Wednesday, December 9, 2020

RISKS and MITIGATION STRATEGIES

   

I am often asked about risks. As an Oncologist, one has to understand the potential risks of how many ways cancer can manifest and the associated management with all its various interactions with the human body. The riddle is a complex one. It oozes with a myriad of signs and symptoms that need a solution. So, Risk management becomes a big part of cancer care. And the oft-repeated Hippocratic injunction which was actually mentioned and should be attributed to an English physician Thomas Sydenham In, 1860 reminds us, and remains the guardrail of protection for the patient, “Primum Non-Nocere!” (Above All Do No Harm).

Overall mortality increases with time


RISK

Risk, therefore, is nothing more than a manifestation of a known and unknown hazard. In our daily lives, we encounter hazards that we consciously and unconsciously avoid. Mostly these are known, and always from the lens of our view, filtered possibilities. If an AI chip was embedded in the human cortex or one was wearing a virtual display, the probabilities of such risks based on computed hazards would constantly be displayed in the field of view. But then we would be cyborgs, all of us. For instance, a 0-1% chance of tripping on a low table while negotiating a room in daylight increases to a probability to 90% in the dark. The only mitigation strategy is the known layout of the room and the frequency of negotiating that room, which reduces the risk. So, a known hazard can be mitigated better through knowledge and understanding. Our brains are such marvelous organs that subconsciously plot out the probabilities and the net result from the behind the eyeball calculations comes up with “nah not going there, too risky.”



SMOKING

Allow me to dwell on a few risky things that humans are wont to. Smoking for instance is a well-known risk to cause disease. The manifestation of that disease can be in the form of emphysema and heart disease all the way to the development of Cancer. The risks increase with the number of cigarettes and the number of years smoked. For instance, it is a known axiom that a 20-pack year history of smoking (1-pack smoked per day for 20 years or 2 -packs for 10 years) has a much higher risk of developing lung cancer than a non-smoker. On the obverse side, 80-90% of lung cancer deaths have smoking as the main causal factor. Male smokers are 23 times more likely to develop lung cancer, while women are 13-times more likely, compared to never-smokers. Genes are at play in that variance.


Why the risk in smoking, one might ask? The answer is in the 7000 chemicals contained in the cigarette smoke. Almost 69 Polycyclic aromatic hydrocarbons or PAHs (aromatic amines, benzene and the like) and their reactive intermediates are implicated in the cancer development process. https://www.ncbi.nlm.nih.gov/books/NBK294309/ From a basic science point of view, these aromatic amines and their carbo-carbons have an affinity for the nucleophilic sites present on the DNA. These DNA adducts once gaining the piggy-backed ride are critical in causing mutation and damage to the protective mismatch repair enzymes (these enzymes rewrite the wrong of the DNA sequence during replication). A study by Ding et. al found 1,013 nonsynonymous somatic mutations in 163 of the 188 tumors were identified, including 915 point mutations, 12 dinucleotide mutations, 29 insertions, and 57 deletions due to smoking. https://pubmed.ncbi.nlm.nih.gov/19064552/ A more recent study found after analyzing the entire Exome of 188 smoking related lung cancer cases that there was a 12.0 events per megabase! (So much harm from a puff of smoke). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3557932/

So, the data from this smoking hazard is brutally strong, yet people still smoke! Their rationale is based on a self-served motive of “let me enjoy a smoke.” Unfortunately, the “later” happens as the future becomes the present in most enjoying that smoke. Risk mitigation should always be balanced when thrill-seeking or immediate desire fulfillment, in the present with some concern for the future.

Why do people ignore warnings is because of “Risk Appetite” and “Risk Tolerance?” In the business world, the definitions are quite simple, and they bleed well into our daily realities too:



RISK APPETITE AND TOLERANCE in Business & Life

 

Risk appetite is the level of risk that an organization is willing to accept while pursuing its objectives, and before any action is determined to be necessary in order to reduce the risk.

 

Risk tolerance on the other hand, reflects the acceptable variation in outcomes related to specific performance measures linked to objectives the person seeks to achieve.

 

People make choices with an asymmetry of information and thus lack the ability to process and manage decisions properly.  Risk appetite is where one is willing to reach the maximum limit of their personal level of tolerance and Risk tolerance is where one is willing to accept a certain level of harm from potential hazards in lieu of maximizing the potential of benefit. Between appetite and tolerance, there are a set of guardrails in the decision-making process. These guardrails guide an individual between the lanes of harm and the potential of reward. Between failure and success, between error and trial and between riding a bicycle and watching with desire and between what might have been to what is, lies the path of life. Similarly, when it comes to business innovations the risks are always being closely scrutinized to minimize harm while maximizing the potential future benefits. In simplistic terms, a mountain is a known hazard, and flying into it is mission failure and thus a risk. The problem of an unknown or unquantified hazard gives us all shivers and makes those ills appear unsurmountable until someone brave enough ventures further than the mind’s eye into the thicket and proceeds to create new guardrails for success. Thus, is born the term Risk Arbitrage in investment deals where an investor may profit from the difference in the trading price of the target stock, and the acquirer’s valuation of the stock. Although this seems as a win-win situation, the caveat is when the deals falls short or the valuation is negotiated down below the valuation price. A savvy investor might buy a stock for its price appreciation but hedge his bets with a put option to protect on the downside should the stock price go south. Essentially trading stocks is a chess game much like in life but more as a high roller derby, prying to maximize profits and minimize losses.

 

RISK IN AVIATION

 


In the aviation world where many of us travelers partake in, we all realize the risky nature of flying in a large aluminum tube filled with hundreds of fellow human beings, but we are willing to use the option because it is the fastest way from here to there, by suspending the disbelief of potential harm. Aviation is a risky enterprise to some extent. Managing an aircraft especially with dependence on automation has some risks. Several harrowing airline disasters litter the historical landscape: from the Tenerife disaster between KLM and PanAm Airways to Japan Airline 123 to Air India flight 182 and more recently the Malasian Airlines flight 17,  wherein each disaster hundreds perished due to human error. Although these disaster claim headlines, the risks of such occurrences are miniscule in the scheme of things.  The United States Aviation Regulations Part 121 (governs Commercial Airlines) shows that from 1983 -2000 the fatality rate was 0.03 per 100,000 flight hours. And this risk has declined to 0.006 accidents per 100,000 flight hours. That is equivalent to ONE fatal accident for every 16,300,000 flight hours based on the National Transportation Safety Board (NTSB). In comparison, the General Aviation Aircraft fatality rate is much higher at 0.84/100,000 flight hours. Consider that risk against driving a car. The fatality risk is 23 per 100,000 hours of driving. So, it is more dangerous to drive to the airport than to take the flight to one’s destination. Risks are everywhere where the eye can see. We walk through a field of risks each day and through each night. We negotiate the path of observing and quantifying the myriads of risks consciously or unconsciously in our passage through time. Humans have the gift of such wondrous abilities. Animals too have such potential: A deer knows the risk from an approaching lion in the wild as a duck does from a steely-eyed alligator in the lake. The flight from risk and towards safety is every life’s reach.



RISK IN COVID times & the March to Madness

 

And that brings me to the current debacle that has unfolded across the world. SARS COV2 or COVID19 as it is called has the attention of 7.3 billion people on it. Answers come in a slow drip as the steeled doors are locked and the key has gone missing. Many theories abound about this 80-140 nanometer (0.00003937 inches) virus. We find an inordinate amount of human intervention as mitigation strategies. Shutdown and lockdowns and Restricted Outdoor activity and restaurant closures and bar closures including other forms of commerce that feed the household each day. There is a plethora of graphs of the increasing cases on a daily basis. Not to mention that the case largesse (called “Casedemic” by some) is based on flawed scientific methodology. The vaunted PCR test, it turns out gives false-positive results at an alarming rate when the thermal Cycle threshold is raised above 27. And yet most tests are being performed at 35 as they finger the non-infectious RNA remanents and falsely posit them as True COVID cases. The real numbers remain cloaked in mystery as the mountain of erroneous data gets compiled and disseminated for consumption. The mortality numbers below give a vivid picture of reality.

 



The other side of this midnight, however, shows a different viewpoint. Infection fatality rates have ranged from 0.00% to 1.63% and corrected values ranged from 0.00% to 1.31%.

When reviewed across 32 different locations, the median infection fatality rate (IFR) was 0.27% (corrected 0.24%). Most studies were done in pandemic epicenters with high death tolls. Median corrected IFR was 0.10% in locations with COVID-19 population mortality rate less than the global average (<73 deaths per million as of July 12, 2020), 0.27% in locations with 73-500 COVID-19 deaths per million, and 0.90% in locations exceeding 500 COVID-19 deaths per million. Among people <70 years old, infection fatality rates ranged from 0.00% to 0.57% ( or up to 99.43% risk) with median of 0.05% (or 99.95% risk) across the different locations (corrected median of 0.04%). When one looks at the excess mortality on an average year and compares with the past years, it was an increased blip. That blip, however, has to be taken with a grain of salt, since all deaths occurring, whether, Heart failure, COPD, Diabetes, Cancer, Accidents on the road or at home and those related to Opioid abuse and other vicissitudes of life during this period of such heightened alertness are being recorded as COVID deaths.



The true Death Rate is somewhat circumspect, at best as well. Knowing the foregoing it brings us to the question of real risk. It is unfortunate that the term “science” is being used to propel one’s career through fear-mongering. Given the tumult of politics for advantage, a chance of tenure as a professor, or gaining a governmental position of power, or increasing one’s own heightened narcissistic recognition by the peers, the projected asymmetry of information is loathed, to give us real risks that can be comprehended and easily used by the populace for risk mitigation. In spite of the fraction of fractions of the risks from death from this virus, the drama continues to unfold on television and social media as an Armageddon and a “Dark Winter.” There are calls for “The Great Reset” and for a “New Normal” on a daily basis. And each of these terms has widely nefarious interests of the few against the many. “Wear a mask,” “Stay home,” “Don’t question the science’” are the clarion calls of the day. One wonders as to the motive and reasoning and reminded of Feynman’s words that “science is (and has always been) a culture of doubt.” But then questioning any of the unfolding quasi-science is considered tantamount to heresy. The harm from shutdowns and lockdowns is in thousands of lives that the “experts” and Governors of some states refuse to acknowledge. There is this new-found sickly power and control over others that would have Tantalus lusting.

 


COVID Protections?

Let us look at some issues as dictated under the guise of “evidence’ by “experts” and their collaborators: The Media. Stay Indoors and Wear masks. On the former , there are ample data sets that prove that most transmissions occur in an enclosed environment. This is attributable to limited air movement and poor ventilation. The aerosolized viral particles, after the fluid medium of transmission, dries out, are free to find another human refuge through contact (and by contact, I mean hand to mouth or nostrils or eyes) or direct inhalation in the vicinity. How far do the aerosolized particles go is dependent on the breath, the sneeze, or a cough, where the expulsive force can be as much as 60 miles per hour at the exit point. So, to force indoor activity is tantamount to a forced infection among the household. This was confirmed when Governors of five States sent convalescing COVID patients into Nursing Homes and caused the harm of thousands of deaths among the vulnerable population (all of these politicians still evade the harm they caused and point fingers at others. On the subject of masks, there are more questions. The current scientific data suggests, COVID19 has a 80-140 nanometer size and the N95 mask protects against particulate matter in the 300-nanometer range 95% of the time. So, for all practical reasons, the 140nm particle is free to glide through the N95 mask with impunity. The Surgical mask however restricts particles of 100nm size. But reuse of such masks is not recommended since degradation from use (saliva, breath, sneeze, cough) is common and these masks are not meant to be used for hours at an end for protection. Doing so causes the exhaled breath biological particulate matter to stagnate on the inside and touching the masks as most people do will do the same on the outside of the mask. Meanwhile,  the colorful cloth masks whether from Rodeo Drive or Walmart are absolutely useless to prevent transmission of the virus, period.

WHAT TO DO?

So, what to do? It goes back to the time tested hygienic preventative measures. If you are sick isolate yourself in the interest of others or till you have recovered. Wash hands before eating. Do not put fingers in your mouth, nostrils or touch your eyes and go outdoors where the breezes and sun act as natural disinfectants. Improve your overall health by exercising and eating a better diet, not smoking and reduced drinking also help. Besides better therapeutics against the COVID are available to prevent harm to us humans against this virus. Stay tuned for success.

Perhaps we as scientists must seek the truth rather than strive for the next richer rung of the ladder. Perhaps we should stick to facts and the truth rather than made up pseudoscientific talking points. And perhaps, this ask is a bridge too far. The journalists continue the farce of asking the meaningless non-science questions to pursue a narrative that fits in the 10-second television segment and their intent, and continues to evade ones that are on everyone else’s lips. Stifled by the “Woke” and the politically correct crowd, the pre-determined pursuit of falsehoods continues, and the gyre widens and widens, while the center teeters on losing control. What is left, is critical thinking and reason, logic and understanding, to bring us back from the abyss of this wild and risky ride. What we should fight for is real science, our cherished liberties, and freedoms and the way of life now being actively usurped by the virtue signaling, snake oil-carpetbaggers littering the landscape.

It is time to get REAL…!

Wednesday, December 2, 2020

2020 - The Year the Music Died

 



The promise of a new decade began in earnest. On December 31st, 2019, the bells were ringing, the crystal ball slowly dropped ready to crown the year in perfect unison to the cheer of the crowd as the countdown pulled it down to its vaunted perch. The glow and excitement, the singing, hollering, crowd infused, and drunk with the hope of a brighter future to come were filled with hope and dreams. What innovations may evolve, what dreams may come true, what happiness and loves would flourish, what friendships would evolve, all thoughts were buried in that one moment of joyous celebration.

 

But that was many moons ago.

 

An 80-160 nanometer RNA monster cloaked in a protein shell was dreamt up in the confines of four walls, glass partitions, and a bright white sterile confines of the Wuhan laboratory in China. Perhaps the escape from this “Alcatraz” was an unfortunate hiss of the loss of a positive pressure environment of a Biosafety lab, or perhaps it was inadvertent contamination, and a minor infraction led to the runaway uncontained debacle.

 

The physical drama would soon be broadcast across the globe.

 

Soon began the dance and drama of containment. It first sparked in Wuhan, Hubei Province of China. All of China was immediately cut off from the Province. Containment processes ensued and video information of forced encampment of citizenry spread far and wide. Street spraying, a 10-day make-shift-hospital, and images of overrun hospital emergency rooms started happening in that far away land from the western shores. Amused by the goings-on in these distant shores, a cadre of pontiffs began to swell here and elsewhere. These self-appointed experts in the western lands began to sing. The song was initially quite conciliatory and harmonizing evoking feelings of nothing can hurt us. Some false prophets claimed to keep the borders open to all travelers from China. No, they cried, this is paranoia, nothing can harm us. All were in a state of a temporary kumbaya.

 

Then the change came. The psyche preprogrammed from the earlier visuals began to play…

 

A spark in the state of Washington ignited the fuel of concern. The monster was here! Soon the spread would come. And it came. Another spark ignited in the densely populated skyscraping land on the eastern shores of the United States and all hell broke loose.

 

In that sinister spread, something else emerged.

 

The call for a strict discipline to conform to the call of “Science.” Sprouting in the midst were a few who took that call seriously and started invoking the term at every street corner of the social media where a gathering of eyeballs was glued to their feed. Charts and Graphs were everywhere. The exponential rise of the infections was teased statistically and the exponent kept on getting higher to make the graphs worse and worse. Amid these trying times images of inundated tired and overworked doctors, nurses, and healthcare workers gowned and masked emerged and broadcast across the world. Italians, Spaniards, French, Danish, and Americans.

 

The deluge of the suddenly ill grew.

 

A make-shift hospital in New York (The Jacob Javits Center) was built, while a large Navy ship coasted and anchored near Manhattan to take on any excess patients sickened from the virus. But no ambulances of the ill came around to fill those excess beds. Yet the calls from the political leaders grew, claiming lack of this and that. Meanwhile some politicians exacerbated the deaths in their states by sending virus-infected idviduals into the Nursing Homes where the vulnerable population of the aged was resident. Men and women dressed in white coats appeared on television to new-found fame advocating for more of everything in packages and less of everything related to liberty and freedom. Whereas protecting the elderly and vulnerable was need, mandates for all to acquiesce to the mandates was the want.

 

The organ of innovation resolved to create.


The Public-Private enterprise emerged, and all the levers moved, the gears switched, and the mechanics of the newly crafted Rube-Goldberg machine produced. Innovation occurred at the whoosh of the breeze. Mountains of innovations were suddenly at hand to be deployed and used.

 

The carpetbaggers were never too far behind.


The newly appointed tele-evangelical scientists clamored for more. More masks, more gowns, more of everything. And more was created in a short flash of time. In that whole drama was a desire to create more testing. Machines were built and logistics created to distribute the emergent technology across the country and thence to the rest of the world. 

 

Testing was the new norm. People lined up in their cars to get a swab inserted in their nostrils to discover if the virus had entered their body’s realm. Many were proclaimed positive through the magic of the Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) tests. The positive tests grew and call for a shutdown and lockdowns from the ignorant leaders who relied on their pseudo-scientific health advisors (some with degrees in sociology, others in social service, and yet others in computer science). In all this drama a white knight emerged. He took on the mantle as a spokesperson with his impeccable credentials in bureaucracy. He seemed to waffle a bit, initially taking his cue from a non-physician head of the World Health Organization. He first implied that there was no risk to the United States from the virus, and then changed it to a serious threat. He also maintained the mask-wearing was useless as a protective mechanism against the virus in line with the WHO and then suggested that masks should be worn at all times. He then stated that vaccines would put an end to the “pandemic” and then stated that even after the vaccination distancing and masks should continue to be worn. The cases grew as the PCR machines chugged along falsely giving positive results as they churned out 35-40 thermal-cycles determining non-infectious fragments of the viral RNA.


The decline of the laughter and joy became evident.


Meanwhile, where once children played in the yards, swirled around in merry-go-rounds, swung from the swings, swished down the playground slides were silent at homes, tied to the outside world through the medium of social media. The creators of the social media were hard at work broadcasting pseudo-science and virtue signaling, warping the young and flourishing minds with their version of the “new norm.”

 

Children more susceptible to such subtle and nuanced broadcasts without the link of companionship to other children started a new and sustained epidemic within society. Depression. Teen and adult suicides increased. The fragmentation of the family unit began to show deeper cracks as the finances took a hit.

 

The toll on commerce grew exponentially.


Companies were shut down since workers needed to be “protected” and adults lost their jobs since companies could no longer bring in the revenues from unsold products that filled their inventories.  Adults could not bring in the paycheck to pay for their family’s needs. A disruption of the cohesive family networks suddenly started fragmenting the fabric of society had a loose thread that slowly began to unravel. The politicians meanwhile jockeyed for position to control and used the “pandemic” to their advantage. The floodgates of the sham however would soon open. The deluge would soon follow. And all of the worlds would dearly pay.


A few groups started rioting and destroying commercial and private properties to send political messages across the land. These were considered "peaceful protests" as homes and property burnt to the ground. Something sinister was at play.

 

Masks became the in thing.


The cloth and surgical masks, it turned out, do not, and never did protect against viral infections. The former has a 90+% chance of failure and the latter about 45+% of failing to protect. The N95 masks do help but if used for more than 2 hours at a time, harm the individual wearing it from a whole host of harm of rebreathing exhaled air, acidity in the mouth, periodontal disease, and the consequences resulting from that; coronary artery disease, intestinal illnesses, and change in the microbiome of the mouth and the GI tract resulting in a decline in the robustness of the immune system. 

 

Where once was joy, depression ensued. Where once was music, a daily broadcast of “cases” and “death counts” played, plucking the detuned strings of society. Dissonance followed. Further jarring the fragile mental framework of a society teetering on the edge of its stable psychological limits. 

 

11 months later, cars still drive on roads, albeit much fewer. Aircraft still dot the skies but are few and far between. The car industry and the airline industry are in shambles. Their Earnings per share declining faster than a lead bullet speeding down a well. Malls are shuttering as brick and mortar retail shops have few to none consumers strolling around looking for things to buy to warm up their families with joy and some happiness. Meanwhile, a few mega-companies like Google, Facebook, Apple, Amazon, etc. capturing personal data of the citizens are selling information to evaluate and control the habit of the population at large while making large sums of money for themselves, earning billions of dollars an hour from the decimated smaller businesses that lie flailing for their last breaths.

 

The once glorious, happy, and harmonious world has become a shell of its past. The music seems to have died in the soul of this and other nations. The schools are forcibly closed by governmental mandates for absolutely no reason, yet the term "Science" is proclaimed to be behind all such decrees. Experts are clamoring for placing more restrictions on citizens, made to socially distance to limit interaction, and mask-wearing is enforced to further limiting any and all social human interaction. Some are being bullied by authorities, others handcuffed and processed. This goes on as the same politicians enforcing the mandates are also releasing convicted criminals from the prisons under the guise of the virus.

 

A plague is upon us and it is not the virus!