Jeffersonian vs. Jacksonian Democracy

Jeffersonian vs. Jacksonian Democracy Both Jefferson and Jackson were fighting for the interests of farmers against the commercial and mercantile interests of the country. Jefferson was portrayed as a man of the people, but he remained a wealthy planter who tended to associate only with other elites. His mannerisms were much more upper-class. Jefferson talked about limited government yet his actual practices as President differed. He maintained the bank of the US, authorized the Louisiana Purchase and pushed for stronger party cohesion, all things that many Democrats opposed.Jackson was also a wealthy farmer, but he had come from a poorer region and did not have â€Å"wealthy parents. † He was much more comfortable mixing with people of lower social and economic classes. He was also much more focused on attacking the mercantile classes, particularly his refusal to renew the charter for the Bank of the US. Thomas Jefferson and Andrew Jackson were two influential political figur es in two very different eras. Each formed their own democracy that helped shape the way people think about American government.They had their differences and yet they also had their similarities. Viewpoints between the two democracies will be analyzed in political, economic, social, and religious aspects. The Jeffersonian and Jacksonian Democracies were alike and different to each other in the area of politics and economics. The conditions which a citizen was considered eligible for office holding was similar. In the Jeffersonian Democracy, an eligible citizen was one that was average rather than rich and well born.Jackson declared all ordinary and intelligent white citizens equally qualified to serve. He eventually started what is known as the â€Å"spoils system† in which long-term officeholders were removed for rotation. Then how they chose candidates to be President was done differently. In Jefferson's time the two highest voted candidates became the President and the Vi ce-President of the United States. In Jackson’s time a candidate was chosen by a nominating convention and the President and Vice-President ran for their offices separately.Both men's attitude toward the Bank of the United States was similar. Jefferson encouraged State banks and was originally opposed to the national bank. Jackson and his followers strongly opposed the Second Bank of America. He won the â€Å"Bank War† by having federal income deposited in state banks, while he continued to draw money out of the national bank. The political and economic conditions of the Jeffersonian and Jacksonian Democracies were equally related and different. However, the social and religious aspects were quite clear.Each man’s attitude toward minorities (including slaves, women, and Native Americans) were closely related. For example, Jefferson doubted that white civilization and Indian â€Å"savagery† could coexist and although he said that men were born to freedom n ot to slavery he still held many slaves. He felt strongly that women had a single purpose in life: marriage and subordination to a husband. Jefferson saw no reason to let them vote since women were never called upon to discuss politics or anything really for that matter.In the same manner, Jackson turned away from extending egalitarian policies to slaves and women received little betterment, although many reforms were taking place in the time of the Jacksonian Democracy. Jackson, who also led an expedition against in Spanish Florida in 1818, forced thousands of Native Americans to march from Georgia to Oklahoma on the infamous â€Å"Trail of Tears. † Each man viewed education in opposite opinions. One of the many bills Jefferson proposed was the Bill for General Education, which â€Å"allowed everyone, without regard to birth or wealth, to have as much free education as each person was fitted for. On the other hand, Jackson and his followers opposed programs such as educati onal reform and the establishment of public education. He believed that schools restricted individual liberty by interfering with parental responsibility and undermined freedom of religion by replacing church schools. How the separation of church and state was accomplished was different. Jefferson proposed the Statute for Religious Freedom, separating church and state and removing the private right of religious belief from control by public law.Jackson believed that a strong federal government restricted individual freedom and he was against religious reform. The social and religious viewpoints of Jefferson and Jackson had their similarities and their differences. It is clear to see how distinct the similarities and differences were between the Jeffersonian and Jacksonian Democracies. They are shown in the areas of politics, economics, social life, and religion. Their viewpoints, opinions, and or ideas all helped establish the strong democracy that America has today.

Respond To Pupils’ Use Of Home Language

Karen is working with a small group of children who have brought a toy in from home and have been asked to talk about it to the rest of the group. Ben is from Wales and has a very broad accent which is different from other children in the group, who are from London. When Ben stands and starts to talk a girl in the group starts laughing with her friend and tries to imitate him. What should Karen do? Why is it important not to ignore the pupils who laugh? Karen should talk to the girls who were laughing and explain that every person is a unique individual and we all have differences.They may not have intended to upset Ben or realise the impact their behaviour could have on him. She should ask the girls how they would feel if somebody laughed at them because of their accent or their appearance or other factor that is beyond their control. Considering the feelings of other people should always be encouraged. It is extremely important not to ignore this behaviour as pupils may think that it is acceptable to do this. Ben could become upset and feel isolated, which could have a serious impact on his self-confidence.His work may also be affected, he may not want to attend school, become withdrawn or even start to display unacceptable behaviour himself. To help promote diversity, Ben should be encouraged to talk to his peers about where he is from. If Ben speaks Welsh, he could teach a few basic words to the class. At Meadow View, some teachers encourage children to answer the register in a different language. A situation like this would be ideal to educate students about Ben’s background and hopefully make him feel included and accepted amongst his classmates.

Management Of Transient Ischaemic Attacks Health And Social Care Essay

The NICE guidelines and the National Stroke Strategy ( 2008 ) emphasises the importance of measuring all patients with a suspected TIA within a hebdomad and all high hazard patients within 24 hours. This is to enable originating appropriate direction. This includes life manner steps such as weight decrease, smoking surcease, cutting back on intoxicant etc. in add-on to turn toing hazard factors for shot. Suitable patients are referred for surgical intercession. This systematic reappraisal will look at all these issues and expression at the grounds for medical and surgical intercessions and the timing of the surgery, the type of surgery etc. Around 15,000 people per twelvemonth have a suspected TIA but presently merely 35 % of people are investigated and managed in a timely manner. There is a 20 % hazard of shot within the first 4 hebdomads after shot. Investigating and handling bad patients with TIA within 24 hours could bring forth an 80 % decrease in the figure of people who go on to hold a full shot. The hazard of shot after a TIA is approximately 12 % in the first twelvemonth and so about 7 % per twelvemonth thenceforth. There is a high hazard of shot in the seven yearss after TIA, perchance every bit high as 10 % . The hazard of shot, bosom onslaught or vascular decease is about 10 % a twelvemonth. This is approximately seven times the hazard in the background population. [ From thee Stroke Website ]PurposesThe intent of this reappraisal is to discourse the rapid appraisal and early direction aimed at cut downing ischemic encephalon harm, and in the instance of TIAs, forestalling subsequent shot. This will be achie ved by utilizing the most recent and up-to-date grounds from the literature.IntroductionA transeunt ischemic onslaught ( TIA ) is defined as an acute loss of focal encephalon or monocular map with symptoms enduring less than 24 hours and which is thought to be caused by unequal cerebral or optic blood supply as a consequence of arterial thrombosis, low flow or intercalation associated with arterial, cardiac or hematologic disease. [ Hatano 1976 – Page 1 G.Book ] . More late in 2002, Albers et Als proposed a revised definition for TIA, adding that there is no grounds of acute infarction on encephalon imagination. Infracted tissue is non ever obvious on imagination and so this definition has non yet been widely adopted. Stroke is the 3rd most common cause of mortality in the developed universe and there are a figure of preventable causes. Over the past 30 old ages, the direction of shot has changed at a phenomenal rate. New probes help direct patient choice for specific therapies and may well increase the opportunity of a successful curative result. Specialists have seen a broad scope of therapies introduced for the direction of TIAs and acute ischemic shot. These progresss have led to a theoretical account displacement in intervention, which is apparent in the protective direction of shot victims today.Methods( See ‘Methods ‘ in Appendix 1 ) .Epidemiology of TIAFor us to understand the clinical direction of TIAs and shots, to be after clinical services or to plan randomised controlled tests, and to mensurate the overall impact of interventions, it is of import to understand the epidemiology of TIAs and shots. Each twelvemonth at that place are about one million shots in Europe. [ Sudlow and Warlow – Pg 3 G.Book ] . Approximately 25 % of work forces and 20 % of adult females can anticipate to hold a shot if they live to be 85 old ages old and shot is the 2nd most common cause of decease worldwide. [ Murray and Lopez 1996 – Pg 3 G.Book ] . Mortality information underestimates the true load of shot since in contrast to coronary bosom disease and malignant neoplastic disease, the major load of shot is chronic disablement instead than decease [ Wolfe page 4 g.book ] . Strokes cause 23 % of healthy old ages lost and about 50 % of old ages of life lived with disablement in Europe. Stroke causes many secondary unwellness such as ; dementedness, depression, epilepsy, falls and breaks. In the UK the costs of shot are estimated to be about twice those of coronary bosom disease, accounting for about 6 % of entire NHS outgo. [ Rothwell 2001 – Pg4 G.Book ] . In add-on to shots, TIAs are besides common, and it is estimated that 54,000 TIAs occur yearly in England. Rothwell and Warlow estimate that about 20 % of shots are preceded by a TIA. MRI of patients who have suffered a TIA lasting longer than an hr shows that over 50 % have seeable countries of infarction. Technically they have non suffered a ‘stroke ‘ but a intellectual infarction. This emphasizes that TIA and shot are a continuum. The epidemiology of TIA is a batch more ambitious than that of shots since patients with TIAs are more heterogenous and present to a assortment of different clinical services, if they present to medical attending at all. Furthermore, dependable diagnosing of TIA requires early and adept clinical appraisal, as there is no diagnostic trial for TIA, doing epidemiological surveies really labour intensive and expensive.Aetiology and Clinical PresentationThe causes of TIAs are the same as the causes of shot, with the caution that the huge bulk of TIAs appear to be caused by ischemia instead than haemmorhage. In a TIA it is of import to find the site of the cerebrovascular lesion since this narrows down the likely implicit in aetiology and enables appropriate aiming of probes. The differential diagnosing of TIA differs from that of shot due to the transeunt nature of its symptoms. Hints in the history and on scrutiny can direct the tester to the likely underlying cause, enabling specific intervention to commence and secondary bar. [ Pg 113 G. Book – first parity ] A diagnosing of TIA is supported by a sudden oncoming and definite ‘focal ‘ symptoms, sudden oncoming and definite focal symptoms in the history and grounds of vascular disease on scrutiny [ manus et Al Pg 104 G. book ] . The most common of the symptoms can be seen in Table Ten:SymptomsFrequency ( % )Unilateral failing, weightiness, or awkwardness 50 Unilateral sensory symptoms 35 Dysarthrias 23 Transient Monocular Blindness ( Amaurosis Fugax ) 18 Dysphasia 18 Ataxia 12 Bilateral coincident sightlessness 7 Dizziness 5 Homonymic Hemianopia 5 Diplopia 5 Bilateral Motor Loss 4 Dysphagia 1 Crossed Sensory and Motor Loss 1 The symptoms of a TIA enable classification of onslaught by arterial district affected ; carotid in about 80 % or vertebrobasilar in 20 % . This has of import deductions for farther probe and secondary bar. There are no trials to corroborate a TIA, and the gilded criterion method of diagnosing remains a thorough clinical appraisal every bit shortly as possible after the event by an experient shot doctor, although the coming of new imaging techniques, peculiarly diffusion weighted MRI has allowed the diagnosing to be made or excluded with more certainty in some patients.Probes and Imaging/Diagnosing techniquesThe function of imaging in TIA is to corroborate the diagnosing, confirm the vascular district affected ( where the lesion may be ) , and to place those people who would profit from carotid intercession. [ 1- pg 8 Imaging Guidelines ] . The chief modes for imaging the encephalon parenchyma are CT and MRI. These are progressively being used to measure the intellectual vasculature in TIAs. In TIAs and minor shots neuro-imaging is required to: Exclude stroke mimics Distinguish between haemorrhagic and ischaemic events Determine the Aetiology, eg: carotid stricture with lesions in multiple vascular districts Identify patients at high hazard of early recurrent shot, in order to aim suited intervention. Sensitivity and specificity of different imaging modes varies with the pre-test chance, the nature of the lesion, the hold from event to imagination, whilst expertness in imaging techniques besides varies greatly. Hence when doing determinations about imagination after TIA, the pick of imagination will depend on all these factors, every bit good as patient safety, tolerability and contraindications. For illustration see Table X, for the advantages and disadvantage of CT versus MRI in TIA and minor shot. [ Page 132 – G.Book ] .Imaging ModalityAdvantagesDisadvantagesConnecticutLow Cost and broad handiness Low sensitiveness for little acute ischemic lesions Superior sensing of haemmorhage in early stage Low sensitiveness for mimics, particularly tumors. Radiation exposure IV contrast is nephrotoxic and potentially allergenic.Magnetic resonance imagingSuperior sensitiveness for shot mimics Patient tolerability and contraindications Provides predictive information. Superior sensing of bleeding in the subacute and chronic stage Table – Advantages and Disadvantages of CT and MRI in minor shot and TIA. In cohorts of patients with suspected TIA who were referred straight for scanning by primary attention doctors, prior to expert reappraisal by a shot doctor, rates of alternate diagnosings were high, likely reflecting high rates of misdiagnosis prior to imaging. [ Lemesle et Al 1998 – G.Book Page 132 ]Non-Radiological Probes for TIAFirst-line probes include ; basic blood and urine trials at presentation. Table Ten shows the baseline non-imaging trials for TIAs and shots.ProbeDisorders detectedFull Blood Count Anemia Polycythaemia Leukemia Thrombocythaemia/thrombocytopenia Erythrocyte Sedimentation Rate/ C-Reactive Protein Vasculitis Infective Endocarditis Hyperviscosity Myxoma Electrolytes Hyponatraemia Hypokalaemia Urea Nephritic Damage Plasma Glucose Diabetess Hypoglycemia Plasma Lipids Lipemia Urine Analysis Diabetess Nephritic Disease Vasculitis Second-line probes must be chosen suitably since the likeliness of a relevant consequence depends on the choice of patients and farther probe will incur more cost. [ Page 174 G.Book ] . Cardiac jobs such as AF – echocardiogram may demo atrial thrombus, aneurism of the anterior wall of the left ventricle with mural thrombus, atrial myxoma or left side valve disease. Cardiac monitoring may demo paroxysmal AF. Doppler surveies of the carotid and vertebral arterias may demo contracting. This probe may be followed by Carotid angiography and Carotid endarterectomy if stricture is a least 70 % . It may be argued that full probe for CHD should be initiated, as the most common cause of decease after TIA is MI. Table 1 Secondary probes by the specializer servicesShort-run forecast after TIARecent research has shown that the hazard of shot instantly after TIA is considerable [ Giles and Rothwell 2007, pg 195 G.book ] . However, this poses a challenge to clinical services because it leaves many TIA sick persons at a hazard of a major shot in the short term. Predictive tools have been developed to place patients at high and low hazard in order to inform public instruction, assistance effectual triage to secondary attention and direct secondary preventative intervention. Datas from population-based surveies and tests suggest that 20 % of patients with shots have a preceding TIA. [ Rothwell and Warlow 2005 – Pg 195 G.Book ] . A recent systematic reappraisal identified 18 independent cohorts, all published since 2000, describing shot hazard in 10,126 patients with TIA [ Giles and Rothwell 2007 – Pg 196 G.Book ] . 3.1 % shot hazard at two yearss and 5.2 % shot hazard at seven yearss.ABCD2 score – proof? i? See Document 48395 – Page 9 of 27.A new marking system for two twenty-four hours hazard of shot following TIA, dubed ABCD2. The Hazard factors employed in the ABCD2 marking system for 2 twenty-four hours hazard of post-TIA can be seen in table Ten:Hazard FactorValuessPointsAge a†°? 60 old ages1Blood Pressure lift ( either/or ) Systolic a†°? 140 millimeter Hg Diastolic a†°? 90 millimeter Hg1Clinical Features ( either/or ) Unilateral failing Speech damage without failing21Duration of TIA a†°? 60 min 10-59 min21Diabetess Yes/ No1( Reference = Johnston SC et al – Lancet 2007 369 ( 9558 ) :283-292. )Recognition of Symptoms and delays to directionPressing direction of patients with TIA depends upon the right acknowledgment of symptoms and appropriate action by patients and their fleet triage to specialist attention where probe and intervention are quickly initiated. Public consciousness and behavioral surveies are missing, nevertheless, one survey of cognition among the general populace indicated that 2.3 % of a indiscriminately selected sample of people in the USA have been told by a doctor that they had a TIA, based on self-report in a telephone study conducted in 2003 [ Johnston et al – Pg 239 G.Book ] . However an extra 3.2 % of respondents recalled symptoms consistent with TIA but had non sought medical attending at all and accordingly had non been diagnosed by a physician. Of those with ‘diagnosed ‘ TIA, merely 64 % had seen a physician within 24 hours of the event. Merely 8.2 % right related the definition of TIA, and 8.6 % were able to place a typical symptom. This suggests that frequent public instruction is required non merely on the nature of a TIA but besides what to make in the event of one.Recognition ToolsSeveral tools have been devised to help the right acknowledgment of shot and TIA symptoms. In the pre-hospit al scene, FAST, LAPPS and CPSS have been designed for usage by exigency services to guarantee rapid conveyance of patients to specialist attention. In the exigency puting ROSIER mark has been designed to help exigency doctors in diagnosing. The chief purpose of these tools has been to increase the Numberss of patients showing to hospital within three hours and, therefore, addition eligibility interventions. However due to the increasing accent on rapid direction for minor shot and TIA, their usage in informing public instruction and right diagnosing of minor shot and TIA is likely to go more widespread. The ABCD system was so developed to foretell the early hazard of shot following a TIA, and one of its chief utilizations has been in triage between primary and secondary attention. [ Rothwell et all 2005 – pg 241 G. book ] .Discussion of the Management of TIAs – Critical Reviewing( Use Diagrams and Tables ) Although the acute intervention of major shot, TIA and minor shot have many common elements, there are of import differences. In the acute intervention of TIA, the purpose is secondary bar of a disenabling shot, which might follow in the immediate hours and yearss after the initial event, as opposed to reversal of any neurological shortage caused by the shot itself. To cut down the hold in intervention, improved public instruction and improved triage to secondary attention and coordinated patient direction in specialist units are critical facets of intervention in TIAs. However there is a greater focal point on pressing, effectual secondary bar for TIA and minor shot. Although the construct of TIA arose in the 1950s and interventions for it were proven effectual, it was non until 2007 that the first studies were published on the feasibleness and effectivity of pressing appraisal and intervention of TIA in specialist units [ Rothwell 2007 – Pg 239 G.Book ] .Lifestyle AlterationAll tobacco users, including those with a history of shot or TIA, should be advised to halt, and intercessions such as guidance, nicotine replacing should be used if needed to assist them accomplish this. [ 257-263 ] . Avoiding extra intoxicant is reasonable and everyone including those who have suffered from a TIA or shot, should avoid heavy imbibing. Although a twosome of units of intoxicant per twenty-four hours may protect against future vascular events. [ 274-276 ] Reducing dietetic salt intake reduces BP, peculiarly in the aged with high BP, possibly ensuing in long term decrease in vascular events. It may besides assist those on antihypertensive medicine to halt their intervention without a rise in BP. It is advisable for old TIA or stroke sick persons to cut down consumption of concentrated fat, since it produces moderate decrease in cholesterin degrees, which are associated with little decreases in vascular events. [ 279-281 ] . Corpulent persons should be encouraged to lose weight utilizing dietetic or if necessary pharmacoligcal or surgical intercessions. All patients should have general advice about a healthy diet, low in concentrated fats, with plentifulness of fish, fruit, fiber and veggies. These intercessions have good effects on vascular hazard factors and seem likely to bring forth little decreases in vascular results despite there being no clear grounds that they do. [ 286-289 ]The Medical Management – Secondary PreventionNumerous interventions have been shown to forestall shot in the long term after a TIA, including antiplatelet agents such as acetylsalicylic acid, clopidogrel, and the combination of low-dose acetylsalicylic acid and extended release dipyridamole [ CAPRIE 1996 – pg241 GB ] ; blood force per unit area take downing drugs [ PROGRESS 2001 ] ; statins [ Amarence et Al 2006 ] ; anticoagulation for atrial fibrillation [ European atrial sibrillation test survey group 1993 ] ; and endarterectomy for diagnostic carotid arteria stricture & gt ; or equal to 50 % [ Rothwell 2003-04 ] . If the effects of all these interventions are independent, combined usage of all these intercessions in the appropriate patients would be predicted to cut down hazard of recurrent shot by 80-90 % [ Hackam and Spence 2007 Pg241 GB ] . However tests of intervention in acute shot suggest that the benefits of several of these intercessions are even greater in the acute stage, until late there has merely been few dependable informations on the benefits of ague intervention after TIA. NICE guidelines suggest that appraisal and probe should be completed within one hebdomad of a TIA. [ Wolfe 1999, Johnston 2006, NICE 2008 – pg 242 GB ] . Rapid intervention of TIA can forestall up to 80 % of recurrent shots. [ Rothewell Pg 285 GB ] . There is considerable grounds associating to the effectivity of assorted interventions to cut down the hazards of vascular events after TIA and shot. See Table 1:DrugTestTreatmentAspirinCastAspirin versus placebo within 48 hours of major ischemic shotISTAspirin versus placebo ( and SC heparin versus placebo ) acutely after major ischemic shot.Anti-thrombotic Trialists ‘ CollaborationMeta-analysis of tests analyzing antiplatelet agents in patients at high hazard of occlusive vascular disease. DipyridamoleClairvoyances 2Aspirin and Modified Release Dipyridamole versus placebo in a 2Ãâ€"2 factorial design started within 3 months of TIA or ischemic shot.EspritAspirin versus acetylsalicylic acid plus dipyridamole started within 6 months of TIA or minor shot. ClopidogrelMatchClopidogrel versus acetylsalicylic acid plus clopidogrel within 6 months of ischemic shot or TIA.CharismaAspirin versus acetylsalicylic acid plus clopidogrel in patients with cardiovascular disease or multiple hazard factors ( including ischemic shot )FASTERAspirin versus acetylsalicylic acid plus clopidogrel in the ague stage after TIA or minor ischemic shot. Antihypertensive DrugsAdvancementPerindopril plus or minus Indapamide versus placebo after TIA or ischemic shot in patients with or without high blood pressure. Cholesterol-lowering drugsHorsepowerSimvastatin versus placebo in patients with coronary disease or other occlusive vascular disease including TIA or shot.SPARCLAtorvastatin versus placebo started within 1 to 6 months of TIA or ischemic shot. Table: Major tests and meta-analyses lending to the grounds base for medical intervention in secondary bar after TIA and ischemic shotVariation in intervention worldwide:Unsurprisingly there is considerable international fluctuation in how patients with suspected TIA are treated in the acute stage, possibly due to the historical deficiency of grounds. For case, Gallic and German health care systems provide immediate exigency inmate attention and the average infirmary stay is about seven yearss [ albucher ] , whilst other systems ( such as Canada ) provide non-emergency outpatient clinic appraisal [ Johnston and Smith 1999, Goldstein 2000 – pg 242 ] . For illustration a Canadian survey showed that in more than one tierce of the patients, antithrombotic therapy was non prescribed on discharge. In the UK, the standard agencies of appraisal and direction is a neurovascular outpatient clinic ( â€Å" TIA Clinic † ) [ Intercollegiate working party for Stroke 2004 – Pag e 242 ] .Antiplatelet AgentsSeveral big controlled tests have now compared antithrombotic therapy ( antiplatelet or anticoagulant agents ) versus control in acute ischemic shot these have been big and have provided dependable grounds on safety or efficaciousness. Antiplatelet drugs such as acetylsalicylic acids can be effectual in the secondary bar of ‘serious vascular events ‘ ( Stroke, MI, and Vascular decease ) [ 12 from the IST survey ] . If taken for a few old ages after a myocardial infarction, ischemic shot, or transeunt ischemic onslaught ( TIA ) , antiplatelet therapy typically avoids about 40 serious vascular events per 1000 patients treated. In acute ischemic shot there is significant thrombocyte activation, which can be inhibited by acetylsalicylic acid. [ 2,14,15,16 from IST ] . Aspirin was by far the most widely studied antiplatelet drug in the ATT ( antithrombotics triallists coaction ) reappraisal. Among about 60,000 high hazard patients, excepting those with acute ischemic shot, aspirin entirely reduced the odds of a serious vascular event by one one-fourth. Almost 10,000 of these patients had a anterior TIA or ischemic shot. Aspirin significantly reduced the comparative odds of a serious vascular event by 17 % , matching to an absolute hazard decrease of 30 per 1000 over 3 old ages. Controversy has surrounded the most appropriate dosage of acetylsalicylic acid, clinicians have argued about doses runing from 30 milligrams to 1500 mg. [ 158-160 Big book chapter 16 ] . Theoretical grounds suggest lower doses might in fact be more good than higher doses. After sing all the available grounds from direct and indirect comparings in bad patients, it seems sensible to reason that acetylsalicylic acid at a dosage of 75-150 mg day-to-day is every bit effectual as higher doses and is most appropriate for long-run secondary bar of serious vascular events to maximise benefits and to minimise inauspicious effects. Doses below 75 milligrams day-to-day may be as effectual, but this still remains rather unsure. Patients with TIA or acute shot, should be treated with acetylsalicylic acid every bit shortly as operable after encephalon imagination has excluded bleeding. Sandercock et al 2003 reviewed two really big randomised controlled test ( International Stroke Collaborative Group 1997 ( IST ) and Chinese Acute Stroke Trial Collaborative Group ( CAST ) which together randomised over 40,000 patients. Sandercock clearly established that get downing aspirin therapy within the first 48 hours of acute ischemic shot avoids decease or disablement at six months for about 10 patients per 1000 patients treated. A farther 10 patients per 1,000 treated will retrieve wholly. intracranial and extracranial bleeding are reported with aspirin therapy but this has low rates, and it is offset by the benefit of excess lives saved. In the IST, patients were allocated, in an unfastened factorial design, to intervention policies of: 300 milligrams aspirin daily, Lipo-Hepin, the combination, or to ‘avoid both acetylsalicylic acids and Lipo-Hepin ‘ for 14 yearss. In the CAST, patients were allocated, in a double-blind design, to 1 month of 160mg aspirin day-to-day or fiting placebo [ Get references 156 and 157 from Chapter 12 -Big Book ] . There is no clear consensus about whether acetylsalicylic acid should be given before encephalon imagination. This is applicable in state of affairss where entree to imagination is delayed or where drugs could be administered by ambulance staff. [ IST 1997 ] There is besides no clear grounds that any peculiar dosage of acetylsalicylic acid is more effectual that others. However symptoms of aspirin toxicity are dose-related, so the smallest effectual dosage should be used. Initial dosage of 150-300mg per twenty-four hours is advised for the acute stage, followed by long-run intervention with 75-150mg per twenty-four hours. Patients intolerant to aspirin should be treated with clopidogrel or with dipryidamole, these newer agents are well more dearly-won than acetylsalicylic acids.Alternate Antiplatelet therapies/regimensAspirin acts on merely one of a figure of tracts taking to platelet activation and so thrombosis. Antiplatelet drugs moving through different tracts might hence be more effectual than aspirin if given as options to, or combined with, acetylsalicylic acid. Several recent big tests have provided information about alternate antiplatelet regimens. Clopidogrel V acetylsalicylic acid: A systematic reappraisal of RCTs of a thienopyridine V acetylsalicylic acid in bad patients identified 10 relevant tests in 26,865 patients. Aspirin was compared with clopidogrel in one test of 19,185 patients with ischemic shot and with ticlopidine in the staying nine tests in a sum of 7,633 patients, most of whom had a recent TIA or minor shot. Thienopyridines modestly and significantly reduced the odds of a serious vascular event compared with acetylsalicylic acid. [ 174 from chapter 16 BB ] . No important inauspicious effects were found in footings of bleeding. On the other manus the thienopyridines were associated with lower hazard of GI shed blooding. [ 174 ] . Few tests that have compared clopdogrel and ticlopidine have straight suggested better safety and tolerability with clopidogrel, doing it the theienopyridine of pick on safety evidences [ 183-185 BB ch 16 ] . In drumhead, clopidogrel is every bit effectual as acetylsalicylic acid and slightly perchance more so. The high cost of clopidogrel and the uncertainness of any extra benefit compared to aspirin do it unreasonable to propose that it should replace aspirin as the first pick antiplatelet drug for all patients at high vascular hazard. It is a sensible alternate antiplatelet drug for patients with a history of TIA or minor shot, who are truly allergic to aspirin. There is presently no grounds from RCTs to back up the usage of combination of clopidogrel plus acetylsalicylic acid to forestall vascular events in patients with TIAs. Antiplatelet therapy reduces the hazard of perennial vascular events after TIA. Most test informations concerns aspirin nevertheless, clopidogrel { CAPRIE Steering commission 1996 ) and drawn-out release dipyridamole ( Sivenius 1991 ) have besides been shown to be effectual in their ain mechanisms of action.Combination Antiplatelet therapy:The combination of acetylsalicylic acid and dipyridamole is more effectual than aspirin alone [ Diener et Al 1996, Halkes et al 2006 ) . This combination shows a comparative decrease in the hazard of perennial shot of around 30 % compared with aspirin entirely. On the contrary, the combination of clopidogrel and acetylsalicylic acid was non superior to clopidogrel entirely in secondary bar after shot, TIA or other vascular disease in the MATCH and CHARISMA tests. [ Diener et al 2004, Bhatt et al 2007 ] . However there was no important tendency towards benefit from combination antiplatelet intervention in the MATCH test, there was besides a higher hazard of bleeding after 18 months in the combination therapy, which was non evident until 4 months into the test. Consequently, it is possible that draw a bead oning along with a short class of clopidogrel may be effectual in the ague stage after a TIA and minor shot. Antiplatelet agents: – prevent extension of arterial thrombus, prevent thrombocyte collection in microcirculation, prevent re-embolisation from embolic beginning, cut down release of eicosanoids and other neurotoxic agents. Aspirin: – inhibits COX-1, cut downing dislocation of arachadonic acid to thromboxane A2 and thrombocyte granule release. Clopidogrel and other thienopyridines: – encirclement of thrombocyte membrane ADP receptors, suppressing ADP-dependent thrombocyte activation and granule release. Dipyridamole: – Inhibition of phosphodiesterase, doing lift of intracellular thrombocyte cyclicAMP and a attendant decrease in Ca suppressions ; this thrombocyte activation and granule releases. [ TABLE 24.2 – Page 287 G.B ]Anticoagulation and patients with AF:Immediate therapy with decoagulants such as LMWH, unfractionated Lipo-Hepin, and heparinoids in patients with acute ischemic shot is non associated with net short- or long-run benefit [ IST 2007 – Berge 2007, Wong et Al 2007 – Pg 258 GB. ] . These agents cut down the hazard of DVT and PE, but are associated with important hazard of intracranial bleeding, which is dose dependent. Patients in AF after a presumed TIA benefit from anticoagulation in the long-run to forestall a farther shot. However, the best clip to get down therapy after an ischemic shot is ill-defined as the hazard of bleeding is hard to foretell. [ IST – Donnell 2006 – pg 258 GB ] . Patients in AF who have a TIA should be given anticoagulation therapy if there are no contraindications [ European Atrial Fibrillation Trial Study Group 1993,1995 ] . Recent surveies have shown that Coumadin is every bit safe as acetylsalicylic acid in aged patients with AF [ Rash et Al 2007, Mant et al 2007 ] . Patients with presumed cardioembolic TIA or stroke secondary to other causes should surely have antithrombotic therapy. Besides they may profit from anticoagulation in other cardiac fortunes, but at that place have been no randomised controlled tests in state of affairss other than non-valvular AF. Anticoagulation is non effectual in secondary bar of shot for patients in sinus beat. Warfarin intervention to a mark INR of 3-4.5 was associated with important injury due to a big addition in major hemorrhage complications, particularly intracerebral bleeding, in patients with old TIA – in the Stroke Prevention in Reversible Ischaemia Trial ( SPIRIT ) [ Algra et al 1997 ] The subsequent Warfarin versus Aspirin in the Secondary Prevention of Stroke ( WARSS ) test of aspirin versus Coumadin for patient in fistula beat and without cardioembolic beginning or with more than 50 % CAS ( carotid artery stricture ) showed no extra benefit for Coumadin at a mark INR of 1.4-2.8 [ Redman and Allen 2002 ] . There has been uncertainness as to whether anticoagulation is preferred to antiplatelet intervention for the secondary bar of ischemia relate to intracranial coronary artery disease. A robust randomised dual unsighted test ( WASID – Warfarin-Aspirin Diagnostic Intracranial Disease ) test of Coumadin, to a mark INR of 2-3, versus acetylsalicylic acid to 1300 milligrams per twenty-four hours in patients with 50-99 % stricture of a major intracranial arteria showed no important benefit for Coumadin over aspirin [ Chimowitz et Al 2005 – pg 287 G.B ] . In fact, Coumadin was associated with increased rate of bleeding and other inauspicious events ; as a consequence the survey was stopped early. However patients having Coumadin were in the curative scope for merely 63 % of the clip. Curative INR appeared to be associated with a much reduced incidence of ischemic shot and cardiac events, proposing that anticoagulation may supply increased benefit over acetylsalicylic acid if curative INR can be maintained much more systematically.FASTER: [ Kennedy FASTER et Al 2007 – pg 246 ]The FASTER randomised controlled pilot test, studied the benefit of clopidogrel versus placebo and Zocor versus placebo initiated within 24 hours of symptom onset in patients with TIA or minor shot, all were treated with aspirin [ Kennedy et Al 2007 – pg246 GB ] . The survey was stopped early owing to failure to recruit patients, likely due to the increased usage of lipid-lowering medicines during the survey period.Blood Pressure and Lipid take downi ng agents:There is some robust grounds from randomised tests to demo that blood force per unit area and cholesterin lowering are effectual for secondary bar of shot. The PROGRESS survey of perindopril and Lozal showed that BP decrease with an ACEi and diuretic get downing several hebdomads or months after TIA reduces the hazard of subsequent shot by about a 3rd. There is a positive correlativity between cholesterin and hazard of ischemic shot. Cholesterol take downing with lipid-lowering medicines reduces the hazard of shot in patients with old shot, coronary or peripheral vascular disease or diabetes. The Heart Protection Study 2002 did non demo a decrease in hazard of perennial shot on lipid-lowering medicines [ Collins et Al 2004 – pg 288 ] , perchance because patients were at low hazard of shot return since the incident shots occurred on mean 4.6 old ages before the survey oncoming. However the subsequent SPARCL test of Lipitor in patients who had had a shot or TIA within one to six months before survey entry showed a reduced overall shot hazard [ Amarenco et Al 2006 – page 288 ] . However there was a important parallel addition in hazard of hemorrhagic shot had been found in the HPS in the 3280 patients with old shot or TIA [ Collins et Al 2004 pg 288 ] . Lipid-lowering medicines should non, hence, be used in patients with old intracerebral bleeding unless there is a strong indicant related to the hazard of ischemic events.Cholesterol-lowering drugs:Meta-analyses found that larger decreases in LDL Cholesterol led to larger decreases in hazard of major vascular events and its constituent results, proposing that attachment to a statin regimen bring forthing a 1.5mmol/L decrease in LDL cholesterin would take to a decrease of about one tierce in the comparative hazard of major vascular events. The full benefits of cholesterin take downing with a lipid-lowering medicine emerged over the 2-3 old ages of intervention and continued for each twelvemonth that intervention was continued thenceforth. HPS was the largest of the RCTs in this meta-analysis. It included over 20,000 people. In a subsequent RCT, the SPARCL test, non included in the meta-anlysis, patients with a recent shot ( about all ischemic ) or TIA and no known coronary bosom disease were indiscriminately assigned to either atorvastatin 80 mg day-to-day or placebo for 5 old ages. The difference between HPS and SPARCL in the effects of of shot or TIA could be explained by opportunity, different intervention regimens, enlisting of patients earlier after their event in SPARCL, or a different balance between ischemic and hemorrhagic shot results. Both tests found similar comparative decreases of approximately 20 % in ischemic shot, and a 70 % or more increased relation hazard of hemorrhagic shot. Both tests found comparative decreases with a lipid-lowering medicine of approximately 20 % in major vascular events. [ See 119-120 ref from BB page 811 ] . There is really good grounds for routinely sing the usage of drawn-out lipid-lowering medicine intervention to take down cholesterl degrees in allpateints at high hazard of any type of major vascular event, including those with a anterior ischemic shot or TIA, and irrespective of the baseline cholesterin concentration. Treating 1000 people with a anterior ischemic shot or TIA for 5 old ages with a lipid-lowering medicine will take to the turning away of over 50 major vascular events. The grounds clearly suggests that cholesterin take downing with a lipid-lowering medicine should be considered in everybody with a history of an ischemic cerebrovascualr event. Lipid-lowering medicines are non recommended for those patients whose untreated cholesterin or LDL choleserol degrees are below 3.5 mmol/L in cholesterin and below 2.6 mmol/L in LDL choleseterol. It is besides non recommended to order a lipid-lowering medicine for patients with a history of intra intellectual bleeding ( ICH ) but no ischemic vascular events, since really few of these patients were included in the two chief RCTs. For those patients with a history of ICH who are besides considered to be at peculiar high hazard of future ischemic shot or coronary events, it is likely sensible to order a lipid-lowering medicine [ Page 814 Big Book ] . Evidence besides suggests that it may be good to get down the lipid-lowering medicine therapy in the first few yearss after the TIA. [ 134 Large book page 815 ] . To reason on lipid-lowering medicines ; intervention tends to get down with a lipid-lowering medicine every bit shortly as the diagnoss is made of a TIA with a baseline entire cholesterin of & gt ; 3.5 mmol/L or LDL cholesterin & gt ; 2.6 mmol/L. Both simvastatin 40mg day-to-day and atorvastatin 80mg daily have been shown to be good in these patients.SURGICAL INTERVENTION120,000 people have a TIA or shot every twelvemonth in the UKat least 10,000 might be suited for CEA yet merely 4500 are being performed each twelvemonth. Recently published NICE guidelines suggest that CEA should be done on appropriate patients in 2 hebdomads of presentation. There have been unacceptable holds between symptom and surgery in the UK. Merely a fifth of diagnostic patients have surgery within two hebdomads, which is the recommended NICE guidelines. Diagnostic CEA is pressing and should hold precedence over elected surgery. The recent GALA test shows that the first 1001 UK patients had a average hold between symptoms and surgery of 82 yearss [ 7 from BLUE BMJ Research article )Carotid Endarterectomy – Evidence of its benefitSurgical remotion of the atheromatic plaque from within the carotid arteria – the carotid endarterectomy ( CEA ) . Tests have proven that it is an effectual intervention for the secondary bar of shot in selected patients. CEA is associated with a assortment of possible complications such as shot and decease [ Naylor Ruckley, Bond et al – GB Ch 25 ] . It is apparent that surgery clearly prevents stroke in patients with diagnostic terrible CAS, but at a monetary value: hazard of shot as a effect of surgery, cost of surgery, hazard of other complications of surgery, cost of probes for choosing suited patients. Nowadays there is concern in the UK as to which patients should be offered surgery. [ 374 375 – BB- Ch 16 ] . As a consequence of big RCTs, it is now clear that CEA of late diagnostic terrible CAS about wholly abolishes the high hazard of ischemic shot over a period of 2-3 old ages. [ 369-371,445-447- Ch 16 BB ] . A clear advantage to surgery is shown when the diagnostic stricture exceeds 80 % diameter decrease of the arterial lms utilizing the ECST method ( European Carotid Surgery Trial ) , which is different to 70 % utilizing the NASCET method. In the NASCET test, CEA reduced the comparative hazard of shot by 65 % compared to medical intervention. The hazard of shot in patients with less than 60 % ( ECST ) stricture is so low, the hazard of surgery is non worthwhile for them. For patients with between 60 % and 80 % ( ECST ) stricture there is still some uncertainness as some of these may be at immense hazard of shot who gain from surgery. Whether the benefits of CEA or stenting in patients with symptomless stricture warrant the hazards and cost is still ill-defined, peculiarly in an epoch of improved medical interventions. ACST and ACAS, had absolute decreases in five-year hazard of shot with surgery were similar: 5.3 % and 5.1 % , severally.Carotid Stenting:Carotid stenting is less unpleasant and less invasive than carotid endarterectomy, and is more convenient and quicker. It is carried out under LA. Some little tests have compare stenting with CEA, and suggested that the procedural shot complication rate of stenting was similar to that of CEA and that there are fewer shots in the long-run. They besides showed that stenting might hold a higher hazard of shot and decease than CEA, and a higher rate of restenosis. The SPACE test is the largest survey comparing CEA with carotid stenting.Timing of SurgeryOptimum timing of surgery has been a extremely controversial subject [ 473-474 – ch 16 BB ] . Surgery should be performed every bit shortly as it is moderately safe to make so, given the really high early hazard of shot during the first few yearss and hebdomads after the TIA in patients with diagnostic CAS. [ 16-475 – ch 16 ] . In stable patients there is no difference between early and subsequently surgery. Thus for stable patients with TIA, benefit from endarterectomy is greatest if performed within 1 hebdomad of the event. [ 390 ch 16 ] However in exigency carotid enarterectomy patients with germinating symptoms ( sucha s stoke in development, crescendo TIA ) had a high operative hazard of shot and decease of 19.2 % which was much greater than that for stable patients 9390 – 477 ch 16 ] . Therefore there is still uncertainness about the balance of hazard and benefit of surgery within 24-72 hours of the presenting event. [ 475 478 479 – hc 16 ] . Merely a minority of patients with TIA are possible campaigners for carotid endarterectomy ( CEA ) or stenting, make up one's minding on surgical intercession instead than medical intervention entirely can be hard. In the ECST 30 % of patients with 90-99 % stricture had a shot in three old ages, 70 % did non. Both ECST and NASCET have two values for the stricture and this difference has been down to the manner the two tests underwent at that place angiographic techniques and to what extent the techniques used to mensurate stricture were accurate. ECST i? 70 % NASCET i? 50 % – WHY THE Difference? ? THE BIG AUDIT The DoH stroke scheme recommends that CEA should be carried out within 48 hours of symptoms, when the hazard of shot is highest, in patients with TIA who are neurologically stable. [ 17 BMJ ARTICLE ] . To accomplish this, utilizing FAST will assist public to recognize TIA and early shot [ 17 BMJ article ] . And the ABCD2 mark helps primary and secondary services to place those patients with TIA who are at highest hazard of shot. [ 18 BMJ Art. ] .Future Directions – How Potential Future Research may be designed to get the better of spreads and challengesMentionsAppendix 1:MethodsLiterature Search StrategyA controlled hunt scheme was employed to obtain informations from medical databases such as PubMed, EMBASE, MEDLINE ( Via PubMed ) , Web of Science, Science Direct ( Elsevier ) , and The Cochrane Library. I besides used the University MetaLib system. I used the capable hunt subdivision and selected ‘Health and Medicine ‘ as the chosen subject of research. It helped further my hunt for e-journals and articles. The systematic hunts were performed in September 2010 to place suited surveies and reappraisals that were published from 2000 until the present twenty-four hours ( i.e from the past ten old ages ) . Although some robust randomised controlled surveies were included which were necessarily dated back beyond this day of the month scope. Drawn-out hunts were made via cyberspace web sites and manual searching of diaries. Recently published, well-conducted systematic reappraisals and primary surveies were selected for inclusion in this systematic reappraisal. Interlending and Document Supply was besides used as a service provided by the Lancaster University Library, to recover some diary articles.Key WordssTranseunt Ischaemic Attack, TIA, TIA Management, Treatment, Current therapy, Anti-coagulation, antiplatelet drugs, acetylsalicylic acid, clopidogrel, dipyridamole, combination therapy, cerebrovascular accident, secondary bar.Using MeSH and seeking different Fieldss by using bounds enabled me to polish my consequences from databases. Any articles found within this hunt were so critically appraised ; their relevancy to this systematic reappraisal was besides so decided.Relevant diaries that were non found on the library MetaLib system, were searched for on Google Scholar and the page was taken straight to the database beginning site and so searched within the peculiar database archives. These include: Stroke, The Lancet, New England Journal of Medicine, European Journal of Vascular and Endovascular Surgery, Journal of Vascular surgery, An nals of Vascular surgery.

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Saunders notes that supporters of embryonic stem cell research contend that the research is beneficial to humankind; however, Saunders argues, the Nazis used this same reasoning to Justify research on the mentally ill, the disabled, and the feeble-minded. Prentice and Saunders are senior fellows at the Family Research Council, a onservative Christian think tank and lobbying organization. As you read, consider the following questions: 1. Why does Prentice claim that therapeutic cloning will lead to reproductive cloning? 2. What was the point of the Nuremberg Code, according to Saunders? 3. Why does Saunders say that therapeutic cloning violates the Nuremberg Code? Part I Cloning always starts with an embryo. The most common technique proposed for human cloning is called somatic cell nuclear transfer (SCNT). This cloning is accomplished by transferring the nucleus from a human somatic (body) cell into an egg cell which has had its chromosomes removed or inactivated. SCNT produces a human embryo who is virtually genetically identical to an existing or previously existing human being. Proponents of human cloning hold out two hopes for its use: (1) the creation of children for infertile couples (so-called reproductive cloning), and (2) the development of medical miracles to cure diseases by harvesting embryonic stem cells from the cloned embryos of patients (euphemistically termed therapeutic cloning). All Human Cloning Produces a Human Being All human cloning is reproductive. It creates†reproduces†a new, developing human intended to be virtually identical to the cloned subject. Both reproductive cloning and therapeutic cloning use exactly the same technique to create the clone, and the cloned embryos are indistinguishable. The process, as well as the product, is identical. The clone is created as a new, single-cell embryo and grown in the laboratory for a few days. Then it is either implanted in the womb of a surrogate mother (reproductive cloning) or destroyed to harvest its embryonic stem cells for experiments (therapeutic cloning). It is the same embryo, used for different purposes. In fact, the cloned embryo at that stage of development cannot be egg and sperm. Trying to call a cloned embryo something other than an embryo is not accurate or scientific. Biologically and genetically speaking, what is created is a human being; its species is Homo sapiens. It is neither fish nor fowl, neither monkey nor cow†it is human. Created in Order to Be Destroyed Therapeutic cloning is obviously not therapeutic for the embryo. The new human is specifically created in order to be destroyed as a source of tissue C, as Robert P. Lanza and colleagues report in a 2000 JAMA article]: [Therapeutic cloning] requires the deliberate creation and disaggregation ofa human embryo. Most cloned embryos do not even survive one week, to the blastocyst stage, when they are destroyed in the process of harvesting their cells. Experiments with lab animals show that even these early embryos have abnormalities in genetic expression. Beyond the abnormalities caused by the cloning procedure, embryonic stem cells from cloned embryos will still face problems for their use, including the tendency to form tumors, and significant difficulties in getting the cells to form the correct tissue and function normally. Therapeutic Cloning Leads to Reproductive Cloning Because there is no difference in the nuclear transfer technique or the cloned embryo, allowing therapeutic cloning experimentation to proceed will inevitably lead to reproductive cloning. The technique can be practiced and huge numbers of cloned embryos produced. In fact, the lead scientist of the South Korean team that first cloned human embryos in February 2004 in a press conference on their experiments that the cloning technique developed in their laboratory cannot be separated from reproductive cloning. His statement affirms what others have pointed out before: allowing therapeutic cloning simply prepares the way for eproductive cloning. Human cloning is unsafe and unnecessary. There are no valid or compelling grounds†scientific or medical†to proceed. A comprehensive ban on human cloning is the only sufficient answer. Part II As Dr. Prentice has shown, cloning indisputably destroys innocent human life. This basic truth should lead the world to reject human cloning. However, in an effort to extricate human cloning from this ethical vise grip, its supporters attempt to draw a distinction between human life, which begins at conception, and human personhood, which begins only at their say-so. Unfortunately, the arbitrary denial f personhood to human beings has a long and cruel history. The Nuremberg Code, formulated in the years after World War II, is particularly instructive with regard to the current debate on human cloning. For instance, when the principal author of the report on human cloning issued by the National Academy of Sciences testified before the Presidents Council on Bioethics, he stated that reproductive cloning would violate the Nuremberg Code: The Nuremberg Code, with which I am in full agreement, outlines those kinds of things you would not simply [do] for the sake of knowledge that involve human subjects. The Nuremberg Code The Nuremberg Code is a body of ethical norms enunciated by the Nuremberg Tribunal, which, after World War II, had the responsibility of Judging the actions of the Nazis and their allies. The point of the code was to restate and apply the established ethical norms of the civilized world. Nazis Deemed Some Life Unworthy Nazi laws had defined Jews and other undesirables as non-persons. Eventually, camps and killed. However, before the killing in the camps began, the Nazis had engaged in an extensive campaign of euthanasia against the mentally and physically handicapped, which not only foreshadowed but also prepared the way for the xtermination camps. In his book The Nazi Doctors, Robert Jay Lifton draws our attention to a book titled The Permission to Destroy Life Unworthy of Life, written during the campaign. Lifton writes: [It was] published in 1920 and written Jointly by two German professors: the Jurist Karl Binding and Alfred Hoche, professor of psychiatry at the University of Freiburg. Carefully argued in the numbered-paragraph form of the traditional philosophical treatise, the book included as unworthy life not only the incurably ill but large segments of the mentally ill, the feeble-minded, and retarded and deformed children. T]he authors professionalized and medicalized the entire concept; destroying life unworthy of life was purely a healing treatment and a healing work. The Nazis were determined to cleanse the genetic pool to produce better Aryans. Nazi officials announced that under the direction of specialists all therapeutic possibilities will be administered according to the latest scientific knowledge. The result of this therapeutic treatment of inferior lives was that eventually a network of some thirty killing areas within existing institutions was set up throughout Germany and in Austria and Poland. In their book, The Nazi Doctors and the Nuremberg Code, George Annas and Michael Grodin reveal that: At the same time that forced sterilization and abortion were instituted for individuals of inferior genetic stock, sterilization and abortion for healthy German women were declared illegal and punishable (in some cases by death) as a crime against the German body. As one might imagine, Jews and others deemed racially suspect were exempted from these restrictions. On November 10, 1938, a Luneberg court legalized abortion for Jews. A decree of June 23, 1943, allowed for abortions for Polish workers, ut only if they were not Judged racially valuable. Later, the Nazis created the extermination camps for the Jews and other inferior races. In the camps, Nazi doctors engaged in cruel experiments on the Jews, Gypsies, Poles, and others. They exposed them to extreme cold to determine the temperature at which death would occur. They injected them with poisons to see how quickly certain lethal elements moved through the circulatory system. They subjected twins to all manner of disabling and brutal experiments to determine how genetically identical persons reacted to different conditions. Some of the experiments were nonetheless designed to preserve life†not of the subject, but of, for example, German pilots who were forced to parachute into freezing ocean waters. Everyone agrees the Nuremberg Code prohibits reproductive cloning. What relevance does it have for therapeutic cloning? If human embryos are human beings, then therapeutic cloning, which creates an embryo only to destroy it in the process of exploiting its stem cells, violates a cardinal principle of the Nuremberg Code: There is to be no experimentation on a human subject when it is known that death or disabling injury will result. Regardless of the good that might be produced by such experiments, the experiments are of their very nature an immoral use of human beings. Subverting the Meaning of Healing Recall how the Nazis subverted the meaning of heali ng. Recall how they used the them. Recall that the Nazis eliminated those unworthy of life in order to improve the genetic stock of Germany. Recall how the Nazis undertook lethal experiments on concentration camp inmates in order, in some cases, to find ways to preserve the lives of others. The point is not to suggest that those who support therapeutic cloning are, in any sense, Nazis. Rather, the point is to cause each of us to think deeply about whether there is any essential difference between the reality of those Nazi experiments and therapeutic cloning. As we have shown, each case involves a living human being, and that human being is killed in the aim of a perceived higher good. Cloning proponents try to distinguish between the two cases by saying that the cloned human being has no potential. But in each case, it is the actions of other human beings that rob the first of potential (in the first case, the actions of Nazi executioners; in the second, the laboratory technicians). In either case, the human ubject is full of potential simply by being a living human being. Of course, almost miraculously, many of the inmates of the camps did survive when the allies rescued them. Equally miraculously, frozen embryos have been implanted in a womans womb and brought to live (and healthy) birth. As we have shown, every embryo is not merely potentially a life, but [is an] actual life, a human being from the first moment of existence. Furthermore, any living human embryo has the inherent potential to develop into a healthy baby. It is disingenuous for supporters of cloning to claim the cloned human embryo is only potential life because they plan o mandate by law that it be destroyed before it can come to birth. Regardless of its location, the human embryo, by its nature, is full of potential, unless the actions of adult human beings deprive it of the opportunity to realize that potential. Guard Against Inhuman Acts [Russian author] Alexander Solzhenitsyn, a man who chronicled and suffered under another ideology that denied the dignity of each and every human being, observed, Gradually it was disclosed to me that the line separating good and evil passes not through states, nor between classes, nor between political parties either, but right hough every human heart, and through all human hearts. This line shifts. Inside us, it oscillates. Solzhenitsyn did not regard the perpetrators of brutal crimes in his own country as inhuman monsters. Rather, he saw the essential truth†they were human beings, engaged in immoral acts. They engaged in those acts by dehumanizing the persons on whom their brutality was inflicted, and they did so in the name of (perhaps in the passionate belief in) a greater good. But Solzhenitsyn reminds us that, unless we are willing to admit that, for the best as well as for the orst of motives, we are also capable of inhuman acts, we will have no guard against committing them. No one is safe from brutality so long as we think that it is only inhuman others who are capable of inhuman acts. Rather, we will be secure when we are willing to look honestly at the objective reality of our acts, while realizing that we, too, are capable of acts that violate the inherent dignity of another, and refuse to engage in such acts despite the good we believe would result from doing otherwise. In the debate over the cloning and destruction of embryonic human beings, this essential truth must be our guide. Books Brian Alexander Rapture: How Biotech Became the New Religion.

Properties of Dopamine in Chemistry

Properties of Dopamine in Chemistry Chapter 2. Literature Review 2.1 Introduction In recent years, natural adhesion has attracted increasing attention in the material engineering field. This can be mainly attributed to the marine mussel as it has a strong ability to attach to various surfaces in an aqueous environment where they reside. These surfaces vary from natural to synthetic, and inorganic to organic.[49-51] Previous studies on the mussel adhesive protein have discovered that 3,4-dihydroxy-L-phenylalanine-lysine sequences, may be the main contributor for the versatile nature of the marine mussel.[52, 53] Dopamine, having a similar structure with this sequence, may provide a new platform for bioengineers to physically or chemically enhance the performance of other biomaterials. Several papers have already been published regarding the use of dopamine to augment other biomaterials, such as poly (ethylene glycol), carbon nanotubes and nanofibers. The first part of this review will briefly introduce the basic properties of dopamine which will be followed by its applications 2.2 Properties of Dopamine Dopamine’s properties can be divided into chemical and adhesive properties. The chemical properties mainly focus on the autopolymerization in aerated basic solutions and polymerization of dopamine based on vinyl groups. The adhesive property is dopamine’s most significant feature which gives dopamine its advantage as a biomaterial. 2.2.1 Chemical Properties 2.2.1.1 Autopolymerization in Aerated Basic Solutions Messersmith and coworkers first reported that dopamine is able to auto-polymerize in aired Tris buffer of pH 8.5.[8]. The process of dopamine autopolymerization with a pre-existing substrate results in polydopamine (PDA) films being deposited on the substrate surface. Longer substrate exposure times and higher reaction temperatures result in thicker PDA films being formed.[54] Regardless of the surface type, the inserted PDA films can be coated on the desired surface, even poly(tetrafluoroethylene) (PTFE), known for its anti-adhesive property.[8] 2.2.1.2 Polymerization of Dopamine Based on Vinyl Groups Polymers carrying pendant dopamine are normally obtained by radical polymerization of vinyl monomers with protected or unprotected dopamine. When meditating protected dopamine carried by polymers with double bone, borax (Na2B4O7 ·10H2O) is widely used as the protecting reactant in order to keep dopamine from forming an annular bidentate catechol subunit.[55] Normally, the polymerized reaction of protected dopamine happens in a liquid solution and forms linear chains. Deprotection reaction usually occurs in an acidic environment and results in the polymer carrying dopamine. Dimolybdenum trioxide[56], 1-dromotoluene[57] and denzophenone chloride[58] can also be used as protecting agents. Zhang et al.[59] designed a novel polymer poly (n-acryloyl dopamine) that possesses high adhesion to wood, especially when mixed with polyethylenimine (PEI) at about 150 °C. They used a protected double bond dopamine as a monomer and 2,2’-azobis(2-methylpropionitrile) as an initiator via rad ical polymerization, following the deprotection of dopamine in an acid solution. When meditating unprotected dopamine, Lee BP et al.[60] was the first to report a creative hydrogel that copolymerizes modified dopamine with double bond and polyethylene glycol diacrylate via photo initiation by using a 2,20-dimethoxy-2-phenyl-acetonephenone (DMPA) initiator. As a result of this invention, greater attention has been given to hydrogels as a new artificial extracellular matrix (ECM) in the biomedical field. Dopamine belongs to the catechol family which leads to vinyled dopamine to act as an inhibitor.[61, 62], as a result they can react with radicals to inhibit polyreaction. The unprotected dopamine, modified with a vinyl group, is able to undergo free-radical polymerization. Several researches have done this experiment on radical polymerization to prove the reliability of this method.[63-75] The research group led by Metin Sitti, copolymerized a dopamine derivate (dopamine meth-acrylami de) with methoxyethylaceylate to obtain a reversible adhesion on the surface of nonflat glass under dry or wet condition.[65] In another publication, 2-(meth-acryloyloxy) ethyl phosphate was used to copolymerize with dopamine methacrylamide, followed by a complicated cohesion in which the copolymer bonded with positively charged polymer, divalent calcium and magnesium.[71] The chemical properties of dopamine provide the platform of its strong adhesive properties. 2.2.2 Adhesive Property The adhesive property of dopamine is one of the most significant properties of dopamine as it has proved to be very versatile in adhering to various surfaces despite the surface chemistry. The bonding between dopamine and surfaces can be generally distributed to two parts: covalent and non-covalent.[10] Surfaces which possess amine groups or thiol groups can covalently bind to dopamine via Michael addition or Schiff base reactions. However since most surfaces don’t have those groups, non-covalent bonding, like H-bond, Ï€-Ï€ interaction and benzenediolcharge-transfer compounds are preferred to generate a valid layer and metallic chelating.[7, 53, 76-87] In a high pH environment, metal ions and medal oxides have a high chance of being hydroxylated or hydrated, which make chelate with catechol groups of dopamine much easier. This can be seen from many experiments done on polydopamine linking with metal oxides (such as Fe2O3, Fe4O3, ZrO2) through chelating bonding interaction.[82, 84, 85] This can be seen when polydopamine nanoparticle suspensions are added to a solution of KMnO4 with H2SO4. A core-shell nanoparticle structure is created in which the polydopamine act as the core and MnO2 act as shell, followed by blending the KOH solution to obtain MnO2 nanospheres. This ad hesive property of dopamine provides promising opportunities for new bioengineered materials. 2.2.3 CNT For decades, carbon nanotubes (CNT) have been attracting increasing attention because of their superior features, such as thermal conductivity, excellent tensile strength and remarkable conductivity. They have been applied in various different areas, from sensors to catalysis, and from semiconductors to inductors for osteocytes. In order for CNTs to have a wide range of applications, surface modification is necessary. However, during this modification various intermediate reactions steps are required which increase the complexity of the CNT’s fabrication. Dopamine modification has been viewed as an promising alternative, leading to a coated multifunctional CNT with a polymeric shell that has tunable thickness by time, pH value and temperature.[88] The dopamine coating facilitates the addition of alternate modifications to the surface of CNTs, such as gold nanoparticles.[88] What’s more, CNTPDAs, first, were modified with ATRP initiator and then polymerized with diethyla mine methacrylateto to form brushes polymer — poly (dimethylamine-thyl methacrylate) (PDMAEMA) on the surface.[89] Following that the functionalized CNT were quaternized in order to combine palladium nanoparticles on the CNTs’ surface. These two examples indicate the capability of dopamine coated CNTs to bind to metal complexes. 2.3 Applications There are many different applications in which dopamine could be applied in; three of them will be the focus here including applications in hydrogels, nanofibers, and biosening. These fields are of great interest currently as they show great promise for dopamine in bioengineering. 2.3.1 Hydrogel The need of a viscous hydrogel, as a unique material, is dramatically increasing in various biomedical fields. The high performance requirements of adhesive hydrogels are strict and various. This includes being sufficiently adhesive in a wet environment, satisfactory elasticity of artificial tissue scaffold and biocompatible.[60, 90] Moreover, biomedical hydrogels also need a quick sol-gel conversion for avoiding surgical obstruction. Recently, adhesive hydrogel, inspired by strong wet adhesion of mussel and cross-bonding capabilities of dopamine, has been attracted increasing attention and considered as a hopeful candidate to fulfill this technologic niche.[91] Messersmith et al.[92] reported the creation of four different adhesive hydrogels using dopamine derivative (L-3,4-dihydroxyphenylalanine (DOPA)) as end-groups and poly(ethylene glycol) (PEG) as a backbone. The difference of these four hydrogels can be divided into 2 subcategories, linear network and branched network. They applied multiple-angle laser light scattering to study the influences of different oxidative reagents on DOPA oxidation and hydrogel formation. The result showed that gelation time of PEG-DOPA gels relied on oxidative reagents, such as concentration and type. In Lee H.’s report, they also used DOPA and PEG to form hydrogels, but this time they used DOPA modified with methacryloyl chloride and PEG diacrylate instead of pure DOPA and PEG. In order to avoid introducing toxicity of oxidative reagent to the hydrogels and any loss of adhesion, the hydrogels underwent UV initiation.[60] These photo-imitated gels demonstrate appreciable elastic properties for use as a promising biomedical material. Using a similar method Phillip B. Messersmith’s research group also synthesized an adhesive hydrogel, prepared by copolymerizing DOPA with hydrophobic segments of an amphiphilic block copolymer under photo-imitation. The adhesive property of the hydrogel was surprisingly improved in the presence of DOPA in wet condition. The elasticity of the hydrogel was found to be similar to that of soft tissues leading to consider it as a encouraging candidate for biomaterial.[93] Further research conducted by Messersmith and coworkers focused on the biological capabilities of dopamine-PEG adhesive gels. In 2010 they reported that DOPA as end-caps covalently bonded with an amine-terminated 4-arm PEG. The PEG was the core in which oxidative reagents (NaIO4) were added to form an adhesive hydrogel in less than 1 minute.[94] The results of the in vivo test, performed in a murine model, showed the adhesive gels caused minimal inflammation and were stably interfaced with the surrounding tissues for more than 24 months. To form a catena degradable adhering polymer, three materials were reacted to form a semblable branched polymer, including dopamine derivative as end-group, PEG and polycaprolactone (PCL) as a backbone.[95] These polymers are able to form films whose properties, such as swelling capacity and biodegradation, were flexible by changing the ratio, or concentration of these reactants or by adding other additive agents. After coating these adhesive polymer s on a biologic meshes, stronger water-resistant was exhibited when compared with fibrin sealant or cyanoacrylated polymers.[95] Applications for this biomaterial can be extended in the surgical field for hernia repair. Stewart’s group published several papers about adhesive hydrogels based on complex cohesion. In 2010 they created a bio-mimic hydrogel blending with revised gelatin and a copolymer which is obtained by a dopamine derivative reacting with monoacryloxyethyl phosphate in an alkaline condition.[71] The addition of Ca2+ and Mg2+ to the bio-mimic hydrogel could significantly improve the coacervation of the hydrogel, which was applied to tune agglomeration temperature to body temperature. The result demonstrated that the cohesion interaction was biodegradable, perfectly suited for medical applications. In another similar research, an adhesive hydrogel was synthesized by complicated cohesion of a positively charged copolymer and a terpolymer involving a dopamine derivative when its pH was higher than 4.[70] The bonding property of the hydrogel to hydroxylapatite was around 40% of common cyanoacrylate glue. T.G. Park’s group developed a temperature sensitive and injectable tissu e-attachable hydrogel.[96] The hydrogel was synthesized by conjugating hyaluronic acid and dopamine, following by cross-linking with thiol tail-ended Pluronic F127 via Michael addition. The hydrogel precursor exists at room temperature, and a cured hydrogel is formed when brought to a temperature of 37 °C. In a later paper, they used a similar strategy forming hydrogel by blending a dopamine derivative modified chitosan with thiol-capped Pluronic F127 at body temperature.[97] The adjustable gelation time of this block copolymer made it suitable for tissue-repair at 37 °C. The resulting hydrogel dedicated excellent in vivo results, where chitosan served as hemostatic agent and dopamine derivative group acted as adhesive agent to soft tissues. 2.3.2 Nanofiber Tissue engineering tends to use nanofiberous biomaterials instead of a micropores matrix since the filiform and polyporous nanolevel structure allow for artificial extracellular matrix to enhance the fundamental cellular procedures.[98] Nanotechnology reformation have aided in the development of techniques for the production of such a nano-composite materials. Electro-spinning has recently obtained increasing attention, attributing to its briefness and facility for nanofiber fabrication. Through this technique, fibrous structures are easily tuned in order to coordinate it with the extracellular matrix (ECM).[99, 100] So far, this technique has been studied in a range of biological fields, such as bone and skin regeneration. The artificial polymer ECMs usually have difficulties with interfaced reactions between tissues and materials.[101] For electro-spinning nanofibers in applications of biomedicine, it is necessary to physically and chemically combine them with biomolecules or cell-recognizing ligands.[102] This subsequently provides bio-modulating or biomimetic micro- environments to contacting cells and tissues. Dopamine coating can be considered as a simple and versatile approach to modify various synthetic polymers so that they are able to serve in biomedical applications.[49-51] Ku and coworkers[103] firstly reported culturing human endothelial cells on a polydopamine treated electro-spun polycaprolactone (PCL) nanofiber membrane. They used two control groups, pure PCL nanofibers and PCL nanofibers coated with gelatin, to investigate the ability of cell attachment of dopamine. The result of the water contact angle demonstrated that polydopamine uniformly was coated on the PCL nanofibers. Polydopam ine also significantly improve endothelial cells’ attachment on the nanofiber, compared with other non-adhesive substrates. Moreover, endothelial cells culture on PCL nanofibers coated by dopamine had developed cytoskeleton, positive PECAM-1 and vWF expressions and high cell extend.Rim and coworkers[104] designed dopamine functionalized electro-spinning poly(L-lactide) (PLLA) nanofibers with minimal influence on its mechanical performances, like wetting capability and roughness. The polydopamine coated PLLA nanofibers significantly enhanced cell attachment and the degree of spread, contradistinguishing with pure PLLA nanofibers. Meanwhile, its fibrous morphology had changed to more of a polygon shape instead of sphere after the polydopamine coating, which lead to higher DNA content of polydopamine treated PLLA nanofibers. The higher gene expressions of cells cultivated on polydopamine treated fibers indicated better osteogenic differentiation and vasculogenesis. Extensive research regarding the chemical or physical coating of metal on the surface of scaffolds to increase tensile strength has been done.[105] Jungki Ryu et al.[106] used dopamine to process hydroxyapatite deposits on PCL nanofiber by coating it. The result demonstrated a combination of surface activation through dopamine coating and hydroxyapatite mineralization allowing the hybridization of various shapes and surfaces. In other reported, Xie and coworkers[107] considered dopamine as a ‘superglue’, allowing minerals to easily attach to fibrous surfaces. The mechanical properties of mineral functionalized electro-pinning PCL nanofibers, such as stiffness, durability and tensile strength, were near to that of natural bone. Dopamine coated nanofibers show an improvement on existed biomaterials such as their mechanical performances, and cell adhesion. This makes them quite suitable for tissue regeneration and other related bioengineering applications. 2.3.3 Biosensing There is an enormous demand to design highly sensitive and selective biosensors for multiple applications, such as diagnostics, drug screening, and drug discovery.[108] Biosensors usually are in the microscale or nanoscale[109] and there are numerous methods to develop them, such as DNA[110] and antibody-based sensor[111, 112]. Scientists employ dopamine in order to optimize biosensor’s capabilities which have been reported by several research groups. Lui and coworkers first reported that dopamine could be used in a biosensor.[113] They used electricity to oxidize dopamine to form polydopamine on a gold electric pole with existing nicotine. The dopamine-imprinted sensor showed outstanding selectiveness of nicotine and excellent repeatability. Furthermore, Ouyang and coworkers developed a one-step well-defined structure of a dopamine-imprinted sensor.[114] They applied electro-polymerization of o-phenylenediamine (o-PD) and dopamine with existing glutamic acid (Glu). By using a potentiostatic time scan, the sensor exhibited satisfactory stereo selectiveness of bonding L- or D-Glu because their relative synthetic receptor. In a different publication, they designed protein imprinted nanowires which dopamine was also involved.[115] First, the protein-coupled alumina membrane was immersed in dopamine solution followed by an ammonium persulfate solution in order to self-polymerize polydopamine; in which afterward the removal of the atta ched protein is necessary. The nanowires demonstrated constant bonding capability and selectiveness of template proteins due to their cavity structure with bonding spots (like amino group, hydroxyl, Ï€-Ï€ stacking and van der Waals force) that can bind with protein. In another research, Zhou et al. display the creation of magnetic nanoparticles coated by imprinted polymer with a pre-existing template protein.[116] The nanoparticles are able to separate target protein from the mixture. In order to investigate the versatility of the imprinted nanoparticles, they operated on a binding test by using five different proteins excluding the template protein. The result indicated that more than 80% of target proteins were rebinding with imprinted nanoparticles, suggesting imprinted nanoparticles have a bright future to be employed for separating and detecting specific protein. One of the greatest difficulties for biosensors is how to immobilize enzymes on the surface of an electric pole and preserve the enzymes’ functionalities. Wei et al. designed a novel glucose electrochemical sensor, prepared by using a polydopamine film to entrap glucose oxidase and gold nanoparticles.[117] Their research displayed a polydopamine matrix embedded with gold nanoparticles that had high efficiency of immobilizing glucose oxidase. The dopamine film embedded gold nanoparticle biosensor showed a superior sensitivity, good repeatability, linear over broad dynamic range and a low detective threshold. Furthermore, in order to assess adaptability of this sensor, they use it to test glucose concentration in attenuated human serum. The result suggested this biosensor is an attractive material for clinical applications