Difference between revisions of "Team:Uppsala/Human Practices/Market Analysis"
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<h1> Market Analysis </h1> | <h1> Market Analysis </h1> | ||
| − | <p> The iGEM project started with a brainstorm session to decide in which direction we wanted our project to go. But before starting with our project, we had some crucial questions that needed to be answered. What tools are accessible today and what are their limits? Is there a market for a new diagnostic tool with our approach? Is there a need for a new diagnostic tool for large strongyles as well? How do the potential stakeholder or customer feel about using a diagnostic tool based on GMO? </p> | + | <p> The iGEM project started with a brainstorm session to decide in which direction we wanted our project to go. But before starting with our project, we had some crucial questions that needed to be answered. What tools are accessible today and what are their limits? Is there a market for a new diagnostic tool with our approach? Is there a need for a new diagnostic tool for large strongyles as well? How do the potential stakeholder or customer feel about using a diagnostic tool based on a GMO? </p> |
<br> | <br> | ||
| − | <p> To answer these questions we chose to proceed by setting up a meeting up with the company Vidilab (a swedish company working with diagnostics of parasites such as strongyles). Vidilab are everyday users of the current diagnostic tools thus are deeply involved and experienced within the area of our project, making them great consultants. Today horse owners send a stool sample to companies such as Vidilab, who identifies certain parasitic species e.g. small strongyles found in the sample and counts eggs per gram. </p> | + | <p> To answer these questions we chose to proceed by setting up a meeting up with the company Vidilab (a swedish company working with diagnostics of parasites such as strongyles). Vidilab are everyday users of the current diagnostic tools thus are deeply involved and experienced within the area of our project, making them great consultants. Today horse owners send a stool sample to companies such as Vidilab, who identifies certain parasitic species e.g. small strongyles found in the sample and counts the number of eggs per gram dung. </p> |
<br> | <br> | ||
| − | <p> From Vidilab we learnt that this method is not efficient and results vary between companies. All horses have parasites within their intestines, the question you need to answer is what amount of eggs are within the normal range? To get valid results you need to first diagnose a non-infected horse to get a baseline that will be used later on when the horse is more greatly infected. Vidilab uses the guidelines of finding less than 100 eggs per gram dung within a healthy horse corresponds to a low amount, while more than 1000 eggs per gram dung indicates that the horse is infected by a large amount of parasites. Horses with high baseline (more than 1000 eggs per gram dung) can live without symptoms, though they can infect other horses and the paddock with lower baseline (less than 100 eggs per gram dung), which is why you still might want to treat a horse without any symptoms [1]. </p> | + | <p> From Vidilab we learnt that this method is not efficient and the results may vary between companies. All horses have parasites within their intestines, the question you need to answer is what amount of eggs are within the normal range? To get valid results you need to first diagnose a non-infected horse to get a baseline that will be used later on when the horse is more greatly infected. Vidilab uses the guidelines of finding less than 100 eggs per gram dung within a healthy horse corresponds to a low amount, while more than 1000 eggs per gram dung indicates that the horse is infected by a large amount of parasites. Horses with high baseline (more than 1000 eggs per gram dung) can live without symptoms, though they can infect other horses and the paddock with lower baseline (less than 100 eggs per gram dung), which is why you still might want to treat a horse without any symptoms [1]. </p> |
<br> | <br> | ||
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| − | <p> One factor we wanted to analyse with our survey was the | + | <p> One factor we wanted to analyse with our survey was the type of anthelmintics being used by the recipients. Are the treatments similar across the country? Are people aware of what kind of treatment they use? The result showed that the majority uses a combination of several anthelmintics, and that the combination of anthelmintics varies. In Sweden all anthelmintics needs prescription provided by a veterinarian, which means that the individual horse owners cannot treat their horses without a veterinarians approval [3]. This indicates that each treatment plan is unique, and thereby there are existing restrictions to the spread of resistance towards anthelmintics. </p> |
<br> | <br> | ||
| − | <p> From the results it was clear that the three most popular anthelmintics in Sweden are Noromectin (77 people), Ivermectin (59 people) and Cydectin (22 people). The results also showed that out of 300 individual horse owners up to 128 people (42.7 %) didn’t know what kind of treatment they used. This indicates that those individuals trust their veterinarians completely and blindly accept their professional directions. This could be somewhat alarming due to the ongoing spread of resistance towards anthelmintics. To eliminate the risk of spreading the resistance, each horse | + | <p> From the results it was clear that the three most popular anthelmintics in Sweden are Noromectin (77 people), Ivermectin (59 people) and Cydectin (22 people). The results also showed that out of 300 individual horse owners up to 128 people (42.7 %) didn’t know what kind of treatment they used. This indicates that those individuals trust their veterinarians completely and blindly accept their professional directions. This could be somewhat alarming due to the ongoing spread of resistance towards anthelmintics. To eliminate the risk of spreading the resistance, each horse owner should critically review the treatment plan for their horses. </p> |
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<!-- Here you put your paragraphs --> | <!-- Here you put your paragraphs --> | ||
| − | <p> We were interested in studying the dependency between the amount of treatments and diagnoses the horse owners provide for their horses each year. Do they treat their horse(s) without diagnosing them first or are the treatments specific for the horses? In order to do this we analysed | + | <p> We were interested in studying the dependency between the amount of treatments and diagnoses the horse owners provide for their horses each year. Do they treat their horse(s) without diagnosing them first or are the treatments specific for the horses? In order to do this we analysed the relations between answers of the following questions: </p> |
<br> | <br> | ||
<p> <i>1. How often do the horse owners diagnose their horse(s) for parasitic infections per year?</i> </p> | <p> <i>1. How often do the horse owners diagnose their horse(s) for parasitic infections per year?</i> </p> | ||
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| − | <p> The result shown in | + | <p> The result shown in Figure 1 indicates that the majority of the treatments are done after a diagnosis. The factor of having 2 diagnoses for the horses might be a follow up diagnosis to see whether the treatment worked or not. Moreover Figure 1 also shows that a minority treat their horses without having a diagnose on their horses first. This could be due to the individual not being the one in charge of ordering a diagnose or not realising they are doing it, since today it is common to have the diagnosis as a routine [4]. </p> |
</div> | </div> | ||
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<br> | <br> | ||
| − | <p> By studying how often horses are treated per year against respondents attitudes towards GMO, we set out to see if there is any correlation between these factors. The result shown in | + | <p> By studying how often horses are treated per year against respondents attitudes towards GMO, we set out to see if there is any correlation between these factors. The result shown in figure 2 indicates that there is no distinct dependence between these variables. We were expecting that eventually more frequent treatments would correlate to bigger acceptance of GMO suggesting possible wish for more effective/conclusive diagnostics. However it is suggested that openness for GMO is generally high irrespective of the chosen treatment frequency. </p> |
</div> | </div> | ||
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<br> | <br> | ||
| − | <p | + | <p> Figure 3 depicts connection between how often horses are diagnosed per year and respondents attitudes towards GMO. Similarly to Figure 2 there are no clear correlation between these factors. We can however see that the group performing no diagnosing has proportionally biggest fraction of respondents doubting GMO. </p> |
<!-- End of paragraphs --> | <!-- End of paragraphs --> | ||
</div> | </div> | ||
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| − | <p> The results shown in | + | <p> The results shown in Figure 4 indicates that there is no clear pattern in diagnosis frequency and experienced strongyle infections. We can see that most of the respondents diagnoses once or twice per year and about half of all respondents have heard about horses getting severely ill from Strongyle infections. This could indicate a result of the upcoming spread of resistance. This correlation also shows that people who have heard about 7 or more cases of severe illness among horses diagnose their horses twice a year. Also, we can see that the respondents who haven’t witnessed a severe strongyle infection personally, still choose to diagnose their horses for the infection. This is a positive sign since diagnosing is a working method to prevent the chances of spreading the resistance, by controlling the amount of parasites living in either paddocks or within the intestines of horses. This is positive for the proactive work that needs to be done in order to avoid unnecessary, fear induced, treatment contributing to resistance development. </p> |
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| − | <p> We wanted to study whether people aware of resistance also tend to diagnose more often. In | + | <p> We wanted to study whether people aware of resistance also tend to diagnose more often. In figure 5 we can follow this in Sweden and Czech Republic. In Sweden majority of respondents were aware of resistance and no assumptions about this affecting number of diagnosis could be made. In comparison answers from Czech Republic were relatively heterogeneous. The group performing no diagnosis also contained a distinguishably large fraction of people unaware of resistance. This suggests that raising the awareness of resistance to a level of common knowledge could contribute to more frequent diagnosing and ultimately decrease risk of resistance development. </p> |
<br> | <br> | ||
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<p> We also analysed the correlations between the following questions: </p> | <p> We also analysed the correlations between the following questions: </p> | ||
<br> | <br> | ||
| − | <p> <i>1. On a scale of 1 to 5, how concerned are horse owners about strongyles | + | <p> <i>1. On a scale of 1 to 5, how concerned are horse owners about strongyles becoming resistant to dewormers? </i> </p> |
<p><i> 2. How often do the horse owners diagnose their horse(s) for parasitic infections per year?</i> </p> | <p><i> 2. How often do the horse owners diagnose their horse(s) for parasitic infections per year?</i> </p> | ||
<br> | <br> | ||
| − | <p> As previously seen in | + | <p> As previously seen in Figure 6 awareness of resistance Sweden is generally high. However, worth to mention is that the few respondents that answered not believing in resistance were also found in the group using anthelmintics most frequently. In Czech Republic it is relatively more common with more frequent treatment. </p> |
<div class="card-holder"> | <div class="card-holder"> | ||
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<p> Another aspect we wanted to analyse was to see the correlations between the following questions: </p> | <p> Another aspect we wanted to analyse was to see the correlations between the following questions: </p> | ||
<br> | <br> | ||
| − | <p> <i> 1. On a scale of 1 to 5, how concerned are horse owners about strongyles | + | <p> <i> 1. On a scale of 1 to 5, how concerned are horse owners about strongyles becoming resistant to dewormers? </i></p> |
<p> <i> 2. How often do the horse owners treat their horse(s) for parasitic infections? </i> </p> | <p> <i> 2. How often do the horse owners treat their horse(s) for parasitic infections? </i> </p> | ||
<br> | <br> | ||
| − | <p> The results shown in | + | <p> The results shown in Figure 7 indicates that for the Swedish survey higher concern of anthelmintics resistance correlates with more frequent diagnosting. This indicates that the fear of resistance result in more diagnoses. When analysing the Czech it also shows that more worry among the horse owners result in a higher frequency of diagnoses per year. This indicates that the individual horse owners experiences a sense of security by having their horses diagnosed on a regular basis. </p> |
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<p> Another aspect we wanted to analyse was to see the correlations between the following questions: </p> | <p> Another aspect we wanted to analyse was to see the correlations between the following questions: </p> | ||
<br> | <br> | ||
| − | <p> <i>1. On a scale of 1 to 5, how concerned are horse owners about strongyles | + | <p> <i>1. On a scale of 1 to 5, how concerned are horse owners about strongyles becoming resistant to dewormers?</i> </p> |
<p> <i>2. How often do the horse owners treat their horse(s) for parasitic infections? </i></p> | <p> <i>2. How often do the horse owners treat their horse(s) for parasitic infections? </i></p> | ||
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| − | <p> The results shown in | + | <p> The results shown in Figure 8 indicates that most respondents do worry about resistance. However there is no clear trend correlating high concern to more careful treatment as the proportionally the amount of treatments remains approximately the same. This might indicate that the worries within the individual horse owner result in a higher frequency of treatments. When comparing to the Czech figure, Figure 8 also indicates that there is a general higher frequency of treatments. In addition the highest level of worry result in the the highest amount of horse owners who treat their horses more often than 3 times per year. Thereby there is a correlation between worry and treatment. </p> |
<div class="card-holder"> | <div class="card-holder"> | ||
Revision as of 23:09, 17 October 2018
Market Analysis
The iGEM project started with a brainstorm session to decide in which direction we wanted our project to go. But before starting with our project, we had some crucial questions that needed to be answered. What tools are accessible today and what are their limits? Is there a market for a new diagnostic tool with our approach? Is there a need for a new diagnostic tool for large strongyles as well? How do the potential stakeholder or customer feel about using a diagnostic tool based on a GMO?
To answer these questions we chose to proceed by setting up a meeting up with the company Vidilab (a swedish company working with diagnostics of parasites such as strongyles). Vidilab are everyday users of the current diagnostic tools thus are deeply involved and experienced within the area of our project, making them great consultants. Today horse owners send a stool sample to companies such as Vidilab, who identifies certain parasitic species e.g. small strongyles found in the sample and counts the number of eggs per gram dung.
From Vidilab we learnt that this method is not efficient and the results may vary between companies. All horses have parasites within their intestines, the question you need to answer is what amount of eggs are within the normal range? To get valid results you need to first diagnose a non-infected horse to get a baseline that will be used later on when the horse is more greatly infected. Vidilab uses the guidelines of finding less than 100 eggs per gram dung within a healthy horse corresponds to a low amount, while more than 1000 eggs per gram dung indicates that the horse is infected by a large amount of parasites. Horses with high baseline (more than 1000 eggs per gram dung) can live without symptoms, though they can infect other horses and the paddock with lower baseline (less than 100 eggs per gram dung), which is why you still might want to treat a horse without any symptoms [1].
Additionally, different companies are diagnosing during different time of the year, which according to Vidilab provides a huge error in the results. The parasites go through different stages which includes one period were they stay encysted, that won’t show any result during a diagnosis [1]. Thereby the results can be misleading if you diagnose your horse during this time of the year. Another factor to take into consideration is that you need to do follow-ups to be able to analyse whether the parasite are resistant to the anthelmintics used in the treatment plan.
As it follows from above there is no existing quantitative and simple diagnostic tool that measures strongyles efficiently. Thereby we chose to work on making a better system for detecting small strongyles and also looked into the possibility of designing a second Worm Buster, targeting large strongyles. Products like these could compete in the market of diagnostic tools for small and large strongyles or become a complement for companies working within the field of strongyle diagnostics.
In addition, we conducted a survey to receive greater understanding of the individual perspective of the respondents. The survey was translated into 10 different languages (English, Swedish, Russian, German, Czech, Spanish, French, Estonian, Latvian and Italian) and distributed to the respective countries using social media. To make sure that we only would proceed with scientifically validated results, we had to determine how much error we would tolerate, in other words what our lowest limit of answers per survey would be to still have valid results. A good approximate sampling size is, as a rule of thumb at the very least 30 [2], since it translates well between T-distribution and normal distribution. To be more accurate, everything depends on the actual population we wish to approximate the expected value for. The larger sample size the better [2].
To be certain of only proceeding with scientifically validated values, we chose to only proceed with surveys which had gotten more than 50 answers. The amount of answers differed between the surveys and only the Swedish and the Czech versions surveys fulfilled the chosen scientifically validated value of at least 50 participants, see table 1.
Table 1: The table show the translational versions of the survey, sent in the market analysis, with highest amount of answers.
Results from the survey
One factor we wanted to analyse with our survey was the type of anthelmintics being used by the recipients. Are the treatments similar across the country? Are people aware of what kind of treatment they use? The result showed that the majority uses a combination of several anthelmintics, and that the combination of anthelmintics varies. In Sweden all anthelmintics needs prescription provided by a veterinarian, which means that the individual horse owners cannot treat their horses without a veterinarians approval [3]. This indicates that each treatment plan is unique, and thereby there are existing restrictions to the spread of resistance towards anthelmintics.
From the results it was clear that the three most popular anthelmintics in Sweden are Noromectin (77 people), Ivermectin (59 people) and Cydectin (22 people). The results also showed that out of 300 individual horse owners up to 128 people (42.7 %) didn’t know what kind of treatment they used. This indicates that those individuals trust their veterinarians completely and blindly accept their professional directions. This could be somewhat alarming due to the ongoing spread of resistance towards anthelmintics. To eliminate the risk of spreading the resistance, each horse owner should critically review the treatment plan for their horses.
We were interested in studying the dependency between the amount of treatments and diagnoses the horse owners provide for their horses each year. Do they treat their horse(s) without diagnosing them first or are the treatments specific for the horses? In order to do this we analysed the relations between answers of the following questions:
1. How often do the horse owners diagnose their horse(s) for parasitic infections per year?
2. How often do the horse owners treat their horse(s) for parasitic infections?
The result shown in Figure 1 indicates that the majority of the treatments are done after a diagnosis. The factor of having 2 diagnoses for the horses might be a follow up diagnosis to see whether the treatment worked or not. Moreover Figure 1 also shows that a minority treat their horses without having a diagnose on their horses first. This could be due to the individual not being the one in charge of ordering a diagnose or not realising they are doing it, since today it is common to have the diagnosis as a routine [4].
Figure 1. Relations between the “Frequency of diagnoses per year” vs “Frequency of anthelmintic treatment per year”. <1 corresponds to treatments occurring less often than once per year. NA represents the group that did not answer about frequency of diagnosis.
From the surveys we also concluded that a strong majority within both countries (Sweden and Czech Republic) was positive towards the use of a GMO based diagnostic tool, whereas in Sweden the percentage was 83,2% at a total of 370 participants. This is crucial information since, otherwise, there would not be a market for our Worm Buster. We analysed attitude towards GMO on the background of frequency of Strongyle diagnosis and treatment in Sweden. This was done to further study the demand for a product of the Worm Buster sort. Relation between the following questions were investigated:
1. How often do the horse owners treat their horse(s) for parasitic infections?
2. Would the horse owners be open to a diagnosis method that involves genetically modified bacteria if it was proven to be cost-effective, safe and approved by the appropriate agency?
By studying how often horses are treated per year against respondents attitudes towards GMO, we set out to see if there is any correlation between these factors. The result shown in figure 2 indicates that there is no distinct dependence between these variables. We were expecting that eventually more frequent treatments would correlate to bigger acceptance of GMO suggesting possible wish for more effective/conclusive diagnostics. However it is suggested that openness for GMO is generally high irrespective of the chosen treatment frequency.
Figure 2. Relation between the “Frequency of anthelmintic treatment per year” vs “Attitude towards using a GMO based diagnosis tool”. <1 corresponds to treatments occurring less often than once per year.
1. How often do the horse owners diagnose their horse(s) for parasitic infections per year?
2. Would the horse owners be open to a diagnosis method that involves genetically modified bacteria if it was proven to be cost-effective, safe and approved by the appropriate agency?
Figure 3 depicts connection between how often horses are diagnosed per year and respondents attitudes towards GMO. Similarly to Figure 2 there are no clear correlation between these factors. We can however see that the group performing no diagnosing has proportionally biggest fraction of respondents doubting GMO.
Figure 3. Relation between the “Frequency of diagnoses per year” VS “Attitude towards using a GMO based diagnosis tool”. NA represents the group that did not answer about frequency of diagnosis.
We wanted to see whether higher exposure to infection cases correlates to more frequent diagnosting. Answers from the following questions were analyzed:
1. Have the horse owners ever experienced or heard about a horse becoming severely ill or suffering complications caused by small or large strongyles (such as rapid weight loss, colic, diarrhea, inflammation, blood clots)? If yes, how many horses?
2. How often do the horse owners diagnose their horse(s) for parasitic infections per year?
Figure 4. "Frequency of diagnoses per year" vs "Experienced cases of strongyle infections". NA represents the group that did not answer about frequency of diagnosis.
The results shown in Figure 4 indicates that there is no clear pattern in diagnosis frequency and experienced strongyle infections. We can see that most of the respondents diagnoses once or twice per year and about half of all respondents have heard about horses getting severely ill from Strongyle infections. This could indicate a result of the upcoming spread of resistance. This correlation also shows that people who have heard about 7 or more cases of severe illness among horses diagnose their horses twice a year. Also, we can see that the respondents who haven’t witnessed a severe strongyle infection personally, still choose to diagnose their horses for the infection. This is a positive sign since diagnosing is a working method to prevent the chances of spreading the resistance, by controlling the amount of parasites living in either paddocks or within the intestines of horses. This is positive for the proactive work that needs to be done in order to avoid unnecessary, fear induced, treatment contributing to resistance development.
We wanted to study whether people aware of resistance also tend to diagnose more often. In figure 5 we can follow this in Sweden and Czech Republic. In Sweden majority of respondents were aware of resistance and no assumptions about this affecting number of diagnosis could be made. In comparison answers from Czech Republic were relatively heterogeneous. The group performing no diagnosis also contained a distinguishably large fraction of people unaware of resistance. This suggests that raising the awareness of resistance to a level of common knowledge could contribute to more frequent diagnosing and ultimately decrease risk of resistance development.
1. How often do the horse owners diagnose their horse(s) for parasitic infections per year?
2. Are the horse owners aware that using dewormers without an initial diagnosis contributes to resistance (the drug will stop being effective/useful) among parasites to these drugs?
Figure 5. Relation between the “ "Frequency of diagnoses per year"” vs “Knowledge about resistance”. The figure to the left comes from the Swedish survey and the figure to the right comes from the Czech survey. NA represents the group that did not answer about frequency of diagnosis.
We also analysed the correlations between the following questions:
1. On a scale of 1 to 5, how concerned are horse owners about strongyles becoming resistant to dewormers?
2. How often do the horse owners diagnose their horse(s) for parasitic infections per year?
As previously seen in Figure 6 awareness of resistance Sweden is generally high. However, worth to mention is that the few respondents that answered not believing in resistance were also found in the group using anthelmintics most frequently. In Czech Republic it is relatively more common with more frequent treatment.
Figure 6. Correlation between the “Frequency of anthelmintic treatment per year” vs “Knowledge about resistance”. The figure to the left comes from the Swedish survey and the figure to the right comes from the Czech survey. <1 corresponds to treatments occurring less often than once per year.
Another aspect we wanted to analyse was to see the correlations between the following questions:
1. On a scale of 1 to 5, how concerned are horse owners about strongyles becoming resistant to dewormers?
2. How often do the horse owners treat their horse(s) for parasitic infections?
The results shown in Figure 7 indicates that for the Swedish survey higher concern of anthelmintics resistance correlates with more frequent diagnosting. This indicates that the fear of resistance result in more diagnoses. When analysing the Czech it also shows that more worry among the horse owners result in a higher frequency of diagnoses per year. This indicates that the individual horse owners experiences a sense of security by having their horses diagnosed on a regular basis.
Figure 7. "Worry about resistance" vs "Frequency of diagnoses per year". The figure to the left comes from the Swedish survey and the figure to the right comes from the Czech survey.
Another aspect we wanted to analyse was to see the correlations between the following questions:
1. On a scale of 1 to 5, how concerned are horse owners about strongyles becoming resistant to dewormers?
2. How often do the horse owners treat their horse(s) for parasitic infections?
The results shown in Figure 8 indicates that most respondents do worry about resistance. However there is no clear trend correlating high concern to more careful treatment as the proportionally the amount of treatments remains approximately the same. This might indicate that the worries within the individual horse owner result in a higher frequency of treatments. When comparing to the Czech figure, Figure 8 also indicates that there is a general higher frequency of treatments. In addition the highest level of worry result in the the highest amount of horse owners who treat their horses more often than 3 times per year. Thereby there is a correlation between worry and treatment.
Figure 8. "Worry about resistance" vs "Frequency of anthelmintinc treatments per year". The figure to the left comes from the Swedish survey and the figure to the right comes from the Czech survey.
Conclusions
From the Swedish survey we learned that not everyone diagnoses their horses before treating them with anthelmintics. This could lead to an increment of the resistance towards anthelmintics, which is why we want to make it as easy as possible to diagnose horses in a quantitative manner. This would allow treatments to be customized based on the amount of strongyle burden. To assist this statement we simulated extension of strongyle infections upon anthelmintic treatments of different frequency. Comparing our model to the current average treatment frequency we could suggest treatment optimizations in order to decrease risk of resistance development. Read more about the model here .
By giving the possibility to perform this at home and interpret the result yourself, we believe that we would make the diagnosing procedure easier. We believe that a more user friendly method would contribute to a increment in the amount of diagnosting.
References
[1] Vidilab., “Riktlinjer för tolkning av provsvar och behöver jag avmaska?” (2018). Vidilab. https://www.vidilab.se/fakta/hast/riktlinjer-for-tolkning-av-provsvar/. Retrieved 2018-10-02.
[2] Greenwood, Joseph A. and Sandomire, Marion M., "Sample Size Required For Estimating The Standard Deviation as a Percent of Its True Value" (1950). U.S. Navy Research. Paper 34. http://digitalcommons.unl.edu/usnavyresearch/34. Retrieved 2018-10-09.
[3] Tove Forslund., “Avmaskning häst” (2018). Veterinären.nu. http://veterinaren.nu/hast/bra-att-veta/avmaskning/avmaskning-hast. Retrieved 2018-10-11.
[4] Lind EO, Rautalinko E, Uggla A, Waller PJ, Morrison DA, Höglund J. 2007. Parasite control practices on Swedish horse farms. Acta Veterinaria Scandinavica 49: 25. Retrieved 2018-10-15.