmannI, Bunni M, Priest DG, Noordhuis P, Schornagel JH, Pinedo HM, Peters GJ and Assaraf YG (1998). A structurally altered human reduced folate carrier with increased folic acid transport mediates a novel mechanism of antifolate resistance. Journal of Biological Chemistry 273 30189-30198Tai N, Schmitz JC, Chen TM and Chu E (2004) Characterization of cis-acting regulatory element in the proteincoding region of human dihydrofolate reductase mRNA. Biochemical Journal 378 999-1006Zunino F and Capranico G (1990) DNA topoisomerase II as the primary target of antitumor anthracyclines. Anti-Cancer Drug Design 5 307-317Wang JC (1996) DNA Topoisomerases. Annual Review of Biochemistry 65 635-692Kasahara K, Fujiwara Y, Sugimoto Y, Nishio K, Tamura T, Matsuda T and Saijo N (1992) Determinants of Response to the D NA Topoisomerase II Inhibitors Doxorubicin and Etoposide in Human Lung Cancer Cell Lines. Journal of the National Cancer Institute 84 113-118Chen AY, Yu C, Gatto B, and Liu LF (1993) DNA minor groove-binding ligands A different class of mammalian DNA topoisomerase I inhibitors. Procedings of the National academy of Sciences of the USA 90 8131-8135Povirk LF (1996) DNA damage and mutagenesis by radiomimetic DNA-cleaving agents bleomycin, neocarzi
Impact and Application of NanoengineeringIsayah WedderburnThe wonders of nano engineering science abduct This chuck is going to inform you on the wonders of nanotechnology and how it bathroom cleanses our lives in the future. Also, the distinguishable ship canal in which nanotechnology is assessed as an entirety in regards to it existence a benefit for the future or malignful. We forgo explore the determination of the researching into nanotechnology.Identifying and evaluating the purpose of the researchIn the next week read a hand on nanotechnology to gain a foundation on how nanotechnology works and what it is. deep down the first two weeks of the project read 2 journals on the health check application of nanotechnology and the theory of nanotechnology to understand nanotechnology is and how to it could impact on our future to produce a great discernment on nanotechnology.In the next 5 days using the schooling gained doneout online research and reading a book constr uct a plan of different analytical techniques that dirty dog be utilise to evaluate nanotechnology ( i.e. systemology, evaluation and summary) and come to a conclusion.OverviewA nanometre is a billionth of a metre. (Report in co-operation with the OECD supranational Futures broadcast 2016,p 6) Nanoscience is the consume of phenomena and manipulation of materials at atomic, molecular and macromolecular scales in frame to understand and form properties that differ significantly from those on a larger scale. (Report in co-operation with the OECD International Futures Programme2016) DS1Nanotechnology is any design, structure, systems of materials or materials when working from 1-100nm. Nanotechnology involves an array of scientific disciplines such as chemistry, physics, biology and electronics and engineering. It has been around since the ninth century. However, modern technology enables us gain an insight and thus be able to exploit the working of nanotechnology. Additionally, it has legion(predicate) advantages that whitethorn able to develop civilization and breaks our lives or may be a drawback to society and pose got more than harm than good.Nanotechnology would be paramount to future of humanity receivable to the fact that it has some(prenominal) desirable applications, not only that, it is employ in a enormous amount of different fields. Therefore, itll help the world develop and get through improves the public assistance on a global scale. The up and coming field has many potential contributions to medical specialty. (Report in co-operation with the OECD International Futures Programme 2016,p16)DS2 be in possession of said Nano devices could be apply for encapsulation on that point ar Nano capsulises that are used for cancer patients. The capsule (quantum dot) travels to the site of the tumour without damaging healthy cells then diffuses and releases the toxins at an enamor rate, killing the target tumour. A similar method actin g could be used to detect diseases in patients at the around primitive stage to foil any evilal progression. Nonetheless, in the clinical field extensive trials develop to be photographn for the drug to be deemed suitable. This substance that all the health check applications of nanotechnology will take the longest to come to fruition. Drug delivery is would be the roughly profitable application of this technology. Thus billions or trillions of dollars should be invested into this.The most popular use and potential billet of nanotechnology is the Nanotube. It is made of carbon and a carbon nanotube is a cylinder of carbon atoms covalently bonded together. The nanotube popularity stems from its properties and structure. (Richard Booker, Earl Boysen 2005,P 68) A sheet of graphite is very strong because of the interlocking carbon-to-carbon bonds. The graphite sheets can slide across each opposite easily, which makes graphite useful as a lubricant. The tensile strength of the nanotube is close to 100 times greater than that of steel of the same diameter. According to Report in co-operation with the OECD International Futures Programme (Report in co-operation with the OECD International Futures Programme 2016,P10) Therefore, carbon nanotubes could be used for car to absorb a significant amount of damage due to its high tensile strength or gurder that b prohibit instead of rapturing in an earthquake. (Report in co-operation with the OECD International Futures Programme 2016,P 9) However, there are problems with the nanotube, one of which is it is concentrated to interact with different materials. For instance for functionalisation (changing the properties of nanotube by chemically vertebral column it with other chemicals) to occur the nanotubes take in to be reacted with a polymer. But this reduces the kernel of its properties. Nonetheless, Scientists are trying to discover a way to overcome this crop without inhibiting the properties of the nanotu be.Social applications of Nontechnology(Richard Booker and Earl Boysen, 2005DS3)Nanotechnology is still in its infant stages. Nonetheless, itll blossom easily and become intertwined into most fields nanotechnology will become an integral part of our lives like mobile phones.(Richard Booker and Earl Boysen, 2005DS4) Albeit, nanotechnology has a lot of potential to surface the way for the next revolution to become something great. However with new technology there are always social, economic and ethical issues that we have to consider, to conquer commercialization for the new product. As nanotechnology is still progressing humanity is unaware of the detriment to the environment or the damage to the concourse of the future generation that may transpire. Unfortunately, there have been recent studies to that show toxicity exist through the result of using nanomaterials. Additionally, government and corporations are observing the effect on nanotechnology with gm crops to human health due to the fact that itll affect the chain, finally it may bring forth damage to humanity. Furthermore, there have been experimental results that cause major concern single-walled nanotube can cause lesions in the lungs of rats. 15 percent died from suffocationA plethora of people have trepidation for the division that will become more apparent surrounded by rich and poor countries nanotechnology will cause exclusively developed countries will be benefiting from the reward of research due to having sufficient money to plenty produce and distribute the products stemming from nanotechnology. (Richard Booker and Earl Boysen, 2005) Countries with less-educated works would be unable to repugn in the nano technology-related future due to a lack of knowledge. Benefits in medicine will be focused on financial issues and wont be shared equally. Therefore, poor countries wouldnt be able to improve their medicine to improve peoples lives and/or wellbeing.Some governments had the privilege to invest money into nanotechnology with genetically engineered foods in the super market shelves. Which causes controversial quarrel and an uproar due to the dangers if nano foods and pesticides that may impede on the health of others. (Richard Booker and Earl Boysen, 2005) inadequateer countries. To conclude there are many negative aspect of nanotechnology to consider. Humanity should ask the question does the plus of nanotechnology outweigh the negatives?EvaluationThere many benefits of nanotechnology. The advantages are that it can be used in many different disciplines and scientific fields. Because scientist are nurture more about nanotechnology everyday there are more discoveries that could be made to benefit a lot of people. The options are limitless.On the other hand nanotechnology has concerning disadvantages. The disadvantages are scientists dont know the damage that could be caused to the environment and peoples health. Poor countries may face the most difficultyDS5. Overall, the benefits of nanotechnology outweigh the disadvantages because scientists could find various ways to overcome to the difficulties as they could make more instruments to understand how atoms and materials work. Nanotechnology will cause a great paradigm shift because itll be gnarled in many fieldsDS6. There have been trillion of dollars invested into to nanotechnology and an astronomical time install into it. Therefore, it would be wise to ensnare our time to good use and allow nanotechnology to come to fruition.SummaryDS7More time should be time and money should be invested into nanotechnology so we can develop it further. It has great potential and it should not go to waste.Ethicality of researchDS8The tec should always bring integrity, fairness and honesty to ensure anyone involved in an experiment is safe and it give you a piece of chief as you are being honest. Integrity in tells no coercing or deceiving the people involved. This means the participant should be w illing to volunteer cultivation they have the right to withdraw from the research at any stage. satinpod involves considering the impact on people lives and environment to judge if the research or experiment will be pragmatic and will be more beneficial than a hindrance. In addition, is the experiment morally right? Because there could me more benefits than harm but the lives of test subjects may be put at risk or harmed. That is the most significant aspect to take into account. The scientist carry out primary research must always be explicit in what they tell the participants of what will occur so they dont have a failed understanding. For example they should be aware of the possible outcomes of the research, the associated demands and discomfort people may experience. If the experiment may cause danger to a persons sprightliness the experts conducting the research must have strong justifications of why it is necessary. It is vital that there is academic integrity. Thus you must h ave permission to use apt property such as journals. And you shouldnt assume you have automatic permission. universe ethical is crucial because it protects the scientist from losing their job, losing money or in some cases being arrested it protects anyone involved in research to be protected as well.MethodologyDS9The method used to collect data was by reading books to gain an insight as to what nanotechnology is. Looking at different journals online and implying which one is the most relevant to the subject. At each stage the way information was sedate is by writing down ideas and knowledge obtained from secondary research to think of a logical order to structure the findings. This allows the project to be coherent. The utilization of the researcher is to find important a sufficient amount of information to implement into the project. There isnt much way the personal behaviour of the researcher can be effect because the research is secondary. The best research method for gaini ng textual data was by reading it thoroughly and observing as which data will be relevant. Then extracting and compiling the relevant research. For the project numerical data wasnt needful to understand nanotechnology, although it could have been used to pick up and think about the subject on different angles. (April Klazema ,june 12,2014DS10, )The main end between objectivity and subjectivity is in the way that these arguments are presented. infixed information whether it is in written or spoken form is in the main considered to be a single persons opinion. It has a viewpoint, or possibly a bias, regardless of the information it provides. Remember to referenceBudgetingDS11Borrowing books were free because they were borrowed from the library. This means there was no need to purchase any books. The journals were free and the library paid approximately 20 for the journals viewed. The journals used were free as they came from a free source on Google. There was no need to print any resources as you can access the journals online. It cost 2 to purchase lines and plain paper from the shop to write ideas down and make a plan.AppendicesReferencesDS12Nanotechnology for dummies Richard Booker and Earl Boysen 2005Opportunities and risks of Nanotechnologies , Report in co-operation with the OECD International Futures Programme 20016April klazema. 2014. mark vs. Subjective Writing Understanding the Difference. ONLINE Available at https//blog.udemy.com/objective-vs-subjective/. Accessed 12 June 2014. develop countWords 1,952DS1Incorrect referencing style.DS2Incorrect referencing style used.DS3This need to be at the end of the sentence with the period after the last bracket.DS4Another way you could have used this reference is Albeit, broker and Boysen (2005) suggestsAlso, in-text reference used is incorrect.DS5A reference would be needed to support this statement.DS6Such as?DS7You could have added further context to your summary. You raised a lot of good points in y our body. How could further research impact/improve nanotechnology? Which area of nanotechnology could use further research during this stage in its education? You could have brought some of these questions into context at this stage.DS8What ethical constraints would this field of study face? And how would you address them?DS9Good.DS10No the format for in-text Harvard referecingDS11GoodDS12This is not the format for Harvard referencing.
Friday, March 29, 2019
Trends in UK despoil Statistics Over Timetheme statistics ab kayoed wickedness in England and Wales feature been collected and published by the Home Office since 1805 (Clarke, 2006). Originally, the statistics scarcely intromitd proceedings and convictions data from the courts. However, in 1857, data about crimes reported to and record by the police were too introduced in to the statistics, with the introduction of the latter, the g every adornn manpowert seized the opportunity and could exercise all oersight over what was whence a highly topical anaesthetic anaestheticised policing structure accountable at the local political level (Clarke, 2006, p. 7), meaning that the presidential term could watch over the statistics produced by the police when it came to politics. This essay is going to savour at the figures for foil from these statistics provided, and comment and discuss the arch of assail over the last long hundred course of studys, and will also look at the ori gin and location of these statistics and how they put up changed and the impact the changes be in possession of had on sack.There be humankindy several(predicate) commentarys to the word attaint in the English langu geezerhood. But overall it is non all that hard to define because most of the definitions broadly have the aforesaid(prenominal) concept of what queer is. One definition of Rape, comes from Randy Thornhill and Craig Palmer, who define mess up as copulation resisted to the best of the dupes ability unless such resistance would in all likelihood result in death or serious injury to the victim or in death or injury to individuals the victim unremarkably protects (Thornhill Palmer, 2000, p. 1). However, they do also acknowledge that other sexual assaults such as oral or anal penetration of a man or a woman infra(a) the same conditions, can also be classed as rape (Thornhill Palmer, 2000, p. 1). A nonher definition of rape comes from Merriam-Webster, which d efines Rape as unlawful sexual activity and usually sexual intercourse carried out forcibly or under threat of injury against the will usually of a pistillate or with a person who is beneath a certain age or incapable of valid consent because of amiable illness, mental deficiency, intoxication, unconsciousness, or deception (Merriam-Webster, 2017, p. 1). However, the main legal definition comes from government legislation website, by The National Archive, under the knowledgeable Offences do 2003 which defines Rape as(1) A person (A) commits an law-breaking if- (a) He intentionally penetrates the vagina, anus or mouth of some other person (B) with his penis, (b) B does not consent to the penetration, and (c) A does not fenceably believe that B consents. (2) Whether a belief is mediocre is to be determined having regard to all the circumstances, including any steps A has taken to ascertain whether B consents. (3) Sections 75 and 76 apply to an offence under this fragment. (4 ) A person blameable of an offence under this section is liable, on conviction on indictment, to impounding for life. ( versed Offences deport, 2003, p. 1). In addition to this, the familiar Offences Act 2003 also has definitions of rape for rape offences committed against kidskinren under the age of 16 and even younger children, who argon under the age of 13. The definition for rape or other sexual activity of a child under 16 is as followsThe elements of the offence are(A) aged 18 or over intentionally causes or incites another person (B) to prosecute in an activitythe activity is sexual, andeither (B) is under 16 and (A) does not reasonably believe that B is 16 or over, or(B) is under 13.(Sexual Offences Act, 2003, p. 1)Finally, the Rape of a child under 13 is defined as(1) A person commits an offence if- (a)he intentionally penetrates the vagina, anus or mouth of another person with his penis, and (b)the other person is under 13. (2) A person guilty of an offence under thi s section is liable, on conviction on indictment, to imprisonment for life. (Sexual Offences Act, 2003, p. 1).Now that the definition of rape has been outlined, we can now move on to look at the trend of rape over the last long hundred years and how it has changed over time and the reasons for it. If we look at the graph for Rape over the last 120 years, we can see that there has been a huge increase in the amount of rape that has taken place compared to the amount of whitlow misemploy that has occurred.As we can see from the graphs below, the trend for Rape has squarely increased over the last 120 years. redden though the graph for Criminal Damage shows that the trend for Criminal Damage has increased, we can see from the chart that criminal damage peaked in 2008/09 and then the figures started dropping, resulting in the trend decreasing.As far as rape goes, the main increase has been over the last 20 years, mainly because of the modernistic laws that were introduced in the Se xual wellness Act 2003 replacing the old laws of the Sexual Health Act 1956.As can be seen from the graph, after the un apply laws were introduced in the Sexual Health Act 2003, the rate of rape per year increased by 2561 between the year 2001/02 and 2002/03. This is because the Sexual Health Act 2003 introduced the new law that allowed for to a greater extent sexual offences to be classed as rapes. For compositors case, ahead this new law, it can be seen from the two bar charts below that the rape of a child under 16 or even under 13 wasnt even enter by the police until 2004/05 when Sexual Health Act 2003 was properly taking form.Further to this, the rape of a female in general wasnt even preserve by the police in these statistics until 1995 as can be seen in the graph below. A reason for this can be because before 1991, it was legal for a husband to rape his wife. This was suggested by Sir Matthew Hale, in Historia Placitorum Coronea, who stated that the husband cannot be gui lty of a rape committed by himself upon his lawful wife, for by their mutual matrimonial consent and contract the wife hath given herself up to her husband, consent which she cannot back out (Hale, 1736, p. 629).However, after this case, that rule was abolished by the judge hence making matrimonial rape illegal. Despite this, female rape wasnt recorded pre-1995 because it wasnt until 1994 when S.1 of the Sexual Offences Act 1956 was substituted by S.142 of the Criminal Justice and general Order Act 1994 to include marital rape, and so added the following to the definition of rape(3) A man also commits rape if he induces a married woman to have sexual intercourse with him by impersonating her husband.(4) Subsection (2) applies for the purposes of any enactment. (Criminal Justice and Public Order Act, 1994, p. 1). After this law was introduced, female rape started to be recorded by the police.Furthermore, two feminist researchers, Jalna Hanmer and Sheila Saunders, found that the e ncounters that women faced by men everyday were not revealed in the abomination Survey for England and Wales (CSEW) because the CSEW is not knowing to disclose information of that kind of nature. This suggests that rapes which may have occurred prior to 1995 were only reported to the police in the last decade. This may have been because of the changing in the social construction of the police, meaning that there are more female officers now than there apply to be, which dedicates rape victims more in all probability and willing to talk to instead of male officers. In addition to this, ball club has also changed to provide more victim support for rape victims by establishing rape centres for victims (Hanmer Saunders, 1984).However, having said this, we are looking at police recorded crime statistics. These statistics are not exactly exact because there are some rapes or crimes not recorded by the police at all. This is because we are looking statistics from the Crime Surve y for England Wales. According to a Crime Statistics 2006 report, by the then Home Secretary of State Charles Clarke, even though there is a lengthy history of reported and recorded crime statistics, that were used to judge police act, the statistics, for a while now, have been document as having a number of weaknesses (Clarke, 2006, p. 7). He went on to outline cardinal main weaknesses in the statistics from the CSEW. He stated First, there have been perpetual claims that the police adjust their crime statistics to improve measured reported performance (Clarke, 2006, p. 7), meaning that the statistics recorded by the police are not exactly, as they have been adjusted so that the police look more liable and it looks as though they have high performance. Second, the processes and categories used by local police to record crime have historically had a significant degree of local variability this has do it difficult both to make comparisons among local forces and to form aggregat es to provide a meaningful national jut (Clarke, 2006, p. 7). This suggests that the categories that police use to categorise the crimes, are only clear to the local police who have created these statistics, as the statistics are mainly based on the crime in their area, which makes things very ambiguous in the grand system of things, when a bigger give of crime rates in England and Wales. Third, the picture that emerges from recorded crime is potentially distorted by the unknown and rebellious variability in the publics reporting of crime to the police (Clarke, 2006, p. 7). This weakness proposes that when the crimes are recorded, the statistics are not entirely accurate because it is not possible to assure how many people from the public reported a crime, and how many of the statistics have been adjusted by the police like the first weakness. However, the then radical secretary did state that whilst the problems we have remain, there have been several attempts made over the y ears to address these perceived problems that are there in the Crime Survey for England Wales.These weaknesses are a big factor in the statistics we have for rape, as they came from the CSEW. As the weaknesses mentioned in the report exist, our statistics for rape may not be entirely accurate. This leads us to believe that there may have been more rapes reported by the public but not recorded by the police, and of those that were recorded, only a few maybe accurate as the others may have been adjusted to make the police look more efficient. A further problem this creates for the statistics we have is that, like the split second weakness mentioned above, some rape statistics may not have been recorded in the survey by the police as they may not have fell into any of the categories that the police were using to define rape. This could mayhap have had a major impact on the statistics we have, hence, impacting the graphs that have been used above to illustrate the trend of rape.To summ arise, this essay has looked at the overall trend of rape over the last 120yrs and compared it to the trend of Criminal Damage statistics over the last 120yrs, to show the trend of rape over this period. This essay then delved deeper into the main statistics and broke them down into figures of rape over the last 20 years and then went even further and showed the trends of rape of females of different ages, for example under 16s and under 13s. After that, this essay looked at reasons as to why the statistics are showing what they showed and then went onto discuss the location of where the statistics were found and outlined the problems with the CSEW. Because of these weaknesses, the essay finally looked at how the weaknesses impacted on the rape statistics that we had and used to illustrate the trend of rape from 1898 to 2014/15 which has increased.ReferencesClarke, C. (2006). Crime Statistics An Independent review. capital of the United Kingdom Home Office. Retrieved March 19, 2017, from http//webarchive.nationalarchives.gov.uk/20110218135832/http/rds.homeoffice.gov.uk/rds/pdfs06/crime-statistics-independent-review-06.pdfCriminal Justice and Public Order Act. (1994, November 3). Criminal Justice and Public Order Act 1994. Retrieved March 13, 2017, from The Government polity Website The National Archive http//www.legislation.gov.uk/ukpga/1994/33/section/142Hale, S. M. (1736). Historia Placitorum Coronae The History of the Pleas of the Crown (Vol. 1). Oxon (Oxfordshire) overlord Books Ltd.Hanmer, J., Saunders, S. (1984). Well-founded fear a community study of violence to women. capital of the United Kingdom Explorations in Feminism Collective (Great Britain).Merriam-Webster. (2017). Rape. Retrieved February 27, 2017, from Merriam-Webster Online Dictionary https//www.merriam-webster.com/dictionary/rapeSexual Offences Act. (2003, November 20). Sexual Offences Act 2003. Retrieved February 27, 2017, from The Government Legislation Website The National Archive http//www.legislation.gov.uk/ukpga/2003/42Thornhill, R., Palmer, C. T. (2000). A Natural History of Rape Biological Bases of Sexual Coercion. Cambridge The MIT Press.
Management Of Acute Coronary SyndromeAcute coronary thrombosis thrombosis thrombosis syndrome encompasses a collection of three astute processes related to myocardial ischaemia. These complicate unstable angina pectoris, non-ST elevation myocardial infarction (NSTEMI), and ST elevation myocardial infarction (STEMI). Myocardial ischaemia is caused by inadequate perfusion in spite of appearance the myocardial create from raw stuff due to oxygen shoot exceeding oxygen supply.In a healthy person the amount of oxygen required by the myocardium (O2 inquire) is refractory by heart rate, myocardial contractility, myocardial wall stress, and afterload. As explained by Antman, et al (2012), oxygen supply to the myocardium requires a satisfactory level of oxygen-carrying subject of the blood (determined by the inspired level of oxygen, pulmonary function, and hemoglobin parsimony and function) and an adequate level of coronary blood f diminished. The coronary vass have the qualif ication to adjust their level of resistance to adapt to the increase oxygen demand required by the myocardium during certain times (such as during forcible exertion).ischaemic heart disease is typically caused by atherosclerosis, which is a buildup of establishment inner(a) the lumen of the coronary vessels. The emergence of atherosclerosis in the vessels does non proceed everywherenight. Antman, et al. (2012) instal that atherogenesis in humans typically occurs over a purpose of m whatsoever years, usually many decades and that growth of atherosclerotic plaques probably does not occur in a smooth, linear fashion provided discontinuously, with periods of pro muckleal quiescence punctuated by periods of rapid evolution.The process of atherosclerosis begins with an abundance of lipoproteins in the blood stream. These lipoproteins bind to the walls of vessels and argon eventually deposited within the intima of the arteries. To counteract this process, phagocytes are sent in to the vessel to attack these foreign particles (Antman et al., 2012). Once the phagocytes are within the intima, they mature into macrophages and become lipid-laden foam kiosks (Antman et al., 2012). As these plaques advance calcification occurs. This process is scene to be a key step in the unionizeation of atherosclerotic plaques (Antman et al., 2012).Normally this narrowing of the vessel lumen does not cause tit inconvenience or discomfort. Eventually, however, these plaques whitethorn rupture. At this point platelet energizing occurs, which eventually pass ons to clot formation at the sight of the plaque. This clot, or thrombus, whitethorn break off and lodge in a coronary vessel. These ii processes are a usual pathogenic finding with sub sagacious coronary syndrome (Lincoff, Califf, Anderson, Weisman, Aguirre, Kleiman, Harrington Topol, 1997). A partial occlusion of the coronary vessels due to a ruptured plaque/platelet complex causes unstable angina or a NSTEMI. In this case, the oxygen demands of the heart gougenot be met. A complete occlusion causes a STEMI (Anderson, Adams, Antman, Bridges, Califf, Casey Jr, Chavey II Wright, 2011), which eventually leads to myocardial cell death.Discussion/AnalysisThe fatality department providers are oftentimes the first line of defense in the management of uncomplaining roles with titty ache. The ability to quickly assess whether or not the cause of authority pain is potentially fatal is of great importance. sarcastic toilet table pain foot be broken down in to non-cardiac and cardiac causes. Non-cardiac causes include pneumothorax, pulmonary embolism, and Boerhaaves syndrome. Acute coronary syndrome is among several cardiac causes of emergent breast pain.An accurate diagnosis of the cause of chest pain requires several key components. These include patient history (including put on the line factors), physical enquiry, diagnostics, and labs.HistoryHistory is instrumental during the evalu ation of a patient with chest pain. Ischemic chest pain is often described as a fearful pressure or squeezing and is genuinely described as the feeling of an elephant sitting on my chest. Typically this pain is described as substernal chest pain which radiates to the neck, jaw, or down the left arm. excess dilate regarding the onset of chest pain place in addition serve as Copernican clues. For example, pain on exertion that resolves with rest suggests stable angina, whereas modern onset chest pain or chest pain at rest suggests unstable angina. A good method to differentiate cardiac from non-cardiac chest pain is whether the pain improves after presidentship of nitroglycerin (NTG). If the pain is relieved by NTG it is considered to be likely due to cardiac causes. Additional details suggesting cardiac origin are shortness of breath, nausea +/- vomiting, diaphoresis, and the social movement of syncopal/near-syncopal episodes.It is main(prenominal) to note that a patient wi th chest pain often have a silent or atypical demonstration. This is specially received in elderly men (Woon Lim, 2003) and diabetics (Tabibiazar Edelman, 2003). A patient with an atypical presentation may present with shortness of breath but lack the classical symptom of angina pectoris which radiates to the jaw or left arm. Commonly these patients plain of a feeling of indigestion or epigastric discomfort. Thus it is truly important to consider ACS in these patients.The presence of try factors plays an important use in the evaluation of chest pain, especially in a patient with known disease. The landmark Framingham warmness Study showed that cardiac pretend can be influenced by diet, lifestyle, and familial risk factors (Oppenheimer, 2005). The much than risk factors that a person carries, the greater their risk of developing ischemic heart disease. These risk factors are generally grouped into two categories those that are modifiable and those that are not. Risk fact ors amendable are as followsTobacco smoke (American Heart Association, 2012)High blood cholesterol (AHA, 2012)High blood pressure (AHA, 2012) natural inactivity (AHA, 2012)Obesity and overweight (AHA, 2012)Diabetes mellitus (AHA, 2012)Risk factors that cannot be changed include develop- 82% of people who die of coronary heart disease are 65 (AHA, 2012) masculine sex (AHA, 2012)Heredity- this includes both family history and race (AHA, 2012)Risk is high among Mexican Americans, American Indians, native Hawaiians and some Asian Americans (AHA, 2012)Patients presenting with unstable angina or NSTEMI have variable levels of risk of cardiac death and ischemic cardiac events (Antman, Cohen, Bernink, McCabe, Horacek, Papuchis, Mautner Braunwald, 2000). The trial conducted by Antman et al. (2000) set out to develop a unanalyzable risk build that has broad applicability, is easily calculated at patient presentation, does not require a computer, and identifies patients with different resp onses to treatments for UA/NSTEMI. In doing so, the TIMI risk score was created. The scores are calculated exploitation a score of 1 for each risk factor (7 total categories) assigned to a wedded patient. According to Antman, et al (2000) the score determines the patients risk of death, myocardial infarction, or severe ischemia. Antman, et al. (2000) found 7 prognostic variables that increase a patients risk. These areAge 65 years or olderAt least 3 risk factors for coronary artery disease (male, dyslipidemia, smoking, hypertension, diabetes mellitus, obesity family history)Prior coronary stenosis of 50% or moreST-segment deviation on cardiogram at presentationAt least 2 anginal events in prior 24 hoursUse of aspirin in prior 7 daysElevated serum cardiac markersIn TIMI 11B/ESSENCE, event range increase significantly as the TIMI-score increases (Antman et al., 2000). A score of 0/1 showed a 4.7% event rate 8.3% for 2 13.2% for 3 19.9% for 4 26.2% for 5 and 40.9% for 6/7. This lan dmark pair of trials allows practitioners a quick assessment of a patients risk of suffering a serious cardiac event.Physical interrogationPhysical exam is also a key component in the evaluation of a patient with chest pain, as many clues can suggest acute coronary syndrome. Unstable vital signs can be an important hint that the patient has suffered an MI. A general examination may reveal a patient who is diaphoretic and/or using appurtenance respiratory muscles. The cardiovascular exam could reveal a new murmur, S3/S4 gallop, or JVD. Finally, during the pulmonary exam rales may be heard upon auscultation. diagnosticsDiagnostic testing is an essential part of the evaluation of a patient presenting with chest pain. Several important diagnostic utensils were introduced to the emergency department in the last mentioned half of the 20th century that greatly improved the diagnosis and explosive charge of acute coronary syndrome.ElectrocardiogramThe introduction of coronary worry un its in the 1960s allows physicians to utilize the cardiogram ( electrocardiogram) to monitor potential fatal arrhythmias in patients with acute myocardial infarction (Julian, 1987). Shortly thereafter the portable electrocardiogram became commonplace within the emergency department to assist in name complications of acute coronary syndrome (Drew, et al, 2004). A patient presenting with myocardial ischemia allow for typically have symmetrically-inverted T waves in leads V2-V6 (Dubin, 2000). As the name suggests, a STEMI is an ST-segment elevation myocardial infarction, though ST-segment elevation can occur with Prinzmetals angina in absence of an infarction (Dubin, 2000). Additionally, the ECG allows us to evaluate chagrin of the heart in the form of the presence of Q-waves. Q-waves are the first downward deflection of the QRS complex (Dubin, 2000). As Dubin (2000) explains, a positive Q-wave MI mustinessLack a preceding spike in the QRS complexBe at least 1 mm wideor make an am plitude of 1/3 the QRS complexAn additional benefit of the ECG is that it allows the practitioner to identify the location of an acute event. Each lead corresponds to a particular location of the heart. For example, leads II, III, and AvF are the inferior leads and reflect the inferior portion of the heart.Due to the relatively high particularity but low sensitivity of the 12 lead ECG in diagnosis of acute coronary syndrome, a group of researchers in Canada recently set out to enhance ischemia detective work by conducted a trial which added a new criteria using a three vessel specific leads derived from the traditional 12 lead ECG (Horacek, Mirmoghisi, Warren, Wagner Wang, 2008). This trial showed a statistically significant improvement in the ability of the vessel specific lead protocol to detect ischemia (Horacek et al., 2008). Horacek et al. (2008) found the following sensitivity and specificity for conventional STEMI criteria versus that of the vessel specific leads (VSL) vasS ensitivitySpecificityLeft Anterior Descending74% conventional, 91% VSL97% conventional, 97% VSLRight Coronary Artery60% conventional, 70% VSL94% conventional, 94% VSLLeft Circumflex Artery36% conventional, 71% VSL deoxycytidine monophosphate% conventional, 100% VSLTotals Set60% conventional, 76% VSL96% conventional, 96% VSLBased on these results, Horacek et al. (2008) concluded that using vessel specific leads can identify acute ischemia better than existing STEMI criteria. While a STEMI criteria using vessel specific leads has yet to become a main cling within the stock emergency room protocol, this probe provides exciting new improvements in the detecting and management of patients with ACS.Serum BiomarkersThe use of biochemical markers to detect cardiac cell death significantly evolved in the 1980s and 1990s. Initially, nonspecific markers such as aspartate transaminase and total creatinine kinase were used to detect myocardial necrosis (Lewandrowski, subgenus Chen Januzzi, 2 002). During the mid-1990s the more cardiac specific enzymes CK-MB became the gold trite for detection of myocardial injury (Lewandrowski et al., 2002). CK-MB, which ordinarily rises 4-9 hours after the onset of angina, was not without its shortcomings. CK-MB may be falsely elevated due to several different causes, including recent backbreaking exercise or skeletal muscle damage, or renal bereavement (Vivekanandan Swaminathan, 2010). In the late 1990s a more predictable biomarker, troponin I, was introduced for more accurate detection of acute coronary syndrome (Heeschen, Goldmann, Moeller Hamm, 1998). According to Heeschen et al. (1998), Troponin I can be evaluated at the bedside in the emergency room and has a higher diagnostic sensitivity for the detection of acute myocardial infarction (60% vs 48%) when compared to CK-MB. The reason for this improvement in accuracy is that troponin I is not found in skeletal muscle tissue or renal distress (Heeschen et al., 1998). As Hees chen et al. (1998) demonstrated in a head to head study that cTnI test systems produced no positive results in patients with end-stage renal failure and acute or chronic skeletal muscle injury, whereas 30% and 71% of the patients, respectively, had increased CK-MB mass c one timentrations. One disadvantage of troponin I, however, is that it has a refuse sensitivity for the detection of acute myocardial infarction compared to that of CK-MB (Heeschen et al., 1998). This is due to an increased level of cTnI in patients with unstable angina (Heeschen et al., 1998). For this reason, a typical workup for a patient with chest pain in the emergency room includes both cTnI and CK-MB assays, which are draw at presentation and every 3-6 hours thereafter (Ross, Bever, Uddin Hockman, 2000).ImagingA common component of a chest pain protocol is a chest x-ray. This is normally either a standard AP/lateral series or a portable chest x-ray if the patient is unable to go about out of bed. The ches t x-ray is useful to eliminate other feasible causes of chest pain, such as an aortic aneurism or a pneumothorax.Contrast-enhanced computed tomographic angiography, or CTA, has become an integral part of the management of acute coronary syndrome due to its high sensitivity and specificity (Hoffman, Truong, Schoenfeld, Chou, Woodard, Nagurney, Pope Udelson, 2012). According to the ROMICAT-I study performed by Hoffman et al., (2012), CTA is an effective way to rule out myocardial infarction or ischemia as well as major cardiovascular events over the beside 2 years from presentation. The data presented in ROMICAT-I showed that patients undergoing CTA decreased their infirmary stay by 7.6 hours compared to standard therapy (Hoffman et al., 2012). Additionally, 50% of CTA patients were discharged from the hospital within 8.6 hours of presentation versus only 10% of patients undergoing standard therapy (Hoffman et al., 2012). Finally, the mean time to diagnosis was significantly decrea sed with the CT group versus the standard group (Hoffman et al., 2012). Overall, CTA was shown to fasten time spent in the hospital and time to diagnosis when compared to standard therapy for acute coronary syndrome. This is important to note considering the importance of quick coronary reperfusion of STEMI patients (Trost Lange, 2011). An additional observation was that these benefits were achieved without an increase in the cost of care (Hoffman et al., 2012). at that place was no overall difference between the groups in incidence of myocardial infarction 30 days after initial presentation (Hoffman et al., 2012). It is important to note that a patient undergoing a CTA is exposed to increased radiation. Additionally, patients undergoing CTA were more likely to undergo invasive coronary procedures when compared to standard evaluation.Based on this data, a question arises as to whether every patient presenting with possible acute coronary syndrome should undergo a CTA. The populati on studied in ROMICAT-I consisted of low to intermediate risk patients. Overall, CTA was shown to decrease the time to diagnosis and hospital stay for patients with possible ACS. In contrast, CTA increases a patients exposure to radiation and increases the likelihood that these patients go away undergo an increase in invasive coronary procedures. These factors should all be considered when evaluating a patient presenting with chest pain.TreatmentPharmacologicAspirin proto(prenominal) aggressive aspirin (ASA) therapy (162-325mg followed by 81-162mg daily) is currently recommended for all patients with acute coronary syndrome, unless contraindicated (Kirk, Kontos Diercks, 2011).Plavix (Clopidogrel) According to the CURE trial Clopidogrel has been shown to provide a 20% reduction in cardiovascular death, MI, or stroke for NSTEMI patients with positive biomarkers or ischemic ECG changes (Kirk et al., 2011). It is important to note that the significant anti-platelet benefits of Clopid ogrel administration should also be weighed against the increased risk of bleeding events if the patient may be a candidate for coronary artery bypass surgery.Antianginal AgentsNitroglycerin (NTG) NTG is commonly administered by EMS respondents but can also be ordered once the patient arrives in the emergency department, typically sublingually or in the form of Nitro awaye. Nitroglycerin dilates the coronary arteries, which reduces myocardial oxygen demand (Trost Lange, 2011). For this reason, it is important to evaluate the patients baseline blood pressure. If SBP is less than 100, caution should be used.Morphine endovenous morphine may be given in the event that chest pain is not relieved by NTG administration. Morphine reduces ventricular preload, thereby decreasing myocardial O2 demand (Trost Lange, 2011).Beta-Andrenergic Blockers Beta-blockers decrease demand on the heart by decreasing heart rate, blood pressure, and myocardial contractility (Trost Lange, 2011). In a patient presenting with ACS, IV Lopressor is typically the agent of choice. These are especially effective agents in patients with elevated blood pressure or tachycardia. It is important to evaluate relevant contraindications to beta-blocker therapy, such as HRCalcium-Channel Blockers Diltiazem and verapamil improve cardiac O2 supply by vasodilation of the coronary vessels, reduce O2 demand by reducing afterload, and reduce heart rate and contractility (Trost Lange, 2011). Calcium-channel blockers are second line treatments for ACS and are typically reserved for patients who are unable to call back a beta-blocker (Trost Lange, 2011). Contraindications include sick sinus syndrome, 2 or 3 AV heart block, hypotension, acute MI with pulmonary congestion, atrial fibrillation or flutter with accessory bypass tract, and ventricular tachycardia, severe left ventricular dysfunction, and cardiogenic shock (Epocrates, 2012).Antithrombotic therapy Antithrombotic therapy is recommended in a patient with suspected ACS, unless contraindicated (Trost Lange, 2011).Unfractionated heparin is unproblematic to administer (IV) and is apace reversible with protamine in the event of bleeding. (Trost Lange, 2011). As with any antithrombotic, there is a risk of bleeding so these patients require blotto monitoring.Low molecular weight heparin is more predictable, has a lower incidence of thrombocytopenia, and does not require monitoring (Trost Lange, 2011). LMWH is the preferred agent for a more conservative, ischemia-guided strategy to prevent in hospital death or myocardial infarction (Trost Lange, 2011).Bivalirudin is an antithrombotic agent that does not cause thrombocytopenia (Trost Lange, 2011). It has been shown to be equally as effective as unfractionated heparin or LMWH but with a significantly lower rate of bleeding (Trost Lange, 2011).Oxygen administration should be administered for patients who are short of breath, showing signs of shock, or O2 saturation nigh Step for NSTEMI or Unstable Angina PatientsIf a patient is considered to be high risk, such as a patient is at risk of future ischemia or infarction, an early invasive strategy is recommended (Trost Lange, 2011). For these patients, cardiac catheterization should be performed within 24-48 hours of admission (Trost Lange, 2011). In a low risk patient, a more conservative treatment is typically recommended. For these patients, catheterization is only recommended if repeated or provocable ischemia occurs (Trost Lange, 2011). TIMI scores are a valuable tool to assess the patients risk and to guide the practitioner on the appropriate next step.Next Step for STEMI PatientsPrompt coronary reperfusion is paramount in patients presenting with STEMI (Trost Lange, 2011). A door-to-balloon time of less than 90 minutes is considered to be the goal (Trost Lange, 2011). If the patient presents to a adeptness without a percutaneous coronary intervention facility the patient should be eitherTreated wi th fibrinolytic therapy if not contraindicated (Trost Lange, 2011)OrTransferred to a nearby PCI facility (Trost Lange, 2011).ConclusionAcute coronary syndrome is spectrum of diseases typically caused by atherosclerotic disease. Emergency department practitioners must be able to rapidly diagnose and manage ACS patients in order to potentially preserve singular heart muscle. While treatments for ACS have improved dramatically over the past 30 years, several recent innovations have brought upon exciting new possibilities for the care of these patients. These include new vessel specific ECG leads, cardiac specific biomarkers, and the use of computed-tomographic angiography to assess patients with possible ACS.One component of the management algorithmic rule that has not changed is the need for a strong history and physical examination to aid in diagnosis. Urgency in obtaining diagnosis cannot be disturbed enough, and patients presenting with STEMI should be rapidly sent for PCI or transferred to a facility with PCI capabilities.
Thursday, March 28, 2019
The Disparity between a Hobbsian World and the World of Candide In an anarchistic Hobbsian man, man leads a purely egotistical existence, perpetually waging state of war against his fellow men. In this terra firma Nature subsists as a acting field for evolution only the strong and cunning survives, and even extract results in life that is nasty, brutish, and short (Hobbes). However, with restraints (that is, government), a Hobbsian world can crest into society. According to Hobbes, those who wish to subside from natural anarchy must implicitly surrender some personal freedom in exchange for societal order. Hobbes philosophies influenced many of his contemporaries and subsequent intellectuals, including Voltaire, demonstrated in his satire, Candide. At premier glance, Candide seems to be a strict manifestation of Hobbsian philosophy an anarchistic world centered around war, relieved only through the yield of personal freedom for communal order-Eldorado and the garden. Yet af ter a thorough interrogatory of the work, one recognizes that the characters in Candide are not Hobbsian. Hobbsian man is innately selfish and ambitious while Voltaires characters are not. Perhaps some characters in Candide are driven through their misfortunes as a result of their avarice however, this foible can not be ascribed as innately human. Instead, avarice, in the world of Candide, arises as a byproduct of the fallibility of man-made institutions (that is, religious and educational), which are the immemorial targets of Voltaires satire. Thus, the world of Candide, although structured like a Hobbsian world, contains men that are not Hobbsian. This d... ...the inability to cooperate. Or perhaps Voltaire suggests that the world can be controlled more(prenominal) effectively if the man-made institutions that he is satirizing could be somehow reorganized. All in all, Voltaires subtle divergence from strict Hobbsian philosophy enables him to pose perhaps unanswerable questio ns about mankind and our potentials.Works CitedBottiglia, William. Candides Garden. Voltaire A Collection of Critical Essays. newly Jersey Prentice-Hall, Inc., 1968. Hobbes, Thomas. Of Religion. ed.Smith,Lacey Baldwin and Jean Reeder Smith. The Past Speaks. 2nd ed. 1 vol. Lexington Heath, 1993. Richter, Peyton. Voltaire. Boston Twayne Publishers, 1980. Tsanoff, Radoslav. Voltaires Candide and the Critics. atomic number 20 Wadsworth Publishing Company, Inc., 1966. Voltaire. Candide. New York Viking Publishers, 1996.
capital of Wisconsin vs Marsh entirelyUpon the Declaration of Independence, a plan of confederation was offered to be wide-awake for the colonies. This plan, known as The Articles of Confederation, established a league of friendship among the states alternatively than a national presidential term. The most significant fact about the created political science was its weakness, it could not enforce even the limited powers it had. In crowd Madisons words, in his Federalist Paper 10 complaints are e verywhere heardthat our governments are too unstable. The states had won their freedom except had been unable to form a nation. They fought among themselves, suffered from severe economic depression, and came close to losing the recreation they had won in war. These political and economic factors generated pressure for the creation of a new national government and a disposition. In Madisons view, politics was overrun by different factions, which were groups of people who shared the aforesaid(prenominal) interests, different from other people or the opinion of the whole. These factions, he thought, prevented the government from its most important task, which in his opinion was to protect the owners of the land and property. The ownership of the land was divided according to peoples different skills, faculties, and according to Madison, the protection of these faculties is the first object of the government. And since the bulk of the people were farmers and poor, and since those who hold and those who are without property have ever create distinct interests in society, Madison wanted a constitution that would give the government the power to control the majority. In his address to the American Bar Association, Thurgood Marshall criticizes the constitution by saying that I do not believe that the content of the Constitution was forever fixed at the Philadelphia convention. In his opinion the government that they devised was defective from the beginning, mean ing that the Constitution required several amendments before it became what people today give as the basic structure of the American government. The constitution is very different today than what the framers began to construct two centuries ago. Marshall thinks that there was very much wrong with the original document, he finds many inherent defects, but is free to admit that it was a product of its times and embodied a via media that, under other circumstances, would not have been made. By this he means the contradiction between promising liberty and justice for all and denying both from blacks.
Wednesday, March 27, 2019
The Complex Character of Amanda in The Glass Menagerie Amanda Wingfield in The Glass Menagerie furnishes an excellent example of a carefully crafted, tortuous character whose speech and action arise from the psychological be created by the playwright. In his character description, Tennessee Williams starts his reader on the road to discovering Amandas complexity. AMANDA WINGFIELD the mother. A atomic woman of great but confused vitality clinging frantically to a nonher(prenominal) time and place. Her characterization must be carefully created, not copied from type. She is not paranoiac, but her life is paranoia. There is much to admire in Amanda, and as much to love and pity as there is to laugh at. for certain she has endurance and a kind of heroism, and though her foolishness makes her unwittingly savage at times, there is tenderness in her slight person. (Williams 781) Before the jump lines are spoken Amandas complexity is established(Falk 126) by the nuances and contrast s given here. This staple fibre description must be laid over all converse and action throughout the play so as to preserve the fullness of Amandas character at times when only portions of her nature are being exhibited. The complexity of Amandas character directly affects her action and dialogue with her children. In her subroutine as mother she exhibits an overwhelming desire to see her children succeed in life. In trying to... ...ding Plays. Boston Allyn, 1990. 307-314. Bigsby, C.W.E. A Critical Introduction to Twentieth-Century American Drama. Vol. 2. Cambridge Cambridge UP, 1984. Falk, Signi. The Southern Gentlewoman. Modern Critical Interpretations Tennessee Williams The Glass Menagerie. ed. Harold Bloom. NY Chelsea House Publishers, 1988. Jackson, Esther Merle. The Broken creative activity of Tennessee Williams. Madison & of Wisconsin P, 1965. Parker, R.B., ed. Twentieth Century Interpretations of The Glass Menagerie. Englewood Cliffs Prentice, 1983. Williams, Tenness ee. The Glass Menagerie. Masterpieces of the Drama. Ed. Alexander W. Allison, Arthus J. Carr, Arthur M. Eastman. fifth ed. NY Macmillan, 1986. 779- 814.