[HN Gopher] Prostate cancer can be precisely diagnosed using a u...
       ___________________________________________________________________
        
       Prostate cancer can be precisely diagnosed using a urine test with
       AI
        
       Author : samizdis
       Score  : 177 points
       Date   : 2021-01-21 16:06 UTC (6 hours ago)
        
 (HTM) web link (phys.org)
 (TXT) w3m dump (phys.org)
        
       | m3kw9 wrote:
       | How does a test get standardized? Is there something like drug
       | trials where you need to show accuracy instead of efficacy?
        
       | rozab wrote:
       | So they used a neural net with only 4 parameters?? And they
       | haven't compared the performance to a simple regression?
        
       | zerof1l wrote:
       | This article reads more like PR than research. Research is based
       | on 76 urine samples which is way too little. In the paper,
       | there's little info on model hyper-parameters as well as how they
       | trained and tested them. I suspect they overfitted their model,
       | meaning it just learned all the samples. If that's not the case,
       | the only other explanation for such high accuracy is that there's
       | a very obvious correlation and a human would be able to diagnose
       | cancer with high accuracy also, meaning you don't need any AI.
        
         | trhway wrote:
         | >The team developed an ultrasensitive semiconductor sensor
         | system capable of simultaneously measuring trace amounts of
         | four selected cancer factors in urine for diagnosing prostate
         | cancer.
         | 
         | it would be interesting if they run as a control a human
         | looking at those measurements.
         | 
         | One can also wonder how many other cancers can be detected by
         | dipping a chip in urine and whether those chips can be just
         | made into a smartphone accessory for home/field use.
        
         | Nowado wrote:
         | > there's a very obvious correlation and a human would be able
         | to diagnose cancer with high accuracy also, meaning you don't
         | need any AI
         | 
         | IF (big if) that's the case, arguably you still prefer
         | something that runs on some electricity in few servers instead
         | of having thousands of human diagnosticians who need to be
         | housed, fed, educated, entertained and later retired.
        
         | caycep wrote:
         | Granted...through some weird HHS/medicare loophole, this is
         | commercializable. Our center has a AI "stroke/clot" detector
         | algorithm software, that's based on a training set of 50 CTs.
         | It's ok, say at a 2nd year medical student level at reading
         | images, i.e. not to the point anyone would trust them. But if
         | the clinical writes in their documentation that the software
         | was utilized to analyze the images, the hospital gets an extra
         | couple grand of reimbursement from the insurance company,
         | apparently. Exactly what rules apply here, I don't know.
        
         | ttymck wrote:
         | > Research is based on 76 urine samples which is way too little
         | 
         | I'm sure I'm out of my depth, but I feel compelled to point out
         | that reputable clinical research can be done on even smaller
         | samples[0].
         | 
         | I want to make sure we aren't conflating the training set and
         | the test/validation/holdout set [1] -- I interpreted the
         | article as stating "76 samples in the test set" and assumed the
         | training set is far larger.
         | 
         | [0]: https://stats.stackexchange.com/questions/2541/what-
         | referenc....
         | 
         | [1]: https://www.datarobot.com/wiki/training-validation-
         | holdout/
        
           | z77dj3kl wrote:
           | It really depends on the model. If you're estimating a mean
           | from a distribution with low variance, 76 can be quite
           | enough. But for any even half-involved ML model, that's
           | nothing.
        
           | ska wrote:
           | Your interpretation is wrong, unfortunately.
           | 
           | The paper is really about developing a multi-marker sensor
           | approach for screening.
           | 
           | The analysis, however was done on a small set "Obtained data
           | from 76 urine specimens were partitioned randomly into a
           | training data set (70% of total) and a test data set (30% of
           | total). " Later on it states the 76 samples are from 51
           | individuals.
           | 
           | So the GP complaint is correct in this case. They are
           | comparing a RF approach and a NN approach - there isn't much
           | detail in the paper but it's most likely the analysis is
           | problematic. I suspect this was done because the group is a
           | collection of hardware and clinical folks, not statisticians,
           | and the paper would have benefited by review by a biostats
           | person.
           | 
           | You are quite right generally that for some models and some
           | effects, a relatively small verification set can be
           | effective.
        
           | thegginthesky wrote:
           | That's right, sample size can vary a lot depending on several
           | factors such as:
           | 
           | * Experiment design
           | 
           | * Sampling techniques
           | 
           | * Methodology being used on the model
           | 
           | But normally with a small sample size a bigger emphasis
           | should be put on performing the appropriate statistical tests
           | on the sample and validating it carefully, before applying
           | any model. There are a lot of assumptions that should be
           | validated if you are working with small data.
           | 
           | Unfortunately, I don't have access to the complete paper to
           | verify the methodology used, so take it all with a grain of
           | salt.
        
             | samizdis wrote:
             | The paper may be read here:
             | 
             | https://sci-
             | hub.do/https://pubs.acs.org/doi/10.1021/acsnano....
        
           | dekhn wrote:
           | There's a great paper about small sample sizes in the context
           | of experimental surgeries (where usually the work is done at
           | a single regional hospital on 3 patients): "If nobody died,
           | is everything OK?" It's cited in Glantz's Primer on
           | Biostatistics.
        
           | Blikkentrekker wrote:
           | "significant results" can be yielded from 76 samples,
           | provided they all be independent, and one can practically bet
           | that they are not.
           | 
           | But this is a claim of accurate diagnosis which requires more
           | than simple significance. The a.i. being demonstrated to
           | simply be better than chance would be a significant result,
           | which is obviously not a spectacular standard for diagnoses.
           | 
           | The issue is that the meaning of "significant" is very often
           | overrated. It means nothing more than " _We are highly
           | confident that there is a stronger effect than zero._ "; --
           | this does not mean this effect is particularly large, and
           | most importantly, it does not mean the effect is universal.
        
             | mbreese wrote:
             | From Supplemental Table S2 in the paper:
             | 
             | Non cancer patients: 26, Cancer patients: 25
             | 
             | So, they only had 51 individuals in the study. Then they
             | actually divided the patients in to 3 groups: normal, PCa
             | with pre-DRE, and PCa with post-DRE. The cancer patients
             | thus had 2 samples, pre and post-exam: 26 + (2*25) = 76.
             | 
             | Given the false positive rate of PSA screening, I would
             | imagine that including more normal samples would have been
             | more beneficial here. The method of analysis is pretty
             | interesting though, which is where I think the novelty is
             | for this paper. I assume that a more thorough clinical
             | trial is planned with better numbers. This paper looks like
             | it is more of a validation of the device than anything
             | else.
        
         | ghastmaster wrote:
         | Agreed. This article raises more questions than answers. How
         | were the samples obtained? What does "almost 100 percent
         | accuracy" mean? What was the source of non positive samples?
         | How many total samples were there?
        
       | bcatanzaro wrote:
       | This isn't AI. It's a random forest with FOUR inputs and ONE
       | output. The fact they put a huge big blue AI brain in their paper
       | to represent this algorithm tells me this is mostly hype.
        
         | plaidfuji wrote:
         | What's the cutoff on number of inputs/outputs/parameters for an
         | empirical model to be considered "AI"?
        
       | williesleg wrote:
       | Just put your mouth diaper back on.
        
       | brundolf wrote:
       | How do clinical trials work for ML? Since the system is largely a
       | black-box, I imagine that the slightest alteration (training on
       | more data, tweaking any parameters) would require totally re-
       | doing a full gamut of trials, wouldn't it?
        
         | Kuinox wrote:
         | A lot of thing are blackbox. There also things that we think we
         | understand, but we do not, thats why we have methodologies like
         | double blind testing to assert that the blackbox is indeed
         | working, and it's behavior is stable enough to be used as a
         | tool.
        
         | swsieber wrote:
         | I'm not sure why you would need to re-do a full gamut of trials
         | for anything except deciding that the current type of data
         | collected was insufficient.
         | 
         | Presumably you record all data, and just split it into test and
         | train sets, and you're off to the races.
        
           | brundolf wrote:
           | I guess it makes sense that unlike for actual treatments, for
           | diagnostic systems you could just "re-use" the test data from
           | past trials and not have to gather a whole new dataset
        
         | 5440 wrote:
         | I'm a regulatory consultant for AI software and submit several
         | AI/ML FDA submissions per week. Overall, I've submitted 100+
         | AI/ML submissions to date. Generally, FDA has been really
         | focused on locked algorithms even though there has been some
         | guidance lately stating the the new Good Machine Learning
         | Practice (GMLP) will provide some allowance for iterations
         | without submitting new 510ks. I will say that a number of
         | companies are slightly tuning their algorithms without FDA
         | resubmission within the confines of the FDA Guidance
         | "https://www.fda.gov/regulatory-information/search-fda-
         | guidan...". That said, most companies most companies are just
         | leaving their specifications at sensitivity/specificity of 80%
         | which gives them some leeway to improve above those limits. In
         | truth most companies are above 97%-99%. While most of the
         | submissions I work on are MRI/CT image related, I'm starting to
         | get a lot more in the predictive space centered around ovarian
         | (CA125), breast or PSA cancer scores. Lately pathology AI is
         | escalating rapidly.
        
           | brundolf wrote:
           | Thanks for the informed and informative answer! I love how
           | common it is on HN to hear from someone with first-hand
           | knowledge of a topic
        
       | m00dy wrote:
       | where can I find their paper ?
       | 
       | note: I've got the link
       | https://pubs.acs.org/doi/10.1021/acsnano.0c06946
        
         | ackbar03 wrote:
         | You can read it on a boat; You can read it with a goat; You can
         | read it in the rain; You can read it on a train; You can read
         | it in a box; You can read it with a fox; You can read it in a
         | house; You can read it with a mouse; You can read it here or
         | there; You can read it anywhere!
        
         | harveywi wrote:
         | I would recommend a quiet, distraction-free environment.
        
         | samizdis wrote:
         | https://sci-hub.do/https://pubs.acs.org/doi/10.1021/acsnano....
        
           | boogies wrote:
           | ([PDF], if blocked paste your url into sci-hub.st or .se, or
           | whatever URLs are listed on
           | https://en.wikipedia.org/wiki/Sci-Hub -- which got them from
           | https://nitter.dark.fail/sci_hub before
           | https://news.ycombinator.com/item?id=25779367. They came for
           | the big bad orange man, too few spoke up, and now they've
           | come for open access to other knowledge.)
        
         | [deleted]
        
       | gfxgirl wrote:
       | So this is super awesome if true and I hope they can use the
       | technique for other cancers.
       | 
       | I'm curious though, my bf says his doctor asks if he wants a PSA
       | at his checkup. His doctor then goes on to explain that pretty
       | much all men eventually get prostate cancer and there's not much
       | you can do about it and you're far more likely to die of
       | something else first so, not really much reason to get the PSA
       | 
       | Anyone have any other info? Is there actually treatment and is it
       | worth while?
        
         | aclsid wrote:
         | That doesn't seem to match reality, where you have some men
         | living past 100+ years. But I'm not a doctor so...
        
           | inglor_cz wrote:
           | Not every cancer is created equal. I helped an urologist
           | typeset his PhD thesis about prostate cancer treatment in TeX
           | (he used some math equations within) and he told me the same.
           | 
           | Some cancers are aggressive and some are slooooow. In younger
           | patients, cancers tend to move fast and kill fast. But a slow
           | prostate cancer in a 70 y.o. may be better left as it is,
           | because the risks of the operation may actually be higher.
           | 
           | This, of course, is a difficult judgment call and belongs to
           | the experts only.
        
             | ChefboyOG wrote:
             | I always wonder about bias in these statistics around age.
             | 
             | It makes intuitive sense to me that a cancer diagnosed in a
             | young patient, who is below the common screening age, is
             | probably being diagnosed because it is presenting serious
             | symptoms (i.e. is growing fast).
             | 
             | Cancers diagnosed in a 70 year old, on the other hand,
             | would seem much more likely to be diagnosed while they are
             | asymptomatic and relatively contained, or to be cancers
             | that have been growing slowly for a long time (more likely
             | as the 70 year old has been alive longer).
             | 
             | Obviously, I don't know if this is the case or not. If
             | anyone has experience in this field, I'd love to hear about
             | it.
        
         | e40 wrote:
         | NAD, but male. That's bad advice. Prostate cancer found in old
         | men is likely to go untreated, but certainly not younger men.
         | 
         | Your bf should switch Dr's.
        
         | vharuck wrote:
         | There are things that can be done, especially if the tumor is
         | small and hasn't spread to adjacent organs. I'm not an expert,
         | but in general, solid tumors are _much_ more easily treated if
         | caught early. Still,  "watchful waiting" is a totally valid
         | option for early-staged prostate tumors.
         | 
         | That said, the doctor might be trying to benevolently prevent
         | unnecessary tests, stress, and treatment. Some people hear
         | "cancer" and rush into risky treatments. This is part of the
         | reason the United States Preventative Services Task Force
         | "demoted" asymptomatic PSA screening from "recommended" to
         | "have a talk with your doctor." Their review of the studies
         | didn't show that screening asymptomatic men resulted in a large
         | reduction in mortality. Mostly because prostate cancer is so
         | common and often develops slowly. Somewhat because treatment
         | can bring its own dangers.
         | 
         | At first, in 2012, they recommended against it. Then doctors
         | and patients' groups protested, so now it's "have a talk." We
         | are now starting to see the result of that first decision in
         | the increasing incidence of late-staged prostate cancer.
         | 
         | All this is to say: PSA screening's not a bad idea as long as
         | you can keep perspective if it comes back positive. Out of the
         | major cancer types, prostate cancer has one of the highest
         | 5-year net survival rates [0]. It's over 95% in my state[1].
         | 
         | [0] Net survival tries to exclude the risk of death from other
         | causes. So 100% net survival for a cancer diagnosis means
         | there's no difference from a similar person who didn't have
         | cancer.
         | 
         | [1] The official statistic from the CDC may be lower, but I
         | disagree with some adjustments they make. I believe they force
         | the data to fit their mental model.
        
         | gumby wrote:
         | It's basically true that most men have it and live with it for
         | a long time (even decades) -- one can see the evolutionary
         | reasons not to select against it.
         | 
         | However some cases are more aggressive and will have a negative
         | impact or even kill them.
         | 
         | The problem, as with most cancers, is to figure out which ones
         | are worth treating rather than risk iatrogenic consequences.
        
         | DanBC wrote:
         | https://www.hardingcenter.de/en/early-detection-of-cancer/ea...
         | 
         | Take 1000 men over the age of 50 and give them PSA and DRA for
         | about 15 years. Take 1000 other men over 50 don't give them PSA
         | nor DRA over the same time.
         | 
         | > About 10 out of every 1,000 men with screening, and 12 out of
         | every 1,000 men without screening died from prostate cancer
         | within 16 years. This means that 2 out of every 1,000 people
         | could be saved from death from prostate cancer by early
         | detection using PSA testing. This was not reflected in overall
         | mortality.
         | 
         | Over all about 322 men died in both groups, so it doesn't seem
         | to make much difference to all cause mortality.
         | 
         | However, in the group who was screened we see 155 people had a
         | false alarm (and that includes unnecessary tissue removal), and
         | 51 men with non-progressive cancer had unnecessary treatment
         | (that sometimes includes impotence or incontinence).
         | 
         | The most important question you can ask a doctor is _what
         | happens if we don 't do this?_
         | 
         | There are different types of prostate cancer. Some are very
         | slow growing and people tend to die with it, not of it. There
         | are aggressive types of prostate cancer that do kill people,
         | but these tend not to be found in time to make much difference
         | to populations at the moment.
        
           | ChefboyOG wrote:
           | I think it's important to have some conception of a personal
           | "risk tolerance" when it comes to screenings.
           | 
           | Personally, I've had false alarms and dealt with that stress,
           | and I still find that screenings are worthwhile. Having seen
           | family members/friends die of cancer, I don't find the
           | additional and potentially unnecessary discomfort of
           | screenings to be too much of a cost.
           | 
           | At the same time, I'd never judge someone for feeling the
           | opposite, particularly in cases like prostate cancer, wherein
           | most people die "with it, not of it" as they say.
        
         | ohazi wrote:
         | A PSA test is easy and non-invasive and I personally wouldn't
         | skip it. But keep in mind that it doesn't have a lot of
         | diagnostic accuracy by itself, and the false positive rate can
         | lead you to do things that are more invasive than necessary.
         | Family history should be considered.
         | 
         | If the numbers are low, you're probably good. If the numbers
         | are high, it isn't necessarily bad, but it could be good excuse
         | to keep a closer eye on things. You might do additional PSA
         | tests and look at whether it's trending up or down. A biopsy
         | might be suggested, which is more invasive, and _can_ be more
         | accurate, but it also depends on where the doctor is able to
         | collect the tissue -- if they miss the spot, a biopsy could be
         | inconclusive or contradictory.
         | 
         | Finally, if you have prostate cancer and the numbers are bad
         | and your doctor tells you that it needs treatment, the common
         | treatment seems to be high intensity focused ultrasound (HIFU),
         | which is unpleasant and invasive, but it isn't surgery, and it
         | isn't anywhere near as damaging as radiation, and apparently it
         | works rather well.
        
         | LinuxBender wrote:
         | There is probably some truth in all men eventually getting it,
         | but there are for sure contributing factors that increase and
         | decrease risk. I've run across many of these by mistake in my
         | nutritional research on nih.gov. That is a great starting place
         | to find some of the research.
        
         | zwieback wrote:
         | I had prostate cancer 10 years ago when I was 42, prostate
         | surgically removed and doing fine now.
         | 
         | I also heard from urologists that everyone eventually gets it
         | but normally you can outrun it. If you have an aggresive
         | variety or get it when you're young you should definitely do
         | something about it.
         | 
         | The tricky part is that the current PSA test is not specific
         | enough to avoid the stress and extra human cost of
         | overtreatment so a better test would be great.
         | 
         | Everything else is pretty straightforward in terms of diagnosis
         | and there are decent treatment techniques, I had a simple
         | needle biopsy that confirmed the cancer but for many men this
         | test (although easy-peasy in my case) is scary, expensive and
         | often confirms there's no cancer at all.
        
         | randcraw wrote:
         | Your BF's doctor is uninformed and offering bad advice.
         | 
         | Fact is, most men over age 70 do have elevated PSA due to small
         | amounts of low grade prostate cancer cells (Gleason score of
         | 3+3). Usually it advances slowly, never growing beyond the
         | bounds of the prostate gland before the patient dies from some
         | other cause.
         | 
         | But an elevated PSA (over 1 and below 10) in someone younger
         | than 70 should not be ignored. Often a second PSA test is done
         | perhaps a month later to confirm the first score and to see if
         | the number is rising quickly. If repeated tests do not show PSA
         | elevation AND the score is low, often the urologist will
         | recommend a "monitor it, and wait and see" strategy.
         | 
         | If the PSA number is high or is rising, the next step is to get
         | a biopsy where 12 to 18 samples of tissue are taken from the
         | prostate to see how much of the gland has cancerous cells
         | (Gleason 3, 4, or 5).
         | 
         | I know something about this topic because a routine PSA test at
         | age 55 showed that I had asymptomatic cancer in 80% of my
         | prostate. Luckily it was removed surgically. But if my doctor
         | was as casually unconcerned as your BF's doctor, my cancer
         | would have metastasized and by now it would be incurable.
        
           | fasteo wrote:
           | >>> Your BF's doctor is uninformed and offering bad advice.
           | 
           | I wouldn't go that far. In your n=1 case it seems clear that
           | not monitoring PSA would have been an error, but there exists
           | a debate on the risk/benefit of this test. Namely, the
           | unnecessary suffering that it can inflict to a healthy person
           | with elevated PSA.
           | 
           | This is a good review [1]
           | 
           | "To screen or not to screen for prostate cancer? This remains
           | an important question. Screening relies on a highly imperfect
           | measure, the prostate-specific antigen (PSA) blood test,
           | which is prone to false-positive results. And with mounting
           | evidence that survival benefits from screening pale in
           | comparison with the harms from overtreatment -- particularly
           | incontinence and impotence -- the pendulum has steadily swung
           | away from it. Still, screening research continues, in the
           | hopes that some lifesaving benefits may be found."
           | 
           | [1] https://www.health.harvard.edu/blog/new-study-once-again-
           | cas...
        
             | randcraw wrote:
             | I'm keenly aware of the PSA debate. Policy about its proper
             | use been see-sawing back and forth for a decade.
             | 
             | Starting about 10 years ago, just before it mattered to me,
             | official policy decided to NOT screen using the PSA test.
             | The belief was that underinformed primary care docs were
             | overreacting to a high PSA number and ordering too many
             | biopsies which often led to "unnecessary" infections. Of
             | course, the right response was to do a better job of
             | interpreting the test results, ideally to refer the results
             | to a more expert urologist _before_ doing a biopsy, not to
             | cut back on the test.
             | 
             | Given its low cost ($50) and very high sensitivity, the PSA
             | test provided a very valuable service that could be
             | equalled by no other test. Physical exam is often wrong,
             | missing a large fraction of positive cases of cancer. And
             | biopsies introduce infection most often in older patients.
             | Younger ones can tolerate biopsy better, but were
             | disallowed from PSA screening entirely due to this
             | overprotective policy.
             | 
             | The right solution was clearly to interpret the PSA test
             | results more judiciously by introducing more expertise
             | prior to biopsy, knowing that PSA is overly sensitive for
             | diagnosing cancer. Fortunately the official policy has
             | since been reversed, and PSA has returned to routine use --
             | now with inclusion of a second test or a urologist prior to
             | biopsy.
             | 
             | The same blunder took place in mammographies at about the
             | same time. Too many false positives led to too many
             | biopsies and thus routine screening with mammography was
             | deemed unacceptable and it was deprecated as well.
             | Fortunately that overreaction has also ended.
             | 
             | Sensitive medical tests are essential. Overreaction to
             | possible misinterpretation of positive results by inexpert
             | GPs is the problem, not the test itself. I routinely thank
             | the stars above that my GP was expert enough to know that.
        
         | oleander73 wrote:
         | It is true that in old men there is a large percentage of slow
         | growing mostly harmless prostate cancers, but you can also get
         | it if you are younger (or it can be aggressive) and then
         | treatment is possible (and required). The advantage of doing a
         | PSA test is however not clear cut, because having a (slightly)
         | elevated PSA can be caused by a benign enlarged prostate or
         | prostatitis. This is why this new test is worthwhile (if it
         | really works).
         | 
         | Source: I'm 47 and have prostate cancer (metastasized, so
         | incurable but there are still a number of treatment options to
         | improve quality and quantity of life).
        
           | singingfish wrote:
           | The way PSA is a useful marker is not the absolute value but
           | the rate at which it increases. If the doubling time of your
           | PSA is too high it means you're at risk of prostate cancer
           | and need further investigation. Get it done twice in your 30s
           | and 40s and more regularly when older than that.
        
           | btam wrote:
           | What exactly do you mean by "a large percentage"?
           | Cancer.org[1] says that it's 1 in 8 men during their
           | lifetimes, the parent post says "almost all men get it at
           | some point" -- where is this info coming from?
           | 
           | [1]: https://www.cancer.org/cancer/prostate-cancer/about/key-
           | stat...
        
         | the-dude wrote:
         | My father was treated for prostate cancer with internal
         | radation pellets.
         | 
         | I don't know the time between the 'treatment' and his death,
         | could be anything from 12 - 24 months. I know at least one of
         | the pellets had started 'wandering'.
         | 
         | He died of acute leukemia and I suspect that had to do with the
         | radation. However, I am not pursuing research into this, it
         | won't bring him back. He was 63 years old.
        
         | ojbyrne wrote:
         | Unless your boyfriend is 70+, this is lots of bad advice.
         | 
         | 1. 1 in 8 men are diagnosed with prostate cancer.
         | 
         | 2. Second leading cause of cancer death among men.
         | 
         | 3. There are treatment options. With treatment, 15 year
         | survival rate is 95%.
         | 
         | All of that info can be found here:
         | https://www.cancer.org/cancer/prostate-cancer/treating.html
        
       | randcraw wrote:
       | This news begs a big question: How much does this new test cost?
       | That will decide how it might be adopted.
       | 
       | This test requires a chip rather than a simple lab assay. If the
       | cost of the test is comparably as low as PSA ($50) it could
       | entirely replace PSA for screening. However, if the chip is more
       | expensive than PSA, it still may be very useful -- as a second
       | test _after_ a PSA screening test reports a high number but
       | _before_ a biopsy.
       | 
       | If this new test could diminish the number of infections from
       | unnecessary biopsies that worry policymakers, routine PSA
       | screening combined with this test could become a low-risk no-
       | brainer new standard.
        
         | elicash wrote:
         | My dad had prostate cancer a few years ago, which was treated
         | successfully with radiation. He now gets his PSA score twice a
         | year -- once with his annual physical, and 6 months later with
         | his cancer doc.
         | 
         | I wonder whether the biosensor could be something patients like
         | him could have at home. (Also, now I'm imagining Apple telling
         | customers they can urinate on the next generation of the
         | watch.)
        
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