Thursday, October 31, 2019

Discuss the contrasting literary styles used in James Baldwin's Essay

Discuss the contrasting literary styles used in James Baldwin's Sonny's Blues and Tim O'Brien's The Things They - Essay Example Literary Analysis Paper The stories of James Baldwin and Tim O’Brien have a common element amongst them, mentioned explicitly; the attribute of undergoing struggle. In O’Brien’s book, struggle and hardships can be seen through the eyes of American soldiers fighting in the Vietnam War, whereas in Baldwin’s tale, Sonny is seen fighting life and addictions in order to patch his relationships with other people around him as well as himself. ‘The Things They Carried’ is about experiences that the soldiers, led by Tim O’Brien went through, which included tangible as well as intangible important elements. These included emotions and feelings like fear, dread and guilt, as well as the kind of machines and guns which formed an inherent part of their routine lives in the War. ‘Sonny’s Blues’ is about a young heroin addict, set in a post World War era, depicting a great amount of political and economical tension raging in Ameri ca at the time, with respect to culture and the old arts. The book is a story full of symbolism; in this particular tale, O’Brien has marked a very vivid description of all the objects that the various soldiers carry with them.

Tuesday, October 29, 2019

Is social networks a waste of time Essay Example | Topics and Well Written Essays - 750 words

Is social networks a waste of time - Essay Example The article starts with the cons of social networks and as to how it is decreasing productivity amongst the workers. But this decreased productivity is not the only problem posed by the social networks as the problem expands to the younger generation. The younger ones have also been indulged with the social networks and it is found that many of them even log in to their accounts when they are in school. Thus it is not only affecting their school hours but is also affecting the way that they study. However in the conclusion the author puts forward different views about social networking. According to him the advantages overweigh the disadvantages if the portals are used perfectly. He believes that the students should be encouraged to use it in accordance to the positive uses of the portal so that the disadvantages can be minimized. I agree with Bernhard Warner as he puts both the disadvantages and advantages of social networks. But in my view the younger generation should be discourag ed to a certain extent so that the social networks do not hamper their study life. I agree with the view of Warner when he puts forward the views about the workers losing productivity because of excess usage of these networks. However these workers can use these social networking sites to their advantages. In some cases it is seen that the workers advertise through social networks and this can prove to be an advantage for many companies. In some way the companies can increase their productivity rather than the view put down by Warner. Similarly the theme of the article is the effect of social networking on students. Warner believes that the young generation uses social networks even in the schools during classes and this can prove to be a disadvantage for the schooling system. In my view he is quite right in putting forward the concern for these students as at such a tender age attentiveness is quite necessary in understanding the basic concepts of a subject. In my view social netwo rking can be a waste of time when used in unusual circumstances and the circumstances in which the students are using the social networks is quite wrong. In order to limit the usage of social networks in a schooling system certain measures are necessary. It is not necessary to completely stop the students from accessing these social networking sites but it is necessary that the students are kept under observation so that they do not access it in unusual times. Warner cites creativity as an advantage of the social networking sites if the students use it in the right way. Research has also shown that there are some educational benefits associated with social networking if it is used in the right way. I personally think that social networking does allow creativity to exist if used in the right way (Science Daily 2008). It can help to diffuse information all over the world about important topics such as HIV and poverty. Warner believes that the students should be encouraged to use socia l networking sites in a positive way so that this creativity can exist in these students. In my view they should be encouraged but a limit should also be enforced upon them where these social networking sites do not interfere with their academics. I also use Facebook as a communicating device through which I can easily talk to my family back home. In some case it is seen that social netwo

Sunday, October 27, 2019

Diagnosis of Systemic Lupus Erythematosus (SLE)

Diagnosis of Systemic Lupus Erythematosus (SLE) Systemic lupus erythematosus is a multi-systemic autoimmune disease that was first described in 1941, by Klemperer and colleagues (Gonzalez-Buitrago and Gonzalez, 2006). It is a disease that can attack almost any 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). SLE is a disease that has a strong correlation to defects in apoptosis; however no specific cause of the disease is known (Arbuckle et al, 2003). The prevalence of the disease is worldwide; however it commonly affects people of African descent, particularly in Europe and Northern America (Kumar et al, 2009). Environmental triggers are known to contribute to the disease manifestation; although genetic links have also shown association with all HLA classes (I, II, III) on chromosome 6. Other transcription factors such as IRF5, STAT and proteins such as PTPN22 have also been seen to contribute to the manifestation (Mal e et al, 2006). SLE is particularly common between the ages of 15-50, where patients present with positive antinuclear antibodies (ANA). ANA are a group of heterogenous antibodies that are capable of binding to components of the nucleus, resulting in damage of DNA. The initial screening method for patients with AIDs such as SLE is via the ANA test. 80-90% of patients with SLE present with a positive ANA (Bonilla et al, 2007), however other AID such as Sjà ¶grens syndrome, Rheumatoid arthritis, Autoimmune hepatitis, Scleroderma and Polymyositis Dermatomyositis, also see positive results. Antigen specific assays such as extractable nuclear antigen (ENA) and double stranded DNA (dsDNA) must then be performed to confirm a diagnosis, as approximately 70% of patients with SLE have antibodies to dsDNA (Rahman Isenberg, 2008). Positive results can be seen within the aging population as the immune system begins to deteriorate. Nilsson et al, (2006) supports this and found that positive ANA results were fo und particularly in elderly patients over 85 years. 90% of patients with SLE are women, suggesting a hormonal link (Rahman et al, 2008). Hormonal imbalances are seen in women with SLE, thus it becomes difficult to maintain immune tolerance. Increased oestrogen levels result in increased antibody production and Th2 response, whilst decreased levels of androgens depress the response resulting in an abnormal immune response (Danchenko et al, 2006). 1.2 The clinical significance of ANA testing The 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 rash which is commonly seen on the face (Figure 1.1). In 1982 the American 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 must be met, for a definite diagnosis of SLE. The criterion for SLE includes symptoms, immunological and haematological tests. Points 10 and 11 are of particular importance, as they are confirmatory of SLE. A study by Arbuckle et al, (2003) examined the onset of SLE in 130 patients and found that 115 patients had positive indirect immunofluorescence (IIF) ANA, before diagnosis. 1. Malar Rash A butterfly rash usually seen on the face 2. Discoid rash red, scaly patches on skin that cause scarring 3. Photosensitivity Skin rash as a result of unusual reaction to sunlight 4. Oral ulcers Oral or nasopharyngeal ulceration 5. Nonerosive Arthritis tenderness or swelling of joints 6. Pleuritis or Pericarditis Pleuritis inflammation of the pleura, the lining of the pleural cavity surrounding the lungs Pericarditis small amount of fluid builds up between the two layers of the pericardium. 7. Renal Disorder Persistent proteinuria Cellular castsmay be red cell, hemoglobin, granular, tubular, or mixed 8. Neurologic Disorder Seizures 9. Hematologic Disorder Hemolytic anemiawith reticulocytosis Leukopenia Lyphopenia Thrombocytopenia 10. Immunologic Disorder Anti-DNA: antibody to native DNA in abnormal titer Anti-Sm: presence of antibody to Sm nuclear antigen Positive finding of antiphospholipid antibodies on: 11. Positive Antinuclear Antibody An abnormal antinuclear antibody by immunofluorescence Once a positive ANA test has been performed there is no reason to repeat the test, however if clinicians have a strong suspicion of an evolving connective tissue disease (CTD) negative 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 can also be tested to investigate SLE; however these may not always aid all patients (Egner, 2000). 1.3 History of ANA testing and how the diagnosis of SLE evolved The ANA test has been around for over 40 years and is the most widely performed autoantibody test, worldwide. The test is commonly performed within Immunology laboratories and has evolved very little over the years. ANAs originated from lupus erythrocytosms, also known as the LE cell phenomenon. LE cells were discovered in 1948 by Hargrave, who saw that patients with SLE have polymorphonuclear leukocytes, which had phagocytosed nuclei, within the bone marrow (Hepburn, 2001). Following the discovery, Lee 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 human tissue (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, c aused alterations to cells within slides, thus altering 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 detection There are many techniques available for the testing of ANAs; these can be seen in the UK National External Quality Assessment Service (UKNEQAS) report found in Appendix 1. 1.4.1 Indirect immunoflourescent (IIF)-ANA Indirect 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 using IIF was developed by George Friou in 1957, where initially substrates such as chicken erythrocytes were used (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 time consuming and laboratories could no longer manage rodent houses as they required expert attention. Commercial companies then began to produce ready to use tissues substrates, offering a greater sensitivity. However as many commercial substrates are now available, variability between kits, manufactures, substrate, conjugate and the degree of cellularity (good monolayer of cells and a number of mitotic spindles), make it difficult to standardise methods of detection and reporting. In order to produce accurate results, substrates must be present in the correct phase of the cell cycle (Figure 1.3). Identification of IIF-ANA patterns is dependant on the true state 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 differentiated. A mix of mitotic and non mitotic forms of cells are needed 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 sensitivity for the testing of SLE as they were composed of human laryngeal squamous cell carcinoma, allowing 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 big step forward in identifying patients with the ribonucleoprotein complex (anti-Ro). The anti-Ro antigen is particularly significant in patients with SLE as it offers a poor prognosis. However this antigen is seen to overlap between different autoimmune diseases such as Sjà ¶grens syndrome, thus the detection of the antigen must be precise. The Ro (SS-A) antibody is seen to target protein antigens associated with small RNA molecules known 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 devise 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 diag nosis of SLE. They have aided in reducing the number of ANA negative 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 limit the identification of the different epitopes of the Ro antigen. At present HEp-2000 substrate can only identify the 60kDA Ro antigen; but since the 52kDA Ro antigen also exists, patients with this epitope are missed. A study by Cozzani and colleagues (2008) looked at 5,949 people over a 5 year period. All participants were photosensitive and 2,315 of these had connective tissue disease (CTD) such as SLE. The study found that the anti-Ro was easy to identify on HEp-2000 slides with a sensitivity of 81% according to the Altman test, of accuracy. However a study 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 study was negative for IIF-ANA, but was shown to have a positive Ro antigen by EIA. A study by Dahle et al, (2004), looked at HEp-2 and compared three ANA methods; Enzyme immunoassay (EIA), double radial immunodiffusion (DRID) and IIF. 3,079 patients were examined and overlapping 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, identified as negative or weak 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 required following the ANA test. This agrees with Morozzi et al, (2000), who suggest 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 thi s study suggest that EIA has the ability to detect the different epitopes, preventing 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 significant 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 staining. A fluorescein/protein (FP) molar ratio is employed, with in-house diluted conjugates. The ratio varies between kits, however a 1:3 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 gives little information so arent used. Due to the use of fluorescence conjugate, slides fade overtime, thus it is particularly important to determine results as soon as possible as photographs are not taken. As IIF varies daily due to slides and condition of the microscope, it would be appropriate to carry out daily checkerboards to see which working dilution is best 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. Experienced 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 individuals severity of disease and can prove beneficial to clinicians. Serial dilutions at 1:10, 1:20, 1:40, 1:80, 1:160 and 1:320 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 aged over 60 (Shmerling, 2003). Peterson et al, (2009) found that beside patients with SLE patients, other diseases also present with positive ANA titres. 1:20 healthy people presented with a positive ANA and the number of positives increased to 1:3, with a dilution of 1:40. To reduce the number of fals e positives, titres are commonly performed at 1:80. 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 fetal 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 1:40 was employed. As workload increased titrations became laborious 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 clinicians 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. Similarly 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 Binding Site (Figure 1.6). These slide processors ensure that all samples are prepared quickly, reliably and accurately, avoiding cross reactivity in sample preparation. Slide processors perform IIF via indirect antibody reactions as seen in Figure 1.7. Patient 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. Another 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 independent 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 improve 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 reported. The use of barcode readers can overcome this problem. Homogenous Homogenous 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-Smith Speckled Speckled 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 Tissue Disease (MCTD). Patients with Scleroderma and Sjogrens Syndrome also present with positive results. Centromere Centromere pattern is seen in 57-82% of patients with CREST syndrome and Raynauds. The suspected antigen is CENP A, CENP B, CENP C. Nucleolar Nucleolar Pattern seen in patients with Scleroderma. There are multiple 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 same cells, substrate and conjugate they were able to report the same staining patterns. Over 157 laboratories across Belgium participated and each looked at 9 different samples. Looking at the results it is clear that after considering the variable 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, replacement with EIA or bead technology 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 ELISA kits consisting of a range of antigens, significant in the diagnosis of SLE were used. The study showed correlation between IIF and ELISA, where sensitivity for IIF was 88%, whilst that for ELISA 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 as says, 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 Nifli et al, (2006) compared routine technology in a selection of Clinical Immunology laboratories and analyzed 11088 samples, using IIF and ELISA at the University Hospital of Heraklion in Greece. Results showed a highly 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 ANA Many 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 categorised 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 failure and to overcome the subjectiveness of IIF-ANA. The ELISA assay can be performed either 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 wells with individual antigens can be used, allowing multiple antigen recognition and analysis. Both ELISA/EIA operate 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 proportional 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 q uantitative result (Branda et al, 2009). ELISA are a versatile assay, where the amplification 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 inadequa te incubation times may produce little signal amplification resulting in false negative results (Castro and Gourley, 2010). 1.4.2.1 Anti-dsDNA Anti-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 nucleosomes. 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 risk of lupus nephritis flare, thus detection is crucial as it helps to determine the therapy required for treatment. à ¯Ã‚ Ã‚ ¡-actinin (100kDA) is a microfilament skeletal 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 involvement (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 DNA. In the assay bound and free DNA is separated 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 relatively 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 reproducible 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 still 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 Fa rr 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 used 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 Immunology. 1.4.2.2 Anti-ENA Positive 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, immunoblotting, counter 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). Gel 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

Friday, October 25, 2019

journalism Essay -- essays research papers

When journalism is chosen as a career, society tends to have a stereotypical image of a group of photographers chasing celebrities. If not, then an image of an anonymous person writing biased comments about current affairs, trying to manipulate the truth. However, their real work earns them every cent they deserve unlike the heartless lawyers who earns millions for defending criminals. The work of journalism, on the hand, consists of interviewing and attending events in all conditions in order to gather news and information for public interest. This is followed by further research into the background information then assessing suitability of reports and articles for public. The process is much more difficult than expected, especially with the requirement of interpreting news at the same time commenting on public’s behalf within an established style and format. Although the hard work usually comes to a good income, certain qualities and skills are needed. The qualities and skills required mainly evolve around their general knowledge and English skills. All journalists must be able to write clear, concise, objective, and accurate material in a limited time. It also requires the ability to work under pressure and in long, irregular hours under any weather conditions. As the job could be undertaken in different areas, journalists must have good communication skills to gather news from sources and in cases of working on radio or television, must be able to interpret the informat...

Thursday, October 24, 2019

Do Prisons Work Essay

This study will examine the effectiveness of current prison treatment programs in Australia, New Zealand, South East Asia, United States of America in rehabilitating or reforming an individual and coinciding recidivism rates upon a prisoners release. Prison based treatment programs for sex offenders in Western Australia, New South Wales and New Zealand are examined and recidivism rates compared. Treatment programs for offenders with drug and alcohol issues and the various strategies within the criminal justice system such as diversion, education and drug court programs are examined and differences explained. Rehabilitation programs such as education, life skills, employment and cognitive behavioural treatment are explained and research discussed. Conclusions will be drawn outlining programs with the highest level of recidivism both in Western Australia and globally. The â€Å"nothing works† mantra (Martinson) 1974, is seen to be refuted and treatment is seen to be successful when it is matched to the criminogenic needs of the offender (MacKenzie, 2006). Future recommendations are made in regards to the need for correctional staff to assess each offender as an individual with different needs, and to therefore implement programs that will give the offender the best change of reform or rehabilitation (MacKenzie, 2006). There are many treatment and rehabilitation programs currently used in corrections around the world aimed at reducing recidivism (MacKenzie, 2006). A heuristic approach classifies various strategies into incarceration, treatment programs and rehabilitation (McKenzie, 2006). These interventions represent different strategies for controlling crime in the community, and have some theoretical rationale for expecting a reduction in crime, despite being different in the mechanism anticipated to produce the reduction (MacKenzie, 2006). Incarceration deprives the prisoner of opportunities to commit crime, usually through detention in prison or in some states capital punishment (McKenzie, 2006). Rehabilitation is based on the premise that people can change, and if assessment is to contribute to rehabilitation it must be capable of measuring change (MacKenzie, 2006). The Static 99 risk assessment measure is an International Tool that is currently used to assess recidivism levels of sex offenders (Hoy & Bright, 2008). Rehabilitation orientated treatment programs include education, cognitive skills and employment (MacKenzie, 2006). Correctional educational programs are seen to have optimistic results in lowering levels of recidivism in prisoners (Stevens & Ward, 2007). Kaki Bukit Prison School based in Singapore is seen to be successful in reducing recidivism by aiming to creative a learning environment based on Peter Senge’s book â€Å"The Fifth Discipline† (Senge, 1990). Part of the discipline involves inmates engaging in the â€Å"The Reflective Thinking Process† (Oh, 2007), an education programme which aims to assist prisoners in reflecting on past destructive behaviour and to encourage appropriate restitution. The school is supported by a multidisciplinary team of teachers, prison officers and counsellors who work together to help students in their studies and in their journey of change to become responsible, thinking citizens (Tam, 2007). For inmates who completed their studies at Kubit Bukit Centre and were released in 2000 and 2001, the 2 year recidivism rate was 24% (Oh, 2007). Acacia, Western Australia’s only private run prison, is operated by Serco and aims to bring service to life (Needham, 2009). Storybook Dads is an example of this and aims to rehabilitate prisoners, break the cycle of reoffending and close the gap between a child and his father (Needham, 2009). The program opens up a broad range of educational opportunities ranging from writing their own stories to learning how to use a computer (Needham, 2009). The main objective of the program is to empower fathers and for children to feel loved, which then improves the lives of the prisoner’s children (Needham, 2009). Prisoners are given the opportunity to record their child’s favourite bedtime story on a CD with sound effects, personal message and CD cover (Needham, 2009). Current research indicates that fathers who have been imprisoned tend to withdraw from life outside the prison and subsequently lose contact completely with their children (Needham, 2009). Statistics show that six out of ten children whose father is a current or ex- prisoner become involved in criminal activities and consequently find themselves in similar situations to their father’s in prison (Needham, 2009). The Storybook Dad’s program runs in eighty prisons in the United Kingdom and maintains family connections and reduces reoffending (Needham, 2009). The National Fatherhood Initiative runs a similar programme called the Incarcerated Father’s Program which operates at Branchville Correctional Centre in Indiana (Gosnell, 2006). It is similar to Storybook Dad’s programme in helping prisoners reunite with their children and families (Gosnell, 2006). One study monitored 186 men for three years after release from prison with only five returning (Gosnell, 2006). Three men returned for small offences whilst two came back on a long term basis indicating low levels of recidivism, when in comparison seventy percent of men released from prison normally return within an average of one to three years (Gosnell, 2006). Prison based treatment programs offered in Western Australia for sex offenders are the Sex Offender Program, Indigenous Sex Offender and Intellectually Disabled Offender (Macgregor, 2008). Community based maintenance programs are offered for each type of offender, the current program for disabled people being the Safe Care Program (Macgregor, 2008). In Australia, most treatment programs for sex offenders are based on cognitive behavioural therapy aimed to target the criminogenic needs or risk factors of offenders (Macgregor, 2008). If these needs are altered the chances of changing the criminal behaviour are higher in the range of 10-30% (Blud, 1999). The programs are seen to be effective in that they work to alter many of the cognitive deficits displayed by offenders (Blud, 1999). They target the known risk factors for sexual reoffending which are cognitive distortions, empathy deficits and wide ranging self regulation (Hoy & Bright, 2008). A Western Australia study in 2002 measured recidivism rates of 2165 sex offenders referred to the treatment unit from 1987 to 1999 (Greenberg, 2002). The study compared treated offenders with non-treated offenders, with no significant findings on effects of treatment on sexual recidivism (Greenberg, 2002). Systematic differences between the non-treated and treated group in the Western Australian study, such as indigenous status, risk category, and length of sentence may have impaired comparisons of groups (Lievore, 2004). Inconsistencies across the data, methodological limits may have limited the study from being able to identify less significant treatment outcomes, and to identify sources (Greenberg, 2002). At present a prison based treatment program designed for adult sex offenders is offered in every Territory and State Australia, despite many having yet to be evaluated (Macgregor, 2008). An evaluation conducted in New South Wales on the Custody Based Intensive Treatment program for high risk offenders (Hoy & Bright, 2008) compared recidivism rates of 117 treated offenders with those predicted by the STATIC 99 risk assessment measure, an internationally used tool that assesses the recidivism risk of sex offenders (Hoy & Bright, 2008). STATIC 99 risk probabilities are based on a large sample of sex offenders in the United Kingdom and Canada (Hanson & Thornton, 2000). The study found that 8. 5% of sex offenders treated at the Custody Based Intensive Treatment programs committed further sexual offences in 3. 5 years, compared with a predicted sexual recidivism of 26% (Hoy & Bright, 2008). An evaluation was conducted on the Te Piriti Special Treatment Program for child sex offenders in New Zealand (Nathan, Wilson & Hillman, 2003). Te Piriti incorporates cognitive behavioural therapy methods in combination with Tikanga Maori, holistic practices derived from world view and a desire to understand the universe (Nathan, 2008). This study compared recidivism rates of Te Piriti graduates with a control group used in the Kia Marama study (Nathan, 2008). In comparison with the non-treated group’s sexual recidivism rate of 21%, a small 5. 7% of offenders who completed the programme at Te Piriti reoffended sexually (Nathan, 2008). Maori sexual offenders were also found to have a positive response to the program (Nathan, 2008). Only 4. 41% of Maori offenders reoffended sexually after receiving treatment at Te Piriti (Nathan) 2003 compared with 13. 58% of Maori Kia Marama graduates (New Zealand Corrections, 2003). These results are supportive of the argument that programs are more effective in reducing sexual recidivism when the design and implementation are attuned to the cultural background of the offenders (Macgregor, 2008). Currently, there are various strategies within the criminal justice system that respond to offenders with drug and alcohol issues (Makkai & Payne, 2003). At one end of the spectrum is the diversion by police of first offenders or low level offenders into education or treatment programs (Makkai & Payne, 2003). At the other end, is the diversion of repeat drug dependent offenders facing imprisonment into intensive drug court programs (Makkai & Payne, 2003). Drug courts aim to divert both men and women offenders (Freeman, Karski & Doak, 2000). The elements of the New South Wales drug court program are treatment; social support and the development of living skills; regular reports to the court; and regular urine testing (Freeman et al. , 2000). During the twelve month program, participants are expected to stabilise their lives by not using drugs to address health issues, and to cease criminal activity (Freeman et al. ,). Ideally, they consolidate their situation and develop life and job skills, and financially reintegrate fully, becoming financially independent (Freeman et al. ,). Analysis of the data indicates a high success rate, with only thirteen percent of the participants having committed an offence on completion of the program, indicating a low level of recidivism (Freeman et al. ,). A promising approach to combating illicit drug use has been implemented at the Metropolitan Women’s Correctional Centre in Victoria (Peachy, 1999). Carniche program includes core courses in drug awareness, drug education and Alcoholics Anonymous, which provides a group therapy environment and a twelve step program based on abstinence and group support (Peachy, 1999). The program runs for three to four months, after which the prisoners are reintegrated into the mainstream prison population (Peachy, 1999). The program involves a maximum of ten prisoners who live in a residential unit separate from the main prison population who participate in intensive drug group and individual counselling (Peachy, 2000). The program has not been evaluated for its effect on offender recidivism and its success may depend on the support available to prisoners upon release (Peachy, 2000). A new program for women offenders, titled Reconnections, completed its pilot phase at Bandyup Women’s prison in September 2009 (Porter, 2009). The program was based on therapeutic interventions to assist women in looking at past trauma and abuse in addressing their offending behaviour (Porter, 2009). Although the program was scheduled to commence in early 2010, funding problems prevented the commencement of the program (Porter, 2009). Despite the program failing to commence prison doors at Bandyup continue to open to volunteers and visitors, a move imprisoned women value (Department of Corrective Services, 2005). The Western Australian Department of Justice allows over 3,000 volunteers who provide support for victims of crime, prisoners and juvenile detainees (Department of Corrective Services, 2005). Western Australia’s drug rehabilitation is seen to be a part of the whole sentencing process both in prison and the community for a prisoner’s release on parole (Cox, 2007). There is a continuum drug users who go through the Perth Drug Court’s treatment programs are less likely to reoffend than those sent to prison (Cox, 2007). Recidivism rates for offenders using the court’s drug treatment programs were 17 percent lower than those for offenders sent to prison (Cox, 2007). The study assessed 250 drug users, dealt with the Drug Court who were charged with offences such as burglary, theft or fraud between 2000 and 2003 (Cox, 2007). In comparison to Western Australia one in every 100 adults is locked up in America and there punitive corrections system do not follow a Western approach, incorporating resources such as Drug Courts to help prevent re-offending (McClatchy, 2008). Kansas has been seen to rethink incarceration policies, with a focus on reserving prison for the worst criminals who pose a real danger to society (McClatchy, 2008). Kansas’ only drug court, in Lyon County, has slashed offender rearrest rates almost by half. (McClatchy, 2008). In California, a study found that in a two-year period, drug courts cost $14 million but saved tax-payers more than $43 million over the costs of sending offenders to prison (McCatchy,2008). Kansas Department of Corrections has had success with a new parole re-entry program, including a pilot project in Wichita that gives parolees more support and helps them to keep on the straight and narrow (McClatchy, 2008). Corrections Secretary Roger Werholtz has seen the new philosophy dramatically cut re-offender rates state-wide and reduced recidivism (McCatchy, 2008). Spectrum Addiction Services offers residential treatment, outpatient, detox and domestic violence service for substance abusers and Correctional Recovery Academies in Massachusetts, Georgia and Rhode Island (Astell, 1995). The treatment strategy supported by Spectrum is based on behaviour and based on self-esteem, participant’s feelings, and self-revelation much as the 12 step program of Alcoholics Anonymous (Astell, 1995). Spectrum views the way to fight recidivism is behavioural, teaching people the skills to stay straight (Astell, 1995). A situational approach to drug abuse may be another avenue to explore when examining the Vietnam War (Astell, 1995). Many American soldiers who were involved with heroin use in South East Asia did not bring the habit home, indicating that some drug abuse is situational (Astell, 1995). In the mid 1970’s a pessimistic assessment of rehabilitation programs by Robert Martinson asserted that â€Å"nothing works† in correctional treatment (Cullen & Gendreau, 2000). However recent reassessment using methods of meta-analysis has found that offender treatment programs do reduce problem behaviour (Cullen & Gendreau, 2000). Effective programs are those which recognise the importance of individual differences and the measurement of these factors when assessing what programs and interventions would be most suitable for each offender (Harland, 1996). Privatisation of prisons is seen to be a positive solution to improving treatment programs and reducing associated recidivism in developing more of a restorative framework to treatment programs (Corporate Responsibility, 2007). This involves emphasising the importance of good relationships between prisoners and staff, the need to recognise the impact of cultural differences when implementing programmes and matching an officer of suitable culture and temperament to best assist the needs of the prisoner (Corporate Responsibility, 2007). Further study is indicated as being required for WA Sex Offenders with little research being available for this group of offenders when compared to other states in WA (Cullen & Gendreau, 2000). Systematic differences between the non-treated and treated group in the Western Australian study, such as indigenous status, risk category, and length of sentence may have impaired comparisons of groups (Lievore, 2004). Inconsistencies across the data, methodological limits may have also limited the study from being able to identify less significant treatment outcomes, and to identify sources (Greenberg , 2002). A recommendation for improved research design is suggested in the implementation of a similar tool as the Static 99 in Australia which is currently only available internationally in measuring sexual recidivism (Mackenzie, 2006). Another finding from reviews of the studies is the large difference of amount of research completed for drug-offenders in comparison with other offenders, such as women prisoners and sex offenders which is currently limited (MacKenzie, 2006). Given the current concern about the increasing amount of drug offenders entering the correction system it is apparent as to why there is uch a large number of evaluations of programs being completed for these offenders (MacKenzie, 2006). Although the role for corrections appears to be a current challenge, it is hoped that with further research, funding , availability of treatment programmes and education of prison officers in addressing individual and cultural differences, that the offender be given the greatest chance for rehabilitation, reform and consequently a life of freedom outside the prison bars (MacKenzie, 2006).

Wednesday, October 23, 2019

How sympathetic a character Essay

Upon reading Aristophanes’ Wasps for the first time, Procleon, the antihero of the play, evokes a strange sort of sympathy. The part of us that wants to rebel against the system identifies with his character, and admires the way in which, in the second half of the play, he â€Å"does what the man in the street would really like to do† (K Dover) and generally places himself above authority. Aristophanes loads Procleon’s character with vulgarity and nastiness, but does it in such a way that an audience seeing the play for the first time will focus on sympathizing with him as the `heroic’ character more than his deep-seated and twisted darker side. For instance, in the first scene we see Procleon trapped inside his own home, treated not like a villain or monster, but a mentally ill obsessive, or trialophile. â€Å"†¦ The more you warn him, the more he goes to court. That’s why we’ve had to bolt him in and guard the house for fear he gets out. † The way the two slaves describe Procleon’s personality is quite comic. They describe him as a sad old man. He then tries to escape later on by holding on to the bottom of a donkey as it comes out of the house, in a parody of Odysseus in Homer’s Odyssey. On one hand, we find his wit amusing, and he tries to mirror the cunning of Odysseus, and on the other hand we laughingly pity him for trying such an idea, especially onstage as it looks absurd. Aristophanes is poking fun at the latest trend in Athenian society in the ridiculous person of Procleon. However, Athenian litigiousness and trial mania are not his only target. In his conversion from his former juryman’s life, Procleon becomes a caricature of an upper-class snob engaging in one of the well-heeled set’s favourite addictions: dressing up in your finery, attending drinking parties and meetings of secret societies and going on drunken rampages through the streets, beating up passers by, knocking over statues, mauling slaves and women, etc. By the end of the play, it’s hard to tell whether Procleon is ny better off for having traded a poor man’s pastime for a rich man’s. In the first half of the play, we  see Procleon as a bloodthirsty bastard, a sadistic slave to Cleon whose only friends are the similarly savage, vespine jurymen. Just seeing this feeble army of nasty old men, we find immediate comedy. On the surface, nothing about Procleon seems too bad, just a rather crazed old man with a strange obsession. â€Å"He enjoys voting defendants down: he is comically sadistic. † – D. MacDowell However, when we look deeper into the play and Procleon’s character, we see that there is a far darker and more sinister side to him. First of all, there is the fact that the only reason he enjoys sitting on the jury so much is so that he can wreak pain and suffering upon innocent people. â€Å"I long to come to court with you, some solid, lasting harm to do. † There is also the way in which he treats his daughter, in a rather incestuous manner. â€Å"she leans over to give me a kiss – and fish out those three obols with her tongue! † â€Å"spends his days in the infliction of pain on others and his evenings in running his hand up his daughter’s skirt. † – K Dover.