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.
46 is also the average age for a first-time Porsche buyer.
Those photographs are stunning – and haunting. Thanks for sharing them.
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."
This article is biotech-specific, but I'd be curious to know more about how the venture debt landscape looks for tech startups.
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.
[1] http://en.wikipedia.org/wiki/Antibody-drug_conjugate [2] http://en.wikipedia.org/wiki/Brentuximab_vedotin
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
Although applicable to more than just tech writing, James Altucher offers some interesting pieces of advice on becoming a better writer: http://www.jamesaltucher.com/2011/03/33-unusual-tips-to-bein...
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."
Agreed! Almost like a freemium model for legal services.
Theory of relativity hacker workspace: http://tobifairley.com/blog/wp-content/uploads/2009/05/alber...
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."
Source: http://blakemasters.tumblr.com/post/22660214207/peter-thiels...
Considering it is a movie about getting a PhD, I'm surprised they didn't try to fund it through an NSF grant!
I don't have the requisite knowledge to comment on fields other than the life sciences, and I certainly agree with your point that every new scientific and technological advance necessarily has to be more sophisticated than the one(s) that it's built upon. But the notion that the past was chock-full of low-hanging fruit just waiting to be picked seems exaggerated and doesn't give enough credit to the people who did all that work that, in hindsight, looks easy, trivial, and obvious, but at the time certainly required significant insights, advances, and effort.
John LaMattina, former president of R&D at Pfizer, weighs in: http://www.forbes.com/sites/johnlamattina/2012/03/02/there-h...
Two lines from the article:
Scientists and engineers expand the size of the economic pie; lawyers mostly work to divide it up differently. Whenever possible, work to be a person who creates things, instead of a person who tries to take stuff created by someone else. There is an infinite amount of work in science because the universe is big and we don’t really understand it and we probably never will. New answers to questions in science yields more questions.
Greenspun makes and attend to his discussion of what grad school in the sciences is like, especially this, his main point: “Adjusted for IQ, quantitative skills, and working hours, jobs in science are the lowest paid in the United States.”
In other words, science is good for society but bad for the individual, from a purely economic standpoint.
You raise another good point here, that the allowable side effect profiles for cancer drugs are much less stringent than for drugs indicated for less life-threatening diseases.
Good question. I'm an author on both of the new CD47 studies, so I'll try to answer this for you:
1. CD47 appears to be higher on tumor cells than on normal cells. In general, the higher the expression of a marker on a diseased cell versus a healthy cell, the more of a therapeutic window/index [1] that is available for a treatment to specifically target diseased cells.
2. Inhibiting the anti-phagocytosis (i.e., "don't eat me") signal is only half of the equation. There are also pro-phagocytosis (i.e., "eat me") signal(s) that also are present [2] and that play a role in whether, and how well, macrophages, and other phagocytes, can phagocytose a cell. "Eat me" signal(s) also differ between normal and cancer cells, adding more nuance to the situation.
[1] Therapeutic index: http://en.wikipedia.org/wiki/Therapeutic_index
[2] A paper examining a putative "eat me" signal, as it relates to CD47: http://stm.sciencemag.org/content/2/63/63ra94.abstract
Jonathan Rothberg is skeptical: http://www.forbes.com/sites/matthewherper/2012/02/18/who-dou...
I thought this was an excellent point by Reid:
“Contrary to what many bestselling authors and motivational gurus would have you believe, there is not a ‘true self’ deep within that you can uncover via introspection and that will point you in the right direction,” Hoffman writes. “Yes, your aspirations shape what you do. But your aspirations are themselves shaped by your actions and experiences. You remake yourself as you grow and the world changes. Your identity doesn’t get found. It emerges.”
I think it may be smart that AMD is focusing on easily-producible SoCs in products designed for emerging markets. Might be a better way to differentiate themselves than going head-to-head on performance.
they must invent the company that will wipe Google out before someone else does it.
That's a great turn of phrase. Nicely done!
It would have been nice to see Amazon here as well.
According to their SEC filing, Amazon's sales were 87.5% from products and 12.5% from services.
Link: http://yahoo.brand.edgar-online.com/displayfilinginfo.aspx?F...