Evolution of Virulence in the Ebola Virus

Evolution of Virulence in the Ebola Virus The Ebola virus is a member of the Filoviridae family of virus and is the pathogen responsible for Ebola Hemorrhagic Fever, an emerging disease that appears in infrequent epidemic outbreaks mainly in sub-Saharan Africa. The Ebola Virus is composed of several distinct subspecies, ranging from the extremely virulent Ebola Sudan and Ebola Zaire Viruses to the asymptomatic (in humans) Ebola Reston. Many outbreaks of Ebola Hemorrhagic Fever display mortality rates approaching 90%. Application of evolutionary concepts of disease and virulence evolution can be used to help explain this high level of virulence. Another important factor is the possible presence of less virulent outbreaks of Ebola Hemorrhagic Fever that go unreported due to small scale and lack of characteristic virulence A further understanding of the selective mechanisms behind virulence may suggest strategies to impose selection for less virulent strains of the virus and to develop possible vaccines, thus helping to curb th e deadly effect of Ebola outbreaks. The Filovirus family contains the Ebola Virus genus and the closely related Marburg Virus. Both of these genera are known to cause extremely dangerous hemorrhagic fever type illnesses. These Viruses are contain a single strand of negative RNA and typically measure 1400 nm in length with a diameter of approximately 80 nm. The various species of Ebola virus sporadically infect both human and non-human primates, causing Ebola Hemorrhagic Fever. Recent evidence suggests that the virus may have a natural reservoir in various bat populations. The virus sporadically jumps from this natural host species (in which it is avirulent) to host species such as chimpanzees, macaques, gorillas and humans where it typically exhibits high virulence. The mechanisms of this transition and the role of reservoir hosts is poorly understood at present (Leroy et al 2005) The Virus is transferred through direct contact with infected bodily fluids, most frequently by means of direct contact with an infected individual. Contaminated medical implements can also spread the infection in medical settings, especially during early stages when an epidemic has not yet been fully realized. In many of the early outbreaks this was a major means of transmission, due to the presence of the virus and nature of its transmission being poorly understood. Local funerary customs also contributed to the spread of the disease. Isolation of infectious patients, proper disposal of contaminated remains and excreta and use of efficient sanitation and barrier nursing techniques can effectively prevent transmission during an outbreak. It is important that these measures be implemented immediately upon suspicion of Ebola Hemorrhagic Fever in order to minimize spread of the virus within the community (Ebola virus disease in southern Sudan 1983). Initial during initial stages of infection the Ebola virus selectively targets dendritic cells, monocytes and macrophages, which spread through the circulatory and lymphatic systems to the liver spleen and lymph nodes. From here the virus can efficiently spread throughout the body. The infected monocytes and macrophages also release massive amounts of cytokines, helping to trigger virus-induced shock by causing damage to the endothelial structures. Infected dendritic cells are prevented from releasing costimulatory cytokines necessary for the production of T-cells, preventing sufficient immune response to the infection (Aleksandrowicz et al 2008). Symptoms of Ebola Hemorrhagic Fever usually manifest 2-21 days after infection. Initial symptoms include fever, weakness, aches in the muscles and joints, sore throat. These progress to rash, impaired liver and kidney function and in some cases both external and internal bleeding due to deterioration of the vascular lining (World Health Org anization). The massive release of cytokines and virus particles from monocytes and macrophages impairs the function of endothelial tissue, allowing it to become permeable to water and macromolecules (Aleksandrowicz et al 2008). Gastro-intestinal bleeding is a common symptom, and is frequently associated with lethal cases. (Ebola Haemorrhagic Fever in Zaire 1978) The First known outbreaks of the Ebola virus occurred nearly simultaneously in Zaire (modern Democratic Republic of the Congo) and Sudan in 1976. These outbreaks, although close both geographically and chronologically were caused by two distinct subspecies of the virus (Ebola Zaire and Ebola Sudan respectively). The Zaire outbreak was centered in the village of Yambuku and its environs. 318 cases were reported in this epidemic, of which 280 were fatal (mortality 88%). All cases in this epidemic were tied to either close contact with a confirmed case or receiving a parenteral injection at the local hospital (Ebola Haemorrhagic Fever in Zaire 1978). Early cases in the Sudan outbreak were textile workers from the town of Nzara. 151 of the 284 reported cases were fatal (mortality 53%) (Known Cases and Outbreaks of Ebola Hemorrhagic Fever). Three years later, in August of 1979 another, smaller scale outbreak occurred in Nzara and the nearby town of Yambio, resulting in 34 cases, with 22 f atalities (65% mortality) (Center for Disease Control, 2006). Communities affected by these outbreaks share several characteristics. One of the most significant of these is the nature of available medical care. All were served by small, undersupplied and understaffed hospitals. Unsanitary conditions within these hospitals and the prevalence of family members carrying out day to day care for afflicted individuals being allowed the virus to spread quickly through the local population. The Yambuku hospital utilized five needles and syringes for prenatal, inpatient and outpatient wards, with little sterilization between uses. This fact alone almost ensured transition of the virus between patients in the hospital. Lack of barrier nursing practices also allowed high transmission to the staff (11 of the 17 medical staff died as a result of Ebola Hemorrhagic Fever) and caregivers as well A high prevalence of infection was found amongst individuals present at funerals of deceased patients in all outbreaks. The reproductive success of a pathogen is dependent upon its ability to replicate itself and to infect new hosts by transfer of its propagules. Rapid replication can increase a pathogens chance of transference, but this requires a greater toll on the hosts system and is likely to lead to an increased chance of host mortality. Due to this, there is believed to be a natural correspondence between a pathogens growth rate and virulence. The relationship between these two factors is explained by the trade-off hypothesis of virulence evolution. This theory largely replaced the commonly accepted idea that a parasite or pathogen should evolve towards avirulence, but it not fully accepted. The avirulence theory assumed that a parasite low virulence would maximize a pathogens overall lifetime reproductive success by increasing the time of infection to nearly infinite limits. The reasoning behind this theory has been explained thusly: The parasite makes a profession out of living at its neighbours expenses and all its industry consists of exploiting it with economy, without putting its life in danger. It is like a poor person who needs help to survive, but who nevertheless does not kill its chicken in order to have the eggs (Van Beneden 1875). The frequent down trend in virulence from the time a pathogen is introduced to a novel population was offered as evidence for this theory. The trade-off theory developed when evolutionary ecologists began to question the avirulence theory. It proposes that there is a link between ease of transmission and virulence. According to this theory, virulence is an outgrowth of a rapid replication rate in the pathogen, which strains host resources and reduces host fitness (resulting in host mortality). The Trade-off theory links the variables of virulence, transmission and host recovery in a relationship summarized by the following mathematical model: (Alizon, Hurford, Mideo Van Baalen 2009) In the above equation R0 represents the pathogens baseline reproduction ratio, in this case a measure of relative fitness. The S value is the number of susceptible hosts within a population. ÃŽÂ ² represents rate of transmission, ÃŽÂ ± is the death rate in the host due to infection (virulence), ÃŽÂ ¼ stands for the natural death rate in the host population, and ÃŽÂ ³ is a factor representing the recovery rate from the infection. According to this model, any change in virulence, transmission rate or recovery rate will have an effect on the other two variables. A high transmission rate will typically go along with a high virulence and low recovery rate. The reproductive success of a pathogen comes from successfully balancing these variables to maximize R0 (Alizon et al). High Virulence will allow for high reproduction and transmission, but only up to a point. Natural selection should favor strains that are able to maximize this trade-off. Eventually, virulence can reach a l evel where the increased transmission is no longer balanced out by the risk of dying along with a host before being able to jump to a new one. This is especially true in isolated host populations or other conditions that limit horizontal transmission, which could possibly explain the low virulence and chronic nature of some infections. Virulence is typically defined as morbidity and mortality of the host organism as a result of parasite or pathogen activity. Measurements of a pathogens virulence are traditionally given in terms of parasite induced death rate (PIHD). This definition is suitable for a general discussion of a disease as it includes all deleterious effects on the host. A more specific and narrow definition is required in order to examine selective pressures on the evolution of virulence in a disease, however. The generalized definition, according to Ebert and Bull in their work on virulence evolution, fails to differentiate between virulences effects on host and pathogen fitness, and therefore fail to give an accurate assessment of selective pressure on the pathogens evolution. For this reason it is important to consider specific aspects of the host/pathogen system (such as means of transference, rate of pathogen growth, etc) before drawing conclusions about the selective pressures for increased or red uced virulence in the pathogen (Ebert Bull 2008). In the case of the Ebola virus and Ebola Hemorrhagic Fever virulence can be discussed in terms of host death. Unlike with some pathogens, death of the host does not immediately end transmission of the virus. Some studies indicate that the corpse can remain infectious for several days after death. Several epidemics have been traced to contact between the index case and the contaminated remains of a chimpanzee (Ivory Coast 1994, Gabon 1996, Gabon 1996-97) (Chart) and contaminated monkey meat may have played a role in the index case of the initial 1976 Zaire outbreak (Ebola Haemorrhagic Fever in Zaire 1978). Ebert and Bull define three general stages of evolution in a pathogen transferring to a novel host and the selective pressures involved in each. The first phase includes the initial interactions between a pathogen and the novel host. In some cases this infection is not capable of horizontal transfer between hosts in the novel population. Other situations involve short chains of secondary infection from the index infection. Infections in this phase are likely exposed to great selective pressures, as they are in an entirely new environment, one for which their genes may or may not be particularly suitable. Genes that may not have had a measureable fitness effect in the pathogens normal host environment can suddenly exert great selective pressure. Because of this there is frequently a great range of virulence expressed by different pathogens during this phase. The second phase occurs during the period when a pathogen has established a foothold within the novel population. It follows the epidemic infection model and increases rapidly within the population, because of this rapid growth it is possible for a pathogen to evolve rapidly in this phase. Selective pressure on the host can also be extreme in this phase. The second phase also applies when a mutation in a parasite that has already obtained equilibrium within a host population is significant enough that it gains a selective advantage over other strains and spreads rapidly. Ebert and Bulls third phase is reached when a pathogen has become firmly established within a host population. Pathogens in this phase are well adapted to the host, but will still experiences selective pressures due to host demographic and environmental changes. The Ebola virus, in human hosts, remains largely within the first phase, although it could be argued that it briefly enters the second phase on a local level during some outbreaks. It causes short lived epidemics when it does infect a human population, but fails to survive long term and become an endemic pathogen. During this initial stage the virus can be exposed to great selective pressure as it is in an unusual host. Evolutionary dynamics within an epidemic scenario, as proposed by Bolker et al, favor pathogens with a high growth and transference rates, and the high virulence that is associated with them, due to the large number of susceptible hosts in the novel population. This differs from a pathogen in later stages, which has reached dynamic equilibrium with the host. These situations tend to select for moderate virulence and longer duration of infection. (Bolker et al). A possible explanation for the extreme virulence in Ebola outbreaks may simply be reporting bias. Many of the early and milder symptoms of Ebola Hemorrhagic Fever are quite similar to those of other diseases endemic to the region, such as malaria, and measles. Some outbreaks are actually mistaken for cases of other diseases until post-infection laboratory tests detect particles of an Ebola strain. A 1994 outbreak in gold mining camps in Gabon (52 cases, 60% mortality) was believed to be a yellow fever epidemic until almost a year after the last case. It is possible that less virulent strains of the virus are simply mistaken for other common infections, treated as such, and never reported (CHART). Ebola virus antibodies were detected in sera from 18% of adults in the 1979 Nzara outbreak who were not infected. This is evidence that It is likely that sporadic infection is more common than can be appreciated from these dramatic outbreaks, which probably represent the extreme of the inter action between man and the virus. (Baron et al). This fits in with the inherent virulence variance in phase one pathogens suggested by Ebert and Bull above. Other factors that can affect the evolution of virulence in a pathogen are host population density and ease of transmission. These factors are frequently interrelated, as both directly influence the number of susceptible hosts a pathogen is able to infect during its lifespan. A high density of susceptible hosts (such as when a pathogen is emerging in a novel host population) is likely to greatly increase greatly increase a pathogens reproductive success, and select for pathogens that can replicate quickly and take advantage of the abundant hosts. Likewise, easy transition from one host to the next also selects for pathogens that are able to rapidly replicate and seize the day, as it were. Both of these conditions, which favor pathogens with high growth rates, also favor high virulence in accordance with the Trade-off hypothesis (Ebert Bull 2008). The abovementioned concepts and principles fit in with epidemiological data from outbreaks of Ebola Hemorrhagic Fever. Initial outbreaks of Ebola Hemorrhagic Fever took place within areas with a relatively high concentration of susceptible hosts. The 1976 outbreak centered on the Yambuku Mission Hospital is a good example. This hospital served as the primary medical facility for a local population of around 60,000 as well as travelers. This facility was relatively small, having 17 staff members and holding 120 beds in its crowded wards. It also processed some 6000-12000 outpatients on a monthly basis. Combine this with the five improperly sterilized syringes used to administer injections (the primary dosage method at this facility) and a severe lack of barrier nursing procedures. This would appear to be an optimal situation for the transmission of pathogens that spread through contaminated body fluids. According to the Trade-off Hypothesis and the selective conditions outlined above, pathogen strains that have high reproduction rates (and hence high virulence) would be at a distinct selective advantage. Cases cared for out of the hospital setting would also tend to favor quickly reproducing and more virulent pathogens. Horizontal transfer by physical contact is directly affected by the concentration of virus particles in a contaminated fluid; hence a virus with a higher reproduction rate would be able to successfully exploit a given number of transfer opportunities. This setting lacks the direct viral inoculation by contaminated needle present in the hospital setting, which would perhaps result in less effective transmission. This would also favor more strongly virulent pathogens, which reproduce quickly and successfully exploit transmission opportunities (Ebola Haemorrhagic Fever in Zaire 1978). The conditions present during the 1976 Sudan outbreak were largely similar. Transmission occurred mainly to family members providing nursing care (without barrier nurs ing techniques) and through contaminated medical equipment and direct contact in a hospital setting. These conditions would also seem to favor more virulent pathogens. Other examples of particularly high virulence outbreaks (in terms of host mortality) also occur under conditions with large amounts of close contact between potential hosts, likely resulting in high transmission. Examples of these situations are found in the 1994 and 1996-97 Gabon outbreaks, which took place at a mining camp and (initially) a remote forest camp respectively. Both of these outbreaks featured transmission of numerous secondary infections through close contact with infected individuals. According to the Trade-off hypothesis, high transmission rates are linked to high levels of virulence. By reducing rate of transmission it may be possible to artificially select for less virulent strains. In the hospital and home care setting, hosts suffering from highly virulent strains with high symptom manifestation (high virulence) are likely to transmit the virus to other hosts, favoring virulent strains. Application of sanitation and barrier nursing practices can reduce transmission of the virulent strains present under these conditions. This could potential favor any less virulent strains, i.e. ones that do not manifest severe symptoms that require hospitalization and are unlikely to be fatal, present in the environment. This could gradually reduce overall virulence over the course of the outbreak. Even if less virulent strains are not present, prevention of transmission is likely to slow and eventually stop the outbreak as the number of remaining susceptible hosts is reduced through various means (Ewald 2004). The Ebola Virus and Ebola Hemorrhagic Fever present an interesting case for evolution of virulence in a pathogen. The periodic outbreaks of the disease offer examples of how selective pressures imposed on a pathogen follow the predictions of the Trade-off hypothesis linking virulence (and attendant host mortality) with rate of transmission. This hypothesis and the conclusions it suggests fit with data observed in outbreaks of virulent Ebola Hemorrhagic Fever. Conditions of dense susceptible host population and rapid and effective transmission seem to demonstrate high incidences of virulence indicating that there may be selective pressure for virulent strains under these conditions. Evidence of strains showing low virulence is suggested by the Ebola virus presence in a natural reservoir species and by the formation of antibodies by healthy individuals not linked to current epidemics. Due to this (presumed) variation amongst strains and the relationship between transmission and virulen ce proposed by the Trade-off hypothesis, reduction of transmission of the virus in hospital and homecare settings may lead to a reduction in strain virulence in prolonged outbreaks.

Lin Article Critique Essay

However, when splitting the forty patients into two treatment groups, the clients were split randomly. This places twenty participants in each subgroup. Pyrczak (2008) suggests that number of participants can be so small that generalizing would be inappropriate. At the conclusion of the study caution was given to the small sample size provided, but it was noted that â€Å"the sample size was more than sufficient to detect meaningful statistical differences, a major goal of all treatment studies† (Lin et al. , 2004). This indicates that a generalization was drawn from the target group of residential drug rehabilitation clients and was not drawn from a diverse source. Some participant dropped out of the study resulting in a 35% completion rate (Lin et al. , 2004). This low rate does effect generalizing the findings of the study. The participants were similar on relevant variables in that all of the patients were diagnosed with a mental disorder, had a history of a chronic addiction, a poor response to treatment and relapse, legal issue related to addiction and little motivation to change (Lin et al. 2004). Critique of Procedures The procedures followed in acquiring participants in this study initially were not chosen at random. The forty-three patients selected for the study were from a residential drug treatment center that had specific criteria preferred by the researchers. However, when the patients were separated into treatment groups, â€Å"they were randomly assigned to FT or ADC† (Linn et al. , 2004). The treatments described in this study are sufficiently explained in detail. The researchers describe ADC, alcohol and drug counseling as a common treatment plan for substance abuse. The article is written in more descriptive detail about forgiveness therapy for the reason that its effectiveness is being tested. The treatments were administered by a therapist trained in both FT and ADC therapy with more than twenty years of therapeutic counseling experience. The treatments that were administered were monitored by taping the therapy sessions with a member of the team arbitrarily selecting the tapings for review of â€Å"consistency between expected and delivered treatments† (Linn et al. 2004). The same therapist conducted all the therapy sessions so that the personal effect is eliminated as a factor from this study. The therapist used the same methodology in both types of treatment programs. The setting for the experiment was a natural setting in the sense that it was not conducted in a laboratory. The therapy sessions took place within the current living environment of the rehabilitation residential facility. The researcher considered attrition in this study stating that, â€Å"given the high levels of mobility and chaos that characterize the lives of this client population, this dropout rate is not unusual. However, the sample size was more than sufficient to detect meaningful statistical differences, a major goal of all treatment studies† (Linn et al. , 2004). Critique of Instrumentation The evaluating instruments for the research did not include actual items in the research, but did explain in great detail the description of each instrument. The researchers also included research that supported validity of each assessment. Specialized formatting and detail was used when the instruments were administered in random order and the response format was provided. Restrictions were placed upon the research when the patience were initially chosen with the three dispositions of a chronic addiction with relapse, psychiatric diagnoses, poor response to treatment with low motivation to change, and legal issues dealing with substance abuse (Linn et al. , 2004). Multiple methods are used to collect information on each variable within this research. The EFI, BDI-II, CSEI, STAI, SSTAEI and vulnerability to drug use scale were used to obtain data on each patient and use for statistical analysis (Linn et al. , 2004). The researchers provided sources and well researched information for each published instrument. The self-report assessments were not administered anonymously, therefore, there is some reason of doubt that information obtained from patients could have been influenced by â€Å"social desirability or response-style biases† (Linn et al. , 2004). This researcher believes steps were taken to keep the instrumentation from influencing any overt behaviors due to the fact that all patients were exposed to the same therapist as a constant, expected occurrence, causing little deviation from the expected schedule.

A Review of Journal Writing

A Review of Journal Writing The Hidden Treasure of Journal Writing Your mind is going to be relieved of the should concentrate on the issue and can instead start to concentrate on the solution. Because you require something that it is possible to write in your journal, your mind will forever watching for new ideas that it is possible to write down. Good, as you're answer is accurate. Because there is absolutely no incorrect answer. The Upside to Journal Writing You will have to continue to keep your audience in mind while you write, since there might be personal experiences and observations you're prepared to share with your professor but not your classmates. Students are in a place to learn the ability of organization and attention to detail in their very own writing. Lots of people want to maintain a journal but are fearful of facing the blank page. Ultimately, a summer journal isn't a way to help adult learners continue their progress, but nevertheless, it may be used a s something to appear back on when he or she achieves their target of becoming literate. Meditating can clear your mind and do away with all the mental clutter that's holding you back. Attempt to write three or more pages of content without thinking much of what you're writing. Instead, you may use your journal for a place to brainstorm and form your points. Not all challenges are simple to overcome, so if you discover yourself in a situation you do not understand how to overcome, write about possible solutions in your everyday journal. Journal Writing Fundamentals Explained Therapeutic journal writing has changed into a popular self-help tool. For those who haven't kept a journal, you may not know. Get the journal you're going to decorate. At times, a journal is also known as a diary. You can also see book journals to better understand different kinds of journals which can be created. Our collection also has a number of journals designed for a certain subject, like science notebooks and math journals. The 5-Minute Rule for Journal Writing Writing a journal ought to be an enjoyable experience. Writing informally in a journal is an excellent means to become more at ease with writing, particularly if you're in work which doesn't require plenty of writing. Any journal entry will gain from some moments of reflection before you get started writing. Writing a journal entry differs for everybody. You may be interested in script writing examples. Don't hesitate to begin writing down ideas of what you're interested in or feel you ought to be writing about. You don't should title it before you begin writing though. You might also have a look at reflective writing examples if you want more help in all kinds of writing. If you want to find out more about how to become an author and hone your writing skills, in addition to finding an agent and getting published then click the hyperlink below. It is possible to observe where you left off on each specific project, and transfer the info over all at one time. Setting a time will allow you to stay focused and block you from getting carried away. If you would like to maintain a journal the identical way that you might a personal blog, but keep it private, Penzu is a wonderful alternative. Journal Writing - Dead or Alive? At the conclusion of each journal entry, you could opt to compose comments on the total content, usage of la nguage and ideas expressed. The next step is to begin a new journal entry by writing today's date at the peak of the webpage. You can decide to switch areas of focus whenever you grade an entry. If students have a tendency to find restless and shed interest by the conclusion of the lesson, you are going to want to slot in journal writing at the start of the lesson when their concentration level is high. You are also going to be in a position to become more creative and strong. Students will need to revisit similar tasks to boost their confidence as problem solvers and their understanding of problem solving. Then the actual experiment began. Whenever you're having a difficult time deciding what things to write in a journal, you almost certainly have a mind which is full of different things happening in your life. A lot of people write in a journal only to keep track of what's going on their life. Doing so daily functions as a reminder until, as time passes, the behavior be comes something done with very little or no conscious thought. The Good, the Bad and Journal Writing If you commence writing down your gratitude, you'll almost certainly begin showing how grateful you're, which may be an inspirational type of private improvement. As easy as it looks, journaling is a rewarding activity that could reap many advantages. By scheduling precisely the same times, journaling will turn into a natural and normal portion of your agenda which you can look forward to. There are many grid templates it's possible to pick from or customize the grid and questions yourself to concentrate on the fields of life that you want to track. Whatever They Told You About Journal Writing Is Dead Wrong...And Here's Why Whoever has kept a journal will testify to the benefit. Then you may choose to continue to keep your journal private or share it with your social networking groups or the whole world. A journal is an excellent place to compose lists. Your journal does n ot need to be aesthetically pleasing. Instead, think of just one specific food which you want to cut from your diet plan. To begin with, journal therapy might not be effective with individuals who experience cognitive or intellectual challenges. Learning how to capture various voices on paper can help you with dialogue for stories or scripts. Not everybody is comfortable expressing themselves, so writing a letter that isn't meant for everyone to read is a means to come to terms with your feelings. Writing without direction can cause some superb creations, but nevertheless, it may also lead to writer's block and hours of being unproductive. Through writing, you're encouraging your child to learn more about the corners of her or his mind.

The Role Of Advice To Small Business - 1159 Words

I do not deny that the purpose of the business (if it moves beyond an idea) will be to connect businesses with consultants. As stated in my response dated 29 May 2017: â€Å"Given the success of the clusters program in particular, I began thinking about how you could change the model of advice to small business to increase engagement. I also wondered what role new and emerging platforms such as the internet and mobile applications (apps) could have in facilitating such a paradigm shift. I considered (and am still considering) ways to take this research forward, including a completing a Doctoral Thesis around the problem and applying for a Churchill Fellowship to investigate models used overseas.† (my underlining) In other words I am†¦show more content†¦This extends to respecting the confidentiality of official information should I leave public service employment. Further Considerations In response to the statement that I have continually failed to provide full and frank details about my interest in Entrepreneurial Edge â€Å"despite being repeatedly being requested to do so since April 2017†. After completing the Declaration of Interest form in April as directed I believed that a discussion would be initiated to consider its contents. Specifically, under the manager/supervisor’s section it states that they are to outline the basis of the employee’s declaration and â€Å"Where available provide further background and/or details obtained through discussion with the employee.† (my underlining) In addition, Ms Emma Freeman’s email dated 7 April 2017 stated she would work with the delegate and me to determine and agree on an appropriate management plan. At no time from when I lodged the declaration on 11 April 2017 to when it was signed by Ms Freeman on 18 April 2017 was there a request for further information or any discussion with me regarding its contents. References by Ms Freeman to previous discussions were informal workplace conversations, except for a single, short, meeting on 7 April 2017 between Mr Grant Stidiford, a/Executive Director, Ms Freeman and myself where it wasShow MoreRelatedFranchising ( 10 Points ) Essay792 Words   |  4 Pages(10 Points) I. What steps should you, the prospective U.S.-based franchisee take when establishing outlets in foreign countries? Research the potential market, including its size and the potential acceptance of the franchise concept. Inventory the business climate for U.S. businesses operating within the foreign country. Assess the state of the current and anticipated economic and financial environment. Try to obtain information regarding government restrictions. 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