Dance MagersSome good discussion in the comments. I liked the ending personally.
Brilliant, weird noir series True Detective had its season finale last night, and the ending probably wasn't what most viewers expected. There were a lot of problems with the way this mystery was resolved, but the show did do one thing gloriously right. Spoilers ahead!
    
|
This is the $1,200 'Slap It' lamp designed by artist Joseph Begley. You can pinch it or slap it to turn it on and off. Me? I'm gonna TAP DAT. Know what I'm saying? I don't even know what I'm saying. You ever motorboated an ass before? Because I have. Plus one time at the rec center I found a female CPR doll and we became boyfriend/girlfriend in a broom closet.
Keep going for a brief video.
Thanks to TBTMH, a butt-squeezing professional.
Dance MagersJohn
When Bilbo and the dwarves escaped Thranduil's kingdom, they did so in empty wine barrels, rushing down the forest river, fighting wood elves and the rapids simultaneously. Their escape was a breeze compared to what director Peter Jackson and the actors went through to make the scene, as this Wired video reveals.
|
|
Dance MagersCrazy
We've all heard stories of the miraculous tomb of King Tutankhamun, son of the rebel king Akhenaten who believed in monotheism. Trying to learn more, Egyptian scientists recently sequenced his DNA. Here's how their discoveries became racially and politically charged events.
|
|
I swear this has existed in other forms before (maybe in New York?), but Airpnp is an internet app that connects people who need to use the bathroom with people who are willing to let strangers use their bathrooms for a fee. Fine, but if anybody pisses in my bathtub or smears shit on the walls I will force-feed you one of those mints that turns toilet water blue. Also, only one visitor at a time -- I can't have some couple using my sonic toothbrush as a sex toy.
The founders are both born and raised New Orleanians and during the Mardi Gras they routinely experienced the pain point of having no place to legally urinate. This problem is often solved by using what is known as a "rogue pee." If caught the person faces a weekend in Orleans Parish Prison. Yet this stiff penalty doesn't stop thousands upon thousands of "rogue pees." This clearly demonstrates the demand for a legal alternative. Entrepeeneurs Travis Laurendine and Max Gaudin decided to capitalize on this golden opportunity starting with Mardi Gras 2014.Rogue peeing, huh? Is it still considered rogue if you just piss your pants? Because if I was at Mardi Gras that's what I would do. Probably without even knowing it. I can get really drunk. You know how many mornings I've woken up not knowing where I am? Zero. You know how many afternoons I've woken up not knowing where I am? Every single one. All I know is whoever lives here owns a pink laptop, and it isn't password protected. Thanks to Alice, who wants as few people using her restroom as possible. SAME. Although I will let anyone piss in my roommate's hamper for $1.
In news that shouldn't surprise anybody whose friends ask them to come fix their computer before trying turning it off and on again, a recent technology based email survey revealed a healthy percentage of Americans are dumb as shit when it comes to computers. Plus obese.
77% of respondents could not identify what SEO means. SEO stands for "Search-Engine Optimization" 27% identified "gigabyte" as an insect commonly found in South America. A gigabyte is a measurement unit for the storage capacity of an electronic device. 42% said they believed a "motherboard" was "the deck of a cruise ship." A motherboard is usually a circuit board that holds many of the key components of a computer. 23% thought an "MP3" was a "Star Wars" robot. It is actually an audio file. 18% identified "Blu-ray" as a marine animal. It is a disc format typically used to store high-definition videos. 15% said they believed "software" is comfortable clothing. Software is a general term for computer programs. 12% said "USB" is the acronym for a European country. In fact, USB is a type of connector. Despite the incorrect answers, 61% of the respondents said it is important to have a good knowledge of technology in this day and age.There's some speculation as to how accurate the survey was, which was administered to 2,392 adults aged 18+ via a multiple-choice email, but honestly, based on the few times I've gone out and interacted with society, I'm surprised the numbers weren't even higher. You think the average American knows what RAM is? The average American writes their name in the blank for their birthdate on job applications. Thanks to Thaylor H, who knows everything there is to know about technology and should be named technology president. Awesome, your first order of business should be assigning me a cushy government job in the internet p0rn division.
Dance MagersGood read
Dance MagersI really like what the creator said here:
"But I'm also sort of surprised by how far afield they're getting. Like, why do you think we're tricking you? It's because you've been abused as an audience for more than 20 years. I cannot think of anything more insulting as an audience than to go through eight weeks, eight hours with these people, and then to be told it was a lie—that what you were seeing wasn't really what was happening. The show's not trying to outsmart you.
....
It's not The Sixth Sense?
It really isn't. Exactly. I knew the guy was dead as soon as he showed up after being gut shot in the second close. It was the same thing with The Usual Suspects. It was like, "Wait a minute. Don't tell me this whole thing is just a lie. Because if it just a lie, what parts of the movie were true? Maybe none of it. What did we just sit here watching?
Shyamalan twists, unless you can really pull them off artfully, are a cheap gimmick. They are a bullshit magic trick that gets in the way of real storytelling. Certainly, being surprised by plot elements is great — it is preferable that the audience cannot see what is coming. But more important than clever plot mechanics is the way the story affects the characters — what the narrative does to them, how it changes them, what it teaches them, and what they gain or lose in the process.
|
|
Dance MagersVery interesting
This is Mercury the two legged cat. He was found at five weeks old with no front legs. Now he's having the time of his life. The folks that adopted him set up a Facebook page called Raising Mercury with a ton of pictures and you can find a bunch of videos at their Youtube page. I just spent a solid twenty minutes watching them. He's a precious angel. My dog? My dog just shit on the floor by the bookcase because she refuses to go to the bathroom outside when its raining even though I did it myself to show her there was nothing to be afraid of. Neighbor wasn't thrilled about it, but I hate that guy anyways. You want to describe my bare ass to the police, go for it.
Keep going for several more pics and videos.
Thanks to lilco, for reminding me there are still beautiful people in the world.
Dance MagersGood read
I sometimes write about the relationship of the problem of evil to evolution. Darwinian natural selection is a rather unpleasant business, you see, making you wonder why a loving God would employ it as his method of creation. My experience with anti-evolutionists has been that this is a point of special concern for them. Virtually every book proposing to reconcile evolution with Christianity devotes a chapter to this (or at least a major section), and some theologians write whole books about it. I devote a chapter to it in Among the Creationists.
You hardly need Darwin to point out that evil and suffering is a problem for theism, but evolution does contribute something to the discussion. Many of the standard replies that are offered in response to the problem plainly do not apply to evolution. For example, it is sometimes claimed that the evil people do to one another is the price we pay for the greater good of possessing free will. Others argue that suffering is necessary for “soul making,” which is to say that suffering is not truly bad as it makes it possible to work toward spiritual perfection. The suffering in nature, it is sometimes argued, is necessary as the price for a functional ecosystem. Regardless of whether or not these arguments are successful, it is clear that none of them address why God would employ Darwinian natural selection as his mechanism of creation.
Of course, there is certainly no shortage of evolutionary theodicies on offer. The point is simply that a specifically evolutionary theodicy is necessary.
In making this argument, however, I do not mean to suggest that I think the traditional replies to the problem of evil are adequate. In the current issue of Philosophy Now, Jimmy Alfonso Licon, a graduate student in philosophy at the University of Maryland, argues that the free will defense is simply inadequate as a response to the problem. The article is not freely available online, so you will have to make do with a few excerpts.
The article begins with a lucid statement of the problem. I like the way he puts it:
Imagine someone who claims to love their children, but they constantly neglect them–they are never home, and their children are often hungry and unprotected. We would rightly be sceptical that they cared for their children at all. It looks like they don’t actually care. So too with God: it seems that with all the suffering in the world, there couldn’t be any such benevolent, omnipotent God.
Licon now explores three problems with the free will defense, all of them persuasive in my view. Here’s the first:
The first problem is that a good action (e.g. feeding thousands of hungry people) is morally permissible, while an evil action (e.g. killing thousands of people) is not. However, the reason feeding thousands of hungry people is morally preferable to killing them has little to do with our capacity to have chosen differently. Rather, it is because people have intrinsic moral worth.
Although this should be remarkably obvious, it cuts deeply against the free will defense. To appreciate why, consider the following: although choosing to do good while you have the capacity to do evil may be a kind of good itself, there are plenty of instances where this good is not good enough to justify the kinds of evil that are potentially unleashed by it. So although there may be moral value to some degree in our capacity to do tremendous evil, in that it provides us the opportunity to freely choose to do the right thing, this good is not absolute. Consider an example from history. Could allowing Hitler the ability to choose the good outweigh the suffering he actually inflicted, on Jewish people and others?
In the interest of keeping this post to a reasonable length, I’ll skip over the second problem, which is that when someone exercises their freedom to do evil, they are robbing others of their own freedom. The third reason is this:
The worry is that in any other context, we reject anything that resembles the free-will defense.
Suppose that the police know that Jones is about to rob a bank and kill a number of civilians in the process (perhaps they know his getaway plan involves killing innocent bystanders as a way of creating a distraction). Suppose further that the police have enough evidence to justify arresting and convicting Jones for some previous crime before he gets the chance to rob the bank. The choices are as follows: the police could either allow Jones to go through with the bank robbery, respecting Jones’ freedom to engage in violent activity (call this option Freedom); or they could preemptively arrest him, preventing unnecessary violence–but unfortunately, this would only come at the expense of his freedom to engage in terrible violence (call this Safety) It should be clear that the Freedom option is what we would prescribe on the advice of the free-will defense, and that this is precisely the option that God allegedly chooses: He fails to intervene, even where there is a horrific amount of suffering, because this would undermine our free will.
…Clearly, between these two solutions, Safety is morally far better than Freedom. The value of human life is far greater than our ability to freely act in morally repugnant ways, or to refrain from acting in those ways.
Skipping ahead to Licon’s conclusion:
In conclusion, although it is good to have the freedom to choose between right and wrong, the free-will defense gets the moral weights wrong. It places too much weight on freedom, and not enough weight on the lives and well-being of innocents.
This is all well-said and convincing. I would further note that the moral callousness of the free-will defense becomes even more clear when you factor in further aspects of certain popular forms of Christian theology. Not only did those Jews who were murdered in the holocaust have their freedom in this life taken from them, but, unless they found Jesus prior to their deaths, they are now spending eternity in Hell. All so that Hitler would not have his free-will curtailed.
What would have been the harm if God, having noted that Hitler was determined to go through with his plan to kill the Jews, had caused him to fall down the stairs? Whose freedom would have been threatened by that? God, we are told, intervenes in human affairs all the time. He causes miracles and answers prayers. Some argue that God works His will in the world by hiding behind quantum indeterminacy. The ID folks tell us that God personally designed all manner of biochemical systems. You cannot hold to such beliefs and then balk at the notion of Him intervening in human affairs to forestall appalling evil.
And if you are horrified by the thought that He would behave like a hit man, I would simply note it is morally acceptable to kill in the defense of others, which is what God would have been doing in this case. Moreover, since He routinely condemns people to eternal damnation, it hardly seems apropos to get squeamish now. (Spare me the retort that God does not condemn anyone, but people freely choose an eternity in Hell by rejecting Jesus in this life.)
The free will defense is probably the strongest counter to the problem of evil that has been devised. That it fails so completely tells you something about the magnitude of the problem.
This is a video of freshly married Elegado and Datan's Final Fantasy themed wedding. They were matrimonied dressed as Squall and a White Mage. Many guests weren't familiar with the Final Fantasy series though, but were encouraged to dress as their favorite characters from anything. The father of the bride came as Darth Vader and the mother of the bride as Alice in Wonderland. I was not invited. The reception took place at Fernwood Gardens in the Philippines in case you were wondering just how less cool the Marriott Courtyard ballroom my reception took place in was. I'm joking, I'm not married. But if and when I am, the reception is going to be on the moon. You're all invited, but one of you has to give me and my new wife a ride. And, just so we're clear, we will be having loud, zero-gravity sex in the back of your spaceship on the way.
Keep going for the video.
Thanks to Mark, threadbare and Aliza, who are all invited to be groomsmen or flower girls.
Dance MagersKluckstintine!
Producer Gale Anne Hurd reveals something that will last beyond this season into next on The Walking Dead. Check out a Hunger Games set photo and a Game of Thrones behind-the-scenes video — and does a Legend of Korra promo what we think it shows? Plus, new looks at Arrow, Person of Interest, and Being Human! Spoilers now!
|
|
The King in Yellow, an 1895 collection of short stories by Robert Chambers, is now a bestseller on Amazon, where it hit number nine on its list of top-selling books thanks largely to io9's article on its role on True Detective.
|
|
This is Badfish Extracts' cannabis infused beef jerky. It's currently being evaluated by third-party tester Santa Cruz Labs to see how potent it is before hitting the market. That's the thing about cannabis edibles -- you never know what you're getting yourself into. Sometimes you eat something and an hour later you don't feel anything. And other times you eat something and an hour later you feel like you are f***ing TRIPPING. Then you pass out and wake up and you are STILL HIGH AS A SPACESHIP. Man, those were the days. "Were?" *wink* WERE (everybody smile and wave to parole officer Morales).
Thanks to T-Dunk, who made me think of Dunkaroos and now I want Dunkaroos.
Dance MagersNew text for you Kluck
And that's just one of the many mistakes in what Indian news organizations are calling the "Error Terror" incident. The textbooks in Gujarat also get basic facts of Indian history wrong, including when Mahatma Gandhi died. As someone says in the above video, "This is as bad as it gets."
|
|
Dance MagersWow this is crazy
Neuroscientists have taken us one step closer to an Avatar-like world after demonstrating a brain-to-spinal-cord interface that allowed a "master" monkey to remotely control the hand movement of an "avatar" monkey who was completely unconscious.
|
|
Dance MagersInteresting
A new study suggests dogs and cats can see things that are invisible to humans — from psychedelic stripes on flowers to flashy patterned feathers on birds. Scientists say the secret behind this remarkable "superpower" is ultraviolet light detection.
|
|
This may be the pinnacle of human invention. Sports Illustrated had the fantastic idea to shoot supermodel Kate Upton into the sky and then film her while she floated around in a bikini. Now we all know what Kate Upton looks like at Zero-G in a swimsuit. The answer, unsurprisingly, is great.
|
|
Dance MagersLove the snowman
Japanese-American animator Jimmy Teruaki Murakami was known as the Father of Irish Animation. He directed the films The Snowman and When The Wind Blows, and also worked on Narnia and Christmas Carol movies. And he directed the live-action Battle Beyond the Stars. He died the other day, aged 80.
|
|
Dance MagersWe gone.
Good news! A computer has solved the longstanding Erdős discrepancy problem! Trouble is, we have no idea what it's talking about — because the solution, which is as long as all of Wikipedia's pages combined, is far too voluminous for us puny humans to confirm.
|
|
Dance MagersHoly shit
Before Jesus arrived and his divine father chilled out, the Old Testament God was, ironically, kind of a hellraiser. He was not a nice guy. He really liked killing people. And he may have actually been insane, if his willingness to randomly murder devout worshippers like Moses was any indication. Here are the 12 craziest, most awful things God did in the Old Testament, back before that wacked-out hippie Jesus softened him up.
|
|
Dance MagersSounds good to me
Finally a Knight Rider remake we can get behind. Chris Pratt and Danny McBride could be teaming up to bring back the series all about some bro and his talking car. Love it.
|
|
Dance MagersInteresting article. Definitely points out some flaws on how the study could be more iron clad, but this sums it up well:
"Now that the data are more mature, the investigators could do what they couldn’t do before, namely to make an estimate of how much overdiagnosis was occurring in the study. (Overdiagnosis is the detection of disease that doesn’t need to be treated, disease that would never progress within the lifetime of the patient to endanger her life.) The authors noted that at the end of the screening period, there was an excess of 142 breast cancer cases in the mammography arm compared to the control arm (666 versus 524). By fifteen years after enrollment, the excess became constant at 106 cancers, which was 22% of all screen-detected breast cancers. Because the mortality rates were the same between the mammography versus control groups, these cancers represent overdiagnosis."
The last couple of weeks, I’ve made allusions to the “Bat Signal” (or, as I called it, the “Cancer Signal,” although that’s a horrible name and I need to think of a better one). Basically, when Bat Cancer Signal goes up (hey, I like that one better, but do bats get cancer?), it means that a study or story has hit the press that demands my attention. It happened again just last week, when stories started hitting the press hot and heavy about a new study of mammography, stories with titles like Vast Study Casts Doubts on Value of Mammograms and Do Mammograms Save Lives? ‘Hardly,’ a New Study Finds, but I had a dilemma. The reason is that the stories about this new study hit the press largely last Tuesday and Wednesday, the study having apparently been released “in the wild” Monday night. People were e-mailing me and Tweeting at me the study and asking if I was going to blog it. Even worse, the PR person at my cancer center was sending out frantic e-mails to breast cancer clinicians because the press had been calling her and wanted expert comment. Yikes!
What to do? What to do? I wanted to jump right ahead and blog it immediately here, as my more “Insolent” persona. On the other hand, this was big. This was serious. Above all, this was about something directly relevant to my clinical specialty. Those of you who follow me both here and at my non-pseudonymous blog know that I tend to like to save things that are big, serious, and directly relevant to my clinical specialty for that blog, with a crosspost here. Oh, hell, I crosspost almost all of my posts published there sooner or later because I don’t want to waste material. In a way I’m glad I waited. The reason is that it gave me time to cogitate and wait for reactions, which is always more fun.
After my obligatory navel-gazing explanatory introduction that infuriates some and entertains others, let’s jump into the study itself. It was published in the BMJ and is, as the title tells us, the Twenty five year follow-up for breast cancer incidence and mortality of the Canadian National Breast Screening Study: randomised screening trial. Before we delve into the findings, I should take a moment to explain what the Canadian National Breast Screening Study (CNBSS) actually is. The first thing you need to know is that this study has been contentious since its very beginning. In particular radiologists have been very critical of the study. One radiologist in particular, whom we’ve encountered before, pops up time and time again in articles critical of the CNBSS. This doesn’t mean that the criticisms of the study aren’t invalid, but this particular radiologist, given his track record, did send up a red flag regarding critics of this study, given some of the truly badly thought out criticisms he’s leveled at other mammography studies, most notably about a year ago.
The study, conceived in the late 1970s and begun in 1980, the CNBSS was a randomized clinical trial that was designed to answer two questions, depending upon the age group: (1) to compare regular breast examination to breast examination plus screening mammography (age 50-59) and (2) compare screening mammography plus “usual care” (age 40-49). These were questions that had arisen from the only existing large study published at the time, the New York Health Insurance Plan (HIP) Study, which in 1963 had randomized (without informed consent) women between the ages of 40 and 64 such that around 30,000 received annual two-view mammography and clinical breast examination for three screens, with another 30,000 serving as controls who received “usual care” (i.e., clinical breast examination). The results, first published in 1977, indicated a statistically significant reduction in breast cancer mortality of 23%. However, no benefit was seen in the 40-49 year old age group. Also, over an eight-year period after diagnosis, breast cancer cases that were positive only on mammography when screened had a case fatality rate of 14%, compared to 32% for cases positive only in the clinical examination and 41% for cases positive on both modalities. The thought at the time was that the reason no difference was seen in younger women was because the incidence of breast cancer is so much lower in women aged 40-49 than it is in women aged 50-64. As I’ve discussed many times before, the less common a disease is in a population being screened, the more false positives there will be and the harder it will be to detect a decline in mortality from that disease due screening because the smaller (on an absolute basis) any such decline will be. That’s almost certainly why the early mammography studies that led to the implementation of widespread mammographic screening programs for the most part were unable to demonstrate a benefit in terms of preventing death from breast cancer in women under 50.
In any case, the HIP Study had raised the question of what the incremental benefit of screening mammography was over “usual care,” which included, in most cases, regular visits to one’s primary care doctor and breast self-examination, described in the introduction to the study reported last week thusly:
In 1980 a randomised controlled trial of screening mammography and physical examination of breasts in 89,835 women, aged 40 to 59, was initiated in Canada, the Canadian National Breast Screening Study.4 5 6 7 It was designed to tackle research questions that arose from a review of mammography screening in Canada8 and the report by the working group to review the US Breast Cancer Detection and Demonstration projects.9 At that time the only breast screening trial that had reported results was that conducted within the Health Insurance Plan of Greater New York.10 11 Benefit from combined mammography and breast physical examination screening was found in women aged 50-64, but not in women aged 40-49. Therefore the Canadian National Breast Screening Study was designed to evaluate the benefit of screening women aged 40-49 compared with usual care and the risk benefit of adding mammography to breast physical examination in women aged 50-59. It was not deemed ethical to include a no screening arm for women aged 50-59.
So basically, there were two parts to this study: Mammographic screening plus regular clinical breast examination versus usual care in women aged 40-49 and mammographic screening plus regular clinical breast examination plus regular clinical breast examination alone in women aged 50-59. Here’s the study schema:
Women with any abnormal findings, be it on physical examination or mammography, were referred to a special review clinic directed by the surgeon affiliated with the study center, where, if indicated, diagnostic mammography was performed. (This study was carried out at 15 screening centres in six Canadian provinces, located in teaching hospitals or in cancer centers). I deem it important right here to emphasize yet again that all of these mammography studies were carried out in asymptomatic women (i.e., women who didn’t have any symptoms or lumps in their breasts). The reason I consider it important is that screening and diagnostic mammography are frequently confused in the minds of the lay public, and there is no controversy about what a woman who detects a lump in her breast or whose doctor detects one should do: Get it checked out with diagnostic mammography and (often) ultrasound, sometimes complemented with MRI. That’s the difference between diagnostic and screening mammography. Diagnostic mammography is done with the intention of working up an abnormality found on physical examination or screening mammography to determine if it needs to be biopsied. Pontification thus ended, I now point out that women who needed biopsies got them done by a surgeon to whom their primary care doctor referred them, and women who were thus diagnosed with cancer underwent treatment by surgeons and oncologists chosen by their primary care doctor.
Study subjects who enrolled had a physical examination (clinical breast exam) and were taught breast self-examination by trained nurses. Then they were randomized according to the schema above as described in the protocol:
Irrespective of the findings on physical examination, women aged 40-49 were independently and blindly assigned randomly to receive mammography or no mammography. Those allocated to mammography were offered another four rounds of annual mammography and physical examination, those allocated to no mammography were told to remain under the care of their family doctor, thus receiving usual care in the community, although they were asked to complete four annual follow-up questionnaires. Women aged 50-59 were randomised to receive mammography or no mammography, and subsequently to receive four rounds of annual mammography and physical examination or annual physical breast examinations without mammography at their screening centre.
In reporting the results, the investigators refer to the mammography plus breast physical examination arm in both age groups as the mammography arm, and the no mammography arms (usual care for women aged 40-49 and annual breast physical examinations for women aged 50-59) as the control arm. Also, the study is often referred to in two ways. The arm for women aged 40-49 is often referred to as CNBSS-1, and the arm for women aged 50-59 is often referred to as CNBSS-2. Just to make that clear.
So let’s get to the results. But before I do, let’s look at the last times the results were reported for this study, the 13 year followup in 2000 for CNBSS-2 and the 11-16 year followup in 2002 for CNBSS-1. The first report on CNBSS-2 showed no difference in breast cancer-specific mortality between the two groups in women aged 50-59; actually, the numbers showed slightly more deaths in the screening group, but that difference was nowhere near statistically significantly different. Although there was an unwritten assumption that there was likely to be a benefit to the addition of mammographic screening that just hadn’t shown up yet because the followup time was too short, the authors were forced to conclude that “our estimates of effect exclude a 30% reduction in breast cancer mortality from mammography screening” and that “chance is an unlikely explanation for our findings.” In the second study reporting the results for CNBSS-2, the investigators concluded:
After 11 to 16 years of follow-up, four or five annual screenings with mammography, breast physical examination, and breast self-examination had not reduced breast cancer mortality compared with usual community care after a single breast physical examination and instruction on breast self-examination. The study data show that true effects of 20% or greater are unlikely.
In other words, as of 2002, no benefit to adding mammography to routine care in women under 50 or to regular clinical breast examination in women 50-59 had yet been observed. The current study, unfortunately, completes the trend. Here’s the graph of all cause mortality (all deaths of study participants):
And here’s the graph for breast cancer-specific mortality (women who died of breast cancer)
As you can see, the curves line up almost exactly. There is no statistically significant difference. There’s not even a whiff of a hint of a statistically significant difference.
Now that the data are more mature, the investigators could do what they couldn’t do before, namely to make an estimate of how much overdiagnosis was occurring in the study. (Overdiagnosis is the detection of disease that doesn’t need to be treated, disease that would never progress within the lifetime of the patient to endanger her life.) The authors noted that at the end of the screening period, there was an excess of 142 breast cancer cases in the mammography arm compared to the control arm (666 versus 524). By fifteen years after enrollment, the excess became constant at 106 cancers, which was 22% of all screen-detected breast cancers. Because the mortality rates were the same between the mammography versus control groups, these cancers represent overdiagnosis.
One notes that this number is remarkably similar to the estimates of overdiagnosis found in other clinical trials and epidemiological studies of mammography that I’ve discussed over the years. For example, way back in 2008, I discussed a study that suggested that 22% of breast cancers detected by screening mammography spontaneously regress.
Whoa. Maybe I shouldn’t have been so skeptical of that result when I wrote it up. And I’m not alone in noting how strikingly similar this number is to the rate of overdiagnosis in other studies. In an accompanying editorial, Kalager et al note the same thing, pointing out that “the amount of overdiagnosis observed in the previous randomised controlled trials is strikingly similar (22-24%).” Of course, there are others, many other studies, and in fact the 22% estimate is rather at the low end of some of the more recent studies. For example, the most recent “blockbuster” mammography study estimated the rate of overdiagnosis to be between 22% and 36%, depending upon the parameters used in the investigators’ model. One study that I discussed even suggested that one in three mammography-detected cancers were in fact overdiagnosed and overtreated, and I said:
Don’t get me wrong. There is no doubt that mammographic screening programs produce a rate of overdiagnosis. The question is: What is the rate? Unfortunately, the most accurate way to measure the true rate of overdiagnosis would be a prospective randomized trial, in which one group of women is screened and another is not, that follows both groups for many years, preferably their entire life. Such a study is highly unlikely ever to be done for obvious reasons, namely cost and the fact that there is sufficient evidence to show that mammographic screening reduces breast cancer-specific mortality for women between the ages of 50 and 70 at least, the latter of which would make such a study unethical. Consequently, we’re stuck with retrospective observational studies, such as the ones analyzed in this systematic review.
Well, the CNBSS is a randomized trial that follows women for their entire lives. Whatever its flaws (which will be discussed in the next section as I try to put it into context), it’s about as close to what I wanted four and a half years ago as we’re ever likely to get, which means that an overdiagnosis rate of somewhere around 20% or so is probably about as good an estimate of overdiagnosis of breast cancer by screening mammography as we’re ever likely to get. The problem, of course, boils down to two issues. First, we can’t tell which cancers diagnosed by screening mammography are overdiagnosed; i.e., which ones will never progress within the lifetimes of the women for whom they’re detected to endanger their lives. That leaves us a mandate to treat them all. Second, there is the question of whether this level of overdiagnosis is “worth it” for the level of benefit in reducing breast cancer mortality provided by screening mammography. The first problem, of course, can be solved by better predictive tests to separate the nasty players from the overdiagnosed players, but the second question is not so easy to answer.
Another important point is that this is the only large randomized study reported in the era of effective multimodality therapy with surgery, adjuvant chemotherapy regimens (chemotherapy administered after initial treatment to reduce the risk of recurrence), adjuvant Tamoxifen (Tamoxifen blocks the action of estrogen and can be used to decrease the risk of recurrence of tumors that respond to estrogen), and radiation therapy. This brings up the question of whether the reduction in mortality from breast cancer that we have observed since 1990—contrary to what you frequently hear, mortality from breast cancer is indeed falling and has been falling since around 1990—is primarily due to better treatment rather than earlier detection. There have been studies published over the last five years that suggest that this might be the case. But is it?
Predictably, as always happens after a study like this, the knives came out, mostly wielded by radiologists. As is often commonly the case, the criticisms were a mixture of the reasonable, the ridiculous, and the obviously turf-protecting. What’s depressing about many of the criticisms of the study is that too many of the people making them seem unaware (or seem to deny) some very basic concepts about screening, namely overdiagnosis, overtreatment, lead time bias, and length bias. I’ve discussed them all before on multiple occasions, pointing out that the early detection of cancer does not always result in improved survival, and more sensitive tests can often lead to upstaging and more aggressive therapy without benefit. I’ve discussed overdiagnosis already. Lead time bias is a situation where early detection of the cancer doesn’t result in improved survival but only appears to do so because the disease is detected earlier and the patient lives longer with it. The best explanation of overdiagnosis (besides mine, of course) I’ve ever found can be read here. Length bias simply describes the tendency of screening to detect more slowly growing, indolent tumors. These problems have led to a major rethinking of prostate cancer screening and is beginning to do the same for breast cancer screening.
Indeed, the 15-25% reduction in breast cancer mortality cited by mammography proponents translates to an absolute risk picture in which averting one death from breast cancer with mammographic screening for women between the ages of 50-70 requires screening 838 women need to be screened over 6 years for a total of 5,866 screening visits, to detect 18 invasive cancers and 6 instances of ductal carcinoma in situ (DCIS). As reported in the New York Times treatment of this study, approximately 1 in 424 women in the CNBSS received unnecessary cancer treatment. In other words, mammographic screening is very labor- and resource-intensive, and a lot of women have to be screened to save one life. As I’ve also said many times in the past, whether this is “worth” it is more a value judgment than a scientific judgment, although that value judgment has to be informed by accurate science.
Of course, the CNBSS is not without shortcomings. Indeed, it’s been attacked nearly from its earliest reports, mostly by radiologists. Indeed, it’s instructive to peruse the criticisms posted after the article (one advantage of BMJ journal articles). They range from the reasonable to real howlers. For example, not surprisingly, Daniel B. Kopans, a professor of radiology at the Harvard Medical School and someone who’s well known for attacking any study that questions mammography, particularly after the USPSTF guidelines were published in 2009 and who earlier gave us this howler:
This is simply malicious nonsense,” said Dr. Daniel Kopans, a senior breast imager at Massachusetts General Hospital in Boston. “It is time to stop blaming mammography screening for over-diagnosis and over-treatment in an effort to deny women access to screening.”
He was referring to H. Gilbert Welch’s study published in late 2012 in the New England Journal of Medicine that found a high degree of overdiagnosis due to mammography. As I pointed out at the time, Dr. Kopan was completely wrong, and overdiagnosis as a pitfall of screening programs exists. He’s also known for saying things like this in about the members of the USPSTF task force that to the USPSTF recommendations published in 2009:
I hate to say it, it’s an ego thing. These people are willing to let women die based on the fact that they don’t think there’s a benefit.
It’s therefore not surprising that after the BMJ article, Dr. Kopans makes the same sorts of statements, statements echoed in an article entitled We do not want to go back to the Dark Ages of breast screening, by Dr. László Tabár and Tony Hsiu-Hsi Chen, DDS, PhD published on AuntieMinnie.com, described as providing “the first comprehensive community Internet site for radiologists and related professionals in the medical imaging industry” and in a statement on the American College of Radiology website. Many of the criticisms are shared, although Dr. Tabar does appear to me a bit disingenuous when he says that “Canadian trials could not evaluate the independent impact of mammography because of the confounding effect of physical examination.” I suppose that’s why they compared physical examination to physical examination plus mammography in the 50-59 year old group.
Dr. Kopan’s first criticism was that the quality of the mammograms was below state of the art, even for the 1980s. Indeed, Dr. Kopans has made these arguments before for the last 24 years. However, as has been pointed out, the purpose of the CNBSS was to examine whether the addition of mammography added anything to breast cancer screening and resulted in decreased mortality from breast cancer using community-based settings, in other words, using mammography as it was practiced in the community. Moreover, as others have pointed out, the quality of mammography increased over time. In any case, this and many of the criticisms leveled by Dr. Kopans and others have been fairly convincingly refuted CNBSS investigator Cornelia J. Baines, the latter of whom published an article entitled Rational and Irrational Issues in Breast Cancer Screening and by an article in which Kopans himself was a coauthor, which showed that, although only 50% of mammograms had satisfactory image quality in 1980, by 1987 85% were judged to have satisfactory quality.
Perhaps the most serious charge made by Dr. Kopans is that there was misallocation of nastier cancers to the control arm. In other words, he charges:
In order to be valid, randomized, controlled trials (RCT) require that assignment of the women to the screening group or the unscreened control group is totally random. A fundamental rule for an RCT is that nothing can be known about the participants until they have been randomly assigned so that there is no risk of compromising the random allocation. Furthermore, a system needs to be employed so that the assignment is truly random and cannot be compromised. The CNBSS violated these fundamental rules (6). Every woman first had a clinical breast examination by a trained nurse (or doctor) so that they knew the women who had breast lumps, many of which were cancers, and they knew the women who had large lymph nodes in their axillae indicating advanced cancer. Before assigning the women to be in the group offered screening or the control women they knew who had large incurable cancers. This was a major violation, but it went beyond that. Instead of a random system of assigning the women they used open lists. The study coordinators who were supposed to randomly assign the volunteers, probably with good, but misguided, intentions, could simply skip a line to be certain that the women with lumps and even advanced cancers got assigned to the screening arm to be sure they would get a mammogram. It is indisputable that this happened since there was a statistically significant excess of women with advanced breast cancers who were assigned to the screening arm compared to those assigned to the control arm (7). This guaranteed that there would be more early deaths among the screened women than the control women and this is what occurred in the NBSS. Shifting women from the control arm to the screening arm would increase the cancers in the screening arm and reduce the cancers in the control arm which would also account for what they claim is “overdiagnosis”.
Make no mistake, Dr. Kopans is accusing the investigators running the CNBSS of scientific fraud here. I’m surprised he’s so bold about it. You’d think he’d have strong evidence to back up this charge. You’d be wrong. If what Dr. Kopans said were true, then the Canadian government should be going after the investigators. The authors themselves are aware of this charge and even answered it in their article:
We believe that the lack of an impact of mammography screening on mortality from breast cancer in this study cannot be explained by design issues, lack of statistical power, or poor quality mammography. It has been suggested that women with a positive physical examination before randomisation were preferentially assigned to the mammography arm.12 13 If this were so, the bias would only impact on the results from breast cancers diagnosed during the first round of screening (women retained their group assignment throughout the study). However, after excluding the prevalent breast cancers from the mortality analysis, the data do not support a benefit for mammography screening (hazard ratio 0.90, 95% confidence interval 0.69 to 1.16).
I actually agree with Dr. Kopans on this one point: Only women with no physical findings should have been randomized to screening mammography. That is perhaps the biggest flaw in the design of the CNBSS. However, excluding women diagnosed with a cancer on the first round of mammography, as the authors argue, and finding no difference in breast cancer mortality do rather argue that it probably didn’t make a difference. The author also points out that another criticism, apparently leveled by Siddhartha Mukherjee in The Emperor of All Maladies, that the women in the mammography group were somehow at a higher risk for cancer. The authors point out that breast cancer was diagnosed in 5.8% of women in the mammography arm and in 5.9% of women in the control arm (P=0.80), showing that the risk of breast cancer was the same in both groups. Finally, there were reasons for why the allocation was done the way it was, and the explanation was not unreasonable;
Randomization was performed by the center coordinators after nurse examiners had clinically examined the participants. Center coordinators were blind to the results of the breast examination.
What in fact was the situation vis-a-vis randomization?
Most tellingly there was no incentive for screening personnel to subvert randomization. The CNBSS protocol required that anyone with an abnormal finding on CBE [clinical breast examination] had to be referred to the study surgeon who would order a diagnostic mammogram when clinically indicated. Symptomatic women require diagnostic mammography, not screening mammography. It was not necessary to “place” as claimed [24] clinically positive participants in the mammography arm of the study in order for them to get a mammogram.
In the CNBSS there were more than 50 variables (demographic and risk factors) which were virtually identically distributed across control and study groups, clear evidence of successful randomization [25,26].
That certainly decreases—although it does not completely eliminate—my concern about the original design. There have also been other studies before that looked for evidence of subversion of randomization in the CNBSS and have failed to find evidence of nonrandom allocation of patients sufficient to affect the results of the trial. As was pointed out by a commenter after the BMJ article named Rolf Hefti, Dr. Kopans never mentions these studies that disagree with his conclusion, fails to note counterarguments that have been made to his accusations, and disingenuously complains about the low rate of detection by mammograms alone (32%), even though that number is consistent with the rates reported in the 1990s—years after the screening period for the CNBSS.
And so the battle rages on, same as it ever was. What amuses me most about this is the seeming underlying assumption that the CNBSS investigators wanted to find no benefit due to screening mammography. My guess is that they were horribly disappointed at the results. No one does the enormous amount of work and spend the money to do a large multicenter trial involving tens of thousands of women because he wants to end up with a negative study, to the point that he would be willing to mess with the randomization to make it happen. The assumption underlying Dr. Kopans’ accusation is ludicrous.
I’m going to give you my bottom line, although it’s going to sound wishy-washy. Does the CNBSS “prove” that screening mammography is useless? Of course not, not any more than any single study ever could, given such a complex issue as screening for breast cancer. The CNBSS is a flawed study that could possibly be a false negative, such that any true benefit in terms of prevention of breast cancer mortality by mammography is buried in statistical noise. However, it is not nearly as flawed a study as its critics, such as Dr. Kopans and Dr. Tabár, would have you believe, nor is it a fraudulent study, as Dr. Kopans would apparently have you believe. It is the result of a group of investigators doing the best they could with the materials they had based on the knowledge they had in the late 1970s and must be weighed against all the other studies examining mammography finding benefit or no benefit. Moreover, it is not new information. It’s just a longer term followup of results first reported in the early 1990s and last reported more than ten years ago.
That being said, I still think it’s entirely appropriate for the study authors to conclude that “the data suggest that the value of mammography screening should be reassessed.” This isn’t a new conclusion, either. It’s part of an evolution that’s been going on since before the USPSTF released its guidelines back in 2009. You’ll remember that back then I characterized those recommendations, which included not beginning routine mammographic screening until age 50, as “not the final word.” Clearly the CNBSS won’t be the last word, either, but it should be included as part of the evidence base for the reevaluation of mammography screening guidelines.
What doesn’t help is denial that overdiagnosis is a real phenomenon and rejection of the now irrefutable contention that detecting a cancer earlier does not necessarily result in improved survival. There are some who are arguing that because that patients with tumors detected by mammography only in this study had better five year survivals than patients with tumors detected clinically, it means the mammography is worthwhile. That’s a horrible argument, because in reality increased survival as observed in this study is, if anything, evidence in favor of overdiagnosis, an observation that was made, shockingly, in an article published in The Atlantic, given how much nonsense about medicine has been published in that magazine before. As I pointed out before, decreases in mortality, not necessarily improvements in survival, are the gold standard that shows a screening test (as opposed to a treatment) really does work.
Radiologists also argue that imaging technology is so much better today than it was in the 1980s. Even mammography itself is much better. This is undoubtedly true, but better, more sensitive imaging, while it could potentially make modern mammography screening programs more effective in preventing breast cancer, could also greatly exacerbate the problem of overdiagnosis. Overdiagnosis is real, and there are diminishing returns on the detection of cancer. If treatment of screen-detected cancers, adjusted for lead time bias, doesn’t clearly result in improved survival, then there’s a problem.
The point, obviously, is to find the “sweet spot,” which maximizes the benefit of screening and minimizes the harms due to overdiagnosis and overtreatment. Based on current evidence, of which the CNBSS is just one more part, I’m more and more of the opinion that our mammography screening guidelines need to be tweaked and personalized because the current “one size fits all” regimen is probably too aggressive for most women at average risk for breast cancer. It’s an evolution in my thought that’s been going on for years. In any case, in any statement I’d put something in there about determining what the “sweet spot” is for mammography. It’s also reasonable, for now at least, to stick with existing guidelines, with perhaps more of a personalized approach to screening of women between ages 40 and 49. That’s what I intend to do until new evidence-based guidelines emerge. And emerge they will, likely within a year.
ADDENDUM: Dr. Miller’s response to the criticisms leveled at the CNBSS have been published, and he very convincingly put Dr. Kopans and others in their place.
You can keep your Dark Knights and Tumblers. For my money, the best Batman movie is still Tim Burton's 1989 version starring Michael Keaton, and this 30-minute documentary, shot during filming, reminds us all how ground-breaking the movie was.
|
|
We have yet to discover any signs of an extraterrestrial civilization — a prospect that could quite literally change overnight. Should that happen, our sense of ourselves and our place in the cosmos would forever be shaken. It could even change the course of human history. Or would it?
|
|
Two episodes into the series, True Detective dropped a reference to one of the strangest, most compelling tales in the canon of weird fiction: Robert W. Chambers' The King in Yellow, a collection of short stories published in 1895. Knowing this book is key to understanding the dark mystery at the heart of this series.
|
|
