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

What it is like to be young and a teenager!

From when you turn from twelve to thirteen you have become a teenager; you have rights and responsibilities now!! At the age of a teenager you might think the whole world is in front of you, which it is, but there are big demands. When I became one I thought wow, I am a teenager, but now after being one for 3 and a bit years I am starting to realise that it isn't so great after all. I have heard that your teenage years are supposed to be some of the best years of your life, is that so? At the age of thirteen I have left primary school and have now faced the big girls and boys at high school. Two years passed and the work rate increased. In year nine the first of many challenges has started, your Key Stage 3 SAT's, at this time you think its ages until I sit in this same sports hall and do your real GCSE's which for some people, will be the start of a completely new chapter in the life of a teenager. So far in being a teenager all that has happened is a lot of work, but there are some privileges of being a teenager at the age of sixteen you have the right to go out and buy a packet of cigarettes legally, you are also able to have sex and even have and raise a baby, but it is not till you are eighteen that you are allowed to have a credit card, or buy alcohol legally. Are these good privileges? Or not? Just before you take the GCSE tests you have to decide what you want to do. The decision is your own and the correct one needs to be made, the pressures are now starting to become apparent and it can be a stressful time for some that feel that they have to perform well. There are others who are thinking if only I had listened that little bit or a lot extra in class instead of messing around or talking with friends, and of course there are the people who go into the hall and think I have nothing to lose I don't need many passes, because what I want to be you don't need grades and all I can do is my best. The pressure at this stage are not just on the pupils, the teachers may sometimes be as nervous, and they may be thinking did I teach the write things and did we revise the correct thing which will come up. These are all things to do with school, but you do usually spend 32 hours and 55 minutes in the place. At these ages peer pressure can become a big part of someone's life the things that stick in your head could be â€Å"Everyone's doing it†, â€Å"Its only one†, â€Å"Your such a loser†, â€Å"Chicken† and no one at this age wants to be left out and on there own. Is this really what being a teenager is like? So maybe being young isn't as good as it sounds!!

Human Resource Management †Recruitment and Selection Essay

1. A report distinguishing between traditional personnel management and the new approach to human resource management, outlining their historical development. 2. The Human Resource department in TD Travel Group. Its role and purpose in the organization. Task 2 1. An analysis of the objectives and the process of human resource planning. 2. An evaluation of the systematic approach to recruitment for NIS Europe. 3. An investigation of the selection procedures used for NIS Europe and TD Travel Group. 3. Evaluation and Conclusion 4. Bibliography Task 1 TASK 2 AN ANALYSIS OF THE OBJECTIVES AND THE PROCESS OF HUMAN RESOURCE PLANNING. Human resource planning is the task of assessing and anticipating the skill, knowledge and labour time requirements of the organisation and initiating action to fulfill those requirements. Human resource planning involves a strategy for the: * Recruitment * Retention * Utilisation * Improvement, and * Disposal of the human resources of a business. It needs to look at the following factors: * What are the skills and abilities of the current workforce? * What skills and abilities the organisation needs in the future? * Where can the organisation find its future supply of labour? * What are the future objectives of the business likely to be? * How will the business manage and obtain its human resources to meet these objectives? In order to plan Human Resources effectively a business has to undertake considerable research. Here is a table showing the things companies have consider when planning human resources: What is happening now? * Organisational Objectives * Analysis of staff numbers and age * Wage rates * Work loads * Key skills * Labour turnover * Absenteeism What do we expect to happen to the demand for products / services and therefore labour? * Changing technology * Sales forecasts * Market research * New product development * Managerial skills * Wage Rates * Union Agreements What do we expect labour supply to be like in the future? * Local unemployment / employment trends * Local skills and availability * Demographic changes * Legislation * Government training schemes * Quality of local education, housing and transport * Competition for workers All these issues raise questions, which the human resource plan should cover. The plan should include: * Organisation development * Training and management development * Recruitment, redundancy and redeployment * Appraisal and job evaluation * Promotion prospects Human Resource Planning (HRM) is a form of risk management. It involves realistically appraising the present and anticipating the future (as far as possible) in order to get the right people into the right jobs at the right time. This may seem simple at first, short of staff – hire some new staff, too many staff – make redundancies. Unfortunately its not that simple anymore and that is why human resource planning is necessary. Why Human Resource Planning is necessary: It is increasingly important to look beyond the present and short-term future to be able to prepare for contingencies. This will help to exercise control over as many variables as possible, which influence the success and failure of a business. For example, for highly skilled or specialised jobs, it will be more difficult to find replacement staff with the right skills quickly, therefore the need for new staff will have to be anticipated in advance to give enough time for extra training to be given without leaving the company short staffed and unable to provide an efficient service. For example, in the travel industry, reservation staff need to be fully trained on the computer reservation system (CRS) and have a full understanding of fares and ticketing, otherwise there would be a minimum of a six month training period, which would leave the business vulnerable and unable to provide good quality service Redundancies are not as easy to make anymore. It is a much slower more costly experience, not only in financial terms but also in loss of reputation as a secure employer. This in itself may make it harder to recruit labour when required. Rapid technological change is leading to a requirement for manpower, which is both more highly skilled and adaptable. Labour flexibility is a major issue, which means that the career and retraining potential of staff are at least as important as their actual qualifications and skills. They must be assessed in advance of requirements. In the selection process trainability is one of the most popular innovations of the HRM era of personnel management. The UK still suffers from particular skill shortages, despite high unemployment levels, for example nurses at Macclesfield Hospital, 20 nurses from the Philippines have had to be employed, as there was a shortage of suitably skilled staff in the UK. The scope and variety of markets, competition and labour resources are continually increased by political and economic moves such as the unification of Germany, the opening of Eastern Europe and continuing progress towards European Union. Computer technology has made available techniques which facilitate the monitoring and planning of manpower over fairly long time spans: manipulation of manpower statistics, trend analysis, modeling and so on. THE PROCESS OF HRP There are three main factors in HRP: * Forecasting Demand * Forecasting Supply * Closing the gap between demand and supply FORCASTING DEMAND The Demand for labour must be forecast by considering several factors: The objectives of an organisation – Organisations will normally devise a strategic plan, which will set out its objectives. This will be the responsibility of the directors who will devise their plan after discussion with the most senior managers. In some cases the directors of companies may decide to change the strategy of the business completely. This could involve getting rid of the senior managers and replacing them with a new managerial team, which can put the new strategy into place more efficiently. This happened both at British Airways and at Tesco’s where it was decided that a complete change of image was needed to improve profits. Most of the top management were replaced and in both cases the strategy was successful. This sort of strategy will obviously affect the demand for labour in general and / or for particular skills. Manpower utilisation – how much labour will be required given the expected productivity or work rate of different types of employee’s and the expected volume of business activity. Productivity will depend on capital expenditure, technology, work organisation, employee motivation and skills, negotiated productivity deals and many other factors. The cost of Labour – including overtime, training and other incentives, and therefore what financial constraints there are on the organisations manpower levels. Environmental factors – trends in technology and markets that will require organisational change, because of threats or opportunities. The recession in the 90’s created conditions in which expectations of labour demand in the short term were low: downsizing of staffs and delayering of organisation structures were the trend. FORCASTING SUPPLY The available supply of labour will be forecast by considering the following factors: * The skill base, potential trainability and current and potential productivity level of the existing workforce * The structure of the existing workforce e.g. age distribution, skills, hours of work, rates of pay etc The likelihood of changes to the productivity, size and structure of the workforce, caused by, wastage (turnover by resignation and retirement), promotions and transfers, absenteeism and other staff movements; this will require information on: * The age structure of staff (forthcoming retirement or family start-up) * Labour turnover for a comparable period * Promotion potential and ambitions of staff Other causes of changes in productivity are employee trainability and motivation, which may increase productivity and flexibility. Organisational, technological and cultural changes are factors, which may affect employee productivity and loyalty. The present and potential future supplies of skilled labour in the environment – that is, the external labour market. The HR planner will have to assess and monitor factors such as: * Skill availability, locally, nationally and internationally (e.g. within the EU) * Changes to skill availability due to education and training initiatives (or lack of these) * Competitor activity which may absorb more or less of the available skill pool * Demographic changes – areas of population growth and decline, the proportion of younger / older people in the workforce in a particular region, the number of women in a workforce etc. * Wage and salary rates in the market for particular jobs CLOSING THE GAP BETWEEN DEMAND AND SUPPLY A deficiency of labour may be met by: * Internal transfers and promotions, training and development * External recruitment or improvement to recruitment methods * Extension of temporary contracts, or contracts of those about to retire * Reducing labour turnover by reviewing possible causes (e.g. pay and benefits) and improving induction and socialisation * The use of freelance / temporary / agency staff * The development of flexible working methods and structures * Encouraging overtime working * Productivity bargaining to increase productivity * Automation (increasing productivity, and / or reducing the need for human labour) A surplus of labour may be met by: * Running down manning levels by natural / accelerated wastage * Restricting or freezing recruitment * Redundancies (voluntary and/or compulsory) * Early retirement incentives * A tougher stance on discipline, enabling more dismissals * Part time and short contract working, or job sharing * Eliminating overtime and peripheral workforce groups * Redeployment of staff to areas of labour shortage. This may necessitate diversification by the organisation, to find new work for the labour force, and/or plans for multi-skilling, so that the workforce can be flexibly deployed in areas of labour shortage as and when they emerge. There are also external constraints on HR planners when considering any of the above such as, UK legislation and EU directives, regulations and court rulings, the employer brand or reputation and other factors must be taken into account when planning to hire, ‘fire’ or alter working terms and conditions. Labour turnover is the number of employees leaving an organisation and being replaced. The rate of turnover is often expressed as the number of people leaving as a percentage of the average number of people employed, in a given period of time. The term natural wastage is used to describe a normal flow of people out of an organisation through retirement, career or job change, relocation etc. AN EVALUATION OF THE SYSTEMATIC APPROACH TO RECRUITMENT AT NIS EUROPE. Recruitment is the phase, which immediately precedes selection. Its purpose is to pave the way for selection procedures by producing, ideally the smallest number of candidates who appear to be capable either of performing the required tasks of the job from the outset, or of developing the ability to do so within a period of time acceptable to the employing organisation. The main point that needs to be made about the recruitment task is that the employing organisation should not waste time and money examining the credentials of the people whose qualifications do not match the requirements of the job. A primary task of the recruitment phase is to help would-be applicants to decide whether they are likely to be suitable to fill the job vacancy. This is clearly in the interest of both the employing organisation and the applicants. The current approach to recruitment within NIS Europe works in six stages. Stage One – Determining the vacancies Human resources would confirm what resources are needed and determine as to whether or not they wanted to fill the vacancy. This very much depends on the aim and objectives of NIS Europe. Stage Two – Considering the sources internally and externally If appropriate they would advertise the vacancy internally, or think of possible transfers. HR within NIS always gives this very careful consideration and where possible favour’s this option first for the following reasons: – * Existing employees are know to the organisation and are generally familiar with its customs and practices * The cost and time that recruitment, selection and induction procedures consume can be significantly reduced * Internal recruitment may be used as a means of career development, widening opportunities and stimulating motivation amongst existing employees If the vacancy were not filled internally then they would look to external sources. Dependent on the vacancy this would be via one of the two main means: – * Through employment agencies – governmental, institutional and private commercial * Advertisements in newspapers and journals Stage Four -Preparing and publishing information NIS Europe feels that this aspect of the recruitment process requires very special attention and skill. It is their objective to publish information, which fulfils the following conditions: * It is succinct and yet gives a comprehensive and accurate description of the job and its requirements * It is likely to attract the attention of the maximum number of potentially suitable candidates * It gives a favourable image of the organisation in terms of efficiency and its attitude towards people * It does not contravene employment laws concerning sex and racial discrimination Along with the submission of curriculum vitae, NIS Europe standard procedure is for each applicant to submit a NIS Europe application form. This falls in line with equal opportunities and allows NIS to obtain standard information about the applicant, that on a curriculum vita may be omitted. See appendix for job advert and application form. Stage Five – Processing and assessing applications When all the applicants have been received by the due date, the next task is to select those applicants who, on the evidence available, appear to be the most suitable as future employees of NIS Europe and therefore, worth the time and cost of further examination in the selection procedures. The screening process is based on the published requirements for the job. It involves a scrupulous study of the information provided by the applicants, a comparison of this information with the job requirements, and then a final decision as to whether to accept or reject the applicant at this stage. Stage Six – Notifying applicants Once the selection process from the applicants has taken place, the final step is to notify the chosen applicants of the arrangements for the selection procedures, and the rejected applicants that they have not been chosen. The letter to the successful applicants will have full details about the arrangements for the selection procedures, i.e. time and place. NIS Europe ensures that all letters informing applicants of the result of applications are sent as soon as possible. THE EVALUATION OF THE SYSTEMATIC APPROACH FOR NAVIGANT INTEGRATED SERVICES EUROPE Below is an evaluation of the recruitment procedure for Navigant Integrated Services (NIS). The aim of this evaluation is to determine whether NIS recruitment procedures succeed in getting a suitable person for the job advertised and at an acceptable cost. The methods for auditing the recruitment process follow these performance indicators: – Total numbers of applicants received: Dependent on the type of vacancy NIS Europe can expect to receive on average around a dozen applicants for an advertised job vacancy. They have recently advertised for an accounts co-ordinator and have received over 30 applicants. They have admitted by not stating the salary this has interested applications, covering a wide range of experience, or in some cases very little experience. Time taken to locate applicants: Most vacancies within NIS are usually filled within one month of the advert being placed. Cost per applicant: NIS calculates à ¯Ã‚ ¿Ã‚ ½1000.00 per applicant, including the initial training. Time taken to process applications: NIS normally processes their applications within one week. Number of female /minority/ disabled applicants: NIS does not meet this indicator. They predominantly employ females; they have one minority employee and no disabled employees. When this was discussed with our HR department they advised this was nothing discriminate. The travel industry is known as being a female dominated environment and there have never been any disabled applicants at NIS. If there were any disabled or other minority applicants, they would go through the same process, as other applicants and no preferential treatment would be given. Number of qualified applicants: 90% of applicants are qualified for the job advertised. NIS biggest employment is of reservation staff for the travel industry. If they obtain a new account they will need to recruit fairly quickly, training is costly and time consuming so it is important that they stipulate qualified applicants only, at the advert stage, which is why they have a good success rate in finding candidates quickly for the vacancy advertised. Number of qualified female/minority/disabled applicants: About 70% of our applicants are female and qualified. NIS has very few minority or disabled applicants applying. Cost effectiveness of the recruitment methods: Dependent on the type of job will determine where NIS Europe advertises for staff. If they are looking for reservation agents they would normally get in touch with one of the industries recruitment agency’s. Most staff within the industry registers with the agencies. Many years ago jobs were advertised in industry papers the trend now leans towards recruitment agencies. Dependent on the level of salary the agencies take a percentage. For example on a salary of 17,000 they would take 10% of the gross salary. As the salary increases so does the percentage. Although working with an agency can work out costly, they do have a majority of the qualified personnel on their database and therefore gives NIS access to qualified personnel straight away. Monitoring the make-up of the workforce: NIS Europe workforce is split into the following departments and the make up of the workforce is as follows: – Reservations – within the Travel, Hotel & Conference reservations department, NIS employs 60 staff in this department, 10% of the workforce is male, 88.33% are female, none are disabled and only one staff member is a minority employee. * Sales and Marketing – NIS employs eight staff in this department, 37.5% of the workforce is male and 62.5% are female. None are disabled or minority employees. * Accounts – NIS employs four staff in the department, 25% are male and 75% are female. None are disabled or minority employees * HR – NIS employs two staff in this department, 100% are female. None are disabled or minority employees. * IT – NIS employs five staff in this department, 100% are male. None are disabled or minority employees. * Top line management – The top line management of NIS is made up of four. 25% is female and 75% are male. None are disabled or minority. From the above information it is evident that there are three groups of employees that are underrepresented at NIS Europe, male, disabled and minority. Attitude Surveys: Once you under taken employment with NIS Europe, they do not require you to fill in an attitude survey asking you if you were satisfied with the stages of recruitment and selection process. AN INVESTIGATION OF THE SELECTION PROCEDURES USED AT NIS EUROPE AND TD TRAVEL GROUP. Selection is the part of the employee resourcing process, which follows on from recruitment. It essentially involves the identifying of the most suitable of the potential employees attracted to the organisation by recruitment efforts. The crucial importance of selecting people who can meet the requirements described in the job description and person specification hardly need to be stressed. It is equally evident that mistakes in selection can have very serious consequences for corporate effectiveness. Such mistakes may adversely affect colleagues, subordinates and clients. Employee incompetence may lead to costly mistakes, loss and waste of valuable resources, accidents and avoidable expenditure on training. Employee selectors face an inevitable dilemma. They have to carry out a vitally important task, but one that at the same time is fraught with problems to which there are either no answers or no easy answers. The abiding problem is the dependence on subjective human judgment. We must take into consideration, that fallible human beings devise so-called objective lists. For example some person specifications require certain attitudes and attributes, such as conscientious or able to stand pressure, how can the selectors identify these requirements in a person whom they do not know during the short acquaintance of the selection process. In view of the importance and difficulties of the task, employers need to take selection most seriously. Appropriate investment at this stage can and will be cost-effective if it avoids the possibly enormous and incalculable cost that faulty employee selection may produce. For example, NIS Europe recently employed an operations manager through a recruitment agency, within six weeks of employment it was evident to NIS that he was not capable of the job he had been employed to do. Therefore NIS had to terminate his employment at a cost to the company of approximately à ¯Ã‚ ¿Ã‚ ½8,000. Other errors of the selection process could include lack of skill or experience of interviewers, stereotyping by the interviewer in the absence of more detailed information and incorrect assessment of qualitative factors such as motivation, honesty or integrity. Various selection methods are used to try to reduce the risks by gathering as much relevant information about the candidate as possible. Currently NIS Europe is working with UMIST on a competencies project where NIS is contacting their client base to investigate in terms of service, what their expectations of NIS Europe are. The information collated in turn will then be translated into competencies and then used in the selection process. Following on from our earlier systematic approach to recruitment is the systematic approach to selection Point five & six of the systematic approach to recruitment overlaps with the first & second point of the Systematic approach to selection. Stage One – Processing and assessing applications When all the applicants have been received by the due date, the next task is to select those applicants who, on the evidence available, appear to be the most suitable as future employees of NIS Europe and TD Travel Group and therefore, worth the time and cost of further examination in the selection procedures. The screening process is based on the published requirements for the job. It involves a scrupulous study of the information provided by the applicants, a comparison of this information with the job requirements, and then a final decision as to whether to accept or reject the applicant at this stage. Stage Two – Notifying applicants Once the selection process from the applicants has taken place, the final step is to notify the chosen applicants of the arrangements for the selection procedures, and the rejected applicants that they have not been chosen. The letter to the successful applicants will have full details about the arrangements for the selection procedures, i.e. time and place. NIS Europe ensures that all letters informing applicants of the result of applications are sent as soon as possible. TD Travel Group operates a very informal selection procedure. If the curriculum vitae are up to standard the applicant will be called for an interview, nothing will be advised on paper, arrangements are made on the telephone. If the curriculum vitae do not have the correct qualifications for the job it will be discarded straight away and no call to advise the applicant will be made. Stage Three – Possible interviewees â€Å"Possibles† will then be more closely scrutinised, and a short-list for interviews drawn up. Ideally this should be done by the HR specialist and the perspective manager of the successful candidate, who will have a more immediate knowledge of the type of person that will fit into the culture and activities of his department. In TD Travel Group’s case, John Owen (the operations Director) would be solely responsible for this stage, as there is no human resources department employed. At NIS Europe Barbara Sutton (Human Resources Director) and the line manager of the relevant department would be jointly responsible. Stage Four- Inviting candidates from the short list for interviews At this stage the company would require successful candidates to complete a standardised application form if not already submitted at the outset. NIS Europe standard procedure is for each applicant to submit a NIS Europe application form along with the curriculum vitae at the first stage for applying for the job. See appendix for application form. This falls in line with equal opportunities and allows NIS to obtain standard information about the applicant, that from a curriculum vita may be omitted. TD Travel Group have no standard information that is required and work off the submission of a curriculum vitae only. Stage five – Interview potentially qualified candidates. Since the interview is likely to continue to play a major role in the selection process, it seems sensible to adopt a realistic approach, which means making the best possible use of the interview. There are many different types of interview including: * One-to-one interviews – these are the most common selection method. They offer the advantages of direct face-to-face communication, and opportunity to establish rapport between the candidate and interviewer. Each has to give attention solely to the other and there is potentially a relaxed atmosphere, if the interviewer is willing to establish an informal style. * Panel Interviews – A panel may consist of two or three people who together interview a single candidate, most commonly, a personnel manager and the departmental manager who will have responsibility for the successful candidate. NIS Europe use the above forms of interview, however they also have other interviewing techniques, which can be panel interviews or one to one interviews, such as: * Audition interview – this is predominantly to assess people in leisure and service industries; it focuses on personality versus skill. This would involve exercises, which display the personality of the candidate as well as the skills. * Criteria based interview – these are specific questions which highlight predetermined behavior which you are looking for e.g. if you need an outgoing person you would ask a question â€Å"If somebody came into the room how would you put them at ease?† You would rate the response as positive or negative. * Behavioral event interview – ideally this interview is a taped interview. The interviewer would have a competence list on a chart and when questions asked and in turn answered, the competencies would be marked off. TD Travel has a much more informal interview technique. It is generally a panel interview conducted by the Operations Director with the General manager and also the Sales and Marketing Director. There are no set techniques; it is more of a formal chat about skills and qualifications, outlined on the curriculum vitae. Stage six – Selection testing Once the interview has taken place, some companies go one step further by inviting candidates for a selection test. These tests are all standardised so that an individuals score can be related to others, reliable in that it always measures the same thing and is non discriminatory. These can be in various forms: * Intelligence or cognitive testing – these test memory, ability to think quickly, perceptual speed, verbal fluency and problem solving skills. See appendix. * Aptitude tests – these are designed to predict an individuals potential for performing a job or learning new skills. * Personality tests – these may measure a variety of characteristics such as the applicant’s skill in dealing with other people, ambition, motivation or emotional stability. See appendix. * Proficiency tests – these measure the ability of the applicant to do the work involved e.g. a typist would be asked to type, and a salesperson would be asked to sell. Td Travel does not use selection tests at all. Most people are employed through word of mouth, as travel is a very incestuous business. NIS Europe use personality and aptitude tests. Stage seven – Checking references of short listed candidates References provide further confidential information about the perspective employee. A reference should contain: * Straightforward factual information confirming the nature of the applicant’s previous jobs, previous employment, pay and circumstances of leaving * Opinions about the applicant’s personality and other attributes. At least two employer references are desirable, providing necessary factual information, and comparison of personal views. NIS Europe and TD Travel Group offer the successful candidate the job subject to checking the references. Stage eight -Institute follow-up procedures for successful applicants The follow up procedures include: * Offer of employment – Assuming that the right candidate has by now been identified, an offer of employment can be made. It is common for an oral offer to be made. With a negociated period for consideration and acceptance. * Draw up a contract or written particulars – this should include all terms, conditions and circumstances of the offer must be clearly stated and negotiable aspects of the offer and timetable for acceptance should be set out, in order to control the closing stages of the process * Arrange work permits if required – Work permits are required of people coming into the UK for employment * Plan induction – Induction is a formal programme, designed and carried out by HRM to introduce new employees to the organisation, in all its social as well as work aspects. Stage nine- Review all candidates Review un-interviewed candidates and sort out those that my be kept on file for possible future use. Send standard letters to unsuccessful to applicants and holding letters to those being kept on file. NIS Europe will hold candidates on file for a maximum of one year. TD Travel group do not use this procedure, they would start their informal recruitment process again as and when required. SUMMARY OF THE SELECTION PROCESS FOR TD TRAVEL GROUP AND NIS EUROPE It is evident from the above information that NIS Europe carries out a more formal selection procedure than TD Travel Group. This is down to the fact that NIS Europe have more employees than TD Travel Group, and therefore see it necessary to have a HR department.

Lgbt Substance Abuse Treatment Best Practices - 2822 Words

LGBT Substance Abuse Treatment Best Practices: An Annotated Bibliography Introduction Practice with special populations led to an inquiry regarding LGBT substance abuse and best practices. What was interesting in looking through the existing research is that there is really not a huge breadth of information out there regarding the LGBT population in relation to substance abuse and best practices. The importance of this subject was made apparent by the lack of concrete evidence for particular models of treatment when working with the LGBT community as a whole. Due to the lack of LGBT specific treatment evidence based outcomes, the search focused on comparisons of outcomes between LGBT and heterosexual participants in treatment programs, gay†¦show more content†¦A search of the Campbell Collaboration and Cochrane Collaboration (systematic reviews) yield no information on the topic of the LGBT community and substance abuse/use or chemical dependency. Because the LGBT community is often subject to discrimination within the healthcare system as a whole, it is crit ical for providers of substance abuse treatment programs to be aware and able to assist those who exist outside the heterosexual norm. LGBT individuals are, in general, less likely to disclose their sexual orientation or gender identity for fear of real and perceived discrimination. Being able to provide LGBT affirming and/or specialized services for those in the community seeking assistance through traditional channels seems to be the next logical step forward. There still seems to be quite a lot of work done in the research field to identify what works best in terms of treatment for the LGBT population however, evidence is showing that if a LGBT person feels welcomed and comfortable within a chemical dependency treatment program, the outcomes of program persistence and adherence is higher. Topic Outline/Critical Points Substance Abuse in the LGBT Community Finlon MSW, C. (2003). Substance abuse in lesbian, gay, bisexual, and transgender communities. Journal of Gay Lesbian Social Services, 14(4), 109-116. This article outlines the lack of knowledge in relation to substance abuse and the LGBT community. An online search was