Personalized medicine: Time for one-person trials

Studies that focus on a single person — known as N-of-1 trials — will be a crucial part of the mix. Physicians have long done these in an ad hoc way. For instance, a doctor may prescribe one drug for hypertension and monitor its effect on a person’s blood pressure before trying a different one. But few clinicians or researchers have formalized this approach into well-designed trials — usually just a handful of measurements are taken, and only during treatment.

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First, there is a growing interest in ‘omics’ assays that expose people’s unique characteristics at the molecular level. Researchers and clinicians are assaying people’s blood metabolites (their metabolome) and the microbes in their bodies (their microbiome) as well as their DNA and RNA9. Second, cheap and efficient devices that collect health data are becoming available, such as the Apple Watch, continuous glucose monitors and portable electroencephalogram (EEG) monitors. Lastly, governments and life-sciences funding bodies worldwide are increasingly supporting a more targeted approach as well as patient engagement in medicine, such as through the US Patient-Centered Outcomes Research Institute, established in 2010.

This article primarily focuses on one-person trials in the context of drug research. Personally, I think they have just as much potential in nutrition research as well; after all, while generic dietary guidelines can be effective, the only way to truly optimize health is through individualized research and trial-and-error. These studies have been done before, which is why it’s silly to dismiss something simply because it goes against conventional wisdom—if it’s worked for one person, it can work for many.

Artificial light is a drug

Artificial light impacts nearly every biological system, and it doesn’t even take very much to have an appreciable effect (think: checking your smart phone or watching a television show on your iPad in bed at night). In this study, adding 4 hours to the usual 12 hours of light slammed the autonomic nervous system, disrupting sympathetic input into brown adipose leading to a significant increase in body fat “despite not eating more or moving less.”

Ben Brooks goes JPG only

I’ve long believed that Fuji processes images better than anyone else, and shot RAW + JPG from day one when my X100S arrived. RAW photography has its place when changes need to be made or money is on the line. For the rest, if your camera produces better-than-good-enough images by itself, let it be.

Just about every reason Ben presents for going JPG-only is a reason echoed throughout the Fuji community:

  1. Classic Chrome: this is Fujifilm’s latest film simulation mode and most of the time the colors are stunning. I shoot 90% of my shots with it.
  2. Velvia: again, another film simulation that has been replicated in many filter packs, and never as perfectly as on Fujifilm cameras.
  3. Accurate Previews: I used to spend my time editing the photos to find the colors that represented either what I am seeing, or want to see in the image. Now I can flick through the film simulations quickly and find the one that matches my minds eye. Shooting in black in white is phenomenal too, I can see through the viewfinder in black and white and therefore see exactly how my final shoot will look.
  4. Noise control: way better processing on the Fuji than I could ever get in Lightroom. Now I don’t see noise.

Plus, foregoing RAW reduces the desire to edit for the sake of editing. I myself have often deemed a Fuji JPG better than anything I’ve been able to whip up in Lightroom, yet still published the RAW shot because I was convinced that my “creative vision” was superior to the camera’s computer. I’ve since learned better.

It’s certainly worth mentioning that Fuji is the only system that’s ever been able to make me give up RAW photography. (I’ve used Nikon, Canon, and Panasonic in past lives.) I’m sure other companies do just fine, but like I said, Fujifilm has always processed images better. Its long film-based experience shines.

Neue Haas Unica

Neue Haas Unica™ is Monotype’s revival of a typeface that has attained almost mythical status in the type community. Unica® was an attempt to create the ultimate sans-serif – a hybrid of Helvetica, Univers and Akzidenz Grotesk. Designed by Team ’77 and released to great acclaim in 1980, Unica went missing under a heap of legal disputes and has never been available as a full, digital typeface. Until now.

I love this font so much that I’ve implemented it site-wide here at conormcclure.net, replacing PT Sans. This necessitated lowering the body font-size to 15px to maintain the desired look, but I think it turned out wonderfully. If something loads incorrectly, the stylesheet should fall back to Helvetica. Let me know how you like it!

A few "standing desk" best practices

April 3, 2015

The Wirecutter recently published a nice piece on standing desk best-practices. For the most part I enjoyed the article and thought it contained some valuable insights. I’d like to underscore a few key points:

To determine your ideal height for your monitor and keyboard, stand up straight and bend your elbows so that your forearms are parallel to the ground. Wherever your hands are, that’s the ideal height for your keyboard. And whatever is at eye level, that is your ideal monitor level. Create your desk around those dimensions.

It’s a little simplistic, but for the most part this will work. Standing hunched over is hardly better than sitting hunched over. Your monitor should definitely be eye level—looking straight ahead. Forearms at a right angle is a start, though I’d take it a step forward and force you to keep your elbows close to your ribcage instead of out in front of your body. Ultimately, this setup might place you a bit closer to your desk than you’re comfortable with, but it’s a tad more ideal.

Set up your desk near something that you can lean on from time to time, which will help you shift your weight around.

Yep. Standing versus sitting doesn’t have be quite such a dichotomy; leaning is a fantastic way to rest from prolonged standing without reverting to full-flexion in a chair. In our apartment, we use bar stools.

Get comfy shoes or, even better, go barefoot. If it’s not going to freak anyone out, go ahead and take off your shoes. But if you need footwear, keep a comfy pair of flats at the office that you can change into for standing.

This is correct, but backwards. Barefoot is always the best way to stand. If barefoot isn’t possible, then “flat” is the next keyword, not necessarily “comfy.” Converse and Vans are two brands that come to mind—look for no heel. If you’re a woman, standing in high heels at your standing desk is counterproductive.

Get a standing mat. They are pretty cheap and can make a huge difference in your comfort throughout the day, especially when you start standing for extended stretches of time.

I’m still not sold on the usefulness of standing mats. It’s easy to see why comfortability should be prioritized, but in reality, it doesn’t need to be; after all, your standing desk exists for better health. If going barefoot for long periods of time is uncomfortable, your goal should be to train that, not eliminate the discomfort with a mat. Put bluntly: if you can’t use your standing desk without a mat for support, you’re a wimp.


Of course, there are a couple of tips that The Wirecutter failed to mention that I am notoriously strict about. First, you have to stand (and walk, and do everything) with your feet straight. It will save your life. If you’re a duck-footed walker, fix that yesterday. Second (I know it’s awkward and we like to make jokes about it) you have to keep your butt squeezed and abs on—about 20% of “full throttle.” This serves to prevent excess lordosis and is the final forgotten step in good posture.

The Disease of Being Busy

This disease of being “busy” (and let’s call it what it is, the dis-ease of being busy, when we are never at ease) is spiritually destructive to our health and wellbeing. It saps our ability to be fully present with those we love the most in our families, and keeps us from forming the kind of community that we all so desperately crave.

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It doesn’t have to be this way.

In many Muslim cultures, when you want to ask them how they’re doing, you ask: in Arabic, Kayf haal-ik? or, in Persian, Haal-e shomaa chetoreh? How is your haal?

What is this haal that you inquire about? It is the transient state of one’s heart. In reality, we ask, “How is your heart doing at this very moment, at this breath?” When I ask, “How are you?” that is really what I want to know.

Are Low-Salt Diets Necessary (or Healthy) for Most People?

Researchers from the University of Copenhagen and myself recently analyzed 167 published trials that measured the effect on blood pressure from reduced sodium. We found that in the studies involving only subjects with normal blood pressure, sodium restriction had no significant impact. That means there is no scientific justification for a U.S. sodium policy directed at the entire population, because 65% to 70% of Americans have normal blood pressure and thus wouldn’t benefit from lowering their salt intake.

Thoughts on the new MacBook(s)

March 16, 2015

You may know that it’s early 2015 and I’m still rocking a mid-2010 MacBook Pro. It’s the longest I’ve ever owned a computer and, to be honest, I wouldn’t recommend it. I was eagerly awaiting Apple’s event last week, anticipating some badass MacBook updates. I was a little disappointed.

For me, the archetypal MacBook Pro is the ideal machine—a perfect mixture of power and portability—and with that in mind, I’m not especially drawn to the new MacBook. For one, the scarcity of ports (an intentional design decision meant to force portability on the user) means this computer is not likely to be used in a desktop-style setting. And indeed, the machine is so thin that its working innards are relatively weak by necessity; RAM tops out at a disappointing 8 GB, and the processing power is slower than even the baseline MacBook Air.

All of this might seem like a distraction in the direction of metric-chasing; no one needs crazy fast processing power, graphics, and RAM, right?

But on that same note, no one needs 13.1 mm thin computers either. The pursuit of portability has to eventually reach a point of diminishing returns—this notebook can only get so thin before I just don’t need that anymore. The thinner and lighter notebooks get, the less space there is for working parts, and more space needs to be filled with extra battery to make the damn thing usable. The same phenomenon is happening with the iPhone. I’ve long said: I’ll gladly take something that’s 5 mm thicker and equal parts faster and with longer battery life.

As Gabe said in his article “Considering MacBooks”:

I think Apple continues to draw a heavy line between adolescent and adult computing. The MacBook line is for college students and the MacBook Pro line is for people that make a living with their computers.

I myself am a college student, but am also an “adult computer” user—I want power, speed, and possibilities. Last week’s updates to the MacBook Pro line were indeed “modest”, if not “half-assed.” I’m not eager to upgrade my computer given Apple’s latest advancements. Their focus on portability and other silly features (Force Touch?) have neglected the other spectrum of MacBook power users who want massive speed and battery. (I’m not even talking about the Thunderbolt vs. USB-C fiasco. Make up your minds, for our sake.)

If, for every innovation in portability, Apple made an equal and opposite innovation in portable power, I’d be sold on a top-of-the-line MacBook Pro. But that just doesn’t seem to be the direction Apple is interested in going, and I’m not enthused about that.

What, exactly, is the Dietary Guidelines for Americans Committee's case against saturated fat?

There’s news going around that the 2015 Dietary Guidelines for Americans will no longer set upper limits on fat calories or dietary cholesterol intake. This is great news, because these metrics have long been known to not correlate to heart disease risk factors like we once thought.

The question still remains: why does the update not exonerate saturated fat? Meta-analysis upon meta-analysis have repeatedly confirmed that the correlation is weak, if not nonexistent. The linked article looks at the evidence put forth by the DGA committee and finds that “most of the document is dreadfully written and repetitively displays a circular logic.”

Also, anecdote is anecdote, but still:

Where are the blogs where people rave about how replacing butter with margarine has fixed their health problems? Millions of people take statins - where are the stories from statin users about the improvements to their lives? You will find more negative stories from statin users online. You might find stories of improved cholesterol, but where is the increased vitality and reversal of obesity and type 2 diabetes? Oh, wait.

Quick thoughts on the new Google Calendar iPhone app

March 10, 2015

Today Google released the much-anticipated Google Calendar app for iPhone (yep, no iPad support yet.) It’s free on the App Store and is worth a look, but I won’t be using it.

I had a lot of fun using Inbox, Google’s recent Gmail app, until Outlook for iOS stole my heart. Point being: Google has been cranking out some quality producitivty apps for iOS, and I’ve grown fond of their material design look and pleasant combination of power user features and simplicity.

However, there are a few key features preventing me from using Google Calendar for longer than five minutes. For one, and this is probably an issue for very few people, I’ve grown to rely on using the app icon badge to display the current date, something which Fantastical does fantastically. (Hah!) Second, there’s no landscape support to be found, which, on the iPhone 6 Plus, is a huge lost opportunity. Finally—the biggest problem of all—the app’s damn name is so long that is displays as “Google Cal…” on the homescreen, which is absolutely hideous. Unusably hideous.

I had high hopes for this app, but it just doesn’t pack the necessary features (or looks) to draw me away from my beloved Fantastical.

David duChemin uses Fuji X on the job

When I shot photos professionally, I used Nikon—but I was an outdoor sports photographer, and the D200 (at the time) proved to be the perfect mix of price and performance for the job, especially given the lens selection. Ever since purchasing the Fuji X100S and falling madly in love with it, I’ll likely forever be a Fuji X photographer. It’s always fascinating to read about “pros” who use the Fuji system in their professional lives.

(Now I just need to finally get around to reviving the photoblog.)

My experience with nootropics

March 6, 2015

I’d like to begin a series of blog posts that attempt to catalog the nootropics I have tried or plan on trying, the reasoning and mechanisms behind them, and to help distill the heinously complicated workings behind them to you, the lovely reader. I originally set out to write one massive article, but that grew too cumbersome. Instead, we’ll start with baby steps.

We colloquially refer to nootropics as “smart drugs.” These can be any and all compounds, natural or not, safe or not, which enherently, through their own mechanisms or cascading effects, can enchance performance. This is, after all, the ultimate goal. My own interest in these stemmed from an ever-increasing workload in life: work, school, this blog, my physical fitness pursuits, and the rest. The demand grew too great, the supply too low; a fix was needed.

Since I am playing the long game—that is, finding the perfect balance between performance and longevity—I will automatically dismiss compounds found to be dangerous in and of themselves. For instance, Modafinil and related substances, popularized by Dave Asprey, excel in ameliorating the symptoms of narcolepsy and, as a result, can be used and abused for ridiculously-productive all-nighters. However, sleep is perhaps one of the most potent and natural nootropics on the planet, so Modafinil is out. Sleep, however, is in, and so is any supplement that might enhance sleep quality. Someone like me, neurotic, detail-oriented, and compelled to optimize, will go all out here. Others, like my poor girlfriend, don’t have to. Indeed, across the Internet, the word “nootropic” has become associated with strange and sketchy white powders and illicit substances—one might be reminded of the film Limitless. This is simply not the case: a nootropic is not a magic performance pill, but any edge is still an edge.

Of course, all of this should be taken as it is: an n(1) experiment. A single-subject experimental design. Anecdote. I, being myself, research to no end, and believe that I understand the intricate mechanisms, safety, and effective doses of all of these things. But ultimately if it doesn’t work for you, then it doesn’t work.

Over the next few weeks, I’d like to roll out more articles which lay out my personal regimen and strategies in more detail. I’ll likely start with the basics and move more complex from there; after all, much of what we consider nootropic could also be considered a basic deficient vitamin or mineral (Vitamin D, for example) or something like a simple lifestyle change (diet, exercise, sitting less.) It doesn’t have to be alienating. We should all be pursuing excellence.

In the end, I’ll likely compile this information into a standalone page which can act as a reference guide to anyone interested (there might be a couple of you.)

The new maximalist running shoe trend

The process of reading this article, which details many runners’ obsession with these new moon-man maximalist shoes, was one huge eye-roll for me, especially because it’s coming out of the New York Times and everyone will take it for the gospel. Years of research and two books in particular—Born to Run and Ready to Run—have me convinced otherwise: huge, cushioned shoes are mostly a marketing scheme, and should ultimately be viewed as a tool, not a solution. Indeed, perhaps the problem is not the shoe, but the runner?

My eye-roll was averted by the final paragraph of the story, a quote from Jay Dicharry, author of Anatomy for Runners:

“Of course what’s on your feet is important,” Dicharry said. “But there is a lot of evidence to show that people who spend more time improving their bodies as opposed to shopping for shoes are the ones who are going to run better.”

The problem with Apple’s price tag cheerleaders

If the iPhone 7 comes in a $40,000 18-karet Rose Gold option to match the Apple Watch 3, with a $10,000 alligator leather case option, then I’ll worry. Apple Watch is one product, it’s untested, and it’s unknown. It’s a big, expensive experiment to see if Apple can use fashion to put a (potentially) useful gizmo on people’s wrists, and we don’t know how it will turn out.