On break from blogging

So I figured I'd leave a quick note up here disclosing that I probably won't be blogging at all in the next month (not that the two past months have been particularly prolific). I'm working pretty much non-stop to rush a publication for submission. Work, eat/sleep/exercise, hang out with the girlfriend, repeat all over.

Two things keep me going:

1. It's fun, not work.

2. I need to focus and think constantly about this project. No distractions. However, stress and worrying are utterly useless and I will have none of that.

See you all in December!

My Gamified Life: Fitocracy

I mentioned in a previous post that I've made it a habit to exercise, and so I don't have to expend any mental energy to get myself there (I have plenty of other things on my mind). But I think the best way to keep a habit is to make it FUN, each and every day.

Gamification: It takes tremendous self-discipline to motivate oneself today based on some imagined/abstract healthy future. Instead, the best way is to INCENTIVIZE yourself on a day-to-day basis to exercise. Now, having society pay people to exercise would be impractical. But remember: a huge number of people play Farmville and World of Warcraft for days non-stop just to win virtual points. The incentive is further reinforced long-term by mechanisms such as leveling up, completing quests, reaching achievements, and receiving virtual tokens of support from friends. Incentives can be entirely virtual and cost nothing. Microsoft got its employees to volunteer their time to find bugs in Windows 7 by giving them virtual points People did a mind-numbing task (finding software bugs) over and over and over without pay, just because it was fun to get virtual points and compete against other employees.

Guess what? There IS a website that gives you points for working out, gives you fitness quests RPG-style, and lets you socialize all at the same time. I've been using Fitocracy since November 2011, and I think it's crazy everyone isn't using it.

The beauty of Fitocracy is the combination of two features:

1) Incentive system that lets you track your progress. This is simply fun. During my workout, I use the iPhone app to easily enter in my exercises as I'm doing them. At the end of the workout, it rewards points based on the type of workout, the # of reps, and the # of sets (generally, points are compound lifts > isolated lifts > cardio). I automatically get a good sense of how much I accomplished, and I feel like I've earned something. I don't think twice about working out. After you accumulate a certain number of points, you level up. People give each other "Props" just like Facebook's "Likes." There are also quests and achievements. As further encouragement, it automatically graphs your progress on each exercise for you.

2) Social network. Fitocracy boasts about 230,000 users, and many of them are fitness enthusiasts and personal trainers (and a disproportionate number of cardiologists and orthopedic surgeons). And yes, lots of nerds too. You can easily find people who match your fitness interests. Many of them post pictures of themselves (i.e. before and after transformation) so you can see what kinds of results they're getting. You can see EXACTLY what exercises they do down to the last detail. Got a question for one of them? Need advice? Just ask.

Typical workout entry

These two features synergize. For example, Fitocracy has a universal set of "Achievements" that anyone can obtain. These are things like "Bench press your body weight" or "Deadlift 2X your body weight" or "Run 200 miles total." For the longest time, I was in awe of other people with the 15-pullups achievement- I started out just struggling to get the 5-pullups achievement. In the back of my mind I thought "well I'm not THAT intense- and probably won't ever get there." But then I read one profile and figured out how quickly that person went from 3 to 15 pullups… and it was less than a year. And what kind of motivation do you think I got when I achieved it last month? The habit is self-perpetuating and only gets stronger over time.

Myths: Just talking to more experienced people on Fitocracy is a great way to re-educate yourself. There's a lot of fitness controversies out here, but here are some myths that are pretty much completely debunked:

1) "I don't want to weightlift because I don't want to get bulky- I just want to get toned". OK it takes many years for a guy to bulk up lifting weights every day (unless they take steroids- not recommended). How long do you think it takes for a woman who has >10X lower testosterone? Women will slim down with weightlifting because muscle takes up a lot less space than fat. If you take 10 minutes to look around Fitocracy, you'll rapidly find dozens of counter-examples to the bulky myth (like this and this). The bulky women you see in magazines are either on steroids or are in the <5% of women who have naturally high testosterone.

2) "Deadlifts are bad for your back, and squats are bad for your knees." I used to get back pain and it's completely stopped since I started doing deadlifts. I used to get knee pain if I ran too much and now it's never a problem. You can only injure yourself if you have bad form, and Fitocracy lets you talk directly to other people (like personal trainers) about your form. Some people even post videos of themselves so others can critique them.

3) "Everyone needs cardio." Only necessary if you have a family history of heart disease or if you're training for a sport that involves a lot of cardio. Weightlifting is enough.

4) "Situps reduce belly fat." Actually, probably the best way to reduce belly fat (or any type of fat, because spot reduction is impossible) is squats because maintenance of the big muscles will divert energy from your fat reserves.

5) "High-protein diets kill your kidneys." It increases your kidney blood flow, working it harder, but that doesn't mean it's damaging your kidneys. Think of it as exercising your kidneys. Sure, people with kidney failure will worsen it if they eat more protein, but that's no different than trying to lift heavy boxes immediately after breaking your leg.

I think we're entering an age where traditional sources of information like fitness magazines and celebrity workouts have pretty much lost their value compared to just talking to other regular people like you and me who have made real progress. If you look in magazines, everyone is airbrushed and all the men are on steroids, and they don't do anything but work out. You have no way to verify the information they give you. On Fitocracy, you can see literally thousands of actual success stories from people who are just as busy as you. Along those lines, Reddit Fitness FAQ is also an excellent source of information.

Here's my shameless invite link.

Track your performance over time.

iPhone app

Work is Play: Stop focusing on your job's relevance

Recently, I've been reading the autobiography of Richard Feynman, the Nobel prize winning physicist. He reveals that after working at Los Alamos developing the atomic bomb, he fell into depression and a creative rut. One day he decided he was going to stop focusing on solving problems for societal benefit, significance, or any other purpose. He would simply play with science. He would work on the quirkiest problems, without any regard as to their relevance. One day he saw a colleague throw a dinner plate into the air and noticed that the ratio of the wobble to the spinning appeared to be 2:1. So he spent a huge chunk of his time trying to work out equations for it. Guess what? It got him out of his rut- he stopped caring that others might be judging him for spending his tenured faculty time on silly things. He could just dive in and think about the physics. And the equations he worked out happened to describe an analogous phenomenon in quantum mechanics, forming the basis for his Nobel Prize.

I entered my PhD fascinated by the basic biology behind aging and its implications for society. I  preferred thinking about science in the abstract rather than the labwork which I saw as hard work, a necessary evil. A lot of protocols are mindless because they are so well established- you just have to do them as manual labor. Early on I made a lot of mistakes in lab. It was very slow and I found myself procrastinating on my project, even ignoring reading papers because it would just stress me out by reminding me of labwork. Feedback loop initiated: I felt overwhelmed by how much stuff I needed to do, and I felt bad that I seemed so behind, especially compared to other people. Whenever I did make progress, the solution was so simple that I found myself regretting and blaming myself for not doing it earlier. So I started procrastinating even more.

But certain forms of procrastination are ultimately beneficial.

One purpose of this blog is to carefully consider and publicize my efforts to make deliberate changes in my life: One common question I get is, "how do you have time for blogging? Or any of this??" You could also ask how I have the mental energy for any of this.

Yes, that is the PhD. I get to choose how I spend all of my own time. Some scientists think as a PhD student you should be focused so much on your scientific work that you don't have time for anything else. I disagree. I think you should be dedicating all of your time to training yourself to be the most effective intellectual possible. You have to figure out for yourself how to do that- there are many avenues that don't involve working. 

• Stopping myself from wasting time on the Internet?  A no-brainer.
• Managing negative thoughts? Your self-talk can be a massive hindrance to your productivity. 
• Fitness? Exercise grows new neurons in your hippocampus, prevents depression, and improves cognitive function. 
• Learning other subjects? I solved a major problem in lab by analogy after reading the blog of someone describing an entirely different problem. 
• Practice writing? Last year I was really really slow at writing analysis papers for classes. When it comes to publishing, I can't let being out of practice get in my way.
• Trying new things? If you can get yourself in the habit of jumping into things you know nothing about, you will have no problem getting started on that new method which will yield the best data.
• Idea generation? Good ideas in science are a needle in a haystack. But if you don't have a haystack in the first place, you won't find the needle.

Hence, everything I am doing outside of lab IS contributing to my PhD work, by investing in my most precious resource: myself. Doing these things takes time and focus. By focusing on side projects OUTSIDE of work, I was able to get started without any of the negative feelings about my work. Like Feynman, I stopped caring about what I was "supposed" to do- and that enabled me to just get started.

Changing myself has changed the way I look at my work. 

Sure, I still don't gain any enjoyment from the physical act of conducting wetlab experiments. But one habit I've formed is to ask myself: What do I actually enjoy? What could I actually enjoy about my work?

•      Figuring stuff out
•      Talking to others and coming to a revelation together
•      Control over my own time
•      Trying new things

By mentally focusing on these things in lab, I enjoy my work way more even if there are aspects that I'm still impatient with. Nowadays, I tend to push the mindless protocols to the end of the day and just listen to the Daily Show or podcasts in the background. I'm relaxed. No longer are they a problem.

I really started only addressing this in earnest this month. When I started focusing all my efforts into lab and nothing else, I almost gave up. Negative thoughts returned, I felt overwhelmed and regretful that I "wasted" time on all these side projects. But my focus kept up and survived, because I had trained my own brain this past summer on those very side projects. 

Now I'm working way more hours in lab than ever before and every moment of it makes me happier- all because I changed the way I look at my work. When I need a break, I take a break. But I've discovered it's possible to make working extremely long hours sustainable- but it requires effort to restructure your mind so that it is sustainable.

When Richard Feynman was a child, he spent most of his time playing with science, building quirky ideas in his makeshift lab. While studying college physics, he conducted elaborate experiments on ant behavior, even though they had no relevance to physics. But by making work into play, his crazy-busy career became sustainable for him. It reminded me of one comment on my 1st grade report card: "He loves playing with math. He loves playing with science." 1st grade me was pretty wise- I have much to learn from him.

I'm lost. What's my purpose in life?

I have a personal mission statement and constitution. I try to review it at least once a week to revise it and reflect on how well I've lived it the last week, and to plan on how I'll better live it.  In my constitution I have principles and values written out, such as "I will have fun at failing," and "I will not judge other people." Sometimes I succeed, sometimes it's like I've forgotten this list exists. What is perhaps more important than the constitution is the mission statement. I have not been very happy with the life purpose I've defined for myself. It's vague but it's the best one I've come up with. The only thing I'm really happy with is that I deliberately chose a purpose that I thought most other people wouldn't understand on any level (I'm weird- I embrace it). I'm told that reflecting on my life purpose should bring me to tears. That you can find your life purpose by sitting down and writing hundreds of "life purpose" statements until you find the one that makes you cry. I've tried that, but nothing gives me that emotional "umph." And I've been worried that I can't find it.

Sometimes I think, hey I just need to focus. #1 Work on finding a proper life goal everyday. #2 Have some flexible plan for advancing that life goal each and every day. #3 Make sure by the end of each day I've met some milestone and feel like I've made progress. Then things will work out.

Not only is this focus hard, I'm also not sure it's the best plan anymore. I've been worried that I don't have a satisfying life purpose, but I think now that the worrying is the real problem. It's occupying me with trying to find some "ideal" life path and so I feel like I don't have enough time to experiment with new things. 

Society teaches us to focus on the career progression (in science it's undergrad => grad student => post-doc => junior faculty => tenure), or the life progression significant other => married => family => house in suburbs. If you don't make progress, others are trained to ask you why you haven't. Some people are happy with it, but a lot of people aren't. Some people think it's necessary, and they don't want to wander off it because it's risky. But you know what? I think a lot of it has to do with life/career progressions being pre-defined for you.  If you find your own reason to get married and buy a house that you won't pay off for 10 years, a reason that is made for you and only you, you'll be a lot happier with it.

This pre-defined path through life can sometimes feel like a prison. So we rebel against it, and we often go overboard and rebel in unhealthy ways. People party a lot, do drugs, cheat on their significant others, quit their jobs without a plan. Most of the time people do this to a lesser extreme, where we might simply lose focus on our work and do our own thing for a while. We might grow in new ways, but then reality sets in and your boss yells at you and you realize your peers have published 3 papers while you have nothing to show. So you freak out and go back to the pre-defined path. You feel bad. Nothing you feel bad about can ever be maintained (omg I HAVE to do this or else my career tanks). So it starts to fail. You work long hours but your work doesn't go anywhere, and it's because you feel bad about it. It's a hell-on-earth prison. So you rebel against it, and it starts all over again.

These are meanderings. We have to deal with societal expectations, but we also have to find our own way. Finding a correct balance- no, the correct MIX of the two is critical. And what's the best way to address something that is critical? Find a way to make it fun. Then you'll do it each and every day, and you won't worry about it.

I recently served on a panel to discuss graduate and medical school with a group of high schoolers applying to college. Every other question was along the lines of "What should I be doing right now to make sure I get into medical school?" It didn't bother me so much that they already "knew" what they wanted to do right out of high school- sure, it's naive, but I have confidence that they'll properly re-evaluate once they are exposed to more life choices during college. What did bother me was that they thought they would be trapped in whatever career path they chose, so they were scared to death that if they didn't optimize everything in their education that they would be stuck in some unhappy mediocre position. That they had to choose their career path NOW so that they could do everything right in the pre-defined life progression. Society is pushing students to imagine some ideal path through life, and if you just follow that you'll be all set for life. I was sucked into this for way too long, until I really started to reflect on what I wanted to get out of life.

Over the past year, I've been focusing on internalizing the mantra "Don't think life is good vs. life is bad. Think about what you can do right now to make it better, regardless of whether it's subjectively good or bad." It's self-managing your own thoughts. But I've really only been applying it to the "what" and the "how" of life. Not the "why" quite yet, and I realized this month that this has been a constant source of distress that I haven't been able to really address until recently.

My goal now is to be lost. And I'm going to have a ton of fun doing it.

Last-minute edit: Yesterday I found a life purpose statement that brings me to tears. But that just moves the bar up, and I bet tomorrow I will subjectively feel just as lost. Finally, this post was motivated by the first question in this Q&A by James Altucher. I have found his blog to one of the most thought-provoking ones out there, even if I don't agree with him. And his honesty is an inspiration to anyone who feels like they have hide their failures to prevent society from judging them- which is everyone.

Friday Links: eat your egg yolks, avoid antimicrobial soap

Most of this post will be about egg yolks, but I'll start with the following PSA: if a soap is labeled "antimicrobial," don't use it. Just don't use it.

http://cebulka26.wordpress.com/2012/08/16/triclosan-its-in-everything-but-is-it-warranted/

If I see antimicrobial soap at a restaurant, I don't use it. I just wash with hot water. This concise and informative blog post from Ania (fellow MD/PhD) reminded me of why I do this. The active ingredient is triclosan, but I doubt it's very active anymore because it's in a bazillion products. Many of the microbes that we would theoretically want to kill are probably already immune to it. Continued use will just give microbes more and more chances to evolve resistance to not just it but also all related antibiotics, resulting in antibiotic-resistant bacteria that could kill a lot of people. The Black Death wasn't much fun, so I hear.

The fact is, there's currently zero evidence that antimicrobial soap helps prevent infection compared to regular soap. And given the potential health risks that Ania outlines (triclosan could affect your hormones, muscles, cancer…), why the hell would you use it? You're better off not using soap at all.

Egg yolks OMG!!

http://www.dailymail.co.uk/health/article-2188265/Eating-egg-yolks-bad-smoking-speeding-coronary-artery-disease.html?ito=feeds-newsxml

For some reason, the least-significant studies seem to get the most publicity, and the media likes to create outrageous headlines like "eating eggs yolks as bad as smoking." Incredibly misleading and not at all implied by the paper- especially when you consider that the audience is the public-at-large. For some people cutting back on egg yolks is prudent (but not at all proven to be beneficial), but should average 25 year olds avoid egg yolks as they should avoid smoking? Absolutely not, and the lack of context in this article is irresponsible.

First, some conceptual background: when you drink a lot of water, do you get water intoxication? No, you pee it out. Guess what? You excrete cholesterol through your liver into your digestive tract, and you can simply make less cholesterol. Your body reacts to greater cholesterol intake by decreasing cholesterol synthesis, and you end up with the same amount in your blood. The cholesterol that your body makes on a daily basis is significantly greater (about 3-5 fold) than what is recommended in your diet. Thus, your body can easily handle twice as much cholesterol consumption as normal, and eating more cholesterol per se does not increase your blood cholesterol. Your body needs cholesterol, and it will handle it as needed.

If you don't eat this, your body will probably make it instead and you'll end up with the same blood cholesterol either way. OK, maybe not for this many egg yolks, but you get the idea.

Of course, if you drink TONS of water (>12L), you can get water intoxication (this happens to ill-informed marathon runners). So there's a point at which cholesterol intake will start adversely affecting your blood cholesterol, and yes high blood cholesterol is a huge risk factor for heart disease. Furthermore, individuals with kidney disease will not be able to deal with water overload. Similarly, if you already have cholesterol imbalances (due to genetics, age, obesity, microbiome perturbation, whatever) then you should start watching your cholesterol intake, because the mechanisms to keep your blood cholesterol in check have already been overwhelmed.

Getting to the study, I have many objections:

1. Glaring source of recall bias. Egg yolk intake is self-reported in a questionnaire. But how many people actually keep track of their egg yolks? I'm guessing extremely few- and any variable that people do not consciously track is subject to huge memory bias. Furthermore, egg yolk intake is really hard to estimate, because eggs are used in all sorts of foods (bakery items, etc). I certainly would not trust my own estimation. And there is a huge source of memory bias in this study: people with the worst heart disease (regardless of the cause) are far more likely to "remember" that they ate a lot of egg yolks. We know that people's memories are heavily biased by their situation, and there is a pre-conceived notion out there that egg yolks are "supposed" to clog your arteries. People naturally look for an explanation for their disease, and if they find an easy explanation (eg egg yolks), then they will sub-consciously alter their memories to believe that they ate more egg-yolks. The memory effect should get stronger with greater severity of disease, and so all of the results of this paper could be explained by recall bias. Furthermore, the study itself can influence people's memories. You're going around a clinic full of worried people asking them how many eggs they eat. At least subconsciously, people are going to start blaming eggs for their health, even if they ate the same # of eggs as the next person.
2. The study population is heavily biased. The patients are already attending a vascular clinic! As I mentioned, there are likely sub-populations for whom cholesterol intake will increase their blood cholesterol (morbidly obese individuals, patients with familial hypercholesterolemia who are genetically unable to regulate their own cholesterol, etc). Those are the sub-populations whose cholesterol homeostasis mechanisms are already out of whack, and they are the ones most likely to be attending the clinic.
3. The data is nothing but correlative. Eating egg yolks (self-reported, again) is shown to be correlated with artery blockage. Sure, they use some statistical analysis to show that the effect is still present after you adjust for "coronary risk factors" but many risk factors are still unknown (yay science!), so you can't adjust for everything. The problem is that there are thousands of variables out there, and they are all correlated with each other to different degrees. People who live in a certain part of the country might eat foods rich in cholesterol, but guess what- that might also be the most polluted part of the country. Or there is a virus circulating in warm climates that increases your risk. Or people in that part of the country might be older, etc. If you look at 1000 variables, eventually you'll find one that fits simply by chance.
4. Simplistic clinical endpoint. Small point, but they just looked at neck artery blockage. Artery blockage, even if systemic, does not translate to disease. It's a risk factor like any other, and like all risk factors it doesn't affect all individuals in the same way.

Plant Zen

http://www.disneyresearch.com/research/projects/hci_botanicus_drp.htm

http://www.benchfly.com/blog/forget-wireless-keyboards-and-touch-your-plant-instead/

Finally, I have no idea what to make of this. You can hook up a plant (any plant, like a potted plant) to your computer, and somehow an electrode in the soil can tell what part of the plant you're holding. So you can control your computer by touching a plant. Is this a hoax?

I predict that eventually we'll be able to hook up anything to computers. But I think it will take a little more than just sticking an electrode into the soil.

wtf?

Alzheimer's: commentary on treatment strategies

My goal is that any reader can take something away from this Alzheimer's post, regardless of their experience in medicine or science. It's Friday Links-driven, but with far more of my own commentary/explanation than normal.

First up: an article about a clinical trial for Alzheimer's treatment that appears to have failed. While I don't research Alzheimer's, I'm going to argue in this blog post that 1) single "magic bullet" treatments are unlikely to ever work for a chronic complex disease that develops over many decades like Alzheimer's (once the disease has actually manifested symptomatically), but 2) single "magic bullet" prevention methods might work for specific patient sub-populations. In this case, different prevention methods would work for different sub-populations. Meanwhile 3) Broad, non-specific treatments that target multiple biological processes are better for stabilizing Alzheimer's after it's been diagnosed (discussed in the second link). Note that this is NOT the same as combination therapy.

http://www.technologyreview.com/view/428592/pfizer-disappointed-with-first-results-for/?ref=rss

Bapineuzamab is an antibody that recognizes and binds to beta-amyloid, one of the molecules involved in the pathogenesis of Alzheimer's (note that I don't say it's the cause or even a significant cause). For my non-biomedical readers, this is a common treatment strategy nowadays. Say protein X causing disease Y is floating around in the space between cells in your body. Specific antibodies can be made to bind specifically to protein X which physically blocks protein X from damaging other things ("neutralization"). Furthermore immune cells are then able to recognize the antibody bound to protein X, and clear protein X from the body. This strategy is used in treatment of diseases like rheumatoid arthritis and lymphoma, and it works wonders.

But Bapineuzamab failed to have any effect on Alzheimer's progression in this Pfizer trial. Why? I'm going to use my extraordinary powers of hindsight (dig deep- you probably have this ability too!) and say that it probably has far more to do with the fact that beta-amyloid is just a tiny piece of the puzzle for Alzheimer's than any problem with the drug. Bapineuzamab probably recognizes beta-amyloid just fine, and it might even clear beta-amyloid from the body. But I doubt that clearance of beta-amyloid would have any effect on Alzheimer's. Why? Because it's too late.

The trial looked at treatment of early-to-moderate Alzheimer's, but Alzheimer's develops over decades. For a while, it's just Mild Cognitive Impairment (MCI), but lots of people get MCI and never progress to Alzheimer's. So figuring out a way to predict Alzheimer's progression through things like blood tests and brain imaging is all the rage now (see third link). And that's why the trial focused on Alzheimer's rather than pre-Alzheimer's. But in the patients that do progress, what's going on?

The length of time that it takes for Alzheimer's to develop means that, even if beta-amyloid were to be the ultimate cause, then beta-amyloid can trigger numerous other biological processes that are themselves damaging to the brain. By the time someone has Alzheimer's symptoms, these "secondary processes" are already robust so more damage is occurring independent of beta-amyloid, and a lot of neurons are already malfunctioning or dead. This fundamentally alters the biology of the brain so that treatments are unlikely to reverse anything, and multiple causes of degeneration make it unlikely that single treatment would slow the progression of the disease. I won't review the ginormous body of literature implicating all sorts of things in Alzheimer's pathogenesis, but I'll take a couple as an example.

One way to abstract Alzheimer's (see picture below) is that everything causes everything else. It's a complicated feedback loop (or feedback web) where a bunch of biological processes all cause and worsen each other over a period of many years. For example (highlighting a tiny portion of the feedback web), extracellular amyloid or intracellular tau (hallmarks of protein misfolding) acting on one subset of neurons might interfere with normal breakdown of neurotransmitters, as well as directly causing neurons to fire inappropriately. Too much excitation of nearby neurons results in excitotoxicity (killing those cells) or in inappropriate activation. The brain might remodel in reaction, forming new synapses that result in electrical feedback loops that reinforce each other. The resultant clinical and subclinical seizures might interfere with brain function long after the damage is done. As neurotransmitters start to diffuse inappropriately due to synaptic dysfunction, they start affecting other cells indiscriminately, and damage may occur to brain's extensive blood system. This allows in immune cells that further alter the blood vessels to essentially break down the blood-brain barrier.  This lets in various molecules that again might cause excitotoxicity or protein misfolding, and maybe it even lets in bacteria. So damage leads to biological response that causes more damage, leading to further responses etc.

All of these processes cause each other, and all of them cause disease. Targeting a single initiating factor (which varies from patient to patient) might work for prevention, but not for treatment.

Importantly, many of the damaging processes are variations of normal brain biology. For example, microglia (kind of like the brain's immune system) see damaged neurons and eat them up. If you remove the source of damage, it is perfectly possible they continue eating up neurons instead of letting the neurons recover after the damage. There are medical examples where a disease has manifested for so long that cells that normally act to ameliorate a disease are "locked in" to their action even when it's no longer necessary, and they end up causing damage themselves (for example tertiary hyperparathyroidism). I think of this as part of the more general inflammatory response that occurs whenever there is damage- all sorts of immune cells react to initial damage and can end up causing more damage than the original insult (if you think that makes no evolutionary sense, it actually does. I might expand on that in a future post).

What about prevention? Note that things like excitotoxicity, brain remodeling, and breakdown of the blood-brain barrier can in turn cause beta-amyloid buildup. So there's no reason why beta-amyloid had to be the initial insult- in many (most?) patients beta-amyloid is probably secondary to another biological process. In these cases, drugs targeting beta-amyloid production and degradation probably would not have any preventative effect, because beta-amyloid was not the initial cause. However, there are subsets of patients where beta-amyloid is implicated as a major genetic cause (mutations that affect beta-amyloid production like in Down's syndrome, ApoE4, and presenilin). Prevention using Bapineuzamab is conceivable in those patients, as it would stop the secondary processes from occurring in the first place. However, if we found in another sub-population that inappropriate inflammation due to immune system malfunction (kind of like an autoimmune disease), then prevention would involve anti-inflammatory drugs (Aspirin? IVIg? Prednisone?). Thus, preventative measures for Alzheimer's would be specific to the patient's initial cause(s) of degeneration, which can vary widely depending on the patient.

http://www.technologyreview.com/news/428546/study-suggests-alzheimers-disease-can-be/?ref=rss

On the bright side, a very small trial showed stabilization of Alzheimer's with treatment with IVIg (intravenous immunoglobulin). IVIg is simply the mix of the collection of antibodies isolated from multiple human volunteers. There are antibodies against everything- bacteria, toxins, some human proteins, etc. The authors here speculate that there is an antibody targeting amyloid-beta, tau, or some other molecule. While this might be part of the picture, I worry that researchers might go after specific antibodies (which is just like the above Bapineuzamab trial). I challenge the notion that IVIg's broad and non-specific effects are a disadvantage. While one might think it's not 'optimized' for Alzheimer's treatment, the very fact that Alzheimer's involve a complicated web of numerous biological processes means that we need to target them all at the same time. Thus, a non-specific treatment with numerous antibodies doing many different things might in fact be the key to IVIg's efficacy.

For example, IVIg is used in the treatment of autoimmune disease, dampening down immune responses. How it accomplishes that is unclear (and is a bit counter-intuitivee since antibodies MEDIATE the immune response), but it is believed that it both interferes with the specific endogenous antibody that causes disease, as well as flooding the system with so many antibodies that it diverts the immune system from inflammation. Perhaps IVIg is dealing with the inflammatory component of Alzheimer's? Perhaps it interferes with the endogenous cells/antibodies that are damaging the brain? Thus, trying to narrow down the treatment to a single antibody or a few antibodies would eliminate some of the broad effects of IVIg that would be critical for influencing the numerous biological processes. This is different from combination therapy because we're looking for one or two treatments to influence many things (100+) things at once, rather than multiple (3-5) treatments for multiple (3-5) things.

Also note that IVIg only stabilized the disease, it didn't reverse anything. That's because the damage is done- the neurons are dead and the brain has remodeled itself. At this point, Alzheimer's could only be reversed by making new neurons by stem cell therapy. Because many of those dead neuronal circuits likely encoded specific memories and personality traits, we would need to find a way to program those back into the new neurons. Those would be Sci-Fi technologies that haven't even been imagined yet.

http://www.technologyreview.com/news/428480/an-alzheimers-warning-25-years-before-symptoms/?ref=rss

More on prevention: you need to be able to predict who is going to get the disease in order for a prevention to fulfill a cost-benefit analysis (since preventative treatments might have their own side effects, and you don't want to expose people who will never get the disease to unnecessary risk). This brain imaging study suggests that this is possible, at least in one inherited subtype of the disease.

http://www.newscientist.com/article/dn22128-alzheimers-villain-cures-multiple-sclerosis-in-mice.html

I'll just leave with you an interesting tidbit- they used beta-amyloid injected into the body cavity of mice to reverse multiple sclerosis (MS). What? Isn't beta-amyloid bad? But this sort of goes with my idea that injecting IVIg "distracts" the immune system from attacking brain cells, just like beta-amyloid might "distract" the immune system from attacking myelin sheaths in MS. I think the lesson here is: We need to think outside of the box and consider counter-intuitive treatments to deal with these complex diseases.

August goals; capturing your thoughts on paper

20th post! Not doing any special post to celebrate- I'm just noting it. I considered an epic, deep post (yeah, right) but today is going to have to be quick- it's a busy week as usual.

You all know that I was a little obsessed for a while with setting goals and tracking them. I developed a single system in Evernote and stuck with it. The rigidity was definitely worth it- I developed a lot of discipline and I got used to reminding myself of my goals frequently. Furthermore, I really liked having just a few primary goals for the month that I stick by, not letting myself get so excited about other ideas that I lose focus. What I've found is that this really makes me feel like I have a "theme of the month" which is great motivation. But now I've moved into an experimental phase, playing with incentives and expanding my thoughts on what I truly want to accomplish. You know, the "why" rather than the "what." Recently I've tried two new systems, one of which is described below in my August goals. I think I'll save the other for a post in the near future (it's a web + smartphone app).

My August goals are:

1) Make tally marks each time I lose focus at work. This is a neat trick and it's helped me a lot in the last week. Essentially I have a sticky note on my laptop keyboard that says "Focus." I catch myself every time I feel like I'm about to do something unrelated to the task at hand (such as randomly checking Facebook or the news for no reason), unless I explicitly give myself permission to do it. I make a tally mark, remind myself of why the task I was performing was important, and get back to work. If I actually get to the point of checking Facebook and getting distracted, then I make two tally marks. During breaks, I may explicitly give myself permission to visit a particular website, and even then I make sure I don't continue clicking on links forever.

1a) Make tally marks each time I find myself having negative thoughts. This is auxiliary to the first point, and is accomplished in the exact same way. There's no point to worrying incessantly about something. Whether something is going badly or not is useless information to me- in fact it will just distract me from doing what I need to do. If something is worrying me, then I should ask myself "Can I do anything about it? Right now?" If the answer is no, I stop worrying and focus on something I can actually influence. If the answer is yes, I either do it or make plans to do it. This is a game I've been playing in my head for a while, and I found that having an object (piece of paper) to dump this on helps me push away the thoughts that are bothering me. That brings me to my next goal.

2) Keep a pocket Moleskine journal. I've resisted keeping a dedicated paper journal for many months now. I figured- I have Evernote to record all my thoughts! Everything backed up in one place! But it's just too clunky on my iPhone while I'm on the go, and I really need to be able to draw diagrams and integrate them with the text. Accessing a stickied page in a paper journal is so much faster than pulling up the relevant note on my computer. I tried a Hipster PDA for a bit but it didn't work out. Anyways, I've used this for the past week to develop my thought processes on my values, my short- and long-term goals, my ideas, etc. Putting it on paper (or Evernote) helps you pare down the bazillion things going on in your head to just the most important things. I originally disliked the lack of structure in the Moleskine (and you can't copy/paste templates like in Evernote)- but I've come to understand that forcing yourself create a system from scratch for organizing your thoughts is important for, well, personalizing your personal development. By the way, if you haven't started recording your thoughts and goals in any way, I highly recommend you start. If time is a worry, just know that it will save you time. Here's a wealth of productivity systems you can implement in a Moleskine.

My red Moleskine. On my computer for size comparison- it fits neatly into my pocket.

A page from my Moleskine. I made a thought process flowchart in response to feeling guilty about not getting enough done in lab. I asked myself a couple of key questions that completely modified my perceptions and put the work I did that day in context. In the end I concluded that my other priorities were more pressing and so I was at peace with myself. Those key questions are labeled 1, 2, 3, and 4 in the flowchart and lead to specific actions I should take (eg not worry or find a specific way to fix it). Then I solidified it in a Moleskine flowchart- so I can refer back to it in the future so I don't stress myself out in the future unnecessarily.

3) Be productive in the evenings learning information or a new skill that is unrelated to labwork. I don't think I have time this month to keep a consistent side project up on top of my Moleskine experimentation, so I figure why not just keep my mind fresh. I'm reading a book about dishonesty (thanks Dale!), learning some coding, learning some memory tricks, doing logic puzzles, and whatever else. The primary reason I'm keeping busy at night is that I've found it helps me sleep a lot better than if I just watch 30 YouTube videos.

Finally, I have started using a productivity web app for my goal tracking. I'm using it to remind myself of a bunch of other goals that I'd ideally like to accomplish a few times a week. Because of the way the website works, I don't need to think about them as much as my primary goals, so I don't have the focus issue that arises when I have too many goals. I will share after I explore it a bit more.