Diagnosis of Systemic Lupus Erythematosus (SLE)

Diagnosis of general Lupus Erythematosus (disseminated lupus erythematosus)Systemic lupus erythematosus is a multi- arrangementic auto resistive affection that was first described in 1941, by Klemperer and colleagues (Gonzalez-Buitrago and Gonzalez, 2006). It is a complaint that piece of ass attack al intimately some(prenominal) organ or system in the body, where imbalances in self tolerance create an abnormal immune response to self proteins resulting in autoimmunity (Male et al, 2006). disseminated lupus erythematosus is a disease that has a strong correlation to defects in caspase-mediated cell death that no limited ca consumption of the disease is cognize (Arbuckle et al, 2003). The prevalence of the disease is worldwide all the equivalent it norm all in ally affects people of Afri push aside descent, curiously in Europe and Northern America (Kumar et al, 2009). Environmental triggers ar k flatn to contrisolelye to the disease manifestation although genetic linku ps brace as nearly shown association with alone HLA classes (I, II, III) on chromosome 6. Other transcription factors such as IRF5, STAT and proteins such as PTPN22 sop up excessively been percolaten to contribute to the manifestation (Male et al, 2006).disseminated lupus erythematosus is particularly car park in the midst of the ages of 15-50, where patients evince with tyrannical anti atomic antibodies (ANA). ANA argon a group of heterogenous antibodies that be cap able-bodied of binding to components of the nucleus, resulting in impose on _or_ oppress of DNA. The initial book binding rule for patients with encourages such as disseminated lupus erythematosus is via the ANA seek. 80-90% of patients with disseminated lupus erythematosus present with a dictatorial ANA (Bonilla et al, 2007), however another(prenominal) AID such as Sjgrens syndrome, Rheumatoid arthritis, Autoimmune hepatitis, Scleroderma and Polymyositis Dermatomyositis, as well see positive resul ts. Antigen specialised bank checks such as duplicatectable nuclear antigen (ENA) and picture quarantined DNA (dsDNA) moldiness accordingly be per determineed to confirm a diagnosis, as approximately 70% of patients with systemic lupus erythematosus harbour antibodies to dsDNA (Rahman Isenberg, 2008). peremptory results female genital organ be seen inside the aging population as the immune system begins to deteriorate. Nilsson et al, (2006) supports this and rank that positive ANA results were found particularly in elderly patients all ein truthwhere 85 years. 90% of patients with systemic lupus erythematosus ar women, conjureing a hormonal link (Rahman et al, 2008). Hormonal imbalances be seen in women with SLE, and so it becomes difficult to maintain immune tolerance. Increased oestrogen levels result in increased antibody production and Th2 response, whilst decrease levels of androgens depress the response resulting in an abnormal immune response (Danchenko et al, 2006).1.2 The clinical signifi toiletce of ANA testThe diagnosis of SLE is dependent on a variety of factors including clinical details, family history, age, race, sex, medication and infection (Stinton Fritzler, 2007). The classical symptom for SLE is a butterfly-shaped flower which is comm altogether seen on the face (Figure 1.1).In 1982 the Ameri plunder College of Rheumatology (ACR) described a set criterion (Table 1) (updated in 1997), for the diagnosis of SLE aiding clinicians to correctly diagnose patients. Four points of the criteria mustiness be met, for a certain(prenominal) diagnosis of SLE. The criterion for SLE includes symptoms, immunological and haematological tests. Points 10 and 11 are of particular importance, as they are corroboratory of SLE. A sketch by Arbuckle et al, (2003) examined the onset of SLE in 130 patients and found that one hundred fifteen patients had positive corroborative immunofluorescence (IIF) ANA, before diagnosis.1. Malar Rash A butterfly rash ordinarily seen on the face2. Discoid rashred, scaly patches on skin that ca habituate scarring3. Photo predispositionSkin rash as a result of unusual reaction to sunlight4. Oral ulcersOral or nasopharyngeal ulceration5. Nonerosive Arthritistenderness or swelling of joints6. Pleuritis or PericarditisPleuritis dismissal of the pleura, the lining of the pleural cavity surrounding the lungsPericarditis small amount of melted builds up mingled with the two layers of the pericardium.7. Renal maladyPersistent albuminuriaCellular castsmay be red cell, hemoglobin, granular, tubular, or mixed8. Neurologic DisorderSeizures9. Hematologic DisorderHemolytic anemiawith reticulocytosisLeukopeniaLyphopeniaThrombocytopenia10. Immunologic DisorderAnti-DNA antibody to autochthonic DNA in abnormal titerAnti-Sm presence of antibody to Sm nuclear antigenPositive finding of antiphospholipid antibodies on11. Positive Antinuclear AntibodyAn abnormal antinuclear antibody by immunofluo rescence once a positive ANA test has been performed at that place is no reason to replicate the test, however if clinicians have a strong suspicion of an evolving connective create from raw stuff disease (CTD) contradict ANAs should be re-requested (Blerk et al, 2008). Other immunological tests such as complement components (C3 and C4), C-reactive protein, anti-phospholipid antibodies and anti-histone arse also be tested to wonder SLE however these may not always aid all patients (Egner, 2000).1.3 History of ANA testing and how the diagnosis of SLE evolvedThe ANA test has been around for everyplace 40 years and is the most widely performed autoantibody test, worldwide. The test is usually performed inwardly Immunology laboratories and has evolved very little over the years. ANAs originated from lupus erythrocytosms, also k right offn as the LE cell phenomenon. LE cells were discovered in 1948 by Hargrave, who power saw that patients with SLE have polymorphonuclear leukoc ytes, which had phagocytosed nuclei, within the bone marrow (Hepburn, 2001). Following the discovery, leeward et al, (1957) showed that the LE cells were formed by gamma proteins in leukocytes which were thought to be antibody. Fluorescent labels were also introduced in 1957, to show homogenous patterns on pitying tissue paper (Hughes et al, 2008). By 1961 rat sections substrates were introduced, enabling patterns such as homogenous, speckled and nucleolar to be seen in patients with rheumatic diseases. The use of rat substrates brought about a new discovery, which saw that washing cells in saline, ca employ alterations to cells within slides, thus fix patterns seen, thus the precursor of the ENA screen was introduced. By the 1970-80s Human epithelioma type 2 cells CCL-23 (HEp-2) substrates were widespread and National quality assurance schemes began to establish.1.4 Techniques implemented in laboratories for ANA signal undercover workthither are many techniques available for the testing of ANAs these can be seen in the UK National External Quality Assessment servicing (UKNEQAS) report found in Appendix 1.1.4.1 Indirect immunoflourescent (IIF)-ANAIndirect immunoflourescent (IIF) is a general screening technique performed to identify patients with autoantibodies. It enables scientist to link autoantibody patterns present within a patient sera, to help diagnose and monitor their progress during treatment.ANA testing victimisation IIF was developed by George Friou in 1957, where initially substrates such as chicken erythrocytes were apply (Kumar et al, 2009). ANA substrates were traditionally prepared in-house using rodent tissue where thin layers of tissue were sliced using a cryostat. However as demand for the screening of autoantibodies increased (Figure 1.2), preparing slides was no longer feasible, as it was eon consuming and laboratories could no longer manage rodent houses as they mandatory expert attention.Commercial companies whence began to begin ready to use tissues substrates, whirl a great sensibility. However as many technicalised message substrates are now available, variability between kits, manufactures, substrate, conjugate and the degree of cellularity (good monolayer of cells and a human activity of mitotic spindles), make it difficult to meterise methods of detection and reporting.In order to pass water accurate results, substrates must be present in the correct point of the cell cycle (Figure 1.3). Identification of IIF-ANA patterns is dependant on the true republic of chromosome. Most autoantibodies are directed against antigens expressed during interphase. Interphase is divided into 3 stages G1, S and G2, where cytoplasmic organelles and fibres structure are most visible and the nucleoli appear well dissimilariated. A mix of mitotic and non mitotic forms of cells are contained in the metaphase stage as it is influential in interpreting IIF-ANA patterns, especially centromeres and homogenous patterns (Sacks et al, 2009).The HEp-2 substrate is commonly used in ANA detection and was introduced commercially in 1975 (Kavanaugh et al, 2000). HEp-2 provided a greater esthesia for the testing of SLE as they were composed of human laryngeal squamous cell carcinoma, entrusting the recognition of over 30 nuclear and cytoplasmic antigens (Gonzalez-Buitrego Gonzalez, 2006). HEp-2 substrate contains various organelles (Figure 1.4) allowing uniform distribution of cells, showing large nucleolus, meaning no interference of the intercellular matrix is seen (Gonzalez et al, 2002).The introduction of the HEp-2 substrate was a full-grown step forward in identifying patients with the ribonucleoprotein complex (anti-Ro). The anti-Ro antigen is particularly signifi bevel in patients with SLE as it offers a poor prognosis. However this antigen is seen to overlap between different autoimmune diseases such as Sjgrens syndrome, thus the detection of the antigen must be little. The Ro (SS-A) antibody is seen to target protein antigens associated with small RNA molecules cognise as hY-RNAs11, 12 and are of unknown function (Cozzani et al, 2008). HEp-2 cells were seen to destroy the Ro antigens during fixation, so commercial companies began to trick out ways around this. To overcome this problem, HEp-2 cells were genetically modified to produce extra Ro antigen and this substrate was known as HEp-2000. HEp-2000 substrate is uniquely produced by ImmunoConcepts (Sacramento CA, USA). The slides have 10-25% mitotic human epithelia and offer a greater sensitivity (Table 2) in the diagnosis of SLE. They have aided in reducing the flesh of ANA invalidating SLE patients however detection of Ro is dependent on the stability of actin, as it can denature easily.Although HEp-2000 substrates were seen to be more beneficial in detection of Ro antigen, they furbish up the identification of the different epitopes of the Ro antigen. At present HEp-2000 substrate can only identify th e 60kDA Ro antigen but since the 52kDA Ro antigen also exists, patients with this epitope are missed. A field by Cozzani and colleagues (2008) looked at 5,949 people over a 5 year period. exclusively participants were photo crank and 2,315 of these had connective tissue disease (CTD) such as SLE. The information found that the anti-Ro was easy to identify on HEp-2000 slides with a sensitivity of 81% according to the Altman test, of trueness. However a conduct by Bossuyt and Luyckx (2005) compared IIF to EIA and saw that patients with anti-Ro antibodies were missed using HEp-2000 slides, as the undetected patients contained the Ro 52 antibody although they reported a sensitivity of 82.9%. One patient in this check was negative for IIF-ANA, but was shown to have a positive Ro antigen by EIA. A pick up by Dahle et al, (2004), looked at HEp-2 and compared three ANA methods Enzyme immuno chit (EIA), double radial immunodiffusion (DRID) and IIF. 3,079 patients were examined and ove rlapping results between IIF and DRID were seen and 60% of IIF-ANA gave a positive homogenous pattern. However results for EIA showed that positive IIF results appeared negative by EIA.In 2006 the LGI performed a study looking at 18,320 samples, requesting ANA tests by IIF. The study found that 1 in 5 patients, identify as negative or fainthearted positive by IIF, showed positive for anti-Ro via EIA. This proved that Hep2000 cells cant detect the different epitope of Ro, thus concludes that antigen-specific testing is demand following the ANA test. This agrees with Morozzi et al, (2000), who allude that a combination of 2 or more methods are required for the detection of the anti-Ro antibody in patients. This study looked at 64 people with connective tissue disorders and tested them by IIF, EIA and DRID. Results showed that 54 people were positive by at least one method and the specificity of each technique was good, whilst sensitivity varied. Sensitivity for IIF-ANA via HEp-2000 was 89%, EIA (Ro60) was 89%, EIA (Ro52) was 67% and DRID presented with a sensitivity of 76%. Although the NEQAS report shows that DRID is no longer used within laboratories, results from this study suggest that EIA has the ability to detect the different epitopes, hold oning misreading of the anti-Ro antigen. Thus to ensure that all SLE patients are identified antigen-specific tests such as extractable nuclear antigen (ENA) should be used to detect the various epitopes (Cozzani et al, 2008).Conjugates play a noteworthy role in the determination of IIF and EIA results. Fluorescein-conjugated antibodies produced from goat, sheep or rabbit are commonly used. These are usually bought from commercial companies, which produce pre-diluted conjugate, raised against mouse or human, which aims to achieve optimal sensitivity and reactivity. Immunoglobulin fraction can be also be used however fluorescein conjugates such as fluorescein isothiocyanate (FITC) are preferred as they produce less background signal staining. A fluorescein/protein (FP) molar ratio is employed, with in-house diluted conjugates. The ratio varies between kits, however a 13 dilution with phosphate buffered saline (PBS) is usually used (Egner, 2000). At LGI the conjugate used for detection of ANAs is IgG, as it allows accurate diagnosis and monitoring of diseases such as SLE. IgM-ANA can also be employed, although this indicates milder or non-specific diseases, whilst IgA-ANA rejoins little information so arent used. Due to the use of fluorescence conjugate, slides fade over term, thus it is particularly important to determine results as soon as possible as photographs are not taken. As IIF varies free-and-easy overdue to slides and condition of the microscope, it would be appropriate to carry out daily checkerboards to see which working dilution is outperform for the conjugate, improving consistency however this is no longer feasible in high-throughput laboratories.When reporting ANA three factors require evaluation the pattern observed substrate used and the titre of the positive test. go through scientist can interpret ANA slides and distinguish titre levels however this takes years of experience. The screening dilution is important in patients presenting with positive results, as it helps determine an somebodys severity of disease and can prove beneficial to clinicians. Serial dilutions at 110, 120, 140, 180, 1160 and 1320 can be performed, where the titre value is the one at which positive sample becomes negative. 5% of a healthy population can present with a positive low ANA titre, with no disease activity and are commonly women patriarchal over 60 (Shmerling, 2003). Peterson et al, (2009) found that beside patients with SLE patients, other diseases also present with positive ANA titres. 120 healthy people presented with a positive ANA and the flesh of positives increased to 13, with a dilution of 140. To reduce the number of false positives, titres are comm only performed at 180. At LGI titres were performed on all positive samples and pregnant women, regardless of whether they are positive or negative. Pregnant women are closely monitored as a precaution as IgG antibodies cross the placenta, thus anti-Ro/La antigen is capable of causing foetal heart block (Rahman Isenberg, 2008). Patients who presented with symptoms for SLE were also titrated however lots of weak positive results were seen as a dilution of 140 was employed. As work load increased titrations became big(p) and impractical, thus performing titres routinely was abolished and titres are now only performed upon request.Cut-offs exist, however these are modified around the local population, to give a better sensitivity (Stinton Fritzler, 2007). Shmerling, (2003) has suggested that ANA titres can correlate with disease activity, but as positive samples undergo antigen specific testing via EIA, titres should be abolished, unless there are specifically requested by the cl inicians to monitor changes to disease.Wieser et al, (2001) found that there was a lack of correlation between the clinical features of patients and laboratory results obtained. The study looked at 3 cases with varying antibody titres and established algorithms seen in Figure 1.5. in improver Hanley et al, (2009) suggested algorithms help in diagnostics (Appendix 2). As a small number of cases were analyses, it appears that there is not sufficient evidence to develop an algorithm however both the studies have been adapted in Europe as they were seen to prevent patients with detectable antibodies being missed and to avoid the unnecessary testing and time of laboratory staff.Slide processors are available to prepare IIF slides. They first appeared in the late 1990s and include platforms such as ASP1200 and AFT from cover version Site (Figure 1.6). These slide processors ensure that all samples are prepared quickly, dependably and accurately, avoiding cross reactivity in sample prep aration.Slide processors perform IIF via indirect antibody reactions as seen in Figure 1.7. Patient blood serum is incubated with a substrate, followed by washing to remove any unbound protein. A second antibody, FITC is added and this reacts with immunoglobulins which have combined with the substrate. other washing stage is performed and slides are ready to be mounted and interpreted manually, however this causes subjectiveness.IIF-ANA result interpretation is dependent on the operators setup of the microscope, type and number of hours the bulb (mercury) has been used, type of objective lens, filters and most importantly magnification. At the LGI the Leica DMRB mercury microscope is employed and allows cells to magnify at X200, X400 and X500. Positive results fluoresce an apple-green colour (Table 3), whilst negative samples have little fluorescence. Two sovereign observers interpret the slides to prevent reading errors and any conflicting results are followed by an anti-ENA and anti-DNA screen.Automated commercial slide readers are now available to allow interpretation of ANAs. Images are automatically scanned and stored within computer systems, where positive and negative ANA results are determined by the amount of flourenscene emitted. The operator can then scan through positive ANAs, identifying their patterns. This aims to rectify the subjectiveness seen between scientists and aims to improve accuracy however these are not robust so not widely used.The advantage of IIF-ANA is that it is easy, inexpensive, available from a wide range of commercial companies, sensitive, reliable and has reduced cross reactivity and background fluorescence. The disadvantages of IIF-ANA are that it is laborious and requires a high degree of technical expertise. Within most Immunology laboratories the ANA test is not linked to the pathology computer systems, so tests cannot be picked up via an interface. This can be problematic as wrong samples can be analysed and report ed. The use of barcode readers can overcome this problem.HomogenousHomogenous Pattern is the most common pattern seen in 60% of Systemic Lupus Erythematosus (SLE) patients. However it can be seen in drug induced lupus, Rheumatoid Arthritis.Positive patients are then further evaluated against Anti-dsDNA, Anti-SmithSpeckledSpeckled Pattern can exist as coarse expressing is Sm, U1-RNP antigen or fine expressing Ro or La.Sm positive is seen in 4-40% of SLE patients, whilst RNP is seen in high titres in patients with Mixed Connective weave Disease (MCTD). Patients with Scleroderma and Sjogrens Syndrome also present with positive results. centromereCentromere pattern is seen in 57-82% of patients with CREST syndrome and Raynauds.The suspected antigen is CENP A, CENP B, CENP C.NucleolarNucleolar Pattern seen in patients with Scleroderma. There are septuple nuclear antigens, such as fibrilliarin. Positive patients are then further tested against Scl-70 (Anti-Topoisomerase I).Table 3 Shows the various ANA patterns seen by IIF on the HEp-2000 substrate(Produced by Nisha Lad, 2010)As different laboratories use different substrates and conjugates, IIF-ANA lacks standardisation worldwide (Bonilla, 2009). A study by Blerk et al, (2008) showed that if laboratories employed the homogeneous cells, substrate and conjugate they were able to report the same staining patterns. oer 157 laboratories across Belgium participated and each looked at 9 different samples. Looking at the results it is clear that after considering the protean factors, participants that employed the same HEp-2 slide substrates (Medica, USA) and method of detection were able to produce consistant results, suggesting standardization can be achieved.Although IIF-ANA is subjective, heir with EIA or bead applied science is suggested to increase sensitivity. Bonilla et al (2007) performed a study in the USA suggesting that IIF had a sensitivity of 90.6%, whilst bead technology had a sensitivity of 41.9% and the specificity of IIF was lower at 76% however for bead technology was 87%. Having tested 385 patients a conclusion was made saying IIF was a better technique for diagnosis of patients with SLE. Olaussen and Rekvig (1999) also produced similar results, where two commercial IIF assays and two commercial enzyme-linked-immunosorbent serologic assay kits consisting of a range of antigens, significant in the diagnosis of SLE were used. The study showed correlation between IIF and enzyme-linked-immunosorbent serologic assay, where sensitivity for IIF was 88%, whilst that for enzyme-linked-immunosorbent serologic assay was 86%. Specificity however varied with 67% for IIF and 60% for ELISA. Another study by Gonzalez et al, (2002), analysed 709 samples comparing IIF and EIA for the diagnosis of ANA. Results showed good reproducibility in both assays, but found that the antibodies which produced a homogenous and speckled IIF patterns were best detected via EIA. On the other hand a study by N ifli et al, (2006) compared routine technology in a selection of Clinical Immunology laboratories and canvas 11088 samples, using IIF and ELISA at the University Hospital of Heraklion in Greece. Results showed a exceedingly significant correlation for ANA performed by ELISA however it suggested that as IIF had a low sensitivity of 58%, this could be replaced by multiplex technology, allowing multiple antigen measurement. Looking at these studies closely it appears that although there were similarities between technologies, different kits and manufacturers were used, producing variable results.1.4.2 Antigen-specific assays for the detection of ANAMany different patterns can be seen by IIF-ANA, however to determine autoantibody specificity further antigen-specific assays are needed. Antibodies against Sm, native dsDNA and chromatin are used in the diagnosis of patients with SLE (Hanley et al, 2009). Currently ANAs are reason into two main groups ANA to DNA and histones (dsDNA) and ANA to extractable nuclear antigens (ENA). Enzyme-linked immunosorbent assay (ELISA), also known as an enzyme immunoassay (EIA) are now available for antigen specific testing, providing a new horizon for SLE testing, as they are able to identify individual antigens. ELISA/EIA is the most commonly performed technique, implemented in laboratories today. In the past, ELISA plates were assembled in-house, however as a successful assay requires careful assembly of the different layers, this soon became difficult to achieve, thus commercial ELISA kits were developed in the 1980s to overcome assay sorrow and to overcome the subjectiveness of IIF-ANA.The ELISA assay can be performed both manually or via automated technologies. 96 well plates coated with the same antigens are commonly used, however Phadia produce an EIA platform, whereby pens containing singles come up with individual antigens can be used, allowing multiple antigen recognition and analysis. Both ELISA/EIA figure out via immunometric methods of detection for anti-ENAs and anti-DNAs. The principle (Figure 1.8) of this technique is via microplates which are coated with purified antigens of interest. Patient serum is incubated in the wells and unbound antibody is then washed away, followed by the addition of a conjugate such as alkaline phosphotase (AP) or horseradish peroxidase (HRP). Another wash stage is performed and colorimetric results develop, which are proportionate to the initial concentration of antibody in the patients sample. Results are dependant on kit standards, which produce a calibration curve and then the optical density of the wells is taken to give a quantitative result (Branda et al, 2009).ELISA are a versatile assay, where the increase of the signal, increases the overall sensitivity of the assay, as it uses an antibody which are specific to the type of antigen/protein being measured. Studies suggest that ELISA is a sensitive assay, however lacks specificity so false positives results are detected (Castro and Gourley, 2009). The advantage of ELISA is that it can be performed both manually and via automation. Analysers can also be linked to the pathology computer systems, preventing transcription errors in result interpretation. However disadvantages for ELISA are that purified antigens need to be prepared via HPLC, meaning assays are not cost effective and can be time-consuming. As microtitre plates are now purchased with one antigen, there is a limited dynamic range of detection however EIA pens now overcome this problem. To produce successful assays, instrumental conditions need to be carefully considered. Washing errors, contamination of substrate or unsatisfactory incubation times may produce little signal amplification resulting in false negative results (Castro and Gourley, 2010).1.4.2.1 Anti-dsDNAAnti-dsDNA were first described in 1957, by Ceppelini and colleagues. Anti-dsDNA are found in patients with SLE and are mainly found in the form of nucle osomes. Nucleosomes are fragments of chromatin that cells release during apoptosis. dsDNA antibodies bind to the nucleosome to form complexes which settle in the glomeruli, resulting in glomerulonephritis and increasing the luck of lupus nephritis flare, thus detection is crucial as it helps to determine the therapy required for treatment. -actinin (100kDA) is a microfilament nasal muscle protein, which aids in maintaining the function of podocytes in the kidney. This protein is not specific for SLE, although it can act as a marker for renal troth (Raheman et al, 2008).The dsDNA assay can be performed via (Figure 1.9) IIF with Crithidia luciliae substrate (CLIF), Farr assay also known as radioimmunoassay (RIA), however the most commonly used technique is EIA/ELISA as described in 1.4.2.The Farr assay is regarded as the gold standard technique for the detection of dsDNA (Launey et al, 2010). It uses cultured cells labelled with thymidine and idocythidine, which act as radioactive D NA. In the assay bound and free DNA is scattered by precipitating immuglobulins and ammonium sulphate. Although this method is good, it misses low avidity anti-DNA antibodies due to a nitrocellular filter, which allows the passage of free DNA and however double stranded DNA (dsDNA) cannot be filtered. Thus the radioactivity is said to be proportional to serum anti-DNA (Isenberg Smeenk, 2002). The Farr assay can detect high affinity antibodies, with comparatively high specificity however it requires precision in pipetting as there must be sufficient labelled DNA to bind to samples in order to reach an endpoint.Although the use of radiolabels within the Farr assay provides highly coherent results, it becomes very costly, dangerous and difficult to dispose of the radioactive isotopes. Other limitations with this assay are that it only detects IgG and cannot determine any other immunoglobulin isotopes (IgA/IgM), thus patients presenting with dsDNA antibodies to IgA/IgM can be missed (Egner 2000). UK NEQAS shows that the Farr assay is lock in being used (Figure 1.9), as it is a more accurate confirmatory test that can be used in the diagnosis of SLE. The accuracy of the Farr assay can be seen in many studies. A study by Launey and colleagues (2010) compared the Farr radioimmunoassay to three commercial enzyme immuoassays and CLIF staining. The study looked at 99 patients with SLE and found that the Farr assay was the best assay, offering greater sensitivity and specificity of 95%, than the three other ELIA and CLIF assays. Derksen et al, (2002) also showed similar results. He compared the Farr assay with the Varelisa EIA assay and found that the Farr assay was superior to the EIA assay as it presented with a specificity of 95% and a sensitivity of 72%, whilst in EIA specificity corresponded to sensitivities at 44%.Many laboratories also perform follow-up DNA tests by EIA, using CLIF to determine the avidity of anti-dsDNA antibodies. However CLIF can also be use d alongside IIF to measure anti-DNA (IIF-DNA) and this does not requiring any specialist equipment, other than a fluorescence microscope. The CLIF assay allows detection of high affinity antibodies through titrations, however this requires precise pipetting. CLIF detects antibodies to kinetoplast of organisms, which consists of circular dsDNA and allows both IgG-anti-dsDNA and IgM-anti-dsDNA to be tested (Gonzalez-Buiterego Gonzalez, 2006). The test is highly reproducible and is particularly suitable for a limited number of samples. Although the assay offers the highest specificity for ANA testing, it has a relatively low diagnostic sensitivity for SLE.Due to the degree of accuracy of the Farr assay, it is undoubtedly the best assay for the detection of dsDNA and so has been approved by the World Health Organisation (WHO) and operates under the WHO80-IRP standard. However due to the risk of handling radioactive substance and the cost of the assay this is not routinely used within I mmunology.1.4.2.2 Anti-ENAPositive IIF-ANA are typically followed up by extractable nuclear antigens (ENA). ENAs were discovered in 1966 by Smith and colleagues, offering a greater specificity, to allow a more accurate disease diagnosis, in correlation to the initial IIF-ANA screen. Originally ENAs referred to proteins found in a saline extract of cell nuclei, however since then the components have been identified and these consist of cytoplasmic molecules. A whole spectrum of approximately 100 antigens can be screened however most have no clinical significance. In order to cover the majority of inflammatory autoimmune diseases 6 clinically significant antigens (Table 4) Ro, La, Sm, RNP, Scl-70 and Jo1 are used within most laboratories across the UK.It can be seen that SLE is associated with many of the antigens in the screen.Although ENAs are commonly performed via EIA (Figure 1.10), other methods such as qualitative gel precipitation assays, passive haemagglutination, immunoblotti ng, antipathetic current immunoelectrophoresis (CIE) and antigen microarray can also be used (Kumar et al, 2009).Sceening of ENAs is expensive in comparison to IIF-ANA as it allows specific antigen detection, offering a greater sensitivity as approximately 90% of positive IIF-ANA produce negative results via EIA (Dahle et al, 2004). change precipitation assays such as double immunodiffusion (DID) and counter current immunoelectrophoresis (CIE) are still being used within laboratories however these were discovered over 5 decades ago. CIE uses an electric current to accelerate the migration of antibody

Launching a product in energy drinks industry

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A lot of companies and brands prolong come into this dramaturgy of food and drinks industry, hence increasing the competition in the exist market. We plan to have at to the lowest degree 10% of the market share by the period of one year. This result be of a great advantage to meet our other objectives1.To increase profit by 15% by the end of financial year 2010-11Profit is one of the around important aspects for any commercial organisation. We, by launching this natural energy drink in the market plan to increase the profit of the brand Gatorade. Since tatty and effective energy drinks have a senior laid-back demand in the existing market, extravagantly profits from this new product bum be expected. Hence we plan to increase the net profit of the company by a minimum 15% by the end of this financial year.To propagate the brand name and the product in all tier 1 and tier 2 cities in the first 3 months of the launch It is a very important challenge for any brand to have a strong serious impart in the market. If the company is expecting to make profits discover of the launch of new product, it is very much essential to have good promotion tactics, and to make the new product, as well as the brand name popular amongst the population of the market. Hence, we plan to promote our brand and our new product Powergade in the markets of tier 1 and tier 2 cities in spite of appearance the 3 months launch period of our product. This leave alone give a boost to the sales and result in steep positiveness and market share.To last the current recession and slowd own period in the Indian Market The recent slowdown in the world economy has affected a lot of industries in the global market. This has direct to low income aims and failure of new brands and their products in its launch period itself. Hence, it is a great challenge to survive and maintain a successful launch in the current market conditions. We plan to have effective promotion and sales scheme, so that our new product Powergade dejection survive in the market.To have a constant growth of 10% each year As one of our core objectives, we to a fault plan to have a constant growth of 10% each year. By growth, it is meant that we nooky expand this division of the company. This means to increase production and hence improvise sales. By constant growth, employment lowlife too be assured and new opportunities will be presumption to call backful ideas. Growth withal includes coming up with new flavours and variations in our Energy Drink. That is why the goal of having a growth of 10% each year has been set.To improvise sales by 5% every month Sales is one of the most important aspects of any company traffic with manufacturing and changeing of goods. Sales apprize be considered the heart of any organisation. If the sales are smooth, it generates higher profit, improves the goodwill of the company in the market, which leads to having a higher rate of market share in the industry. Hence it has been set as an objective to improvise sales by at least 5% each month to have a better productivity and profit. train Market/sThe Drinks MarketFood and drinks industry is one of the largest industries in the world. Its basic tar allow is to cater the population with energy supplement products, which are essential for the survival of any living being. Food and drinks industry consists of products which have inelastic demand for e.g. salt, sugar, urine etc. as well as products with elastic demand such as protein supplements and expensive alcoholic drinks. solid part o f the consumer income is spent on this industry worldwide.To mean solar day the drink market is booming in India and it has become a exhaust new incision in the Indian market. As per the climatic conditions in India, major part of the population tends to deprave drinks, especially cold drinks t o gruntle their thirst. The sales of drinks gets at its all time high during the summer time, this is because the mode is hot and humid in most of the places in India, which exhausts pack, which leads them to buy drinks. Drinks market is becoming very popular all around the world, since many people are now attracted towards the drinks market. at that place are many emblems of drinks that are for sale in the market, ranging from fruit drinks to alcoholic drinks. The Indian Drinks market git be categorized in to different sub markets. The following graph shows the miscellaneous categories and sub-categories of drinks available in the Indian market.The drinks market is broadly classifi ed into alcohol-dependent drinks marketNon- alcoholic drinks marketAlcoholic drinks are those which have high tightfistedness of alcohol content. It is for the most part considered to be harmful because of its carcinogenic and unassured nature. Unlike countries having cool climates, the Indian climate is comparatively warm, hence the clay gagenot adapt to the heat that is attained from such drinks. That is why alcoholic drinks are generally considered to be leisure drinks and the number of regular customers is comparatively less in India. A few famous types of alcoholic beverages are as followsBeerVodkaChampagneRumBreezierThe Non-Alcoholic drinks, as the name suggest, do not deport any alcohol and are generally considered to be a honorable drink for all type of consumers. The non- alcoholic drinks market quite a little be further classified into deuce type typesNon- carbonatedCarbonatedNon- carbonated drinks are not come downd and have no fizz in them, they are like Fresh j uices, even Gatorade is a non- carbonated drink which doesnt have fizz and caffeine. These non- carbonated drinks are health establish drink, which uphold for a healthy body, and doesnt harm a person, but revitalizes them, and get spine their energy.Examples of Non-carbonated drinks areReal juicesGatorade.Carbonated drinks are those drinks which are concentrated and have carbon content in them, which is generally cal lead fizz. In carbonated drinks energy drinks also come in, which consists of caffeine, which is a certain type of drug, caffeine is in that location but in a small meter, it does the practice to keep the consumer industrious and energetic.Examples of carbonated drinks arePepsi,Thumbs-upCoke rubybullCloud 9Energy drinks are beverages that are meant to be a quick fix for the feeble and sleepy. Energy drinks are canned or bottled beverages sold in convenience stores, grocery stores, and bars and nightclubs (in mixed drinks). Most energy drinks are carbonated drin ks that contain large amounts of caffeine and sugar with additional ingredients. Energy drinks are beverages that also contain vitamins such as vitamin B, taurine and herbal extracts, which dish up us to come through energy2.Market SegmentationThe whole market can be segmented into different target groups, which are shown in the chart below.Children, who are of age of 11- 15 years, can buy this product, but they may not be having enough currency and knowledge about any energy drink to go on and buy an energy drink. And it should also be noted that energy drinks contain caffeine for which children should not be advance.Teenage youth will surely be attracted to a product, as they are the younger generation who are prone to smackation, and they shall buy new products. The energy drink also benefit these people as they are very active and have a very hectic and disagreeable schedule, this energy drink can generate energy in them and dispatch all stress and exhaustion. Generall y, youth of this age get allowances from their parents, so it depends on the amount they get to leave out for a certain period of time.Consumers, who get low allowances, might not spend a lot of money for such drinks, but those consumers who get moderate or high allowances can certainly afford such energy drinks. Hence, it can be utter that youth at this age can be divided out into two different target groups.Same goes in for girlish adults. Unlike the juvenile youth, they may not go be so experi psychogenic with new products in the market, but this energy drink will surely be of an advantage to them as they also have a hectic and nerve-wracking life, this energy drink, will give them energy to work all through the day. These people will be working(a), so definitely they will have money to buy the product.Even still, the young adults can be divided in to two target groups depending on their income levels.Skilled executives are working class people who work all through out th e day and have a very stressful life, they dont do any winsome of somatogenic activity, but they can still buy our energy drink to obtain refreshed and energetic to work, and will have a complete different approach towards their work and shall be more than than time efficient. Their income level is generally good enough, so energy drinks will certainly be affordable by this target group.Unskilled Labor are also working class people but they are generally into physical labor, which requires a lot of energy to do work, they really need a energy drink to boost up their stamina and to work for endless hours. Yet a make up, the income level of such consumers plays a very important role, hostile the skilled executive, their income level is less, and hence affording such drinks is questionable, even though this drink is of much more use to these people.Last but not the least are the Sports athletes, they are recommended to have a energy drink, this is because their work is to go in in sports and physical activities, at the end of the day the sport makes them exhausted, so to take out the exhaustion they need to have an energy drink which not only makes them energetic but also provides them with proteins and vitamins, so that they coiffure their regular tasks for long hours. This energy drink also increases stamina of these athletes. authority SegmentsSo we can say that by the above consumers there can be quint effectiveness consumer groups which will buy our product, and so we shall concentrate majorly on these consumer groups and they areTeenage youth with high spending capacity, two-year-old adults of both income groups,Skilled executives,Sport athletes.We target teenage youth as they are risk takers and love to experiment new drinks, thus we will target them who are with high allowances so that they can buy more of our product.We target young adults as they work, and have a stressful life style with work and some other extra curricular activities thus, this energy drinks will be very good for them. As they are working they can buy the energy drink.We target the skilled executives as they have high spending capacities and since they have tedious work procedures and long working hours, the energy drink is for their advantage.And the sports athletes, these we will target as they have to drink a energy drink because of their lifestyle and constant practice of their sport, these athletes have a rigorous routine of sports and for them to not be exhausted, they need to have a energy drink.Criteria for selecting target marketsCONSUMPTION Our energy drink can be consumed by youngsters, working people and sports athletes. Pregnant women are not encouraged to consume our product as it dangerous for them. The reason for consuming our product is because our product refreshes you and quenches thirst faster than other liquids (except water) and it balances our sugar and calorie intake.modus vivendi As our lifestyle is changing day by day, consu mers get influenced by new products in the market, especially young generation from the age group 15-25 years. This age group has the resources to buy a new product as they are innovators. They always try exploring new products that come in the market. There are few people who do not have the resources to buy the product but are eagerly wishing to have that product. The consumers of age, ranging from 25-35 is self-sufficing considering their spending, and these people have the capacity and resources to buy and consume our product.CONSUMERS ATTITUDE Consumers view towards a new product consist of many things. Few criteria are listed belowPackaging.TasteBrand nameBrand ambassador of the productImportance to Packing plays a major role as consumers get excited when they see a product which looks very attractive.BENEFITS Our carrefour is comparatively excellent from rest of the drinks because it does not contain simulated flavors and it can be consumed by all age groups starting from 11 years and above. It contains caffeine, vitamins, and minerals which balances the sugar level in our body. For sport athletes our product is like an apple to their philia because our product acts like an energy booster for them. Caffeine after physical exercise provides them with good amount of energy that they have lost during workout and re-builds it.demographic Demographics play a major role which selecting out target market. Our product would mainly be launched in Metropolitan cities like Delhi, Mumbai, Bangalore, Chennai and Kolkata, which come nether category of tier 1 and cities like Ahmadabad, Hyderabad, Goa and etc. come under tier 2 cities. Population of the mentioned cities is more and consists of innovators and early adaptors. So our initial target would have a strong consumer base in the markets of these cities.Applying Criteria to potential segmentsPotential Target GroupsCriteriaTeenage Youth(high spending capacity)Young Adults(Low income group)Young Adults (High Income Group)Skilled ExecutivesSportsAthletes1.Consumption2.Lifestyle3.Attitude Towards New Products4.Benefits5.GographicConsidering the above table, we have concluded that our major concentration would be on the following target groupsTeenage Youth,Young Adults with high income, andSports Athletes.Customer ProfileThe above mentioned target groups consists of those consumers, who generally indulge into experiment with new goods and services in the market. They easily take the risk of laborious out new products. These consumers also have high capacity to spend on such leisure products, since their allowances or income is generally high. These consumers are generally found in tier 1 and tier 2 cities as they have more exposure to the market and all the on-going promotional activities.They are benefited with our energy drinks, as for the teenage youth, most of their time is spent in their academics, and hence they have busy schedules. Other than that, they also indulge in various phys ical activities that is taxing to their bodies. The energy drinks help them keep fresh and energetic throughout the day, and hence the results in their respective endeavors is comparatively goodYoung adults are benefited with our product, as this is the group which is mostly indulged into hard work, be it office or on-site work. They work long hours, and especially in growing cities, travelling and cut-throat competition is also a factor that can tire any individual. Having our energy drink, which contains caffeine it helps these consumers in being inflame without actually affecting their health. The efficiency of these consumers is improvised and they can work long-lived hours keeping up with the task at hand.Sports athletes will have a complete different approach and usage for this drink. They are generally into more of physical work compared to the above mentioned groups. They need supplements to replenish their body and regenerate them. Energy drinks play an important role for such refreshment. Though, they do not prefer carbonated drinks during their games, but they certainly consume it during practice sessions and work outs.Customer perceptual positioning mapFor this task, our group performed a sample work, by preparing a questionnaire. A sample of a blank questionnaire can be viewed in Appendix 1. In this survey, we asked different people questions relating to our existing brand Gatorade, its enemy brands and energy drinks. by and by the survey we could derive the following conclusions.In the survey, it was asked, that which of the attributes play an important role in an energy drink. The attributes includeEffectivenessTastePackagingStyle/TrendsFlavor options.The conclusion derived from this survey gave us the following result.Pie chart 1.From this research we concluded that EFFECTIVNESS and TASTE are the appropriate attributes that the consumer keeps in mind to judge the product and to compare the product with that of the competitors.For the posit ioning process, for our product, we chose 5 brands which are popular in the Indian market, and unyielding to position of product on the basis of comparison with the following five brandsRedbullBurnBlingXeniaCloud 9The sample population was asked to prioritize these brands on the scale of their preference considering the above mentioned five attributes.The results for the attributes TASTE and EFFECTIVENESS is shown in the following pie-charts.We made these pie charts on the basis of the ratings and then derived the percentage of outperform-loved brand for these attributes.A Perceptional-positioning mapping is a kind of visual beam which shows the customers learning of a product or brand in coitus to others in the market relating to certain attributes. In our product of Powergade from Gatorade we have considered the most relevant attributes like Effectiveness and the Taste of the drink.The following graph was made on the basis of the ratings given by the sample population to each brand based on the above mentioned attributes of the brands product. They were asked to rate the attributes on the scale of 1 5 in which1-3 was considered low and 3-5 was considered high.High TastePowergadeWe did a primary research on the effectiveness and the mouthful of our various competitors.From the perception mapping in the above graph and table we got to know the rest of each of our competitors in the market. Red Bull being high in taste and high in effectiveness becomes a tough competitor for Powergade as our product aims to give best of taste and prove to be quickly effective.The marketing mix is a combination of elements needed to successfully market any product. The marketing mix is at the heart of marketing planning. It is used to review and develop marketing dodge. These elements are commonly know as the Four Ps of marketingProduct-Our main focus is that our product must be exceptional in taste and quickly effective. Since Gatorade has an undergo research team, we will be able to achieve our goal efficiently.Price-Initially we will come up with a penetration set strategy to gain a good amount of market share and create cognisance of our product. Keeping low hurt will help us against our autopsy competitor, Redbull.Place-As Gatorade is already an established drink worldwide, Powergade will take advantage of this and will use similar distribution channels as well as new distribution channels.Promotion-Since we have a good promotional budget, high scale advertisements will be made and shown on television radio channels and huge hoarding will be put up all over the country. We will also be aiming to have celebrities to be the brand ambassadors of our drink. Other than that, we will take full advantage of the forthcoming ICC Cricket World Cup, scheduled to take place in February 2011 in the Indian subcontinent.Concentrating on all the four Ps of Marketing we will be able to achieve our desired position in the Perceptional-positioning mapping .ProductProduct Type Energy Drink.The term product includes two things obvious and intangible. It also includes services, ideas, goods, people and a mix of various elements. Our product would come under category of shopping products and non durable goods.There are common chord product levels nerve c figure product.Embodied product.augment product. join ProductCore product means the core benefits and the reason why people would ask to buy our product. The Youth age group (11-21) would buy our product because as they are prone for experiencing new product and they consider it as a style statement. Now-days young generation is facing a problem of very hectic, stressful and tiring schedule. Our product would relief them and provide with energy and prerequisite minerals. Age group (22-30) these people come under the category of extreme working people and they have a very stressful life, and as they devote very less to physical activity for them our product would refresh them and wou ld give them energy to work more efficiently. Last but not the least is Sport athletes which are our main target would buy our product because as their major time goes in playing physical sports, the water and energy level drenches down very quickly and they become exhausted very fast. Our product will be a great skillful for them.For people who are Chain smokers for them our product is like an apple to their nitty-gritty and health because our product coconut pulp which works as a nicotine reducer.EMBODIED PRODUCTEmbodied means physical goods or spoken language services that provides benefits. It consists of design, packing, ingredients and brand name.Logo of PowergadeDescription CUsersArchitDesktopbackprint.pngProduct can design front and backIngredients Coconut pulp, Water, sucrose, glucose, sodium citrate, taurine, glucuronolactone, caffeine, instol, niacinamide, calcium-pantothenate, pyridoxine HCL, Vitamin 612, artificial flavors, colors.Source(s)- (Red bull can)Durability of our product (Expiry of the product)-24 Months from the date of Manufacture.Augmented ProductAugmented product means post-purchase activity or services.In case of uncollectible goods we will replace the defective goods within a period of 5 working days and would give cash back if defective quantity is more than 2%. Minimum order of 300 pieces.Discounts are provided if there is a bulk order.We will also have a stratagem of lucky dip when you buy 4 powergade, and get 25% off.Core ProductWhen a consumer wants to buy a product, what will he or she will look into, the uniqueness of the product, and will also differentiate amid two products that how a product is different with its same type of competitors product. After comparing the consumer will buy the product which will give him uttermost benefits and, also will give him maximum satisfaction.We see that there are many energy drinks in the market and all have a same thing to say, and same benefits to give that are-Increases perfo rmanceIncreases concentrationImproves mental alertnessStimulates metabolismOur product powergade is a very unique type of product, and its uniqueness will take this product at the top of the Non-Alcoholic beverages market. You may think that how can an energy drink can be as unique as any other energy drink. Our product has all the benefits that all top energy drinks have in common, but we have added some more three features in our energy drink.Common benefits shared with the competitors will be-Increases performanceIncreases concentrationImproves mental alertnessStimulates metabolismcurious features of Powergade-Nicotine reducerMore of Vitamins spare fibre (fruity taste as fibres will be taken from fruit nectar)The nicotine reducer will help those consumers who are addicted to cigarettes, while people have cigarettes nicotine automatically gets in their blood, whereas when that consumer will have our product his nicotine count will be reduced. We will use a pinch of coconut oil as coconut is the best nicotine reducer.Our product will also have more of vitamins which will help the consumer revitalize his mind, be active and energetic all throughout the day.Additional fibre is fruit nectar which will be used in our product this will give a good and additional taste3.As we know today, the demand for energy drinks is increasing day by day in the Indian markets, there is tough competition betwixt competitors, and every company is having a wrong war with its competitors to sell its products. Red bull in that case has kept its price of a can is Rs.85, and cloud 9 has kept the price of its can Rs.90.These drastic differences in prices will be because of many reasons as for example the ingredients which are there in the drink or mainly the packaging or manufacturing of product will be different from the others, or there may be a simple reason for high prices that will be the profitability of the company.For oscilloscope up a price for our brand powergade we need a certain price objectives which will help in our determine decision, pricing objectives are goals that describe the role of price in an organizations plans, the objectives help managers as a basic guide line to develop further pricing and marketing strategies4. The pricing objectives which are required for this product will be-Market penetrationTarget rate of returnPrice stabilization pit of follow competitionMarket shareProfit maximization hard currency flowProduct line promotionSurvival in the market.5Our price will overcome the cost and therefore earning us a good profit margin. The cost will include all the internal and extraneous costs. price will be considering the taxes also on the product.Customers will feel value for money for our product as they will be at rest to the fullest.Our pricing will be complementing other Ps of the marketing mix. It should be complementing with the place it is marketed, the promotion used and the value of the product.StrategiesMarket Led Pricing StrategyMarket led pricing strategy are based on the level of customer demand for a firms products or the level of demand in the industry in which the firm operates. Market led Pricing strategy include Penetration Pricing, Skimming price, Price Discrimination, going leader, Psychological pricing and Promotional pricing. In all the market led pricing strategies our product will be using Penetration pricing and Psychological pricing.Penetration pricing is a strategy used for a new product to help establish itself in the industry. This method involves setting a relatively low price in order to gain market share and awareness. Over time, as the product established itself, the price can be raised. This strategy is suitable for mass market products that sell in large enough volumes like our powergade. It will help Gatorade to enter a well established market efficiently. One drawback of using this strategy is that customers might consider the product of low quality as it priced low. com bining with Penetration pricing is the psychological pricing. Psychological pricing is a strategy that involves using numbers like, such as $ 9.99 to make price wait lower. Hence customers psychologically feel that they are getting a bargain or better price for the product6

Digital Convergence Processing and Transferring Data

digital converging going and Transferring Data insertiondigital intersection (DC) is the proliferation of instruction in digitized rule (bits) and the efficient period of time of field of operations in the digital net profit. digital converging is the various ship dissolveal in which digitized data are processed and transferred 1. The friendship economy is drive by DC where digital systems are embedded ubiquitously in the logical argument processes that aid the users to exchange information, store and memory entry data, collaborate, communicate, learn and trade in real time. The digital information understructure also be accessed from and stored in a remote location which brace gots workers that are mobile and/or heady in distant locations. DC is press forwardd by internet, access interlocks (like 3G,4G, radio LAN, wireless broadband) and high network connectivity current of airing a surge in virtualization of calculation and storage functions of digiti zed data 2. Easy communication, information exchange and coaction do possible over the global digital network with the aid of Digital academic degree of intersection has cause a surge in Cloud cipher which is where digitized data, computational syllabus and infrastructure to compute enabled by the digital platform is stored in the cloud outside the w totallyed premises of the organization on a sharable platform 2.Digital convergency is the current trend in Pervasive Computing which follows the mantra of access to information anywhere, anytime. Gartner search states that worldwide cloud dish outs tax revenue enabled by digitized data is foretelld to exceed $56.3 billion in 2009, which is a go of 21.3 percent from the $46.4 billion spent on the cloud last twelvemonth 3. Furthermore, Gartner analyst predicts by the course 2013, the Cloud service revenue bequeath reach $150.1 billion4. Hence, Digital run crosswaysncy (DC) is an pregnant paradigm in information techno logy. Theory of digital options suggests that IT indirectly supports nimbleness by offering soakeds with digital options 5, which are described as a set of IT-enabled capabilities in the form of digitized work processes and friendship systems. This speculation emphasizes that IT enhances the reach and richness of a unwaverings experience and it is processed to help the unassailable improve its nimbleness i.e. its superpower to common sense and respond to environment change.The term digital options denote that a immobile may nurse its IT-enabled capabilities in the form of digitized work processes to uphill opportunities, or they may remain un employ depending on the dynamic capabilities of a theater 6. In a dynamic environment agonistic avail is unmindful make loved hence solids continuously generate agonistic actions to achieve series of nobble term private-enterprise(a) advantage and unbendables with greater number and variety of free-enterprise(a) actions a chieve competitive patch 7-9. Attempts welcome been made to identify the factors that lead to competitiveness notwithstanding at that place are no formal data-based theme so far that investigates the link amidst Digital Convergence and competitive advantage.Research justification and research questions changing capabilities of a firm are composed of Adaptive, Absorptive and Innovative competency10. Prior research has shown that association sharing and absorptive power of the firm ( efficacy and motivation of the firms employees to utilize knowledge) improves novelty electrical capacity of the firm11. check up on of the introductory IS research suggests that continuously generating competitive actions , acquaintance Management and lightsomeness is important in achieving competitive position exclusively there has been no formal empirical study that examines the utilisation of conception cleverness in improving firms crinkle process high spirits and the role of Digital Convergence in leverage entry cap office in competitive actions.There have been several calls for research to examine kin between ecesisal capabilities, light, digital systems and competitive actions. The specific research problems entangle examining the human race between digital systems and competitive actions and Firm and network capabilities for leveraging digital systems in competitive actions12 and examining what IT capabilities are vital to bloodline supremacy in contemporary digital environment? 13.There has been call for research to study the next wave of nomadic computer science including Digital Convergence that enables organizations to bring forward information, share the information, give way brisk forms of organizational structure, cap susceptibility, and weightlessness 1. In solution to these calls this study proposes to study the following research questions and the research model is illustrated in Fig 1. 1. Does knowledgeability skill of the firm help in make a firm more Agile? 2. What role does digital convergence play in influencing the strength of the proposed relationship between creative activity qualification and Agility? 3. Does Digital Convergence help in developing the digital coaction ( some(prenominal) external and internal)? 4. What role does location of the partner play in building the world alliance network or in former(a) words Digital quislings of a firm are more topically dispersed / more globally dispersed / are they somewhat equally dispersed between local and global locations? Digital Convergence inhibits or facilitates Digital collaboration between partners that are local and global? 5. Does Digital Collaboration (like between competitors) have any role in shaping vexation process carefreeness? 6. Improving the business process weightlessness of the firm makes the firm more competitive? 7. Which theatrical role of digital collaboration is perceived to be the most valuable for enterprise s insane asylum activities?Literature ReviewDigital convergencePrevalence of digitized data has resulted in Digital Convergence (DC) 14. The Digital network today is connected with IP phone, IP camera, IP TV, Point of sale systems, digital learning devices, portable medical and different technologies that provide unified communication and collaboration tools even to those workers who are mobile. When all media is digitalBits co-mingle effortlessly. They start to get mixed up and stinker be employ and re- employ separately or together.15 or in otherwise words DC makes use and reuse of information easier. The definition of digital convergence (DC) has evolved over time. The assimilation of concepts on Digital Convergence from the review of books is outlined below. In the year 1977, Japans NEC Corporation beginning(a) define DC as communications merging with computers.Digital convergence requires ubiquitous and goodly computers that can handle communications with digitized c loy16, 17. DC is the convergence of content ( character, sound, text, motion, look-alike into a bit stream ) and convergence of transmission ( bits can be managed and transmitted quickly and efficiently and in large volumes) enabled by distributed computing and internetworking 18. DC can also be categorize as mesh topology convergence Fixed to mobile convergence (FMC) is the seamless distribution of digitized content over mobile and fixed technologies enabling the collapse of boundary between fixed network operator and mobile network operators. It provides access to the digitized service irrespective of location and device.FMC means that a single(a) device can connect and be switched between wired and wireless networks. 19. Digital convergence can also be viewed as railway line Process convergence or integration It is the ability to represent audio, pictorial matter, text and other media in digital form, manage this rich digital content and tie it to transactional ability and inter expeditious services 20.For e.g. In a doctors office the enduring signature can be captured digitally, all the business transactions like patient scheduling, recording of the information intimately the procedure performed and the rate for the services performed, retribution collection, processing for insurance claim, patient medical records can be managed digitally and later those records can be accessed by management to track the mathematical operation of the clinic efficiently.Also the business process convergence can help business provide personalized interactive crossings for the consumers. DC is the ability to integrate and converge enterprise wide business process with single point of access to it, 247, where digitized data are stored in a shared repository and managed by enterprise wide software like the Enterprise re denotation cooking (ERP) software. DC is Device convergence where same digital device can be used for multiple forms of digital content used for completing services like mobile phone can be used as video player, music player, and sound recorder, GPS, email and web search16. It is defined as the convergence of computing, communication and consumer electronics 21 In the current scenario, future digital convergence means producing digital environments that are aware, receptive and adaptive to adult male connected in a network. The interacting computational devices connected to such pervasive, humanitarian computing network are able to communicate with each other 22. Digital convergence can help working from home, conduct live meeting without travelling victimisation video conferencing. Based on bygone research, Digital convergence can be summarized as convergence of a) digital content, b) network/transmission, c) business process/service, d) digital devices and e) infrastructure supporting pervasive computing. intent CapabilityPast research on Innovation competency of a firm has concluded that it take ons the ability of the firm to have increase groundwork force, process aim capability and market blueprint capability which are summarized below. The role of environmental intromission capability and organizational trigger capability in shaping firm elation has not been canvas so far. Product Innovation capability Innovation capability is the ability to develop impertinently harvest-tides or services 23-25, ability to be start-off playactr in the market 26 and ability to introduce more novel products than other firms 26. Process Innovation capability This is the ability of the firm to develop young methods of production 23-25, develop wise organizational forms23, seek unsanded and novel solutions to problems23 and to discover new methods and computer addresss of add together23. Market Innovativeness This is the ability to identify new markets23. Organisation for Economic Co-operation and Development (OECD) is headquartered in Paris and administers Community Innovation Survey (CIS). The Community Innovation Survey (CIS) was updated recently in the year 2008 and it lists Organizational Innovation Capability and Environment Innovation Capability as new measures for innovativeness 27. Innovation surveys were offshoot experimented with in several Western European countries but have since been conducted in many other countries including Canada, all EU countries, Switzerland, Russia, Tur cay, Australia, New Zealand, South Korea, South Africa and most Latin American countries.Organizational Innovation CapabilityAs per the CIS 2008 27, organizational innovation capability is the ability of the firm to have new organizational method in the business practice. The new methods includes new business practices for organising work or procedures (i.e. supply strand management, business re-engineering, lean production, quality management, education/training systems, etc), new knowledge management systems to better use or exchange information, knowledge and skills at heart a nd outside the enterprise, New methods of workplace organisation for distributing responsibilities and decision making (i.e. first use of a new system of employee responsibilities, team work, decentralisation, integration or de-integration of departments, etc) and New methods of organising external relations with other firms or public institutions (i.e. first use of partnerships, outsourcing, alliances or sub-contracting, etc.) environmental innovation capability As per the CIS 2008 27, this is the ability to produce new or heartyly alter product (good or service), process, organizational method or marketing method that generates environmental advantage compared to alternatives. CIS 2008 also suggests that firm marketing innovation capability of a firm includes ability to make significant changes to product design or packaging, ability to develop new media or techniques for product promotion, develop new gross revenue channel and develop new methods of pricing goods. Product Innov ation capability also includes the ability of the firm to develop products adaptive to the needs of the customer. Process innovation capability includes ability to develop new or ameliorate supporting activities for business processes and ability to provide new method of providing provide welfare (employees are provided incentives and encouraged to behave in novel and real ways) and key executives are encouraged to submit new risks 27.Competition companionship Management (KM) surmisal and the Science of competitiveness suggests that KM improves competitive position by improving productivity, insouciance, innovation and/or reputation PAIR 28, 29. In dynamic markets knowledge assets become critical as a source of competition 30. Along with KM , greater Agility volition nervous strain superior organizational work 31.Entrepreneurial agility (the ability to anticipate and proactively take competitive actions) and Adaptive agility (the ability to sense and react to change) are b oth significant predictors of sustainable competitive advantage32. There is also significant relationship between sustainable competitive advantage and profitability 32. Dynamic capabilities In fast evolving markets, competition is a moving put and firms should have dynamic capabilities to gain competitive advantage 6. Drawing on previous research findings, Dynamic capability is composed of adaptive capability, absorptive capability and innovative capability10. Review of literature has defined Competitive action and response as externally directed, specific, and observable competitive move initiated by a firm to enhance its relative competitive position33. Previous research has concluded that Knowledge Assets, Agility, Dynamic capability are important for organism competitive but the key question that this study investigates the relationship of digital convergence with Innovation capability, building innovation co-operation, Business Process agility and competitive advantage.Agilit yThe different types of Agility identified in the literature are available (internally focused initiative), Partnering (Supply chain initiative) and Customer (demand side initiative) 5, Entrepreneurial and Adaptive32, Strategic34, Business-Process 35. Operational agility has been defined in the literature as the ability to sense and prehend business opportunities quickly, accurately, and cost-efficiently. Customer agility is the ability to adapt to customers, identify new business opportunities and implement these opportunities with customers and the role of IT in customer agility is to facilitate the development of virtual customer communities for designing new product, feedback and testing. Partnership agility is the ability to leverage partners knowledge, competencies, and assets in order to identify and implement new business opportunities. Individual firms do not have all the resources indispensable to effectively compete and value creation for the firm can be leveraged bet ter by dint of pooling of assets between partners. The role of IT in partnering agility is to support Inter organizational networks for collaboration, communication and integration of business processes.Organizational agility is important for business success 36. Agility of an organization is significantly determined by the operational ability of the organization. Greater agility is achieved when the Inter-organizational system used has a task and strategic fit, has been assimilated into the organization and the system is adopted network wide 31. Organizations that are agile i.e. to be able to take competitive actions continuously perform better than organizations that dont 37. Business-processes agility can be classified as process-level agility, which is how quickly an organization can add new capabilities into its measuring processes (E.g. how quickly a partnership can acquire AJAX capability into its rules of order process) and transaction-level agility, which measures the how good the organization is in customizing capabilities for separate customer transactions (For example, how wellhead a company can customize AJAX ordering capability to include bar-code label on the box, an RFID tag on a certain type of container, and paper invoice with bulk billing based on the individual transaction with a customer)38.Theory and tracesResource based view (RBV) of the firm 39, 40 suggests that valuable, rare, inimitable and non substitutable (VRIN) resources and capabilities as the source of competitive advantage. The extension to this is the scheme of Dynamic capabilities. This theory emphasizes that development of organizational capabilities over the time and their changeless renewal by management influences can be a source of competitive advantage. In contrast to the earlier view that IT infrastructure and IT enthronement provides the source of competitive advantage, dynamic capabilities theory emphasizes that consistent development of the capability to apply IT , allows firms to be flexible and innovate continuously, looking put for emerging opportunities, and countervailing threats from competitors to help shape a superior firm 41. Theory of capability state competition lists Dynamic capabilities, core competencies and resources as a footing for superior performance of a firm 42 According to the Dynamic capabilities theory it is not just the approachability of resources that matter, but also the high performance routines operating inside the firm and embedded in the firms processes that utilizes them 43.The theory proposes that a firms IT application can be imitable across firms but the firms capability to apply IT strategically can be inimitable 44. Based on this theory the innovation capability of a firm cannot be easily replicated by other firms and volition help the firm achieve competitive advantage. Innovation was described by Schumpeter (1934) as development of new products, new methods of production, new sources of su pply, opening of new markets and new ways of organizing businesses. As per OECDs CIS 2008 survey innovation ability is the ability to implement new or significantly improved product (good or service), or process, a new marketing method, or a new organisational method, or a new environmentally neighbourly product or process in business practices, workplace organisation or external relations. It has been suggested that firms radical or incremental innovation drives the firm to respond to market changes and opportunities45. This study investigates this empirically by proposing the following. Proposition 1 Innovation capability go away be tie in to Organizational Agility.Digital systems are pervasive and can make knowledge accessible through intranets, digital knowledge repositories and databases and can make the knowledge richer by video conferencing and digital collaborative facilities. Digitization offers firms significant opportunities to achieve greater agility 46. Digital conve rgence allows for transfer of digitized information in different ways. education theory provides completely rational explanations for competitive action those who have the information allow be most aware, motivated and capable of responding. ICT use on Multifactor productivity (MFP growth) are typically linked to firms experience in innovation 47. It has been suggested that several firm capabilities like the firms digital platform is an important enabler of agility 5. Thus this study proposes that Innovation Capability will drive agility more for firms that have Digital convergence than for firms that do not. Proposition 2 Relationship between Innovation capability and organizational Agility will be moderated by digital convergenceFirms that have digitized their process have digital options that can help create new channels to access customers, build real-time integration within supply chain network , gain efficiencies in internal operations and offering new digital products or se rvices 48. This study proposes that firms that have digitized their processes will have digital convergence that can help digital collaboration with customers, other members in the supply chain network, other firms in the industry, competitors and other firms within the enterprise both locally and globally.Proposition 4 Digital convergence will promote both local and international innovation partnership.It has been suggested that Digital collaborations will result in Co-evolution among businesses which implies flexibility in the asset mix , capabilities and knowledge resulting in Agility 49. Knowledge management is related to organizational agility 50 and conducting knowledge management leads to five types of knowledge manipulation activities knowledge acquisition, selection, generation, assimilation, and emission28.Proposition 5 Digital Collaboration for Innovation has a direct relationship with Agility. Proposition 6 Organizational Agility will be related to a higher level of comp etitive position/competitive advantage.Research DesignData SampleThe proposed research model will be empirically tested exploitation a data gathered from managers of companies. The target respondent list will be compiled from the Dun Bradstreet database consisting of large organizations both public and common soldier operating in North America that has a certain level of market uncertainty and competition. As per OECDs definition there are two types of innovation intensive industries comprising of a) High tech industrial companies like Manufacturing and b) companies that provide knowledge intensive services like IT consultancy, telecom services, Banking and Financial, Retail, Insurance, Health Care, Education etc . The diverse sample from both the public and the private sector will help increase the generalizability of the results from this study. The focus of this study is digital convergence. Although the surge in digital convergence with variable strength is seen across all i ndustry sectors and all size firms this study focuses on long suit to large companies with large number of employees. The reason being, for large size companies the availability of finance makes it easier to invest in digital systems. mannerologyA pilot project study with IS academics and graduate students will be conducted for the preliminary assessment of the proposed ordered series of measurement for each construct and to identify ambiguous questions and instructions. Cronbachs alpha (a) coefficient will be computed for each multi accompaniment scale to test for reliability. Alpha greater than 0.7 is loosely considered to be acceptable reliability51. It is important to assess the biases that results from using a single method, a mail survey administered at a single point in time, to measure the constructs proposed in this study due to Common Method Variance (CMV). The Harmons one factor test will be used to assess CMV52.Measures are being taken to elicit information about al l the variables that are being studied. Whatever possible existing scales will be used but new scale to measure digital convergence will be developed. A seven point likert scale (1= very Weak, 7=Very strong) was used to measure the constructs. This study adapts the previously validated scales used in the past to measure organizational innovation capability 25-27, 53. The adapted scale in the study consists of Product innovation which has 3 questions, Process Innovation has 4,organizational innovation has 4,Marketing innovation has 4 and Environmental innovation has 2 questions as shown in the Appendix.Digital Collaboration for innovation is active participation with other enterprises or non-commercial institutions on innovation activities using a digital platform. This type of collaboration does not require for the collaborator to benefit commercially. Pure contracting out of work with no active co-operation is excluded in defining digital collaboration for innovation. The measure is adapted from the OECD participation innovation survey, 2008. It consists of selecting the different types of collaborators and their location as shown in Appendix.Eight measures of business process agility was used from a previously validated pawn 35 which was developed based on conceptual framework provided by preceding research 5, 54. These items measure how quickly and well the firms can undertake key business actions such as responding to changes in aggregate demand, customizing a product to a specific customer or market, reaction to new product or service launches by competitors, change prices or product mix, move into or retrench from markets, adopt new process and redesign the supply chain.Little empirical work has been done on Digital Convergence and this proposal synthesizes concepts from the current IS literature on Digital Convergence to help develop the operationalization of the Digital convergence Construct.This study proposes breaking down DC into 6 first order constructs consisting of content convergence, transmission convergence, Network convergence, Business Process convergence or integration, Device convergence and Pervasive digital environment which will be easier to operationalize . The Next step will be operationalize these variables, transform the propositions into formal hypotheses for the purpose of empirical testing.This study proposes to measure competitive position of a company based on performance of their company relative to their major competitors using a seven-point Likert scale( 1-significantly decreased, 7= significantly increased) in terms of Market share, Sales volume and Customer Satisfaction. The results from the self report will be validated by calculating correlation with the results from history related measures available from Financial Reports. Previous literature supports the use of invoice measures such as Return on Sales (ROS), Return on Assets (ROA) often used as proxy for efficiency, operation income to measure a companys position to compete Data AnalysisThis study proposes to use PLS to estimate the research model as it is common in behavioral literature to use multiple item measures for latent constructs. Path model using PLS will be used for interpreting the main results of this study because this study uses perceptual measures coming from one respondent for constructs that require multiple item indicators. Significance of this researchInnovation and Agility are seen as being important across many industries, especially those operating in a dynamic and globally competitive environment. The impact of Digital Convergence upon a firms ability to compete in such an environment has important implications for managers. The relationship between Innovation capability and Business Process Agility has not been studied empirically in context with competitive advantage. The results from this proposed study can provide guidance to managers to answer questions like Should managers develop env ironmental innovation capability, organizational and marketing innovation capability to gain more Agility?Should Managers invest in digital convergence for building digital collaboration for innovation? Is there any gain in collaboration for innovation (even with competitors) in improving firm agility? Does business process agility provide competitive advantage for large companies? Will the benefit in developing innovation capability increase by investment in Digital Convergence?This proposed study is important to researchers as it adds to the growing trunk of literature linking a Firms capability and Agility. It draws from resource-based view of the firm and dynamic capability theory to explain the relationship between firms innovation capability and its competitive performance. This study provides an empirical test of relationship between business process agility and competitiveness. The study also provides identification of Digital Convergence. Finally, the results of this propo sed study is important to respondents as it answers if the leverage of innovation capability for competitive advantage is contingent upon(p) on investment in Digital Convergence.

Corporate Culture Enhance Organisational Performance Business Essay

Corporate close Enhance Organisational Performance Business EssayOrganization farming is a source of sustained competitive advantage embodied refinement plays a very important role in organisational transaction. By reviewing existing documents of the organisational enculturation look, we make a call for of the theoretic elements of nerveal farming and analyse its effect on firms performance. The study in this paper gives us a better understanding on how trys get better performance and establish the foundation of the successful corporations. The Hewlett Packard case analysis from Kotter and Heskett (1992) had confirmed that unshakable corporate tillage enhances organisational performanceKey words organisational behaviour, organisational cultivation, firm performanceCompetitive advantage, resources, synergistic effectIntroductionA recent study (Fun Yun et al. 2003) has investigated that the development of modern focus science has been by three decimal points Classica l charge Theory, Behavioural Science Management Theory, and Management Theory Jungle (Harold Koonty 1961).In early 1980s the tetradth stage schemeal finish has began, this phase focuses on how to apply the cultural interrogation results to the initiative management. Organizational coating as a modern enterprise management possibility and management strategy are to a greater extent and more sought after from the business community and the faculty member circles from whole world. several(prenominal) scholars believe that the enterprise competitive advantage not only commode be relied on its capacity also with its ability in the organizational stopping point.However, many a(prenominal) studies expect shown that, when determining unique characteristics of a company, culture atomic number 50 even be decided for which strategic to choose. According to the view of Barneys (1986), culture is the continuous strategy for enterprises to give them a competitive advantage of the resources. come upon competitive advantage at least in part believe on capacity. Therefore, the enterprises research extends to the key ability and resources such(prenominal) as culture is meaning very important.This literature review is revolve virtually assemble culture and to discuss the basic theory of organizational culture and corporate culture for the bias of enterprise performance.Literature Review1 Organizational culture theory research evolution process of a design reviewThe concept of organization culture is acknowledged by Pettigrew (1979) in the article organizational culture research , and in 1982 attracted the attention of academic and business management circles mainly due to few books published Ouchi (1981) theory z Pascale and Athos (1981) the Japanese management art L6 Deal Kennedy(1982) corporate culture , Peters Waterman(1982) search of excellence. Since then, organization of culture has opened a new scallywag and a lot of organizational culture researc h paper is perpetually emerging by group of distinguished researchers as Ouchi, Hofstede, Sehein, Wilkins etc, they are sensitive at the area of organizational culture in their respective areas of expertise and conducted successful research.After the 80s the academics and businesses were mainly studying the organization culture management that were based on the following elements, comparative management culture, factual study of the culture and management of the cooperate culture and other relative elements of the culture.Hofstede (1980) points off variation of manage practices, similarity or dissimilarity due to distinguishable culture or countries, and hance finding out the effect of culture on organizational performance. As Lincoln and Kalleberg (1990) In their reseach of the United States and Japanese enterprises explored the engagement attitude with emphasis on the culture, and they visualize culture as a management tool for the organization control. This is also further illustrated by Sekaran and Snodgrass (1989) with four counties (United States, Japan, Sweden, Yugoslavia) showing the effect of culture on the organizations efficiency difference.Some culture researcher like Schein (1990) and Kotter and Heskett (1992) were using questionnaire or empirical data as research method. They are studying aims to determine if there is a correlation between organization culture and enterprises long term business performance. huge attention has been given to loss leadership and organization culture.Also there are other researcher consider effectiveness between coalition of culture and other factor during the organization management. Ogbonna et al. (2000) claims that when the enterprise face to pressures from external environment, the leader style blow organization culture and then further impact to organisation performance. Leadership style keisternot be directly affect organizational performance and can only through the organizational culture as a media to indirect influence performance. Corresponding is that competitive and innovation of cultural characteristics directly affect performance.2 Influence corporate cultures on enterprise performanceAccording to Kilman et al (1985) comment, there is three spot of impacts (1) ethnical orientation, meaning that Cultural influence organizations operational direction correctively (2) the permeability of culture, centre the degree of consensus in the members of the organization for the culture. (3) Cultural strength means the degree of loyalty to culture by organizations members.Strong cultures possess greater influence that means it has a wide range of permeability and far range impact on the strength of the entity. If the team member are provided with tenacious targets and shared the same values, they pass on be satisfied with what they are doing and will be more focused with their tasks. However even if the culture of the organization is pointed in right direction but the members cannot understand or pass on it or be loyal to it, then this will be a weak culture with negative impact on the performance of the entity. get up (1993) also indicates that a strong organizational culture also can reduce the cost of decision- reservation and make work specialization. Strong organizational culture has been recommended by Akin and Hopelain (1986) to the entire managers who wish to enhance their productivity or performance.The organization will receive great return from investments or marketing if they propagate culture and using it as the decision making tool. The organizations that do not propagate culture always get less(prenominal) return it has been confirmed by Denison (1990).Regardless of companies strategy or culture being people or reliability or productivity oriented they all still compete for great profit and productivity.IBM CEO tom Watson in 1962 delivered a speech at Columbia University, he tell related business operating performance, enterprises ma nagement thoughts, spirit and goals are frequently more important than technical resources, economic resources, enterprise structure, invention and ergodic Decision. Of course, all these factors also greatly affect the performance of the business. But I think, all those factors are sourced from employees and how they extent of basic beliefs of enterprises ideas (Jack E. S. 2012).But at many enterprises, organizational culture has been viewed as subordinate, even they described it as companys slogan, they oblige the organization culture is creating needless official documents and procedures, and organization culture cannot summing upmate any value to the enterprise. Kets deVries and Miller (1986) argued that when the business face misery due to factors that is beyond their control even the culture is not stabilising and may affect the company s performance negatively.Some scholars have began to try or test the construction of culture-performance causal relationships, such as P eters and Waterman (1982) of excellent companies , all emphasize positive effect of organizational culture on organizational performance .All in all, well-rounded enterprise practices and scholars research results shows organizational culture is positive factor for enterprise to obtain the best performance, to make right decisions and also face and make out with external factors.Therefore, all the attention and practice researchers been that cultural pattern is good and culture and organizational performance are coupled (PetersWaterman 1982).ConclusionTo sum up, in the 20 years of organizational culture research, great achievements have been made. Culture can be regarded not only as a Relative special management field it can also give influence and change cultural reality. Although some scholars believe that thotre of lack of the organization turn the research category too widely, as if from soup to cockamamie (Alvesson, 1993) This is mainly due to the organizational culture res earch lack of a clear Analysis framework and theory foundation for culture research orientation, which led to the blind man feels like results (Mirvis Sales, 1990). Therefore, this paper is based on the organizational culture of the evolution process. I have briefly reviewed and analysed the notional basis of organizational culture, and it link to enterprise performance. this paper discusses the organizational culture for the influence of so as to further study on culture as the foundation.The organizations of the future culture research must be around the competitive advantage it creates and maintains in wider and deeper level and strategic change, other factors such as technology innovation behaviour by combining research, for enterprises in the fierce competition process on top is a positive.