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."
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.
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.
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.
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
Fair enough. Every program I was accepted to, though, did not grant you candidacy from the start as you first had to complete your courses and pass one or more exams.
...a PhD-candidate is usually a first year PhD-student...
This is actually not true. PhD students have to advance to candidacy, which requires completing a set amount of coursework and passing a qualifying exam; this usually takes 1-2 years. Therefore, most first-year PhD students are not yet PhD candidates.
I would say the best realization of this article is that entrepreneur is a state of mind. A willingness to create from nothing in the face of extreem adversity.
I agree with this. I came across the following definition of an entrepreneur, which I also really liked: "[the] definition of an entrepreneur is someone who makes things happen despite not controlling the resources necessary to achieve them."
90% of BlackBerry users will never change the battery on their device. 100% of BlackBerries have a stupid door on the back which allows you to remove the battery and eventually becomes very loose and slides off.
True, but it was sometimes the only way you could do a hard reboot on those things!
From Apple's website: "Before being named CEO in August 2011, Tim was Apple's Chief Operating Officer and was responsible for all of the company’s worldwide sales and operations..."
How does being responsible for all of the company's worldwide sales make Tim Cook not a sales guy?
Mark Andreessen, paraphrased: "Salespeople can be very good at optimizing a company over a 2-4 year period. The [Andreessen-Horowitz] fake hedge fund trade is: when a sales guy replaces a product guy as CEO, go long 2 years, then short."
