Saturday, September 28, 2019

US Impeachment Inquiry: My Prediction

As a political theorist I never really stick my neck out to try to make predictions about how the real world of politics will unfold (which is like trying to predict the weather!). But here I will detail what I think is the most likely outcome of the current impeachment inquiry into President Trump- I think Trump will actually resign before the end of the year.

I know this outcome will sound very unlikely given how tenacious a political opponent Trump is (he doesn't back away from any fight), but in this case I actually think he has backed himself into a corner with no real exit option. If the Trump Administration delays/obstructs the impeachment inquiry it will look very bad for him politically (costing him re-election). And if he provides the documents and testimony Democrats are seeking things will look even worse for him (they already look unsalvageable in my opinion, either because he will be impeached or at least lose the election as more troubling details come to light). And what this does is put the Republicans in Congress and the Senate in a "no win" situation. So far many of these players have remained quite. But they can't stay like that for long.

Many political pundits have expressed puzzlement with the fact that the Trump Administration released the phone memo this week that paraphrased the conversation between President Trump and President Zelensky. It certainly was out of character given that his modus operandi is to be uncooperative. Some pundits have suggested the Trump Administration released the memo because they think there is nothing to hide. I actually suspect the opposite is the case. I think it is very likely that the Trump Administration already realized that this recorded phone conversation to the Ukraine President, in conjunction with the whistle blower's complaint, and the attempts to cover it all up are BIG issues and ones that Trump's Presidency is unlikely to survive. I think the memo was released as the first (gradual) part of the resignation process. And now the Trump Administration's focus will be on how to have Trump exit in a manner that (1) makes him look as good as possible- which in Trump's eyes is as the victim of the liberal media and a Democratic conspiracy and (2) leave the Republican Party intake. That is the best end-game for both Trump and for the Republican Party (not to mention also for the American people!).

That is just my two cents worth as an uniformed observer trying to make sense of political developments south of the border. It is a very sad state of affairs, but also one that could be very instructive to the future health of American politics.

Cheers,
Colin

UPdate: and (3) before Trump resigns, he will try to inflict maximal damage on the Democratic party and their potential Presidential candidates. Of course that has always been on his radar anyways (and what caused his impeachment problems), but it will get even worse (and has since to whistle blower story broke last week).

Cheers,
Colin

Thursday, September 12, 2019

Off-Target Toxicity in Cancer Drugs


Science Translational Medicine has this interesting article. The abstract:

Ninety-seven percent of drug-indication pairs that are tested in clinical trials in oncology never advance to receive U.S. Food and Drug Administration approval. While lack of efficacy and dose-limiting toxicities are the most common causes of trial failure, the reason(s) why so many new drugs encounter these problems is not well understood. Using CRISPR-Cas9 mutagenesis, we investigated a set of cancer drugs and drug targets in various stages of clinical testing. We show that—contrary to previous reports obtained predominantly with RNA interference and small-molecule inhibitors—the proteins ostensibly targeted by these drugs are nonessential for cancer cell proliferation. Moreover, the efficacy of each drug that we tested was unaffected by the loss of its putative target, indicating that these compounds kill cells via off-target effects. By applying a genetic target-deconvolution strategy, we found that the mischaracterized anticancer agent OTS964 is actually a potent inhibitor of the cyclin-dependent kinase CDK11 and that multiple cancer types are addicted to CDK11 expression. We suggest that stringent genetic validation of the mechanism of action of cancer drugs in the preclinical setting may decrease the number of therapies tested in human patients that fail to provide any clinical benefit.


Cheers,
Colin

Sunday, September 08, 2019

Small Experiment Appears to Reverse Aging in Humans!



Nature News has this interesting news item on a small experiment in humans to reverse the process of biological aging!

The details:

For one year, nine healthy volunteers took a cocktail of three common drugs — growth hormone and two diabetes medications — and on average shed 2.5 years of their biological ages, measured by analysing marks on a person’s genomes. The participants’ immune systems also showed signs of rejuvenation.

....Checking the effect of the drugs on the participants’ epigenetic clocks was an afterthought. The clinical study had finished when Fahy approached Horvath to conduct an analysis.

Horvath used four different epigenetic clocks to assess each patient’s biological age, and he found significant reversal for each trial participant in all of the tests. “This told me that the biological effect of the treatment was robust,” he says. What’s more, the effect persisted in the six participants who provided a final blood sample six months after stopping the trial, he says.
The abstract from the study:

Epigenetic “clocks” can now surpass chronological age in accuracy for estimating
biological age. Here, we use four such age estimators to show that epigenetic aging
can be reversed in humans. Using a protocol intended to regenerate the thymus, we
observed protective immunological changes, improved risk indices for many age‐re‐
lated diseases, and a mean epigenetic age approximately 1.5 years less than baseline
after 1 year of treatment (−2.5‐year change compared to no treatment at the end of
the study). The rate of epigenetic aging reversal relative to chronological age acceler‐
ated from −1.6 year/year from 0–9 month to −6.5 year/year from 9–12 month. The
GrimAge predictor of human morbidity and mortality showed a 2‐year decrease in
epigenetic vs. chronological age that persisted six months after discontinuing treat‐
ment. This is to our knowledge the first report of an increase, based on an epigenetic
age estimator, in predicted human lifespan by means of a currently accessible aging
intervention.



Cheers,
Colin

Friday, August 30, 2019

Study on the genetic basis of human sexuality

Nature News has the scoop here on the latest study (published in Science here) into the genetics of sexual orientation.

A sample from the news item:

The largest study to date on the genetic basis of sexuality has revealed five spots on the human genome that are linked to same-sex sexual behaviour — but none of the markers are reliable enough to predict someone’s sexuality.

....Although some researchers and LGBTQ advocates might question the wisdom of conducting this kind of research, Birney says that it’s important. There has been a lot of sociological research on same-sex sexual behaviours, he says, but this is an incredibly complicated topic. It’s time to bring a strong, biologically based perspective to the discussion, Birney says.

The abstract for the study:

Twin and family studies have shown that same-sex sexual behavior is partly genetically influenced, but previous searches for specific genes involved have been underpowered. We performed a genome-wide association study (GWAS) on 477,522 individuals, revealing five loci significantly associated with same-sex sexual behavior. In aggregate, all tested genetic variants accounted for 8 to 25% of variation in same-sex sexual behavior, only partially overlapped between males and females, and do not allow meaningful prediction of an individual’s sexual behavior. Comparing these GWAS results with those for the proportion of same-sex to total number of sexual partners among nonheterosexuals suggests that there is no single continuum from opposite-sex to same-sex sexual behavior. Overall, our findings provide insights into the genetics underlying same-sex sexual behavior and underscore the complexity of sexuality.


Cheers,
Colin




Saturday, August 24, 2019

Global Suicide Data

Science has informative data on global suicide statistics. Some of the findings:

-Most countries are seeing declines, for reasons that include restrictions on access to lethal means and improved mental health care.

-Gun deaths in the United States: More than 57% of gun fatalities in the United States in 2017 were suicides, nearly 24,000 people.

-Compared with other age groups, suicides among young people are rare.

-Globally, men are far more likely to die by suicide than women.

Cheers,
Colin

Monday, July 29, 2019

Review of "The War of Art"



Many thanks to those who turned out for the Philosophy Meetup reading group of Steven Pressfield’s book The War of Art. Here I provide my own comprehensive review and evaluation of the book.

This book was certainly different from the academic books I typically read. I really enjoyed it. Lots of it resonated with me (I do aspire to write non-fiction one day… my own battle with RESISTANCE ha ha!).

So why read this book? I think anyone facing obstacles in their personal lives – be it with writing, or switching careers, or ending an unhealthy marriage, or moving to a new city, or entering retirement, or re-entering dating, etc.- will stand to benefit from reading this book. I think the spirit with which to approach this book is as follows: Pressfield is like a team coach, gathering us together in the locker room before a big game. His goal, as our coach, is to inspire us to do our best- with the singular goal to increase the odds of our winning the game.

The general goal, as Pressfield states it early on in the book, is to help us bridge the gulf between the life we live, and the unlived life within each of us. He draws on his experience as a (once struggling) writer. It is an inspiring and insightful read. I am happy to have Pressfield as my coach, giving me a kick in the butt when I need a kick, to help me closer align my current life to the unlived life within me.

The dominant theme in Part 1 of the book is that the thing that prevents us from accomplishing what we want to accomplish in life is Resistance. We often overlook how our internal belief system can constrain and conspire to limit what we achieve in life. “I am not talented enough to be a published author!”. “No one else will love me”. “I can never lose weight!”. Such beliefs can erode a person’s creative potential, keep them in an unhappy marriage and out of the gym. As our motivation coach, Pressfield wants to raise our level of consciousness so we are aware of how our belief systems stifle our aspirations. And by doing so we can be better prepared to overcome the limitations we impose upon ourselves.

What stands between the life we live, and the unlived life within us, argues Pressfield, is what he calls Resistance. Resistance is the enemy! And the book aspires to help us identify, and ultimately, conquer Resistance in our personal lives.

Resistance can arise when aspiring to pursue your calling (e.g. painting, writing), launching a new business, pursuing your spiritual advancement, romantic relationships and parenthood, education, getting fit, overcoming an unhealthy habit or undertaking an action that requires ethical or political courage. Resistance is invisible, and as such is a sly enemy! But we feel it, it emits an energy. It tries to prevent us from doing our work. Resistance arises from within. Pressfield describes Resistance as “self-generated and self-perpetuated”. It is insidious, implacable, impersonal, infallible, universal, it never sleeps, it plays for keeps, it is fueled by fear, etc.

When the finish line is in sight, argues Pressfield, that is when Resistance is most dangerous. As we get closer to our aspirations resistance hits “the panic button!”, a counterattack to thwart us from achieving what we really want in life. Perhaps you bail on resigning from your current, unhappy, job after you finally get that dream job offer. Or you finally meet a great person for dating but get cold feet and call it off before risking getting your heart broken.

We must be aware of the symptoms of Resistance, such as victimhood (a strategy that doesn’t require honest work or any contribution), and choice of a partner (someone whose coattails we can ride on or whose adoration we use to prevent them from overcoming their own Resistance).

What does Resistance feel like? Bored. Restless. Guilt. Unsatisfied. It can become critical and lead to depression.

Resistance and Fundamentalism: Pressfield argues we didn’t evolve to live as individuals, rather we are wired tribally- to act as part of a group. We don’t know how to be alone, how to act as free individuals.

A contrast is made between the artist and the fundamentalist. The artist is creative and positive, the fundamentalist is destructive and negative. The latter is a philosophy of powerlessness. And when it comes to fear, Pressfield notes that fear is actually a good thing! “The more scared we are of a work or calling, the more sure we can be that we have to do it” (40).

Pressfield argues a fixation on healing can be a form of Resistance- telling yourself you need to heal completely before undertaking the work to achieve what you want. “Resistance knows that the more psychic energy we expend dredging and re-dredging the tired, boring injustices of our personal lives, the less juice we have to do our work” (50).

Rationalizations, argues Pressfield, is Resistant’s right-hand man (57), the spin doctor. My favourite quote from Part 1: “If Resistance couldn’t be beaten, there would be no Fifth Symphony, no Romeo and Juliet, no Golden Gate Bridge. Defeating Resistance is like giving birth. It seems absolutely impossible until you remember that women have been pulling it off successfully, with support and without, for fifty million years” (57).

Part Two of the book is titled “Combating Resistance: Turning Pro”, and Pressfield draws a contrast between the amateur and the pro. The latter overcomes Resistance. The qualities that define a pro are as follows (p. 69-70):

(1) We show up every day
(2) We show up no matter what
(3) We stay on the job all day
(4) We are committed over the long haul
(5) The stakes for us are high and real
(6) We accept renumeration for our labour
(7) We do not over identify with our job
(8) We master the techniques of our job
(9) We have a sense of humor about our jobs
(10) We receive praise or blame in the real world

The professional understands *delayed gratification* (p. 75). So this could apply to a writer who persists through having her book rejected by multiple publishers, the single person who persists through bad dates to wait to meet the right partner for a loving relationship (without quitting dating or settling for a bad relationship) or the person who works their way to a promotion that pays off with more rewarding work.

Professionals know fear can never be overcome (p. 79). Fear of rejection is part of the game, accept it and persist in the face of it.

Professionals do not hesitate to ask for help (p. 85). I think this is a crucial insight in the book. We often think we can do things alone or that asking for help is a sign of weakness. Knowing you need help, and asking for it, is a sign of strength not weakness!

The final part of the book is titled “Beyond Resistance: The Higher Realm”. I admit that, as an atheist, there were elements of this concluding section, about angels, muses and “physical forces”, that had me scratching my head more than once. Pressfield notes that some will feel uncomfy with his terminology, and that we should just think of it in terms of “impersonal forces” like gravity. That is what I have tried to do. The angels and muses are forces that work as our allies to overcome Resistance. Resistance prevents us from becoming who we were born to become.

Pressfield makes a Jungian-style contrast between The Self and the Ego, the latter is the home of Resistance. The Ego likes things the way that they are. Whereas The Self craves creativity and growth! The Ego believes in material existence- it does the important job of getting things done in the material world. Pages 136-38 contrast the different stances The Self and Ego take on death, time and space, whether people are similar or different, the supreme value (love vs self-preservation), and god.

My favourite part of this section of the book was, hands down, the discussion of hierarchy vs territory. We can achieve “psychological security” in one of two realms- within the hierarchy of a group, or by our connection to a territory. The former is our default setting- think of being an awkward teen trying to fit in with your “clique of friends” (paradigmatic example of a hierarchy). As we mature, and acquire the experiences and pain and growth of life, we shift to the territorial alternative.

P. 150 details why the hierarchy orientation is fatal to the artist- it makes you compete against others, equate your happiness with your rank in the hierarchy, treat others based on their rank (rather than their humanity). But the artist must do their work for their own sake, not for the validation that comes via hierarchy. In the hierarchy mindset we are always looking outwards- what can people do for me? how do I boost my standing? etc. But you never look within (which is how growth and creativity occur!).

We all have territories, Pressfield’s examples are- for Stevie Wonder it is the piano, for Arnold Schwarzenegger the gym and for a writer it is writing. A territory provides sustenance, sustains us without any external input, it can only be claimed alone, it can only be claimed by work, and it returns exactly what you put into it.

Pressfield’s suggested test to reveal your territory is this- imagine you are the last person on earth, what activities would you do? This test stripes away any hierarchical considerations.

That completes my summary of the book. Now for my overall evaluation.

As I noted above, I think the spirit to take this book is that of a coach motivating you before a game. As such, I think this is a great book that can actually help (especially creative people) people improve their lives and realize their aspirations. The positive big picture message is: Identify Resistance in your life, aspire to turn “pro”, and embrace your territory vs hierarchy. However I have some caveats.
I do not believe that following the advice of this book is necessarily a recipe for living a flourishing life. And the reason for this is that Pressfield, for the most part, treats the issue as if we only have one “pro” aspiration. And as such, he does not give enough attention to the realities of the tradeoffs that must inevitably be made in life for most pros and aspiring pros.

If your only pro aspiration is to be a writer, then yes this book will be instructive. But if you also aspire to go “pro” as a spouse, parent, employee, athlete, etc. you run into the predicament of how to find balance between these competing aspirations. The aspiring writer in you might see your desire to start the day at the gym (rather than writing) as simply Resistance. Or the time you invest in getting your kid’s lunches ready for school, or driving them to their extra curriculum activities after school as Resistance. But the reality is most of us have a few aspiring “pro” goals going on *simultaneously*. The real work is thus navigating through these often conflicting commitments. Simply saying “go pro!” doesn’t help us navigate the terrain of managing many, often competing, pro aspirations.

Like a coach before a soccer game who is only focused on “winning the soccer game at all costs!”, Pressfield’s analysis often misses the big picture that we have a multitude of identities and goals and aspirations. He often invokes elite athletes as examples, like Arnold and Tiger. And while these athletes certainly dominated in their respective sports, I am not sure they are exemplary examples of the type of flourishing humans we should strive to emulate. It is possible to invest too much in some aspirations, at a cost of your overall wellbeing. And there are circumstances where someone is better off giving up certain goals and aspirations that they are not likely to realize, otherwise they risk depression and persistent frustration. This is the idea of “adaptive preference formation”. Pressfield might reply that this is all Resistance-speak, but I think there are nuances and complexities that make the issue more complicated than that.

These caveats notwithstanding, I really enjoyed The War of Art. It has compelled me to take a long and hard look at my own Resistance in life, and inspired me to grow and develop in ways I probably wouldn’t have without Pressfield’s “pep talk” before the big game! Highly recommended read.

Cheers
Colin

Tuesday, July 23, 2019

3 Interesting Studies Published This Past Week

We live in an age where the news, which helps us form an understanding of our complex world and the problems within it, is becoming increasing dominated by social media. And the latter often contains dramatic video of events in the world. Such events often do not actually constitute a “news worthy” story but are rather like driving past a car crash on the highway- everyone stops to take a look. And because people are hyper-connected to social media, they are bombarded with such images on a daily, even hourly, basis.

Truly newsworthy stories are stories that are grounded in important facts, offered with nuanced analysis and a narrative that reveals significant empirical insights about the world and our predicament in it. Almost all these things are missing when the news becomes—"click this amateur phone video now and share”!

Just one (recent) case in point- the news story from last week about someone using their feet to navigate an ipad on the plane would never make the news if there was no video to watch. For example, imagine a newspaper headline that reads “Someone used their bare feet on an Ipad”…. Full story on page 2, along with the story “Some guy on a train picked his nose!”

Every day someone is doing something gross somewhere. This is not real news in the 21st century. Stories like the barefeet ipad guy are fuel for social media venues like Twitter, where millions are happy to comment on, and retweet, such stories. I believe this is a sad reflection of the reality of our times.

To help guard, as far as is possible, my own perception and understanding of the world from being skewed by simplistic narratives (i.e. the story of humanity is one of “oppressor vs oppressed”), unrestrained emotions or unrepresentative impressions, I try to minimize my exposure to such low-value news and instead try to keep abreast of what the latest scientific findings are in different areas of enquiry.
I am always on the lookout for scientific studies that come to conclusions that challenge popular “folk wisdom”, including my own intuitions and assumptions. This past week I noticed 3 such studies that are worth mentioning.

The first is the surprising finding, reported in the Proceedings of the National Academy of Sciences, that white US police officers are not more likely to shoot minority citizens than black or Hispanic officers. The researchers found that the strongest factor in predicting the race of a person fatally shot by a police officer were violent crime rates where the shooting took place. A quote from the news item:

“"If we want to reduce the rates at which people from minority racial groups are shot by police, we need to address differences in crime rates between races," Johnson said. "That involves considering what causes those differences, like racial disparities in wealth, unemployment and education. I'm not saying that's easy. We asked a difficult question, and the answer ended up being difficult."

A second intriguing study I came across, published in The American Psychologist, reports the encouraging results of poll data from 30000 US adults between the years 1946-2019. The results suggest that gender stereotypes have significantly changed in the past 70 years. From the News report:

Competence stereotypes changed dramatically over time. For example, in one 1946 poll, only 35% of those surveyed thought men and women were equally intelligent, and of those who believed there was a difference, more thought men were the more competent sex. In contrast, in one 2018 poll, 86% believed men and women were equally intelligent, 9% believed women were more intelligent and only 5% believed men were more intelligent.
This doesn’t mean that the legacy of patriarchy has been abolished, far from it. But it is important to take notice of the progress and victories that have been achieved over the past number of decades. So this report is a reminder to us that our understanding of the “problems of today” must be informed by an accurate portrayal of the realities of today (vs from nearly a century ago).

And the third interesting study I came across was this one, also in the PNAS, which found that social media has limited effects on teenage life satisfaction. This is one I am especially interested in as the parent to teen boys. A sample from the news item:

This is the first large-scale and in-depth study testing not only whether adolescents who report more social media use have lower life satisfaction but also whether the reverse is true. Before this study scientists had little means of disentangling whether adolescents with lower life satisfaction use more social media or whether social media use leads to lower life satisfaction….
The authors conclude: 'Applying transparent and innovative statistical approaches we show that social media effects are not a one-way street, they are nuanced, reciprocal, possibly contingent on gender, and arguably trivial in size'.


These 3 interesting studies, which admittedly are not the final word on race and police shootings, gender competence stereotypes and the impact of social media on teens, will not make the news to compete with the news story of barefoot ipad guy. But all 3 studies remind us of the reality that our common perceptions of reality can often be incorrect, outdated, “intuitive hunches” that contravene what the data reveals, etc. When our news is filtered to us via social media I believe it can exacerbate these problems.

Cheers,
Colin