Analysis of Two Pictures by Dorothea Lange Essay Example for Free

Analysis of Two Pictures by Dorothea Lange EssayDorothea Lange is one of the Americas most renowned documentary photographers. Yet her works can non be considered as purely documental. Lnges ability to demonstrate the inner valet de chambre of her heroes and her masterful photographic techniques placed her works in the middle between photography and art. In this paper I will attempt to review and break up two Langes photographs gentle Erosion in California (Migrant bugger off) and Child and Her Mother. I am going to analyze them in terms of style, symbolism and influence on future Langes career and development of the art of photography. Human Erosion in California and Child and Her Mother are separated with the period of three years being make in 1936 and 1939 respectively. This was a time when Lange was about forty and her talent flourished reaching its highpoint. At that time she made her name as a accessible critic, as her matter of primary concern was the fate of poor a nd dispossessed quite a little . Human Erosion in California is probably her most famous check touching this theme. More broadly, Lange was interested in the plenty as they are and people in different situations.The Child and Her Mother is more a psychological than social work, or, better to say, a work on human psychology in a stagnating society. Here Lange could apply her experience she received working with Maynard Dixon and in the portrait studio to develop her own original style . The picture that subsequent became known as Human Erosion in California or Migrant Mother was originally made in California in 1936. This picture that became almost an iconic vision of the Great Depression depicts Florence Owens Thompson, a Cherokee muliebrity whose husband died in 1932 leaving her with five children and expecting the sixth child.Describing their meeting Lange wrote I did not ask her name or her history. She told me her age, that she was 32. She said that they had been living on frozen vegetables from the surrounding fields and birds that the children killed. She had just sold the tires from her car to buy food. Lange has made several(prenominal) pictures of the same model to find the best perspective. The most famous of the pictures she made demonstrates a prematurely aged woman sitting in a plurality with two underage children cuddling to their mother. The woman looks both tensed and tired.Her look can not be called desperate, she rather seems to be disappointed and desolated. A woman can not afford herself to become frustrated as she has to care of the babies. Despite of all her grieves she looks strong and decisive. This picture places a model in the sum while the details of the background are unimportant. Much later Thompson told that Langer promised her not to publish the picture and to send her a copy, yet she did neither. Officially the picture was made for the government and Lange never received royalties for it, but this work was a landmark tha t contributed greatly to her success.20 000 pounds of food arrived to the camp where the picture was made after event of the picture, but Thompson has not received any since she had already moved in search of work . Durden observes that many of Langes pictures focus on the expressive likely of the bodys gesture . This is true for the Migrant Mother, but this feature of Langes work can be most obviously illustrated by the Child and Her Mother. The picture was made in 1939 in the Yakima Valley near Washington. It is slight famous than the Migrant Mother, yet not less brilliant as it presents another aspect of Langes talent.Child and Her Mother is a socio-psychological work combining the view of a teenage frustration with social blunders. From the artistic point of view Lange used a different composition in this picture. In contrast to static Migrant Mother this photograph presents course and tensed rhythm. A child, who can also be perceived as a young girl downcasts her eyeball l inking against the wire fence while cautiously observed by her mother. Both stand on a sandy desert land burned by sun, but the mother attempts to cover her eyes while the daughter keeps them open.It appears that the girl is trying to escape the life that her mother has lived in order to overcome sadness and poverty . Langes work in the times of the Great Depression are not unique. Not less famous are, for example, works of Arthur Rothstein. Yet Lange is distinguished by her profound sympathetic intellectual not of the social phenomena, but of the people suffering from it. This is a kind of female view of the Great Depression as an event that revealed the hidden sides of peoples characters. For this reason Langes pictures would hardly be lost in the stream of her contemporaries works.Works Cited 1. Partridge, Elizabeth. Restless Spirit The Life and Work of Dorothea Lange. Puffin, 1991 2. Meltzer, Milton. Dorothea Lange A Photographers Life. Syracuse University Press 1st Syracuse Un iversity Press Ed edition, 2000 3. Durden, Mark. Dorothea Lange. Phaidon Press, 2006 4. Spirn, Anne Winston. Daring to Look Dorothea Langes Photographs and Reports from the Field. University Of Chicago Press, 2008 5. Maksel, Rebecca. Migrant Madonna. Smithsonian magazine, March 2002. http//www. smithsonianmag. com/arts-culture/Migrant_Madonna. html retrieved April 27, 2009.

Government Control and Subsidy of Energy vs. Private Sector Investment Essay Example for Free

Government Control and Subsidy of Energy vs. Private Sector Investment EssayA subsidy is a payment from the disposal to a business to encourage the continual use or development of a technology or product that is considered to be useful or beneficial to the society. Most often, the money (or subsidies) is coming directly from taxpayers. This is where Milton Friedmans signature phrase, theres no such thing as a free lunch comes in to play. A unit of a product or service may be free for one person, mortal or something is enduring an opportunity cost. Currently, renewable readiness sources such as wind and solar power are being subsidized by slightly $24 billion a year because of the perceived environmental benefits that go along with green technologies. However, renewable muscle companies such as Solyndra have bypast bankrupt and the government has supported them to keep them running via subsidies. The argument for continuing these subsidies is that wind and solar are still in the start-up phase in the industrial world and have not yet reached large scale marketplaces. Unfortunately, it is highly unlikely that these companies ordain ever be largely profitable because renewable energy, with a few exclusions, are unable to reach the profitable market margin that generating plants fueled by coal, natural gas or thermonuclear can.While the government tries to focus their support on said renewable energies, only providing limited tax breaks for the private oil companies, the US private sector has produced a substantive increase in oil. 2011 was the third consecutive year of higher domestic oil production and, at the same time, natural gas output reached an incomparable high. Over the past five years, about two thousand new jobs have been created in the oil and gas industry while employment development for renewable energies has been limited at best. With many of the recent failures of several renewable energy companies, employment has declined in this area during several periods. The renewable industry will also struggle to prosper because they rely too heavily on the government for support. The government has taken billions of dollars and will place it in this industry with unretentive to no return for the enrichment of the economy and society. Friedman makes a rather sarcastic comment on activities like this by saying, If you put the federal government in bear down on of the Sahara Desert, in 5 years thered be a shortage of sand. This is an example of rent-seeking.Rent-seeking is a term, used by economists, to describe actions that take in a political process of taking wealth of others and getting essentially a loss of wealth. Without the incentive to compete to raise and gain money, the renewable energy industry doesnt feel the need to produce more efficient and cost effective products or services. On the flip side of that, since most companies in the oil industry are in the private sector, the profit alone is a large enoug h incentive to supply valued goods and services at reasonable prices. If private sector companies do not continually improve or develop, they will quickly be weeded out. Since the private markets are unimpeachably competitive, they are continually searching for the sweet spot in the market that assures a large and readily available supply of energy and the cleanest yet operational balance of the usage of our limited resources, all at the lowest price possible.Despite the fact that for more than a decade, there has been a large bar direct taxpayer support, renewable energy still cannot meet the market demand and, therefore, the subsidies for these areas should be significantly reduced if not completely done away with. If politicians are truly concerned with cutting greenhouse gas emissions, a better allocation of federal spending would be to target subsidies and incentives towards natural gas and nuclear power plants. These clean-burning fuels can heat our homes, power our vehicle s, and generate electricity for Americas households and industries a lot more cheaply and reliably than renewable energy can. If America is not careful, it will quickly fall into crony capitalism.Crony capitalism, in layman terms, is where private businesses focus on doing political favors rather than the consumer market because the government uses spending, regulations, and subsidies to benefit businesses that provide political support. Instead of trying to pick winners and losers, the government should create a competitive marketplace with fair rules, no subsidies, and put up the private sector to prosper. One great aspect of America is the freedom to continuously change business strategies and marketing to adapt to change. Like Milton Friedman said, Many great deal want the government to protect the consumer. A much more urgent problem is to protect the consumer from the government.

Knowledge Of Nursing Watsons Theory Of Human Caring Nursing Essay

Knowledge Of Nursing Watsons Theory Of Human Caring Nursing EssayThe improvements in health sustenance system have placed a burden on the nurses workload and responsibilities. Along with this burden, nurses have often disregarded their caring attitude when faced with onerous situations. Jean Watson, famous for her Theory of Human Caring, wants the nurses to learn to cope with the complexities arising in every circumstance and to find ways of preserving their caring practice. The aims of this paper are the quest to utilize the synthesized literature regarding Jean Watsons conjecture in order to evaluate its relevance to my personal experience. To utilize the theory to guide client-centered care and provide its implications to my upcoming care for practice.Literature ReviewJean Watson views caring as the most valuable attribute nursing has to offer to humanity, yet caring has received little emphasis than other aspects of nursing over time (Watson, 2006). She believes that the d isease might be cured but illness would still remain because without caring, health is not fully attained (Watson, 2006). Caring is the essence of nursing and it connotes responsiveness between the nurse and the uncomplaining (Watson, 2006). The ten carative factors, transpersonal caring relationship and the caring occasion institute the elements of the Theory of Human Caring (Watson, 2006). In a study done by Ryan (2005) states that the nurses who were involved in her research have all agreed that they espouse and enact the caring theory in their everyday practice despite the obstacles that envelops them. The common theme found in the articles and was also emphasized in the theory are the use of effective communication and the nurses caring moments spent with the patients (Watson, 2006). Watson defined caring moments contact between patient and the nurse and the impact of the nurse to the patient that can produce a threatening or secure environment (Watson, 2006). Clarke (2009) also believes that these moments transform both the patient and nurse and binds them together. However, Hau (2004) opposed this by stating that the tone time spent in practicing holistic care is often unnecessary and unappreciated by other patients. She further stated that accurate nursing assessments, fitting technical skills and abundance of medical resources are the main factors that facilitate the patients speedy treatment and discharge (Hau, 2004). However, Christiaens, Abegglen Rowley (2008) believes that it is a fact that a number of physical symptoms grow from mental/emotional/ uncanny problems and improvements in quality of life are gained from it is through an effective holistic, client-foc utilize caring that will improve their quality of life. To further validate this belief, a comprehensive meta-analysis of 130 studies done conducted by Kristine Swanson (1999) reported that patients who received an effective holistic care have improved emotional-spiritual nearly b eing, decrease infirmary costs, and an increase in trust relationships as opposed to those who did not receive quality holistic care who experienced decreased healing, vulnerability and lingering mediocre memories.Critical AnalysisBased on the literature gathered, Sharon, the nurse who was a part of my personal experience demonstrated an exceptional application of Jean Watsons theory in her practice. According to Watson, health cannot be fully attained without caring and my experience was an example of an excellent holistic care in combination with suitable technical nursing skills. Sharon attended to my post-operative state by providing me her presence and prompt responses to my non-verbal cues. Sharons caring impact made a huge difference to my emotional well being which resulted to an overall positive impression during my hospital stay. I felt empowered despite my non-verbal condition because I knew my concerns were being responded to and I felt secured season I was under her care. Watson believes that the theory of caring is an endorsement of professional nursing identity and what Sharon demonstrated throughout my care is what embodies the nursing profession. The theory could be used not only by nurses that are working in a hospital setting but also in places faced with oppression, natural disasters, pauperisation and in dependableice. Watsons theory emphasizes the humanistic aspects of nursing in combination with scientific knowledge, so it can be also applied in research by decision ways on how to deliver nursing care efficiently and in means that is acceptable to the patient. It guides the nurse to go beyond the application of technical nursing skills and show more concern towards the subjective and deeper meaning of the patient towards his/her health situation. Integration of the theory in my future nursing practice will advocate in managing my priorities in order to spend uninterrupted time with my patients and pay attention to their fears or con cerns regarding their care. It will aid in removing my biases and accepting the patient as unique individual regardless of their physical appearance, socioeconomic status, emotional needs or level of compliance. Lastly, it will remind me that every patient needs my imperious support, positivity and encouragement to facilitate a faster recovery of not only the physical aspect of their stay but also the emotional/spiritual as it is a factor that will improve their quality of life.ConclusionThe Theory of Human Caring can give language to what was before just thoughts and ideas regarding nursing. It guides nurses so that they can see, learn and express their own unique role in health care. Moreover, this theory shall bring the nurses to a realization that we need to elapse ourselves from a state that views nursing not as a job, but as a gratifying profession-a life-giving, life-receiving career for a lifetime of growth and learning.

MGMT Methylation Status and Glioblastoma Multiforme Outcome

MGMT Methylation Status and Glioblastoma Multiforme OutcomeABSTRACTBackground O6 methylguanine-methyltransferase (MGMT) booster station methylation has been associated with increase option among patients with glioblastoma multiforme (GBM) who were treated with various alkylating agents. We examined the relationship in the midst of MGMT methylation status and clinical outcome in freshly diagnosed GBM patients treated with BCNU wafers (Gliadel).Methods MGMT promoter methylation in desoxyribonucleic acid from 122 newly diagnosed GBM patients treated with Gliadel was determined by a Quantitative methylation-specific polymerase chain reaction assay (QMSP) and correlated with overall excerpt (OS) and comeback-free survival (RFS).Results The MGMT promoter was methylated in 40 (32.7%) of 122 patients. Overall median survival was 13.5 months (95%CI 11.0-14.5) and recurrence-free survival (RFS) was 9.4 months (95%CI 7.8-10.2). After adjusting for age, KPS, extent of resection, temozolom ide (TMZ) and radiation therapy (RT), newly diagnosed GBM patients with MGMT methylation who were treated with Gliadel had a 15% decrement in hazard of death compared to patients with unmethylated MGMT (Hazard ratio 0.85, 95%CI 0.56-1.31). Patients aged over 70 with MGMT methylation and treated with Gliadel had a significantly longer median survival of 13.5 months compared to 7.6 months in patients with unmethylated MGMT (p=0.027). A similar significant difference was excessively plunge in senior(a) patients with a median recurrence-free survival of 13.1 versus 7.6 months (p=0.01) for MGMT methylated and unmethylated, respectively.Conclusions Methylation of the MGMT promoter in newly diagnosed GBM patients who were treated with Gliadel followed by RT and TMZ, was associated with significantly improved survival compared to the non-methylated patient population with similar treatment. For the elderly population, methylation of the MGMT promoter was associated with significantly be tter OS and RFS. worldGlioblastome multiforme (GBM) is the most common primary brain neoplasm, with a median survival of less than two days 1. To age, only two different alkylating agents have been guiden to be consistently associated with prolonged survival temozolomide (TMZ) and the locally delivered BCNU wafers (Gliadel) 1-3.Gliadel wafers (Eisai Inc. for Arbor Pharmaceuticals, LLC) are implanted and locally deliver Carmustine (also know as (1,3-bis(2-chloroethyl)-1- nitrosourea (BCNU)) at the site of tumor resection, allowing for a higher concentration of local chemotherapeutic doses while minimizing systemic adverse effects 2-4. These wafers provide a controlled- release form of local chemotherapy for approximately 3 weeks 4, 5.Methylation of the MGMT promoter in gliomas was found to be an important predictor of the tumor responsiveness after several(prenominal) cytotoxic regimens 6, including BCNU treatment 7. It was found that expression of the desoxyribonucleic acid repa ir protein, O6 methylguanine-methyltransferase (MGMT), results in GBM resistance to alkylating agents. Alkylating agents cause cell death by binding to desoxyribonucleic acid, most commonly to the O6 position of guanine, and forms cross-links surrounded by adjacent desoxyribonucleic acid strands. This cross-linking of ikon strand DNA is inhibited by the cellular DNA-repair protein MGMT.In this study, through a unique analysis of 122 patients with newly diagnosed GBM who were treated with Gliadel, we retrospectively examined the association between MGMT promoter methylation status and survival.METHODSPatients and Tumor SpecimensWe retrospectively reviewed 185 patients with newly diagnosed GBM who received Gliadel after tumor resection, at Johns Hopkins Hospital in Baltimore, USA, between July 1997 and December cc6. Of these patients, only 122 patients had stored samples that were addressable for MGMT analysis. The clinical, radiological and hospital course of these patients were retrospectively reviewed. Age and gender were recorded, as well as Karnofsky performance score (KPS) at sequence of diagnosing, tumor location, time to recurrence and dates of death were recorded. Overall survival (OS) was calculated from the time of surgery to death, and recurrence free survival (RFS) was calculated from the time of surgery to time of recurrence or censored at the last time of follow-up. GBM was histologically confirmed in all cases. Extent of surgical resection was determined based on a postoperative MRI performed Treatment AlgorithmGliadel wafers were typically not implanted in patients after tumor resection when the tumor largely extended into the ventricles or was multifocal.DNA ExtractionAfter initial patient de-identification, all original histologic slides from the GBM specimens were reviewed to reconfirm the diagnosis of GBM by a senior neuropathologist (PB). A representative forget with tumor was retrieved for DNA extraction. Histologic slides from the f ormalin-fixed, paraffin- insert tissue were obtained. wholeness representative slide was stained with HE and the tumor was marked by the senior neuropathologist (PB). An additional atomic number 23 correlating unstained 10 micron slides were also obtained. The tumor cells in the unstained slides were microdissected according to the marked HE stained reference slide. DNA was extracted from paraffin embedded tissue after xylene deparaffinization. The microdissected tissue was digested with 1% sodium dodecyl sulfate (SDS) and 200ug/mL proteinase K (Roche, Nutley, NJ) at 48C for 48 hours, followed by phenol/chloroform extraction and ethanol precipitation of DNA. Extracted DNA was dissolved in either LoTE (2.5 mM EDTA, 10 mM TrisHCl pH 8) or distilled water.Bisulfite TreatmentExtracted DNA was subjected to bisulfite treatment, to convert unmethylated cytosine residues to uracil residues. Briefly, 2 g genomic DNA from each sample was treated with bisulfite exploitation the EpiTect Bisu lfite kit (Qiagen, Valencia, CA) according to the manufacturers instructions. converted DNA was stored at -80oC.Methylation compendiumBisulfite-modified DNA was used as a template for fluorescence-based real-time PCR. Amplification reactions were carried out in triplicate in a final volume of 20 L that contained 3 L bisulfite-modified DNA 600 nmol/L concentrations of forward and reverse primers 200 nmol/L probe 0.6 units platinum Taq polymerase (Invitrogen) 200 mol/L concentrations each of dATP, dCTP, dGTP, and dTTP and 6.7 mmol/L MgCl2. Primers and probes were designed to specifically amplify the promoter of MGMT and the promoter of a reference gene, ACTIN B primer and probe sequences and tempering temperatures are provided in Table 1. Amplifications were carried out using the following profile 95C for 3 min followed by 50 cycles at 95C for 15 s and 60C for 1 min. Amplification reactions were carried out in 384-well plates in a 7900 sequence detector (Perkin-Elmer Applied Biosyst ems) and study by a sequence detector system (SDS 2.2.1 Applied Biosystems). Each plate included patient DNA samples, positive controls (Bisulfite-converted Universal Methylated merciful DNAStandards (Zymo Research) in serial dilutions 20ng to 2pg) and molecular grade water was used as a non-template control. The -actin gene was used to normalize and act as an internal load up control. The methylation ratio was the ratio of values for the gene-specific PCR products to those of the ACTIN B and then multiplied by 1,000 for more efficient tabulation.Statistical MethodsThe overall survival (OS) time was defined from the date of initial diagnosis of the disease (surgery) to the time of death or censored at the time last known alive. The recurrence-free survival (RFS) was counted from the date of initial diagnosis of the disease to the time of disease recurrence or censored at the time last known alive and recurrence-free. Probabilities of OS and RFS were reckond using the Kaplan-Meie r (KM) method 15 and compared using Log-rank test. Confidence intervals were calculated using the method of Brookmeyer and Crowley14. Cox proportional hazards model 16 was used to estimate the association between OS or RFS and MGMT methylation status, treatments and well known indication factors. Schoenfeld residuals were used to test the proportionality of factors in Cox proportional hazards models. Radiation status was treated as a stratification factor in the Cox regression model. TMZ has FDA approval for newly diagnosed GBM patients aged between 18-70. Subgroup analyses were performed for patients who were aged over 70. All p values were two-sided. All analyses were performed using the Statistical Analysis System, version 9.2. MGMT was considered as promoter methylated if the methylation ratio was higher than 8, and unmethylated if below 8.RESULTSPatient PopulationSix hundred patients with newly diagnosed GBM underwent craniotomy between 1997 and 2006, at the Johns Hopkins Hosp ital. One hundred eighty five patients received Gliadel (30.8%) after tumor resection. Methylation specific PCR was performed in 122 of the 185 patients (66%) because 63 patients did not have sufficient paraffin embedded tumor tissue for MGMT analysis. The characteristics of the patients and type of treatments are shown in Table 2. The clinical course of forty patients who had methylation of MGMT promoter was compared to 82 patients without promoter methylation of MGMT. The similarity of distri unlessions among patients characteristics, and treatments between MGMT methylated and unmethylated is also shown in Table 2. in that location was a slightly male predominance in both groups. The median age of the MGMT methylated group was 65.5 years compared to 60.5 years in the non-MGMT methylated group (p=0.59). closely of the patients in both groups had KPS score of 80 (p=0.67). Most of the patients in both groups underwent gross total resection (GTR) (85% vs. 74% in the methylated and non-MGMT methylated group, respectively), (p=0.19).Most of the patients in the MGMT methylated and non-MGMT methylated groups received post-operative radiation therapy (RT) (80% and 72% respectively). However, on that point were 31 patients (25%) without radiation treatment recorded in their medical chart. Only 33% and 29% of MGMT methylated and non-MGMT patients, respectively, were treated with TMZ due to majority of patients was treated prior to 2005 when RT+ TMZ became the stadnadrd of charge for the newly diagnosed GBM patients.Overall SurvivalThe Kaplan-Meier estimate of the median OS for the122 patients with newly diagnosed GBM was 13.5 months (95% CI 11.0, 14.5). Median OS for those with MGMT methylation was 13.9 months (95%CI 9.5, 17.1) compared to 12.9 months (95%CI 10.9, 14.5) (p= 0.86) in patients non methylated. Univariate and multivariate association of survival with treatment factor, baseline prognostic factors, and MGMT methylation status are shown in Table 3. There was a 15% reduction in hazard of death (Hazard ratio 0.85, 95%CI 0.56-1.31) for patients with MGMT methylated tumor compared to those with MGMT unmethylated tumor after adjusting for age, KPS, extent of resection, TMZ and RT. A subgroup analysis was performed among 35 patients who were 18-70 years old and treated with Gliadel, RT and TMZ ( Gliadel+ Stupps regimen) 1. The median OS was 19.8 months (95% CI, 14.5, 22.2) in this subset of patients. There was no statistically significant difference in OS among these 35 patients with MGMT promoter methylation (median OS20 months,95% CI 9.2, 37.0), compared to patients without MGMT promoter methylation (median OS 18.9 months, 95% CI 11.9, 22.2), (Table 4).Only two out of 30 elderly patients aged above 70 years were treated with TMZ, one was MGMT methylated and another was not. Among these elderly patients, those with MGMT promoter methylation showed a significantly longer median survival of 13.5 months (95% CI, 0.49, 17.1) compared to 7.6 months (95% CI, 2.9, 9.4) when the MGMT promoter was non-methylated (p=0.027). A similar significant difference in median recurrence-free survival was also found in elderly patients where the median survival was 13.1 versus 7.6 months (p=0.01) for MGMT methylated and unmethylated, respectively.The overall median recurrence-free survival was 9.4 months (95%CI 7.8-10.2) for all patients. There was no difference in RFS between patients 18-70 years old with and without MGMT methylation.DISCUSSIONIn this study we investigated the significance of MGMT methylation status in a series of 122 patients with newly diagnosed GBM who underwent surgical resection and implantation of Gliadel wafers. The results of our series show a reduction in hazard of death for patients who were MGMT methylated compared to non-methylated. Interestingly, this effect was much more profound in the elderly group of 35 patients who were older than 70 years old when they were diagnosed with GBM. Elderly patients who were MGMT methylated had significantly better OS, compared to non-methylated (13.5 vs. 7.6 months respectively, p=0.027).The methylation of the MGMT promoter region leads to a reduced ability to repair DNA damage induced by alkylating chemotherapeutic agents 7. Methylation of the MGMT promoter was found to be associated with responsiveness to alkylating chemotherapeutic agents such as temozolomide 6 and BCNU 7, and an increase in OS and feeler free survival. The median survival of patients who received the combination of Gliadel, temozolomide and radiation therapy in our age group ranged between 18.9 to 20 months, six months greater than that for the radiation therapy and temozolomide historic cohort 1 (Figure1). For patients younger than 70 years old, the median survival of the MGMT methylated sub-group was slightly greater that MGMT non-methylated.KPS in a known prognostic factor for patients with brain tumors 8. Most of the patients in our study cohort had poor KPS of less than 80. Still, our results were in line with the report of Lechapt-Zalcman et al. 9 who assessed the prognostic impact of MGMT promoter methylation in patients with newly diagnosed GBM that received Gliadel in addition to radiation therapy and temozolomide. The OS of their study cohort was 17.5 months. Patients with MGMT methylation had a significantly longer OS of 21.7 months compared with patients without MGMT methylation who had OS of 15.1 months.Two recent phase III clinical trials in the elderly age of patients with malignant astrocytoma, the NOA-08 10 and Nordic trials 11, demonstrated that temozolomide therapy alone was not inferior to radiotherapy alone, and methylation of the MGMT gene promoter was associated with a benefit from temozolomide. However, there is a concern that combination therapy of radiation therapy and temozolomide may be less active and less well tolerated in the elderly population 12. European organisation for Research and Treatment of Cancer (EORTC)-26981/ National Cancer Institute of Canada (NCIC) CE3 trial have suggested that with increasing age, the relative benefit of addition of temozolomide to radiotherapy decreases and the patients suffer from increased chemotherapy-associated side effect such as neutropenia, lymphocytopenia, thrombocytopenia , raised liver-enzyme concentrations infections and thromboembolic events. As opposed to systemic chemotherapy with its limitations, local delivery of Gliadel wafers may be promising in this subset of patients. Chaichana et al. compared 45 elderly patients who were treated with Gliadel to 88 elderly patients who did not receive Gliadel 13. The survival for older patients who received Gliadel was significantly longer than for patients who did not receive Gliadel (8.7 months vs. 5.5 months respectively, p=0.007). The median survival of MGMT methylated in elderly patients in the current cohort was doubled. These results may support the use of Gliadel in this sub-population.LimitationsThere ar e several limitations to this study. Its retrospective nature carries a potential bias. Moreover, the time period of this study ended in 2006, only one year after temozolomide became the standard of care in the treatment of GBM, thus most of the patients were not treated with the combination of temozolomide and radiation therapy. Furthermore, because this is a tertiary referral center, there is a bulk of patients who were operated in this center, but received further neuro-oncology treatments elsewhere, near their home, and therefore, their complementary oncology treatment is not available. Still, this large and unique cohort of patients with newly diagnosed GBM who were operated in one tertiary center provide novel data that may assist in optimizing and personalizing the treatment for GBM patients.

The Manufacturing Of DNA Vaccines

The Manufacturing Of deoxyribonucleic acid VaccinesA detailed externalise and layout of the set for the manufacturing of desoxyribonucleic acid vaccines was developed. The factors foremost in the endeavor and layout of the desoxyribonucleic acid vaccines forwardness were compliance to current exhaustively manufacturing practices (cGMP), restrictive guidelines, health, pencil eraser and surround, effective take, optimum material and effect flow, effective dissipatedliness, minimisation of contamination and enhance maintenance. The total office ara is 108m X 91m (9828m2) and plant/ output signal atomic number 18a is 32m X 20m (640m2) with space for early expansion. To reduce the impact of airborne particles, congener humidity, pressure and temperature on the rightness, efficacy, and recourse deoxyribonucleic acid vaccines product, a containment/clean inhabits of class 100 was founding with cookled-air environment with access via airlock, HVAC and high efficiency p articulate air (HEPA) filters. In order to conform and adopt to current pricy manufacturing practices (cGMP) and regulations, the following key theatrical role of cGMP were incorporated into the design, organization master plan (VMP), standard operating procedures (SOPs), appropriate timber control (QC), cleaning-in-place (CIP), sterilisation-in-place (SIP), expert personnel, documentation, health, prophylactic and environment, utilities required and neutralize treatment demonstrate. The entire barf timeline was estimated with the aid of Gantt chart project way proficiency to be a year and 4.5 months with savoir-faire to literatures on similar projects.1.1 IntroductionThe demand for DNA vaccines for gene therapy, vaccination and for the treatment of diseases such as cancer, malaria, swine flu, HIV, melanoma, and so on is on the increase (Prather et al., 2003 Williams et al., 2009). This is beca do DNA vaccines triggers cellular and humoral immune responses, safe and st able (Prather et al., 2003). on that pointfore, there is need to design manufacturing quick-wittedness for DNA vaccines production to meet the rising demand. However, the design, operations and layout of the manufacturing speediness must conform and comply to standards, stipulations and guidelines stipulated by regulatory authorities such as the U.S. Food and Drug Administration (FDA), Medicines and Healthc be products Regulatory Agency (MHRA), European Medicines rating Agency (EMEA), World Health Organisation (WHO) and the regulation of the country in which the facility is to be constructed. In addition to meeting this regulations and guidelines the DNA vaccines production process, design and premises of its manufacture must conform to swell design practices (GDP) and current good manufacturing practices (cGMP) (Shamlou, 2003 Przybylowski et al., 2007).The commercialised weighing machine production of DNA vaccines is justified by economics/cost, health, safety and environm ent, compliance to legal standards and production at a lower place Good Manufacturing Practices (GMP) (Shamlou, 2003). This is to master that manufacturing processes are controlled and performed according to design specifications and practicable procedures in order to ensure that musical note is built into the product (DNA vaccines) to mark safety, efficacy, purity and identity legitimately (Przybylowski et al., 2007). In addition, GMP requirements are open ended, however the International Society of Pharmaceutical Engineers (ISPE) has enumerated the principal step to current GMP which let in standard operational procedures (SOPs), qualification and validation of process performance, design, graphic symbol control testing, adequate process control, sterilization in place (SIP), cleaning in place (CIP), layout design, quality management, documentation and audit of facility as necessary to ensuring specification and maintenance of product identity and compliance to regulations (WHO, FDA, MHRA, etc.) and current good manufacturing practices (cGMP) (Day, 2004).The issue of location for the manufacturing facility is crucial to its profitability as it is influenced by newfangled material supply, transportation, utilities, environmental impact, waste disposal, local comm building blocky considerations, personnel, climate, plant size of it and availability of land (Sinnott, 2005). Moreover, before the design and inst each(prenominal)ation of a new facility for pharmaceutical and biopharmaceutical product manufacture, an environmental impact assessment (EIA) is perform and sanctioned (Davda, 2004). Hitherto, the design of any manufacturing facility must integrate the design of a treatment process and safe disposal of the waste generated to specified legal standards by regulatory authorities and ward off/minimise harm to health and safety of personnel, environment and product contamination. The manufacturing facility layout must be designed to aid good raw material flow, waste flow and personnel flow virtually the factory to reduce risk, cross contamination and ensure that production activities and factory operations are performed smoothly and follow a defined procedure. The pharmaceutical manufacturing process must be conducted in clean environment and clean rooms in which the temperature, pressure, air borne particles and sexual relation humidity are controlled to specified conditions by regulators (U.S. FDA, WHO, ISO, MHRA, etc). All these are the component of current Good Manufacturing Practices (cGMP) to build quality assurance, consistency and safety of therapeutic product (DNA vaccines) to human life (Signore and Terry, 2008). The entire operations and activity should be performed by trained and competent personnel and quality management for a satisfactory quality assurance (QA/QC).1.2 Aims and objectives1. The defined goal of this project is to develop a detailed design and layout of a manufacturing facility for the productio n of DNA vaccines for commercial scale, applying current Good Manufacturing Practices (cGMP) and in compliance to regulatory guideline (FDA, FDA, MHRA, WHO, etc.).2. Provide detail methods for qualification and validation of the design and layout, performance, quality control and enumerate the personnel/staff involved in the project.3. Estimate the timeline of the project.2.1 Process overviewDNA vaccines production mainly starts on a bench scale through pilot scale to large scale production (Ferreira et al., 2000 Bequette et al., 2004). The design of a large scale facility for the manufacturing of DNA vaccines involves the selection of suitable plasmid DNA DNA constructs/vectors (ColE1-type vectors, pUC vectors, pBR322 plasmid vector, etc.) that go away replicate at high copy numbers, the production microorganism cell bank (Escherichia Coli), subsequently followed by fermentation process in the bioreactor under optimum conditions and control media (temperature, pH, pressure, etc. ) to maximise cell growth, cell lysis to break the cells to release the DNA, isolation by precipitation of genomic DNA, cell debris, proteins and RNA, purification by anion exchange chromatographic technique because DNA is negatively charged, formulation and blending, unproductive filling, packaging and storage in the fridge (Ferreira et al., 2000 Prather et al., 2003 Przybylowski et al., 2007).2.2 Design of flowsheetThe conceptual design of the process flowsheet for DNA vaccines production under cGMP was based on the knowledge of the process block diagram in Fig.1 above and the performance of the associated unit operations. The process flowsheet shown in Fig.2 is interconnection of the various unit operations, fermentation, the downstream processing (cell lysis, precipitation, clarification and concentration, primary purification (anion-exchange chromatography) and secondary purification (size exclusion chromatography)) and blending and formulation of the bulk product into usable form (Prazeres and Ferreira, 2004). some(prenominal)ly pieces of equipment in the process flow sheet are designed to conform and comply with standard and code of practice of either International Organisation for normalisation (ISO), British Standard Institution (BSI), American Petroleum Institute (API), American Society for Testing Materials (ASTM), American National Standard Institution (ANSI), etc. to ensure safety, selection of suitable material of construction, and to a fault equipment manufacturers work to produce facilities according to standardized design and size (Sinnott, 2005). Also individually pieces of equipment are hygienically designed with good polished surfaces and piping for easy CIP and SIP, elimination of dead zones and sharp edges to avoid microbial growth and contamination and constructed with stainless steel material to eliminate contamination. The final product DNA vaccines are sterilely filled into vials and stored at -20oC in the freezer (Przybylowski e t al., 2007).3.1 Site layout designThe site layout was designed to prevent product contamination, environmental pollution and to safeguard the health and safety of personnel. The various unit operations shown on the process flowsheet in Fig.2 and the ancillary buildings required to support the manufacturing facility for DNA vaccine production are laid out to give an economical flow of raw materials to final product storage, flow of personnel and waste around the production site to conform to good manufacturing practice (GMP), reduce risk and product contamination (Sinnott, 2005 Signore and Terry, 2008). The site layout design in Fig.3 was done with consideration to future expansion of the DNA production. Clean rooms, waste treatment area, hazardous process and raw materials were isolated and arranged for safety of product, personnel and environment. The size of the site is 108m X 91m (9828m2) as shown in Fig.3 and the ancillary buildings and support services required for the manufac turing facility areStorages for raw materials and DNA vaccines.Quality control laboratory.Maintenance workshops and warehouse.Utilities steam, compressed air, bureau generation, refrigeration, water (WFI), CO2, N2 etc.Cleaning-in-place (CIP) and Sterilisation-in-place (SIP).Effluent treatment and disposal plant.Process control roomAdministrative officesFire stations and other emergency services creature comforts required include roads and car parks, first aid centre, canteen, security, rest room, changing room, training room and visitors centre.3.2 Facility layout designThe detailed design and layout of the DNA vaccines production rooms and equipment is designed to minimise risk, reduce cross contamination, permit effective cleaning and sterilisation of external and internal surfaces of process equipment by the use of clean in place (CIP) and sterilisation in place (SIP), enhance maintenance and control of clean rooms temperature, pressure and relative humidity (RH) under standard operating procedures (SOPs) (Przybylowski et al., 2007). The facility layout design also considered the cleanrooms, equipment and the flow of materials and personnel as key factors that impact on manufacturing cost, operational procedures and productivity (Drira et al., 2007). The DNA vaccines manufacturing facility layout design is 32m X 20m (640m2) in size as shown in Fig.4 to ensure efficiency and safety of the production environment and manufacturing process which are dependent on the layout of the facility (Jacobson et al., 2002).3.2.1 Cleanrooms/containment designOne of the principles of GMP is cleanliness and aseptic operations to prevent product contamination by microorganisms, particulate generated during plant operations and changes in room conditions (temperature, relative humidity, etc.). Therefore, DNA vaccines which are biological drugs are manufactured in clean rooms, that is, a room in which the air quality (airborne particles), the temperature, the pressure and rela tive humidity are controlled to prevent contamination by impurities, dust and microorganisms in the atmosphere and in the ambient air, in order to protect its purity, efficacy and safety (Sutherland, 2008). The layout and design of the production rooms was according to the International Standards Organisation (ISO) 14644-1 cleanrooms classification shown in Table 2 below. The raw materials, fermentation, purification, blending and formulation and product storage clean rooms are designed for class 100 biosafety cabinet fitted with high efficiency particulate air (HEPA) filters and HVAC systems to ensure the entry of clean air into the cleanrooms and blend of dirty air inside the rooms (Sutherland, 2008). The flow of air in and out of the cleanrooms is laminar. Other components of the cleanrooms includeSeparate airlocks for entry and exit doors for personnel, raw materials and waste products.An inlet port for fresh purified air.An exit vents fitted with activated carbon filter to pur ify contaminated air before discharge to ensure environmental safety (Sutherland, 2008).Cleanrooms air pressure is maintained below atmospheric to prevent outward leakage.Nonslip floors, electricity, light appropriate and aseptic processing hood.Humidifiers to maintain and control cleanrooms relative humidity and temperatures4.1 Raw materialsVariations in raw materials composition is known to impact on the quality of DNA vaccines produced and also the operations of the plant. Therefore, raw materials require quality control check before employ. The raw materials, reagents and utilities required for the DNA vaccines manufacturing facility are plasmid DNA vectors, nutrients, glucose, water for injection (WFI), sterile air, salt, buffer readiness (to stabilise pH of fermentation), liquid due north N2, and antibiotic, alkaline, master cell bank (MCB) and working cell banks (WCB). These are placed in the quarantine storage room and undergo quality control testing to ensure that specif ication are met before employ for DNA vaccines production for quality assurance (QA/QC). The flow of materials from the raw materials to the final product (DNA vaccines) is shown in FIG. above and the final DNA vaccines products are stored in a sterile room in a freezer at -20oC (Przybylowski et al., 2007).4.2 PersonnelThe compliance to current good manufacturing practices (cGMP) and regulatory guideline depends on people and good management structure. It is essential when developing new facility to integrate all relevant personnel from production, logistics, quality control and engineering in the inception phase of the design and layout. Therefore, for a satisfactory quality assurance of the DNA vaccines production, facility design and layout, the interactions and inputs from various disciplines such as chemists, chemical engineers, biochemical engineers, biologists, microbiologist, pharmacists, civil engineers, project managers, mechanical engineers, electrical engineers, archite ct, cost engineer and many others are required to carry out defined capers and responsibilities. The flow of personnel around the designed facility layout during operations is shown in FIG.4.3 Qualification and validationThe qualification and validation of pharmaceutical manufacturing facilities at regular intervals is an integral part of good manufacturing practices (GMP). This is documentary evidence that assures that the DNA vaccines production facility is performing satisfactorily and consistently to specification for the intended purpose (Day, 2004). To do this, a validation master plan (VMP) is drawn up which include design qualification (DQ), installation qualification (IQ), operational qualification (OQ) and performance qualification (PQ) to confirm that all was done according to specifications (Day, 2004 Chaloner-larsson et al., 1997). However, an internal audit of the facility and instruments is also conducted to ensure compliance and implementation of cGMP and regulatory guidelines.4.3.1 Design qualification (DQ)Design qualification is carried on the following production pieces of equipment of the manufacturing facility such as bioreactor, centrifuge, anion-exchange chromatography, size exclusion chromatography, microfiltration system, ultra-filtration system, HVAC systems and lyophilizer, for handicap and documentation as a prove to show that the equipment designs conforms to regulatory standards such as ISO 9000, BSI, etc.4.3.2 Installation qualification (IQ)The IQ is a documented verification that confirms that the manufacturing facility layout, HVAC systems, supporting(a) utilities (steam, CIP, SIP, etc.) and process equipment are built and installed in compliance to the designed specification and manufacturers recommendations (Chaloner-Larsson et al., 1997). The IQ document for each equipment/system contains name of equipment/system, description, model and identification number, the location, service requirements, any safety feature, date, personnel and approver.4.3.3 Operational qualification (OQ)The OQ is the documentary verification of the manufacturing facility to confirm that each pieces of equipment operates in accordance to designed specifications and operation conditions and volition consistently (Day, 2004). This is accomplished by testing control systems, alarms, switches, and providing standard operations procedures (SOPs) for the operations of the manufacturing facility.4.3.4 Performance qualification (PQ)Performance qualification (PQ) is a documented verification that confirms that the manufacturing facility and the supporting utilities will consistently perform to required specification under the designed operating ranges to production the DNA vaccines. The following systems and pieces of equipment are authorise for performance check purification processes, bioreactor, HVAC systems, autoclave, CIP, SIP, oven, pure steam generation system, purified water and water for injection systems, centrifuge and l yophilizer.4.4 Quality assurance and Quality control (QA/QC)The consistent production of DNA vaccines to meet therapeutic specification of safety, purity, efficacy and potency depends on good quality assurance and quality control (QA/QC) performed by competent persons (QP). Quality control of the DNA vaccines is one of the key component of current good manufacturing practices (cGMP) and regulatory guideline of U.S. FDA, WHO, MHRA, ISO 9000 etc. It involves testing procedures employed to check that the DNA vaccines product are uniform from batch-to-batch and raw materials used for its production meet the specification, quality and standard. The quality control testing laboratory consists of the following assays for determining quality of raw materials and product purity, efficacy and safetyHigh performance liquid chromatography (HPLC) to determine the percentage of RNA, supercoiled and nicked.pH meter test for residual buffer salts and alkaline.Agarose gelatin electrophoresis (AG E) test for plasmid DNA vaccine purity, determine RNA and genomic DNA presence in the product.Gas chromatography test for the presence of ethanol, determine plasmid sizeFlame ionization detector (FID) test for the presence of isopropanol in the product.Transfection/Immunofluorescent staining test for potency of plasmid DNA vaccines.Kinetic chromogenic genus Limulus amoebacyte lysate (LAL) test to quantify the presence of endotoxin in the productSodium dodecylsulfate polyacrylamide gel electrophoresis (SDS-PAGE) test for the quantity of proteins in the product (DNA vaccines).GeneQuant spectrophotometer test to quantify the purity of the DNA vaccines product.Bicinchoninic acid (BCA) assay quantify the amount of proteins present in the bulk product.Mass spectrometer, measuring, weighing, recording and control instruments calibrated regularly. The analytical instruments are authorise to ensure performance.The DNA vaccines must meet at least minimum specification, purity, effica cy, safety and quality set by regulatory authority after sterile filling before released (Przybylowski et al., 2007 Prather et al., 2003).4.4.1 Product testingPrior to the release of the DNA vaccines after blending and formulation, the quality control department must test each batch for purity, identity, efficacy, safety and potency using the analytical assays mentioned above, and if the result does not meet regulatory specifications the batch will not be released (Prazeres and Ferreira, 2004). Table 1 below shows an example of DNA vaccines purity and quality specification.4.5 DocumentationDocumentation of all the activities and operations is a key requirement for GMP, regulatory bodies, and helpful for management structure, traceability of every batch history, planning, elimination of errors, effective communication, records keeping and design and layout of the DNA vaccines facility. Regulatory authorities such as FDA, EMEA and WHO require documentary evidence as prove that the DNA vaccines facility will perform consistently in compliance to cGMP. The DNA vaccines project documentation include standard operational procedures (SOPs), design qualification, installation qualification, facility layout design, specification sheets for each pieces of equipment, performance qualification, quality control records, process flow sheet, site plan, personnel records, licence, commissioning, validation master plan (VMP), packaging, labelling, etc. both on paper and electronically (Signore and Terry, 2008 Sinnott, 2005).4.6 UtilitiesUtilities are the support services required for effective design, layout and manufacturing process of DNA vaccines, they includePotable water, USP purified water used for cleaning in place (CIP) to clean process equipment.Water for injection (WFI) used for media preparation, fermentation media and rinsing of equipment after CIP.Clean steam for sterilisation in place (SIP) to sterilise the process equipment after each batch.Electricity for lig htening, instrumentation, analytical instrument, etc.Sterile gases such as filtered sterile air for fermentation process, nitrogen N2 for working cell bank storage, heating, ventilation and air-conditioning (HVAC) system.Refrigeration for the storage of the DNA vaccines product at -20oC.4.6.1 Heating, Ventilation and Air-Conditioning (HVAC) SystemHeating, ventilation and air-conditioning (HVAC) system is a component of the production clean rooms design and layout, it plays a vital role in ensuring that the manufactured DNA vaccines product quality, efficacy, safety and purity is not wedged by room temperature, relative humidity (RH), air borne particles, pressure and cross contamination in accordance to standards and classifications of rooms by ISO 14644-1, US Fed. Std. 209, BSS5295, EEC, etc. (Zyl, 2005). The HVAC systems for this manufacturing facility includeHigh efficiency particulate air (HEPA) filters to control air borne particles, dust and microorganisms of the clean rooms.D esiccant dehumidifiers/refrigerated dehumidifiers are used to monitor and control the temperature and relative humidity (RH) of the rooms in order to comply with raw materials and DNA vaccines product requirement.Airlocks and air handling unit (AHU) are put in place for pressure monitoring, control and maintenance of pressure cascade with the production rooms.4.6.2 Water and clean steam systemsPurified water, water for injection (WFI) and clean steam are essential utilities generated on site and distributed for use in DNA vaccines production, clean-in-place (CIP), sterilisation-in-place (SIP), and media preparation (Robbins, 2010). In order to ensure safety, purity and efficacy of the DNA vaccines the water used for its production is sterile water for injection (WFI). The WFI is produced from purified water by distillation/reverse osmosis to meet the required standard of purity specified by the coupled State Pharmacopeia (USP) (pH 5.0-7.0, nonpyrogenic and antimicrobial agent). The WFI is stored at elevated temperature (80-95oC) to eliminated microbial growth, and the system constructed with stainless steel to eliminate contamination (Robbins, 2010). The WFI system design is shown in FIG.4.7 pay off treatment and managementThe system for treating the waste generate from the DNA vaccines manufacturing facility is an integral part of the design of the facility, layout and good manufacturing practices (GMP). The major waste generate from the production process are genomic DNA of the host cells, RNA, proteins, cell debris, salts, endotoxins and plasmid isoforms (Ferreira et al., 2000). The waste is treated to regulatory standards (BS, ISO, etc.) to avoid harm to health and safety of personnel and environment (HSE), pollution and eliminate cross contamination of the product. The system for treating the waste is illustrated in FIG. below WWWWIncinerationAutoclavedWasteDischargeAutoclave4.7.1 Health, Safety and Environment (HSE)The DNA vaccines production microorga nism poses some hazard. The environmental impact assessment (EIA) of the DNA vaccines production system therefore becomes a key part of the design and layout of the manufacturing facility (Prazeres and Ferreira, 2004). However, the environmental impact assessment (EIA) study and the design will require approval from environmental protection agency before the facility is built (Davda, 2004). To ensure that health, safety and environmental regulations are met, the process design and layout is geared towards minimisation of waste generation, safety of product, safety and health of personnel and incorporation of waste treatment process before discharge to the environment. In addition, the personnel will also be provided with personal protective equipment (PPE) such as hand gloves, gowns, goggles, etc. to work with.4.8 formula and regulationThe manufacture of DNA vaccines is highly regulated to ensure that it is safe, efficacious and pure for humans, and also its production carried out in accordance to current GMP (Plumb, 2005). Therefore, before the DNA vaccines can be marketed they must be licence from the relevant regulatory bodies such as the Medicines and Healthcare products Regulatory Agency (MHRA) in the get together Kingdom, the Food and Drug Administration (FDA) in the United States, the EMEA, WHO and so on (Smith and Dennis, 2001). The manufacturing facility used for the production of the DNA vaccines must be licence in any case (Plumb, 2005). These licences are obtained if and only if the manufacturing facility design, layout and premises of its manufacture conform and comply to current good manufacturing practices (cGMP) and with regulatory standards, guidelines and specifications stipulated by MHRA, FDA, WHO, EMEA, ISO, etc. Hitherto, the company must also provide detailed documentary evidence about the safety, purity and efficacy of the DNA vaccines and the consistency of its manufacturing process. Signor and Terry reported that the incorporation o f current good manufacturing practices (cGMP) into good design practices (GDP) at the inception of the manufacturing facility will ensure that regulatory conditions are met (Signor and Terry, 2008). The regulatory guidelines specify the requirements for the pharmaceutical manufacturing facility, not the methods to achieving it. The regulatory bodies functions include safeguard public health, licensing, monitoring DNA vaccines post-marketing, regulating clinical trials and publish quality standards.5.1 Project timelineThis project has a definite start, middle and end, which consist of several activities ranging from the environmental impact assessment and design approval, construction to commissioning executed in a defined order to bring the project to completion. It is the function of the project manager to plan, schedule and control these tasks/activities in a specified sequence and allocate materials, manpower, machinery and money to ensure that the project is completed on time (G ray and Erik, 2008). There are several project management techniques available in the literature, but to estimate the timeline of this project the Gantt chart technique was employed, which a plot of each task against time. Each bar represents a task/activity, length of the bar corresponds to the duration of the task and the position indicate the start and finish times. The timeline for key activities of the project are shown in FIG below, the Gantt chart was prepared with reference to (Davda, 2004). The entire project is expected to take a year and 4.5 months from the Gantt chart.6.1 Recommendations1. Legislations and regulations are subject to changes with emergent of healthy technology, therefore the design of the manufacturing facility should be above the current specifications and standards.2. A well defined and detail engineering drawings and specifications that does not require much interpretation.3. A good relationship between project design team with relevant regulatory aut horities and encouragement of their input will fortify the design of the facility and compliance to cGMP.4. Ensure that all designs, installations and utilities are validated according to validation master plan (VMP) and are working according to design and specification of regulatory bodies.5. Compliance with current good manufacturing practices (cGMP) at the inception of the design phase of the facility.6. The DNA vaccines production facility should be designed and layout to harmonized the various regulations by different bodies such the US FDA, UK MHRA, EU, Japan, ISO, WHO, etc. to boost market for the product.7. The process parameters such as temperature, pH and pressure must be carefully controlled to assure batch-to-batch identity in final product.7.1 ConclusionIncorporating current good manufacturing practices (cGMP) from the beginning of the design and layout phase of the DNA vaccines facility, the production processes and to the manufacturing premises will ensure that all re gulatory specifications are met.

Dead Sea :: essays research papers

General Purpose To inform Specific purpose The audience depart know that the d.o.a. Sea is free of all plant and aquatic life, why the sea is so salty and the health benefits.Thesis or commutation idea The Dead Sea has a unique environmentMain Points a.The Dead Sea is one of the saltiest bodies of water anywhereb.The Dead Sea is devoid of all plant and aquatic lifec.The Dead Sea area has become a major center for health look for and treatment induction You know why they call it the dead sea? Because absolutely nothing live in it. It is some of the salties water anywhere in the world. My love for geology grew turn out of an experience with a friend whos child was doing a earth science project on plate tectonics and needed help. Ill never swallow up the recognize of the book Earth in Motion it left a lasting impression on me and led me to study more on this subject. Ive been reading about this for approximately 10 years and am always amazed at the new material I find . My lates t discovery was that the Dead Sea is one of the salties bodies of water anywhere, that it is devoid of all plant and aquatic life and that it has become a major center for health research and treatment.I.The Dead Sea is one of the salties bodies of water anywhereA.The Dead Sea is completely landlockedB.The Dead Sea is continually fed water from the rivers and streams access down off the mountains that surround it.1.No river drains out of the Dead Sea2.The only way water gets out of the sea is through evaporationII.The Dead Sea is devoid of all plant and aquatic lifeA.The water in the Dead Sea is deadly to most living thingsB.Even though the Sea is deadly to most living things humans are remarkably adaptable to the seas salty conditions. Humans can swim is the Dead Sea, just kindred they swim in the ocean1.Humans dont really swim in the sea, instead they just hang out2.Because of th extremely high concentration of disolved mineral salts in the water its density is way more that th at of fresh water, which means are bodies are more buoyant in the Dead Sea.III.The Dead Sea area has become a major center for health research and treatmentA.The Dead Seas deep black grave sediment, previously covered with water at times of higher sea level, are being mined for therapeutic purposes and for the preparation of cosmetic products under the name Black Mud.

Rhetoric In The Media Essay -- essays research papers

Many times we hear things through media and dont actually listen to what they may say. When people hear something through mass media, they dont realize that there is a persons point of view stated in the story. And many times what people dont tick is that there is no such thing as an objective point of view. This is called Rhetoric when somebody states their point of view using words that either convey an audiences opinions one way or another. Rhetoric can be found in many places such as a T.V add or a commercial, magazine articles and advertisements, the news, and even radio commercials. Watching the regular news as I frequently do, I always hear the way a newsman speaks virtually a topic and immediately I know the view that that particular newsperson takes. This happens in many instances, but one time in particular caught my attention. A newsman was doing a story on vandalism. Usually you hear about vandalism on abortion clinics and harassment of that sort, and usually the reporter uses the words Anti-abortionists to describe the people who commit these crimes. One the other hand this time was different. The reporter was doing a story on vandalism that happened on a church billboard, outside the church, and the billboard said something having to do with pro-life and the choice that they believed in. Later that night there was a huge black question scoring that was spray painted on that saying. The reporter desc... Rhetoric In The Media Essay -- essays research text fileMany times we hear things through media and dont actually listen to what they may say. When people hear something through mass media, they dont realize that there is a persons point of view stated in the story. And many times what people dont see is that there is no such thing as an objective point of view. This is called Rhetoric when someone states their point of view using words that either sway an audiences opinions one way or another. Rhetoric can be found in man y places such as a T.V add or a commercial, magazine articles and advertisements, the news, and even radio commercials. Watching the regular news as I frequently do, I always hear the way a reporter speaks about a topic and immediately I know the view that that particular reporter takes. This happens in many instances, but one time in particular caught my attention. A reporter was doing a story on vandalism. Usually you hear about vandalism on abortion clinics and harassment of that sort, and usually the reporter uses the words Anti-abortionists to describe the people who commit these crimes. One the other hand this time was different. The reporter was doing a story on vandalism that happened on a church billboard, outside the church, and the billboard said something having to do with pro-life and the choice that they believed in. Later that night there was a huge black question mark that was spray painted on that saying. The reporter desc...