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…!

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