The Mega Manufacturing

Mega Manufacturing is a manufacturer of sports shoes for men and women. They are investigating each department in order to cut back on spending in order to eliminate wastes of resources. One potential waste is coming from the cutting department. The waste of material is costing the company monitory resources that could further benefit the company if allocated elsewhere. Several solutions have been discovered with the cutting process but if the problem were to be solve d there is both a salary saving and the elimination of waste, in this particular department. However the solution lies with the employees of this department and the solution will cost some of them their jobs. The variables effecting the disclosure of this information vary from one's need for monitory income, to the esteem of the position. Management is facing several possible decisions that include employee employment assurance to cost savings and company bottom line figures. Their decisions are founded on management decisions, employee motivations and resistance to innovations and the notion of getting these resistant employees to adopt the innovations. First, the management decisions regarding the cutting process and the problems that are associated with them. The notion that the skilled workers of the cutting department are aware of a solution to the problem with the breaking dies indicates that there is a solution to the problem. On the standpoint of the company, investigation into the proper use and successful completion of the cut using the die needs to be resolved. The die eliminates wastage and will speed up productivity of the cutting process. It will also make the individual machine operator more efficient which will conclude with the elimination of several positions may allocated more resources previously spent on employee salaries. This cost savings will free up allocations previously spent on overhead and allocated to other departments that may increase spending in order to increase sales, or add more to the stockholders bottom line. As a machine operator aware of this notion that relinquishing this information could cost him/her their job, there needs to be some cause for hesitation. The workers are paid on an hourly base so the increase of efficiency will also allow management the ability to cut hours, which will also hurt the workers. If faced with this dilemma I would have to first find out if the solution the breaking dies were legit. Because of the two-month time delay in the manufacturing of the dies I also have to worry about the productivity of the department on the half of the workers if future layoffs were in sight. I would also have to know if the cost savings would be passed on the consumer and how these variables will effect sales. If demand for the product were to increase there may be no need for lay offs. However if there was a need to make cuts in the workforce there would be need to evaluate each individual on the grounds of seniority and skill level to insure proper staffing of the department and explore options of moving personal to other departments. So my conclusion to the dilemma facing this question has to many variables but I have explored decisions with regards to time and company proposals of use of the freed resources. There are two motivating factors that our cutters face in the dilemma with regards to the die cutting information they include the following: Maslows Hierarchy of Needs, and Herzberg's Two- factor Theory. First, Maslow's Hierarchy of needs. The worker is at a job that provides substance for himself and possibly a family. The information and innovation that the die implantation brings may disrupt his/her ability to provide so without so assurance of the continued employment and income potential; the worker will not relinquish the information needed for successful inauguration of the die cutting process. However, if that assurance were provide their would be increased productivity in the department and successful integration of the project will fill Maslows notion that people thrive for accomplishment, and the efficiency of the department will bring this idea to reality. There may also be negative connotations that may be brought about As well. If there were that worker who was fearful for their job might relinquish this vital information to management for assured employment, this also demonstrates Maslows basic survival needs theory. Second is Herzbergs two-factor theory, called dissatisfies or hygiene factors. They include such notions of working condition, benefits recognition and possible promotional opportunities. The employee is unwilling to do anything that may jeopardize their livelihood. Implication of this process will result in lay offs that may damage this security. This will also pose a threat to the workers acceptance among peers. If layoffs are inevitable there may develop groups within the department of loyal skilled labors who pose a greater chance of employment after the downsizing. This is a possible threat even if the project is just in consideration, which may impose productivity problems while implication is in the process, and future problems if the project is discarded due to the already imposed loyalty among the divided department. There is also the factor if employees resistance to change with the implication of the new cutting process. There are several factors of habit, security, economic factors, fear of the unknown and lastly selective information processing that influence these factors of resistance. Employees develop habits in the work place that become routine and habitual and allow the worker to become part of the department and allow the worker develop routines that increase productivity. Security issues factor in the employee's unwillingness to change, in fear of loosing their jobs. Economic factors develop when the worker fears that change will lower their income, tying into the security concerns. Fear of the unknown indicates that humans are unwilling to change when the ends of the means is unknown. Selective information processing is the individual perception of the relevance of the change. If the individual feels that the change is unnecessary they are reluctant to change.

Infant Observation Essay Essays

Infant Observation Essay Essays Infant Observation Essay Paper Infant Observation Essay Paper Physical Development SG spent most of the clip the observation was done asleep. When SG was awake though. a few experiments were conducted to prove her physiological reactions. SG showed consistent marks of every physiological reaction except the Stepping. and Tonic cervix physiological reaction. SG was non able to keep her caput up independently yet. and didn’t show any marks of other motor development mileposts ( Berk 2010. 107. ) SG’s eating wonts seemed to be on a agenda with her kiping wonts every bit good. SG was being bottle Federal. She ate shortly after the observation began and awoke once more shortly before the observation ended. Cognitive Development â€Å"Piaget believed that babies and yearlings think with their eyes. ears. custodies. and other sensorimotor equipment† ( Berk 2010. 152. ) On Piaget’s Sensorimotor Stage. SG would be classified in sub phase two. This categorization was based on the manner SG would open her oral cavity for a bottle and a conciliator. Besides when SG awoke and needed bottle she would shout until she saw her female parent enter the room. SG’s linguistic communication development merely consisted of weeping and cooing. The baby seemed to merely shout when she needed a diaper alteration or to be fed. Social and Personality Development SG seemed to overall be a happy babe. During the observation the baby showed no marks of gripes. The female parent and male parent of SG were really caring and provided a good stable place for her. SG was non neglected by neither the female parent nor male parent. Both parents seemed to be patient and loving towards the baby. SG would shout when she needed to be fed or have her nappy changed and her female parent would alter it and comfort her weeping. SG was fed twice during the observation. Once at the beginning by her female parent. and subsequently on during the observation by SG’s uncle. The baby took the bottle good when it was given by the female parent. Opposed to when SG’s uncle tried to feed her. she didn’t take the bottle so good at first. SG’s uncle had merely seen her twice earlier. The fact that SG struggled to take the bottle from her uncle shows marks of Erickson’s theory of Trust V misgiving. â€Å"Basic trust versus misgiving consequences in trust when the kid receives sympathetic and loving attention. The leery babe can non number on the kindness and compassion of others. so she protects herself by retreating from people. † ( Berk 2010. 184 ) Important Information learned By detecting Infant SG. I realized that although the parents were demoing a batch of love and compassion by keeping SG they besides may hold deferred some of her motor accomplishments. A kid must be given the chance to construct strength and research their environment. It seemed that they were â€Å"suffocating† her in a manner. Not leting her to develop as rapidly. Which is non needfully a bad thing because she’s a babe. but harmonizing to the text edition SG seems to be a small slow in the developmental procedure. Mention Berk. L. E. ( 2010 ) . Development through the Lifespan. 5th erectile dysfunction. Allyn A ; Bacon.

Teach Reading With Word Families

Teach Reading With Word Families An emphasis on sounding out words with isolated phonemes often leads students to dread reading and think of decoding as some sort of mystical power. Children naturally look for patterns in things, so to make reading easier, teach them to search for predictable patterns in words. When a student knows the word cat, he can pick out the pattern with mat, sat, fat, etc.   Teaching patterns through word families- rhyming words- facilitates fluency, giving students more self-confidence and a willingness to use prior knowledge to decode new words. When students can recognize the patterns in word families, they can quickly write/name members of the family and use those patterns to nail down more words. Using Word Families Flash cards, and thrill and drill work to a certain extent, but providing your students with a variety of activities keeps them engaged and increases the likelihood that they will generalize the skills they acquire. Rather than using worksheets that can turn students with disabilities off (demanding the use of fine motor skills), try art projects and games to introduce word families. Art Projects Artistic word sorts with seasonal themes capture kids imaginations and use their enthusiasm for a favorite holiday to introduce and reinforce word families. Paper Bags and Word Families:  Print a variety of related words, then ask your students to cut them apart and put them in bags labeled with the corresponding word families. Turn them into trick or treat bags with crayons or cutouts (or buy some at the dollar store) and use them as a centerpiece in your classroom before Halloween.  Or draw Santas sack for Christmas, and label them with a word family. Then instruct students to sort words written on presents cut from construction paper into the appropriate sacks.   Art Project Sorts:  Draw or print Easter baskets and label each with a word family. Ask students to write associated words on Easter egg cutouts, then glue them to the corresponding basket. Display the word family baskets on the wall. Christmas Presents:  Wrap tissue boxes in Christmas paper, leaving the opening at the top exposed. Draw or print Christmas tree ornaments shapes and write words on each one. Ask the students to cut and decorate the ornaments, then drop them into the proper gift box. Games Games engage students, encourage them to interact appropriately with their peers, and give them an entertaining platform on which to build skills.   Build Bingo cards with words from a word family, then call out the words until someone fills all of their squares. Occasionally insert a word that doesnt belong in that particular family and see if your students can identify it. You can include a free space on the Bingo cards, but dont allow students to use it for a word that doesnt belong to that family. Word ladders use the same idea. Following the pattern of Bingo, a caller reads the words and the players cover steps on their word ladders. The first student to cover all of the words on the ladder wins.

CREATING AND STARTING A NEW BUSINESS VENTURE Essay

CREATING AND STARTING A NEW BUSINESS VENTURE - Essay Example We will focus on selling wine directly to the customers and also they can order the product through telephone and our website. During the initial stage, my agency will concentrate only on sales and marketing of wines. We will make a commitment of offering innovative services to our customers. They can get wine cases delivered to their homes or party areas and offices. We will offer free delivery service to all customer orders irrespective of the quantity or value of the order. Our main strategy in business is to evolve a membership scheme for our customers on yearly, quarterly or monthly basis. The customers can become members of our club and our membership will be categorized into three types i.e. platinum, gold and silver. The members will be issued with a card through which they can place the orders and they will get yearly dividend. We will get the products supplied through several manufactures so that we can meet the personalized requirement of each customer and sell through our outlets and other sellers and restaurants. We intend to start our wine shop in London because of the ever growing demand for wine in this area. At the initial stage of our business, we will concentrate only on sales and after getting a market share we will try to produce our own brand apart from selling vintage wine of a specific group of elite clientele. Our aim will be to provide the best quality wine from good wine producers across the globe at a reasonable price in London and also to facilitate free any time delivery to attract large volume of customers. From a market survey it has been revealed that the marketability of wine in the London city and its other parts is quite high, especially in the case of vintage wines. There are a lot of clubs, restaurants and other organizations where wine is consumed in large quantity. Most of the

Applied ethics ( ethics in marketing) Essay Example | Topics and Well Written Essays - 1000 words

Applied ethics ( ethics in marketing) - Essay Example The theory emphasizes the need for people to learn how to break bad habits of character for example greed or anger (Chonko, & Hunt, 1985). The advertisement I choose from the news is on the Embassy Cigarettes. On the theory of deontological, the company marketing has the obligation to adhering to the moral rules. This implies that when marketing this brand of cigarettes, they should not give any misleading information about the product. Marketers must clearly indicate the contents that have been used to make the cigarettes on the packet. The contents indicated must genuine, only those that were used without any additional materials or omitting some of the ingredients. This a moral ethic as the consumer gets to know what was used in the making of that product and based on that information, consumers will make decisions. When all the content is genuinely on the packet, the user will read through that information and based on it, they will be able to decide whether to buy it or not. Marketers must ensure that the information they display is not misleading to the product consumer (Gibson, 2000). The marketers of the Embassy Cigarettes must focus on the second theory of marketing ethics, the teleology theory. Based on their advertisement, the marketers should consider what action their decision might have to the consumer after using the product. The teleology theory emphasizes that the company has the obligation of taking care of the customer. The product should not affect the user after using it, due to the false information given to it. For example, if the marketers omit to include an ingredient used in the manufacture of the cigarette on the packet, it is not ethically correct. This because a consumer will make a wrong decision in case the product consist an ingredient that causes complications to their health. When they buy and use the product, they are sure

How might an anthropologist analyse a mainstream film Essay

How might an anthropologist analyse a mainstream film - Essay Example The depiction of the characters in the movie is not only racist in more ways than one, it is also extremely sexist. It takes historically inaccurate facts and places the burden of a sexist society upon the tribes of America. The vision that the director and the makers of the movie endorse is extremely problematic and make for disturbing viewing when looked through with a postcolonial and feminist approach. The dissection of the movie in this paper shall then proceed with the gaze of an anthropologist. Another factor that shall be looked into is the fact that Gibson’s movie was a mainstream one and hence factors in popular notions regarding other cultures. This then brings in the elements of reception and the cultural attitudes that are prevalent in the American and also global population. What sections of the population are targeted is also something that needs to be discussed here. This paper shall seek to look at these elements of the debate and also a psychoanalytic approac h into the understanding of why certain races are depicted as they are in popular culture. However, there is another side to this debate. The changes that are introduced into the idea of the Mayans represent the idea of difference between the city and the forest within Mayan culture. The movie is then an indictment of Mayan elite culture that according to Gibson had degenerated into a set of mindless rituals. The city becomes the center of all forms of evil that Gibson associates with Mayan culture. This is then contrasted with the culture that is prevalent within the geographical confines of the village. This village is then the site of family and bonding between different members of the same society. It is a self-sufficient unit that is understood to be a space where traditional aspects of Mayan life are followed without there being a corruption of these ways. There is however, also the presence of technology in the form of traps and other devices that smoothen the life of the peo ple in the villages. There is thus, an endorsement of the idea of the â€Å"noble savage† as Jean Jacques Rousseau thought of it. It discussed the idea of man in a pure state which made him not merely a savage but also a noble one that was purer than the man who had been corrupted by civilization (Basic Concept: Primitivism and the Noble Savage). Throughout the movie, aspects of Mayan culture are denigrated and the only character whose perspective is taken for a large part of the movie is that of the protagonist, Jaguar Paw. The movie traces the life that this character leads where a process of colonization takes place between different tribes within America. The fickleness of power is made clear in this kind of transfer of power takes place very frequently. One of the people who were met by Jaguar Paw is later seen as a captive within a matter of a few days. All of this leads to the series of human sacrifices that take place at the Mayan temple in an effort to appease the Ma yan god Kukulkan. The degeneration of the culture of the elite and those that live in the city are talked of in this movie. The connection between Jaguar Paw and the nature of his homeland is repeatedly stressed. This can also be seen in the way in which the forest decimates the people of the city who seek to kill Jaguar Paw. The connection between Jaguar Paw and his homeland’

Naked Eye Single Tube Osmotic Fragility Test

Naked Eye Single Tube Osmotic Fragility Test The effectiveness of one tube osmotic fragility screening in detecting BTT was first introduced by Kattamis C. in 1981.(56) NESTROFT is the rapid simple and cost effective screening test. 2.15.1 Principle The principle of NESTROFT is based on the limit of hypotonicity that the red cell can withstand. There is a pronounced decrease in osmotic fragility of red cells in ÃŽÂ ²-thalassemia(57) Cells with a decreased surface/volume ratio, have a limited capacity to expand in low osmolarity solutions and lyse (rupture) at a higher concentration of sodium chloride than do normal biconcave red cells. Therefore, thalassaemic cells that are hypochromic and fLatter have a greater capacity to expand and thus have decreased osmotic fragility. (58) 2.15.2 Clinical Implications The different saline concentration is used in NESTROFT test to detect spherocytosis and BTT. Positive test is due to reduced osmotic fragility of red cells at 0.36% buffered saline. Manglani M et al in 1997 studied 165 cases (with MCV Recent published data has shown that the NSTROFT can be a very useful screening tool for ÃŽÂ ²-thalassemia Trait. (5, 63-66) Different studies show that NESTROFT with 0.36% saline could detect 96-100% of heterozygotes with ÃŽÂ ²-thalassemia. Study published in Indian J Pathol Microbiol, 2002 concludes NSTROFT to be 92.5% sensitive and 95.2% specific for screening of red cell microcytosis.(67) The test proves to be simple, cheap, easy to perform and adaptable for mass screening coming close to an ideal screening test. According to a recent study conducted at PNS Shifa Hospital Karachi, NESTROFT has a Positive Predictive Value of 85.38% and Negative Predictive Value of 97.66%, this correlates to international published data. The diagnostic accuracy was 94.6 % (63) NESTROFT done with 0.36 % buffered saline solution provides more accurate results compared to the other concentrations tested.(5) Routine use of haematological data from automated cell counters may complement the result s of the NSTROFT.(64) 2.16 Supravital Stains Supravital stains are a group of special stains for demonstration of intracellular inclusions in the living tissues. Common supravital stains used are methylene blue, new methylene blue, brilliant cresyl blue (BCB), methyl violet, crystal violet and azure B. Supravital stains in thalassemia are done for the demonstration of reticulocytes and Hb H inclusions as and when indicated. In thalassaemia carrier screening reticulocyte count does not have a diagnostic value. However in the detection of ÃŽÂ ±-thalassaemia, especially Hb H disease, the brilliant cresyl blue stain will detect the characteristic Hb H inclusion bodies. Supravital stains (brilliant cresyl blue or new-methylene blue) are able to stain residual mRNA in immature red blood cells. There are now several automated electronic cell counters able to perform a reticulocyte count using specific RNA staining.(68) Reticulocyte numbers and maturation levels have been studied in different haemoglobinopathies and the results have been correlated with the degree of ineffective erythropoiesis. Laura C. et al in 2003 studied 219 samples from patients with Sickle Beta-thalassemia (n=7), HbSC disease (n=11), BTT (n=33) and IDA (n=47) and non-anaemic individuals(n=60). They found patients with HbS trait (0.83%), IDA (1.18%) and BTT (1.53%) showed Reticulocyte parameters similar to non-anaemic group (1.18%). A non-responsive bone marrow does not release reticulocytes in sufficient numbers to compensate for the degree anaemia. The authors concluded that the absolute number and immaturity fraction were higher in BTT than normal individuals, but without statistical significance.(69) 2.17 Haemoglobin Electrophoresis Hemoglobin electrophoresis (also called Hgb electrophoresis), is a test that measures the different types of hemoglobin in the blood. The method used is called electrophoresis, a process that causes movement of particles in an electric field, resulting in formation of bands that separate toward one end or the other in the field. 2.17.1 Types of Electrophoresis 2.17.1.1 SDS-PAGE SDS-PAGE (Sodium Dodecyl Sulfate Polyacrylamide Gel Electrophoresis) is a common type of electrophoresis used for analyzing proteins, which separates proteins according to their size. The SDS is a protein denaturing detergent that causes unfolding of protein molecule. The detergent binds to the polypeptide in a 1:1 ratio with each segment of the protein to give it a charge. The movement of protein polypeptides through the gel occurs at different rates depending on size. 2.17.1.2 Agarose Gels Agarose gels electrophoresis is used for separation of RNA and DNA molecules. Like SDS-PAGE, this separates the molecules based on charge and size. DNA molecules are negatively charged, so they move through the gel quickly depending on size. Smaller DNA fragments move more quickly than larger ones due to friction resistance. 2.17.1.3 Electrofocusing Electrofocusing analyze the charge and pH values of proteins. A container is filled with a gel solution that has an increasing pH gradient. The amino acids that form polypeptides have different acidic or basic charges. The protein travels through the gel, obtaining or losing protons depending on its charge. As the protein particle moves through the gel, it eventually becomes neutral and gets stuck in an isoelectric position. 2.17.1.4 Capillary Capillary electrophoresis is a method similar to SDS-PAGE. It separates molecules based on their charge and mass. Molecules are placed in rows called capillaries filled with conductive, electrolyte fLuid. The analytes move in a speed relative to their charge and mass. This method is an older technique introduced in the 1960s. SDS-PAGE is usually preferred in labs. 2.17.1.5 Native Gels Native gels are similar to SDS-PAGE, except the detergent (SDS) is not used to denature proteins. Native gels are only able to separate proteins up to 2,000 kDa in size. Because the proteins are left folded, the dyes used are also different than SDS-PAGE. Hemoglobin electrophoresis is the method for identification and quantification of variant Hbs. Electrophoretic methods have been developed that allow for separation at alkaline pH 8.4 on cellulose acetate and at acidic pH 6.2 on agarose gels. These provide a clear background, allowing for quantification of the Hb present by densitometric scanning.(47) Cellulose acetate electrophoresis may be used for qualitative identification of variants, but also with elution for quantitation of the haemoglobins, A2, A, S, D, Lepore, ÃŽÂ ±-chain variants, Hb H and Hb Barts. Agarose gel electrophoresis is not a satisfactory screening technique because it cannot distinguish many abnormal haemoglobins from Hb A. However it can separate the C group into three fractions: HbC, O-Arab, and Hb E plus HbA2. The method can also distinguish Hb S from Hb D, Hb F from Hb A, Hbs Little Rock, Rainier and Bethesda from Hb A, and Hb H from Hb I. (68) The diagnosis of BTT relies on an accurate estimation of HbA2 levels.(69) Raised HbA2 level (>3.5%) is the gold standard for the diagnosis of BTT. Subjects found to be positive in preliminary screening tests by Red cell indices, DFs and NESTROFT are confirmed for thalassemic carrier status by various methods such as cellulose acetate electrophoresis, microcolumn chromatography, capillary isoelectrofocussing and HPLC (high performance liquid chromatography). Subjects with HbA2 levels of 3.5% and above are considered to have BTT. However precautions have to be taken when HbA2 levels fall between 3.3 and 3.7%. In such cases it is recommended to repeat the assay to rule out technical error or treat the patient for IDA before the analysis is repeated.(60) According to the Thalassemia working party of BCSH General haematology Task force both electrophoresis and elution from cellulose acetate or microcolumn chromatography are recommended. They suggested that precision and accuracy of automated scanning densitometry was inadequate for HbA2 estimation. (70) 2.18 Isoelectric focusing (IEF) IEF is another popular method used by laboratories that have a large number of specimens or very small sample volumes that perform newborn screening. This electrophoretic method utilizes carrier ampholytes, small proteins that are able to carry both current and pH (Zwitterions). When the current is applied to the support medium, the ampholytes will gradually establish a pH gradient throughout the gel (for example, a pH range of 6 to 8 for Hb analysis). IEF gives better separation of Hb variants that show similar mobilities on alkaline electrophoresis, which are much sharper. Hb variants such as Hb-Malmo, show separation from HbA which is not seen on alkaline electrophoresis. Minor bands such as HbH, Hb-Barts and Delta chain variants are easily seen.(71) Figure 2.6 Examples of many hemoglobin variants and their migration patterns on Isoelectric focusing. 2.19 Capillary isoelectric focusing (CIF) CIF is a useful analytical technique for characterization of protein mixtures and determination of protein isoelectric points. It is particularly useful in separation of protein glycoforms, characterizing protein microheterogeneity, and resolution of charge variants. The capillary focusing process is analogous to conventional isoelectric focusing in gels, while the requirement for zone mobilization is unique to the capillary format with on-tube detection. A variety of mobilization methods have been described, and the selection of the mobilization method for a particular application depends on the capillary type, the instrument configuration, and the type of proteins to be analyzed. Capillary IEF is generally successful for proteins with a molecular weight up to about 150,000 that exhibit good solubility in aqueous buffers, but may be unsatisfactory for large or hydrophobic proteins.(72) 2.20 Globin chain electrophoresis It is an ancillary procedure in which haemoglobin lysate with mercaptoethanol and 8mol/L Urea to dissociate the globin chain is used. It is run both at alkaline and acid pH. It gives additional information on haemoglobin variants that have similar mobilities by other methods.(71) Globin chain electrophoresis is run at both alkaline and acid pH because some hemoglobin variants show slight differences in mobility at the two pHs. This method often gives additional information on hemoglobin variants that have similar mobilities by other methods. In confusing cases, this method may be useful to document the presence of both an ÃŽÂ ± and a ÃŽÂ ² chain variant Examples of different hemoglobin variants on globin chain electrophoresis are shown in Figure 2.6. (www.cap.org/apps/docs/cap_press/hemoglobinatlas_intro.pdf) Figure 2.7.Examples of hemoglobin variants on both acid (pH 6.2) and alkaline (pH 8.9) globin chain electrophoresis. Source: Adopted from hemoglobin atlas. (www.cap.org/apps/docs/cap_press/hemoglobinatlas_intro.pdf) 2.21 High-Performance Liquid Chromatography (HPLC) HPLC is a method that has been available for many years. Cation-exchange HPLC is emerging as the method of choice for the initial screening of Hb variants.(56) Run lengths have been shortened from more than 20mins to 6 to 7mins. These instruments are approved by U. S. Food and Drug Administration (FDA) for the measurements of HbS, A2 and F. These instruments generally utilize a weak cation exchange column. Gradually increasing the ionic strength of the eluting solution causes the Hb protein to come off the column at a particular retention time. This method has a advantage that HbC does not coelute with HbA2, however HbE and HbO-Arab still coelute with HbA2 with this method.(71) 2.22 DNA Analysis The DNA analysis is gold standard for detection of carrier state of ÃŽÂ ²-thalassemia. The prenatal diagnosis of affected couple should be carried out to prevent the birth of thalassemic child by selective abortion of affected foetuses. It is essential to characterize the DNA mutations of the parents for prenatal diagnosis of affected couple. The methods available to study DNA mutations are allele specific oligonucleotide (ASO) screening, (73) reverse dot blot, and restriction endonuclease allele recognition.(74) The ASO method is for detection point mutations, nucleotide insertion or deletion in genomic DNA. In this method ASO probes of 18-20 per sequence are used. DNA is denatured and dot blotted on to a nylon membrane and then hybridized to different probes. In reverse dot blot probes are attached to the membrane and DNA hybridizes with dot corresponding to the mutation. A recent method is amplification refractory mutation system (ARMS) technique in which specific primers against normal and mutant sequences are used.(60) More than 150 mutations causing beta-thalassemia have been reported from different parts of the world.(74) Studies conducted in Pakistan show the five most common mutations are IVS1-5 (G-C), IVS1-1 (G-T), Fr 41-42 (-TTCT) Fr 8-9 (+G) and deletion 619 bp.(75) Ahmed et al found that there are important ethnic and regional differences in the prevalence of mutations. The five most common mutations, IVSI-5 (G-C) (37.3%), Fr 8-9 (+G) (25.9%), del 619 (7.0%), Fr 41-42 (-TTCT) (6.7%) and IVSI-1 (G-T) (5.4%), constitute 82.3% of the total. Fr 8-9 (+G) is the most common mutation in Northern Pakistan (41.3%), whereas IVSI-5 (G-C) is the most frequent mutation in Southern Pakistan (52.2%). (76) 2.23 Prenatal Diagnosis The availability of prenatal diagnosis added a new option to couples at risk for major haemoglobinopathy, leading to a significant change in the effectiveness of screening and counseling in hemoglobinopathy prevention. Prenatal diagnosis of both ÃŽÂ ±- and ÃŽÂ ²-thalassemia was carried out for the first time in the 1970s using globin chains synthesis analysis in fetal blood, obtained by fetoscopy or placental aspiration around the nineteenth week of gestation. The advent of DNA analysis and the introduction of chorionic villi sampling resulted in a notable improvement in prenatal diagnosis because it could be performed generally at 10 to 12 weeks of gestation. Fetal DNA can be obtained also from aminocytes at 15 to 17 weeks of pregnancy. The reported risk of fetal loss with this procedure ranges from 0.5 to 4.5%. After sampling, fetal DNA analysis is performed by the PCR-based methods mentioned for carrier detection procedures. In general, the mutation to be detected in the fet us is first identified in the parents. The results of DNA analysis are very accurate, but misdiagnosis may occur for several reasons (failure to amplify the target DNA fragment, mispaternity, maternal contamination, and sample exchange). However, the risk of misdiagnosis can be significantly reduced using a number of precautionary measures, such as fetal DNA analysis for selected polymorphic markers.(35) Fetal cells, known to be present in the maternal circulation, represent an attractive, noninvasive approach to prenatal diagnosis. Fetal cells, immunological isolated for their low purity, can only be used for prenatal diagnosis of ÃŽÂ ²-thalassemia in women whose partners carry a different mutation. Recently, this problem has been overcome by development of a technique able to isolate single fetal erythroblasts from maternal blood by microscopic micromanipulation, making possible the analysis of both fetal genes in a single cell. However, this procedure is associated with several technical and biological problems and it is not widely applicable.(35) The discovery of free fetal DNA in maternal plasma provided the basis for developing another method for noninvasive prenatal diagnosis. However, because free maternal DNA is also present, the application to prenatal diagnosis of thalassemias would be possible only to exclude paternally derived pathologic alleles different from the mot hers mutation.(35) The advent of DNA amplification has made it possible to define the geneotype of a single cell biopsied from cleaving embryos (preimplantation diagnosis) and to analyze the polar body obtained during the maturation of the oocyte (preconceptional diagnosis). These procedures avoid the need to terminate affected pregnancies and permit the transfer of only healthy embryos established from in vitro fertilization. Successful experiences in many couples with this approach have been reported in hemoglobinopathies. However, preimplantation genetic diagnosis is a technically challenging, intensive procedure, which requires the close collaboration of a team of specialists. (35) To date, programmes for ÃŽÂ ²-thalassemia prevention based on carrier screening, genetic counseling, and prenatal diagnosis are on-going in several areas at risk in Mediterranean countries, with a marked decline in the incidence of thalassemia major. Effective preventive programs have also been established in countries such as United Kingdom, where thalassemia is a rare disorder that affects diverse minority ethnic groups. Special attention should be given in these programmes to the different religious and social issues and to the different attitude towards prenatal diagnosis of the various ethnic minorities. In case the mutations are not identified linkage studies using restriction fragment length polymorphisms (RFLP) or globin chain synthesis by cord blood sampling are the other options used for prenatal diagnosis. (60) In 1999, Maheshwari M and colleagues suggested fLow chart for carrier detection and prenatal diagnosis of thalassemia. (Figure 2.7) In 1994 the thalassemia working party of British Society of Hematology suggested guidelines for investigation of the ÃŽÂ ± and /ÃŽÂ ² thalassaemia traits. (Figure 2.8) Figure 2.8. FLow chart for carrier detection and prenatal diagnosis of thalassemia. Source: Adopted from Maheshwari M, Arora S, Kabra M, Menon PSN. Carrier screening and prenatal Diagnosis of Beta-thalassemia. Indian Pediatr 1999; 36: 1119-1125. Figure 2.9. FLow chart for thalassemia carrier detection suspected on red cell indices Source: adopted from Guidelines for investigation of the ÃŽÂ ± and /ÃŽÂ ² thalassaemia traits, The Thalassaemia Working Party of the BCSH General Haematology Task Force J Clin Pathol 1994;47:289-295 Prevention is better than cure. It is important to develop prevention programmes for thalassemia prevention where there is high frequency, to avoid fatalities from untreated thalassaemia cases, the expense and difficulty of providing optimum treatment for patients which creates a burden on patients, families and national health services. Thalassaemia patients may be left untreated (indeed, they often die without a diagnosis) or grossly under-treated. At the same time, quality of treatment is firmly linked to both survival rates and quality of life. (Thalassemia International Federation, 2003). The countries where prevention programmes are effective resulting in increased survival of thalassemia major patients in comparison to countries where preventive strategies do not exist. (Figure 2.6) Graph A Graph B Figure 2.10. Graph A: Age distribution of thalassemics in a country without prevention Patients are mostly infants (non-prevention) and children (early deaths) Graph B: Age distribution of thalassemics in a country with full prevention treatment. There is gap in early years with patients mostly in their mid-twenties. Source: Adopted from Prevention of thalassemia other hemoglobinopathies, Thalassaemia International Federation, 2003.