Multinational company Research Paper Example | Topics and Well Written Essays - 3000 words

Multinational company - Research Paper Example In order to find out reasons for divergence in work attitude of Japanese and German employees, the study has also assessed professional orientation of employees from mentioned countries. In the final section, on the basis of theoretical and empirical research findings, a relativistic overtime payment model has been proposed. Implementation of the recommended model has also been discussed in the report. Concept of statistical performance management has been used to formulate the proposed recommendation. Almost 30 years ago, Hofstede (1980) had developed the concept of cultural dimensions in order to understand ways in which cultural and personal orientation of people differs with change in geographic locations. In such context, Dong and Liu (2010) argued that organizational leaders not only need to manage cultural diversity, but also have to deal with diversity of expectations of employees nourished in different cultural dimensions. Consideration of research works of Jamal (2005) reveals the fact that, multi-national enterprises (MNEs) face three levels of problems in managing cultural diversity such as, cross-cultural knowledge sharing, development of team collaboration among cross-cultural employee pool and standard reward system for all employees. It is evident from the theoretical argument that MNEs face range of difficulties while managing different perspectives of cross-cultural diversity within organizational environment. In such a backdrop, a new leader of an organization h as approached the researcher, who is working as a consultant, to develop a report by evaluating reasons for the employees in Japan and Germany to have different attitudes towards work. From previous study, it has been found that Japanese employees are happy to work additional hours without pay, while German employees expect to be paid for every extra hour of work. As part of the report, the study will use the concept of cultural dimensions in order to understand

Why might we consider justice to be an essentially contested concept Essay - 1

Why might we consider justice to be an essentially contested concept - Essay Example It is the hope of this brief analysis that the reader will come to a more full and complete understanding of the way in which societal recognition of justice has come to be defined as well as some of the core drawbacks to the way in which this term impacts different individuals and points of view in different ways. Firstly, one of the core interpretations that were presented by Plato, and individuals before and after him, was that moral virtue is ultimately the definitive aspect of justice. Naturally, within such a definition, two distinct words stand in contrast with one another (Plant, 2011). First of these is â€Å"moral† and the second one is â€Å"virtue†. Unfortunately, these two are not mutually exclusive and necessarily involve compliments of one another as a function of their own definition; lending the reader to realize that a situation of philosophical analysis is somewhat adulterated by this reality (Rawls, 2011). Further identifications and definitions were predicated upon the fundamental or tacit/innate concept of justice and the belief that it was given by God/god/gods. Although this interpretation was useful in helping individuals to understand the natural rights and concepts of justice that helped to define a given political system, these also fell short due to t he fact that they leveraged an understanding â€Å"justice† that was predicated upon a particular belief system or religion. Naturally, this was also fundamentally flawed as it promoted one particular set of ideals and interpretations over a litany of others (Ryan, 2009). A further issue that exists is the fact that even if it is understood in terms of a universal application of fairness and equality under the law, it will invariably place a particular worldview, ethnicity, or culture as a barometer for the way in which this concept should be defined and administered. Looking into the current exhibition of the justice system in most of the developed

Unit 5 IP Introduction to american court system Essay

Unit 5 IP Introduction to american court system - Essay Example Government, n.d.) and on common and â€Å"statutory law† (Ponzetto & Fernandez, 2008). Normally a criminal code will comprise offences which are acknowledged in the jurisdiction, penalties which might be imposed for these particular kinds of offences and some general provisions. I, recommend that, the case concerning Jones February 6, 2005 in the Sedgwick County, Kansas needs to be filed in the district court under state law on the premise that his assistance facilitated adequate evidence on Smith and Thompson to obtain convictions. Based on two prior convictions of Jones for possession of cocaine, it would be appropriate to file his case in federal court, where the highest sentences are available. On the other hand, because of his cooperation, it may be better to file the case in the Sedgwick County, Kansas, and district court under state law. Jones has been found to have possessed more than 50 grams of drug as the Probation Department contends and his level of offense would have been 32, which, with category of III of the criminal history, would result in a sentencing range of 151 to 188 months. â€Å"After a jury trial at which Jones was found guilty of unlawfully possessing more than five g rams of a substance containing cocaine base (commonly known as â€Å"crack†  844(a).  cocaine) in violation of 21 U.S.C.  §Ã¢â‚¬  (United States Court of Appeals, Second Circuit, 2012). The case against Smith can be file under the federal law. In this case, Smith has sold cocaine to undercover agents on two occasions: July 12 and August 3, 2005. However, no previous offences have been recorded against his, though he seems to have engaged in selling drugs to his friends and acquaintances for a while. Drug selling is the one of the gravest crimes that affect the society in the present day. Anybody engaging in such nefarious activities needs to be awarded the maximum punishment for the crime. maximum punishment. Cocaine comes

A Brave New World-perspective analysis Essay Example for Free

A Brave New World-perspective analysis Essay Imagine Brenda, a woman who will not under any circumstances trade her life in order to be conditioned, and then live as a Beta in the Brave New World (BNW), universe. If this is the case, then Brenda could not consistently accept Hedonism. This is due to the definition of Hedonism, the amount and intensity of bodily pleasure in Brave New World (BNW), and the amount and intensity of bodily pleasure here in real life. The definition of Hedonism leads one to maximize the amount of pleasure and minimize the amount of pain: The only thing intrinsically good in life is pleasure, and the only thing intrinsically bad in life is pain. Other things in life have extrinsic value they can lead to either pain or pleasure, but do not produce the sensations by themselves. However, Hedonists are only concerned with pleasure and pain, as these are the only intrinsic values. The distinctive factor that determines a better life from a worse one, is the amount of net pleasure in ones life. The net pleasure is determined by subtracting the amount of pain in ones life from the amount of pleasure. Notice that Hedonism only determines better lives from worse ones, not good from bad. To make the distinction between good and bad is an arbitrary decision and cannot be measured through a comparable medium such as net pleasure. Quantitative Hedonism states that quantity and intensity are the only criteria that determine just how good a certain pleasure is. If all pleasures differ only in quantity and duration, then the world in BNW is a dream for hedonists. Ones life in BNW is conditioned to be content and happy with ones, job, class in life, and the daily schedule of life. This schedule for ones life never changes and so delivers a maximum amount of pleasure due to being happy and content. High pleasure in BNW also comes from the open sexual relations between people. Basically, it is encouraged from childhood to have as many sex partners as possible, therefore maximizing the amount of pleasure from sex. The drug of choice in BNW is called Soma, and it delivers an amazing feeling without any hangover effect like alcohol. This drug is distributed daily at ones work to maximize ones amount of body pleasure. With all of these factors enhancing pleasure, it is also important to state that not much causes pain for ones life in BNW. There are no personal relationships to cause pain, jobs and education are  given specifically for people, and life is very much planned and repetitive. This repetition is what maximizes the amount and duration of pleasure in BNW lives. In real life, there does not exist anything like the above mentioned pleasures, in either quantity or duration. Therefore, when comparing the net pleasure of a life in BNW to a real earthly life, a hedonist finds that BNW lives have a higher net pleasure, and are thus far better. This is because they in BNW have much more intrinsically good pleasure, and much less disappointment and intrinsically bad events. So, if Brenda refuses to trade her life in order to be conditioned and live a BNW life, then she could not consistently accept hedonism because trading her life would give her a higher net pleasure, and by definition, a bett er life. Brenda still could accept hedonism if she accepted qualitative hedonism, based on Mills distinction between higher and lower pleasures. According to Mills, certain pleasures have a distinct higher value than other pleasures. This can be due to a mere preference for one pleasure over another, with the preferred pleasure having more intrinsic value because it is preferred, and thus more net pleasure. This can also be due preferring higher intellectual mind pleasures, as opposed to body pleasures like those in BNW. Mills distinction goes hand in hand with qualitative hedonism, which adds quality to the criteria distinguishing pleasure (intensity and duration). Higher quality pleasure are generally thought to be intellectual and creative pleasures as compared to bestial pleasures. Intimate relationships can also be thought of as being a higher quality pleasure. It is not substantial, however, that these higher pleasures merely exist for a hedonist, these higher pleasure must contribute to a higher net pleasure in life in order to be of value. Since there are absolutely no intellectual or intimate pleasures in BNW, the argument could be made that the intellectual and intimate pleasures in real life give higher net pleasure, and thus a better life. This theory also takes into account the pain that may be caused by relationships or by not attaining certain intellectual milestones. However, the argument can be made that the pleasure derived from these higher pleasures far surpasses any pain caused by them and guarantees a higher net pleasure than any life in BNW. If Brenda adopts this method of thinking, then she could both accept hedonism and still not  want to trade her life for a life in BNW. A qualitative hedonist, in order to consistently believe that actual life is better, must claim that the overall net pleasure one receives in real life is more than the net pleasure one receives in the BNW universe. One must claim that experiences in actual life, including but not limited to intellectual and intimate pleasures, produce more net pleasure than a life of bestial pleasures in BNW. This includes all of the pain and hardships experienced in real life, but not in BNW. The argument is that even with all of this pain, the net pleasure is still higher in real life. This is also what Brenda must adhere to if she wishes to not trade her real life for a conditioned BNW life.

Use of Reflective Practice in Nursing Essay -- Professional Growth thr

In this essay, I will be summarizing and exploring my understanding of reflective practice. Reflective practice is the process of learning through and from experience towards gaining new insights of self and practice (Boud et al 1985; Boyd and Fales, 1983; Mezirow, 1981, Jarvis, 1992). This generally involves examining assumptions of everyday practice. It also requires the individual practitioner to be self-aware and to critically evaluate their responses to practice situations. The point is to recapture practice experiences and think about them critically in order to gain new understandings and so improve future practice. This is understood as part of the process of life-long learning. This process of learning from reflection brings self-awareness, gaining knowledge and enhancing communication skills, were the key learning points that I learnt within this discussion. From this discussion itself I learnt new features and ways which gave me the ability to learn how to enhance my communication skills. I have also gained knowledge from on-line discussion with members of the group who have shared their knowledge and acquiring from literature. However, this process of continuously learning gave me a deeper insight of new features and methods that allowed me to challenge myself by merely sharing knowledge within an on-line discussion. In reflective practice, practitioners engage in a continuous cycle of self-observation and self-evaluation in order to understand their own actions and the reactions they prompt in themselves and in learners (Brookfield, 1995; Thiel, 1999). The goal is not necessarily to address a specific problem or question defined at the outset, as in practitioner research, but to observe and refine practice in gen... ... R. (2011). ABC of Action Learning. Gower Publishing Limited; Surrey Schon, D.(1983)The Reflective Practitioner. New Yorks Books. EGAN, G. (2007) The Skilled Helper.9th ed. Belmont:Brooks/Cole Cengage Learning. SUSAN, W. W. and IAN McGILL (1989) Making Sense of Experiential Learning, London, United Jarvis, P. (1992) Reflective practice and nursing. Nurse Education Today, 12(3), 174-181. LINDA, D. R. and MARY, W. (2001) Principles and Practice of Informal Education, London, Routledge Falmer Mcgill, I and Beard, L. (2001) ‘Action Learning: a guide for professional. Management & educational development’ Oxon: Routledge. Mezirow, J. (1981) A critical theory of adult learning and eduaiton. Adult Education,32(1), 3-24. Schà ¶n, D. A. (1987) Teaching artistry through reflection-in-action, In Educating the reflective practitioner (pp. 22-40) San Francisco

Review Article †Rheumatoid Arthritis & Il-6 Essay

Introduction Rheumatoid arthritis (RA) is an inflammatory autoimmune condition principally causing synovial joint inflammation and cartilage erosion. The pathogenesis encompasses intricate cellular and humoural manifestations, and vascular reactions that result in the infiltration of the synovium by white blood cells, of which release inflammatory mediators, inclusive of Interleukin-6 (IL-6). IL-6 serum levels of RA patients as shown by Capell et al. (1993) displayed a median of 55 IU/ml, as compared to that of healthy controls of 10 IU/ml. With a wide-ranging pleiotropy endorsed by both a membrane-bound (IL-6R) and soluble (sIL-6R) receptor, and by the relative omnipresence of the trans-membrane protein gp130, IL-6 endorses a pro-inflammatory effect via its influence on numerous cell types and signalling-pathways. As a result, heightened levels of IL-6 aids in the promotion of osteitis, sequential joint damage, pain/discomfort and impaired function in RA patients. Pleiotropy of IL-6 Interleukin 6 exerts effects on numerous pathways contributing to the pathophysiology of RA. IL-6 as it is called today has been known by several names that exemplify its pleiotropy for example, hepatocyte-stimulating factor known to cause the induction of C-reactive protein (CRP); due to IL-6 association with synovial fibril aggregation has been known as Amyloid protein; a thrombopoietin; both B-cell differentiation and stimulating factor 2; plasmacytoma growth factor; and cytotoxic T-cell differentiation factor. It also causes the differentiation of Th17 cells; is a causative factor in adhesion molecule expression on the surface of endothelial cells, and is involved in the differentiation to mature from precursor osteoclasts cells (REF!!). IL-6 Recptor binding IL-6 implements its influence via a protein complex primarily comprised of a membrane bound IL-6R and a glycoprotein comprised of two intra-cytoplasmic transducer sub-units, gp130. When IL-6 binds to membrane bound IL-6R (mIL-6R) it causes homo-dimerisation of the gp130 sub-units, of which triggers intra-cytoplasmic signal transduction. Whilst expression of gp130 is relatively omnipresent upon the surface of the body’s cells (Akil, et al., 2008), IL-6R is most prominently located on hepatocytes, macrophages, monocytes, neutrophils and select lymphocytes. However, (sIL-6R) of which is systemic also binds IL-6, and just as mIL-6R, can also engage with gp130 for sIL-6-gp130 trans-signalling (REF!). Synoviocytes, for example do not express mIL-6R but do express gp130. Raised levels of IL-6 in the synovium is a characteristic biomarker of RA (Attar, et al., 2010), and Kim, et al. (1996) states enhanced IL-6/sIL-6R in synovial fluid increased the risk of joint destruction, as IL-6 stimulates endothelial cells to express adhesion cytokines and other molecules of which attract inflammatory cells to synovial membrane (Romano, et al., 1997) thus could contribute to exemplifying the significance of sIL-6R in RA pathophysiology. sIL-6R is formed by either an incomplete proteolytic enzymic dissection of mIL-6R or alternative splicing of mRNA (REF!!). With the aforementioned ubiquitous nature of gp130, mIL-6R and systemic sIL-6R, increasing evidence REFERENCES SEE NOTES!! shows that a non-membrane bound, systemic, soluble gp130 (sgp130) found in higher circulatory concentrations than that of sIL-6, also binds IL-6/sIL-6R, thus functioning as a redundency factor inhibiting the cytoplasmic signal-transducing potential of mgp130 REFERENCES SEE NOTES!!, (IL-6/IL-6 receptor system and its role†¦) thus serving as a natural inhibitor of IL-6 signalling (IL-6/IL-6 receptor system and its role†¦). Intracellular signalling gp130 dimerisation brings Janus Kinases (JAKS), a receptor-associated protein complex, into close proximity causing a trans-activation of the two molecule types. Auto-phosphorylation of JAKS occurs, of which causes intracellular signal transduction by recruiting signal-transducers and activators of transcriptions (STAT) that form either hetro or homo dimers and migrate to cell nucleus effecting target gene transcription of various physiological processes (REF). IL-6 can be detrimental to human physiology (REF!), thus expression of proteins known as the suppressors of cytokine signalling (SOCS) function as a negative-feedback system, and are activated by STAT’s. The regulation of the JAK-STAT signalling pathway by SOCS is more specifically down-regulated by SOCS 3 (REF!). SOCS 3 binds JAK’s causing negative-regulation thus functioning as an auto-regulatory mechanism, by inhibiting JAK activity. IL-6 and the Adaptive Immune System The trans-signalling of IL-6 is known to cause the induction of pre-B-cell-colony-stimulating factor (PBEF) in fibroblast cells of the synovium (Bryant, et al., 2006), and since PBEF upon its discovery was considered a B-cell differentiation cytokine(McNiece et al., 1994), it could be considered plausible that IL-6-induced PBEF and the IL-6 maturation of B-cells, collectively contribute to RA. It has been found the effect of IL-6 on plasmablasts indirectly induces the production of B-cell antibodies by assisting elements of CD4+ T-cells (of which act upon activated B-cells) due to elevated IL-21 production (Bond, et al., 2009), thus IL-6 may potentially be a co-adjuvant to humoural immunity enhancement (Bond, et al., 2009). Enhanced levels of the RA associated Rheumatoid Factor are located in the IgA, IgG and IgM isotypes (Ahmed, et al., 2010), and citruline antibodies located in serum and joints, can be linked to the plasmablast-induced antibody production of IL-6 (Ahmed, et al., 20 10). IL-6 enhances T-cell proliferation where they have been mitogen stimulated (Mihara, et al., 2002). IL-6 also impacts T-cell development (Mihara, et al., 2002). Along with transforming growth factor (TGF)- ÃŽ ², IL-6 contributes to Th 17 differentiation, an effector T cell with pro-inflammatory elements, and is further compounded by Th 17 production of the pro-inflammatory cytokine IL-17 (Bettelli, et al., 2007). Interestingly, without IL-6, TGF- ÃŽ ² induces Treg production, of which are Th 17 cell suppressors (Hirota, et al., 2008). CD4+ Th cells have been considered Th 1 and Th 2 based upon their cytokine-producing characteristics (Diehl and Rincon, 2002). Th 1 and Th 2 produce IFN-á µ § and IL-13 respectively, of which are both pro-inflammatory molecules, however whereas IL-6 bolsters IL-4 induced differentiation of Th 2, it causes the inhibition of IL-12 induced differentiation of Th 1 (Diehl and Rincon, 2002). Acosta-Rodriguez, et al. (2007) found that in vitro levels of IL-1ÃŽ ² – induced Th 17 polarisation of naà ¯ve human CD4+ T-cells were heightened by IL-6 involvement. More research however, is required to make clear the full extent of IL-6 role in human Th 17 cell development, in vivo. During inflammation, neutrophils of which are essential inflammatory mediators, systemically increase substantially, resulting in relative neutrophilia. Endothelial cells, macrophages and monocytes all emit IL-6. Neutrophils are directly affected by IL-6 due to the expression of IL-6R. Filer, et al. (2005) found that co-cultured endothelial cells and fibroblasts extracted from synovial fluid of RA patients caused an increase in IL-6 and neutrophil recruitment. Adhesion molecules, of which it has been shown in the work of Woodfin et al. (2010) to be required in the transmigration of neutrophils, are augmented by IL-6 such as vascular cell adhesion molecule – 1 (VCAM) and intracellular adhesion molecule – 1 (ICAM) of which produce chemokine production. Thus neutrophils being the most numerous and systemic of leucocytes have a strong initial synovial presence and is bolstered by the amplification of the inflammatory cascade, contributing to the inflammatory escalation during acute-phase response; and findings from animal and human studies revealed that the blockade of IL-6 caused a reduction in neutrophil levels at inflamed sites (Hashizume, et al., 2008), as well as a reduction in systemic neutrophil counts in RA patients (Deguchi, et al., 2003 and Broll, et al., 2006),thus indicating a prominent role for IL-6 in neutrophilia. IL-6: Acute to Chronic Farnarier, et al. (2003) suggests the transition from acute to chronic inflammation as emphasised by a shift of biomarker from neutrophil to monocyte, is influenced by IL-6. It was found that if stimulated for a number of hours by inflammatory cytokines, neutrophils switched from the production of IL-8 and transitioned to monocyte chemoattractant protein-1 (MCP-1) (Yamashiro, et al., 1999). sIL-6R is released from neutrophils of which in turn causes the chemokine release of endothelial cells, thus Romano, et al. (1997) suggests the IL-6 – sIL6R complex contributes to the release of MCP-1 from endothelial cells. As earlier discussed, neutrophil-count was found to be directly associated with the blockade of IL-6R?!; and endothelial cells expressing the gp130 but not the IL-6R, thus reliant upon the IL-6 – sIL6RÃŽ ± complex for induction of MCP-1 release, i.e. the release of monocyte, not neutrophil specific chemo-attractants (Gres, et al., 2001), it would appear IL-6 tran-signalling plays an integral role in the transition from acute to chronic inflammation via neutrophil and endothelial cells. *CHART SHOWING CELLS THAT RELEASE IL-6!!* IL-6 induces a disintigrin and metalloproteinase with thrombospondin motifs (ADAMTS) and matrix metalloproteinase (MMP) proteinases of which are pivotal in the degradation of extracellular matrix. IL-6 more specifically, has been shown to induce ADAMTS-4 and MMP’s 1, 2 and 13 production in cells lining the synovium and chondrocytes (Hashizume and Mihara, 2009; Hashizume, et al., 2010; 2012). However, it has been suggested the IL-6 – sIL-6R complex has bearing on the extracellular matrix turnover, as it causes generation of tissue inhibitors of MMP’s (TIMP’s) in synovium fibroblasts and chondrocytes (Dayer, et al., 1998 and Hashizume, et al., 2012). The drug tocilizumab (TCZ), an IL-6 inhibitor reduces MMP-3 blood serum levels of RA patients (Garnero, et al., 2010), and has been show to restore biomarkers associated with cartilage turnover (Dayer, et al., 1998). Thus, in RA patients the reduction of IL-6 activity appears to be a mediatory factor in sustainment of healthy joint cartilage. Angiogenesis is a key process in the local inflammatory process. Neovascularisation of the synovium and other angiogenic processes such as hyperplasia of synovial cells and permeation by inflammatory cells are characteristic processes in pannus development and RA pathology (Ballara et al., 2001). In addition to notable constituents of the inflammatory process such as monocytes and T cells, both of which as stated previously have affiliations with IL-6 expression (CITATION OF A FEW), levels of a key angiogenic specific growth factor Vascular Endothelial Growth Factor (VEGF) has also been associated with systemic levels of IL-6, as demonstrated in the work of Hasizume, et al., 2009 and Hagihara, et al., 2003 revealing IL-6 induces VEGF production from synovial cells. VEGF induces proteins that contribute to the breakdown of endothelial basement membrane, including MMP’s, of which increases the permeability of blood vessels, thus allowing enhanced infiltration of inflammatory constituents (Delisle, et al., 2010). VEGF levels accordingly, have been shown to coincide with the articular severity of RA (Hagihana, et al., 2003), and has shown a reduction in response to TCZ (Hagihana, et al., 2003), of which correlates with findings of a semi-quantitative assessment by Akoi, et al. (2011) using ultrasonography that found TCZ responsible for a marked reduction in RA neovascularisation. Bone Remodelling Bone remodelling is a highly regulated process in which mature bone tissue is removed by osteoclasts and formation by osteoblasts. The pathogenesis of RA favours bone loss (resorption) via the excessive production of osteoclasts. Anecdotal evidence by Kazuto et al. (1996) revealed synovial fluid highly +ve for IL-6 –sIL6R complex from RA patients, stimulated increased formation of osteoclasts in mouse co-culture of osteoblast and bone marrow cells. This study coincides with research by Balena, et al. (1994) of which indicated that mice deficient in IL-6 displayed no significant changes in gross or trabecular bone structure. In human studies, biopsies of RA patients revealed that peri-articular bone loss was found to correlate with local excessive presence of IL-6 (Sugiyama, 2001), and work by Garnero et al. (2009) showed the administration of TCZ to RA patients in a multi-centre double-blind placebo-controlled study yielded an increase in bone-formation markers, with a decrease in bone-resorption markers. Collectively, research suggests IL-6 has a negative effect on bone mass. Acute-phase response Acute-phase response is an innate immune reaction in which IL-6 is notably involved via the stimulation of hepatocytes, and is a key inducer of the acute-phase protein CRP. CRP is considered a dependable biomarker of inflammation and RA activity as serum half-life remains constant due to its inflammatory-induced, hepatic-stimulated production being the exclusive systemic determinant and due to its noted increase in RA serum levels (Hirshfield and Pepys, 2003). Anaemia Approximately 1-in-4 RA patients will suffer symptoms of anaemia within the first year (Figenschau, Nikolaisen and Nossent, 2008). The hormone hepcidin, produced in the liver and integral in stemming the metabolism of iron, has been shown in vitro to increase in presence due to IL-6 stimulation of hepatoma cells (Ganz, 2003). This study correlates with Gabayan et al. (2004) in which IL-6 induced patients experienced a 7.5 fold increase in hepcidin production. Anaemia in RA patients, as a result of a hepcidin-IL-6 axis, has limited but supported credence. Osteoporosis has also shown a correlation with IL-6. As mentioned earlier, healthy bone metabolism requires adequate regulation of osteoclasts and osteoblasts, in which excessive IL-6 expression and the Th17 derived IL-17 (Gillespie, et al., 1999) both contribute to excessive osteoclast formation (Campbell et al., 2005). This has also been found to be the case in transgenic mice (De et al., 2006; and Choy and Dayer, 2009) in which bone formation was reduced, and negative ossification was reported. As shown, there are comparable cross-over aspects of IL-6 pathology between RA and osteoporosis. Treatment As highlighted throughout this review, IL-6 plays a pleiotropic pathophysiological role in RA, thus would make an ideal therapeutic target. The most promising and note-worthy of treatments at present, TCZ interrupts IL-6 induced trans-signalling. Numerous studies have shown promising results including a phase III clinical trial in 2005 using the ACR (American College of Rheumatology)* RA activity measure, which had improvement measures of 89, 70 and 47% at ACR’s of 20, 50 and 70 respectively at 52 weeks, in patients treated with TCZ. This multicentre, double-blind placebo-controlled trial by Hashimoto et al. (2004) showed bone resorption and joint destruction could potentially be completely prevented (Kishimoto, 2010), as exemplified when a culture of patient synovial and peripheral mononuclear cells, extracted from the same patients showed that osteoclast generation was completely prevented (Hashimoto et al., 2004; Kishimoto, 2010). At 6 weeks within this study, it was also found that IgG, CRP and serum amyloid A levels all normalised. It has also been suggested that TCZ aids in Th17 differentiation, hence IL-17 production, thus aids in the improvement of RA symptoms (Kimura and Kishimoto, 2010). Other notable studies such as the SAMURAI (Study of Active controlled Monotherapy Used for RA, an IL-6 Inhibitor) and LITHE (TociLIzumab safety and THE prevention of structural joint damage trial) served to enhance conscensus. This humanised, monoclonal antibody has now been approved in many countries^^. 286 With a wide-ranging pleitropy, IL-6 has the most profuse SF and systemic cytokine presence in RA pathophysiology, and coincides with cartilage erosion and disease activity. It has a role in elements of B-cell differentiation and increasing evidence suggests a definite yet ambiguous role in Th17 differentiation. IL-6 has several key positions in immune and inflammatory processes (recruitment, permeation and adhesion of inflammatory elements), and bone and joint degradation, of which over-expression causes adversity, such as release of hepcidin and CRP from the liver contributing to anaemia and inflammation, osteoporosis and pannus development. It plays a key role in the cross-over from acute-to-chronic disease. TCZ has shown much promise in RA therapy by inhibiting IL-6 expression. *ACR 20, 50 and 70 = improvements of 20%, 50% and 70% in disease activity, respectively. ^Disease Modifying Anti Rheumatic Drugs. ^^Japan , April 2008, Europe, January 2009 and USA, January 2010. PUT IN ABSTRACT: The IL-6R, sIL-6R and gp130 system is known as IL-6 trans-signalling References: Capell, H. A., Crilly, A., Madhok, R., Watson, J., 1993. Serum interleukin 6 levels in rheumatoid arthritis: correlations with clinical and laboratory indices of disease activity. 52 (3): 232 — Annals of the Rheumatic Diseases. [ONLINE] Available at:http://ard.bmj.com/content/52/3/232.full.pdf+htm. [Accessed 23 December 2012]. Angelo, L. S., Hong, D. S., Kurzrock, R., 2007. Interleukin†6 and its receptor in cancer. Cancer – Wiley Online Library. [ONLINE] Available at:http://onlinelibrary.wiley.com/doi/10.1002/cncr.22999/pdf. [Accessed 01 January 2013]. Bussolino, F., Ciliberto, G.,Faggioni, R., Fruscella, P., Hinsbergh, V. 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Slavery Before And After The Civil War

In this chapter it tells a story about slavery before and after the Civil War. It explains the United States provision of slavery and how some people were misled on who ended slavery, how it was Abraham Lincoln and not John brown who was hung later in 1859 for his crimes. It later goes into graphic detail of how slaves were kept into slavery by whipping and separating families. It sort of reminds of the movie 12 years a slave I would recommend it. It’s sad but true story of how black people were treated back then.John Brown was hung by the state of Virginia with the approval of the national government for his failed plan to take hold of the federal arsenal. The US Government would not accept an end to slavery by mutiny, but only under circumstances controlled by whites, and only when essential by radical and profitable needs of the North. It was Abraham Lincoln who was able to do just that by putting together the interests of the wealthy and interests of the blacks.What came n ext was that Lincoln was elected there was an extensive series of procedure clashes between the South and North. The rattle was not over the issue of slavery, but that the South saw Lincoln and the Republicans as a risk to their pleasant way of life. So when Lincoln was elected ultimately 11 states split from the Union. The Association was formed thus beginning the Civil War. In an effort to end the war, in September 1862, Lincoln announced his primary Emancipation Proclamation.This was a military move, giving the South 4 months to stop protesting or else their slaves would be freed, if they complied slavery would be unharmed in the states that came over to the North. The Proclamation also opened up the Union army to the blacks. On January 1, 1863, urging antislavery forces. Later in April 1864 Senate had approved the Thirteenth Amendment, declaring an end to slavery, and in January 1865, the House of Congresses followed. The Fourteenth Amendment declared that â€Å"all persons bor n or naturalize in the United States† were citizens.This restricted states’ rights regarding racial equality. The Fifteenth Amendment said: â€Å"The right of citizens of the United States to vote shall not be denied or abridged by the United States or by any State on account of race, color, or previous condition of servitude. † This opened the door for senate to pass laws making it a crime to deprive African Americans of their rights, like allowing blacks to enter into contracts and buy homes and what not. With these laws African Americans formed political organizations.They were nevertheless held back for several years by Andrew Johnson, who became president while serving as Vice President under Lincoln when Lincoln was killed at the end of the war. Johnson banned bills that helped Blacks and allowed states to return the Union without promising equal rights for blacks. Johnsons’ actions did not sit well with Senators and Congressmen. Later in 1868, Congr ess nearly succeeded in accusing Johnson but was one vote short in the Senate. Later that year, Republican contender Ulysses Grant would win the presidential election by 300,000 votes over Johnson.This again opened up doors for blacks, were being elected into southern state legislatures and the US Senate & Congress. Black women were also helping to rebuild the postwar south; black children were going to school. Even though it looked like Negroes were on their way to becoming equal there was still a lot of hostility and dependency on whites for work and supplies. The south used economic power to form the Ku Klux Klan (known as KKK) and other extremist groups. It wasn’t long until things were almost back to where it started.