Critique @ MindSay 
constructive criticism
The List
1. The Harry Potter series...I haven't read them from a critical point of view, and it's a nostalgia thing.
2. The Historian...I've had the book for a year or two now, and still haven't read it.
3. Stardust...loved the movie, heard the book is much better.
4. Fight Club...I'll be reading this with two of my friends sometime in the near future anyway.
5. Pride and Prejudice...one of my favorite stories of all time.
6. The China Garden...really wanna rip apart some parts of this. They just bother me. And the other parts are so steeped in lore that I can mostly overlook the bad parts.
I'll be adding to that when I can think of something else. In the mean time, I've got the first Harry Potter before me, awaiting my attention.
A very large clinical trial (~10,000 women) is underway to assess the usefulness of the Oncotype Dx gene profile for selecting treatment for early stage estrogen receptor positive breast cancer: the TAILORx Trial. The trial sponsors will ask women with breast cancer to undergo Oncotype Dx testing (for which they will be billed $3650) and then assign them to three risk groups based on their recurrence score. (The groups are defined using different cut-off’s for this trial than those used for the study done on the NSABP B-20 tumors.) Women in the low risk score group will get hormonal treatment (tamoxifen or one of the newer “aromatase inhibitor” class of drugs). Women in the high risk group will get chemotherapy and hormone therapy. The women in the intermediate group will be randomly assigned to receive either hormone treatment alone or a combination of hormone and chemotherapy.
A least four concerns make this trial seem premature. First, the chemotherapeutic "validation" of Oncotype Dx is based on one small, old chemotherapy trial. Second, TAILORx does not incorporate many other old and new prognostic indicators that might trump Oncotype Dx in some circumstances. Third, not enough information exists about how the Oncotype Dx score might interact in a confounding way with specific hormone treatments, chemotherapy drugs, and regimens. Finally, far too many non-random, non-blinded choices are afforded to patients and physicians in TAILORx to make for decent "science".
TAILORx is based on a retrospective analysis of a small, non-random sample of assays performed on preserved tissue. The ability to use this old material to obtain reproducible gene profiles is an amazing technological feat, to be sure. But only 651 of about 2300 patient results were available. The chemotherapy used in the NSABP B-20 dates to the 1970's. Substantial evidence supports a conclusion that these regimens improve prognosis for many patients. But two of the agents (methothrexate and 5-fu) are not often employed today. The third agent, cytoxan, has lost popularity over concerns that it may lead to late complications like second malignancies. Meta-analysis of the many thousands of patients treated with chemotherapy indicates that the B-20 drugs are not as effective as newer drugs like the taxols and adriamyin.
So inspite of the fact that the paper describing the results for the 651 patients uses the word "prospective" five times, it is actually a retrospective survey, not a clinical trial. This might matter for a woman who is enrolled in TAILORx because she cannot be sure that the Oncoype Dx group studied really is representative of the group she is in. And remember that much of the power of the argument for Oncotype Dx is contained in the one subgroup that contained only 47 patients.
A second concern revolves around the lack of consideration of many other older and newer prognostic variables when deciding whether a patient falls into "Group 2" (the intermediate risk group) as defined here:
Group 2 (Primary study group; ODRS 11-25): Patients are stratified according to tumor size (≤ 2.0 cm vs ≥ 2.1 cm), menopausal status (postmenopausal vs premenopausal vs perimenopausal), planned chemotherapy (taxane-containing [i.e., paclitaxel, docetaxel] vs nontaxane-containing), and planned radiotherapy (whole breast with no boost planned vs whole breast with boost planned vs partial breast irradiation planned vs no planned radiation therapy [for patients who have had a mastectomy]). Patients are then randomized to receive either hormonal therapy alone or combination chemotherapy and hormonal therapy.
For example, tumor size, tumor dna ploidy, quantitative level of estrogen receptor, tumor lymphovascular invasion, per cent of dividing cells ("s phase"), Ki 67 expression and many other features and meaurements have been used to stratify patients for risk of treatment failure. (Some of these features can make a woman with a very small tumor (<1 cm) eligible for inclusion in the trial, an acknowledgement of their possible importance). And of course, clinical features on presentation may predict risk of failure. Mammographically discovered cancers may have a different prognosis compared to those discovered by the patient feeling a mass, for example.
Under TAILORx rules, a 48 year old woman with a palpable 4.9 cm cancer that is high grade with lymphatic invasion, weakly estrogen receptor positive, Ki 67 expression and an S phase of 20 and a Oncotype Dx score of 23 (intermediate risk) could be randomly assigned to tamoxifen alone.
Some will argue that the hypothetical patient described above would be unlikely to have an Oncotype Dx score as low as 23. (The B-20 Oncotype Dx analysis used 18 to 31 to define the intermediate risk group. The range was changed to 11-25 for TAILORx, possibly because her2+ patients are excluded - more on this below.) This is probably true, since the Oncotype Dx score does correlate to some extent with many "traditional" indicators. However, if the above hypothetical patient exists, few cancer physicians would advise tamoxifen alone. This would result in one of two outcomes for our hypothetical patient.
First, the woman would not likely be offered the TAILORx trial. Or, if she were offered the trial and the randomization resulted in tamoxifen alone, she would be advised to withdraw from the trial and receive chemotherapy. Either way, the results from TAILORx will be compromised. If patients on the "edges" of the "groups" are manipulated to get the "right" treatment, the trial results will be of little use, because the "borderline" cases are the very ones that present the most difficult decisions, and the Will Rogers phenomenon will be in play to distort the results.
A third concern that may make TAILORx premature is the paucity of information about how the Oncotype Dx predictive power might be affected by the choice of hormone and chemotherapy agents. The TAILORx protocol allows each physician to choose a chemotherapy regimen and/or hormone agent. Some might still choose the B-20 CMF and tamoxifen regimen for patients perceived to be at lower risk (within the intermediate group), while others might choose "dose dense" taxol containing aggressive treatment for a patient like the hypothetical one described above. There are many reasons why this may lead to errors.
The gene for glutathione S-transferase (GST) GSTM1 is one of the 16 predictor genes in Oncotype Dx. The presence of this gene tends to improve prognosis. The problem is that this gene also affects the metabolism of some cancer drugs. Anticancer drugs that have been shown to be substrates for GSTs are, for example, chlorambucil, melphalan, cytoxan metabolites, and steroids. Indirect evidence for a role of GSTs in modulating drug effects through deactivation of drug-generated hydroperoxides or other reactive oxygene species exists for adriamycin, mitomycin C, carboplatin, and cisplatin, but not taxol. Some have postulated for other malignancies like acute leukemia in children that gstm1 confers a favorable prognosis because it changes chemotherapy metabolism. Oncotype Dx does not identify which patients have one copy of GSTM1 (a null polymorphism) and which have two copies. Remember B-20 chemotherapy often included cytoxan but never taxol.
Another gene in Oncotype Dx is her2. Patients with tumors that express her2 are exluded from TAILORx. This gene is a prototype marker for chemotherapy selection since the drug Herceptin works very well when it is expressed and not at all if it isn't. B-20 contained a number of her2 positive patients and herceptin was not available in that era. So the Oncotype Dx used in TAILORx is a different one than the one tenuously "validated" in B-20. If the her2 gene is a totally independent predictor, the change might not matter. But her2 does interact with other cancer genes, for example the Src family. Src is a family of proto-oncogenic tyrosine kinases originally discovered by J. Michael Bishop and Harold E. Varmus, for which they won the Nobel Prize.
Bag1 is another gene in Oncotype Dx and it interacts with the estrogen receptor (alpa) mechanisms which can control cancer growth. Does it interact with tamoxifen (studied in B-20) the same way as the aromatase inhibitors included in TAILORx (but not in B-20)? BAG1 seems to predict respone to tamoxifen but how it predicts benefits from other hormones or chemotherapy is less clear.
TAILORx is constructed on a tenuous foundation based on a very small number of observations (remember the 47 patieint subgroup) and on many exrapolations based on assumptions. Some of these may seem niggling, such as the fact that B-20 used age 70 and tumor size 4cm as cut offs and TAILORx uses 75 and 5 cm. Yet B-20 found a suggestion that age and chemotherapy effectivenes interact and that tumor size affects prognosis.
And, one more thing: how can "partial breast radiation" be allowed in a non-random way? This would imply that partial breast radiation has become an acceptable "standard of care". Where are the appropriately powered randomized trials that support this implication? Don't be fooled into thinking that an analysis of this non-randomly assigned "stratification" can answer any useful question.
Stratification (i.e., prospective randomization within smaller, rigidly predefined clinical subroups) is often employed in clinical trials (though purists might argue that this is unnecessary in trials with a large number of outcome events). But TAILORx is not stratified by rigidly predefined criteria. Rather it will permit thousands of patients and physicians to choose among a rich buffet of treatment options related to local therapy ((type of node sampling (any type among many permitted), type of mastectomy (any type among many), lumpectomy (any type among many), radiation (type of radiation, partial/whole radiation), chemotherapy (literally thousands of combinations and permutations of drugs and doses) and hormones (serms and aromatase inhibitors).)
Stratification might make sense if it were based on close to totally objective (not really ever possible in the real world) and independent classifications. Stratification makes no sense if it based on thousands of differing views and biases related to the risks and benefits of a multitude of differing therapies. Those decisions will be largely based on the very risk assessment conderations that the TAILORx trial is supposed to answer.
"Although technological advances will further improve our understanding of breast cancer and will contribute to tailoring treatment to the individual patient, our experience with adjuvant CMF over 30 years confirms that the effects of such a regimen are long lasting and may benefit patients with favourable and unfavourable prognostic indicators, at the cost of minimal long term sequelae." This is how Dr. Bonadonna himself described in 2005 (emphasis added) results from the chemotherapy regimen that is still often called "Bonadonna CMF". "Tailoring treatment" is the holy grail but TAILORx is designed too clumbsily to trump 30 years of better designed clinical trials.
Monks from the Order of the Brothers of the Statistic will study the scripture that flows from TAILORx and will be able to devine all the potential biases and confounders by utililizing probabilistic testing based on dubious underpinnigs that may well result in some very "significant" and small "p" numbers. Cultists who worship at that particular altar of "evidence based" medicine will travel about with their power point slides of life table graphs and p values carried to the fourth decimal point, Genomic Health will turn a profit for the first time and its shares will skyrocket, and another level of the temple known to heretics as the "House of Cards" will have been constructed.
Or maybe the results will look so powerful that even a skeptic like me will be convinced (or fooled).
TAILORx may be another example of the technological imperative in action. TAILORx reflects the fervent need of patients and doctors for a simple "black box" method for making difficult choices. The admonition of H.L. Mencken bears remembering: "For every complex problem, there is a solution that is simple, neat, and wrong."
Freudian translation...? I'm thinking (1) says that I see Jason as some type of unobtainable person (like a character in a show) and possibly fake (because lets face it, soap opera ppl aren't exactly the best at acting)? I've no idea about the dark hair and beard. Possibly that I feel he's wearing a mask? Although if that's the case, it must be subconciously...because right here right now I don't think that. My initial response to (2) is that I'm recognizing that I'm attracted to guys who are "quiet" (like a mime) and closed - perhaps guys who aren't open to having a relationship, even though they're flirting? *shrug* I really would like to take a class or read a book or something on interpreting dreams.
Other updates include:
*Getting my hair cut! Wooooot! And possibly low lights and/or high lights. :) Btw, it's going to be ridiculously shorter ;)
*Going to campus today to grind my stone. Plan to see Greg and/or go out to dinner.
*I hate Lithography. I'm totally uninspired to come up with any creative imagery. Especially when I know that all Hilton will do is bitch and moan about it, cut it down, and basically say it's shit. He'll use his whole "A good drawing printed badly is a bad print and a bad drawing printed well is still a bad print" on me, then he'll turn to Micah who will have drawn a Windex bottle and a salt shaker (a sequel to his 409 bottle and cup--which, by the way, were completely out of perspective and proportion. Oh oh, AND because he was a dumb ass the "409" printed backwards) and say "This is printed nicely." God he's such an ass hole.
They were:
Letter to a Christian Nation
by Sam Harris
The End of Faith: Religion, Terror, and the Future of Reason
by Sam Harris
God Is Not Great: How Religion Poisons Everything (Hardcover)
by Christopher Hitchens
Before proceeding to review these, I should state that I "read" all of these as audiobooks, as part of my daily commute to work, and out and about doing chores about town. Otherwise I simply wouldn't have the time to read them. I do read printed books of course, and very much enjoy doing so, but there's only so much time I have to devote to this. While with my drive times, what usually happens is that I will sicken and tire of commercial radio yet again and rebel by either checking out or purchasing good quality non-fiction Audiobooks.
By far my favorite of the three was the last one, read by the author himself, Christopher Hitchens, in his solemn, educated British voice. I don't always agree with Hitchens, but like a broken clock, then man can still be right at least twice a day. God is Not Great is a brilliant tour de force of the evils and stupidities of religion that still threaten our world and, as the subtitle has it, "poisons everything".
Next favorite on my list was Sam Harris's painfully short but concise Letter to a Christian Nation, his answer to objections sent to him by theists in response to his earlier book The End of Faith. In condensed version, it is a point-by-point polemic against mainstream North American Christian-Conservative ideology as it now stands and its decidedly negative impact on public discourse and rational public policy (or lack thereof--rationality that is--on account of religion's still considerable influence in these United States.).
The End of Faith starts out strong, and I must admit of a need to adjust my own position and views as a result of reading this provocative book. I was at least partially persuaded of Harris's thesis. But not completely. While I suspect he is right in his assertion that mere secular liberals understate and downplay the harmful & hostile aspects of religion, in particular in Islam, by the same token, though he pays lip-service to anti-Imperialist critique, he quickly dismisses such critique out of hand as irrelevant, to hammer home his own brand of Islamophobia. Harris over-stretches, I think, and cites some pretty dubious "Liberal Hawks" to shore up his thesis....Alan Dershowitz? Paul Berman of Dissent (which, by the way, should be more properly called Assent these days--assent to the project of Empire, which has always been a bipartisan affair)...that Paul Berman?? Um, no.
Hitchens is also nominally pro-war, and has been more belligerently so in other fora, but he soft-pedals this in God is Not Great. And I would be the first to say that anyone accusing either Hitchens or Harris of being Bush-lovers are wrong and way off base.
Part of my biggest parting of ways with both of them stems from the fact that I am a 9/11 Skeptic, while they basically accept the "official" story at face value. If I were not a 9/11 Skeptic, I would probably see the world much more as Harris and Hitchens do. But because I am, I cannot.
if there's some generalizations i can make about the people i've conversed with on here/at large (i figure it's irie to make generalizations about our species as ONE, but if you/i try to get any more particular than that, it becomes racism really fast), it's that we are all a) STUBBORN b) INSINCERE c) PARANOID d)INCONSIDERATE e) CRIMINALLY IGNORANT and f) DELUSIONAL (this list could get really long really fast)... I am a firm believer that all humans are more or less the same (at the very least we all have more things in common with each other than things which make us "different") in that we all have the ability to make the same decisions as each other one moment to the next... our freedom binds us, in a way (not to mention our fucking genes)... and surely we all have a common destiny just as we share a common past, so i don't see any harm in speaking of humanity (or the western world breed thereof (i feel too ignorant of the East to speak of it with any semblance of authority...)) as ONE. I AM a fucking human-- there's my credibility right there... so why do i think what i think about what we are/how we behave? read on...
stubborn
why are we stubborn? because we're fucking lazy (btw, if you're the type of person who gets offended by the F-bomb but can sit and read a newspaper without flinching/cringing, you can suck a dick, right now)... we prefer to learn as little as possible... so we learn someone's take on something once, etch it into our skulls, and henceforth consider it to be gospel, or at least "reality"... we seem inclined towards regurgitation rather than analyzation... we'd rather vaunt our "knowledge" like a trophy than augment it in any way... knowledge evolves like life, the universe, and everything... stubbornness is counter-evolutionary... it's a ball-and-chain, the companion of fools who live in perpetual fear of being exposed as fools...
insincere
why are we insincere? because we're taught to be... we're taught to not want to be "different" to the point that we become petrified of being construed as different by any douche-bag who happens to happen upon us... who gives a fuck what douche-bags think of you? we're all douche-bags and we're all bombarded with stupid thoughts on the regular, so why would we discard our own stupid thoughts, and yet take the stupid thoughts of others to heart? consider the source, people...
I haven't been everywhere, but i'd bet alot that north america (yes i'm a bloody canuck but i totally consider any american to be interchangeable with any canadian... same shit, partially different pile... fools abound...) is home to the most insincere society on earth... we're afraid to be ourselves, to indulge in irrational/"abnormal" whims and whatnot, because boys are taught to be clint eastwood and girls are taught to be... i dunno, fucking shirley temple... men are supposed to be bold and women are supposed to be pretty... and we're all supposed to be people of action (act first, and if there's any time left, think then, if you want)... what do you expect when you're raised primarily by a faceless, brainless, lifeless corporation? mass media/society wants your money, and is indifferent to anything of significance... i wrote about insincerity a while ago, though, so consult that if you can stomach any more of this...
paranoid
this one came as a surprise... in the safest place to live in the history of the world, one would think paranoia would be a thing of the past... but it's thriving... why? again, i think this is a learned trait... the history that you may or may not have learnt, is saturated with violent conflict to the point that the term "history" is synonymous with "the history of war"... and as every history is written by someone with a vested interest/bias in whatever conflict they're summarizing, there is always a good side and a bad side in our half-assed sources of information... so, we end up believing that some humans are inherently good, and some bad... everyone on earth wants the same short list of things, people... there are no alien monsters amongst us (and if there are, i'd suggest you leave them be)... there are just people who make bad fucking decisions for one reason or another... i've noticed that paranoia is especially popular amongst religious devotees (christains, in a western context (dammit-- i guess i'm now a racist by my own definition...))... for this, i blame the myth of the devil... christians seem to go to sleep every night thinking there's a wolf at the door... i say if you believe that evil is ubiquitous, you haven't been using your bloody better judgement... have you ever met an evil baby? that's cause none of them are! we teach them to be evil because we're so goddamned inept at teaching anyone anything... we teach them to be paranoid, we put them on the defensive from the get-go, we teach them that the worst thing to be in life is a victim (as opposed to a transgressor)... bollocks! there is nothing more humourous/pathetic/sad to me than seeing an adult scream and flee from a fucking bee or spider or something of that sort, something that obviously does not pose a serious threat to them (and even if you're allergic, there's no reason to fucking scream, though running is understandable...)... but this is what our governments do on a global scale, and we just follow our leaders like the fucking monkeys we are... still afraid of spiders, snakes, and such, even though we dissect them en-masse and could eradicate them on a lark if we chose... fucking metaphors get convoluted sometimes... bear with me folks... what i'm saying is this: what is there left on earth for us to fear beyond ourselves? nothing, so we invent imaginary enemies to fear, to fight, to give us a sense of purpose... purpose has become synonymous with deluded paranoia... if you have to fear anything, fear the fucking future... fear for your grandchildren... fear your fear... fear the muzzle of a gun in your face, but until that happens, stop wasting your fucking time (one of my buddies won't let me swear on his site so i'm kind of venting here-- deal with it)... i dunno... it seems there are many real and immediate threats to our livelihoods but they all seem to come from the same place: our outlandishly luxurious, unsustainable life-styles... i fear for the fate of mother nature, and everything that comprises it (including US), but i have to assume (yes, yes, assumption is the mother of all evil, but it's also the only way any science could ever get done) that fears based upon science are worth investigating... maybe many of us are such paranoid freaks out of sheer boredom... to spice up our otherwise mundane and bland lives... that's pretty weak, if that's the case... drama is ubiquitous already, we don't need to invent any...
inconsiderate
by inconsiderate i don't mean that we fail to follow traditional customs etc, but that we simply don't revere/respect life the way we should ( i hate it when my shit could be construed as "preachy", i am no pillar of reason, just a humble philosopher who has to take a stand somewhere in order to be able to conscionably communicate anything that could be construed as useful to anyone... (and damn it all, i hate it when i revert to extreme wordiness when i feel that i'll be widely misinterpreted)) ... common courtesy is lacking sure, but that's just because nobody has sensibly defined it... consideration is essentially the ability to put oneself in the shoes of others... why don't we do that more? you guessed it, cause we're a bunch of lazy pussies... there seems to be no shortage of self-love out there, but when it comes to loving our brothers and sisters, we just can't find the time or rally the effort required... we're so worried of being victimized somehow that we fail to relate to the droves of people who actually are the victims of circumstance and negligence... and this willful ignorance just serves to compound the problems of the real victims, and otherwise doesn't serve any useful purpose at all... if i could say one word to everyone on earth it would be: RELATE! relate to everything under the sun... i find it easier to relate to certain animals than i do to relate to certain people but i still try... i happen to like challenges though, and this one can be tough, as there is no precedence for it, like most of the tough ones... that's why we tend to leave them alone... i don't find anything as enticing as a problem that has yet to be solved... and if we are to exist unforseeably into the future, we will eventually need some general guidelines about how to treat people/life half-decently... the golden rule is a good start, but i personally haven't met many christians who abide by it, so i think we'll need a medium other than religion (say, LOGIC) in which to transmit such guidelines... maybe if people were a little more in touch with their inner selves, their TRUE self, we wouldn't have to transmit such guidelines (we shouldn't have to) at all... we are all born with such innate wisdom... where does it go? does our fear chase it away?
criminally ignorant
uh... here's a fucking newsflash: the earth, as of 2007, is our sole lifeline in the universe. here's another: the earth is finite... there are a finite number of atoms on our planet... everything you do affects a finite number of atoms on our planet... therefore, everything you do affects our planet... so watch where you step you (metaphorically) fat bastards... I don't think i can make this point any clearer... meditate upon it, young grasshoppers...
delusional
do i need to elaborate on this word/idea? what you believe does not alter what is. unless, of course, you act upon your beliefs and start dicking around with god's perfect plan (ha! i love tempering my fastballs with a sinker every now and again)... all the wishful thinking in the world doesn't amount to a hill of beans... if you can't defend/justify/rationalize your beliefs, you have no business believing them... but if you persist to believe in spite of common sense, you become delusional... if delusion is what you want from life then go to sleep... otherwise, as the mythical satan once said: "awake, arise, or be forever fallen!"
and i'm spent... if you have read this far, you will most likely have felt some provocation at some point or another... i encourage you to give into it... defending my beliefs helps me to define them... did you notice any common threads throughout the rant? are most of my grievances attributable to our ingrained and socially enhanced fear? i suppose i'd say so... do i expect too much from a pack of relatively well-groomed monkies? maybe, but none of the shit i mention seems too much to ask, does it? if there can be peace anywhere, there can be peace everywhere... if anyone is good, life is good... if anyone can be logical, we can all be logical... such are my assumptions.
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