Quality management focuses attention on continuous improvement Essay Example for Free

Quality management focuses attention on continuous improvement Essay Th e work of W. Edwards Deming is a cornerstone of the quality movement in management. 27 His story began in 1951, when he was invited to Japan to explain quality control techniques that had been developed in the United States. â€Å"When Deming spoke,† we might say, â€Å"the Japanese listened. † Th e principles he taught the Japanese were straightforward, and they worked: Tally defects, analyze and trace them to the source, make corrections, and keep a record of what happens afterward. Deming’s approach to quality emphasizes constant innovation, use of statistical methods, and commitment to training in the fundamentals of quality assurance. One outgrowth of Deming’s work was the emergence of total quality management, or TQM. Th is process makes quality principles part of the organization’s strategic objectives, applying them to all aspects of operations and striving to meet customers’ needs by doing things right the fi rst time. Most TQM approaches begin with an insistence that the total quality commitment applies to everyone in an organization, from resource acquisition and supply chain management, through production and into the distribution of fi nished goods and services, and ultimately to customer relationship management. The search for and commitment to quality is now tied to the emphasis modern management gives to the notion of continuous improvement—always looking for new ways to improve on current performance. 29 Th e goal is that one can never be satisfi ed; something always can and should be improved upon. Evidence-based management seeks hard facts about what really works. Looking back on the historical foundations of management, one thing that stands out is criticism by today’s scholars of the scientifi c rigor of some historical cornerstones, among them Taylor’s scientifi c management approach and the Hawthorne studies. The worry is that we may be too quick in accepting as factual the results of studies that are based on weak or even shoddy empirical evidence. And if the studies are fl awed, perhaps more care needs to be exercised when trying to apply their insights to improve management practices. Th is problem isn’t limited to the distant past. 30 A book by Jim Collins, Good to Great, achieved great acclaim and best-seller status for its depiction of highly successful organizations. But Collins’s methods and fi ndings have since been criticized by researchers. 32 And after problems appeared at many fi rms previously considered by him to be â€Å"great,† he wrote a follow-up book called How the Mighty Fall. 33 Th e point here is not to discredit what keen observers of management practice like Collins and others report. But it is meant to make you cautious and a bit skeptical when it comes to separating fads from facts and conjecture from informed insight. Today’s management scholars are trying to move beyond generalized impressions of excellence to understand more empirically the characteristics of high-performance organizations—ones that consistently achieve highperformance results while also creating high quality-of-work-life environments for their employees. Following this line of thinking, Jeff rey Pfeff er and Robert Sutton make the case for evidence-based management, or EBM. Th is is the process of making management decisions on â€Å"hard facts†Ã¢â‚¬â€that is, about what really works—rather than on â€Å"dangerous half-truths†Ã¢â‚¬â€things that sound good but lack empirical substantiation. Using data from a sample of some 1,000 fi rms, for example, Pfeff er and a colleague found that fi rms using a mix of well selected human resource management practices had more sales and higher profi ts per employee than those that didn’t. 35 Th ose practices included employment security, selective hiring, self-managed teams, high wages based on performance merit, training and skill development, minimal status diff erences, and shared information. Examples of other EBM fi ndings include challenging goals accepted by an employee are likely to result in high performance, and that unstructured employment interviews are unlikely to result in the best person being hired to fi ll a vacant position. 36 Scholars pursue a variety of solid empirical studies using proven scientifi c methods in many areas of management research. Some carve out new and innovative territories, while others build upon and extend knowledge that has come down through the history of management thought. By staying abreast of such

Abraham Van Helsing Essay Example for Free

Abraham Van Helsing Essay Innocence, chastity, purity, and married life are just a few things that made up the ‘image’ of the nineteenth century Victorian woman. During this time, it was greatly looked down upon if a woman chose to stay single, as she would be pitied and dubbed a â€Å"whore†. Lucy Westenra is one of the main characters in the novel, Dracula by Bram Stoker. Lucy is a beautiful young lady whose innocence and virtuous being draws three suitors to her. Although, this portrayed innocence is not the only thing that is drawing these men towards her. Lucy has a sexual appeal to her personality, much different than her best friend Mina Murray and the typical Victorian woman. This sense of sexual desire will eventually lead her right into the dangerous and evil arms of Count Dracula. The Count only has the ability to attack willing victims, which is why the sexually driven Victorian woman, Lucy Westenra is the first character to become victimized by Dracula’s deadly spell. Count Dracula was an evil, lustful vampire who wanted nothing but power and control. He lived in an Eastern European country called, Transylvania. The Count preyed on any individual who would make him feel in control and powerful of the situation. This is why Lucy Westenra was targeted and made Dracula’s first victim. The first peculiar account Lucy and Mina experience was when they see a Russian ship wrecked near the shore and hear that the there was no life aboard and the captain had died holding a crucifix in his hands. Soon after the account, Lucy started mysteriously sleep walking many night in a row into the grave yard near her home. One night, Mina had awoken the Rowatt 3 find Lucy missing and not in her bed, she then found her outside with a creature with beaming red eyes hunched over her. Mina tried to save her friend but by the time she got over there, the creature was gone. In the morning Mina had found strange dots on Lucy’s neck and after struggling for weeks Lucy became deathly sick and started to change before everyone’s eyes. Unknowingly, she was transforming into a super natural and dangerous form of herself while dead and lying in a cold grave. â€Å"Indeed, it is not only Lucy and Mina who are dramatically transformed in the draining, but Dracula himself, whose transformations are much more varied and complex than those of his victims.† (Pg. 238, Viragh) Count Dracula had stripped this woman of her innocence and virtue by changing her to an evil vampire just like him. Dracula now had control over Lucy but only because she was willing to let him control her. In the nineteenth century, straying away from who a woman is supposed to be according to the Roman Catholic Church is heresy. A woman was never to be with more than one man, but was to be married and completely faithful to her partner. This century was ruled by â€Å"the belief that an individuals sex and sexuality form the most basic core of their identity, potentiality, social/political standing, and freedom† (Pg. 1, Ridgway) Lucy Westenra had a completely different mindset as she expressed in a letter to her dear friend Mina. â€Å"Why can’t they let a girl marry three men, or as many as want her, and save all this trouble?† (Pg. 66, Stoker) After Lucy states these words in her letter, she immediately admits to her thoughts and actions being heresy. Just because she confessed Rowatt 4 to this sin against the church and her beliefs does not simply alleviate Lucy’s sexual desire. This difference between Lucy and other nineteenth century virtuous women was not just a phase of rebellion, it was psychological. Lucy is fully aware that she is desired by many men and she lets that get into her head, essentially she is feeding off the attention. This vulnerability and openness is why Lucy Westenra is Count Dracula’s first and easiest target. The first time the Count starts to get into Lucy’s head is after her and Mina see the wrecked boat upon shore, containing the containers of dirt. These were Dracula’s sleeping quarters. This fact was not known by the women at the time, but soon after this event is when Lucy starts to sleep walk. This sleep walking is not a coincidence but is psychologically connected to her sinful desires of lustfulness. Count Dracula only has the power the attack willing victims, which could only mean Lucy knew in her subconscious what she was doing by going out to the cemetery at nights. This spell Dracula puts on Lucy is the same spell he put on the three women who now life in Dracula Castle with him. These women were just as innocent and virtuous as Lucy was and are now sex crazed and evil just as the Count is. This â€Å"spell† was a way to undermine women so that Dracula would feel powerful and controlling over them. In essence, Lucy Westenra was a seemingly virtuous nineteenth century Victorian woman who actually had underlying sexual desires. These desires made Lucy vulnerable to Count Dracula, who was consumed with gaining control over his victims. Because of her lustful manor, Lucy was drawn to the attack of Dracula and fell under his deep spell. From then on there was no turning back. Works Cited Stoker, Bram. Dracula. 1897. New York: Oxford University Press, 1990. Viragh, Attila. Can The Vampire Speak? Dracula As Discourse On Cultural Extinction. English Literature In Transition, 1880-1920 56.2 (2013): 231-245. MLA International Bibliography. Web. 25 Sept. 2013. Ridgway, Stephan. â€Å"Victorian Sexuality† in â€Å"Sexuality and Modernity† originally written as a lecture for Sociology at Sydney University, 1996. Isis Creations. Web. 12 Nov. 2010.

Allogeneic MCSs to make Cartilage for Knee Function

Allogeneic MCSs to make Cartilage for Knee Function INTRODUCTION: 1.1 What is Osteoarthritis? Articular cartilage is a highly resilient hyaline tissue composed of chondrocytes and surrounded by extracellular matrix present in a joint which act as shock absorber, protects the bones from the friction and wear and helps in smooth movement of the joint (Bhumiratana et al. 2014). Osteoarthritis is a disease of joint where lack of cartilage causes musculoskeletal pain and restriction of the movement or disability of the joint for the patient. (Ahmed and Hincke, 2010) (Duthey, 2015). Reasons for cartilage damage are: The impact / blow caused during sport activities or accident Wear and tear because of overuse of a joint (Observed in elderly people) Lack of movement (Medical News Today, 2017) Figure No.1. Osteoarthritis Affected Region Image Source: www.osteoosteoOsteoarthritisresearchuk.org Osteoarthritis can affect any joint present in the body. As the knee-joint Osteoarthritis is the most common type of Osteoarthritis, in this report, we will discuss about knee-joint Osteoarthritis only. Tibiofemoral and patellofemoral are the two articular surfaces that the knee consists of. As it can be seen in the below image, the damaged cartilage, reduces the gap between joint and friction is generated between the bones which ultimately results in bone erosion and causes muscle pain or inflammation or restriction to the movement. Figure No.2. Osteoarthritis affected Knee Image Source: http://www.bupa.co.uk/health-information/directory/o/Osteoarthritis Osteoarthritis is estimated to affect 250 million people worldwide. Osteoarthritis sufferers include men and women, children and adults. And according to World Health Organization, 30% of men and women over the age of 65 have Osteoarthritis (Woolf and Pfleger, 2003). Worldwide, 9.6% of men and 18.0% of women over the age of 60 years have symptomatic Osteoarthritis. Approximately 80% of those with Osteoarthritis will have limitations in movement, and 25% cannot perform their major activities of daily life (Duthey, 2015). Figure No.3. Prevalence of Osteoarthritis of Knee Image Source: Burden of major musculoskeletal conditions, Bulletin of the WHO 2003 1.2 Treatments available for Osteoarthritis: There are various ways to cure Osteoarthritis when it is at the initial level, such as: Exercise and weight loss Bracing Medication Viscosupplementation Nutritional supplements (Duthey, 2015). But when it becomes incurable by exercise and medication, surgical operations must be performed. Surgical procedures include: Debridement i.e. Smoothening of the cartilage using surgical instruments Marrow Stimulation, a treatment which helps in regrowth of cartilage in the joint (but this process is less reliable) (Treatment Options for Osteoarthritis in the Knee, 2017). Mosaicplasty, a process where the cartilage from some other joint of body is used. But this process has size limitations (Medical News Today, 2017). Autologous Chondrocyte Implantation, a treatment in which a small part of no-load bearing cartilage is removed from the joint of the patient by Arthroscopy, regrown and multiplied in the laboratory and then implanted back in the body by a procedure called arthrotomy. (Cartilage Repair, 2017) (Ahmed and Hincke, 2010) (Duthey, 2015). Even though the Autologous Chondrocyte Implantation seems effective and easy, it has many disadvantages such as: The patients cartilage sample must be removed by a medical procedure, marked/tagged and treated separately just like blood sample. This treatment requires big Logistics and Supply Chain. It requires a lot of time (approximately 6 weeks) for cells to multiply. Hence, till then the patient will suffer from pain (Peretti et al. 2000). 1.3 Proposed Treatment for Osteoarthritis: All these problems can be solved by Allogeneic Human Mesenchymal Stem Cell. For autologous transplant donor and receiver are same, whereas for allogeneic transplant, the donor and the receiver are different. The selection of the donor must be done carefully cause if the tissue type, i.e. HLA (Human Leukocyte Antigens) doesnt match, the patients body will treat the transplanted organ or tissue as a foreign body. It might result in GVHD i.e. Graft Vs Host Disease. It is a fatal immune system response against stem cell transplant (Si et al. 2011). Selection of donor for allogeneic transplant: Syngeneic (i.e. Twins) It is the perfect HLA match, but very few people have a twin. HLA- matched relative (sibling) It is the second preferred option as HLA will be closely matched. HLA-matched unrelated donor, it can be possible to find a donor whose HLA matches to the patient. HLA-mismatched family member, even though the HLA doesnt match, it has great chance that patients body may accept it. Umbilical cord blood, stem cells retrieved during birth of the patient and preserved in a cell bank. It will be safest of all but stem cells must be available (Flomenberg et al. 2004). Hence, allogeneic implant will make sure that the patient wont have to undergo two medical procedures, as seen in autologous chondrocyte implantation. 1.4 What are HMSCs? HMSC means Human Mesenchymal Stem Cells. They are multipotent cells, which have the ability to transform into bone, muscle, fat or cartilage, etc. upon the proper simulation of providing environmental conditions in the laboratory. They have potential for regeneration (Si et al. 2011) (Li, LHeureux and Elisseeff, 2011) (Wei, 2013). Figure No.4. Potential of MSCs Image Source: http://www.medicalnewstoday.com/articles/241215.php Figure No.5. Mesenchymal Stem Cells Image Source: http://www.cytopeutics.com/IntroductionOfStemCells.html For knee restoration, cartilage cells are needed. Hence, the MSCs will be simulated for cartilage development. MSCs exists in almost all tissues. These cells can be easily obtained from bone marrow, adipose tissue, cord cells and molar cells, fetal liver, muscle, and lung (Ahmed and Hincke, 2014) (Si et al. 2011). 1.5 Product delivery to the Patient: For blood transfusion, the blood group and presence of Rh factor is checked and the matching blood is introduced into the body. Similarly, after checking the tissue (HLA) match, the best matching cells are chosen and regrown exponentially in the controlled environment of a laboratory. When the required number of cells, shape, and size is achieved, the cartilage is implanted into the patient via an open joint surgery named arthrotomy. This implanted cartilage will function exactly as that of the original cartilage. This cartilage will function properly for approximately 10 years (Ahmed and Hincke, 2010). 1.7 Functioning of the product in the patients body: Since, the HLA was matched, and the cartilage is manufactured using MSCs which has the same functional properties and characteristics that of the original cartilage, the function of the joint will return to normal. There wont be any complication after the treatment and that graft will be accepted by the body as a part of it, it wont be treated as a foreign body. MANUFACTURING FEASIBILITY REVIEW: 2.1 Current Manufacturing Technology and Scope for Future: Currently, the knee restoration is done via other surgical procedures. But because of those procedures have many limitations and they give only temporary relief, allogeneic Mesenchymal Stem Cell therapy will replace them in the coming time. Mesenchymal Stem Cell therapy is currently under development. Various tests are being performed on them in the laboratory (Ahmed and Hincke, 2010). First, the bone marrow or adipose tissue or cord sample is collected from the donor. Then the mesenchymal stem cells are separated out from other cells, such as fat or muscle by centrifugation or apheresis. These two density separation processes are feasible only for liquid. For the extraction from solid tissues, the slices of tissue are digested by the enzymes such as trypsin or collagenase. It breaks the bonding of cells i.e. the extracellular matrix (ECM) that holds the cells. Hence, the cell line is found (Li, LHeureux and Elisseeff, 2011). Then the cells are harvested. During the cell culture process, there are various parameters that need to be monitored, little inconsistency will result in subnormal product or it might be just a waste of product. Temperature, humidity, oxygen, pH level of the cell culture reagent, nutrient supply and waste removal are the physical parameters and cell count and cell viability are the biological parameters that need to be monitored (Schwamb, Puskeiler and Wiedemann, 2015). Once the desired number of cells is achieved, boundary for CMB (Condensed Mesenchymal Cell Bodies) is set. Then the cells are condensed to increase the seeding density as the cartilage requires higher seeding density. Then the fusion of the CMB happens. Now this fused CMB is pressurized against a porous decellularized bone matrix to create dense cellular region i.e. cartilage (Bhumiratana et al. 2014). As the knee joint is a mechanical tissue, physical stimulation is needed for its development. However, excessive stimulation can lead to cartilage damage (Ahmed and Hincke, 2010). Cartilage then sticks to the surface of that bone matrix and takes its shape while growing around it. Then it is removed from the bone matrix to implant into the knee joint of the patient (Bhumiratana et al. 2014). Figure No.6. Condensed Mesenchymal Cell Bodies Fusion Image Source: http://www.pnas.org/content/111/19/6940.abstract Currently, only culture plates and culture flasks are being used for allogeneic Mesenchymal Stem Cells as it is still in testing phase (Schwamb, Puskeiler, and Wiedemann, 2015). Figure No.7. Culture flasks and plates Image Source: https://www.shutterstock.com But monitoring all these parameters becomes very hard when using flasks and plates. And the cells need to be shifted into bigger containers frequently. Also, flasks and plates are not useful for mass production because of size limitation and economic consideration. Hence, a device named bioreactor can replace them and still perform all those tasks efficiently. Figure No.8. Bioreactor for mass Cell Culture Image Source: http://www.bioc.rice.edu/bios576/nih_bioreactor/NDL_Bioreactor%20Page.html It is a container which is feasible for both aerobic and anaerobic cell culture and can be used for suspended as well as immobilized cells (Sandhya Anand, 2017). It can be operated in batch, fed batch and continuous mode. As MSCs are surface anchorage dependent, the extra agitation or stirring might result in damage to the tissue. And the MSCs require oxygen to grow, so it will be an aerobic, immobilized, batch production bioreactor. (Martin, Wendt and Heberer, 2004) (Oragui, Nannaparaju and Khan, 2011). 2.2 Challenges in mass production of MSCs: Large scale in vitro expansion of MSCs is very complex because maintaining cells quality attributes such as identity, potency, purity and safety is extremely hard. It is hard to monitor that the cells are not undergoing any quality changes while expansion and harvesting. Another challenge is obtaining required no of cells and their recovery. MSCs are not suspension type, but anchorage dependent therefore the surface area for anchorage and proliferation must be taken into account. As allogeneic treatments are supposed to be for a lot of people, hence the required no of cells must be extremely large. There are 3 major and 3 minor types of HLAs in MHC Class I and 3 major and 2 minor types of HLAs in MHC Class II. So, there are lots of variants to manufacture and maintain for the cartilage manufacturer. 2.3 Clinical Demand for Dosage: Even though there are 250 million people suffering from Osteoarthritis and 3.6% of them are suffering from knee Osteoarthritis i.e. 9 million people. More than 600,000 knee replacements are performed each year in the United States alone (A Nation in Motion, 2017). In UK 160,000 knee replacement surgeries are performed every year (Joint replacement statistics, 2017). As the cartilage manufactured in the laboratory exhibit almost similar properties that to the natural cartilage, it is expected to last approximately 50-60 years (i.e. Average human life) if there are no unexpected tragedies. Hence, once treated properly, the patient wont have to worry about the joint in his life again. 2.4 Supply Chain for Product: Figure No.9. Formation of Master Cell Bank First the cell line is chosen for culturing, it can be a well-known cell line or a newly found cell line. After certain passages, when the desired number of cells is achieved, the Master Cell Bank will be established. In this case, many Master Cell Banks are needed as there are many types of tissues. Then one portion of master cell bank will be used for research purpose, i.e. the working cell bank and the rest will be cryopreserved for future use. Good manufacturing practice protocol should be followed during cell culturing. Figure No.10. Clinical Process for Cell Culturing The working cell bank will be used for manufacturing of cells for mass production after testing is performed. Several production runs (i.e. Passages) will be performed to obtain the required number of cells. Then the cells will be cryopreserved in central storage and distributed via local channels until there is a patient who needs them. 2.5 Risk Assessment: The main aim of risk assessment is to prevent transmission of diseases, and avoid harm to individuals and the environment. In many countries, the performance of risk assessment is a legal requirement. (University of Manitoba) Risk Impact Probability of Occurrence Mitigation Strategy Tissue/cell origin Rejection of Cells Low Thorough testing of cell line Lack of Donor History Transmission of Disease Low Choosing a donor carefully Mismatch of HLA Graft vs Host Disease Intermediate Careful matching of HLA Environmental Changes Change in cell Quality High Close monitoring of environmental conditions Plasma Derived Material Cell line contamination with unwanted cells High Proper filtration of MSCs (Herberts, Kwa and Hermsen, 2011) 2.6 Biosafety Measure: Depending upon the as the product is human derived, Biosafety Level 2 practices, equipment and facilities are chosen. It is most suitable for clinical, diagnostic and teaching purposes. Laboratory personnel must maintain hygiene while entering and exiting the lab. Decontaminated of potentially infectious material must be done before disposal, either by a disinfectant, or by autoclaving. Personal protective equipment is only required when there is a possibility of exposure to hazardous material. The laboratory must be isolated from the general building. Laboratory personnel must be trained in handling pathogenic agents. Access to the laboratory should be limited during the work. Certain procedures in which infectious aerosols or splashes may be created biological safety cabinets or other physical containment equipment should be used and the rest can be performedÂÂ   on the open bench. Biosafety level 2 is suitable for indigenous moderate-risk agents. This includes various microbes that cause mild disease to humans, or are difficult to contract via aerosol in a lab setting, human derived blood, body fluid, tissues, or primary cell lines (Inc, 2017). PROCESS MAP AND CELL GROWTH ANALYSIS: 3.1 Process Map: Figure No.11. Process Map for HMSC Therapy Process Description: Cell lines are created/chosen for each type of tissue (HLA). Shipping of the tissue sample to cell therapy processing facility. HMSC isolation and culturing in culture chambers (manual production using culture flask or culture plate) or bioreactor is performed. Fresh HMSCs are then tested for various parameters such as identity, potency, purity and safety, the modifications are done. Aliquoting of HMSC samples (i.e. Master Cell Bank) is done. Freezing and storage at -196 ÂÂ °C in Vapor Liquid Nitrogen (i.e. Cryopreservation) for future reference and use is done (Inc, 2017). Cells are thawed i.e. their temperature is brought up to normal room temperature and further increased to 37 ÂÂ °C (Normal Body Temperature) for best cell growth result (Inc, 2017). Cell characterization per release Criteria for Thawed HMSCs Expansion of thawed HMSCs using an incubator and/or bioreactor for production. Activation of HMSCs into final cell therapy product. Shipping of final product to medical treatment centre. Implantation of the cartilage into the patient by open joint surgery, i.e. arthrotomy (Harel, 2013). Cell Growth Analysis: As there are many types of tissues (HLA), testing for all of them must be performed and validated. Hence, the whole process will be repeated several times for each type of cells. Input Data: Desired seeding density= 1 million/ml Duration of Passage= 72 hours Doubling Time= 36 hours Efficiency= 80% (Average efficiency) Input Vial contains= 1.00E+09 cells Dose per Patient= 1.00E+09 cells =1 vial of dose Growth Rate= Ln (2) /Doubling Time= 0.019254 Seeding Density 1,000,000 Passage Duration 72 Doubling Time 36 Efficiency 0.8 Input Vial 1.00E+09 Growth Rate 0.019254 Phase 1 15 Patients Flask Dose Per Patient 1.00E+09 T25 MCB Creation Real SA Input Ideal SA Output Note T75 Thaw 1.00E+09 800.00 8.00E+08 All Flask of Same Size T175 Passage 1 700 6.40E+08 2560.00 2.56E+09 4*T175 T500 Passage 2 2500 2.05E+09 8192.00 8.19E+09 5*T500 T650 Passage 3 7800 6.55E+09 26214.40 2.62E+10 6*T1300 T1300 Passage 4 26000 2.10E+10 83886.08 8.39E+10 1*T26000 T3250 T6500 T26000 MCBs Created 21.51 Equivalent Vials 83.89 Cells Per 5-Layer flask 3.90E+09 Phase 1 Real SA Input Ideal SA Output Note Thaw 3.99E+09 3195.66 3.20E+09 Passage 1 3000 2.56E+09 10226.11 1.02E+10 6*T500 Passage 2 9100 8.18E+09 32723.56 3.27E+10 7*T1300 Dosages 3.27E+01 2.62E+01 For Phase 1 Testing 21 Master Cell Banks will be created in a 5-layer flask (T3250). It would be equivalent to the size of 83.89 input vials after 4 passages. From those 21 cell banks, 1 will be thawed and the rest will be cryopreserved. That 1 cell bank will be chosen as working cell bank and will be harvested for production. During Phase 1, treating 30 patients will be the target. Hence, 30 vials of doses should be manufactured during phase one. Every time 20% loss of cells is considered while changing the flask. And During passages, exponential growth will take place. Formula for Exponential Growth is: The Ideal surface area is calculated by: Flask size was kept uniform during every passage. And Actual Surface Area was always chosen less than Ideal Surface Area to maintain the desired density and environment. Flask of capacity 5-Layer was chosen for MCB creation. Calculations for MCB, Number of doses, After successful testing of phase 1, phase 2 will begin where 300 patients will be treated. So, 300 vials of cells will be required. PHASE 2 Real SA Input Ideal SA Output Note Thaw 3.99E+09 3195.66 3.20E+09 Passage 1 3000 2.56E+09 10226.11 1.02E+10 6*T500 Passage 2 9100 8.18E+09 32723.56 3.27E+10 7*T1300 Passage 3 32500 2.62E+10 104715.39 1.05E+11 5*T6500 Passage 4 104000 8.38E+10 335089.26 3.35E+11 4*T26000 Dosages 3.35E+02 For Phase 2 Testing After successful testing of phase 1 and phase 2, phase 3 will begin when mass production will start and 100s of 1000s of people will be treated with allogeneic HMSC derived cartilage. PHASE 3 Real SA Input Ideal SA Output Note Thaw 3.99E+09 3195.66 3.20E+09 Passage 1 3000 2.56E+09 10226.11 1.02E+10 6*T500 Passage 2 9100 8.18E+09 32723.56 3.27E+10 7*T1300 Passage 3 32500 2.62E+10 104715.39 1.05E+11 5*T6500 Passage 4 104000 8.38E+10 335089.26 3.35E+11 4*T26000 Passage 5 312000 2.68E+11 1072285.63 1.07E+12 12*T26000 Passage 6 1066000 8.58E+11 3431314.00 3.43E+12 41*T26000 Passage 7 3406000 2.75E+12 10980204.81 1.10E+13 131*T26000 Dosages 1.10E+04 For Phase 3 Since, there are 7 passages the process to manufacture 11000 vials will require approximately 25 (considered an extra time for changing flask) days. And at that rate 15 batches will be produced per year and approximately 165000 patients can be treated per year. As there are 6 types of tissues (HLA) total number of patients treated will be 990000 approximately. It will be equivalent to 11% of global demand. Using Bioreactor for Phase 3: Instead of using Culture flasks or plates, a bioreactor can be used for cell culturing. To check which of these two techniques will be more efficient, all the parameters are kept same. And total time of 7 passages will be considered as one passage time for bioreactor. Passage Duration 504 Doubling Time 36 PHASE

Innocence lost in John Boyne’s Boy in the Striped Pajamas :: John Boyne, Boy in the Striped Pajamas

The Boy in the Striped Pajamas is a fictional tale of the unlikeliest of friends: the son of a Nazi commandant and a Jewish concentration camp inmate. Written by John Boyne and published in 2006 by David Fickling Books, the story was made into a major motion picture in 2008. The novel, set in Nazi Germany, begins when nine-year-old Bruno and his family must move from their lovely home in Berlin to a new house in an unfamiliar place called "Out With." Tempted to explore his new environment, Bruno is told that there are certain places that are "Out Of Bounds At All Times And No Exceptions." Unable to fight his adventuresome spirit, however, Bruno ventures forth into the unknown one afternoon. Bruno comes upon a fence that he follows until he sees a young boy sitting on the other side of the fence. The shoeless boy is wearing striped pajamas and a cloth cap. Bruno also notices that the boy is wearing an armband with a star on it. Bruno makes fast friends with the boy, Shmuel, and they quickly discover that they share the same birthday. The boys discuss their families and where they are from. At the end of their first meeting, Bruno asks Shmuel why there are so many people on his side of the fence and what they are doing there. A few days later, Bruno's father has dinner guests; the man's name is "the Fury" and his date is called Eva. Bruno instantly dislikes the couple. Bruno's sister Gretel, whom he refers to as "the Hopeless Case," is smitten by the man and tries hard to impress him and his lady friend. Bruno, however, is disgusted by his sister's behavior and her budding romance with a young soldier. Much like Bruno hears "Auschwitz" as "Out With," he also incorrectly hears "the FÃ ¼hrer" as "the Fury." Boyner masterfully tells the story from Bruno's perspective; it is clear that the innocence of Bruno's childhood remains intact despite the fact that he is living on the periphery of a death camp and has met Adolf Hitler. Bruno continues to explore the woods near his house and often finds himself at the fence spending time with Shmuel. Bruno brings him food, and the friends lament the fact that they cannot explore together or play a game of football. Shmuel confides in Bruno that he is unable to find his father and he is worried.

The Continued Importance of Books Essay -- essays research papers

Many people don’t realize the potential of books. It is a highly emotional even when a serious book collector takes a well bound book of favorite content into his or her hands; it is as though they are holding and cherishing an invaluable and exquisite piece of art. Books have been an issue of many of religions and even militant factions and yet, they remain today providing us with places to go, an escape from reality, and higher knowledge. First and foremost, books are free voyages to anywhere in the world. You can open a book and with the flick of your eyes and the will of your imagination, be where ever the book takes you. If the book is about Ireland, then you can read about the country as though you were there and the only limitations as to how real it may be, is your own imaginatio...

International impact on Telephone Company :: essays research papers

International Internet Telephony has been evolving since its introduction in mid-1990s. With the Information Technology changing rapidly, different companies that work in telecommunications market are using various strategies to stay competitive. The main change has been noticed has been when more and more companies become IP carriers and multiple services providers whereas certain companies have refrained from any expansion into new infrastructure.   Ã‚  Ã‚  Ã‚  Ã‚  For a growing number of telecommuting workers, a cell phone, a PDA, and a high-speed laptop can be indispensable tools for earning an honest day’s pay. Thus telecommunication companies have to stay competitive in today’s tough market to survive. For example, AOL recently began to offer â€Å"AOL anywhere†, service that allows users to check their email, instant messages, news headlines, stock portfolios, and other key features any time and anywhere. Or there is another service that is available only for AOL members – it is AOL TV that allows its users to do those essential to the users everyday things with their TV. AOL has always been known for providing â€Å"the most convenient and easiest-to-use interactive service available,† and that is why AOL is one of the competitors for telephone companies such as Qwest or AT&T. (http://www.corp.aol.com/whoweare.html) AOL is also the only truly global interactive service provider, offer ing AOL services in 16 countries in 8 languages.   Ã‚  Ã‚  Ã‚  Ã‚  With the development of technology, customers’ demand is increasing as well. And Thus telephone companies are doing everything they can â€Å"to be on top† of the market. For instance, in 1999, Qwest Communications International, Inc. had an investment into Rhythms NetConnections Inc. for performance-class digital subscriber line (DSL) connectivity to addition that Rhythms has agreed to provide space to Qwest in their local facilities for collocation of call processing equipment and to use Qwest as its preferred web hosting provider. Rhythms provides high-speed networking solutions for remote access to private networks and the Internet. (http://www.qwest.com/about/media/pressroom/1,1720,162_archive,00.html?printVersion=1&xmlFilename=1999Apr07162&storyId=162) As Qwest’s competitor, â€Å"AT&T's continued financial strength helped underwrite growth and improvement, from the multi-billion-dollar digitalization of its entire network, through a sustained move into the international market and nearly 200 countries, to major mergers and acquisitions.† (http://www.att.com/history/history2.html) For example, in 1998, AT&T had invested over $70 billion in the company's future and redefining its services and products. In 1999, AT&T extended its reach through the local service businesses, broadband cable companies and wireless providers that were acquired in the past several years. â€Å"More than 75 percent of its capital investment went into growth businesses, up from 60 percent in 1998.

Why Are Teenagers Stressed?

Why Are Teenagers Stressed? BY Testators Can you trust everything you see or hear now-a-days? The media Is full of constant propaganda, propaganda which brainwashes the minds of young people. Children as young as 3 are already worrying about their appearances, as seen on the television shows such as ‘Toddlers and Tiaras. ‘ I believe the media has a much stronger impact on teenagers than any other age group. Everywhere you go, there will always be that â€Å"look,† that celebrities have and that every young person aspires to look like.Teenage girls will go to all extents in order to achieve the media's perception of a beautiful woman, when in fact few teenagers know that what they are seeing In magazines and on billboards are not In fact real humans, but they are what society has created. When parents think their children are safe at home, they are wrong. Young people's minds are being filled with poison which is also known as the perfect image.Shows such as ‘ Keeping up with the Sardinian,' Toddlers and Tiaras,' ‘America's next top model,' ‘Jersey Shore,' and '16 and Pregnant,' are giving teenagers the wrong idea that you must be ‘slim, fake, very award, and covered In make-up' to be considered anything near beautiful. Shows such as these are giving the Impression that you must be a specific way to be successful and/or notorious. This already creates large numbers of very unconcealed women, as they feel they are not ‘beautiful, ‘because they are not covered in make-up.These types of situations create stress for teenagers as they feel they must look a certain way to be deemed beautiful. When asked, 87% of British teenagers claimed to be unhappy with their physiques and 64% of those under 13 had already turned to tenting In order to lose weight as stated by In the Dally Mall Newspaper article. Many teenagers are pressured by their families Into doing well in their GASES_ This makes them feel like they must do well in order to keep their families happy. I can speak from personal experiences when I say that I felt even more pressured because I knew that my family were expecting good grades from me.This creates a large amount of stress for teenagers as they feel they must do well in order to make their families proud and In order to go to university to get a good job. It is said by the majority of the elder generation that going to university means that you will have a better future as you will get a good Job, which entails a larger salary as opposed to someone who did not attend university. This is not necessarily true as people who do not attend university can still manage to get a well-paid Job. Also, family members may expect their child to do a specific profession which the child themselves does not want to do.This means that the teenager Is pushed into schools which allow the best support in he subjects which will open pathways to these careers. This can also create higher levels as s tress as teenagers are being forced Into doing a subject they do not wish to do, which makes it more challenging to succeed, thus creating more stress. The teenagers which come from working class families, unfortunately, have it a lot harder than those that come from middle class or upper class families. A working class teenager may be pressured by their families to get a job as soon as possible in order to help out their living situation.This can create stress because distributing enough mime for school and work can not only be exasperating but It can also be difficult. At the case for those which come from working class families. Not only can teenagers be stressed from working, they can also be stressed as they are being put into a situation where money is a problem and they are constantly living under the threat that certain necessities may be cut off due to an outstanding bill payment or something as extreme as being kicked out the house. Society has a large impact on the amount of stress that a teenager has.By society I mean all things surrounding hem, media (as I previously discussed), friends, and the general public. Whether you want to admit it or not, everywhere you go, everything you do, you are always being judged, by everyone. Many people are aware of this whilst others aren't. The fact that we live in a country where everyone is Judged by the color of their skin, the way they present themselves and by their appearances makes it a more difficult place to fully be accepted. This applies stress to young people as they feel they need to be accepted in society by becoming something that they are now.The factor which disheartens me the most is that in society you are expected to be a specific way In order to be accepted and if you are anything other than ‘perfect,' you are looked upon as ‘morally wrong. ‘ Which leads me onto my next point, the general public (specifically the older generation) has generalized teenagers as being anti-so cial and rude when in fact only a minority of teens are actually this. By generalizing an age group based upon a few individuals can make it more challenging for the younger generation to speak their mind and have their voices heard.This also creates stress by making teenagers feel as if they are not important because of what they are depicted as. To sum up, teenagers have many reasons to feel like they have a build-up of stress, but I believe the two main factors are family and education as most of teenagers spend the majority of their time either in school and/or in the presence of their families. This means that they are constantly being told what to do, what to achieve and what is expected of them. Which makes life as a teen more difficult than it needs to be.