I'd like to see these data normalized against parental income, education level, etc. My hypothesis is that there wouldn't be much difference in academic performance for homeschooled vs. non-homeschooled students. In other words, my guess is that having parents with some financial means who place on emphasis on education is what drives academic performance, not whether the child spends their day in a classroom or their house.
Exactly. Take entrepreneurship: the founder is rewarded financially if he/she succeeds but is punished financially if he/she fails. The banks, on the other hand, were rewarded financially when they made money for their clients (in the form of performance bonuses), but were bailed out when they failed to carry out their job successfully. This asymmetry is antithetical to capitalism.
I like how Nassim Taleb put it: "the incentive system put in place by financial companies has produced the worst possible economic system mankind can imagine: capitalism for the profits and socialism for the losses."
One should also beware the insurance industry - it has essentially the same incentive structure.
Sell cheap insurance while times are good - take profit/options/stocks and leave.
When a catastrophe happens - go bankrupt and allow the government/people to socialize the losses for improper risk management. They also take advantage of socialized protection such as national defence, fire-fighters, police officers and ambulance drivers. They don't have to pay for them in proportion to the reward they receive for their services (society pays for them). Hence their risk is mitigated by society whilst privately profiting from our shared risk.
Insurance is a great thing (no doubt about it!) - but these moral hazards exist in many systems around the world and they must be addressed.
This is also why insurance is so highly regulated - the ability for financial impropriety and abuse is just too damn high!
Correct. This tumor-mediated disorganization of the blood-brain barrier (BBB) is what enables cytotoxic drugs to reach larger cancerous brain lesions, which explains why these growths often show a clinical response. Under normal circumstances, many cytotoxic drugs cannot cross the BBB.
This study details the use of a peptide-drug conjugate; these are drugs with peptides (small proteins) chemically conjugated to cytotoxic drugs.
The idea behind these conjugated drugs is that the peptide portion of the drug hones in on a specific biological target and the conjugated cytotoxic drug then kills the cells that have been recognized by the peptide (think warhead and payload). In this case, the peptide recognized prostate-specific membrane antigen, which is expressed on prostate cancer cells, and the cytotoxic drug was one derived from Thapsia garganica, the toxic weed (cytotoxic drugs being isolated from plants is nothing new, of course).
A more common class of these conjugated therapies are called antibody-drug conjugates[1], where an antibody molecule (instead of a peptide) is linked to a cytotoxic drug. There is currently one of these drugs, Brentuximab vedotin, FDA-approved for the treatment of cancer[2]. There are many more under preclinical or clinical development.
So if prostate cancer has metastasized, and we target the cancer, do we do so at the hazard of exposing the healthy prostate cells to the same fate?
Do the cells of other cancer-prone organs produce similarly specific antigens?
If so, how do we avoid the situation where we eliminate (for instance) melanoma tumors of the brain and lungs only to have the patient's skin kill itself off completely?
I think that all of your questions come down to two core concepts: therapeutic index and antigen stability.
For therapeutic index, you want to identify and target antigens that show the largest difference between cancerous tissues and normal tissues (i.e., antigens with a large therapeutic index). In other words, you'd want your drug to bind to an antigen that's present at a higher level on the prostate cancer cells than the normal prostate cells, such that the normal cells are spared.
For antigen stability, you ideally want your drug to target an antigen whose expression is maintained in metastatic lesions. In other words, if a cancer metastasizes from a primary site to a distant organ, and the antigen your drug targets is maintained on the cancerous cells that have made their way to the distant site, then that is a more therapeutically amenable target then one whose expression is lost upon tumor metastasis.
Do those explanations answer your questions well? Let me know if you'd like me to clarify more.
Just to be clear, this $100,000 was spent to possibly identify a potential treatment for one person's cancer, not one type of cancer in general.
In other words, this was a $100,000 diagnostic test with no guarantee that an actionable diagnosis would result. By that, I mean that the results of the sequencing analysis either (a) might not pinpoint a driver mutation or (b) might pinpoint a driver mutation that does not have an efficacious drug available to act on that mutation. Also, all caveats about tumor heterogeneity and evolution, etc., apply.
An integrating sequencing approach involving the analysis of normal and cancerous cells to identify actionable mutations is the best we have for now, but it is still a hugely expensive, time-consuming, and technically-challenging process with an enormous failure rate associated with it. Nonetheless, I think it's terrific that, in this instance, it yielded valuable and actionable information that resulted in a meaningful clinical result. One step at a time!
Earlier this year in the Harvard Business Review, Jody and Matt Miller wrote about a phenomenon that is similar in spirit to that of freelancing hackers, which they dubbed supertemping:
"Supertemps are top managers and professionals—from lawyers to CFOs to consultants—who’ve been trained at top schools and companies and choose to pursue project-based careers independent of any major firm."
It is pretty interesting to see freelancing become a "first-class citizen" in the high-skilled employment world, whereas previously it wasn't widely accepted beyond a few select occupations.
"Only in recent history has "working hard" signaled pride rather than shame for lack of talent, finesse, and, mostly, sprezzatura." — Nassim Nicholas Taleb
There have been a bunch of studies recently that show praising kids for being smart or talented, rather than working hard, can cripple their development. So, it hardly surprises me.
