Effect of Oxidative Stress on HAGE Expression

Effect of Oxidative Stress on HAGE Expression Cancer is a group of diseases which involves uncontrolled cell growth, metastasis and invasion of cells to other tissues via lymph node or blood. Cancer is caused by many factors such as (i) Chemicals such as tobacco, alcohol, asbestos etc., (ii) Viral infections such as Human Papiloma Virus, Epstin Barr Virus, hepatitis B, C etc., (iii) Ionizing radiations such as X-Rays, UV-Rays, Gamma Rays etc., (iv) Hereditary factors such as mutations in BRCA 1 and BRCA 2, p53 mutations, APC gene mutations, Retinoblastoma gene mutation etc., (v) Hormones which promote growth proliferation such as growth hormones, estrogen, progesterone etc. Cancer is classified into malignant and benign tumours. Malignant tumours are mostly liquid tumours which metastasize to other tissues via lymph node and blood. Benign tumours are mostly solid tumours which stay at one particular tissue and seldom migrate. Malignant and Benign tumours are re classified on the type of cell and tissue from which they originate. They are classified as follows: i) Carcinomas: These are the malignancies of the epithelial cells, which line the internal organs of the body and also present on the surface the body such as skin. ii) Sarcomas: These are solid tumours present in connective tissues such as bones and lymph systems (Crowley 2006) Furthermore the tumours are classified according to (i) site of origin as in lung cancer, breast cancer etc., (ii) type of cell such as rhabdomyosarcoma and acute lymphocytic leukaemia. (Ruddon 2007) The progression from a normal cell to malignant one involves the dysregulation of genes implicated in the control of normal proliferation / death over many years. These are normal functions regulated by proto-oncogenes and tumour suppressor genes. Proto-Oncogene And Tumour Suppressor Gene Protooncogene is found to be normally expressed in all vertebrates including humans. It is also found to be expressed in some insects and yeasts. Protooncogenes play an important role regulating normal cell growth and differentiation. They also perform functions such as signal transduction and mitogenic signal execution RAS, MYC, TRK, ERK are some examples of protooncogenes (Novakofski 1991). Oncogenes are derived from protooncogenes during the process of carcinogenesis. The formation of active oncogene leads to abnormal cell proliferation and thus contributes to the formation of tumour (Alitalo and Schwab 1986). A protooncogene can be converted into an oncogene in a variety of ways such as (i)Transduction induced by retroviruses which cause the integration viral DNA with the host. This DNA on translation give rise to viral proteins which cause the activation of protooncogene, thereby leading to cancer. (ii) Mutation within the protooncogene leading to an increased activity of the pr otein. (iii) chromosomal translocation where the gene for proto oncogene is translocated to other loci, which cause its abnormal expression. For eg in the translocation of abl in chromosome 9 to bcr region chromosome 22 as found in Philadelphia chromosome (Rowley 1973) (iv) Amplification induced by gene duplication, mis-regulation of gene which leads to overexpression of protooncogenes. (Todd and Munger 1999) Unlike oncogenes, the tumour suppressor genes normally inhibit cell growth in variety of ways such as (i) repressing the genes important for cell cycle progression. For eg., pRb (retinoblastoma ) controls the G1 stage by being hypophosphoryated and not allowing the release of transcription factor E2F which promotes G1-S transition. (ii) Stopping cell cycle on detecting DNA damage. DNA damage induces p53 which now leaves from its interacting partner Mdm2 and increases the activity of p21. This p21 protein then inactivates cyclin dependent kinases which are essential for cell cycle progression, (iii) Apoptosis may also be promoted by p53 when damage is irreversible. (iv) inducing DNA repair proteins to repair DNA damage and prevent abnormal cell proliferation. (Yoshida, et al. 2000) There are a number of mechanisms by which a cancer cell survives in a body. This is illustrated in the diagram below.(Weinberg and Hanahan, 2000) Treatment The choice of therapy depends upon the location and stage / grade of the tumour, as well as the health of the patient. There are a number of therapies for treating cancer such as surgery, chemotherapy, radiaotherapy, hormonal therapy etc., The deregulation of many genes in cancer cells leads to the over-expression of altered proteins which can be used as biomarker which can provide help for the diagnosis and / prognosis of the treatment but can also be used as potential target for immunotherapy. Cancer antigens and their classification Tumour antigen is an antigenic substance produced in the tumour cells and triggers an immune reaction in the host. They are useful in identifying tumour cells and are used in cancer therapy. Tumour antigens are classified as Cancer testis antigen, Differentiation antigens, Tumour specific unique antigens, Overexpressed Self Antigens, Viral antigens, Post-translationally, Oncofoetal antigens, Idiotypic Antigens as shown in the table below Copied from (Li, et al. 2005) Amongst all these categories, cancer testis antigen represent the most promising group of antigen to be used in future immunotherapeutic interventions due to their restricted expression to mainly to tumour cells with the exception of placenta and testis which are immune-privileged sites and therefore would not pose any real issue for the risk of autoimmunity.(Simpson, et al. 2005) HAGE HAGE also known as DDX43 and CT13 antigen belongs to this category of antigens and was first identified by Martelange et al using cDNA subtraction approach of a human sarcoma cell line.(Martelange, et al. 2000)Using rational hybrid analysis, it was found that HAGE gene is located on chromosome 6. HAGE was found to be overexpressed in several tumours. There is a low expression of HAGE in normal tissues since the expression is regulated by hypermethylation HAGE is also over expressed in tissues such as testis, placenta, and ovaries. HAGE is usually expressed at the m-RNA level though recent studies in melanoma cells suggest that HAGE could also be expressed at the protein level.(Mathieu, et al. 2010) The name DDX43 comes from the fact that HAGE also belongs to another group of protein known as Dead box proteins and referred to as DDX43. (Abdelhaleem 2004) Dead box proteins These proteins were discovered in the late 1980s. (Gorbalenya, et al. 1989)Dead box proteins belong to the family of RNA helicases and play an important role in the transcription, post transcriptional modifications such as splicing, transport, translation, decay and biogenesis of ribosomes. NTP hydrolysis provides energy to these enzymes and they unwind dsRNA or disrupt RNA-Protein interaction. DDX and DHX are widely studied Dead Box Proteins. There are many classes of DDX and HAGE belongs to DDX43. They are so named because they contain the amino acids D-E-A-D (Asp-Glu-Ala-Asp) in one of their motifs namely Motif II. Besides they also contain motifs such as motif I, Q-motif, motif VI, motif Ia, Ib, III, IV and V as shown in the diagram below. These motifs bestow properties such as ATP binding and hydrolysis, RNA interaction, remodelling activity etc to these proteins. The consensus sequence of DEAD box family is shown below Copied from (Linder 2006) Regulation and Function of HAGE Both function and regulation of HAGE have not been studied in great detail (Scanlan, Simpson and Old 2004). In normal tissues HAGE expression is regulated by DNA hypermethylation, Histone modifications such as histone aceylation, histone deacylation and histone methylation. However in cancer, there could be many mechanisms of upregulation of HAGE. The most commonly thought mechanism is the demethylation of DNA which leads to HAGE over-expression. (Roman-Gomez, et al. 2007) HAGE could also be induced due to transformation of normal cells during cancer or due to the action of oncogenes. HAGE might also be induced randomly. HAGE may play a role in pre-mRNA splicing, ribosome biogenesis, transcription and initiation of translation. (Rocak and Linder 2004) This project will focus on Head and Neck Cancer. Head and Neck Cancer Head and Neck cancer are the cancers that arise from the upper aerodigestive tract such as nasal cavity, oral cavity, pharynx, larynx and paranasal sinuses. Most of them are of squamous cell carcinoma type of the head and neck and have been given the acronym -SCCHN or HNSCC. (Argiris, et al. 2008). The diagram of the anatomy of the head and neck is illustrated below Copied from (Wu, et al. 2009) More than half a million patients are diagnosed with head and neck cancer every year. Head and Neck cancer in fact accounts for more than 3-10% of the cancers(Gourin and McMains 2005). Smoking, alcohol, chewing of betel leaf with tobacco and areca are the major risk factors for this cancer. Recently, HPV type 16 has been identified as one of the causes for head and neck cancer and account for 40% (Goodger and McGurk 2000) The progression of this tumour is complicated. It progresses from the normal features to hyperplasia, mild dysplasia, moderate dysplasia, severe dysplasia, carcinoma, invasive carcinoma and metastasis. The progression may be caused by due to genetic instabilities such as loss of heterozygosity of chromosome 9p21, inactivation of of p16 and loss of 3p, loss of 18q, inactivation of PTEN, some translocations, 17Beta heterozygosity or TP53 mutation. (Argiris, et al. 2008) Copied from (Argiris, et al. 2008) Interestingly HAGE was found the John van Geest group to be overexpressed in 40% of HNSCC cancers (unpublished data) and although much of its function is now emerging no information exist at the moment regarding the regulation of its expression. However it has been observed that cells left for longer period of time in the incubator had a significantly higher expression of HAGE at the mRNA and protein level. Aim of this project The observation that HAGE was over-expressed in 40% of HNSCC led to hypothesis that cells under stress i.e lack of nutrients, decrease oxygen level, as well as other factors influence HAGE expression. Moreover it has been found that HAGE is also expressed in 20% of Acute Myeloid Leukemia and 50% Chronic Myeloid Leukemia as well as many solid tumours such as HNSCC (Adams, et al. 2002). This suggests that there must be something in common between these 2 very different forms of cancer. CML and solid tumours are known to have a high expression of reactive oxygen species (ROS), therefore it might be possible that ROS induces HAGE expression. Thus this project will focus on the effect of oxidative stress has on HAGE expression. The effect of other stress such as temperature may also be investigated. METHODS Cell Culture The PCI 13 and PCI 30 cell lines would be supplied by Prof E Tatour. These cell lines are specific for Head and Neck cancer. The cells would be grown in RPMI 1640 +10%(v/v) FCS+2mM L-glutamine and incubated at 37oC and 5%C02 atmosphere. Extraction of m-RNA The culture media would be removed and washed with DPBS(Dulbeccos phosphate buffer saline). Then DPBS will be removed followed by the addition of RNA-STAT 60. RNA pellets would be then retrieved and re-suspended in ddH2O. RNA extracted is then quantified using NANODROP 8000 UV spectrophotometer. RNA would be then added in measurement wells of the spectrophotometer. The spectrophotometer would be read at 260 and 280nm and the amount of RNA will be calculated. The RNA concentration is calculated in  µg/ µl before being adjusted to 1 µg/ µl by ddH2O. RNA samples would be then stored at -80oC and used for conducting RT-PCR and RTq-PCR in the future. RT-PCR (Reverse Transcriptase PCR) From the extracted RNA cDNA will be synthesized. 2  µg of RNA sample will be mixed with 1  µl of oligo-dT primers and diluted to 15  µl of ddH20 in an Eppendorf tube. All RNA samples would follow the same process. UNO Thermoblock will be used to heat the tubes to 70 °C for 5 min which allows the primer-RNA annealing. 10  µl of reverse transcriptase mix, which will be prepared by mixing Muloney Murine Leukemia Virus 5-X buffer, dNTPs, RNasin RNAse inhibitor, M-MLV-reverse transcriptase and ddH20. The tubes will be then pre-heated in a water bath at 39.2 °C for 80 min which allows cDNA synthesis. Tubes will be removed and kept again in the UNO-Thermoblock and heated to 95 °C for five minutes which stops the reaction. These tubes would be stored at -20 °C for future use. Real Time qPCR cDNA generated from RT PCR will be used as a template and the reagents used will be (i) 6.25 µl iQ Sybr Green, (ii) 0.5 µl gene specific sense primer (iii) 0.5 µl gene specific anti-sense primer, (iv) 4.75  µl ddH20 and 0.5 µl cDNA template. These reagent mixtures will be added to all tubes for a specific gene. Samples will be usually carried out in duplicate with a negative control that contains the reaction mixture without cDNA. Rotogene 6000 real-time qPCR analyser will be used to carry out RT qPCR. Relative gene expression using 2ΔCT method will be calculated with the help of the expression of housekeeping genes HPRT-1, HSP-27 and HSP-90. The primers which will be used in real time qPCR experiment is given below. These primers are supplied by mwg-Eurofins. The primers have a stock concentration of 100pmol/ µl and will be diluted to a working concentration of 10pmol/ µl. From this working 0.5 µl (5pM) of primers will be used. Total Protein extraction Cells will be grown to 75% confluence in T75 flasks. Cells will be trypsinised, washed and re-suspended in DPBS and these cells will be then counted using trypan blue. Cells will be diluted to 1X106/ml using DPBS and 5 X106 cells would be taken in a 1.5ml eppendorf. Centrifugation will be done to pellet the cells. The supernatant will be discarded and lysis buffer containing a cocktail of RIPA buffer and 10% protease inhibitor will be added to the pellet. The eppendorf tube will be then placed on a tube rotator at 4 °C for 30 min. It will be then kept on ice for 30 min. Cells will be again centrifuged at 14000 RPM for 30 min at 4 °C. Aliquot of the supernatant will be prepared to be stored at -20 °C for future use. Total Protein Assay Total protein assay will be carried out using BioRad Dc protein assay reagents. Series of dilutions (0.2,0.4,0.5,0.8,1.0,1.5,2.0mg/ml) will be created using stock BSA solution with the concentration of 10 mg/ml. Protein extracts and standards would be tested in triplicates and duplicates respectively. Assays will be performed in 96-well round bottom plates. 25 µl and 200  µl of reagent A and B will be added to all the samples and the samples will be incubated at room temperature for an hour. Proteins will be then read at 750nm and their concentrations would be calculated based on the standard values. Western Blotting 30  µl of sample will be loaded into the wells of SDS PAGE gels. 1X tris-glycine-SDS will be used as the running buffer. A known molecular weight ladder will also be run alongside the samples. Initially 70V current will be applied to aid the migration of proteins through the 5% stacking gel. Once the proteins reach the 10% separating gel, 90V current will be applied. After the proteins run through the gel, they will be transferred to the PVDF membrane with the help of liquid transfer. This membrane will be prepared by washing with 10% methanol for 5 seconds, ddH2O for 5 min and transfer buffer for 10 min. Liquid transfer will be carried out using the following steps. 1. Cold transfer buffer will be used to immerse a gel frame. To this gel frame a sponge pre soaked in transfer buffer will be placed Then a filter card, gel, PVDF membrane, another filter card and a second pre soaked buffer sponge will be placed in order starting from the first filter card. Proteins will be transferred with the help of electric current of 100V applied for one hour. After completion, membranes will be cut and treated with different antibodies.10% (w/v) Marvel milk solution will be used to wash the membrane for one hour at room temperature. This washing blocks the non-specific binding sites. The blocking solution will be then discarded and the antibody diluted to 10% (w/v) in Marvel milk solution will be added. This antibody coated membrane will be agitated overnight on a plate rocker at 4 °C. The next day there would be 3, 10 min washes with TSBT(Tris-Buffered Saline-Tween-20). During these washes the membrane vessel will be agitated in plate orbital shaker at room temperature. After completing the washing process, a secondary antibody specific to the primary antibody will be added. The steps for adding the secondary antibody are same as the primary antibody addition except for the fact that no overnight incubation is required and the secondary antibody will be incubated only for one hour while being agitated on the shaker at room temperature. The marker will also be stained using streptavidin-HRP secondary antibody. After performing the above step the membranes will be developed. Membrane development will be performed by placing the membrane in a tray and washing it with ECL reagent. The membrane would be then exposed for a certain period of time using CCD camera. Assay for ROS-DCFDA Stress Test Stock Solution Preparation The stock solution of Hanks Buffered Salt Solution (HBSS)will be prepared according to the manufacturers protocol. DCFDA(2,7-dchlorofluoroscein -diacetate) Assay To test ROS levels DCFDA test will be performed. Before conducting the DCFDA assay, the standardization of optimum concentrations of H2O2 and DCFDA for detecting cell stress should be performed. It is important to note that H2O2 should be added only sub-lethally and should not be added in proportion which may cause cell death. The PCI 13 and 30 cells will be plated out in two 24 well plates. 1ml of each type of cells plus RPM1640 10% FCS media will be added to 8 wells per plate and will be incubated overnight at 37 °C. The media will be removed the next day and increasing concentration of DCFDA will be added to both plates and the cells will be incubated with Tinfoil wrapping to prevent light exposure and incubated at 37oC for 30 min. The cells will be then washed and then cold HBSS will be added. After this step the cells will be stressed with increasing concentration of H2O2 (see diagram below). The cells will then be again wrapped in tin foil and placed on a rocking platform for 15 min. The same method will be followed for treating other wells with different concentrations of DCFDA. Experiments will be performed at least twice for each cell line. H2O2 will be removed after 15 min and cells will be trypsinised with 100microL trypsin and Versene. 800 microL of DPBS will be added to one of the 2 wells an d will be pipetted thoroughly so as to remove the cells from the well surface. This will be then transferred to the other well and then 1ml of solution would be transferred to Flow associated cell cytometry (FACS) tube for analysis. The same procedure will be carried for other sets of wells. DCFDA fluorescence would be measured using Gallios flow cytometer and results would be analysed in Kaluza program. Time Line For The Project During the month of May, all techniques such as Western Blotting, mRNA/protein extraction, Real Time PCR will be learnt. This time is indicated in red colour in the graph below. This will overlap with the time duration, from May to the end of June, during which hydrogen peroxide experiment will be performed as per written in the method section and the expression of HAGE will be monitored at both the mRNA and protein level. Also from the start of June to the end of July repeat experiments will be performed and if time permits, the effect of thermal stress on HAGE expression will also be investigated. This is indicated in the graph below. SUMMARY Cancer Testis Antigens (CTA) are antigens that are expressed in a variety of tumours. They are usually absent in normal tissues with the exception of testis and placenta where they are expressed as self tolerant antigens. Since these antigens have strong immunogenicity and their expression is mostly restricted to tumours, they are ideal targets for cancer immunotherapy. Therefore much research is ongoing for the identification of CTA. Recently helicase antigen HAGE was identified as a CTA and was found to be over-expressed in HSNSCC, AML and CML. Thus there might be a common link between these different types of cancers. Moreover ROS is known to be induced in all these tumours and it may be possible that ROS causes increased expression of HAGE. Thus the aim of this project would be to investigate the effect of oxidative stress on HAGE expression. HAGE expression would be analysed both at the m-RNA and protein level in two cell lines namely PCI 13 and PCI 30 using techniques such as m-RNA extraction, RT PCR, Western Blotting and Protein assay. The ROS level would be evaluated using the DCFDA assay. Since the mechanism of HAGE regulation is unknown, positive result in the project would help in elucidating a mechanism by which HAGE could be regulated.

The Sisters Mainini and Lucia in Tsitsi Dangarembga’s “Nervous Conditions”

One of the most successful pieces of literature from Africa is the novel of the Zimbabwean native Tsitsi Dangarembga, â€Å"Nervous Conditions†.   The novel talks about the situation of African women and the predicaments they have to face on a daily basis. Dangarembga seems to argue that there is a sort of entrapment of women within the society stripping women of genuine freedom and an unprejudiced position in the society. It is expressed by the narrator and protagonist of the story, a young African girl named Tambudzai in her line â€Å"†¦my story is not after all about death, but about my escape and Lucia’s, about my mother’s and Maiguru’s entrapment, and about Nyasha’s rebellion† (Dangarembga 1) Dangarembga’s beautifully constructed novel strives to provide suggestions on how to avoid such gender related entrapments that are biased to patriarchy. This is a prevalent vicious cycle of powerless women is not only present in Africa, but all over the globe as well. To communicate the issues of African women, Dangarembga had created an ensemble of African Women that have varying voices to represent women of different views regarding the role of women in they society. If we were to relate Dangarembga’s Nervous Conditions to a painting, it seems like she had used different colours and varying strokes through her beautifully designed characters. In the heart of this painting are the sisters Ma’Shingayi, more commonly called â€Å"Mainini†, and Lucia. The sisters have contrasting personalities but interestingly their differences can still lead the readers towards insights regarding the role of women in the society. Let us first discuss the character of Mainini, since she has a much closer relation to the protagonist, who is her daughter. Mainini could be described as a supportive mother—that is for the case of her dead son Nhamo, but not for Tambudzai. Mainini became very devastated by the death of her son, to whom she had worked hard to provide education. After the unfortunate death of her investment, her son, she became a negative thinking character. She thinks maliciously and more often jealously of others that are around her.   Their hard life adds more to Mainini’s negative outlook in life. Mainini plays an important role in the text as the narrator thinks of her as a representation of a repressed woman. The book characterizes Mainini as too submissive and obedient. Her being subservient makes her prone to abuse by opportunists.   Because if this trait, her way of thinking evolved into something that sort of paranoid, that others will always take advantage of her.   This can lead her to a vicious conclusion that there are no reasons for a person to be kind, because this world runs under a dog-eat-dog system. The narrator describes her mother Mainini through this line â€Å"†¦who suffered from being female and poor and uneducated and black so stoically† (Dangarembga 86) This line suggests that Mainini is the representation of the disempowered woman. The saddest aspect about Mainini is that she herself views herself as powerless. It seems that Mainini is already worn-out by all the burden that she carries. She had expressed her exhaustion from her life through this line â€Å"†¦the business of womanhood is a heavy burden†¦how could it not be? Are not we the ones who bear children† (Dangarembga 16) That line just suggests that Mainini recognizes that there is inequality in terms of gender. She questions why women are not compensated and treated as equal to men. She had thrown this question when she notices that men can act lazy while it is regarded as unwomanly to act in such a way. On the other hand, we have Mainini’s sibling Lucia. Lucia can be considered an opposite of Mainini interms of personality and outlook in life. The book had described Lucia as someone who has a strong personality. In fact, ther personality was so strong that people were afraid of her specifically because they suspect Lucia to be a â€Å"witch† and a â€Å"prostitute†. Dangarembga had designed Lucia’s character as surrounded by mystery and malice. Lucia’s role in the narrative seems to be a thinking character. She would throw witty and smart lines like â€Å"even if you ignore me†¦it doesn’t mean I am not here† (Dangarembga 125) Another of her positive trait is that she is a warm-hearted and caring person. But despite those positive traits, Lucia is perceived by their community negatively. She is viewed to be a sexually promiscuous woman and she becomes the topic of gossipers in their community. It is believed in the story that Lucia has affairs with â€Å"†¦men who did not want to settle down but who were often very rich†¦Ã¢â‚¬  (Dangarembga 127) Lucia is also considered as a talkative and expressive individual.   Lucia in fact lectures woman whom she thinks are being abused because of clinging unto conventional nations about womanhood. Lucia’s way of thinking can also be traced to the disempowerment of women in their community. But unlike Mainini, Lucia had developed a positive outlook and disposition. Lucia becomes an admirable character in the story as she is the only one speaking a witty tone. We can interpret that her kind of mindset is due to the fact that she recognizes that their society is like a prison for women, but however the men take advantage of her, they can’t take advantage of her free mind. Lucia’s open-mindedness highlights the flaw that makes women inferior to men in terms of societal roles. Just like here sister Mainini, Lucia had had her share of misfortunes and abuses. She was sexually abused by Takesure, a womanizer who has no means of supporting those he impregnates, and forced to be one of his many concubines. A villager had said â€Å"†¦look at that Lucia! Ha! There is nothing of a woman there† (Dangarembga 126). The villager may had jumped to that conclusion because the more conventional notion about womanhood is far from the characteristics of Lucia. What the critics of Lucia fail to see is that she had jumped over the fence that is set by the society and traditions. She had deconstructed the stereotypes that are much associated with womanhood such as being subservient and proper. Lucia’s character may have wanted to communicate to the readers that these â€Å"societal fences† are set up with patriarchal thinking, they will always be in favour to men. What the characters of Mainini and Lucia had shown us are different ways of thinking by a woman. Their kind of thinking does not only exist in books, these kinds of mentalities of women also exist in the real world, sometimes in even more extreme forms. The character of Mainini tells us a story that we can consider as common. Women remain silent and meek even though they are being abused deliberately. They don’t fight, and does not want to fight, the vicious cycle of women abuse. That is because they think that being abused is their role as a woman. This way of thinking is never good for any woman. As the character of Mainini had shown us, her self-induced repression makes her treat everybody with hostility. On the other hand, Lucia had shown us that some traditions and standards had to be brought down in order for women to achieve genuine freedom from male dominated societies. Lucia had shown us that an open-mind can break through the chains that bounds women. Mainini and Lucia had shown us that it is all a matter of choice, whether a woman should choose to be abused or to be free. Works Cited Dangarembga, Tsitsi. Nervous Conditions. Seattle, WA: The Seal P, 1989.      

Prisoner Rehabilitation Essay

The rising inmate population and overcrowding in prisons is a problem. A lot of this problem comes from repeat offenders who have had a lack of prison rehabilitation. People have two different views about the prison system. The first is that prisons are â€Å"jails† and that everyone in the â€Å"jails† should suffer for their crimes. They feel since they are criminals and do not abide by the rules of society they should not be able to become part of a society. Others view prisons as correctional facilities where prisoners can accept their mistakes and be rehabilitated, eventually being assimilated. I feel that that â€Å"jails† are from criminals such as rapists, murders and other criminals that clearly will never be able to accept the rules society and show no hope of being rehabilitated. On the other hand I feel that some criminals see the light of there mistakes while in prison and want to move on and hopefully never return to prison. But prisoners loathing for prison alone cannot guarantee prisoners to not end up in the same position once free. Prisoners need to be cured in more ways than fearing punishment. I feel these prisoners need to be rehabilitated to the point that at the end of there sentence they realize that committing crimes is only a way out and feel they will not fall back into a life of crime and be ready to enter society as a free man with some aspirations of a law abiding life. But usually this never happens because of the way prison rehabilitation is. Prison Rehabilitation is mostly the experience of prison itself where you go in to a place that makes you live around criminals and never get out of the criminal mind state and never can grow to realize your mistakes and move on in your life. Towards the end of your sentence there is usally no help to integrate back into society at all, which is the most critical time for help. It seems to me that during the last years of a prisoner who has a good prison record’s sentence they should be eligible to enroll in correctional prisons that weren’t required to be paroled but provided a alternative to â€Å"jail† and provided you with not only more freedoms than jail but an opportunity to make it a smaller step into the real world than coming right from jail. This correctional facility soul purpose would be to rehabilitate while still providing similar jail atmosphere. It would be mandatory to take high school or college classes or be trained in certain vocational areas where your grades would determine eligibility. Along with these classes there would be a series of other classes that would integrate you back with society. This would be totally up to the prisoner to maintain and get the most out of this because that is what you have to do to succeed and be rehabilitated.

The global health threat of climate change - Free Essay Example

Sample details Pages: 13 Words: 3807 Downloads: 1 Date added: 2017/06/26 Category Environment Essay Type Analytical essay Tags: Climate Change Essay Did you like this example? Climate change is the biggest global health threat of the 21st century. Effects of climate change on health will affect most populations in the next decades and put the lives and wellbeing of billions of people at increased risk. During this century, earths average surface temperature rises are likely to exceed the safe threshold of 2 °C above preindustrial average temperature. Rises will be greater at higher latitudes, with medium-risk scenarios predicting 2-3 °C rises by 2090 and 4-5 °C rises in northern Canada, Greenland, and Siberia. With this current situation, the whole of U.K. population is at risk considering the changing patterns of disease, water and food insecurity, vulnerable shelter and human settlements, extreme climatic events, and population growth and migration. Although vector-borne diseases will expand their reach and death tolls, especially among elderly people, will increase because of heat waves, the indirect effects of climate change o n water, food security, and extreme climatic events are likely to have the biggest effect on global health (Prof A. Costello FRCPCH, S Ball BSc, C Patterson LLB). Aside from the bigger picture of climate change we still need to consider the leading global risk for mortality, Hypertension is responsible for 12.8% (7.5 million) of total deaths worldwide, according to a new report issued by the WHO. The report also identified hypertension as responsible for 3.8% of years of life lost due to premature death plus years of healthy life lost due to illness and disability (known as disability-adjusted life years) (Colin Mathers, PhD, coordinator for mortality and burden of disease at the WHO). Majority of the U.K. population is exposed to a total of 8 risk factors (hypertension, alcohol use, tobacco use, high body mass index, high cholesterol, high blood glucose, low fruit and vegetable intake, and physical inactivity) account for 61% of loss of healthy life years from cardiovascular dis eases, and 61% of cardiovascular deaths. The same risk factors account for more than three fourths of deaths from ischemic and hypertensive heart disease. The Shift of affairs from national level to global status is influencing health challenges. On top of domestic problems, all countries must now deal with the international treat of transferring health risk. These new challenges are demanding forms of international cooperation, which, if developed, may also help to reconcile general national self-interest with international mutual interest. Economic globalization has been the fundamental driving force behind the overall process of globalization over the last two decades. It has been characterized both by a dramatic growth in the volume of cross-border flows and by major changes in their nature. International trade has grown at an accelerating pace nearly 8.6% per year (Bull World Health Organ vol.79 no.9 Genebra 2001). We cannot underestimate the implications of these cha nges for health. In addition to their own domestic problems, all countries must now deal with the international transfer of risks. The most obvious case of the blurring of health frontiers is the transmission of communicable diseases. Again, this is not a new phenomenon per se. The first documented case of a transnational epidemic was the Athenian plague of 430 b.c.7 The Black Death of 1347, which killed one-third of the European population, was the direct result of international trade. In the sixteenth century the conquest of the mighty Aztec and Inca empires was an early example of involuntary microbiological warfare through the introduction of smallpox. More recently, the global spread of the influenza pandemic of the early twentieth century accounted for far more casualties than did WorldWar I. What is new is the scale of what has been called microbial traffic. The explosive increase of world travel produces thousands of potentially infectious contacts daily, and jet plane s have made even the longest intercontinental flights briefer than the incubation period of any human infectious disease. Thus, a Peruvian outbreak of cholera turned into a continental epidemic in a matter of days in the early 1990s. Drug-resistant strains of tuberculosis have traveled from detention centers in Russia to Paris in just a few hours. Likewise, the Asian tiger mosquito, a potential vector for dengue fever virus, was introduced into the United States in the 1980s in a shipment of used rubber tires imported from northern Asia. These are all examples of what is called our new biocultural era, generated by radical changes in our environment and lifestyles according to Man and Microbes author Arno Karlen. Indeed, to make matters more complex, it is not only people, microbes, and material goods that travel from one country to another; it is also ideas and lifestyles. Smoking provides a clear example. Whenever a legal or regulatory battle against the tobacco companies is wo n in a State, everyone rejoices for the public but trembles for the consequences in other countries, because those very victories give those same companies the incentive to look for new markets with less stringent regulations. Already about four million people die from smoking-related causes every year. By 2020 that number will grow to ten million, making tobacco the leading killer worldwide. 1.2) 40 years ago, activities in international health were the domain of The World Helath organization (WHO), governments (based on bilateral agreements), and non-governmental organisations. This has changed. Today, new players (such as the World Bank and, increasingly, the World Trade Organisation) have an influence on international health. As globalisation of trade and markets takes hold, new coalitions and alliances are forming to examine and deal with the direct and indirect consequences on health. A new cooperation in international health, voicing concerns about rising potential inequal ities in health, both within and between countries is on the scene (G.Walt. Globalisation of international health The Lancet) Health systems around the world are facing similar challenges; many of them, as we just discussed, are related to globalization. Developed countries are witnessing problems of cost explosion, irrational use of technologies, and consumer satisfaction. Developing nations are dealing with problems of access to care, quality of services, and unregulated growth of the private sector. The communication revolution provides the opportunity to exchange information about the challenges facing national health systems and about the initiatives to deal with them. In addition to that, there are international private sectors that are willing offers assistance to health organizations globally, Utilizing there experiences and advancements. To be informative, such exchange should be based on sound evidence about alternatives, so that we may build a solid knowledge base of w hat really works that may be transferred across countries when it is culturally, politically, and financially reasonable. This obviously implies a strong international influence on health care. 1.3) European Countries had joined together in an effort to better the standards of health practices on workplaces. An example of this is the European Network for Workplace Health Promotion (ENWHP). Since it was established in 1996, this has been the vision of the European Union. The Network was founded when the European Union adopted the Programme of Action on Health Promotion, Education, Information and Training to improve public health standards in Europe in which workplaces were accorded a special role. Health promotion for employees has after all verifiable effects and serves the common interest as well as promoting social and economic prosperity. Since it was established, the ENWHP has grown steadily with a current 31 members from national safety and health and public health organiza tions from the EU Member States, Switzerland and countries of the European Economic Area. Over these years the EU has made quite an impact: successfully formulating a general definition for workplace health promotion (WHP) in Europe; developing standardised criteria for good quality WHP and publishing reports with models of good practice from a wide range of industrial sectors. The ENWHP has also developed a European toolbox of successful practices and identified strategies to help keep workers longer in employment. In addition, national networks were established by the Network in recent years on national level to disseminate information on WHP to a wider audience. However, to turn our vision into reality there still remains much to be done. A large number of companies and organisations still need to be convinced that WHP is a worthwhile investment. We are confident that by working together on our new initiatives, including our campaign to promote healthier lifestyles at work, we will continue to be successful over the coming years (European Network for Workplace Health Promotion). Workplace health promotion (WHP) is not just theoretical. It is taking place in enterprises and organisations with practical programmes running on-site. But, if the WHP measures are to bring real and long term improvements for the employees and to become a model for success, their quality must be guaranteed. The European Union membership on such organization is clearly giving a big impact on each of its countries industries. Workplaces in most of the EU members are now being complaisant to the standards that are being established. References 1. McMichael AJ, Beaglehole R. The changing global context of public health. Lancet, 2000, 356: 577-582. 2. Yach D, Bettcher D. The globalization of public health, I: threats and opportunities. American Journal of Public Health, 1998, 88: 735-738. 3. Yach D, Bettcher D. The globalization of public health, II: the convergence of self-interest and altruism. American Journal of Public Health, 1998, 88: 738-741. 4. Lee K. Globalization and the need for a strong public health response. European Journal of Public Health, 1999, 9: 249-250. 5. Globalisation of international health The Lancet, Volume 351, Issue 9100, Pages 434-437 G.Walt 6. Dr. Maria Dolores Solà ©, Dr. Karl Kuhn Chairpersons of the ENWHP 2.1) Costs of benefits for environmental awareness in a health care perspective will depends on the size, sector, structure, market, culture and the regulatory context. Norms and values have implications on research, how you view the relationship between environment, Health care and Profitability. Legislation is the main influencing factor for companies to do environmental changes. Adopting an environmental awareness policy may have several items to consider: Perspectives on regulation International policy and voluntary initiatives Strategies and the environment Environmental Manage ment Systems and Standards Environmental Reporting Environmental Management Accounting There are three perspectives to consider in strategic environmental policy: External influences (Industry structure, market, environmental risks, regulatory influences, customers, NGOs) Firm context (market strategy, internationalisation, organisation structure, environmental risks etc.) Network (Dependency relationships with suppliers and customers and their environmental problems. A company with more control can have a more offensive environmental strategy) There are three sets of issues to consider in strategic environmental policy: Risk (higher for multinational companies) Supply chain management Green capabilities Regulating environmental awareness and policies may lead to the following: Pollution haven (a country attracts investors thanks to lax or no regulation) Flight (Investors leave a country because of strict regulation) Innovation (Strict regul ation forces companies to innovate) Protectionism (Regulation to protect certain companies from competition) Cooperation (companies cooperate with regulators) In addition to all implication is the accounting aspect. Environmental management accounting plays a key role in establishing and adopting an environmental awareness policy. Here are four different definitions to environmental costs: The costs of business impacts on the environment and society for which firms are not legally accountable (also called externalities or external costs) The financial burden for firms as a consequence of environmental regulation The costs of environmental measures All costs that are relevant for environmental management Cost calculation should also be used for the following reasons: Internal communication External communication Policy formulation Capital budgeting Negotiations Cost allocation 2.2) Based on the economics of adopting a policy of environment al awareness, in order to maintain the environment it should be managed accordingly. Part of the over all preparatory set up in adopting a policy is the Environmental Management System (EMS). An environmental management system will also include improvement cycles. An EMS is that part of the overall management system which includes the organisational structure, responsibilities, practices, procedures, processes and resources for determining and implementing the organisationas overall aims and principles of action with respect to the environment. The actions to be should encompass the totality of organisational, administrative and policy provisions to be taken by a firm to control its environmental influence. The organization should be identifying environmental impacts and legal obligations, the development of a plan for management and improvement, the assignment of responsibilities and the monitoring of performance. According to Prof.dr. Ans Kolk of Amsterdam Business School You s hould check and act. The organization must also educate its stakeholders, influencing them to act in the maintenance process through Sustainable development and Social responsibility to maintain the goal in the environment. Every action will always be rooted back to the goal of sustainability through responsibility. 2.3) In order to measure workplace health and safety we need engage in several assessments first. Through Risk management we are able to assess the risk of a specific process involved in a workplace. Risk management is an ongoing process that should be undertaken now, if it has not been done before, When any new work is planned including laboratory/workshop/course work, When planning or making a significant change, After an incident, at regular intervals appropriate to the nature of the workplace and the hazards present and when legislative obligations including regulations change. We also need to consider the Hazard of the specification versus the risk. A hazar d is something with the potential to cause harm. This can include chemical substances, plant, live electricity, work process and/or other aspects of the work environment. Risk on the other hand is the likelihood that illness, injury or even death might result because of the hazard. Here are the basic steps in indentifying: Identifying the Hazard Assess and prioritize Risk Analysing the risk involves determination of the: Consequences outcome of an incident Exposure interaction with hazard Probability likelihood that consequences will occur once individual is exposed In order to further assess risk and hazard in the workplace, you can also use a risk calculator. Here is how to use a Risk Score Calculator: Estimate the Probability Estimate the Exposure Identify the Consequences Determine the Risk After the steps in identifying the risks and hazards of the work environment and the job itself, we need to assess the control measures that are esta blished in the organization. The control measures should adequately control the risks; not create other risks and allow the staff to do their work without undue discomfort or distress. There will be a need to develop work procedures in relation to control measures, which may involve clearly defining responsibilities of management, supervisors and workers. Most organization uses the Hierarchy of Control Measures: Eliminate the hazard is the first choice. The ideal solution is to get rid of the hazard completely. This is the most effective control measure and should always be considered first. If the hazard cannot be eliminated completely there are a number of control options that can be used to prevent or minimise exposure to the risk: Substituting a less hazardous material, process or equipment; Redesigning the equipment or work process; Isolating the hazard through engineering separating the worker from the hazard; Administrative controls involve minimising exposure to a risk through the use of procedures or instruction. This could involve limiting the exposure time to a particular hazard such as noise or radiation; Personal Protective Equipment (PPE) is used as a last resort when exposure to risk is not or cannot be minimised by other means. PPE is worn by people as a final barrier between themselves and the hazard. This measure does not control the hazard at the source but relies on behaviour modification for its success. The success of this control is dependent on the correct PPE being chosen, worn correctly, used correctly and maintained in good condition. Administration and the use of personal protective equipment are the lowest priority on the list of controls. These controls should NOT be relied on as the primary means of risk control until the. All relevant persons must be knowledgeable about the control measures being implemented; in particular, the reasons for the changes. We need to check if adequate supervision to verify that the control measures are being implemented and used correctly. We also need to know if the measures are being monitored and reviewed. Monitor: Chosen control measures have been implemented, as planned? Control measures are working and are adequate? Did the implementation of the control measures create other hazards? Review: Has anything changed over time since the process was implemented? Is the control of risks still adequate? Was the risk management process conducted effectively? References: Risk Management Code of Practice 2007: Department of Employment, and Industrial Relations Australian Standard AS/NZS 4360:2004 Risk management Workplace Health and Safety Act 1995 Workplace Health and Safety Regulations 2008 3.1) Protecting the health and safety of employees or members of the public who may be affected by your activities is an essential part of risk management and must be led by the board. Failure to include health and safety as a ke y business risk in board decisions can have catastrophic results. Many high-profile safety cases over the years have been rooted in failures of leadership. Health and safety law places duties on organisations and employers, and directors can be personally liable when these duties are breached: members of the board have both collective and individual responsibility for health and safety. By following this guidance, you will help your organisation find the best ways to lead and promote health and safety, and therefore meet its legal obligations. The starting points are the following essential principles. These principles are intended to underpin the actions in this guidance and so lead to good health and safety performance (The Health and Safety Executive (HSE) has further advice on leadership for small businesses and major hazard industries). An organisation will never be able to achieve the highest standards of health and safety management without the active involveme nt of directors. External stakeholders viewing the organisation will observe the lack of direction.( Health and safety leaders in the public and private sectors (HSE).) Here are the responsibilities of an organization to its employees as the law stated: provide a written health and safety policy (if they employ five or more people); assess risks to employees, customers, partners and any other people who could be affected by their activities; Arrange for the effective planning, organisation, control, monitoring and review of preventive and protective measures; Ensure they have access to competent health and safety advice; Consult employees about their risks at work and current preventive and protective measures. Failure to comply with these requirements can have serious consequences for both organizations and individuals. Sanctions include fines, imprisonment and disqualification. For many organisations, health and safety is a corporate governance issue. The board should integrate health and safety into the main governance structures, including board sub-committees, such as risk, remuneration and audit. Guidance on the Corporate Governance requires companies to have robust systems of internal control, covering not just narrow financial risks but also risks relating to the environment, business reputation and health and safety. The organisation will find itself facing service improvement targets. Using corporate and clinical guidance, it set about taking a whole systems approach to managing corporate risk, giving one of its directors responsibility for the leadership of health and safety for the first time. Health and safety is also made a key item on the board agenda. This will result in a much better integrated health and safety management system that increases the opportunity to identify and manage all corporate risks, and a much more open culture, improving reporting and monitoring. The board actively promotes a culture that gives st aff the confidence to report incidents. Addressing health and safety should not only be seen as a regulatory burden. It offers significant opportunities. Benefits can include: Reduced costs and reduced risks -employee absence and turnover rates are lower, accidents are fewer, the threat of legal action is lessened; Improved standing among suppliers and partners; A better reputation for corporate responsibility among investors, customers and communities; Increased productivity employees are healthier, happier and better motivated. In addition, heres a list of responsibilities and actions that should be done and addressed regularly in the executive level of the organization: Health and safety should appear regularly on the agenda for board meetings. The chief executive must give the clearest visibility of leadership, but some boards find it useful to name one of their numbers as the health and safety champion. The presence on the board of a health and safet y director can be a strong signal that the issue is being taken seriously and that its strategic importance is understood. Setting targets helps define what the board is seeking to achieve. A non-executive director can act as a scrutineer ensuring the processes to support boards facing significant health and safety risks are robust. 3.2) While organizational interest in diversity continues to grow, many programs that support diversity initiatives are faltering. As a consequence, the valuing diversity movement now stands at an important crossroads. To say that todays choices and the actions taken will determine the ultimate success or failure of this vitally important initiative is no exaggeration (Marilyn Loden, IMPLEMENTING DIVERSITY). Workplace diversity refers to the variety of differences between people in an organization. That sounds simple, but diversity encompasses race, gender, ethnic group, age, personality, cognitive style, tenure, organizational function, edu cation, background and more. Diversity not only involves how people perceive themselves, but how they perceive others. Those perceptions affect their interactions. For a wide assortment of employees to function effectively in a healthcare organization, human resource professionals need to deal effectively with issues such as communication, adaptability and change. Diversity will increase significantly in the coming years. Successful organizations recognize the need for immediate action and are ready and willing to spend resources on managing diversity in the workplace now. Benefits of Workplace Diversity An organizations success and competitiveness depends upon its ability to embrace diversity and realize the benefits. When organizations actively assess their handling of workplace diversity issues, develop and implement diversity plans, multiple benefits are reported such as: Increased adaptability. Have a diversified organization has its own challenges which needs to be manag ed effectively. Implementation of diversity in the workplace policies This can be the overriding challenge to all diversity advocates. Armed with the results of employee assessments and research data, they must build and implement a customized strategy to maximize the effects of diversity in the workplace for their particular organization. Successful Management of Diversity in the Workplace Diversity training alone is not sufficient for your organizations diversity management plan. A strategy must be created and implemented to create a culture of diversity that permeates every department and function of the organization (Greenberg, Josh Diversity in the Workplace: Benefits, Challenges and Solutions). Here are approaches to better manage diversity in a work place: Assessment of diversity in the workplace Development of diversity in the workplace plan Implementation of diversity in the workplace plan Foster an attitude of openness in your organization Promote di versity in leadership positions Utilize diversity training Don’t waste time! Our writers will create an original "The global health threat of climate change" essay for you Create order