An NIH grant proposal I wrote for a Regenerative Engineering class

 

A Combinatorial Treatment for Spinal Cord Injury: A Research Proposal

Specific Aims

Spinal cord injury (SCI) is a traumatic and complex condition that often results in chronic sensory and motor paralysis below the level of injury. There are approximately 17,000 new SCIs in the U.S. each year and on average 62% of these injuries have been incomplete [28]. However, basic research has focused more attention on treating motor complete SCI for a number of reasons. Many reactionary cellular mechanisms alter the microenvironment following acute SCI inhibiting functional nerve regeneration. Mechanisms including robust inflammation and glutamatergic excitotoxicity cause massive cell death. Formation of an astroglial scar and myeline accumulation inhibit the growth and reconnectivity of axons [22].

There are many types of therapies aimed at various mechanisms although two recent therapies have been shown to be very promising. Bioscaffolds that bridge the cavity caused by SCI can be seeded with stem cells and neurotrophic factors to induce axonal growth, guidance and regeneration [12].

In addition, several recent studies have shown that applying electrical stimulation to the spinal cord can induce involuntarily and ultimately voluntary step-like movements in motor complete SCI patients. These same studies claim that residual effects such as the ability to activate lower extremity muscle groups are seen even after the stimulation is turned off [5].

This proposal will investigate the efficacy of a bioscaffold seeded with appropriate stem cells and neurotrophic factors implanted at the time of spinal fusion following incomplete SCI. We will then determine how a specific therapeutic regiment focused on noninvasive electrical stimulation can enhance the regenerative capacity of the spinal cord.

 

Aim 1: To engineer a bioscaffold seeded with stem cells and neurotrophic factors to induce axonal growth and guidance

Our goal is to design a neurospinal scaffold that will facilitate axonal growth and guidance. The scaffold will be optimized for biocompatibility, biodegradation, morphology and ultimately SCI specific nerve regeneration. The propriospinal interneuron network (PN) will be targeted as a possible regenerative substrate. Because the PN contains neurons that sprout laterally into grey matter as well as neurons that connect spinal cord segments together, it is a very promising target for complete and incomplete SCI regeneration [6].

Aim 2: To use noninvasive electrical stimulation to neuromodulate the lumbosacral spinal cord circuitry to induce step-like movements

Targeting the lumbosacral circuitry with electrical stimulation has been shown to induce involuntary step-like movements in both healthy individuals and individuals who have suffered motor complete SCIs [9]. We believe that electrical stimulation may activate dormant pathways that project supraspinally to the lumbosacral central pattern generator (CPG). This will be the first human trial to test noninvasive electrical stimulation on patients with incomplete SCI.

Significance

While treatment of motor complete paralysis is important for providing proof of concept it is considered to be by far the most difficult type of SCI to treat clinically. On the other hand, incomplete SCIs hold far more potential for regeneration and functional recovery which is why we are proposing to treat this population with our multifaceted approach first.

If successful this strategy will be completely noninvasive, aside from the obvious spinal fusion following SCI, and will not be as intense as current SCI therapy paradigms. Furthermore, if patients reach our predicted goal it will enhance the health and quality of life while reducing the degree of disability for thousands of children and adults who have been paralyzed due to SCI.

 

Innovation

Due to the novelty of both technologies there has never been a study designed to determine the synergistic effects of a surgically implanted bioscaffold and noninvasive electrical stimulation on SCI regeneration. Our approach is unique in that we are attempting to bridge the spinal cord lesion as well as stimulate motor circuits below the level of injury. We believe that treating SCI from the top-down and from the bottom-up holds more potential for regeneration than either method alone. With the success of recent electrical stimulation of complete SCI we believe there is reason to have very high expectations for patients with incomplete SCI.

Preliminary Data: Bioscaffolds

Scaffolds offer the advantage of concentrating appropriate factors at a specific site and enhancing neural regeneration through contact mediated axonal guidance [17]. Scaffolds can also be seeded with stem cells, neurotrophic factors, nucleic acids material and other pharmacological drugs as needed. This method of delivery is aimed at improving efficiency of the drug or stem cell delivered and reducing the side effects of conventional drug delivery such as multiple injections [4]. SCI leaves a very hostile environment that is not conducive to axonal growth or regeneration as stated above. Using a bioscaffold can help in the physical and chemical reorganization that is needed to promote proper growth and reconnection of spinal cord axons [13, 15]. Scaffolds have been used in every area of tissue engineering for a long time however, neurospinal scaffolds are the most complicated and least studied due to the intrinsic complexity of the CNS. Still, there have been many studies investigating how a neurospinal scaffold should be engineered with positive results [12].

 

 

The figures above describe the data that were collected from a number of behavioral tests administered to rats who were given a unilateral (incomplete) SCI. Groups were assigned as such, one with a bioscaffold seeded with neural stem cells (NSCs), one with only a bioscaffold, one with only NSCs and one control group. (A) Data from the BBB open-field walking test for the ipsilateral side of SCI shows that the bioscaffold+NSC group scored significantly higher than both the bioscaffold only and NSC only groups. (B) BBB open-field walking test for the contralateral forelimb showing very similar data. (C) Data from an inclined plane test where the upward orientation was not altered significantly but the downward orientation was. The bioscaffold+NSC group improved significantly from day 14 onward. (D) Represents the righting reflex results. The bioscaffold+NSC group shows a significantly higher percentage of righting compared to other groups. (E) Represents the percentage of animals with a normal pain response. (F) Represents the percentage of animals with a spastic response to the same painful stimuli. Figures were taken from [23], description was adapted from [23].

Preliminary Data: Non-invasive Electrical Stimulation

A recent study [5] have successfully induced step-like movements using an invasive epidural stimulation device in four complete SCI patients. The patients regained the ability to move their legs after several weeks, and in one case several months of training with the electrical stimulation. However, the epidural device had to be surgically implanted along the patients’ lumbar spinal vertebrae. In addition, leg movement was only seen when the epidural stimulation device was on, no residual effects were seen. Instead of an invasive stimulation a new form of noninvasive electrical stimulation is suggested instead of the epidural device. This non-invasive method is known as transcutaneous electrical nerve stimulation (TENS). TENS is not new in itself but applying this method of stimulation to the spinal cord is relatively new. TENS works by strategically placing electrodes onto the skin above the spinal cord, specifically at the lumbosacral junction in humans. In a more recent study [5] five motor complete SCI patients who were at least two years post injury were able to move their legs in a gravity neutral position while the TENS unit was activated. Surprisingly, after a number of training sessions each of the five patients showed some degree of movement without the TENS unit turned on. Because this study was done in motor complete SCI patients who were at least two years post injury we have every reason to believe that an acute, incomplete SCI patient will respond even better to the TENS stimulation

Lower extremity EMG activity during voluntary movement occurred only with epidural stimulation in four individuals with motor complete spinal cord injury.

Lower extremity EMG activity during voluntary movement occurred only with epidural stimulation in four individuals with motor complete spinal cord injury. EMG activity during attempts of ankle dorsiflexion (A) without stimulation and (B) with stimulation. Force was not collected for Patient B07. Electrode representation for each subject denotes the stimulation configuration used. Although stimulation was applied throughout the time shown in B, in all four subjects EMG bursts were synchronized with the intent to move. Grey boxes are cathodes and black boxes are anodes, white boxes are inactive electrodes. Stimulation frequency varied from 25 to 30 Hz.

Figure and Description were taken directly from [9].

Approach: Bioscaffold Design           

Several conditions must be met in order to maximize reconnectivity and subsequent functional recovery. Biocompatibility is the most important characteristic to consider when designing a SCI model scaffold due to the risk of inflammation which could cause further neurological damage [8]. Furthermore, biodegradability is crucial, especially in the SCI model where removal of a non-degradable scaffold would warrant secondary surgery which may result in unnecessary complications. After the scaffold has assisted in axonal growth it should degrade through endogenous enzymatic activity. Another quality to consider is that of mechanical strength. The SCI scaffold will not have to stretch or expand but it will need to be able to withstand a certain amount of pressure caused by inflammation. The morphology of a bioscaffold for SCI should also be highly porous and contain large pore sizes, allowing for cell attachment and axonal growth.

For the reasons stated above, a chitosan scaffold with collagen hydrogel as a filler is proposed. Chitosan is a natural, biodegradable polymer used extensively by tissue engineers. The scaffold will contain the extra cellular matrix proteins fibronectin and laminin which have been shown to improve cell adhesion and axonal guidance [8]. Furthermore, evidence has shown that axons and axonal growth are extremely sensitive to the surface and architecture of scaffolds. Specifically, microchannels have proved successful in extending neurite growth with an optimal channel diameter of 20-30 nanometers [16]. For this reason the chitosan scaffold will be a solid conduit instead of an injectable scaffold. The scaffold will also be seeded with appropriate cells and neurotrophic factors that can modulate regeneration.In most cases after SCI the axons of the injured neurons will retract proximally and distally from the site of injury leaving a gap or cavity in the spinal cord [10]. Therefore, it will be beneficial to seed the bioscaffold with stem cells that will directly replace the cells that died. A popular stem cell line used for inducing spinal cord regeneration are neural stem cells (NSCs). NSCs are stem cells that are committed to becoming neural cells and are believed to facilitate spinal cord regeneration by differentiating into, and thus directly replacing, lost neurons and glial cells (Iwanami et al., 2005). Another advantage of NSCs is that they are believed to facilitate host axonal growth, that is, axons that survived the SCI, by secreting neurotrophic factors. For these reasons we are choosing NSCs to seed our chitosan bioscaffold. Several neurotrophic factors have been identified as playing important roles specific to the propriospinal interneuron network (PN) in axonal regeneration and plasticity. Brain-derived neurotrophic factor (BDNF) contributes to regeneration by promoting plasticity and increasing remyelination (Fouad et al., 2012). Specifically, BDNF administered to the cortex resulted in a greater number of propriospinal axon sprouting and a more complete preservation of corticospinal tract (CST) axons [26]. Additionally, ciliary-derived neurotrophic factor (CDNF) prevents degeneration of axons after axotomy [26] and glial derived neurotrophic factor (GDNF) has been shown to promote plasticity of the PN directly [10]. Other members of the neurotrophin family, including NT-3 and NT-4 are known for promoting axonal sprouting and growth [19]. These five neurotrophic growth factors are among some the most extensively studied and are well described in spinal cord regenerative literature [2]. Therefore, they will constitute the basis of the neurotrophic factors that will be seeded into the bioscaffold.

Approach: Noninvasive Electrical Stimulation Design

As soon as our recruited patients would be able to begin conventional physical therapy following a SCI we will instead start them on a therapeutic plan centered on noninvasive electrical stimulation. We will work with Thomas Jefferson University Hospital in Philadelphia, PA to recruit eight individuals who have recently suffered an incomplete SCI. We are attempting to recruit two groups of four, each group being comprised of similar injuries (ie. Level, type and severity of injury). We will begin our study by applying the TENS at the lumbosacral junction tonically for 45 minutes at a time or as long as the patient can stand the stimulation. We will have two sessions a day, five days a week for 90 days. The default stimulation parameters we will use will be adapted from Edgerton et al. from his 2015 study which are 8v at 15Hz. We will also record EMG data at three time points (d=30,d=60,d=90) from three groups of muscle synergies including hip, knee and ankle. The hip flexor, quadriceps and hamstring muscles. From the ankle we will record from the plantar flexor and plantar extensor. We will compare the data we collect from incomplete controls.

Potential Problems

The bioscaffold approach may result in a number of clinical issues. It will be difficult to personalize the bioscaffold to each SCI until we have a much better understanding of the different types of SCI and how different types of bioscaffolds work in each environment. Also, the solid conduit bioscaffold has a higher risk of causing inflammation and further neurological damage in comparison to an injectable scaffold. However, the bioscaffold allows for much more effective targeting of stem cells and neurotrophic factors and thus a higher potential for successful regeneration. The balance between the regeneration and inflammation of the solid conduit and injectable scaffold needs to be investigated further. There are a few potential problems with the TENS therapy. Patients may not be able to tolerate an intensity of electrical stimulation that is sufficient to provide the response needed for regeneration. Also, some patients will undoubtedly be able to tolerate higher levels of stimulation which may make interpreting results complicated. Some patients may need longer and more frequent electrical stimulation which may render the noninvasive method pointless at which point the patient may want to

End Goals

At the end of 90 days our goal is that at least 6 out of 8 of our patients will be able to take a few steps with the help of parallel bars, a walker or crutches. We expect that 6 out of 8 of our patients will be able to bear at least 75% of their body weight. We believe that being treated with a bioscaffold and training for 90 days with the TENS unit these SCI patients will improve significantly relative to controls. Further studies may want to address the relevancy of Lokomat training in addition to TENS therapy. Although at least one study determined that Lokomat training was no more beneficial than conventional physical therapy there may be reason to investigate the effect of the TENS with the Lokomat training. This may be a promising combination because TENS stimulation is thought to stimulate a central pattern generator and the Lokomat helps the patient to generate rhythmic walking motion.

 

 

References

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  5. Edgerton, VR, Gerasimenko, Yury P., et al. “Noninvasive reactivation of motor descending control after paralysis.” Journal of neurotrauma 32.24 (2015): 1968-1980.
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  20. Sekiya, I., Larson, B. L., Smith, J. R., Pochampally, R., Cui, J. G., & Prockop, D. J. (2002). Expansion of human adult stem cells from bone marrow stroma: conditions that maximize the yields of early progenitors and evaluate their quality. Stem cells, 20(6), 530-541.
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  23. Teng, Y. D., Lavik, E. B., Qu, X., Park, K. I., Ourednik, J., Zurakowski, D., … & Snyder, E. Y. (2002). Functional recovery following traumatic spinal cord injury mediated by a unique polymer scaffold seeded with neural stem cells. Proceedings of the National Academy of Sciences, 99(5), 3024-3029.
  24. Thoenen, H. (1990). Ciliary neurotrophic factor prevents the degeneration of motor neurons after axotomy. Nature, 345, 31.
  25. Weishaupt, N., Blesch, A., & Fouad, K. (2012). BDNF: the career of a multifaceted neurotrophin in spinal cord injury. Experimental neurology, 238(2), 254-264.
  26. Vavrek, R., Girgis, J., Tetzlaff, W., Hiebert, G. W., & Fouad, K. (2006). BDNF promotes connections of corticospinal neurons onto spared descending interneurons in spinal cord injured rats. Brain, 129(6), 1534-1545.
  27. Wyndaele, M., & Wyndaele, J. J. (2006). Incidence, prevalence and epidemiology of spinal cord injury: what learns a worldwide literature survey?. Spinal cord, 44(9), 523-529.

 

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We are not so small

Here’s the thing though… we aren’t small in the grand scheme of things. We are everything in the grand scheme of things.

There either is God or there is not. There is either some sort of higher power responsible for everything, or there is not. In the case of God, humans are everything in the grand scheme (pretty much no matter the religion). However, if everything that exists is a cosmic accident, we are also everything, because in that case there is no grand scheme and as best we can tell the rest of the universe is a desolate wasteland mostly filled with rocks and gas (besides all the nothing). In that case, Earth, and humanity, is a shining beacon in a sea of nothing.

Drilling down even further, to those in your Sphere of Influence and Perception, you mean more than all the nothingness in the universe. And those in your Sphere mean more to you in some way than all the rest of the universe. Your co-worker dying means more to you than an entire solar system imploding somewhere out there.

The very fact that you can appreciate the moon makes you more important than the entire lifeless universe. It’s only because of humanity that the moon means anything at all.

Edit: Yes, yes, “but aliens”. Replace “humanity” with “intelligent life” and we’re still part of an astonishingly elite club in the universe.

 

 

Taken from /r/Man_or_Monster on a reddit thread.

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Hubble Ultra-Deep Field

IDL TIFF file

IDL TIFF file

Arguably HUBBLE’s most important image to date

The Hubble Space Telescope aimed its lens at a very small region of space, about 1/10 of the size of the moon as viewed from Earth, where initially there was nothing to see but darkness. NASA aimed the telescope in an area of apparent darkness in an attempt to look for bright, distant objects. The telescope collected light from this region of the sky for over three months (September 24, 2003 through January 16, 2004). The HUDF was taken in a region of the sky with a low density of bright stars in the near field, allowing for better viewing of dimmer, more distant objects. The Hubble captured and recorded light in the full range from ultra violet to near-infrared spectrum. Looking back approximately 13 billion years the HUDF image shows objects that existed between only 400 million and 800 million years after the big bang. That is, the light from these galaxies were emitted 13 billion years ago, about 8.5 billion years before our Earth had even formed. These photons have been essentially traveling through the universe for the entire history of (space) time. There are approximately 10,000 galaxies in the image. With the exception of four stars (you can see them twinkle), virtually every spec of light visible is an entire galaxy containing anywhere from a thousand (10^3) to a hundred trillion stars (10^14) each. These galaxies are some of the very first to from, indeed able to form in our universe. Interestingly, to observe the entire sky with the same sensitivity, the Hubble would need to observe continuously for a million years.

 

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Another way HIV is being cured…

This article identifies two membrane bound proteins and how they effect HIV. The proteins, SERINC5 and SERINC3 are transmembrane proteins that exist in the host cells that HIV likes to attack (usually the immune systems fighter T cells). The researchers showed how HIV-Nef, a protein associated with the development of AIDS seems to counteract SERINC3 and SERINC5 lowering their expression and allowing the infection rate of HIV in the body to soar. Researchers are very excited about drugs that could potentially target and inhibit this HIV-Nef protein to help lower the efficiency of all enveloped virus’s. In fact, using this method the researchers, using proteomics to find where the viral DNA was located, found that it reduced the infectivity of HIV 100 fold. This means that compared to a normal patient with HIV, a patient who has had these cell surface proteins inhibited has 100 times less HIV DNA in their fighter T cells.

Scientists have known for twenty years that Nef plays an important role in the development of AIDS and these studies seem to finally give a glimpse into how Nef does this. With the Nef protein silenced, or even greatly reduced we could potentially stop the development of AIDS in people who have already been infected with HIV. Interestingly, the HIV virus only contains nine genes in the form of single stranded RNA. To reproduce and continue to infect other cells, the DNA virus needs to actually invade the cell and take over some of it’s machinery. In turn, one virion of HIV can multiply exponentially inside an organism. Nef, one of the nine genes, is responsible for sequestering the SERINC3 and SERINC5 transmembrane proteins so that they cannot reach the surface of the cell. With the Nef protein inactivated, the SERINC3 and SERINC5 proteins are able to reach the surface of the cell membrane. Somehow these proteins prevent the HIV from injecting it’s genome, effectively stopping the virus from spreading. Researcher’s are hoping that this Nef-activated mechanism is not specific to HIV, or even enveloped virus’ but might be a universal tool in the fight against all viral infections.

http://www.nature.com/nature/journal/v526/n7572/full/nature15400.html

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Gene Editing as a Potential Cure for HIV

dt_140710_hiv_virus_rna_800x600This article talks about how scientists are using new gene editing technology to disrupt and potentially destroy viral DNA. In this case scientists at Kyoto University used the CRISPR Cas-9 system to disrupt the DNA. The article first describes briefly what the CRISPR Cas-9 does. CRISPR stands for clustered regularly interspaced palindromic repetitions. Basically, it is a section of DNA, first discovered in bacteria, that can be utilized as a defense mechanism to protect a cell from viral infection. The CRISPR Cas-9 system is an RNA guided (or guide-RNA, aka gRNA) nuclease system. Let’s first take a look at what happens when a cell becomes infected by a virus. For example, we can look at the human immunodeficiency virus (HIV). HIV is a retrovirus meaning (among other things) it is a single-stranded RNA virus which incorporates itself into the host cells DNA through reverse transcriptase. HIV is interesting because of it’s ability to lie completely dormant for so many years. For simplicities sake lets say that the virus infects the cell and begins to attack immediately. In the large majority of these cases the host cell will die, however, if the host cell manages to survive it can do something very interesting and useful-assuming our cell has the CRISPR Cas-9 system. The CRISPR system will basically send out proteins that can read the amino acid sequence of the viral DNA. It then imbeds these copied sequences back into it’s own DNA code. Many short guide RNA strands can now be made. These strands will go off and associate with their matching sequence on the viral DNA. Lastly, an enzyme called Cas-9 will come and bind to these sites and make a double stranded cut in the viral DNA. After many of these double stranded cuts have been made in the viral DNA, the virus can no longer make many of it’s proteins and can no longer function correctly. What’s even more important is that this virus can not replicate itself so it cannot re-infect this cell, or any other cell in the organism. And, perhaps most importantly for our cell, because the viral DNA has been sequenced into this CRISPR region of it’s own DNA, all of this cells daughter cells will be immune to this virus. The CRISPR Cas-9 system then, is like a permanent vaccine that the cell gives to itself and all its descendants.

The researchers at Kyoto University attempted to edit and block the HIV virus that can lie dormant in the host cell sometimes referred to as a latent reservoir (LTR). Anti-retroviral therapy is able to keep active replication of HIV in check. The problem is that the LTR is always there and until now, has been resistant to therapy. The researchers report that when LTR-targeting CRISPR Cas-9 components were transfected into fighter T cells (the cells that HIV infects), the expression of LTR was significantly reduced. The researchers also report that the CRISPR Cas-9 may be a very useful tool in curing HIV.

 

Kyoto Study:

http://www.nature.com/articles/srep02510

 

Brief Introduction into CRISPR Cas-9

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Resistance to Cancer in Elephants

The paper I chose to summarize involves a study done on elephants to determine why they rarely get cancer. For decades elephants have been known to be super resistant to cancer and until recently no one knew why. Researchers from University of Utah and Arizona State University in collaboration with Ringling Bros. Center for Elephant Conservation believe they have found the answer. The secret seems to lie in the DNA code of elephants. The DNA of the largest land animal on Earth contains 38 copies of a certain gene that codes for p53, which is a tumor suppressor. Thirty-eight that is, compared with just two copies in humans. Furthermore, the researchers believe that elephants may have a more aggressive way to target and destroy pre-cancerous cells. Joshua Schiffman, a co-senior author, says, “Nature has already figured out how to prevent cancer. It’s up to us to learn how different animals tackle the problem”. For many years elephant health has been a real mystery. Because elephants have about 100 times more cells overall compared to humans, they should be 100 times more susceptible to a cell malfunctioning and becoming cancerous. This study also confirmed, by looking at a large database of elephant deaths, that elephants die of cancer between two and five times less often than humans. That is, elephants have a 5% cancer mortality rate compared to between 11% and 25% in humans. The researchers analyzed the genome of the African elephant and discovered at least 40 variations of the cancer suppressing gene p53, 38 of which are retrogenes meaning they are variations of the same basic gene. The researchers also drew blood from many of the elephants and performed some interesting experiments. One experiment they did was subjecting the DNA of the elephants to damage which can be a facilitator of cancer. The elephant cells reacted by committing apoptosis. The researchers mentioned that because elephants are so massive and have so many cells they should be extinct by now due to the increase in risk of cancer. They believe that the elevated levels of the p53 gene is natures way (through evolution) of preventing cancer. Humans with Li-Fraumeni disease contain only one active p53 gene (as apposed to the normal two), and the researchers compared the blood tests from the elephants with humans who suffer from the disease. They found that after subjecting the DNA of both groups to damage the elephant cells committed programmed death five times more often than human cells from people with Li-Fraumeni disease. The researchers concluded that more p53 expression may lead to a much stronger resistance to cancer. As usual more research is needed to fully understand exactly how this gene could be used or studied to help better resist cancer in humans I just hope elephant blood doesn’t become as valued as their ivory.

ARTICLE REFERENCED:

http://jama.jamanetwork.com/article.aspx?articleid=2456041

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Interpreting Data and The Rosenhan Experiment

The lens in which we interpret data and experiments is crucial and can often become a hindrance, a blind spot on our lens if you will. For example, if we are evaluating a patients neurological condition and we have a doctrine in mind, say phrenology, we are more likely than not to find  something that we are looking for (a false positive). If we have instead, a doctrine of localization when we are examining the patient we will more likely than not find evidence for localization. The same holds true for a theory of neuroplasticity and each separate type of plasticity.What can be alarming is when we are presented with identical data, yet come up with two entirely different theories of explanation. This kind of subjective theory is dangerous in science and needs to be considered when we are conducting experiments and interpreting data and as we are reading over results of experiments and studies alike. This is exactly what double-blind studies attempt to guard for by taking away any preconceived notion of what a patient is (or is not) receiving. Double blind studies essentially strip away the subjective thoughts and opinions and leave us with objective data. I do not know if there is a science that isn’t vulnerable to this type of mistake. Certainly, the softer fields of philosophy and psychology are the most vulnerable with chemistry and physics being the least. Although, I would say that theoretical physics is very susceptible to this subjective error. Not only because theoretical physics necessarily involves making difficult predictions but additionally because the field is just so incredibly complicated.

Speaking of theEinstein famously disliked the implications of quantum mechanics that revolutionized physics in the first three decades of the 20th century. During international physics conferences Einstein would routinely pester Niels Bohr and the rest of the quantum mechanics founders, conjuring up thought experiments that seemed to contradict quantum theory.  After much dismay and some clever thinking Bohr would come up with an answer, usually by the end of the conference. The point I would like to make here is that even two of the smartest people who ever lived disagreed fundamentally about the same sets of rules and equations. Science, and especially in complex fields like theoretical physics, how you interpret data can be a very tricky business indeed. In fact, there were many new and often radical theories being proposed to explain the experimental results of quantum mechanics. This lead to something called The Copenhagen Interpretation which lead by Bohr, attempted to lay down a clear concise interpretation of the very odd world we were just beginning to discover. So, more objectivity leads to less room for interpretation but at some point complexity makes simple interpretation all but impossible.

Another great example of how we can misread and misinterpretation is The Rosenhan Experiment. This was a famous experiment conducted by a Stanford psychologist and professor who wanted to investigate the validity of psychiatric diagnoses. He and his colleagues (12 in total) attempted to get admitted into various mental hospitals across the U.S. The pseudo-pataients, as they were dubbed, confessed that they were experiencing tried auditory hallucinations. All twelve of them were admitted and diagnosed with psychiatric disorders. Following admission the pseudo-patients acted normally and after some time (I am not sure exactly how long) they told the staff that their auditory hallucinations had resided. All were forced to admit to having mental disorders and had to agree to take anti-psychotic drugs. The average time spent in the mental hospitals by the pseudo-patients was 19 days and upon release all but one patient was diagnosed with schizophrenia in remission. The second part of the experiment was not planned by Rosenhan but occurred when an offended psychiatric hospital administration challenged Rosenhan to send pseudo-patients to their facilities claiming they could spot the fakes. After a few weeks the psychiatric hospital released their results. Out of 193 new patients the hospital had seen 41 were labelled as potential pseudo-patients, in effect, patients who were lying and faking their symptoms. In reality however, Rosenhan had sent exactly zero pseudo-patients to the hospital. How could this hospital think that more than a fifth of patients they saw were faking it?

In science and medicine mistaking a false positive as a true positive is at best embarrassing and at worst deadly. Interestingly, evolution has programmed organisms to detect false positives and to react to them if they were true positives. This makes sense if we consider how animals interact in the wild. Consider a rabbit getting scared by a rustling in the bushes. Even if the rustling is nothing but the wind it is always optimal for the rabbit to respond as if the rustling was a lion. In other words it is much more favorable, evolutionarily, to be mistaken about a false positive than it is to be eaten.

Further Reading on The Rosenhan Experiment:

http://psychrights.org/articles/rosenham.htm

https://en.wikipedia.org/wiki/Rosenhan_experiment

Further Reading on The Copenhagen Interpretation:

https://en.wikipedia.org/wiki/Copenhagen_interpretation

Further Reading on Data Analysis:

https://en.wikipedia.org/wiki/Data_analysis

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The True Value of A Neuroscience Degree

The long term effect of my neuroscience degree is not about the extremely complex and detailed knowledge I have memorized to pass exams. It is the fact that I have a very solid foundation of neuroscience on which to build upon. In most areas I will have a basic understanding, in some areas I will have a very proficient understanding and in a few areas that I was (and still am) most interested in I will have an advanced understanding in. But, the real value of my degree is that I now have, at the very least, a basic understanding of just about any given field of neuroscience (behavioral, cognitive, immunology, endocrinology, virology, etc.) or any field related to neuroscience (genetics, epigenetics, optogenetics, stem cell therapy, etc.). The true value of studying neuroscience the past few years is not specifically what i’ve learned, but what I am now capable of learning. You can not just jump into a field like neuroscience, or chemistry, or physics and have any kind of comprehensive understanding of the science after a few months or perhaps even a year, no matter how hard you study. No matter how hard you work it takes a certain amount of time and a certain amount of exposure to the hundreds, thousands of concepts and ideas and theories and historical breakthrough’s to achieve any sort of grasp on your field as a whole. You need to hear things and read things over and over again if they are going to stick with you long term. It is like joining a new culture and learning a new language, quite literally in many aspects. You must get a feel for the science you’re studying, an understanding of it’s past and knowledge of it’s present state. Anyone can memorize brain related words and pathways but without context they are close to meaningless. I once heard that  becoming an expert in a field of science takes a decade and I think this probably true.  Three years ago I would not have been able to read a scientific article and come away with any real understanding. Now I feel confident that I can read almost any scientific article and come away with, at the very least, a proficient understanding of what I read, and that is what I am most proud of.
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What do you think?

“From a long view of the history of mankind, seen from, say, ten thousand years from now, there can be little doubt that the most significant event of the 19th century will be judged as Maxwell’s discovery of the laws of electrodynamics. The American Civil War will pale into provincial insignificance in comparison with this important scientific event of the same decade.”

-Richard P. Feynman

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How Come Some People Believe In the Paranormal?

This article described the science of belief. Belief in the super natural such as ghosts, belief that the government is hiding aliens from the public, belief that bigfoot is real are some of the things that researchers were interested in. While being in a STEM field I consider myself to be some what of a skeptic and I take pride in not believing in everything I read and watch. For me, personally, there needs to be a certain amount of scientific professionalism at the very least and I usually look for peer reviewed articles or double blind studies as the best proof of truth. With that said, I think there is always an amount of trust we must give to what we are reading no matter the subject matter. For example, we of course cannot hear and see directly all the information we take in so we have to trust what we are reading is true. It is up to each person individually to set there own standard of truth, although I think many people may not have a standard at all. Things get even more complicated when we move away from the objective sciences into the world of opinionated politics. In summary, the research team gave people a test to measure what kind of thinkers they were. The test differentiated between intuitive thinkers and reflective thinkers. I don’t think the test is a very good parameter for someone’s belief in a certain phenomena as belief is something that develops over a lifetime and takes into account family and social environment, cultural norms, personal life events, as well as intelligence and curiosity. Nonetheless, researchers reported that the reflective thinkers, who were supposed to be more cautious and perhaps skeptical than their intuitive counterparts, were less likely to believe things like their astrological sign and phenomena like UFO’s or bigfoot. I think this article is very interesting and gets to the heart of belief and truth in science, a topic that cannot be under valued, especially in today’s world.

REFERENCE:

http://www.scientificamerican.com/article/how-come-some-people-believe-in-the-paranormal/

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