Friday, August 28, 2015

WHAT IF...



What if I am wrong and everyone else is right? How will I reconcile my thoughts to the reality? Indeed what if I am right and everyone else is wrong? What do I do?



These scenarios play out in our lives daily. Risk mitigation strategies are nothing more than links of multiple “What ifs!”  The actuarial data creates the template and probability thrashes out through the Bayesian lens, numbers that speak to the risks. All is contained. All is accounted for. All is measured.

Is it?

Yet, yet the blood curdling thought turns black the phantasmagoria of the colorful dream when the “What if” chimes in. And it does, if one does not swim in the lake of delusions.

Let me take you on a short aviation encounter of the real kind…

Flying as we all know has known risks. The fatality rate of commercial operators as in Airlines and General Aviation is a miniscule 0.42 per 1,000,000 passenger miles travelled while Auto accident related fatality rates are 3.4 per 1,000,000 passenger miles travelled or 10 fold more. So neither modes of travel are exempt from risk. And if you carry this thought forward, it seems that the drive to the airport is almost 10 times more hazardous than the flight itself.



Since we are inclined to toast the virtues of aviation and link them to the nearby disciplines of medicine and in some cases of business, let us carry this heavy ball and chain further. I commented while delivering a lecture on Aviation Safety, “What if things don’t go the way you anticipate?” There was silence. “What if you run out of fuel in the air?” A hand arose from the rear of the room. “You wouldn’t let that happen!” the voice claimed.



“What if the High Pressure turned into a Low Pressure area and you were faced with head winds instead of tail winds as calculated in your trip planning?” Again the hand raised, “Set the plane down at a nearby field, anticipate the potential based on the speed, fuel and distance calculations.”
What if you are over a mountainous terrain?” I countered. This time there was silence. Inspiration hit the back of the mind that had been responding, “Set the plane down before the mountainous region, fuel up again and then continue the journey.”



“What if there were no airports within a 50 mile radius?” Stumped? Not really, the Phoenician hand rose again, “You have to anticipate that when you begin your journey!” She was right again!
Having found one listener who was engaged, I switched tack, “What if you lose engine power on take-off at 400 feet?” A hand rose across the sea of heads, this time from the back again but the other side of the room, “Go back to the airport!” The baiting was over and the opening I had been waiting for had arrived.



“If you make a turn back to the airport below 700 feet universally that is a no, no! As you turn you lose the vertical component of lift and the potential for stall and spin is extremely high. So the only option is to land straight ahead or 30 degrees left or right of the departure end of the runway wherever there is an open field.” I paused and a few heads nodded. “This brings me to another question, what do you think the main reasons are for doing a traffic pattern at a non-towered airport?” More hands raised, a cacophony of, “See other aircraft in the pattern, arriving and departing and any potential hazards on the airfield itself, such a waste of time, waste of fuel, totally unnecessary” were the main thrusts. “What about using the traffic pattern as a means to observe both the departure end and the arrival end of the runway for the potential of what if?” Blank stares greeted me on that. “What if you lose an engine on departure from the same airport and having surveyed the field on arrival, knowing the terrain surrounding the airport, one can safely figure out a location to set down the aircraft and walk away from potential of harm.” The bulbs of inspiration and understanding lit up. Hey that makes sense was the general brightness that illuminated the attendees.



What if, is a game of chance and played by those that seek not to rely on luck but on mitigating the potential of risk. In business, the smart money always plays the game. Ever see Shark Tank on TV, it is all about the potential of success vs the potential of Risk. The ratio above 1 gains an investment from the Wealthy Sharks while those with an irrational number (fraction) go home. The Sharks look for fiscal trends of the business, the emotional needs and the desires of the public at large, the investment costs and their Return on Investment (ROI) through acquisition of part of the business. Sharp, shrewd and uncannily business wise!

In medicine too doctors continually play the game in their minds and when discussing cases with colleagues. What if I give this medicine, how would the heart react to it and what would that do to the kidney function and how would that affect the lungs. Or this chemotherapy or biologic therapy harms the heart x% of times and the benefits are y%, if the y% exceeds the x% substantially then it’s a go otherwise search for another option. Oh by the way, if you didn’t know this, here is a clue, the practice of medicine is every bit art as it is science. Don’t let the pundits and experts fool you otherwise, they for the most part sit and push papers.



Life is a game of chance and not as the current cookbooks concocted in the ivory tower realms of population medicine purport. Each human is unique and each human has a unique genetic signature that determines a different response than what might have worked within the 2 standard deviations of the normal distribution curve for the majority. My genetic signature is as unique as yours, like East and West and never the twain shall meet in health nor in disease manifestation nor in the response to similar treatment. We are a unique species conceived of a 25,000 gene product built on the foundation of a four nucleic acid code. Now that is impressive in terms of uncanny diversity within a 7 billion population spread across the globe!



Technology can crunch numbers faster than the human mind! Yes, but what if a 50% benefit based on a 95% Confidence Interval is the metric utilized to treat an individual that has a completely different set of genomic signature and does not comport to the “landmark study” being used as the template for treatment? What if the numbers in the medical study were derived from a subset of population that does not equate to the region from whence this patient came? What if the “large” data set of a 1000 patient in that study is a very small subset of a larger population that does not represent the whole even within the 95% Confidence interval and even after the Bayesian rules have been brought into play, but skews it downwards to an alpha of 10 or more in reality? What if we are wrong in using population statistics to govern the health of individuals? What if?

"What if" scenarios are thought experiments without real consequences. These are designed solely to appoint a guardian of luck as you travel across your chosen path. Humans have the uncanny ability of using this argument and making appropriate decisions as they wade through the murky waters of chance.

What if you are right and they are wrong? What if…

Sunday, August 23, 2015

THE "1s" & THE "0s"



"...the touch of the hand  and the sound of the voice Live on in the soul always" -Spencer Free


It was the faintest of voices calling my name, half hesitant, half deliberate and all desirous to communicate. I remembered the face but the name had slipped a long time ago. I smiled, too embarrassed to hide my ignorance and blurted out into a higher than normal pitched hello. Loudness does not hide ignorance, neither does changing subjects. She said, “You don’t remember me do you?”

She was in her seventies, carried herself with dignity, dressed well and had her grey hair cut perfectly to her face. She introduced herself to me as I mumbled my apologies. “You know,” she said in her mild mannered voice, “It sure is nice to see you again.” It had been a long time since I had seen Betty. She took my hand in hers with a smile of gratitude.



“How are you?” I asked, trying mightily to carry the communication forward. “I am fine, thanks to you!” she said. And just like that her history tumbled across the screen of my mind.

It had been a long day and I was on my way home and a vascular surgeon friend called. His voice was shaky and his sentences incomplete conveyed the angst. “Are you around?” He asked. “Listen,” he ignored my answer because it was lost amidst his anxious words. “I have a bleeder in here and I need some help.” With those words, I made a quick exit off the freeway and was back at the hospital. The oozing operating site, the saturated dressings and the pinging machines signifying danger filled the recovery room. The nurses immune to the sounds carried about their work with efficiency and measured pace only their flushed faces depicted the anguish within. We spent the evening and most of the night summoning blood products and other pharmaceuticals to contain the bleeding. Just after midnight, the blood pressure stabilized and the intravascular clotting mechanism abated. The elements stabilized and the acidity and elemental imbalance seem to correct partially. She opened her eyes and responded to questions. It was time to find a place to rest.

The storm however continued for her for two more days, the collapsing pressures, the replaced blood products and their own complicating tincture of illness magnified by the blossoming viral infection that she had arrived in the hospital with, unbeknownst to the surgeon. Life took hold and no matter how hard the undiscovered country’s reaper tried to extract the fighting spirit from this lady, she held fast. Four days after she was well enough to enter the post-surgical floor and ten days later, she was on her way home. She and I had many chats by her bedside. She was a woman of faith. She was lady with a prodigious sense of quiet strength. She had an amazing sense of understanding while I droned on about what had happened and how her strength had saved her own life. She listened gratefully, but never interjected her thoughts or questioned what was being said. She had Grace.

And here she stood all 5 feet 3 inches of her frame, complete with her independence, courage and the gift of undeniable strength. “I am so glad to see you again.” She said, “I have been meaning to thank you for helping me through during the difficult time. You saved my life and I will forever be grateful.”

“No, no!” I protested, “It was your strength and courage that got you through.” She closed her eyes and quietly said, “I know better doctor.” With that she smiled gave me a hug. Such human Grace!

Touching a soul as she touched mine gives warmth and comfort beyond all measure. It is a human treasure of gifting love and friendship. It is that rare thing called “the human touch!”

And then without warning in that shrinking open space between humans, she confided her fears, “You know doctor, it is not the same as it used to be.” I knew where the conversation was leading, but held my tongue. “The doctors don’t have time for patients anymore. They are constantly being harassed by their staff to take phone calls, figure out the billing codes, all the while their eyes are glued to the computer screen. Even their questions and answers are echoes off the screen. They are so harried that they rarely look at you. It feels like we are all numbers in the marketplace.” Her face reddened a bit, she paused then the apologies tumbled, “I don’t mean to sound disparaging, but I do miss those days of being comforted, of a hand on the shoulder, of a kind word. I miss telling my doctors about my family now, because they cut it short anyway. I only tell them what I think they want to hear sometime.”

Confessions such as these must make us wonder what we have wrought. There lies the bleeding ghost of humanity, all vapor and cloud, immersed within the confines of a hard fought intellect. An intellect that caters to the demands of its vices and none of the humanity’s virtues, cold and icy to the touch of the probing fingers of past thought, it is huddled in a warm embrace with the devil in the numbers. A society so adrift and rudderless in the vast measureless oceans of space where gravity fears to tread that all manners of vision seem arbitrary and capricious.

One human living or dying is but a “1” or “0” respectively in the emotionless graphic curve, “0s” are meaningless to the “1s” that live for the optimization of rules for the many. The “0” has but no measure, no distinction, it is the past erased, it has ceased to exist. The “1” has but a mis-measured sense of time advocating the non-value of the “0” not wanting to know that the “zeroness” will be upon him or her who is pontificating, soon.


In the end it is about humanity, how we live with one another and not about the things that we desire momentarily. After all a human touch will always be more powerful than the brand new digital wonder on one’s wrist. ! Speak about the many disenchanted souls filling their stomachs with antidepressants as they fill their minds with “nothingness.”  The mind of man does through the body of time conjure up concepts that are tuned to certain interests. Those concepts that ultimately succeed over time are most in tune with the commonest of sense and the basics of humanity.

Thursday, August 6, 2015

QUANTIFICATION OF UNCERTAINTY

Or…the philosophical Neuro-babble of scientism!


This whole thing about digital is getting “curiouser and curiouser” by the day. When you throw in the barrage of hyperbole, the whole mix is a labyrinthine network of chaos. Facts and opinions merge into a single syllabic “wow” from the pedantic crowd that consumes latte with every breath.

So this next coming of the “sliced bread” is the digital what’s what that will take us into the 22nd Century. Hey but the 21st Century just began, so can we give this 0-100 in nanoseconds to the future a bit of a rest?

Artificial Intelligence (AI) will be the in thing, they say. Who, you might ask? Those in love with their abilities to discern the future, that is! Those that hide in dark closets and code and decode the subject of life but may not have lived it yet or never will from within the confines of their dark rooms. “Too abstract for you, this is?” as Yoda would ask.

I will take my cues from the functional Magnetic Resonance Imaging and from the perch of the Single Positron Emission Computerized Tomographic reveal. Why? Read on… it might make sense. In an abstract sort of way, it does to me.


The human mind is a rich diverse group of billions of neurons (brain cells) that converse electrically, collude, recruit and develop denatured protein memories within. The more the force of thought resident on a particular path, the more delineated the path. Imagine a path less traveled like the jungle infested forest facing Prince Phillip before he can kiss Snow White. However, if the same path is well traveled, minus the evil vain-queen-witch, it becomes a paved highway over time from travel. This paving is a function of experiential gains. The plasticity in the brain of pruning (or hacking away if you prefer as in the case of Prince Phillip to see his lost love) is a daily function of the brain. Oh yes, doesn’t matter how old or young you are, pruning makes the world go around from 0 to 100+ years. The thoughts become the actions and lo and behold our world changes. But how do or can we register those thoughts and from that create the epistemic nature of the action? And if we can, can we then objectify the precursor to any action or behavior? Ah dear readers, there is the slope that provides us with equal measure of frills, thrills and spills.


Scientists are tripping over in the philosophical realm of neurobiology and neuro-functional anatomy with a multitude of hardware to peer into the moment by moment of each firing neuron to simulate brain function. Indeed, they claim, we may be able to pocket your mind into an iPod one day, Moore’s Law be damned! But there are a few roaches I see in that prospect. For instance, let us take the most admired one called fMRI or (functional Magnetic Resonance Imaging) as a means of deciphering the brain’s activities. You must have seen the glossy images of colored tripped brains of individuals in response to some stimulation or behavior or action? I am sure you have. If you haven’t here are a few images to re-polish that paradigm…


What happens with an fMRI anyway? My simplistic viewpoint, and it is simplistic, is that when a stimulus is provoked, say an image of something to provoke a reaction from the individual’s brain, there is increase in energy output from select recruited neurons that identify the site of activity, eg. Temporal lobe or the occipital lobe where vision and memory merge and if an action is desired  then the Parietal lobe comes into play, but through it all the cognitive orders of action thru assimilation of the diverse stored data banks come mostly from the prefrontal cortex (herein called the decision maker). Are you with me thus far? Okay, so the color infuses into the brain images and voila! According to these experts, we have identified the active components of the brain. Repeat that experiment many times and average out the response, create a Bayesian apriori bank of information and then create a p-value of 0.05 or 95% Confidently Bounded Interval (CI) as the threshold and if the firing neurons cross that threshold, the computer registers the data with plethoric hues. The stronger the p-value of 0.05 or 95% Confidently Bounded Interval (CI) as the threshold and if the firing neurons cross that threshold, the computer registers the data with plethoric hues. The stronger the p-value less than 0.04, 0.03, 0.02…0.0001 the higher the coloring labels just like the weather maps go from a light green for drizzle to a magenta within red color for humongous storms based on radar reflectivity. Is that all good so far? Ok so now let us look at how that activity is determined within the fMRI.

fMRI machines use something called BOLD or Blood Oxygen Level Dependent a mechanism promoted by Seiji Ogawa. The idea being that brain activity would require nutrients in the form of sugar and that will necessitate need for oxygen to create the ATP (Adenosine Triphosphate) to liberate a phosphate group to create energy for the brain cellular activity. And that is how the fMRI was born. Two inherent conflicts arise when viewed from this simplistic viewpoint:

One, if energy is used immediately for the activity, then there should be an immediate deficit recorded in the deoxyhemoglobin (hemoglobin that binds with oxygen and the “de” represents removal of oxygen for delivery to tissues) and

Two, the BOLD activity takes place about 5 seconds after the evoked stimulation and response (Why the delay-or representation of a flat line on the BOLD scale?).

The fMRI machines construct the brain image into 3-D pixels called voxels, (Consider “Volumized-pixels”) each about 5cm in size. The complete activity of the brain at any instant can be recorded using a 3-D grid of 60 x 60 x 30 voxels. These machines register information every second of the 3 minute session creating 30 million plus data points. Indeed when we look at a picture, any picture placed in front of us many thoughts creep into our minds and through the act of parallel processing the information presented and that bound within our personal experiential data banks, the individual response is elicited.

In other words, my response to a green grassy knoll might elicit a desire to hit a golf ball, yours might want to lie down in the sun with a book to read. So the p-value thus used as threshold tends to negate the true experiential responses that do not climb above the artificial alpha of threshold so placed as the arbiter of reality. So, then what exactly does fMRI tell us? The simple answer is “some measured brain activity based on delayed oxygen utility to different parts of the brain” that we are trying mightily to cubby-hole into “cause and effect.”  Does that debunk the mounds of fMRI data flowing through the neuro-scientific literature? Not exactly, but it does bring into question the current vogue of misrepresentation and somewhat blind acceptance.



Now let me launch into the SPECT scan rage of the season that keeps giving us brain images like laundry detergent boxes of different colors. What exactly is SPECT? It is imaging of a single photon emission released by the neuron due to increased oxygen entry within the cell. This single photonic emission when pulsed together via a computer program and again based on the threshold of an arbitrarily placed p-value gives us beautiful red, green, blue and magenta images of areas differentiated by those areas depleted in oxygenation activity and those turgid with a surfeit of the same element. The difference is that the fMRI is a computerized tomographic image (slices put together by a computer algorithm) versus SPECT, which is a 3 dimensional planar radio-nucleotide imaging format. (Radio-nucleotide is essentially a material that joins with a specific cellular target (oxygen in this case) and emits a gamma emission (radiation) for the detector to detect and the computer to assimilate into a 3-D image). The difference is obvious but the human endeavored legion of stories as to “cause and effect” multiply exponentially. Some go as far as delineating sexual, aggressive, criminal, sociopathic behaviors on such images and the laity buys it “hook, line and sinker” as the next greatest thing since sliced bread.

Now let us take this whole house of cards worth of information and stoke the beast of Artificial Intelligence. All I can say is it will take a long time to match the equivalence of the human brain. I say that because of the data from Harris Georgiou a neuroscientist who in using the voxels concept in fMRI has determined: “that a typical voxel corresponds to roughly three million neurons, each with several thousand connections with its neighbors. However, the current state-of-the-art neuromorphic chips contain a million artificial neurons each with only 256 connections.” Thus the parallel function within the brain occurs at a much higher structural and functional level given that there are, as previously mentioned, our brains are operating about 50 tasks at once. Imagine the division of labor, concept enhancement or reduction, sensing, feeling, importing and exporting information, comprehension etc. the task of the brain is immense and it’s power needs are a mere 20 watts! Now that is some Bang for the Buck!

This study in Science by Hilbert and Lopez tells us of our accomplishments and what might remain under the dusty future (http://www.sciencemag.org/content/332/6025/60 ) concludes: We estimated the world’s technological capacity to store, communicate, and compute information, tracking 60 analog and digital technologies during the period from 1986 to 2007. In 2007, humankind was able to store 2.9 × 1020 optimally compressed bytes, communicate almost 2 × 1021 bytes, and carry out 6.4 × 1018 instructions per second on general-purpose computers. General-purpose computing capacity grew at an annual rate of 58%. The world’s capacity for bidirectional telecommunication grew at 28% per year, closely followed by the increase in globally stored information (23%). Humankind’s capacity for unidirectional information diffusion through broadcasting channels has experienced comparatively modest annual growth (6%). Telecommunication has been dominated by digital technologies since 1990 (99.9% in digital format in 2007), and the majority of our technological memory has been in digital format since the early 2000s (94% digital in 2007). So if one were to calculate the information storage within the brain given that we have about 100 billion neurons each and each of the neurons has a minimum of 1000 to 10,000 connection which translates to 100 trillion to 1 quadrillion data points or between 100-1000 terabytes of information yield. Due to the continuous increase in actual brain storage of information, now the estimates have reached a staggering 2.5 petabytes or 2500 terabytes. That is some order of magnitude one would say! Compile the memory bank to the connectivity (or "Connectome" as the experts call it to look super-intelligent) and you have a ginormous maze of data flow!


After all that, here is the crux of the neuro-babble matter. AI is a long ways away from mimicking the human brain. True, that IBM’s “Big Blue” can beat Kasparov in the game of chess and Watson can beat the Jeopardy champion, but can it tell the difference of an infant’s crying need between a diaper change and hunger or a cuddle, like a mother can? Didn’t think so! So those stories of computers becoming doctors are highly exaggerated in my opinion. Maybe someday we as humans will have computer chips installed to enhance our memories, cognitive skills etc. but even then the primary base of operation will remain with the human brain – add to, not in lieu of.



So in the end, thus far we can make lots of assumptions about what the brain is doing, but really we don’t have a clue. We appear smart with all the purported calculations and the probability assumptions and yet the main ingredient of “humanness” remains lacking from that large metal box filled with CPUs.

The quantification of uncertainty is a philosophical conundrum as much as it is a mathematical maze. Yet through it all in keeping the scion of truth from imploding, ambiguity has to be given its due share in the process of scientific discovery. One without the other implies abject ignorance.

Medical Research once considered the paragon of statistical research methodology is creaking under the weight of this mathematical jargon. The literature is getting burdened with “ambiguity proofed” positive results through statistical fiat that imply little progress in understanding. Thus ensuring that the “native hue of resolution is sicklied o’er with the pale cast of thought…”

On a more human level… “Have a great day!” (Let Watson figure that out!)