What led to the development of postmodernism in architecture

What led to the development of postmodernism in architecture Post modernism was devised from its previous movement, modernism and first began to emerge around the states of America in the 1960s but really took off around the early 1970s when it came to England and Europe and became a movement. It still continues to influence modern architecture today. The most obvious design traits can be seen in architecture; features that best represent this style include bold, visual exteriors, designs that are functional yet contain architectural characteristics that have been seen before but combining these with exciting, colourful, fresh designs. An example of this is the Portland building; Oregon designed by Michael Graves. (See Fig.1) This block of government offices built in 1980 has a very decorative exterior and has become an icon of Post modernism. Post modernism came about when modernist views were being rejected by many people and architects although there where still some whom where in favour of the current modernist ideas, yet still recognized the need for further development within this style to take place as the world fast continued to modernise around them, this saw the beginnings of Postmodernism. This quote from Michael Graves gives his view on how modernism designed everything to be machine like, which worked, although buildings should be made decorative and not so set in the modernist ways: While any architectural language, to be built, will always exist within the technical realm, it is important to keep the technical expression parallel to an equal and complementary expression of ritual and symbol. It could be argued that the Modern Movement did this, that as well as its internal language; it expressed the symbol of the machine, and therefore practiced cultural symbolism. But in this case, the machine is retroactive, for the machine itself is a utility. So this symbol is not an external allusion, but rather a second, internalized reading. A significant architecture must incorporate both internal and external expressions. The external language, which engages inventions of culture at large, is rooted in a figurative, associational and anthropomorphic attitude.1 In this quote Graves refers to the modernist movement and how they designed their buildings to be like machines, extremely clean, sleek and purely functional with no needless design features. His view is not to think that the inside of a building should be run as a machine but to think of the building as a whole and to think outside the modernists clean cut lines and un decorative architecture. Unlike the modernist architecture previous to this movement the post modernism architecture is usually quite ornamental, new but also borrowing some features from the past, such as bringing colour back into architecture which taken away for modernist era. There is quite a lot of rivalry between the two movements, modernists strongly believe in form follows function, their architecture showing functional, formalized shapes and spaces, where post modernists believe in not necessarily form over function but making their functional buildings a lot more visually dynamic and I suppose more of an experience. There is no true reality not even your own2 This is a saying from the late 90s which reflects post modernists views. They felt you need to question reality and think outside the box where as the modernists believed in questioning authority, their thinking that if people looked into why things are designed the way they are and the truth is to be discovered then tradition would be questioned. The postmodern architecture features shameless aesthetics different from anything before, they have a more organic feel and stand out. The post modern era also found the use of different materials being used with in architecture than before, whether it be the colour or the specification of the material that was to be desired. The two main materials used in postmodern architecture are stone and glass. The stone is bold and comes in a very wide range of colours, which stuck to the postmodernist ideas. The glass was used a lot especially in America and large city buildings, office blocks and skyscrapers such as Le 1000 de la Gauchetiere in Canada, its the tallest skyscraper in Montreal. (See fig.2) This was built a bit later on, in 1992 but still shows strong postmodern values. For example the distinctive triangular copper roof and four copper capped entrances at each of the tower base corners. The structural core is constructed from concrete and steel and the exterior consists of glass in a metal frame. The form used in postmodern buildings is also very contemporary, the building function is still important for the designers but compared to the modernist buildings the forms, shapes and look of the buildings are almost there for the designers sake, not for any specific reason other than good aesthetics. As I said before there is almost a collision of beliefs between the two movements, though most of the dislike at the time was focused towards the post modern architecture as the modernist architectures such as Le Corbusier, Ludwig Mies van der Rohe and Walter Gropius had put the belief into the people that a building that was almost wholly based on function was the best way. So when post modern architects such as Frank Gehry, Robert Venturi and Eero Saarinen started designing buildings that where thinking outside the slick, functional, simple design box of modernism and completely aesthetical and almost quite wacky there was quite an uproar and possibly a confusion as people started t o question what was right for the future of architecture? Were the new buildings functional enough and would the new buildings stand the test of time? As the people began to accept the more complex designs of the post-modern world the buildings began to become popular and more and more architectures began to come round to the idea. In todays architecture you can clearly see the inspiration from these initial designs and that architects and designers have turned modernist ideas on their head, by carrying on the idea of aesthetically pleasing designs and almost having more fun with their design rather than just focusing on the function. So how exactly did Postmodernism come about? Well as I have just confirmed the strongest link/lead to postmodernism was obviously the modernist designs lack of decoration, but I also looked at some other factors that could have lead to the development of postmodern architecture. As is well known, the lead to postmodernism was when people started to reject the views of the modernist movement, though how did this come about? And why did people start to reject the modernist ways? The rejection of modernism first came from architects In their works. In Europe Aldo Rossi documented his views of the current art movement, while in America Raunch and Scott Brown expressed similar views on the need for development of the modernist architecture. Though the most influential change came from the work of Robert Venturi. He famously wrote the book Complexity and Contradiction in architecture in 1966 which attacked the modernism of international style, with his strong views on his dislike for modernism. In the writing he replaces Miles van der Rohes (a modernist architect) modernist phrase less is more with : less is a bore. Blatant simplification means bland architecture This quote is just a brief look to his views in the piece, he continues throughout rejecting the moral, clean cut ways of modern architecture for elements that are more a blend of features than pure. Frank Gehry seems to be a name that frequently appears when investigating post modernism architecture. His Designs were very contemporary, bold and different to what had been seen before. He denied that his work was post modernist or that it even fit into any category other than something totally new. This would not happen with a modernist architect as; although the designs are different all modernists buildings tend to have the same features, sleek and following function so much that there is not a lot of individuality between the designs. Where as post modernist architecture is all so decorative and ornamental that each design is unique. Just by looking at a few of Frank Gehrys designs you can definitely tell that they are individual although they do fit in with the post modern category his architecture has moved beyond the modernist era being based on geometric and organic forms. As Gehry says himself : Not every person has the same kinds of talents, so you discover what yours are and work with them. Dont try to be me, or try to be Frank Lloyd Wright, or try to be I M Pei. Try to be yourself. You have to understand what drives people to build buildings. 4 One of Gehrys most creative pieces that represent this is The Frederick R Weisman Art Museum at the university of Minnesota, 1993(See Fig 3). The University officials chose Frank Gehry to design the teaching museum for the campus because of his attention to needs of people that use his buildings and his unique stunning designs. The museums exterior is constructed of amazing, sticking shapes made from brushed stainless steel on one side over looking the Mississippi river creating an abstract image of a waterfall and a fish. The other side of the building is on the side of the campus and blends in with the existing sandstone and brick buildings by using terra cotta coloured bricks. Frank Gehry was also commissioned to design an expansion to the building that was meant to have been completed in 2009 though due to financial reasons it will be built by next year. This shows that post modernism continues to inspired designers today and is still popular. An example of an architect that is continuing post modernism design to todays architecture is Santiago Calatrava. Born in 1951 when the postmodern movement was just starting to come about, Calatrava grew up with the organic architecture from the era. Obviously heavily inspired by it he has continued post modernism on in his own works. He has designed many buildings, which are very well known such as the Museum of tomorrow in Rio de Janerio in Brazil and Liege Guillemins TGV station in Belgium. La Rioja, Bodegas Ysios in Spain is one of his designs, which is not so famous though still unique, and particularly show his postmodernism inspiration (See Fig 4). This building is situated amongst vineyards in Spain where la Rioja Alavesa wine is produced, the company wanted a building that would store the made wine and be a place where guests can test the wine. The design definitely meets the criteria and is very functional; there is separate part for the storing of the wine, making it and a tasting area. Although this could have been enough just in a plain rectangular building but in true post modernist style he has also added some amazing design features, the main feature is that the roof, it continues the shapes of the surrounding hills, creating a wavy organic shape. The material he has used for the roof design is aluminium panelling, which reflects the sunlight making it look even more special contrasting with the calm vineyard surrounding. I have researched the lead to post modern architecture and touched on how it has affected modern design today. Now to conclude this essay I will some up my findings of what led to post modernism in architecture. Post modernism first emerged in the 1960s and became a movement in the early 1970s, its routes stemmed from its previous movement, modernism. Modernists had a very strong belief in form follows function, their views where that a building should be purely functional and machine like which worked well but didnt leave a lot of an imagination for design features and all the buildings began to have a lot of the same features. In the 1960s some architects began to recognise this and voiced their opinions in their written works, which made people realize that designs could be a bit more exciting. The most influential architect in this realisation was Robert Venturi, in his well known writing complexity and contradiction in architecture he strongly expressed his dislike for modernist architecture, stating that less is a bore and that buildings do not have to be all about function, they can still be functional and have design features. This contributed to the lead to post modernism. One of the architects I found whos name kept appearing when looking at post modern architecture is Frank Gehry. His designs are functional but with amazing design features using organic forms and patterns to shape the buildings. As is with most post modernist architecture different organic and bold shapes are a big feature of the building making every design unique unlike the similar designs of the modernist era. Although Gehry do es not class his buildings to be post modernist or in fact fit into any category, his designs are definitely fitting with the era and he seems to share the same views as the post modernists. Buildings like Frank Gehrys continue to influence designers today such as Santiago Calatrava whos modern day designs very much resembles that of post modernist architecture. Part II Book review on: 20th Century Architecture by Jonathan Glancey The 20th Century Architecture explores the roots of modern architecture and explains how the history and the ever-changing social and political conditions helped shape and build the world we live in today. In this book, as the foreword states, by writing the book Jonathan Glancey attempts to achieve informing the reader of an introduction to architecture of the 20th Century, not to cover every aspect of the subject, as he says himself, The subject is very vast and no book can realistically cover the entire history of the twentieth century architecture. If I could it would either be too heavy to carry or else set in such a tiny type that it would be unreadable. This quote also I think captures the way the book is written, very informative yet quite light hearted. The book covers 8 of movements of 20th century architecture: Arts and Crafts, Classicism, organic, Modernism, Post-Modernism, Robotic, Cities and Futures. Each movement has a its own section which is started by a page for a brief explanation of the movement then examples of architecture significant to that time. Each piece of architecture has its own page with a full colour photo to show what it looks like and a section about the designer and the building, why it was built and how it relates to the movement and others in that time. I found the book easy to read, and was able put down at any time and pick back up from where I left off. I particularly like the no jargon take and the fact that you dont have to know an awful lot if anything on architecture or the history of the 20th century. The book is very informative if you read the whole thing or if you just flick to a specific section you are interested in. I originally did this but found that I wanted to read on further. This is as Jonathan Glancey intended as would most authors, wanting to get the attention of the reader and want to read on from their own will, as he says in the book: If this makes you want to find out more then it has done its job. If it encourages you to want to be an architect then good luck. I think he has definitely achieved his original intentions for the book. I borrowed this book from the local library but I would definitely consider buying a copy to keep as a reference book. From reading and sourcing from other architectural books, I think this fits in to the subject very well. Id says it is more aimed at students, people who are interested in architecture and starting architectures. I dont think the book would be so suitable for experienced architects and architect fanatics as it informs you of buildings and architects that this group would probably already know of, thought the may still find it informative about the movements and to find out when the movements happened and why. Over all I think this is a good book and deserves the positive comments it has picked up from press and other readers.

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. 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Automobile and Large Mass Essay

There was once a little boy of 6 years old called Lewis. One day, as he was looking out of the car window on his way to school, he discovered that a large mass of grey smoke was forming just above his dad’s car. Somewhat alarmed, Lewis looked at the other cars on the road to find out if they too had a cloud of grey smoke chasing them. To Lewis’ surprise, all the cars travelling on the motorway had the grey smoke hovering around them. There was once a little boy of 6 years old called Lewis. One day, as he was looking out of the car window on his way to school, he discovered that a large mass of grey smoke was forming just above his dad’s car. Somewhat alarmed, Lewis looked at the other cars on the road to find out if they too had a cloud of grey smoke chasing them. To Lewis’ surprise, all the cars travelling on the motorway had the grey smoke hovering around them. There was once a little boy of 6 years old called Lewis. One day, as he was looking out of the car window on his way to school, he discovered that a large mass of grey smoke was forming just above his dad’s car. Somewhat alarmed, Lewis looked at the other cars on the road to find out if they too had a cloud of grey smoke chasing them. To Lewis’ surprise, all the cars travelling on the motorway had the grey smoke hovering around them. There was once a little boy of 6 years old called Lewis. One day, as he was looking out of the car window on his way to school, he discovered that a large mass of grey smoke was forming just above his dad’s car. Somewhat alarmed, Lewis looked at the other cars on the road to find out if they too had a cloud of grey smoke chasing them. To Lewis’ surprise, all the cars travelling on the motorway had the grey smoke hovering around them. There was once a little boy of 6 years old called Lewis. One day, as he was looking out of the car window on his way to school, he discovered that a large mass of grey smoke was forming just above his dad’s car. Somewhat alarmed, Lewis looked at the other cars on the road to find out if they too had a cloud of grey smoke chasing them. To Lewis’ surprise, all the cars travelling on the motorway had the grey smoke hovering around them. There was once a little boy of 6 years old called Lewis. One day, as he was looking out of the car window on his way to school, he discovered that a large mass of grey smoke was forming just above his dad’s car. Somewhat alarmed, Lewis looked at the other cars on the road to find out if they too had a cloud of grey smoke chasing them. To Lewis’ surprise, all the cars travelling on the motorway had the grey smoke hovering around them. So Lewis asked his father: â€Å"Dad, what’s that grey smoke above our cars? † Lewis’ father was a little surprised by the question, but answered: â€Å"Well, Lewis, it’s called pollution. † There was once a little boy of 6 years old called Lewis. One day, as he was looking out of the car window on his way to school, he discovered that a large mass of grey smoke was forming just above his dad’s car. Somewhat alarmed, Lewis looked at the other cars on the road to find out if they too had a cloud of grey smoke chasing them. To Lewis’ surprise, all the cars travelling on the motorway had the grey smoke hovering around them. So Lewis asked his father: â€Å"Dad, what’s that grey smoke above our cars? † Lewis’ father was a little surprised by the question, but answered: â€Å"Well, Lewis, it’s called pollution. † There was once a little boy of 6 years old called Lewis. One day, as he was looking out of the car window on his way to school, he discovered that a large mass of grey smoke was forming just above his dad’s car. Somewhat alarmed, Lewis looked at the other cars on the road to find out if they too had a cloud of grey smoke chasing them. To Lewis’ surprise, all the cars travelling on the motorway had the grey smoke hovering around them. So Lewis asked his father: â€Å"Dad, what’s that grey smoke above our cars? † Lewis’ father was a little surprised by the question, but answered: â€Å"Well, Lewis, it’s called pollution. † There was once a little boy of 6 years old called Lewis. One day, as he was looking out of the car window on his way to school, he discovered that a large mass of grey smoke was forming just above his dad’s car. Somewhat alarmed, Lewis looked at the other cars on the road to find out if they too had a cloud of grey smoke chasing them. To Lewis’ surprise, all the cars travelling on the motorway had the grey smoke hovering around them. So Lewis asked his father: â€Å"Dad, what’s that grey smoke above our cars? † Lewis’ father was a little surprised by the question, but answered: â€Å"Well, Lewis, it’s called pollution. † â€Å"Pollution? What’s pollution? † asked Lewis, waiting intrigued for his father’s answer. â€Å"Well, for example, it’s that grey smoke you can see above our cars. Cars that run on petrol or diesel give off gasses into the atmosphere, which are very bad for all living beings and the planet too. Today you can see a lot of the grey smoke because it hasn’t rained for a long time,† answered his father. There was once a little boy of 6 years old called Lewis. One day, as he was looking out of the car window on his way to school, he discovered that a large mass of grey smoke was forming just above his dad’s car. Somewhat alarmed, Lewis looked at the other cars on the road to find out if they too had a cloud of grey smoke chasing them. To Lewis’ surprise, all the cars travelling on the motorway had the grey smoke hovering around them. So Lewis asked his father: â€Å"Dad, what’s that grey smoke above our cars? † Lewis’ father was a little surprised by the question, but answered: â€Å"Well, Lewis, it’s called pollution. † â€Å"Pollution? What’s pollution? † asked Lewis, waiting intrigued for his father’s answer. â€Å"Well, for example, it’s that grey smoke you can see above our cars. Cars that run on petrol or diesel give off gasses into the atmosphere, which are very bad for all living beings and the planet too. Today you can see a lot of the grey smoke because it hasn’t rained for a long time,† answered his father. There was once a little boy of 6 years old called Lewis. One day, as he was looking out of the car window on his way to school, he discovered that a large mass of grey smoke was forming just above his dad’s car. Somewhat alarmed, Lewis looked at the other cars on the road to find out if they too had a There was once a little boy of 6 years old called Lewis. One day, as he was looking out of the car window on his way to school, he discovered that a large mass of grey smoke was forming just above his dad’s car. Somewhat alarmed, Lewis looked at the other cars on the road to find out if they too had a cloud of grey smoke chasing them. To Lewis’ surprise, all the cars travelling on the motorway had the grey smoke hovering around them. So Lewis asked his father: â€Å"Dad, what’s that grey smoke above our cars? † Lewis’ father was a little surprised by the question, but answered: â€Å"Well, Lewis, it’s called pollution. † â€Å"Pollution? What’s pollution? † asked Lewis, waiting intrigued for his father’s answer. â€Å"Well, for example, it’s that grey smoke you can see above our cars. Cars that run on petrol or diesel give off gasses into the atmosphere, which are very bad for all living beings and the planet too. Today you can see a lot of the grey smoke because it hasn’t rained for a long time,† answered his father. cloud of grey smoke chasing them. To Lewis’ surprise, all the cars travelling on the motorway had the grey smoke hovering around them. So Lewis asked his father: â€Å"Dad, what’s that grey smoke above our cars? † Lewis’ father was a little surprised by the question, but answered: â€Å"Well, Lewis, it’s called pollution. † â€Å"Pollution? What’s pollution? † asked Lewis, waiting intrigued for his father’s answer. â€Å"Well, for example, it’s that grey smoke you can see above our cars. Cars that run on petrol or diesel give off gasses into the atmosphere, which are very bad for all living beings and the planet too. Today you can see a lot of the grey smoke because it hasn’t rained for a long time,† answered his father. d by the question, but answered: â€Å"Well, Lewis, it’s called pollution. † â€Å"Pollution? What’s pollution? † asked Lewis, waiting intrigued for his father’s answer. â€Å"Well, for example, it’s that grey smoke you can see above our cars. Cars that run on petrol or diesel give off gasses into the atmosphere, which are very bad for all living beings and the planet too. Today you can see a lot of the grey smoke because it hasn’t rained for a long time,† answered his father. Lewis spent a while pondering on this, and began to put two and two together. If the grey smoke was bad, and it was all because of cars, then why were there so many cars on the road? â€Å"Dad,† said Lewis slowly, â€Å"If the grey smoke is pollution and is bad for us, why are we going to school in a car? † â€Å"So I can get to work on time, son. The bus or metro would make us late,† answered his father. It was Spring. As soon as the cold weather went, it came back again. The sun seemed ashamed to show his smily face for more than the odd morning. To top it all, loads of people were sick. A spectacular chucking-up bug was going around the school. If anyone looked so much as a bit pasty in class, the teacher would grab an empty litter bin and tell them to hold it close by. Minutes later the school secretary would be calling Little So and So’s mother and telling her to get over quickly and collect her sick child. The bug even got poor Isis, who was NEVER off school. Like everything else about her, Isis’s attendance record was usually perfect – but not this week, because there was no way she could come in. She texted Katie: â€Å"Poor me, I feel so rotten! Chucked up 6 times. Is that a world record? † Katie had so far escaped the bug. She was very careful about washing her hands and not going near anyone who coughed or spluttered. She asked her mother what could be done for Isis, and she suggested an ancient witch’s remedy made from mint leaves and mandrake’s root. ‘Sounds great,’ said Katie, â€Å"Why don’t witches cure everyone? ’

Essay on Global Inflation and Unemployment - 1279 Words

Article summary This article by Andrew McCathie posted in EarthTimes and titled â€Å"European inflation climbs unemployment at 12-year high was posted on Friday July 30 2010. The article reports that food and energy costs have played a critical role in driving up inflation in the 16-member eurozone. The rates of unemployment remained stagnant to its highest level during this time. Introduction The recent global financial crisis that affected not only America but also Europe and other parts of the world resulted in massive unemployment. This is due to the high costs of operation that many corporations faced forcing them to cut on labor costs. There is need for European government interventions to avert this social crisis and prevent†¦show more content†¦This value is of much significance to investors as it has an effect in inflation rates (Cencini, 2008). The global financial crisis has had multiple effects in different industries in different countries. Analysis Consumer price index This is the overall cost of goods and services that are bought by an average consumer. This index is used in measuring the cost of living over a given period of time. When there is a rise in consumer price index, a typical family has to spend more money in order to maintain their standard of living. Inflation is a term that is used to describe a situation where the overall price level of an economy is rising (Mankiw, 2008). Inflation From the above graph, it can be seen that since July 2009, the consumer price index has always been increasing in Europe. This increase in consumer price index has been pushing inflation higher and higher. This has resulted in decreased profitability of most European corporations thus cutting down on costs by retrenching some staff hence causing unemployment. If this is not checked, then there is a chance that this will be a vicious cycle that will occur throughout the years. When massive unemployment occurs, the average purchasing power of an economy reduces. This could have an effect of forcing corporations to increase prices of their goods and services in order to maintain profitability. The net effect of this is increase in consumer price index further driving theShow MoreRelatedThe Australian Government’s Implementation of the Economic Stimulus Plan746 Words   |  3 PagesInflation can be described as the sustained increase in the general level of prices over a given period of time, usually one year. Inflation can have negative effects on many of the key economic outcomes such as economic growth, exports, international competitiveness and income inequality. 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