I got the idea for this post from the question Tim Ferris asked Dom D’Agostino in his podcast1. He asked what tools he would use if he got advanced cancer today.
I will try to expand this question taking as an example Ovarian Cancer.
What would I do if someone I love has Ovarian Cancer?
First of all, you need to be aligned with your physician and discuss which other things you can do to fight against this disease. Although standard care may not be enough, if we combine several ideas together, we can raise our chances of curing cancer.
All the things discussed here are supplemental, don’t ignore your doctor.
In our society, the word “cancer” has a negative connotation and many feel as if there is nothing we can do about. Nowadays, cancer death rates have declined and more people survive the disease. Just in the US, the death rate has dropped 27% in the last 25 years2.
Be optimistic and think there are many things we can do about it. Many are aware of the “placebo” effect, but you have to know also the “nocebo” effect: if you believe something is going to kill you your brain will act against you making things worse3.
Fasting would be one of the first things I would do. There are many protocols you could follow, being daily fasts (24 hours without eating) the more aggressive. D’Agostino suggested that it’s possible to use fasting to trigger our bodies’ natural garbage clearing mechanisms (autophagy) in order to clean up pre-cancerous cells.
Fasting is thought to impair energy metabolism in cancer cells, inhibiting their growth and rendering them susceptible to clinical treatments4. If mixing with chemotherapy it also can sensitive the tumor for its therapeutic effects while having fewer side effects in healthy cells5.
There are a couple of protocols you could follow: time-restricted feeding or 5:2 Intermittent Fasting, being the first one easier to follow and with great benefits if we follow a Ketogenic Diet (next item).
The Ketogenic Diet has been long used for treating epilepsy in children or to manage seizures. In recent years, this diet has been investigated for treating other diseases.
You have to think of glucose as the enemy since is the primary source of energy for the majority of cancer cells, these cells can’t use ketones effectively as fuel because defects on mitochondria6.
Regarding our case for Ovarian Cancer, as discussed by Cliff Harvey7, although these cancer cells seem to be able to get energy from adjacent adipocytes it doesn’t seem that this is affected by a diet rich in fat. The idea remains the same:
Dietary interventions should focus on reducing total fuel availability to cancer cells and also on reducing known drivers of cancer growth and proliferation.
It’s also suggested by Harvey to use a modified version of the ketonic diet:
So, it is known that low-carbohydrate diets reduce known cancer drivers like IGF-1, reduce average glucose and insulin levels, and do not predispose to greater triglyceride/fatty acid availability. Furthermore, ketone levels (βOHB) do not need to be excessively high, and for the purposes of ovarian cancer treatment, a modified ketogenic diet approach, rich in phytonutrients, sufficient in protein (to reduce muscle-wasting), and not excessively high in fat (so as to allow for sufficient fueling without excessive βOHB levels) is likely to be both safe and, based on the extant literature, may also improve cancer outcomes versus standard care.
D’Agostino also agrees on having a higher amount of protein in the diet to avoid sarcopenia (muscle loss due to cancer), a modified Atkins diet with 30% of proteins and 70% fats, with enough vegetables for its phytonutrients while also taking MCTs and exogenous ketones (this helps to reach a “fasting state” rapidly without the stress of 24 hours fasts).
Have in mind to include good fat in the diet: eggs, salmon, olive oil, coconut oil, nuts, etc. Take for instance nuts, those who include them in the diet have a lower incidence of cancer8. All this will help with improving body composition and lowering insulin & insulin-like growth factor-I (IGF-I)9.
Metformin is an old drug that is being used for treating Diabetes and is also being investigated for its effects on longevity. Metformin works by suppressing glucose production in the liver. This lowers the body’s overall levels of glucose.
Citing D’Agostino again, he suggests to take it to the point is causing side effects and then stay there.
Regarding Ovarian Cancer, there is promising data suggesting that Metformin is cytotoxic to these cancer cells and would help with the treatment10.
Now is the time for a radical change in your life and start focusing on you and your health.
The main objective is to lower your stress and anxiety. If you have chronic stress you are in fact suppressing your immune system, which is a critical component for fighting cancer. Dr. Gabor Maté insists on this idea: if you don’t say “no” enough your body will say it in the form of illness. You can watch any of his talks or read his book11.
I’ve written a small book on the topic of changing habits for a less stressful life, which you can grab for free at https://leanpub.com/refactoryourmind. Small things like meditation, gratitude, or living with less can help to manage your stress and boosting your immune system.
This could act in synergy with CAR T-cell therapy in case you’re a good candidate for this therapy12.
You’ve probably heard in the news. You should avoid red meat to lower your cancer risk13.
Red meat is associated with an increased risk of colon and rectum cancer, and evidence also suggests it is associated with some other cancers, such as prostate and pancreatic cancer. Examples of red meat include beef, pork, and lamb.
Although now protein will be an important part of your diet for not losing muscle mass, you should base your protein from vegetable sources, eggs, or fish.
A healthy microbiota is also a critical part of your body14:
The bacterial population of the gut microbiome outnumbers human cell by approximately 10-fold [150], and is sometimes referred to as the ’forgotten organ’ due to its increasingly recognized role in multiple physiological and pathological processes.
Be sure to incorporate probiotics and prebiotics. An example would be instead of consuming dairy products like milk or cheese, take Kefir instead. Kefir is a powerful probiotic. Some researchers suggest that Kefir has anti-cancer properties15.
Sulforaphane, a component that is found in vegetables like broccoli and cabbage could act as an anticancer substance too16.
Xenograft experiments in vivo confirmed that sulforaphane effectively suppressed tumor growth by inhibiting ovarian cancer cell proliferation through targeting tumor‑related signals
Although there is no clear evidence yet for ingesting sulforaphane in a pill, I would totally rise the ingestion of vegetables containing this substance.
There are many things we could do. The most important thing is having the right mindset and let people help you. I do hope some of these tips could make an impact fighting against cancer and that in 10 years this will be a disease of the past. We will see!
Ferriss T. Dom D’Agostino on Fasting, Ketosis, and the End of Cancer [Internet]. Available from: https://tim.blog/2015/11/03/dominic-dagostino/
Simon S. Facts & Figures 2019: US Cancer Death Rate has Dropped 27% in 25 Years [Internet]. 2019. Available from: https://www.cancer.org/latest-news/facts-and-figures-2019.html
Nocebo [Internet]. Available from: https://en.wikipedia.org/wiki/Nocebo
Cabo R, Mattson MP. Effects of Intermittent Fasting on Health, Aging, and Disease. New England Journal of Medicine. 2019;381(26):2541–51.
Eske J. Can fasting help fight cancer? [Internet]. 2019. Available from: https://www.medicalnewstoday.com/articles/324169
Seyfried TN, Yu G, Maroon JC, D’Agostino DP. Press-pulse: a novel therapeutic strategy for the metabolic management of cancer. Nutrition & Metabolism. 2017;14(1).
Harvey C. Are Low-Carb & Keto Diets ‘Bad’ for Ovarian Cancer? [Internet]. 2020. Available from: https://cliffharvey.com/are-low-carb-keto-diets-bad-for-ovarian-cancer/
Aune D, Keum N, Giovannucci E, Fadnes LT, Boffetta P, Greenwood DC, et al. Nut consumption and risk of cardiovascular disease, total cancer, all-cause and cause-specific mortality: a systematic review and dose-response meta-analysis of prospective studies. BMC Medicine. 2016;14(1).
Cohen CW, Fontaine KR, Arend RC, Alvarez RD, Leath III CA, Huh WK, et al. A Ketogenic Diet Reduces Central Obesity and Serum Insulin in Women with Ovarian or Endometrial Cancer. The Journal of Nutrition. 2018;148(8):1253–60.
Tang G, Guo J, Zhu Y, Huang Z, Liu T, Cai J, et al. Metformin inhibits ovarian cancer via decreasing H3K27 trimethylation. International Journal of Oncology. 2018;0(0).
Mate G. When the Body Says No [Internet]. 2013. Available from: https://youtu.be/c6IL8WVyMMs
CAR T-cell Therapy and Its Side Effects. Available from: https://www.cancer.org/treatment/treatments-and-side-effects/treatment-types/immunotherapy/car-t-cell1.html
Red Meat and Processed Meat Consumption [Internet]. 2020. Available from: https://progressreport.cancer.gov/prevention/red_meat
Zinger A, C. Cho W, Ben-Yehuda A. Cancer and Aging - the Inflammatory Connection. Aging and disease. 2017;8(5):611.
Sharifi M, Moridnia A, Mortazavi D, Salehi M, Bagheri M, Sheikhi A. Kefir: a powerful probiotics with anticancer properties. Medical Oncology. 2017;34(11).
Kan S, Wang J, Sun G. Sulforaphane regulates apoptosis and proliferation‑related signaling pathways and synergizes with cisplatin to suppress human ovarian cancer. International Journal of Molecular Medicine. 2018;0(0).
A couple of definitions for those who aren’t familiar with these terms:
Test Driven Development: (TDD) Is the practice in Software Engineering of writing the tests before the code itself for a particular feature. This helps simplifying the problem to solve while you build your solution incrementally.
Brain Computer Interface: (BCI) An interface that reads activity from your brain in order to communicate with a computer without using devices like keyboard or mouse.
Neuralink is the company most famous trying to achieve a good BCI. The primary focus will be helping those patients with cervical injuries. A known approach is using a bidirectional BCI, which will read activity from the brain while also stimulating the sensory cortex, closing the loop and helping bypassing the nerve injury.
But can we use BCI? I want it now 😩
There are some options out there that you can play around with. OpenBCI is a popular one. Other more commercials are Mindwave or Emotiv.
If you feel adventurous you can build your own following instructions at OpenEEG. Be careful with the risks:
However, if there is an isolation failure in the EEG unit due to an accident, or faulty design, or faulty parts, or faulty construction, and the EEG subject touches a live mains voltage in their environment, the mains voltage will take the shortest route to earth, which is through the subject’s body. This electric shock passing through the head is likely to have severe consequences.
I ended up picking a device from Mindwave, since I didn’t have much time for playing around it wouldn’t make sense investing in a more expensive device.
For a quick demonstration what I wanted to achieve is to execute tests each time I had 2 blinks. Technically I’m not using the electrical activity from the brain, but from the muscles in the eye in charge of performing a blink. But the idea is the same. I’m giving an order from my brain to execute a command in my computer, which is faster than using a shortcut with the keyboard or using the mouse.
After researching a bit on how to connect to the device I’ve found is not that complicated using JavaScript. Once you have the ThinkGearConnector running with the logging option enabled you will be able to interact with the device:
After you should provide some configuration options, like app name, format etc.
Then you should be ready for listening the data from the Mindwave device. Normally you will get values for your meditation/attention current state as well as values for each type of your brain waves:
You can get those with the following code:
Now for our demo project, I want to detect 2 blinks in a row. Luckily, the device
tell us when a blink is detected with its detected blink strength. This is good for tuning out
accidental blinks. You will receive a property in the JSON called blinkStrength
with its corresponding
value.
So with the following code we can detect when 2 blinks are detected and execute a command of our choice. In this case we will run tests with Jest.
I recorded a video so you can see it in action:
Obviously, I won’t use this while I’m coding, the device is not that comfortable, but will see in the future :)
If you want to see the code you can find it in Github.
]]>In Neuroscience it is common to have repeated measurements over time of changes occurring in physiological or endocrinological variables. Here is an example of a repeated measurement of cortisol (using fake data):
As you can see we have 6 different measurements of cortisol at different times. This could become a problem in statistical analyses since we would have many different values to compare from. That’s why the area under the curve (AUC) is often used for incorporating multiple time points.
As mentioned by Pruessner et al. (2003):
The computation of the AUC allows the researcher to simplify the statistical analysis and increase the power of the testing without sacrificing the information contained in multiple measurements
The point is clear, AUC will help us to simplify our analyses in many cases.
Within AUC we have two different types of formulas which will serve for different purposes:
- AUCg: Area under the curve with respect to ground.
- AUCi: Area under the curve with respect to increase.
AUCg
This formula can be derived from the trapezoid formula. As seen in the following figure a trapezoid is made by triangles and rectangles with the help of time points and values recorded in each time point:
With the help of the figure is easier to understand the data we need to calculate the formula:
- The measurements (m1 - m6)
- The time differences between measurements (t1 - t6)
With the following formula we will be able to calculate the total area under the curve of all the measurements and provide a single data value which will be useful for our analyses (e.g. calculating the overall diurnal cortisol secretion).
Also, this formula can be further simplified in the case that time differences between measurements are identical. Those time differences won’t be included in the formula now:
AUCi
There is another formula for another area of interest showed in the following figure:
We can see that the reference is the value of the first data point and not zero. Contrary to AUCg this helps highlighting changes over time. That’s why the name of the formula receives the name of Area Under the Curve respect to the Increase.
The formula is similar to the one we saw with AUCg. The difference is that we should remove the area between ground and the first data point:
And as in the other formula we can remove t if the time distance is constant between different measurements:
That’s it! I actually wrote this post for myself, but I hope this can be useful for anyone. Cheers! 🕵️
Pruessner, J. C., Kirschbaum, C., Meinlschmid, G., & Hellhammer, D. H. (2003). Two formulas for computation of the area under the curve represent measures of total hormone concentration versus time-dependent change. Psychoneuroendocrinology, 28(7), 916–931. https://doi.org/10.1016/S0306-4530(02)00108-7
]]>Recently, thanks to a recent article by Yang, J. H. [1] I discovered a good analogy of aging with the Shannon diagram depicted in The Mathematical Theory of Communication, dating back in 1948.
In this diagram basically there is a source of information that is encoded into a signal and then transmitted to the receiver, with the downside of having a noise component that alters the signal.
This could be a good analogy with aging, since what differentiates a young cell with an old cell is not the information source, but its noise component, which is way bigger in an old cell. Both a young and an old cell have virtually the same genome, the difference between them is epigenetic, meaning that an old cell has a different pattern of gene expression, which results in the cell losing its identity and not behaving as it should.
What is this noise source? The best chance is to look at our telomeres, the shorter the telomeres are for a given cell, the biggest noise it produces, altering the gene expression. This effect has been named TPE or Telomere Position Effect [2].
Case 1: Long Telomeres
Case 2: Short Telomeres
In the above example we can see that an altered gene expression results in a reduced number of collagen proteins, and hence contributing to skin aging.
This is all an oversimplification but good for explaining aging to non scientists:
Aging is not just wear and tear, in fact our cells have been around for billions of years. In a living organism if we are able to reduce the noise source, in this case resetting telomere length, we will again have an unaltered signal and young cells. Is that simple? Soon we will see how this goes in humans 🤷, it has already been proved right in mice 🐭🐭.
[1] Yang JH, Griffin PT, Vera DL, Apostolides JK, Hayano M, Meer MV, et al. Erosion of the Epigenetic Landscape and Loss of Cellular Identity as a Cause of Aging in Mammals. 2019;
[2] Robin JD, Ludlow AT, Batten K, Magdinier F, Stadler G, Wagner KR, et al. Telomere position effect: regulation of gene expression with progressive telomere shortening over long distances. Genes & Development. 2014;28(22):2464–76.
]]>In this capitalism era there is always the struggle to be more productive to be ahead of your competitors. Since we can’t change that (yet), here I’ll show you some tips to increase your brain health which will help with your productivity & happiness. Many tips come from Neuroscience (Brain Health Institute) and others from my own experience. Let’s get into it:
Yes, doing exercise is the best way we know for brain health, better than any other cognitive activity. You just need to find what you like and add it into your daily routine.
Exercise is better, but that doesn’t mean you shouldn’t exercise your mind as well. Best case scenario is that your work has any form of cognitive activity. Learn a new language, learn a new skill, play a video game (don’t overdo it) [1] or just go to a place you’ve never been.
Your diet plays a big role but every person is different (nutrigenomics). You should find which foods work best for you. I’m sure eating pizza & soda won’t help with your concentration. Salmon & salad probably will 😏
You need a balance in life, and you shouldn’t be always working. Taking care of your inner circle (friends & family) is a priority and also good for your brain health. We are social animals after all 🐒
This may be the most important factor. Even if you do everything right in this list but have a bad night’s sleep all will fall apart… I’m sure you’ve experienced this. Your mood and learning abilities will be a lot worse.
In fact, we’re the only species that are depriving sleep in purpose, and nature couldn’t have developed a mechanism to circumvent this situation. You should know that sleep is critical for your glymphatic system, which “cleans” your brain of waste during the night. Even some elite players know the importance of sleep and sleep in the range of 10 hours per day, which is also important for recovery.
Ray Allen gave a simple tip that you could try doing: Go to bed early (between 9pm-11pm), you’ll notice the next day you are motivated and with more energy.
You can’t perform well if you’re sick (duh!), Easy to say, but still, many people suffer from stress and anxiety these days. If you’re stressed your immune system won’t work at 100%, so put your health as a priority and not your work.
You must have a plan, you must find a reason for living, or the so called “Ikigai”. Many just don’t know and not have that self awareness. If you don’t know what you want to do in life you need to pause and think, instead of going on autopilot with daily routines. From Robert Greene words:
“Just being aware that you now have a plan is enough to lift you out of that depression”
It’ll be much easier to endure life if you have a plan and you follow it step by step. Petty concerns won’t matter now 🤷
It’s preferable that in your work you have views to nature. Your attention will be far better. This has been found in a study where an attention-restoring experience can be as simple as looking at nature [2]
It is also important that you are as close to a nature setting as you can be, since the quality of the air in your workplace can make a huge difference. For instance, it’s been shown that with exposure to lower levels of Volatile organic compounds (VOCs) or CO2 your cognitive performance increases [3]. Another reason to escape from big polluted cities.
This will help you not being reactive to your phone and avoid training your brain to be distracted. Even just avoiding your phone the first 30 minutes will help. Jim Kweek gives this advice in the following video:
It’s been found in recent research that we are more productive if we work in brief “stints” rather in marathon style (see detailed blog post about in [4]; if your surname is Kipchoge you’re cleary an outlier)
Just working from 9 to 6 doesn’t make sense from how our brains work, is just something cultural. It’s way better if you have breaks in between that refreshes your mind, like exercising, meditating, taking a walk, etc. Also if you possess a different chronotype you may feel more productive in the evening rather than in the morning.
Great achievers didn’t work long hours and spend the whole day at work, you also need to enjoy your life, and as I like to say even if you’re not working your brain has “background workers” which are working for you without noticing. I’m sure your best ideas had come from relaxation periods and not from hitting your head on the desk table.
[1] Kühn S, Gleich T, Lorenz RC, Lindenberger U, Gallinat J. Playing Super Mario induces structural brain plasticity: gray matter changes resulting from training with a commercial video game. Molecular Psychiatry. 2014;19(2):265–71.
[2] Tennessen CM, Cimprich B. Views to nature: Effects on attention. Journal of Environmental Psychology. 1995;15(1):77–85.
[3] Schmidt S. Brain Fog: Does Air Pollution Make Us Less Productive? Environmental Health Perspectives. 2019;127(5):052001.
[4] https://medium.com/feel-the-blog/want-to-feel-more-productive-try-not-working-b16b706db9f4
* Awesome photos come from https://unsplash.com/
]]>Measuring blood cell telomere length (TL) has become a popular approach among researchers. Some even claim that you can extend your telomeres through meditation or exercise, but can we trust this measurement?
Not really.
Blood cell TL is a dynamic feature which during periods might undergo considerable losses and during other periods show stability or even be extended. These measurements reflect the mean TL of a number of immune cell subpopulations. And since the status of the immune system, i.e. cell activity, proliferation rate, cytokine levels etc., is not constant we would expect this to be reflected also in blood cell TL (Svenson et al., 2011).
As seen in this figure from Fossel (2018) it seems better if we were able to measure TL from Stem Cells (in this case from the Hematopoetic Stem Cell compartment).
Quoting Fossel:
“Even if the “average age” of the white cells (i.e., the average telomere length) has improved, it is not because we have relengthened any particular telomere, but because we are sampling a different and newer population of white cells. In short, serial sampling of peripheral white cells is not as reliable as we wish it were. In real life (i.e., in clinical measurements of peripheral white cell telomeres), it’s not as bad a watching an urban neighborhood over a fifty year period, but the assumption that we can relengthen telomeres in peripheral cells is usually based on wishful thinking rather than on an understanding of white cell population dynamics. We can certainly measure peripheral white cell telomere lengths over time, but interpreting differences in telomere lengths is chancy and should be taken with a grain of salt. It rarely means what researcher would like you to believe it means.”
I’m not saying though that exercise or meditation don’t help. Long exposure to chronic stress is detrimental for your telomeres, since cortisol downregulates telomerase activity (Choi, Fauce, & Effros, 2008). But saying that you can re-extend your telomeres and become younger it’s a whole different thing. You’ll be able to slow down your telomere loss, but in no way you are going to reverse human aging unless heavy clinical interventions become available (i.e. gene theraphy).
So blood cell TL has any use? It certainly has. One use case would be to assess your immune competence. If you have short telomeres in your immune cells you’re in a higher risk for getting an infection (Helby, Nordestgaard, Benfield, & Bojesen, 2017).
Hope this helps to make some clarifications 🙂
Choi, J., Fauce, S. R., & Effros, R. B. (2008). Reduced telomerase activity in human T lymphocytes exposed to cortisol. Brain, Behavior, and Immunity, 22(4), 600–605. https://doi.org/10.1016/j.bbi.2007.12.004
Fossel, M. (2018). Telomere Editorial - Perspectives on Telomeres and Aging. OBM Geriatrics, 3(1), 1–1. https://doi.org/10.21926/obm.geriatr.1901031
Helby, J., Nordestgaard, B. G., Benfield, T., & Bojesen, S. E. (2017). Shorter leukocyte telomere length is associated with higher risk of infections: a prospective study of 75,309 individuals from the general population. Haematologica, 102(8), 1457–1465. https://doi.org/10.3324/haematol.2016.161943
Svenson, U., Nordfjäll, K., Baird, D., Roger, L., Osterman, P., Hellenius, M. L., & Roos, G. (2011). Blood cell telomere length is a dynamic feature. PLoS One. https://doi.org/10.1371/journal.pone.0021485.t001
]]>“Learning How to Learn”, this is by far one of the skills you should master. I recently took the Coursera course “Learning How to Learn: Powerful mental tools to help you master tough subjects” and I encourage you to do the same.
Well, I know almost everyone is busy as hell and won’t have the time to take the course. So, here I’ll summarize some of the key points made during the course:
Recall is better
Sometimes through highlighting or conceptual maps we get the illusion that we’re learning, while in fact the mere act of recalling produce better results for learning. This is backed up from research1.
What we recall becomes more recallable in the future. In a sense you are practicing what you are going to need to do later
They also pointed to one article where they offered this advice:
Immediately after every lecture, meeting, or any significant experience, take 30 seconds — no more, no less — to write down the most important points. If you always do just this, said his grandfather, and even if you only do this, with no other revision, you will be okay.
This advice is reinforcing a key idea of how our memory works. “Use it or lose it”. The more you use a neural circuit the stronger it gets.
Interleave your studies
Making a point to review for a test, for example, by skipping around through problems in the different chapters and materials can sometimes seem to make your learning more difficult. But in reality, it helps you learn more deeply.”
Test yourself often! Just don’t read your material and make some highlights.
To Really Learn, Quit Studying and Take a Test
Process builds walls
Studying everything one day before the exam won’t help you develop long term memories. You may pass your exam, but few days after you will forget your material.
Instead, you should get into the habit of practicing a bit every day. With practice you will increase the myelination within your neurons2 and as one professor once told us:
CREB, an important transcription factor needed for developing long term memories3, is only activated after several days of practice.
He was eager to measure our levels of CREB instead of making us to pass a test. But, luckily for us he abandoned the idea. Doing biopsies into our brains wouldn’t be very ethical I’d say.
Remember: “Strong walls shake, but never collapse”
Pomodoro technique
The Pomodoro technique is a widely known approach to working/studying in sprints of 25 min without distractions.
Before starting… “It is perfectly normal to start with a few negative feelings about beginning a learning session—even when it’s a subject you ordinarily like. It’s how you handle those feelings that matters.”
Also, this technique will help you to focus in the process and not in the final product. It’ll help you to avoid multitasking too:
a) Human beings cannot multitask.
b) The more you think you’re good at multitasking, the worse you’re at doing it.
Plan your quitting time
Planning your quitting time is critical! You need time also for exercising and sleep, activities which are essential for your memory. Also, during these relaxation periods new solutions to problems will pop up into your mind. So if you’re stuck with something: “Give your subconscious an assignment.”
They relate to these relaxation periods as your brain being in a “diffused” mode. In this mode your brain will create newer and broader connections. On the contrary, when you’re working in some task your brain will be in a “focused” mode using a narrower neural circuit.
Eat your frogs in the morning
It’s better to start with the most difficult/least pleasant task in the morning. Make also appointments to yourself to work on hard tasks every day (e.g. half an hour a day). Remember that willpower is a scarce resource, so use it wisely.
Avoid Einstellung
Einstellung refers to a person’s predisposition to solve a given problem in a specific manner even though better or more appropriate methods of solving the problem exist4.
Acknowledge this effect and be always eager to learn new things or new approaches to future problems!
Chunking
When you learn something new you create a “chunk”. Hence the term “chunking”. In the course they recommend not to use extra time once you create a chunk:
Once you’ve got the basic idea down during a session, continuing to hammer away at it during the same session doesn’t strengthen the kinds of long-term memory connections you want to have strengthened. Worse yet, focusing on one technique is a little like learning carpentry by only practicing with a hammer. After a while, you think you can fix anything by just bashing it.
Is better to practice a bit every day instead of having just one long session. Also the more chunks you create from different subjects the better:
The more fields of knowledge you cover, the greater your resources for improvisation.
The ability to combine chunks in new and original ways underlies a lot of historical innovation.
Handwrite your notes
It’s been suggested that handwriting your notes may be better than just transcribing notes using a laptop5. So dust off your pens and go back in time to take notes as you once had!
Memory Palace
This is an ancient technique for efficient recall of a set of items. Reading from Wikipedia:
“The items to be remembered in this mnemonic system are mentally associated with specific physical locations.The method relies on memorized spatial relationships to establish, order, and recollect memorial content”
Haven’t tried much myself this technique yet, but I sure will do in the future.
Bonus
Here are a couple of ideas taken from the course that may help you in your quest for learning:
“Law of Serendipity: Lady Luck favors the one who tries”. Lucky are for those who see the unexpected, listen intuition and try.
“Perseverance is a virtue of the less brilliant.” Santiago Ramón y Cajal
When I was a kid I struggled with Peg Solitaire. I found it almost impossible to find a solution and my best score was having 2 pegs left. You win the game if you are left with only 1 peg left.
I gave up on the problem. But then, some years later I started at the University with my first adventures on programming with C++. There was an “Aha!” moment when I learnt about some algorithmic technique called Backtracking. Basically, Backtracking allows you to explore all possible solutions for a given problem. If it goes through some path where it can’t a find solution it “goes back” and tries a new path.
So the only missing thing was how to model the Peg Solitaire board and its movements. Easy peasy. We could just model the board as a 7x7 matrix. I then assigned some numeric codes depending on if the peg is present (1), not present (0) and if the position is outside of the board (-1).
Regarding movements for a given position within the matrix we should check all possible movements if any. For instance, for the position within the matrix [1, 3] a valid movement would be moving the peg to the right. This would be the resulting matrix:
You could check the original code in C++ or a refactored solution in Ruby (the refactor is not complete, so feel free to improve the solution and submit a pull request).
Here a relevant bit from the C++ code:
Here you could check the solution found by the above scripts:
So here you have a clear example of Transfer of Learning. Hopefully this will inspire you to solve similar problems.
Happy coding! 💻
]]>Hace ya unos años ayudé en la Universidad Politécnica a desarrollar una herramienta que facilitara la implantación de prácticas ágiles en equipos de trabajo. Si bien son conocidas en el mundo de la informática, voy a destacar aquí algunas de ellas que tendría sentido aplicar en ciencia y/o investigación.
1 - Reducir las interrupciones o cambios de contexto que afectan en su trabajo a los miembros del equipo
Es bastante frecuente que te interrumpan si te encuentras en un espacio de trabajo rodeado de gente. El problema es que al interrumpirte puedes perder el foco de lo que estés haciendo y necesites de al menos 15 minutos para volver a coger el ritmo.
Una solución para atajar este problema es el uso de aplicaciones de mensajería instantánea (ej. DiscordApp). De esta manera podrás pedir ayuda a tu compañero de trabajo y que él responda cuando pueda. Solo interrumpiremos cuando sea realmente importante.
2 - Formar equipos pequeños y procurar que mantengan sus integrantes.
Cuesta tiempo que los equipos se formen y se entiendan, mas que es muy difícil de gestionar un equipo demasiado grande.
3 - Visualización de todo el trabajo pendiente encargado al equipo.
Es fundamental el uso de herramientas que permitan visualizar el trabajo pendiente y que faciliten la colaboración. No es ágil que solo el jefe de proyecto sepa lo que queda por hacer. Un buen ejemplo es el uso de Trello.
4 - Que los integrantes del equipo puedan encargarse de diferentes tipos de actividades (ojalá de todas), aunque puedan ser especialistas en alguna(s) de ellas.
Esto es crítico para evitar los cuellos de botella. Si la única persona que sabe realizar una determinada actividad cae enferma se convierte en un gran problema para el equipo. Tu “bus factor” ha de ser alto.
5 - No abusar de las horas extras, negociar y re-planificar oportunamente para evitarlo
No por trabajar más horas vas a ser más productivo. Es más importante saber priorizar a la vez que tener un balance en tu vida. No descuides tus amistades, y gasta tiempo en mejorar tanto tu salud mental como física.
Estoy seguro de que has tenido mejores ideas cuando estabas realizando un paseo o una ducha relajante que estando enfrente del ordenador.
6 - Evitar invertir esfuerzo en adelantar trabajo que no esté comprometido y/o no esté cercano a su entrega.
Evita tu propio sabotaje y termina las tareas que tienes empezadas antes de embarcarte en otras nuevas. Los nuevos proyectos siempre generan mayor motivación pero asegurate de acabar antes los que ya empezaste hace unos meses.
7 - Gestión continua y multicriterio del trabajo pendiente para que esté siempre debidamente priorizado.
Es normal que tus prioridades cambien y por ello el trabajo que te quede por hacer ha de estar siempre priorizado.
8 - Limitar el trabajo en proceso (WIP), es decir, la cantidad de unidades de trabajo que tiene el equipo en una determinada actividad.
Con esto mejoramos la productividad y los continuos cambios de contexto. Ya lo dijo Elsa Punset y Daniel Goleman, la multitarea agota al cerebro y es mejor centrarse en pocas actividades que tener tu mente apuntando a 100 direcciones distintas
9 - Promover la sencillez en todos los aspectos. Ofrecer la solución más simple y mínima que pueda ser satisfactoria para el cliente.
A menudo somos demasiado perfeccionistas. Por ejemplo, al redactar un artículo le damos muchas vueltas a ciertas secciones cuando finalmente, el revisor seguramente apuntará a alguna parte que tu ya pensabas que estaba bien. Menos es más, ten en cuenta siempre la ley de Pareto.
10 - Abordar y entregar trabajo terminado de forma incremental.
Es mejor que cuanto antes revisen tu trabajo para saber si estás en la dirección correcta. Con ello evitaremos el re-trabajo que se da en casos cuando ya has terminado un trabajo que estaba mal planteado desde el principio.
Puedes encontrar más prácticas ágiles en:
http://agile-roadmap.tuneupprocess.com/
]]>It’s just a matter of time that we will soon be able to reverse human aging. Does this mean that we will cure age-related diseases?
Yes, most likely.
One of the approaches that is gaining popularity is relengthening the telomeres of our cells. Telomere attrition is considered one of the primary hallmarks of aging (López-Otín, Blasco, Partridge, Serrano, & Kroemer, 2013), influencing also other secondary hallmarks (cellular senescence, epigenetic alterations…).
This approach becomes “simple”: if we’re able to reset telomeres’ length we’ll be able to reset gene expression, while increasing molecular turnover, cell maintenance and DNA repair (Fossel, 2002; Robin et al., 2014).
No need to kill anyone to become young again.
But ok now, how do we relengthen our telomeres?
Naturally, telomerase is the enzyme that relengthes telomeres in humans. Telomerase acts a reverse transcriptase (Telomerase Reverse Transcriptase or TERT), adding to the DNA the complementary DNA (cDNA - sequence TTAGGG) using its RNA template (Telomerase RNA Component or TERC).
Unfortunately, telomerase is not active in our somatic cells. What then? This is where gene therapy comes to the rescue.
Gene therapy requires three things (Daya & Berns, 2008):
1) Identification of the defect at the molecular level (telomerase deficit)
2) A correcting gene (hTERT)
3) A way to introduce the gene into appropriate host cells (i.e., a vector - AAV9)
In our case we are interested in expressing telomerase in brain cells in order to prevent/cure Alzheimer’s disease. Adeno-Associated Virus are of special interest for this purpose, since they represent nature’s vectors for the delivery and expression of exogenous genes in host cells (Daya & Berns, 2008). Particularly using the serotype 9, since it has the capacity of crossing the Blood-Brain-Barrier (BBB). In that manner, we can infect brain cells, preferentially neurons and astrocytes (Foust et al., 2008; Manfredsson, Rising, & Mandel, 2009; Bernardes de Jesus et al., 2012).
How does AAV works?:
AAV9 confers the benefit of a high transduction (i.e. introducing DNA into cells) efficiency in a wide range of tissues, but if we’re interested in targeting Alzheimer we should worry about microglia.
Microglia is of special interest for Alzheimer. Apart from being the immune sentinels of infection, they are also involved in the maintenance of brain homeostasis, in roles such as the control of neuronal proliferation and differentiation, as well as in the formation of synaptic connections (Ginhoux, Lim, Hoeffel, Low, & Huber, 2013). If we want to cure Alzheimer, we must restore microglial function, specially its degradative capacity that will avoid amyloid plaques to form in the first place (Solé-Domènech, Cruz, Capetillo-Zarate, & Maxfield, 2016; Yeh, Wang, Tom, Gonzalez, & Sheng, 2016).
Does AAV9 transduces microglia efficiently? It seems not. Here is where cell-specific promoters should be used. Both F4/80 and CD68 had already be proven to be successful transducing microglia (Cucchiarini, Ren, Perides, & Terwilliger, 2003; Rosario et al., 2016).
In summary, a gene therapy that makes possible to rescue senescent microglial cells to make them young again becomes promising for battling against neurological age-related diseases. Not only Alzheimer, but in a similar manner we’ll be able to fight against Parkinson, Huntington and others.
Bernardes de Jesus, B., Vera, E., Schneeberger, K., Tejera, A. M., Ayuso, E., Bosch, F., & Blasco, M. A. (2012). Telomerase gene therapy in adult and old mice delays aging and increases longevity without increasing cancer. EMBO Molecular Medicine, 4(8), 691–704. https://doi.org/10.1002/emmm.201200245
Cucchiarini, M., Ren, X. L., Perides, G., & Terwilliger, E. F. (2003). Selective gene expression in brain microglia mediated via adeno-associated virus type 2 and type 5 vectors. Gene Therapy, 10(8), 657–667. https://doi.org/10.1038/sj.gt.3301925
Daya, S., & Berns, K. I. (2008). Gene Therapy Using Adeno-Associated Virus Vectors. Clinical Microbiology Reviews, 21(4), 583–593. https://doi.org/10.1128/CMR.00008-08
Fossel, M. (2002). Cell Senescence in Human Aging and Disease. Annals of the New York Academy of Sciences, 959(1), 14–23. https://doi.org/10.1111/j.1749-6632.2002.tb02078.x
Foust, K. D., Nurre, E., Montgomery, C. L., Hernandez, A., Chan, C. M., & Kaspar, B. K. (2008). Intravascular AAV9 preferentially targets neonatal neurons and adult astrocytes. Nature Biotechnology, 27(1), 59–65. https://doi.org/10.1038/nbt.1515
Ginhoux, F., Lim, S., Hoeffel, G., Low, D., & Huber, T. (2013). Origin and differentiation of microglia. Frontiers in Cellular Neuroscience, 7. https://doi.org/10.3389/fncel.2013.00045
López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2013). The Hallmarks of Aging. Cell, 153(6), 1194–1217. https://doi.org/10.1016/j.cell.2013.05.039
Manfredsson, F. P., Rising, A. C., & Mandel, R. J. (2009). AAV9: a potential blood-brain barrier buster. Molecular Therapy, 17(3), 403–405. https://doi.org/10.1038/mt.2009.15
Robin, J. D., Ludlow, A. T., Batten, K., Magdinier, F., Stadler, G., Wagner, K. R., … Wright, W. E. (2014). Telomere position effect: regulation of gene expression with progressive telomere shortening over long distances. Genes & Development, 28(22), 2464–2476. https://doi.org/10.1101/gad.251041.114
Rosario, A. M., Cruz, P. E., Ceballos-Diaz, C., Strickland, M. R., Siemienski, Z., Pardo, M., … Chakrabarty, P. (2016). Microglia-specific targeting by novel capsid-modified AAV6 vectors. Molecular Therapy - Methods & Clinical Development, 3, 16026. https://doi.org/10.1038/mtm.2016.26
Solé-Domènech, S., Cruz, D. L., Capetillo-Zarate, E., & Maxfield, F. R. (2016). The endocytic pathway in microglia during health, aging and Alzheimer’s disease. Ageing Research Reviews, 32, 89–103. https://doi.org/10.1016/j.arr.2016.07.002
Yeh, F. L., Wang, Y., Tom, I., Gonzalez, L. C., & Sheng, M. (2016). TREM2 Binds to Apolipoproteins, Including APOE and CLU/APOJ, and Thereby Facilitates Uptake of Amyloid-Beta by Microglia. Neuron, 91(2), 328–340. https://doi.org/10.1016/j.neuron.2016.06.015
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