Friday, November 17, 2017

MY FIRST LOVE



Spoken language is simple and direct. There is action in every sentence spoken. Nothing hidden, except that which is in the mind of the speaker. And what is spoken is what the speaker intends to say. The written word on the other hand, has no such constraint. I can make you think thoughts that you might never have dreamt of or make you sit beneath an oak tree with cool breeze of the evening and a setting sun slowly dying in its warmth. Ah, and I can take you to a place where you have never been, wide open fields of greens, undulating hills and valleys with a few large weeping willows overhanging their leaves in despair for company. But I shan’t do that today.  I will let those that do such things take you, if you are willing, to nirvanas where eternal blossoms grace the fields.  Today, I will tell you about my first love. What a ride it has beed.  It lasted for a career. It was replaced by a beautiful girl who became my wife and was subrogated to the next lower level. But it still remained a love for me for a while.

"Today, I will tell you about my first love."

This love thing, there is mystery in it. One can spend a lifetime delving into it and know very little. For instance, when I was younger, I had this notion that everything there was to know, had already been discovered and so there was nothing for me to venture into. But as I grew up poking holes in thoughts and other assumed realities, which clustered around and made some orbit the stellar magic cast by seasoned older people with thick rimmed glasses who had grown frown lines and large noses, I soon realized that they were faced with the same dilemma that I was; what is real?

Now mind you the context within which these words find the digital ink on the screen remains an enigma. True knowledge is never true for long. Something always comes along to overshadow it. Take the Ptolemy assumption and one would live and breathe it daily till Galileo comes along and with a simple telescope turned the whole egocentricity on its head and he almost literally lost his head over it.

"True knowledge is never true for long."

Ideas that ignite thoughts always bring in a charm of snake-oil sniffers. There is money to be made. And a snake-oil sniffer will not be denied his Dollar or Shilling or Yuan. His, is progress in the Kaching world not in the toil of searching for truth. Progress however, is a matter of experimentation, isn’t it? A thought is buried deep within someone’s mind that makes him or her sitting on the edge of the bed at night, wondering through sleeplessness, "how to" until the break of dawn. These ideas are then transformed into energy to experiment, to verify, to validate and thence to produce for others to benefit. Innovation has never been about money. If it is, it will never make any. Innovation is about passion and love. For snake-oil men it is all about money, period.

"For snake-oil men it is all about money, period."

See this circumstantiality always takes me onto paths that, well, are less travelled. Rocky, sometimes, painful seldom, yet in the end for the most part, rewarding. So, let me linger on those pesky distillers of snake-oil a moment longer. These many, undaunted soldiers of limited value create hurdles upon hurdles for innovators, lying to them, cheating from them and usurping their ideas only never to be able to fully realize the thinker’s thought. And in that, lies the solace for the innovator. But the unceasing tiresome volleys of “do this and that” keep coming. For each stride brings wealth to the snake-oil group. They measure for measure’s sake and then demand everyone should “Follow that measure,” because to all others it is gospel. They force-feed misinformation and disinformation even to the intellectuals who at times succumb to the tantalizingly perceived value these wretched beings project and thus in doing, lose their soul in the process. The deeper the intellectuals sink into the desire of “self,” the further they are beholden to those that drive these desires. The world sinks slowly into chaos as common sense becomes rare and people rush on the streets with their eyes wide open and their minds paralyzed shut, committing the only act they know how to do; go through the day.

"The deeper the intellectuals sink into the desire of “self,” the deeper they are beholden to those that drive their desire."

Okay, yes, I must tell you, for this writing is getting long in the tooth. My first love was medicine. It spoke to me of things that were impossible. The human body, a massive collection of individual cells, each finely tuned to perform a finite set of functions. Those tiny, itty-bitty vessels are the ghost within the human machine. Vessels with many stowaways that function as a collective in perfect harmony. And the magic of this grist mill is replenishment; as some cells tire, they are replaced by new ones. All happens in the quiet of the circumstance, painlessly and efficiently. The beat goes on. The dance of cells continues until it cannot anymore.

There is magic, for instance, in embryology; of how the parts become, from so simple a fertilized egg. There is splendor in the human parts as they grow and enlarge and a create a field, realized as anatomy that dissects each part to understand its visible limitations and its anchors. All parts beautifully form fed into a gorgeous frame. And then there is physiology; a fecund land of function that binds the anatomical parts. The mechanics defined, each part versatile and committing to the function of the whole. Inspired by this choreography of the anatomical parts, a living breathing being is installed on this Gaia. The perfect image of the homo-sapien. These are the visible beings. What goes on inside to keep the chemistry of action is a wonder to behold. There are the invisible things that only peering through microscopes reveal. However more and more magnification right down to the electron level can make one see the workings of the city within the tiny little cell; its power structure enclosed in the mitochondria and the humors that flow as electronic signals from the surface of the cell to its nucleus where marching orders for building materials, proteins and proliferation are undertaken creating a symphony of cell growth and division. All this happening deep within through the tightly knit chemistry of electrical impulses. Such essence of magic is never perceived to the idle mind, only one that lurks at the periphery of inquisitiveness. This molecular microbiology of life’s essence is the magic crafted by unmeasured and innovative intellect.

But let me not forget, when pathos strikes the discordant cell, there lies the human dignity of help, nurture, nourish and rebuilding. The understanding to limit such pathos is the discourse of a few learned and humble minds. These minds that spend their days, learning, for there is a lot to learn, and then putting that knowledge to test, to heal. To heal, there I said again, "TO HEAL!" The days turn into nights, and into days and the world turns over and over as a lifetime passes in the service of humanity.

"The understanding of such pathos is the discourse of a few learned and humble minds."

That my dear reader is medicine; my first love. But now sadly it is slowly dying. The scaffolding is all that remains. The snake-oil men have destroyed all but the skeleton. They have sucked out the humor, the sinews and the skin of this wondrous joy and left the gangly skeletal remains flailing in the wind, subject to their whims. The joy of learning and experimenting has been replaced by useless information that does not make for intelligent understanding. Knowledge testing shams are rampant. No where is the desire to inquire about experience. Experience they say is nothing. Really? Discordant information is like plastering a fa├žade with hidden struts to hold it up as in a movie set. No substance, just form. These snake-oil people have loud megaphones and they constantly blast away their cymbals and beat their drums till all is cacophony.They compare humans to machines. Slowly eroding the sense of value by conjuring up value where none exists. And then they come for the kill; "attest to the expressed need for testing of their made up standards, conjured up in catacombs of their ivory towers" or die a professional death. Ah but were it so simple but that the mind has bad dreams. Slowly the desire to understand dies and such is the penalty of misunderstood regulatory fiat designed for metrics, impose willy nilly to the detriment of the vulnerable, the sick and the infirmed. 


That love is lost by the deeds of all these hedonistic snake-oil souls and yet the desire to win back its worth still remains strong amongst a few. Please don't let them destroy it. I beseech those that have the will and the strength to fight for the sanity of real human intellect in science in general and medicine in particular, to reform and remake the love that I once loved so dearly.

"I beseech those that have the will and the strength to fight for the sanity of real human intellect."

Monday, October 23, 2017

NIRVANA HEALTH?

Do you have a blender? Of course you do. Almost everyone does. Now take a few ingredients:

1.       Patient centered.
2.       Shared Responsibility
3.       Patient determined diagnostic tests
4.       Google
5.       Expert opinions
6.       Population Medicine
7.       Genetics
8.       Epigenetics
9.       Medical Apps
10.   Digital Electronic Medical (Health) Records

Put them in the blender and press the switch. And what do you get?

CHAOS!

Remember Mark Cuban’s self-monitoring regimen of serialdiagnostics?  Now add to that the new Arizona law that allows patient to seek diagnostic tests on demand, sponsored and perhaps lobbied, I believe by at least one private company Theranos, now defunct because of fraud, hubris and conceit. and then for good measure throw in the $1000 genome sequencer (available soon from MinION) and what will you have? I am all for low costs and freedom to violate the vein where truth flows, but shouldn't we also have the wherewithal to understand the information that elixir of life holds and its true meaning?

Otherwise we have, health-ism on steroids! Think Road Rage was a 2014 issue, think again. Wearables, forget them our sodium and potassium levels will be on TV just like the lady that walks smiling at everyone and finally levels with her co-conspirators in the ad that her cholesterol dropped by a few % points because of the pill. And what does that mean exactly for her health anyway? Now we find out…little. But that ad sold the pill to the tune of many billions of dollars and may reach $1 Trillion by 2020  .

Information is great if one can interpret it. Information is good if it can be assimilated and the individual can draw an understanding from it. (And there is no political correctness here about how smart the average person is) Even an above intelligent person, (reference to the average intelligent person cannot be found anywhere) with a science background but without the medical reasoning will be lost in the cold waters of the Atlantic Ocean just like Mr. DeCaprio in the Titanic or the warm waters in a pool in Hollywood, your call.


You see, and this is not a paternalistic statement, when fear envelops a person, reason is thrown to the wind. Everything becomes dark as fear and caution arrive at the doorstep. So yes Mark Cuban is a very smart business man and he has tens of interpreters of maladies available to him that assign risks as related to his medical tests. Do we all have that capacity? Yes you say, I have Google! Sure you do as does the rest of the world. But is the information in Google easily assimilated? For instance can you easily figure out what the following paragraph means? And then we circle back to is Mark Cuban correct in his interpretation?

“MIR-21 expression was demonstrated in 63 (79%) pancreatic cancers ( 1+ in 49, 2+ in 14 ) compared to one of 12 (8%, p < 0.0001) benign pancreas and 12/45 (27%, p < 0.0001) chronic pancreatitis. None of the benign tissues demonstrated strong miR-21 expression. Although miR-21 expression did not correlate with tumor size, differentiation, nodal status, or T stage, strong miR-21 expression was predictive of poorer outcome compared to absent or faint/focal miR-21 expression in patients with node negative disease (median 27.7 months vs. 15.2, p=0.037). Nodal status was also predictive of survival (p=0.029)”

Or for that matter, here in this article is the inverse of the loop-hole of expression, and benefits are told through the worm-hole of inhibition…

“This strategy was explored in the current study, where p53 downstream target miR-34 was restored in p53-mutant pancreatic cancer MiaPaCa2 cells with a high level of Bcl-2 and low levels of miR-34s, resulting in downregulation of Bcl-2 and Notch1-2, together with the inhibited clonogenic cell growth and invasion; increased apoptosis and G1 and G2/M arrest in cell cycle; and sensitization to chemotherapy and radiation. miR-34 restoration could thus re-build, at least in part, the p53 tumor suppressing signalling network in pancreatic cancer cells lacking functional p53. This multi-mode action of miR-34 provides a therapeutic advantage over the siRNA-based therapies in that miR-34 has multiple targets, can work on multiple cell signalling pathways at the same time, leading to synergistic effects which may translate into improved clinical efficacy for pancreatic cancer patients with p53 deficiency and advanced disease.”

Interpretation is filtered through the lens of one’s experience. Reasoning is based on critical evaluation that is derived from years of knowledge gathering and experience, sifting through what was evidence to what is evidence now and only through squeezing the fruits of your labor through the ethereal filter of the cognitive cloth, the nectar of reason appears. I doubt that Google searches can deliver that. Sergey might disagree.

So yes, the world is agog with patient centricity but rational decisions can be irrational in times of stress. Take for example the rate of the C-Difficile infection rate differencesbetween the Northeast

where everyone seems to know everything, the C-Diff rate is 8/1000 hospital patients. In the South the rate is 5/1000 hospitalized patients. Here the prodigious use of antibiotics is the culprit- a problem both at the consumer demand level and the physician care-delivery level. Judicious use of therapy is equally as important as the reasoned use of diagnostics.

Speaking of Genetics, now there is where real information will flow; and lots of it. But will anyone be able to accurately decipher it. Probably not well. Even geneticists have problems merging the science of DNA (easy) with miRNA (not so easy) and that to translatable proteonomics (even more difficult). Our thinking that one gene defect equates to one disease is unfortunately archaic. Now we have come to realize that even mutations within the BRCA 1 gene segment have varying consequences on health.


From there we have come to the “BRCAness of breast cancer disease process.” Things do go bump during a lifetime with the jumping genes or transposons as Barbara McClintock called them; mating, fusing, halving at will, to always create the “fittest” model of human being.“The progeny of two (such) sister cells are not alike with respect to the types of gene alteration that will occur. Differential mitoses also produce the alterations that allow particular genes to be reactive. Other genes, although present, may remain inactive. This inactivity or suppression is considered to occur because the genes are ‘covered' by other non-genic chromatin materials. Gene activity may be possible only when a physical change in this covering material allows the reactive components of the gene to be ‘exposed' and thus capable of functioning." -- Barbara McClintock”
BRCA 1 & 2 Gene Segments


Such inner experiments by the DNA are not uncommon. So it is better to realize the shades of meanings before we start touting the virtues of genomic diagnostics. We could end up ruining lives and for their “forever,” live in a state of fear of a hazard that never materializes, like a benign nodule in the lung on X-Ray. Yet the fear throws them into the caves of depression and enforces consumption of fifteen different pharmaceutical agents via televised broadcasts of longevity and that, my dear friends in some cases becomes the norm.

Just before we go drinking that “milkshake of nirvana health” from the blender, let us consider the consequences of such a drink. Shall we?

Above all do no HARM!

Thursday, October 19, 2017

A G36 CROSS-COUNTRY TO REMEMBER


It is quite compelling when with a guilty sense of the “rush,” you fly closer to the ground and watch it slipping by at a quickened pace. When your heartbeat matches the tick of the clock in the rhythmic resonance and you proclaim, “Ah Life!”

Now mind you, it has happened before but nothing like this. I’ve flown different aircraft for many years and my favorite one had been the laminar flow version with a turbocharge attached. I started flying the low to mid-teen dry-hypoxia inducing air with a nasal cannula stuck in my nostrils. It was good, looking at the GPS winding down the time and winding up the speed. It was good. But something was missing…

Then came the day when I and a friend picked up a 2007 G36 from Nevada. I had to bring this gorgeous beast all the way to the East Coast. But, there was a caveat; A new 0-timed engine that had to be treated with gloved hands and the travails of an October month. Gloved hand care, we gave it but the October sun was complicit in our delights only for half the way.

So, we, my Bonanza flying friend with close to 5000 hours in a three engine TBO-ed V-tail, decided that 7500 feet would be the best-case scenario to keep the 75% power schedule at 20 degrees Rich of Peak across the hills for ring seating and cylinder smoothened cross-hatching mechanism. And that, was what we did! Ever run a mile in 20 seconds? Well that is how it feels as your heart races and the body is comfortably seated held up in the air by a set of powerful wings!


The late-afternoon departure from Carson City, NV was ordinary with my first shot behind the yoke and a G-1000. We navigated close to Victor 6 Airway as possible, so we could have communication with the Air Traffic Control, playing the valleys as we went along. “We’ll turn left around that outcrop and then right around that one.” The G-1000 showed the outcroppings as elevated terrain in yellows and reds. The Red color were peaks above our flight altitude. Soon, the dry bed turned into drier bed of arid land with outcropping of mountains at 9000 and 10,000 feet poking their tops around us. An endless desert of possibilities. The G-1000 at times not happy with the GPWS proximity alerts piped in with “Terrain, Pull Up, Pull Up” warnings. Happily, it was VFR with scattered layers above and the big blue above and a nifty steady 10-knot tailwind of a 23 knot crosswind along the way. In reasonable smooth air, we gave the peaks a wide berth, swinging through the flatter valleys. Ever ride a motorbike on a winding road? It feels like that at a much slower but more thrilling pace. After all we were not in a kerosine burner tied to our backs like the Jetman. 


The ground rolled by faster than the TAS at 174 knots by a few knots as we got closer to Salt Lake City and then the wonders of nature just usurped the entire thoughtfulness, leaving me speechless. The purple Salt Lake, the mountain range and the causeway splitting the purple salt bed from the blue water, all merged to create a dreamscape one sees conjured up by movie directors and CGI experts.


The Salt Lake Approach (KSLC) was unlike the high-powered-rat-a-tat East Coast ATC.


Quiet, discerning and very helpful. Near Ogden (KOGD) we climbed to 9,500 feet at the gentle urging of the controller and soon the blotches of red turned into pinpoint red peaks to negotiate again and terrain clearance was safe and legal.


Finally, we arrived late in the evening at a plateau hosting a 10,000-foot runway aptly named Rock Springs (KRKS). 


The next morning at sun up and after a thorough preflight evaluation of the IO-550B and its confines, which remained speck-less, we departed into the smooth air of the rising sun. Gorgeous is all I can say. The G36 revved up to its broadcast 174 knots at 7,500 feet again and off we went looking for Don Quixote leaning against the Wind Farm silos that floated by. The terrain after Cheyenne, Wyoming started to fall a bit and we entered into some crosswind with a small headwind component. The cloud deck below went from scattered to a solid undercast and the only way into Des Moines was via Instrument Rules.


A bit about the G-1000 and its integrated Autopilot. It is like an airliner. Nary a twitch, the magenta line and the approach all beautifully choreographed in a seamless dance. The barometric pressure changes, you input the data and the “George” or “Jeeves” does your knob-bidding. Use the FLC and a touch of reduced power and it claims the new lower altitude preselected at the cruise speed. Ah the wonders of gizmos and the ease of flying never cease. Essentially, after a fuel stop at Sydney, Nebraska (KSYD) we filed Instruments to KDSM (Des Moines, Iowa), we had to go down to the DH (Decision Height) at 200 feet above ground to go below the clouds, on the ILS approach into KDSM. After breaking out, I took over the controls from "George" and made a soft 15 knot right crosswind landing on Runway 5. “Man,” I thought, “this G36 makes a pilot look good!”


Departing KDSM was a blur of clouds and in-between layers. The autopilot negotiated the magenta line with expertise, any master aviator would be envious. A little rain here and there, but mostly clouds and minor turbulence, the rest was all grey. There is isn’t much poetry in those next 5 and ½ hours that ensued, except ATC making our straight magenta line into a warped crooked one to get to our destination around some busy airspaces. Arrival was a non-event in 800-foot ceiling, light rain and 7-mile visibility and we were back to sea level residency.

The story of this travel was the G36. Comfortable, OMG as one would say, Awesome! Humming all the way for 13+ hours with less than half a quart of oil. Now that is what I call a machine’s machine. if you ever happen to encounter this kind of possibility, take it! You will thank me for it.



Loved it. What a wonderful adventure, attributable to the folks who made this beautiful flying machine; Beechcraft Bonanza G36.

Hats off to them!!