Sunday, April 24, 2016

What advice would people give to someone who struggles with delaying gratification?


At its core, this is a question about habits, specifically, how to lose harmful habits and how to make beneficial ones. Requires focus, discipline and persistence. To do what? To invest the time and energy necessary to accurately diagnose the three essential parts of a habit, namely, it's cue, reward and routine. A few years back, Charles Duhigg came up with this comprehensive infographic to help deconstruct habits.



As the graphic explains, accurate diagnosis is necessary and requires time, energy and interest to experiment. Experimentation in turn is necessary to uncover the cue and reward system underlying a harmful habit.

A crucial idea is Keystone Habit, i.e., the power of some habits to trigger a chain reaction of other habits. An ecological concept that finds its place in anything from healthy microbiota to sociology, implicit in keystone is the notion that some habits are simply more powerful than others. Thus, the process of deconstructing habits involves as well identifying those that are keystone. Unsurprisingly, willpower or self-discipline is a core keystone habit. 

For e.g., some weight-loss studies showed that forcing oneself to form the new habit of keeping and logging entries in a food journal, i.e., a food log, turned out to have unexpected benefits. For many participants a once-weekly exercise even became daily and helped them notice previously undiscerned patterns in their behavior, plan healthier menus and make more conscious decisions about eating healthier food. Though Duhigg wrote an entire book on the Power of Habit, his New York Times article on the same topic is sufficient to get the idea: How Companies Learn Your Secrets
 
Obviously an obstacle in the quest to change habits, cognitive dissonance is another necessary factor to consider. It arises from different systems we have for assigning value. Thus, diagnosing the source of conflict between different valuation systems with respect to a harmful habit, say, habitual unhealthy snacking, is also necessary (see figures below from Rangel, Antonio, Colin Camerer, and P. Read Montague. "A framework for studying the neurobiology of value-based decision making." Nature Reviews Neuroscience 9.7 (2008): 545-556. http://worthylab.tamu.edu/Course...).


Other tips that could help include
  • Starting with baby steps, i.e., scaling down the scale of change one seeks, something not so easy to do since the ego often demands or seeks a much more ambitious scope. However, though difficult, setting realistic goals is necessary.
  • Not giving up immediately at the first sign of setback.
  • Being patient with and forgiving of oneself.
Finally, any number of tips and tricks aren't going to do the trick by themselves. Habit is the result of many, largely unconscious, decision making processes. Intellectually deconstructing them can be relatively easy, even fun. Emotionally engaging with the process is the hard part. Unless engaged in the process both intellectually and emotionally, habit changing is likely to fail.


https://www.quora.com/What-advice-would-people-give-to-someone-who-struggles-with-delaying-gratification/answer/Tirumalai-Kamala


Sunday, April 17, 2016

Why are research papers on things that have no practical benefit for society funded by the government? This topic came up in reference to how an ideal government should function.


Ideal government. Ideal for whom? One person's meat is famously another person's poison.

Averaging <5%, R&D is a minuscule part of government expenditure
It's misleading to debate government spending on research in general, and on so-called 'frivolous' research in particular without considering the total amount of government spending. Governments spend a lot of money on lots of things. What proportion is on R&D? Minuscule. That's as true in the US (2.85% of 2011 GDP spent on R&D) as it is in India (0.76% of 2007 GDP spent on R&D) (see table below), where the already meager amount the government spends on R&D is only decreasing, not increasing. By and large, governments, especially the larger, wealthier ones tend to spend astronomical amounts on stockpiling weapons and munitions even when millions of their citizens don't get enough to eat. Scope and scale of arguably frivolous public funded R&D literally fades into insignificance when examined from this perspective.


 
As for everyone having the basic necessities, is there even one country to have succeeded in this endeavor? With its share of the poor and homeless, even the wealthiest and most powerful country in the world, the US, is unable to ensure that every one of its citizens has the basic necessities. Should its government should stop funding basic R&D? That's tortured logic or more accurately, torturing logic.

Practical benefits of science are typically unforeseeable
How to assess the value of government-funded research? Is it only that which yields immediate practical use? We'd then have to include German Nobel prize winner, Fritz Haber, whose weaponization of chlorine gas was of obvious immediate practical benefit to his country's government during the First World War. Rather than laudable, the point of this inglorious and downright shameful example is to highlight the folly of focusing exclusively on foreseeable practical benefits of public funded R&D.

History also teaches that many things of immediate practical benefit turn out be long-term banes. Developed accidentally by Allied industrial chemists trying to help their side win the Second World War, the self-evident practical benefits of plastics such as polyethylene meant that the post-WWII human took to using it in unprecedented numbers and in arguably all aspects of life. Emblematic of long-term bane, toxic chemicals such as BPA (bisphenol-A) and phytoestrogens leaching from plastics cause long-term damage to the health of not just humans but other life forms as well while plastic refuse is quite literally choking ocean life itself to death as a vast toxic plastic landmass builds on the Pacific Ocean.

Thus immediate, foreseeable practical outcome alone is an inadequate benchmark to judge the value of public funded R&D. OTOH, public funded R&D has several, largely invisible long-term benefits to society. At the very least, it helps establish research infrastructure and culture, i.e., a scientific temper among its populace. An invaluable common good, can't put a price on scientific temper. It also provides stable, gainful, long-term employment to many. Even if their scientific output is middling, their consumption helps the country's economy. Educated people are also more likely to invest in their children's education. Predicated on the way in which social networks operate, this in turn further helps embed scientific temper within the larger society.

Another self-evident truth to consider is that smart people are unlikely to waste their talent and time on research projects that they find unfulfilling. If public funded R&D is indeed disproportionately spent on fruitless fishing expeditions, it's more likely to be the output of careerist scientists, and as we explored already, there's value to be mined from their ranks as well.

As for highly abstract notions with no foreseeable practical benefit, what could be more emblematic of that than Quantum mechanics? Its calling card, casual defiance of Newtonian mechanics, the very stuff of woolly-headed dreaminess. And yet from lasers and transistors to cancer diagnostics (MRI; Magnetic Resonance Imaging), a long line of practically unforeseen practical benefits have ensued from it over the past century.

Since innovation isn't a command function, the wild card of serendipity weaves the necessary magic
Practicalities aside, is innovation even a command function? Even a cursory look at the history of science leads to incontrovertibly conclude no. Rather, innovation through the ages shares the common thread of serendipity.

According to Royston M. Roberts, after reading the fairy tale adventures of 'The Three Princes of Serendip' (i.e., Serendib or Ceylon or Sri Lanka), who 'were always making discoveries, by accidents and sagacity, of things which they were not in quest of...', Horace Walpole coined this word in a letter to his friend Sir Horace Mann, 1st Baronet in 1754 to explain the basis of his own accidental discoveries (Amazon.com: Serendipity: Accidental Discoveries in Science (9780471602033): Royston M. Roberts: Books). The list of serendipitous discoveries is legendary, legion and grows by the day. From X-rays and Quinine to Penicillin and Velcro to Oral Contraceptives and Viagra.

However, serendipity is not synonymous with accident. As Pasteur famously said, 'chance favors only the prepared mind'. Thus, innovation can't be ordered into existence nor can one stumble into it by accident. Yet many of the most important discoveries were the product of serendipity, which is accidental discovery but not accident. What gives? Insatiable curiosity, and breadth and depth of knowledge certainly seem to be the common mainstays among these famous examples. What else?

When Carl Djerassi was hired in 1949 to lead a research team at Syntex, 'an oral contraceptive was not in anyone's plans' (Amazon.com: Serendipity: Accidental Discoveries in Science (9780471602033): Royston M. Roberts: Books). An ancillary goal of his team was to synthesize a molecule that could mimic the biological effect of estradiol, a female hormone used for treating puberty- and menopause-related disorders. Instead they accidentally ended up synthesizing one that mimicked progesterone. Progesterone, of course, is 'nature's contraceptive' since it inhibits ovulation during pregnancy. Thus, the first oral contraceptive resulted from serendipity, not from a utilitarian command directive from management on high. Freeing womanhood, indeed society itself, from the drudgery and curse of unplanned pregnancy, it can be argued that woman's liberation itself may not have been possible without the serendipitous oral contraceptive.

Djerassi's team's goal was synthetic estradiol. Rigidly sticking to their programmatic goal would have dictated throwing the artificial progesterone in the trash. A prepared mind means to be able to accurately appraise the value of accidental discoveries, as Dejrassi's team did. This isn't something programmable by a rationally designed utilitarian system. Rather it's inculcated within a larger cultural framework that values curiosity and the capacity to synthesize knowledge from information, and that imbues an intuitive sense of value.

I recently read an article on Rajaram Bhapkar. Much like the indomitable Dashrath Manjhi, made famous in a recent Bollywood film, who connected his village with the outside world through his own backbreaking labor, Bhapkar built roads in the craggy hillsides surrounding his village on his own initiative. The astonishing innovation? 'On a particularly challenging downhill road from Khandoba mandir, Bhapkar asked a few engineers for help. When they refused, he turned to two donkeys. He filled two bags with gravel and pierced holes in them, tied them to the donkeys and sent them downhill. He then constructed the road on the trail left by the gravel. “Now, structural engineers visit and tell me it is a marvel and ask who is the engineer behind it. I point to the donkeys,” said Bhapkar, with a laugh (Mountain man and donkeys). That's ingenuity of the highest order. Not a degree from Harvard or MIT or IIT but sheer undeniable native ingenuity.

As long as human societies continue to throw up the Rajaram Bhapkars in our midst, innovations will remain reliable engines. That's a takeaway for sure. Role of governments? Innovation not being a command function, it would suffice if governments are able to rein in the addictive and hypnotic hold of political expedience and power long enough to engender a culture that stably values and upholds scientific temper within its midst, come what may.




https://www.quora.com/Why-are-research-papers-on-things-that-have-no-practical-benefit-for-society-funded-by-the-government/answer/Tirumalai-Kamala


Sunday, April 10, 2016

What questions can I expect to recieve at a science congress? I submited a poster to a medical student congress and my topic is ECG changes in long-term cannabis users (I did an ecg on 40 young adults to see the long term effects of cannabis consumption). What kind of questions might the board ask me after my presentation? I'm nervous.

Nervousness presenting data in front of peers and experts. Especially experts. They know so much more. No way to know everything about the subject or all the answers to all the possible questions the experts could ask. Seems like a surefire recipe for public embarrassment. Starting out in science where data and poster presentations are par for the course, these kinds of non-productive ruminations are commonplace. Since I'm not an expert on heart physiology, ECG, cannabis and its effects on physiology, I can't provide a list of possible questions about your poster. However, I'm going to suggest a way to approach your predicament that empowers you during your poster presentation and relieves the nervousness. In fact it's an empowering way to approach poster and data presentations in general so the particulars are moot anyway.

In hindsight, spending time trying to think of all the possible questions someone might ask and trying to prepare adequate responses is a waste of time. A realization that was an epiphany for me showed me why. The epiphany was that no one can know work I did as well as me. When we present data from work we did, we are the best experts on it simply because we did it. We know everything about it A to Z in a way no one else possibly could.

If there is one thing you could take away from this answer, I hope it would be that no one at that congress or anywhere else for that matter could possibly know as much about the work in your poster as you do. You did the ECG on those subjects, you know all the little details that went into that work because you did them.

Yes, this is a psychological tool to feel self-confident when presenting in front of an expert audience but one that's rooted in fact. It's just a fact that's not easily self-evident, that the person who does a piece of work is the world's greatest expert on that piece of work simply because they did it.

If it helps, you could also think of your study and the wider world it belongs in in terms of the microcosm and macrocosm, respectively. The microcosm? Something on which you are the expert and no one else, what you did, why you did it, even the mistakes you made and the limitations of the study. The macrocosm? The implications, the past studies that led to your study, heart physiology, the ECG technique, cannabis and its effects on physiology. The macrocosm is where the experts and their pesky questions enter the picture. You likely know some of that macrocosm but not all and likely some experts at that medical student congress will know more, and that's the source of your nervousness. But hopefully, now your nervousness will be tempered by the fact that even those experts can't compete with you in the domain in which you alone will be the expert at that poster presentation, the microcosm, the work you did.

This approach relieves the mind of all that pressure of performance, replacing non-productive rumination with productive focus. Now, even if you don't know all possible questions and their answers, instead of being only a source of embarrassment to turn away from with all haste, an unanticipated question during your poster presentation becomes an opportunity to engage with the asker. More than anything else, it allows the mind to enter the scene open to engagement rather than anticipating to flee, and that makes all the difference.


https://www.quora.com/What-questions-can-I-expect-to-recieve-at-a-science-congress/answer/Tirumalai-Kamala


Sunday, April 3, 2016

Do western drug companies test more dangerous drugs on the poor in India, and should they be held accountable?


Doubtless, regardless of their location, badly run clinical trials are anathema, delaying development of much-needed treatments and cures, shaking public confidence in biomedical research, and eroding public trust in the biopharmaceutical enterprise.

Who's accountable for clinical trial mishaps in India?
Let's not forget that a clinical trial in India typically has multiple partners, only one or few of whom may be a foreign entity funding the trial, be it a pharma company or a non-profit. When a clinical trial goes wrong, who's responsible? Only the foreign entity? If someone answers yes, they also have to explain why, something impossible to do. OTOH, vilifying only the foreign partner(s), one of the many entities involved in a clinical trial, certainly makes for some easy poutrage. For example, in the case in question, the Phase V HPV (Human Papilloma Virus) vaccine trials consisted not of dangerous drugs, as the question sensationally asserts, but rather of two HPV vaccines, Gardasil and Cervarix, approved for use in many countries years ago, with the former approved in 121 countries as of 2011 (1). As well, it wasn't sponsored by a western drug company but by PATH (global health organization), a non-profit that over the years has become the largest beneficiary of public health funding from the Bill & Melinda Gates Foundation. So with the predictable misinformation out of the way, let's examine global clinical trial responsibility through this trial's lens.

Typically, foreign drug companies can't conduct clinical trials directly. They need local partners, for legal, logistical, operational and cultural reasons, partners such as ICMR (Indian Council of Medical Research), DCGI (Drug Controller General of India), state and central governments, different ministries, public health departments, etc., who know the local laws, rules, regulations and language, and most importantly know and/or oversee the local infrastructure. Thus emerges a daisy chain of partners with different expertise and priorities. Issue is whether each of these partners is equally well-versed in conducting clinical trials.

With decades of experience under its belt, the foreign pharma or non-profit entity knows or should know how to conduct clinical trials. OTOH, the local partners may typically not be as well-versed, especially in crucial details such as importance of informed consent, and need for careful monitoring and reporting of adverse events. These weren't learned by clinical trial professionals in one smooth, fell swoop either. Countries well-versed in conducting clinical trials today went through their share of the learning curve, unfortunately often at the expense of hapless trial participants. *, **, ***, ****.

What about the responsibilities of the local partners? Each trial partner has a stake in ensuring that clinical trials uphold the highest standards of ethics and medical care, all of which which begs the question why they would be or ever become badly run in the first place. As clinical trials increasingly globalize, hiccups are inevitable because the core issue is culture clash. From all accounts, this was the situation with this Indian clinical trial. How well trial partners communicate across their daisy chain, particularly in plugging crucial knowledge gaps with respect to risks and risk assessments, is key. Not sufficient to explain what to do when and how but also why. If the local partner on the ground pays lip service to informed consent or adverse outcome monitoring, it's not just a question of who's responsible but also why it turned out that way. This is where cultural differences weigh in. Maybe the foreign trial partner explained what adequately but not why. So, who's responsible? Everyone involved, not just the foreign entity. Investigations revealed the trial in question had a two-fold problem (2, 3).

1. Informed consent, a cornerstone of clinical trials. Medicine already walks a tightrope between patient autonomy and welfare. Life itself doesn't come with a risk-free guarantee so it's unrealistic to expect medicine, let alone experimental medicine, to do so. This is only accentuated in a clinical trial, where the risks of a possible drug/intervention remain largely unknown. After all, one of the purposes of clinical trials is to reveal such risks. Clinical trial participants need to understand these risks as fully as they can, understand that their participation comes with inherent risks. Sometimes those risks may be minor such as local, temporary injection site reactions yet they range all the way to life-threatening. Comprehensively explaining these risks is the purpose of informed consent. Since this trial involved minors, parents/guardians were required to give informed consent. Instead in thousands of cases, teachers and school principals were found to have signed them, even when the children concerned had parents/guardians.

2. Adverse effect, another cornerstone of clinical trials. One of the purposes of clinical trials is to carefully monitor and assess harmful effects of any drugs/interventions. Perhaps nowhere else is the phrase, 'safety in numbers' more appropriate than in medicine. More people assessed for a drug/vaccine's safety during its journey to approval through the clinical trial process, more robust the data that underpin its safety profile. Investigations revealed this particular trial had paid lip-service to monitoring and recording adverse events.

As an entity well-versed in clinical trials, PATH, the foreign non-profit that conducted this trial had no excuse whatsoever for the lapses in informed consent and adverse effect monitoring. What about the local partners though, ICMR, DCGI, the state governments of Gujarat and Andhra Pradesh where these trials were held, the schools the girl participants were recruited from? After all, as we proceed lower down the daisy chain, don't we also come closer to increasing personal responsibility for the welfare of minors? Thus, in this case, ICMR and DCGI also bear responsibility at the national level while the local governments, and local departments of education, public health and child health bear responsibility at the local level. Public scrutiny of clinical trial mishaps is a public good only when it's accurate and impartial.
Other open questions which remain unanswered:
  • Did PATH adequately train and monitor the ground staff, especially on the issues of informed consent and adverse event monitoring?
  • Did ICMR and DCGI monitor and ensure that PATH adequately trained the ground staff?
  • Who monitored the ground staff during the course of the trial? Was it PATH, ICMR, DCGI, local public health department? Was the monitoring responsibility clearly delineated and did it have checks and balances?
  • What kind of recording and monitoring systems were in place to ensure participant safety?
More entities involved, more difficult to identify and assign blame. Be it an individual or group, taking responsibility when things go wrong is often akin to the proverbial flying pig. Yet mishaps like this trial offer an opportunity to examine and improve the global clinical trial blueprint, especially the weak links in the chain the open questions reveal. Finally, when it comes to accountability, it's not just a question of who but also how. With respect to how, monetary fines could be imposed on the foreign entity. What about the local partners? Reprimand or fire local and/or senior officials? Obviously, when it comes to global clinical trials, more productive to develop processes for accountability ahead of time, not impose them ad-hoc in a haphazard and reactionary manner. In particular, potential legal redressals need to be developed proactively.

Potential benefits of clinical trials to countries like India
Self-righteous indignation can easily create a fog that obscures sound thinking. Clinical trials are hugely expensive. A more pragmatic approach shows that basing them in countries like India could be a common good from multiple standpoints,
1. Drug companies save costs substantially. Less it costs to bring a drug to market, lower the drug company needs to price it to recuperate R&D costs. In other words, drug companies lose the fig leaf of high R&D costs in pricing new drugs outrageously.
2. Historically, drugs approved post-WW II were largely tested on white men. That's hardly representative of the global human population. By basing clinical trials in countries like India, the diversity of population tested increases, theoretically improving drug efficacy and safety profile data.
3. Conducting clinical trials in countries like India can be an opportunity for meaningful technology transfer. As life expectancy increases globally, healthcare consumes increasing proportions of countries' wealth and infrastructure. Need for more novel drugs and therapies is becoming more, not less, inevitable. In turn, conducting more clinical trials to develop them becomes more, not less, inevitable. Makes it all the more worthwhile for a country like India to thoroughly learn how to conduct them properly, rigorously and ethically.
4. Conducting clinical trials is and should be considered an opportunity for a country to use as leverage to bargain to gain better access and price to drugs and therapies, both old and novel, for its population. 


Bibliography
1. Haupt, Richard M., and Heather L. Sings. "The efficacy and safety of the quadrivalent human papillomavirus 6/11/16/18 vaccine Gardasil." Journal of Adolescent Health 49.5 (2011): 467-475.
2. Final Report of the Committee appointed by the Govt. of India, (vide notification No. V.25011/160/2010 - HR dated 15th April, 2010,) to enquire into“Alleged irregularities in the conduct of studies  using Human Papilloma Virus (HPV) vaccine” by PATH in India, Feb 15, 2011. http://icmr.nic.in/final/HPV%20P...
3. PARLIAMENT OF  INDIA RAJYASABHA  DEPARTMENT-RELATED PARLIAMENTARY STANDING COMMITTEE SEVENTY-SECOND REPORT On ALLEGED IRREGULARITIES IN THE CONDUCT OF STUDIES USING HUMAN PAPILLOMA VIRUS (HPV) VACCINE BY PATH IN INDIA (DEPARTMENT OF HEALTH RESEARCH, MINISTRY OF HEALTH AND FAMILY WELFARE) (Presented to the Rajya Sabha on 30th August, 2013) (Laid on the Table of Lok Sabha on 30th August, 2013). http://www.preventdisease.com/ne...


https://www.quora.com/Do-western-drug-companies-test-more-dangerous-drugs-on-the-poor-in-India-and-should-they-be-held-accountable/answer/Tirumalai-Kamala