50% – 75% of cases of Covid-19 are asymptomatic - <AUTHOR> https://www.repubblica.it/salute/medicina-e-ricerca/2020/03/16/news/coronavirus_studio_il_50-75_dei_casi_a_vo_sono_asintomatici_e_molto_contagiosi-251474302/?ref=RHPPTP-BH-I251454518-C12-P3-S2.4-T1 <comment><USER2> I live in Japan and I experience mild symptoms since last Wednesday but not sure if my symptom is due to Covid-19. In Japan, You have meet two conditions to take a CPR test.

1\. the symptoms with fever of 37.5 degrees or more continue for 4 days or more (for the eldery and those with underlying disease, "4 days" becomes "2 days")

2\. you have strong laxity (malaise) or breathlessness (dyspnea), or you have underlying diseases (diabetes, heart failure, respiratory diseases (such as chronic obstructive pulmonary disease))

I don't meet the first condition, so I was refused to take a test, but I still have chest tightness and consistent coughing. I wonder where the number "37.5" comes from, and 4 squeal days!? If the article in question is true, these two conditions are totally meaningless.

So why is taking a PCR test so hard in Japan? Most people believe it is due to Olympic. The Japanese prime minister, Shinzo Abe, still believes we can hold Olympic as planned at this point. To that end, they want to hide the case of infection as possible. I feel strong anger towards my government since they care more about Olympic than human lives.

At this point, Olympic will be inevitably postponed. I hope my government is smart enough to loosen the conditions and let people to take PCR tests immediately…

<comment><USER3> I think there is a more reasonable explanation why they are not testing you. Simply because they wouldn't do anything with that information anyway. If the test is positive they'll send you home to quarantine telling you to call back if your fever worsens. If the test would show negative, they'd tell you, guess what; "please call back if your fever worsens, and stay in quarantine anyway".

So the information doesn't really matter.

In Sweden once they change tactics from trying to track each and every case, and who they might have gotten it from etc, to a a strategy more about just accepting that it's spreading and trying to limit the spread in general, and protect the weak. Then they also stopped doing testing here.

Unless you are in a risk group, the test doesn't really make a difference.

<comment><USER4> > Unless you are in a risk group, the test doesn't really make a difference.

If the test is positive, you can self-quarantine _and notify everyone you 've been in contact with that they need testing_. Then any one of those people that tests positive can do the same thing, etc. etc.

If you don't do any testing, you end up with a bunch of positive but asymptomatic carriers wandering around unknowingly infecting other people.

South Korea is taking this approach and they seem to be doing a lot better than most other countries.

<comment><USER5> Indeed and it probably makes much of the difference why active cases in Korea have kind of leveled off while in Europe they are growing about 25%/day. And just a reminder that's 800x a month.

<comment><USER6> Is it possible for the number of cases counted to go up simply because more testing is occurring, while the number of people with the virus has leveled off?

</comment></comment></comment></comment></comment><comment><USER7> I wonder if this will be like H1N1.

At first we only identified extreme cases and we had these terrifying reported fatality rates.

Then we identify more and more mild or asymptomatic cases and the rates drop and drop.

We've already seen how CFR was reported as 3 or 4%. Then on the cruise ship full of people over 60 it's 0.7%. If there are lots of mild or asymptomatic cases it will likely be much lower.

H1N1 was identified as having a scary 0.4% CFR early on and was later found to be much lower, but we didn't know until after the fact.

An example report from 2009:

[https://www.who.int/immunization/sage/1.Briand_epi_7th_July_...](https://www.who.int/immunization/sage/1.Briand_epi_7th_July_2009_\(rev_6July_09\).pdf)

In the end it may have killed over half a million people in 2009 - but for some reason people barely noticed. (Tangent: I wonder if it's partly the changing media landscape from 2009 to 2020.)

<comment><USER8> The WHO predicted that 150 million people would be killed by avian flu

[https://www.google.com/amp/s/amp.theguardian.com/world/2005/...](https://www.google.com/amp/s/amp.theguardian.com/world/2005/sep/30/birdflu.jamessturcke)

Using the same logic that had lead to the severe predictions for cv19.

For swine flu they promoted and stood by a CFR of 60%. Again turned out to be nonsense; nonsense known at the time to others

[https://jech.bmj.com/content/62/6/555.abstract](https://jech.bmj.com/content/62/6/555.abstract)

<comment><USER9> Overestimates of the severity of the threat have much less harmful consequences than underestimates. For a start, actual casualty statistics are not independent from mitigation actions taken.

<comment><USER8> > Overestimates of the severity of the threat have much less harmful > consequences than underestimates.

We didn't take the estimates for SARS and h1n1 as "seriously" as now, and they are just as if not worse than this.And look what happened.

<comment><USER9> I think Asian countries took the estimates pretty seriously. I think both would have been worse if they didn't, especially SARS.

</comment></comment></comment></comment></comment><comment><USER10> > "The vast majority of people infected with Covid-19, between 50 and 75%, are > completely asymptomatic but represent a formidable source of contagion".

The Professor of Clinical Immunology of the University of Florence, Sergio Romagnani

> Asymptomatic infection has been reported, but the majority of the relatively > rare cases who are asymptomatic on the date of identification/report went on > to develop disease. The proportion of truly asymptomatic infections is > unclear but appears to be relatively rare and does not appear to be a major > driver of transmission.

[https://www.who.int/docs/default-source/coronaviruse/who- chi...](https://www.who.int/docs/default-source/coronaviruse/who-china-joint- mission-on-covid-19-final-report.pdf)

> Clinical and epidemiological data from the Chinese CDC and regarding 72,314 > case records (confirmed, suspected, diagnosed, and asymptomatic cases) were > shared in the Journal of the American Medical Association (JAMA) (February > 24, 2020), providing an important illustration of the epidemiologic curve of > the Chinese outbreak. There were 62% confirmed cases, including 1% of cases > that were asymptomatic, but were laboratory-positive (viral nucleic acid > test).

[https://www.ncbi.nlm.nih.gov/books/NBK554776/](https://www.ncbi.nlm.nih.gov/books/NBK554776/)

Weird discrepancy on the order of 75x. I'd love to trust the experts, but who? I am leaning towards truly asymptomatic spread being rare, since you get infected by SARS-CoV-2, not COVID-19 (COVID-19 is the disease), the level of uncertainty of 25% is higher than for other reports, and the main reported mode of transmission is through symptomatic cough droplets.

<comment><USER11> The Italian number (75%) comes from testing everyone in a village of 3000 people. The Chinese number (1%) comes from testing everyone who comes to hospitals and maybe their family members. I would guess that the Chinese sample was selected for people displaying symptoms (asymptomatic people will not go to the clinic), while the Italian number biases for people early in the course of the disease. For the purposes of public health and controlling disease spread, the Italian number is more meaningful.

Note also that it is possible the virus has evolved to spread more easily, which in the context of a lot of screening and social distancing of symptomatic people would mean more asymptomatic spreading.

<comment><USER12> How are the South Korean's coming up with such few positives if the disease is presumably spreading among the 70% with no symptoms?

<comment><USER11> Most "asymptomatic" people will show symptoms within two weeks, so aggressive cluster/contact tracing works. South Korean local goveenment staff are following the credit card use, transit use, and other daily movements (CCTV logs) for every confirmed case, then issue two week self-isolation orders to those who shared a workplace, restaurant, cafe, church, or elevator with the confirmed case. Since most cases get a short lived fever or cough within two weeks, SK has been able to stop most transmission chains. I'm actually a bit confused about the scope of SK testing. It looks like everyone with symptoms is being tested, as well as quarantined health care workers and quarantined people from high risk groups, but I'm not sure whether asymptomatic people are tested at the end of their quarantine period.

<comment><USER9> Yup. Apparent efficacy of the South Korean approach versus more generalised 'self-isolate if you have symptoms' instructions would be a point in favour of the disease being often asymptomatic [for extended periods]

</comment></comment></comment></comment></comment><comment><USER13> I'm not a confirmed case, but I'm a 90% sure case based on symptoms and symptoms of people I have been in close contact with, and so far the experience has been relatively mild, in the literal sense. The primary discomfort has likely been the anxiety of how the tightness in my chest might progress (which ironically can also cause chest tightness).

I'm in a low risk group. I had lethargy and high fever the first day of symptoms (a little over a day after high contact exposure to my suspected source), then no fever (or very mild fever, can't tell because I have no thermometer), dry eyes, consistent mild chest tightness and occasional cough for the following two days (to present). The person I believe I contracted it from is also in a low risk group and had a sore throat and persistent cough for about 5 days, and is currently asymptomatic. She had been going about her business thinking it was just a cold for the duration of her symptoms.

Testing is still difficult in my area, and many folks with mild symptoms like the aforementioned aren't even attempting to get tested, so I suspect the true numbers are about 10x-50x the reported confirmed cases. This is good in that it means the death rate is also off by that factor, but bad in that there will not be enough fear/incentive for the primary carriers (young adults) to adhere to adequate social distancing. It's an unfortunate externality when an infectious disease has discriminatory consequences.

<comment><USER14> > I suspect the true numbers are about 10x-50x the reported confirmed cases. > This is good in that it means the death rate is also off by that factor, but > bad in that there will not be enough fear/incentive for the primary carriers > (young adults) to adhere to adequate social distancing.

If the death rate is off by 10x-50x, isn't this approaching the death rate of seasonal influenza, in which case we didn't actually need to adhere to social distancing in the first place?

<comment> j-pb That doesn't add up, if it wasn't worse than seasonal influenza, then Italys hospitals wouldn't be overwhelmed.

<comment><USER8> Italy did everything wrong.

They basically turned hospitals into covid19 infection parties.

<comment><USER15> do you have sources for that ? i'm extremely interested in understanding why italy seems to be suffering that much compared to other countries. If it's just a matter of being the first, or if it's also something specific to them.

<comment><USER16> As a side note - and JFYI - Italy's situation is very nuanced, as you can see on this map (divided by region):

[http://opendatadpc.maps.arcgis.com/apps/opsdashboard/index.h...](http://opendatadpc.maps.arcgis.com/apps/opsdashboard/index.html#/b0c68bce2cce478eaac82fe38d4138b1)

In the North (and particularly in Lombardy) the situation is dramatic, in the center and in the south it is not (yet) that bad.

Basically the lock-down (started on national level on the 10 th of March) seemingly - and for the moment - managed to work to reduce the spread of the infection in other regions.

The previous lock-down (limited to some cities/provinces of the north) was only a couple days before and evidently too late to be effective.

</comment></comment></comment></comment></comment></comment><comment><USER3> I have shortness of breath, cannot go up the stairs in our house without having to stop and rest. 37 years old and otherwise quite healthy. Have underlying autoimmune disease, and am on immunomod. Coughing and light fever. I've had this for 5 days. When I called the hospital they told me to come in and get tested, but when I came to the hospital they did not test me.

The doctor told me, it wouldn't make a difference anyway. No matter what the test would show he would tell me the same thing: go home, isolate yourself, and come back if your fever worsens.

Once your area reach a certain number of persons affected, there is little use to try to track each one. When they have changed to a strategy of trying to protect the weak, and just slow down the spread. Testing doesn't really add much value or information.

<comment><USER17> I hope you get better soon.

I think your comment describes very well the economics of the pandemic when it spreads further. Basically you can treat everyone with Corona-like symptoms like a corona patient. It doesn't make much difference anymore. Isolation and monitoring of the condition.

If it's a severe common cold the advice isn't that much off, too.

</comment></comment><comment><USER18> I keep hearing "masks are useless". If every person who has any cough or any chest tightness or any sore throat, however mild, put on a mask, wouldn't that stop the spread?

I live in Japan. It started here earlier but didn't explode. Nothing is closed. Business as usual. _everyone_ wears masks.

Most cases in Hokkaido. Maybe because it is much colder there and easy to overexposed and tax the immune system.

<comment><USER19> I think some of the logic behind "masks are useless" is that if people believe masks will prevent it, they'll get too reckless about going out as long as they have a mask. Sadly many people wear masks incorrectly and other people will wear masks that don't actually block viral particulates while out there acting more dangerously than otherwise, spreading disease.

IIRC anything below N95 isn't going to do much, and from experience (yay wildfires) I can say wearing N95s is _very uncomfortable_. Incidentally even physicians wearing proper PPE (n95 or better, etc) can still catch COVID, so it wouldn't be appropriate to say that those are good enough.

It's certainly better than nothing - I'd prefer it if everyone out and about was wearing masks - but the risk of false security leading to dangerous behavior is strong, and we already have issues with mask supplies, so it makes sense to discourage it.

<comment><USER20> That's very convoluted reasoning. I think the main goal of surgical masks for entire population would be to limit amount of virus floating in the air. They are also good at stopping people from touching their faces.

IMO the goverments should make masks mandatory, even if it's DYI mask made from few layers of tshirt. And start teaching people how to use them and why.

<comment><USER19> If the supply was there I'd absolutely agree. At least in the US it's very hard to get adequate masks right now (this is partly due to a failure to maintain supply, there were some news stories recently about how a local manufacturer was begging the government to invest in this so he could maintain production)

</comment></comment></comment></comment><comment><USER21> If a virus takes a week to develop symptoms, and doubles every 3.5 days, that's exactly what do you would expect: after a week 3/4 of the cases are new and too early to detect symptoms.

asymptomatic proportion sampled at a moment grows exponentially with incubation period, it means nothing about who will eventually develop symptoms.

</comment><comment><USER22> In case this thread doesn't gain momentum, some more (potentially interesting) discussion on Reddit [1].

Particularly this post [2]:

> I wonder if they plan to follow up and monitor... From the Diamond Princess > they initially found 50% of people had no symptoms. However upon following > them over the course of weeks that dropped down to about 18%. Due to the > long incubation period it can take some time to determine if someone is > truly asymptomatic or just not symptomatic yet.

[1] [https://www.reddit.com/r/Coronavirus/comments/fjuj24/5075_of...](https://www.reddit.com/r/Coronavirus/comments/fjuj24/5075_of_covid19_cases_are_completely_asymptomatic/)

[2] [https://www.reddit.com/r/Coronavirus/comments/fjuj24/comment...](https://www.reddit.com/r/Coronavirus/comments/fjuj24/comment/fkpkiac)

<comment><USER23> On an unrelated note, I just noticed this entire time I've been reading "asymptomatic" as "asymptotic". I thought it was cases that happen in the limit as severity goes to zero.

<comment><USER24> Some news services have referred to asymptotic spread but it's just hyperbole.

<comment><USER25> Your obtuse reply isn't even tangentially related to the line of discussion.

<comment><USER24> I feel it's unfair that people have disrespected the trifecta you achieved here.

</comment></comment></comment></comment></comment><comment><USER26> "Everyone we found to have Covid-19 had serious symptoms, so we don't want to waste money testing you if you don't!"

I feel this is a trillion dollar mistake, testing more aggressively like South Korea means that you don't have to deploy the army and quarantine people. I had mild symptoms and they refused to test me, what am I to do? Self quarantine without a notice and hence without pay? I could work from home, but most can't so they will just go to work as normal and spread it. And now it is all over the world so only drastic measures will help.

<comment><USER27> I'm not sure if you're quoting something or paraphrasing a position you disagree with.

If it's a paraphrase, I'm not so sure it's a fair one.

In the United States, for example, we are urging people not to be tested unless they have severe symptoms. The reason for that is _not_ to save money, but it's for a lack of testing capacity. As a policy we would much _prefer_ to be testing even the mild suspected cases. But we don't (currently) have the testing capacity to do so.

So I think the lack of testing of mild cases (at least in the United States, and I suspect in other countries) is more a reflection of our rationing priorities than it is a reflection of our spending priorities.

If the testing capacity becomes unconstrained and we (or other countries) _still_ fail to test mild cases.

<comment><USER28> The lack of testing capacity was a choice.

<comment><USER27> Yes, absolutely. The lack of testing capacity was a total failure of the government.

After the acute phase of the crisis, we should investigate what happened in great detail.

But the advice about _who_ should get a test is based on the testing capacity we have now. If we _hadn 't_ failed at testing capacity, we would be recommending more users get tested.

So, if the critique is: "we failed to produce adequate testing capacity", then I absolutely agree. If the critique is instead: "The recommendation of who gets a test is bad", then I disagree. The recommendation is correct given the test capacity failing.

The solution is not to recommend everyone gets tests, because they can't! Those tests are being rationed. The solution is to rapidly improve out testing capacity.

</comment></comment></comment></comment><comment><USER29> Asymptomatic for the entire duration of infection? That sounds bad for reducing R but good for the health of the individual.

<comment><USER30> I would assume that asymptomatic person has a lesser concentration of virus and hence would be less contagious than the really sick ones

<comment><USER31> If you're asymptomatic, you're not coughing droplets everywhere, which ought to make you less contagious

<comment><USER32> On the other hand, some people (e.g. myself) keep sneezing and coughing the whole winter every winter, so I definitely wouldn't consider those _symptoms_ without either headache, body ache, throat pain or fever...

</comment></comment></comment></comment><comment><USER33> The original source of the linked article is a letter by Prof. Sergio Romagnani, sent to the newspaper Corriere Fiorentino, published here on March 15:

[https://corrierefiorentino.corriere.it/firenze/notizie/crona...](https://corrierefiorentino.corriere.it/firenze/notizie/cronaca/20_marzo_15/dobbiamo- cambiare-rotta-ef23a500-669a-11ea-a40a-86d505f82a96.shtml)

As follow-up, they interviewed him, published on March 17:

[https://corrierefiorentino.corriere.it/firenze/notizie/crona...](https://corrierefiorentino.corriere.it/firenze/notizie/cronaca/20_marzo_17/tamponi- tutti-bivio-adesso-cominciamo-ospedali- edb36ab4-682c-11ea-8372-e06aa5c607e8.shtml)

<comment><USER34> Very interesting, thanks.

Translation of the follow-up article: [https://translate.google.com/translate?hl=&sl=it&tl=en&u=htt...](https://translate.google.com/translate?hl=&sl=it&tl=en&u=https%3A%2F%2Fcorrierefiorentino.corriere.it%2Ffirenze%2Fnotizie%2Fcronaca%2F20_marzo_17%2Ftamponi- tutti-bivio-adesso-cominciamo-ospedali- edb36ab4-682c-11ea-8372-e06aa5c607e8.shtml)

</comment></comment><comment><USER35> That sounds like the perfect way for a disease to spread. Do nothing to most.

<comment><USER36> The best evolutionary strategy for a virus is to not cause any disease at all.

<comment><USER37> Better still, it would make the host feel unusually social.

<comment><USER38> There is a paper that showed that the flu virus makes people more socialable.

It was done with students who took flu vaccine. They found people socialised more after they had the vaccine (and thus, were a little bit infected) compared to before.

A literature review looked at the study and came up with the negative explanation - that people felt more secure or relaxed after getting the vaccine as they felt safer. Or were more nervous about needles before.

Ancedote:

I think I have covid-19 and the days before symptoms I felt unusually anxious to get outside and amongst fellow humans. I'm usually an introvert and stay inside mostly so it was notable.

Suggestion:

Online interview people with symptoms now to collect data on peoples behaviour in the days before symptoms showed, when they were infected but not showing, compared to 2 weeks before.

<comment><USER39> A vaccine does not make people "a little bit infected". Vaccines are deactivated virii, so your body develops the antibodies, without any actual infection.

<comment><USER40> That's not totally true the live Polio Vaccine used a live weak infectious virus. Which had the advantage of conferring immunity to unvaccinated people. At the expense of very rarely reverting and causing full blown disease. Far as I know it's no longer being used because of that.

</comment></comment></comment></comment></comment></comment><comment><USER41> Guys, don't underestimate this pandemic, wear plastic gloves, FFP3 masks and if possible protective glasses when you are going outside. Leave your shoes out of the door and wash frequently your hands.

</comment><comment><USER42> Yet another full population study estimates: "We estimated the asymptomatic proportion at 17.9%" - [https://www.medrxiv.org/content/10.1101/2020.02.20.20025866v...](https://www.medrxiv.org/content/10.1101/2020.02.20.20025866v2)

<comment> adam-a I read this study and the recorded figure is around 50%. They're using some probability estimation based on the 50% discovered cases to account for people who had mild symptoms but not at the time they were tested (potentially after they left the ship). They identify flaws in the study though: the passengers were mostly old, so they are more likely to be symptomatic. They also didn't test everyone on the boat, only vulnerable, or symptomatic people, so their base numbers are missing some number of asymptomatic cases. It's not a perfect study and I think you could take 19% as a low bound on the figure and in wider society 50% is plausible.

</comment></comment><comment><USER43> It's a largely academic question, at least in terms of mortality and treatment. If you're asymptomatic, you're unlikely to get tested, and you'll never even know you had it. On the other hand, if you have enough symptoms to be tested, you have a higher mortality risk than asymptomatic cases by definition, so the overall mortality rate doesn't matter to you anyway.

Where it _does_ matter (a lot) is in containment, where we should assume many more people are contagious than the reported cases, so the average individual risk of catching it is much higher.

</comment><comment><USER44> This article on hacker news a couple of days ago could explain a lot of this. There is a possibility that a very large number of the asymptomatic positive tests are in fact false-positives. This could be good news for the world, but I'm not betting on that yet. [https://www.ncbi.nlm.nih.gov/pubmed/32133832](https://www.ncbi.nlm.nih.gov/pubmed/32133832).

<comment><USER45> Wouldn't it be great news if so many are asymptomatic or mild? It might explain why China seems to have so few current cases given its population. Maybe many people have already caught it and now have some form of immunity.

<comment><USER44> I suppose you have a point there. I was thinking that it could be bad that so many are spreading without knowing it.

Also, if many are asymptomatic, and the test is creating a large number of false-positives for those that are asymptomatic, there is a chance that this crisis is not as big as we think it is. Let's hope...

</comment></comment></comment><comment><USER46> Occam's Razor would imply that the "asymptomatic non-transmissive" cases are really just false positives. The only work I've seen on false positives is these guys, who estimate the FP rate for the active nucleic acid test screening at 75% chance of there being a 'false positive rate' greater than 47%.

[https://pubmed.ncbi.nlm.nih.gov/32133832/?fbclid=IwAR3LHLplR...](https://pubmed.ncbi.nlm.nih.gov/32133832/?fbclid=IwAR3LHLplRtmPZED3jt_Hjf2ZKysmDcXMU5LgVgNPcqNAtb9EzcQBKMtCIoI)

</comment><comment><USER47> Interesting, but it doesn't change the fact that health systems are overwhelmed.

If the rate of hospitalization is 15-10%, lockdowns seems the only realistic option.

</comment><comment><USER48> We've known this for a while. Everyone will get it. You might have it now. Nothing will happen. Still, quarantine for a while because you'll give it to an older person or kid. This isn't about a 20-something year old getting sick. Let your anti-bodies make yourself non-contagious. We are all kindergartens and this is chickenpox basically.

<comment> grey-area That means 1-2 million deaths in the US according to the latest modelling from Imperial Collage London, so it's likely all countries will proceed to full lockdown for months at some point soon.

<comment><USER49> This just isnt true. Look at china. Their new cases per day have now dropped to effectively zero. Under 100,000 people got it, and deaths are around 6,000. Keep in mind this is for a population of 1.3 Billion. US population is 300 million. Please explain how 2 million people are gonna die in this country.

<comment> grey-area The paper explains how, these are not my figures but they do seem credible, this is the modelling team advising the uk gov and the gov has adjusted their strategy to suppression in response (the tactic in China), but the economic impact of that is pretty dire too, and it means tough choices.

The measures in China were draconian and long lasting (large cities on lockdown for months), and they managed to contain it because they were first hit and it had not spread far. It has already unfortunately spread widely in the UK and US.

</comment></comment></comment></comment><comment><USER50> MOST COVID19 CASES ARE ATYPICAL AND NOT REPRESENTED BY ADVERTISED SIDE EFFECTS

ATYPICAL SIDE EFFECTS: Light Fever, Severe Lightheadedness, Long Duration Headache, Sore Throat, Severe Body Aches, Tight Chest, Very Light Cough No Phlegm, Sharp Edged Flush on Cheeks with Pale Circle Surrounding Lips, Slight Runny Nose, Lethargy, Confusion, Hot Flashes, Inconsistant Diarrhoea Without Discomfort, Trouble Focusing on Conversations, Shakiness, No Issues Breathing Until Exercise, Flush After Taking Anti-Inflammatories, Very Shakey Legs on Rising, Swollen Lymph Nodes (under arms), Nervous System Issues: Anxiety, Change in Perception of Senses, Insomnia These symptoms will cycle and not present at the same time which is indicative of COVID19

YOU WILL NOT HAVE THE COUGH OR FEVER YOU EXPECT AND MOST PEOPLE BLAME IT ON STRESS,ALLERGIES,COLD,FLU,ETC.

DO NOT TAKE NAPROXEN, IBUPROFEN OR ANY ANTI-INFLAMMATORIES

Example Symptom Progression From an Interview:

" I've been so tired and so winded and just kind of moody and had a constant headache for a week and hot flashes mostly at night where it felt like I had a fever but only at night, random coughing. I figured it was just the weather and stress. Then last night came to a head—terrible brain fog yesterday could barely hold a convo, would shake (like when you're blood sugar crashes) when I'd try to get up and do something, Had the worst migraine ever last night and terrible nausea and was throwing up. Then today this is my face with a huge rash."

Examples of Corona Rash:

[https://imgur.com/a/dXz52rR](https://imgur.com/a/dXz52rR)

</comment><comment><USER51> During the US coronavirus task force briefing just an hour ago, one of the heads of the HHS suggested (without outright saying) that one of the reasons (just one of them) the US is lagging on testing is because they're concerned about the efficacy of tests other countries are running. High false-positive and false-negative rates were both mentioned, in "tens of thousands of tests" distributed to other countries.

There's an underlying truth to this disease that no one has a grasp on right now, and the only way we get to it is the widespread execution of _accurate_ tests. That doesn't happen quickly. Just think about that the next time you feel mad about our testing situation; a core doctrine of medicine (at least in our country) is First, Do No Harm. Telling someone they're infected, when they're not, is doing harm. Telling someone they're clear, when they're not, is doing harm. Enacting policy based on numbers derived from a bad test is doing harm.

And, most importantly, the single thing that represents the entire point of the doctrine: doing nothing is not doing harm.

<comment><USER52> >because they're concerned about the efficacy of tests other countries are running. That's rich. I understand that the US developed test had a lot more issues that the standard not-invented-here one.

And a lot of countries do the test twice, and only act on double positives or double negatives.

>doing nothing is not doing harm How can this be OK? People will spread it if they think they are not sick.

<comment><USER51> > And a lot of countries do the test twice, and only act on double positives > or double negatives.

The false-positivity or false-negativity of a test is not independent across multiple runs. Its not like each test rolls a dice and decides if it wants to be accurate or not. Its more accurately based on the human being tested; a false-positive test for one human would increase the likelihood for a subsequent false-positive test on that same human. Double-testing helps, but its not the solution.

> How can this be OK? People will spread it if they think they are not sick.

First, do no harm. This often means the first response for doctors is to do nothing (and gather information), until they're certain enough that their actions will not result in harm. Doing nothing is not causing harm; the harm has already come to their patient. The doctor is not the cause of that harm; the world caused it. Its a core responsibility of a doctor to not make it worse accidentally.

Sure, people may spread it if they think they're not sick. But what if a doctor provides a false-negative result to an asymptomatic patient? Now, that patient has been told by a doctor "you're fine". They go back to work. Now, they're spreading it. "My doctor said I'm fine, this little cough is probably just a cold." Patient doesn't go back to get it checked out again.

What if they provide a false-positive result to an asymptomatic patient? "Wow, that's crazy. I must have just gotten lucky" the patient says. Two weeks later, they leave quarantine after getting an accurate negative result. A month later, they actually contract the disease. "But, that's impossible. I already had it! My other doctor told me so, he even gave me a Test." Can coronavirus re-infect patients? Now, we're not so sure. Panic. Research studies. The truth is obscure.

This is how doctors everywhere operate, and this is true at the FDA/CDC more than nearly every other country. Our standards for drug development, testing kit development, etc are among the most stringent in the world. It would take a disease far, far more deadly than the coronavirus to compromise them.

</comment></comment></comment><comment><USER53> Let's talk about false positives: there seems to be no solid estimate regarding common Cov-19 tests. I've seen numbers from 40% to 85% in papers suggesting at least a high number, some of which will probably be sloppily classified as "asymptomatic" cases.

<comment><USER42> I read that the false positive rate is extremely low (below 1%).

False positives are not a huge problem when you are only testing people with symptoms. False positives would only become a problem when you are doing a large number of tests on people who have no symptoms (e.g. 1% of 1 million people when close to none have the virus).

I think your numbers are the detection rate: false negative rate is high (up to 40% for early tests).

</comment></comment><comment><USER54> Another thread about a Chinese study on this topic:

[https://news.ycombinator.com/item?id=22598803](https://news.ycombinator.com/item?id=22598803)

</comment><comment><USER55> I saw a discussion of this on reddit, there was NOT info on if these individuals eventually developed symptoms, so take this with a grain of salt.

</comment><comment><USER56> Why is this post title in English while the actual article linked is in Italian?

Shouldn't they have to match?

</comment><comment><USER57> The best way or reducing new positives test-results is by not allowing any new testing.

</comment><comment><USER58> So, how do I know if I am one of those asymptomatic cases?

<comment><USER59> Assume and act as if you are.

</comment></comment><comment><USER18> Here's another question: isolation... and then what?

Sit at home until 2021 when we maybe have a vaccine?

I don't see how we make this virus disappear so while I can see how people staying at home can stop the spread, what happens when they leave? Back to square one?

Maybe UK approach is better.

Maybe we should infect young people deliberately. Here's Netflix, some books, some video games, some virus, stay at home for 2 weeks. Build up herd immunity. Get a paper, move on.

That's UK approach except they wait for clusters to pop up. Why not make them? Control the infection rate.

If the chances are everyone gets infected would be better to chose when!

<comment><USER60> Isolation is too slow the spread. Let the currently sick people get treated, then let the next wave of people catch the virus, once the hospitals have more capacity again. The virus is not _that_ dangerous (under 1% fatality) as long as the healthcare system does not collapse.

</comment></comment><comment><USER61> Holy cow......I really need to learn Italian

</comment><comment><USER62> How reputable is this paper?

<comment><USER63> Very. Repubblica and Corriere are the two main newspapers in Italy, and they are both quite reliable. Repubblica is left leaning, Corriere is right leaning.

</comment></comment><comment><USER64> Googly translation:

[https://translate.googleusercontent.com/translate_c?depth=1&...](https://translate.googleusercontent.com/translate_c?depth=1&nv=1&rurl=translate.google.com&sl=auto&sp=nmt4&tl=en&u=https://www.repubblica.it/salute/medicina- e- ricerca/2020/03/16/news/coronavirus_studio_il_50-75_dei_casi_a_vo_sono_asintomatici_e_molto_contagiosi-251474302/%3Fref%3DRHPPTP- BH-I251454518-C12-P3-S2.4-T1&usg=ALkJrhjf5jbEmuELu9C0C1rvhLi7PpCuHQ)

</comment><comment><USER65> Does that mean 25-50% are severe? Is this a bimodal distribution?

<comment><USER66> Probably not, the other 25-50% get symptoms of which 80% are mild and 20% severe.

</comment></comment><comment><USER67> not super surprising - plenty of other diseases are similar.

Even serious things like HIV are contagious for a long time while being completely asymptomatic.</comment>


The war on WikiLeaks and why it matters - <AUTHOR> http://www.salon.com/news/opinion/glenn_greenwald/2010/03/27/wikileaks/index.html

<comment><USER2> _Of course, there's a personal psychology to it, that I enjoy crushing bastards, I like a good challenge, so do a lot of the other people involved in WikiLeaks. We like the challenge._

It's comments like this that regularly put me off Wikileaks. If you do the job they do then I believe very strongly you should be driven by a desire for truth (not a desire to crush anyone) and also be _objective_. I don't always 100% see that in their actions.

<comment><USER3> No one crazy enough to work on wikileaks would be in it for something as intangible as "the truth." At least these guys are willing to admit they're after the adrenaline rush one gets from destroying people you disagree with.

<comment><USER2> _destroying people you disagree with._

Isn't there a slight irony there... (in the use of the word destroy).

If that is their aim I don't think Wikileaks can really take the moral high ground over the recently released intelligence document concerning them ;)

 _something as intangible as "the truth."_

Possibly truth was an unfortunate choice of word. "Objective" was the key part i meant to get across.

<comment><USER4> again, i'm tired of repeating this, but wikileaks, at least to my mind, is not a news organization, it's a medium for whistleblowers to release information. can't be objective!

it's a job for news organizations and journalists (some of whom might be supporters or volunteers of wikileaks) to analyze and present this released information objectively.

<comment><USER5> It would be nice if it were so simple -- wikileaks is just a version of YouTube.

But they're not. They don't publish everything they get. They have an agenda. And they don't seem to have publication guidelines, which even YouTube (and every other quasi-anonymous publisher) has. In addition, everything they publish is supposed to be against the wishes of some national government somewhere.

Nope. Once they gave up neutrality, they're not a publishing channel. They're a political cause masquerading as a public service.

<comment><USER6> What have they acquired and not published?

<comment><USER7> I would imagine they don't publish things that they cannot verify as probably true, or things that aren't newsworthy.

On the other hand, here's something they _did_ publish: a leak of their own donor list. <http://www.newswiretoday.com/news/46864/>. I see that as pretty good evidence of their integrity.

<comment><USER8> According to a WikiLeaks member, they publish all true and false documents together with a judgment whether they think it's true/false and why. For example, they published a fake Steve Jobs medical report together with a note why they considered it a fake. They do have criteria (e.g. no self-made write- ups, no publically available documents), but nothing against boring or false stuff.

[http://blog.chaosradio.ccc.de/index.php/2009/08/24/cr149-wik...](http://blog.chaosradio.ccc.de/index.php/2009/08/24/cr149-wikileaks/) (if you understand spoken German, that is)

</comment></comment></comment></comment></comment></comment></comment></comment><comment><USER9> This whole saga is probably the best thing that could happen to WikiLeaks. Huge increase for their visibility, which in turn increases the value of the role they play.

<comment><USER10> Provided that they're not currently being played by some intelligence org that fed them bogus data. A huge increase in visibility leading up to a huge flameout could set them back years.

\-----

This whole saga seems to me like WikiLeaks is trying to have it both ways. On the one hand, they style themselves as the intelligence organization of the people, doing serious and valuable work releasing information in the people's interests. On the other hand, they get upset when other intelligence organizations try to bully them, and they play the "mean CIA detained a 17 year old kid" card.

Wikileaks provides a valuable service, but they need to tread carefully. Releasing the wrong information could get some of our spies killed. If that happens, I suspect the CIA "bullying" will get much more severe.

</comment></comment><comment><USER11> Key quotes from the article:

"At exactly the time when U.S. government secrecy is at an all-time high, the institutions ostensibly responsible for investigation, oversight and exposure have failed. The American media are largely co-opted, and their few remaining vestiges of real investigative journalism are crippled by financial constraints...

The need for independent leaks and whistle-blowing exposures is particularly acute now because, at exactly the same time that investigative journalism has collapsed, public and private efforts to manipulate public opinion have proliferated. This is exemplified by the type of public opinion management campaign detailed by the above-referenced CIA Report, the Pentagon's TV propaganda program exposed in 2008, and the ways in which private interests covertly pay and control supposedly "independent political commentators" to participate in our public debates and shape public opinion."

</comment><comment><USER12> I still am confused by the WikiLeaks budget request -- $200k minimum exclusive of salaries per year just to keep the lights on? $600k with a couple salaries?

JYA did this with cryptome for YEARS as a hobby.

<comment><USER13> Even though I agree that the figures are strangely high, I wouldn't actually hold it against them if they just said they want to keep some for themselves. If they're really followed by spooks, detained and threatened - I guess they could use some reward for all of that. It's not something you sign up for with the minimal wage. (when they went public about those incidents, I assumed they're at least a bit worried about "disappearing")

But yeah - showing what is the money spent for would be a good idea.

<comment><USER14> Perhaps someone will leak their budget document.. if only there was a suitable place to leak it to.

<comment><USER15> <http://www.wikileak.org> did publish a Wikileaks partial financial donors list. It also ended up on wikileaks.org. See [https://firstname.lastname@example.com/ssl/wikil...](https://firstname.lastname@example.com/ssl/wikileak/2009/02/follow- the-money---wikileaksorg-partial-donors-list-email.html)

</comment></comment></comment></comment><comment><USER16> Some parts of the leaked anti-Wikileaks document don't seem too objectionable. For example, one of the main recommendations that Salon highlights, and appears shocked by, is that the government should deter leaks by identifying and firing the individuals responsible. Isn't that totally normal and expected policy, though? If some CIA or Pentagon documents get leaked, the obvious response is going to be them trying to figure out who leaked them.

<comment><USER17> When a government employee leaks a document, a crime has been committed. The government's job in this case is to prevent its employees from committing crimes.

If instead it takes on its own propaganda effort do discredit a private nonprofit, something stinks.

The CIA is largely a propaganda organization, by the way. One wonders how many Iranian tweets are being funded by US tax dollars and CIA operations.

In my opinion it's completely scary to think that there might be a campaign to discredit wikileaks, but it's a huge relief to see that that document was itself leaked, suggesting that at least some government employees are aware of possible excesses committed by their departments.

If a government agency wanted to discredit wikileaks and didn't feel empowered to simply assassinate the people running it, it could use all sorts of time tested approaches to discredit/discourage it.

<comment><USER18> _The CIA is largely a propaganda organization_

[citation needed]

<comment><USER19> I don't think this is seriously in question, is it? For an historical example, see <http://en.wikipedia.org/wiki/Operation_Mockingbird> .

<comment><USER18> Thanks for the example. Yes, it was a serious question - I thought the CIA was largely an intelligence gathering agency. I hadn't heard of this before.

<comment><USER20> The CIA has three main responsibilities:

1\. On the ground intelligence gathering (ie - Bribing a reluctant member of a militant group for information on their operations and physical location). Example: <http://en.wikipedia.org/wiki/Curveball_(informant)>

2\. Analysis of gathered intelligence and policy recommendation (how trustful is the information from the above described asset, does it mesh with what is already known, and if it is what course of action should be taken). Example: Philip Seymour Hoffman's character in Charlie Wilson's War, <http://en.wikipedia.org/wiki/Charlie_Wilson%27s_War>

3\. Clandestine operations (carrying out of policy recommendations in #2 that can't be performed by traditional military forces, say the group in question is determined to present a credible threat and needs to be neutralized but is headquartered in Iran). Example: Bay of pigs invasion, <http://en.wikipedia.org/wiki/Bay_of_Pigs_Invasion>

</comment></comment></comment></comment></comment></comment><comment><USER21> I'm getting a 404 on that link. Here's Google's Cache: [http://18.104.22.168/search?q=cache:U4sLRJe_pBUJ:www.salon....](http://188.8.131.52/search?q=cache:U4sLRJe_pBUJ:www.salon.com/news/opinion/glenn_greenwald/2010/03/27/wikileaks+site:http://www.salon.com/news/opinion/glenn_greenwald/2010/03/27/&cd=2&hl=en&ct=clnk&client=safari)

</comment><comment><USER22> Yet another link that's broken on the iPhone due to a botched mobile site implementation. When will they learn?

<comment><USER23> Click on 'full site', go back to HN and try again.

</comment></comment><comment><USER5> I support the idea of open government enormously. We make too many things secret, and a government with so much secrecy is not responsive to its citizens.

Having said that, I also support the idea that some things -- some very few things -- should be kept secret.

Wikileaks does not seem to discriminate between these things.

Therefore I cannot in good conscience support Wikileaks with their mission to make everything they find public. If, as the article indicates, they're in it for personal kicks then that makes it all the worse.

It's 2010. You'd think the average person/whistleblower would have enough ability to self-publish for the entire world to see, right? If Wikileaks isn't providing some kind of independent, third-party vetting or creating some standards for what can be published or not, what value do they bring to the table?

<comment><USER24> > Wikileaks does not seem to discriminate between these things.

And how can someone without a clear view of the whole picture distinguish between both? And who do you want to arbitrate what should and what should not be secret?

<comment><USER25> I think the test should be whether the document has moral or just tactical significance. To give examples from the article:

Guantanamo Bay interrogation manual? Moral significance; leak.

Possible US use of chemical weapons? Moral significance; leak.

US order of battle for 2009? No moral significance; don't leak.

And in the interest of fairness:

Al-Qaida interrogation manual? Leak.

We need a picture of both/all sides' dirty laundry, and Wikileaks doesn't really give that.

<comment><USER24> > We need a picture of both/all sides' dirty laundry, and Wikileaks doesn't > really give that.

Just don't expect Wikileaks to be a one-stop-shop for leaked documents.

And, BTW, I doubt Al Qaeda has such a document. That's not their style to document everything. One may interpret that as one of their major tactical strengths.

</comment></comment></comment></comment><comment><USER17> Fortunately Google is going to help out by hosting a wikileaks server, as part of its goal of ending government censorship.

<comment><USER26> You're a one man spam army on this idea of Google hosting a WikiLeaks mirror... Not to say it's not a good idea, but I don't think this is the place for such pestering.

<comment><USER17> haha... Well I feel sort of bad doing it b/c I love google... I just think it needs to be pointed out. It might help people realize a) the silliness of Google pretending to be fighting censorship and b) that they should donate to wikileaks.

<comment><USER27> "Nor can we accept government or corporate funding and maintain our absolute integrity." from their fundrising drive section. The last time I've looked Google was a company.

<comment><USER17> I think Google would have far more impact upon wikileaks via pagerank tweaks than via funding (if it wanted to). But in any case if Sergey had any balls he'd make a public statement praising wikileaks. It doesn't take balls to criticize the Chinese government.</comment></comment></comment></comment></comment>


Scientists Fix Genetic Risk Factor for Alzheimer's Disease in Human Brain Cells - <AUTHOR> https://gladstone.org/about-us/news/scientists-fix-genetic-risk-factor-alzheimers <comment><USER2> I'll take a stab at explaining this. Neuroscientists and biomedical researchers, feel free to chime in with corrections.

In biomedical researchers, the strength of evidence of your data correlates with how close it is to modeling the human body. So, in general, strength goes as follows:

Animal cell cultures < animal tissue < _in vivo_ animal models <= human cell culture < human tissue < in vivo human trials (phases 1-3)

In this study, the researchers studied the ApoE4 subtype of the ApoE protein (involved in fat metabolism). The gene coding for this protein has been associated with greater risk of getting Alzheimer's disease then other subtypes, so it has been a target of study for a while now.

These researchers cultured brain cells that were differentiated from stem cell lines. Here's how they did it:

Skin from Alzheimer's patients and healthy patients (so apoe4 vs apoe3 containing cells) -> induced back to stem cell precursors -> differentiated into neurons

What they found was the following:

-neurons with apoe4 had production of Alzheimer's hallmarks (Tau phosphorylation, ABeta, neuron degeneration)

-neurons with apoe3 had less to none of these changes.

-editing the apoe4 gene to apoe3 prevented the changes from occurring.

-gettig rid of the apoe4 gene completely prevented the changes from occurring.

-giving a drug that changed the protein structure from apoe4 to apoe3 prevented the changes from occurring.

<comment><USER2> I'm shamelessly pulling all of this from the paper abstract, which you should find here: [https://www.nature.com/articles/s41591-018-0004-z](https://www.nature.com/articles/s41591-018-0004-z)

As for what this means: it's exciting, and if these researchers can prove that the drug is safe in animals and humans they can probably proceed with trials on Alzheimer's patients with the apoe4 gene.

But that's the thing: this discovery, while cool, is relevant to only some of the patients dealing with Alzheimer's that have the ApoE4 gene. This isn't a unifying mechanism to how Alzheimer's occurs in all patients, as it doesn't tackle the problem of patients with apoe3 getting Alzheimer's. Nonetheless it is still relevant especially for early onset, which is more strongly associated with this gene.

<comment><USER3> Hopefully the results can be generalized to other experiments? Possibly the techniques they used?

</comment></comment></comment><comment><USER4> There was another interesting publication about Alzheimer's Desease last week: It appears to be possible to detect the misfolded amyloid‐β protein in a blood sample many years before symptoms develop:

[http://embomolmed.embopress.org/content/early/2018/04/04/emm...](http://embomolmed.embopress.org/content/early/2018/04/04/emmm.201708763)

<comment><USER5> Interesting but not sure there is a clear benefit of knowing ahead of time when there's no treatment available. Knowing how you will end will significantly affect your outlook on life.

<comment><USER6> My mother has Alzheimer's, and I have the ApoE4 gene. Knowing is better.

The only other options are (a) knowing after it's too late to do anything, or (b) knowing at the exact moment science makes a discovery. Since we can't know (b) ahead of time, we're left with either knowing ahead of time, or too late.

Knowing sucks, but it sucks less than any other option.

<comment><USER7> The only counter argument to this I could imagine would be the one I often hear used for other brain abnormalities; i.e. if the knowledge of a potential health problem instigates a mental health issue, ignorance could be better.

I subscribe to your opinion, however.

</comment></comment></comment></comment><comment><USER8> This is a nice article and is a great example of a few technological advances that are making now an incredible time to start a biotech company: massive increase in genomic data and advances in biology (in this case stem cells) to enable better modeling of whether things will work in humans

It costs up to $2.6B to develop a drug. The majority of this is not out of pocket spend on developing the drug, but the cost of risk -- all the money spent on drugs that end up failing. The biggest driver of the cost of failure is failing in Phase 2. Phase 2 trials are the first test of whether a drug is effective in humans. Prior studies look at animal or cellular models of effectiveness, or safety in humans. It can cost $50-100M+ to get to phase 2

Genomic data is one of the most cost efficient ways to predict whether a drug will work in humans. certain mutations, like apoe4, are strongly correlated with disease risk and prognosis. Of course this does not imply causality, but researchers can tease this out with established models. Clinical trials of drugs based on genetic markers have greatly increased odds of success

Genetic biomarkers also enable smaller studies -- rather than study big heterogenous population to find a signal, you can do so with a smaller homogenous population.

This is all very important for Alzheimer's, a field where trials are big and expensive and failure is the norm

The other advance is the ability to easily create neural cells from skin cells. As the paper says, mice are very different than humans, especially neurologically. But it's hard to study human neurons in the lab. The ability to turn skin cells into stem cells and then into other cells enables this (previously only embryonic stem cells were available). So researchers can perform experiments to determine causation in a model that is much better predictor than typical mouse models

There has been a lot of work in cancer developing genetically targeted drugs, but it is not as common in other fields. Part of the challenge is getting enough data, and part of it is that data alone isn't enough, you really need the biological hypothesis to come first

</comment><comment><USER9> Relevant link concerning attenuating Alzheimer's by a fat rich diet: [https://www.mdedge.com/clinicalneurologynews/article/145220/...](https://www.mdedge.com/clinicalneurologynews/article/145220/alzheimers- cognition/fueling-alzheimers-brain-fat)

</comment><comment><USER10> Does anyone know if the genetic testing companies like 23 and Me tell you if have the apoE4 gene mentioned in the article?

<comment><USER11> [Edited to remove incorrect, outdated info about apoE4 data]

23andMe offers information on ApoE4 now that they have FDA approval. You can also use Promethease to get additional information on SNiPs if you want. Here's how.

1\. Get a DNA analysis from 23andMe or similar.

2\. Download your raw genetic data. If you use 23andMe, you can download your raw genetic data here: [https://you.23andme.com/tools/data/download/](https://you.23andme.com/tools/data/download/)

3\. Upload your data to [https://promethease.com/](https://promethease.com/)

Before you do this, you might want to visit ApoE4.Info and consider what you will do with the information once you have it. [https://www.apoe4.info/wp/thinking-about- testing/](https://www.apoe4.info/wp/thinking-about-testing/)

<comment><USER12> This is wrong info. 23andMe has reinstated the Alzheimer's report as of last year.

</comment></comment></comment><comment><USER13> "Scientists have been unclear about why apoE4 is so much more damaging to brain cells than other versions of the protein."

Without a solid why, doesn't this constitute correlation, and not cause?

I'm curious where the line gets drawn, and why that's so.

<comment><USER14> The first step is often to notice a correlation. The causation was found here:

> Treating human apoE4 neurons with a structure corrector eliminated the signs > of Alzheimer's disease, restored normal function to the cells, and improved > cell survival.

The actual mechanism is not necessarily important for a treatment to be successful.

<comment><USER13> Yes. But what about unintended consequences? What if this cures a symptom but creates something else?

<comment><USER15> It's definitely a roll of the dice but I'd venture to say that, aside from constant pain and suffering, pretty much anything else is better than Alzheimer's.

<comment><USER13> I agree. It makes sense.

This was probably not the best example given the context. None the less, without a clear and proven why any "cure" could be risky.

<comment><USER14> > None the less, without a clear and proven why any "cure" could be risky.

The "why" is not as important as you might think. There are many drugs for which we don't know _why_ they work, but we have clinical trials to test for their effectiveness and safety.

And clinical trials are more important than knowing the "why". For example, if you know why a drug inhibits such and such genes, then that is nice to know, but that doesn't tell you what other effects the drug has.

</comment></comment></comment></comment></comment></comment><comment><USER16> Isn't this also groundbreaking because we never previously know why apoe4 contributed to Alzheimer's. What the mechanism was?

</comment><comment><USER17> Alzheimer's is not a neuron disorder. This paper should not have been published.

<comment><USER18> Care to elaborate?

I know there are theories that it's linked to inflammation (etc), but it clearly has _some_ effect on neurons. It's not clear whether reversing those effects also reverses the disease (the anti-Abeta antibody stuff has been disappointing), but given that neurons are.....important for cognition, it doesn't seem totally insane to think that they are somehow involved in AZ too.

</comment></comment><comment><USER19> Seems to have already been known in 1993, according to Wikipedia?

"The best known genetic risk factor is the inheritance of the ε4 allele of the apolipoprotein E (APOE).[45][46]" where [45] is from 1993.

What's new? Am I misunderstanding something?

<comment><USER20> They know more about what happens at the protein level, and they can fix it by adding compounds that fix the errant protein

</comment></comment><comment><USER21> really scary. Can you imagine the CIA create a small molecule that interferes with ApoE3 to give and ApoE4 phenotype?! Inducing dementia in terrorists and then allowing them to return home??!! or Inducing dementia in suspected spies? or inducing dementia on political dissidents?

Or can you imagine the use of this small molecule (which btw is undetectable in the blood) for nefarious political purposes? Have the democrats already used it on our president??!!

<comment><USER22> >Inducing dementia in terrorists and then allowing them to return home??!! or Inducing dementia in suspected spies? or inducing dementia on political dissidents?

I mean... none of that would actually stop the terrorists, spies or dissidents. It wouldn't be any better than, say,getting stabbed with a ricin tipped umbrella[0].

>Have the democrats already used it on our president??!!

No, unfortunately, he's just like that.

[0][https://en.wikipedia.org/wiki/Georgi_Markov](https://en.wikipedia.org/wiki/Georgi_Markov)</comment></comment>


Gates Foundation research can't be published in top journals - <AUTHOR> http://-t-be-published-in-top-journals-1.21299 <comment><USER2> The link is broken (or, actually, incorrect), the correct link is the following:

[http://www.nature.com/news/gates-foundation-research-can- t-b...](http://www.nature.com/news/gates-foundation-research-can-t-be- published-in-top-journals-1.21299)

</comment><comment><USER3> Dupe: [https://news.ycombinator.com/item?id=13404978](https://news.ycombinator.com/item?id=13404978)</comment>


Ask HN: Where should I save all the great links I find on the web? - <AUTHOR>

I was recently put on to http://www.pulpmags.org/ from reading HN. I found this page so interesting that I wanted to save it for later/ever. There are also a good amount of songs and/or artist that I stumble across, and want to save their stuff as well. There are definitely other links too (ex. Pictures, articles, videos, etc.).
What is a very nice web application where I can save these links? Ideally, I want something that is very efficient and graphically pleasant (like a bookshelf).
These are links that I could learn to love, or just mean a lot to me, so I am tired of losing them, or saving some here and there, or having a list of just titles (that's just kind of blah when you're looking through media related content).
Sorry if everybody already knows about this obvious place. Thank you in advance for taking the time to help! <comment><USER2> Heh, I wrote delicious originally for this.

It was preceeded by a text file called "links" in my home directory. Try that?

Alternatively, I currently use [http://pinboard.in/](http://pinboard.in/)

</comment><comment><USER3> Anyone have experience with del.icio.us (now delicious.com)? I've wanted to try it for some time to discover links based on what I've bookmarked, but am hesitant because of privacy concerns and what have you.

<comment><USER4> It used to work ok, but it was recently sold again [1], and a week ago I found that "Discover" doesn't work anymore for some reason (shows 3 old links). There is no support forum too, so I can't even ask why is that.

Tried Diigo, but it looks abandoned, there are some glaring bugs too (recent links tagged "news" are from 2011, for example).

[1]: [http://dealbook.nytimes.com/2014/05/08/delicious-social- site...](http://dealbook.nytimes.com/2014/05/08/delicious-social-site-is-sold- by-youtube-founders/)

<comment><AUTHOR> [https://raindrop.io/](https://raindrop.io/) looks pretty nice. Was discussed here [https://news.ycombinator.com/item?id=7608302](https://news.ycombinator.com/item?id=7608302)

</comment></comment></comment><comment><USER5> I use Google Bookmarks - [http://www.google.com/bookmarks](http://www.google.com/bookmarks) \- and a bookmarklet in chrome.

</comment><comment><USER6> It's a very special place: it's called a Bookmarks file. You can even have folders with subfolders so that you can find what you want very quickly.

<comment><AUTHOR> There is really no need to be a jerk.

I'd like to grab a cup of coffee, sit down on the sofa, and scroll through pages, comics, songs, videos, or whatever I may have saved, and then choose the content that I would like to read, watch, or listen too. All of which have pictures so I can see the cover of what I am about to open up. Part of something that makes an experience are visuals. A page with just text seems kind of blah from the jump, in regards to this situation.

Why do people like coffee shops? The environment, for the most part.

OR..

Isn't the way Steve Jobs became successful was realizing that people didn't want to just look at text?

I could really go and on with examples.

</comment></comment><comment><USER7> [https://pinboard.in/](https://pinboard.in/)

<comment><AUTHOR> Thanks. Although I was looking for something free (I did not mention that). And something a little more graphical right from the result, rather than just a text result, if you will. Nonetheless, still a cool application. I do like how you can find other's bookmarks, that's neat.

<comment><USER7> $10, one time payment, is very good for this service.

</comment></comment></comment><comment><USER8> [https://www.instapaper.com](https://www.instapaper.com) is a good service. However I find this more suitable for long form articles not multimedia.

</comment><comment><USER9> I use Evernote for this purpose. You can save just the URL or clip the whole page. I use it for saving links that are then available across all my devices.

<comment><AUTHOR> That's a great solution. I've had an account, but I just haven't used it much. After just testing it out again, I am going to go with that.

I do wish after you bookmark something that you could change the thumbnail to a custom image or something. The few that I have bookmarked have pretty bad thumbnails... oh well.

All in all, this (web clipper) is really cool.

Appreciate it.

</comment></comment><comment><USER10> Why not save all website you love on a word file. And save that word file in your laptop or computer

<comment><AUTHOR> That would work. It just seems like there are better options. For instance, just being able to access it from all devices, on the fly, is nice.

Think I am going to go with [https://raindrop.io](https://raindrop.io) I really like their interface, so far. And if they ever shut down, I can just export all my bookmarks!

<comment><USER11> great, that doesn't sound like an advertisement at all!

<comment><AUTHOR> I assure you that is not an advertisement.

</comment></comment></comment></comment><comment><USER12> Pinterest?

<comment><AUTHOR> That would hit the graphically pleasing part, and it's nice to see related things, and other peoples stuff, but I do not think (could be wrong) that you could easily export your bookmarks if you ever wanted to move them to a different service.</comment></comment>


Learning to Love JavaScript - <AUTHOR> http://ontwik.com/javascript/google-io-2011-learning-to-love-javascript/

<comment><USER2> I learned a ton and only watched half of it. This guy can really break things down.

</comment><comment><USER3> Does anyone know what he's using to present those slides? I really like the transition animation and how it shows the edges of the next/prev slides.

<comment><USER4> Similar to this: <http://slides.html5rocks.com/>

</comment></comment><comment><USER5> I learned some new things from the video! Thx!!</comment>


Say "No" to Templates - <AUTHOR> https://multi-programming.com/ecommerce-templates-is-bad-idea <comment><USER2> Huge pop-up overlaying the entire screen, and the "close" button was off the screen, requiring that I resize, and then move around to hunt it down.

So I ask myself - why should I take advice from them about web site/page design?

Perhaps that's unfair and unreasonable, but the lesson for people here on HN is that the way you present your information absolutely affects how seriously people take you, and whether they will bother listening to you at all.

But then, you probably knew that.</comment>


Show HN: Customizing Sheet Metal for Laser-Cutting - <AUTHOR> Hi HN,
We've launched a public beta for customizing sheet metal. Right now it's only for rectangular objects. Before we create alike configurators for the other shapes we'd really appreciate your feedback.
https://metalscut4u.com/calculation/?id=1
Choose a SURFACE TYPE Choose THICKNESS Choose FORM "Rectangle/Square" Enter "Width" and "Length" and then launch "Customize my Shape" <comment><USER2> I'm not sure that in a "production" setting, step by step specification is better than a "full featured" dashboard. Supposing I have ten parts, the step by step process is a slow way to communicate it. A random access form is probably better for sophisticated users (and sophisticated users are a bigger segment of the sheet metal market than first timers).

Don't misunderstand me, the program shows a lot of work and polish. But animated transitions are low priority if I'm ordering sheet metal. When I'm ordering sheet metal, my time is probably money.

Good luck.

<comment><AUTHOR> Yes, you're totally right: it's a lot of clicking around even before you get to actually start designing. With a full featured dashboard we could offer a walk-through for first-timers and switching between a professional and prosumer mode/menu.

Thank you for your feedback brudgers!

</comment></comment><comment><AUTHOR> Thank you all for your input so far!

What do you think about a feature where you can upload your own design files/.dxf and check for manufacturability and get a quote? Not so much regarding market size etc. but versus the offering of ready-to-make shapes?

</comment><comment><USER3> I would find this easier working from shape first.

Did precision layout for many years. Looks promising.

It was not clear the part would arrive bent, or just cut?

<comment><AUTHOR> Thanks ddingus, Yes, we're definitely include bend objects in Version 2. For now, just cutting. Did you have any specific 3D object in mind?

<comment><USER3> I don't. And can flatten anything I want easily.

Have done it every way, from old school descriptive geometry, bend deduction, neutral surface.. you name it.

I asked about already bent pieces wondering about your market. Not everyone can bend. You may sell more, if you offer that.

Looks like you are headed that way. :D

</comment></comment></comment><comment><USER4> How do you differentiate from protocase.com?

<comment><AUTHOR> For everything beyond custom electronic enclosures you should choose our approach ;)

Yes, their approach of having identified basic shapes that serve as a good starting point to customize these to one's individual specifications seems to be the same. Most of the times we all have quite similar problems we need solutions for, but just a little custom.

Have you used their services before? What did you like and what did you dislike? How could they service your needs better? Thanks @matt_the_bass for making us think about our offering

<comment><USER4> I've used them for a number of years for low volume sheet metal parts. They are more expensive dive than a local shop but they are ALWAYS fast turnaround and never have a problem. I can't tell you how many issues I've had with various machine shops over the years. I wish they did more complicated machining too.</comment></comment></comment>


Cool iPhone app lets you acoustically measure distances of up to 25 meters - <AUTHOR> http://iqtainment.wordpress.com/acoustic-rule

<comment><AUTHOR> Check out the discussion on Reddit, and grab some promo codes: [http://www.reddit.com/r/iphone/comments/m9scx/hello_riphone_...](http://www.reddit.com/r/iphone/comments/m9scx/hello_riphone_it_took_me_200_hours_to_make_this/)</comment>


Log4PHP 2.0.0 Released - <AUTHOR> http://email@example.com

<comment><AUTHOR> The proper link: [http://mail-archives.apache.org/mod_mbox/logging-log4php- use...](http://mail-archives.apache.org/mod_mbox/logging-log4php- user/200912.mbox/<email@example.com>);

</comment><comment><USER2> Here's a link to the project: <http://incubator.apache.org/log4php/>

</comment><comment><USER3> The link 404s</comment>


Human settlement of Mars in 2023 - <AUTHOR> http://mars-one.com

<comment><USER2> I hesitantly vote this up, not because I'm buying it, but because I love the topic, and would love to see HN talk about the concept of colonizing Mars. My understanding is that the biggest problem with terraforming it is the lack of magnetif field and the low gravity, yeah?

To be honest, I'd find it more interesting if it were a single, large, transparent container landed on Marsian soil, and then the inside was made (through means of repeatable large scale activity, not just pumping in air,) it was made into a green house. Then put a live web feed up.

A single room showing the potential of life on Mars is, to me, far more inspiring than people living in pods and having to use space suits to walk around.

<comment><USER3> I wonder if future generations of humans from the colony would become taller and heavier because of the lower gravitation.

<comment><USER4> The people in the space station have the odd problem of being a couple of centimeters taller and outgrowing their chairs when they go home after a few months. Described by Dutch astronaut Andre Kuipers here:

[http://blogs.esa.int/andre-kuipers/2012/05/15/ik-pas-nog- in-...](http://blogs.esa.int/andre-kuipers/2012/05/15/ik-pas-nog-in-het- stoeltje-van-mijn-sojoez/?lang=en)</comment></comment></comment>


Handcuffed, drugged with ketamine: Truth behind Thai cave rescue - <AUTHOR> https://www.news.com.au/world/asia/handcuffed-drugged-with-ketamine-truth-behind-thai-cave-rescue/news-story/172803c159e20de5cef5dee324266d30 <comment><USER2> FTA: "This was to ensure that if he did wake up from his ketamine slumber, he wouldn't try to rip off his face mask, endangering both his life and that of his rescuer," Cochrane writes.

Cave diving is extremely dangerous. There should be no criticism about how the rescuers chose to go about it.

<comment><AUTHOR> Agreed, they got it done. That's all that counts. They're heroes.

</comment></comment><comment><USER3> this article reads like a condemnation, but it looks like the decisions were made to maximize the likelihood of successful live extraction. And those decisions were made by experts under the gun. So I feel like the article is criticizing without accepting the reality of the situation.

</comment><comment><USER4> I guess I don't understand why they would freak out while being rescued.

<comment><USER2> Scuba diving takes training, it's not like breathing normal air. Add the possibility for claustrophobia and darkness fear. There is a very high possibility for irrational behavior.</comment></comment>


Does a single Arc instance serve all Hacker News traffic? - <AUTHOR>

I'm excited for a tidier, more practical Lisp but curious about how efficient the initial public Arc implementation will be for web apps. <comment><USER2> My guess is this question is coming from a Ruby developer.

<comment><AUTHOR> No, but the dependency on "horizontal scaling" for medium-traffic web apps is more common due to Rails and one reason I ask.

<comment><USER2> I didn't mean it in a negative sense.

Indeed, but horizontal scaling has been common before Rails and will be common after Rails, since most web apps are stateless and transaction based. So, even though Apache and mod_blah only runs as one process, you can still horizontally scale. With rails it is apparently common to have more than one process per server.

</comment></comment></comment><comment><USER3> Yes.

<comment><USER4> Is it threaded?

<comment><USER3> Yes.</comment></comment></comment>


Fury Road: Even the B-ROLL Is Awesome - <AUTHOR> https://www.youtube.com/watch?v=hatTUJT0Kxg

<comment><USER2> I don't want a director's cut of this movie, I want 5 blu-ray's full of whatever cool footage they shot for this movie.</comment>


Exposing Python 3.6's Private Dict Version - <AUTHOR> http://jakevdp.github.io/blog/2017/05/26/exposing-private-dict-version/ <comment><USER2> > Python uses many dictionaries in the background: among other things, local > variables

Just a minor correction, Python doesn't use dicts for local variables, `locals()` is a lie, it creates a dict from scratch. Internally each frame has an array of locals whose values correspond to the names in the code object's co_locals.

<comment><USER3> > `locals()` is a lie, it creates a dict from scratch.

Are you sure? The behavior I see suggests otherwise...

        >>> a = 1
        >>> d = locals()
        {'a': 1, 'd': {...}}
        >>> b = 2
        {'a': 1, 'd': {...}, 'b': 2}
        >>> d['b'] = 123
        >>> b
        123
        >>> d is locals()
        True

<comment><USER4> The REPL essentially operates at the global scope, which is represented as a dictionary. Variables local to a function are not stored in a dictionary, however:

        def main():
            a = 1
            d = locals()
            print d
            d['b'] = 123
            print b
            print d
            print d is locals()

        main()

Which prints

        {'a': 1}
        Traceback (most recent call last):
          File "test.py", line 23, in <module>
            main()
          File "test.py", line 19, in main
            print b
        NameError: global name 'b' is not defined

<comment><USER5> That's because the compiler doesn't know the locals() dictionary will be modified at runtime, so it treats b as a global variable (which happens to be undefined).

To show that not even changes to existing local variables work, try

      def main():
          a = 1
          d = locals()
          print d
          b = None
          d['b'] = 123
          print b
          print d
          print locals()
          print d is locals()

which prints

      {'a': 1}
      None
      {'a': 1, 'b': 123}
      {'a': 1, 'b': None, 'd': {...}}
      True

I.e. changes to the dictionary returned by locals() are ignored, and calling locals() again overrides the previous values.

</comment></comment></comment></comment><comment><USER6> Raymond Hettingers presentation this year at Pycon was also interesting.

Modern Python Dictionaries A confluence of a dozen great ideas PyCon 2017 - [https://www.youtube.com/watch?v=npw4s1QTmPg](https://www.youtube.com/watch?v=npw4s1QTmPg)

</comment><comment><USER7> I watched an earlier version of Raymond's talk and I skimmed through the other one. One thing that I think they both mention is that to take advantage of some of these improvements you need to set every attribute any instance of your class will ever set on the __init__ method.

This is probably a good practice anyway. I'm curious now how I can test and see if I'm taking advantage of this or not. I wonder if using the attrs module will also make use of this new feature.

<comment><USER8> I'm starting to wonder whether it wouldn't be a better design to forget about classes for most use cases, instead only use namedtuples and have a bunch of functions defined that take one type of namedtuple in their first argument. You can easily bind this by doing my_applied_func = functools.partial(my_func, my_named_tuple). This design IMO has a few advantages compared to classes:

* __repr__ comes for free.

* converting all members to a list or dict comes for free.

* converting a list or dict TO a namedtuple comes for free.

* more restrictive in what you can do with data structures inside the namedtuple - may lead to a cleaner design where you think about pulling apart the data into multiple tuples at an earlier point in the prototype phase.

* You by design won't make functions into instance methods that depend on multiple data tuples.

* Need to extend a function to deal with different types of tuples? You now don't need to refactor an instance method into a first class function, instead just dispatch and be done.

* Inheritance can be solved with the above method as well. This may actually be more maintainable than class based inheritance, since you see all the logic for a specific function explicitely (or explicitely dispatched) in one place.

The only reason I can think of to still use a class: If you can heavily profit from inheritance or if you need to program against an "interface" like dict- or listlike behavior or comparison operators.

<comment><USER7> A lot of your points are solved with attrs. I suggest reading up on it if you haven't already. [http://www.attrs.org/en/stable/](http://www.attrs.org/en/stable/)

I think organizing / refactoring a bunch of named tuples would be a mess. In one code base I maintain I switched a bunch of namedtuples to attrs classes and the code instantly became more readable / maintainable.

The downside to the namedtuple is that it's a tuple and can be unpacked as one.

for x, y in points: print x, y

# vs.

for p in points: print p.x, p.y

# ... now go and add a z to the point class and see what happens to your code.

<comment><USER8> I don't get your point about unpacking yet to be honest. Both your code examples work fine with namedtuples I think. Adding additional attributes is better in the second example, which is why it is to be preferred, but that works with namedtuples as far as I understand.

<comment><USER9> Adding a member to the tuple requires updating all code that unpacks it.

Adding an attribute doesn't impact any code that doesn't use the attribute.

<comment><USER8> Yes, that's why you usually don't use unpacking for a namedtuple. This works just fine without me adding additional 3rd party packages:

> from collections import namedtuple

> Point = namedtuple('Point', ['x', 'y'])

> points = [Point(3,4), Point(5,2)]

> for p in points:

> print(p.x, p.y)

</comment></comment></comment></comment></comment></comment><comment><USER10> Thank you for this, it was a very interestingread.</comment>


The $100M 'Business Club' Crime Gang - <AUTHOR> https://krebsonsecurity.com/2015/08/inside-the-100m-business-club-crime-gang/ <comment><USER2> Can someone explain how they get the money out? I understand that they hack a company, send themselves money to a bank in China... and then? Can't the chinese just trace the money and go tell the bank to give it back? Do they use money mules to get the money in cash, if so how do they distribute it to the many members?

<comment> jay-saint The article references recruiting _Money Mules._ These are typically people hired or coerced into using cloned bank cards to withdraw cash from ATMs.

<comment><USER3> Yeah, and either those get no punishment at all - because they're considered victims - or a light punishment. They can't link back to whoever gave them the orders either.

</comment></comment></comment><comment><USER4> The fascinating thing is, there's already Russian propaganda in that article's comments - called web brigades.

They just mention that there is no conflict between Russia and Ukraine, although Russia send unofficial armed troups to Ukrain :p, because they didn't allowed the coupe of "obama's" administration.

The problem is, America didn't send any troops to Ukrain, Russia did:

[http://www.telegraph.co.uk/news/worldnews/europe/russia/1165...](http://www.telegraph.co.uk/news/worldnews/europe/russia/11656043/My- life-as-a-pro-Putin-propagandist-in-Russias-secret-troll-factory.html)

[https://en.wikipedia.org/wiki/Web_brigades](https://en.wikipedia.org/wiki/Web_brigades)

<comment><USER5> It isn't Obama's coup. It's Victoria Nuland and the Big Oil coup. Here's a video of Victoria Nuland of the Department of State claiming U.S. has spent $5 billion since 1991 to 'build democratic institutions' in Ukraine, at around 07:30. Take note of the sponsorship flags by Chevron and ExxonMobil in the background. Note how she uses the word 'invested'.

[https://www.youtube.com/watch?v=2y0y-JUsPTU#t=448](https://www.youtube.com/watch?v=2y0y-JUsPTU#t=448)

IMO that is evidence of past U.S. interference in Ukraine's political affairs.

Next time you pay for a Uber ride - remember the government has spent at least that much for every person in the U.S. to interfere in Ukraine politics, a country all the way up to the border of Russia.

Last time the reverse happened to the U.S, they tried to assassinate Fidel Castro, blockaded Cuba into poverty and invaded the country with 1500 soldiers and 8 B-26 bombers.

<comment><USER6> Those "flags" just mean they sponsored whatever conference this is at. The video nor the other stuff doesn't say which conference it is.

It's funny how the US is damned if it does and damned if it doesn't in these cases. "Big oil" might or might not be even interested in how Ukraine/Russia works out, beyond the usual "can we do business there?" concerns. Isn't it simply that competitors to Russian control over Ukraine need partners offshore for oil operations?

I know people who have had to travel to Cote Ivorie to do work, and it's an uncomfortable thing to have to do. They have a number that can call if they need to be evacuated. Not that this has been executed, but it has come up in discussions with the customer there.

After all, we could just turn our backs and let Putin have whatever he wants.

When we look back historically at the 1953 Iran coup, that sure as heck was oil oriented, but it was the British government ultimately that requested CIA involvement. Nationalizing other people's oil assets has certain ... risks associated with it. This is at very least much more subtle than that.

<comment><USER7> Oh yeah, its because theyre "damned if they do damned if they dont" all right. Like pushing a color revolution so you can coopt the powrr base is just a "oopsie well we might as well because wed be viewed as damned anyway!" Sort of thing. Does HN really buy this obvious shill propaganda?

<comment><USER6> I don't buy "shill propaganda" because I watch a couple of metric tons of CSPAN every year. The big companies just sponsor these things blindly. It's all rather bland. They do it sort of blindly - and it's not exactly Riefenstahl. It's very grey-corporate boring.

I just meant "damned if you do; damned of you don't" to bring up the odd position Americans find themselves in four generations against the natural grain of American isolationism. The infamous American provincialism is well- won.</comment></comment></comment></comment></comment>


Ask HN: Is target="_blank" becoming outdated? - <AUTHOR>

While browsing a few blogs today, I clicked on an outbound link. To no surprise, it opened a new window. I understand that everybody wants to keep people on their site for the longest amount of time possible, but I have a hunch. I tend to manually middle click when I'd prefer to open a window in a new tab. Perhaps it's just us techies (or me), but I see usage of target="_blank" slowly becoming unnecessary as the general population learns the key combinations to make their own decisions.
What are everyone elses thoughts on this common-place technique? Does a window popup irk you as much as it does me nowadays? It really may just be applicable to tech sites.
I'm guilty of using target="_blank" on my blogs as well. I'm rethinking this one... <comment><USER2> Opening new browser windows has been on the Top 10 list of design mistakes of 1999:

<http://www.useit.com/alertbox/990530.html>

I hate it, if the back button breaks. I know many people who use the back button as one of the main elements of the browser. I have been present several times, when somebody got really angry because of a broken back button. So I would recommend the following rule as best practice:

Don't ever break the back button!

It takes much work and creativity to make visitors love websites. We should not ruin that hard work by a silly design decision like target="_blank".

Also, the target="_blank" is a relic from the time of framesets. This time is over.

</comment><comment><USER3> target="_blank" is horrible. It was a stupid thing in the beginning, and remains to be awful to this day.

If I want to open something in a new tab or window, I will do so, no website should tinker with my tabs and windows, be it opening new ones or anything else: it's none of its business. Opening a new tab without MY approval is about as bad as spying on other tabs or attempting to interfere with them in any other way.

Middle click and the open in new tab/window context menu option in most browsers is there for a reason, have been there for years, and most people I know (techies and non-techies alike) know how to use it, and was one of the first things they learned to use when they met with a web browser.

</comment><comment><USER4> I know from experience that most people don't know the key combos to open in their chosen windows.

I always use Ctrl + T, but when I'm demonstrating something or somebody is watching me browse they almost always ask what I have done when I use the combo.

It's dangerous to assume that your readers are as technically proficient as yourself. But I can see in certain citations why it might be applicable, e.g. on Hacker News the majority of their readers are going to know the keyword shotcuts because that's their target market.

I do think that the blog choosing for you can be a pain, but the combos still work on the majority of links and for those who don't know them you can keep them on your site by using the target= in the link HTML, probably the best of both worlds.

</comment><comment><USER5> I think for user's that don't really understand how to open something in a new tab or new window, they might not really want to leave your site when clicking on an external link. But who knows, if they leave, they could come back.

</comment><comment><USER6> On more business oriented web apps, I use it to create separate windows when generating reports; i.e. web-generated PDFs don't have an exit button. There it is VERY useful.

I still use it on some sites, knowing not everyone knows how to create new browser windows by right-clicking links, and I do find it a pain myself on sites that don't use it, and I forgotten and have to page back to get to where I was before. So since I prefer it, and I find it convenient, I go with it.

</comment><comment><USER7> A plugin that changed the color of the cursor if a new window would open upon hovering over such links would be great.

here's one way: [http://www.binaryturf.com/firefox-visually-identify-links- op...](http://www.binaryturf.com/firefox-visually-identify-links-open-window/)

</comment><comment><USER8> Wow, I didn't realize what a pain target="_blank" was. I'm definitely guilty of using it.

Have you considered changing your browser settings so a new tab opens instead of a new window? On Firefox its edit-preferences-tabs-'open new window in new tab instead'

<comment><USER9> He probably does, but that's no justification for using it. If I left-click on a link, that means I _don't_ want it to open in a new tab or window.

</comment></comment><comment><USER10> target="_blank" may or may not be a minor annoyance to some users. I've personally never gotten a complaint about it on any sites i've built/run. Just like every other tool it has it's uses. The standard way I've been seeing it used is to open links to new sites in new windows/tabs and open links that keep the user on your site in the same window/tab.

I don't see anything wrong with continuing to use it.</comment>