sniperjoe360

Many hypothesis, one of my favorite, however not at all proven, is the heavy use or sautee / stir fry cooking over gas stove. That’s like second hand smoke exposure at least a few times a day

Paw Patrol?

Really impressive results. The real victory here wasn't the breakthrough drug, which many have pointed out is another flavor of PD-1 inhibition (Nivolumab, Pembro) It's the patient selection - careful curation of MSI status with Next Gen Sequencing. Clinically it has already been implemented and is changing the outcomes of thousands of patients every year.

Really very cool, the time savings alone for places without autocontours is perhaps an hour per patient. Would be cool to see the following features in the next update - please dm if you want to collab!

1. Longitudinal comparison of images over time for response assessment 2. Prediction of radionecrosis vs. brain metastases 3. Flags for hypertrophy or atrophy of normal organs (i.e. cardiomegaly, splenomegaly) Easy to do based on volume

Odds for a never smoker aren't well estimated, but I'd say it's in the single digits. Definitely less than 5%. It depends on one's radon exposure, asbestos exposure, exposure to gas stoves/coal burners, smog pollution, and genetic background. Many lung cancers in non-smokers are driven by single gene alterations (i.e. EGFR, ALK)

Your second question is also interesting. For a nonsmoker to get to 25% lung cancer risk, I guess he/she would have to live past 80, which few people do.

Your statement that we all probably get cancer eventually is mostly true - as we age there is an accumulation of mutations which eventually should cause cancer. Some super-elderly people in their 90s and 100s may have more senescent cells than others, and paradoxically lower their risk of new cancer later in life.

As an oncologist, the cause is unknown. But it's not so simple to point fingers at one cause. For example someone who is a heavy smoker (ie. a pack a day) gets cancer at a rate of 25% in their lifetime should they live to age 80. It's a delicate interplay between genetics, development, and environment. We should identify all modifiable risk factors and change our behavior to reduce exposure to them.

I wouldn't have my brain frozen unless we have a better understanding of the fundamental stuff that makes up consciousness. The mind is more than the neurons and synapses. Yes it's a necessary condition to have a brain but consider the following anecdotes:

1. Under anesthesia, the neurons within the brain are fully connected and have access to blood and other resources of the body, yet it is not functioning at all. No pain, respiratory drive, no memory

2. Patients with large parts of their brains removed, or large parts of their brains injured by stroke, can recover fully to a point that is functionally indistinguishable from their previous intact state.

Definitely a great new modality

Benefits - Can target tumor noninvasively with active imaging. No damage of nearby blood vessels.

Cons - Sound waves can only penetrate a few centimeters into the body. Also need a liquid medium to travel, ie. Can't target brain tumors because of the skull, can't target lung tumors due to presence of air.

This material has radiation shielding properties far worse than just lead - lead which is cheaper and easier to manufacture

Pure tungsten on the other hand is very good and can even shield beta particles

3A is a pictoral representation of 3C...I still don't see the difference.

I too am calling bullshit, although for different reasons. Take a look at Figure 3A. Is there really that big of a difference between THC and CBD treated vs. not treated images? To me, a seeing person with eyes, no.

I completely agree with you. If there was even one response I would be much more optimistic. Since there is no clinical signal this is at best a proof of concept and safety.

"Five patients had stable disease, and the other 11 had disease progression as best response on therapy"

great science, but disappointing clinical results

Cheeky of him to use -2022 in the exponent reflecting the year of publication

> It is possible to replace the exponent −2022 in Theorem 1 by a larger (negative) value if the current arguments are modified, but we will not discuss it in this paper.

> [2022-04-26] Larry: Since you think I should come in for at least $2B... I'm in for $2B Elon: Haha thankss:)

This got me laughing. Who are these oligarchical men and why do they have so much $$

The way I see it, this whole article seems to reframe the age old debate between utilitarians and deontologists (moralists) He tries to bridge the two philosophies by suggesting a more vivid imagination of the future consequences increases the present utility. Then you will do what you ought to do, not just out of duty, but also out of a better appreciation of how to maximize future utility for others.

But in the end, such an approach is a bit unsatisfying. Like the trolley problem, such a framing of consequences in purely utilitarian terms comes out ultimately to be value judgement on the threshold of utility that would cause you to act. A value judgement is subjective, and how do you make the subjective decision? Utilitarian or deontology?

Do I have a solution? Absolutely not. Just pointing out this just a reframing of an old dilemma.

Yes keep going! It is hard to see one and have it covered under your insurance, but in America (if you are in the US) you can just pay out of pocket if your insurance doesn't cover it, or requires several hoops to jump through in order to get a referral.

You can also ask your primary care doctor to give you a referral. Most will oblige.

Out of pocket, the fee is probably a few hundred dollars for an hour consultation.

Best of luck!

It sounds orthogonal because it is orthogonal. But it's true and I provided the original source to back up my claim. Hospice and palliative medicine is an accepted by all major faiths.

Physician assisted suicide is another seperate issue - and "pulling the plug" on a comatose patient is NOT euthanasia. That is hospice and palliative care.

You're beating the straw man my friend...

On the contrary, the "religoius crap" is the guiding reason why we have modern hospice and palliative care at all. From the creator of modern hospice's biography posted at the hospice she founded:

https://www.stchristophers.org.uk/about/damecicelysaunders

"Cicely's strong Christian faith was a fundamental factor in her commitment to the dying"

You can still do something about it, perhaps see a rheumatologist? That collection of symptoms seem to be right in their wheelhouse

I took Dr. Jones' course at Princeton and found it extremely reasonable. In fact hundreds of students over 10+ years took his course at Princeton and no one wrote a petition as far as I know about the difficulty of the course.

I suspect this is because the test format at Princeton is rarely multiple choice, and mostly essay or problem solving based. Maitland Jones' class fits the bill in that the problems are mostly about synthesis of organic compounds.

It is hard because it requires you to memorize dozens of reactions and their respective limitations, however there is not always "one right answer" as long as you can accomplish the synthesis of the molecule in a reasonable fashion.

The class taught me to think in 3D about chiralty, and also how to problem solve through multi-step synthesis from simple products.

I'm now a physician and I credit all of my understanding of organic chemistry to Dr. Jones and Gingrich who worked with him on laboratory portion. It was a perfectly fine class, hard but totally doable with a lot of effort.

To put on my best British accent "complete rubbish".

The UK runs world-class trials in adoptive cell transfer and other cell based therapies for cancer. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4442586/

I surmise it was the radiation, chemotherapy, and surgery that contributed most to a 5+ year survival and no evidence of disease. This is available worldwide. Adoptive cell transfer has a complete response rate of 10-30% in unselected patients.

By far the most important recent advance in metastatic colon cancer is PDL1 directed immunotherapy for microsattelite instable colon cancer. This is also readily available in the UK

Source: I am a cancer doctor in the US and I treat colorectal cancer

I think it might happen in diagnostic specialties like pathology and radiology. But in situations in which "speaking to patients" is required - many of whom cannot write, much less use a computer, you need nothing short of AGI.

I think you misunderstand me, which is mostly my fault for not writing more clearly. Don't worry, your fears are not realized.

I have dedicated my life and career to treating cancer patients, prolonging their overall survival however incremental. My avocation is exactly what you talk about when you talk about the tire, sock, or tree. Every day I wake up and do that, and it's just not possible if one does not want their patients to live longer with good quality of life.

I think nihilism exists only there if you view death as the ultimate end of everything. My view is the very opposite, that life has meaning and death is a part of life, and so it too has meaning. So you and I agree on that. I try to get my patients to view death as meaningful too when it cannot be avoided.

At the same time, where I think the misunderstanding takes place is this: I too have also seen chemotherapy and radiation and surgery injure and kill patients prematurely. People should listen up if their doctor is telling them to hold off on additional treatment. It's not giving up, but in the vein of "do not harm." It may shorten your life.

Some articles for you to consider

Early Palliative care prolongs life https://www.nejm.org/doi/full/10.1056/nejmoa1000678

This article captures it well https://www.nytimes.com/2009/08/20/health/20doctors.html

As a cancer doctor, what really stuck out to me was the author's deep anxiety and unsettled thoughts on his own death. I gather he loves life very much and meditating on this topic causes a lot of mental anguish. He is fearful and dreading the pain, financial, and social implcations effect of his death on himself and his family. He is unsure of his own resilience, calling his beautiful prose on the topic "virtue signaling", then later ending with a declaration of fortitude. All this I think adds to his suffering.

This despairing view of death is not inevitable. With all respect to the writer, who I do not know at all, I think perhaps his suffering comes from the illusion that through science we are, in a semblance, "in control." The fact that the patient "on [his] insistence", asked his doctor another round of chemotherapy is troubling to me. Chemotherapy is intrinsically designed to stop cellular replication, and may shorten life if a therapeutic ratio does not exist. But he wanted it - perhaps hoping it would make him live longer.

We are not in control of the central processes of life. We can at best tinker and nudge, and prolong life with the tools of science. Even "cures" for cancer result in a few decades more of life. Lazarus raised from the dead, lived a while longer and then died again.

So I try to guide my patients away from the concept of death as avoidable. Chemotherapy and radiation and surgery are just temporary fixes, nothing ultimate to put your hope in.

Death is inevitable, and can have meaning to it too. Yes the experience of death brings suffering, and fear, but also a time of reconciliation, clarity, and ultimately peace. Why is it this way? Faith in God and the afterlife is one answer, transcending the self is another, the quantum nature of space-time is another.

Any way you approach it, death is in the realm of metaphysics, incomprehensible and mysterious to our scientific worldview - and, I think importantly, reductive to assign a normative value as "bad."

Hi guys, first great effort and as someone who worked in a metabolomics lab I know how amazingly sensitive and rich the information one can gather even from a small amount of blood.

That said, the million dollar question you have to answer in healthy persons is "how is this better than normal lab tests? (CBC, CMP, TSH, UA)?" For example regarding diabetes - there is HbA1c and microalbuminuria, both of which can detect abnormal glucose years before diabetes and prevent it.

If you can prove that these tests add value to the battery of already very cheap and ubiquitous tests, then you will have widespread adoption.

Clinical metabolomics is a very nascent field and best of luck to you!

I hear you friend, you've been to the highest of highs and lowest of lows and now are like a surfer back on dry land thinking of the last big wave, or a soldier back from war wandering around a flower garden. The cognitive dissonance of your otherwise great life with the life you thought you would be living makes every moment unenjoyable and meaningless.

As someone in healthcare who takes care of depression, the pills, TMS, and ketamine are not meant to cure depression. They are meant to decrease the risk of impulsivity, improve function, and decrease suicide.

To get out of depression, you have to find meaning again in the life you were given, and then faithfully follow that which gives you meaning so that you do not become lost again.

Religion is perhaps mankinds best answer because many philosophers who thought about these very questions of meaning were religious thinkers. Ecclesiastes is a great book to read.

Yes, agree with everything factual you said. I guess the problem isn't the compound itself but rather not enough information regarding its use.

I personally keep tylenol in the house because it's probably the best non-narcotic non-NSAID pain medicine.

We use it all the time in patients who are elderly with decreased renal function because they don't do well with opiates or NSAIDs (ibuprofen)

Although perhaps true about FDA clearance, I wouldn't be alarmist and characterize the effective dose as "dangerously" close to the LD50.

The highest dose that therapeutically is used is about 1000mg per dose. The fatal dose is about 15 times that amount.

To put it into perspective, a patient would have to be willfully taking 45 tylenol (325mg/pill) all at once to cause lethal liver damage. Doses like that are usually not accidental.

This paper makes a lot of sense. As a doc, I've seen literally several hundred patients with portions of their brain removed or damaged, some of them very extensive (>20% of the brain). Yet many are completely asymptomatic, and many others regain full function and memory with time and physical therapy. It's led me to conclude that the function of the brain isn't tied 1:1 to the structure of the brain as we had all been taught.