With surgeries becoming more accessible and the solution to treating certain diseases that could potentially be fatal, the emergence of prosthetic limbs has definitely been an important medical advancement. One of the earliest prostheses used was a wooden toe discovered on an Egyptian mummy. Throughout the years, implantable prostheses such as hip and knee replacements have helped many patients return to their normal lives. Study of tissues and discovery of stem cells by Drs. James Till & Ernest McCulloch has allowed scientists to generate whole organs and tissues through tissue engineering, allowing them to perfectly match the organs to the patients, thereby reducing the risk of any complications.
The problem with prostheses
However, despite this, implantable prostheses have their disadvantages. For example, they have a very little active role since they mainly act as a form of structural support. Certain actions such as moving individual fingers in a hand replacement are proven to be difficult since this relies on the work of muscles. Artificial joints are often made out of synthetic materials and these get rejected by the body, causing further illnesses. Moreover, they have a relatively short lifespan of around 5 years, meaning they will need to be constantly replaced: this could cause financial problems for some families. Recently, a new process called Targeted Muscle Reinnovation has been brought up which allows scientists to connect individual nerves to the remaining muscles, and therefore make it easier to perform complicated movements. However, the process of creating and testing this is manually tiring for the user.
So how has Artificial Intelligence helped us?
In 2017, a group of researchers created a computer-controlled prosthetic arm that could perform elaborate movements and carry out complex activities. The process doesn’t require the user’s efforts, thereby making it easier for them. Previously used prosthetics were controlled through EMG sensors placed on the skin. This new method makes it easier for testing out the models. Furthermore, these AI-controlled prostheses respond to nerve signaling patterns, allowing them to produce multiple movements simultaneously. A new technique has also evolved called regenerative peripheral nerve interface (RPNI) relies on wrapping a small piece of muscle around an amputated nerve to produce signals which can then be amplified.
AI is slowly being used to introduce intelligence to these artificial prostheses and this will hopefully make them more accessible to people in the future. All current models are just prototypes and are yet to be made available for use.
For more information, check out these links:
This scientific article was written by Marijan Hassan on 23/01/2023
Recently I have been reviewing and watching content regarding our rapid advancements in technology which has given us the ability to replace body parts with prosthetics or other artificial devices. However, with this ability a significant ethical question arises of whether it is ethical to enhance our bodies beyond their natural capabilities. I drew inspiration for this post from the video by the Pew Research Centre included at the end.
One of the key ethical concerns surrounding replacement body parts is the question of what it means to be human. Humans have historically viewed themselves as distinct from other animals because of our unique combination of physical, emotional, and intellectual capacities. The introduction of artificial enhancements to our bodies could blur the lines of what it means to be human, and could even lead to the creation of new, non-human species. This raises important questions about how we define humanity, and what the implications of altering our bodies could be for our identity as humans.
Another ethical issue that arises with replacement body parts is the potential for inequality. While the technology for artificial replacements has become more accessible in recent years, it still remains out of reach for many people, particularly those in less developed countries or who do not have access to proper healthcare. If only a select few individuals are able to afford or access these enhancements, it could lead to a new form of inequality where those who can enhance their bodies are more advantaged than those who cannot.
There is also the concern that replacement body parts could become a form of social pressure. If certain enhancements become popular or even necessary to keep up with societal norms, it could create an environment where people feel pressured to modify their bodies even if they do not want to. This could lead to a lack of individual autonomy and could even be seen as a form of discrimination against those who choose not to enhance their bodies.
However, there are also arguments in favour of replacement body parts and enhancing our bodies. One of the primary benefits is the ability to improve the quality of life for individuals who have experienced physical limitations due to injury or illness. By replacing a lost limb or enhancing an impaired sense, individuals can regain their independence and improve their overall well-being.
Additionally, the development of replacement body parts has the potential to drive medical innovation forward. The same technology used to create prosthetics and artificial enhancements could also be used to develop new treatments for a variety of medical conditions however it would inevitably also be used military purposes as well.
To summarise the ethics of replacement body parts and the idea of enhancing our bodies is a complex issue with no easy answers. While there are certainly concerns about the potential implications of modifying our bodies, there are also clear benefits to individuals and society as a whole. As we continue to advance in technology and medical innovation, it will be important to carefully consider the ethical implications of these advancements and to work towards a future where everyone has access to these life-changing technologies.
I have always had an interest in the ethics behind scientific research, in particular the discussions around using human tissues in research. However, the case study of the Alder Hey Organs Scandal was mentioned in the law and ethics lecture and I had never heard of anything like it. It certainly piqued my interest as retaining childrenâs organs without consent or permission seemed such a baffling concept to me.
An ethical minefield
Alder Hey is an NHS hospital in Liverpool that was the centre of a scandal when in 1999 it came to light that during post-mortem investigations of children between 1988 and 19951, the pathologists were retaining the organs of the deceased children without the knowledge or consent of their parents2. This blatant âharvestingâ of organs reminded me of a book I read recently entitled âNever Let Me Goâ by Kazuo Ishiguro. To summarise, the book is the story of 3 children who grow up and realise they are clones of members of the public, and their role is to âdonateâ their organs until they eventually pass away. I found the dystopian science fiction nature of the book incredibly fascinating, and it shocked me how events that are eerily similar to those in the book have actually happened in most peopleâs lifetimes.
Why were the organs retained?
After the lecture I wanted to find out more about how activities that could well be described as âdystopianâ managed to occur, bypassing the consciences of those involved. I initially assumed that the organs had been used for donations to children that needed transplants, but after thinking more about it whilst doing my research I realised that the organs would not be of use by the time the post-mortem occurred. Then why were the organs taken? Upon reading some journal articles from the years following the scandal I found out that many of the organs were not histologically examined, or used for educational and research purposes.
The reason the organs were retained (even for no apparent purpose) lies in the vague wording of the Human Tissue Act 1961 in which pathologists could retain tissues if there was a lack of objection, rather than informed consent. Therefore, by not informing the parents of the children about the reality of post-mortem procedures, there was a lack of objection and thus the ability to retain the tissues1. However, this cannot justify the utter devastation experienced by the parents of these children, who already had experienced the awful loss of a child, as they came to the realisation that their child had been incompletely buried.
Additionally, I researched more about Dr Van Velzen, who was mentioned in many of the papers I read. I discovered that he was a pathologist who was struck off the General Medical Council for storing over 1000 organs from 850 children in jars in a dirty cellar as they slowly decomposed3. This is a particularly uncomfortable revelation as it is practically impossible to justify the decisions made by Dr Van Velzen.
Moving forwards
I found researching this case further incredibly insightful because I was unaware of anything like this happening in the recent past, and there was so much to find out. Cases like the Alder Hey Scandal have a huge importance in future scientific ethics discussions to ensure history does not repeat itself. The scandal led to the Human Tissue Act 2004, which clearly outlines the need for explicit consent for retention of tissues for research or other reasons.
Reference List:
Burton, J. L and Wells, M., (2002). The Alder Hey affair. In: Archives of Disease in Childhood (86/1). London: BMJ. pp. 4-7. DOI: https://doi.org/10.1136/adc.86.1.4
Bauchner, H. and Vinci, R., (2001). What have we learnt form the Alder Hey affair? In: British Medical Journal (322/7282). London: BMJ. pp. 309-310. DOI: https://doi.org/10.1136%2Fbmj.322.7282.309
Dyer, O., (2005). Alder Hey pathologist is struck off medical register. In: British Medical Journal (330/7506). London: BMJ. p. 1464. DOI: https://doi.org/10.1136%2Fbmj.330.7506.1464-a
Before I begin this blog on philosophical arguments and medical consents, it should be noted that there usually is no ârealâ definitive ethical answer to an argument as I follow JS Millâs view that knowledge is not infallible, and that All sides contain plausible explanations. Truth, lies, or partially true, should be brought together in discussion (JS Mill, On Liberty).
Case analysis
In the paper by Murray (1990), the author stated many legal cases through out the history, providing evidence in how the medical consent was progressed. From the legal cases provided, in general, it can be observed that utilitarianism and deontology were combined. Although mainly, in the cases where informed consent was present, patient-centred deontological view is followed, and that the surgeons will respect patientsâ individual liberty, and oneâs right to oneâs body. Some examples containing the theoretical traits are:
Luka v Lowrie, 136 N. W. 1106, Michigan 1912: A child, who experienced a crash injury to his foot, was deemed by the surgeons that amputation was necessary. Normally, a child would not be considered to have competence for consent, therefore the parents should grant consent to the surgery. However, the parents were unavailable for discussion during the duration of the surgery. Without consent, the surgeon, after consulting with several physicians, performed the amputation. From this case, it can be justified based on act utilitarianism, where the goal of an action should be to achieve the maximum amount of happiness. Had the surgeon acted in a strong deontological view, and that the surgeon absolutely respects individual liberty and consent, the childâs situation may have turned another way.
In re Melideo, 390 N. Y. S. 2d 523, New York, 1976: Mrs. Melideo received a dilatation and curettage of the uterus for diagnostic purposes. The patient developed significant bleeding soon after. The patient however, refused blood transfusions based on her religious belief. The court ultimately ruled that blood transfusion should and was not ordered to the patient, since the patient has consent competency. This follows the patient centred deontological view, where certain rules are unethical to be broken no matter the circumstances, and the patient has the ultimate right. Interestingly, in this case, there are two layers of deontological reasoning present. The first layer exists in the surgeons who acts as the âagentsâ. The surgeons respected the rule for a patientsâ liberty based on the patient centred deontology, and the patient followed the basic deontology view where the decisions should never break certain rules laid upon oneself.
The two cases above represented how the two views can be at play at the same time instead of counter arguing. The deontological approach respects oneâs autonomy and liberty, while the utilitarianism view fulfils certain situations where emergency consents are needed. Murray confirmed this in one of the conditions for emergency consent: the proposed treatment is for the ultimate benefit of the patient.
One possible reasoning for this might be the importance of liberty from both viewpoints. In an action-based context, such as the world-famous trolly cart problem, where 5 people will die if you donât push the lever, and 1 person will if you do, the deontologist will not push the lever, only if the person has a doctrine to never kill in their mind. The utilitarian will push the lever for the maximum amount of happiness. This may make the utilitarianism seem like a violation of some individual liberties in some cases.
However, in the context for information, Mill argues that even though some truth may result in harms, they should still not be suppressed. The reason for this is that Mill follows the empiricism of knowledge, that knowledge can only be gained by experience, and that future knowledge (or truth) cannot be known. Therefore, suppressing the truth will assume its infallibility, which contradicts to Millâs empiricism. This also supports the importance of information transparency to the patients so construct patientsâ well-rounded judgement toward the procedure.
“Had the patient, judged as a reasonable and prudent person, been provided adequate information about the procedure and its risks prior to consenting to the procedure, or if some material risk had been presented, would the patient have refused to proceed with surgery?”
This leads to another philosophical debate on free will and determinism. From the determinism point of view, Paul Ree is an example, that he holds a hard deterministic view. Ree believes that every decision was made from past events, and that an association of causation is present. Ree also argues that free will is an illusion since the causes are internal. For example, when a rock was thrown, the causation was observable, and it is external. Those events can be replicated and proven, given the exact force applied and other factors such as wind speed. To say that the rock has free will would not be plausible. From this logic, internal factors such as body chemistries or past experiences leads to determined behaviours of a person or an organism. Ree gave the example of a donkey between two of the same haystacks. If the donkey was observed to turn left and eats the left haystack, externally, it would seem like the donkey has free will, but what about hidden factors? The wind may be blowing towards the donkey from the left side, or a hidden body behaviour gathered from past experiences. Therefore, since some factors were internal and unobservable, and created the illusion. Ree believes that if the exact past causation, both internal and external were recreated to the exact same extent, the donkey would still choose to turn left. Same as when a person makes certain decisions.
While not many philosophers support purely on free will, many of them believes that free will and determinism can exist at the same time (Compatibilism). Compatibilists argue that if only causal determinism exists, there wonât be any needs for moral responsibilities. Since determinism argue that only one path was available to the person, and that person must act in that way. Therefore, there isnât a responsibility for that personâs action. To apply moral responsibilities then, free will will be required. For compatibilism, theories vary. But Fischerâs (1994) theory can provide a supporting ground for information transparency in medical consent. Fischer provides an element called regulative control which is a control agent that can bring and refrain one from doing certain behaviours. As a result, different paths open for one to choose at that exact moment. For medical consent, the importance for surgeons to provide patients a clear view of the procedure surfaces. Therefore, the compatibilist view justifies the need for risk disclosure that it provides the patients a clear, rational judgement when they are competent for consent.
From the example and arguments above, medical consent is constructed on the foundation of individual liberty. While it can be fitted into many different philosophical debates. For novel medical research, personally I would argue for the respect of liberty and autonomy, and transparent communications for patients to create rational and justified decision. Yet, certain context may prove otherwise and incite debates.
If youâve taken any lecture within the realm of cell biology â be it about cell division, transport, signalling, and so on â youâve most likely encountered an experiment involving the use of HeLa cells. I certainly did, and after repeatedly seeing images of those strange, purple cells on my lecture slides, it made me wonder âWhat exactly is so special about HeLa cells that they are used in virtually every experiment to do with human cells?â This blog post is about these cells: what exactly makes them so remarkable, their polarising legacy, and the important bioethical discussions they raise about medical consent and racism.
What are HeLa Cells?
HeLa cells are an immortal cell line derived from the cervical cancer cells of Henrietta Lacks, a 31-year-old black woman and mother of five. They are the oldest and most used human cell line in scientific research and have contributed to countless scientific studies since their discovery in 1951.
Lacks was a patient at Johns Hopkins Hospital, Baltimore, Maryland in 1951, being treated for a very aggressive form of cervical cancer. Several months before her death, a sample of her tumour was given to George Gey, the head of tissue culture research at Hopkins at the time. Gey had been searching for an immortal human cell line to study cancer with for two decades and he had finally struck gold: Lacksâ cells multiplied faster than any cells he had ever seen, reproducing an entire generation every 24 hours. Unfortunately, it was this rapid and unlimited division that caused Lacksâ cancer to metastasise to virtually every organ in her body within months. She passed away on October 4, 1951.
The dicey bioethics of HeLa cells
It is quite difficult to put into words just how impactful Henriettaâs cells have been on medical research. They were used to develop the polio vaccine, study leukaemia, AIDS, and cancer, and more recently, help develop COVID-19 vaccines. Since their isolation, HeLa cells have been used in more than 70,000 scientific studies around the world as of 2022. There is a darker side to this story, however.
After her passing, Henrietta Lacks was buried in an unmarked across from her familyâs tobacco farm in Virginia. For the next twenty-odd years, her family had no clue her cells had been shipped worldwide and were being used pioneering medical research. It wasnât until 1975 that the Lacks family even were made aware about the widespread use of her cells in said research.
Henriettaâs cells were taken without her consent, which was legal at the time. Since then, policy changes have been made, and ethical guidelines for medical research have been put in place like the Declaration of Helsinki, which places emphasis on the informed consent of patients. In the USA, changes are being attempted to be made to the Common Rule, the set of ethical policies for research with human subjects, to make its consent rules more far-reaching.
Racism in science and Henriettaâs legacy
In my opinion, what Lacksâ story really highlights is the racism that has historically plagued science, particularly medical research and services in the United States. Hopkins, where she was treated, was one of the few American hospitals at the time that would admit black people. None of the multiple biotechnology companies whose research benefitted from her cells have financially compensated her family. In the 1840s, James Marion Sims, known as the âfather of modern gynaecologyâ, infamously conducted experimental gynaecological surgery on enslaved black women without anaesthesia. There was also the Tuskegee Syphilis Study, when hundreds of black men in the 1930s were denied treatment for syphilis by researchers so the progression of their symptoms could be studied. I have linked further reading on both cases and more general scientific racism at the end of this blog.
While it is important to reflect on these past injustices, what the Lacks family would like to shift the focus is to is the legacy of Henrietta herself. In 2010, the Henrietta Lacks Foundation was established by Rebecca Skloot, the author of a book about Lacks, which awards grants to her descendants and other family members of people whose bodies were used without consent in research. In 2020, on her centennial year, the Lacks family started the #HELA100 initiative to celebrate her life and legacy.
Henrietta loved to dance and cook. She dressed stylishly and wore red nail polish. And most importantly, in the words of her grandson: â[Her cells] were taken in a bad way but they are doing good for the world.â
My thoughts
I wanted to write about Henrietta Lacks for my blog post because as someone who wishes to work in biomedical research in the future, I will probably end up working with these cells myself and I think it is important to highlight the legacy of these cells: both the unjust way in which they were acquired, and what we and the scientific community at large can learn from these past injustices so we do not repeat them.
As a woman of colour myself, I have rather mixed feelings on HeLa cells. It is chilling thinking about the horrific treatment people of colour, and especially women of colour have faced in historical medical research. However, HeLa cells have done so much good for the world and do so for all ethnicities. As long as we acknowledge the story of Henrietta and continue to compensate her descendants, I think HeLa cells can continued to be used in research.
Much progress has been made on bioethics and informed consent in medical research and treatment since that extraction was made from Henrietta’s tumour all the way back in 1951. However, as biotechnology continues to advance and gene editing and the like becomes more commonplace, the door has opened to once again start having these important discussions on how to ethically apply these new technologies.
References
Johns Hopkins Medicine (2023) The Importance of HeLa Cells, Johns Hopkins Medicine. The Johns Hopkins University, The Johns Hopkins Hospital, and The Johns Hopkins Health System Corporation. Available at: https://www.hopkinsmedicine.org/henriettalacks/importance-of-hela-cells.html (Accessed: March 8, 2023).
Martinez, I. (2022) What are HeLa cells? A cancer biologist explains, The Conversation. The Conversation Trust. Available at: https://theconversation.com/what-are-hela-cells-a-cancer-biologist-explains-169913 (Accessed: March 8, 2023).
Nature (2020) Henrietta Lacks: Science must right a historical wrong, Nature. Springer Nature. Available at: https://www.nature.com/articles/d41586-020-02494-z (Accessed: March 8, 2023).
Skloot, R. (2000) Henrietta’s Dance, Johns Hopkins Magazine. Johns Hopkins University. Available at: https://pages.jh.edu/jhumag/0400web/01.html (Accessed: March 8, 2023).
The Immortal Life of Henrietta Lacks by Rebecca Skloot is a great non-fiction book about Lacks and HeLa cells, and goes into great detail on the ethical issues of race and class in medical research. There is also a film adaptation of the same name that can be watched on HBO and HBO Max.
We all know the effects of a late night, especially if we need to get up early in the morning. We’re more irritable, less focused and less alert. I previously thought that symptoms of extreme sleep deprivation of around 48 hours or more, might be similar. However, this is not the case. Interestingly, in extreme cases, your perception of reality can become very distorted and you may experience intense hallucinations. The first symptoms can be seen within 24-48 hours of no sleep.
What is Microsleep?
Sleep is essential for maintaining pathways in the brain that are important for forming memories and retaining information. I wanted to focus on one symptom that can been seen in both minor and extreme cases, known as microsleep. During microsleep, your brain is not processing external information and you have a reduced response to external stimuli such as noise. This happens for around 10 seconds and most people may not realise it happening. Have you ever been stuck at a red light and felt yourself drift off even though your eyes are still open?
Attached is a podcast with Professor Russell Foster talking about the effects of sleep deprivation and the relationship between sleep and mood disorders and abnormal cognitive behaviour. Here he discusses microsleep and the long-term effects of night shifts. This is a trustworthy source as he has scientific explanations for his conclusions but uses language that is easy to understand.
How can we further our understanding of extreme sleep deprivation?
Brain waves can be measured with the help of an electroencephalogram (EEG) and fMRI scans to show active areas of the brain whilst sleep deprived and compare this to the patient when well rested. The benefits of these methods are that the patient can remain awake so a real-time impression of the brain can be made. However, the patient must be made aware of the short and long-term risks associated with sleep deprivation and in order for the study to be controlled, the patient may need to be observed to ensure they are not asleep.
This was discovered in a 2018 study on sleep deprivation, where results were gathered from 760 participants, where first symptoms, around 24-48 hours in, included:
Distorted perception
Anxiety
Depersonalisation – an altered sense of self where you feel disconnected from your own thoughts and body.
Loss of time and sense of orientation
From 48 hours:
Hallucinations
Delusions
Disorientation
Depression
Euphoria
Anger/Hostility
From 72 hours:
Complex hallucinations – including visual, sensory and auditory disturbances.
Elaborated delusions
Aggressive attacks
Mood changes
This is because the brain still undergoes R.E.M (rapid eye movement) phase whilst awake so you experience a dream-like state whilst still awake. This has been observed in multiple experiments and is known as sleep deprivation psychosis.
Many ethical questions arise when trying to conduct experiments to understand sleep further. When mice have been tested in the past, they have all died as a result of sleep deprivation. So, extreme caution must be taken when testing humans. Older experiments can tell us what happens when we don’t just miss an hour per night, but go weeks without any sleep.
This YouTube video briefly highlights the different attempts made by scientists throughout history to further our understanding of sleep that had unfortunate effects. This video is animated and in laymen’s terms so is highly engaging and easy to understand.
Conclusion and Reflection
I chose this topic because it had a really interesting link between science and ethics. I find the topic of sleep fascinating, and what makes this topic even more interesting is that it is incredibly difficult to study. Nowadays, it is considered unethical to conduct experiments exceeding 48 hours of sleep deprivation. After watching the videos and listening to the podcasts, I found myself wondering if sleep deprivation is described as a physical or mental health illness.This means the topic of sleep is one big mystery and there is still so much we don’t know, or may never know.
As a second year psychology student, I was provided many choices for my semester 2 optional module. However, I became torn between cognitive neuroscience and engineering replacement body parts. I ended up choosing this module as I wanted to learn more about prothesis and stem cells. Recently, I have been watching many episodes on NHK wherein prothesis was being discussed and I found these very interesting, ultimately influencing my decision to choose this module. One of the episodes focused on a guitarist who was born with congenital limb deficiency yet she is able to play guitar with a device that her dad developed. As someone who is also interested in guitar myself, I found myself engaged in the episode and wanted to learn more about prothesis and other aspects that compromise engineering replacement body parts.
My name is Megan and I’m currently on BSc Biomedical Sciences. I love to read and play archery in my spare time. I’ve grown up with mild to moderate Sensorineural and Conductive Hearing Loss in both ears. I wear Phonax Marvel hearing aids (above) to help me navigate various environments and reduce background noise so that I can follow what is going on around me.
At birth, I didn’t pass the initial Otoacoustic Emissions test. After further testing, my parents realised I couldn’t hear properly. However, this was masked by glue ear. I was properly diagnosed with Bilateral (hearing loss on both sides) Sensorineural loss after i had grommets inserted at 18 months. Later, I was also diagnosed with permanent conductive loss due to hypermobility (not glue ear). However, the permanent conductive loss fluctuates.
You might be wondering … what is Sensorineural and Conductive Hearing Loss? A sensorineural hearing loss is caused by the loss or damage to the tiny hair cells located in the cochlear or the inner area. This means that the tiny hair cells in my cochlear can no longer transmit sound from the inner ear through the auditory nerve in the brain. Conductive Hearing Loss for me is caused by problems with the three small bones in my ear, as they do not conduct the sound properly.
The reason why I chose this module was because I am interested in learning more about how hearing aids and cochlear implants work, as well as the latest advancements in hearing technology. It’s a very personal subject to me.
As a natural scientist, my interests remain very broad, however, I mainly focus on organic chemistry and aspects on immunology and pharmacology. I began studying cellular biology in my first years at University, but have since diverted my interest along the immunotherapy pathway focusing on selective toxicity.
This module will allow me to extend my understanding of real-life applications and ethics behind the closed doors of engineering replacement body parts. I am particularly intrigued to look closer at the medical ethics aspect of the module, as a future in ethics or patent law is something I am considering. Equipping myself with the knowledge and reasoning behind the implications of stem cells and medical devices, will help me to learn the foundation of assembling scientific reasoning which I can apply to further and current examples in the medical industry and impact such inventions will have on society.
I am excited to explore prosthesis and the mechanics involved in installing false limbs, something which I have never looked into before. This module is very significant and I believe it is important to spread the awareness behind new and technological advancements.
In line with the ethos of the Natural Sciences course, this interdisciplinary module focuses on improving student skill set beyond written exams, via reflective learning and interactive discussions.
A short video describing the key aspects of medical ethics.
When looking at University degrees, I came across Biomedical Engineering which immediately struck my attention as I love the idea that something you have built could potentially improve the life of many people. However, my lack of maths and physics understanding led me to choose a different degree.
One particular research that I found particularly interesting was something known as a Sapien transcatheter heart valve, which is a valve that can be introduced to the patient without the need of an open heart surgery.
The valve is introduced through the femoral artery and the inflation of a balloon allows it to be placed in the correct place in the heart, allowing patients without the ability to undergo complex procedures to obtain a new heart valve.
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