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a 6 page paper double spaced on my topic domestic violence and social issue trauma. APA format with a citation page and a title page. I need this by tomorrow morning.

ENGL 101 – Fall 2021 Michael Amrozowicz, Instructing Final Research Paper Description and Guidelines – 20 Points Due Date: On Blackboard by 5:00PM on Wednesday, 15 December Your final research paper will consist of a 6-8 page typed and double-spaced paper and any supporting materials you’d like to include such as notes, outlines, and drafts that show your working process. Your paper’s structure should look something like the inverted pyramid we discussed in class for our Midterm Portfolio. Your topic/social issue is the large end on top, and you should concentrate on focusing in on detail and specificity as the paper progresses, as it moves from topic/social issue to thesis statement/argumentative claim (the middle level of the pyramid) to textual support (the bottom, pointed end of the pyramid). You are building on the work you’ve done for the Midterm and Research/Thesis Projects, and you should be revising the material you composed for those projects for inclusion in your final paper. But when I say revise, I mean revision: do not simply copy and paste from your earlier projects. The material you revise must be contextualized and adapted to fit into the argument of your final paper. I will deduct points for copy-and-pasting earlier work. You will need to choose and work with three secondary sources for your final paper. These are to be articles from peer-reviewed journals in the library’s databases, book chapters from books found in the library, or other credible sources you may have found for your Research/Thesis Project. The materials that we read for class is not to be counted in this number, although you are welcome to use them for establishing topics/social issues/definitions that you will be discussing in your paper. Paper Structure: Topic and Social Issue: This should comprise the first page or so of your paper. What set of ideas are you working within? What’s your range, your field of ideas? You should be explaining what topic and social issue you will be working with in this first paragraph/page. This is where you should expand the first paragraph or two of your Midterm draft to account for the information you’ve found about your topic since then, and also to hone in on a specific discourse or element of your social issue that you might have identified since your Midterm. Claim: Your claim should comprise the second paragraph/page of your paper. Your claim should say and argue something specific about your social issue and how it works. Follow the structure set forth in the Research/Thesis Project and the book Writing Analytically. This is where you’ll revise your revised thesis statement to explain to your readers what you will be arguing in your paper and how you will be arguing it. It will also be helpful to give your readers a road map for how to travel in your paper, i.e. how to read it. In the last couple of sentences of this paragraph you can explain to your readers what the structure of the paper is and how it works. Support: Your analysis and development of your argument about your social issue should comprise the next 3-6 pages of your paper. Here you will also use your secondary sources to support your argument and to provide you with any terminology that will help you explain your argument in the context of your social issue. Make sure you remember to define and contextualize the material you use from your secondary sources. These sources should be used to support your claim in some way – don’t simply throw a discussion of them in as filler. You should list ALL the texts you discuss in a works cited page (MLA format – see the MLA Handbook on our Blackboard page for how to do this) to be included at the end of your paper. Further strategies for developing an analytical research essay: 1. Use “The Method” (Writing Analytically 37-39) to develop a set of observations and questions about evidence. 2. Push those observations to conclusions by asking the question, “So what” and filling in the statement, “This seems to be about X, but it may also be about Y” (see: WA, Chapter 4). 3. Throughout your essay, be sure to ground each observation in concrete textual detail (specific terms, concepts, images, quotations, etc.), and be sure to follow every observation with an answer to the (silent) question, “so what,” to ensure that each paragraph is both grounded in detail and pushing towards analysis and interpretation. 4. Be sure to proofread your paper before you hand it in; watch out, especially, for sentence fragments, comma splices, run-on sentences, errors in agreement and reference, faulty sentence structure, misused punctuation (commas, apostrophes, etc.), and spelling errors. 5. Finally, be sure to avoid: over-generalization, personal judgment, naturalizing assumptions, and plot summary (see: Writing Analytically, Chapter 2). Common stylistic errors and mechanical problems and how to fix them: Punctuating quotations within sentences (placement of quotes, commas, periods inside quotation marks, semi-colons outside quotations, and page numbers just before the final punctuation of your sentence) –> Susan said, “hello!”; Cruso responded with a loud grunt (Coetzee 14). Splitting infinitives –> My dog likes not only to run, but also to eat sticks. Subject-verb agreement, especially around prepositional phrases –> The imprisonment of cars by towing companies is a vicious and brutal practice. (Writing Analytically, 314-16). Possessives v. plurals –> mothers vs. mother’s /it’s vs. its (Writing Analytically, 320-21). Comma splices and compound sentences (Writing Analytically, 311-314). Miscellaneous comma errors (Writing Analytically, 321-23). Faulty parallels or shifts in sentence structure (Writing Analytically, 316). Use of passive or weak verbs –> It is the nature of all mankind to park without paying attention to street cleaning signs. Better to say: people ignore street cleaning signs when they look for parking. Overly broad/general statements—watch any sentence that begins with the words “human nature,” “human kind,” “mankind,” “men,” “women”; you get the idea… Verb tenses—always watch to make sure your tenses make sense in a given sentence. Also, when you describe the action that is happening in a novel, you speak of it in the present tense –> Crusoe skins his goats and teaches his parrot to call his name. It’s okay to use the first person singular, and speak as an “I.”
Table of Contents Introduction Similarities Differences References Introduction During the imperialist era of the 19th century, there was a common stereotype held in the west that a nation’s might was measured by the extent of its political power over regions out of the main state. This stereotype was largely accepted by the Japanese elites during the Meiji era that lasted between 1868 and 1912 and in which Japan took up modernization operations. Based on its economic, technological, and educational advancements, Japan escaped the colonized lot of Asia and joined the ranks of colonizers. In its desire to spread out into East Asia, Japan encountered resistance and fought wars with China and Russia to gain control of Taiwan and Korea. Japan marched into Taiwan in 1895 and later Korea in 1910 and ruled them until its defeat in World War II of 1945 to China, the USSR, and the United States of America. There are lots of similarities and differences in the Japanese colonial rule of Taiwan and Korea. This paper seeks to address these similarities and differences between the Japanese rule of Taiwan and Korea. Similarities To support production and market development, Japan highly valued infrastructure and achieved this through the development of railway networks and ports in Korea and Taiwan (Lee, 2010). “Japan invested heavily on Industry and infrastructure” (Aviles, 2009), a good infrastructure was necessary for transportation of agricultural produce to Japan and shipment of ammunitions to army posts. There was miniature development in terms of infrastructure in Taiwan at 1900; 20years later, it had a railway stretching for over 600 kilometers and more than 3000 kilometers of road and port services. Japan discouraged the establishment of the local religious beliefs in both colonies and endorsed its faith, Shintoism. In Taiwan, Buddhists and Taoinist religious convictions were downcast and prosecuted for Shinto to be established. The local Taiwan population was encouraged to pay regular visits to the jinja (Japanese shrine) and was expected to worship taima every morning (Duus, Myers,
Memorandum writing (Military Memorandum Pre-Writing ).

This assignment can be completed after completing chapter 1 of your textbook and reading the documents provided for you in assignment section 1. The problem you will solve is described below, after the assignment overview, and involves using soldier fatality data to determine an intervention strategy.Writing Requirements This assignment is the first of four steps in completing the military memorandum. This assignment will require you to articulate an understanding of the problem and the audience, by answering the questions about the problem below. Then you will demonstrate an ability to solve, understand, and explain a statistical problem in language appropriate to the professional status and background of the audience you are addressing by completing a draft of your military memorandum. To understand what you are expected to do in the memorandum review the Military Memorandum Guide. You may also want to look at the rubric on assignment 1.4 to see how the final assignment in this memorandum series will be graded. The linked Military Memorandum Pre-writing Example provides an illustration of how the assignment should be laid out. You will be expected to follow the provided format for presenting the material, a practice that will extend into your professional life. You are expected to use editing software to review your work for grammar and punctuation errors prior to turning it in. What will you be graded on? This assignment will be graded on completeness ONLY. However, it is the document on which you will get feedback from your classmates, so you should produce your best work, in order to get the best possible feedback. Be sure to look at the assignment rubric to assure that you have completed the required elements prior to turning in the assignment,Problem Definition Questions Read the problem description at the bottom of this assignment. Then, cut and paste each question below into your assignment and provide the answers below each question. These answers will be located on a separate page before the memorandum. This page will NOT be included in the final memorandum. What problem you have been asked to address? While you are using statistics to support a particular answer, the question you are being asked to address is not a formula or a description of the calculations you will complete. You need to describe the problem you are being asked to solve in plain language. How can the data provided inform an intervention recommendation? What is the outcome you are supposed to provide in this memorandum? a) To whom have you been asked to address this memorandum (find the name of the CURRENT person holding the job and their official title)? b) What is this person likely to need from you? (You may need to do a quick internet search of this role.)a) Who will you be copying this memorandum to (they are a secondary audience). b) What are the addressees likely to need from reading the memorandum? (This is a critical thinking exercise, so research what the addressees’ responsibilities are and use that to think about what they need to know from you).Problem Description: The United States military has been involved as a peace-keeping force in a humanitarian effort to prevent further genocide in the country of Lorian. Many soldiers have died in this effort. The government has recently approved the use of emergency funds to reduce the loss of soldiers’ lives, but funding will only support one initiative. The officer in charge of the theater of operations, your commanding officer, has asked you, a military engineer, rank of Lieutenant, to evaluate the situation and recommend a course of action to reduce the number of soldier fatalities and enable the peace-keeping force to remain in place. Analyze the provided data regarding soldier fatalities in a one-month period and make a recommendation regarding what the government and military should do. Audience: Any time you prepare a professional document, you should consider the audience (Links to an external site.)that you are writing the document for. You should tailor the content, language, tone, and structure of the document to the audience you are addressing. This document is being prepared for senior-level government and military members. Ask yourself what they can be reasonably expected to know about this topic, and what they need to know to make an informed decision. Address the memorandum to The Current United States Secretary of Defense (Find the current Secretary of Defense’s name and title). Provide carbon copies (cc)’s to:The House of Representatives Defense SubcommitteeThe United States Senate Defense SubcommitteeTone: The Audience for this document requires that the style (Links to an external site.) is precise and professional.Utilize plain language when describing your analysis, as you cannot assume all readers will be statistically literate. However, there are also some who will understand statistics and will want to understand the statistical logic that you used to determine your recommendation.Start the document with a summary that readers can read to understand the essential elements of the document – the context of the issue, what is being examined and how, and the recommendation you will make.Develop the document around a direct, coherent message (thesis), (Links to an external site.)and clear evidence (Links to an external site.)to support it.Do not use contractions, slang or colloquialisms (Links to an external site.), clichés (Links to an external site.), abbreviations, or text message shortcuts.Edit and check grammar and spelling before turning the document in. Data: The attached data spreadsheet documents the causes of the deaths of soldiers who died in the most recent full month. Each number on the attached spreadsheet identifies the cause of the death of one soldier who died in that month. The cause of death represented by each number is identified in the table below. Use the data from the entire month in your calculations. Soldier Fatalities DataData Coding: Cause of Fatality Code Typhus 1Dysentery2Cholera 3Staph infection4Fragment wound 5Burn wound6Gunshot wound7Exploding ordnance wound 8Blood hemorrhage 9RubricCA 1.1 P&S 2020 S (1)CA 1.1 P&S 2020 S (1)CriteriaRatingsPtsThis criterion is linked to a Learning OutcomeProblem Definition QuestionsAll “Problem Definition Questions” have been seriously addressed.1.0 ptsAll “Problem Definition Questions” have been seriously addressed0.6 ptsThe “Problem Definition Questions” have not all been addressed or have not all been addressed seriously0.0 ptsProblem Definition Questions are missing or not addressed seriously1.0 ptsThis criterion is linked to a Learning OutcomeMemorandum HeaderA complete memorandum header is included. This means the required items are included, laid out correctly, and the information for each item is included.0.5 ptsA complete memorandum header is included0.3 ptsA memorandum header is included but is incomplete0.0 ptsThe memorandum header is missing0.5 ptsThis criterion is linked to a Learning OutcomeResearchA minimum of 2 Sources used to support your recommended intervention are identified in the correct location0.25 ptsFull Marks0.0 ptsNo Marks0.25 ptsThis criterion is linked to a Learning OutcomeSummaryA “Summary” section is included0.5 ptsA “Summary” section is included0.0 ptsA “Summary” section is missing0.5 ptsThis criterion is linked to a Learning OutcomeAnalysisAn “Analysis” section is included0.5 ptsAn “Analysis” section is included0.0 ptsA “Analysis” section is missing0.5 ptsThis criterion is linked to a Learning OutcomeBar GraphA bar graph that enhances the understanding of the document and is easy to read is included0.5 ptsAn easy to read, fully labeled bar graph is included0.3 ptsA bar graph is included but is poorly done in one of the following ways – the title is missing, it is not fully labeled, it is not easy to read, it is poorly organized0.0 ptsThe bar graph is missing0.5 ptsThis criterion is linked to a Learning OutcomeConclusionA “Conclusion” section is included0.5 ptsA “Conclusion” section is included0.0 ptsA “Conclusion” section is missing0.5 ptsThis criterion is linked to a Learning OutcomeSignatureA “Signature” section is included, complete and laid out correctly0.25 ptsA “Signature” section is included, complete and laid out correctly0.15 ptsA “Signature” section is included, but in incomplete and/or laid out incorrectly0.0 ptsA “Signature” section is missing0.25 ptsThis criterion is linked to a Learning OutcomeCarbon CopyA “Carbon Copy” section is included and correctly identified0.25 ptsA “Carbon Copy” section is included and is correctly identified0.15 ptsA “Carbon Copy” section is included but incorrectly identified0.0 ptsA “Carbon Copy” section is missing0.25 ptsThis criterion is linked to a Learning OutcomeAppendixAn “Appendix” section is included, laid out on its own page and titled correctly0.25 ptsAn “Appendix” section is included0.0 ptsAn “Appendix” section is missing0.25 ptsThis criterion is linked to a Learning OutcomeTableA table that concisely identifies the data is included, titled, fully labeled, and laid out and organized well0.5 ptsAn easy to read, fully labeled table is included0.3 ptsA table is included but is poorly done in one of the following ways – the title is missing, it is not fully labeled, it is not easy to read, it is poorly organized0.0 ptsThe table is missing0.5 ptsTotal Points: 5.0
Memorandum writing (Military Memorandum Pre-Writing )

Impacts Of Social Networks On Social Behaviour

Social network sites have become a global phenomenon that plays important roles in our society today. It is a social milieu that allows individuals to present themselves, communicate with one another and to maintain relationships. These SNSs (Facebook, LinkedIn, Twitter, and MySpace) are rapidly increasing visibly among the University students. Social network does not only influence students learning outcome but it also help the University students to attain social acceptance as well as adapting to University culture which may play central role towards improving their learning outcome. Several researchers revealed that SNS as technological tools can be used to effectively improve student-student and student-teacher interactions in higher institutions. In this regards SNS plays a prominent role in learning environment as a major conduit for getting resources, knowledge, and social support and also provides help for students preparing for or/ finding employment. On the other hand, many researchers observed that students spend several hours in a day attending to different social network sites even during lecturers and library sessions thus creating distractions and reducing the time to focus on their studies. This discourse therefore reviews the benefits and obstacles of social networks on social behaviour and academic performance of students. It also reviews the attitude of students towards the use of technology, SNS and how social network can improve learning style as it portends great promise towards enhancing their academic performance. 1.0 Introduction Academic institutions all over the world especially in developed countries have made tremendous investment in computer and internet infrastructure with the hope that this would result in the utilisation of web-based knowledge resources which may leads to significant increase in academic performance and productivity of students or staff (Oskouei, 2010) . However, this investment may not have yielded the desired goals of increasing learning quality and productivity of the students because these resources are used for both academic and non-academic works (Oskouei, 2010). It has been estimated that young adults are the highest computer and internet users in the world population today, about 46% of them uses it for completing school assignment, 36% for e-mail or instant messaging and 38% for playing computer games (DeBell and Chapman, 2006). Social network sites which are online communication tool that have existed less than a decade allows its users to create public and private profile thus enabling them to interact with people in the same network (Boyd and Ellison, 2008). Social networks can be defined as web-based activities that allow individuals to build public and/or semi-public profiles within a confined system; articulate and connects to list of other users with which they are connected; view and check their list of connections with the ones created by others inside the system(Boyd and Ellison, 2008, Kirschner and Karpinski, 2010). Examples of the new phenomenon of social networks are MySpace, Facebook, LinkedIn, and Twitter. Facebook is the leading social network in many countries followed by Twitter and LinkedIn in popularity. It has been reported that Facebook have 901 million monthly users and more than 125 billion friends connected at the end of March, 2012 (Karpinski et al., 2013). The positive and negative impacts of social network on students’ social behaviour and academic achievement can be examined by their engagement, collaborative work, creativity, distraction, and grade point average (GPA). Research has shown that students participation on social networks have a positive connection to their engagement, and negative connection to their academic performance. Many researchers indicate that students’ academic performance can be increased by enhancing their engagement, and it has been stated that students’ engagement has a significant predictor of their academic performance (Wise et al., 2011). The relationship between students’ academic engagement and their academic performance is in agreement with (Junco, 2012). They reported that students’ engagements are powerful forces for psychosocial development and academic success. Social networks have the potentials of improving learning styles, as they provides alternative to traditional teaching format such as creation of online classroom community, and also enhancement of student-teacher and student-student interaction (Merchant, 2012) Social network increases social interactions and allows easy communication between, families, friends, neighbourhoods and global communities. Most social networks incorporate lots of communication tools like mobile connectivity, blogs, photos and video sharing which allows cross-posting to each other as desired by the users (Merchant, 2012) It has been reported that social network interactions allows quality relationships, connectedness, positive behaviours and also sharing of relevant information have been observed on social network sites (Martin

Art History

essay help online
Please answer each question as a separate paper. Thank you.

#1. Discuss the structures, motivations and qualities of terrorist groups.#2. Evaluate how the Diplock Commission was set up to look at ways of dealing with the legal aspects of controlling terrorism in a democratic society.#3. Analyze Iran?s involvement in sponsoring global terrorism.#4. Evaluate the threat that may be posed to the U.S. from international terrorists entering via Central and South America.

Book: Terrorism Today: The Past, The Players, The FutureJeremy R. Spindlove & Clifford E. Simonsen, 2017

Social Issues that Impact Families

Social Issues that Impact Families.

Throughout this unit, you have learned about many changes and social problems
that impact families. In this Assignment, you will choose one of the three
following social problems that impact families: divorce, one-parent families,
family violence.
Project Specifics:
Your paper should be between 800 and 1000 words, double spaced, not
including your title and reference page. No points will be deducted if APA formatting is incorrect, points can be
deducted if there is no attempt to cite references. Use the textbook and at least three outside references from the library
or other reputable sources to support your project. Please use the Research, Citation, and Plagiarism document found in Doc
Sharing to help you with formatting your project, or ask your professor
for assistance.
Part I: Begin your paper with a discussion of the social problem you have
chosen and explain why you have chosen this particular social problem.
Part II: As human services professionals, it is important to be able to
view social problems from multiple perspectives. There are often many people
involved in a social problem. Some of the different people involved in social
problems like divorce, one-parent families, and family violence are the mother,
the father, and children. All of these people will be impacted by the problem in
a unique way, and they may have different perspectives about what is occurring.
With Part II, you are going to have the opportunity to examine the social
problem you chose from multiple perspectives.
If you chose divorce or one-parent families, discuss how the parents and the
children involved view the issue. If you chose family violence, discuss how the
abused woman, and the children involved view the issue.
Part III: Conclude your paper by discussing how society views the social
problem that you wrote about. In addition, discuss your role as an advocate. How
can you work to create awareness and teach others about diversity and
Your paper should be between 800 and 1000 words, double spaced, not including
your title and reference page. While no points will be deducted if APA
formatting is incorrect, points can be deducted if there is no attempt to cite
references. Use the textbook and at least three outside references from the
library or other reputable sources to support your paper. Please use the
Research, Citation, and Plagiarism
Social Issues that Impact Families

Multiple Sclerosis (MS): Pathophysiology and Management

Multiple Sclerosis (MS): Pathophysiology and Management. Multiple sclerosis (MS) is an autoimmune inflammatory disease, in which multiple lesions or plaques are formed within the brain and spinal cord. It can be characterised as a demyelinative disease of the central nervous system that is associated with relative loss of the myelin sheath and axon. The hallmark feature of the disease is the loss of this myelin sheath which leads to scarring and various other symptoms including muscle weakness and visual disturbances. The myelin sheath is a vital component of the axon as it provides protection and insulation (figure 1). Demyelinization of the sheath exposes the underlying axon and can lead to defects in synaptic transmission. In healthy individuals, myelin repair is spontaneous however in patients with MS this repair process occurs slowly or not at all. The integrity and functioning of the nervous system relies on myelinated neurons which allow fast and efficient transfer of electrical impulses and when this function is impaired it can contribute to complete or partial loss of central nervous system (CNS) functions. MS can be a potentially debilitating disease with unpredictable results and sadly there is no cure, however there are some treatments available that assist in the management of the disease. There has been noted beneficial effects with either immunosuppressive or immunomodulatory therapies, though these effects are somewhat reserved as patients responses to treatment are variable (lassmann, 2002). There have been many investigations into the use of novel immunomodulatory therapies, in particular, those using sex hormones such as oestrogen and testosterone. It is thought by many (Voskuhl 2002, Eikelenboom et al 2009, Nicot 2009) that gender is a contributing factor to the initiation and course of MS and that underlying mechanisms of the disease can be linked to sex hormones. The contribution of sex hormones and their actions in the management of the disease will be further discussed. The immune system plays fundamental role in Multiple Sclerosis The immune system can be linked to the gender differences in MS, as sex hormones are thought to affect the immune systems cytokine response (Eikelenboom 2009). It has been perceived that cytokines play an important, however complex, role in the pathogenesis of multiple sclerosis, as well as many other inflammatory diseases (Imitola et al, 2005). The disease is thought to be initiated by the release of Th1 cells which have a pro-inflammatory affect (Figure 2). Subsequent to this is an anti-inflammatory response that is mediated by the Th2 cytokines. MS is thought to occur in genetically susceptible individuals in whom Th1 autoimmunity is activated, thus multiple sclerosis is seen primarily as a Th1- mediated auto-immune disese (Gold et al, 2009). One of the more recent theories on MS pathology is that the establishment of the disease is thought to be triggered by an imbalance between Th1 and Th2 cytokine responses (Van den Broek et al 2005). It has been known for some time that gender and gonadal hormones can influence and modulate the immune cytokine response (Schuurs et al 1990, Van den Broek et al 2005). The differences between males and females are first seen during teenage years when testosterone levels in males and oestrogen levels in females start to increase. Furthermore, multiple sclerosis is more common in those who have reached sexual maturity and the disease can be influenced by other changes in hormone levels such as menopause and menstruation (Smith et al 1992). Thus, factors such as gender, that contribute to sex hormone levels, and cytokine regulation and secretion are fundamental in understanding MS pathogenesis. Gender issues in Multiple Sclerosis There have been several studies that have linked gender to the clinical course of MS (Voskuhl 2002 , Reipert 2004). Females have been found to be most frequently affected by MS and this is the case in many other auto-immune diseases (McCarthy 2000). Also, there is higher disease prevalence and better prognosis amongst women with the disease (Whitacre et al 1999). The severity of the disease may often be greater in men, as both sexes follow a different course of the disease. The onset of MS in males is linked with the beginning of the decline in bioavailability of testosterone in healthy men (Reipert 2004). Therefore, susceptibility and severity of the disease between men and women are frequently contrasting. The causes of gender specificity remain unclear; however current interpretations may push towards identifying factors that lead to female bias in MS. Due to the fact that females are dominated by the the disease, it can be proposed that differences in sex hormones may offer protection to males against the disease. The influence of sex hormones in Multiple Sclerosis It has already been established that gender plays a role in MS susceptibility. These differences can be explained by differences in sex hormones and their affect on the brain i.e. roles in damage and repair. Female to male ratios are seen to be approximately 2:1. MS susceptibility has been tested in EAE mice models (Figure 3) and the outcome has been that female mice are most susceptible when compared to male mice (Voskuhl et al, 2001). Sex hormones, oestrogen and testosterone may offer neuroprotection. For many years, it has been known that the prevalence of multiple sclerosis is higher in females than it is in males. This is often the case in many auto-immune diseases. Therefore, it is fair to say that sex hormones play specific roles in the immune responses of these auto-immune diseases such as Multiple sclerosis and Rheumatoid Arthritis (Cutolo 1997). Research into the roles of sex hormones in the immune system has been of topic sincethe 1950’s and 60s (Kappas et al 1963). It is differences in production and secretion patterns of cytokines that seems to vary between males and females with MS and each sex hormone is associated with different clinical manifestations of multiple Sclerosis. Therefore, the concentrations of sex hormones within the body during a certain period can influence the production of cytokines, which in turn affects disease severity and recovery. Oestrogens Oestrogen can been described as an immunomodulator and its concentrations can vary within the body and can rise or fall, for example pregnancy, menstruation and menopause. The effects of oestrogen on the immune response have been studied in both In vivo and In vitro environments. In particular its effects on cytokine production have been noted. Also, it is thought that oestrogens have two effects on the immune system; one involving the suppression T cell development and the other stimulation of antibody production (Van den Broek). Oestrogen is one of the most researched sex hormones, which is thought to have a protective and favourable affects against the progression and clinical course of MS (Eikelenboom et al 2009). This effect is shown in pregnancy, particularly during the third trimester, where the levels of Oestrogen (and progesterone) are high (Figure 4) . The urine of nonpregant and pregnant women was tested for levels of oestrogen. In non pregnant women, the ratio of estriol to estron plus estradiol was approximately 1:1 compared to 10:1 in pregnant women (Drača et al 2006). These increased levels of oestrogens are thought to delay MS progression, which is beneficial. It was found that MS patients experienced clinical improvement during pregnancy (VOSKUHL ,2007) and decreased relapse rates. However, these effects are not permanent and subside post-partum. There may be periods of disease exacerbation post partum, where there is an increase in relapses (Sandyk 1996). Although pregnancy offers favourable disease conditions, these effects have not been conclusively shown to have long term effects. This theory has been supported in EAE, where a reduction in EAE was most prominent during late pregnancy. In addition, Van den Broek has shown that castrated female mice experience a delay in the onset of the disease, when supplemented with oestrogens. This may be indicative of disease modification by hormones. Furthermore, oral contraceptives, containing oestrogen may have similar effects in altering the course of the disease (Jama and archives journals 2005), however long term effects have not been extensively confirmed. Thus, the beneficial effects must outweigh the side effects of long term use for sufficient justification. As previously mentioned Th1 and Th2 cells are involved in the mediation of the disease. Using the EAE animal model, it has been demonstrated that oestrogens promote a Th2 phenotype, which is considered to have anti-inflammatory affects (offner et al 2006). These protective effects seen in EAE, propose the use of oestrogen as a possible therapy for multiple sclerosis. During periods of high oestrogen levels, there is seen to be a decrease in pro-inflammatory cytokines such as TNF-α and an increase in suppressor cytokines such as IL-10, which are known to be beneficial on the clinical manifestations of Multiple Sclerosis. Furthermore, oestrogens have been shown to inhibit the production of nitric oxide and TNF-α, which are both toxic to myelin producing oligodendrocytes (Bruce-keller et al 2000). Past findings suggest that oestrogens used as hormonal supplementation may be beneficial in menopausal and post menopausal MS patients (Sandyk 1996). It was found that the risks hormonal replacement therapy outweighed the benefits in healthy menopausal women; however the risk/benefit ratio was thought to be more tolerable in women with autoimmune disease (Soldan et al 2003). Testosterone Testosterone has many functions; however one of the less recognized is its role in nervous system development. Testosterone, as well as oestrogen, is seen as an immunomodulator, however each sex hormone has differing roles in MS. It has been suggested by clinical studies that testosterone could offer neuroprotection that could be useful in the management of MS (Gold et al 2008). Testosterone can offer direct or indirect neuroprotection. Free testosterone may pass the blood brain barrier to directly modulate neuronal cells or it may be converted into oestrogen in the brain, acting indirectly (Bialek et al 2004). The possible protective effects of testosterone have mainly been investigated by studying the effects of castration of male animals. It has been demonstrated that testosterone can decrease the production of inflammatory cytokines that appear to contribute to the pathogenesis of MS (D’Agostino et al 1999). Moreover, a shift towards Th2 immunity has been noted in testosterone treated EAE mice, suggesting the potential use of testosterone in treatment of auto- immune diseases such as multiple sclerosis. Gold et al explored the immune-modulatory effects of testosterone on a group of males, clinically defined for MS. An anti-inflammatory effect was seen due to a decrease in IL-2 and DTH (delayed type hypersensitivity) responses and an increase in TGFβ-1. Also, testosterone was shown to increase the production of BDNF (brain derived neurotrophic factor) and has a suggestive neuroprotective effect in MS. BDNFs were the first neurotrophin to be detected in inflammatory lesions (Hohlfeld 2008). BDNFs may have a role in limiting the damage caused by inflammation. Furthermore, there has been a link between MS severity and production of BDNFs (Bialek et al 2004). More damage to the white matter was associated with decreased levels of BDNF. Oestrogen and testosterone in the management of MS Oestrogens The current observation that oestrogens produced during pregnancy subdue clinical manifestations of MS and other auto-immune diseases, has lead to the use of oestrogen therapy in patients whom are not pregnant and suffer severely from MS . There has been suggestion that this type of therapy will be able to mimic the Th1 to Th2 shift that is seen during pregnancy and is correlated with improved clinical symptoms. Oestrogen treatments such as oestriol and oestradiol may offer protection against the clinical severity of MS, as its effects have been shown in EAE (Gold et al 2009). The mechanism of protection that is offered by oestrogens is thought to exert anti-inflammatory processes, by affecting the cytokine response. Treatment with oestrogen has been shown to protect oligodendrocytes from cytotoxic attack (Sur et al 2003). This can be seen as beneficial as oligodendrocytes are responsible for producing myelin proteins that are need for nerve insulation and conductivity. The loss of myelin integrity and function can leave the individual vulnerable to MS. Many clinical studies have been carried out that have aimed to determine the effects of oestrogens for the management of MS. One particular study performed by Soldan et al involved the treatment with oral oestriol. The study intended to showcase the immunological effects of oestriol and the results showed significant decreases in CD4 and CD8 T cells. As well as these results, significant increases in anti-inflammatory cytokines, IL-5 and IL-10 and decreases in pro-inflammatory cytokines, TNFα were observed. The alterations in cytokine secretions were linked to reductions in lesions seen in monthly MRIs. Overall, it can be suggested that oestriols can influence the course of MS. Oestrogens can regulate gene transcription, acting via oestrogen receptors, ER α and ER β. It has further been assessed whether or not oestrogen treatment was gender specific (Palaszynski et al 2004). It was found that the expression of ER α and ER β were equal in both genders and the disease severity was found to decrease in both males and females with oestriol treatment. Moreover, a decrease in proinflammatory cytokines resulted after oestriol treatment in both males and females. This reveals that therapies need not be gender specific and also a potential use of oestrogen treatment for men, as well as women. Testosterones Recent studies and clinical trials have been able to highlight the roles of testosterone in the management of multiple sclerosis. It is well known that testosterone offers protection to males which may be why they are less susceptible to MS and other auto-immune diseases, compared to females. One recent pilot study conducted by Sicotte et al treated 10 male MS patients with gel testosterone. The results concluded an improvement in spatial and working memory performance; however no changes in inflammatory immune responses were noted in MRI. Overall, the study indicated that testosterone was a safe potential treatment and it was well tolerated. Although the treatments have shown success, more investigations are required to further evaluate the neuroprotective roles of testosterone in the management of MS. Overall, it can be said that testosterone can be protective in MS. The cytokine responses vary between males and females which may explain why men are less affected by MS. These cytokine differences could be due to testosterone (Liva at al 2004). Conclusion From the numerous studies that have been undertaken to further understand and explore the roles of Oestrogens and testosterones in disease initiation and progression, it can be concluded that sex hormones may have powerful anti-inflammatory and neuroprotective functions. In spite of there being no specific treatments that are able to offer improvements to the long term prognosis of the disease, there has been increasing evidence to suggest that gender and hormonal profile can affect therapy and that these factors should be taken into account (Nicot 2009). Using a gender based approach in the management of Multiple Sclerosis may be beneficial as many studies have pointed towards the importance of sex hormones in the pathogenesis of the disease. It has been acknowledged that sex hormones have roles in MS pathology therefore can be utilised in potential therapeutic measures for the treatment of the disease. It is known that immune mechanisms that promote the release of pro-inflammatory cytokines lead to a more severe and progressive disease and the mechanisms that promote the release of anti- inflammatory cytokines have shown to be protective (Palaszynski 2003). Sex hormones such as oestrogen and testosterone have been shown to encourage a shift towards an anti-inflammatory immune response which is favoured in multiple sclerosis. Therefore, oestrogen and testosterone are promising candidates for the treatment and management of multiple sclerosis as they posses anti-inflammatory and neuroprotective traits. Multiple Sclerosis (MS): Pathophysiology and Management